Lipid accumulation is a hallmark of the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment, yet effective strategies to reprogram this lipid-rich niche and restore anti-tumor immunity remain limited. Here, we show that diacylglycerol O-acyltransferase 1 (DGAT1) as a tumor-intrinsic metabolic checkpoint that promotes immune evasion. DGAT1 inhibition rewires tumor lipid metabolism by promoting increased fatty acid uptake and redistribution, thereby depleting extracellular free fatty acids that impair CD8⁺ T cell function. Mechanistically, decreased palmitate availability alleviates endoplasmic reticulum stress, preserves FOXO1 activity, and supports stem-like CD8⁺ T cell differentiation. This competitive lipid remodeling enhances memory potential, restrains terminal exhaustion, and sensitizes PDAC tumors to PD-1 checkpoint blockade in vivo. Together, our findings identify tumor-immune lipid crosstalk as a key barrier to effective immunity in PDAC and establish DGAT1 as a promising therapeutic target to restore T cell function and improve immunotherapy response.

e15635 Background: The neoadjuvant PD-1 inhibitors plus chemoradiotherapy (nCRT) has improved complete response (CR) rates in patients with locally advanced rectal cancer (LARC). However, the optimal radiotherapy strategy—particularly whether simultaneous tumor-focused dose intensification can further potentiate immunotherapeutic efficacy—remains unclear. This study evaluates pucotenlimab combined with dose-intensified nCRT and explores whether this approach enhances tumor response and clinical outcomes in LARC. Methods: This prospective, single-arm phase II study enrolled patients with pMMR/MSS LARC (cT3–4 and/or N+, M0; tumor ≤10 cm from the anal verge). All participants received neoadjuvant, dose-intensified radiotherapy (57.5 Gy in 25 fractions) targeting the primary tumor and involved nodes, combined with concurrent capecitabine and pucotenlimab (anti-PD-1). This was followed by two cycles of consolidation therapy with pucotenlimab plus capecitabine and oxaliplatin (CAPOX). Based on treatment response and patient preference, patients underwent either radical surgery or a watch-and-wait (W&W) strategy. Subsequently, all patients completed four additional cycles of pucotenlimab plus CAPOX. The primary endpoint was complete response (CR), defined as either pathological CR (pCR) or clinical CR (cCR). Results: From August 2024 to December 2025, 36 patients were enrolled. 63.89% (23/36) cases with tumors were located ≤5 cm from the anal verge, including 38.89% (14/36) with ultra-low tumors (≤3cm). High-risk features (T4a/b, mesorectal fascia involvement, positive lateral lymph nodes, N2 disease, or extramural venous invasion) were present in 88.89% (32/36) of patients. At the data cutoff, 24 patients had completed response evaluation after consolidation therapy, 9 underwent surgery and 15 adopted a W&W strategy. The pCR rate among surgical patients was 55.56% (5/9). All 15 patients in the W&W group achieved cCR, resulting in an overall CR rate of 83.33% (20/24). Organ preservation was achieved in 62.50% (15/24) of all evaluable patientsand in 78.58% (11/14) among those with low rectal tumors. No treatment related death was reported. Conclusions: Pucotenlimab plus dose-intensified chemoradiotherapy achieved a high complete response rate with rapid tumor regression after just two consolidation cycles in patients with pMMR/MSS LARC, including those with high-risk and ultra-low tumors. This immunochemoradiotherapy regimen offers strong early tumor control and significant organ-preservation opportunity, particularly for very low rectal cancers. These promising findings warrant further validation in larger, comparative trials. Clinical trial information: NCT06770270 .

Background: Skeletal muscle depletion predicts poor outcomes in gastrointestinal cancers, but whether volumetric three-dimensional (3D) body composition adds anything over the standard two-dimensional (2D) single-slice approach in colorectal cancer (CRC) patients receiving chemoradiotherapy is unclear. We quantified CT-derived sarcopenia and directly compared 2D and 3D body composition metrics from a fully automated deep learning pipeline. Methods: We retrospectively analyzed 368 patients with CRC. Body composition was quantified automatically from CT using SMAT-BC, a pipeline combining TotalSegmentator-based vertebral localization with an nnU-Net Residual Encoder XL network incorporating a Transformer bottleneck for four-class tissue segmentation. Single-slice L3 (2D) and L1–L5 volumetric (3D) indices were derived. The primary endpoint was overall survival (OS); recurrence-free survival (RFS) was secondary. Cox proportional hazards models with bootstrap optimism correction were used. Measurement reproducibility was assessed in 25 external TCGA-COAD cases. Results: Sarcopenia was strongly associated with both overall and recurrence-free survival (unadjusted OS HR 2.16, 95% CI 1.55–3.00; unadjusted RFS HR 1.83, 95% CI 1.36–2.47; both raw p < 0.001; adjusted OS HR 1.89, 95% CI 1.57–2.28; adjusted RFS HR 1.44, 95% CI 1.22–1.70; FDR-adjusted p < 0.0001 for both). L3 single-slice indices were strongly correlated with volumetric indices (r = 0.91 for muscle index) and added discriminant value over the clinical model for overall survival (optimism-corrected C-index: clinical 0.602 (95% CI 0.578–0.626), clinical + 2D 0.631 (95% CI 0.609–0.654), clinical + 3D 0.599 (95% CI 0.574–0.624); DeLong p = 0.002 for clinical + 2D vs. clinical, FDR-adjusted p = 0.006). The 2D- and 3D-augmented models yielded overlapping bootstrap confidence intervals and were not clinically meaningfully different in this cohort (OS ΔC = +0.032, 95% CI +0.013 to +0.051; FDR-adjusted p = 0.006; RFS ΔC = +0.008, 95% CI −0.011 to +0.027; FDR-adjusted p = 0.612). Conclusions: Automated CT-derived sarcopenia is an independent predictor of survival in CRC patients receiving chemoradiotherapy. In our cohort, single-slice L3 measurement matched or exceeded volumetric discrimination, but the 2D- and 3D-augmented models yielded overlapping bootstrap confidence intervals for both endpoints: for overall survival, the DeLong FDR-adjusted p value for the 2D-versus-3D contrast was 0.006, and 0.612 for recurrence-free survival. Because no non-inferiority margin was pre-specified, the 2D–3D comparison is presented as exploratory, and we make no formal claim of non-inferiority or equivalence for either endpoint. The findings support single-slice L3 measurement as an efficient biomarker for risk stratification but warrant external validation in larger prospectively designed cohorts.

TPS159 Background: The liver is the most common site of metastasis in colorectal cancer, and liver metastases represent the primary cause of death among these patients. Achieving no evidence of disease (NED) to attain a disease-free state can significantly prolong overall survival. This study aims to evaluate the conversion rate and safety of adding tislelizumab to standard therapy regimens in patients with initially unresectable CRLM. Methods: This study enrolled patients with MSS-type CRLM. After the MDT assessed and confirmed potentially resectable disease, patients were stratified into two cohorts based on RAS status. The RAS wild-type cohort received tislelizumab combined with cetuximab and FOLFOX. The RAS mutant cohort received tislelizumab combined with bevacizumab and CAPOX. The primary endpoint was the conversion rate, and secondary endpoints included objective response rate (ORR), disease free survival (DFS) and safety. This clinical trial was registered at ClinicalTrials.gov (NCT05409417). Clinical trial information: NCT05409417 .

INTRODUCTION:The therapeutic efficacy of Colorectal Cancer (CRC) is often compromised by resistance to the standard chemotherapy agent oxaliplatin. METHODS:This study obtained single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database. Differentially Expressed Genes (DEGs) between resistant and sensitive epithelial subpopulations were identified, followed by enrichment analysis. Pseudotemporal trajectory and cell-cell communication were analyzed using Monocle2 and CellChat, respectively. The candidate drug was predicted by Connectivity Map (cMAP) analysis. External validation included assessment of the EpC2 signature in an oxaliplatin-resistant cell line dataset (GSE76092), survival analysis using The Cancer Genome Atlas (TCGA) cohorts, and re-analysis of the GSE179784 dataset to assess the reproducibility of EpC2-like subpopulations and their DNA Damage Repair (DDR) scores. RESULTS:Cell subpopulations were divided into 10 clusters. Among them, epithelial cells comprised 5 subpopulations, with EPC2 identified as a potential oxaliplatin-resistant subset. DEGs were enriched in the TNF and IL-17 pathways. External validation confirmed the enrichment of EpC2 in resistant cell lines and its association with poor survival. Pseudotemporal trajectory revealed that epithelial cells underwent state transitions, forming two distinct branches. The resistant group exhibited enrichment in RNA splicing and NF-κB pathways. Cell-cell communication analysis revealed interactions involving MDK- NCL and PPIA-BSG. Dasatinib was predicted as a candidate drug. DISCUSSION:We identified an oxaliplatin-resistant subpopulation of Epithelial Cells (EpC2) in CRC, elucidated its multi-layered resistance mechanisms, and integrated multi- omics and cMAP database analyses to predict a potential intervention drug. CONCLUSION:This study provided potential therapeutic possibilities for oxaliplatin resistance, contributing to CRC treatment.

PurposeThe ovarian metastases originating from colorectal cancer (CRCOM) develops rapidly and lethally. Previously, the genetic alterations and metastatic pathway in CRCOM were not well understood. The aim of this study is to explore the special molecular phenotype and dissemination patterns of CRCOM.MethodsThe whole-exome sequencing (WES) was performed on 65 matched tissue samples from 11 CRCOM patients, including 11 primary colorectal cancer (CRC) with 11 matched normal tissues, and 43 multi-site metastases (including 15 CRCOMs and 4 patients had bilateral ovarian metastases (OMs). Genetic landscape, neoantigens, tumor clonal origin and spread of CRCOMs were analyzed. TCGA-COAD dataset combined with our data were used for survival analysis and validation of the findings.ResultsThere was significant intertumoral heterogeneity among patients with CRCOM and intra-tumoral heterogeneity among multiorgan metastases. 19 genes were inferred as the potential driver genes of CRCOM. USP7 and RPA1 were HRD-related mutations and potential to serve as predictive biomarkers in OM. The putative neoantigen number of the primary CRC and OM varies widely among patients. The OM showed an immune desert state, extremely deficient in each subtype of immune cells. According to COSMIC signatures features, the CRCOM patients were divided into two groups, which are different in overall survival (OS) (median OS, 720 days vs 360 days, P = 0.074) and genetic alterations. Two metastatic patterns of CRCOM were summarized, which were primary CRC to OM, and metastases to metastases (including lymph node metastases (LNM) to OM, peritoneal metastases (PM) to OM, and other metastases to OM). Interestingly, the sources of bilateral OM might be different in the two patients.ConclusionThis study presents a better understanding the heterogeneity of the genetic characterizations and metastatic pattern in CRCOM. The subtypes of CRCOM with USP7 mutation, more copy number alterations, lower neoantigens, and immunoscore have a worse prognosis.

Background:Colorectal cancer with peritoneal metastases (CRCPM) exhibits high recurrence post-cytoreductive surgery (CRS). This study evaluated tumor tissue biomarkers and combined circulating tumor DNA (ctDNA) and methylation analysis via ultra-deep next-generation sequencing (NGS) for recurrence prediction. Methods:CRCPM patients undergoing surgery were enrolled (n=21). Blood samples was collected at preoperative and postoperative, and tumor and adjacent tissues were collected. NGS assessed ctDNA and methylation in blood samples, while tumor mutations and methylation were analyzed in tumor. Recurrence was determined via imaging. Outcomes included progression-free survival (PFS) and overall survival (OS). Results:Of 17 patients with paired pre-/postoperative ctDNA testing, preoperative ctDNA levels were higher in those with extraperitoneal metastases versus peritoneal-only disease (0.1064 vs 0.0037). Postoperative ctDNA positivity correlated with 100% peritoneal recurrence. ctDNA-positive subgroups showed shorter PFS (HR=2.5; 95% CI:1.6-6.6). Patients persistently ctDNA-negative pre-/postoperatively had improved PFS versus those with positivity (HR=5.07; 95% CI:0.53-48.38). ctDNA methylation positivity was observed in all extraperitoneal metastasis cases and 70% of peritoneal-only cases. Baseline methylation positivity predicted worse OS overall and in peritoneal-only subgroups. Postoperative dual negativity for ctDNA and methylation correlated with better OS. Tumor mutations in EPHB1 (P = 0.012), ARFRP1 (P = 0.048), and ATR (P = 0.048) were significantly associated with PFS. Conclusion:Dynamic ctDNA and methylation monitoring, and tumor mutation profiling, may serve as sensitive biomarkers for early recurrence detection in CRCPM underwent CRS. These tools could enhance recurrence prediction and guide clinical management.

Background:Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15-30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC.Materials and methods:The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate.Results:From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months.Conclusion:In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.

3614 Background: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of about 15%–- 30% for locally advanced rectal cancer (LARC). This PRECAM study aimed to investigate the efficacy and safety of neoadjuvant short-course radiotherapy combined with CAPEOX plus Envafolimab in Patients with Microsatellite Stable (MSS) LARC, redefining the standard of care (SOC) for LARC. Methods: The study is an open-label, prospective, single-arm, phase II clinical study . Eligible patients with MSS LARC were consecutively enrolled. Participants received short-course radiotherapy (25Gy/5f) with subsequent two cycles of CAPEOX (capecitabine and oxaliplatin) and 6 cycles of Envafolimab (subcutaneous injection, 150 mg, QW ) followed by total mesorectal excision surgery. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoint was major pathologic (MPR) rate and safety. Results: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study. Remarkably, The pCR rate was62.5% (20/32), and the (MPR) rate was 75% (24/32). Furthermore, 65.6% (21/32) patients achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%), with two cases of Grade 3 adverse events. Surgical procedures were performed in all 32 cases, with minor complications observed. During the follow-up period of up to 20 months, no recurrence or death were reported. Conclusions: Short-course radiotherapy combined with CAPEOX plus Envafolimab showed favorable pCR rate with manageable adverse effects and surgical complications in LARC, underscoring the potential of the combination therapy for MSS LARC. A Randomized controlled trial is warranted for further exploration and validation. Clinical trial information: NCT05216653 .

BACKGROUND Prophylactic loop ileostomy is an effective way to reduce the clinical severity of anastomotic leakage following radical resection of rectal cancer. Incisional surgical site infection (SSI) is a common complication after ileostomy closure. AIM To evaluate the efficacy and safety of the micro-power negative pressure wound technique (MPNPWT) in preventing incisional SSI. METHODS This was a prospective, randomized controlled clinical trial conducted at a single center. A total of 101 consecutive patients who underwent ileostomy closure after rectal cancer surgery with a prophylactic ileostomy were enrolled from January 2019 to December 2021. Patients were randomly allocated into an MPNPWT group and a control group. The MPNPWT group underwent intermittent suturing of the surgical incision with 2-0 Prolene and was covered with a micro-power negative pressure dressing. The surgical outcomes were compared between the MPNPWT (n = 50) and control (n = 51) groups. Risk factors for incisional SSI were identified using logistic regression. RESULTS There were no differences in baseline characteristics between the MPNPWT (n = 50) and control groups (n = 51). The incisional SSI rate was significantly higher in the control group than in the MPNPWT group (15.7% vs 2.0%, P = 0.031). However, MPNPWT did not affect other surgical outcomes, including intra-abdominal complications, operative time, and blood loss. Postoperative hospital stay length and hospitalization costs did not differ significantly between the two groups (P = 0.069 and 0.843, respectively). None of the patients experienced adverse effects of MPNPWT, including skin allergy, dermatitis, and pain. MPNPWT also helped heal the infected incision. Our study indicated that MPNPWT was an independent protective factor [odds ratio (OR) = 0.005, P = 0.025)] and diabetes was a risk factor (OR = 26.575, P = 0.029) for incisional SSI. CONCLUSION MPNPWT is an effective and safe way to prevent incisional SSI after loop ileostomy closure.

Supplementary Table S2. Detailed information of human pancreatic tissue array.

Supplementary Figure S1. In vivo CRISPR screens to identify critical drivers of immune evasion; Supplementary Figure S2. Effects of Ripk2 depletion on tumor growth; Supplementary Figure S3. RIPK2 is overexpressed in human and mouse PDAC tissues; Supplementary Figure S4. Ablation of RIPK2 disrupts the desmoplastic TME; Supplementary Figure S5. RIPK2 modulates the immune profile and impairs anti-tumor T cell response; Supplementary Figure S6. RIPK2 restricts the activation and effector states of CD8+ T cells by impairing antigen presentation; Supplementary Figure S7. RIPK2 promotes MHC-I trafficking to lysosomes via NBR1; Supplementary Figure S8. RIPK2 ubiquitination promotes NBR1-mediated MHC-I degradation; Supplementary Figure S9. RIPK2 ablation potentiates the efficacy of PD-1 blockade; Supplementary Figure S10. Diagram illustrating RIPK2-mediated degradation of MHC I through autophagy–lysosome system.

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy because of its aggressive nature and the paucity of effective treatment options. Almost all registered drugs have proven ineffective in addressing the needs of patients with PDAC. This is the result of a poor understanding of the unique tumor–immune microenvironment (TME) in PDAC. To identify druggable regulators of immunosuppressive TME, we performed a kinome- and membranome-focused CRISPR screening using orthotopic PDAC models. Our data showed that receptor-interacting protein kinase 2 (RIPK2) is a crucial driver of immune evasion of cytotoxic T-cell killing and that genetic or pharmacologic targeting of RIPK2 sensitizes PDAC to anti–programmed cell death protein 1 (anti–PD-1) immunotherapy, leading to prolonged survival or complete regression. Mechanistic studies revealed that tumor-intrinsic RIPK2 ablation disrupts desmoplastic TME and restores MHC class I (MHC-I) surface levels through eliminating NBR1-mediated autophagy-lysosomal degradation. Our results provide a rationale for a novel combination therapy consisting of RIPK2 inhibition and anti–PD-1 immunotherapy for PDAC. Significance: PDAC is resistant to almost all available therapies, including immune checkpoint blockade. Through in vivo CRISPR screen, we identified that RIPK2 plays a crucial role in facilitating immune evasion by impeding antigen presentation and cytotoxic T-cell killing. Targeting tumor-intrinsic RIPK2 either genetically or pharmacologically improves PDAC to anti–PD-1 immunotherapy. See related commentary by Liu et al., p. 208. This article is featured in Selected Articles from This Issue, p. 201

Supplementary Table S1. MAGeCK analysis of CRISPR screen results to identify regulator of immune evasion in orthotopic PDAC mouse models.

Given that anastomotic leakage (AL) is a severe complication of low anterior resection (LAR) for rectal cancer, ileostomy is the most common method for reducing the severity of AL, which in turn has stoma-related side effects. A self-developed technique named the stent-based diverting technique (SDT) not only protects the anastomosis but also avoids the stoma. From December 2021 to March 2023, 80 patients were randomized into the ileostomy arm (n = 43) or the SDT arm (n = 37). Demographic characteristics, laboratory test results, surgical outcomes, and oncological features were compared between the groups. For the primary endpoint, the incidence of severe complications was 14.0% in the ileostomy arm and 8.1% in the SDT arm (relative risk=0.58, 95% confidence interval=0.156-2.163, p=0.494). For the second endpoint, the incidences of mild and total complications were comparable. The shorter the hospital stay, the lower the cost and quality of life, which could be improved by the SDT procedure. This prospective randomized clinical trial preliminarily evaluated the usefulness of SDT after LAR for patients with rectal cancer, suggesting that SDT might be an alternative operation for patients who need to receive ileostomy after rectal surgery.

Colorectal polyps detected during colonoscopy are strongly associated with colorectal cancer, making polyp segmentation a critical clinical decision-making tool for diagnosis and treatment planning. However, accurate polyp segmentation remains a challenging task, particularly in cases involving diminutive polyps and other intestinal substances that produce a high false-positive rate. Previous polyp segmentation networks based on supervised binary masks may have lacked global semantic perception of polyps, resulting in a loss of capture and discrimination capability for polyps in complex scenarios. To address this issue, we propose a novel Gaussian-Probabilistic guided semantic fusion method that progressively fuses the probability information of polyp positions with the decoder supervised by binary masks. Our Probabilistic Modeling Ensemble Vision Transformer Network(PETNet) effectively suppresses noise in features and significantly improves expressive capabilities at both pixel and instance levels, using just simple types of convolutional decoders. Extensive experiments on five widely adopted datasets show that PETNet outperforms existing methods in identifying polyp camouflage, appearance changes, and small polyp scenes, and achieves a speed about 27FPS in edge computing devices. Codes are available at: https://github.com/Seasonsling/PETNet .

Globally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest developments in our understanding of the clinical and molecular features of gastrointestinal signet ring cell carcinoma (SRCC). Additionally, we have compiled a list of potential therapeutic targets or biomarkers, as well as an examination of the current treatment options and the possible mechanisms of formation.

134 Background: Chemoradiation is the standard neoadjuvant treatment for locally advanced rectal cancer. Microsatellite stable (MSS)/ mismatch repair proficient (pMMR) rectal cancer rarely responds to immune checkpoint inhibitor monotherapy, but combination with chemoradiation may improve sensitivity of MSS/pMMR tumors by inducing immune-stimulatory effects. Therefore, we aimed to investigate the efficacy and safety of patients treated with neoadjuvant preoperative short-course radiation followed by envafolimab plus CAPEOX for MSS/pMMR locally advanced rectal cancer. Methods: This is an open-label, single-center, phase ¢ò study. Patients (pts) with locally advanced rectal adenocarcinoma with MSS/pMMR were eligible. MMR protein expression was tested by immunohistochemistry (IHC) £¬and MSI status was confirmed by NGS (next generation sequencing). All pts included in this study underwent neoadjuvant short-course radiation (total dose of 5¡Á5Gy) in the first week after enrollment, then followed by 6 cycles of envafolimab (anti-PD-L1 inhibitor,150mg, d1, subcutaneous injection, QW) plus 2 cycles of CAPEOX in the next six weeks, and subsequently underwent total mesorectal excision (TME) in the ninth week. The primary endpoint is pathological complete response rate. Secondary endpoints include tumor regression grade (TRG), 3 year disease free survival, overall survival, toxicity, and quality of life (QoL). Results: This study intends to recruit 32 pts, and a total of 21 pts were enrolled from January 2022 to September 2022. Overall median age was 67 (42-79) years. 12 pts completed study designed treatment protocol (envafolimab plus CAPOX) followed with TME procedures, and 9 pts are still undergoing neoadjuvant treatment. All 12 pts achieved major partial response (MPR) evaluated by diffusion-weighted magnetic resonance imaging (DW-MRI), and 8 pts (8/12,76.6%) achieved pCR. During neoadjuvant treatment period, 20 pts (20/21, 95.2%) presented with treatment-related AEs (TRAEs) of any grade, 18 pts (18/21, 85.7%) had grade 1-2 and one each pts had grade 3 and 4 thrombocytopenia (2/21, 9.5%). The most common TRAEs were sensation of rectal tenesmus. Conclusions: Neoadjuvant preoperative short-course radiation followed by envafolimab plus CAPEOX in MSS/pMMR locally advanced rectal cancer achieved a promising pathologic response. Meanwhile, this combination neoadjuvant therapy is safe and worthy of application to clinical practice. (Funded by Sir Run Run Shaw Hospital Zhejiang University School of Medicine.) Clinical trial information: NCT05216653 .

Objective and Impact Statement. Distinguishing tumors from normal tissues is vital in the intraoperative diagnosis and pathological examination. In this work, we propose to utilize Raman spectroscopy as a novel modality in surgery to detect colorectal cancer tissues. Introduction. Raman spectra can reflect the substance components of the target tissues. However, the feature peak is slight and hard to detect due to environmental noise. Collecting a high-quality Raman spectroscopy dataset and developing effective deep learning detection methods are possibly viable approaches. Methods. First, we collect a large Raman spectroscopy dataset from 26 colorectal cancer patients with the Raman shift ranging from 385 to 1545 cm − 1 . Second, a one-dimensional residual convolutional neural network (1D-ResNet) architecture is designed to classify the tumor tissues of colorectal cancer. Third, we visualize and interpret the fingerprint peaks found by our deep learning model. Results. Experimental results show that our deep learning method achieves 98.5% accuracy in the detection of colorectal cancer and outperforms traditional methods. Conclusion. Overall, Raman spectra are a novel modality for clinical detection of colorectal cancer. Our proposed ensemble 1D-ResNet could effectively classify the Raman spectra obtained from colorectal tumor tissues or normal tissues.