Phase II Trial of Organ Preservation Program Using Short-Course Radiation and Folfoxiri for Rectal Cancer (SHORT-FOX): Clinical Response Outcomes.

Patients (pts) with rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy may be safely observed and spared surgical sequela. We studied a neoadjuvant strategy to increase rates of cCR. We conducted a single arm phase II study of short-course radiation followed by FOLFOXIRI for pts with >T2N0 or low T2N0M0 rectal cancer (NCT04380337). Pts underwent 25 Gy/5 fractions + 5 Gy/1 fraction boost followed by FOLFOXIRI (8 cycles). Primary endpoint of cCR was assessed at 8 weeks following chemotherapy. Those who achieved a cCR or near cCR could be surveilled. cCR required both flat white scar on endoscopy and mrTRG1-2. Assuming a one-sided type 1 error of 0.1, power of 0.9, a null cCR of 0.2 versus an alternate cCR of 0.4, our sample size was 37 pts. Between May 2020 and April 2023, 37 pts enrolled (Table). 25 pts (67.5%) had at least one high risk feature (cT4, extramural vascular invasion [EMVI], N2, threatened circumferential resection margin [CRM], positive lateral node). All pts completed radiation while 32 (86.5%) pts completed all chemotherapy. At primary endpoint assessment, 9 (24%) pts had cCR on both endoscopy and MRI. 14 (37.8%) pts had cCR on endoscopy but residual tumor on MRI: 9 (24.3%) of these pts pursued watch and wait while 5 (13.5%) proceeded to surgery. Of those 9 pts who pursued watch and wait, 5 had local regrowth while 4 had delayed cCR on imaging. Of the 5 pts who went to surgery, all had residual tumor on surgical specimen. All pts who had cCR on MRI also had cCR on endoscopy. In this population with high-risk rectal cancer, 24% achieved a cCR on both MRI and endoscopy at primary outcome assessment. A significant portion of pts had discordant MRI and endoscopy findings, emphasizing the importance of multimodality response assessment and close follow-up for both delayed cCR and local regrowth. [ABSTRACT FROM AUTHOR]