IINVOLVED FIELD RADIATION THERAPY (IFRT) ± LOW-DOSE TOTAL BODY IRRADIATION (TBI) FOR LOCALIZED INDOLENT B-NHL: FINAL ANALYSIS OF RANDOMIZED EORTC TRIAL 20971-22997
Author(s): ,
Igor Aurer
Affiliations:
Division of Hematology, Department of Internal Medicine,University Hospital Centre Zagreb,Zagreb,Croatia;Medical School,University of Zagreb,Zagreb,Croatia
,
Pierre Soubeyran
Affiliations:
Institute Bergonie,Bordeaux,France
,
Philip Poortmans
Affiliations:
Radiation Oncology,B.Verbeten Instituut,Tilburg,Netherlands;Radiation Oncology,Institut Curie- Hôpital de Paris,Paris,France
,
Max Beijert
Affiliations:
Radiation Oncology,UMC Groningen,Groningen,Netherlands
,
Samy El Badawy
Affiliations:
Radiation Oncology,National Cancer Institute,Cairo,Egypt
,
Lena Specht
Affiliations:
Oncology,Rigs Hospitalet University of Copenhagen,Copenhagen,Denmark
,
Bastiaan Ta
Affiliations:
Radiation Oncolgy,Maastro Clinic,Maastricht,Netherlands
,
Richard van der Maazen
Affiliations:
Radiation Oncology,Radboud University Medical Center,Nijmegen,Netherlands
,
Francisca Ong
Affiliations:
Radiation Oncology,Medisch Spectrum Twente,Enschede,Netherlands
,
Anouk Neven
Affiliations:
Headquarters,EORTC,Brussels,Belgium
,
Bart Meulemans
Affiliations:
Headquarters,EORTC,Brussels,Belgium
,
Catherine Fortpied
Affiliations:
Headquarters,EORTC,Brussels,Belgium
Berthe MP Aleman
Affiliations:
Radiation Oncology,Netherlands Cancer Institute,Amsterdam,Netherlands
EHA Library. Aurer I. 06/12/20; 293653; EP1164
Prof. Dr. Igor Aurer
Prof. Dr. Igor Aurer
Contributions
Abstract

Abstract: EP1164

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Indolent B-NHLs (iNHL) are incurable with standard systemic therapy. Some patients with localized disease can be cured with radiation therapy (RT); addition of systemic therapy has not been shown to increase the cure rate. iNHL are radiosensitive, responding to very low doses of radiation. We therefore hypothesized that low-dose TBI might improve the cure rate of IFRT by eliminating microscopic disseminated disease.

Aims
The EORTC Lymphoma Group and EORTC Radiation Oncology Group performed this phase 3 randomized trial to test whether addition of low-dose TBI prior to IFRT improve outcomes of patients with localized iNHL.

Methods
Patients with previously untreated iNHL stages 1 and 2, in whom nodal areas that had to be irradiated could be encompassed in a single radiation volume were randomized to receive TBI (total 1.5 Gy in 10 fractions given in 2 weekly courses, 2 weeks apart) followed after 4 weeks by IFRT, or IFRT only (total dose 26-40 Gy in 13-20 fractions). The primary endpoint was PFS. Secondary endpoints included response to TBI and OS. The original plan called for inclusion of 344 patients in 6 years. The enrollment was closed due to poor accrual after 9 years and the final analysis additionally postponed because the outcome of the control arm was better than anticipated.

Results
Between 2000 and 2009, 203 patients were entered into the trial. Seven patients were ineligible, mostly due to histology; 4 did not start the allocated treatment. Baseline clinical characteristics (gender, stage, pathological subtype) were well balanced between treatment arms. Median age was 54 years (range 21-85); 84% of the patients had follicular lymphoma; 36% had stage 1 disease without measurable tumor mass (whole tumor extirpated for diagnostic purposes), 39% stage 1 with measurable tumor mass and 25% stage 2. Toxicity of TBI, evaluated before starting IFRT, was minimal: 1% of patients had moderate mucosal edema, 1% patchy mucositis and 1% ulceration. In the TBI+IFRT arm, CTCAEv2 gr. ≥3 neutropenia, thrombocytopenia and anemia were observed in 3, 1 and 1% of patients, respectively, in comparison to none in the IFRT-only arm. TBI resulted in CR or CRu in 33.3% and IFRT (±TBI) in 81% of patients with a measurable tumor mass. There were no significant differences in response rates between the two arms. After a median follow-up of 13 years, PFS rates in the TBI+IFRT arm were 67% at 5 years, 56% at 10 years and 41% at 15 years and in the IFRT-only arm 58%, 46% and 33% (Fig). This difference was not significant (HR 0.9; 95% CI=0.62-1.3, p=0.559 adjusted for stage and LDH). OS rates at respective time-points were 89%, 83% and 67% in the TBI+IFRT arm and 92%, 84% and 68% in the IFRT-only arm (HR 1.21 (0.69-2.12), p=0.501 adjusted for stage) (Fig). Of the 49 (24%) of patients that died, in 10 the cause of death was lymphoma, in 16 second primary tumor, in 5 cardiovascular disease and in 18 other or unknown causes. The distribution of causes of death was not significantly different between the two arms.

Conclusion
The addition of low-dose TBI to IFRT does not significantly improve PFS or OS of patients with previously untreated localized iNHL. More than two thirds of these patients remain alive after 15 years with second primary malignancies being the single most important cause of death.

Session topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Keyword(s): Follicular lymphoma, Indolent non-Hodgkin's lymphoma, Radiotherapy

Abstract: EP1164

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Indolent B-NHLs (iNHL) are incurable with standard systemic therapy. Some patients with localized disease can be cured with radiation therapy (RT); addition of systemic therapy has not been shown to increase the cure rate. iNHL are radiosensitive, responding to very low doses of radiation. We therefore hypothesized that low-dose TBI might improve the cure rate of IFRT by eliminating microscopic disseminated disease.

Aims
The EORTC Lymphoma Group and EORTC Radiation Oncology Group performed this phase 3 randomized trial to test whether addition of low-dose TBI prior to IFRT improve outcomes of patients with localized iNHL.

Methods
Patients with previously untreated iNHL stages 1 and 2, in whom nodal areas that had to be irradiated could be encompassed in a single radiation volume were randomized to receive TBI (total 1.5 Gy in 10 fractions given in 2 weekly courses, 2 weeks apart) followed after 4 weeks by IFRT, or IFRT only (total dose 26-40 Gy in 13-20 fractions). The primary endpoint was PFS. Secondary endpoints included response to TBI and OS. The original plan called for inclusion of 344 patients in 6 years. The enrollment was closed due to poor accrual after 9 years and the final analysis additionally postponed because the outcome of the control arm was better than anticipated.

Results
Between 2000 and 2009, 203 patients were entered into the trial. Seven patients were ineligible, mostly due to histology; 4 did not start the allocated treatment. Baseline clinical characteristics (gender, stage, pathological subtype) were well balanced between treatment arms. Median age was 54 years (range 21-85); 84% of the patients had follicular lymphoma; 36% had stage 1 disease without measurable tumor mass (whole tumor extirpated for diagnostic purposes), 39% stage 1 with measurable tumor mass and 25% stage 2. Toxicity of TBI, evaluated before starting IFRT, was minimal: 1% of patients had moderate mucosal edema, 1% patchy mucositis and 1% ulceration. In the TBI+IFRT arm, CTCAEv2 gr. ≥3 neutropenia, thrombocytopenia and anemia were observed in 3, 1 and 1% of patients, respectively, in comparison to none in the IFRT-only arm. TBI resulted in CR or CRu in 33.3% and IFRT (±TBI) in 81% of patients with a measurable tumor mass. There were no significant differences in response rates between the two arms. After a median follow-up of 13 years, PFS rates in the TBI+IFRT arm were 67% at 5 years, 56% at 10 years and 41% at 15 years and in the IFRT-only arm 58%, 46% and 33% (Fig). This difference was not significant (HR 0.9; 95% CI=0.62-1.3, p=0.559 adjusted for stage and LDH). OS rates at respective time-points were 89%, 83% and 67% in the TBI+IFRT arm and 92%, 84% and 68% in the IFRT-only arm (HR 1.21 (0.69-2.12), p=0.501 adjusted for stage) (Fig). Of the 49 (24%) of patients that died, in 10 the cause of death was lymphoma, in 16 second primary tumor, in 5 cardiovascular disease and in 18 other or unknown causes. The distribution of causes of death was not significantly different between the two arms.

Conclusion
The addition of low-dose TBI to IFRT does not significantly improve PFS or OS of patients with previously untreated localized iNHL. More than two thirds of these patients remain alive after 15 years with second primary malignancies being the single most important cause of death.

Session topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Keyword(s): Follicular lymphoma, Indolent non-Hodgkin's lymphoma, Radiotherapy

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