Renal cell carcinoma (RCC) is one of the top ten tumors over the world. RCC is not sensitive to radiotherapy and chemotherapy. Therefore, it is necessary to find new targets for the treatment. CircRNAs are a special type of noncoding RNAs, which play important roles in many types of cancer. In this study, we found circ_000558 was upregulated in RCC cells, and it elevated the proliferation ability of RCC cells. The relationship between miR-1225-5p and circ_000558 or ARL4C was predicted via circBank and circular RNA interactome and confirmed by dual-luciferase reporter assay. Then, the effects of circ_000558/miR-1225-5p/ARL4C on RCC cell proliferation and apoptosis were assessed by CCK-8 assay. The results revealed that the knockdown of ARL4C significantly reduced RCC cell proliferation and overexpression of circ_000558 could significantly induce RCC cell proliferation after miR-1225-5p treatment further promoted the inhibitory ability of ARL4C knockdown. Overall, our study suggested that circ_000558/miR-1225-5p/ARL4C network was related to the RCC cell proliferation. This finding could provide new targets for the treatment and prognosis of RCC.

152 Background: Fruquintinib is a highly selective, and potent oral inhibitor of VEGF receptor 1, 2, 3 and has been recommended as a third-line treatment for mCRC patients (pts) in China because of its low toxicity, favorable ORR and survival benefit. FOLFOX/FOLFIRI is the preferred chemotherapy regimens of first-line for mCRC pts according to the NCCN guideline. Our study aimed to investigate the efficacy and safety of fruquintinib plus mFOLFOX6/FOLFIRI as first-line therapy in advanced mCRC pts. Methods: In this prospective, open-label, multi-center, single-arm phase 2 study (NCT05004441), pts who are diagnosed with unresectable mCRC, without prior systemic threated are recruited. RAS/BRAF status should be detected to exclude BRAF mutations before enrollment. Pts receive fruquintinib (3mg, QD, PO, Q4W) in combination with mFOLFOX6/FOLFIRI (Q2W) for up to 8 cycles. Pts with SD or above are followed by maintenance therapy (fruquintinib 3mg, QD, PO, Q4W, capecitabine 850mg/m2, BID, PO, D1-7, D15-21, Q4W) until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: Based on a data cutoff of September 2, 2022, 19 pts have been enrolled and treated, of which 13 pts have efficacy evaluation data. Media age is 60 (range: 50-73) years and 62% pts are male. 7 (54%) pts harboring RAS mutations while the remaining pts are wild-type (wt). 54% treated with mFOLFOX6. At a median follow-up of 5.9mo, all 13 pts are still on treatment. In best overall response assessment, the ORR is 77%, with 10 (77%) partial response (PR). Stable disease (SD) is 3 (23%) with a DCR of 100%. Median PFS has not yet reached. Safety profile exhibited that the regimen is tolerable and mainly grade 1/2. Grade 3 treatment-related adverse events (TRAEs) are neutrophil count decreased (23%), GGT increased (15%), leukopenia, AST increased and hypertension accounted for 1% respectively. No pts have serious adverse events. Conclusions: Combination treatment with fruquintinib plus mFOLFOX6/FOLFIRI as the first-line therapy followed by fruquintinib plus capecitabine maintenance in advanced mCRC pts shows promising efficacy and manageable safety profile. Longer follow up data with PFS, and OS will be presented. Clinical trial information: NCT05004441 .

3611 Background: Endorectal brachytherapy has been used as palliative or preoperative treatment for advanced or locally advanced rectal cancer, with moderate radiation induced toxicity. This study aimed to explore the efficacy of high-dose-rate 192Ir brachytherapy combined with external beam radiotherapy (EBRT) in total neoajuvant treatment (TNT) of distal rectal cancer. Methods: From January 2017 to December 2022, eligible rectal adenocarcinoma patients were assessed as clinical stage II -III, with primary tumor located in distal rectum (≤5 cm from anal verge). The local staging was determined using endorectal ultrasound and magnetic resonance imaging (MRI). In addition, cases included in this study underwent preoperative semiweekly endorectal brachytherapy of 8-12Gy/2-3F/1-1.5w, followed by EBRT of 45-50.4Gy/25-28F, fluorouracil-based concurrent and consolidation chemotherapy. The brachytherapy was image-guided volume-adapted, and delivered by multi-channel 192Ir source applicators with different diameters. Radiation proctitis was graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: A total of 40 cases were enrolled in this retrospective study, biopsy-proven and diagnosed as clinical stage II (n = 8), stage III (n = 32). The rates of T4 and positive circumferential resection margin (CRM) were 35% and 87.5% respectively. The median value of the interval from completion of radiotherapy to operation was 86 days (interquartile range: 75-98 days). After neoadjuvant treatment, 2 cases were undergoing the watch-and-wait strategy with sustained clinical complete response (cCR), 38 patients received operation and R0 resection rate was 97.4%. The pathological complete response (pCR) rate was 28.9%, and major pathological regression rate was 67.5%. The theoretical rate of anus preservation was 62.5%, including 6 of 21 cases underwent abdominoperineal resection but achieved pCR, 17 cases underwent low anterior resection or intersphincteric resection, and 2 cases with sustained cCR. After a median follow-up of 37 months (range 12-68 months), the 3-year disease-free survival, local-regional reccurence-free survival and overall survival was 81.1% (95%CI: 64.3%-91.2%), 94.9% (95%CI: 80.6%-98.5%) and 96.9% (95%CI: 82.1%-99.4%), respectively. No patients experienced Grade ≥3 radiation proctitis. The median Wexner fecal incontinence score of anus-preserving cases was 1 (range 0-8). Subgroup analysis showed that the complete response rate (pCR or sustained cCR) was lower in cases received 2 fractions brachytherapy than those received 3 fractions (27.8% vs 36.4%). Conclusions: The addition of image-guided volume-adapted high-dose-rate 192Ir endorectal brachytherapy boost to TNT could improve the pathological tumor response and anus preservation rate in distal locally advanced rectal cancer.