Rectal Cancer Research Articles

Trend of gastrointestinal and liver diseases in China: Results of the Global Burden of Disease Study, 2019.

China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019. The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported. The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends. The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring and is likely to continue with many public health strategies implications.

Deciphering colorectal cancer radioresistance and immune microrenvironment: unraveling the role of EIF5A through single-cell RNA sequencing and machine learning.

Radiotherapy (RT) is a critical component of treatment for locally advanced rectal cancer (LARC), though patient response varies significantly. The variability in treatment outcomes is partly due to the resistance conferred by cancer stem cells (CSCs) and tumor immune microenvironment (TiME). This study investigates the role of EIF5A in radiotherapy response and its impact on the CSCs and TiME. Predictive models for preoperative radiotherapy (preRT) response were developed using machine learning, identifying EIF5A as a key gene associated with radioresistance. EIF5A expression was analyzed via bulk RNA-seq and single-cell RNA-seq (scRNA-seq). Functional assays and in vivo experiments validated EIF5A's role in radioresistance and TiME modulation. EIF5A was significantly upregulated in radioresistant colorectal cancer (CRC) tissues. EIF5A knockdown in CRC cell lines reduced cell viability, migration, and invasion after radiation, and increased radiation-induced apoptosis. Mechanistically, EIF5A promoted cancer stem cell (CSC) characteristics through the Hedgehog signaling pathway. Analysis of the TiME revealed that the radiation-resistant group had an immune-desert phenotype, characterized by low immune cell infiltration. In vivo experiments showed that EIF5A knockdown led to increased infiltration of CD8+ T cells and M1 macrophages, and decreased M2 macrophages and Tregs following radiation therapy, thereby enhancing the radiotherapy response. EIF5A contributes to CRC radioresistance by promoting CSC traits via the Hedgehog pathway and modulating the TiME to an immune-suppressive state. Targeting EIF5A could enhance radiation sensitivity and improve immune responses, offering a potential therapeutic strategy to optimize radiotherapy outcomes in CRC patients.

Number of lymph nodes retrieved in patients with locally advanced rectal cancer after total neoadjuvant therapy: post-hoc analysis from the STELLAR trial.

The current gold standard for extraperitoneal locally advanced rectal cancer is total neoadjuvant therapy (TNT) followed by total mesorectal excision. This research explored the number of lymph nodes in patients with locally advanced rectal cancer after TNT and its correlation with survival. This is a post-hoc analysis based on the STELLAR trial, including patients with locally advanced rectal cancer from 16 tertiary centres who were randomized for short-term radiotherapy followed by chemotherapy (TNT group) or long-term concurrent chemotherapy group followed by total mesorectal excision between 2015 and 2018. This lymph node-related analysis is based on the TNT group. Subgroups were differentiated based on the lymph node harvest (below the median number: limited lymphadenectomy group, and greater than/equal to the median number: extended lymphadenectomy group). The primary outcomes were overall survival and disease-free survival (DFS). Correlations with clinical/pathological variables, lymphadenectomy categories and use of adjuvant chemotherapy were explored. Among the 451 patients enrolled in the STELLAR trial, 227 patients (50.3%) were assigned to the TNT group, including 29.5% females. The median number of lymph nodes retrieved in the TNT group was 11.0. Patients in the limited lymphadenectomy subgroup exhibited worse overall survival than those with extended lymphadenectomy (HR 2.95 (95% c.i. 1.47 to 5.92), P = 0.001). The overall survival was similar in the ypN0-limited and ypN1-extended subgroups (HR 0.38 (95% c.i. 0.11 to 1.30), P = 0.109). Adjuvant chemotherapy was associated with better overall survival and DFS than no adjuvant chemotherapy overall (P < 0.001) and in the limited lymphadenectomy subgroup (P < 0.001). However, there was no significant difference in overall survival or DFS with or without adjuvant chemotherapy in the extended lymphadenectomy subgroup (P = 0.887 and P = 0.192, respectively). In the STELLAR trial, the median number of lymph nodes harvested was 11. In patients with limited lymphadenectomy, the use of adjuvant therapy after TNT was beneficial and correlated with better prognosis compared with patients who did not receive adjuvant chemotherapy.

A Review of Neoadjuvant Therapy and the Watch-and-Wait Protocol in Rectal Cancer: Current Evidence and Future Directions.

The treatment of rectal cancer underwent a significant change with the introduction of total mesorectal excision (TME), which substantially improved recurrence rates. However, TME is associated with complications such as fecal incontinence and poor bladder control, especially in tumors located near the anal verge. The watch-and-wait (WW) protocol has emerged as an alternative for patients achieving a clinical complete response (cCR) following neoadjuvant radiochemotherapy. This narrative review, developed according to the Scale for the Assessment of Narrative Review Articles guidelines, evaluates neoadjuvant treatments and the WW protocol for rectal cancer. Literature was sourced from the PubMed database using specific search terms related to neoadjuvant therapy and the WW protocol, resulting in 63 articles selected for discussion. Neoadjuvant treatment, including chemoradiation and short-course radiotherapy, is indicated for T3 and T4 rectal adenocarcinomas. Studies like the German Rectal Cancer Study Group and the PRODIGE 23 trial have shown the benefits of preoperative treatment, including improved disease-free survival and reduced local recurrence rates. However, challenges in adopting the WW protocol include the risk of local regrowth and distant metastasis. Immune checkpoint inhibitors have shown promise in mismatch repair-deficient patients, yet the data are insufficient to fully endorse WW for these cases. The WW protocol is viable for selected rectal cancer patients, with ongoing debates regarding criteria for inclusion. Key challenges include accurately identifying cCR and managing patients with near-complete responses. MRI and endoscopic evaluation are crucial for assessing treatment response, although achieving a pathological complete response remains uncertain. The WW strategy offers a potential organ-preserving approach in rectal cancer management but requires careful patient selection and comprehensive risk-benefit discussions. Further research is needed to refine criteria for inclusion and optimize treatment protocols, enhancing outcomes while minimizing invasive interventions.

Racial comparisons in treatment of rectal adenocarcinoma and survival in the military health system.

Racial disparities in treatment and outcomes of rectal cancer have been attributed to patients' differential access to care. We aimed to study treatment and outcomes of rectal cancer in the equal access Military Health System (MHS) to better understand potential racial disparities. We accessed the MilCanEpi database to study a cohort of patients aged 18 and older who were diagnosed with rectal adenocarcinoma between 1998 and 2014. Receipt of guideline recommended treatment per tumor stage, cancer recurrence, and all-cause death were compared between non-Hispanic White and Black patients using multivariable regression models with associations expressed as odds (AORs) or hazard ratios (AHRs) and their 95% confidence intervals (CIs). The study included 171 Black and 845 White patients with rectal adenocarcinoma. Overall, there were no differences in receipt of guideline concordant treatment (AOR = 0.76, 95% CI = 0.45 to 1.29), recurrence (AHR = 1.34, 95% CI = 0.85 to 2.12), or survival (AHR = 1.08, 95% CI = 0.77 to 1.54) for Black patients compared with White patients. However, Black patients younger than 50 years of age at diagnosis (AOR = 0.34, 95% CI = 0.13 to 0.90) or with stage III or IV tumors (AOR = 0.28, 95% CI = 0.12 to 0.64) were less likely to receive guideline recommended treatment than White patients in stratified analysis. In the equal access MHS, although there were no overall racial disparities in rectal cancer treatment or clinical outcomes between Black and White patients, disparities among those with early-onset or late-stage rectal cancers were noted. This suggests that factors other than access to care may play a role in the observed disparities and warrants further research.

Dose tracking assessment for magnetic resonance guided adaptive radiotherapy of rectal cancers

BackgroundMagnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient’s daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy.MethodsNineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{a}\ ext{d}\ ext{a}\ ext{p}}$$\\end{document}), a second plan (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{I}\ ext{G}\ ext{R}\ ext{T}}$$\\end{document}) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{T}\ ext{P}}_{\ ext{a}\ ext{d}\ ext{a}\ ext{p}}$$\\end{document} and\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:{\ ext{T}\ ext{P}}_{\ ext{I}\ ext{G}\ ext{R}\ ext{T}}$$\\end{document}was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters.ResultsNinety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{D}}_{15\ ext{c}\ ext{c}}$$\\end{document} values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\ ext{D}}_{5\ ext{c}\ ext{c}}$$\\end{document} values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements.ConclusionsMRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Survival Analysis, Clinical Characteristics, and Predictors of Cerebral Metastases in Patients with Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer globally and a leading cause of cancer-related deaths. While liver metastasis is common, brain metastasis (BM) is rare, occurring in 0.1% to 14% of cases. Risk factors for BM include lung metastasis at diagnosis, rectal cancer, and mutations in RAS and KRAS genes. Due to its rarity, guidelines for BM screening and treatment are limited. The aim of this study is to identify the clinical characteristics and predictors of BM at the time of the initial diagnosis of CRC. We evaluated patients ≥18 years old with metastatic colorectal cancer and brain metastases at diagnosis from the SEER database (2010-2021). A retrospective cohort study was conducted to analyze overall survival and predictive factors for brain metastasis, utilizing multivariate logistic regression, Kaplan-Meier survival analysis, and the Cox proportional hazards models, with p-values < 0.05 considered significant. Out of 24,703 patients with metastatic colorectal cancer (mCRC), 228 (0.92%) had brain metastasis (BM) at diagnosis. BM was more prevalent in average-onset mCRC (≥50 years) compared to early-onset (<50 years) (1% vs. 0.55%, p = 0.004). Certain factors, such as older age and adenocarcinoma subtype, were associated with BM. Additionally, Asians/Pacific-Islanders (HR 1.83 CI: 1.01-3-33, p = 0.045) and American Indians/Alaska Natives (HR 4.79 CI 1.15-19.97, p = 0.032) had higher mortality rates, while surgical treatment and chemotherapy were linked to decreased mortality. Patients with BM had significantly worse overall survival (6 months vs. 21 months, p < 0.001). BM in mCRC is uncommon, but it is associated with significantly worse outcomes, including markedly reduced overall survival. Our study highlights several critical factors associated with the presence of BM, such as older age and specific racial/ethnic groups, which may inform risk stratification and early-detection strategies. Our findings emphasize the need for heightened awareness and screening for BM in high-risk mCRC patients, as well as the inclusion of these patients in clinical trials to explore tailored therapeutic approaches aimed at improving survival and quality of life.

Dealing with rectum motion during radiotherapy: How can we anticipate it?

IntroductionIntra- and inter-fraction rectum motion is important for pelvic radiotherapy (RT). This study assesses how RT session duration, the presence or the absence of an intra-rectal tumour, and the distance from the anorectal junction (ARJd) impact rectal motion. Materials and methodsAnalyses used cone-beam computed tomographies (CBCTs) from RT patients treated for rectal and prostate cancer. Three structures were evaluated: (1) the entire rectum in patients without a rectal tumour (RectumProstate); (2) the non-invaded portion (RectumRectum) and (3) the tumour-invaded portion (RectumTumour) in rectal cancer patients.Intrafraction motion was assessed using the Hausdorff distance 95% and the Mean distance-to-agreement between structures delineated on the first CBCT and the 2 subsequent CBCTs within a same RT session. Interfraction motion was quantified by comparing structures delineated on the planning-CT and the first CBCT of each session.Linear mixed model evaluated rectum motion in relation to time, tumour presence, and ARJd, respectively. ResultsWe included 10 patients with and 10 without rectal cancer, collecting 385 CBCTs. A significant correlation (p < 0.05) between rectum motion and RT session duration was found. Intrafraction motion was significantly higher in prostate cancer patients (RectumProstate motion > RectumRectum and RectumTumour, p < 0.01). For interfraction motion, only the mean distance to agreement was significantly higher for RectumProstate (p < 0.05). Motion increased significantly with ARJd for all three structures (p < 0.001). ConclusionsSession duration, absence of a tumour, and ARJd are associated with larger intra- and interfraction rectal motion. This highlights the need for tailored RT treatment, including online-adaptive RT, to manage intra- and interfraction variations. Rectal motion should be handled differently for patients with prostate cancer and those with rectal cancer.

Physical activity at diagnosis is associated with tumor downstaging after neoadjuvant chemoradiotherapy in patients with rectal cancer

BackgroundPatients with rectal cancer are often treated with neoadjuvant chemoradiotherapy, followed by a waiting period and surgical resection. Good or complete response to neoadjuvant chemoradiotherapy might enable organ preservation, which highlights the need to increase response rates. Pre-clinical studies suggest that physical activity during neoadjuvant chemoradiotherapy may improve tumor downstaging. PurposeTo investigate whether physical activity and physical functioning of patients with rectal cancer at diagnosis are associated with tumor downstaging after neoadjuvant chemoradiotherapy. Materials and methodsPatients were included if they participated in the Dutch Prospective ColoRectal Cancer Cohort, a nationwide cohort providing an infrastructure for scientific research, and received neoadjuvant chemoradiotherapy for rectal cancer. Tumor downstaging was dichotomized into good/complete or moderate/poor downstaging. Physical activity (total physical activity, moderate-to-vigorous physical activity (MVPA), and Dutch physical activity guideline adherence) and physical functioning were assessed using questionnaires. Logistic regression analyses were performed to examine associations of physical activity and physical functioning with tumor downstaging, adjusted for relevant confounders. Results268 patients (aged 62 ± 11 years, 33 % female) with rectal cancer were included. Patients with moderate (OR = 2.07; 95%CI = 1.07 – 4.07; p = 0.03) or high (OR = 2.05; 95%CI = 1.05 – 4.07; p = 0.04) levels of MVPA were more likely to have good/complete tumor downstaging than patients with low levels. No significant associations with tumor downstaging were found for total physical activity, Dutch physical activity guideline adherence, and physical functioning. ConclusionsWe found augmented tumor downstaging in patients with rectal cancer with moderate or high levels of self-reported MVPA before the start of neoadjuvant chemoradiotherapy compared to patients with low levels.

Different Metabolic Associations of Hepatitis C With Colon and Rectal Cancers: A 9-Year Nationwide Population-Based Cohort Study

BackgroundWhether HCV infection is associated with colorectal cancer (CRC) development remains inconclusive. MethodsA nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted. ResultsFrom 2003 to 2012, 1:2:2 propensity score-matched HCV-treated [interferon-based therapy ≥ 6 months, surveys for CRC (n = 9017), colon cancer (CC) (n = 9,022) and rectal cancer (RC) (n = 9,033), HCV-untreated and HCV-uninfected cohorts CRC (n = 18034), CC (n = 18,044) and RC (n = 18,066) were enrolled. The HCV-uninfected cohort had the lowest cumulative incidence of CRC (0.117%; 95% CI: 0.062%-0.207%), whereas the HCV-treated (0.966%; 0.375-2.122%) and HCV-untreated (0.807%; 0.485%-1.280%) cohorts had similar incidences (P = .0662); HCV infection [reference: HCV-untreated cohort, HCV-treated: hazard ratio (HR): 0.598; 95% CI HR: 0.337-1.059; HCV-uninfected: 0.250; 0.138-0.456] and age ≥ 49 years (3.128;1.751-5.59) were associated with CRC development. The HCV-untreated cohort had the highest cumulative incidence of CC (0.883%; 0.371-1.839%), while HCV-treated (0.478%; 0.110-1.518%) and HCV-uninfected cohorts (0.147%; 0.071-0.284%) had similar incidences (P = .4853); HCV infection (HCV-treated: 0.474; 0.232-0.971; HCV-uninfected: 0.338; 0.184-0.62), male sex (2.18; 1.301-3.654), age≥ 49 years (4.818; 2.123-10.936) and diabetes (1.983; 1.205-3.262) were associated with CC development. A higher RC cumulative incidence was noted in the HCV-untreated cohort (0.332%; 0.151-0.664%) than in the HCV-uninfected cohort (0.116%; 0.054-0.232%) (P = .0352); HCV infection (HCV-treated: 0.691; 0.295-1.617; HCV-uninfected: 0.424; 0.207-0.867), age ≥ 49 years (3.745, 1.576-8.898) and stroke (3.162; 1.366-7.322) were associated with RC development. ConclusionsThe baseline associations were HCV infection and age ≥ 49 years with CRC; male sex and diabetes with CC; and stroke with RC. Anti-HCV therapy might reverse the risk of HCV-related CC but not RC.

Spectral CT in the evaluation of perineural invasion status in rectal cancer.

To investigate whether preoperative spectral CT quantitative parameters can assess perineural invasion (PNI) status in rectal cancer. Sixty-two patients diagnosed with rectal cancer who underwent preoperative spectral CT were retrospectively enrolled and divided into positive and negative PNI groups according to histopathologic results. The CT attenuation value (HU) of virtual monochromatic images (40-70keV), spectral curve slope (K(HU)), effective atomic number (Zeff), and iodine concentration (IC) from spectral CT were compared between these two groups using t test or rank sum test. A nomogram was established by incorporating the independent predictors to assess the overall diagnostic efficacy. The area under the ROC curves (AUCs) were compared using the DeLong test. The preoperative spectral CT parameters (40-70keV attenuation, K(HU), Zeff, and IC) were significantly higher in the PNI-positive group compared to the PNI-negative group (all p < 0.05). The highest predictive efficiency of PNI was observed at 40keV attenuation, with an area under the curve (AUC), sensitivity, specificity, and accuracy of 0.847, 81.8%, 72.5%, and 75.8%, respectively. Binary logistic regression demonstrated that the clinical feature (cN stage) and 40keV attenuation were independent predictors of PNI status. The nomogram incorporating these two predictors (cN stage and 40keV attenuation) exhibited the best evaluation efficacy, with an AUC, sensitivity, specificity, and accuracy of 0.885, 86.4%, 77.5%, and 80.6%. Spectral CT quantitative parameters proved valuable in the preoperative assessment of PNI status in rectal cancer patients. The combination of spectral CT parameters and clinical features could further enhance the diagnostic efficiency.

Impact of Metastatic Lymph Node Ratio on Survival and Prognosis in Rectal Carcinoma: A Retrospective Cohort Study.

Objective This study aimed to evaluate the impact of the metastatic lymph node ratio (mtLNR) on survival outcomes and prognosis in patients with rectal carcinoma, in comparison with other clinicopathological factors. Methods A retrospective cohort analysis was conducted on 97 patients with rectal adenocarcinoma who underwent surgical treatment at Erol Olçok Training and Research Hospital between January 2017 and December 2022. The inclusion criteria consisted of patients over 18 years of age and the absence of hematological disorders or concurrent inflammatory conditions. The patients' demographic data, tumor characteristics, surgical details, lymph node (LN) status, mtLNR, and survival outcomes were analyzed. The optimal cutoff value of mtLNR for predicting mortality was determined using receiver operating characteristic (ROC) curve analysis. Kaplan-Meier survival analysis was employed to estimate overall survival (OS) and disease-free survival (DFS), and differences between groups were evaluated using the log-rank test. The Cox proportional hazards model was used to calculate hazard ratios (HRs) for all-cause mortality. Statistical significance was set at p<0.05. Results The mean age of the patients was 70.31 ± 11.57 years, with 65.98% being male. Low anterior resection (LAR) was performed in 83.51% of the patients, and laparoscopic surgery was conducted in 26.8%. The median OS for the entire cohort was 24 months (range: 3-60). Patients were divided into two groups based on mtLNR, with the cutoff value set at 0.2183. A high mtLNR was significantly associated with poorer DFS and OS (p=0.021 and p=0.003, respectively). Moreover, patients with an mtLNR>0.2183 exhibited significantly higher rates of recurrence, lymphovascular invasion (LVI), and perineural invasion (PNI) compared to those with a lower mtLNR (all p<0.001). The optimal cutoff value of mtLNR predicted mortality with a specificity of 81.4% and a sensitivity of 48.1% (area under the curve (AUC) 0.662, p=0.012). Kaplan-Meier analysis showed a significant difference in survival between the two groups; the risk of all-cause mortality was 3.71 times higher in patients with mtLNR>0.2183 (p=0.002). Conclusion The mtLNR is a strong determinant of survival and prognosis in patients with rectal carcinoma. High mtLNR values are associated with worse survival outcomes and more aggressive tumor characteristics. The findings suggest that mtLNR should be considered in clinical decision-making processes. These results indicate that mtLNR could be a valuable prognostic tool in clinical decision-making.

Cross-sectional investigation of the distribution characteristics and prognostic significance of lateral lymph nodes in patients with rectal cancer.

Information about the distribution characteristics and prognostic significance of lateral lymph nodes (LLNs) on primary computed tomography (CT) scan in rectal cancer patients is lacking. Between January 2013 and December 2016, patients with pathologically proved rectal cancer and pretreatment abdominal enhanced CT in our department were screened. We firstly redivided LLNs into seven categories based on their locations. Then, the number and distribution of all measurable LLNs and the characteristics of the largest LLN in each lateral compartment were recorded. Furthermore, we investigated the long-term outcomes in patients with different LLN characteristics and LLN risk scoring. A total of 572 patients were enrolled in this study. About 80% of patients had measurable LLNs, and most patients developed measurable LLNs in the obturator cranial compartment. Lateral local recurrence (LLR) was observed in 20 patients, which accounted for 83.3% of the local recurrence (LR). Patients with the largest LLN short-axis diameter >10 mm had a poor prognosis, which was similar to that in patients with simultaneous distant metastasis (SDM). Patients with LLN risk scoring ≥2 had a worse prognosis than those with LLN risk scoring <2, while better than those with SDM. This study suggests that LLR is the main locoregional recurrence pattern. Most rectal cancer patients have measurable LLNs on primary CT scan. However, patients with enlarged LLNs <10 mm or LLN risk scoring <2 still have a significantly better prognosis than patients with SDM, which indicated the potential value of locoregional treatment for these LLNs.

Hypofractionated Radiation Therapy: A Cross-sectional Survey Study of US Radiation Oncologists.

For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions. From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered. A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns. HFRT is safe, effective, and beneficial, yet underutilized-particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.

127 Prospective Study on Lars Incidence and Severity in Rectal Cancer: Comparing CRT Alone and CRT Followed by Tme

127 Prospective Study on Lars Incidence and Severity in Rectal Cancer: Comparing CRT Alone and CRT Followed by Tme

Factors Associated with Leakage after Reversal of Protective Stoma in Patients with Locally Advanced Rectal Cancer Following Curative Resection and Anastomosis

IntroductionAnastomotic leakage (AL) is a significant complication in colorectal surgery with numerous general and specific risk factors. The determinants of colorectal AL following the reversal of a protective defunctioning ileostomy remain unclear and warrant further investigation. Material and MethodsData from April 2008 to December 2014 were collected and retrospectively reviewed for 361 consecutive patients who underwent protective ileostomy reversal following curative resection with anastomosis for rectal cancer. The baseline, treatment, and oncological variables of patients associated with post-reversal AL were evaluated using univariate and multivariate logistic regression analysis. The impact of AL on long-term survival outcomes was assessed using Kaplan-Meier survival analyses. ResultsIn a study of 361 patients, 52 (14.4%) experienced leakage following stoma reversal, manifesting at a median of 5.7 months. Multivariable logistic regression analysis revealed that an anastomosis located less than 7 cm from the anal verge (OR 2.82, p = 0.008), a side-to-end anastomotic configuration (OR 2.02, p = 0.036), involvement of the circumferential resection margin (OR 6.46, p = 0.043), and adjuvant radiotherapy (OR 4.69, p = 0.003) significantly predicted post-reversal AL. Notably, five-year overall survival (63.4% vs. 90.3%, p < 0.0001) and disease-free survival (46.9% vs. 71.1%, p = 0.001) were significantly lower in patients with post-reversal AL. ConclusionsOur analysis identified several clinicopathological factors associated with post-reversal AL, which is linked to a significant decrease in long-term survival and oncological outcomes. Alleviating these adverse effects necessitates ensuring early detection and effective management of leaks among high-risk patients.

Lymphovascular invasion is a dominant risk factor for lymph node metastasis in T2 rectal cancer.

Background and study aims Surgical resection is standard treatment of T2 rectal cancer due to risk of concomitant lymph node metastases (LNM). Local resection could potentially be an alternative to surgical treatment in a subgroup of patients with low risk of LNM. The aim of this study was to identify clinical and histopathological risk factors of LNM in T2 rectal cancer. Patients and methods This was a retrospective registry-based population study on prospectively collected data on all patients with T2 rectal cancer undergoing surgical resection in Sweden between 2009 and 2021. Potential risk factors of LNM, including age, gender, resection margin, lymphovascular invasion (LVI), histologic grade, mucinous cancer, and perineural invasion (PNI) were analyzed using univariate and multivariate logistic regression. Results Of 1607 patients, 343 (21%) with T2 rectal cancer had LNM. LVI (odds ratio [OR] = 4.21, P < 0.001) and age < 60 years (OR = 1.80, P < 0.001) were significant and independent risk factors. However, PNI (OR = 1.50, P = 0.15), mucinous cancer (OR = 1.14, P = 0.60), histologic grade (OR = 1.47, P = 0.07) and non-radical resection margin (OR = 1.64, P = 0.38) were not significant risk factors for LNM in multivariate analyses. The incidence of LNM was 15% in the absence of any risk factor. Conclusions This was a large study on LNM in T2 rectal cancer which showed that LVI is the dominant risk factor. Moreover, low age constituted an independent risk factor, whereas gender, resection margin, PNI, histologic grade, and mucinous cancer were not independent risk factors of LNM. Thus, these findings may provide a useful basis for management of patients after local resection of early rectal cancer.

292. CHEMOTHERAPY AND CHEMORADIOTHERAPY FOR ADENOCARCINOMA OF THE OESOPHAGUS AND JUNCTION WITH OLIGOMETASTASES: RESULTS OF THE TNT-OES-1 TRIAL

Abstract Background Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are both effective as neoadjuvant regimens for esophageal and junctional cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy. Although TNT is increasingly used in rectal cancer, there are no data on combining e.g. FLOT and CROSS in esophageal cancer. This phase-II study aimed to evaluate the feasibility and safety of the TNT FLOT-CROSS combination in esophageal and junctional adenocarcinoma patients with oligometastatic disease. Methods Patients with oligometastatic (defined as a maximum of four lesions in up to two organs, excluding lymph nodes) esophageal adenocarcinoma were treated with four biweekly cycles of FLOT followed by response evaluation (CT-scan). Patients without disease progression (RECIST v1.1) proceed to CROSS. Afterwards, response was assessed by CT-scan, endoscopy with biopsies and endoscopic ultrasonography with fine-needle aspiration on indication. The multidisciplinary tumor board discussed whether patients could proceed to four additional cycles of FLOT or local therapy of metastases and/or esophagectomy. Primary endpoint was tolerability of TNT FLOT-CROSS, defined as the proportion completing four cycles of FLOT and five cycles of chemoradiotherapy. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), toxicity and the proportion proceeding to local therapy of metastases and/or esophagectomy. Results Twenty patients (85% males, median age 62.5 years (interquartile range 58.3-66) were included of whom 16 (80%) had a single metastatic lesion. Eighteen patients (90%) successfully completed FLOT and fifteen (75%) completed TNT FLOT-CROSS (Figure 1). Toxicity mainly consisted of grade 1-2 leukopenia/neutropenia during FLOT, leading to treatment delay in twelve patients and dose-limiting of oxaliplatin in one patient. One patient had malaise grade 2. No grade 3-5 toxicities occurred during CROSS. Following TNT FLOT-CROSS, ten patients underwent four additional cycles of FLOT and toxicity resulted in treatment delay and dose reduction in seven patients and hospitalization in two patients. Six patients underwent esophagectomy of whom two underwent local treatment of metastases. The 1- and 2-year PFS was 56% and 48%. Three months after TNT FLOT-CROSS completion, DCR was 73%. Conclusion(s) This study showed that sequencing TNT FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity and promising efficacy. In follow-up to this study, the TNT-OES-2 study will assess the efficacy and feasibility of TNT FLOT-CROSS and TNT CROSS-FLOT in patients with resectable nodal-positive adenocarcinoma of the esophagus or esophagogastric junction.

MRI Predicts Residual Disease and Outcomes in Watch-and-Wait Patients with Rectal Cancer.

Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT. Participants enrolled in the OPRA trial who underwent restaging MRI were eligible for inclusion in the present study. Radiologists classified participants as having clinical complete response (cCR), near-complete clinical response (nCR), or incomplete clinical response (iCR) based on restaging MRI at a mean of 8 weeks ± 4 (SD) after treatment. Oncologic outcomes according to MRI response category were assessed using Kaplan-Meier curves. Logistic regression analysis was performed to identify imaging characteristics associated with RD. Results A total of 277 participants (median age, 58 years [IQR, 17 years]; 179 male) who were randomized in the OPRA trial had restaging MRI forms completed. The median follow-up duration was 4.1 years. Participants with cCR had higher rates of organ preservation compared with those with nCR (65.3% vs 41.6%, log-rank P < .001). Five-year disease-free survival for participants with cCR, nCR, and iCR was 81.8%, 67.6%, and 49.6%, respectively (log-rank P < .001). The MRI response category also predicted overall survival (log-rank P < .001), distant recurrence-free survival (log-rank P = .005), and local regrowth (log-rank P = .02). Among the 266 participants with at least 2 years of follow-up, 129 (48.5%) had RD. At multivariable analysis, the presence of restricted diffusion (odds ratio, 2.50; 95% CI: 1.22, 5.24) and abnormal nodal morphologic features (odds ratio, 5.04; 95% CI: 1.43, 23.9) remained independently associated with RD. Conclusion The MRI response category was predictive of organ preservation and survival. Restricted diffusion and abnormal nodal morphologic features on restaging MRI scans were associated with increased likelihood of residual tumor. ClinicalTrials.gov identifier: NCT02008656 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Milot in this issue.

550P The impact of mismatch repair status on accuracy of clinical staging in upfront resected stage II/III rectal cancer in the Netherlands

550P The impact of mismatch repair status on accuracy of clinical staging in upfront resected stage II/III rectal cancer in the Netherlands