The Impact Of Radiotherapy To Bulky Disease After R-Chop Chemotherapy In Aggressive Lymphoma: Results From Two Prospective Trials Of The German High-Grade Non-Hodgkin-Lymphoma Study Group (Dshnhl) For Elderly Patients With Dlbcl

Purpose/Objective(s)The role of radiotherapy (Rx) in the treatment of aggressive lymphoma remains controversial. Depending on stage, response to chemotherapy, and different chemotherapy regimens, radiotherapy concepts regarding target volume, and doses differ widely in different treatment schedules. To find out the impact of radiotherapy to bulky disease after R-CHOP14 chemotherapy, two prospective trials were designed. In the superior arm of the RICOVER60 trial (which compared 8x vs. 6x R-CHOP14 chemotherapy ± Rituximab) elderly patients with CD20-positive aggressive lymphoma were treated with 6x R-CHOP14 plus radiotherapy to bulky disease (R-CHOP14-Rx). To study the relevance of radiotherapy to bulky disease, a subsequent prospective study was initiated with no radiotherapy after 6x R-CHOP14 (R-CHOP14-no Rx).Materials/MethodsIn the R-CHOP-Rx trial, 117/306 (36%) of patients had Rx to bulky disease after 6x R-CHOP14. In the subsequent R-CHOP-no Rx trial, 166 patients subjected to the same criteria as in the RICOVER60 (R-CHOP-Rx)-trial were recruited and received 6x R-CHOP14 without Rx. The outcome of the patients of both trials was compared with regards to EFS, PFS, and OS. Bulky disease (pretreatment tumor diameter ≥7.5 cm) was irradiated in a modified involved node target volume concept with a total dose of 36 Gy in conventional fractionation.ResultsPatients from both studies were well balanced for many prognostic factors, but patients in R-CHOP-no Rx were older (71 vs. 69 years; p = 0.018) had more advanced-stages (60% vs. 50%; p = 0.037) and more extranodal involvement (63% vs. 53%; p = 0.024), but bulky disease was more frequent in the R-CHOP-Rx-study (38% vs. 29%; p = 0.038). There was no difference in overall response regarding CR/CRu (76% vs. 78%), progressions (55% vs. 65%) or relapse after CR/CRU (8% vs. 10%). Regarding patients with bulky disease, those with additional Rx had a 25% better 18 month EFS (68% vs. 43%; p = 0.002), a 10% better PFS (77% vs. 67%; p = 0.123) and a 4% better OS (80% vs. 76%; p = 0.509) compared to R-CHOP-no Rx. The lower EFS-rate for no Rx-patients was due to patients with bulky disease achieving partial remission (PR) after 6x R-CHOP, whereas in patients with CR/CRu a benefit of additional Rx could not be shown.ConclusionsElderly patients with bulky disease achieving a PR after 6x R-CHOP14 have a significantly better EFS after 36 Gy radiotherapy than those without radiotherapy. Patients in CR/CRU seem to have no additional benefit from radiotherapy to bulky disease. Purpose/Objective(s)The role of radiotherapy (Rx) in the treatment of aggressive lymphoma remains controversial. Depending on stage, response to chemotherapy, and different chemotherapy regimens, radiotherapy concepts regarding target volume, and doses differ widely in different treatment schedules. To find out the impact of radiotherapy to bulky disease after R-CHOP14 chemotherapy, two prospective trials were designed. In the superior arm of the RICOVER60 trial (which compared 8x vs. 6x R-CHOP14 chemotherapy ± Rituximab) elderly patients with CD20-positive aggressive lymphoma were treated with 6x R-CHOP14 plus radiotherapy to bulky disease (R-CHOP14-Rx). To study the relevance of radiotherapy to bulky disease, a subsequent prospective study was initiated with no radiotherapy after 6x R-CHOP14 (R-CHOP14-no Rx). The role of radiotherapy (Rx) in the treatment of aggressive lymphoma remains controversial. Depending on stage, response to chemotherapy, and different chemotherapy regimens, radiotherapy concepts regarding target volume, and doses differ widely in different treatment schedules. To find out the impact of radiotherapy to bulky disease after R-CHOP14 chemotherapy, two prospective trials were designed. In the superior arm of the RICOVER60 trial (which compared 8x vs. 6x R-CHOP14 chemotherapy ± Rituximab) elderly patients with CD20-positive aggressive lymphoma were treated with 6x R-CHOP14 plus radiotherapy to bulky disease (R-CHOP14-Rx). To study the relevance of radiotherapy to bulky disease, a subsequent prospective study was initiated with no radiotherapy after 6x R-CHOP14 (R-CHOP14-no Rx). Materials/MethodsIn the R-CHOP-Rx trial, 117/306 (36%) of patients had Rx to bulky disease after 6x R-CHOP14. In the subsequent R-CHOP-no Rx trial, 166 patients subjected to the same criteria as in the RICOVER60 (R-CHOP-Rx)-trial were recruited and received 6x R-CHOP14 without Rx. The outcome of the patients of both trials was compared with regards to EFS, PFS, and OS. Bulky disease (pretreatment tumor diameter ≥7.5 cm) was irradiated in a modified involved node target volume concept with a total dose of 36 Gy in conventional fractionation. In the R-CHOP-Rx trial, 117/306 (36%) of patients had Rx to bulky disease after 6x R-CHOP14. In the subsequent R-CHOP-no Rx trial, 166 patients subjected to the same criteria as in the RICOVER60 (R-CHOP-Rx)-trial were recruited and received 6x R-CHOP14 without Rx. The outcome of the patients of both trials was compared with regards to EFS, PFS, and OS. Bulky disease (pretreatment tumor diameter ≥7.5 cm) was irradiated in a modified involved node target volume concept with a total dose of 36 Gy in conventional fractionation. ResultsPatients from both studies were well balanced for many prognostic factors, but patients in R-CHOP-no Rx were older (71 vs. 69 years; p = 0.018) had more advanced-stages (60% vs. 50%; p = 0.037) and more extranodal involvement (63% vs. 53%; p = 0.024), but bulky disease was more frequent in the R-CHOP-Rx-study (38% vs. 29%; p = 0.038). There was no difference in overall response regarding CR/CRu (76% vs. 78%), progressions (55% vs. 65%) or relapse after CR/CRU (8% vs. 10%). Regarding patients with bulky disease, those with additional Rx had a 25% better 18 month EFS (68% vs. 43%; p = 0.002), a 10% better PFS (77% vs. 67%; p = 0.123) and a 4% better OS (80% vs. 76%; p = 0.509) compared to R-CHOP-no Rx. The lower EFS-rate for no Rx-patients was due to patients with bulky disease achieving partial remission (PR) after 6x R-CHOP, whereas in patients with CR/CRu a benefit of additional Rx could not be shown. Patients from both studies were well balanced for many prognostic factors, but patients in R-CHOP-no Rx were older (71 vs. 69 years; p = 0.018) had more advanced-stages (60% vs. 50%; p = 0.037) and more extranodal involvement (63% vs. 53%; p = 0.024), but bulky disease was more frequent in the R-CHOP-Rx-study (38% vs. 29%; p = 0.038). There was no difference in overall response regarding CR/CRu (76% vs. 78%), progressions (55% vs. 65%) or relapse after CR/CRU (8% vs. 10%). Regarding patients with bulky disease, those with additional Rx had a 25% better 18 month EFS (68% vs. 43%; p = 0.002), a 10% better PFS (77% vs. 67%; p = 0.123) and a 4% better OS (80% vs. 76%; p = 0.509) compared to R-CHOP-no Rx. The lower EFS-rate for no Rx-patients was due to patients with bulky disease achieving partial remission (PR) after 6x R-CHOP, whereas in patients with CR/CRu a benefit of additional Rx could not be shown. ConclusionsElderly patients with bulky disease achieving a PR after 6x R-CHOP14 have a significantly better EFS after 36 Gy radiotherapy than those without radiotherapy. Patients in CR/CRU seem to have no additional benefit from radiotherapy to bulky disease. Elderly patients with bulky disease achieving a PR after 6x R-CHOP14 have a significantly better EFS after 36 Gy radiotherapy than those without radiotherapy. Patients in CR/CRU seem to have no additional benefit from radiotherapy to bulky disease.