Durable Complete Remission and Long-Term Survival in FDG-PET Staged Patients with Stage III Follicular Lymphoma, Treated with Wide-Field Radiation Therapy.

Michael P Macmanus,H Miles Prince,Gail Ryan,Rachel Brown,Max Wolf,Andrew Wirth,Belinda A Campbell,Rodney J Hicks,Mathias Bressel,John F Seymour

doi:10.3390/cancers12040991

Abstract

Advanced-stage follicular lymphoma (FL) is generally considered incurable with conventional systemic therapies, but historic series describe long-term disease-free survival in stage III disease treated with wide-field radiation therapy (WFRT), encompassing all known disease sites. We report outcomes for patients staged with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and treated with CT-planned WFRT, given as either comprehensive lymphatic irradiation (CLI) or total nodal irradiation (TNI). This analysis of a prospective cohort includes PET-staged patients given curative-intent WFRT as a component of initial therapy, or as sole treatment for stage III FL. Thirty-three PET-staged patients with stage III FL received WFRT to 24–30Gy between 1999 and 2017. Fifteen patients also received planned systemic therapy (containing rituximab in 11 cases) as part of their primary treatment. At 10 years, overall survival and freedom from progression (FFP) were 100% and 75%, respectively. None of the 11 rituximab-treated patients have relapsed. Nine relapses occurred; seven patients required treatment, and all responded to salvage therapies. A single death occurred at 16 years. The principal acute toxicity was transient hematologic; one patient had residual grade two toxicity at one year. With FDG-PET staging, most patients with stage III FL experience prolonged FFP after WFRT, especially when combined with rituximab.

Highlights

Follicular lymphoma (FL) is a common mature B-cell malignancy, characterised by a long natural history, remarkable sensitivity to radiation therapy (RT) [1] and high response rates to immunochemotherapy [2]
We report disease control and toxicities for patients with stage III follicular lymphoma (FL) treated with curative-intent wide-field radiation therapy (WFRT) in the PET era
Two patients were ineligible for analysis, because the RT was delivered for management of relapsed disease after prior therapy

Summary

Introduction

Follicular lymphoma (FL) is a common mature B-cell malignancy, characterised by a long natural history, remarkable sensitivity to radiation therapy (RT) [1] and high response rates to immunochemotherapy [2]. Grade 3B follicular lymphoma is biologically akin to the aggressive diffuse. Cancers 2020, 12, 991 large B-cell lymphoma [3] and is managed . Stage III FL, where disease is confined to nodal sites on both sides of the diaphragm, but without bone marrow or visceral involvement, is typically grouped with stage IV in the “advanced disease” category in current management paradigms and in modern clinical trials [9,10]. Advanced FL is widely considered to be incurable with any current therapy, except allogeneic hematopoietic stem cell transplantation, which is applicable in an extremely small proportion of patients [11]. Complete remission is usually achieved following induction therapy with immuno-chemotherapy [12,13,14]

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