Outcome of hyperfractionated radiotherapy in chemotherapy-resistant non-Hodgkin’s lymphoma

Abstract

Lymphoma patients exhibiting chemotherapy-resistant disease not amenable to further intensive chemotherapy (CT) approaches often have rapidly progressive disease and a poor prognosis. Those with predominant local symptoms are often referred for palliative radiation therapy (RT). Accelerated RT may have a higher biologic effect for such rapidly proliferating tumors. This effect may offer improved local control compared to conventional fractionation. We have selectively treated patients with chemotherapy-resistant Non-Hodgkin’s Lymphoma (NHL) with a hyperfractionated accelerated radiation regimen (40 Gy in 30 fractions, given twice daily over 3 weeks). Their clinical outcome is retrospectively reviewed, focusing on tolerability and local control. There were 34 patients treated with the accelerated RT regimen from 1997 to 2003. Total dose ranged from 3990 cGy to 4050 cGy in 30 fractions, over a median overall treatment time of 22 days (range 5–29 days), given twice daily (BID) to the involved field. Two patients did not complete the treatment as planned but were included in the outcome analysis. Involved field (IF) nodal irradiation was given in 74% (n = 25), and extranodal IF radiation was given to 26% (n = 9). Treatment sites were: neck (n = 7), axilla (n = 9), neck and axilla (n = 2), mediastinum (n = 3), other supradiaphragmatic (n = 7), infradiaphragmatic (n = 6). The median follow-up was 4.41 years. Response was assessed within 3 months of completing RT, and classified as CR (includes unconfirmed CR), PR, and no response (NR). Local control was defined as maintenance of local CR, or lack of progression of the local disease in the PR patients. Failure outside of the RT volume was regarded as distant disease. The median age was 50 years and there were 20 male (59%) and 14 female (41%) patients. At initial diagnosis, 56% (n = 19) were stage I or II, and 44% (n = 15) were stage III or IV. Bulky disease (≥ 10cm) was present in 35% (n = 12). The histology at diagnosis was: follicular: 11, (grade I: 4, grade II: 3, grade III: 4), diffuse large B-cell: 14, PTCL: 2, Burkitt-like: 1, mantle cell: 2, NK cell: 2, plasmacytoma/lymphoma: 1, and T-lymphoblastic: 1. HIV status was positive in 2 patients. CT was given as initial treatment in 32 patients (94%); most commonly CHOP (81%, n = 26). RT alone was given to 2 patients initially, followed by CT as a secondary modality upon relapse of disease. The majority of patients (71%, n = 24) were refractory to initial CT; the remaining patients had relapse of disease after initial treatment. Prior to receiving accelerated RT, 3 patients failed one CT regimen, 15 failed 2 regimens, and 16 failed ≥3 regimens. Stem-cell transplant was received by 15% (n = 5) as part of their salvage treatment prior to accelerated RT. Following accelerated RT, CR was obtained in 32% (n = 11), PR in 65% (n = 22), and 3% (n = 1) had no response (NR). Local control was obtained in 73% of patients. The overall survival was 24%, 15%, and 9% at 1, 2, and 3 years, respectively. Progression of disease was present in 82% of patients at 1 year, and 85% had progression at 2 and 3 years. Disease was locally progressive in 27% of patients. Distant progression of disease was present in 73% of patients at 1 year, and in 76% of patients at 2 and 3 years. The accelerated RT regimen was well tolerated. Grade 1 dermatitis was the most commonly reported side-effect (32%, n = 9). Grade 2 dermatitis, mucositis, esophagitis and dysphagia were reported in one patient each. There were two grade 3 toxicity, dermatitis: 1 and mucositis: 1. Toxicity was not reported/documented in 9 patients. Accelerated hyperfractionated RT for chemotherapy-resistant lymphoma provided local control in 73% of patients, and was well tolerated therefore providing excellent palliation in this group of patients. This result is encouraging and deserves further study with a comparison to conventional fractionation regimens