Purpose: Residual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT). Methods: We retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50–50.6 Gy for the planning gross tumor volume and 41.8–45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). Results: After surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610–0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. Conclusion: The nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.

Background: Compared to male cancer patients, female patients have a higher incidence and severity of adverse events (AEs) associated with anticancer treatment. The mechanism underlying these disparities is largely unknown, especially in the context of radiotherapy. Notably, the composition and metabolism of the gut microbiota differ between sexes, and such differences have been implicated in multiple physiological and pathological processes. In this study, we aimed to investigate the sex differences in hematologic toxicities during chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and to explore the potential role of the gut microbiota in mediating these differences. Materials and Methods: This real-world study included 329 patients with LARC receiving neoadjuvant chemoradiotherapy (nCRT). Hematologic AEs were evaluated according to Common Terminology Criteria for Adverse Events 5.0. 16S rRNA sequencing, metatranscriptome sequencing, and metabolome detection were performed on longitudinal fecal samples. Mendelian randomization analyses were performed to investigate the correlation between stem cell and gut microbial traits. Results: In this cohort, females had a higher severity of hematologic AEs than males. Using integrated longitudinal multi-omics data, we identified sex-biased bacterial species (e.g., Parasutterella excrementihominis and Bifidobacterium adolescentis ) and microbiota-mediated arginine metabolism associated with hematologic toxicities. Gut microbiome-mediated arginine metabolism is associated with an abundance of hematopoietic stem cells and may be involved in the occurrence of sex-biased radiotherapy-induced hematologic AEs. Conclusion: These results indicate that the differences in gut microbial composition and metabolism between the two sexes are associated with the sex-biased hematologic AEs induced by nCRT. Females require greater attention regarding the hematologic toxicity of chemoradiotherapy, and that gut microbes may serve as potential targets for sex-tailored strategies to restore hematopoietic function following chemoradiotherapy.

The aim of this study was to explore the impact of including or excluding the ischiorectal fossa (IRF) within the clinical target volume during neoadjuvant chemoradiotherapy (NCRT) using intensity modulated radiotherapy, in locally advanced lower rectal cancer (LALRC). We retrospectively analysed the data of 220 LALRC patients who received NCRT followed by abdominoperineal resection between January 2009 and January 2015. Six patients were excluded because of loss to follow-up, 90 patients received IRF irradiation (IRF group) while 124 patients did not (NIRF group). Survival, patterns of recurrence, and treatment toxicities were compared between the two groups. Overall, patient/treatment variables were well balanced except for surgical technique. Perineal wound complications in the IRF and NIRF groups, were 40.0 and 24.2%, respectively (p = 0.010); corresponding 3-year perineal recurrence rates, local recurrence free survival, overall survival, and distant relapse free survival were 4.4% vs. 2.4% (p = 0.670), 88.1% vs. 95.0% (p = 0.079), 82.6% vs. 88.4% (p = 0.087), and 61.9% vs. 81.0% (p = 0.026), respectively. Multivariate analyses demonstrated the following factors to be significantly related to perineal wound complications: irradiation of the IRF (odds ratio [OR] 2.892, p = 0.002), anaemia (OR 3.776, p = 0.010), operation duration > 180 min (OR 2.486, p = 0.007), and interval between radiotherapy and surgery > 8 weeks (OR 2.400, p = 0.010). Exclusion of the IRF from the clinical target volume during NCRT using intensity-modulated radiotherapy in LALRC could lower the incidence of perineal wound complications after abdominoperineal resection, without compromising oncological outcomes.