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    Optimal neoadjuvant strategy for signet ring cell carcinoma of the rectum-Is TNT the solution? Kazi Mufaddal,Jain Divakar,Padhy Amita Sekhar,Menon Munita,Desouza Ashwin,Sukumar Vivek,Gori Jayesh,Ostwal Vikas,Ankathi Suman Kumar,Saklani Avanish Journal of surgical oncology INTRODUCTION:The results of total neoadjuvant therapy (TNT) for locally advanced rectal cancers (LARC) cannot be extrapolated to signet-ring cell cancers (SRCC) that have an extremely aggressive biology. METHODS:A retrospective study comparing long course chemoradiation (CTRT) against short course radiation (SCRT) and 12 weeks of chemotherapy for high-risk LARC. Primary endpoints were treatment failure and disease-free survival (DFS) RESULTS: CTRT was given to 74 (59.7%) and SCRT/Chemotherapy to 50 patients (40.3%). Additional chemotherapy was required in 54.1% and 28%, respectively. Except for nodal staging, no other MRI parameter down-staged. Treatment failures were seen in 33.9% and 25.8% had progression. The peritoneum was the commonest site of progression (59.4%). Of the patients that were surgically explored, 63.7% had R0 resections and pathological complete response was seen in 9.7%. At a median follow-up of 35 months, 56.5% had DFS events with a 3-year DFS of 39.5%. Recurrences were noted in 45.1% after curative resections and the 3-year OS/DFS of these patients were 67.2%/56.4%. On multivariate regression, the type of preoperative therapy did not influence treatment failures or DFS. CONCLUSIONS:SRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses. 10.1002/jso.26637