Radiation Oncology/NHL/Treatment high grade

Aggressive Lymphomas Diffuse large B-cell lymphoma NK/T-cell lymphoma Anaplastic large cell lymphoma Limited-stage aggressive histology Three subgroups of patients with different outcomes and recommended treatment: Based on Stage-modified International Prognostic Index Proposed classification: From 15210737 (No abstract), Miller TP. "The limits of limited stage lymphoma." J Clin Oncol. 2004 Aug 1;22(15):2982-4. "Very Limited" - Stage I or IE with 0 stage-modified risk factors. 90% 5-yr survival. Treat with CHOP(3) + RT. "Limited" - Stage I, IE, II, IIE (no bulky II) with 1 or more risk factors 70% 5-yr survival. Treat with CHOP(3) + RT. "Advanced" - Bulky II or bulky IIE. 50% 5-yr survival. Treat with CHOP(8). Historical Overview RT alone standard of care until 1980. For laparotomy-verified Stage I, results very excellent. For non-verified Stage I, and particularly Stage II, results were poor Stage I: all comers 5-year OS ~50%; laparotomy-staged 5-year OS >90% Stage II: all comers 5-year OS ~20%; laparotomy-staged 35-55% University of Chicago experience suggested that recurrences were not prevented by extended fields, and that Stage II patients should be treated with chemotherapy Around 1980, several small trials demonstrated that adding chemotherapy after RT improved survival. The intent was to control microscopic systemic disease and reduce the size of the radiation fields. Stage I: 5-year RFS 94-100% Stage II: 5-year RFS 72-78% Based on experience in advanced disease, observational studies around the same time suggested that chemotherapy alone was sufficient. CHOP became established as the standard therapy in Stage III/IV disease, and began to be used for Stage I/II trials as well This resulted in SWOG-8736 Phase III trial, which compared CHOP x8 cycles alone to CHOP x3 cycles with involved field RT, in low risk patients (Stage I and non-bulky Stage II). Early results showed a survival benefit for the combined arm, and established it as the standard of care Unfortunately, long-term update (abstract only) showed an excess distant failure rate in the combined modality arm after 5 years, suggesting that CHOP x3 is not sufficient to control the systemic disease in these patients ECOG-1484 Phase III trial randomized higher risk patients (Stage I bulky/extranodal and Stage II) to CHOP x8 cycles alone versus CHOP x8 cycles + involved field RT. There was a disease-free survival benefit, but no overall survival benefit GELA 93-1 Phase III trial evaluated CHOP x4 + involved field RT with dose-intense ACVBP in IPI=0 patients <60 years old. There was a clear survival benefit to ACVBP. This strategy however did not gain wide acceptance in the USA due to its toxicity Finally, GELA 93-4 Phase III trial compared CHOP x4 alone versus CHOP x4 + involved field RT in IPI=0 patients >60 years old. There was no difference in EFS or OS. However, follow-up is still short, and there is a concern about more long-term failures as in SWOG-8736 The already complicated situation became even more complicated with the introduction of Rituxan. Several trials established CHOP-R as superior to CHOP The exact role of RT and CHOP-R in the treatment of Stage I/II aggressive lymphomas needs to be clarified Primary RT British National Lymphoma Investigation, 2004 (1974-1997) 15026794 -- "Long-term follow-up of patients treated with radiotherapy alone for early-stage histologically aggressive non-Hodgkin's lymphoma." (Spicer J, Br J Cancer. 2004 Mar 22;90(6):1151-5.) Retrospective. 377 patients treated with RT alone for early-stage diffuse large-cell lymphoma 10-year cause-specific survival: <60 years 75% vs. >60 years 47% (SS) Conclusion: RT alone not sufficient, even in elderly 1986 3518561 — "Factors predicting survival in adults with stage I and II large-cell lymphoma treated with primary radiation therapy." (Kaminski et al, Ann Intern Med 1986) 148 pts. Stage I-II large cell lymphoma, treated with RT with or without adjuvant chemo. 5-yr freedom-from-relapse was 25% and OS 35% for those with RT on one side of diaphragm; for those with transdiaghragmatic RT or RT + chemo, FFR and OS both 67%. Chemo-RT RT +/- Chemotherapy 6406037, 1983 (1974-78) — "A randomized study of radiotherapy versus radiotherapy plus chemotherapy in stage I-II non-Hodgkin's lymphomas." Nissen NI et al. Cancer. 1983 Jul 1;52(1):1-7. Randomized. 73 pts. Stage I-II. Extended field RT +/- vincristine, streptonigrin, cyclophosphamide and prednisone. Fewer relapses in combined modality group but overall survival similar. Rituximab-Chemotherapy +/- RT Ongoing DSHNHL-2004-3 -- "Phase III Randomized Study of Immunochemotherapy Comprising Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, and Prednisone (R-CHOP) With Versus Without Radiotherapy in Patients With Previously Untreated, Low-Risk, Aggressive, B-Cell Non-Hodgkin's Lymphoma". Also known as UNFOLDER 21/14 study. Arm 1: R-CHOP-21 x6 alone Arm 2: R-CHOP-21 x6 + IFRT Arm 3: R-CHOP-14 x6 alone Arm 4: R-CHOP-14 x6 + RT MD Anderson; 2010 (2001-2007) 20713859 -- "Benefit of Consolidative Radiation Therapy in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP Chemotherapy." (Phan J, J Clin Oncol. 2010 Aug 16. [Epub ahead of print]) Retrospective. 469 patients, DLBCL. Stage I-II 40%, Stage III-IV 60%. Chemo 6+ cycles R-CHOP in 70%, RT given IFRT 30-39.6 Gy in 30% after chemo CR. Median F/U 3 years Outcome: On MVA, RT influenced OS and PFS. In matched-pair analysis (Stage I 44 pairs, all stages 74 pairs), RT improved OS (HR 0.5 and 0.3) Conclusion: Significant improvement in OS and PFS in patients who received consolidative RT after R-CHOP SWOG 0014 (2000-2002) 18413640 -- "Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014." (Persky DO, J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14.) Phase II. 60 patients, aggressive NHL, limited-stage disease and at least one adverse prognostic factor (nonbulky Stage II, age >60, WHO PS2, elevated LDH). R-CHOP x3 followed by IFRT 40-46 Gy. Median F/U 5.3 years Outcome: 2-year PFS 93%, 4-year PFS 88%. 2-year OS 95%, 4-year OS 92%. Compares favorably with historical SWOG 8736 4-year PFS 78% and OS 88% Conclusion: Addition of R to CHOP + IFRT met prespecified criteria of efficacy; but continued relapse Pre-Rituximab Chemotherapy +/- RT GELA LNH93-4 (France) (1993-2002) -- CHOP x4 vs. CHOP x4 + RT Randomized. Stopped early after no difference on interim analysis and new evidence showing Rituximab benefit. 576 patients. Age >60, localized Stage I-II aggressive lymphoma, IPI 0. Arm 1) CHOP x4 alone vs. Arm 2) IF-RT 40 Gy (involved nodes/extranodal + adjuacent uninvolved nodes) 7-year update, 2007 17228021 -- "CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte." (Bonnet C, J Clin Oncol. 2007 Mar 1;25(7):787-92.) 5-year EFS: CHOP 61% vs. CHOP/RT 64% (NS). Survival affected by Stage II and male sex Relapses: CHOP local 47%, distal 37%, both 16%; CHOP-RT in-field 21%, out-of-field 66%, both 13% Second cancers: 29 (14%); 9 in CHOP alone vs. 20 in CHOP-RT Subset analysis (49 patients) showed no benefit to RT in bulky disease either (small #) Conclusion: No advantage to adding RT Comment: As a result of this study and GELA93-1, GELA abandoned RT in first line treatment of localized aggressive lymphoma. CHOP-R is used instead Editorial 17228015 -- "Role of radiation therapy in localized aggressive lymphoma." (Ng AK, J Clin Oncol. 2007 Mar 1;25(7):757-9.) GELA LNH93-1 (France)(1993-2000) -- ACVBP vs. CHOP x3 + RT Randomized. 647 patientss, <61 years, localized Stage I or II aggressive lymphoma (Working Formulation: diffuse mixed, diffuse large (80%), or immunoblastic; or anaplastic according to Kiel), no age-adjusted IPI adverse features. Stage I 67%, extranodal involvement 49%, bulky disease 73%. Arm 1) CHOP x 3 + involved-field RT vs Arm 2) ACVBP plus sequential chemo consolidation (MTX, leucovorin, etoposide, ifosfamide, Ara-C). RT one month after last cycle of CHOP, 39.6 Gy. Involved field was involved nodal group and adjacent uninvolved nodes. 5-years; 2005 15788496 - "ACVBP versus CHOP plus Radiotherapy for Localized Aggressive Lymphoma." (Reyes F, N Engl J Med. 2005 Mar 24;352(12):1197-205.) Median F/U 7.7 years Outcome: 5-year EFS ACVBP 82% vs CHOP-RT 74% (SS), true for both bulky and non-bulky subsets; OS 90% vs 81% (SS) Conclusion: In younger patients, ACVBP + consolidation is better than CHOP x3 + RT Comment: ACVBP arm used higher doses of doxorubicin and cytoxan with higher dose intensity than CHOP and used a consolidation phase with different drugs not used during induction. National Medical Center, Mexico (1989-97) -- Residual disease: RT vs. Observation Randomized. 166 patients, DLBCL, high-intermediate/high clinical risk, with residual disease (<5 cm mass) after chemotherapy. Arm 1) RT 30/20 vs Arm 2) observation. 2005 16260856 — "Residual disease after chemotherapy in aggressive malignant lymphoma: the role of radiotherapy." (Aviles A, Med Oncol. 2005;22(4):383-7.) Median F/U 13.5 years Outcome: 10-yr PFS RT 86% vs observation 32% (SS). Of 57 relapses in the observation arm, 31 were in the site of initial residual disease, 23 disseminated. 10-year OS 89% vs 58% (SS). Conclusion: Salvage RT improves outcome in patients with residual disease after chemotherapy SWOG 8736 (1988-1995) -- CHOP x8 vs CHOP x3 + RT Randomized. 401 patients, intermediate/high grade (Working Formulation), Stage I-IE, or non-bulky (<=10 cm) II/II-E. 67% Stage I, 73% IPI 0-1. Arm 1) CHOP x 8 vs Arm 2) CHOP x 3 + involved field RT. RT dose was 40 Gy, with a boost to 50 Gy for residual disease (majority received 45-50 Gy) 5-years; 1998 9647875 — "Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma." (Miller TP, N Engl J Med. 1998 Jul 2;339(1):21-6.) Outcome: 5-yr PFS CHOP-RT 77% vs CHOP 64% (SS), OS 82% vs 72% (SS). PFS by IPI: 0-1 77%, 2 60%, 3 34% Toxicity: 2 deaths (CHOP arm neutropenia, RT arm RILD), Grade 4 CHOP 40% vs. RT 30% (p=0.06) Conclusion: CHOP x3 + RT superior to CHOP x8 8-years; 2001 Abstract "CHOP Alone Compared to CHOP Plus Radiotherapy for Early Stage Aggressive Non-Hodgkin's Lymphomas: Updated of the SWOG Randomized Trial." (Miller TP, Blood 98: 724A, 2001, abstr 3024.) Median F/U 8.2 years Outcome: 7-year FFS curves overlap (NS), 9-year OS curves overlap (NS). Continuous decline, with no plateau By risk factors (age >60, elevated LDH, PS >1, Stage II): 5-year OS no RFs 94%, 1 RF 71%, 3 RFs 50% Conclusion: Excess late (>5 years) relapses and deaths in CHOPx3-RT arm negate initial benefit. CHOPx3 + RT remains best standard treatment for Stage I and non-bulky Stage II, but optimal treatment may include more/different systemic chemo Histology; 2004 ASH Abstract -- "Histologic Subtypes Do Not Confer Unique Outcomes in Early-Stage Lymphoma: Long-Term Follow-Up of SWOG 8736." (Spier CM, Blood (ASH Annual Meeting Abstracts) 2004 104: Abstract 3263) Outcome: 10-year OS and FFS no difference, no survival plateau. No difference by histology. Only 1 CNS failure (in a patient with testis involvement; none in Burkitt's Lymphoma) Conclusion: Histology should not be used to exclude early stage intermediate/high grade patients Comment: Trial was trying to address if addition of RT can reduce amount of chemo required. Results from the abstract update suggest that 3 cycles of CHOP are insufficient, even in this reasonably low risk population, due to higher rate of late (>5 years) failures ECOG 1484 (1984-1992) - CHOP x 8 + RT vs CHOP x8 Randomized. 352 patients, 172 assessable for +/- RT. Diffuse aggressive lymphoma (Working Formulation: diffuse large cell (80%), diffuse mixed large cell and small cell, and diffuse small cleaved cell). Stage I with risk factors (mediastinal or retroperitoneal involvement; or bulky disease > 10 cm), Stage IE, Stage II-IIE (68%). Patients in CR after 8 cycles of CHOP were randomized to Arm 1) 30 Gy involved-field RT vs Arm 2) observation. If PR, 40 Gy. 6-years; 2004 15210738 — "Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484." (Horning SJ, J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21.) Median F/U for CR patients 12 years CHOP x8 outcome: 69% assessable. CR 71% (n=172 assessable for +/- RT), PR 29% (treated with RT). Most patients with Stage II bulky disease had PR RT randomization outcome (n=172): 6-year DFS RT 73% vs. control 56% (SS, p=0.05). 10-year OS 68% vs. 65% (NS) RT boost outcome (n=71): 31% CR rate, median OS 9.9 years. Overall, 10-year DFS 78% for all patients treated with chemo + RT Conclusion: After CHOP x8, low-dose RT provided better local control and DFS, with no impact on OS Historical Series British Columbia (1980-98) 308 pts. Chemo x 3 followed by involved-field RT. 2002 11773170 — "Brief chemotherapy and involved-region irradiation for limited-stage diffuse large-cell lymphoma: an 18-year experience from the British Columbia Cancer Agency." Shenkier TN et al. J Clin Oncol. 2002 Jan 1;20(1):197-204. Median f/u 86 mo. OS and PFS 80% and 81% at 5 years and 63% and 74% at 10 years. Subgroups with high risk disease based on IPI had worse outcomes and need more aggressive treatment. 1987 3296898, 1987 — "Brief chemotherapy and involved field radiation therapy for limited-stage, histologically aggressive lymphoma." Connors JM et al. Ann Intern Med. 1987 Jul;107(1):25-30. Original report Milan, 1993 (1985-90) - 8478665 — "Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas." Tondini C et al. J Clin Oncol 1993 Apr;11(4):720-5. Non-randomized. 183 pts. CHOP x 4 (or x6 if only PR). RT to 40 Gy to involved sites and 36 Gy to adjacent uninvolved regions. CR 98% after chemo/RT. 5-year RFS and OS 83%. Tucson/British Columbia, 1989 - 2671279 — "Long-term follow-up and analysis for prognostic factors for patients with limited-stage diffuse large-cell lymphoma treated with initial chemotherapy with or without adjuvant radiotherapy." Jones SE et al. J Clin Oncol. 1989 Sep;7(9):1186-91. 142 pts. Two prospective trials, treated with CHOP with or without RT. RFS 82% at 5 yrs. No difference between groups. NCI, 1989 2788716 -- "Treatment of localized aggressive lymphomas with combination chemotherapy followed by involved-field radiation therapy." (Longo DL, J Clin Oncol. 1989 Sep;7(9):1295-302.) Prospective. 47 patients, Stage I/IE with aggresive lymphoma. Treated with Pro-MACE-MOPP x4 cycles followed by 40 Gy IFRT. Median F/U 3.5 years Outcome: 96% CR; toxicity 5% hospital admissions Conclusion: Safe and effective Primary Chemotherapy CHOP +/- Rituxan DSHNHL RICOVER-60 (2000-2005) -- CHOP-14 vs. CHOP-21, R-CHOP vs. CHOP Randomized, 4 arms. 1222 patients, DLBCL, age >60. Stage I-II 50%, Stage III-IV 50%. 2x2 design, CHOP-14 6 cycles vs. 8 cycles; and Rituximab vs. placebo. Arm 1) CHOP-14 x6 vs. Arm 2) CHOP-14 x8 vs. Arm 3) R-CHOP-14 x6 vs. Arm 4) R-CHOP-14 x8. RT 36 Gy given if initial bulky disease or extranodal disease (34%). Primary end point EFS. 3-years; 2008 18226581 -- "Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60)." (Pfreundschuh M, Lancet Oncol. 2008 Feb;9(2):105-16. Epub 2008 Jan 15.) Outcome: 3-year EFS CHOP-14 x6 47% vs. CHOP-14 x8 53% vs. R-CHOP-14 x6 66% vs. R-CHOP-14 x8 63%; OS 68% vs. 66% vs. 78% vs. 72%. Using CHOP-14 x6 cycles as baseline, all intensified regimens SS improved EFS; OS only for R-CHOP-14 x6 cycles Conclusion: Six cycles of R-CHOP-14 should be preferred treatment in elderly, no benefit for more cycles of chemo GELA 98-5 (1998-2000) -- CHOP vs. R-CHOP Randomized. 399 pts. 60-80 years old, Stage II-IV. Randomized to CHOP x8 vs R-CHOP x8 (both arms CHOP-21) 5-years, 2005 15867204 -- "Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte." (Feugier P, J Clin Oncol. 2005 Jun 20;23(18):4117-26.). Median F/U 5-years. Median follow-up 5 yrs. 5-year EFS: CHOP 29% vs. R-CHOP 47% (SS). Median EFS CHOP 1.1 years vs. R-CHOP 3.8 years (SS) 5-year outcomes: PFS 30% vs. 54% (SS); DFS 45% vs. 66% (SS); OS 45% vs. 58% (SS) 2002: 11807147 — "CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma." Coiffier B et al. N Engl J Med. 2002 Jan 24;346(4):235-42. Conclusion: Addition of Rituxan leads to significant improvement for elderly patients; benefit in both low- and high-risk groups by IPI ECOG 4494 / CALGB / SWOG Intergroup -- CHOP vs. R-CHOP Abstract, 45th annual ASH meeting (Dec 2003) — "Rituximab-CHOP versus CHOP with or without maintenance rituximab in patients 60 years of age or older with diffuse large B-cell lymphoma (DLBCL): an update." Habermann TM et al. Blood 2004; 104:40a (abstract 127). MabThera trial -- CHOP vs. R-CHOP Randomized. 18 countries. 824 patients, <60 with DLBCL, Stage II-IV, IPI 0-1, or bulky Stage I. Treated with CHOP x6 vs. CHOP-R x6. RT given for bulky and extranodal disease 3 years, 2006 16648042 -- "CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group." (Pfreundschuh M, Lancet Oncol. 2006 May;7(5):379-91.). Median F/U 2.8 years 3-year outcomes: OS CHOP-R 93% vs. CHOP 84% (SS), EFS 79% vs. 59% (SS) Prognostic groups: favorable (IPI=0, no bulk) and unfavorable (IPI=1, bulk, or both) Conclusion: CHOP-R is effective ACVBP vs. CHOP GELA, 2003 - 12920037 - "Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma." Tilly H et al. Blood. 2003 Dec 15;102(13):4284-9. Randomized. Poor-risk aggressive NHL, elderly pts (ages 61-69), at least one aggressive factor on age-adjusted IPI. Randomized to ACVBP vs CHOPx8. No XRT. ACVBP consisted of induction phase and CNS prophylaxis followed by sequential consolidation. 635 pts. No diff in CR. 5-year event free survival 39% (ACVBP) vs 29%, and overall survival 46% vs 38%. More CNS relapses in CHOP group. Conclusion: Despite higher toxicity, ACVBP results in better EFS and OS Historical Series 1980 7002279, 1980 — "Management with chemotherapy only of stage I and II malignant lymphoma of aggressive histologic types." Cabanillas F et al. Cancer. 1980 Dec 1;46(11):2356-9. 30 pts. CR in 88%. 85% freedom-from-relapse. 1979 85006, 1979 — "Chemotherapy of localised histiocytic lymphoma." Miller TP. Lancet. 1979 Feb 17;1(8112):358-60. Original CHOP paper by Miller and Jones? Chemotherapy regimens CHOP - cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisone H is for hydroxydaunomycin (doxorubicin). O is for Oncovin (vincristine). ACVBP doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone. Often used with a consolidation chemotherapy regimen using different drugs. Hyper-CVAD - cytoxan, vincristine, Adriamycin, decadron RICE - Rituxan, Ifosfamide, Carboplatin, Etoposide ESHAP - Etoposide, Methylprednisolone (Solu-medrol), High-dose Ara-C, and Cisplatinum For CSF prophylaxis: IV and intrathecal methotrexate and ara-C Chemotherapy technique USA Survey, 2004 15381684 -- "Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin's lymphoma: a nationwide study." (Lyman GH, J Clin Oncol. 2004 Nov 1;22(21):4302-11.) Survey. 567 oncology practices, 4522 patients treated with CHOP, CHOP-R, CNOP. Relative dose-intensity (RDI): 53% patients received RDI less than 85% of minimum 6-cycles; Elderly: 60% patients received <85% of minimum RDI Predictors: age >60, advanced disease, poor PS, no prophylactic colony-stimulating factor use Conclusion: Patients frequently receive reduced dose in potentially curable NHL; better support recommended RT technique Dose-Response British National Lymphoma Investigation; 2011 (1997-2005) 21664710 -- "Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial." (Lowry L, Radiother Oncol. 2011 Jul;100(1):86-92.) Randomized, 640 pts w/ stage I-IV, aggressive non-Hodgkin's lymphomas, mostly DLBCL. Most treated as part of first-line therapy; 79% received prior chemotherapy. Control arm: 40-45 Gy in 2 Gy fractions. Experimental arm: 30 Gy in 15 fractions. No difference in complete response rate, freedom from local progression, overall survival between dose levels. 5-year freedom from local progression 83.5% high dose vs. 82.2% low dose. Separate group of indolent NHL randomized to 40-45 Gy vs 24 Gy also showed no difference in outcomes. Review: 12633576, 2003 — "Influence of differing radiotherapy strategies on treatment results in diffuse large-cell lymphoma: a review." Nieder C et al. Cancer Treat Rev. 2003 Feb;29(1):11-9. For pts achieving CR, 30 - 30.6 Gy for <6 cm tumor, 40 Gy for 7-10 cm, 45 Gy for larger. For less than CR, insufficient data. MDACC; 2001 (1988-96) 11163493 -- "Dose-response analysis for radiotherapy delivered to patients with intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to CHOP-based induction chemotherapy." (Wilder RB, Int J Radiat Oncol Biol Phys. 2001 Jan 1;49(1):17-22.) 294 pts w/ Stage I-IV, intermediate-grade or large-cell immunoblastic lymphomas. Treated on 2 prospective trials. Recommend dose of 30 Gy - 30.6 Gy for tumors < 3.5 cm with CR after 3 cycles of chemotherapy. Recommend 39.6 Gy for tumors 3.5-10 cm with CR. Recommend 45 Gy for tumors > 10 cm with CR. U. Florida; 1999 10348285 -- "The impact of radiotherapy dose and other treatment-related and clinical factors on in-field control in stage I and II non-Hodgkin's lymphoma." (Kamath SS, Int J Radiat Oncol Biol Phys. 1999 Jun 1;44(3):563-8.) 285 pts w/ Stage I-II NHL (72 low grade, 92 intermediate to high grade, 21 unclassified). 159 treated w/ RT alone, 126 combined modality. 95 treatment failures with 12 in-field failures. Most failures occurred in contiguous non-irradiated areas. Whole-abdomen irradiation Washington University; 1994 (1978-1990) 8029434 -- "Non-Hodgkin lymphoma: whole-abdomen irradiation as an adjuvant to chemotherapy." (Valicenti RK, Radiology. 1994 Aug;192(2):571-6.) Retrospective. 39 patients with abdominal NHL, modified three-way abdomen irradiation Toxicity: decreased blood counts, enteritis Conclusion: Safe adjunct to chemo