The Adult Survivor of Hodgkin Disease: Falling Through the Cracks From the Publishers of Consult Guys The Adult Survivor of Hodgkin Disease: Falling Through the Cracks COPYRIGHT © 2017, ALL RIGHTS RESERVED

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Yesterday I saw a 63-year-old man as a new patient Yesterday I saw a 63-year-old man as a new patient. He moved to our town 1 month ago and had an employment physical at his company, and his blood pressure was mildly elevated. He was told to see an internist and saw me. Guys: I need your advice. He has a history of Hodgkin lymphoma diagnosed at age 21 (42 years ago). He recalls that he presented with painless adenopathy. He remembers that he had staging splenectomy and that he underwent mantle and paraaortic radiation therapy. He doesn’t remember much more but does remember being told that he was cured. He followed up with an oncologist for 5 years but ended follow-up after that time. He did not remember much else but says that he was cured. I obtained components of his prior medical record and the best that I could determine the history is as follows: Age 21: Painless adenopathy. Staging splenectomy. Stage I HL Rx: Mantle and paraaortic XRT (?dose) 6 months later: Relapse. Stage 4 HL Rx: Chemo: MOPP 5 years after initial rx: HL remains in remission, hypothyroid, infertile, hyperlipidemia, Cure thyroid supplement, no lipid-lowering therapy No follow-up in the past 37 years. Exam: BP 160/92, HR 80 No adenopathy Splenectomy site healed Labs: Hgb 13.5, Plts 400K, WBC 8.0 (normal diff) TSH (3.0) So while he was sent to me for evaluation of hypertension there is much more to his story. Cholesterol 326, TG 148, HDL 42, LDL 154 Can you advise me as to what I should – or should not– be doing for this man who was treated and apparently cured of Hodgkin lymphoma 42 years ago and last seen in medical follow-up 37 years ago. Copyright © 2017

Staging Before 1960s: Incurable 1960s Staging Early stage Stage I: single lymph node region or extralymphatic organ Stage II: two or more lymph node regions same side of diaphragm Advanced stage: Stage III: involved node regions both sides of diaphragm Stage IV: disseminated additional extralymphatic involvement

Approach to Treatment 1960s, 1970s Staging laparotomy and splenectomy Early stage Extended-field high-dose XRT Advanced stage Chemotherapy Alkylating agents MOPP ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine)

Approach to Treatment 1980s Staging: imaging studies Early stage: extended-field XRT Advanced stage: chemotherapy (ABVD)

Approach to Treatment 1990s Staging: imaging studies Chemotherapy (ABVD) + limited-field lower-dose XRT

Approach to Treatment 2000s Staging: imaging studies Early stage Chemotherapy (ABVD) Further limiting of XRT field and dose Advanced stage Combination chemotherapy Limited radiation therapy in some Remission: >80-85%

Cumulative incidence of cause-specific mortality of long-term HL survivors. Republished with permission of American Society of Hematology, from Current survivorship recommendations for patients with Hodgkin lymphoma: focus on late effects, Andres Ng, 124, 23, 2014; permission conveyed through Copyright Clearance Center, Inc. ©2014 by American Society of Hematology

The Risk After Cure Second malignancy 10- to 15-year latency Solid tumors Radiation therapy Younger age at Hodgkin disease treatment Smoking

Second Tumor Breast cancer in women Women treated age <30 Mantle radiation Latency to breast cancer 10-15 years

Schaapveld M, Aleman BM, van Eggermond AM, Janus CP, Krol AD, van der Maazen RW, et al. Second Cancer Risk Up to 40 Years after Treatment for Hodgkin's Lymphoma. N Engl J Med. 2015;373:2499-511. [PMID: 26699166] doi:10.1056/NEJMoa1505949.

The Risk After Cure: Other Cancers Lung cancer Directly related to radiation dose Linked to alkylating agents Tobacco Gastrointestinal cancer Esophagus, stomach, pancreas, colon Related to radiation dose Chemotherapy

The Risk After Cure: Cardiovascular Disease Mantle field radiation therapy Anthracycline (ABVD) Up to 6X incidence: CAD Less likely to have typical angina Valvular heart disease Cardiomyopathy Pericardial constriction Hypertension, tobacco, hyperlipidemia, physical inactivity further increase risk

The Risks After Cure Hypothyroidism Neck XRT Infertility Pelvic XRT Alkylating agents Aggressive salvage therapy Standard ABVD does not affect fertility Neck muscle weakness Mantle XRT >15-20 years after XRT Dropped head syndrome

Surveillance HLS Treated by Mediastinal XRT Yearly history and physical CAD Valvular heart disease Cardiomyopathy CHF Conduction disease Carotid disease CV risk factors and treat If screening suggests CV dx, imaging studies as indicated Lipid panel every 1-2 years

Surveillance HLS Treated by Mediastinal XRT Asymptomatic Transthoracic echocardiogram Initial: 5 years after exposure in high-risk patients High risk: mediastinal XRT >15 Gy, one or more cardiac risk factors Initial: 10 years after exposure in others Follow-up: every 5 years Stress test for CAD detection 5-10 years after exposure in high-risk patients Lancellotti P, Nkomo VT, Badano LP, Bergler-Klein J, Bogaert J, Davin L, et al; European Society of Cardiology Working Groups on Nuclear Cardiology and Cardiac Computed Tomography and Cardiovascular Magnetic Resonance. Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2013;14:721-40. [PMID: 23847385] doi:10.1093/ehjci/jet123

Surveillance HLS Treated by Mediastinal XRT Breast cancer screening in women National Comprehensive Cancer Network Annual mammogram 8-10 years post Rx or at age 40, whichever comes first Add breast MRI to mammogram if XRT between ages 10-30 Late Effects of Childhood Cancer Guideline Annual mammogram, breast MRI, or both for women who had received chest XRT >20 Gy starting at age 25 or 8 years after treatment, whichever comes later Lung cancer screening in high-risk patients (tobacco use) Low-dose CT Frequency?

Surveillance Thyroid function Neck XRT: annual TSH Annual skin cancer exam of radiation field Abdominal-pelvic XRT (>30 Gy) Colonoscopy beginning age 35 or at 10 years post XRT (whichever comes first) and repeated every 5 years

Can You Lower the Risk? Splenectomy or splenic XRT Immunization (pneumococcal, meningococcal, influenza) Cardiac risk factor reduction-Rx Physical activity >2-2.5 hours of cycling or walking per week

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Our Patient 63-year-old man 42 years following Hodgkin lymphoma treatment Splenectomy Chest and paraaortic XRT Chemotherapy Hypothyroid Hyperlipidemia Hypertension

Our Patient Treat cardiac risk factors Hypertension Hyperlipidemia Treat hypothyroidism Cardiac surveillance Echocardiogram Stress test Cancer screening Skin exam Colonoscopy Immunization (pneumococcal, meningococcal, influenza) Exercise plan

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