Quality-of-Life Outcomes and Toxic Effects Among Patients With Cancers of the Uterus Treated With Stereotactic Pelvic Adjuvant Radiation Therapy

Abstract

IMPORTANCEAdjuvant radiation plays an important role in reducing locoregional recurrence in patients with uterine cancer. Although hypofractionated radiotherapy may benefit health care systems and the global community while decreasing treatment burden for patients traveling for daily radiotherapy, it has not been studied prospectively nor in randomized trials for treatment of uterine cancers, and the associated toxic effects and patient quality of life are unknown. OBJECTIVE To evaluate acute genitourinary and bowel toxic effects and patient-reported outcomes following stereotactic hypofractionated adjuvant radiation to the pelvis for treatment of uterine cancer. DESIGN, SETTING, AND PARTICIPANTSThe Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS) phase 1/2 nonrandomized controlled trial of patients accrued between May 2019 and August 2021 was conducted as a multicenter trial at 2 cancer centers in Ontario, Canada. In total, 61 patients with uterine cancer stages I through III after surgery entered the study.INTERVENTIONS Stereotactic adjuvant pelvic radiation to a dose of 30 Gy in 5 fractions administered every other day or once weekly.MAIN OUTCOMES AND MEASURES Assessments of toxic effects and patient-reported quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and endometrial EN24) were collected at baseline, fractions 3 and 5, and at 6 weeks and 3 months of follow-up. Descriptive analysis was conducted, calculating means, SDs, medians, IQRs, and ranges for continuous variables and proportions for categorical variables. Univariate generalized linear mixed models were generated for repeated measurements on the quality-of-life scales.RESULTS A total of 61 patients were enrolled (median age, 66 years; range, 51-88 years). Tumor histologic results included 39 endometrioid adenocarcinoma, 15 serous or clear cell, 3 carcinosarcoma, and 4 dedifferentiated. Sixteen patients received sequential chemotherapy, and 9 received additional vault brachytherapy. Median follow-up was 9 months (IQR, 3-15 months). Of 61 patients, worst acute gastrointestinal tract toxic effects of grade 1 were observed in 33 patients (54%) and of grade 2 in 8 patients (13%). For genitourinary worst toxic effects, grade 1 was observed in 25 patients (41%) and grade 2 in 2 patients (3%). One patient (1.6%) had an acute grade 3 gastrointestinal tract toxic effect of diarrhea at fraction 5 that resolved at follow-up. Only patient-reported diarrhea scores were both clinically (scores Ն10) and statistically significantly worse at fraction 5 (mean [SD] score, 35.76 [26.34]) compared with baseline (mean [SD] score, 6.56 [13.36]; P < .001), but this symptom improved at follow-up. CONCLUSIONS AND RELEVANCE Results of this phase 1/2 nonrandomized controlled trial suggest that stereotactic hypofractionated radiation was well tolerated at short-term follow-up for treatment of uterine cancer. Longer follow-up and future randomized studies are needed to further evaluat...

Benefits of Adopting Hypofractionated Radiotherapy as a Standard of Care in Low-and Middle-Income Countries

“…[15][16][17][18][19] Data are also accruing supporting the use of hypofractionated radiotherapy for head and neck and gynecologic cancers. [20][21][22][23][24][25] More efficient utilization of resources through the adoption of hypofractionated radiotherapy approaches for some of the most common malignancies, particularly breast and prostate cancer, has the potential to address many of the factors contributing to the disparity in cancer outcomes seen between LMICs and high-income countries (HICs). In this literature review, we aim to examine the potential benefits of adopting hypofractionated treatment approaches in LMICs and the current state of hypofractionated radiotherapy in these settings.…”

Are We Finally Ready for the Widespread Adoption of Stereotactic Radiation in Gynecologic Cancers?

“…They will also report locoregional failure and disease-free survival as secondary end points.Leung et al 1 discuss the use of hypofractionation in prostate and rectal cancers as a rationale for their treatment regimen. [3][4][5] However, both rectal and prostate pelvic SBRT trials to date have used 25 Gy in 5 fractions instead of the higher dose of 30 Gy in 5 fractions used by Leung et al 1 Although the rationale to more closely approximate a tumor dose of 45 Gy in 25 fractions is appreciated, this strategy also results in a higher equivalent total dose in 2-Gy fractions to normal tissue than does 25 Gy in 5 fractions. For example, in the prostate cancer PACE B trial ("International Randomised Study of Laparoscopic Prostatectomy vs SBRT and Conventionally Fractionated Radiotherapy vs SBRT for Early Stage Organ-Confined Prostate Cancer"), 5 although neither acute GI tract nor genitourinary toxic effects were different between groups, the timing of the development of the adverse effects was earlier in the group that received SBRT.…”

“…To address this concern, the investigators of SPARTACUS II 2 have added an assessment 3 weeks after treatment. One limitation of the study by Leung et al 1 was the variation in treatment schedule after initiation of the study. This variation led to the initial 13 patients being treated once per week and the remaining 48 patients being treated every other day.…”

“…In this issue of JAMA Oncology , Leung et al present the first prospective phase 1/2 single-group trial, The Stereotactic Pevlic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS), of accelerated hypofractionation/stereotactic body radiation therapy (SBRT) for postoperative pelvic radiation in patients with stage I to III uterine cancer. In total, 61 patients were accrued between May 2019 and August 2021 and received 30 Gy in 5 fractions, using either once a week (13 patients) or every other day (48 patients) treatment schedules.…”

“…Leung et al discuss the use of hypofractionation in prostate and rectal cancers as a rationale for their treatment regimen . However, both rectal and prostate pelvic SBRT trials to date have used 25 Gy in 5 fractions instead of the higher dose of 30 Gy in 5 fractions used by Leung et al Although the rationale to more closely approximate a tumor dose of 45 Gy in 25 fractions is appreciated, this strategy also results in a higher equivalent total dose in 2-Gy fractions to normal tissue than does 25 Gy in 5 fractions.…”