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

Abstract

In this issue of JAMA Oncology, Leung et al 1 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. The primary end point was physician-reported acute gastrointestinal (GI) tract and genitourinary toxic effects. There are many potential benefits to a shorter radiation treatment schedule, as the authors discuss. The benefits include quicker time of completing systemic therapy in advanced uterine cancer, decreased financial challenges owing to travel, lost wages, and housing that may be needed to facilitate weeks of treatment, and decreased exposure to highrisk hospital settings during the height of the COVID-19 pandemic. The authors found at a median follow-up of 9 months (IQR, 3-15 months) that rates of acute GI tract toxic effects of grade 1 and 2 were 54% and 13%, respectively, and acute genitourinary toxic effects of grade 1 and 2 were 41% and 3%, respectively. Treatment with stereotactic radiation would have been deemed too toxic if more than 20% of patients had grade 3 or higher toxic effects.It is important to note that this study is a phase 1/2 singlegroup trial that reported only on acute toxic effects and quality of life. No outcome data are presented; thus, the findings are not ready for widespread adoption. In fact, the authors have opened a phase 2 randomized clinical trial (SPARTACUS II), 2 randomizing patients between 30 Gy in 5 fractions vs the conventional 45 Gy in 25 fractions, with a primary end point of acute bowel toxic effects. 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. The PACE B trial found that by weeks