K30 Case Presentation David Andorsky August 26, 2008

Case Presentation 58M with several months of fatigue and 40 lbs weight loss Early satiety No fevers or chills Upper and lower endoscopy unrevealing PMH unremarkable No medications No recent travel or sick contacts

Case Presentation Physical Examination Low grade fever (38.0 C) Chronically ill appearing 1-2 cm cervical and L supraclavicular adenopathy Splenomegaly (3cm below costal margin)

Case Presentation Laboratory data: Imaging (CT chest/abd/pelvis) WBC 4.3 (50% polys, 13% lymphs, 35% monos) Hgb 6.0, MCV 70, platelets 177 Albumin 2.0, ALT 87, AST 117, TB 0.7 Imaging (CT chest/abd/pelvis) Supraclavicular, peri-esophageal, portocaval adenopathy, and splenomegaly

Case Presentation Key features: Differential diagnosis: Lymphadenopathy Splenomegaly Anemia Cachexia Mild LFT abnormality Differential diagnosis: Lymphoma Other malignancy Infection (esp tuberculosis or fungal) Sarcoidosis

Diagnosis Diagnostic procedures: Diagnosis: Excisional lymph node biopsy Bone marrow biopsy Diagnosis: Classical Hodgkin’s Lymphoma, involving lymph node and bone marrow

Hodgkin’s Disease Sir Thomas Hodgkin (1798 – 1866) Described in 1832, “On Some Morbid Appearances of the Absorbent Glands and Spleen.”

Hodgkin’s Disease Characterized by giant, binucleate Reed-Sternberg cells Other lymphocytes are not in themselves malignant, but are stimulated to grow by the RS cells

Hodgkin’s Disease - Epidemiology Bimodal distribution – younger patients (teens-20s) and older patients (60s-80s) Some cases appear to be related to EBV. Exact mechanism unclear. (40% of all US cases; nearly 100% of HIV-associated). Source: http://seer.cancer.gov/faststats

Staging and Treatment Stage I and II: chemotherapy and radiation Stage III and IV treated with chemotherapy

Risk-Adapted Therapy Don’t want to overtreat low risk patients, since this will increase the number of treatment-related side effects Don’t want to undertreat high risk patients, since relapsed disease develops resistance to therapy and is much harder to cure Major issue in cancer therapy today. For some disease, treatments are highly effective, but toxicity (both acute and chronic) is considerable

Hodgkin’s: Second Malignancies 40 excess cancers per 10,000 patients/year Lung and breast – associated with radiation therapy Acute leukemia – associated with alkylating chemoRx Risk of death from second cancer: 14% over 20 years Risk for solid tumors still elevated 20-30 years after treatment for Hodgkin’s Evolution of treatment Decreased use of radiation Decreased use of alkylating agents Risk of death at 20y: 33% from HD, 14% from second cancer, 20% from all other causes

Hodgkin’s Disease Risk Factors Albumin <4.0 g/dL Hemoglobin <10.5 g/dL Male sex Age >45 Stage IV disease WBC > 15K Lymphopenia (<600/mm3 or <8% total) Albumin level of <4.0 g/dL. Hemoglobin level of <10.5 g/dL. Male sex. Age of 45 years or older. Stage IV disease. White blood cell (WBC) count of at least 15,000/mm3. Absolute lymphocytic count of <600/mm3 or a lymphocyte count that was <8% of the total WBC count. 5 y freedom from prorgession: - 0-3 risk factors: 60-80% after first line chemo - 4-7 risk factors: 40-50% after first line chemo (Hasenclever D, Diehl V: A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med 339 (21): 1506-14, 1998) Hasenclever D, Diehl V: N Engl J Med 339 (21): 1506-14, 1998

Hodgkin’s Disease Risk Factors Albumin <4.0 g/dL Hemoglobin <10.5 g/dL Male sex Age >45 Stage IV disease WBC > 15K Lymphopenia (<600/mm3 or <8% total) Albumin level of <4.0 g/dL. Hemoglobin level of <10.5 g/dL. Male sex. Age of 45 years or older. Stage IV disease. White blood cell (WBC) count of at least 15,000/mm3. Absolute lymphocytic count of <600/mm3 or a lymphocyte count that was <8% of the total WBC count. 5 y freedom from prorgession: - 0-3 risk factors: 60-80% after first line chemo - 4-7 risk factors: 40-50% after first line chemo (Hasenclever D, Diehl V: A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med 339 (21): 1506-14, 1998) Hasenclever D, Diehl V: N Engl J Med 339 (21): 1506-14, 1998

Risk Stratification Hasenclever D, Diehl V: N Engl J Med 339 (21): 1506-14, 1998

High risk patients: ABVD vs escalated BEACOPP ABVD = standard combination chemotherapy for advanced HD Escalated BEACOPP = more intensive regimen Better disease-free and overall survival compared to standard regimens* More toxic * V Diehl, NEJM 2003

Case Presentation Given high risk features, patient treated with escalated BEACOPP During first cycle, presented with neutropenia and septic shock  ICU Discharged to home after 10 days in hospital Chemotherapy modified to ABVD

Case Presentation Patient completed 6 cycles of chemotherapy PET-CT after 2 cycles negative (good prognostic sign) Developed bleomycin pulmonary toxicity after completing therapy Most recent PET-CT 15 months after diagnosis shows no evidence of disease

Conclusions Future of oncology is individualizing treatment plan for each patient Specific treatments for disease subtypes Variations in treatment intensity based on risk More aggressive therapy sometimes needed, but it comes at a cost Need for rigorous randomized trials to determine treatment with best risk:benefit ratio

NEJM oct 5, 2007 CPC NEJM June 12, 2008 CPC