Chemoradiotherapy For Rectal Cancer Research Articles

Sialyltransferase ST6GAL-1 mediates resistance to chemoradiation in rectal cancer

Locally advanced rectal cancer is typically treated with chemoradiotherapy followed by surgery. Most patients do not display a complete response to chemoradiotherapy, but resistance mechanisms are poorly understood. ST6GAL-1 is a sialyltransferase that adds the negatively charged sugar, sialic acid (Sia), to cell surface proteins in the Golgi, altering their function. We therefore hypothesized that ST6GAL-1 could mediate resistance to chemoradiation in rectal cancer by inhibiting apoptosis. Patient-derived xenograft and organoid models of rectal cancer and rectal cancer cell lines were assessed for ST6GAL-1 protein with and without chemoradiation treatment. ST6GAL-1 mRNA was assessed in untreated human rectal adenocarcinoma by PCR assays. Samples were further assessed by Western blotting, Caspase-Glo apoptosis assays, and colony formation assays. The presence of functional ST6GAL-1 was assessed via flow cytometry using the Sambucus nigra lectin, which specifically binds cell surface α2,6-linked Sia, and via lectin precipitation. In patient-derived xenograft models of rectal cancer, we found that ST6GAL-1 protein was increased after chemoradiation in a subset of samples. Rectal cancer cell lines demonstrated increased ST6GAL-1 protein and cell surface Sia after chemoradiation. ST6GAL-1 was also increased in rectal cancer organoids after treatment. ST6GAL-1 knockdown in rectal cancer cell lines resulted in increased apoptosis and decreased survival after treatment. We concluded that ST6GAL-1 promotes resistance to chemoradiotherapy by inhibiting apoptosis in rectal cancer cell lines. More research will be needed to further elucidate the importance and mechanism of ST6GAL-1-mediated resistance.

Tumor-Infiltrating PD-1+ Immune Cell Density is Associated with Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer

BackgroundElevated tumor-infiltrating T-cell density is associated with favorable outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Here, we evaluated the significance of programmed cell death 1 (PD-1)-positive cells, regulatory T cells, and macrophages in response to CRT and prognosis. Patients and MethodsWe assessed CD8+, PD-1+, FOXP3+, CD68+, and CD163+ intratumoral and stromal cell densities by immunohistochemistry using pre-treatment biopsies from 275 patients with rectal cancer treated with neoadjuvant CRT. We determined the impact of these measurements on response to CRT and survival. Response to CRT was determined by tumor regression grade (TRG) of surgical specimens, with good responders defined as TRG3-4. ResultsIntratumoral CD8+ and PD-1+ cell densities were significantly higher in good responders than in poor responders, whereas stromal CD68+ cell density was significantly lower in good responders as compared with poor responders. The multivariable analysis revealed high intratumoral CD8+ and PD-1+ cell densities to be independently associated with good responders (CD8: odds ratio [OR], 2.27; 95% confidence interval [CI], 1.21 – 4.34, P = .010; PD-1: OR, 1.97; 95%CI, 1.03 – 3.84, P = .039), and improved recurrence-free survival (CD8: hazard ratio [HR], 0.56; 95%CI, 0.32 – 0.98, P = .044; PD-1: HR, 0.37; 95%CI, 0.19 – 0.71, P = .002). Only high intratumoral CD8+ cell density was associated with improved overall survival (P = .022). ConclusionPre-treatment high intratumoral PD-1+ and CD8+ cell densities were independently associated with good response to CRT and improved recurrence-free survival, with high intratumoral CD8+ cell density additionally associated with improved overall survival. These values may serve as predictive and prognostic biomarkers in rectal cancer.

Predicting response to neoadjuvant chemoradiotherapy in rectal cancer: from biomarkers to tumor models.

Colorectal cancer (CRC) is a major contributor to cancer-associated morbidity worldwide and over one-third of CRC is located in the rectum. Neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection is commonly applied to treat locally advanced rectal cancer (LARC). In this review, we summarize current and novel concepts of neoadjuvant therapy for LARC such as total neoadjuvant therapy and describe how these developments impact treatment response. Moreover, as response to nCRT is highly divergent in rectal cancers, we discuss the role of potential predictive biomarkers. We review recent advances in biomarker discovery, from a clinical as well as a histopathological and molecular perspective. Furthermore, the role of emerging predictive biomarkers derived from the tumor environment such as immune cell composition and gut microbiome is presented. Finally, we describe how different tumor models such as patient-derived cancer organoids are used to identify novel predictive biomarkers for chemoradiotherapy (CRT) in rectal cancer.

Using Multi-Scale Convolutional Neural Network Based on Multi-Instance Learning to Predict the Efficacy of Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Background: At present, radical total mesorectal excision after neoadjuvant chemoradiotherapy is crucial for locally advanced rectal cancer. Therefore, the use of histopathological images analysis technology to predict the efficacy of neoadjuvant chemoradiotherapy for rectal cancer is of great significance for the subsequent treatment of patients. Methods: In this study, we propose a new pathological images analysis method based on multi-instance learning to predict the efficacy of neoadjuvant chemoradiotherapy for rectal cancer. Specifically, we proposed a gated attention normalization mechanism based on the multilayer perceptron, which accelerates the convergence of stochastic gradient descent optimization and can speed up the training process. We also proposed a bilinear attention multi-scale feature fusion mechanism, which organically fuses the global features of the larger receptive fields and the detailed features of the smaller receptive fields and alleviates the problem of pathological images context information loss caused by block sampling. At the same time, we also designed a weighted loss function to alleviate the problem of imbalance between cancerous instances and normal instances. Results: We evaluated our method on a locally advanced rectal cancer dataset containing 150 whole slide images. In addition, to verify our method’s generalization performance, we also tested on two publicly available datasets, Camelyon16 and MSKCC. The results show that the AUC values of our method on the Camelyon16 and MSKCC datasets reach 0.9337 and 0.9091, respectively. Conclusion: Our method has outstanding performance and advantages in predicting the efficacy of neoadjuvant chemoradiotherapy for rectal cancer. Clinical and Translational Impact Statement—This study aims to predict the efficacy of neoadjuvant chemoradiotherapy for rectal cancer to assist clinicians quickly diagnose and formulate personalized treatment plans for patients.

Association between microsatellite instability and tumor response to neoadjuvant chemoradiotherapy for rectal cancer

PurposeThe relationship between microsatellite instability (MSI) and tumor response after neoadjuvant chemoradiotherapy (nCRT) in rectal cancer remains unclear. The present study aimed to evaluate the association between MSI and tumor response to nCRT in rectal cancer treatment.MethodsPatients with rectal cancer from 2 tertiary hospitals who underwent nCRT, followed by radical surgery, were included. The microsatellite status was determined using a PCR-based Bethesda panel. Tumors with a Dworak’s tumor regression grade of 3 or 4 were considered to have a good response. Predictive factors for a good response to nCRT were analyzed.ResultsOf the 1,401 patients included, 910 (65.0%) had MSI results and 1.5% (14 of 910) showed MSI-H. Among all the patients, 519 (37.0%) showed a good response to nCRT. A univariate analysis showed that MSI-H tended to be negatively associated with a good response to nCRT, but no statistical significance was observed (7.1% vs. 24.1%, P = 0.208). Multivariate analysis showed that well-differentiated tumors were the only predictive factor for good response to nCRT (odds ratio [OR], 2.241; 95% confidence interval [CI], 1.492–3.364; P < 0.001). MSI status tended to be associated with the response to nCRT (OR, 0.215; 95% CI, 0.027–1.681; P = 0.143).ConclusionMSI-H was not associated with response to nCRT in patients with rectal cancer.

Physical activity programmes for patients undergoing neo-adjuvant chemoradiotherapy for rectal cancer: A systematic review and meta-analysis.

Background:Patients diagnosed with localized rectal cancer should undergo Neoadjuvant Radio-Chemotherapy (NACRT) followed, a few weeks later, by surgical resection. NACRT is known to cause significant decline in the physical and psychological health of patients. This literature review aims to summarize the effects of a prehabilitation programme during and/or after NACRT but before surgery.Methods:Articles included in this review have been selected by two independent researchers on Pubmed, Google Scholar, and Cochrane databases with the following terms: “Rectal Cancer AND Physical Activity” and “Exercise AND Rectal Cancer.”Results:We obtained 560 articles. We selected 12 of these, representing 7 series but only one randomized study, constituting 153 patients in total. Most studies included have considerable variation in their prehabilitation programmes, in terms of supervision, training content, frequency, intensity, duration, and temporality, in regard to NACRT and surgery. Implementing a prehabilitation programme during NACRT seems feasible and safe, with adherence ranging from 58% to 100%. VO2max (maximal oxygen consumption during incremental exercise) was improved in three of the studies during the prehabilitation programme. No significant difference in the step count, 6-minute-walk test, or quality of life was seen.Conclusions:Prehabilitation programmes during NACRT for localized rectal cancer patients are safe and feasible; however, due to considerable variation in the prehabilitation programmes and their small size, impact on fitness, quality of life, and surgical outcome are unknown. Larger randomized studies are needed.

Factors Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer: The Experience of a Single Institution with 269 Patients (STONE-01).

Simple SummaryNeoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision is currently the standard of care for locally advanced rectal cancer (LARC). This retrospective cohort study evaluated the pathological response after CRT in relation to treatment factors and patient and disease factors in order to find useful indicators to further improve the efficacy of CRT and create tailored therapeutic approaches. To date, the optimal timing for surgery after CRT has not been established. In literature, there are controversial results regarding the risk of higher surgical morbidity and perioperative complications due to delayed surgery. In our study carried out on 269 consecutive LARC patients, among the items analyzed, an interval time from CRT to surgery of >8 weeks was the only independent significant factor for pCR and downstaging.Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27–0.93 and p = 0.003; OR: 0.42, CI: 0.24–0.75, respectively). Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.

Cost-Effectiveness of TME Alone vs. Neoadjuvant Chemoradiotherapy for Stage II and III Rectal Cancer

<h3>Purpose/Objective(s)</h3> The role of neoadjuvant chemoradiotherapy in rectal cancer is rapidly evolving. Neoadjuvant chemoradiotherapy (nCRT) reduces the risk of local recurrence in rectal cancer patients, but is associated with increased adverse events, costs, and prolonged treatment time. Pre-operative risk stratification of patients into low- and high-risk categories for local recurrence may identify populations that benefit from nCRT, despite these additional costs. Although total mesorectal excision (TME) alone and nCRT with TME (nCRT/TME) are both in clinical practice, no cost-effectiveness analysis comparing these two treatment approaches in rectal cancer has been published. We sought to determine the cost-effectiveness of primary TME versus nCRT with TME for patients with rectal cancer. <h3>Materials/Methods</h3> We developed a Markov model to simulate the 3-year outcomes of 1 million hypothetical patients as treated on the OCUM trial (NCT 325649) with histologically confirmed invasive carcinoma of the rectum (cT2 to cT4, mC0) with distal tumor margin less than 16 cm from the anal verge undergoing either primary TME or nCRT followed by TME. To calculate the incremental cost-effectiveness ratios, we used utilities and probabilities from the literature and costs from Medicare fee schedules and the Healthcare Bluebook. We discounted utilities and costs at 3% annually. Willingness to pay (WTP) was defined at ICER of $100 000 or less per quality-adjusted life-year (QALY). 1-way sensitivity analyses were performed varying selective model inputs to account for uncertainty. Probabilistic sensitivity analysis (PSA) was conducted. <h3>Results</h3> TME was the dominant strategy compared with nCRT and TME (incremental cost-effectiveness ratio, -$158,201.86/QALY). TME and nCRT/TME were associated with costs of $32,518 and $70,583 and QALYs of 1.91 and 1.67, respectively. TME remained the dominant strategy across all 1-way sensitivity analyses in cost, utility states, and probabilities with the exception of the utilities of the health states post-TME and post-nCRT/TME. When the utility of TME treatment fell below 0.4, nCRT/TME became the dominant strategy. Conversely, when the utility of nCRT/TME treatment rose above 0.69 (.1 above the baseline TME utility), nCRT/TME became the dominant strategy. PSA with 1,000,000 samples revealed TME was the cost-effective strategy in 67.4% of trials. <h3>Conclusion</h3> In patients with rectal cancer, TME was the cost-effective strategy compared with nCRT/TME. TME remained the cost-effective strategy across a range of tested variations in cost, probabilities, and utilities but was sensitive to the utility of TME and nCRT/TME. The results of this study contribute to the growing body of literature decreasing usage of nCRT/TME for patients with rectal cancer, particularly if they have low risk of local recurrence.

Organoids as a Robust Preclinical Model for Precision Medicine in Colorectal Cancer: A Systematic Review.

Patients with locally advanced or metastatic colorectal cancer (CRC) display heterogeneous responses to standard-of-care therapy. Robust preclinical models of malignancy in the form of patient-derived tumor organoids (PDTOs) have recently come to the fore in tailoring patient care to a personalized medicine level. This study aimed to review the literature systematically regarding PTDOs and gauge their impact on precision medicine in the management of CRC. A PRISMA-compliant systematic review of the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases was performed. The results were categorized based on the primary objective of the individual studies as follows: organoid use in predicting effective hyperthermic intraperitoneal chemotherapy (HIPEC), systemic chemotherapy in CRC, or neoadjuvant chemoradiotherapy in rectal cancer. The literature search found 200 publications, 16 of which met the inclusion criteria. Organoid models of primary and metastatic CRC have been increasingly used to assess clinical responses to standard therapy. Marked heterogeneity exists, matching the responses observed in clinical practice with ex vivo drug and radiation screening. Repeated correlation between organoid and patient sensitivity to forms of HIPEC, systemic chemotherapy, and chemoradiotherapy has been observed. Patient-derived tumor organoids are the latest tool in predictive translational research. Current organoid-based studies in precision medicine have shown their great potential for predicting the clinical response of patients to CRC therapy. Larger-scale, prospective data are required to fully support this exciting avenue in cancer care.

Computed tomography-derived biomarker for predicting the treatment response to neoadjuvant chemoradiotherapy of rectal cancer.

Malignant tumor essentially implies structural heterogeneity. Analysis of medical imaging can quantify this structural heterogeneity, which can be a new biomarker. This study aimed to evaluate the usefulness of texture analysis of computed tomography (CT) imaging as a biomarker for predicting the therapeutic response of neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer. We enrolled 76 patients with rectal cancer who underwent curative surgery after nCRT. Texture analyses (Fractal analysis and Histogram analysis) were applied to contrast-enhanced CT images, and fractal dimension (FD), skewness, and kurtosis of the tumor were calculated. These CT-derived parameters were compared with the therapeutic response and prognosis. Forty-six of 76 patients were diagnosed as clinical responders after nCRT. Kurtosis was significantly higher in the responders group than in the non-responders group (4.17 ± 4.16 vs. 2.62 ± 3.19, p = 0.04). Nine of 76 patients were diagnosed with pathological complete response (pCR) after surgery. FD of the pCR group was significantly lower than that of the non-pCR group (0.90 ± 0.12 vs. 1.01 ± 0.12, p = 0.009). The area under the receiver-operating characteristics curve of tumor FD for predicting pCR was 0.77, and the optimal cut-off value was 0.84 (accuracy; 93.4%). Furthermore, patients with lower FD tumors tended to show better relapse-free survival and disease-specific survival than those with higher FD tumors (5-year, 80.8 vs. 66.6%, 94.4 vs. 80.2%, respectively), although it was not statistically significant (p = 0.14, 0.11). CT-derived texture parameters could be potential biomarkers for predicting the therapeutic response of rectal cancer.

Pretreatment Neutrophil-to-Lymphocyte Ratio Associated with Tumor Recurrence and Survival in Patients Achieving a Pathological Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Simple SummaryPatients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiotherapy have been associated with excellent long-term prognosis. However, approximately 9% to 12% of patients with a pathological complete response have been reported to experience tumor recurrence and thereby experience poor outcomes. Identifying predictors of recurrence in patients with a pathological complete response is crucial for precise medicine. The neutrophil-to-lymphocyte ratio is a widely available biomarker of systemic inflammation and affects colorectal prognosis. The study aimed to assess the association between neutrophil-to-lymphocyte ratio and oncological outcomes in rectal cancer patients exhibiting a pCR. We found that a pretreatment high neutrophil-to-lymphocyte ratio (≥3.2) was an independent predictor of reduced overall survival and disease-free survival in patients with locally advanced rectal cancer who achieved a pathological complete response to neoadjuvant chemoradiotherapy. Our findings demonstrate that the neutrophil-to-lymphocyte ratio helps identify patients with a pathological complete response who are at high risk of tumor relapse and might facilitate patient selection for precise medicine.The clinical influence of the neutrophil-to-lymphocyte ratio (NLR) in predicting outcomes in patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) has seldom been investigated. We retrospectively recruited 102 patients with LARC who achieved a pCR to NACRT and the association of NLR status with survival and tumor recurrence in the patients was analyzed. Thirteen patients (12.7%) developed tumor recurrence. A high NLR (≥3.2) was significantly associated with tumor recurrence (p = 0.039). The 5-year OS rates in patients with a low NLR and patients with a high NLR were 95.1% and 77.7%, respectively (p = 0.014); the 5-year DFS rates in patients with low NLR and patients with a high NLR were 90.6% and 71.3%, respectively (p = 0.031). The Cox proportional hazards model indicated that an NLR of ≥3.2 was an independent poor prognostic factor for DFS (hazard ratio [HR] = 3.12, 95% confidence interval [CI] = 1.06–9.46, p = 0.048) and OS (HR = 6.96, 95% CI = 1.53–35.51, p = 0.013). A pretreatment high NLR (≥3.2) was a promising predictor of reduced OS and DFS in patients with LARC who achieved a pCR to NACRT.

Watch and Wait Approach After Neoadjuvant Chemoradiotherapy in Rectal Cancer: Initial Experience in the Indian subcontinent.

Patients with locally advanced rectal cancer (LARC) that have a complete clinico-radiological response after neoadjuvant chemoradiation (NACRT) can be offered nonoperative or watch and wait (W&W) management. This study assessed the compliance and outcomes of such patients at our institute. Thirty-six patients with locally advanced low-lying rectal cancers treated between December 2013 and November 2018 and had a near-complete clinical response (ncCR) or complete clinical response (cCR) after completing NACRT and were reluctant to undergo surgery were included. They were followed up at 3 monthly intervals with a combination of pelvic MRI, digital rectal examination, and sigmoidoscopy. Twelve weeks after chemoradiation, 24 (67%) patients had cCR and 12 (33%) had ncCR. All the 36 patients were kept on the W&W protocol. At a median follow-up of 35 (range 17-72) months, six (17%) patients developed local regrowth, one fromthe cCRgroup, while five were from the ncCR group. Four of the six patients underwent surgery for local disease (three had sphincter preserving resections and one had abdominoperineal resection), and one of these also hadliver metastatectomy. Two of the six patients refused surgery, giving a compliance rate of 94.5%. Three of the 36 patients (8%) had distant metastasis, one had liver metastasis, one had leptomeningeal metastasis, and the third who refused surgery at regrowth developed lung metastasis. Thus, of the 36 patients on the W&W protocol, organ preservation rate was 80%. Local regrowth free DFS was 92.4%, and OAS was 96% at 3years. W&W approach after cCR and ncCR to NACRT in LARC is acceptable with reasonable compliance and with good outcomes.

Concurrent use of statins and neoadjuvant chemoradiotherapy for rectal cancer: a systematic review and meta-analysis.

Statins are used primarily in patients with cardiovascular disease. More recently, they have demonstrated benefit in oncology patients. In vitro models have shown decreased rectal tumor cell viability in cells receiving chemoradiation and statin therapy. In vivo models have been less clear. This study aims to elucidate the impact of concurrent use of statins on the efficacy of neoadjuvant therapy for rectal cancer. Search of Medline, EMBASE, and CENTRAL was performed. Articles were included if they reported complete pathological response (pCR), long-term oncologic outcomes, or chemoradiotherapy-induced toxicity in patients with rectal cancer receiving concurrent statin and neoadjuvant therapy. A pairwise meta-analyses was performed using inverse variance random effects. From 1564 citations, six studies with 726 patients on statin therapy (24.5% female, age: 63.6years) and 1863 patients not on statin therapy (35.6% female, age: 60.9years) were included. There was no significant difference in pCR rate between patients on statin therapy and patients not on statin therapy (RR 1.23, 95%CI 0.98-1.54, p = 0.08). Similarly, no difference existed between groups in long-term oncologic outcomes (5-year overall survival: RR 1.03, 95%CI 0.86-1.24, p = 0.75; 5-year disease-free survival: RR 1.04, 95%CI 0.85-1.26, p = 0.73). Chemoradiotherapy-induced toxicities were similar between groups. The concurrent use of statin and neoadjuvant therapy did not significantly impact short- or long-term oncologic outcomes in patients with rectal cancer. Yet, despite pooling of data, this study remained inadequately powered. Larger, prospective studies are required to further elucidate the impact of statins on patients undergoing neoadjuvant therapy for rectal cancer.

Histopathological, Radiological, and Demographic Factors Predicting the Response to Neoadjuvant Therapy for Rectal Cancer

While the treatment for early stage rectal cancer is surgery, when a diagnosis is made at a locally advanced stage, it is recommended to start treatment with neoadjuvant chemoradiotherapy. Therefore, it is important to determine which patients will respond best to neoadjuvant treatment. The aim of this study was to investigate which hematological, histopathological, and radiological parameters can predict the response to chemoradiotherapy. A retrospective examination was made of 43 patients who underwent surgery following neoadjuvant chemoradiotherapy because of locally advanced stage rectal cancer. Demographic data were collected from the patient files, and the radiological, histopathological, and laboratory findings before neoadjuvant chemoradiotherapy were compared with the findings after treatment. In the postoperative evaluation, a pathological complete response was determined in 25.50% of the patients. Lymphovascular invasion, perineural invasion, and absence of necrosisis were seen to be statistically related to major response (p < 0.05), and in patients where the tumor was closer than 6cm to the anal verge, the response was better CONCLUSION: When the findings were examined, histopathological lymphovascular invasion, perineural invasion, the presence of necrosis, and the anal verge distance were evaluated as parameters predicting the response to neoadjuvant chemoradiotherapy in rectal cancer.

Is Metformin Associated With Improved Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer?

Efforts to determine whether metformin can increase the effectiveness of neoadjuvant chemoradiotherapy in rectal cancer have increased in recent years. However, retrospective studies have yielded inconclusive results. The aim of this study was to compare oncological outcomes and survival after neoadjuvant chemoradiotherapy in patients with rectal cancer taking metformin versus in those not taking metformin. This study analyzed 423 consecutive patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy and curative surgery between January 2010 and May 2020; of these, 59 were taking metformin and 364 were not taking metformin. Patients taking metformin had a lower proportion of tumor regression (6.8% versus 22.0%, P=0.012) as well as a lower proportion of patients achieving a pathological complete response (6.8% versus 20.6%, P=0.011). In the multivariate analysis, independent predictors of pathologic complete response were not taking metformin (OR: 5.26, 95% CI: 1.12-24.85, P= 0.035) and cT2 stage (OR: 3.49, 95% CI: 1.10-11.07, P= 0.034); the interval was also an independent predictor of tumor regression (OR: 1.78, 95% CI: 1.06-2.96, P= 0.028). No differenceswere observed insurvival between groups. Metformin was not associated with better tumor responses or survival after neoadjuvant treatment.

PO-1264 Predictive factors of pathological response to neoadjuvant chemoradiotherapy in rectal cancer

PO-1264 Predictive factors of pathological response to neoadjuvant chemoradiotherapy in rectal cancer

PO-1269 C-Reactive Protein as predictive factor for response to chemoradiotherapy in Rectal Cancer

PO-1269 C-Reactive Protein as predictive factor for response to chemoradiotherapy in Rectal Cancer

OC-0623 SMAD3 expression and genetic variation could predict response to chemoradiation in rectal cancer

OC-0623 SMAD3 expression and genetic variation could predict response to chemoradiation in rectal cancer

OC-0402 Metabolomics as predictor of treatment response in neoadjuvant chemoradiation for rectal cancer

OC-0402 Metabolomics as predictor of treatment response in neoadjuvant chemoradiation for rectal cancer

Beneficiaries of radical surgery among clinical complete responders to neoadjuvant chemoradiotherapy in rectal cancer.

This study aimed to identify patients who benefit from radical surgery among those with rectal cancer who achieved clinical complete response (cCR). Patients with locally advanced rectal cancer (LARC; stage II/III) who achieved cCR after neoadjuvant chemoradiotherapy (nCRT) were included (n = 212). Univariate/multivariate Cox analysis was performed to validate predictors for distant metastasis‐free survival (DMFS). A decision tree was generated using recursive partitioning analysis (RPA) to categorize patients into different risk stratifications. Total mesorectal excision (TME) was compared with the watch‐and‐wait (W&W) strategy in each risk group. Two molecular predicators of CEA and CA19‐9 were selected to establish the RPA‐based risk stratification, categorizing LARC patients into low‐risk (n = 139; CA19‐9 < 35 U/mL and CEA < 5 ng/mL) and high‐risk (n = 73; CA19‐9 ≥ 35 U/mL or CEA ≥5 ng/mL) groups. Superior 5‐y DMFS was observed in the low‐risk group vs. the high‐risk group (92.9% vs. 76.2%, P = .002). Low‐risk LARC patients who underwent TME had significantly improved 5‐y DMFS compared with their counterparts receiving the W&W strategy (95.9% vs. 84.3%; P = .028). No significant survival difference was observed in high‐risk patients receiving the 2 treatment modalities (77.9% vs. 94.1%; P = .143). LARC patients with cCR who had both baseline CA19‐9 < 35 U/mL and CEA < 5 ng/mL may benefit from radical surgery.