Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy

Bastiaan G Wortman ,Linda Mileshkin,Paul Bessette,Hans W Nijman,Viet Do,Stephanie M De Boer,Dionyssios Katsaros,Mary Mccormack,Hein Putter,Ina M Jürgenliemk-Schulz,Karen Whitmarsh,Remi A Nout,Anthony Fyles,Pearly Khaw,Carien L Creutzberg,Melanie Powell ,Henry C Kitchener ,Cathalijne Post ,Ludy Lutgens ,Romerai D’amico ,Marie Baron ,Susan A Brooks ,Christine Haie-Méder ,E Astreinidou

doi:10.1016/j.ijrobp.2021.09.042

Abstract

Radiation therapy techniques have developed from 3-dimensional conformal radiation therapy (3DCRT) to intensity modulated radiation therapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AEs) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer. Data on AEs and patient-reported quality of life (QoL) of the PORTEC-3 trial were available for analysis. Physician-reported AEs were graded using Common Terminology Criteria for Adverse Events v3.0. QoL was assessed by the European Organisation for Research and Treatment of Cancer QLQC30, CX24, and OV28 questionnaires. Data were compared between 3DCRT and IMRT. A P value of ≤ .01 was considered statistically significant due to the risk of multiple testing. For QoL, combined scores 1 to 2 ("not at all" and "a little") versus 3 to 4 ("quite a bit" and "very much") were compared between the techniques. Of 658 evaluable patients, 559 received 3DCRT and 99 IMRT. Median follow-up was 74.6 months. During treatment no significant differences were observed, with a trend for more grade ≥3 AEs, mostly hematologic and gastrointestinal, after 3DCRT (37.7% vs 26.3%, P = .03). During follow-up, 15.4% (vs 4%) had grade ≥2 diarrhea, and 26.1% (vs 13.1%) had grade ≥2 hematologic AEs after 3DCRT (vs IMRT) (both P < .01). Among 574 (87%) patients evaluable for QoL, 494 received 3DCRT and 80 IMRT. During treatment, 37.5% (vs 28.6%) reported diarrhea after 3DCRT (vs IMRT) (P = .125); 22.1% (versus 10.0%) bowel urgency (P = 0039), and 18.2% and 8.6% abdominal cramps (P = .058). Other QoL scores showed no differences. IMRT resulted in fewer grade ≥3 AEs during treatment and significantly lower rates of grade ≥2 diarrhea and hematologic AEs during follow-up. Trends toward fewer patient-reported bowel urgency and abdominal cramps were observed after IMRT compared to 3DCRT.

Highlights

Radiotherapy techniques have developed from 3-dimensional conformal radiotherapy (3DCRT) to intensity-modulated radiotherapy (IMRT), with better sparing of the surrounding normal tissues
Study population Between September 15th 2006 and December 20th 2013, 660 eligible and evaluable patients were included in the PORTEC-3 trial, 333 received radiotherapy and 327 chemoradiotherapy; 559 (85.0%) received 3DCRT, 99 (15.0%) patients received intensitymodulated radiotherapy (IMRT), and for two patients the type of technique was unknown (Figure 1). 3DCRT consisted of three-field, four-field or multiple field radiotherapy techniques
Radiotherapy target areas did not differ significantly between the two techniques, with only 38 patients receiving paraaortic radiotherapy. 574 (87.0%) patients were evaluable for quality of life (QoL), of whom 493 (85.9%) received 3DCRT, 80 (13.9%) IMRT and for 1 the technique was unknown (0.2%)

Summary

Introduction

Radiotherapy techniques have developed from 3-dimensional conformal radiotherapy (3DCRT) to intensity-modulated radiotherapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AE) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer. With IMRT and VMAT, the radiation dose is delivered more conformally to the target volume and the dose to the adjacent organs at risk (OAR) is reduced, compared to 3DCRT, without compromising clinical outcome.[1,2,3,4,5,6] With the introduction of more advanced radiotherapy techniques, it is expected that treatment related AE for pelvic radiotherapy can be reduced. The aim of the current study was to investigate whether use of IMRT in the PORTEC-3 trial was associated with reduced physicianreported AE and fewer patient-reported symptoms

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Methods

Results

Discussion

Conclusion