Once or twice a week, What's best?: Joint acute toxicity analysis of the phase II hypo-FLAME trials
OC-0922
Abstract
Once or twice a week, What's best?: Joint acute toxicity analysis of the phase II hypo-FLAME trials
Authors: Lisa De Cock1, Cédric Draulans1, Floris J. Pos2, Sofie Isebaert3,1, Robin De Roover3, Uulke A. van der Heide2, Robert J. Smeenk4, Martina Kunze-Busch4, Jochem van der Voort van Zyp5, Hans de Boer5, Linda G.W. Kerkmeijer4,5, Karin Haustermans3,1
1KU Leuven, Oncology, Leuven, Belgium; 2The Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands; 3University Hospitals Leuven, Radiation Oncology, Leuven, Belgium; 4Radboud University Medical Centre, Radiation Oncology, Nijmegen, The Netherlands; 5University Medical Centre, Radiation Oncology, Utrecht, The Netherlands
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Purpose or Objective
Prostate stereotactic body radiotherapy regimens (SBRT) vary in dose, fractionation and overall treatment time (OTT). Finding the optimal OTT is challenging as on the one hand a shorter OTT increases disease control in conventional fractionated regimens, while, on the other hand, a shorter interfraction time interval could influence the toxicity rates negatively. We investigated the impact of an OTT reduction from 29 days, using a once weekly (QW) schedule (hypo-FLAME trial), to 15 days, using a semi-weekly (BIW) schedule (hypo-FLAME 2.0 trial), on acute toxicity for whole prostate gland SBRT including a simultaneous integrated focal boost.
Material and Methods
Patients with intermediate- or high-risk prostate cancer (PCa) were enrolled in either the phase II prospective multicenter hypo-FLAME or hypo-FLAME 2.0 trial. All patients were treated QW or BIW with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the multiparametric MRI-defined tumor(s). The primary endpoint of both trials was radiation-induced acute genitourinary (GU) and gastrointestinal (GI) toxicity measured using the CTCAE criteria. Acute toxicity results of both schedules were compared using a multivariate binary logistic regression model, adjusting for potentially confounding factors as age, T-stage, cardiovascular disease, diabetes, hormone therapy and baseline toxicity.
Results
One hundred and one hundred twenty-four patients were enrolled in the hypo-FLAME and hypo-FLAME 2.0 trial, respectively. The majority of patients (70.5%) were classified as high-risk PCa according to the EAU risk classification. No grade ≥ 3 GU or GI toxicity was reported independent of the treatment schedule. The 90-days cumulative incidence of grade 2 GU toxicity was significant lower in the QW treated group with 34.0% compared to the BIW treated cohort with 47.5% (p = 0.011). The prevalence of grade 2 GU toxicity increased during treatment and reached a maximum at week 3 (34.5%) for the BIW schedule and at week 5 (25.5%) for the QW schedule (Figure 1). There was no significant difference in 90-days cumulative incidence of grade 2 GI toxicity with 7.4% and 5.0% for the BIW and QW scheme, respectively (p = 0.290).
Figure 1 CTCAE v4.0 and v5.0 (A) genitourinary (GU) and (B) gastrointestinal (GI) toxicity by timepoint for the once weekly (QW) and the semi-weekly (BIW) schedule. Grade ≥ 2 = grade 2 or worse adverse event.
Conclusion
The OTT of focal boosted prostate SBRT may safely be reduced from 29 days to 15 days in patients with intermediate- and high-risk PCa, given no grade ≥ 3 GU or GI toxicity was reported in both treatment groups. Based on the comparison between the QW and BIW schedule, patients should be counselled regarding the short-term advantages of a more protracted schedule.