1. K30 Case Presentation
David Andorsky
August 26, 2008

2. 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

3. 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)

4. 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

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

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

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

8. 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

9. 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:

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

11. 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

12. 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 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

13. 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): , 1998)
Hasenclever D, Diehl V: N Engl J Med 339 (21): , 1998

14. 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): , 1998)
Hasenclever D, Diehl V: N Engl J Med 339 (21): , 1998

15. Risk Stratification
Hasenclever D, Diehl V: N Engl J Med 339 (21): , 1998

16. 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

17. 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

18. 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

19. 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

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