Small Cell Lung Cancer
Sam Wang
Outline
– Small Cell Lung Cancer
SCLC - Background
• SCLC Incidence:
– ACS 2007: All Lung CA incidence: 213,000
– 13% of all lung CA (~27,000)
Natural History of SCLC
• SCLC is distinguished from NSCLC by its rapid
doubling time, high growth fraction, and the early
development of widespread metastases
• Although considered highly responsive to
chemotherapy and radiotherapy, SCLC usually
relapses within two years despite treatment
• Overall, only three to eight percent of all patients
with SCLC (10 to 13 percent of those with limited
disease) survive beyond five years
SCLC Histology
• SCLC is a “small blue round cell tumor” from
neuroendocrine cells
• Classifications:
– oat cell (lymphocyte-like), fusiform, polygonal
– OR classical, large cell neuroendocrine, combined
SCLC/NSCLC
• “crush” artifact
• Immunohisto tests:
– TTF1+ (adeno & SCLC)
Lymph Node Stations
1
2
3a
3b
4
5
6
7
8
9
10
11-14
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highest mediastinal
upper paratracheal
pretracheal
retrotracheal
lower paratracheal
AP window
Para-Aortic (above 5)
subcarinal
esophageal
pulmonary ligament
hilar
interlobar, lobar, segmental, subsegmental
Lymph Node Stations
Clinical Presentation of SCLC
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Smokers (almost exclusively)
Cough 75%
Hemoptysis in 50%
Dyspnea and chest pain 40%
Constitutional symptoms 10 to 15%
Clubbing 16 to 29%
pneumonia, weight loss
SCLC Paraneoplastic Syndromes
• SIADH
• ectopic ACTH production- Cushing’s synd
• Eaton-Lambert Myasthenic syndrome
– proximal muscle weakness that improves on
repetition (“facilitation”)
• Hypercalcemia
• Peripheral Neuropathy
Workup
• Labs: CBC, chem, LFTs, LDH
• CT chest/abd/pelvis
• Brain imaging (CT or MRI) (up to 30%
have brain mets at presentation)
SCLC Staging
• Limited Stage (1/3)
– confined to 1 hemithorax
– disease fits within a tolerable radiation port
• Extensive Stage (2/3)
– doesn’t fit
• Recommend also use TNM staging, as for
NSCLC
Where does SCLC metastasize to? “BALLS”
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Brain (30%)
Adrenal (20-40%)
Liver (25%)
Lung
Skeleton (35%)
Prognostic Factors
• The host factors of poor performance status and weight
loss
• Stage (limited versus extensive).
• In extensive disease, the number of organ sites involved
is inversely related to prognosis
• Metastatic involvement of the central nervous system,
the marrow, or the liver is unfavorable compared to other
sites, although these variables are confounded by the
number of sites of involvement.
• In most trials, women fare better than men, although the
reasons for this are not known.
• The presence of paraneoplastic syndromes is generally
unfavorable
Survival
• Limited Stage:
– Median OS: 14-24 months
– 5-yr OS: 20%
• Extensive Stage:
– MedianOS: 6-11 months
– 5-yr OS: 2%
Treatment – Limited Stage SCLC
• Concurrent chemoradiation
– Chemo: cisplatin/etoposide q3wks
– Radiation: 150 cGy BID to 4500 cGy (Turrisi)
OR 180 QD to 50-70Gy. (54Gy?)
• Sequential chemo, then RT.
• If CR, then PCI
– 2500/10, 3000/15, or 2400/8
– Auperin (NEJM 99)
Treatment – Extensive Stage
• Chemo
• RT for palliation only
Treatment Fields for SCLC
• Cover primary disease & known positive
LNs w/ 1.5-2cm margin.
• Do you cover elective mediastinal nodes
for SCLC?
• Cord limit @ BID: <36Gy
• Lung V20 < 20-30%
• Heart D50 < 25-40Gy
Turrisi (NEJM 340(4):265-271, 1999)
“Twice-Daily Compared With Once-Daily
Thoracic Radiotherapy In Limited SmallCell Lung Cancer Treated Concurrently
With Cisplatin and Etoposide”
Turrisi - Methods
• 419 pts (’89-’92) with LS-SCLC
• Concurrent Chemo x4c (cis/etopo) q3w
• Radiation
– Group 1: 1.8 Gy QD to 45 Gy
– Group 2: 1.5 Gy BID to 45 Gy
• Bilateral mediastinal and ipsilateral hilar
adenopathy
• Prophylactic Cranial Irradiation if CR
– 25 Gy/ 10 fx
Turrisi - Esophagitis worse in BID arm
Turrisi – Survival
2y
5y
Turrisi – Overall Survival
P=0.04
2-year
5-year
Daily
41%
16%
Twice-daily
47%
26%
Turrisi – Local & Distant Failure
• Local Failure
– QD RT:
– BID RT:
52%
36%
(p=0.06)
• Local and Distant Failure
– QD RT:
– BID RT:
23%
6%
(p=0.01)
Turrisi - Conclusions
• BID more effective than QD
– Benefit: 10% absolute increase in overall
survival @ 5yrs
– Cost: 15% increase in high grade esophagitis
Turrisi - Criticisms
• QD only went to 45 Gy
• Fractionation still open question
• New CONVERT trial: 66 Gy QD vs 45 BID
– Starts Jan 2008.
Auperin Meta-Analysis of PCI (NEJM 1999)
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PCI for LS-SCLC if CR after chemo
Meta-analysis of 7 trials (1965-95)
Dose Fx: 800x1 to 4000/20.
Improved 3yr OS 20.7% v 15.3%.
Incidence of brain mets decreased from
58% to 33% @ 3yrs.
• Better if PCI <4mo from chemo start
• No assessment of neurocognitive fxn
But what about PCI for ES-SCLC?
• Slotman, EORTC, ASCO 2007
• RCT, 286 pts w/ ES-SCLC
• If any response to chemo x4c, then
randomized to +/- PCI
• PCI reduced risk of symptomatic brain
mets 14.6% v 40.4% at 1 yr.
• Improved 1-yr OS 27.1% vs 13.3%.
Quiz
According to the original VA definition, which of the
following patient presentations would be classified as
limited-stage small cell lung cancer?
A. A 3-cm left upper-lobe lung tumor and a right hilar lymph
node
B. A 3-cm left lower-lobe tumor with a malignant pleural
effusion
C. A 7-cm right upper-lobe lung tumor with a right hilar
lymph node
D. A 7-cm right upper-lobe lung tumor with a right anterior
cervical lymph node
According to the original VA definition, which of the
following patient presentations would be classified as
limited-stage small cell lung cancer?
A. A 3-cm left upper-lobe lung tumor and a right hilar lymph
node
B. A 3-cm left lower-lobe tumor with a malignant pleural
effusion
C. A 7-cm right upper-lobe lung tumor with a right hilar
lymph node
D. A 7-cm right upper-lobe lung tumor with a right anterior
cervical lymph node
Which of the following statements does NOT
describe a feature of small cell lung carcinoma?
A. Most patients are smokers.
B. Abundant mucin production is associated.
C. Paraneoplastic syndromes are associated.
D. A majority of cases have neurosecretory-type
granules.
Which of the following statements does NOT
describe a feature of small cell lung carcinoma?
A. Most patients are smokers.
B. Abundant mucin production is associated.
C. Paraneoplastic syndromes are associated.
D. A majority of cases have neurosecretory-type
granules.
A patient presents with a 3-cm solitary small cell lung tumor
in the right upper lobe. Results of other imaging studies
are negative for metastatic or nodal disease. Mediastinal
biopsy specimens are nondiagnostic. Which of the
following statements about management options is
FALSE?
A. Surgery is contraindicated.
B. Chemotherapy has a role.
C. Radiation therapy may have a role.
D. Concurrent chemoradiation therapy is an option.
A patient presents with a 3-cm solitary small cell lung tumor
in the right upper lobe. Results of other imaging studies
are negative for metastatic or nodal disease. Mediastinal
biopsy specimens are nondiagnostic. Which of the
following statements about management options is
FALSE?
A. Surgery is contraindicated.
B. Chemotherapy has a role.
C. Radiation therapy may have a role.
D. Concurrent chemoradiation therapy is an option.
The addition of radiation therapy to the thorax
improves survival for patients with limited-stage,
small cell lung cancers. The median survival
time for patients is how many months?
A. 9 to 12
B. 14 to 18
C. 20 to 24
D. 26 to 30
The addition of radiation therapy to the thorax
improves survival for patients with limited-stage,
small cell lung cancers. The median survival
time for patients is how many months?
A. 9 to 12
B. 14 to 18
C. 20 to 24
D. 26 to 30
Which of the following statements about
prophylactic cranial irradiation (PCI) for patients
with small cell lung cancer is true?
A. It may be considered for patients with a
complete response to treatment.
B. It should be delivered concurrently with
chemotherapy.
C. It is commonly administered at 2 Gy per fraction
to 40 Gy in 4 weeks.
D. There is no decrease in CNS failure for patients
who receive PCI.
Which of the following statements about
prophylactic cranial irradiation (PCI) for patients
with small cell lung cancer is true?
A. It may be considered for patients with a
complete response to treatment.
B. It should be delivered concurrently with
chemotherapy.
C. It is commonly administered at 2 Gy per fraction
to 40 Gy in 4 weeks.
D. There is no decrease in CNS failure for patients
who receive PCI.
Which of the following symptoms is most
common in patients presenting with
primary tracheal malignancies?
A. Dyspnea
B. Hemoptysis
C. Hoarseness
D. Pneumonia
Which of the following symptoms is most
common in patients presenting with
primary tracheal malignancies?
A. Dyspnea
B. Hemoptysis
??? NOT SCORED
C. Hoarseness
D. Pneumonia
• True or False: Abnormalities in p53 are
moerree common in small cell lung cancer
than in non-small cell lung cancer.
• True or False: Abnormalities in p53 are
moerree common in small cell lung cancer
than in non-small cell lung cancer.
• TRUE
When hyperfractionated radiotherapy is delivered
concurrently with chemotherapy for limited stage
small
cell lung cancer, which one of the following is
CORRECT?
A. Local control is improved.
B. Survival is improved.
C. Brain metastasis is decreased
D. Local control and survival are improved.
E. Local control and survival are improved, while
brain metastasis is decreased.
When hyperfractionated radiotherapy is delivered
concurrently with chemotherapy for limited stage
small
cell lung cancer, which one of the following is
CORRECT?
A. Local control is improved.
B. Survival is improved.
C. Brain metastasis is decreased
D. Local control and survival are improved.
E. Local control and survival are improved, while
brain metastasis is decreased.
In small cell lung cancer, the use of prophylactic
cranial irradiation (PCI) for patients with a
complete response to induction therapy has been
shown to improve the absolute overall survival by
which one of the following?
A. 9.1% at 5 years
B. 9.8% at 3 years
C. 7.4% at 5 years
D. 5.4% at 3 years
E. 10.1% at 7 years
In small cell lung cancer, the use of prophylactic
cranial irradiation (PCI) for patients with a
complete response to induction therapy has been
shown to improve the absolute overall survival by
which one of the following?
A. 9.1% at 5 years
B. 9.8% at 3 years
C. 7.4% at 5 years
D. 5.4% at 3 years
E. 10.1% at 7 years
Identify each of the nodal stations for lung cancers listed
below:
401. 4
402. 7
403. 10
A. High mediastinal.
B. Low paratracheal.
C. Subcarinal
D. Hilar
E. Subaortic
Identify each of the nodal stations for lung cancers listed
below:
401. 4
Low paratracheal
402. 7
Subcarinal
403. 10
Hilar
A. High mediastinal.
B. Low paratracheal.
C. Subcarinal
D. Hilar
E. Subaortic
Regarding lung cancer patients: (True or False?)
404. The most common second cancer for non-small cell
lung cancer patients is lymphoma.
False
405. The most common second cancer for small cell lung
cancer patients is liver cancer.
False
406. The incidence rate for non-smell cell lung cancer
patients developing another lung cancer is 1-2% per
year.
True
Regarding lung cancer patients: (True or
False?)
407. To treat the second primary lung
cancer, surgery is not a viable modality.
False
408. Aerodigestive cancers do occur among
smokers who have lung cancers.
True