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*, Cathalijne C. B. Post, Melanie E. Powell, Pearly Khaw, Anthony Fyles, Romerai D'Amico, Christine Haie-Meder, Ina M. Jurgenliemk-Schulz, Mary McCormack, Viet Do, Dionyssios Katsaros, Paul Bessette, Marie Helene Baron, Remi A. Nout, Karen Whitmarsh, Linda Mileshkin, Ludy C. H. W. Lutgens, Henry C. Kitchener, Susan Brooks, Hans W. NijmanEleftheria Astreinidou, Hein Putter, Carien L. Creutzberg, Stephanie M. de Boer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Purpose
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.

Methods and Materials
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.

Results
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.

Conclusions
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.
Original languageEnglish
Pages (from-to)390-399
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume112
Issue number2
DOIs
Publication statusPublished - 1 Feb 2022

Bibliographical note

The PORTEC-3 study was supported by a grant from the Dutch Cancer Society (UL2006-4168/CKTO 2006-04), the Netherlands. PORTEC 3 was supported in the United Kingdom by Cancer Research UK (grant number C7925/A8659). Participation in the PORTEC-3 trial by the Australia and New Zealand Gynaecologic Oncology Group (ANZGOG) and the Trans-Tasman Radiation Oncology Group (TROG) was supported by the NHMRC Project (grant number 570894, 2008) and by a Cancer Australia Grant (awarded through the 2011 round of the priority-driven Collaborative Cancer Research Scheme and funded by Cancer Australia). Participation by the Italian MaNGO group was partly supported by a grant from the Italian Medicines Agency AIFA (FARM84BCX2). Canadian participation in the PORTEC-3 trial was supported by the Canadian Cancer Society Research Institute (grant numbers 015469, 021039).

Disclosures: C.L.C. reports grants from Dutch Cancer Society during the conduct of the study, and, outside the submitted work, grants from Varian, nonfinancial support from Elekta, and other from Merck. H.W.N. reports grants from aduro, nonfinancial support from Merck, grants from Immunicum, personal fees from Merck, other from Vicinivax, nonfinancial support from Biontech, and grants from the Dutch Cancer Society, all outside the submitted work. H.W.N. also reports a patent T cell marker pending. P.B. reports grants from AstraZeneca, Tesaro, Clovis, Merck, IQVIA Biotech LLC, the Canadian Cancer Trials Group, and Pfizer, all outside the submitted work. R.N. reports grants from the Dutch Cancer Society, the Dutch Research Council, Elekta, Varian, and Accuray, all outside the submitted work.

Acknowledgements—We would like to thank the following participating groups and their respective coordinating teams, principal investigators, staff, and clinical research teams at the groups' participating centers and all data managers: the Dutch Gynecological Oncology Group (the Netherlands), the National Cancer Research Institute (United Kingdom), the Australia and New Zealand Gynaecologic Oncology Group, the Mario Negri Gynecologic Oncology group (Italy), Fedegyn (France), and the Canadian Cancer Trials. The radiation therapy quality assurance QA done by the TROG/ANZGOG teams is gratefully acknowledged. We thank all patients who participated in the PORTEC-3 trial and contributed by filling in the questionnaires throughout the follow-up period.

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