Ablative-dose radiotherapy (A-RT) may result in durable local control and encouraging survival for patients with locally advanced pancreatic cancer (LAPC). A subset of patients with LAPC are eligible for exploration after completion of induction chemotherapy and A-RT. Outcomes for this subset of patients are yet to be described.

This was a single-institution retrospective analysis of patients who had LAPC treated with induction chemotherapy and A-RT (≥98 Gy biologically effective dose using 15 to 25 fractions in 3- to 4.5-Gy/fraction), then subsequently underwent surgical exploration.

During a 6-year period, 34 patients with LAPC underwent exploration after induction chemotherapy and A-RT. Chemotherapy was given before A-RT to all the patients, with the majority receiving FOLFIRINOX (94 %). The median time to exploration after completion of A-RT was 75 days. Pancreaticoduodenectomy was the most frequent procedure (n = 18), followed by distal pancreatectomy (n = 7), and resection was aborted in nine patients (26 %) after discovery of distant (n = 6) or locally unresectable (n = 3) disease. Vascular resection or divestment was required for 56 % of the patients. There were no postoperative pancreatic fistulae. However, clinically significant ascites were observed in 36 % of the resected patients. A major pathologic response was observed in 17 % of the resected specimens upon final pathologic review. Postoperative mortality within 90 days occurred for two patients (5.9 %). The median overall survival for the entire cohort was 31 months from the date of diagnosis and 24 months from completion of A-RT.

Resection of LAPC is feasible for a select cohort of patients after A-RT, with encouraging 2-year overall survival.

With the results of several recently published clinical trials, this guideline focused update provides evidence-based recommendations for the indications and dose-fractionation regimens for neoadjuvant radiation therapy (RT), optimal sequencing of RT and systemic therapy in the context of total neoadjuvant therapy (TNT), and considerations for selective omission of RT and surgery for rectal cancer.

The American Society for Radiation Oncology convened a multidisciplinary task force to update 3 key questions that focused on the role of RT for patients with operable rectal cancer. The key questions addressed (1) indications for neoadjuvant RT, (2) selection of neoadjuvant regimens, and (3) indications for consideration of a nonoperative management (NOM) or local excision approach after definitive/preoperative chemoradiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation.

For patients with stage II-III rectal cancer, neoadjuvant RT was strongly recommended; however, among patients deemed at lower risk of locoregional recurrence, consideration of omission of neoadjuvant RT was conditionally recommended in favor of neoadjuvant chemotherapy with a favorable treatment response or upfront surgery. For patients with T3-T4 and node-positive rectal cancer undergoing neoadjuvant RT, a TNT approach was strongly recommended. Among patients with higher risk of locoregional recurrence, TNT with chemotherapy before or after long-course chemoradiation was strongly recommended, whereas TNT with short-course RT followed by chemotherapy was conditionally recommended. For patients with rectal cancer for whom NOM is a priority, concurrent chemoradiation followed by consolidation chemotherapy was strongly recommended. Selection of RT dose-fractionation regimen, sequencing of therapies, and consideration of NOM should be determined by multidisciplinary consensus and based on disease extent, disease location, patient preferences, and quality of life considerations.

The task force proposed recommendations to inform best clinical practices on the use of RT for rectal cancer with strong emphasis on multidisciplinary care. Future studies should focus on further addressing optimal treatment regimens to allow for more personalized recommendations based on individual risk stratification and patient priorities regarding quality of life.

Background/Objectives: The study aimed to compare the treatment effectiveness of patients with locally advanced rectal cancer undergoing standard neoadjuvant therapy or total neoadjuvant therapy. It also sought to identify prognostic factors for disease-free survival and overall survival and parameters predictive of pathological complete response. Materials and Methods: A retrospective analysis was conducted on 239 patients diagnosed with locally advanced rectal cancer between 2016 and 2022 at several medical centers in Turkey. Clinical data, including neoadjuvant chemoradiotherapy types, chemotherapy regimens, surgical outcomes, and survival metrics, were collected. Statistical analyses included chi-square tests, Kaplan-Meier survival analysis, and Cox proportional hazard models to evaluate prognostic factors for disease-free survival and overall survival and logistic regression to identify predictors of pathological complete response. Results: Among 239 patients, 46.9% received total neoadjuvant therapy, while 53.1% underwent standard neoadjuvant therapy. Total neoadjuvant therapy was associated with a significantly higher pathological complete response rate (45.5% vs. 14.9% in standard neoadjuvant therapy; p < 0.001) and longer disease-free survival (median 124.2 vs. 72.4 months). The 3-year overall survival rate for all patients was 90.7%, and disease-free survival was 76.8%. Multivariate analysis identified pathological complete response (HR: 2.34), total neoadjuvant therapy (HR: 5.12), and type of surgery (HR: 8.12) as independent prognostic factors for disease-free survival, and pathological complete response and absence of lymphovascular invasion as independent prognostic factors for overall survival. Logistic regression analysis showed that total neoadjuvant therapy (OR: 4.40) and initial neoadjuvant chemotherapy (OR: 2.02) were independent predictors of achieving pathological complete response. Conclusions: Total neoadjuvant therapy significantly improves pathological complete response rates, disease-free survival, and overall survival in patients with locally advanced rectal cancer compared to standard neoadjuvant therapy. Total neoadjuvant therapy and achieving pathological complete response are strong independent prognostic factors for both disease-free survival and overall survival, suggesting that a more intensive neoadjuvant approach may lead to better outcomes in locally advanced rectal cancer. The increased pathological complete responses rate with total neoadjuvant therapy has created an opportunity for the development of new treatment modalities and the advancement of non-surgical management strategies in the future.

Determining the optimal interval between neoadjuvant chemoradiotherapy (NCRT) and surgery in patients with locally advanced rectal cancer (LARC) remains crucial for improving treatment outcomes. Extending the interval may increase rates of pathological complete response (pCR), potentially enhancing survival and reducing recurrence.

This retrospective cohort study included 226 patients with LARC who underwent NCRT followed by surgery. ROC analysis was used to establish the optimal interval between NCRT and surgery for achieving pCR, and multivariate logistic regression assessed independent predictors of pCR. Spline regression further analyzed the relationship between surgery timing and the probability of pCR.

ROC analysis identified 10.5 weeks as the optimal interval, showing increased pCR rates within this period. Multivariate analysis confirmed that surgery interval (OR = 2.603, P = 0.045) significantly predicted pCR. Both ROC and spline regression indicated that a 9-11-week interval maximizes pCR probability. Notably, the comparison of postoperative complications between groups with surgery intervals ≤10 weeks and >10 weeks showed no statistically significant differences (P = 0.518).

An interval of 9-11 weeks between NCRT and surgery optimizes pCR rates without increasing postoperative risks. This timeframe may serve as a favorable window for surgical intervention to enhance outcomes in rectal cancer patients.

Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) has shown promise in achieving pathologic complete response (pCR) and enabling organ preservation through watch-and-wait (WW) strategies. However, implementation of WW protocols in diverse patient populations and safety-net hospitals faces unique challenges. The objective of this study is to evaluate TNT outcomes and identify barriers to WW implementation in a predominantly Hispanic safety-net hospital in South Texas.

A retrospective review was conducted of 40 LARC patients treated with TNT at an academic tertiary referral center in South Texas between 2018 and 2023. Patient demographics, disease characteristics, and pCR rates were analyzed. A survey of multidisciplinary providers assessed perceived institutional and patient-related barriers to WW implementation.

The cohort was 70% Hispanic, with a median age of 54 years. Most patients had advanced disease at diagnosis (57.5% T4, 65% N2). The pCR rate was 18.5% (5/27) among patients undergoing surgery. Re-review of MRIs for pCR patients revealed that 2/5 had minimal residual disease. The provider survey identified MRI quality variability, lack of dedicated treatment coordinators, and concerns about patient compliance and financial barriers as key obstacles to WW implementation.

Despite advanced disease presentation in a predominantly Hispanic population, TNT achieved pCR rates comparable to international trials. Institutional and patient-level barriers to WW were identified, informing the development of a tailored WW protocol for this unique patient population.

At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2-3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences.

The treatment of locally advanced rectal cancer (LARC) has steadily progressed over the past four decades, with recent focus shifting towards total neoadjuvant therapy (TNT). This survey aims to elucidate the perceived surgical challenges faced by Austrian colorectal surgeons performing total mesorectal excision (TME), focusing on the increased complexity and surgical difficulty introduced by intensified treatment regimens.

A comprehensive survey was conducted among Austrian colorectal surgeons to explore various aspects of managing and performing TME following TNT. The survey included questions on the general management of LARC within their institutions and utilized a five-point Likert scale to assess the respondents' perceptions and experiences regarding surgical precision and post-operative morbidity associated with TNT.

A total of 31 surgeons (54% response rate) completed the survey. Regarding multidisciplinary therapy preferences, 56% of respondents preferred conventional neoadjuvant therapy regimens, with 32% favoring chemoradiotherapy and 24% opting for short-course radiotherapy, while 31% chose TNT. The majority of respondents (65%) reported quality differences in tissue dissection during TME following TNT, with 57% experiencing difficulties in identifying tissue planes and 47% noting increased tissue fragility. Increased bleeding was reported by 32% of respondents. In cases of regrowth after a watch-and-wait approach, 64% observed quality changes in tissue dissection, and 47% noted tissue fragility.

The survey results indicate that TNT impairs surgical precision due to changes in tissue quality and challenges in identifying surgical planes. Given the critical importance of surgical precision in achieving low local recurrence rates in mid-to-low LARC, these challenges could significantly impact patient outcomes. Further prospective studies are required to elucidate the extent of these effects.

Neoadjuvant chemotherapy followed by esophagectomy is the usual approach to manage esophageal squamous cell carcinoma (ESCC). The optimal interval to operate after completion of neoadjuvant chemoradiotherapy (NACRT) still remains controversial.

A prospective study was conducted to observe and compare postoperative complications and pathological outcomes in patients with squamous cell carcinoma of the esophagus who underwent NACRT followed by surgery within 8 weeks or after 8 weeks of NACRT completion. The pathological complete response was assessed using the Mandard tumor regression grade. Morbidity and mortality were compared and were graded using the Clavien-Dindo scale.

The study included 50 patients, 19 patients in the < 8-week group and 31 in the > 8-week group study. Patients underwent thoracoscopy-assisted esophagectomy with neoesophagus formation using gastric conduit. There was a significant difference in mortality between the two groups, with three mortalities in the < 8-week group and none in the other group (p = 0.022). Postoperative complications and pathological outcomes did not have a statistically significant difference between the two groups.

The pathological response in ESCC cases does not appear to be impacted by the interval between NACRT and surgery; nevertheless, early surgery was associated with a higher risk of mortality.

The management of locally advanced rectal cancer has changed drastically in the last few decades due to improved surgical techniques, development of multimodal treatment approaches and the introduction of a watch and wait (WW) strategy. For patients with a complete response to neoadjuvant treatment, WW offers an opportunity to avoid the morbidity associated with total mesorectal excision in favor of organ preservation. Despite growing interest in WW, prospective data on the safety and efficacy of nonoperative management are limited. Challenges remain in optimizing multimodal treatment regimens to maximize tumor regression and in improving the accuracy of patient selection for WW. This review summarizes the history of treatment for rectal cancer and the development of a WW strategy. It also provides an overview of clinical considerations for patients interested in nonoperative management, including restaging strategies, WW selection criteria, surveillance protocols and long-term oncologic outcomes.

The most detrimental effect of DNA damage from radiation is DNA double-strand breaks, making it critical to identify reliable biomarkers for treatment response in cancer therapy. Gamma-H2AX (γ-H2AX), a marker of DNA double-strand breaks, was evaluated in this study as a potential biomarker for treatment response in locally advanced rectal cancer patients undergoing preoperative concurrent chemoradiation (CCRT).

Thirty patients with locally advanced rectal cancer received preoperative CCRT. Peripheral blood mononuclear cells (PBMCs) were collected at five time points: baseline, 24 hours after the first radiation fraction, mid-treatment, end of treatment, and six weeks post-CCRT. γ-H2AX levels were measured in these samples. MRI was used to assess treatment response based on magnetic resonance tumor regression grade (mrTRG). Patients were classified as responders or non-responders based on mrTRG. T-test and repeated measures analysis of variance (ANOVA) evaluated dynamic changes in γ-H2AX levels, and a multilevel linear regression model analyzed the relationship between γ-H2AX levels and treatment response.

Nineteen out of thirty patients (63.33%) were classified as responders. Significant dynamic changes in γ-H2AX levels were observed between non-responders and responders (P=0.01). The multilevel linear regression model showed a trend towards increased γ-H2AX levels in responders [1.17, 95% confidence interval (CI): -0.02 to 2.34, P=0.053]. Significant differences in γ-H2AX levels were observed from baseline to mid-treatment, end of treatment, and six weeks post-CCRT. Pathologic complete response (pCR) after CCRT was associated with significantly higher γ-H2AX ratios compared to those without pCR (P=0.04). However, no significant difference was identified in the multilevel linear regression model.

γ-H2AX may have potential as a biomarker for treatment response in locally advanced rectal cancer patients undergoing preoperative CCRT, although further validation is required.

Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery.

Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to.

The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01).

TNT does not appear to increase the surgical difficulty of TME.

Locally advanced rectal cancer requires a multimodal treatment. Radiotherapy is being explored for intensification to improve the rates of pathological complete responses (ypCR rates) which are correlated with better outcomes. This study reports a comparison between standard versus escalated doses in a preoperative scenario. The ypCR rates, toxicity, postoperative complications, and disease-free and overall survival at 5 years are described. From 2012 to 2019, 99 patients were analyzed retrospectively: standard arm (mean of 47.5 Gy) vs. dose-escalated arm (mean of 54.3 Gy). All patients were treated with 3DRT in 25 fractions, with concomitant capecitabine and surgery performed according to the total mesorectal excision principles in both arms. The ypCR was reported using the "College of American Pathologist grades"; the gastrointestinal (GI) and genitourinary (GU) toxicity was reported using the "Common Terminology Criteria for Adverse Events" (CTCAE 4.0). The ypCR rates were higher in the dose-escalated group (25% vs. 10.64%; p = 0.07), with a lower rate of non-treatment response (61.36% vs. 38.64%; p = 0.11). No statistical differences between the arms were found in terms of the oncological outcomes, postoperative complications (p = 0.15), second surgeries (p = 0.62), or deaths (p = 0.62). The CTCAE acute GI and GU toxicity were grade I or II in both arms. Our study presents a long-term follow-up in comparative cohorts.

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.

Rectal cancer shows specific characteristics in terms of pattern of recurrence, which occurs commonly at both local and distant sites. The standard of care for locally advanced rectal cancer (LARC) including neoadjuvant chemoradiotherapy, followed by surgery based on the total mesorectal excision principles leads to a reduction in the rates of local recurrences to 6-7% at 5 years. However, the outcomes among those with high-risk lesions remain unsatisfactory. On the contrary, neoadjuvant chemoradiotherapy results in long-term morbidities among those with low-risk lesions. Furthermore, the overall survival benefit of neoadjuvant therapy is still a subject to be debated, except for patients with complete or near-complete response to neoadjuvant therapy. Total neoadjuvant therapy (TNT) is a new paradigm of management of high-risk rectal cancer that includes early administration of the most effective systemic therapy either before or after neoadjuvant radiotherapy with or without chemotherapy prior to surgery with or without adjuvant chemotherapy. TNT potentially improves disease-free survival, even though whether it can prolong survival has been debatable. Recently, neoadjuvant chemotherapy only has been proved to be non-inferior to neoadjuvant chemoradiotherapy in patients with low-risk lesions. This review intends to review the current evidences of neoadjuvant therapy and propose a more customized paradigm of management of LARC.

Despite the increasing use of immunotherapy in treating various cancer types, there is still limited understanding of its impact on surgical complications. We used a national database to examine the difference in surgical outcomes for rectal cancer patients who received standard neoadjuvant chemoradiation plus neoadjuvant immunotherapy and patients who received neoadjuvant chemoradiation only.

This retrospective cohort study used the National Cancer Database (NCDB). We selected patients aged 18-90 with T1-3, N1-2, and M0 rectal cancer who underwent curative-intent surgery between 2010 and 2020. We performed a 1:1 propensity match to control for patient age, sex, Charlson-Deyo comorbidity index, surgical approach, and tumor site. Our primary outcome was difference in surgical outcomes (hospital length of stay, unplanned 30-day readmission, 30-day mortality) between the two groups. Secondary outcomes included days from diagnosis to surgery and pathologic outcomes.

Our study included 26 229 patients, of which 126 received immunotherapy in addition to chemoradiation and 26 103 received only chemoradiation. In our matched population of 125 pairs of patients, patients who received immunotherapy and chemoradiation underwent surgery later compared to patients who only received chemoradiation (median 245 vs. 144 days, p < 0.001). There were no significant differences in median length of stay (5 vs. 5 days, p = 0.202), unplanned 30-day readmission (7 vs. 9, p = 0.617), and 30-day mortality (0 vs. 1, p = 1.000) between the two groups.

Neoadjuvant immunotherapy for rectal cancer is not associated with adverse surgical outcomes. This work can help clinicians optimize treatment protocols and move closer toward strategies tailored to specific patient profiles.

In locally advanced rectal cancer, neoadjuvant treatment has evolved from no preoperative treatment to the addition of radiation and systemic therapy and ultimately total neoadjuvant therapy. Total neoadjuvant therapy is the completion of preoperative radiation or chemoradiation and chemotherapy before surgery in order to maximize tumor response and improve survival outcomes. This review summarizes the literature of the neoadjuvant approaches related to locally advanced rectal cancer and highlights the nuances of selecting the appropriate treatment.

Locally advanced rectal cancer has historically been treated with multimodal therapy consisting of radiation therapy, chemotherapy, and total mesorectal excision. However, recent prospective trials and registry studies have demonstrated similar disease outcomes with nonoperative management for patients who experience an excellent clinical response to radiation and chemotherapy. This article reviews data regarding nonoperative management for rectal cancer, and highlights current challenges and limitations in a point-counterpoint format, in the context of two clinical cases.

Liver metastases are seen in at least 60% of patients with colorectal cancer at some point during the course of their disease. The management of both primary and liver disease is uniquely challenging in rectal cancer due to competing treatments and complex sequence of treatments depending on the clinical presentation of disease. Recently, several novel concepts are shaping new treatment paradigms, including changes in timing, sequence, and duration of therapies combined with potential deescalation of treatment components. Overall, the treatment of this clinical scenario mandates multidisciplinary evaluation and personalization of care; however, there is still considerable debate regarding the timing of liver metastasectomy in the context of the overall treatment plan. Herein, we will discuss the current literature on management of rectal cancer with synchronous liver metastasis, current treatment approaches with respect to chemotherapy, and role of hepatic artery infusion therapy.

Rectal cancer management has evolved over the past decade with the emergence of total neoadjuvant therapy (TNT). For select patients who achieve a clinical complete response following TNT, organ preservation by means of the watch-and-wait (WW) strategy is an increasingly adopted alternative that preserves rectal function and quality of life without compromising oncologic outcomes. Recently, published 5-year results from the OPRA trial demonstrated that organ preservation can be achieved in approximately half of patients managed with the WW strategy, with most local regrowth events occurring within two years. Considering the potential for local regrowth, the implementation of the WW strategy mandates rigorous clinical and radiographic surveillance. Magnetic resonance imaging (MRI) serves as the conventional imaging modality for local staging and surveillance of rectal cancer given its excellent soft-tissue resolution. This review will discuss the current evidence for the WW strategy and the role of restaging rectal MRI in determining patient eligibility for this strategy. Restaging rectal MRI acquisition parameters and treatment response assessment, including important factors to assess, pitfalls, and classification systems, will be discussed in the context of the WW strategy.

The treatment of locally advanced rectal cancer (LARC) has evolved following recent landmark trials of total neoadjuvant therapy (TNT)-the delivery of preoperative chemotherapy sequenced with radiation.

To assess the preferences of colorectal surgery (CRS), radiation oncology (RO) and medical oncology (MO) specialists attending the All-Ireland Colorectal Cancer Conference (AICCC) 2022 regarding the neoadjuvant management of LARC.

A live electronic survey explored the preferred treatment approach and TNT regimen for early-, intermediate-, bad-, and advanced-risk categories of rectal cancer according to the European Society of Medical Oncology (ESMO) guidelines. The survey was preceded by an update from lead investigators of TNT trials (OPRA, PRODIGE-23 and RAPIDO), who then participated in a multidisciplinary panel discussion.

Ten CRS, 7 RO and 15 MO (32 of 45 specialists) participated fully in the survey resulting in a response rate of 71%. Ninety-four percent, 76% and 53% of specialists preferred a TNT approach for patients with advanced, bad, and intermediate-risk rectal cancer, respectively. A consolidation TNT regimen of long-course chemoradiotherapy followed by chemotherapy was the most preferred regimen. Upfront surgery was preferred by 77% for early-risk disease.

This survey illustrated the general acceptance of TNT by rectal cancer specialists attending the AICCC as a valuable treatment strategy for higher-risk category LARC. Whilst the treatment of LARC changes, it remains best practice to individualize care, incorporating the selective use of TNT as discussed by an MDT and in keeping with the patient's goals of care.

Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations of the treatments including induction or consolidation chemotherapy, triplet or doublet chemotherapy, and long-course chemoradiotherapy or short-course radiotherapy. Evidence on TNT is rapidly evolving with new data on clinical trials, and no definitive consensus has been established on which regimens to use for improving outcomes. Clinicians need to understand the advantages and limitations of the available regimens for multidisciplinary decision making. This article reviews currently available evidence on TNT for rectal cancer. A decision making flow chart is provided for tailor-made use of TNT regimens based on tumor location and local and systemic risk.

Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program.

The management of rectal cancer has undergone significant changes over the past 50 years, and this has been associated with major improvements in overall outcomes and quality of life. From standardization of total mesorectal excision to refinements in radiation delivery and shifting of chemoradiotherapy treatment to favor a neoadjuvant approach, as well as the development of targeted chemotherapeutics, these management strategies have continually aimed to achieve locoregional and systemic control while limiting adverse effects and enhance overall survival. This article highlights evolving aspects of rectal cancer therapy including improved staging modalities, total neoadjuvant therapy, the role of short-course and more selective radiotherapy strategies, as well as organ preservation. We also discuss the evolving role of minimally invasive surgery and comment on lateral pelvic lymph node dissection.

Rectal cancer management is constantly evolving through refinements in radiation timing and delivery, modification of chemoradiotherapy treatment schedules, and increasing utilization of minimally invasive surgical techniques and organ preservation strategies. This manuscript aims to provide a synopsis of recent changes in the management of rectal cancer, highlighting contemporary modifications in neoadjuvant approaches and surgical management to enhance the knowledge of surgeons who care for this challenging population.

Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment.

To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade.

This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023.

Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP.

OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test.

There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival.

In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT.

ClinicalTrials.gov Identifier: NCT02008656.

Cancer care guidelines based on clinical trial data in homogenous populations may not be applicable to all rectal cancer patients. The aim of this study was to evaluate whether patients enrolled in rectal cancer clinical trials (CTs) are representative of United States (U.S.) rectal cancer patients.

Prospective rectal cancer CTs from 2010 to 2019 in the United States were systematically reviewed. In trials with multiple arms reporting separate demographic variables, each arm was considered a separate CT group in the analysis. Demographic variables considered in the analysis were age, sex, race/ethnicity, facility location throughout the United States, rural vs urban geography, and facility type. Participant demographics from trial and the National Cancer Database (NCDB) participants were compared using chi-squared goodness of fit and one-sample t-test where applicable.

Of 50 CT groups identified, 42 (82%) studies reported mean or median age. Trial participants were younger compared to NCDB patients (P < .001 all studies). All but three trials had fewer female patients than NCDB (48.2% female, P < .001). Less than half the CT groups reported on race or ethnicity. Eighteen out of 22 trials (82%) had a smaller percentage of Black patients and 4 out of 8 (50%) trials had fewer Hispanic or Spanish origin patients than the NCDB. No CTs reported comorbidities, socioeconomic factors, or education. CT primary sites were largely at academic centers and in urban areas.

The present study supports the need for improved demographic representation and transparency in rectal cancer clinical trials.

Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME.

A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes.

A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001).

NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.

Background and Objectives: Full-thickness trans anal local excision for tumors with favorable response following neoadjuvant therapy for locally advanced rectal cancer (LARC) is a common strategy for organ preservation, but it could be associated with a high rate of postoperative complications. We describe the incidence and pattern of submucosal involvement in surgical specimens following neoadjuvant therapy for LARC and whether limiting local excision of the residual tumor bed to only mucosal/submucosal layers of the rectal wall is sufficient for accurately predicting the ypT status of residual cancer, providing a pathological rationale to replace full-thickness local excision by endoscopic submucosal resection. Materials and Methods: This was a single-institution retrospective study conducted at a teaching community hospital. We reviewed clinical and pathological findings with slides of 82 patients diagnosed with LARC treated at our center between 2006 and 2020. Eligibility criteria mirrored our current organ preservation trials. Results: No tumor was found in surgical specimens in 28 cases (34%). Additionally, 4, 22, 27, and 1 cases were staged as ypT1, ypT2, ypT3, and ypT4, respectively. Residual malignant cells were found in the submucosal layer in 98% of cases with ypT+ stage, with 'skip lesions' in only 2% of cases. Conclusions: A very high incidence of submucosal involvement is noticed in residual tumors after neoadjuvant therapy, providing pathological rationale to study the role of endoscopic submucosal resection as a restaging tool for tumors with favorable response after neoadjuvant therapy when organ preservation strategy is pursued. This study was limited by its retrospective design and relatively small number of patients.

It is widely believed that small rectal tumors are more likely to have a good response to neoadjuvant treatment, which may influence the selection of patients for a 'watch and wait' strategy.

The aim of this study was to investigate whether there is a relationship between baseline tumor length on magnetic resonance imaging (MRI) and response to chemoradiotherapy.

The 96 patients with locally advanced rectal cancer randomised (2:1-intervention:control) in the TRIGGER feasibility study where eligible. Baseline tumor length was defined as the maximal cranio-caudal length on baseline MRI (mm) and was recorded prospectively at study registration. Magnetic resonance tumor regression grade (mrTRG) assessment was performed on the post-chemoradiotherapy (CRT) MRI 4-6 weeks (no later than 10 weeks) post completion of CRT. This was routinely reported for patients in the intervention (mrTRG-directed management) arm and reported for the purposes of this study by the central radiologist in the control arm patients. Those with an mrTRG I/II response were defined as 'good responders' and those with an mrTRG III-V response were defined as 'poor responders'.

Overall, 94 patients had a post-CRT MRI performed and were included. Forty-three (46%) patients had a good response (mrTRG I/II) and 51 (54%) patients had a poor response (mrTRG III/IV). The median tumor length of good responders was 43 mm versus 50 mm (p < 0.001), with considerable overlap in tumor lengths between groups.

Baseline tumor length on MRI is not a clinically useful biomarker to predict mrTRG tumor response to CRT and therefore patient suitability for a deferral of surgery trial.

Total neoadjuvant therapy is an alternative to neoadjuvant chemoradiation alone for rectal cancer and has the benefits of more completion of planned therapy, increased downstaging, earlier treatment of micrometastases, and assessment of chemosensitivity; however, it may increase surgical complications, especially with increased radiation-to-surgery interval.

The study aimed to determine the impact of total neoadjuvant therapy on postoperative complications compared with neoadjuvant chemoradiation alone.

Retrospective cohort study.

Single tertiary referral center.

The patient included was a stage II/III rectal cancer patient who underwent total neoadjuvant therapy or long-course neoadjuvant chemoradiation followed by surgical resection from 2018-2020.

The main outcome measures included severe postoperative complications (Clavien-Dindo grade ≥3).

Of 181 patients, 86 (47.5%) underwent total neoadjuvant therapy and 95 (52.5%) underwent neoadjuvant chemoradiation. There was no difference in severe postoperative complications or any complications. There was also no difference in the rate of complete total mesorectal excision or negative circumferential margin. Total neoadjuvant therapy had a mean operative time of 355.5 minutes and estimated blood loss of 263.6 mL compared with 326.7 minutes and 297.5 mL in the neoadjuvant chemoradiation group. Total neoadjuvant therapy patients had a lower mean lymph node yield than neoadjuvant chemoradiation patients. On multivariable analysis, total neoadjuvant therapy was associated with increased operative time (OR, 1.19; p < 0.001) and estimated blood loss (OR, 1.22; p < 0.001) and decreased lymph node yield (OR, 0.67; p < 0.001). There was no difference in severe complications or any complications.

Selection bias uncontrolled by modeling.

We found no difference in risk of postoperative complications between patients who received total neoadjuvant therapy vs neoadjuvant chemoradiation. Total neoadjuvant therapy patients had longer operations and greater estimated blood loss. This may be a reflection of increased operative difficulty because of increased radiation-to-surgery interval and/or the effects of chemotherapy; however, the absolute differences were small and, therefore, should be interpreted cautiously. See Video Abstract at http://links.lww.com/DCR/C44 .

ANTECEDENTES:La terapia neoadyuvante total es una alternativa a la quimiorradiación neoadyuvante sola para el cáncer de recto y tiene los beneficios de una mayor finalización de la terapia planificada, mayor reducción del estadiage, tratamiento más temprano de las micrometástasis y evaluación de la quimiosensibilidad; sin embargo, puede aumentar las complicaciones quirúrgicas, especialmente con un mayor intervalo entre la radiación y la cirugía.OBJETIVO:Determinar el impacto de la terapia neoadyuvante total sobre las complicaciones posoperatorias en comparación con la quimiorradiación neoadyuvante sola.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:Centro único de referencia terciario.PACIENTES:Paciente con cáncer de recto en estadio II/III que se sometieron a terapia neoadyuvante total o quimiorradiación neoadyuvante de larga duración seguida de resección quirúrgica entre 2018 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:Complicaciones postoperatorias graves (grado de Clavien-Dindo ≥3).RESULTADOS:De 181 pacientes, 86 (47,5%) se sometieron a terapia neoadyuvante total y 95 (52,5%) se sometieron a quimiorradioterapia neoadyuvante. No hubo diferencia en las complicaciones postoperatorias graves o cualquier otra complicación. Tampoco hubo diferencia en la tasa de escisión mesorrectal total completa o margen circunferencial negativo. La terapia neoadyuvante total tuvo un tiempo operatorio promedio de 355,5 minutos y una pérdida de sangre estimada de 263,6 ml en comparación con 326,7 minutos y 297,5 ml en el grupo de quimiorradiación neoadyuvante. Los pacientes con terapia neoadyuvante total tuvieron una media de ganglios linfáticos más bajo en comparación con los pacientes con quimiorradioterapia neoadyuvante. En el análisis multivariable, la terapia neoadyuvante total se asoció con un mayor tiempo operatorio (OR = 1,19, p < 0,001) y pérdida de sangre estimada (OR = 1,22, p < 0,001) y menor cantidad los ganglios linfáticos (OR = 0,67, p < 0,001). No hubo diferencia en las complicaciones graves o cualquier complicación.LIMITACIONES:Sesgo de selección no controlado por modelado.CONCLUSIONES:No encontramos diferencias en el riesgo de complicaciones postoperatorias entre los pacientes que recibieron terapia neoadyuvante total versus quimiorradiación neoadyuvante. Los pacientes con terapia neoadyuvante total tuvieron operaciones más prolongadas y una mayor pérdida de sangre estimada. Esto puede ser un reflejo de una mayor dificultad quirúrgica como resultado de un mayor intervalo entre la radiación y la cirugía y/o los efectos de la quimioterapia; sin embargo, las diferencias absolutas fueron pequeñas y, por lo tanto, deben interpretarse con cautela. Consulte Video Resumen en http://links.lww.com/DCR/C44 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

This article adopts a multidisciplinary approach, including surgery, oncology, radiology and patient perspectives, to discuss the key points of debate surrounding a watch and wait approach. In an era of shared decision-making, discussion of watch and wait as an option in the context of complete clinical response is appropriate, although it is not the gold standard treatment. Key challenges are the difficulty in assessing for a complete clinical response, prediction of recurrence and access to timely diagnostics for surveillance. Salvage surgery has good results if regrowth is detected early but does have imperfect outcomes, with only a 90% salvage rate. Good communication with patients about the risks and alternatives is essential. Patients undergoing watch and wait should ideally be enrolled in prospective registries or clinical trials.

Extramural venous invasion (EMVI) on baseline MRI is associated with poor prognosis in patients with locally advanced rectal cancer. This study investigated the association of persistent EMVI after total neoadjuvant therapy (TNT) (chemoradiotherapy and systemic chemotherapy) with survival.

Baseline MRI, post-TNT MRI, and surgical pathology data from 175 patients with locally advanced rectal cancer who underwent TNT and total mesorectal excision between 2010 and 2017 were retrospectively analyzed for evidence of EMVI. Two radiologists assessed EMVI status with disagreement adjudicated by a third. Pathologic EMVI status was assessed per departmental standards. Cox regression models evaluated the associations between EMVI and disease-free and overall survival.

EMVI regression on both post-TNT MRI and surgical pathology was associated with disease-free survival (hazard ratio, 0.17; 95% confidence interval (CI), 0.04-0.64) and overall survival (hazard ratio, 0.11; 95% CI, 0.02-0.68). In an exploratory analysis of 35 patients with EMVI on baseline MRI, only six had EMVI on pathology compared with 18 on post-TNT MRI; these findings were not associated (p = 0.2). Longer disease-free survival was seen with regression on both modalities compared with remaining positive. Regression on pathology alone, independent of MRI EMVI status, was associated with similar improvements in survival.

Baseline EMVI is associated with poor prognosis even after TNT. EMVI regression on surgical pathology is common even with persistent EMVI on post-TNT MRI. EMVI regression on surgical pathology is associated with improved DFS, while the utility of post-TNT MRI EMVI persistence for decision-making and prognosis remains unclear.

Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer.

In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival.

Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation.

www.

gov NCT05000697; registered on August 11^th, 2021.

Previous randomized trials found that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4-8 weeks, SCRT-delay) results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study sought to confirm these results in a Dutch national database.

Patients with intermediate-risk rectal cancer (T3(mesorectal fascia (MRF)-) N0 M0 and T1-3(MRF-) N1 M0) treated with either SCRT-delay (4-12 weeks) or SCRT-direct surgery in 2018-2021 were selected from a Dutch national colorectal cancer database. Confounders were adjusted for using inverse probability of treatment weighting (IPTW). The primary endpoint was the 90-day postoperative complication rate. Secondary endpoints included the pCR rate. Endpoints were compared using log-binomial and Poisson regression.

Some 664 patients were included in the SCRT-direct surgery and 238 in the SCRT-delay group. After IPTW, the 90-day postoperative complication rate was comparable after SCRT-direct surgery and SCRT-delay (40.1 versus 42.3 per cent; risk ratio (RR) 1.1, 95 per cent c.i. 0.9 to 1.3). A pCR occurred more often after SCRT-delay than SCRT-direct surgery (10.7 versus 0.4 per cent; RR 39, 11 to 139).

There was no difference in surgical complication rates between SCRT-delay and SCRT-direct, but SCRT-delay was associated with more patients having a pCR.

Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system.

Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy×5 with two cycles of XELOX (capecitabine 1000 mg/m² and oxaliplatin 130 mg/m² every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups.

Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT: 91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost.

SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT.

Aim: The authors conducted a meta-analysis to determine the association between time-to-surgery (TTS) after neoadjuvant chemotherapy and patient outcomes in locally advanced gastric cancer. Methods: Electronic databases were searched to identify potential studies, in which the authors compared patient outcomes between those with TTS within 4 (and 6) weeks of completion of neoadjuvant chemotherapy and those after 4 (and 6) weeks. Results: Six studies, including 1238 patients, were eligible for inclusion. Pooled data showed no significant differences in rates of pathological complete response, major pathological response, ypN0, complications, R0 resection and operative time between groups of longer TTS and shorter TTS. Conclusion: There was no statistically advantageous impact of prolonged TTS on pathological and surgical outcomes. Large, population-based studies are warranted.

In locally advanced rectal cancer treatment, neoadjuvant concurrent chemoradiation therapy (cCRT) is the standard of care. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and survival, response to antitumor therapies and also resistance to treatment. We aimed to assess the change in biomarkers associated with TME following standard neoadjuvant cCRT in rectal cancer.

We accessed archival tissue from rectal cancer patients treated with neoadjuvant cCRT at Allegheny Health Network (AHN) facilities over the past 14 years. Pre-treatment and post-treatment biopsies were assayed for PD-L1, CD8+ T-cells, CXCL9, TIM-3, IDO-1, IFN-G, IL17RE, LAG-3, and OX40 in 41 patients.

We found statistically significant upregulation in multiple biomarkers namely CD8, IL17RE, LAG3 and OX40 post neoadjuvant cCRT and a trend towards upregulation, although not statistically significant, in biomarkers PD-L1, CXCL9, TIM-3, IDO-1 and IFN-G expression.

This provides a glimpse into the TME before and after neoadjuvant cCRT. We suggest that the biomarkers noted to be upregulated could be used for designing appropriate clinical trials and development of therapeutic targeted drug therapy in an effort to achieve better response to neoadjuvant therapy, increasing clinical and pathological complete response rates and improved overall outcomes.