Clinical Outcome of Patients with Follicular Lymphoma and Bulky Disease After Rituximab-CHOP Immunochemotherapy with and without Consolidating Radiotherapy.

As the clinical management of patients with bulky disease remains challenging, many centres apply involved-field radiotherapy (IF-RT) after completion of immunochemotherapy. This strategy remains controversial.

To evaluate the benefit of consolidating IF-RT in addition to immunochemotherapy, we retrospectively analyzed relapse patterns and survival of patients presenting with bulky follicular lymphoma (FL). Bulky disease was defined as abdominal/ mediastinal lymphoma mass >7.5 cm and/ or peripheral lymphoma mass >5 cm. All patients were treated within a prospective randomized trial on 126 patients with FL with six cycles of standard CHOP-chemotherapy in combination with 1, 3 or 6 cycles of Rituximab, followed by consolidating IF-RT in patients with bulky disease. 42 eligible patients with bulky disease were identified and form the foundation of this analysis, of which 26 were irradiated and 16 were not, violating the protocol.

With the exception of number of affected nodal regions, there was no significant difference between the irradiated and the non-irradiated group with regards to presenting characteristics (p > .05). Among all patients, bulks were located below the diaphragm in 91%. A second tumour bulk was present in 9 patients (22%). Female to male ratio was 1.3:1, and the median age at diagnosis was 54 years (range 23–73). According to FLIPI, 10% were classified as low risk (0–1), 45% as intermediate risk (2), and 45% as high risk (3–5). B symptoms were absent in 69%. Eleven patients (26 %) had received one course of Rituximab, 17 (41%) three courses and 14 (33%) six courses. There was no significant difference between the irradiated and the non-irradiated group with regards to previous exposure to immunochemotherapy (p = .628). After a median follow-up of 60 months, a total of 21 patients (50%) had progressed or relapsed and 9 patients (21%) had died. With the exception of one patient who died from congestive heart failure following chemotherapy-related cardiomyopathy, the main cause of death was disease progression or relapse. Highly malignant transformation into diffuse large B-cell lymphoma was observed in 5 cases. In the irradiated group, relapse occurred in 12 of 26 patients. Half of these relapses were located within the original bulk or within the bulk plus a new location, and 50% at a new location altogether; 42% occurred within the previously irradiated area. In the non-irradiated group, 9 of 16 patients relapsed. The corresponding rates regarding relapse location were 67% for original plus new location and 33% for new location only. There was no statistically significant difference between exposure to radiotherapy after immunochemotherapy and the likelihood of a relapse per se (p = .751) or at a specific location (p = .66). At the last follow-up, 31% of irradiated patients had achieved CR and 23% PR. Among the non-irradiated group, the corresponding rates were 25% and 19%. There was no significant difference in remission rates at any staging examination throughout the clinical trial between the two treatment groups (p > .05). 6-year progression-free- and overall survival rates were 52% and 80% after IF-RT and 48% and 73% without IF-RT (p = 1.00, p = .68 respectively).

In this analysis, there was no difference in relapse rate, relapse location, PFS and OS between patients with bulky FL treated with and without consolidating IF-RT. Although patient numbers are limited, this is the first analysis of its kind conducted in the Rituximab era.

No relevant conflicts of interest to declare.