Hodgkin lymphoma Clinical presentation and treatment Hodgkin lymphoma

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Hodgkin lymphoma Clinical presentation and treatment

Hodgkin lymphoma Clinical presentation and treatment

Hodgkin lymphoma • Malignant cell is a B lymphocyte • Enlarged lymph nodes important

Hodgkin lymphoma • Malignant cell is a B lymphocyte • Enlarged lymph nodes important clinical sign • Thus: Confusion! – Patients – Students • Q: what is difference with non-Hodgkin lymphomas where in most cases malignant cell is also of B cell origin?

Differences Hodgkin and non-Hodgkin lymphomas (NHL) • Age distribution – NHL : > 60

Differences Hodgkin and non-Hodgkin lymphomas (NHL) • Age distribution – NHL : > 60 years peak incidence – Hodgkin: bimodal • Variabilty of clinical presentation – Hodgkin: limited stage; rarely extranodal – NHL: higher stage; frequently extranodal • Treatment – Radiotherapy very important part of treatment in Hodgkin's disease

Hodgkin lymphoma Clinical presentation In general less complex than NHL! • Lymphadenopathy – Enlarged

Hodgkin lymphoma Clinical presentation In general less complex than NHL! • Lymphadenopathy – Enlarged painless lymphnodes – Supra-diaphragmatic in 90% (cervical, mediastinal) • Hepato-splenomegaly: initially infrequent • B symptoms in 25 -30% • Fever, often periodical; classically Pel-Ebstein • Night sweats • Weight loss (> 10% within 6 months)

Hodgkin lymphoma Clinical Staging • History/ Physical examination • CT scan neck, thorax, abdomen

Hodgkin lymphoma Clinical Staging • History/ Physical examination • CT scan neck, thorax, abdomen • 18 FDG-PET scan • Bone marrow biopsy

Hodgkin lymphoma Ann Arbor staging

Hodgkin lymphoma Ann Arbor staging

Hodgkin lymphoma Standard therapy in 2012 • Stage I/II – Favorable (2 -)3 x

Hodgkin lymphoma Standard therapy in 2012 • Stage I/II – Favorable (2 -)3 x ABVD + 30 Gy IN-RT – Unfavorable 4 x ABVD + 30 Gy IN-RT • Stage III/IV 8 x ABVD

Role of radiotherapy in stage III/IV Hodgkin lymphoma • CR after adequate chemotherapy no

Role of radiotherapy in stage III/IV Hodgkin lymphoma • CR after adequate chemotherapy no radiotherapy • PR after adequate chemotherapy radiotherapy

Treatment Results ?

Treatment Results ?

Survival after Hodgkin lymphoma Radiotherapy and/or chemotherapy radiotherapy No therapy From H. S. Kaplan,

Survival after Hodgkin lymphoma Radiotherapy and/or chemotherapy radiotherapy No therapy From H. S. Kaplan, 1981

Fraction survival Long term survival of Hodgkin lymphoma EORTC/GELA Favier et al, Cancer 2009;

Fraction survival Long term survival of Hodgkin lymphoma EORTC/GELA Favier et al, Cancer 2009; 115: 1680 -1691

Treatment results in Hodgkin lymphoma at 5 years

Treatment results in Hodgkin lymphoma at 5 years

Treatment of Hodgkin lymphoma summary Stage I/II • Excellent results • Future – maintain

Treatment of Hodgkin lymphoma summary Stage I/II • Excellent results • Future – maintain results – reduce (late) toxicity - reduce/ omit Radiotherapy? - reduce Chemotherapy – PET guided treatment (interim; post Tx)?

“Early” interim FDG-PET predicts prognosis M Hutchings et al, Blood 2006; 107: 52 -9

“Early” interim FDG-PET predicts prognosis M Hutchings et al, Blood 2006; 107: 52 -9

Treatment of Hodgkin lymphoma summary Stage III/IV • Results moderate/good (cf DLBCL!) • Future

Treatment of Hodgkin lymphoma summary Stage III/IV • Results moderate/good (cf DLBCL!) • Future – Improve results without increasing (late) toxicity - more intensive chemotherapy? – PET guided treatment • Interim: escalate if positive? • Post Tx: if positive radiotherapy/ HDT+ Au. SCT?

Treatment for relapsed Hodgkin lymphoma • 15 -30% of all HL patients will relapse

Treatment for relapsed Hodgkin lymphoma • 15 -30% of all HL patients will relapse and require secondline treatment • High-dose chemotherapy and autologous stem cell transplantation: - superior over conventional chemotherapy (Linch et al. , Lancet 1993, Schmitz et al. , Lancet 2002) - remains the standard of care for relapsed HL (except very late relapse? )

High Dose CT + Auto. SCT in relapsed HL PFS @ 5 yrs %

High Dose CT + Auto. SCT in relapsed HL PFS @ 5 yrs % OS @ 5 yrs % Relapse 45 -60 50 -65 Primary resistant 20 -30

The reverse of the success Successfull treatment of HL Long term survival Late effects

The reverse of the success Successfull treatment of HL Long term survival Late effects of treatment

m Hodgkin: Late Toxicity of Treatment • Excess mortality – secondary malignancies – cardiac

m Hodgkin: Late Toxicity of Treatment • Excess mortality – secondary malignancies – cardiac disease • Excess morbidity / decreased Q. O. L – – cardiac disease pulmonary disease infertility fatigue

m. Hodgkin : Late Toxicity of Treatment Secondary Malignancies

m. Hodgkin : Late Toxicity of Treatment Secondary Malignancies

m. Hodgkin : Late Toxicity of Treatment Cardiac disease • coronary insufficiency myocardial infarction

m. Hodgkin : Late Toxicity of Treatment Cardiac disease • coronary insufficiency myocardial infarction RR 1. 9 - 3. 7 • acute cardiac arrest RR 1. 9 - 3. 1 • pericarditis • cardiomyopathy • valvular abnormalities RR 1. 4 - 5. 1

m. Hodgkin : Late Toxicity of Treatment Risk Factors for Cardiac Disease • Mediastinal

m. Hodgkin : Late Toxicity of Treatment Risk Factors for Cardiac Disease • Mediastinal RT dose > 30 Gy • Orthovolt RT (before 1967) • Adriamycine containing CT • Age at RT < 20 yr • Hypertension

Veranderingen bestralingsgebied H 9 CT+RT klierregio Klassiek mantelveld Dank aan: R vd Maazen H

Veranderingen bestralingsgebied H 9 CT+RT klierregio Klassiek mantelveld Dank aan: R vd Maazen H 10 CT+RT klier

Treatment of Hodgkin lymphoma • Progress can only be made by including patients in

Treatment of Hodgkin lymphoma • Progress can only be made by including patients in clinical studies!!