Impact of involved field radiotherapy after chop-based chemotherapy on stage III-IV, intermediate grade and large-cell immunoblastic lymphomas

Purpose: To analyze the impact of involved field radiotherapy on local cont rol, freedom from progression, and overall survival in patients with clinic al Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to cyclophosphamide, doxorubicin, vincristine, and prednison e (CHOP)-based induction chemotherapy. Methods and Materials: From July 1989 through October 1996, 32 patients wit h clinical Stage III and 27 patients with clinical Stage IV, intermediate g rade, or large-cell immunoblastic lymphomas were prospectively enrolled on two protocols at The University of Texas M. D. Anderson Cancer Center. None had previously undergone treatment for lymphoma. The median patient age wa s 54 years (range: 26-85 years). There were a total of 172 involved sites o f disease at presentation. All 59 patients received CHOP-based chemotherapy . At least six cycles of chemotherapy were delivered to 92% of the patients . Involved field radiotherapy (39.6-40.0 Gy in 20-22 fractions in 74% of ca ses) was administered to 28/59 (37%) patients beginning 3-4 weeks after che motherapy. Sites were irradiated at the discretion of the treating physicia n. Irradiated and nonirradiated groups were compared in terms of maximum pr e-chemotherapy tumor size and University of Texas M. D. Anderson Cancer Cen ter tumor score. Kaplan-Meier estimates of local control per patient, freed om from progression, and overall survival for the irradiated and nonirradia ted groups were calculated in terms of the stage of disease and treatment d elivered. The resulting curves were compared using the log-rank test. The C ox proportional hazards model was used to assess the prognostic significanc e of tumor size, tumor score, treatment delivered, and stage. Results: The median length of follow-up for all patients was 53 months (ran ge: 4-96 months). The median tumor size at the start of chemotherapy in irr adiated patients was 4.5 cm (range: 0-15 cm) versus 3 cm (range: 0-7 cm) in nonirradiated patients (p = 0.001). The irradiated and nonirradiated group s were not significantly different in terms of tumor scores. Radiotherapy i mproved (p = 0.001) local control (5-year rates: 89% versus 52%) for Stages III and IV combined. This benefit was due to the dramatic improvement (p = 0.0009) in local control for patients with lymphomas measuring greater tha n or equal to4 cm at the start of chemotherapy (5-year rates: 89% for irrad iated patients versus 33% for nonirradiated patients). Radiotherapy also im proved (p = 0.003) freedom from progression (5-year rates: 85% for irradiat ed patients versus 51% for nonirradiated patients) for Stages III and IV co mbined. On multivariate analysis, radiotherapy was the most significant fac tor affecting local control and freedom from progression. Overall survival was not significantly different (p = 0.620) between irradiated and nonirrad iated patients (5-year rates: 87% versus 81%, respectively). When Stages II I and IV were analyzed separately, radiotherapy improved local control and freedom from progression but not overall survival. Radiotherapy was tolerat ed reasonably well, with the main toxicity being moderate myelosuppression. Eleven out of 12 (92%) patients with recurrent disease at the time of thei r last follow-up visit were treated initially with chemotherapy alone. Conclusion: Involved field radiotherapy improved local control and freedom from progression in patients with greater than or equal to4 cm Stage III-IV , intermediate grade, or large-cell immunoblastic lymphomas that responded to CHOP-based induction chemotherapy. Involved field radiotherapy was toler ated reasonably well. (C) 2000 Elsevier Science Inc.