1. ©2014 MFMER | slide-1 Survivorship for “cured” Hodgkin patients – How should we be following them? Carrie Thompson, MD Mayo Clinic Lymphoma & Myeloma 2014

2. ©2014 MFMER | slide-2 Disclosures I have nothing to disclose

3. ©2014 MFMER | slide-3 Outline Surveillance for relapse Screening for late effects Cardiovascular disease Secondary malignancies Psychosocial issues Care models

4. ©2014 MFMER | slide-4 Background: Survivorship 13.7 million cancer survivors in the US ~200,000 survivors of HL Decreased survival compared to general pop SEER Cancer Statistics Review, 1975-2008, NCI. JCO 2003; 21:3431-9

5. ©2014 MFMER | slide-5 Do surveillance scans improve outcomes in HL? Cancer 2014;120:2122-9

6. ©2014 MFMER | slide-6 Surveillance for relapse Negatives of routine scans Radiation exposure False positives Anxiety Cost

7. ©2014 MFMER | slide-7 Surveillance guidelines Physical examination, history, and clinical judgement are the cornerstone of followup Q 3 mos years 1-2, q 4 mos year 3, then q 6 mos years 4-5 Imaging studies NCCN CXR or CT chest and CT A/P q 6-12 mos x 2 yrs Lugano Classification Routine scans are discouraged Scans prompted by clinical indications NCCN.org Version 2.2014 JCO 2014; 32:3059-67

8. ©2014 MFMER | slide-8 Monitoring for Late Effects Cardiovascular disease Secondary malignancies Psychosocial issues Other

9. ©2014 MFMER | slide-9 Congestive heart failure: chemotherapy agents Cytotoxic agents Doxorubicin, cyclophosphamide, ifosfamide, cisplatin, fluorouracil, paclitaxel Targeted agents mTOR inhibitors PI3 kinase inhibitors Trastuzumab Bevacizumab

10. ©2014 MFMER | slide-10 Congestive heart failure in HL Subclinical (asymptomatic, echo abnormal) 27.6% in lymphoma survivors 1 Do not know if this will lead to clinical CHF Clinical CHF 7.2% incidence with 6 year followup 2 May become evident during times of increased cardiac workload Pregnancy, anesthesia, BMT, illness 1 JCO 1998; 16:3502-8 2 Ryberg 1998

11. ©2014 MFMER | slide-11 Coronary artery disease in HL Caused by radiation therapy Prospective study in 294 survivors of HL ≥35 Gy to mediastinum Excluded patients with known CVD Nuclear study and stress test 40 patients (14%) underwent coronary angiography Coronary artery stenosis >50% in 22 patients 7.4% of those screened JCO 2007; 25:43-9 Blood 2007; 109:1878-86

12. ©2014 MFMER | slide-12 CAD in HL Coronary CT angiography in 31 adult survivors of childhood HL with hx radiation therapy ECG, treadmill stress test, echo 12 (39%) patients with coronary lesions 3 (10%) with obstructing lesions on coronary angiogram 2 of these 3 died from CVD All had abnormal ECG, 1 abnormal treadmill, 0 abnormal echo Cancer 2014; Jul 16 Epub

13. ©2014 MFMER | slide-13 Other cardiac diseases Valvular disease Predominantly mitral and aortic valves affected Pericardial disease Historically most commonly affected cardiac structure Conduction system Arrhythmias and QT prolongation

14. ©2014 MFMER | slide-14 Cardiac Follow-Up Expert Guidelines ©2011 MFMER | slide-14 JCO 2011; 29:1885-1892 Annals Onc 2012; 23:Suppl 7 JASE 2014;27:911-39

15. ©2014 MFMER | slide-15 Screening Recommendations: CVD Annual physical exam BP check Lipids every 3-5 years Glucose annually Particularly if hx paraaortic LN xrt Treat cardiac risk factors Lifestyle modifications JCO 2009; 27:5383-89 JCO 2014; 32 Epub

16. ©2014 MFMER | slide-16 Benefits of exercise JCO 2014; 32 Epub

17. ©2014 MFMER | slide-17 Screening Recommendations: CVD Post-radiation therapy If >30 Gy to mediastinum Stress test (exercise stress echo) starting 5-10 years post therapy then q 5 years Post anthracycline chemotherapy If >240 mg/m2 doxorubicin Echo starting 5 years after treatment then q 5 years

18. ©2014 MFMER | slide-18 For female cancer survivors contemplating pregnancy Refer to cardiology if… >240 mg/m2 anthracycline dose >30 Gy radiation to the heart or surrounding tissue Any combination of the above with high-dose cyclophosphamide

19. ©2014 MFMER | slide-19 Late Effects: Secondary Malignancies Breast cancer In those treated for childhood HL, estimated incidence of breast cancer 20% at age 45 Thyroid cancer Lung cancer Risk significantly increases in those who smoke after radiation therapy Gastric/colorectal cancers Sarcoma JCO 2007; 25:1489-97

20. ©2014 MFMER | slide-20 Types of secondary cancers, continued AML/MDS Mostly due to chemotherapy (alkylators) NHL ~5% lifetime risk in those treated for Hodgkin lymphoma Skin cancers

21. ©2014 MFMER | slide-21 Recommendations for those at risk Annual skin exam in irradiated field Annual mammogram (+/- MRI) 8 years after radiation or at age 40, whichever is earlier Colonoscopy 15 years after pelvic, abdominal, spinal irradiation or at age 35 Tobacco cessation ?low dose CT scan chest ?EGD Life-long surveillance Am J Med 2011; 12:1606-12

22. ©2014 MFMER | slide-22 Fertility Issues Very important issue ABVD does not affect fertility Fertility preservation pre-treatment Wait 2 years post-treatment to have children No increase in birth defects, miscarriage, cancer in offspring compared to general population www.fertilehope.org

23. ©2014 MFMER | slide-23 Fatigue 26% of survivors of Hodgkin lymphoma have significant fatigue Higher than general population, other cancer types Fatigue associated with higher symptoms of anxiety and PTSD and lower QOL Unclear etiology, literature suggests may be related to long term health complications JCO 1999; 17:253-61, JCO 2005; 23:6587-95, Thompson 2009

24. ©2014 MFMER | slide-24 Loss of Immunity: for all HL survivors NO live vaccines No shingles vaccine, influenza vaccine live Influenza vaccine annually Tdap/Td q 10 years HPV vaccine if <age 26 Pneumococcal vaccine PCV-13 followed by PPV26 8 weeks later, second dose PPV26 5 years later If <age 60, PPV26 at age 65 http://www.cdc.gov/vaccines/schedules/ hcp/imz/adult-conditions.html

25. ©2014 MFMER | slide-25 Loss of Immunity If splenectomy or splenic RT Meningococcus, HIB, PCV13 at time of treatment PPV23 8 weeks later then 5 years later Meningococcus q 5 years If hematopoietic stem cell recipient More complicated revaccination schedule

26. ©2014 MFMER | slide-26 Depression and Anxiety in Cancer Survivors Depression higher than general population in 1 st 2 years after diagnosis, then no different Anxiety levels higher than general population and tend to persist Lancet Oncology 2013; 14:721-32

27. ©2014 MFMER | slide-27 Anxiety in Lymphoma Survivors and Spouses Lancet Oncology 2013; 14:721-32

28. ©2014 MFMER | slide-28 Survivorship Care Models Primary care providers not trained in care of long-term cancer survivors Communication and coordination of care is key Survivorship care plan Treatment summary Follow-up care plan JOP 2014; Epub 10/14/14 www.asco.org

29. ©2014 MFMER | slide-29 Does education and screening for late effects decrease QOL? Int J Rad Onc Biol Phy 2014; 90:164-71

30. ©2014 MFMER | slide-30 Summary Surveillance for relapse Physical examination, history, and clinical judgement are the cornerstone of followup Late effects Cardiovascular disease, secondary malignancies, fatigue, fertility, loss of immunity, psychosocial issues Coordinated care

31. ©2014 MFMER | slide-31 Thank you! Thompson.Carrie@mayo.edu