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

E. Pollom¹, G. A. Fisher Jr², A. Shelton³, T. Johnson², C. Chen², S. Jackson¹, S. Shaheen², T. L. Holden², J. Y. E. Bien⁴, D. King⁵, A. Morris³, C. Kin³, A. Dawes³, N. Kirilcuk³, L. Vitzthum⁶, E. Rahimy¹, V. Sheth⁷, E. Brown⁸, A. Pratapneni¹, and D. T. Chang⁹; ¹Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, ²Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, ³Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, ⁴Kaiser Permanente Santa Clara Medical Center, Santa Clara, CA, ⁵Department of Medical Oncology/Hematology, Northwell Health Cancer Institute, New Hyde Park, NY, ⁶Department of Radiation Oncology, Stanford University, Palo Alto, CA, ⁷Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, ⁸Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA, ⁹Stanford University, Stanford, CA

Purpose/Objective(s): 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. Materials/

Methods: 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.

Results: 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.

Conclusion: 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 304 – Table 1: Baseline characteristics of enrolled pts

Baseline characteristics	n = 37
Gender
Female	13 (35.1%)
Male	24 (64.9%)
Age, years
Median [IQR]	52.00 [44.00, 61.00]
Race
White	26 (70.3%)
Asian	10 (27.0%)
Native-Hawaiian or Other Pacific Islander	1 (2.7%)
Clinical T Stage
cT2	3 (8.1%)
cT3	26 (70.3%)
cT4	8 (21.6%)
Clinical N Stage
cN0	7 (18.9%)
cN1	15 (40.5%)
cN2	15 (40.5%)
Distance from anal verge on MR, cm
Median [IQR]	7.00 [3.30, 8.80]
Extramural vascular invasion
Absent	24 (64.9%)
Equivocal	5 (13.5%)
Present	8 (21.6%)
Lateral lymph node involvement
Absent	32 (86.5%)
Present	5 (13.5%)
Threatened circumferential margin
No	18 (52.9%)
Yes	16 (47.1%)