Ann M. Maguire, MD, MPH
Clinical Associate Professor
Department of Medicine
April 5, 2014
Educational Objectives
 What makes Cancer Survivors unique?
 What information is needed when transitioning back
to primary care?
 What are some of the key concerns for lymphoma
survivors during the first 5 years after treatment?
Educational Objectives
 What are the most common late effects of lymphoma
therapies?
 Do screening/ preventive care services differ for adult
lymphoma survivors?
 What can a lymphoma survivor do to stay healthy?
Estimated Number of Cancer Survivors in the US from
1975 to 2012
[Estimations
and modeling provided by Angela Mariotto, PhD, based on: Mariotto AB, Yabroff KR,
Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 20102020. J Natl Cancer Inst. 2011 Jan 19;103(2):117-28. Epub 2011 Jan 12
Estimated Number of Cancer Survivors in the U.S. by Site
January 1, 2012 by Site N=13.7 M Survivors)
Estimations and modeling provided by Angela Mariotto, PhD, based on: Mariotto AB, Yabroff
KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States:
2010-2020. J Natl Cancer Inst. 2011 Jan 19;103(2):117-28. Epub 2011 Jan 12.
Estimated Number of Cancer Survivors by Current Age
January 1, 2012 by Site N=13.7 M Survivors)
Estimations and modeling provided by Angela Mariotto, PhD, based on: Mariotto AB, Yabroff
KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States:
2010-2020. J Natl Cancer Inst. 2011 Jan 19;103(2):117-28. Epub 2011 Jan 12.
What is Cancer Survivorship?
 Includes the physical, psychosocial, and economic
issues of cancer, from diagnosis until the end of
life.
 Involves issues related to follow-up, late effects of
treatment, second cancers, and quality of life.
 Survivorship experience is highly individual and is
impacted by short-term, long-term, and late
effects of cancer therapy.
Adverse Effects of Therapy
Treatment Phase
Short-Term
Long-Term
Late-Effects
Post Treatment Phase
Short-Term Effects of Cancer Treatment
 Short-term side effects occur during treatment.
 Examples: nausea, hair loss, pain, fatigue, and
weight loss.
 Resolve after active treatment ends.
 Some symptoms are treatable using medications or
complementary therapies.
Long-Term Effects of Cancer Treatment
 Long-term side effects begin during treatment and
continue after the end of treatment.
 Examples: infertility, neuropathy, vascular
complications related to surgery.
 Symptoms may be treatable to varying degrees.
Late Effects of Cancer Treatment
 Late effects are symptoms that first appear months
or years after treatment has ended.
 Examples: heart failure, osteoporosis, cognitive
problems and second cancers.
 Surveillance for late effects is challenging.
 PCPs are less likely to associate such common
conditions with a remote history of cancer therapy.
 Unique needs for early screening in this population are
not widely known.
Goals of Survivorship Care?
The IOM indicates survivorship care should:
1. Prevent recurring and new cancers as
well as other late effects.
2. Intervene for symptoms that result from
cancer and its treatment.
3. Coordinate the work of specialists and
PCPs to ensure that all of a Survivor’s
health needs are met.
Barriers to Survivor Care
Survivorrelated
Physicianrelated
Healthcare
system-related
• Unawareness of
potential late
effects and future
health risks
• Incomplete
knowledge of
cancer therapy
• Capacity of cancer
treating facilities
• Unfamiliarity of
primary care
providers
• Poor
communication
• Insurance
Oeffinger Peds Blood Canc 2006;46:135-142
Survivorship Care Models
Young Adult Transition
Models
Community-Based
Models
Formalized transition programs
Adult oncology-directed care
Community-based care
Cancer Center Models
Primary oncology care
Specialized LTFU clinic
Shared care
Need-Based Models
RISK-BASED CARE
What are the essential components of
Survivor follow up care?
• Prevent recurrent and new cancers and other late effects
• Monitor for cancer spread, recurrence, or 2nd cancers
• Assess medical and psychosocial late effects
• Manage consequences of cancer and its treatment
• Coordinate with other doctors (Shared Care) so all health
needs met
• Provide routine health promotion
What is Risk-Based Care?
Risk-based care involves a systematic plan of
periodic screening, surveillance, and
prevention that considers a survivor’s
personal health risks predisposed by the
previous cancer and its treatment, genetic
and familial factors, comorbid health
conditions, and lifestyle behaviors.
Follow up care for low risk patients
• Shared care beginning 1-2 years post cancer treatment.
Early transition to PCP-led care.
• You are low risk if the following are true:
•
Cancer was early-stage or low-risk for late effects and recurrence
•
No treatment with alkylating agents, anthracyclines, bleomycin
•
No radiation
•
Mild or no persistent toxicity of therapy
• PCP can provide preventive care and other non-cancer care
throughout treatment for ALL SURVIVORS
Follow up care for moderate risk patients
• Shared Care beginning 5 years post cancer treatment.
Later transition to PCP led care - Increased need for
oncologist to direct surveillance for recurrence.
• You are moderate risk if the following are true:
•
Cancer was moderate risk based on staging and type.
•
Treatment with low-moderate dose alkylating agents,
anthracyclines, bleomycin, or autologous stem cell
transplant
•
Low to moderate dose radiation increasing risk for late
effects
•
Moderate persistent toxicity of therapy
Follow up care for high risk patients
• Shared care starting 1-2 years post treatment .
Increased treatment related complications requires
earlier involvement of PCP and other specialists.
Delayed transition to PCP-led care
• You are high risk if the following are true:
•
Cancer was high risk for recurrence based on staging and
type
•
Exposure to high dose alkylating agents, anthracyclines,
bleomycin, or allogeneic stem cell transplant
•
High dose radiation increasing risk for late effects
•
Multi-organ persistent toxicity of therapy
What is a Survivor Care Plan?
The IOM recommends these 7 elements be included for all
patients:
1.
Personal treatment summary
2.
Identification of possible late and long term effects
3.
Signs of recurrence to watch for
4. Guidelines for follow up care
5.
Identification of providers involved in follow up care
6. Lifestyle recommendations
7.
Supportive resources
Transition to PCP-Led Care
• Timing varies for transition from oncology-led
care to PCP-led care
• Shared care model is optimal for most patients
• Outcomes are better with shared care model.
• Information needed for PCP to lead follow-up
care:
• Treatment summary
• Survivorship care plan – your Oncology team can help
with this if you do not have one.
Follow up Care: First 5 Years
•
Examination by oncologist:
•
•
•
•
Follow CBC:
•
•
•
•
•
Every 3-6 months for years 1-3
Every 6 months for years 4-5
Highest risk of recurrence in first 2 years
Every 6-12 months for up to 10 years
Risk of therapy-related MDS/ Leukemia is 2-3%
Chronic treatment related cytopenias can occur.
Serial imaging/ CT scans as per Oncology
recommendations
Simultaneous Primary care follow-up important
Late Effects
 Late effects of cancer therapy affect the majority of
patients.
 Risk increases gradually over time.
 Cancer survivors are 10 times more likely than
their siblings to develop a serious chronic disease.
 At 30 yrs from cancer diagnosis, 73% will develop
at least 1 chronic condition.
 Late effects depend on the type of cancer therapy.
Nathan, et al. J Clin Oncol 26: 4401-4409; 2008
Factors that contribute to late effects of cancer treatment
Linda A. Jacobs, David J. Vaughn; Care of the Adult Cancer Survivor. Annals of
Internal Medicine. 2013 Jun;158(11):ITCS6:14
(Used with permission from K. Scott Baker, MD)
Common Lymphoma Therapies - ABVD
• ABVD (Adriamycin, Bleomycin, Vinblastine,
Dacarbazine) - Hodgkin lymphoma
• Toxicity includes:
• Acute Myeloid Leukemia (most during the first 5
years)
• Cardiomyopathy/ LV dysfunction, Arrhythmias, and
Valvular disease
• Pulmonary Toxicity – especially Bleomycin + Radiation
• Peripheral Neuropathy
• Infertility (uncommon)
Common Lymphoma Therapies –
RCHOP and CHOP
 RCHOP and CHOP – (Rituxan, Cytoxan,
Adriamycin, Vincristine, Prednisone)
 Toxicity includes:
 Acute Myeloid Leukemia (most during the first 5 years)
 Cardiomyopathy/ LV dysfunction, Arrhythmias, and




Valvular disease
Peripheral Neuropathy
Infertility (uncommon)
Osteoporosis
Metabolic Syndrome
Common High Grade Lymphoma Therapies:
HyperCVAD and Autotransplantation
• HyperCVAD (CHOP drugs alternating with high dose
•
•
•
•
•
methotrexate + cytarabine)
Toxicity is similar to CHOP
Cognitive impairment may be more common if
intrathecal therapy is used.
OR
High dose chemotherapy (such as BEAM) used with auto
transplantation
Transplant patients may have greater treatment related
toxicity due to the higher doses of therapy needed to
ablate the marrow.
Chronic low white count predisposes to infection
Late Effects of Radiation Therapy
 Second cancers
 Endocrine diseases: Thyroid nodules/ cancer,
Hypothyroidism, Gonadal Dysfunction,
Osteoporosis
 Heart disease: Coronary Artery Disease, Heart
Failure, Valve disease
 Cataracts
 Dental problems
 Lung disease: Restrictive, obstructive, interstitial
 Kidney disease: Chronic kidney disease,
Hypertension
 Infertility: Male and Female
Periodic Evaluation for Survivors Treated
with Radiation Therapy
 Yearly complete skin exam
 Yearly eye exam and dental exam
 Yearly UA, BMP, and Blood Pressure
 Yearly thyroid exam, TSH and T4 if neck radiation
 Other evaluation depends upon exposure.
 For chest radiation: PFT and Chest X-Ray plus ECG and
Echocardiogram to screen for heart and lung disease.
 Mammogram or Breast MRI for women
 Evaluation should be done on entry into follow up care
Repeat as needed based on results and symptoms.
Screening for Cardiac Toxicity after
Lymphoma Therapy
 ECHO or MUGA plus ECG at baseline and
periodically depending on results.
 Evaluation should be done on entry into
follow up care and repeated as needed based
on results and symptoms
 Cardiology consultation for patients with
abnormal findings.
Cardiovascular Risk after Lymphoma Therapy
 Survivors have a 2-3 fold increased risk of CVD.
 Risk factors include: Cardiotoxic therapies, HTN secondary to
treatment related CKD or other factors, Obesity/ Metabolic
Syndrome, Dyslipidemia, and Type 2 Diabetes.
 Recommendations: Aggressive risk factor reduction.
 Control and treat lipids early with statins (Screen at age 20
and then every 3 yrs)
 Control Blood Pressure (< 140/90)
 Avoid Smoking
 Screen for Diabetes and treat aggressively (A1c< 7.0)
 Control Weight
 Increase daily physical activity
Osteoporosis
 Steroids, Radiation, and Hypogonadism are the
primary risk factors.
 Radiation may increase risk for osteonecrosis.
 Recommendations:
 Calcium and Vitamin D preferably from diet sources
 Repeat Bone Density testing every 1-2 years
 When appropriate in female patients, consider OCP or
other hormonal therapy. In men, treat low
testosterone.
 Bisphosphonates should be used only when truly
necessary.
 Lack of fracture history and young age increase
chance that bone mass can still be increased.
Infertility and Cancer Therapy
 Risk of gonadal dysfunction/ low sex hormones
increases with older age at time of alkylating agent
exposure.
 Radiation therapy exposure has increased toxicity
at younger ages.
 Recovery of fertility is highly variable.
 Some women regain ovarian function years after
therapy.
Evaluation and Management of Female Infertility
and Gonadal Dysfunction
 Symptoms include:
 Irregular menses or loss of menstruation
 Hot flashes and other symptoms of early menopause
 Recommended Evaluation:
 Hormone testing including estrogen annually
 Treatment: Oral contraceptives up to age of
natural menopause.
 Repeat hormone testing annually off OCP to assess
recovery of ovarian function for the first 10 years after
treatment.
 Reproductive Endocrinology referral as needed.
Evaluation and Management of Male Infertility or
Gonadal Dysfunction
 Symptoms of Low testosteerone include:
 Fatigue and decreased muscle mass
 Low sperm count/ Infertility
 Low libido/ sexual dysfunction
 Recommended evaluation:
 Check hormones including testosterone.
 Semen analysis as indicated to assess fertility.
 Reproductive endocrinology referral as indicated.
 Bone Density testing for patients with low testosterone.
 Treatment: Testosterone gel or shots.
 Sperm production can resume up to 10 years after cancer
therapy.
Risk Factors for Second Cancers
 Radiotherapy
 May increase risk of cancers in the field of radiation including
sarcomas, thyroid cancer, stomach cancer, lung cancer
 Chemotherapy
 May increase risk of Leukemia or MDS
 Hereditary Cancer syndromes/ Genetic risk:
 Lynch Syndrome/ HNPCC (hereditary nonpolyposis
colorectal cancer) increases risk for cancers of bladder,
kidney, prostate, breast, ovary, uterus, stomach, small bowel,
pancreas and liver
 BRCA mutations increase risk for breast and ovarian cancer
 Among older adults, tobacco and alcohol use surpass
cancer treatment as key risk factors for future cancers
Engles and Fraumemi, SEER New Malignancies among Cancer Survivors Ch 12
Second Cancer Risk
Nature Medicine 2011
Second Cancers after Lymphoma Therapy
 Breast Cancer
 Highest risk: RT before age 30 (esp before age 20),
axillary (mantle) RT, continued menses, strong family
history of breast CA
 For a woman who received chest XRT at age 20, lifetime
risk approaches 50%, similar to BRCA + women
 Lung Cancer:
 Highest risk: smokers who received XRT to chest
 Other malignancies:
 Depends on total radiation (RT) dose and area treated.
 Sarcoma (in radiation site), melanoma, thyroid, GI
cancers, Leukemia/ MDS
 Radiation risk is dose dependent, increases
steadily over time and extends beyond 10 yrs
Cancer Screening and Surveillance
 Lymphoma survivors should adhere to USPSTF
recommended guidelines.
 Mammogram and Clinical Breast Exam
 Colonoscopy or other Colorectal Screening
 PAP testing/ Cervical Cancer Screening
 PSA/ Prostate Screening?
 All survivors should have an annual exam with a
primary physician who is aware of your cancer history.
 This is the best way to allow early detection of thyroid
nodules, skin cancers, and other cancers for which there
is no USPSTF screening recommendation.
Breast Cancer after Lymphoma
 Prior lymphoma therapy limits treatment options for
women with breast cancer.
 Breast cancer after mantle radiation may have poorer
prognosis .
 More likely to be hormone receptor negative
 Breast MRI in addition to Mammogram is appropriate
for women with lymphoma treated with chest
radiation at highest risk for Breast Cancer.
 Specific recommendations about which Survivors
benefit from Breast MRI are evolving.
 Ask your Oncologist or Breast Radiologist
Breast Cancer Screening
 Routine surveillance mammography starting age 40
may be insufficient for many lymphoma survivors.
 Mammogram may not be effective screening in young
females, especially those receiving mantel radiation for
Hodgkins before age 30.
 For women with mantel radiation before age 30:
Recommend annual Mammogram and Breast MRI
starting 8 years after therapy or age 25 ,whichever is
last.
 For women with mantel radiation after age 30
Recommend annual Mammogram starting 8 years
after therapy or age 40, whichever is first .
Lung Cancer Screening
 Chest radiation and alkylating agents have only
modest effect on lung cancer risk in non-smokers
and light smokers.
 Among heavy smokers, lymphoma therapy
increases lung cancer risk by 20 fold.
 Low dose Chest CT for lung cancer screening is
now approved for all heavy smokers (> 30 pack
years) and is covered by most insurers
 CT can be ordered by Primary Care physicians.
 Optimal lung cancer screening strategy for nonsmokers unknown
Interventions to Decrease Cancer Risk
 Smoking cessation.
 Decrease alcohol intake.
 Reduce excess weight.
 Minimize UV exposure.
 Minimize exposure to other carcinogens.
 Increase physical activity.
 Increase intake of fruits and vegetables.
LTFU Guidelines, 2006.
Cognitive Impairment after Cancer Therapy
 “Chemo Brain” is commonly reported among many
cancer survivors.
 Impairment may be difficult to document in highly
educated people.
 It has been observed that this form of cognitive
dysfunction may be exacerbated by aging.
 There are few studies and little high quality evidence
to direct interventions.
 Some success has been reported with SSRI
antidepressants and stimulants including modafinil.
 Neuropsych testing is the best way to diagnose
impairment and rule out depression.
Summary
 Life-long risk-based care is recommended for all
cancer survivors.
 Health systems will be challenged to develop
appropriate long-term follow up programs as the
number of survivors continues to grow.
 Use available tools to organize your cancer
treatment history.
 Ask your oncologist to identify most appropriate
areas to target for follow up care.
 Be your own advocate!
“Top 10 Tips for Cancer Patients”
in “No Such Thing as a Bad Day” by Hamilton Jordan
“Tip #10 Your attitude and your beliefs are your
most powerful weapon against cancer.”
Resources
 Journey Forward
www.journeyforward.org
 National Coalition for Cancer Survivorship
www.canceradvocacy.org