Radiation and Hodgkin s Disease: A Changing Field Sravana Chennupati Radiation Oncology PGY-2
History of Present Illness 19 yo previously healthy male college student began having pain in his R shoulder whenever he drank beer. He researched online and read reports of lymphoma and alcohol related pain. No history of B type symptoms PCP ordered a CXR on 9/24 which revealed a mediastinal mass CT scan revealed a 5.8x3cm anterior mediastinal mass Biopsy by mediastinoscopy on 10/7/10
9/24/10 9/24/10 2/27/09
CT 9/24/10
PET CT 10/14/10
Anterior mediastinal mass
Anterior mediastinal mass Classical Hodgkin lymphoma, nodular sclerosis subtype Immunophenotype:CD15, CD30, Pax-5 EBV negative for EBER-ISH
Hodgkin s demographics 6% of pediatric cancers In the pediatric population, most common in adolescence M:F ratio 4:1 for 3-7yo 3:1 for 7-9 yo 1.3:1 for 9-18yo Presentation Usually supradiaphragmatic Painless cervical adenopathy ~75% of adolescents have mediastinal involvement (less common in children <10yo 33%)
Extended Field Radiation Historically, many of these patients with supradiagphragmatic disease were treated with extended field radiation Mantle Field to doses of 35-44Gy
Radiation alone Musculoskeletal growth inhibition Coronary artery disease Cardiomyopathy Pulmonary fibrosis Infertility Secondary malignancy Reduction of Field Size Reduction of Dose
27 patients with localized disease (Anne Arbor Stage I/II) received a involved field of irradiation to 15,20, 25Gy (depending on the age of the patient). With a median follow up of 7.5 years, FFR was 96% and OS was 100% --In long term follow up, growth deformities were decreased compared to prior
Involved Field Radiation Involved Nodes Cervical Supraclavicular Axilla Mediastinum Hila Spleen Para-aortic Iliac Inguinal Femoral Radiation Field Neck and/or supraclavicular a /infraclavicular Supraclavicular/infraclavicular and lower neck Axilla with or without supraclavicular/infraclavicular Mediastinum, hila (if involved), and infraclavicular and supraclavicular a,b Hila, mediastinum Spleen with or without para-aortic Para-aortic with or without spleen Iliac, inguinal, femoral External iliac, inguinal, femoral External iliac, inguinal, femoral a Upper cervical region is not treated if supraclavicular involvement is an extension of the mediastinal disease. b Prechemotherapy volume is treated except for lateral borders of the mediastinal field. Pediatric Radiation Oncology, Halperin et al 2010
Involved Field Radiation For our patient, this would include the mediastinum, infraclavicular and supraclavicular LN regions Goal: treat only the involved LNs as opposed to all normal sized LNs above the diaphragm. The supporting evidence is that most recurrences in patients occur in or near the initially involved LNs
Radiation alone Reduction of Field Size Reduction of Dose Response Adapted Therapy
METHODS: Restaging was done using clinical exam, CT or MRI. PET was not used routinely. CR: complete clearing or only minor residuals in all previously involved regions. Patients with a good partial remission (PR) of >75% reduction in all tumor sites received 20Gy. Those with <75% reduction received 30Gy. Boost to remaining masses >50mL was 35 Gy in both groups. Radiotherapy was restricted to involved fields.if possible, not the entire region of involvement was included but just the initially enlarged nodal area with a generous safety margin
Results Patient breakdown: From 1995 to 2000, 830 patients were accumulated. Median f/u 38 months TG1: 39% of patients TG2: 27% of patients TG3: 34% of patients Chemotherapy results: CR 22% (27%, 22%, 18%) PR>75% 62% PR<75% 12% Event Free Survival: 90% TG1: 94% TG2: 91% TG3: 84% Overall Survival: 97% RFS: superior for patients with RT after PR (93%) than for those w/o RT after CR (89%). This difference was not significant for patients in the TG1 group
Involved Nodal Radiation There hasn t been a clear consensus on what IN means the German group has recently proposed the target volume should encompass the initial volume of the LN before chemo taking the displacement of the normal tissues into account. Margin of 2cm in axial and 3 cm in craniocaudal direction. In the mediastinum, the amount of displaced lung needs to be taken into account and the margin can be smaller.
RT was given to 19.8 Gy with a boost to 30Gy if >75% residual disease and to 35 Gy if >100mL residual disease. CR= volume reduction >95% and <2mL of tissue based on CT or MRI after 2, 4 or 6 cycles of chemo Study design of the German Society of Pediatric Oncology and Hematology Hodgkin s Disease (GPOH-HD) 2002 study for male patients. Girls were similarly treated with standard two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) instead of vincristine, etoposide, prednisone, and doxorubicin (OE*PA) and cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) instead of cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) in treatment group (TG) 2-3.
Methods cont. and Results Following chemotherapy, RT was delivered to initially involved regions. Treated areas were smaller than involved field RT b/c the classical regions were subdivided Upper and lower neck regions Supraclavicular region Upper, mid and lower mediastinum Upper and lower para-aortic regions Patient breakdown: From 2002 to 2005, 573 (287M & 286F) patients were accumulated. Median f/u 58.6 months TG1: 34% of patients TG2: 24% of patients TG3: 42% of patients Chemotherapy results: CR 22% overall, 32% of TG-1 patients PR>75% 62% PR<75% 12% Event Free Survival at 5yrs: 97.4% TG1: 92% (no difference btwn RT and no RT arm) TG2: 88% TG3: 87% Overall Survival: 89%
Semin Radiat Oncol. 2007;17(3):230-242
PET CT 12/16/10 CT scan on 12/9/10: Anteromediastinal residual lymphoma and is nodular conglomerate currently measures 1.8 x 1.1 x3.0 cm. Previous measurements were 2.7 x1.7 x 4.2cm. The craniocaudad measurement of the superior mediastinal lymph node is currently measures 1.1 x 1.1 x 1.5cm. Previous craniocaudad measurement was 4.0 cm
PET CT 12/16/10
COG-AHOD0831 We will test a response-based approach wherein rapid early responders (RER) to the first 2 cycles of ABVE-PC* will be treated with 2 additional cycles of ABVE-PC* and risk-adapted radiation therapy (RT), whereas slow early responders (SER) will receive 2 cycles of ifosfamide/vinorelbine (IFOS/VINO) (a combination proven to be effective in the AHOD00P1 study) in addition to 2 more cycles of ABVE-PC* and risk-adapted RT. PET is used to outline response clear parameters Clear radiation field parameters
Design: long term f/u of 112 pediatric patients treated on two protocols from 1970-1990. Treatment consisted of 6 cycles chemo (MOPPx6 and alternating ABVDx3+MOPPx3) and IFRT to 15Gy with 10Gy boost for patients with bulky disease or partial response after 2 cycles of chemo Results: Median f/u 21 years. 18 pts developed one or more SMN. Leukemias (4), thyroid (5), breast (6), sarcoma (4). For the combined cohort, incidence of first SMN was 17% at 20 years, 29% at 30 years
Treatment Questions If we use RT, what is the appropriate dose? Should this be dependent on the initial or post chemotherapy extent of disease, bulk of disease, organ at risk, and/or age of patient Can the rapidity and the completeness of the response to chemotherapy define the use of RT, and will functional imaging enhance the precision of this approach When RT is administered, then what is the appropriate target volume? Can RT be restricted to initially involved LN rather than chains (or regions) of nodes? In what settings should RT be directed to areas of initial bulk disease or residual post chemotherapy disease?