Radiation Oncology/Hodgkin/Early stage favorable

Hodgkin's Lymphoma: Early Stage Favorable Guidelines American College of Radiology; 2008 18812149 -- "ACR Appropriateness Criteria on Hodgkin's lymphoma: favorable prognosis stage I and II." (Das P, J Am Coll Radiol. 2008 Oct;5(10):1054-66.) Guideline link Favorable prognostic factors NCCN guidelines: no bulky disease, 1-3 involved regions, 1 extranodal site, no B symptoms, ESR <50 ACR appropriateness criteria: no bulky mediastinal disease, 1-3 involved regions, no B symptoms EORTC: age <=50, no bulky mediastinal adenopathy, 1-3 involved regions, no B symptoms and ESR <50, B symptoms and ESR <30 RT Alone: Field Size If patients negative subdiaphragmatic disease by staging laparotomy, Mantle field alone sufficient compared with STNI If patients clinically negative, Mantle field alone insufficient, however, STNI sufficient without requiring surgical staging EORTC H7-Very Favorable -- no staging laparoscopy + Mantle RT 1997 ASTRO Abstract -- "Combination of radiotherapy and chemotherapy is advisable in all patients with clinical stage I-II Hodgkin's disease. Six-year results of the EORTC-GPMC controlled clinical trials 'H7-VF', 'H7-F' and 'H7-U'." (Noordijk EM, Int J Radiat Oncol Biol Phys 1997; 39(2):S173 Very favorable group subset (female, age <40, stage IA, NS/LP histology, ESR <50) treated with Mantle only, without PA field Outcome: 6-year RFS 73%, OS 96% Conclusion: Relapse rate unacceptably high in these clinically staged patients with Mantle RT only; arm closed EORTC H6-Favorable (1982-1988) -- staging laparoscopy + Mantle RT vs clinical staging + STNI Randomized. 262 patients, favorable prognosis (1-2 nodal areas, no bulky disease, no B symptoms and ESR <50, B symptoms and ESR <30). Arm 1) No staging laparotomy, Mantle + PA RT 40 Gy vs Arm 2) Staging laparotomy (-), Mantle RT 40 Gy 1993 7693881 -- ""Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group." (Carde P, J Clin Oncol. 1993 Nov;11(11):2258-72.) Median F/U 5.3 years Outcome: In patients undergoing lap, 33% found lap (+). 6-year FFP laparoscopy + Mantle 83% vs Mantle + PA 78% (NS); 6-year OS 89% vs 93% (NS) Conclusion: No difference between surgical staging + mantle vs clinical staging + STNI EORTC H5-Favorable (1977-82) -- Mantle 40 Gy vs STNI 40 Gy Randomized. 198 patients, favorable (age <=40, ESR <=70, LP/NS, Stage I or Stage II without mediastinal involvement), negative staging laparotomy. Arm 1) Mantle RT 40 Gy vs Arm 2) Mantle RT + PA RT (T11-L4) 40 Gy 1988 2578012 -- "Clinical stages I and II Hodgkin's disease: a specifically tailored therapy according to prognostic factors." (Carde P, J Clin Oncol. 1988 Feb;6(2):239-52.) Median F/U 5.3 years Outcome: 6-year RFS mantle 74% vs mantle+PA 72% (NS); 6-year OS 96% vs 89% (NS) Conclusion: In surgically staged patients, more limited RT (mantle alone) is sufficient RT Alone: Dose German HD4 (1988-1994) -- All IFRT 40 Gy, EFRT 40 Gy vs EFRT 30 Gy Randomized. 376 patients, Stage I-II, no risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated ESR, 3+ involved areas). Involved field RT 40 Gy. Arm 1) EFRT 40 Gy vs Arm 2) EFRT 30 Gy. No chemotherapy 2001 11387364 -- "Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: long-term results of a randomized trial of radiotherapy alone." (Duhmke E, J Clin Oncol. 2001 Jun 1;19(11):2905-14.) Median F/U 7.2 years Outcome: 7-year RFP 40 Gy 78% vs 30 Gy 83% (NS); 7-year OS 91% vs 96% (NS). Worse outcome (RFS 72% vs 84%) with protocol violations Conclusion: 30 Gy dose adequate for clinically noninvolved areas RT vs Chemo-RT German HD7 (1993-1998) -- ABVD x2 + EFRT vs EFRT alone Randomized. 650 patients, Stage IA-IIB without risk factors. Treated with 1) RT alone vs. 2) ABVD x 2 cycles + RT RT same in both arms, given as EFRT 30 Gy + IFRT 10 Gy 2007 17606976 -- "Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial." (Engert A, J Clin Oncol. 2007 Aug 10;25(23):3495-502.). Median F/U 7.2 years 7-year outcome: no difference in survival (92% vs. 94%, NS), but significant difference in DFS RT alone 67% vs. CRT 88% (SS). Treatment relapse more successful for RT only arm Second malignancies: no difference, 0.8% per year, highest in older patients & B-symptoms Conclusion: Combined modality more effective than EF-RT alone EORTC H8-Favorable (1993-1999) -- MOPP-ABV x3 + IFRT vs STNI alone Randomized. 542 patients, Stage I-II supradiaphragmatic HD, favorable (Prognostic score using EORTC H7 criteria 1-5). Arm 1) MOPP-ABV x3 cycles + IFRT (36 Gy if CR, 40-44 Gy if PR) vs. Arm 2) STNI alone (36 Gy + 4 Gy boost to involved fields) 2007 17989384 -- "Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease." (Ferme C, N Engl J Med. 2007 Nov 8;357(19):1916-27.). Median F/U 7.7 years H8-F Outcome: 5-year EFS MOPP-ABV + IFRT 98% vs. STNI 74% (SS); 10-year OS 97% vs. 92% (SS) Conclusion: For favorable disease, MOPP-ABV x3 cycles + IFRT is superior to STNI EORTC H7-Favorable (1988-1993) -- EBVP x6 + IFRT vs STNI alone Randomized. 333 patients with Stage I supradiaphragmatic HL, favorable (prognostic score 1-5). No staging laparotomy. Arm 1) STNI alone (36 Gy + 4Gy boost to involved fields) vs. Arm 2) EBVP x6 cycles + IFRT (36-40 Gy) 2006 16754934 — "Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials." (Noordijk EM, J Clin Oncol. 2006 Jul 1;24(19):3128-35.) Median F/U 8.7 years Outcome: 10-yr EFS STNI 78% vs. EBVP+IF 88% (SS). OS similar at 92%. Conclusion: Combined EBVP x6 + IFRT is superior STNI alone Chemo-RT: RT Dose EORTC H9-Favorable (1998-2004) -- EBVP x6 followed IFRT 36 Gy vs IFRT 20 Gy vs No RT Randomized. Arm 3 stopped early due to >20% of failure. 783 favorable Stage I-II patients enrolled, 619 achieved CR(u) on EBVP x6 and were randomized. Arm 1) 36 Gy IF-RT Arm vs. 2) 20 Gy IF-RT vs. 3) no RT. Arm 3 stopped early due to high recurrence (>20%). 2005 ASCO abstract -- "First results of the EORTC-GELA H9 randomized trials: the H9-F trial (comparing 3 radiation dose levels) and H9-U trial (comparing 3 chemotherapy schemes) in patients with favorable or unfavorable early stage Hodgkin’s lymphoma (HL)." (Noordijk, EM ASCO 2005). Median F/U 2.7 years Outcome: 4-year EFS 36 Gy 87% vs 20 Gy 84% vs. no RT 70% (SS). 4 yr OS 98% in all arms. Conclusion: In favorable patients in CR after 6 cycles of EBVP, omission of IFRT leads to unacceptable failure rate; 20 Gy provides comparable control as 36 Gy HD10 (1998-2002) -- 2x2: ABVD x2 vs ABVD x4; IFRT 30 Gy vs 20 Gy Randomized, 2x2. 1370 pts. Stage IA, IB, IIA, IIB (Note only ~7% of patients had B Symptoms) without risk factors (ie, large mediastinal mass, size >1/3 of the maximum thorax diameter, extranodal disease, 3 or more nodal areas, or elevated erythrocyte sedimentation rate (> 50 mm/h for stages IA, IIA and > 30 mm/h for stages IB, IIB). Randomization #1) ABVD x4 cycles vs ABVD x2 cycles, and randomization #2) IFRT 30 Gy vs IFRT 20 Gy 2009; 5-years ASH Abstract #716 Abstract - "Two Cycles of ABVD Followed by Involved Field Radiotherapy with 20 Gray (Gy) Is the New Standard of Care in the Treatment of Patients with Early-Stage Hodgkin Lymphoma: Final Analysis of the Randomized German Hodgkin Study Group (GHSG) HD10." (Engert A; Dec 2009) Median F/U 6.6 years ABVD Outcome: No significant difference in 5-year OS, FFTF, or PFS between ABVD x 4 and ABVD x 2 (OS 97% vs 97%; FFTF 93% vs 91%; PFS 93% vs 91%). IFRT Outcome: No significant difference between IFRT 30 Gy vs 20 Gy (OS 98% vs 97%, FFTF 93% vs 93%, PFS 94% vs 93%). No difference when all 4 arms compared. Conclusion: 2 cycles of ABVD followed by 20 Gy IFRT is the new standard for GHSG for early favorable HD 2010; 5-years 20818855 -- "Reduced Treatment Intensity in Patients with Early-Stage Hodgkin's Lymphoma" (Engert A, N Engl J Med 2010 Aug 12;363(7):640-652.) For comparison of ABVD 2 cycles vs 4 cycles, no difference in FFTF or OS -- 5-yr FFTF 93.0% (ABVD x 4) vs 91.1% (ABVD x 2). For comparison of RT dose, no differences. Percent of grade 3/4 toxicities higher in group of ABVD x 4 vs ABVD x 2, 55% vs 33 % p=sig and XRT 30 Gy vs 20 Gy, 8.7% vs 2.9% p=sig. 6 treatment related deaths occurred in ABVD x 4 vs 1 death in ABVD x 2. Conclusion: ABVD x 2 + 20 Gy IFRT is as effective as ABVD x 4 + 30 Gy. Chemo-RT vs Chemo Alone EORTC H10 -- PET scan guided early treatment adaptation (omission of RT) See details at: H10 Conclusion: "combined-modality treatment resulted in fewer early progressions in clinical stage I/II HL" EORTC H9-Favorable (1998-2004) -- EBVP x6 followed IFRT 36 Gy vs IFRT 20 Gy vs No RT Randomized. Arm 3 stopped early due to >20% of failure. 783 favorable Stage I-II patients enrolled, 619 achieved CR(u) on EBVP x6 and were randomized. Arm 1) 36 Gy IF-RT Arm vs. 2) 20 Gy IF-RT vs. 3) no RT. Arm 3 stopped early due to high recurrence (>20%). 2005 ASCO abstract -- "First results of the EORTC-GELA H9 randomized trials: the H9-F trial (comparing 3 radiation dose levels) and H9-U trial (comparing 3 chemotherapy schemes) in patients with favorable or unfavorable early stage Hodgkin’s lymphoma (HL)." (Noordijk, EM ASCO 2005). Median F/U 2.7 years Outcome: 4-year EFS 36 Gy 87% vs 20 Gy 84% vs. no RT 70% (SS). 4 yr OS 98% in all arms. Conclusion: In favorable patients in CR after 6 cycles of EBVP, omission of IFRT leads to unacceptable failure rate; 20 Gy provides comparable control as 36 Gy