Harvey J. Mamon, MD, PhD, FASTRO
Radiation therapy is often an integral component of cancer treatment. When prospective, multicenter clinical trials include radiation therapy, studies can benefit from vigorous radiation therapy quality assurance. Historic trials, such as RTOG 9704 and ACOSOG Z0011, have highlighted the importance of integrating robust radiation therapy quality assurance to clinical trials, since failure to adhere to specified radiation therapy guidelines could lead to decreased survival and increased treatment toxicity. In addition, widely variable radiation therapy techniques can pose challenges with interpretation of trial results. On October 1, 2024, Harvey Mamon, MD, PhD, FASTRO, and colleagues presented the abstract, “Radiation Quality Control in the PROSPECT Trial” at the ASTRO Annual Meeting.
The PROSPECT trial is a landmark study that was published in the New England Journal of Medicine in 2023 by Schrag et al. The large study included locally advanced rectal cancer patients (n=1,194) with T2N+, T3N0 or T3N+ disease and patients were required to be eligible for sphincter-sparing surgery. Patients were randomized to neoadjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and surgery vs. the control arm of neoadjuvant FOLFOX followed by concurrent chemotherapy with long-course radiation therapy and subsequent surgery. The study was conducted as a multicentric, randomized, noninferiority with a seamless phase II-III design that was opened at over 200 centers in the United States, Canada and Switzerland.
The Quality Assurance Review Center and study team took on the monumental task of reviewing the radiation therapy plans of the 597 patients who were randomized to the chemoradiation therapy group. The pragmatic study permitted both 3-D-conformal radiation therapy (3-D-CRT) and intensity modulated radiation therapy (IMRT). All radiation therapy plans were scored using the criteria of per-protocol, minor deviation, or major deviation. Physician and patient-reported toxicities as well as quality of life outcomes were also recorded.
The results of the PROSPECT study were widely broadcast last year with the conclusion that patients who received preoperative FOLFOX and surgery had non-inferior disease-free survival compared to the control arm of preoperative chemotherapy and radiation therapy. Local recurrence rate was low, 2% at five years, and notably much lower than other rectal cancer trials.
During Tuesday’s session at ASTRO 2024, the PROSPECT team discussed the radiation therapy quality assurance and compliance details of the control group for the first time. The vast majority (95%) of patients received the planned radiation therapy dose of 5040 cGy and 51% of patients received 3-D-CRT. Very few major deviations (n=3) were reported and most (83%) were treated per-protocol. When comparing the patients treated with minor deviations (n=82) to those treated per-protocol (n=427), there were no significant differences in local recurrence or survival endpoints between the two groups. In addition, there were no differences in recurrence rates, toxicities or patient reported outcomes when comparing the IMRT group to the 3-D-CRT group.
As treatment modalities and planning techniques can vary at different centers, thorough quality assurance of radiation therapy delivery is of utmost importance in multi-institutional clinical trials that include radiation therapy.
The PROPSECT trial is a prime example of excellent radiation therapy quality assurance with 95% of patients in the chemoradiation therapy arm receiving planned dose and 83% receiving per-protocol radiation therapy plans. The PROSPECT team should be commended for their emphasis on quality assurance and study contributions that have included more treatment options for rectal cancer patients.
Abstract 306, Radiation Quality Control in the PROSPECT Trial, was presented during the SS 35 – GI 2: Colorectal Cancer: Innovation through Preservation and Observation session of ASTRO’s 66th Annual Meeting.
