Dr Haroon ur Rashid Assistant professor Radiotherapyoncology Hodgkin

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Dr Haroon ur Rashid Assistant professor Radiotherapy/oncology

Dr Haroon ur Rashid Assistant professor Radiotherapy/oncology

� Hodgkin lymphoma (HL) is characterized by progressive enlargement of the lymph nodes. �

� Hodgkin lymphoma (HL) is characterized by progressive enlargement of the lymph nodes. � It is considered unicentric in origin and has a predictable pattern of spread by extension to contiguous nodes.

 Etiology is unknown. � worldwide incidence of HL is approximately 2 - 4

Etiology is unknown. � worldwide incidence of HL is approximately 2 - 4 new cases/100, 000 population/yr � HL accounts for approximately 5% of cancers in persons 14 yr of age or younger; � it accounts for approximately 15% of cancers in adolescents (15 -19 yr of age)

� EBV (mixed cellularity subtype) � Family history of HL � Low socioeconomic status

� EBV (mixed cellularity subtype) � Family history of HL � Low socioeconomic status

� Reed-sternberg (RS) cell is the hallmark of Hodgkin lymphoma. � It is a

� Reed-sternberg (RS) cell is the hallmark of Hodgkin lymphoma. � It is a large cell (15 -45 µm) with multiple or multilobulated nuclei. � It is neoplastic clone cell originating from B lymphocyte in lymphnode germinal centers. � It can’t synthesize immunoglobulin due to dysregulation of nuclear factor kappa B (NFĸB).

 Lymphadenopathy ( 90% cases) ◦ Usually painless ◦ Cervical LN/ supraclavicular LN are

Lymphadenopathy ( 90% cases) ◦ Usually painless ◦ Cervical LN/ supraclavicular LN are involved in 6080% ◦ Discrete, elastic/rubbery, nontender ◦ Spreads mostly by contiguity from one chain to another

 Mediastinal adenopathy (60%): ◦ 20% of patient have bulky mediastinal disease. ◦ Persistent

Mediastinal adenopathy (60%): ◦ 20% of patient have bulky mediastinal disease. ◦ Persistent nonproductive cough ◦ Superior vena caval symptoms �Enlargement of neck vessels �Hoarseness of voice �Dyspnoea �Dysphagia

 Splenomegaly Systemic symptoms: ◦ Pel-Ebstein fever ◦ Weight loss >10% in 6 months

Splenomegaly Systemic symptoms: ◦ Pel-Ebstein fever ◦ Weight loss >10% in 6 months ◦ Drenching night sweats Bsymptoms ◦ Mild itching may be present in 15 -25% of cases but it is not considered as B symptoms

 Other less common manifestations are ◦ ◦ ◦ Pulmonary manifestation (17%) Neurological manifestation

Other less common manifestations are ◦ ◦ ◦ Pulmonary manifestation (17%) Neurological manifestation (late presentation) Bone disease(2%) Bone marrow infiltration(5%) Liver disease (2%) Renal manifestation

 Haematological manifestation: ◦ Anemia ◦ Neutropenia(50%) ◦ Lymphocytopenia-Due to hypersplenism or BM infiltration

Haematological manifestation: ◦ Anemia ◦ Neutropenia(50%) ◦ Lymphocytopenia-Due to hypersplenism or BM infiltration ◦ Eosinophilia (50%) – due to IL-5 production ◦ In advance stage DAT test frequently positive with hemolysis ◦ Immune thrombocytopenia may be present in 1 -2% cases

Note: Can be further subclassified as A catagories- Asypmtomatic Bcatagories- presence of B symptoms

Note: Can be further subclassified as A catagories- Asypmtomatic Bcatagories- presence of B symptoms

1) 2) 3) 4) CBC: Normocytic normochromic anemia Neutrophilia in 50% cases Eosinophilia in

1) 2) 3) 4) CBC: Normocytic normochromic anemia Neutrophilia in 50% cases Eosinophilia in 50% cases Lymphocytopenia ESR: raiesd S. ferritin: raised CXR: both PA & Lateral view Mediastinal lymphadenopathy Lymphnode biopsy: Presence of RS cell with diffuse infiltration of lymphocyte, histiocyte and many eosinophil & plasma cell

CXR showing mediastinal mass

CXR showing mediastinal mass

For staging: 1) CT scan of neck, chest, abdomen, pelvis 2) Positron emission tomography

For staging: 1) CT scan of neck, chest, abdomen, pelvis 2) Positron emission tomography (PET) scan 3 ) Technitium-99 bone scintography For classification: 1) Immunohistochemistry

1) 2) 3) 4) 5) 6) 7) Liver function test Renal function test S.

1) 2) 3) 4) 5) 6) 7) Liver function test Renal function test S. electrolyte S. uric acid S. inorganic PO 4 S. calcium DAT

 In general ◦ Combined Chemotherapy ◦ Low dose involved field radiation � Intensity

In general ◦ Combined Chemotherapy ◦ Low dose involved field radiation � Intensity Considered Standard therapy of chemotherapy & volume of radiation depends on ◦ Presence of B symptoms ◦ Initial disease staging ◦ Presence of bulky disease

Chemotherapy regimen Corresponding agents ADVD Doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine ABVD-Rituxan Doxorubicin (Adriamycin), bleomycin,

Chemotherapy regimen Corresponding agents ADVD Doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine ABVD-Rituxan Doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine, rituximab COPP Cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine OPPA ± COPP (females Vincristine (Oncovin), prednisone, procarbazine, doxorubicin (Adriamycin), OEPA ± COPP (males) Vincristine (Oncovin), etoposide, prednisone, doxorubicin (Adriamycin), BEACOPP (advanced stage) Bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine

� Most relapse occurs in 1 st 3 year after diagnosis, but relapse after

� Most relapse occurs in 1 st 3 year after diagnosis, but relapse after 10 year have been reported. � Treatment of relapse Nature of relapse treatment Relapse with favorable at diagnosis Relapse with high risk disease Relapse with in 12 month of diagnosis Chemotherapy + LD-IFRT Chemotherapy + Autologous HSCT + radiotherapy

 With the use of current therapeutic regimens, Disease stage event-free survival (EFS) Overall

With the use of current therapeutic regimens, Disease stage event-free survival (EFS) Overall survival (OS) Early-stage disease + favorable prognostic factors Advanced-stage disease 85 -90% >95% 80 -85% 90% With dose intense chemotherapy OS has approached to 100%

 Advanced stage of disease (Stage IIB, IIIB, or IV) The presence of B

Advanced stage of disease (Stage IIB, IIIB, or IV) The presence of B symptoms The presence of bulky disease Extranodal extension (liver) Male sex Elevated erythrocyte sedimentation rate White blood cell count 11, 500/mm 3 or higher Hemoglobin less than 11. 0 g / d l Histology : classical HL Initially not respond to chemotherapy

� Secondary malignancy � Cardiac toxicity � Pulmonary dysfunction � Thyroid dysfunction � Gonadal

� Secondary malignancy � Cardiac toxicity � Pulmonary dysfunction � Thyroid dysfunction � Gonadal dysfunction & infertility � Growth retardation � Psychosocial problem

 During therapy ◦ ◦ Physical exam (LN, Liver, spleen) Lab: CBC, ESR, LFT

During therapy ◦ ◦ Physical exam (LN, Liver, spleen) Lab: CBC, ESR, LFT Imaging : CT scan, PET Organ toxicity monitoring: cardiac function test, Pulmonary function test � Disease monitoring after treatment: by CXR, CT scan � Long term sequelae monitoring: life long