146 Background: Short-course radiotherapy (SCRT) is an option in the neoadjuvant setting of resectable stage II-III rectal cancer, as well as in stage IV disease for local control without delay to initiate systemic treatment. Short-course radiotherapy is reported to be a comparable strategy for locally advanced rectal cancer. Limited data exist regarding the use of short-course radiation therapy when used as part of a non-surgical watch and wait approach. Methods: This is a retrospective analysis of all patients that underwent SCRT for rectal cancer at the Alexander Fleming Institute from 3/2014 to 6/2022. Results: 44 patients were treated with SCRT, 29 (66%) were male, with a median age of 59 years (46-73). Most of the patients had stage IV disease (26, 59,1%) followed by clinical stage II-III (18, 40,9%). 30 (68%) were localized in the middle with 14 (32%) in the lower rectum, by MRI imaging. In locally advanced disease 5/18 had T4 disease and 7/18 had N≥2. 14/18 patients (89%) underwent SCRT followed by consolidation chemotherapy (ChT) and 4 (11%) had induction ChT followed by SCRT. In metastatic disease 14/26 patients (53.84%) underwent SCRT followed by consolidation ChT, 10 (38.46%) had induction ChT followed by SCRT, and 2 (7.7%) received only SCRT. 29 (65.9%) of patients underwent surgery. 17/29(58.6%) had metastatic disease and 12/29 (41.4%) had locally advanced disease. Pathological response rates in operated patients were 2 (6.9%). 8 (18.2%) cases had a clinical complete response (cCR) (n=6 stage II-III and n=2 stage IV). Five (27.7% of the locally advanced group) patients with cCR underwent watch and wait with 1 local recurrence after 14 months. The remainder is disease free with a median follow-up time of 20 months (IC 95%: 15.14-24.85). Those that underwent SCRT following chemotherapy were more likely to have AEs compared to those that had chemotherapy following SCRT (11/30, 36.7% vs 25%, p=0.02). Conclusions: Our work shows that in a subgroup of patients diagnosed with LARC treated with SCRT followed by Chemotherapy, surgical treatment could be deferred after achieving a complete clinical response. The shorter time involved by SCRT allowed for less treatments with similar toxicity to long-course treatment regimens. SCRT is a reasonable option for local disease control in stage IV disease.

Background: Short-course radiotherapy (SCRT) of 25 Gy in five daily fractions is a recommended strategy in the neoadjuvant setting for resectable locally advanced rectal cancer (LARC), as well as in cases of metastatic disease for local control. There is scarce information regarding the use of SCRT for patients who have received nonoperative management.Objectives: To describe the characteristics of patients who received treatment with SCRT for LARC and metastatic rectal cancer, toxicity, and the approach after radiation treatment.Methods: This is a retrospective analysis of all patients who underwent SCRT for rectal cancer at the Alexander Fleming Institute from March 2014 to June 2022. Results:In total, 44 patients were treated with SCRT. The majority were male (29, 66%), with a median age of 59 years (interquartile range 46-73). Most patients had stage IV disease (26, 59.1%), followed by LARC (18, 40.9%). Most lesions were located in the middle rectum (30, 68%). The majority of LARC patients underwent SCRT followed by consolidation chemotherapy (ChT) (16/18, 89%), while most patients with metastatic disease underwent SCRT followed by consolidation ChT (14/26, 53.8%). A clinical complete response (cCR) was documented in 8/44, 18.2% of patients. Most patients with LARC and cCR were managed by a watch and wait approach (5/18, 27.7%). Local recurrence was observed in LARC cases (2/18, 11.1%). Patients who underwent SCRT following consolidation ChT were more likely to have adverse events (AEs) than those undergoing induction ChT following SCRT (11/30, 36.7% versus 3/12, 25%, p = 0.02) Conclusion:In a subgroup of patients diagnosed with LARC and treated with SCRT followed by ChT, surgical treatment could be omitted after they achieved a cCR. Local recurrence was similar to that reported in a previous study. SCRT is a reasonable option for local disease control in stage IV disease, yielding low toxicity rates. Therefore, decisions must be made by a multidisciplinary team. Prospective studies are necessary to reach further conclusions.

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e17055 Background: Prostate cancer (PC) clinical course is variable. It was thought that BRCA1 and BRCA2 mutations were associated with only a small proportion of PC cases. However, recent genomic analysis has revealed that germline or somatic inactivating mutations in genes involved in the homologous recombination (HR) pathway of DNA repair collectively occur in as much as 20%-25% of advanced PC. Referring to the metastatic castration resistant PC (mCRPC) the somatic mutations were recently reported to be up to 12,7% for BRCA2 and 2% for BRCA1. PC is the most frequent tumor among LATAM men. The incidence of de novo metastatic PC is higher in LATAM than other parts of the world, and demographic changes in the region have increased disease burden. However, region-specific information about genomic profiling of this tumor is scant. This study aims to describe the genomic profile patterns of PC, either presenting as metastatic hormone treatment–naive prostate cancers, or locoregional tumors that later evolve to metastatic disease in LATAM pts. Methods: A retrospective observational cohort design was used. The study sample included patients with a confirmed PC diagnosis with adenocarcinoma histology, from 8 academic centers in 3 countries between 1st January 2020 and 30th November 2022 whom had been molecularly tested. Results: Of 185 pts tested, 183 had metastatic PC. Somatic evaluation was done in 49.5% of the pts, while 66.48% have germline test, 13% pts were tested by both methods. Forty-two (22.7%) pts were tested in the metastatic sensitive castration scenario, instead 141 (76.2%) were mCRPC. Actionable mutations were detected in 21 pts (11.35%), being the most frequents PTEN and BRCA2. The median tumor mutational burden was 5 (IQR 0-2.52). No mutation in the following clinically relevant genes were found in our pts: BRCA1, RAD51C, RAD51D, RAD54, PALB2 and BRIP1 (Table1). Between pts with actionable mutations, 27.3% had high volume disease, with a median Gleason score of 9 (IQR 8-9) and de novo metastatic setting in 40.9%. Despite that 25.9% of our pts have a VUS (Variant of unknown significance), only 7 pts (3.8%) access to oncology genomic counseling. Conclusions: In our region, the percentage of actionable mutations found in this population appears to be lower than that reported in studies from other regions of the world, but remarkably the mutations detected are different. This data shows the importance to have mutational data of the population of each region what is heterogeneous among themselves and with respect to other regions of the world. [Table: see text]