Hodgkin's disease

Epidemiology
8,000 cases/year in US

Risk factors
Male to female ratio is 1.3:1
Bimodal age peaks: 20's and 50's
Higher incidence in whites
Family history
EBV infection/history of mononucleosis
High socioeconomic status
Few siblings/Early birth order (affects immunity?)

Pathology
Classical HD (CD15+, CD30+) subtypes
1) Nodular sclerosing: Most common subtype in US
2) Mixed cellularity: Patients are slightly older, men; favorable histology; non-industrialized countries
3) Lymphocyte depleted: Very rare, older patients, worse prognosis
4) Lymphocyte rich: 4% of cases
Non-classical HD (CD15-, CD30-, CD20+, CD45+)
1) Lymphocyte predominant: Most favorable histology (RT alone can cure) but has a higher risk of transforming into NHL; typical presentation is with solitary peripheral node

Clinical
Most commonly involved nodes are cervical (80%) and mediastinal (50%)
Stage with PET-CT
Bone marrow bx if stage III-IV or abnormal CBC/B symptoms

B symptoms
-Recurrent fever higher than 100F
-More than 10% weight loss
-Recurrent drenching night sweats

Risk groupings
-EORTC: Favorable if stage I-II, younger than 50, ESR less than 50 with no B symptoms or less than 30 with B symptoms.  Unfavorable if stage III-IV, 4 or more nodal regions involved, older than 50, ESR above cutoff, bulky disease
-German HD: Similar to EORTC without age limit and with 3 or more sites being unfavorable
-NCIC: Age cutoff at 40 for unfavorable; histology (mixed/LD bad); includes bulky mediastinal disease

Therapy
Early stage
-ABVD x 4 then consolidation RT to 30Gy
-Three European studies established involved field RT as equivalent to subtotal nodal RT
-Recently updated German HD Study Group protocol suggests that 20Gy can provide durable control
-Chemo alone is associated with worse relapse free survival and higher rates of failure requiring transplant but similar overall survival compared with CRT (Mumbia, GELA H9F, NCIC/ECOG)


Advanced/bulky/unfavorable
RT may be indicated in partial responders
Currently RT is not part of standard therapy for complete responders to chemo with stage III-IV disease
(Aleman trial)


Chemo regimens
MOPP = Mechlorethamine, vincristine, procarbazine, prednisone
 -Side effects include n/v, neuropathy, infertility, second malignancy (AML)
ABVD = Adriamycin, bleomycin, vinblastine, dacarbazine
 -Side effects include cardiac damage, pulmonary fibrosis (improved preservation of fertility and fewer second malignancies)
Stanford V = Mechlorethamine, adriamycin, vincristine, vinblastine, bleomycin, etoposide, prednisone
 -RT is a critical part of the regimen (even for stage III-IV) because chemo intensity was lowered to include RT as part of the treatment protocol

Side effects of therapy
Pneumonitis: 5%
Pericarditis: 5% (unclear if still true with modern planning)
Hypothyroidism: 50%
Zoster: 10-15%
L'Hermitte's syndrome: 10-15%
Elevated risk of second cancers (Leukemia 800%, lymphoma 500%, lung cancer 10%, breast cancer 10%)
Elevated cardiac mortality (300%)