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

Abstract

Purpose: To analyze the impact of involved field radiotherapy on local control, freedom from progression, and overall survival in patients with clinical Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based induction chemotherapy. Methods and Materials: From July 1989 through October 1996, 32 patients with clinical Stage III and 27 patients with clinical Stage IV, intermediate grade, 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 was 54 years (range: 26–85 years). There were a total of 172 involved sites of 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 cases) was administered to 28/59 (47%) patients beginning 3–4 weeks after chemotherapy. Sites were irradiated at the discretion of the treating physician. Irradiated and nonirradiated groups were compared in terms of maximum pre-chemotherapy tumor size and University of Texas M. D. Anderson Cancer Center tumor score. Kaplan-Meier estimates of local control per patient, freedom from progression, and overall survival for the irradiated and nonirradiated groups were calculated in terms of the stage of disease and treatment delivered. The resulting curves were compared using the log-rank test. The Cox proportional hazards model was used to assess the prognostic significance of tumor size, tumor score, treatment delivered, and stage. Results: The median length of follow-up for all patients was 53 months (range: 4–96 months). The median tumor size at the start of chemotherapy in irradiated patients was 4.5 cm (range: 0–15 cm) versus 3 cm (range: 0–7 cm) in nonirradiated patients ( p = 0.004). The irradiated and nonirradiated groups were not significantly different in terms of tumor scores. Radiotherapy improved ( 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 ≥4 cm at the start of chemotherapy (5-year rates: 89% for irradiated patients versus 33% for nonirradiated patients). Radiotherapy also improved ( p = 0.003) freedom from progression (5-year rates: 85% for irradiated patients versus 51% for nonirradiated patients) for Stages III and IV combined. On multivariate analysis, radiotherapy was the most significant factor affecting local control and freedom from progression. Overall survival was not significantly different ( p = 0.620) between irradiated and nonirradiated patients (5-year rates: 87% versus 81%, respectively). When Stages III and IV were analyzed separately, radiotherapy improved local control and freedom from progression but not overall survival. Radiotherapy was tolerated reasonably well, with the main toxicity being moderate myelosuppression. Eleven out of 12 (92%) patients with recurrent disease at the time of their last follow-up visit were treated initially with chemotherapy alone. Conclusion: Involved field radiotherapy improved local control and freedom from progression in patients with ≥4 cm Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to CHOP-based induction chemotherapy. Involved field radiotherapy was tolerated reasonably well.