Renaissance of Radiotherapy in Intestinal Lymphoma? 10-Year Efficacy and Tolerance in Multimodal Treatment of 134 Patients: Follow-up of Two German Multicenter Consecutive Prospective Phase II Trials
Authors: Reinartz Gabriele , Molavi Tabrizi Caroline , Liersch Ruediger , Ullerich Hansjoerg , Hering Dominik , Willborn Kay , Schultze Juergen , Micke Oliver , Ruebe Christian , Fischbach Wolfgang , Bentz Martin , Daum Severin , Pott Christiane , Tiemann Markus , Moeller Peter , Neubauer Andreas , Wilhelm Martin , Lenz Georg , Berdel Wolfgang E. , Willich Normann , Eich Hans T. 
Published: March 2020

Abstract

Purpose
This article reports on the long-term impact of radiotherapy adapted to stage, histology, and previous resection in a large cohort of patients with intestinal lymphoma (iL) treated with definitive or adjuvant curative-intent radiation therapy (RT) ± chemotherapy (CHOP, MCP, or COP).

Patients and Methods
In two consecutive prospective study designs, 134 patients with indolent (stage IE–IIE) or aggressive (stage IE–IVE) iL were referred to 61 radiotherapeutic institutions between 1992 and 2003. Patients with indolent iL received extended field (EF) 30 Gy (+10 Gy boost in definitive treatment); patients with aggressive iL received involved field (IF) (EF) 40 Gy by means of stage-, histology-, and operation-adapted radiation fields.

Results
The patients had median age 58 years and were predominantly male (2:1). Histology showed aggressive prevalence (1.6:1), stage IE–to–stage IIE ratio of iL 1.04:1, and localized stages–to–advanced stages ratio of aggressive lymphoma 23:1. Median follow-up was in total 11.7 years: 10.0 years in the first study, GIT (GastroIntestinal-Tract) 1992, and 11.8 years in the second study, GIT 1996. Lymphoma involvement was predominantly a single intestinal lesion (82.1%). Decrease of radiation field size from EF to IF in stage I aggressive iL from GIT 1992 to GIT 1996 resulted in a nonsignificant partial reduction of chronic toxicity while maintaining comparable survival rates (5-year overall survival 87.9 vs. 86.7%, 10-year overall survival 77.4 vs. 71.5%) with nonsignificant difference in event-free survival (5-year event-free survival 82.6 vs. 86.7%, 10-year event-free survival 69.7 vs. 71.5%) and lymphoma-specific survival (5-year lymphoma-specific survival 90.1 vs. 91.9%, 10-year lymphoma-specific survival 87.6% vs. 91.9%). Comparative dose calculation of two still available indolent duodenal lymphoma computed tomography scans revealed lower radiation exposure to normal tissues from applying current standard involved site RT (ISRT) 30 Gy in both cases.

Conclusion
RT adapted to stage, histology, and resection in multimodal treatment of iL, despite partially decreasing field size (EF to IF), achieves excellent local tumor control and survival rates. The use of modern RT technique and target volume with ISRT offers the option of further reduction of normal tissue complication probability.

Implications for Practice
Although patients with intestinal lymphoma (iL) are heterogeneous according to histology and subtype, they benefit from radiotherapy. Prospective study data from 134 patients with indolent iL (stage IE–IIE) or aggressive iL (stage IE–IVE) show 100% tumor control after definitive or adjuvant curative-intent radiation therapy ± chemotherapy. Radiation treatment was applied between 1992 and 2003. Median follow-up in total was 11.7 years. No radiotherapy-associated death occurred. Relapse developed in 15.7% of the entire cohort; distant failure was more frequent than local (4:1). Normal tissue complication probability can be further improved using modern involved site radiation therapy techniques.