Search Results (1,176)

Background/Objectives: Mucinous adenocarcinoma (MAC) is a rare and clinically problematic subtype of rectal cancer, tending to present at an advanced stage and to respond poorly to neoadjuvant therapy. The consistently worse prognosis than that of not-otherwise-specified adenocarcinoma (NOS-AC) is not fully understood, potentially owing to intrinsically more aggressive biology or specific immune evasion mechanisms. We used the IMMUNOREACT multicentre cohort, with external validation in TCGA, to investigate the clinical and immunological features of rectal MAC in detail. Methods: Two hundred patients with rectal adenocarcinoma (16 MAC, 184 NOS-AC) from the IMMUNOREACT 1 (NCT04915326) and IMMUNOREACT 2 (NCT04917263) prospective cohorts were included. To account for the imbalance in baseline characteristics, propensity score matching (PSM) was performed on age, sex, neoadjuvant treatment and TNM stage. The immune microenvironment was characterised using immunohistochemistry (CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, PMS2, CD80), flow cytometry and NanoString PanCancer IO 360™ transcriptomics of adjacent healthy mucosa. Findings were externally validated against TCGA rectal and colon adenocarcinoma datasets. Results: MAC presented at significantly more advanced stage than NOS-AC across all TNM parameters: higher T stage (p = 0.006), N stage (p < 0.001), M stage (p = 0.039) and overall TNM stage (p < 0.001). In the unmatched cohort, MAC was associated with worse overall survival (HR 2.53; 95% CI 1.03–6.23; p = 0.043) and disease-free survival (HR 2.86; 95% CI 1.25–6.55; p = 0.013), but both differences became non-significant after PSM. MAC patients had higher haemoglobin after adjusting for confounders (mean difference [MD] 1.26 g/dL, 95% CI 0.30–2.31, p = 0.012), consistent with a hypothesis of reduced chronic rectal bleeding as a possible mechanism for late presentation. Transcriptomically, MAC showed suppression of HLA class II antigen presentation genes (HLA-DQA1, HLA-DQB1, HLA-DRB1) and myeloid activation genes (S100A8/A9/A12) in adjacent healthy mucosa. Loss of MMR proteins MSH6 and PMS2 in histologically normal mucosa was significantly more frequent in MAC. These findings were replicated in the TCGA cohort, which also showed lower tumour mutational burden and a distinct mucin-associated transcriptomic profile in MAC. Conclusions: The worse outcomes of rectal MAC appear to be driven largely by late-stage presentation, possibly owing to later diagnosis. MAC nonetheless carries a distinct immune phenotype, detectable even in histologically normal surrounding mucosa, that likely contributes to its treatment resistance. These observations provide a basis for developing histotype-specific approaches to both early detection and treatment in this uncommon but clinically challenging tumour subtype. Full article

Background: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) varies considerably, and oxidative stress may modulate radiosensitivity. This study evaluated ischemia-modified albumin (IMA) and thiol–disulfide homeostasis as potential biochemical predictors of pathological tumor regression. Methods: A prospective observational cohort study was conducted to assess pre- and post-treatment oxidative stress biomarkers in patients with LARC receiving capecitabine-based long-course CRT. Serum IMA, native thiol, total thiol, and disulfide levels were quantified spectrophotometrically. Pathologic regression was graded according to the Modified Ryan system as good (TRG 0–1) or poor (TRG 2–3). Receiver operating characteristic (ROC) analyses, Firth-penalized logistic regression, and internal validation using cross-validation, calibration, and decision-curve analyses were performed. Results: Of 38 screened patients, 31 met eligibility criteria and completed CRT, alongside 31 matched healthy controls. Compared with controls, patients had higher baseline disulfide (15.7 ± 5.2 vs. 11.9 ± 3.1 µmol/L; p = 0.012) and IMA levels (0.886 ± 0.062 vs. 0.798 ± 0.048 ABSU; p = 0.006). Poor responders exhibited higher pre-treatment IMA (0.927 ± 0.045 vs. 0.842 ± 0.050 ABSU; p = 0.020) and disulfide levels (18.4 ± 5.2 vs. 13.0 ± 3.8 µmol/L; p = 0.012). Pre-treatment IMA demonstrated the highest predictive accuracy for poor tumor regression (AUC = 0.872; 95% CI 0.751–0.993). In multivariable Firth-penalized logistic regression, elevated baseline IMA was independently associated with poor pathological response (OR = 3.63; 95% CI 1.22–16.20; p = 0.043), whereas negative circumferential resection margin (CRM) status was independently associated with favorable regression (OR = 0.21; 95% CI 0.02–0.71; p = 0.003). The internally validated model demonstrated excellent discrimination (AUC = 0.948; 95% CI 0.866–0.966) and good calibration. Conclusions: Baseline IMA and CRM status were independently associated with pathological response after CRT in LARC. These findings suggest that oxidative-stress biomarkers may have potential value for response stratification; however, the results should be considered exploratory and require external validation in larger independent cohorts before clinical application. Full article

Background: The incidence of early-onset colorectal cancer (EOCRC) has increased worldwide and now represents approximately 10% of colorectal cancers in high-income countries. EOCRC is frequently associated with advanced pathological features, although its clinical behavior and optimal management remain incompletely defined. Methods: We performed a retrospective single-center study including 88 consecutive patients aged ≤50 years who underwent curative-intent colorectal cancer resection between January 2019 and December 2023 at a tertiary referral center. Perioperative outcomes, pathological characteristics, and recurrence patterns were analyzed. Results: The median age was 44 years, and 67% of tumors were located in the colon. Pathological nodal involvement (pN+) was observed in 47.7% of patients, with a high prevalence of adverse features including perineural invasion (62.5%), tumor budding (17.0%), and tumor deposits (15.9%). Minimally invasive surgery was performed in 79% of patients and was associated with shorter hospital stay without increased postoperative morbidity (19.3%). During a median follow-up of 31.3 months [IQR 21.6–44.6], recurrence occurred in 40 patients (45.5%) and was predominantly distant (75.0%). Among patients with recurrence, 21 (52.5%) underwent surgical reintervention, most commonly hepatic and pulmonary resections. Rectal cancer was associated with higher rates of stoma formation and major postoperative complications compared to colon cancer. Conclusions: EOCRC is characterized by a high prevalence of adverse pathological features and a substantial rate of distant recurrence. However, a relevant proportion of recurrences remains amenable to surgical treatment in selected patients. Management in a specialized tertiary center allows achievement of high-quality surgical outcomes and supports an aggressive multidisciplinary approach. Full article

Hydronephrosis caused by malignant ureteral obstruction or radiotherapy-induced ureteral stenosis is a frequent complication in patients with cervical cancer. Effective management requires continuous urinary drainage, which can be achieved either internally through ureteral stent placement or externally via percutaneous nephrostomy. Among available devices, the Allium^TM fully covered nitinol mesh ureteral stent is designed to treat ureteral or urethral strictures while allowing safe and easy removal. However, serious complications have been reported, including uretero-enteric, uretero-arterial, and uretero-vaginal fistulas, pseudoaneurysm, ureteral perforation and sepsis. We report the case of a 44-year-old woman diagnosed in 2020 with stage IIIC1 cervical cancer (FIGO classification) who underwent surgery followed by adjuvant radiotherapy. In 2021, a right metallic ureteral stent was placed to treat ureteral obstruction. Two years later, she presented with right lumbar pain, and abdominal ultrasonography revealed grade III right hydronephrosis. CT scan demonstrated migration of the metallic ureteral stent into the rectal wall. Endoscopic extraction of the migrated stent was successfully performed via colonoscopy. Retrograde pyelography and CT imaging confirmed the presence of a recto-ureteral fistula. A 6 Ch/26 cm double-J ureteral stent was subsequently placed with good positioning and drainage. At the six-month follow-up, replacement of the double-J stent was performed. Imaging studies showed only minor residual hydronephrosis. Although metallic ureteral stents are effective for managing malignant ureteral obstruction, particularly in complex oncologic cases, they are not free of severe complications. The risk appears increased in patients who have undergone radiotherapy, emphasizing the need for careful monitoring and long term follow-up. Full article

Hemoglobin levels play an important role in oxygen delivery to skeletal muscle, and reduced levels may impair muscle function and contribute to sarcopenia, particularly in patients with cancer. The aim of the present study was to evaluate the influence of hemoglobin levels on muscle mass and function in patients with digestive tract cancer. Methods: Patients of both sexes aged up to seventy years with cancers of the digestive system undergoing surgical and clinical treatment at an oncology referral center were included. Hemoglobin levels were assessed using a blood count, and the risk of sarcopenia was estimated using the Mini Sarcopenia Risk Assessment (MSRA). A total of 82 patients were evaluated, with a mean age of 55.4 years. Colon cancer was the most prevalent (41.6%), followed by rectal (18.3%) and stomach (14.6%) cancers. The risk of sarcopenia was estimated at 85.4%, and the prevalence of low hemoglobin levels was 71.9%; 35.4% of patients presented moderate hemoglobin depletion. Hemoglobin levels showed a moderate correlation with gait speed and a slight correlation with calf circumference, handgrip strength, and MSRA score. In conclusion, the risk of sarcopenia and low hemoglobin levels are present in patients with digestive tract cancer. Additionally, hemoglobin levels positively correlate with indicators of muscle function and the risk of sarcopenia. Full article

Background/Objectives: Pelvic radiotherapy (RT) for mid–low rectal and anal cancers frequently causes acute and late vaginal toxicity, including dryness, irritation, and dyspareunia, with a substantial impact on quality of life. Evidence supporting targeted interventions for radiation-induced vaginal mucosal changes remains limited. This exploratory retrospective study evaluated the association between daily use of Colpofix^® Ovules and temporal changes in patient-reported vaginal symptoms and Vaginal Health Index (VHI) scores in women undergoing pelvic RT. Methods: Twenty women treated with pelvic RT or chemoradiotherapy between 2024 and 2025 were included. Vaginal symptoms were assessed using a Numerical Rating Scale (NRS 0–10), and mucosal status was evaluated using the VHI (5–25). Assessments were performed at baseline (T0), end of RT (T1), 3 months (T2), and 6 months (T3). Due to the retrospective nature of the dataset, only aggregated summary values were available; analyses were therefore descriptive and aimed at characterizing temporal trends. Results: A clear and progressive reduction in vaginal dryness, irritation, reduced lubrication, and dyspareunia was observed from T0 to T3, with improvements already evident at T1 and further consolidation at T2–T3. VHI scores increased from a mean of 10.8 at baseline to 21.0 at 6 months, reflecting a consistent trend toward mucosal recovery across all domains. In the anal cancer subgroup, the trend toward improvement in dysuria did not meet conventional thresholds for statistical significance (p = 0.073). At T3, 90% of patients reported perceived benefit (55% marked, 35% mild). No adverse events attributable to Colpofix^® were documented. Conclusions: In this small retrospective cohort, daily use of Colpofix^® Ovules was associated with favorable temporal trends in both vaginal symptoms and VHI scores up to 6 months after pelvic RT. These exploratory findings support further prospective controlled studies to better define the potential role of Colpofix^® in managing vaginal mucosal changes during pelvic radiotherapy. Full article

There is growing interest in non-operative management (NOM) for rectal cancer patients who achieve a complete response to neoadjuvant therapy. The patients’ perspectives of these approaches are limited. Here, we describe a qualitative study where we conducted semi-structured interviews with fourteen rectal cancer patients, including seven men and seven women, who were successfully treated by NOM at our center between 2020 and 2022. The responses were analyzed using the constant comparative method. Four major thematic categories emerged: impact of rectal cancer diagnosis, treatment values, decision-making factors, and the impact of NOM surveillance. Avoidance of a stoma was a major theme in both determining patient treatment values as well as ultimately driving their decision-making. Trust in the treating physician was also found to be a major theme in decision-making. While the psychological burden of surveillance did emerge as a major theme, patients who did not have recurrence were still quite satisfied with their decision to pursue NOM. Limitations of this study include selection bias, the single-center design, and the lack of patients who ultimately experienced recurrence following NOM. As NOM of rectal cancer becomes more commonplace, understanding the patients’ perspectives will ensure appropriate counseling and shared decision-making. Full article

Dormancy is an important factor influencing colorectal cancer (CRC) metastasis through diverse metabolic pathways and cell types. To elucidate its molecular mechanisms, bulk transcriptomic pathway scoring was integrated with single-cell RNA sequencing of epithelial, cancer stem, and immune cells to identify CRC dormancy-associated genes (CDAGs). Twenty-three CDAGs were identified. These genes were found to play a regulatory role in dormancy by participating in metabolic processes affecting energy supply or substance synthesis. In two independent CRC cohorts (GSE41258, GSE41568), machine learning models using these genes distinguished metastatic samples with area under the curve (AUC) of 0.79–0.87. High CDAG expression was associated with better recurrence-free survival in GSE41258 (p = 0.005), which remained significant after adjusting for age, sex, and adjuvant chemotherapy (p = 0.037). The prognostic value was validated in The Cancer Genome Atlas (TCGA) Colon and Rectal Cancer for progression-free survival (p = 0.004). Moreover, 20 CRC dormancy-associated drugs were identified, 12 of which were reported to be associated with CRC, two with experimental evidence of inhibiting CRC metastasis or recurrence. This study provided metabolic-oriented genes for characterizing CRC dormancy, which could distinguish metastatic samples and had independent prognostic value, and offered a foundation for further development of targeted therapeutic strategies. Full article

Background: As survival after colorectal cancer (CRC) has improved, an increasing proportion of patients live beyond five years, making long-term outcomes increasingly relevant. In addition to cancer-related mortality, survivors remain at risk of death from other causes influenced by clinical and psychosocial vulnerabilities. Methods: We conducted a 10-year prospective cohort study including 838 patients with stage I–IV CRC treated in public hospitals in the Basque Country (Spain). Patients were recruited between November 2010 and December 2012 and followed for up to 10 years after surgery. Clinical, sociodemographic, lifestyle, and patient-reported outcomes were collected. Competing risk regression models (Fine-Gray) were used to estimate sub-distribution hazard ratios (sHRs) for CRC-specific and non-CRC mortality, stratified by tumor site and sex. Results: After 10 years, 40% of patients had died, with 66% of deaths attributable to CRC and 34% to other causes. CRC-specific mortality was mainly driven by tumor-related factors, including advanced stage (stage IV: sHR 7.18, p < 0.001) and residual disease after surgery (R1/R2: sHR 2.68; p < 0.001), with larger effect sizes observed in rectal cancer. In contrast, non-CRC mortality was associated with patient vulnerability, including age ≥75 years (sHR 3.57, p < 0.001), absence of adjuvant chemotherapy (sHR 5.59, p < 0.001), anemia, alcohol consumption, and poor functional status. Patients with rectal cancer and women reported poorer baseline quality of life. Sex-stratified analyses suggested differential patterns of vulnerability, with psychosocial and quality-of-life-related factors appearing more relevant in women, whereas lifestyle and clinical factors appeared more prominent in men. Conclusions: Long-term mortality in CRC reflects the interplay between tumor-related factors and patient vulnerability. Competing risk models allow a more accurate characterization of cause-specific outcomes and may help identify high-risk subgroups for tailored follow-up and management strategies. Full article

Background/Objectives: This study evaluated the daily delivered dose in prostate cancer patients using the automated artificial intelligence (AI)-based software Adaptbox (v2.3.2, Therapanacea). The aim was to assess target coverage and organ-at-risk (OAR) exposure. Methods: Twenty patients were included. All received 80 Gy in 40 fractions to the prostate and 56 Gy simultaneously to the seminal vesicles using two-arc VMAT on a TrueBeam STx, with daily CBCT for setup. For each fraction, CBCT images were imported into Adaptbox. A synthetic CT (sCT) was generated using a deep learning algorithm. OARs were automatically segmented, while targets were propagated from the planning CT (pCT) using rigid registration. Dose calculation was performed using Adaptbox’s collapse-cone algorithm. Dose parameters were extracted for each session and compared with planned values. Results: All 800 fractions were analyzed. The planning target volume (PTV) remained consistent with planning, with a maximum deviation of 0.1% for both PTVs. For the rectum, 78.38%, 77.75%, and 78.13% of fractions exceeded planned doses for V_70Gy, V_76Gy and V_80Gy, respectively. One patient had five consecutive fractions with >5% deviation across all rectal metrics. For the bladder, 52.34% of fractions exceeded the planned V_80Gy, and two patients had ≥5 consecutive fractions with >5% deviation; however, this was attributed to contouring inaccuracies. Conclusions: This AI-based workflow enables reliable daily dose reconstruction and can identify clinically relevant OAR dose deviations that may support adaptive interventions, although accurate contouring remains essential. Full article

Locally advanced rectal cancer is commonly treated using total neoadjuvant therapy (TNT), which integrates radiotherapy with systemic chemotherapy to improve tumor downstaging, local control, and long-term oncologic outcomes. Despite its central role in treatment, responses to radiotherapy remain highly heterogeneous. While some tumors undergo complete regression, others exhibit intrinsic or acquired treatment resistance, resulting in incomplete tumor control while experiencing treatment-related toxicity. Understanding the biological determinants that govern radiation sensitivity in rectal cancer, therefore, represents a major clinical challenge. Ionizing radiation induces tumor cell death primarily through the generation of reactive oxygen species (ROS) and DNA damage, particularly DNA double-strand breaks. In addition to nuclear DNA injury, radiation-induced oxidative stress can initiate lipid peroxidation within cellular membranes. When lipid peroxide accumulation exceeds the capacity of cellular antioxidant systems, this process can trigger ferroptosis, an iron-dependent form of regulated cell death driven by phospholipid oxidation. Ferroptotic susceptibility is regulated by interconnected metabolic pathways, including cystine transport through system Xc⁻ (SLC7A11/SLC3A2), glutathione synthesis, glutathione peroxidase-4 (GPX4) activity, iron metabolism, and membrane lipid remodeling. Recent evidence further indicates that ferroptosis intersects with antitumor immunity. Ferroptotic tumor cells release oxidized lipid mediators and damage-associated molecular signals that can influence immune activation, while interferon-γ produced by activated CD8⁺ T cells during immune checkpoint blockade suppresses SLC7A11 expression, limiting cystine uptake and promoting ferroptotic tumor cell death. These findings suggest that ferroptosis represents a mechanistic interface between tumor metabolic vulnerability and immune-mediated cytotoxicity. This interaction is particularly relevant in colorectal cancer biology, where immune checkpoint inhibitors demonstrate clinical benefit primarily in tumors with deficient mismatch repair or microsatellite instability-high (MSI-H) status. The vast majority of rectal cancers are microsatellite stable (MSS) and exhibit limited responsiveness to immunotherapy due to reduced immunogenicity and immune exclusion within the tumor microenvironment. Strategies capable of increasing tumor immunogenicity in this setting are therefore of considerable interest. In this review, we examine the molecular mechanisms linking radiation-induced oxidative stress to ferroptosis and tumor immunity in colorectal cancer, while focusing on the clinical context of radiotherapy in rectal cancer. We discuss how lipid metabolism, iron homeostasis, cysteine-dependent antioxidant systems, and immune signaling pathways converge to regulate ferroptotic vulnerability and radiation response. We further explore the therapeutic potential of integrating radiotherapy, ferroptosis-targeting strategies, and immunotherapy to overcome radioresistance and improve treatment outcomes in colorectal cancer. Full article

Background: Rectal neuroendocrine tumors (r-NETs) measuring 20 mm or less are increasingly diagnosed during colorectal cancer screening, but the optimal depth of endoscopic resection remains uncertain. Endoscopic submucosal dissection (ESD) is well established, whereas endoscopic intermuscular dissection (EID) may provide deeper resection for fibrotic or recurrent lesions. We hypothesized that EID would provide reliable deep-margin clearance without compromising safety. Methods: We retrospectively reviewed 42 consecutive patients treated at a tertiary center between 2018 and 2025. Thirty-two primary lesions underwent ESD and 10 lesions or scars suspicious for deep invasion underwent EID. Primary outcomes were en bloc and R0 resection; secondary outcomes were procedure time, adverse events, and length of stay. Groups were compared with the t, Mann–Whitney U, and chi-square tests. Results: En bloc resection was achieved in all cases. Histology confirmed R0 resection in all 26 primary lesions. Among 16 excision scars, 14 showed fibrosis only and 2 harbored grade 1 NET recurrence; both recurrent lesions were resected R0 with EID. Lesion size and procedure time were similar between groups. No major adverse events occurred. Self-limited intraprocedural bleeding occurred in five patients, and all patients were discharged within 2 postoperative days. Conclusions: Both techniques are safe and effective for r-NETs measuring 20 mm or less, and EID may be preferred for fibrotic or recurrent lesions. Large prospective multicentre studies are needed to validate the depth-tailored use of EID in r-NETs. Full article

Background: In locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the standard treatment. Pathologic complete response (pCR) is strongly associated with favorable long-term outcomes; however, reliable pre-treatment biomarkers for predicting treatment response remain limited. This study aimed to investigate the association between CT-derived adipose tissue parameters and pathologic response following neoadjuvant CCRT. Methods: A total of 61 patients with locally advanced rectal cancer who underwent neoadjuvant CCRT followed by surgery between 2020 and 2024 were retrospectively analyzed. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) parameters, including area, index, and mean attenuation (Hounsfield unit, HU), were measured at the L3 level on pre-treatment CT. Patients were classified into favorable (complete or near-complete response) and unfavorable response groups, as well as response and no-response groups. Statistical analyses included independent t-tests, chi-square tests, and receiver operating characteristic (ROC) curve analysis. Results: In the favorable versus unfavorable response analysis, higher body mass index (BMI), larger VAT area, higher VAT index (VATI), and lower mean VAT attenuation were significantly associated with favorable response (all p < 0.05), whereas SAT-related parameters were not. In the response versus no-response analysis, SAT area and SAT index (SATI), but not mean SAT attenuation and VAT-related parameters, were significantly associated with treatment response (all p < 0.05). BMI was significantly associated with pathologic response only in the favorable versus unfavorable response group analysis, whereas no significant association was observed in the response versus no-response group analysis. Conclusions: CT-derived adipose tissue parameters were differentially associated with pathologic response to neoadjuvant CCRT in locally advanced rectal cancer. VAT parameters, including both quantity and attenuation, were associated with favorable response, whereas SAT parameters were associated with overall treatment response, suggesting compartment-specific roles of adipose tissue in modulating treatment outcomes. While BMI demonstrated a significant association in one subgroup analysis, CT-based body composition analysis may provide more comprehensive and compartment-specific information beyond conventional anthropometric measures, and may serve as a potential imaging biomarker for predicting treatment response. Full article

Background: Response to neoadjuvant therapy in locally advanced rectal cancer (LARC) is heterogeneous, and early identification of non-responders may help optimize treatment strategies and reduce unnecessary toxicity. This study aimed to develop and internally validate a machine learning model based on radiomic features extracted from baseline magnetic resonance imaging (MRI) to predict treatment response defined according to MRI tumor regression grade (mrTRG) at restaging MRI. Methods: In this retrospective single-center study, 86 patients with histologically confirmed LARC who underwent baseline and restaging MRI, neoadjuvant therapy, and surgery were included. Primary tumors were manually segmented on oblique axial T2-weighted images. A total of 107 radiomic features were extracted using PyRadiomics (vrs 3.0.1), with and without N4 bias field correction. Feature selection was performed using LASSO, followed by elastic net–regularized logistic regression. Model performance was evaluated using repeated stratified 5-fold cross-validation (20 repetitions). Treatment response was defined according to MRI tumor regression grade (mrTRG) at restaging, dichotomized into responders (mrTRG ≤ 2) and non-responders (mrTRG ≥ 3). Results: The model achieved a mean area under the receiver operating characteristic curve (AUC-ROC) of 0.73, with an accuracy of 72.5%, sensitivity of 79.2%, and specificity of 50%. Conclusions: Baseline MRI-based radiomics shows potential for identifying patients at higher risk of non-response to neoadjuvant therapy in LARC. However, limited specificity and the absence of external validation restrict immediate clinical applicability. Further validation in larger multicenter cohorts and integration with clinical variables are warranted to improve model robustness and generalizability. Full article

Background: Local recurrence of rectal cancer is a challenging problem for patients and clinicians. Surgical resection is associated with good outcomes if R0 margins are achieved; however, it is often complex, requires suitable patient fitness, and is associated with long term physical and psychological consequences. Meanwhile, continuing technical advances in radiotherapy have enabled the delivery of highly conformal treatment, thereby enabling dose escalation or pelvic reirradiation to be safely considered—either as definitive management or in the neoadjuvant setting—for patients with locally recurrent rectal cancer. Pelvic reirradiation may refer to patients who have received primary rectal radiotherapy with the aim of neoadjuvant downstaging or reducing the risk of locoregional recurrence, versus radiotherapy for a previous unrelated non-rectal pelvic malignancy. Methods: A literature search of pelvic reirradiation for non-metastatic, locally recurrent rectal cancer was conducted for full text articles published over the last 20 years. Additional papers were identified within the references of these papers. Studies focusing on non-rectal cancers, and patients having primary radiotherapy for locally recurrent rectal cancer were excluded. Due to the heterogenicity of the data, no meta-analysis was performed. Results: A total of 15 papers were included, containing a cohort of 840 patients. Several reirradiation modalities were reported, including external beam radiotherapy, brachytherapy, stereotactic ablative radiotherapy and heavy particle therapy (carbon ion). Carbon ion radiotherapy was the most common reirradiation treatment modality utilised with a median cumulative dose of 70.4 Gray (Gy). Treatment response, defined as either complete or partial improvement in tumour size, was only reported in seven studies, and varied from 14 to 88%. Overall 3-year survival was also variable with rates reported between 18 and 85%. These observations may be due to variation in patient selection, treatment intent, and technique. Pelvic reirradiation was associated with acceptable toxicity, low rates of G3+ toxicity, and improved symptom control. Conclusions: Our review describes the multitude of approaches to pelvic reirradiation for locally recurrent rectal cancer. Reviewing the radiobiological and patient outcomes is challenging in view of the degree of heterogeneity in patient selection, treatment approach, and reported outcomes. However, there is consensus that pelvic reirradiation—either for long term control or to downstage prior to definitive surgery—is feasible with potential utility in this setting. Full article