Primary Care after Cancer: Practical Advice for Lymphoma Survivors

1. Primary Care after Cancer:Practical Advice for Lymphoma Survivors Ann M. Maguire, MD, MPH Clinical Associate Professor Department of Medicine April 5, 2014

2. 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? 

3. 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?

4. 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: 2010-2020. J Natl Cancer Inst. 2011 Jan 19;103(2):117-28. Epub 2011 Jan 12

5. 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.

6. 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.

7. 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.

8. Adverse Effects of Therapy Treatment Phase Post Treatment Phase Short-Term Long-Term Late-Effects

9. 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. Short-Term Effects of Cancer Treatment

10. 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. Long-Term Effects of Cancer Treatment

11. 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.

12. Goals of Survivorship Care? The IOM indicates survivorship care should: • Prevent recurring and new cancers as well as other late effects. • Intervene for symptoms that result from cancer and its treatment. • Coordinate the work of specialists and PCPs to ensure that all of a Survivor’s health needs are met.

13. Barriers to Survivor Care Oeffinger Peds Blood Canc 2006;46:135-142

14. Survivorship Care Models Community-Based Models Community-based care Young Adult Transition Models Formalized transition programs Adult oncology-directed care Need-Based Models RISK-BASED CARE Cancer Center Models Primary oncology care Specialized LTFU clinic Shared care

15. 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

16. 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.

17. 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

18. 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

19. 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

20. What is a Survivor Care Plan? The IOM recommends these 7 elements be included for all patients: • Personal treatment summary • Identification of possible late and long term effects • Signs of recurrence to watch for • Guidelines for follow up care • Identification of providers involved in follow up care • Lifestyle recommendations • Supportive resources

22. 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.

23. Follow up Care: First 5 Years • Examination by oncologist: • Every 3-6 months for years 1-3 • Every 6 months for years 4-5 • Highest risk of recurrence in first 2 years • Follow CBC: • 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

24. 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 ClinOncol 26: 4401-4409; 2008

25. Factors that contribute to late effects of cancer treatmentLinda 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)

26. 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)

27. 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

28. 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

29. 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

30. 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-Rayplus 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.

31. 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.

32. 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

33. 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.

34. 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.

35. 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.

36. 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 gelor shots. • Sperm production can resume up to 10 years after cancer therapy.

37. 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

38. Second Cancer Risk Nature Medicine 2011

39. 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

40. 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.

41. 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

42. 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 .

43. 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 non-smokers unknown

44. 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.

45. 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.

46. 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!

47. “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.”

48. Resources • Journey Forward www.journeyforward.org • National Coalition for Cancer Survivorship www.canceradvocacy.org