Discussion
tumor, neutropenia, diarrhea, toxicities, postoperative infection, fistula, deaths
DISEASE, TUMOR, NEUTROPENIA, POSTOPERATIVE INFECTION
In the present study, nCT with mFOLFOXIRI therapy for patients with LARC achieved a pCR rate of 4.3%, which did not meet the primary endpoint. The pCR rate was similar to the 6.6% for mFOLFOX6 in the FOWARC study and was lower than the 17.4% of mFOLFOXIRI in the FORTUNE study [Neoadjuvant radiotherapy is an effective way to improve local control of LARC. In randomized studies of neoadjuvant CRT versus preoperative radiotherapy alone (FFCD9203 [On the other hand, re-evaluation of high-risk factors by MRI after nCT may distinguish patients with different prognosis outcomes. GRECCAR-4 was a randomized phase 2 study in which an nCT plan was established based on the degree of tumor shrinkage after intensive induction chemotherapy (FOLFIRINOX) [A high completion rate of nCT with mFOLFOXIRI was observed in this study: 96% for 3 cycles and 88% for 5 cycles, with manageable toxicities. The incidence rates of the most concerning grade 3/4 toxicities namely neutropenia and diarrhea were 50% and 12%, respectively. There were no treatment-related deaths. The nCT with mFOLFOXIRI did not bring any additional safety problems to surgery. The incidence rates of anastomotic fistula and postoperative infection were 2.2% and 4.3%, respectively. The rates in this study were similar to those reported in the mFOLFOX alone treatment group in the FOWARC study (7.9% and 7.2%, respectively), but were significantly lower than in the two concurrent chemoradiation groups (19.8% and 16.3%, and 18.1% and 14.8%, respectively).Nevertheless, 11/46 (23.9%) patients retained ypN2 disease after surgery. Finally, 14 (30.4%) of 46 patients received postoperative radiation with concurrent capecitabine therapy mainly because they had pathologically node-positive (The present research had several limitations. First, it is a phase 2 single-arm study with a limited sample size. Second, a higher proportion of patients with MRF invasion and EMVI-positive were enrolled, which did not reflect real-world incidence. Third, EMVI and MRF status were post analysis rather than prospective research purposes.In conclusion, nCT with mFOLFOXIRI had a significant down-staging effect on LARC. It was effective in eliminating EMVI, and transforming positive MRF to a negative status, with a favorable safety profile. The long follow-up showed promising DFS and OS times, indicating that initial neoadjuvant treatment with mFOLFOXIRI could allow a certain subset of patients to be free from radiotherapy. This was especially true for those patients bearing high risks who be eliminated after nCT in the re-evaluation and who probably obtaining better survival, and thus, warrant further investigation.