ONCOLOGY MCQS FOR
N E E T- S S ( M E D I C A L
ONCOLOGY AND
SURGICAL
ONCOLOGY)
For NEET-SS, board review and other entrance exams
Volume: 2 (cancers of the endocrine system, sarcomas, skin
cancers, CNS cancers, hematology, miscellaneous cancers,
complications of therapy, supportive care and palliative care)
Dr. Bhratri Bhushan
MBBS, MD (medicine), DM (medical oncology)
Consultant medical oncologist and hematologist
Copyright © 2020 by Dr. Bhratri Bhushan. All rights reserved. No part of this publication may be reproduced, distributed, or
transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without
the prior written permission of the publisher, except in the case of brief quotations embodied in critical reviews and certain other
noncommercial uses permitted by copyright law. For permission requests, write to the publisher, addressed “Attention:
Permissions Coordinator,” at the address: A6, Jindal hospital, Hisar, Haryana, India 125001 www.bhratri@gmail.com
This work is provided “as is,” and the author and the publisher disclaim any and all warranties, express or implied, including any
warranties as to accuracy, comprehensiveness, or currency of the content of this work. This work is no substitute for individual
patient assessment based on healthcare professionals’ examination of each patient and consideration of, among other things, age,
weight, gender, current or prior medical conditions, medication history, laboratory data, and other factors unique to the patient.
The publisher does not provide medical advice or guidance, and this work is merely a reference tool. Healthcare professionals, and
not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis
and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification
of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and
healthcare professionals should consult a variety of sources. When prescribing medication, healthcare professionals are advised to
consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things,
conditions of use, warnings, and side effects and identify any changes in dosage schedule or contraindications, particularly if the
medication to be administered is new, infrequently used, or has a narrow therapeutic range. To the maximum extent permitted
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Dedicated to my father Dr. Bharat Bhushan
PREFACE
W
hen I was preparing for DM entrance, I experienced a dearth of
books on the subject of oncology and the books that were available
were either not updated or were lacking in depth, that was when I
conceived the idea of writing such a book myself.
I have written this book purely from the perspective of an oncologist and by
relying on the highest quality material, most importantly the Bible of
oncology: DeVita , Hellman, and Rosenberg's Cancer Principles &
Practice of Oncology 11th edition. The NCCN guidelines and high impact
journals were also referenced as and when needed. The result is this book,
which will serve the purpose of equipping the exam going (NEET-SS and
board review, along with any other entrance exam where questions about
oncology are asked) doctors with the right tool to test and build their
knowledge.
As the knowledge in the field of oncology is unfolding at an unprecedented
scale and new strategies are being devised at a prolific pace, it is not
possible to provide all of the updated information, all at once. I will be
updating this book periodically for this purpose and I would implore readers
to keep themselves updated by going through the quarterly updates of
DeVita’s oncology that are included with the purchase of the 11th edition
and also the NCCN guidelines.
In case of any queries and suggestions regarding this book, kindly send to:
bhratri@gmail.com
CANCERS OF THE ENDOCRINE SYSTEM
Q. Multiple endocrine neoplasia type 1 (MEN1), which is also known as
Wermer syndrome, most commonly gives rise to tumors of:
1.
2.
3.
4.
Parathyroid glands
Anterior pituitary
Pancreatic islet cells
Adrenal gland
Answer: parathyroid glands
It’s an autosomal dominant disorder that presents in the fifth decade of life.
MEN1 is a tumor suppressor gene present on the chromosome 11q13.
It should be noted here that another syndrome, Werner (note the spelling
difference) is characterized by premature aging and predisposition to
thyroid carcinoma, malignant melanomas, and soft tissue sarcomas.
Q. MEN2A is associated most commonly with:
1.
2.
3.
4.
Medullary carcinoma thyroid
Pheochromocytoma
Parathyroid tumors
Anterior pituitary gland
Answer: medullary carcinoma thyroid
Another syndrome MEN2B is associated with marfanoid habitus, mucosal
multiple ganglioneuromas, and intestinal autonomic ganglion tumors
MEN2 is caused by proto-oncogene RET found on chromosome 10q11.
Q. Carney complex is most often associated with mutations found on
chromosome:
1.
2.
3.
4.
17q
2p
3q
13p
Answer: 17q
Q. Adrenocortical cancers are most commonly are:
1.
2.
3.
4.
Benign and unilateral
Malignant and unilateral
Benign and bilateral
Malignant and bilateral
Answer: Benign and unilateral
Q. VHL type 2 predisposes to all except:
1.
2.
3.
4.
Pheochromocytoma
Retinal angiomas
Central nervous system hemangioblastomas
Non clear cell renal carcinomas
Answer: Non clear cell renal carcinomas
It predisposes to “clear” cell renal carcinomas
It is caused by mutations in VHL found on chromosome 3p.
Q. Which of the following is a hallmark of adrenocortical carcinoma:
1. Overexpression of insulin-like growth factor 2 (IGF2)
2. Overexpression of insulin-like growth factor 1(IGF1)
3. Overexpression of insulin-like growth factor 3(IGF3)
4. Overexpression of insulin-like growth factor 4(IGF4)
Answer: Overexpression of insulin-like growth factor 2 (IGF2)
Q. McCune Albright syndrome is characterised by all except:
1.
2.
3.
4.
Polyostotic fibrous dysplasia
Café-au-lait skin pigmentation
Peripheral precocious puberty
Central precocious puberty
Answer: Central precocious puberty
This is caused by activating mutations in the oncogene GNAS located at
20q13.
There are no clear cut guidelines about its management, especially
regarding excision of pituitary adenoma.
Q. Which of the following is not a part of 3PA syndrome:
1.
2.
3.
4.
Paraganglioma
Pheochromocytoma
Pituitary Adenoma
Parathyroid hyperplasia
Answer: Parathyroid hyperplasia
Q. Which is the most common activating point mutation responsible for
papillary thyroid carcinoma:
1.
2.
3.
4.
BRAF
MAPK
MEK
RAF1
Answer: BRAF
The gene is found on chromosome 7q.
Unlike papillary thyroid cancer, follicular thyroid cancer is rarely associated
with RET or BRAF mutations and more commonly associated with PPARγPAX8 gene rearrangements.
Anaplastic carcinoma of the thyroid is associated most commonly with
TP53 mutations.
Q. Thyroid nodules are fairly common in the general population. What
proportion of thyroid nodules prove to be malignant:
1.
2.
3.
4.
10% to 15%
2-5%
<1%
None of the above
Answer: 10-15%
Thyroid nodules are first evaluated clinically and then TSH should be done.
If TSH is low then a radioiodine thyroid scan should be performed. If this
scan shows hyperfunctioning nodule then chances of it being malignant are
very low and cytologic evaluation is not needed.
On the other hand if the radioiodine scan shows a “cold” nodule then the
chances of malignancy are high and cytology is indicated.
Q. If a thyroid nodule is present and a high-resolution ultrasound of the
neck is performed, which of the following feature will not be associated
with an increased likelihood of malignancy:
1.
2.
3.
4.
Microcalcifications
Nodular hyperechogenicity
Irregular borders and vascularity
A nodule that is taller than wide on transverse view, increase the
likelihood of malignancy
Answer: Nodular hyperechogenicity
In fact, nodular “hypo”echogenicity increases the likelihood of malignancy
Q. Exposure to radiation early in childhood is associated with an increased
risk of papillary thyroid cancers, e.g., Iodine-131 treatment:
1. True
2. False
Answer: false
While it’s true that exposure to radiation is associated with thyroid cancer,
radioiodine treatment is not.
Q. Hashimoto thyroiditis is associated with the risk of development of:
1.
2.
3.
4.
NHL of thyroid
Hodgkin’s lymphoma of thyroid
Thyroid sarcoma
Follicular carcinoma variant of thyroid
Answer: NHL of thyroid
Q. Which of the following thyroid cancers doesn’t arise from follicular cells
(choose more than one option if necessary):
1.
2.
3.
4.
Papillary
Follicular
Anaplastic
Medullary
Answer: medullary
MCT arises from the parafollicular (C) cells
Q. Which of the following syndromes is associated with follicular thyroid
cancer (choose more than one option if necessary):
1.
2.
3.
4.
FAP
Cowden’s
Carney complex 1
Familial nonmedullary thyroid cancer
Answer: all of the above
Q. Which of the following is not a part of the MACIS score used for
prognostication of well-differentiated thyroid cancer:
1.
2.
3.
4.
Age
Tumor grade
Tumor size
Completeness of resection
Answer: tumor grade
There are several criteria used for prognostication of DTC like: AGES (age,
tumor grade, tumor extent, and tumor size), AMES (age, metastatic disease,
extrathyroidal extension, and size), and MACIS (metastasis, patient age,
completeness of resection, local invasion, and tumor size).
Q. Orphan-Annie nuclei are characteristically found in which type of
thyroid cancer:
1.
2.
3.
4.
Papillary
Follicular
Anaplastic
Medullary
Answer: papillary
Q. Which of the following treatment strategies will be incorrect in cases of
papillary thyroid cancer (PTC):
1. A patient with >4 cm PTC should undergo a total or near-total
thyroidectomy
2. Lobectomy may be considered for 1- to 4-cm PTC without any
other high-risk features
3. Prophylactic lateral neck dissection is recommended in PTC
4. Central neck compartment should be dissected during initial
thyroidectomy
Answer: Prophylactic lateral neck dissection is recommended in PTC
While therapeutic lateral neck dissection is to be done in patients having
clinical neck node metastases, a “prophylactic” lateral neck dissection (by
definition done is patients with clinically negative necks).
Q. After thyroidectomy TSH levels should be kept at low levels to prevent
stimulation of any remnant malignant thyroid tissue. Which of the
following is true about the ATA guidelines for the adequate TSH levels to
be maintained in thyroid cancers post operatively:
1. TSH levels of 0.5 to 2 mIU/L are acceptable for patients at low
risk of recurrence
2. TSH levels of 0.1 to 0.5 mIU/L are acceptable for patients at
intermediate risk of recurrence
3. TSH levels of ≤0.1 mIU/L are acceptable for patients at high risk
of recurrence
4. All of the above
Answer: all of the above
Notes on postoperative radioactive iodine thyroid remnant ablation (RRA):
1. RRA is not indicated in low risk disease
2. RRA is indicated in patients with high-risk PTC (defined as
MACIS score >6) or in patients with follicular carcinoma or
3.
4.
5.
6.
Hurthle cell carcinoma
It is performed approximately 6 weeks after near-total or total
thyroidectomy
A low iodine diet is recommended for 1 to 2 weeks and a
pretherapy low dose iodine-131 or iodine-123 scan is done and
then patients are rendered hypothyroid with a goal of increasing
serum TSH to >30 mIU/L to obtain optimal uptake of
radioiodine.
Another way is to increase TSH by using recombinant human
TSH
Posttherapy whole-body iodine scanning is typically performed 1
week after iodine-131 treatment to identify metastases
Q. Papillary thyroid microcarcinomas are defined as PTCs with a maximum
diameter of:
1.
2.
3.
4.
≤10 mm
≤5 mm
≤1 mm
None of the above
Answer: ≤10 mm
Q. What is the recommendation of the ATA guidelines for the management
of a patient of papillary thyroid cancer who underwent thyroidectomy and
relapsed biochemically but in whom imaging studies are negative for
recurrence:
1. Empiric RAI therapy is indicated in patients with significantly
elevated serum Tg (stimulated serum Tg >10 ng/mL with
thyroid hormone withdrawal or >5 ng/mL with recombinant
human TSH)
2. Empiric RAI therapy is indicated in patients with significantly
elevated serum Tg (stimulated serum Tg >5 ng/mL with thyroid
hormone withdrawal or >2 ng/mL with recombinant human
TSH)
3. Empiric RAI therapy is indicated in patients with significantly
elevated serum Tg (stimulated serum Tg >20 ng/mL with
thyroid hormone withdrawal or >10 ng/mL with recombinant
human TSH)
4. Empiric RAI therapy is indicated in patients with significantly
elevated serum Tg (stimulated serum Tg >30 ng/mL with
thyroid hormone withdrawal or >10 ng/mL with recombinant
human TSH)
Answer: Empiric RAI therapy is indicated in patients with significantly
elevated serum Tg (stimulated serum Tg >10 ng/mL with thyroid hormone
withdrawal or >5 ng/mL with recombinant human TSH)
Other indications of empiric RAI therapy in these patients are:
1. Rapidly rising serum Tg
2. Rising anti-Tg antibody levels
It should be noted that up to half of the patients with advanced DTC are
RAI refractory. (RAI-R).
Doxorubicin is approved by the U.S. Food and Drug Administration for the
treatment of
RAI-R DTC
Q. Which of the following chemotherapy agents is approved by FDA for
use in radioiodine refractory papillary thyroid cancer:
1.
2.
3.
4.
Doxorubicin
Paclitaxel
Vincristine
Gemcitabine
Answer: doxorubicin
Q. Anaplastic carcinoma of thyroid limited to thyroid gland without any
invasion to the surrounding structures belongs to stage:
1.
2.
3.
4.
II
IVA
IVC
III
Answer: IVA
It should be remembered that all anaplastic thyroid cancers are staged as
stage IV. Stage IVA are limited to the thyroid, stage IVB are with local
invasion, and stage IVC with distant metastases.
Q. Which of the following modality is not routinely used in the evaluation
of medullary thyroid cancer:
1.
2.
3.
4.
MRI
CT
PET
RAI WBS
Answer: RAI WBS
Radioiodine scan is not useful in MTC because this cancer does not
concentrate iodine.
Q. All of the following are true about management of medullary thyroid
cancer, except:
1. Imaging studies looking for metastatic disease in lungs, liver, and
bones should be performed if neck nodal disease is present or if
the calcitonin is >500 pg/mL
2. Surgical management of MTC includes total thyroidectomy with
central compartment node dissection
3. Postoperatively TSH should be kept at low levels according to
the ATA guidelines to prevent growth of any thyroid cancer
remnant
4. Postoperative RAI is not indicated in MTC
Answer: Postoperatively TSH should be kept at low levels according to the
ATA guidelines to prevent growth of any thyroid cancer remnant
It must be remembered that MTC arises from C cells, which have nothing
to do with iodine uptake. Thus TSH levels don’t need to be maintained to
prevent cancer growth (as opposed to papillary thyroid cancer where TSH
must be maintained at low levels according to the risk of recurrence to
prevent tumor growth). Because C cells don’t take up iodine, RAI therapy
will not be useful and thus not indicated.
Q. Which of the following statements is not true:
1. Vandetanib is approved in advanced MTC based on the ZETA
trial
2. Cabozantinib is approved in advanced MTC based on the EXAM
trial
3. Pazopanib has been studied in advanced MTC in the COMPARZ
trial
4. Sunitinib and sorafenib have been studied in MTC but not
approved
Answer: Pazopanib has been studied in advanced MTC in the COMPARZ
trial
COMPARZ trial was done in RCC, not MTC.
Q. The most common cause of primary hyperparathyroidism is:
1.
2.
3.
4.
Parathyroid adenoma
Multigland parathyroid hyperplasia
Double parathyroid adenoma
Parathyroid carcinoma
Answer: parathyroid adenoma
PHPT is characterized by a high serum calcium and a high or
inappropriately normal PTH.
Q. Shaha and Shah staging system is used for:
1.
2.
3.
4.
Parathyroid carcinoma
Parathyroid adenoma
Both of the above
Neither 1 nor 2
Answer: parathyroid carcinoma
Q. The drug cinacalcet is a:
1.
2.
3.
4.
Calcium channel blocker
Calcium reuptake inhibitor
Calcium efflux promoter
Calcimimetic
Answer: Calcimimetic
This drug is preferred over other drugs for hypercalcemia induced by
parathyroid disorders because of its favorable side effect profile.
Q. The Weiss scoring system is used for:
1.
2.
3.
4.
Pheochromocytoma
Adrenocortical carcinoma
Parathyroid carcinoma
Medullary thyroid cancer
Answer: adrenocortical carcinoma
This score has nine parameters and a score of 3 or more establishes the
diagnosis of ACC. is established when
tumors have a Weiss score ≥3.
Q. Which is/are the criteria adopted by the WHO for defining malignant
pheochromocytoma or malignant paraganglioma:
1. Pheochromocytoma of the Adrenal Gland Scaled Score
(“PASS”)
2. Grading System for Adrenal Pheochromocytomas and
Paragangliomas (“GAPP”)
3. Presence of metastasis
4. All of the above
Answer: presence of metastasis
The first two criteria have been proposed but are not adopted by the WHO.
Q. Which of the following is not a part of the “triad” of symptoms of
pheochromocytoma:
1.
2.
3.
4.
Headache
Palpitations
Hypertension
Diaphoresis
Answer: hypertension
Q. Metanephrine levels, used in cases of pheochromocytoma, may also be
elevated in:
1.
2.
3.
4.
Obstructive sleep apnea
Heart failure
Tricyclic antidepressant use
All of the above
Answer: all of the above
Q. Which of the following is not true about the perioperative management
of hormonally active adrenocortical tumors and pheochromocytoma or
paragangliomas:
1. In patients with hypercortisolism cortisol-lowering agents such
as ketoconazole or metyrapone may be considered before surgery
2. In patients with hypercortisolism, there are chances of adrenal
insufficiency postoperatively, so glucocorticoid replacement
should be initiated immediately after surgery
3. In patients of pheochromocytoma, preoperative α-blockade, salt
and fluid restriction are recommended
4. In patients of pheochromocytoma, a β-blocker agent should only
be initiated after adequate α-blockade due to the risk of
hypertensive crisis secondary to unopposed α-receptor
stimulation
Answer: In patients of pheochromocytoma, preoperative α-blockade, salt
and fluid restriction are recommended
While it is true that preoperative α-blockade has to be done; salt and fluid
“restriction” is not recommended. Salt and fluid are “loaded”, i.e., they are
given in excess amounts in the preoperative period.
Q. For patients with tumor Ki-67 ≥10% and/or AJCC/ENSAT stage III
disease:
1. Adjuvant mitotane is routinely started within 3 months of
resection and continued for at least 2 years
2. Radiotherapy has no role in the adjuvant setting even in patients
who underwent R1 or R2 resection
3. Adjuvant mitotane is routinely started within 3 months of
resection and continued for at least 5 years
4. Adjuvant mitotane is not routinely indicated except in cases of
tumor spill, where it is indicated and should be initiated within a
week after resection
Answer: Adjuvant mitotane is routinely started within 3 months of resection
and continued for at least 5 years
It should be noted here that radiotherapy may have a role in patients who
underwent R1 or R2 resection.
Q. Which cells of the endocrine pancreas produce ghrelin:
1.
2.
3.
4.
A cells
EC cells
P/D1 cells
D cells
Answer: P/D1 cells
Q. In pancreatic neuroendocrine tumors, proliferation status may be
assessed by counting mitoses:
1.
2.
3.
4.
Per 10 high-power microscopic fields
Per 20 high-power microscopic fields
Per 50 high-power microscopic fields
Per 5 high-power microscopic fields
Answer: Per 10 high-power microscopic fields
10 high-power microscopic fields correspond to an area of 2 square mm.
The more commonly used method for determining the proliferation status is
by Ki-67 IHC using the MIB1 antibody., or it can be expressed as mitoses
per 10 high-power microscopic fields (or 2 mm2 ).
Q. On contrast-enhanced multidetector computed tomography (CT), pNETs
characteristically appear:
1.
2.
3.
4.
Hypodense
Hyperdense
Isodense
Variable
Answer: Hyperdense
They appear hyperdense because they are hypervascular.
Q. The gallium-68 DOTATATE PET/CT scan has the ability to obviate the
need for biopsy in many patients with very small pNETs:
1. True
2. False
Answer: true
Q. Which of the following pancreatic neuroendocrine tumors are not
usually malignant:
1.
2.
3.
4.
Gastrinoma
VIPoma
Somatostatinoma
Insulinoma
Answer: insulinoma
Q. If a patient has a nonfunctioning pancreatic neuroendocrine tumor of
size 2 cm or less and observation is chosen, which of the following will not
be advisable:
1. To follow up 3 to 6 monthly and assess for disease progression
and need of therapy
2. A biopsy at the time of diagnosis has to be done and if the patient
has high-grade NET then treatment should be started right away
because then observation will not be an option
3. A biopsy can be avoided if the tumor shows DOTATE positivity
4. None of the above
Answer: A biopsy at the time of diagnosis has to be done and if the patient
has high-grade NET then treatment should be started right away because
then observation will not be an option
A biopsy in this setting is not necessary if the tumor shows DOTATE
positivity.
Treatment options for advanced pNETs:
1. Sunitinib
2. Everolimus: The RADIANT-3 was a phase III trial done in
patients with progressive pNETs and they were randomly
assigned to receive everolimus or placebo. The study
demonstrated clinically and statistically significant benefit in
PFS for patients receiving everolimus.
3. Somatostatin analogs: The PROMID trial evaluated octreotide
long-acting release (LAR) 30 mg every 4 weeks was compared
with placebo among treatment-naïve patients with midgut
NETs. With LAR a progression free survival benefit was
observed compared to patients on placebo.
4. PRRT (peptide receptor radiotherapy): Neuroendocrine Tumors
Therapy (NETTER)-1, (a phase III study) compared four cycles
of 177Lu-DOTATATE given every 8 weeks followed by
octreotide LAR 30 mg every 4 weeks to octreotide LAR 60 mg,
demonstrated significant PFS benefit among patients with
midgut NETs. This trial led to the FDA has approval of
Lutetium (Lu) 177 dotatate for wider indication of
gastroenteropancreatic NETs.
5. Chemo (e.g., platinum and etoposide combination)
Q. All of the following biochemical parameters are diagnostic of ZES
except:
1. Serum gastrin ≥1,000 pg/mL and gastric pH ≤2
2. Serum gastrin 10-fold above the normal range and a gastric pH
≤2
3. A positive secretin test, i.e., a postinjection serum gastrin level
increase of >300 pg/mL
4. A positive calcium stimulation test, i.e., a postinjection serum
gastrin level increase of >395 pg/mL
Answer: A positive secretin test, i.e., a postinjection serum gastrin level
increase of >300 pg/mL
A positive secretin test means a postinjection serum gastrin level increase of
>200 pg/mL.
Q. Gastrinomas are most commonly found in:
1. Proximal duodenum
2. Distal duodenum
3. Pancreas
4. None of the above
Answer: proximal duodenum is the development of type
In patients with MEN1-associated ZES, type II gastric carcinoids may
develop.
The most appropriate treatment for ZES initially is proton pump inhibitors.
Q. Which are the most common functioning pancreatic neuroendocrine
tumors:
1.
2.
3.
4.
Insulinomas
Gastrinomas
VIPomas
Glucagonomas
Answer: insulinoma
Q. Insulin hypersecretion due to insulinoma can be differentiated from
increased insulin levels due to exogenous insulin administration by:
1.
2.
3.
4.
Raised levels of C-peptide in the former
An insulin-to-glucose ratio of 0.3 or less in the latter
Raised sensitivity to glucagon stimulation in the former
None of the above
Answer: Raised levels of C-peptide in the former
C-peptide is not present in exogenously administered insulin.
Q. It has been estimated that 95% of insulinoma are benign. The treatment
of choice of insulinoma is:
1. Observation and glycemic control
2. Enucleation
3. Distal pancreatectomy
4. Diazoxide therapy
Answer: enucleation
Q. Neuroendocrine tumors are most frequent in:
1.
2.
3.
4.
Foregut
Midgut
Hindgut
Occur with similar frequency in all of the above
Answer: midgut
Low-grade tumors (grade 1) are the most common and have a mitotic index
of <2 mitoses/10 high-power fields (HPF) and a Ki-67 <3%. Intermediategrade tumors (grade 2) have a mitotic index of 2 to 20 mitoses/10 HPF and
a Ki-67 of 3% to 20%. High-grade tumors (grade 3) have a mitotic index
>20 mitoses/10 HPF and a Ki-67 >20%
Q. Abnormal urine 5-HIAA levels of >5 mg per 24 hours are diagnostic of
carcinoid syndrome:
1. True
2. False
Answer: true
Q. The most common symptom in carcinoid syndrome is:
1.
2.
3.
4.
Diarrhea
Flushing
Wheezing
Carcinoid heart disease
Answer: flushing
Q. Pellagra may be associated with carcinoid syndrome. The triad of
pellagra includes all of the following except:
1.
2.
3.
4.
Dermatitis
Diarrhea
Dementia
Dysphagia
Answer: dysphagia
Q. Telotristat is used in the treatment of carcinoid syndrome. It is a:
1.
2.
3.
4.
Tryptophan hydroxylase inhibitor
Tryptophan decarboxylase inhibitor
Tryptophan oxygenase inhibitor
Tryptophan synthetase inhibitor
Answer: Tryptophan hydroxylase inhibitor
Q. Multiple endocrine neoplasia (MEN4) is caused by:
1.
2.
3.
4.
Mutation of CDK1B
Transmethylation of H3K4
Mutations in CTNNB1
t(12;16)
Answer: Mutation of CDK1B
MEN4 is a new entity, it is also known as MENX.
SARCOMAS
Q. Myxoid/round cell liposarcomas characteristically have:
1.
2.
3.
4.
t(12;16)
t(11;16)
t(16;16)
t(11;22)
Answer: t(12;16)
Notes on molecular biology of sarcomas:
1. Ewing sarcoma family tumors: t(11;22), t(21;22), fusions of
22q12 with 7p22, 17q22, 2q33; inv 22q12; t(16;21); t(4;19) or
t(10;19); t(X;4). The t(11;22) resulting in EWSR1-FLI1 is the
most common one (>80%)
2. Desmoplastic small round cell tumor: t(11;22)
3. Synovial sarcoma: t(X;18)
4. Alveolar rhabdomyosarcoma: t(2;13), t(1;13)
5. Alveolar soft part sarcoma: t(X;17)
6. Dermatofibrosarcoma protuberans: t(17;22) (>75%); results in
COL1A1-PDGFB
7. Embryonal rhabdomyosarcoma: Trisomies 2q, 8, and 20; LOH
at 11p15
8. E xtraskeletal myxoid chondrosarcoma: t(9;22); t(9;17); t(9;15);
t(3;9)
9. Endometrial stromal tumor: t(7;17)
10. Clear cell sarcoma: t(12;22); t(2;22)
11. Infantile fibrosarcoma: t(12;15)
12. Inflammatory myofibroblastic tumor: they are positive for ALK.
t(1;2); t(2;19); t(2;17);
13. Solitary fibrous tumor: 12q13 inversion
14. Gastrointestinal stromal tumor: monosomies 14 and 22, deletion
of 1p (>25). GIST has three histologic types: Spindle (70%),
epithelioid (20%), and mixed (10%). KIT or PDGFRA mutation
are found in >90%.
15. Desmoid fibromatosis: trisomies 8 and 20
16. Well differentiated/dedifferentiated liposarcoma: 12q rings.
MDM2 and CDK4 amplification is seen in >85%
17. MPNST: NF1 mutation
Q. Which of the following statements is not true:
1. Desmoid tumors occur in patients with familial adenomatous
polyposis
2. Malignant peripheral nerve sheath tumors develop in
neurofibromas in patients with neurofibromatosis type 1
3. In patients with Li Fraumeni syndrome soft tissue or bone
sarcomas constitute 10% of index tumors
4. In patients with sarcomas associated with RB1 gene mutation,
radiation exposure should be avoided
Answer: In patients with Li Fraumeni syndrome soft tissue or bone
sarcomas constitute 10% of index tumors
Soft tissue or bone sarcomas constitute 36% of index tumors in this
syndrome.
Q. The development of angiosarcoma has been associated with:
1.
2.
3.
4.
Lymphedema
Postmastectomy radiation
Both of the above
Neither 1 nor 2
Answer: lymphedema
While it’s true that angiosarcoma develops most often in patients who have
undergone postmastectomy radiation and develop lymphedema of the arm
on that side, it is not a radiation induced sarcoma and the only established
association is with lymphedema.
This is strengthened by the studies that demonstrate that these sarcomas
may develop outside the field of radiation in these patients.
Q. Which is the least common histologic subtype of soft tissue sarcoma
among the options provided below:
1.
2.
3.
4.
Liposarcoma
Leiomyosarcoma
UPS/PMFH
MPNST
Answer: MPNST
The first three are the three most common sarcomas.
Q. Which mutation is most commonly found in desmoids:
1.
2.
3.
4.
Exon 3 of CTNNB1 gene
Exon 2 of CTNNB1 gene
TP53 gene
CDK4/6 gene
Answer: exon 3 of CTNNB1 gene
Q. DFSP is sensitive to imatinib because of constitutive activation of:
1.
2.
3.
4.
PDGFR-beta
PDGFR-alpha
BCR-ABL1
KIT
Answer: PDGFR-beta
Imatinib is a preferred option for treatment of DFSP.
DFSP is the most common dermal sarcoma.
Q. The most common sites of liposarcoma development are:
1.
2.
3.
4.
Upper trunk and extremities
Back and lower limbs
Thigh and retroperitoneum
Affects all areas of the body with equal frequencies
Answer: thigh and retroperitoneum
Liposarcoma can be divided into three main biologic groups: (1)
ALT/WDLS and dedifferentiated liposarcoma (DDLS), (2) myxoid–round
cell, and (3) pleomorphic.
Q. The most common soft tissue sarcoma in infant and children is:
1.
2.
3.
4.
Rhabdomyosarcoma
Leiomyosarcoma
UPS/PMFH
Extaskeletal Ewing’s sarcoma
Answer: rhabdomyosarcoma
Q. All of the following are true except:
1. Embryonal RMS is most commonly found in children and arises
in the orbit or genitourinary tract
2. The botryoid type of RMS originates in mucosa-lined visceral
organs such as the vagina and the urinary bladder
3. Alveolar rhabdomyosarcoma is observed more commonly in
younger children than in adolescents and adults
4. Pleomorphic rhabdomyosarcoma is the most common form of
rhabdomyosarcoma in adults
Answer: Alveolar rhabdomyosarcoma is observed more commonly in
younger children than in adolescents and adults
In fact, alveolar RMS is more commonly present in adolescents and adults.
Q. Antoni A and B areas are found in:
1.
2.
3.
4.
Schwannoma
MPNST
MFH
Angiosarcoma
Answer: schwannoma
Schwannomas are also known as neurilemmomas.
Antoni A area is an ordered cellular region whereas Antoni B area is a
loose, myxoid one.
Q. Which of the following is not true about synovial sarcoma:
1. It most commonly occurs between 15 and 35 years of age
2. Most common site of occurrence is the lower limbs
3. It originates from the synovial tissue of major and sometimes
minor joints
4. Characteristic translocation involves the X chromosome
Answer: It originates from the synovial tissue of major and sometimes
minor joints
The fact is that synovial sarcoma doesn’t arise from the synovial tissue
despite how the name would suggest.
Q. Which of the following is a grading system used for soft tissue sarcoma:
1.
2.
3.
4.
Broders four grade system
NCI three grade system
FNCLCC system
MSKCC two grade system
Answer: all of the above
Q. In a patient of well-differentiated liposarcoma of lower extremity, after
undergoing wide local excision, the final histopathology report shows that
the microscopic margins are positive. What will be the most appropriate
adjuvant treatment:
1.
2.
3.
4.
Observation
Re-surgery to obtain negative margins
Radiation therapy
Adjuvant chemotherapy followed by radiation
Answer: observation
The management of low versus high grade sarcomas is different. And
among the low grade sarcomas, well-differentiated liposarcomas are a
special variety because these patients don’t require any adjuvant treatment
even if margins are positive postoperatively.
Notes on the management of high grade sarcomas:
1. Ewing’s sarcoma and RMS are managed according to the
protocols in place. Most commonly followed protocols utilize
neoadjuvant chemotherapy followed by surgery and then
radiation if indicated. Some patients with Ewing’s sarcoma are
not good surgical candidates, in such patients definitive RT may
provide good outcomes.
2. In other high grade sarcoma histologies, if the tumor size is 5 cm
or less than upfront surgery is done. If the size is more than 5 cm
but less than 10 cm or if the size is 10 cm or more then
neoadjuvant chemotherapy may be used to make surgery
possible/easy/less morbid.
3. Post operatively if the margins are 1 cm or more and tumor size
is 5 cm or less than observation alone is done (any adjuvant
treatment not indicated). If the margins are 1 cm or more and
tumor size is more than 5 cm but less than 10 cm then
brachytherapy or external beam radiotherapy may be considered.
If the margins are 1 cm or more and tumor size is 10 cm or more
then postoperative IMRT is given.
4. Post operatively if the margins are less than 1 cm or positive and
tumor size is 5 cm or less then brachytherapy or IMRT may be
considered. If the margins are less than 1 cm or positive and
tumor size is more than 5 cm but less than 10 cm then
brachytherapy OR external beam radiotherapy has to be given. If
the margins are less than 1 cm or positive and tumor size is 10
cm or more then postoperative IMRT is given.
Q. The mainstay of chemotherapy for advanced sarcomas is:
1.
2.
3.
4.
Ifosfamide
Dacarbazine
Doxorubicin
Cyclophosphamide
Answer: doxorubicin
Notes on systemic treatment of advanced sarcomas:
1. Pazopanib is an option for metastatic non adipocytic soft tissue
sarcoma who had been treated with an anthracycline-based
regimen on the basis of the PFS benefit seen in the PALETTE
trial.
2. Trabectedin shows good responses in myxoid–round cell
liposarcoma and LMS
3. Eribulin is an option for liposarcoma and LMS
Q. Which of the following is not true about uterine sarcomas:
1. After resection of a uterine LMS, adjuvant radiation therapy is
generally not employed unless there is overt pelvic sidewall
involvement. This guideline is supported by the negative results
2. Low-grade endometrial stromal sarcomas carry a t(7;17)
3. In some patients of low grade ESS endocrine therapy may be
indicated
4. High-grade endometrial stromal sarcomas are characteristically
negative for NUTM2A and NUTM2B
Answer: High-grade endometrial stromal sarcomas are characteristically
negative for NUTM2A and NUTM2B
In fact these molecular abnormalities are characteristically present.
Q. The most common site of development of osteosarcomas is:
1.
2.
3.
4.
Distal femur
Proximal tibia
Proximal humerus
Proximal femur
Answer: Distal femur
Q. The most common site of development of Ewing sarcoma is:
1.
2.
3.
4.
Pelvis
Proximal femur
Shoulder girdle
Ribs
Answer: pelvis
Notes:
1. Ewing sarcoma is more common in the axial skeleton whereas
osteosarcoma is more common in the appendicular skeleton.
2. Chondrosarcoma is also more common in the axial skeleton.
3. The epicenter of conventional osteosarcoma lesions tends to be
in the metaphysis, with diaphyseal extension, whereas Ewing
sarcoma often arises in the diaphysis with metaphyseal
extension.
4. Clear cell chondrosarcoma most often arises in the femoral head.
5. Parosteal osteosarcoma favors the posterior distal femur and
periosteal osteosarcoma is found in the anterior tibial shaft.
6. Adamantinoma is most frequently encountered in the tibia and/or
fibula.
7. Chordoma has a predilection for the sacrum and the clivus.
Q. While performing an open biopsy for suspected primary bone
malignancy the dissection planes should be:
1.
2.
3.
4.
Through the muscular planes
Between the muscular planes
Perpendicular to the line of planned definitive resection
All of the above
Answer: Through the muscular planes
The incision plane during an open biopsy must be through the muscular
planes and never between them and it should always be in line with the
planned definitive resection.
Notes on clinical trials in Ewing sarcoma:
1. The North American Intergroup trial INT-0091 randomized
newly diagnosed Ewing sarcoma patients to receive either
standard therapy with vincristine, doxorubicin, and
cyclophosphamide (VDC) administered every 3 weeks or VDC
cycles alternating every 3 weeks with IE cycles. There was a
statistically significant difference in 5-year event-free survival
(54% for patients randomized to VDC versus 69% for patients
randomized to VDC/IE). This benefit was seen only in patients
with localized disease and not in those with metastatic disease.
2. COG protocol AEWS0031 randomized patients with newly
diagnosed localized Ewing sarcoma to receive standard therapy
with VDC/IE cycles alternating every 3 weeks or to the
experimental arm with VDC/IE cycles alternating every 2 weeks.
Patients randomized to the interval-compressed arm had a
significantly greater 5-year event-free survival (73% versus 65%
for patients randomized to the standard arm). This trial
established interval compressed VDC/IE as a new standard
approach for patients with localized Ewing sarcoma.
Q. Which is an appropriate uses of radiotherapy for patients with newly
diagnosed Ewing sarcoma (may choose multiple options):
1.
2.
3.
4.
Definitive radiation therapy for unresectable tumors
Adjuvant radiation for tumors with incomplete surgical resection
Adjuvant radiation for tumors with intraoperative spill
In chest wall tumors with ipsilateral pleural-based secondary
tumor nodules or positive pleural fluid cytology
5. Pathologically involved lymph nodes
6. If after neoadjuvant chemotherapy surgery is performed, tumor
necrosis is 90% or more and inflammatory tissue or coagulative
tumor necrosis is present at the margin (the cytoarchitecture of
the tumor cells is preserved), postoperative radiotherapy is
required.
7. If after neoadjuvant chemotherapy surgery is performed, tumor
necrosis is less than 90% and the cut surface of the resected
tumor shows anything other than normal non reactive tissue
Answer: all of the above
These are the indications of radiation therapy is Ewing sarcoma.
Q. Which of the following trials was done in osteosarcoma that compared
high dose MAP with MAP plus ifosfamide:
1. The North American Intergroup study INT-0133
2. The North European Intergroup study INT-0133
3. The North American Intergroup study AEWS-0133
4. The North American Intergroup study INT-0197
Answer: The North American Intergroup study INT-0133
This trial randomized patients between high-dose MAP chemotherapy or
MAP plus ifosfamide. The addition of ifosfamide did not lead to benefit in
survival outcomes.
Notes: options for relapsed osteosarcoma:
1. Antibody to disialoganglioside GD2
2. Trastuzumab
3. Muramyl tripeptide phosphatidylethanolamine (MTP-PE): it was
studied in the INT-0133 and MTP-PE appeared to prolong eventfree survival only among patients also randomized to receive
ifosfamide
4. Inhaled granulocyte-macrophage colony-stimulating factor (GMCSF)
Q. Which of the following is an absolute contraindication to limb salvage
surgery in bone sarcomas:
1.
2.
3.
4.
Major neurovascular involvement
Very immature skeletal age
Pathologic fracture
None of the above
Answer: none of the above
There is no absolute contraindication to limb salvage surgery (in other
words, there are no absolute indications for an amputation) in bone sarcoma
management. There are, however, relative contraindications to a limb
salvage surgery:
1. Major neurovascular involvement
2.
3.
4.
5.
6.
7.
Very immature skeletal age
Infection
Lack of reconstructive or soft tissue coverage options
Contamination secondary to biopsy technique and complications
Inability to obtain oncologically acceptable margins
Pathologic fracture
SKIN CANCERS
Q. Which of the following is the most common human cancer:
1.
2.
3.
4.
Basal cell cancer of skin
Lung cancer
Squamous cell skin cancer
Melanoma
Answer: Basal cell cancer of skin
Non-melanoma skin cancers are the most common human cancers. BCC is
the most common among them.
The most important risk factor for BCC is exposure to ultraviolet rays. It
occurs most commonly on the sun exposed areas.
Nodular BCC is the most common type of BCC.
Notes on syndromes associated with basal cell cancer of skin:
1. Nevoid BCC syndrome (Gorlin syndrome): an autosomal
dominant disorder characterized by a mutation in the human
patched (PTCH1) gene
2. Bazex syndrome
3. Rombo syndrome
4. Xeroderma pigmentosum (autosomal recessive disorder) in
unscheduled DNA repair, clinically characterized by numerous
NMSCs and melanomas).
Notes on high risk BCC:
1. Tumors of any size located in high-risk areas (nose, eyelids,
periocular skin, lips, chin, ears, temples, mandibular and
2.
3.
4.
5.
6.
7.
preauricular skin, hands, feet, and genitalia)
Tumors located on the cheeks, forehead, scalp, and neck greater
than 1 cm in diameter
Tumors at any site greater than 2 cm in diameter
Tumors with poorly defined clinical borders; recurrent tumors
after prior treatment
Tumors arising in areas of prior RT
Tumors with aggressive histologic features including infiltrative,
morpheaform, and micronodular subtypes
BCCs without any of the above mentioned features are classified
as low-risk tumors
Q. The best surgical approach for treatment of BCC is:
1.
2.
3.
4.
C and D
Mohs microscopic surgery
Wide local excision
Electrodessication
Answer: Mohs microscopic surgery
However, the selection of surgical modality depends on the site, size and
histology etc.
MMS demonstrated an RR of 1% over 5 years. This was superior to all
other modalities, including excision (RR, 10%), C&D (RR, 7.7%), RT (RR,
8.7%), and cryotherapy (RR, 7.5%).
Q. Which of the following is not true regarding the management of BCC:
1. When the surgical approach is contraindicated, RT is a valid
option for management of primary BCC
2. Imiquimod is approved by the FDA for the treatment of
superficial BCCs <2 cm in diameter on the face, neck, trunk, or
extremities
3. Both of the above
4. Neither 1 nor 2
Answer: Imiquimod is approved by the FDA for the treatment of superficial
BCCs <2 cm in diameter on the face, neck, trunk, or extremities
While it’s true that imiquimod is approved by the FDA for superficial BCC
<2 cm in diameter but it can not be used on face.
Q. Vismodegib is approved for use in locally advanced or metastatic BCC.
It is an inhibitor of:
1.
2.
3.
4.
CDK4/6
CTNNB1
Smoothened
HOX
Answer: Smoothened
Q. Which of the following statements is not true about squamous cell
carcinoma of the skin (SCCs):
1. Approximately two thirds of SCCs arise from actinic keratosis
2. The risk of progression to invasive disease for genital
erythroplasia of Queyrat is approximately 2%
3. Therapy for actinic keratosis is generally recommended, because
they have a risk of progression to SCCs
4. When treatment is contemplated for actinic keratosis cryotherapy
is the most commonly used lesion-directed treatment modality
Answer: The risk of progression to invasive disease for genital
erythroplasia of Queyrat is approximately 2%
The risk is about 10%
Other therapies for actinic keratosis are topical pharmacologic therapy with
5-FU, imiquimod, and ingenol mebutate and topical PDT. 5-FU is the oldest
and most commonly used topical field therapy.
Q. Which of the following is a treatment modality for early stage localized
squamous cell carcinoma of skin:
1.
2.
3.
4.
C&D
Excisional surgery or MMS
RT
All of the above
Answer: all of the above
Q. The Bednar tumor is a rare pigmented variant of DFSP:
1. True
2. False
Answer: true
The first-line treatment of DFSP includes WLE or MMS. A PDGF receptor
inhibitor, imatinib, can be used in advanced disease.
Q. Which of the following is not true about melanomas:
1. Cutaneous melanomas arising from the trunk and extremities are
associated high rates of BRAF (40% to 50%), NRAS (20%), or
NF1 (15%) mutations
2. Mucosal and acrolentigenous melanomas, with low rates of UV
radiation exposure, have lower rates of BRAF mutations (5% to
20%) and a relatively higher rate of KIT mutations (5% to 10%)
3. Uveal melanomas have mutually exclusive mutations in the α
subunits of G protein–coupled receptors GNAQ and GNA11
4. The vast majority of BRAF mutations in melanoma do not
involve a substitution V600E
Answer: The vast majority of BRAF mutations in melanoma do not involve
a substitution V600E
In fact, V600E is the most common BRAF mutation
Another common variant is BRAF V600K.
Q. The most common site of occurence of cutaneous melanomas in males
is:
1.
2.
3.
4.
Back
Lower extremities
Chest
Face
Answer: back
The most common sites in males are on the back and in the head and neck
regions. In women, the most common sites are in the lower extremities,
commonly below the knee.
Q. In the clinical context which ultraviolet rays are of the least concern:
1.
2.
3.
4.
UVA
UVB
UVC
All of the above
Answer: UVC
UVC rays are the most carcinogenic but they are not of clinical concern
because they are completely absorbed by the ozone layer and thus they
don’t reach us.
Q. Which is not a part of the “ABCD” of primary cutaneous melanoma:
1.
2.
3.
4.
Asymmetry
Border irregularity
Color variation
Diameter >4 mm
Answer: diameter >4 mm
Diameter >6 mm is part of the “ABCD”.
Q. The most common type of cutaneous melanoma is:
1.
2.
3.
4.
Superficial spreading melanoma
Nodular melanoma
Acral lentiginous melanoma
Lentigo Maligna Melanoma
Answer: superficial spreading melanoma
Notes on melanoma metastatic risk:
1. The best predictor of metastatic risk is the depth of invasion,
measured from the granular layer of the skin to the base of the
primary lesion. This was described by Breslow.
2. Clark et al. defined depth based on the layer of skin to which the
melanoma has invaded. Clark level I melanomas are melanomas
in situ, limited to the epidermis or dermal/epidermal junction.
Clark level II melanomas invade into the superficial (papillary)
dermis, and these are usually RGP lesions. Clark level III
melanomas fill the papillary dermis. Clark level IV melanomas
invade into the deep (reticular) dermis and have significant
metastatic risk. Clark level V melanomas are uncommon and
contain invasion into the subcutaneous fat.
3. It should be noted here that the Clark system is now no longer
used in the AJCC staging.
Q. Sentinel node biopsy may be done in melanoma in which of the
following scenarios, except:
1. For patients with melanomas of 1 mm or more thickness
2. For less than 1 mm thick melanomas with ulceration
3. In melanomas with a mitotic rate of ≥1
4. Pure desmoplastic melanomas
Answer: Pure desmoplastic melanomas
Pure desmoplastic melanomas have a lower risk of spread to lymph nodes.
It must be remembered that in oncology there are very few hard and fast
rules and everything depends on the clinical context and the options
available. In this question pure desmoplastic melanoms is the answer but in
some other questions, the answer may be different.
Notes, systemic treatment options for melanoma:
1. First line therapy in metastatic/unresectable disease that is BRAF
V600E mutation positive: dabrafenib+trametinib,
vemurafenib+cobimetinib, encorafenib+binimetinib
2. First line therapy in metastatic/unresectable disease:
pembrolizumab, nivolumab, nivolumab+ipilimumab
3. Subsequent line therapy options in metastatic/unresectable
disease: high dose IL-2, imatinib in those with mutations of KIT,
larotrectinib for NTRK fusion, binimetinib for NRAS mutated
tumors
4. In stage III resected tumors, pembrolizumab, nivolumab are
options for adjuvant treatment and if the tumor is positive for
BRAF V600E mutation then dabrafenib+trametinib is also an
option.
5. Cytotoxic chemo is also useful in certain situations and agents
like talimogene (T-VEC) also have their place in the
management of very specific situations.
CNS TUMORS
Q. Which of the following is the most common brain tumor:
1.
2.
3.
4.
Meningioma
GBM
Pilocytic astrocytoma
Medulloblastoma
Answer: meningioma
GBM is the most common “malignant” brain tumor.
Meningioma are more frequently found in women.
Q. GBM may be causally linked to which of the following viruses:
1.
2.
3.
4.
HSV
CMV
HIV
EBV
Answer: CMV
Although the link is not strong and further studies are needed but it has
been described.
Notes on genetic syndromes and brain tumors:
1. NF1 is associated with Schwann cell tumors. Optic gliomas,
astrocytomas, and meningiomas
2. NF2 is characterized by bilateral vestibular schwannomas and
meningiomas.
3. Tuberous sclerosis is associated with Subependymal giant cell
astrocytoma.
4. Li-Fraumeni syndrome is a/w malignant gliomas, von HippelLindau syndrome with hemangioblastomas, Turcot syndrome
with medulloblastoma, Gorlin syndrome with medulloblastomas
Q. The 2016 edition of the WHO classification of brain tumors has added
all of the newly recognized entities except:
1.
2.
3.
4.
IDH –wild-type and IDH -mutant GBM
WNT -activated and SHH -activated medulloblastoma
RELA fusion–positive ependymoma
H3 K27M –mutant atypical meningioma
Answer: H3 K27M –mutant atypical meningioma
In fact, the fourth newly added entity in the 2016 update is H3 K27M –
mutant diffuse midline glioma
Q. What percentage of primary CNS tumors arise in the spinal cord:
1.
2.
3.
4.
15
10
20
<5
Answer: 15%
Q. Which is the imaging modality of choice for CNS tumors:
1.
2.
3.
4.
MRI
CT
Integrated PET-CT
Integrated PET-MRI
Answer: MRI
Q. Which of the following doesn’t show enhancement on MRI studies:
1.
2.
3.
4.
GBM
Pilocytic astrocytomas
Pleomorphic xanthoastrocytoma
None of the above
Answer: none of the above
Most of the low grade gliomas generally don’t enhance except options 2
and 3.
Calcifications are characteristically present in oligodendroglioma.
Notes on pseudoprogression and pseudoresponse:
1. Around one third of malignant gliomas show progression on
MRI early in the course of treatment but actually this is because
of necrosis and with time this increased size subsides. This is
known as pseudoprogression.
2. Gliomas treated with antiangiogenic therapy show very rapid
responses which with time are lost and tumor progresses with
worsening of symptoms. This is known as pseudoresponse.
Q. In which of the following CNS tumors cerebrospinal fluid examination
is indicated: (choose more than one option if needed)
1.
2.
3.
4.
5.
Medulloblastoma
Ependymoma
Choroid plexus carcinoma
Lymphoma
Embryonal pineal and suprasellar region tumors
Answer: all of the above
Q. In many situations involving patients of brain tumors, steroids are given
but in which of the following histologies steroids should not be given
empirically:
1.
2.
3.
4.
GBM
Melanocytoma
Lymphoma
Ependymoma
Answer: lymphoma
Steroids are cytotoxic for lymphoma and without proper workup,
administration of steroids may lead to confounding responses and improper
management.
On a different note, anticonvulsants are not routinely indicated in brain
tumors except in clinical situations warrant.
Q. After surgery of malignant brain tumors a postoperative MRI should be
done to assess for any remaining tumor. This MRI should be done:
1.
2.
3.
4.
After 72 hours of surgery
Within 72 hours of surgery
Within a week of surgery
After at least 2 weeks of surgery
Answer: Within 72 hours of surgery
MRI is done before 72 hours to minimize the appearance of nonspecific
contrast enhancement that is related to surgery and might be mistaken for
residual tumor.
Q. A radiation techniques used in the treatment of brain tumors is known as
FSRT, which combines the concepts of SRS and IMRT. FSRT stands for:
1. Fractionated stereotactic radiation therapy
2. Focal stereosurgical radiation therapy
3. Fractionated substereotactic radiation therapy
4. Fractionated suprathreshold radiation therapy
Answer: Fractionated stereotactic radiation therapy
Q. Anaplastic astrocytomas belong to which grade in the WHO
classification:
1.
2.
3.
4.
I
II
III
IV
Answer: III
GBM belongs to class IV
Oligodendrogliomas and ependymomas can be either grade II or grade III
but not I or IV.
Q. Which of the following brain tumors can be effectively treated with
everolimus:
1.
2.
3.
4.
Pilocytic astrocytoma
Pleomorphic xanthoastrocytoma
Subependymal giant cell astrocytoma
Meningioma
Answer: Subependymal giant cell astrocytoma
The first three are grade I tumors. In WHO grade I tumors, generally
surgery is the cornerstone of therapy but radiation may be used in the
adjuvant setting or as a standalone modality in special circumstances.
Q. IDH1 are present in 50-80% of WHO grade II and III astrocytic and
oligodendroglial tumors. These IDH mutant tumors have:
1. Better prognosis than IDH wild-type gliomas of the same
histologic grade
2. Worse prognosis than IDH wild-type gliomas of the same
histologic grade
3. Prognosis is the same in wild-type and mutated tumors
Answer: Better prognosis than IDH wild-type gliomas of the same
histologic grade
Q. Which is the most common IDH mutation occurring in grade II to IV
gliomas:
1.
2.
3.
4.
IDH1 mutation (R132H)
IDH1 mutation (R321H)
IDH2 mutation (R132H)
IDH1 mutation (R321H)
Answer: IDH1 mutation (R132H)
Q. Oligodendrogliomas with 1p- and 19q-codeleted tumors have a better
prognosis than do histologically similar tumors of the same grade without
this codeletion. This codeletion results from:
1. An unbalanced translocation resulting in a combined loss of
chromosomal arms 1p and 19q
2. A balanced translocation resulting in a combined loss of
chromosomal arms 1p and 19q
3. A Robertsonian translocation resulting in a combined loss of
chromosomal arms 1p and 19q
4. An inversion involving the short arm of chromosome 1 and long
arm of chromosome 19q
Answer: An unbalanced translocation resulting in a combined loss of
chromosomal arms 1p and 19q.
Q. Adjuvant temozolomide chemotherapy is recommended in patients with
newly diagnosed non-codeleted anaplastic glioma:
1. True
2. False
Answer: true
Hypermethylation of MGMT promoter, mutations of the IDH1 gene, and
oligodendroglioma histology reduce the risk of progression.
Hypermethylation of MGMT promoter is associated with prolonged PFS in
the chemotherapy and radiotherapy arms.
Q. Anaplastic oligodendroglioma (codeletion 1p/19q) should not be offered
radiotherapy alone, as they demonstrate survival benefit with combined
chemoradiation:
1. True
2. False
Answer: true
Notes on chemotherapy is GBM:
1. After surgery, adjuvant radiation with chemo is indicated.
2. In a pivotal trial, patients were randomized to radiotherapy with
or without concurrent and adjuvant temozolomide. Median and
2-year survival were increased by 2.5 months and 16.1%,
respectively, inpatients receiving temozolomide, and long-term
follow-up showed a persistent survival benefit.
3. In the above mentioned patient population, methylation of the
promoter region of the MGMT gene in the tumor was associated
with superior survival. This happens because MGMT leads to
reversal of the cytotoxic effects of methylating agents like
temozolomide and methylation of promoter region of MGMT
leads to inactivation of MGMT and enhanced cytotoxicity of
temozolomide in these patients.
4. For recurrent glioblastoma VEGF directed therapy
(bevacizumab) in combination with chemo is the mainstay.
Q. Which of the following is a type of posterior fossa ependymoma and
associated with a better prognosis:
1.
2.
3.
4.
Posterior fossa type A tumors
Posterior fossa type B tumors
Posterior fossa type C tumors
Posterior fossa type D tumors
Answer: Posterior fossa type B tumors
There are two types of posterior fossa ependymomas, A and B. Type A
tumors occur in young children (infants) and are more likely to be lateral
(cerebellopontine angle). PFB tumors are diagnosed in older children, are
found in the midline, and have a much better prognosis than PFA tumors.
The management of ependymoma often involves surgery and adjuvant
radiation and chemotherapy plays no role except in very rare situations.
Q. Meningiomas arise from:
1. Epithelioid cells on the outer surface of arachnoid villi in the
meninges
2. Epithelioid cells on the inner surface of arachnoid villi in the
meninges
3. Epithelioid cells on the outer surface of dural villi in the
meninges
4. Epithelioid cells on the inner surface of dural villi in the
meninges
Answer: Epithelioid cells on the outer surface of arachnoid villi in the
meninges
These cells are also known as arachnoidal cap cells .
Q. Which are the most common types of meningiomas:
1.
2.
3.
4.
WHO grade I
WHO grade II
WHO grade III
WHO grade IV
Answer: WHO grade I
Grade I are also known as benign, grade II are also known as atypical and
grade III are known as anaplastic.
It should be noted here that there are no grade IV meningiomas.
Surgery, preferably with a dural margin is the mainstay of treatment.
Q. The Simpson grade of resection associated with the highest risk of
recurrence is:
1.
2.
3.
4.
Grade 6
Grade 5
Grade 4
Grade 3
Answer: grade 5
The Simpson grades are guidelines for defining the extent of resection
performed. There are 6 grades (grade 5 to grade 0), a grade 5 resection
refers to a biopsy only and is associated with near-universal progression.
These grades help in management planning, for example, in general,
adjunctive radiotherapy is not used after Simpson grade 0, 1, 2, and
sometimes 3 resection for grade I meningioma.
On the other hand, in all patients with malignant grade III meningiomas,
regardless of the extent of resection, and those with subtotally resected
grade II meningioma should be offered postoperative irradiation.
Q. Which of the following brain tumors often are estrogen receptor
positive:
1.
2.
3.
4.
Medulloblastoma
Neuroepithelioma
Gliosarcoma
Meningioma
Answer: meningioma
Q. Medulloblastomas characteristically have Homer-Wright rosettes. They
are found in:
1. <40% of cases
2. 40-60% of cases
3. 60-80% of cases
4. >80% of cases
Answer: Less than 40% of cases
Notes:
1. According to the WHO, all medulloblastomas are histologically
grade IV.
2. Medulloblastomas re composed of four different molecular
subgroups:
a.
b.
c.
d.
Wnt
Shh
Group 3
Group 4
3. Medulloblastoma are classified into five variants histologically:
a. Classical
b. Desmoplastic/nodular
c. Medulloblastoma with extensive nodularity
d. Anaplastic
e. Large cell
Q. Which of the following statements about medulloblastomas is false:
1. Childhood medulloblastoma typically arise within the vermis
2. In older patients, they most commonly arise in the lateral
cerebellar hemispheres
3. Upon MRI they are classically hypoattenuated compared with
the adjacent brain and don’t enhance avidly
4. A modified version of the Chang staging system is used for these
tumors
Answer: Upon MRI they are classically hypoattenuated compared with the
adjacent brain and don’t enhance avidly
In fact, they are “hyper”attenuated.
Q. According to the modified Chang system, medulloblastomas that have
spread to ventricular space are classified as:
1.
2.
3.
4.
M1
M2
M3
M4
Answer: M3
M0 represents no tumor dissemination, whereas M1 represents tumor cells
in the CSF. M2 represents presence of gross tumor nodules in the
intracranial, subarachnoid, or ventricular space, and M3 represents gross
tumor nodules in the spinal subarachnoid space. M4 represents systemic
metastasis.
To do this staging, a CSF analysis and MRI of spine are A bone scan, chest
x-ray, and bilateral marrow biopsies should be routinely performed for M2
and M3
stages.
Q. Cerebellar mutism syndrome occurs most commonly after surgery of:
1.
2.
3.
4.
Meningioma
Medulloblastoma
Ependymoma
GBM
Answer: medulloblastoma
This syndrome is also known as posterior fossa syndrome and is
characterized by a constellation of symptoms and signs. It results from
extensive surgery that are often required in cases of medulloblastoma to
achieve gross total resection.
Q. Craniospinal irradiation (CSI) is more commonly used in:
1.
2.
3.
4.
Meningioma
Medulloblastoma
Ependymoma
GBM
Answer: medulloblastoma
Radiation is often combined with chemotherapy (concurrent +/maintenance). Various agents have been studied, most protocols contain
vincristine.
Q. Which are the most common pineal tumors:
1.
2.
3.
4.
Gliomas
Germinomas
PNETs
Lymphoma
Answer: germinoma
Surgery has no role in treatment of germinoma except biopsy. Radiation
with chemo are the modalities of choice.
Q. The surgical approach of choice for pituitary macroadenomas is:
1.
2.
3.
4.
Transsphenoidal
Transcranial
Frontotemporal
Neuronavigational
Answer: transsphenoidal
In patients of hormonally active pituitary adenomas in which the syndrome
persists even after surgery, resurgery may cure the patient although
according to some experts, for the treatment of residual or recurrent
adenomas that cause persistent or recurrent hormone hypersecretion,
radiosurgery may be a better option.
Notes of medical therapy of pituitary tumors:
1. Dopamine agonists (e.g., bromocriptine or cabergoline) are the
most effective therapy for prolactinomas
2. Somatostatin analogs (e.g., octreotide and lanreotide) are
effective for patients with acromegaly and are used when growth
hormone hypersecretion persists after resection. In some of these
patients somatostatin analogs fail and in them a new therapy, the
growth hormone receptor antagonist pegvisomant can be used.
3. For the treatment of increased pituitary corticotropin production
there is no medical therapy and thus to manage the resultant
Cushing disease, ketoconazole is used to reduce cortisol
hypersecretion by the adrenal glands.
Q. Which of the following is/are considered standard treatment(s) of
schwannoma:
1.
2.
3.
4.
Microsurgical resection
SRS
Both of the above
Conservative management
Answer: both of the above
Q. All of the following are true about chordoma except:
1.
2.
3.
4.
They arise with in the pathway of the primitive notochord
They are intradural and encapsulated
They are characterized microscopically by physaliferous cells
Imatinib may be helpful in relapsed cases
Answer: They are intradural and encapsulated
In fact, they are extradural and pseudoencapsulated.
LYMPHOMA
Notes on Ann Arbor staging for lymphoma:
1. Stage I: Involvement of a single lymph node region (I) or single
extranodal site (IE)
2. Stage II: Involvement of two or more lymph node regions or
lymphatic structures on the same side of the diaphragm alone (II)
or with involvement of limited, contiguous, extralymphatic organ
or tissue (IIE)
3. Stage III: Involvement of lymph node regions on both sides of
the diaphragm (III), which may include the spleen (IIIS), or
limited, contiguous, extralymphatic organ or tissue (IIIE), or both
(IIIES)
4. Stage IV: Diffuse or disseminated foci of involvement of one or
more extralymphatic organs or tissues, with or without
associated lymphatic involvement
Note: All stages are further subdivided according to the absence(A) or
presence (B) of systemic B symptoms including fevers, night sweats,
and/or weight loss (>10% of body weight over 6 months prior to
diagnosis).
Q. Which of the following variants of mantle cell lymphoma is
characterized by IGV-mutated cells and has a more indolent course:
1.
2.
3.
4.
Classical
Leukemic
Blastoid
None of the above
Answer: leukemic
There are two variants of MCL: classical MCL, characterized by unmutated
or minimally mutated IGV genes and leukemic, non-nodal MCL,
characterized by IGV-mutated cells and which has a more indolent disease
course.
Q. The characteristic translocation in mantle cell lymphoma is:
1.
2.
3.
4.
t(11;14)
t(11;18)
t(14;18)
t(8;14)
Answer: t(11;14)
It juxtaposes the IGH gene at 14q32 to a region containing the CCND1
gene on chromosome 11q13.
Q. Burkitt lymphoma has which of the following chromosomal
abnormalities:
1.
2.
3.
4.
t(8;14)
t(2;8)
t(8;22)
All of the above
Answer: all of the above
The primary genetic lesion in BL involves the MYC gene on region 8q24
and one of the IG loci on the partner chromosome. In 80% of cases, this is
t(8;14) and in the rest t(2;8) and t(8;22) are found. Sometimes other rare
translocations may be present.
The consequence of these translocations is the constitutive overexpression
of the MYC proto-oncogene.
Interestingly, infection with plasmodium is a risk factor for development of
BL in the endemic areas.
Q. The most common low grade NHL is:
1.
2.
3.
4.
Diffuse large B cell lymphoma
Follicular lymphoma
MALToma
Burkitt lymphoma
Answer: follicular lymphoma
The genetic hallmark of FL is represented by chromosomal translocations
of the BCL2 gene on chromosome band 18q21.
Notes on DLBCL molecular biology:
1. DLBCL is the most common form of B-NHL
2. Genetic lesions specific to GCB-DLBCL include the t(14;18)
and t(8;14) translocations, which deregulate the BCL2 and MYC
oncogenes
Q. The most common chromosomal abnormality in CLL is:
1.
2.
3.
4.
Deletion of 17p
Deletion of 13q
Deletion of 17q
Trisomy 12
Answer: deletion of 13q
Notes, CLL has many genetic abnormalities, like:
1.
2.
3.
4.
Deletion of chromosomal regions 17p
Deletion of chromosomal regions 11q
Deletion of chromosomal regions 13q: most common
Trisomy 12
Q. The genetic hallmark of ALK-positive ALCL is a chromosomal
translocation:
1.
2.
3.
4.
t(2;5)
t(2;2)
t(3;5)
t(1;5)
Answer: t(2;5)
Q. Nodular lymphocyte-predominant Hodgkin lymphoma constitutes
around what percentage of total Hodgkin lymphoma cases:
1.
2.
3.
4.
5
10
15
20
Answer: 5%
Notes on HL:
1. HL is classified into two major subgroups: nodular lymphocytepredominant HL (NLPHL) (~5% of cases) and classical HL.
Classical HL is divided into four: nodular sclerosis, mixed
cellularity, lymphocyte rich and lymphocyte depleted.
2. Reed-Sternberg (RS) are characteristic for HL. They lack many
of the mature B-cell markers such as CD19 and CD20 surface
proteins, but they almost always express the B-cell specific
transcription factor PAX5.
3. RS cells account for less than 2% of the tumor mass.
4. In the world, nodular sclerosis is the most common histologic
subtype of HL. In this type, RS cells often have “lacunar”
morphology.
5. In India mixed cellularity HL is the most common
Q. Which type of Hodgkin lymphoma is most often associated with
Epstein-Barr virus infection:
1.
2.
3.
4.
Nodular sclerosis
Lymphocyte depleted
Nodular lymphocyte predominant
Mixed cellularity
Answer: mixed cellularity
80% of cases of mixed cellularity HL are associated with Epstein-Barr virus
(EBV) infection.
In the Western world, EBV infection is mostly detected in cases of MCCHL
and LDCHL and is less frequently detected in NSCHL and LRCHL.
Conversely, EBV is found in HRS cells in nearly all cases of CHL
occurring in patients infected with HIV.
Table: differences between classical Hodgkin lymphoma and nodular
lymphocyte predominant HL.
Q. Hodgkin lymphoma is characterized by “contiguous” involvement of
lymph nodes. This has implication in management planning as well. Which
of the following type of HL, doesn’t follow the rule of contiguous
involvement and may involve distant sites without intervening nodal
involvement:
1. Mixed cellularity
2. Lymphocyte rich
3. Nodular lymphocyte predominant
4. Lymphocyte depleted
Answer: Nodular lymphocyte predominant
Notes:
There are several criteria in use for risk stratification of early stage Hodgkin
lymphoma. Which one of these will be used, depends on the protocol being
followed as different groups have slightly different guidelines on the
management of early stage Hodgkin lymphoma. Below are summarized the
major criteria proposed by major groups. If a question is asked, without
mentioning a particular group then we must take into consideration all of
these factors.
EORTC
Risk factors
1. Large mediastinal mass (>1/3)
2. Age 50 y and older
3. ESR ≥50 mm/h without B symptoms or ≥30 mm/h with B
symptoms
4. ≥4 nodal areas
Favorable:
CS I–II (supradiaphragmatic) without risk factorsUnfavorable:
CS I–II (supradiaphragmatic) with ≥1 risk factors
GHSG
Risk factors:
1. Large mediastinal mass
2. Extranodal disease
3. ESR ≥50 mm/h without B symptoms or ≥30 mm/h with B
symptoms
4. ≥3 nodal areas
Favorable:
CS I–II without risk factors
Unfavorable:
a. CS I or CS IIA with ≥1 risk factor
b. CS IIB with risk factor 3 or 4 but without risk factors 1 and 2
NCCN
Risk factors:
1.
2.
3.
4.
Large mediastinal mass (>1/3) or >10 cm
ESR ≥50 mm/h or any B symptoms
≥3 nodal areas
>1 extranodal lesion
Favorable:
CS I–II without risk factors
Unfavorable:
CS I–II with ≥1 risk factor (differentiating between bulky disease and other
risk factors for treatment guidelines)
NCIC/ECOG
Risk factors:
1.
2.
3.
4.
Histology other than LP/NS
Age 40 y and older
ESR ≥50mm/h
≥4 nodal areas
Favorable:
CS I–II without risk factors
Unfavorable:
CS I–II with ≥1 risk factor
Q. The management of early stage, favourable Hodgkin lymphoma has
been debated and many trials have been done in an attempt to study the
feasibility of reduction in the chemotherapy drugs administered, in order to
prevent late toxicities but without compromising results. But even in the
most favorable subsets of early Hodgkin lymphoma chemotherapy can’t be
reduced below a certain threshold, as was found in the trials. Which of the
following constitutes the bare minimum treatment option for early stage
favorable Hodgkin lymphoma:
1.
2.
3.
4.
2 cycles of ABVD and 20 Gy of IFRT
3 cycles of ABVD and 20 Gy of IFRT
2 cycles of ABVD and 30 Gy of IFRT
3 cycles of ABVD and 30 Gy of IFRT
Answer: 2 cycles of ABVD and 20 Gy of IFRT
It is based on the results of the GHSG HD10 and GHSG HD13 studies.
On the other hand, in the early stage but unfavorable group of Hodgkin
lymphoma, it may be hazardous to reduce treatment below a threshold of
four cycles of ABVD and 30 Gy of IFRT, unless some means can be found
to select patients for whom further deintensification can be attempted, such
as the use of functional imaging. These recommendations are based on the
European intergroup H9-U study and the GHSG HD11 study.
Q. FDG-PET may be used to modify treatment plan of Hodgkin lymphoma,
known as response-adapted treatment:
1. True
2. False
Answer: true
The RAPID study randomized patients with non bulky early-stage disease
who had an interim PET score of 1 or 2 after three cycles of ABVD to
either 30 Gy of IFRT or no further therapy. The survival outcomes were not
different in the two groups.
Q. At any site uptake moderately increased compared to liver on PET scan
is given a Deauville score of:
1.
1
2.
3.
4.
2
3
4
Answer: 4
Following is the Deauville scoring system:
No uptake above background = 1
Uptake ≤ mediastinum = 2
Uptake > mediastinum but ≤ liver = 3
Uptake moderately increased compared to the liver at any site = 4
Uptake markedly increased compared to the liver at any site = 5
New areas of uptake unlikely to be related to lymphoma = X
It should be noted here that there is no “0” score in Deauville scoring
system.
Q. Which of the following is not a factor used in the prognostication of
advanced stage Hodgkin lymphoma by the international prognostic score
(IPS):
1.
2.
3.
4.
Age 40 years and more
Stage IV
Male gender
WBC ≥15,000 cells/μL
Answer: age 40 years and more
In fact the age criteria used in IPS is 45 years or more.
Other factors that impart a high risk are lymphocytes <600 cells/μL or <8%
of WBC count, or both, albumin <4.0 g/dL and hemoglobin <10.5 g/dL.
Q. Checkpoint inhibitors may be used in Hodgkin lymphoma in all of the
following indication except:
1. In a patient of classical Hodgkin lymphoma that has relapsed
after autologous HSCT
2. In a patient of classical Hodgkin lymphoma that has relapsed
after brentuximab vedotin
3. In a patient of relapsed classical Hodgkin lymphoma who is
ineligible for HSCT
4. In a patient of classical Hodgkin lymphoma post allogeneic stem
cell transplant
Answer: In a patient of classical Hodgkin lymphoma that has relapsed after
brentuximab vedotin
The checkpoint inhibitor nivolumab may be given after failure of auto or
allo-HSCT or in transplant ineligible patients or in those who failed on
second line chemo. But in patients who receive and relapse on brentuximab,
transplant or further chemo is a more suitable option, rather than switching
to nivolumab and not doing a transplant.
In all other indications nivolumab is used but in patients who progress after
alloHSCT, pembrolizumab may also be given.
Notes:
Indications of brentuximab vedotin:
It’s a CD30-directed antibody-drug conjugate (ADC) consisting of chimeric
IgG1 antibody cAC10, specific for human CD30 and the microtubule
disrupting agent, monomethyl auristatin E (MMAE, or vedotin)
It should be noted that brentuximab is never given with bleomycin. And it
should also be kept in mind that brentuximab is not effective in nodular
lymphocyte predominant Hodgkin lymphoma because it is CD30 negative.
1. As first-line therapy for previously untreated Stage III or IV
classical HL in combination with doxorubicin, vinblastine, and
dacarbazine (AVD)
2. As consolidation in classical HL at high risk of relapse or
progression after autologous hematopoietic stem cell
transplantation (auto-HSCT)
3. In classical HL after failure of auto-HSCT or after failure of at
least 2 prior multi-agent chemotherapy regimens in patients who
are not auto-HSCT candidates
4. In previously-untreated systemic anaplastic large cell lymphoma
5. In treatment of systemic anaplastic large cell lymphoma after
failure of at least 1 prior multiagent chemotherapy regimen
6. In primary cutaneous anaplastic large cell lymphoma or CD30
expressing mycosis fungoides ( MF) who have received prior
systemic therapy
7. In CD30-expressing peripheral T-cell lymphomas
Notes:
Infectious agents associated with the development of lymphoma:
1. Epstein-Barr virus
2. HIV-1 infection
3. HTLV-1
4. HHV-8
5. Helicobacter pylori
6. Campylobacter jejuni
7. Chlamydia psittaci
8. Borrelia afzelii
9. HCV
10. MTB
Q. Which of the following is not a part of the international prognostic index
(IPI) used for follicular lymphoma:
1.
2.
3.
4.
Age older than 60 y
LDH > upper limit normal
ECOG performance status ≥2
Hgb <12 g/dL
Answer: ECOG performance status ≥2
It should be noted that there are many types of international prognostic
index (IPI) depending on the lymphoma in question.
The IPI (without any mention of a specific lymphoma) has five factors:
1.
2.
3.
4.
5.
Age older than 60 y
LDH > upper limit normal
ECOG performance status ≥2
Ann Arbor stage III or IV
Number of extranodal disease sites greater than one
But the IPI used for follicular lymphoma, also known as FLIPI has different
set of factors:
1.
2.
3.
4.
5.
Age older than 60 y
LDH > upper limit normal
Hgb <12 g/dL
Ann Arbor stage III or IV
Number of involved nodal areas greater than four
Q. Lymphoblastic lymphomas are mostly of:
1.
2.
3.
4.
T-cell lineage
B-cell lineage
NK/T-cell lineage
Dendritic cell origin
Answer: T-cell lineage
Approximately 85% to 90% of lymphoblastic lymphomas are of the T-cell
lineage,with the remainder being of the B-cell type.
Q. The malignant cells of follicular lymphoma typically show which
immunophenotype:
1. CD19 positive, CD20 positive, CD10 negative, CD5 positive and
CD23 negative
2. CD19 positive, CD20 positive, CD10 positive, CD5 positive and
CD23 negative
3. CD19 positive, CD20 negative, CD10 positive, CD5 positive and
CD23 negative
4. CD19 positive, CD20 positive, CD10 positive, CD5 negative and
CD23 negative
Answer: CD19 positive, CD20 positive, CD10 positive, CD5 negative and
CD23 negative
Q. The treatment of choice for limited stage (I/II) follicular lymphoma is:
1.
2.
3.
4.
Rituximab based chemotherapy for 3 cycles
Rituximab based chemotherapy for 6 cycles
Radiation therapy
Observation
Answer: radiation therapy
It must be clearly understood that follicular lymphoma is an indolent
lymphoma. In stage I and II, radiation is the treatment of choice. But in
stage III and IV, we have to decide if the patient can be observed or should
he be treated. There are criteria to decide for that, known as GELF and
FLIPI criteria.
To repeat once again: in limited stage follicular lymphoma we have to treat
the patient and radiation is the treatment of choice but in advanced stages
we can choose observation and not treat the patient if there are no
indications of treatment.
Table: GELF criteria. If any criteria is present, we may consider treatment.
Q. Which of the following is not seen with maintenance rituximab (versus
no maintenance rituximab) in patients with follicular lymphoma who
respond to initial chemoimmunotherapy:
1.
2.
3.
4.
Increased toxicity
Overall survival improvement
Progression free survival benefit
Higher chances of being in complete response at 2 years
Answer: Overall survival improvement
The PRIMA phase III intergroup trial randomized patients with previously
untreated FL that responded to chemoimmunotherapy to maintenance with
rituximab (375 mg/m2 every 8 weeks for 24 months) or placebo. At a
median follow-up of 36 months from randomization, patients assigned to
rituximab maintenance had a higher rate of PFS and a higher percentage of
patients in CR or CR-unconfirmed at 24 months was also seen 2 years post
randomization in patients receiving maintenance rituximab. There also was
a significantly higher percentage of patients with grade III/IV adverse
events and infections in the rituximab maintenance group. But overall
survival (OS) was not different, even after 10 years of follow-up in the
study.
Notes on follicular lymphoma grade III:
1. FL grade III has been historically referred to as follicular large
cell lymphoma.
2. It is histologically defined by the presence of >15 centroblasts
per hpf
3. It is further subdivided into grade IIIa, where centrocytes are
present, and grade IIIb, where there are sheets of centroblasts.
4. It may be confused with pediatric-type FL, which may occur in
young adults and has “aggressive” histologic features, but is
genetically distinct from FL grade IIIb, pursues an indolent
course, and is associated with an excellent prognosis
5. Follicular lymphoma grade IIIb is treated as DLBCL
Q. CLL immunophenotype is characteristically:
1.
2.
3.
4.
CD5 positive, CD23 positive
CD5 positive, CD23 negative
CD5 negative, CD23 positive
CD5 negative, CD23 negative
Answer: CD5 positive, CD23 positive
Around 40% of CLL cases express CD38. Expression of the tyrosine kinase
ZAP70 is also observed in a subset of cases and correlates with a more
aggressive clinical course.
Mantle cell lymphoma, on the other hand, expresses CD5 and usually lack
CD10 and CD23.
Q. Out of the most characteristic chromosomal abnormalities, which has the
most favorable outcome:
1.
2.
3.
4.
13q deletions
del(11q)
del(17p)
Trisomy 12
Answer: 13q deletions
Q. Patients with small lymphocytic leukemia (SLL) characteristically have:
1.
2.
3.
4.
An absolute lymphocyte count of <5,000/μL
An absolute lymphocyte count of <1,000/μL
An absolute lymphocyte count of <10,000/μL
Diagnosis of SLL doesn’t depend on the absolute lymphocyte
count
Answer: An absolute lymphocyte count of <5,000/μL
Q. Patient of CLL may transform to:
1.
2.
3.
4.
DLBCL
Hodgkin lymphoma
Both of the above
Neither 1 nor 2
Answer: both of the above
The transformation to DLBCL is known as Richter syndrome.
Q. MYD88 activating mutations are characteristic and specific for
lymphoplasmacytic lymphoma:
1. True
2. False
Answer: false
While its true that MYD88 activating mutations are found in most of the
patients of LPL, they are not specific to this disease.
Q. Gastric MALT lymphomas may be associated with Helicobacter pylori
infection. Which of the following is true about these tumors:
1. H. pylori treatment may result in long term disease control in
early stages
2. Patients with a t(11;18) translocation don’t benefit with
eradication of H. pylori
3. If the lymphoma of an early stage fails to respond to H. pylori
then RT is the preferred treatment modality.
4. All of the above
Answer: all of the above
Chemotherapy, immunotherapy, or chemoimmunotherapy is active in this
disease but is generally reserved for patients with disease that is relapsed or
refractory to antibiotic therapy or RT or patients with more advanced-stage
or aggressive disease. Interestingly, MALT lymphoma of the ocular adnexa
is associated with C. psittaci infection.
Q. What is a “double-hit” diffuse large B cell lymphoma:
1. DLBCL with MYC rearrangement and concurrent BCL2 or
BCL6 rearrangements
2. DLBCL with MYC rearrangement and concurrent BCL2 but not
BCL6 rearrangements
3. DLBCL with MYC rearrangement and concurrent BCL6 but not
BCL2 rearrangements
4. DLBCL without MYC rearrangement but with concurrent BCL2
and BCL6 rearrangements
Answer: DLBCL with MYC rearrangement and concurrent BCL2 or BCL6
rearrangements
Double hit lymphomas have a poorer prognosis and in the new WHO
classification, they are classified as a new disease entity.
Q. Which of the following is not true about DLBCL management:
1. The current recommendation for the treatment of advanced-stage
DLBCL is combination chemotherapy with RCHOP for patients
both younger than 60 years and older than 60 years
2. GELA trial reported that eight cycles of RCHOP was superior to
CHOP alone in terms of PFS, disease-free survival (DFS), and
OS, with no added toxicity
3. In the U.S. Intergroup study comparing administering CHOP or
RCHOP given on a different schedule in a similar population
and randomizing responding patients to receive either rituximab
maintenance therapy or no maintenance found PFS benefit of
maintenance rituximab following RCHOP induction
4. The RICOVER-60 trial found no benefit of eight cycles of
RCHOP over six cycles
Answer: In the U.S. Intergroup study comparing administering CHOP or
RCHOP given on a different schedule in a similar population and
randomizing responding patients to receive either rituximab maintenance
therapy or no maintenance found PFS benefit of maintenance rituximab
following RCHOP induction
In fact, maintenance rituximab failed to show benefit.
Notes:
1. Trials comparing RCHOP administered every 21 days (RCHOP21) to RCHOP administered every 14 days (RCHOP-14) found
no benefit of RCHOP-14 and toxicity were increased. Thus
establishing RCHOP given every 21 days for 6 cycles as the
standard of care.
2. A meta-analysis of patients treated on 15 randomized trials with
either conventional therapy or ASCT in first CR showed no
difference in EFS, OS, or treatment-related mortality.
3. The results to date do not support ASCT as a consolidation for
first remission.
Q. In testicular DLBCL which of the following treatment strategies is used:
1. Orchiectomy of the involved testis
2. Systemic or intrathecal methotrexate
3. Prophylactic radiation of the contralateral testis
4. All of the above
Answer: all of the above
Testicular DLBCL is a unique entity as there are higher chances of
involvement of CNS and contralateral testis. For this purpose its
management involves all of the above mentioned options along with
systemic chemo.
Notes on other sites and characteristics, lymphomas of which have high
chances of having CNS spread:
1.
2.
3.
4.
5.
6.
7.
8.
Testis
Ovary
Bone marrow
Breast
Epidural space
Paranasal sinuses
High intermediate or high IPI score
Multiple extranodal sites
There is a CNS-IPI model available for assessing the risk to CNS. It has the
same five parameters used in the standard IPI with the addition of
involvement of the kidneys and/or adrenal glands to define three risk
groups: low, intermediate, and high risk.
Q. Starry sky appearance on histology is seen in:
1.
2.
3.
4.
Burkitt lymphoma
DLBCL
Mantle cell lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma
Answer: Burkitt lymphoma
Notes on Burkitt lymphoma:
1. It generally occurs in the pediatric population
2. It has three major forms:
a. The endemic or African form presents as a jaw or facial
bone tumor at spreads to extranodal sites, including the
ovary, testis, kidney, breast, and especially bone marrow
and meninges.
b. The non endemic form usually has an abdominal
presentation with massive disease, ascites, and renal, testis,
and/or ovarian involvement and, like the endemic form,
also spreads to the bone marrow and CNS.
c. Immunodeficiency-related cases more often involve lymph
nodes and may present with peripheral blood involvement.
BL has a male predominance and is typically seen in
patients younger than 35 years of age.
Q. Hallmark cells are most commonly found in:
1.
2.
3.
4.
Burkitt lymphoma
Mixed cellularity Hodgkin lymphoma
Anaplastic large cell lymphoma
Peripheral cutaneous T cell lymphoma
Answer: Anaplastic large cell lymphoma
Notes on ALCL:
1. It has three distinct clinicopathologic entities: primary systemic
ALCL, ALK positive; primary systemic ALCL, ALK negative;
and primary cutaneous ALCL.
2. Virtually all cases are CD30+
Q. ATLL is associated with HTLV-1 in what percentage of cases:
1. 50
2. 10
3. 72
4. 100
Answer: 100%
The tumor cells of ATLL circulating in the blood have a sunflower or
starburst appearance.
Q. ATLL is a tumor of:
1.
2.
3.
4.
Pre T cells
NK/T cells
CD4+ T cells
CD8+ T cells
Answer: CD4+ T cells
Q. Which are the therapeutic strategies used in cases of posttransplant
lymphoproliferative disorder:
1.
2.
3.
4.
Reduction in immunosuppression
Antiviral therapy
Single-agent rituximab
Chemoimmunotherapy
Answer: all of the above
If the examiner asks what is the “first” step in management of PTLD then
its reduction in immunosuppression in form of a 25% to 50% reduction in
cyclosporine and tacrolimus and discontinuation of azathioprine and
mycophenolate mofetil.
Q. Which of the following is not a diagnostic criteria required for Sézary
syndrome:
1. Absolute Sézary count of at least 1,000 cells/mm3 in the bone
marrow
2. Expanded CD4+ populations and/or loss of antigens such as
CD2, CD3, CD5, or CD4
3. Presence of a T-cell clone in the blood
4. None of the above
Answer: Absolute Sézary count of at least 1,000 cells/mm3 in the bone
marrow
In fact the absolute Sézary count of at least 1,000 cells/mm3 is required in
the blood and not in the bone marrow.
The criteria for the diagnosis of this syndrome are provided by the
International Society for Cutaneous Lymphoma (ISCL), which include an
absolute Sézary count of at least 1,000 cells/mm3 in the blood,
immunophenotypic abnormalities (expanded CD4 + populations and/or loss
of antigens such as CD2, CD3, CD5, or CD4), or presence of a T-cell clone
in the blood.
Notes on mycosis fungoides;
1. Mycosis fungoides, also known as Alibert-Bazin syndrome or
granuloma fungoides, is the most common form of cutaneous Tcell lymphoma.
2. The immunophenotypic profile of MF is one of clonal mature
CD4+CD45RO+ T cells with a marked homing capacity for the
papillary dermis and epidermis.
3. Antigen loss is characteristic of the disease, with loss of CD7,
CD5, or CD2 and dim staining for CD3.
4. Sézary cells express a TH2 phenotype, with secretion of
interleukin (IL)-4, IL-5, IL-6, IL-10, and IL-13.
5. The pruritus characteristic of the disease is related to secretion of
IL-5 as well as other chemokines.
6. One of the most striking features of MF/SS is epidermotropism,
or infiltration of the epidermis by malignant T cells.
7. The pathognomic feature of MF is the Pautrier microabscess, a
collection of clonal malignant cells within the epidermis .
8. Skin-directed modalities include those for localized disease
(radiotherapy, bexarotene, carmustine) and those applicable to
total skin therapy (topical chemotherapy with nitrogen mustard
[NM], phototherapy, and total skin electron-beam therapy
[TSEBT]).
9. Systemic therapy options Interferon-α, vorinostat, alemtuzumab,
mogamulizumab (a humanized anti-CCR4 antibody) and
brentuximab vedotin among others
Q. The most common type of primary CNS lymphoma is:
1.
2.
3.
4.
DLBCL
Follicular lymphoma
High grade lymphoma, NOS
Lymphoblastic lymphomas
Answer: DLBCL
Notes on PCNSL:
1. The common sites are the cerebral hemisphere (38%), basal
ganglia and thalamus (16%), and corpus callosum (14%).
2. It is characterized o n T1-weighted, postcontrast images by
homogeneous enhancement with well-defined borders. It is
typically isointense to hypointense on T2-weighted MRI and has
restricted diffusion on diffusion-weighted imaging (DWI).
Q. The staging system used for PCNSL is:
1.
2.
3.
4.
Ann Arbor
Lugano
McDonalds
None of the above
Answer: none of the above
There is no validated staging system for PCNSL.
Q. The most effective systemic therapy option for PCNSL is:
1.
2.
3.
4.
High dose intravenous methotrexate
Rituximab
Thiotepa
High dose cyclophosphamide +/- steroids
Answer: High dose intravenous methotrexate
The most effective treatment for PCNSL is intravenous, HD-MTX at
variable doses (1 to 8 g/m2), typically utilized in combination with other
chemotherapeutic agents and/or WBRT.
MATRix regimen addition of thiotepa and rituximab to the HDMTX/cytarabine combination
ACUTE LEUKEMIA
Q. Which of the core binding factor targeting chromosomal translocation is
not characteristically found in AML:
1.
2.
3.
4.
t(8;21)
inv(16)
t(12;21)
All of the above are characteristically found in AML
Answer: t(12;21)
The ETV6/RUNX1 (aka TEL/AML1) fusion that is expressed as a
consequence of t(12;21) is more commonly found in pediatric B-ALL and
not in AML.
Core binding factor targeting mutations confer good prognosis to acute
leukemia patients.
Notes on APL (acute promyelocytic leukemia):
1. It is a result of t(15;17) fusion gene
2. The RARα gene on chromosome 17 is fused to promyelocytic
leukemia (PML) gene on chromosome 15.
3. It is classified in low and high risk (based on the WBC count
upto 10000/mm3 or more). Some groups use an intermediate risk
classification as well, that takes into account platelet count as
well.
4. The treatment of low risk APL may be done without chemo and
by using a combination of all trans retinoic acid (ATRA) and
arsenic. The most used of which is the Lococo regimen.
5. The treatment of high risk incorporates ATRA, arsenic and
chemo
6. The cure rates in low risk APL are well above 90% where as
they are lower in the high risk group.
7. There are some variant gene fusions as well like the PLZF/RARα
fusion, resulting from t(11;17). In the patients harboring this
mutation, ATRA is not effective.
Q. Which of the following is not true:
1. Approximately 1% to 2% of de novo AML are BCR/ABL1
rearranged
2. BCR/ABL1 rearrangement is present in 20% to 30% of pediatric
ALL
3. Most patients with ALL express a 190-kDa protein (p190) as a
result of BCR/ABL1 rearrangement
4. In CML patients the BCR/ABL1 rearrangement results in
expression of a 210-kDa oncoprotein (p210)
Answer: BCR/ABL1 rearrangement is present in 20% to 30% of pediatric
ALL
In fact, this rearrangement is present in 20% to 30% of adult ALL and 2%
to 3% of children with ALL.
Q. Activating mutations in FLT3 have been reported in what percentage of
AML patients:
1.
2.
3.
4.
30-35
<20
60-70
They are not found in AML
Answer: 30-35%
They are most commonly internal tandem duplications (ITDs) within the
JM domain that result in constitutive activation of FLT3.
This mutation confers high risk.
Q. A marrow or peripheral blood blast count ≥20% is absolutely necessary
for the diagnosis of AML and if blast percentage is any lower a diagnosis of
AML can’t be made:
1. True
2. False
Answer: false
While its true that according to the WHO a marrow or peripheral blood
blast count ≥20% is necessary for the diagnosis of AML, but it's not always
required. For example, in cases with t(8;21), inv(16), t(16;16) (corebinding factor), or t(5;17) (APL), the diagnosis of AML can be made with
lower blast percentage.
Notes on risk stratification of AML:
The revised European LeukemiaNet classification system:
Favorable risk
1.
2.
3.
4.
t(8;21)(q22;q22.1); RUNX1-RUNX1T1
inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
Mutated NPM1 without FLT3-ITD or with FLT3-ITD low
Biallelic mutated CEBPA
Intermediate
1. Mutated NPM1 and FLT3-ITD high
2. Wild-type NPM1 without FLT3-ITD or with FLT3-ITD low
(without adverse-risk genetic lesions)
3. t(9;11)(p21.3;q23.3); MLLT3-KMT2A
4. Cytogenetic abnormalities not classified as favorable or adverse
Adverse
1. t(6;9)(p23;q34.1); DEK-NUP214
2. t(v;11q23.3); KMT2A rearranged
3. t(9;22)(q34.1;q11.2); BCR-ABL1
4. inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);
GATA2,MECOM(EVI1)
5. −5 or del(5q); −7; −17/abn(17p)
6. Complex karyotype, monosomal karyotype
7. Wild-type NPM1 and FLT3-ITD high
8. Mutated RUNX1
9. Mutated ASXL1
10. Mutated TP53
Q. The 7+3 regimen used in the treatment of AML is:
1. 7 days of cytarabine administered by continuous infusion for 7
days together with 3 days of an anthracycline
2. 7 days of an anthracycline administered by continuous infusion
for 7 days together with 3 days of cytarabine
3. 7 days of cytarabine together with 3 days of an anthracycline
administered by continuous infusion
4. 7 days of an anthracycline together with 3 days of cytarabine
administered by continuous infusion
Answer: 7 days of cytarabine administered by continuous infusion for 7
days together with 3 days of an anthracycline
The dose of cytarabine is usually 100 mg/m2 daily continuous infusion for
7 days (total dose 700 mg/m2) along with three days of an anthracycline
(daunorubicin or idarubicin). The dose of daunorubicin is generally 60
mg/m2 daily for 3 days.
Q. Gemtuzumab ozogamicin is an antibody directed to:
1.
2.
3.
4.
CD30
CD33
CD52
CD22
Answer: CD33
Notes on midostaurin:
1. The RATIFY trial randomized patients of AML to 3+7 plus or
minus midostaurin in patients with FLT3-mutated AML.
Consolidation was with high-dose ara-C with or without
midostaurin and allogeneic stem cell transplant was allowed in
first CR. Those in remission continued their midostaurin or
placebo for maintenance.
2. OS and event-free survival were significantly better for the
patients randomized to receive midostaurin, even after censoring
patients who underwent allogeneic stem cell transplant. This has
led to the approval of midostaurin for the treatment of patients
with newly diagnosed FLT3-mutated AML.
Notes on indications for allogeneic transplant in acute myelogenous
leukemia:
1. First remission ELN intermediate or high risk
2. First remission, age 60 to 75 y Consider if low comorbidity score
First remission, therapy-related, or secondary disease All eligible
Primary induction failure All eligible
Second or subsequent remission All eligible
Relapsed, active disease All eligible
Q. Which of the following is not an adverse prognostic factor in adult acute
lymphoblastic leukemia:
1.
2.
3.
4.
Age <35 years
Leukocytosis of >30000/mm3 for B cell lineage
Leukocytosis of >100000/mm3 for T cell lineage
Early T cell precursor immunophenotype
Answer: age <35 years
In fact, age >35 years is an adverse prognostic risk factor.
Notes on unfavorable prognostic features in adult acute lymphoblastic
leukemia:
1. Age >35 y
2. Leukocytosis >30000/mm3 for B lineage and >100000/mm3 for
T lineage
3. Early T-cell precursor immunophenotype
4. t(9;22)(q24;q11.2), t(4;11)(q21;q23), t(8;14)(q24.1;q32),
complex, low hypodiploidy
5. Molecular profile: IKZF1, CRLF2, TP53, LYL1
6. Treatment Related:
a. Therapy response Time to morphologic CR >4 wk
b. Persistent MRD up to 10 to 12 wk postinduction
Q. Adults with ALL have lower chances of achieving long term disease free
survival compared with pediatric ALL patients:
1. True
2. False
Answer: true
Only 25% to 50% of adults achieve long-term DFS.
Q. Starry sky appearance on microscopy is seen in which type of ALL:
1.
2.
3.
4.
L1
L2
L3
None of the above
Answer: L3
The FAB classification divided ALL based on cell morphology in to three
subtypes:
1. L1 lymphoblasts, which have small to intermediate in size (the
most common type of ALL)
2. L2, which has slightly larger sized blasts
3. L3, which has large blasts, described as having a starry sky
appearance, which were seen in Burkitt leukemia or lymphoma.
Q. The most common type of ALL, the precursor B ALL, shows all of the
following features except:
1.
2.
3.
4.
Surface immunoglobulin positivity
TdT positivity
CD10 (CALLA) positivity
Cytoplasmic CD79a positivity
Answer: Surface immunoglobulin positivity
Notes on ALL immunophenotypes:
1. Of all cases of ALL, 85% are of B-cell lineage, and the most
common form is the precursor B phenotype (also called common
precursor-B-ALL or early precursor-B-ALL); these cells express
a B-cell immunophenotype (CD19, CD22), terminal
deoxynucleotidyl transferase (TdT), cytoplasmic CD79A, CD34,
CD10 (CALLA), and lack cytoplasmic μ and surface
immunoglobulin (sIg).
2. Pro-B-ALL, lacks CD10 expression and may represent an earlier
level of B-cell maturation.
3. Mature B-cell lineage ALL has the immunophenotype of mature
B cells with sIg expression and is seen with Burkitt leukemia or
lymphoma.
4. T-lineage ALL accounts for 15% to 20% of cases. This common
thymocyte type expresses pan T-cell markers, CD2, cytoplasmic
CD3 (cCD3), CD7, CD5, and distinctively shows co-expression
of CD4 and CD8 and expression of CD1a.
5. A more primitive type called prothymocyte or immature
thymocyte type has TdT, cCD3, and variable expression of CD5,
CD2, and CD7, but lacks CD4, CD8, and CD1a. Notably, using
molecular profiling, a distinct subset within the immature
thymocyte group has been identified as early T-cell precursor
with very poor prognosis.
6. Mature T-lineage phenotype expresses the pan T-cell markers,
variable TdT, but lacks CD1a.
Q. All of the following are associated with poor prognosis in ALL except:
1.
2.
3.
4.
t(9;22)
t(4;11)
t(12;21)
Five or more chromosomal abnormalities
Answer: t(12;21)
Other poor prognostic features are t(8;14), low hypodiploidy or near
triploidy.
CHRONIC LEUKEMIAS
Q. The term “philadelphia chromosome” is used for which abnormal
chromosome:
1.
2.
3.
4.
9
22
11
The product of t(9;22) is called the philadelphia chromosome
Answer: 22
The Philadelphia chromosome was described by Nowell and Hungerford as
a “minute” chromosome 22 in CML cells.
The genes juxtaposed by the translocation are ABL1 (Abelson) on 9q34 and
breakpoint cluster region (BCR) on chromosome 22q11.
Q. In patients of CML the breakpoints within ABL1 (on chromosome
9q34)occur most frequently:
1.
2.
3.
4.
Upstream of exon 1b
Downstream of exon 1a
Between exon 1b and exon 1a
None of the above
Answer: between exon 1b and exon 1a
Q. CML is characterized by the Philadelphia chromosome. What is the
minimum number of bone marrow metaphases required to be examined for
classical cytogenetics analysis for the detection of the Ph chromosome:
1. 10
2. 20
3. 30
4. 40
Answer: 20
In up to 90% of the patients, a typical t(9;22)(q34;q11) translocation can be
identified; in the remaining patients, variant translocations are present.
Q. Which of the following is not true about atypical CML patients:
1. They have clinical and cytological features, like basophilia, of
CML but are negative for Ph chromosome or BCR-ABL1
rearrangement on cytogenetics, QRPCR, and FISH analysis
2. In 40% of these patients, mutations in the SETBP1 or ETNK1
genes are detected
3. Atypical CML has a poor prognosis with median survival being
only 2 to 3 years
4. Nonspecific chromosomal alteration may be present in a few
cases
Answer: They have clinical and cytological features, like basophilia, of
CML but are negative for Ph chromosome or BCR-ABL1 rearrangement on
cytogenetics, QRPCR, and FISH analysis
The above mentioned statement is true except the word “basophilia”. These
cases don’t have basophilia.
Q. Which of the following TKI is not approved by US-FDA for the
treatment of CML in any phase:
1.
2.
3.
4.
Dasatinib
Radotinib
Bosutinib
Ponatinib
Answer: radotinib
Radotinib is approved in some Asian countries but not by US-FDA.
There are five TKIs are licensed for CML treatment: imatinib, dasatinib,
nilotinib, bosutinib, and ponatinib.
Notes on adverse effects of imatinib:
1. The common one are related to the inhibition of PDGFR
2. The common adverse effects are edema with weight gain,
conjunctival irritation and lacrimation, scleral and mucosal
hemorrhage, muscle cramps, asthenia, and diarrhea. Skin rash is
also possible, with nummular lesions in lower limbs, trunk, or
forearms.
3. Less frequent AEs include skin hypopigmentation (due to KIT
blockage) and fragility, liver function test (LFT) alterations,
anemia, thrombocytopenia, and neutropenia.
4. Hematologic AEs are considered as such only when occurring in
patients who have already obtained a cytogenetic remission
(CyR).
5. Most of the adverse effects are not severe and are reversible.
Q. Which is not true about dasatinib:
1. DASISION was a major trial studying dasatinib in CML
2. It is more specific than imatinib
3. It is approved for treatment of CML both in the first line and in
later lines
4. The most important adverse effect of dasatinib is development of
pleural and pericardial effusions
Answer: It is more specific than imatinib
In fact it is less specific than imatinib as it inhibits more than 30 tyrosine
kinases, but it is more potent.
Pleural and pericardial effusion are seen in 30% to 40% of patients and are
treated with treatment interruption and supportive therapy with steroids and
diuretics.
Q. Nilotinib is not associated with which of the following side effects:
1.
2.
3.
4.
Edema and muscle cramps
Cutaneous toxicity
Acute pancreatitis
Metabolic syndrome
Answer: edema and muscle cramps
Unlike imatinib, nilotinib is not associated with edema and muscle cramps.
The metabolic syndrome is characterized by hyperglycemia, increased
cholesterol and triglyceride levels, and progression of atherosclerotic
lesions.
Nilotinib is approved in both the first line and later lines of therapy.
ENESTnd was a pivot trial of nilotinib in CML.
Q. Which of the following TKIs inhibits T315I mutated cells in CML;
1.
2.
3.
4.
Bosutinib
Dasatinib
Ponatinib
Radotinib
Answer: ponatinib
Ponatinib is the only TKI that acts on the T315I mutation.
It is not approved in the first line therapy of CML patients.
Its most troublesome toxicity is cardiovascular events that can include both
arterial and venous events (deep vein thrombosis, pulmonary emboli) and
which can develop after a few months of treatment, again at difference with
nilotinib. These events are frequent as they involved 35% (arterial) and 6%
(venous) of patients.
Notes on response monitoring of TKI therapy in CML:
There are three levels of response assessment:
1. The first level of response is represented by the normalization of
cell blood count, and this is called hematologic response. In
order to achieve a complete hematologic response (CHR),
symptom disappearance (if present) and normalization of spleen
size (if splenomegaly is present) must also be obtained.
2. A second level of response is achieved when a “cytogenetic
response” (CyR) is obtained. Such a response is called partial
when the number of Ph-positive metaphases are between 1% and
35% and complete (CCyR) when there is no Ph-positive cell out
of a minimum of 20 evaluated metaphases. The term major
cytogenetic response includes both partial CyR and CCyR.
3. A third level of response is the one produced by the availability
of QRPCR for BCR/ABL1. With this assay, the results are
expressed as the number of BCR-ABL1 molecules divided by
the number of molecules amplified from a control gene (ABL1
or GUSB). Any ratio below 0.1% is called major molecular
remission (MMR); we speak of MR4.0, MR4.5, or MR5 if the
ratio falls below 1/10,000, 1/32,000 or 1/100,000, respectively.
Results obtained in different labs can be made more comparable
by using the International Standard (IS), although a variation by
a factor of at least three to four cannot be eliminated even by this
method. The term complete molecular remission (CMR) applies
when the QRPCR results show no amplification for the BCRABL1 gene.
Q. Which of the following TKIs is not approved for first line treatment of
CML:
1.
2.
3.
4.
Nilotinib
Bosutinib
Ponatinib
Dasatinib
Answer: ponatinib
There are four TKIs presently approved for treatment of CML is the first
line: imatinib, bosutinib, dasatinib and nilotinib.
The usual dosage is 400 mg per day for imatinib, 400 mg per day for
bosutinib, 100 mg per day for nilotinib, and 300 mg twice a day (fasting)
for nilotinib.
Q. When patients of CML on TKI are monitored by QRPCR, what is
considered an “optimal response” at 3 months of continued therapy:
1.
2.
3.
4.
A value of <10%
A value of <1%
A value of <0.1%
There are no defined criteria for PCR obtained levels at 3 months
answer: a value of <10%
Q. In patients of CML treated with TKIs, who achieve a major molecular
response, how often should QRPCR be performedIt is advisable to perform
QRPCR:
1. Every 3 months in the initial 5 years and every 6 to 12 months
thereafter
2. Every 6 months in the initial 5 years and every year thereafter
3. Every 3 months in the initial 5 years and then monitoring with
PCR may be stopped
4. Every 3 months in the initial 2 years and every 6 thereafter
Answer: Every 3 months in the initial 5 years and every 6 to 12 months
thereafter Monitoring by QRPCR must be continued indefinitely as CML
relapses have been documented
This is the conventional view and also the most practised one but as we will
see later that nowadays some patients may be candidates for stopping
treatment with TKIs, in such patients the schedules of performing PCR are
different.
Q. Which of the following is true about second generation TKIs used in the
treatment of CML;
1. Second-generation TKIs uniformly produced a faster and deeper
decrease in BCR-ABL1 messenger RNA values as detected by
QRPCR compared with imatinib
2. Some studies showed a significantly higher CCyR rates at or by
12 months in patients receiving second-generation TKIs
compared with imatinib
3. Some studies showed a significant difference in progression to
AP or BC CML with the use of second generation TKIs as
compared with imatinib
4. No studies showed a significant difference in OS with second
generation TKIs compared with imatinib
Answer: Some studies showed a significant difference in progression to AP
or BC CML with the use of second generation TKIs as compared with
imatinib
In fact, no studies showed a significant difference in progression to AP or
BC CML with the use of second generation TKIs as compared with
imatinib (which essentially is another way of saying that there was no
significant difference in progression free survival between second
generation TKIs and imatinib)
Notes on monitoring of patients of CML:
A. Bone marrow cytogenetics is performed:
1. At diagnosis
2. Failure to reach response milestones
3. Any sign of loss of response (defined as hematologic or
cytogenetic relapse)
B. qPCR using IS is performed:
1. At diagnosis
2. Every 3 months after initiating treatment.
3. After BCR-ABL1 (IS) ≤1% (>0.1%–1%) has been
achieved, every 3 months for 2 years and every 3–6 months
thereafter
4. If there is 1-log increase in BCR-ABL1 transcript levels
with MMR, qPCR should be repeated in 1–3 months
BCR-ABL1 kinase domain mutation analysis is performed in cases of:
1. Failure to reach response milestones
2. Any sign of loss of response (defined as hematologic or
cytogenetic relapse)
3. 1-log increase in BCR-ABL1 transcript levels and loss of MMR
4. Disease progression to accelerated or blast phase
Notes on the definitions of CML blast phase and accelerated phase:
It should be noted here that different institutions follow different criteria
and there are no agreed upon universal criteria. So minor variations are to
be expected in questions being asked, depending on what the examiner has
in mind while framing a particular question.
Definition of CML blast phase according to the International Bone Marrow
Transplant Registry:
1. ≥30% blasts in the blood, marrow, or both
2. Extramedullary infiltration of leukemic cells
Definition of CML accelerated phase according to the Modified MD
Anderson Cancer Center (MDACC) Criteria:
1. Peripheral blood myeloblasts ≥15% and <30%
2. Peripheral blood myeloblasts and promyelocytes combined
≥30%
3. Peripheral blood basophils ≥20%
4. Platelet count ≤100 x 109 /L unrelated to therapy
5. Additional clonal cytogenetic abnormalities in Ph+ cells
Notes on criteria for different kinds of responses and relapse in CML:
1. Complete hematologic response: Complete normalization of
peripheral blood counts with leukocyte count <10 x 109 /L,
Platelet count <450 x 109 /L, No immature cells, such as
myelocytes, promyelocytes, or blasts in peripheral blood, No
signs and symptoms of disease with resolution of palpable
splenomegaly
2. Molecular response:
a. Early molecular response (EMR) - BCR-ABL1 (IS) ≤10%
at 3 and 6 months
b. Major molecular response (MMR) - BCR-ABL1 (IS)
≤0.1% or ≥3-log reduction in BCR-ABL1 mRNA from the
standardized baseline, if qPCR (IS) is not available
c. Complete molecular response (CMR) is variably described,
and is best defined by the assay’s level of sensitivity (eg,
MR4.5)
3. Cytogenetic response:
a. Complete cytogenetic response (CCyR) - No Ph-positive
metaphases
b. Major cytogenetic response (MCyR) - 0%–35% Phpositive metaphases
c. Partial cytogenetic response (PCyR) - 1%–35% Ph-positive
metaphases
d. Minor cytogenetic response - >35%–65% Ph-positive
metaphases
Relapse is defined as:
1. Any sign of loss of response (defined as hematologic or
cytogenetic relapse)
2. 1-log increase in BCR-ABL1 transcript levels with loss of MMR
should prompt bone marrow evaluation for loss of CCyR but is
not itself defined as relapse (eg, hematologic or cytogenetic
relapse)
Notes on criteria for TKI Discontinuation (if all three criteria are met then
TKI therapy for CML may be discontinued):
1.
2.
3.
4.
5.
6.
Age ≥18 years
Chronic phase CML
No prior history of accelerated or blast phase CML
On approved TKI therapy for at least 3 years
Prior evidence of quantifiable BCR-ABL1 transcript
Stable molecular response (MR4; BCR-ABL1 ≤0.01% IS) for ≥2
years, as documented on at least 4 tests, performed at least 3
months apart
7. Access to a reliable qPCR test with a sensitivity of detection of at
least MR4.5 (BCR-ABL1 ≤0.0032% IS) and that provides results
within 2 weeks
8. Monthly molecular monitoring for one year, then every 2 months
for the second year, and every 3 months thereafter (indefinitely)
is recommended for patients who remain in MMR (MR3; BCRABL1 ≤0.1% IS) after discontinuation of TKI therapy
9. Prompt resumption of TKI within 4 weeks of a loss of MMR
with monthly molecular monitoring until MMR is re-established,
then every 3 months thereafter is recommended indefinitely for
patients who have reinitiated TKI therapy after a loss of MMR.
10. For those who fail to achieve MMR after 3 months of TKI
resumption, BCR-ABL1 kinase domain mutation testing should
be performed, and monthly molecular monitoring should be
continued for another 6 months.
Q. Which of the following is not a component of the EURO score used for
risk stratification of patients with CML:
1.
2.
3.
4.
Age
Spleen size below costal margin
Blast percentage in the bone marrow
Eosinophil count
Answer: Blast percentage in the bone marrow
In fact, blast percentage in the peripheral blood is used (not in the bone
marrow).
There are three score of CML risk stratification which have been
extensively used:
1. Sokal: age, spleen, platelet count, blasts in peripheral blood
2. Hasford, also known as EURO: age, spleen size [cm below costal
margin], percent blasts in peripheral blood, percent eosinophils,
basophils, platelet count
3. EUTOS (ELTS): age, spleen size cm below the costal margin,
blasts in peripheral blood
Sokal score, for instance, may be low <0.8, intermediate 0.8-1.2 or high
>1.2.
The implications of this risk stratification are that they can impact treatment
selection. In for example the score is low then we may choose imatinib or
any other second generation TKIs that have been approved for the treatment
of CML in the first line but if the score is high then second generation TKIs
become the preferred choice.
Q. The most common leukemia in western countries is:
1.
2.
3.
4.
CML
CLL
AML
ALL
Answer: CLL
Q. The characteristic immunophenotype of CLL cells is:
1.
2.
3.
4.
CD5+, CD20+, CD23+
CD5+, CD20-, CD23+
CD5+, CD20+, CD23CD5-, CD20+, CD23+
Answer: CD5+, CD20+, CD23+
There is sometimes confusion between CLL and MCL. We can remember
this by using a trick that CLL has two “L” so it is positive for both CD5 and
CD23 whereas MCL (mantle cell lymphoma) has only one “L” in it so it is
positive for only one of these markers: CD5 and negative for CD23.
CD200 is expressed on CLL cells, but not on mantle cell lymphoma cells,
and may be used as a distinguishing marker.
Notes on MBL (monoclonal B lymphocytosis):
1. Around 3.5% of otherwise normal individuals over the age of 40
years may harbor a population of clonal (by light chain analysis)
CD5+/CD19+/CD23+ B cells.
2. These asymptomatic individuals do not have an absolute
lymphocytosis, lymphadenopathy, or other clinical evidence of
CLL.
Q. The most common chromosomal abnormality in CLL is:
1.
2.
3.
4.
Del(13q)
Del(11q)
Trisomy 12
Del(17p)
Answer: del(13q)
Deletion 13q [del(13q)] is the most common chromosome abnormality in
CLL; it is found by FISH as a sole abnormality in 55% of cases, followed
by 11q deletion (18%) [del(11q)], 12q trisomy (16%), and 17p deletion
(7%) [del(17p)].
The prognosis is worst for del(17p).
The prognosis in best for del13q.
The survival times associated with these abnormalities are: 32, 79, 114, 111,
and 133 months for del(17p), del(11q), 12q trisomy, no abnormalities, and
del(13q), respectively.
Notes on diagnostic criteria of CLL:
These criteria are proposed by the International Workshop on Chronic
Lymphocytic Leukemia.
1. A blood monoclonal B lymphocyte count >5 × 109/L, with
<55% of the cells being atypical (prolymphocytes)
2. B lymphocyte monoclonality should be demonstrated with cells
expressing B-cell surface antigens (CD19, CD20, CD23), low
density surface Ig (M or D), and CD5
Q. The monoclonal B cell count specified to distinguish CLL from small
lymphocytic lymphoma (SLL) in patients with palpable lymph nodes or
splenomegaly is:
1.
2.
3.
4.
5000/mm3
10000/mm3
3000/mm3
There is no such distinction and it depends on the
immunophenotype
Answer: 5000/mm3
Q. Wells syndrome is frequently seen in:
1.
2.
3.
4.
CLL
CML
MDS
T-PLL
Answer: CLL
Exaggerated skin reaction to a bee sting or an insect bite (Wells syndrome)
is frequent in CLL.
Notes on certain interesting features associated with CLL:
1. Smudge cells are commonly seen in the peripheral smear,
reflecting fragility and distortion during preparation of the
peripheral smear on the glass slide.
2. A positive direct antiglobulin (Coombs) test is seen in
approximately 25% of cases, but autoimmune hemolytic anemia
(AIHA) of clinical significance is not common.
Q. Which of the following belongs the Rai stage III of CLL:
1.
2.
3.
4.
Lymphocytosis with splenomegaly
Lymphocytosis with lymphadenopathy and hepatomegaly
Anemia with or without lymphocytosis
Thrombocytopenia with lymphocytosis
Answer: Anemia with or without lymphocytosis
Following are the Rai stages of CLL:
0 = Lymphocytosis only
I = Lymphocytosis and lymphadenopathy
II = Lymphocytosis and splenomegaly with/without lymphadenopathy
III = Lymphocytosis and anemia (hemoglobin, <11 g/dL)
IV = Lymphocytosis and thrombocytopenia (platelets, <100,000/mm3)
There is also Binet staging available for CLL, which divides the patients in
three stage groups A, B and C.
Q. Which of the following patients of CLL will not require active
treatment:
1.
2.
3.
4.
A patient with extreme fatigue
A patient with fever
If a patient develops AIHA responsive to steroids
A patient with lymphadenopathy of more than 10 cm longest
diameter
Answer: If a patient develops AIHA responsive to steroids
Treatment may be indicated in patients with AIHA unresponsive to
steroids.
It is an important point to note that not all patients of CLL require treatment
and some may be observed without any treatment (as opposed to, for
example AML or CML, where all patients have to be treated). For this the
IWCLL has proposed criteria for active disease as indications to initiate
treatment:
1. Presence of constitutional symptoms attributable to CLL: weight
loss (>10% of baseline weight within the preceding 6 months),
extreme fatigue (Eastern Cooperative Oncology Group [ECOG]
performance status 2 or higher), fever (temperature higher than
38∘C or 100.5∘F for at least 2 weeks), or night sweats without
evidence of infection
2. Evidence of progressive bone marrow failure characterized by
the development of or worsening of anemia, thrombocytopenia,
or both
3. AIHA or autoimmune thrombocytopenia, or both, poorly
responsive to corticosteroid therapy
4. Massive (>6 cm below the left costal margin) or progressive
splenomegaly
5. Massive (>10 cm in longest diameter) or progressive
lymphadenopathy
6. Progressive lymphocytosis defined as an increase in the absolute
lymphocyte count by >50% over a 2-month period, or a doubling
time predicted to be <6 months
The sixth point is especially confusing and should be read very carefully.
If any of these characteristics is present in a patient then we may initiate
treatment.
Q. Which is preferred treatment for a patient aged 55 years, having IGHVmutated status but without del(17p):
1. Ibrutinib
2. FCR
3. BR
4. Obinutuzumab plus venetoclax
Answer: FCR
Notes on first line therapy of CLL:
1. Tremendous progress has been made in the treatment of CLL,
especially over the recent years.
2. The list of approved protocols is too long and one must read a
thorough reference book for this purpose, like Devita’s oncology
(quarterly updates) or the NCCN. I will try to give a brief
overview of the treatment here.
3. In young (<65 years) who are fit, in young (<65 years) who are
not fit, in old (65 years or more) patients, so essentially in all
patients having del(17p) , the bruton tyrosine kinase inhibitor:
ibrutinib is the drug of choice.
4. In young fit patients not having del(17p) and having IGHV
(immunoglobulin heavy chain) mutated status, FCR is the
therapy of choice (combination of fludarabine,
cyclophosphamide and rituximab).
5. In older patients and those young patients who are not fit to
receive intensive combination FCR chemo, who don’t have
del(17p) and have IGHV-mutated status
some less
intensive chemoimmunotherapy or ibrutinib should be used.
6. In young fit patients not having del(17p) and having IGHV-un
mutated status, treatment options are chemoimmunotherapy or
ibrutinib. Same is true for old or unfit patients.
7. The term chemoimmunotherapy means use of a anti-CD20
molecule, like rituximab, obinutuzumab, ofatumumab and a
chemo molecule like bendamustine, chlorambucil etc.
8. The main clinical implication of choosing ibrutinib over
chemoimmunotherapy is that ibrutinib has to be taken lifelong
but the chemoimmunotherapy is given for a specific duration of
time.
Q. Which of the following drugs used in CLL works on Bcl-2:
1.
2.
3.
4.
Ibrutinib
Idelalisib
Venetoclax
Selumetinib
Answer: venetoclax
Idelalisib is a PIK-3 inhibitor
Selumetinib is not used in CLL.
Q. Which is the most common second neoplasm developing in CLL
patients:
1.
2.
3.
4.
Skin cancer
Lung cancer
Myelodysplastic syndrome
PNH turning into MDS
Answer: skin cancer
Approximately 25% of patients with CLL develop second neoplasms, the
most common benign skin cancer.
Q. CLL may sometimes evolve into a high grade lymphoma, known as
Richter transformation, in what percentage of cases:
1.
2.
3.
4.
1-5
5-10
<2
20
Answer: 1-5%
The exact mentioned percentages are from 2 to 6%.
The prognosis of Richter transformation is poor, with a median survival of
only 6 months.
Q. In high risk patients of CLL, not having del(17p), rituximab maintenance
is recommended:
1. True
2. False
Answer: false
A trial was done that randomized patients to receive rituximab every 3
months for up to 2 years versus observation. There was improved PFS with
rituximab versus observation; there was no difference in OS. There was
also a higher incidence of grade 3/4 neutropenia and infections for patients
who received rituximab.
So in conclusion, CD20 mAb maintenance therapy post-CIT improved PFS,
but not OS, and is associated with neutropenia and infection. It is not
recommended.
Q. Which of the following is not true about hairy cell leukemia;
1. Hairy cells may be seen in the peripheral blood which are twice
as large as normal lymphocytes
2. Bone marrow has a “fried egg” appearance
3. Immunophenotypic analysis of cHCL cells shows the presence of
CD11c, CD23, CD25, CD103, CD123, as well as CD19, CD20,
and CD22
4. BRAF V600E gain of function mutation is found in the cells
from patients with classical HCL
Answer: Immunophenotypic analysis of cHCL cells shows the presence of
CD11c, CD23, CD25, CD103, CD123, as well as CD19, CD20, and CD22
It must be noted that in contrast to CLL, hairy cells are negative for CD5
and CD23 and negative for CD10, CD27, and CD79b.so, the
immunophenotypic analysis of cHCL cells shows the presence of CD11c,
CD25, CD103, CD123, as well as CD19, CD20, and CD22
Notes:
1. HCL can be of two types: classical and variant.
2. The variant cells are negative for CD25 and CD123.
3. In variant HCL, BRAF V600E mutations are not seen
Q. Which of the following is curative in cases of HCL:
1.
2.
3.
4.
Cladribine
Pentostatin
Vemurafenib and dabrafenib
Vemurafenib plus auto-HSCT
Answer: none of the above
It was a trick question, it should be remembered that in HCL there is no
curative therapy for HCL, except perhaps allo-SCT.
Pentostatin (2′ deoxycoformycin) and cladribine (2-CdA) are the nucleoside
analogs and are the mainstay of treatment of HCL.
Because cladribine is given only for one course and pentostatin for many
cycles, cladribine is preferred.
Vemurafenib and other BRAF inhibitors are used in classical HCL, either as
monotherapy or in combination with anti-CD20 drugs. It should be noted
that variant HCL is devoid of these mutations and not responsive to BRAF
inhibitors
Moxetumomab pasudotox is another new drug which is a CD22 mAb-drug
conjugate.
MDS
Q. Which is the most common recurrent abnormality in myelodysplastic
syndromes:
1.
2.
3.
4.
del(5q)
-7
7q+8
Answer: del(5q)
The most common recurrent abnormalities were del(5q) (30%), −7 or 7q−
(21%), and +8 (16%).
Notes on some features MDS:
1. Macrocytic anemia is the most common hematologic feature.
2. One-third patients will undergo transformation into AML.
3. The classification of MDS was recently updated by the WHO
and the reader is advised to read it up from their website.
4. There are many risk assessment (stratification) tools for MDS:
IPSS, International Prognostic Scoring System; IPSS-R, revised
IPSS; WPSS, WHO Prognostic Scoring System; MDAS, MD
Anderson Scoring System; LR-MDAS, Lower Risk MDAS etc.
5. The IPSS and IPSS-R are most commonly used systems. Their
components are:
a. IPSS: bone marrow blasts, karyotype, cytopenia
b. IPSS-R: bone marrow blasts, karyotype, hemoglobin,
ANC, platelet count
c. The IPSS divides patients into Low, Int-1, Int-2 and High.
d. The IPSS-R divides patients into very good, good,
intermediate, poor and very poor risk
e. The karyotype abnormalities in the IPSS-R are:
1.
2.
3.
4.
5.
Very good −Y, del(11q)
Good is normal karyotype, single del(5q), del(12p),
del(20q), or double including del(5q).
Intermediate includes single del(7q), +8, I (17q), +19,
or any double not including del(5q).
Poor includes der(3q), monosomy 7, double including
−7/7q, or three abnormalities.
Very poor is more than three abnormalities.
Q. What will be the optimal initial treatment of a patient with high risk
MDS:
1. Azacytidine for 4 to 6 cycles followed by evaluation for alloHCT
2. Azacytidine for 4 to 6 cycles with response evaluation after
every two cycles and finally evaluation for allo-HCT
3. Azacytidine is continued indefinitely and patients showing
progression on azacytidine are evaluated for allo- or auto-HCT
4. Either decitabine or azacytidine are used for 4 to 6 cycles and
then patients are put on active surveillance
Answer: Azacytidine for 4 to 6 cycles followed by evaluation for allo-HCT
If the patient is not a candidate for allogeneic HCT due to any reason, then
azacytidine should be continued indefinitely.
Another important point to note is that the response to azacitidine is
evaluated after four to six cycles.
Decitabine is also an option and the principles are similar to azacytidine.
Q. In lower risk MDS, anemia is the most common indication for therapy.
In patients with a low endogenous serum erythropoietin level (<500
mU/ml) and low transfusion burden, treatment is begun with an ESA, like
epoetin-α or darbepoetin-α. If no response is seen at 12 weeks then what
should be the ideal next step:
1.
2.
3.
4.
Increasing the dose of ESA
Adding G-CSF
Lenalidomide for non-del(5q) lower risk MDS
Switching to azacytidine
Answer: adding G-CSF
There is no perfect answer to this question and practice varies depending on
the institute.
Lenalidomide and azacitidine have also been used in these patients. Another
interesting treatment option for MDS patients younger than 60 years of
age with a short duration of transfusion dependence, a CD4:CD8 ratio
<2.0, or those with trisomy 8 , immunosuppressive therapy (IST).
In del(5q) lower risk MDS patients who either failed or are not a candidate
for treatment with an ESA, lenalidomide is the treatment of choice.
PLASMA CELL DISORDERS
Q. The preferred method to detect bone disease in multiple myeloma is:
1.
2.
3.
4.
Whole-body low-dose CT
PET-CT
Skeletal survey
MRI survey of abdomen
Answer: whole body low dose CT
Other modalities may also be used, in fact they are frequently used.
Notes on ideal initial treatment strategies for multiple myeloma:
1. If a patient is not a transplant candidate and is fit then preferred
regimens are Bortezomib/lenalidomide/dexamethasone,
Bortezomib/cyclophosphamide/dexamethasone and other
recommended regimens are
Carfilzomib/lenalidomide/dexamethasone and
Ixazomib/lenalidomide/dexamethasone. If the
Bortezomib/lenalidomide/dexamethasone regimen is used then 3
to 4 cycles are given and then the stem cells are collected. The
reason is that lenalidomide may have harmful effects of stem
cells if used for longer duration.
2. If a patient is not a transplant candidate and is frail and not very
fit, then the preferred regimens are:
Bortezomib/lenalidomide/dexamethasone,
Daratumumab/lenalidomide/dexamethasone, Lenalidomide/lowdose dexamethasone,
Bortezomib/cyclophosphamide/dexamethasone. Other
recommended regimens are
Carfilzomib/lenalidomide/dexamethasone,
Ixazomib/lenalidomide/dexamethasone,
Daratumumabm/bortezomib/melphalan/prednisone.
3. If a patient is transplant eligible then there are two strategies:
a. Early transplant: a combination of bortezomib,
lenalidomide and dexamethasone is given for 3-4 cycles
and autologous HCT is done followed by bortezomib
maintenance for high risk patients or lenalidomide for
standard risk patients.
b. Delayed transplant: a combination of bortezomib,
lenalidomide and dexamethasone is given for many more
cycles and transplant is done later
In some cases a tandem transplant (auto-HCT followed by another planned
auto-HCT) or an auto- followed by allo-HCT is done.
Some experts recommend treatment with a combination of carfil zomib,
lenalidomide and dexamethasone in high risk patients to begin with.
Devita oncology has this wonderful table on management of relapsed
myeloma, which everybody should go through.
Q. SLAM-F7 targeting molecule used in multiple myeloma treatment is:
1.
2.
3.
4.
Elotuzumab
Daratumumab
Panobinostat
Selinexor
Answer: elotuzumab
Daratumumab is anti-CD38
Panobinostat is HDAC inhibitor
Pomalidomide is an immunomodulator
Q. In patients of multiple myeloma, to prevent skeletal events
bisphosphonates are indicated. For how long should bisphosphonates are
administered every month in them:
1.
2.
3.
4.
1 to 2 years
3 to 5 years
Indefinitely
Bisphosphonates should ideally be given every 3 months
indefinitely
Answer: 1 to 2 years
The dose of zoledronic acid is 4 mg intravenously over 15 to 30 minutes
every 4 weeks and dose of pamidronate is 90 mg intravenously over at
least 2 hours every 4 weeks.
When bisphosphonates are used, monthly use should be limited to the first 1
to 2 years. Thereafter, the frequency should be reduced to once every 3 to 4
months.
Some trials suggest that a reduced frequency of administration, i.e., once
every 3 months may be as effective as monthly administration.
Q. Extramedullary plasmacytoma is localized most commonly to:
1.
2.
3.
4.
Upper respiratory tract
Lower GI tract
Upper GI tract
Retroperitoneum and thigh
Answer: upper respiratory tract
They are found in the nasal cavity and sinuses, nasopharynx, and larynx in
over 80% of cases.
Q. What is the treatment of choice for solitary plasmacytoma:
1.
2.
3.
4.
40 to 50 Gy of radiation
Surgery followed by 40 to 50 Gy of radiation
40 to 50 Gy of radiation followed by surgery
Surgery alone and radiation only in high risk patients
Answer: 40 to 50 Gy of radiation
Notes POEMS syndrome:
1.
2.
3.
4.
5.
Polyneuropathy
Organomegaly
Endocrinopathy
Monoclonal plasma cell disorder
Skin changes
Almost all patients have either osteosclerotic lesions or Castleman disease.
Q. The treatment of choice for patients of smoldering myeloma is:
1.
2.
3.
4.
Observation
Radiation to involved sites
Low dose myeloma directed therapy
Immunomodulators
Answer: observation
Observation is done every 3 to 6 months.
Q. Which of the following is not an addition entity present in the revised
ISS criteria for multiple myeloma compared with the ISS criteria:
1.
2.
3.
4.
Serum LDH
Chromosomal abnormalities by FISH
PCR multiplex gene analysis
None of the above
Answer: PCR multiplex gene analysis
The ISS criteria are:
1. Stage I: Serum beta-2 microglobulin <3.5 mg/L, Serum albumin
≥3.5 g/dL
2. Stage II: Not ISS stage I or III
3. Stage III: Serum beta-2 microglobulin ≥5.5 mg/L
The R-ISS criteria are:
1. ISS stage I and standard-risk chromosomal abnormalities by
FISH and Serum LDH ≤ the upper limit of normal
2. Stage II: Not R-ISS stage I or III
3. Stage III: ISS stage III and either high-risk chromosomal
abnormalities by FISH or Serum LDH > the upper limit of
normal
The high-risk chromosomal abnormalities by FISH are: presence of
del(17p) and/or translocation t(4;14) and/or translocation t(14;16). It should
be noted here that some centres use different sets of high-risk chromosomal
markers. But the above mentioned ones are most commonly used.
Q. All of the following may be labelled smoldering myeloma except:
1.
2.
3.
4.
Serum monoclonal protein ≥3 g/dL
Bence-Jones protein ≥500 mg/24 h
Clonal bone marrow plasma cells 10%–59%
2 or less focal lesions on MRI studies ≥5 mm
Answer: 2 or less focal lesions on MRI studies ≥5 mm
Diagnostic criteria for smoldering myeloma:
Serum monoclonal protein ≥3 g/dL or Bence-Jones protein ≥500 mg/24 h
and/or clonal bone marrow plasma cells 10%–59% and absence of
myeloma-defining events or amyloidosis
Diagnostic criteria for multiple myeloma:
Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or
extramedullary plasmacytoma and Any one or more of the following:
1. Calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit
of normal or >2.75 mmol/L (>11 mg/dL)
2. Renal insufficiency (creatinine >2 mg/dL) [>177 µmol/L] or
creatinine clearance <40 mL/min
3. Anemia (hemoglobin <10 g/dL or hemoglobin >2 g/dL below the
lower limit of normal)
4. One or more osteolytic bone lesions on skeletal radiography, CT,
or FDG PET/CT
5. Clonal bone marrow plasma cells ≥60%
6. Involved:uninvolved serum FLC ratio ≥100 and involved FLC
concentration 10 mg/dL or higher
7. >1 focal lesions on MRI studies ≥5 mm
Notes on some response categories of multiple myeloma:
1. Stringent complete response: Complete response as defined
below plus normal FLC ratio and absence of clonal cells in bone
marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2
for κ and λ patients, respectively, after counting ≥100 plasma
cells).
2. Complete response: Negative immunofixation on the serum and
urine and disappearance of any soft tissue plasmacytomas and
<5% plasma cells in bone marrow aspirates.
3. Very good partial response: Serum and urine M-protein
detectable by immunofixation but not on electrophoresis or
≥90% reduction in serum M-protein plus urine M-protein level
<100 mg per 24 h
4. Partial response: ≥50% reduction of serum M-protein plus
reduction in 24-h urinary M-protein by ≥90% or to <200 mg per
24 h. If the serum and urine M-protein are unmeasurable, a
≥50% decrease in the difference between involved and
uninvolved FLC levels is required in place of the M-protein
criteria. If serum and urine M-protein are unmeasurable, and
serum-free light assay is also unmeasurable, ≥50% reduction in
plasma cells is required in place of M-protein, provided baseline
bone marrow plasma-cell percentage was ≥30%. In addition to
these criteria, if present at baseline, a ≥50% reduction in the size
(sum of the products of the maximal perpendicular diameters
[SPD] of measured lesions)j of soft tissue plasmacytomas is also
required.
MISCELLANEOUS MALIGNANCIES
Q. The most common histology identified in carcinoma of unknown
primary is:
1.
2.
3.
4.
Adenocarcinoma
Poorly differentiated carcinoma
Squamous cell carcinoma
No specific histology can be identified in most of the cases
Answer: adenocarcinoma
Histopathologic subtyping typically starts with stains such as
pancytokeratin (carcinoma), CD45 (lymphoma), S100 (melanoma), and
chromogranin and synaptophysin (neuroendocrine tumors) to identify the
general class of tumor.
Many adenocarcinomas of unknown primary are CK7+/CK20−, which by
itself is not particularly helpful in confirming a primary site. Squamous cell
carcinomas are characterized by high-molecular-weight keratin (e.g.,
CK5/6) and p63 expression.
Notes on cytokeratin staining:
1. CK7+/CK20− Breast, ovarian, pulmonary, endometrial, thyroid
2. CK7+/CK20+ Upper gastrointestinal (adenocarcinoma)
pancreatic, urothelial
3. CK7−/CK20+ Colorectal, Merkel cell
4. CK7−/CK20− Prostate, hepatocellular, adrenal, cortical
Notes on common pattern of IHC patterns useful in identification of
primary sites:
1. PAX8: RCC, thyroid, ovarian, endometrial, cervical
2. TTF1: Lung adenocarcinoma, thyroid, lung squamous
carcinoma, cholangiocarcinoma, endometrial carcinoma, often
positive in poorly differentiated neuroendocrine tumors
3. Napsin: Lung adenocarcinoma, ovarian clear cell carcinoma,
papillary RCC, rarely positive in thyroid carcinoma
4. GATA3: Urothelial carcinomas, breast carcinoma,
mesotheliomas, chromophobe RCC, salivary duct carcinoma,
pancreatic adenocarcinoma
5. CDX2: Colon adenocarcinoma, gastroesophageal,
pancreaticobiliary adenoma, ovarian,
6. p63 and CK5/CK6: Squamous cell carcinoma
7. Thyroglobulin: Well-differentiated thyroid carcinoma, poorly
differentiated/anaplastic thyroid carcinoma
8. Arginase-1: HCC
9. HepPar-1: Well-differentiated HCC, poorly differentiated HCC
10. PSA: Prostate adenocarcinoma
11. NKX3.1: Prostatic adenocarcinoma
12. Inhibin: adrenocortical carcinoma,
13. ER/PR: Hormone receptor–positive primary breast tumors,
endometrioid carcinomas, ovarian serous carcinomas, uterine
leiomyosarcoma
Q. Presently, what’s the best role of next generation sequencing in cases of
carcinoma of unknown primary:
1.
2.
3.
4.
In refractory cases
In cases with known driver gene mutations
In all cases of undetermined histology
In poorly differentiated carcinoma
Answer: in refractory cases
Notes on asbestos fibers:
Two major groups:
1. Chrysolite
2. Amphibole type: amosite, crocidolite, anthophyllite, actinolite
and tremolite.
Q. Somatic alterations in BAP1 and the resultant BAP1 protein loss is
found in what percentage malignant mesotheliomas:
1.
2.
3.
4.
10
20
50
100
Answer: 50
These alterations are mostly in the form of losses in chromosome 3p where
the BAP1 gene is located.
BAP-1 has also been found to be associated with genetic predispositions to
this disease.
Q. Which virus has been most strongly associated with malignant
mesothelioma:
1.
2.
3.
4.
HPV16
HIV
HTLV-1
SV40
Answer: SV40
Simian virus 40 (SV40) is a DNA tumor virus that has been reported to be
associated with MM.
Q. Which of the following is not true about mesothelioma:
1. Malignant mesothelioma are most commonly of sarcomatoid
type due to the abundance of mesothelial cells
2. The immunohistochemistry shows that mesothelioma cells are
diffusely positive for pankeratin, keratin 5/6, calretinin, and
Wilms tumor 1 (WT1)
3. The tumor cells of mesothelioma are negative for the epithelial
markers TTF1, CEA, Ber-EP4, Moc-31, CD15, PAX-8
4. Thrombocytosis is seen in upto 90% of mesothelioma patients
Answer: Malignant mesothelioma are most commonly of sarcomatoid type
due to the abundance of mesothelial cells
In fact, 50% to 60% of the are of the epithelial type, approximately 10% are
sarcomatoid, and the remainder are biphasic.
Notes:
1. WT1 is the most specific marker for pleural mesothelioma
2. D2-40 is almost always positive in mesothelioma and so is
mesothelin, but they are not specific for mesothelioma.
Q. What’s the chemotherapy of choice for unresectable malignant
mesothelioma:
1.
2.
3.
4.
Cisplatin + paclitaxel
Cisplatin + pemetrexed
Single agent cisplatin
Gemcitabine + erlotinib
Answer: cisplatin + pemetrexed
Q. Trimodality therapy (TMT) for malignant pleural mesothelioma consists
of all of the following except:
1.
2.
3.
4.
Induction chemotherapy
Extrapleural pneumonectomy
Radiation therapy
P/D
Answer: P/D
The ideal patient is younger than 65 years old, has pure epithelial histology,
an absence of lymph node involvement, and is physiologically able to
tolerate pneumonectomy.
Q. Bevacizumab in combination with chemotherapy is useful in malignant
mesothelioma:
1. True
2. False
Answer: true
The Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS),
randomized unresectable mesothelioma previously untreated with
chemotherapy and with ECOG performance 0 to 2 patients to receive
pemetrexed-cisplatin alone or in combination with bevacizumab. OS was
significantly longer with the triplet combination (median, 18.8 versus 16.1
months; HR, 0.77; 95% CI, 0.62 to 0.95; P = .0167).
Based on this study this combination was approved in the first line setting.
Q. Callender classification is for:
1.
2.
3.
4.
Acral melanoma
Uveal melanoma
Intracerebral melanocytic tumors
Merkel cell carcinoma
Answer: uveal melanoma
Callender classification divides uveal melanoma into spindle cell
melanomas (spindle A, spindle B), mixed cell melanomas, and epithelioid
cell melanomas (each associated with a progressively worse prognosis for
survival).
Q. The MOST mnemonic of Dr. Finger, which he proposed for choroidal
melanomas, has all of the following components except:
1.
2.
3.
4.
Orange pigment
Subretinal fluid
Thickness of ≥2.0 mm
Melanocyte infiltration into iris
Answer: Melanocyte infiltration into iris
The most mnemonic is Melanoma= Orange pigment, Subretinal fluid,
Thickness of ≥2.0 mm
On a different note, the biopsy of uveal melanomas is a controversial
subject due to technical difficulties and other concerns. Consensus
indications for uveal tumor biopsy include atypical tumors, metastatic
tumors, patients who require a pathology diagnosis, and for genetic or
molecular analysis.
Notes on treatment of uveal melanomas:
1. Small T1 uveal melanomas: observation is treatment of choice.
Radiation therapy may be offered in some.
2. Intermediate T2 uveal melanoma: radiation therapy is the
treatment of choice. Plaque brachytherapy and proton beam
radiation are the most frequently used techniques.
3. Large T3 and T4 uveal melanomas: radiation should be
considered for the purpose of eye preservation whenever possible
unless there are contraindications for plaque therapy like: tumors
with T4e extraocular extension, basal diameters that exceed the
limits of brachytherapy, blind painful eyes and those with no
light perception vision. With these parameters, enucleation is
generally reserved for melanomas greater than 20 mm in
diameter, melanomas more than 16 mm thick, suspected optic
nerve invasion, select cases of recurrence, and at patient request
Q. Mutations GNAQ and GNA11 are found in what percentage of uveal
melanoma patients:
1.
2.
3.
4.
50
20
85
<10
Answer: 85%
In some cases a BAP1 germline mutation may be found.
Notes on superior vena cava syndrome:
1. The characteristic physical findings are venous distention of the
neck (66%) and chest wall (54%), facial edema (46%), plethora
(19%), and cyanosis (19%).
2. In advanced cases upper extremity may be involved and cerebral
circulation may be impaired.
3. Pleural effusions are common in SVCS, reported to be present in
around two-thirds of cases in some series. They are often chylous
and don’t have malignant cells.
4. Life-threatening symptoms may be there like confusion,
obtundation, stridor or syncope without precipitating factors,
hypotension, or renal insufficiency.
ONCOLOGICAL EMERGENCIES
Q. The most common metastatic cancer giving rise to superior vena cava
syndrome is:
1.
2.
3.
4.
Lung
Breast
NHL
Hodgkin’s lymphoma
Answer: breast cancer
Notes on SVCS:
1. Malignant disease is the most common cause of SVCS.
2. Small-cell lung cancer (SCLC) and squamous cell carcinoma are
the most common histologic subtypes.
3. Breast cancer is the most common metastatic disease that causes
SVCS
4. The prognosis of patients with SVCS strongly correlates with the
prognosis of the underlying disease
5. Central vein catheters are increasingly becoming more common
causes of SVCS.
6. Treatment options are: radiation, endovascular
stenting/angioplasty and surgery
Q. Which of the following is not a part of the triad of Kocher-Cushing
reflex seen in raised intracranial pressure:
1.
2.
3.
4.
Changes in breathing pattern
Arterial hypertension
Bradycardia observed
Pinpoint pupils
Answer: pinpoint pupils
Notes on treatment of increased ICP:
1. The normovolemic patient with increased ICP is positioned with
head and upper trunk slightly elevated
2. Antipyretics should be used
3. Serum osmolality is kept in the high normal range, isotonic
saline solutions are recommended
4. Corticosteroids are used in various doses but benefits of high
doses are not entirely clear and they may be associated with
toxicities. Steroids should not be used if CNS lymphoma is
suspected because using them will lead to diagnostic dilemma as
CNS lymphoma are very responsive to steroids
5. Osmotic diuresis through infusion of hyperosmolar agents such
as mannitol (20% to 25% mannitol solutions given at an initial
dose of 0.75 to 1 g/kg body weight. Repeat dosing at 0.25 to 0.5
g/kg body weight is possible every 4 to 6 hours) or glycerol is an
alternative or additional treatment option for the reduction of
ICP.
6. The most rapid method to decrease ICP is intubation with
mechanical hyperventilation. The partial pressure of carbon
dioxide should be decreased to 25 to 30 mm Hg.
7. Obstructive hydrocephalus constitutes a neurosurgical
emergency. Permanent drainage of CSF through a
ventriculoperitoneal shunt or endoscopic placement of a third
ventriculostomy may be necessary. Although filter systems are
available, ventriculoperitoneal shunting is avoided in patients
with leptomeningeal tumor in order to prevent peritoneal
seeding.
Q. The International Spine Oncology Consortium (SpOC) has proposed the
MNOP algorithm for the management of malignant spinal cord
compression and other such problems. Which is not a component of this
MNOP algorithm:
1.
2.
3.
4.
Morphologic treatment.
Neurologic treatment.
Oncologic treatment.
Preferred treatment.
Answer: morphologic treatment
“M” stands for mechanical.
Q. Which of the following is not seen in tumor lysis syndrome:
1.
2.
3.
4.
Increase in uric acid
Increase in potassium
Increase in phosphorus levels
Increase in calcium levels
Answer: increase in calcium levels
In fact, the levels of calcium are decreased. If you are preparing for
oncology entrance, then you must not answer this question wrong.
A 25% change from baseline in two or more of these electrolytes within 3
days before or up to 7 days after the initiation of therapy is needed to satisfy
the Cairo-Bishop laboratory definition laboratory TLS
Q. Which of the following is not a criterion used in the Cairo-Bishop
laboratory definition of TLS:
1.
2.
3.
4.
Increase in uric acid
Calcium levels
Increased creatinine
Increase in phosphorus
Answer: increased creatinine
Notes:
1. Laboratory TLS (Cairo-Bishop) criteria require:
a.
b.
c.
d.
Increase in uric acid
Increase in potassium
Increase in phosphorus levels
Decrease in calcium levels
A 25% change from baseline in two or more of these electrolytes within 3
days before or up to 7 days after the initiation of therapy is needed.
2. Clinical tumor lysis requires, in addition to laboratory TLS:
a.
b.
c.
d.
Increased creatinine level
Seizures
Cardiac dysrhythmia
Death
Q. What is the first electrolyte abnormality seen in tumor lysis syndrome:
1.
2.
3.
4.
Rise in potassium levels
Fall in calcium levels
Rise in sodium levels
Rise in phosphorus levels
Answer: Rise in potassium levels
TLS is associated with a risk of calcium phosphate crystal deposition
causing tubular obstruction.
Notes on the management of TLS;
1. Preventative measures must be started 24 hours before
chemotherapy administration. Aggressive hydration of at least
3,000 mL/m2/day is required.
2. Urine alkalinization is controversial.
3. Hyperkalemia should be treated with cation exchange resins,
dextrose with insulin, calcium gluconate, and sometimes
sodium bicarbonate and loop diuretics.
4. Hemodialysis should be used in renal impairment and
hyperkalemia not responding to the mentioned measures.
5. Hyperphosphatemia is managed by hydration, oral phosphate
binders, and sometimes dialysis. Oral calcium binders should be
used with caution as they may cause precipitation of calcium
phosphate crystals.
6. Allopurinol (dose adjusted for renal insufficiency) should be
started immediately to reduce the risk of hyperuricemia. If rapid
lowering of uric acid is deemed necessary to avoid renal failure,
rasburicase, a recombinant urate oxidase, can be considered.
Q. Single-dose rasburicase 0.15 mg/kg has since been shown to be as
effective as a 5-day regimen at preventing and managing hyperuricemia in
most adults at high risk for TLS:
1. True
2. False
Answer: true
Q. While treating cancer patients with hyponatremia, osmotic
demyelination
can be avoided by correcting sodium at a rate that does not exceed:
1.
2.
3.
4.
8 mEq/L/day in non-high risk patients
12 mEq/L/day in high risk patients
10 mEq/L/day in non-high risk patients
2 mEq/L/day in non-high risk patients
Answer: 8 mEq/L/day in non-high risk patients
In high-risk patients the rate of correction should be 4 to 6 mEq/L/day.
High-risk individuals include those with a serum sodium level of <105
mmol/L, heavy alcohol intake, advanced liver disease, hypokalemia, and
malnutrition.
Q. If brain metastases are diagnosed at 2 months of the diagnosis of the
primary tumor, they will be known as:
1.
2.
3.
4.
Synchronous
Metachronous
Concomitant
Syncurrent
Answer: metachronous
Brain metastases diagnosed at the same time or within 1 month of primary
diagnosis are known as synchronous and after 1 month they will be known
as metachronous.
Q. Which cancer is the most common cause of brain metastasis;
1.
2.
3.
4.
Lung
Breast
Melanoma
Prostate
Answer: lung
Overall, lung, breast and melanoma are the leading primaries for brain
metastasis.
Q. Which of the following is not a part of the recursive partitioning analysis
used for brain metastasis prognostication;
1.
2.
3.
4.
Age
ECOG performance status
Extracranial metastasis
Primary tumor status
Answer: ECOG performance status
This choice is not entirely false but it’s the best choice among other options
as the other three are clearly components of the RPA. Actually the fourth
factor is RPA is the Karnofsky performance status.
Q. Dexamethasone is typically used in patients with brain metastasis to
reduce peritumoral edema. When it’s given at higher doses symptom relief
is greater but at increased toxicity:
1. True
2. False
Answer: false
Actually, there are data that higher dose dexamethasone (16 mg per day)
demonstrate no advantage compared to lower dose dexamethasone (4 or 8
mg per day), but patients receiving higher doses of dexamethasone had
more frequent side effects.
Dexamethasone is the preferred steroid in this setting because it is devoid of
mineralocorticoid activity.
It should be noted that for patients who are neurologically asymptomatic,
routine use of corticosteroids is not necessary.
Another very important thing to remember is that in patients with brain
metastasis, prophylactic use of antiepileptic drugs is not indicated.
Q. The primary and metastatic tumors within the liver generally derive the
large majority of their blood supply from:
1.
2.
3.
4.
Portal vein
Hepatic artery
Hepatic vein
Superior mesenteric artery
Answer: hepatic artery
In contrast with normal liver cells, which derive most of their blood supply
from the portal vein.
Q. radionuclides like strontium-89 and samarium-153 are commonly used
in clinical practice; they emit which kinds of particles primarily:
1.
2.
3.
4.
Alpha
Beta
Gamma
Photons
Answer: beta
Beta particles have a mean range between 0.2 and 3 mm, thereby
minimizing toxicity to surrounding tissue.
Contraindications to the use of radionuclides include poor performance
status, projected survival of <2 months, extensive soft tissue metastases,
platelet count <60×109/L, recent rapid decrease in platelet count even if
>60×109/L, white blood cell count <2.5× 109/L, and disseminated
intravascular coagulation within 1 month of myelosuppressive
chemotherapy and within 2 months of hemibody radiotherapy. Impending
or actual pathologic fracture and cord compression are also
contraindications for use.
Q. Which of the following is not a high risk feature warranting surgical
fixation of femoral metastasis:
1.
2.
3.
4.
Cortical bone destruction >50%,
Lesions >2.5 cm
Pathologic avulsion fracture of the greater trochanter
Persisting pain after radiation
Answer: Pathologic avulsion fracture of the greater trochanter
In fact, it's the pathologic avulsion fracture of the lesser trochanter, which is
an indication of surgical fixation.
Notes:
Mirels system for classification of bone metastasis has four components:
1. Site
2. Size
3. Radiographic appearance
4. Pain
Notes on pleurodesis for malignant pleural effusion;
1. There is no ideal agent
2. Talc, bleomycin, tetracycline, iodine, and doxycycline have been
used.
3. Bleomycin has reported success rates of 58% to 85%.
Q. Catumaxomab is approved by the European Union for:
1.
2.
3.
4.
IV therapy in malignant ascites
Intraperitoneal therapy in malignant ascites
IV therapy in malignant pleural effusion
Intrapleural therapy in malignant pleural effusion
Answer: intraperitoneal therapy in malignant ascites
It is active in patients with tumors expressing EpCAM.
Q. The malignancy most commonly associated with paraneoplastic
syndromes is:
1.
2.
3.
4.
Small-cell lung cancer
Non small cell lung cancer
NHL
Neuroendocrine tumors
Answer: small cell lung cancer
Notes:
1. The syndromes are often defined as classical when associated
with an underlying malignancy.
2. Classical paraneoplastic syndromes include encephalomyelitis,
limbic encephalitis, subacute cerebellar degeneration,
opsoclonus-myoclonus syndrome, sensory neuronopathy, chronic
gastrointestinal pseudo-obstruction, Lambert-Eaton myasthenic
syndrome (LEMS), and dermatomyositis.
3. Encephalomyelitis is associated with anti-Hu antibodies. The
most commonly associated malignancy is SCLC.
4. Limbic encephalitis is characterized by subacute onset of shortterm memory loss, seizures, and cognitive decline. Antineuronal
antibodies include anti-Hu, anti-Ma2, anti amphiphysin, and antiCV2/CRMP5. The most commonly associated malignancy is
SCLC.
5. Subacute cerebellar degeneration typically presents with
symptoms of ataxia, diplopia, dysphagia, and dysarthria. This
disorder is associated with anti-Hu, anti-Yo, anti-Ri, anti-Tr, antiGluR1, and anti-VGCC.
6. Anti-Hu (ANNA-1): Limbic encephalitis Small-cell lung cancer
Paraneoplastic cerebellar degeneration, Subacute sensory
neuronopathy, Chronic gastrointestinal pseudo-obstruction,
Autonomic neuropathy
7. Anti-Yo (PCA1): Paraneoplastic cerebellar degeneration
8. Anti-CV2 (CRMP5) Limbic encephalitis, Paraneoplastic
cerebellar degeneration, Subacute sensory neuronopathy,
Chronic gastrointestinal pseudo-obstruction, Autonomic
neuropathy, Small-cell lung cancer, thymoma
9. Anti-Ri (ANNA-2) Paraneoplastic cerebellar degeneration, Brain
stem encephalitis, Opsoclonus myoclonus
10. Anti-Ma2 (Ta) Limbic encephalitis
11. Anti-amphiphysin: Sensory neuronopathy
12. Anti-Tr (PCA-tr): Paraneoplastic cerebellar degeneration,
Hodgkin lymphoma
Therapeutic options:
1.
2.
3.
4.
Plasma exchange
Intravenous immunoglobulin
Corticosteroids
Cyclophosphamide
5. Rituximab
6. Amifampridine
Diagnostic Criteria for the Syndrome of Inappropriate Antidiuretic
Hormone Secretion:
Essential features
1. Plasma osmolality <275 mOsm/kg
2. Urine osmolality >100 mOsm/kg
3. Clinical euvolemia
4. Urine sodium >40 mmol/L
5. Normal thyroid and adrenal function
6. No recent use of diuretic agents
Supplemental features
1. Serum uric acid <4 mg/dL
2. BUN <10 mg/dL
3. Fractional sodium excretion >1%
4. Fractional excretion of urea >55%
5. Failure to correct the hyponatremia after intravenous infusion of 0.9%
saline
6. Correction of hyponatremia with fluid restriction
7. Abnormal result on the water test load
8. Elevated plasma ADH levels despite hypotonicity and clinical euvolemia
Vaptans and demeclocycline is used in the treatment of this syndrome.
Q. Which of the following is not true about acanthosis nigricans:
1. It occurs most frequently in the intertriginous areas
2. It is more common in obese persons
3. The most commonly associated malignancy in pancreatic
carcinoma
4. It’s associated with endocrinopathies and insulin resistance.
Answer: The most commonly associated malignancy in pancreatic
carcinoma
In fact, it’s gastric carcinoma.
Q. When tripe palms are not associated with acanthosis nigricans then
which is the most common underlying malignancy:
1.
2.
3.
4.
Gastric
Pancreatic
Lung
Colon
Answer: lung
It’s an interesting question, when tripe palms are associated with acanthosis
nigricans, the most commonly associated malignancy is gastric
adenocarcinoma, whereas in the absence of acanthosis nigricans, the most
common associated malignancy is lung cancer.
Q. Pseudo sign of Leser-Trélat is seen in:
1.
2.
3.
4.
Gastric cancer
Squamous cell esophagus cancer
Colon adenocarcinoma
None of the above
Answer: none of the above
The sign of Leser-Trélat is an acute and explosive appearance of multiple
seborrheic keratoses, usually in the trunk. The most commonly associated
malignancies are adenocarcinomas of the GI tract. The inflammation of
preexisting seborrheic keratosis during chemotherapy is called pseudo-sign
of Leser-Trélat.
Notes:
1. Erythema Gyratum Repens: it is the most common type of
erythematous lesion associated with cancer. The lesions have a
“wood grain” appearance. Underlying malignancies are lung,
esophagus, and breast cancers.
2. Necrolytic Migratory Erythema: it can resemble psoriasis. The
lesions are most common in the groin. It is associated with
glucagon-secreting α-islet cell tumors and glucagonoma
syndrome.Bazex Syndrome
3. Bazex syndrome is most commonly associated with squamous
cell carcinomas of the upper aerodigestive tract.
4. Paraneoplastic Pemphigus is most commonly associated with
NHL.
HCT
Q. Which is the cryoprotectant used for storing stem cells:
1.
2.
3.
4.
Liquid nitrogen
Dimethyl sulfoxide
Heparin sulphate
Dry carbon dioxide
Answer: dimethyl sulfoxide
They are preserved in liquid nitrogen after mixing with dimethyl sulfoxide.
Q. The minimum HPC dose to successfully perform an autologous HCT is:
1.
2.
3.
4.
2 million CD34+ cells per kilogram recipient body weight
2 million CD34+ cells per kilogram donor body weight
3 million CD34+ cells per kilogram recipient body weight
3 million CD34+ cells per kilogram donor body weight
Answer: 2 million CD34+ cells per kilogram recipient body weight
The optimal dose, however, is ≥4 to 6 million CD34+ cell per kilogram
recipient body weight.
Q. Which of the following agents are used in mobilization of hematopoietic
progenitor cells for the purpose of autologous stem cell transplant:
1.
2.
3.
4.
GCSF
Cyclophosphamide
Plerixafor
All of the above
Answer: all of the above
Plerixafor, works by disrupting chemokine receptor type 4 and stromalderived factor tether between the HPCs and marrow stromal cells.
Q. In some patients of multiple myeloma, tandem autologous transplant
may be done. Which of the following is not true about these tandem
transplants:
1. Event free survival and overall survival are increased in patients
who receive tandem transplants compared with those receiving
only one
2. In studies there was no benefit for the second autologous HCT
for patients who were in a very good partial remission or better
after the first autograft
3. Even in the era of present day drugs against myeloma, EFS and
OS are better with tandem transplants
4. High risk myeloma patients are most likely to benefit from
tandem transplants
Answer: Even in the era of present day drugs against myeloma, EFS and
OS are better with tandem transplants
It’s the best choice among the options provided. The results are unclear and
majority indicate that tandem transplants are not much beneficial in the
current scenario.
Notes on conditioning regimens for allogeneic HCT:
1. It serves two purposes: to suppress the patient’s immune system
sufficiently to prevent rejection of donor hematopoietic stem
cells and to eradicate malignant cells.
2. Myeloablative conditioning regimens are very toxic, they don’t
rely much on the graft versus leukemia effect. Examples are
busulfan+cyclophosphamide, cyclophosphamide + total body
irradiation.
3. Reduced intensity conditioning provides sufficient
immunosuppression to achieve donor cell engraftment and rely
to a greater extent on graft versus leukemia effects for tumor
eradication. These regimens are associated with lower transplant
related mortality compared with myeloablative conditioning
regimens.
4. Melphalan is the drug of choice for multiple myeloma
autologous stem cell transplant.
Q. The major histocompatibility complex (MHC) are located on
chromosome:
1.
2.
3.
4.
6p
6q
7q
7p
Answer: 6p
The compatibility of donor and the recipient is assessed at HLA-A, HLA-B,
HLA-C, and HLA-DRB1 genes.
Notes on GVHD:
1. There are two types of GVHD: acute and chronic
2. Acute GVHD is caused by the initiation of innate and adaptive
immune responses by tissue injury caused by cytotoxic
conditioning. T cells play a central role.
3. The pathophysiology of chronic GVHD is more like those of an
autoimmune diseases.
COMPLICATIONS OF TREATMENT
Q. Colon cancer has been associated with bacteremia caused by which of
the following:
1.
2.
3.
4.
Streptococcus pneumoniae
Coxiella burnetii
Streptococcus gallolyticus
Streptococcus bovis
Answer: 3 or 4
It should be noted that Streptococcus gallolyticus was formerly known as
Streptococcus bovis.
Q. Functional asplenia is present after splenectomy or splenic irradiation
and with chronic graft-versus-host disease (GVHD). The most common
pathogen in these patients is:
1.
2.
3.
4.
Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis
Acinetobacter baumannii
Answer: Streptococcus pneumoniae
Patients with functional asplenia are prone to overwhelming sepsis caused
by encapsulated bacteria.
Recommendations by CDC for asplenic patients:
1. Immunization with pneumococcal polysaccharide and
pneumococcal conjugate vaccines and the meningococcal
conjugate and serogroup B vaccines.
2. Immunization of adults with the H. influenzae type B vaccine
3. Immunization is ideally performed at least 2 weeks in advance
of splenectomy.
4. If this is not feasible, immunization is still advisable after the
procedure.
5. Penicillin prophylaxis is advised in asplenic patients to prevent
pneumococcal disease.
Notes on prophylaxis for bacterial infections in patients receiving
chemotherapy or other myelotoxic/immunosuppressive cancer directed
therapy:
1. Prophylaxis for neutropenia is indicated in patients who are
expected to be neutropenic for >7 d. Levofloxacin 500 mg orally
daily is used for this purpose, starting on the first day of ANC
<1,000 and continue until resolution of neutropenia. TMP/SMX
may be used for this purpose.
2. Prophylaxis for Streptococcus pneumoniae is indicated in
patients who underwent splenectomy or splenic irradiation.
Penicillin V-K, 500 mg orally bid is used for this and ideally
patient should be immunized with pneumococcal vaccines.
Prophylaxis for Streptococcus pneumoniae is indicated is also
indicated in chronic GVHD.
Notes on antifungal prophylaxis:
1. Indicated in induction therapy for AML and MDS: posaconazole
200 mg orally tid is drug of choice. In patients unable to take
oral medications or who are intolerant of posaconazole,
alternatives include itraconazole, voriconazole, lipid formulation
of amphotericin B, or an echinocandin.If fluconazole
prophylaxis is used, serial monitoring with serum galactomannan
and/or β-D-glucan should be considered. Begin with initiation of
chemotherapy and continue until resolution of neutropenia.
2. Indicated in acute lymphoblastic leukemia receiving vinca
alkaloid–containing regimen: fluconazole or an echinocandin is
3.
4.
5.
6.
used. Prophylaxis should be continued for the duration of
neutropenia.
Indicated in autologous HSCT recipient during neutropenia:
fluconazole or echinocandin is used. Continue prophylaxis for
duration of neutropenia. Consider no antifungal prophylaxis if
regimen does not have significant mucosal toxicity.
Indicated in allogeneic HSCT recipient during neutropenia:
fluconazole, itraconazole, voriconazole, posaconazole and
micafungin may be used. Prophylaxis should be continued for
the duration of neutropenia.
Indicated in allogeneic HSCT with significant GVHD receiving
intensive immunosuppressive therapy: posaconazole 200 mg
orally tid is drug of choice. Continue prophylaxis for 16 wk and
for at least the duration of intensive immunosuppressive therapy,
whichever occurs later.
Prophylaxis against Pneumocystis jirovecii is:
a. Indicated in allogeneic HSCT recipients, alemtuzumab
recipients or fludarabine recipients. TMP/SMX 1 DS (TMP
160 mg + SMX 800 mg) orally daily or 3 d/wk OR
dapsone 100 mg orally daily OR inhaled pentamidine 300
mg every 4 wk OR atovaquone 1,500 mg/d are used. In
allogeneic HSCT, continue prophylaxis for 2 months after
stopping immunosuppression. In patients treated with
alemtuzumab, continue prophylaxis for 2 mo after the last
dose or until the CD4 count is ≥200/μL, whichever occurs
later.
b. Indicated in patients with gliomas receiving temozolomide
and radiation or corticosteroids (≥20 mg of prednisone
equivalent) for ≥1 mo in the presence of other
immunosuppression or myelotoxic chemotherapy.
Prophylaxis for HSV:
1. Indicated in HSCT recipients (HSV-seropositive recipients),
induction chemotherapy for acute leukemia (HSV seropositive);
considered in patients with recurrent HSV reactivation following
chemotherapy or patients receiving fludarabine and
corticosteroids. Acyclovir 400 mg orally bid or tid OR 800 mg
orally bid OR 250 mg/m2/12 h or valacyclovir 500 mg orally
once or twice (higher doses have been used up to 1,000 mg tid)
or famciclovir 250 mg orally tid are used.
2. In patients with acute leukemia and HSCT recipients, continue
prophylaxis for HSV until resolution of neutropenia and
mucositis. In patients treated with alemtuzumab, continue
prophylaxis for2 mo after the last dose or until the CD4 count is
≥200/μL, whichever occurs later.
Prophylaxis for VZV:
1. Indicated in allogeneic HSCT recipients with a history of
chickenpox or shingles. Acyclovir 800 mg orally bid OR
valacyclovir 500 mg orally daily.
Preemptive therapy for CMV:
1. Patients requiring CMV surveillance: 1. Allogeneic HSCT
recipients who are CMV positive or whose donor is CMV
positive (standard of care) 2. Autologous SCT recipients
receiving a CD34- enriched autograft (should be considered) 3.
Patients treated with alemtuzumab (should be considered)
2. Ganciclovir OR foscarnet OR oral valganciclovir may be used.
3. Time for CMV surveillance: 1. Allogeneic HSCT recipients:
from day 30 to at least 6 mo after allogeneic HSCT, during
periods of GVHD, and until the CD4 count is >100/μL 2.
Recipients of CD34-enriched autologous grafts: from day 30 to
day 100 and until the CD4 count is >100/μL 3. Alemtuzumab
recipients: from the time of initiation until at least 2 mo after
completion of therapy and until the CD4 count is >100/μL,
whichever occurs later.
4. The level of CMV reactivation that triggers preemptive therapy
varies with the method. The CDC recommends any positive
CMV antigenemia (pp65) or two consecutive qualitative PCR
results within the first 100 d, and 5 cells per slide after the first
100 d.
Prophylaxis against CMV:
1. letermovir 480 mg/d (240 mg if concomitant cyclosporine) OR
ganciclovir at the preemptive dose.
2. Treatment is given for the first 100 d and then weekly or
biweekly monitoring and preemptive management are initiated.
3. Prophylaxis with ganciclovir is seldom used.
Prophylaxis against hepatitis B flare:
1. Indicated in patients who are HBsAg positive or have detectable
HBV DNA in the blood at high risk who are about to receive
chemotherapy and are at high risk for hepatitis B reactivation
2. Entecavir 0.5 mg/d Start 7 d before chemotherapy and continue
for 8 wk after completing chemotherapy
3. It should be noted that not all cancer treatments are associated
with the same risk; lymphoma therapy seems to confer the
highest risk.
4. Patients who are HBsAg positive or have detectable HBV DNA
in the blood who are about to receive hematopoietic stem cell
transplant should receive entecavir 0.5 mg/d starting 2–3 wk
before transplant and restart 2 wk after transplant. If the
transplant may be delayed, start entecavir and vaccinate the
donor so anti-HBV immunity will be transplanted. It is not
known how long to continue entecavir in this setting.
Some important points:
1. Fluconazole is effective as prophylaxis against candida, but not
mold, infections.
2. MAbs such as rituximab and ofatumumab may lead to
progressive multifocal leukoencephalopathy (PML), also called
JC virus encephalopathy but there is no effective prophylaxis or
treatment.
Q. Severe neutropenia is defined as an absolute neutrophil count of:
1.
2.
3.
4.
<500 cells/μL
<200 cells/μL
<1000 cells/μL
When the count is below normal and associated with fever
Answer: <500 cells/μL
Severe neutropenia is also defined as an ANC that is expected to decrease
to <500 cells/μL during the next 48 hours.
Q. Which of the following is not a factor in the Multinational Association
for Supportive Care in Cancer (MASCC) index:
1.
2.
3.
4.
Burden of illness
Absence of hypotension
No previous fungal infection
Previous neutropenic fever related admissions
Answer: Previous neutropenic fever related admissions
The MASCC index was designed as a tool to identify adult patients at low
risk of complications.
The factors in the MASCC score are:
1. Burden of illness (no or mild symptoms = 5 points; severe
symptoms = 3 points)
2. Absence of hypotension (5 points)
3. Absence of chronic obstructive pulmonary disease (4 points)
4. Solid tumor or no previous fungal infection (4 points)
5. Absence of dehydration (3 points)
6. Outpatient status (3 points)
7. Age <60 years (2 points)
The points are added up, and patients with a MASCC score of ≥21 points
(of 26 possible) are low risk and can be considered for oral therapy.
Q. What percentage of patients with neutropenic fever have
microbiologically documented infection:
1.
2.
3.
4.
20-30
10-20
40-50
<10
Answer: 10-20%
The breakdown of neutropenic fever is as follows:
1. Fever of unknown origin, 50% to 60%
2. Microbiologically documented infection (frequently bacteremia),
10% to 20%;
3. Clinically documented infection (but without any pathogen
isolated), 20% to 30%
Q. Which is the therapy of choice for invasive aspergillosis:
1.
2.
3.
4.
Itraconazole
Voriconazole
Caspofungin
Amphotericin B
Answer: voriconazole
Q. The drug of choice for mucormycosis is:
1.
2.
3.
4.
Posaconazole
Voriconazole
Amphotericin B
Caspofungin
Answer: amphotericin B
Isavuconazole has also been approved by the FDA for the treatment of
mucormycosis.
Q. All of the following central line associated bloodstream infection usually
require removal of the catheter except:
1.
2.
3.
4.
Coagulase-negative staphylococci
S. aureus
Candida
Mycobacteria
Answer: Coagulase-negative staphylococci
In the other three infections, catheters are usually removed.
Q. The most sensitive method for diagnosis of Clostridium difficile is;
1. Detection of bacterial toxin in diarrhea stool by enzyme
immunoassay
2. Detection of bacterial toxin in diarrhea stool by PCR
3. Detection of bacterial toxin in diarrhea stool by cytotoxin assay
4. Detection of bacterial toxin in diarrhea stool by next generation
sequencing
Answer: Detection of bacterial toxin in diarrhea stool by PCR
Next generation sequencing is not used in diagnosis of C. difficile.
Notes on treatment of C. difficile:
1. It is an antibiotic- associated infection so discontinuation of
antibiotics should be considered.
2. It is classified as: nonsevere, severe, and fulminant. Severe
infection is based on leukocytosis ≥15,000 cells/mL and
creatinine >1.5 mg/dL.
3. Initial therapy for severe or non severe disease is a 10-day course
of oral vancomycin or fidaxomicin, and oral metronidazole only
for nonsevere infection if first-line drugs are not available.
4. Fulminant C. difficile infection, defined as hypotension, shock,
ileus, or toxic megacolon, is treated with vancomycin
administered both orally and per rectum as well as intravenous
metronidazole.
5. Recurrences are treated with fidaxomicin or vancomycin taper
(alone or followed by a course of rifaximin).
6. Subsequent recurrence may benefit from fecal microbiota (stool)
transplantation, which has a cure rate of at least 80% to 90%.
7. Probiotics may be useful in certain cases, who are not
immunocompromised.
Q. Erythropoietin is produced by:
1.
2.
3.
4.
Kidney
Liver
Stromal cells of bone marrow
All of the above
Answer: kidney
Erythropoietin is produced in the kidney, thrombopoietin is produced both
in the liver and kidneys; while the other hematopoietic growth factors are
produced by monocytes and by stromal cells of the bone marrow.
Q. Neutropenia is defined as a granulocyte count of:
1. ≤1,500/μL
2. ≤1,000/μL
3. ≤2,000/μL
4. ≤500/μL
Answer: ≤1,500/μL
According to the Common Terminology Criteria for Adverse Events
version 4.0, neutropenia is defined by a granulocyte count ≤1,500/μL, and
neutropenic infection is assumed for any fever episode occurring when the
neutrophil count is <1,000/μL.
Q. Ancestim is a:
1.
2.
3.
4.
Colony stimulating factor
Tumor necrosis growth factor
Early hepatocyte growth factor
Keratinocyte growth factor
Answer: early hepatocyte growth factor
Notes:
Colony-stimulating Factors:
1. Granulocyte colony-stimulating factor (G-CSF):
a. Long acting
1. Peg-filgrastim
2. Lipegfilgrastim
b. Short acting:
1.
2.
3.
4.
Filgrastim
Lenograstim
Tbo-filgrastim
Filgrastim-sndz
2. Granulocyte-macrophage colony-stimulating factors:
a. Sargramostim
b. Molgramostim
c. Regramostim
Q. Which of the following is thrombopoiesis stimulating agent is approved
for use in chemotherapy induced thrombocytopenia:
1.
2.
3.
4.
Oprelvekin
Romiplostim
Eltrombopag
None of the above
Answer: none of the above
Presently, there is no thrombopoiesis stimulating agent approved for
chemotherapy induced thrombocytopenia. Oprelvekin was initially studied
for this indication but later was withdrawn from the market due to
prohibitive toxicities and lack of effectiveness.
Q. The median survival duration of mature neutrophils in the circulation is:
1.
2.
3.
4.
12 hours
24 hours
3 days
7 days
Answer: 12 hours
The median survival duration of mature neutrophils is approximately 12
hours in the circulation and 3 days in the tissues. The bone marrow contains
a reserve of mature granulocytes to last approximately 7 days. The
development of mature granulocytes from committed myeloid progenitors
takes approximately 10 to 14 days.
Notes on adverse effects of growth factors:
1. Fever and skin reactions
2. Bone pain
3. The most worrisome long-term side effect of colony-stimulating
factors is acute myelogenous leukemia (this risk is higher in
patients aged 65 years and older receiving breast cancer adjuvant
chemotherapy with anthracyclines)
Q. According to the current guidelines, myeloid growth factors be used
prophylactically when the risk of neutropenic infections is:
1.
2.
3.
4.
≥20%
≥10%
≥30%
≥5%
Answer: ≥20%
According to the current guidelines they should be used when the risk of
neutropenic infections is ≥20% and not be used when the risk is ≤10%.
Q. Which of the following statements is true;
1. Platelet transfusions are recommended in all individuals with a
platelet count ≤10,000/μL
2. Prophylactic platelet transfusions are recommended in
individuals with a platelet count of <50,000/μL for whom a
surgical procedure is planned
3. Platelet transfusions are recommended for actively bleeding
patients and are indicated for platelet count <50,000/μL
4. All of the above
Answer: all of the above
It must be noted here that these recommendations are not backed by
substantial evidence, so management of an individual patient is unique and
must be based on all the factors combined.
Q. Which of the following is not true about chemotherapy induced nausea
and vomiting (CINV):
1. Acute CINV is defined as nausea and vomiting that develop
within the first 24 hours after chemotherapy administration
2. Delayed CINV is defined as nausea and vomiting occurring more
than 24 hours after chemotherapy administration
3. Delayed CINV is generally more severe than acute CINV but
lasts longer than the latter
4. Anticipatory nausea and vomiting occur as the result of a
conditioned response to prior episodes of CINV
Answer: Delayed CINV is generally more severe than acute CINV but lasts
longer than the latter
While it’s true that delayed CINV generally lasts longer than acute CINV
the severity of delayed CINV is lesser than acute CINV.
Delayed CINV is best characterized in relation to cisplatin. It peaks
between 24 and 72 hours after cisplatin and gradually dissipates during the
next several days.
Unlike CINV, radiation-induced nausea and vomiting (RINV) has not been
broken down into distinct clinical syndromes. Risk of nausea and vomiting
is generally related to the body area exposed to treatment, with fields
encompassing small bowel and stomach associated with the greatest risk.
Notes on emetogenic potential of chemotherapy agents:
1. High (>90%): Anthracycline/cyclophosphamide combination,
Carmustine >250mg/m2, Cisplatin, Cyclophosphamide (≥1,500
mg/m2), Dacarbazine, doxorubicin 60 mg/m2 or more,
epirubicin 90 mg/m2 or more, ifosfamide 2g/m2 or more per
dose, Mechlorethamine, Streptozotocin, carboplatin AUC 4 or
more
2. Generally questions are asked on the chemotherapy molecules
having a high risk of nausea and vomiting. Moderately
emetogenic agents have a >30 to 90% frequency of CINV, low
emetogenic drugs have a 10 to 30% frequency of CINV and
minimally emetogenic agents have a less than 10% frequency of
CINV.
Notes on doses and schedules of commonly used antiemetic agents:
There is a very wonderful table provided in the NCCN guidelines for this
purpose, the reader is advised to stay updated with it.
This table as well as the next ones in NCCN guidelines keep changing, so
one must periodically review NCCN guidelines thoroughly.
Q. All of the following are associated with moderate frequency of
radiotherapy induced emesis except:
1.
2.
3.
4.
Total nodal irradiation
Hemi body irradiation
Upper body irradiation
Upper abdomen irradiation
Answer: total nodal irradiation
Total nodal irradiation is associated with high frequency of RINV
(radiotherapy induced nausea and vomiting).
Notes on RINV:
1. High: Total-body irradiation, total nodal irradiation
2. Moderate: Upper abdomen, hemi (half) body irradiation, upper
body irradiation
3. Low: Cranium, craniospinal, head and neck, lower thorax region,
pelvis
4. Minimal: Extremities, breast
Q. Which of the following is not true about chemotherapy induced diarrhea:
1. Diarrhea is defined as the frequent passage of loose stools with
urgency. Objectively defined, it is the passage of more than five
unformed stools in 24 hours
2. It is more commonly observed with bolus rather than infusional
administration of 5-FU/LV
3. Female have overall higher incidence of chemotherapy induced
diarrhea
4. Dihydropyrimidine dehydrogenase deficiency is associated with
severe toxicity of normal doses of 5-FU, the diagnosis of DPD
deficiency is usually performed by sequencing of the DPYD gene
from a sample of peripheral blood
Answer: Diarrhea is defined as the frequent passage of loose stools with
urgency. Objectively defined, it is the passage of more than five unformed
stools in 24 hours
Every word in the above sentence is true except “five”. Objectively diarrhea
is defined as passage of more than three unformed stools in 24 hours.
Polymorphisms of another gene TYMS, are also associated with severe
toxicity from 5-FU–based chemotherapy.
Q. Diarrhea occurring at 48 hours after administration of irinotecan should
be managed with:
1.
2.
3.
4.
IV atropine
SC atropine
Loperamide
Leucovorin rescue
Answer: loperamide
Notes on irinotecan induced diarrhea:
1. Irinotecan is associated with two types of diarrhea: immediate
onset (acute) and delayed onset.
2. Immediate-onset diarrhea is caused by acute cholinergic
properties, and it is often accompanied by other symptoms of
cholinergic excess, including abdominal cramping, rhinitis,
lacrimation, and salivation. The mean duration of symptoms is
30 minutes, and they usually respond rapidly to atropine;
premedication with atropine may prevent acute diarrhea.
3. Delayed-onset diarrhea usually occurs at least 24 hours after
drug administration. It is more commonly seen with bolus
regimens and it is more common with 3-weekly dose schedules
than with lower weekly dosing. It results from the deconjugation
of irinotecan’s metabolite, SN-38, by intestinal bacteria, thus
enabling direct effect of the active agent on colonic epithelium.
4. Genetic factors may influence the glucuronidation of SN-38, the
active metabolite of irinotecan, and thus increase the risk of
diarrhea. The homozygous presence of the UGT1A1*28
polymorphism, leading to less efficient glucuronidation of SN38, has been identified as a potential risk factor for the
occurrence of delayed-type diarrhea and grade 3 to 4
neutropenia.
5. Delayed onset diarrhea is best treated with antimotility agents.
6. It should be noted that delayed onset diarrhea is considered more
life threatening than acute.
Q. Which of the following is not a diagnostic criterion of neutropenic
colitis:
1.
2.
3.
4.
Presence of neutropenia (ANC <500 cells/L)
Bowel wall thickening of >8 mm on radiographic imaging
The exclusion of other diagnoses
Absence of other abdominal syndromes
Answer: Bowel wall thickening of >8 mm on radiographic imaging
In fact the criteria regarding bowel wall thickening requires a thickening of
>4 mm.
Q. Which of the following comes under grade 3 diarrhea classification
according to CTCAE:
1.
2.
3.
4.
Increase of <2 loose stools per day over baseline
Increase of 2-3 loose stools per day over baseline
Increase of 4-6 loose stools per day over baseline
Increase of 7 or more loose stools per day over baseline
Answer: increase of 7 or more loose stools per day over baseline
The NCI-CTCAE (Common Terminology Criteria for Adverse Events ) for
diarrhea are:
Grade 1: increase of <4 stools/d over baseline
Grade 2: Increase of 4–6 stools/d over baseline
Grade 3: Increase of ≥7 stools/d over baseline
Grade 4: Life-threatening consequences; urgent intervention indicated
Grade 5: Death
Q. Uridine triacetate is an oral prodrug of uridine, it is used as:
1. A biomodulator of 5-FU
2. A biomodulator of capecitabine
3. An antidote of fluoropyrimidines
4. An inhibitor of thymidylate synthetase
Answer: an antidote of fluoropyrimidines
Notes of management of diarrhea:
1. Uncomplicated diarrhea: Patients with grade 1 or 2 diarrhea with
no other complicating signs or symptoms may be classified as
“uncomplicated” and managed conservatively with oral
hydration and loperamide. Patients refractory to these
interventions should be started on a second-line antidiarrheal
agent such as SC octreotide (100- to 150-μg starting dose, with
dose escalation as needed) or other second-line agents (e.g., oral
budesonide or tincture of opium).
2. Complicated diarrhea: patients with mild to moderate diarrhea
complicated by moderate to severe cramping, nausea and
vomiting, diminished performance status, fever, sepsis,
neutropenia, bleeding, or dehydration and patients with severe
diarrhea are classified as “complicated.” Aggressive
management of complicated cases usually necessitates admission
and involves IV fluids; octreotide and administration of
antibiotics (e.g., fluoroquinolone).
Q. Which of the following statements is not true about ipilimumab induced
diarrhea:
1. Grade 1 diarrhea can be managed symptomatically with
loperamide
2. Grade 2 diarrhea colonoscopy is recommended and treatment
with steroids should be initiated if colitis is observed
3. For the management of grade 3 or 4 diarrhea, first ipilimumab
should be permanently discontinued and corticosteroids should
be initiated
4. For patients in whom IV steroids followed by high-dose oral
steroid therapy does not lead to initial resolution of symptoms
within 7 days, treatment with infliximab is advisable similar to
the therapeutic approach for IBD
Answer: For patients in whom IV steroids followed by high-dose oral
steroid therapy does not lead to initial resolution of symptoms within 7
days, treatment with infliximab is advisable similar to the therapeutic
approach for IBD
This option is not entirely wrong but it is the best choice. The fact is that
infliximab should be initiated if high-dose oral steroid therapy does not lead
to initial resolution of symptoms within 2-3 days.
In refractory cases tacrolimus, mycophenolate mofetil may be needed.
Mucositis
Q. Radiation induced oral mucositis has been associated with:
1.
2.
3.
4.
Increased COX2 activity
Increased COX1 activity
Decreased COX2 activity
Decreased COX1 activity
Answer: Increased COX2 activity
Q. Which of the following therapies may be useful for prevention of
radiation induced oral mucositis:
1.
2.
3.
4.
Amifostine
Cryotherapy
NaHCO3 oral rise
All of the above
Answer: all of the above
Q. Which of the following is not true about radiation induced lung injury
(RILI):
1. The first phase of RILI is the production of reactive oxygen
species (ROS) and reactive nitrogen species
2. The second phase of RILI includes inflammation in response to
injury
3. The last stage of RILI is characterized by a process of repair
4. None of the above
Answer: none of the above
Options 1, 2 and 3 are correct statements.
Notes on cardiotoxicity induced by anthracyclines:
1. Anthracyclines are associated with two types of cardiotoxicity:
reversible acute cardiotoxicity and delayed irreversible dilated
cardiomyopathy.
2. Acute toxicity presents as a myocarditis, pericarditis and
nonischemic cardiomyopathy.
3. Delayed cardiotoxicity presents as fatigue, dyspnea on exertion,
orthopnea with sinus tachycardia, S3 gallop, pedal edema,
pleural effusions, and elevated jugular venous distention.
4. A 5% risk of CM is seen at 400 to 450 mg/m2 for doxorubicin,
900 mg/m2 for daunorubicin, 800 to 935 mg/m2 for epirubicin,
and 223 mg/m2 for idarubicin.
5. There are several risk factors for the cardiotoxicity associated
with anthracyclines like old age, previous cardiac diseases and
concurrent use of trastuzumab, among others.
Q. Usually, the cardiotoxicity induced by trastuzumab is monitored by:
1. Monitoring of LVEF every 4 months during therapy and every 6
months thereafter for up to 2 years
2. There is no need for regular monitoring unless trastuzumab is
concurrently used with anthracyclines
3. Monitoring is generally not indicated but when trastuzumab is
used with pertuzumab then monitoring has to be done every 3
monthly during active treatment
4. In all patients treated with trastuzumab LVEF monitoring should
be done lifelong because of the delayed apoptotic effects of
trastuzumab
Answer: Monitoring of LVEF every 4 months during therapy and every 6
months thereafter for up to 2 years
It is interesting to note that the addition of pertuzumab, a monoclonal
antibody against a different epitope of HER2, trastuzumab and standard
chemotherapy regimens appears to not increase the risk of cardiotoxicity.
Q. In which phase of growth cycles of hair, it is most susceptible to the
toxic effects of chemotherapy:
1.
2.
3.
4.
Anagen
Telogen
Catagen
Exogen
Answer: anagen
Human hair remains in the anagen phase for more than 90% of the cycle.
Notes on fertility preservation in cancer patients, to prevent damage
induced by cancer directed therapies:
1. Females:
a. GnRH analogs (agonists, antagonists)
b. Ovarian cryopreservation and future transplantation
1.
2.
3.
4.
5.
2. Males:
Cortical strip
Whole ovary
Assisted reproductive technology
Embryo banking (partner sperm or donor sperm)
Oocyte banking (cryopreservation or vitrification)
a. Sperm collection via masturbation or surgical retrieval
b. Testicular cryopreservation and future transplantation
Q. Which is the least likely adverse effect associated with erythropoiesis
stimulating agents;
1.
2.
3.
4.
Increased risk of thrombotic events
Hypertension
Pure red cell aplasia
Bleeding diathesis
Answer: bleeding diathesis
There are also concerns that ESAs may diminish locoregional disease
control and survival outcomes in particular tumor types.
Notes on pain in cancer patients:
1. There are three major categories of pain: somatic, visceral, and
neuropathic
2. Patients of cancer pain often suffer from chronic pain that is
defined as pain persisting for longer than 1 month past the
resolution of the underlying insult or that persists for more than 3
months with a less well-defined temporal onset
3. Baseline pain is the average pain intensity experienced for 12 or
more hours during a 24-hour period.
4. Breakthrough pain is a transient increase in pain to greater than
moderate intensity that occurs on a baseline pain of moderate
intensity or less.
Notes on methods commonly used for quantifying pain felt by cancer
patients:
1. The Brief Pain Inventory (BPI)
2. The McGill Pain Questionnaire (MPQ)
3. The Memorial Symptom Assessment Scale (MSAS)
4. The Functional Assessment of Cancer Therapy–General (FACTG)
5. Quality of Life Questionnaire-C30 (QLQ-C30) scale
6. The Edmonton Symptom Assessment Scale (ESAS)
Notes on WHO ladder for pain management:
1. Step 1 of the WHO ladder is nonopioid analgesics that may or
may not be combined with an adjuvant drug.
2. Step 2 of the WHO ladder is for those patients who don’t
experience adequate pain relief from a nonopioid analgesic.
These patients are candidates for a combination of a nonopioid,
such as aspirin, acetaminophen, cyclooxygenase-2 (COX-2)
inhibitors, or other nonsteroidal anti-inflammatory drug
(NSAID), and low doses of opioid analgesics, such as codeine,
tramadol, oxycodone, or morphine, usually dosed at less than
60 mg of oral morphine equivalents (OME) daily .
3. Step 3 is for patients who report either severe pain (often gauged
as greater than 7 in a 0 to 10 scale) or moderate pain that is
inadequately managed after appropriate administration of drugs
at the second step of the WHO ladder. For these patients,
nonopioids are often used in combination with more potent doses
of opioids, and adjuvants. Opioid doses on step 3 are
sometimes greater than 60 mg OME daily.
Notes on tools for nutrition screening:
1. Prognostic Nutritional Index= % risk of perioperative
complication = 158 − 16.6 (albumin; grams per deciliter [g/dL])
− 0.78 (triceps skinfold thickness; mm) − 0.2 (serum transferrin;
g/dL) − 5.8 (delayed-type hypersensitivity reaction; mm)
2. Nutritional Risk Index: 1.519 × the serum albumin (grams per
liter) + 0.417 × (current weight/usual weight) × 100
a. Patients are characterized as malnourished if they have a
score of 100 or less on the Nutritional Risk Index.
There is also a patient based tool:
The Patient-Generated Subjective Global Assessment (PG-SGA):
a. Patient History: weight change, change in dietary intake, gastrointestinal
symptoms, change in functional capacity, diagnosis
b. Physical Exam: loss of subcutaneous fat, muscle wasting, ankle edema,
sacral edema, ascites
c. The previous are combined to create a numerical score to categorize
patients as mildly, moderately, or severely malnourished.
Q. Usually physiologically non stressed cancer patients require:
1. Approximately 1.0 gram per kilogram of body weight per day of
protein and 25 kcal per kilogram of body weight per day of
nonprotein calories and essential fatty acids 1.0 to 2.0 grams per
kilogram per day
2. Approximately 0.8 gram per kilogram of body weight per day of
protein and 20 kcal per kilogram of body weight per day of
nonprotein calories and essential fatty acids 1.0 to 2.0 grams per
kilogram per day
3. Approximately 1.5 gram per kilogram of body weight per day of
protein and 25 kcal per kilogram of body weight per day of
nonprotein calories and essential fatty acids 1.0 to 2.0 grams per
kilogram per day
4. Approximately 1.5-2 gram per kilogram of body weight per day
of protein and 35 kcal per kilogram of body weight per day of
nonprotein calories and essential fatty acids 1.0 to 2.0 grams per
kilogram per day
Answer: Approximately 1.0 gram per kilogram of body weight per day of
protein and 25 kcal per kilogram of body weight per day of nonprotein
calories and essential fatty acids 1.0 to 2.0 grams per kilogram per day
Notes on nutrition in cancer patients:
1. The selection of a formula for EN is based on an assessment of
both nutrient and fluid requirements. The calorie concentration in
balanced formulas can range from 1.0 to 2.0 kcal/mL.
2. Central venous access is necessary to administer PN because of
its hyperosmolarity. Commonly, PN is composed of hypertonic
glucose (25%), amino acids (4.25%), lipids, electrolytes, and
essential vitamins, minerals, and trace elements. The caloric
density of these formulas is usually 1 kcal/mL, and therefore, 2
to 2.5 L of volume a day provides 2,000 to 2,500 kcal and all
essential nutrients. To prevent essential fatty acid deficiency,
patients should receive at least 500 mL of a 20% fat emulsion
containing both linoleic and linolenic fatty acids weekly.