Anorectal dose–effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial. (September 2021)

• Record Type: Journal Article
• Authors: Groen, Veerle H.; Zuithoff, Nicolaas P.A.; van Schie, Marcel; Monninkhof, Evelyn M.; Kunze-Busch, Martina; de Boer, Hans C.J.; van der Voort van Zyp, Jochem; Pos, Floris J.; Smeenk, Robert Jan; Haustermans, Karin; Isebaert, Sofie; Draulans, Cédric; Depuydt, Tom; Verkooijen, Helena M.; van der Heide, Uulke A.; Kerkmeijer, Linda G.W.
• Is Part Of: Radiotherapy and oncology. Volume 162(2021)
• Page Start: 98
• Page End: 104
• Publication Date: 2021-09
• Subjects: FLAME Focal Lesion Ablative Microboost in Prostate Cancer -- EBRT External Beam Radiation Therapy -- GI Gastrointestinal -- OAR Organs At Risk -- bDFS biochemical Disease-Free Survival -- mpMRI multiparametric Magnetic Resonance Imaging -- EAU European Association of Urology -- TURP Trans Urethral Resection of the Prostate -- GTV Gross Tumor Volume -- PTV Planning Target Volume -- CTV Clinical Target Volume -- CTCAE Common Terminology Criteria for Adverse Events -- IQR Interquartile Range -- OR Odds Ratio; Prostate cancer -- External beam radiotherapy -- Focal boosting -- Gastrointestinal toxicity -- Anorectal dose parameters -- Dose-effect relations; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2021.06.033
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: A higher radiation dose to the anorectum is associated with increased overall GI toxicity. Increasing the dose to the anorectum should be weighed against the benefit of focal dose escalation. Further increasing the dose to the tumor without increasing the anorectal dose should be explored. Abstract: Background and purpose: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2). Material and methods: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose–effect relation of the anorectal dose parameters (D2cm 3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute. Results: A dose–effect relation for D2cm 3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13–1.21, p < 0.0001) and 1.20 (95% CI 1.14–1.25, p < 0.0001) for GI toxicity, respectively. Conclusion: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose–effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.