Preoperative Chemoradiotherapy Research Articles

Colorectal cancer-specific IFNβ delivery overcomes dysfunctional dsRNA-mediated type I interferon signaling to increase the abscopal effect of radiotherapy

BackgroundCancer-intrinsic type I interferon (IFN-I) production triggered by radiotherapy (RT) is mainly dependent on cytosolic double-stranded DNA (dsDNA)-mediated cGAS/STING signaling and increases cancer immunogenicity and enhances the antitumor immune response...

Prediction of combination therapy efficacy in patients with locally advanced squamous cell oropharyngeal carcinoma

Background. Oropharyngeal squamous cell carcinoma (OPSCC) is characterized by late-stage diagnosis and high rate of mortality. Combined modality treatment including preoperative chemoradiotherapy (CRT) is the standard of care for OPSCC. The search for criteria for predicting the efficacy of preoperative chemoradiotherapy with a view to prescribe it to those patients for whom it is really indicated and will be effective remains challenging. The aim of the study was to identify serum actin-binding proteins that can predict preoperative therapy efficacy in patients with OPSCC. Material and methods. Blood serum from 45 patients with stage II–IV OPSCC was studied. all patients received preoperative chemotherapy with paclitaxel and carboplatin. Radiation therapy in a standard mode was given 2 weeks after chemothetapy. serum levels of actin-binding proteins (CAP1, fascin, ezrin, gelsolin, and profiling) were determined before treatment using ELISA. Results. complete or partial response to preoperative CRT was achieved in 27 patients. Disease progression or stabilization was observed in 18 patients. A comparison of the serum levels of actin-binding proteins before treatment with those obtained after preoperative CRT showed that the serum level of ezrin was lower in patients who did not respond to preoperative CRT than in patients with partial or complete response to therapy. ROC-analysis showed that the serum level of ezrin of less than 2.50 ng/ml can predict the tumor response to CRT as unfavorable (less than 75 % according to the RECIST scale). The sensitivity was 72 % and the specificity was 71 %. Conclusion. Determination of the serum level of ezrin in patients with OPSCC has a predictive value in relation to preoperative chemoradiotherapy.

Evaluation of the prognostic impact of pathologic tumor regression grade on patients with colorectal cancer after preoperative chemoradiotherapy.

The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.

Treatment Outcome in Locally Advanced Rectal Carcinoma and Its Correlation with Hypo-Fractionated Radiotherapy and Concurrent Chemoradiotherapy

Introduction: Rectal cancer is the second most common type within the large intestine, posing significant health risks globally. In Bangladesh, it ranks high among diagnosed cancers. Improved diagnostic methods aid in early detection, which is crucial for effective management. Treatment typically involves a combination of surgery, radiotherapy, and chemotherapy. Preoperative chemoradiotherapy is a standard approach. However, newer methods like preoperative hypo-fractionated radiotherapy with surgery promise better outcomes, including reduced recurrence rates and enhanced survival, with potential cost and time savings. Aim of the Study: The study aims to evaluate and contrast the efficacy of hypofractionated radiotherapy and concurrent chemoradiotherapy in patients with locally advanced rectal carcinoma. Methods: The study, conducted at the Department of Clinical Oncology at Bangabandhu Sheikh Mujib Medical University Shahbagh, Dhaka, Bangladesh and the Department of Radiation Oncology at the National Institute of Cancer Research and Hospital (NICR&amp;H) in Mohakhali, Dhaka, Bangladesh, aimed to compare treatments for locally advanced rectal cancer over 1.5 years (From January 2018 to June 2019). A total of 80 patients were divided into two groups; Group A received hypofractionated radiotherapy, while Group B received oral capecitabine alongside external beam radiotherapy. Inclusion criteria involved confirmed adenocarcinoma within specified stages, with ethical clearances obtained. Patients underwent evaluations before treatment and response assessments posttreatment. Treatment modalities were defined, focusing on radiotherapy and chemotherapy. Data were analyzed using SPSS software, employing various statistical tests. Results aimed to address study objectives while minimizing biases. Result: The study involved 80 patients, divided into Groups A and B, each with 40 individuals. Group A mainly comprised individuals aged 41-50 (45%), followed by 31-40 (25%). Group B had the highest proportion aged 31-40 (30%) and 41-50 (32.50%). Both groups showed male predominance (1.3:1). Moderately differentiated tumors were common, with Group A having more poorly differentiated tumors. Stage III was predominant pre-treatment (65% Group A, 70% Group B). Most patients presented with per rectal bleeding (80%) and alteration of bowel habits (56.25%). Response rates to treatment were similar between groups. Tumor downsizing was more frequent in Group B. Sphincter-sparing surgery was feasible in both groups with no significant difference. Conclusion: The study comparing preoperative hypofractionated radiotherapy (RT) to concurrent chemoradiotherapy (CCRT) for locally advanced rectal carcinoma found similar efficacy in tumor response, downsizing, and sphincter preservation. Statistical analysis showed no significant differences. Both approaches showed acceptable short-term outcomes, offering clinicians options based on patient and resource considerations.

Evaluation of anorectal function using real-time tissue elastography before and after preoperative chemoradiotherapy

PurposeThis study aimed to clarify the relationship between changes in elasticity and anorectal function before and after chemoradiotherapy.MethodsThis is a single-center prospective cohort study (Department of Surgical Oncology, The University of Tokyo). We established a technique to quantify internal anal sphincter hardness as elasticity using transanal ultrasonography with real-time tissue elastography. Twenty-seven patients with post-chemoradiotherapy rectal cancer during 2019–2022 were included. Real-time tissue elastography with transanal ultrasonography was performed before and after chemoradiotherapy to measure internal anal sphincter hardness as “elasticity” (hardest (0) to softest (255); decreased elasticity indicated sclerotic changes). The relationship between the increase or decrease in elasticity pre- and post-chemoradiotherapy and the maximum resting pressure, maximum squeeze pressure, and Wexner score were the outcome measures.ResultsA decrease in elasticity was observed in 16/27 (59.3%) patients after chemoradiotherapy. Patients with and without elasticity decrease after chemoradiotherapy comprised the internal anal sphincter sclerosis and non-sclerosis groups, respectively. The maximum resting pressure post-chemoradiotherapy was significantly high in the internal anal sphincter sclerosis group (63.0 mmHg vs. 47.0 mmHg), and a majority had a worsening Wexner score (60.0% vs. 18.2%) compared with that of the non-sclerosis group. Decreasing elasticity (internal anal sphincter sclerosis) correlated with a higher maximum resting pressure (r = 0.36); no correlation was observed between the degree of elasticity change and maximum squeeze pressure.ConclusionInternal anal sphincter sclerosis due to chemoradiotherapy may correlate to anorectal dysfunction.

Number of Healthy Teeth Can Predict the Response of Rectal Cancer to Chemoradiotherapy: A Retrospective Study.

It has been reported that the oral and gut microbiomes are associated with the prognosis in patients who undergo surgery, chemotherapy, and radiation for colorectal cancer. This study is the first to identify a correlation between the number of healthy teeth, which is an oral health indicator, and the efficacy of preoperative chemotherapy for rectal cancer. This retrospective single-center study included 30 patients who underwent radical surgery after preoperative chemoradiotherapy (CRT) between December 2013 and June 2021. The relationship between number of teeth before CRT and the efficacy of CRT, CRT-related adverse events, postoperative complications, and long-term postoperative outcomes was examined. The number of healthy teeth was significantly greater in patients with downstaging of their disease than in those without downstaging (P = .027) and in patients with a complete response according to the Response Evaluation Criteria in Solid Tumors than in those who did not have a complete response (P = .014). Patients were divided into two groups according to whether they had ≥15 teeth or ≤14 teeth. There was no significant between-group difference in CRT-related adverse events. The incidence of all postoperative complications and grade II postoperative complications tended to be higher in patients with ≥15 teeth (P = .071 and P = .092, respectively), as did the 5-year overall survival rate (P = .083) and the 5-year disease-free rate (P = .007). The number of healthy teeth predicted the response to preoperative CRT, postoperative complications, and the outcome of subsequent surgery in patients with rectal cancer.

Abstract CT130: Epacadostat with preoperative chemoradiation in locally advanced rectal cancer (LARC): Results of a translational phase I clinical trial

Abstract BACKGROUND: In preclinical studies, we found that the immuno-oncology target and tryptophan metabolizing enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) promotes resistance to radiation in rectal cancer regardless of MSI status. Furthermore, IDO1 inhibition with epacadostat improved tumor radiosensitivity, abrogated immunosuppression, limited distal recurrence, and was radioprotective of the normal intestine. This trial aimed to evaluate the safety of IDO1 inhibition when combined with neoadjuvant short-course radiation (SCRT) and chemotherapy with capecitabine and oxaliplatin (CAPOX) for LARC. METHODS: The primary objective was to determine the recommended phase II dose (RP2D) of epacadostat for combination with SCRT and CAPOX. Secondary objectives included determining antitumor activity as measured by neoadjuvant rectal (NAR) score and pathological or clinical complete responses. During the dose escalation phase, 3 doses of epacadostat (300mg, 400mg, &amp; 600mg BID) were explored. Epacadostat was combined with SCRT (5Gy x 5 fractions) followed by 6 cycles of CAPOX chemotherapy, until the day of surgery (~24 wks). Tissues and blood were collected for correlative studies. A control cohort was generated from patients receiving the same treatment without epacadostat. NCT03516708 RESULTS: Seventeen patients were enrolled from 4/2019 to 8/2023. RP2D of epacadostat in combination with SCRT and CAPOX chemotherapy was determined to be 400mg BID. Two patients experienced dose-limiting toxicities (DLT) at 600mg dose level, one with G2 elevated ALT and another with G3 maculopapular rash. No DLT was reported at other dose levels. Of six patients who underwent surgery, the mean NAR score was 7.46 (SD 7.11; range 0 - 20.4), indicating potentially better response compared to the mean NAR of 17.8 in an institutional 2:1 matched control cohort (p=0.03). Tumor tissue revealed increased IDO1 expression and kynurenine levels in all patient tumors after radiation. After epacadostat, serum levels of kynurenine were reduced while TNFα, IFNγ, and MIP1a were all increased. Global metabolomics and RNAseq revealed a distinct pattern of serum biomarkers and immunophenotype respectively in patients after treatment. Tumoroids were evaluated as ex vivo models of treatment response. CONCLUSION: Epacadostat in combination with SCRT and CAPOX was well-tolerated. An NCI supported Phase 2 trial is ongoing to further evaluate the promising disease responses reported in dose escalation phase. Citation Format: Haeseong Park, Katrina Pedersen, Katherine Huang, Matthew Mutch, Hyun Kim, Nikolaos Trikalinos, Olivia Aranha, Benjamin Tan, Rama Suresh, Lee Ratner, Moh'd Khushman, John Visconti, Kian-Huat Lim, Lauren Henke, Maddie Swiecicki, Jingxia Liu, Parag Parikh, Matthew Ciorba. Epacadostat with preoperative chemoradiation in locally advanced rectal cancer (LARC): Results of a translational phase I clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT130.

Fluorescence guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series

PurposeTattoo markings are often used as preoperative markers for colorectal cancer. However, scattered ink markings adversely affect tumor site recognition intraoperatively; therefore, interventions for rectal cancer may lead to an inaccurate distal resection margin (DRM) and incomplete total mesorectal excision (TME). This is the first case series of fluorescence-guided robotic rectal surgery in which near-infrared fluorescence clips (NIRFCs) were used to localize rectal cancer lesions.MethodsWe enrolled 20 consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 in the current study. The primary endpoints were the rate of intraoperative clip detection and its usefulness for marking the tumor site. Secondary endpoints were oncological assessments, including DRM and the number of lymph nodes.ResultsClip locations were confirmed in 17 of 20 (85%) patients. NIRFCs were not detected in 3 out of 7 patients who underwent preoperative chemoradiation therapy. No adverse events, including bleeding or perforation, were observed at the time of clipping, and no clips were lost. The median DRM was 55 mm (range, 22–86 mm) for rectosigmoid (Rs), 33 mm (range, 16–60 mm) for upper rectum (Ra), and 20 mm (range, 17–30 mm) for low rectum (Rb). The median number of lymph nodes was 13 (range, 10–21).ConclusionThe rate of intraoperative clip detection, oncological assessment, including DRM, and the number of lymph nodes indicate that the utility of fluorescence-guided methods with NIRFCs is feasible for rectal cancer.

Abstract 6683: The abundance of Fusobacteria nucleatum in tumor tissue is a prognostic factor in patients of right-sided colorectal cancer

Abstract Background: A significant association between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Fusobacteria nucleatum (F. nucleatum) is one of the most famous bacteria associated with colorectal cancer (CRC). It has been reported that the abundance of F. nucleatum is associated with colorectal cancer-specific survival (CSS), however it remains unclear for association with F. nulceatum and relapse-free survival (RFS). If F. nucleatum has a significant involvement in tumor progression of colorectal cancer, the abundance of F. nucleatum should be associated with not only CSS but also RFS in colorectal cancer. In this study, we measured the bacterial mass of F. nucleatum in tumor tissue of CRC patients in Stage II-III to explore the differences in prognosis. Methods: We included patients with CRC in stage II-III who underwent surgical treatment at Nippon Medical School Hospital between January 2017 and December 2020 except patients who received preoperative chemoradiotherapy and had multiple cancers. We measured the absolute of F. nucleatum copy number of the DNA exacted tumor tissues using droplet digital PCR. Results: 253 patients with CRC were included. 128 patients had pathological stage II and 125 patients had pathological stage III. Among 253 patients, 104 patients had right-sided CRC, 89 patients had left-sided, and 60 patients had rectal cancer. F. nucleatum was detected in 166 patients (65.6%), and the median of F. nucleatum copy number was 1.08 (range; 0.00 -2791.3). F. nucleatum copy number was more abundant in right-sided CRC than in left-sided and rectal cancer (p= 0.02, p=0.01). There was no significant difference between stage II CRC and stage III. We categorized patients into two groups based on the median cut point of F. nucleatum copy number: the F. nucleatum-high group and the F. nucleatum-low group for comparison with clinicopathological features and prognosis. Patients with high abundance of F. nucleatum exhibited T4 of tumor depth (p=0.03), right-sided CRC (p=0.01), longer tumor circumference (p &amp;lt;0.001), longer tumor length (p &amp;lt;0.001), and no lymph node metastasis (p=0.024). There was no significant difference in relapse-free survival between the F. nucleatum-high group and F. nucleatum-low group among whole patients (p=0.53). Analyzing divided tumor location, in right-sided CRC high abundance of F. nucleatum was significantly associated with shorter relapse-free survival than low abundance (p=0.02), while in left-sided and rectal cancer there was no significant difference (p=0.61). Conclusion: F. nucleatum was more abundant in right-sided CRC and associated with relapse-free survival only in right-sided CRC. F. nucleatum may make a greater impact on right-sided CRC than on left-sided and rectal cancer. Citation Format: Toshimitsu Miyasaka, Takeshi Yamada, Sho Kuriyama, Akihisa Matsuda, Kay Uehara, Seiichi Shinji, Yasuyuki Yokoyama, Goro Takahashi, Takuma Iwai, Kohki Takeda, Shintaro Kanaka, Hiroshi Yoshida. The abundance of Fusobacteria nucleatum in tumor tissue is a prognostic factor in patients of right-sided colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6683.

Anterior versus posterior mediastinal reconstruction after esophagectomy in esophageal cancer patients: a systematic review and meta-analysis.

Esophagectomy is the primary surgical treatment for esophageal cancer, although other treatment approaches are often incorporated, including preoperative chemotherapy and chemoradiotherapy. The two major routes of esophageal reconstruction after esophagectomy are the anterior mediastinal (retrosternal, heterotopic) and posterior mediastinal (prevertebral, orthotopic) routes. However, which of these two routes of reconstruction is the most appropriate remains controversial. This systematic review aimed to compare the efficacy and safety of anterior mediastinal reconstruction with those of posterior mediastinal reconstruction after esophagectomy in esophageal cancer. In January 2022, a literature search of the CENTRAL, MEDLINE, and EMBASE databases was conducted to identify all published and unpublished randomized controlled trials, regardless of language. Eight studies were included for quantitative synthesis. Postoperative death (9/129 and 4/125, risk ratio [RR]: 2.07, 95% confidence interval [CI]: 0.65-6.64) and incidence of anastomotic leak (24/208 and 26/208, RR: 0.95, 95% CI: 0.56-1.62) were not significantly different between the two mediastinal reconstructions. We could not perform a meta-analysis for quality of life, loss of body weight, or postoperative hospital stay due to data limitations. Overall, there was low-quality evidence to suggest that the outcomes of the anterior and posterior mediastinal routes of reconstruction are not significantly different in patients with esophageal cancer.

Preoperative chemoradiotherapy but not chemotherapy is associated with reduced risk of postoperative pancreatic fistula after pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a nationwide analysis

BackgroundPostoperative pancreatic fistula remains the leading cause of significant morbidity after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Preoperative chemoradiotherapy has been described to reduce the risk of postoperative pancreatic fistula, but randomized trials on neoadjuvant treatment in pancreatic ductal adenocarcinoma focus increasingly on preoperative chemotherapy rather than preoperative chemoradiotherapy. This study aimed to investigate the impact of preoperative chemotherapy and preoperative chemoradiotherapy on postoperative pancreatic fistula and other pancreatic-specific surgery related complications on a nationwide level. MethodsAll patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included in the mandatory nationwide prospective Dutch Pancreatic Cancer Audit (2014–2020). Baseline and treatment characteristics were compared between immediate surgery, preoperative chemotherapy, and preoperative chemoradiotherapy. The relationship between preoperative chemotherapy, chemoradiotherapy, and clinically relevant postoperative pancreatic fistula (International Study Group of Pancreatic Surgery grade B/C) was investigated using multivariable logistic regression analyses. ResultsOverall, 2,019 patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included, of whom 1,678 underwent immediate surgery (83.1%), 192 (9.5%) received preoperative chemotherapy, and 149 (7.4%) received preoperative chemoradiotherapy. Postoperative pancreatic fistula occurred in 8.3% of patients after immediate surgery, 4.2% after preoperative chemotherapy, and 2.0% after preoperative chemoradiotherapy (P = .004). In multivariable analysis, the use of preoperative chemoradiotherapy was associated with reduced risk of postoperative pancreatic fistula (odds ratio, 0.21; 95% confidence interval, 0.03–0.69; P = .033) compared with immediate surgery, whereas preoperative chemotherapy was not (odds ratio, 0.59; 95% confidence interval, 0.25–1.25; P = .199). Intraoperatively hard, or fibrotic pancreatic texture was most frequently observed after preoperative chemoradiotherapy (53% immediate surgery, 62% preoperative chemotherapy, 77% preoperative chemoradiotherapy, P < .001). ConclusionThis nationwide analysis demonstrated that in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma, only preoperative chemoradiotherapy, but not preoperative chemotherapy, was associated with a reduced risk of postoperative pancreatic fistula.

Differential clinical outcomes after 3 versus 5 years in a comparison of preoperative chemotherapy with and without radiotherapy in locally advanced rectal cancer: A national cohort propensity score-matched study

BackgroundPreoperative chemotherapy alone might be a good alternative to preoperative chemoradiotherapy for patients with locally advanced rectal cancer, yet long-term real-world data from the same cohort are lacking. MethodsPatients diagnosed with stage II-III rectal adenocarcinoma from 2011 to 2015 were randomly sampled from the SEER-Plus database to evaluate the superiority of preoperative chemoradiotherapy versus preoperative chemotherapy alone. FindingsA total of 1314 eligible patients were enrolled, with a median follow-up of 74.0 months. At 3-year follow-up, neither overall survival (OS) nor cancer-specific survival (CSS) was significantly different between the two treatment groups. At 5-year follow-up, CSS was similar across groups (HR 0.768, 95% CI 0.532–1.108; P = 0.156), but the 5-year OS was significantly better in the preoperative chemoradiotherapy group than in the preoperative chemotherapy group (HR 0.682, 95% CI 0.538–0.866; P = 0.002). Besides, the landmark analysis indicated a direct contrast in the CSS within 3 years (HR 1.101, 95% CI 0.598–2.029; P = 0.756) versus that at 3–5 years (HR 0.597, 95% CI 0.377–0.948; P = 0.027). The landmark analysis also showed directly contrasting OS outcomes within 3 years (HR 0.761, 95% CI 0.533–1.086; P = 0.130) versus those at 3–5 years (HR 0.621, 95% CI 0.451–0.857; P = 0.003). InterpretationIn patients with locally advanced rectal cancer under real-world treatment practices, the addition of preoperative radiotherapy to chemotherapy improves survival outcomes at 3–5 years’ follow-up but not at 3-year follow-up.

Survival benefits of adjuvant chemotherapy for patients with residual pathologic disease after neoadjuvant chemotherapy and surgery for locally advanced esophageal squamous cell carcinoma

Background and purposeAlthough preoperative neoadjuvant chemotherapy (NACT) or chemoradiation is the current standard of care for esophageal cancer in China, the impact of subsequent adjuvant therapy on patient prognosis remains unknown. This study aims to analyze the effect of adjuvant chemotherapy (ACT) on the survival rates of patients who have achieved a non-pathological complete response (non-pCR) after NACT and subsequent surgery. MethodsWe reviewed the data of 2193 patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between January 2006 and January 2016. Of these patients, 46 received NACT and ACT, while 109 received NACT only. Propensity score matching was used to compare 86 patients, with 43 patients in the NACT+ACT group and 43 patients in the NACT group.Univariate analysis was performed using the Kaplan-Meier method and Log-rank test, while Cox regression analysis was used for multivariate analysis. ResultsMultivariate analysis revealed that pathological lymph node status (positive vs. negative) (P<0.001) and treatment modalities (NACT+ACT vs. NACT) (P=0.005) were independent prognostic factors. There was a significant difference in long-term survival rates between the NACT+ACT and NACT groups, with 5-year survival rates of 55.8% vs. 39.5%, respectively (c2=4.270, P=0.039). In patients with ypN+ status, the 5-year survival rate was 31.8% for those who received ACT after NACT and surgery, compared to 10.0% for those who did not receive additional ACT (c2=6.101, P=0.014). The corresponding percentages in patients with ypN- were 81.0% and 65.2%, respectively (c2=1.993, P=0.158). ConclusionAdjuvant chemotherapy should be recommended for locally advanced ESCC patients with residual cancer after NACT and surgery, especially for patients with nodal metastases after NACT.

Role of Preoperative Radiation Therapy for Resectable Gastric Cancer.

While surgery is the primary curative treatment for resectable gastric and gastroesophagealjunction (GEJ) cancer, rates of locoregional and distant recurrence remain high with surgery alone,especially in more advanced disease. Multimodal approaches with perioperative therapy includingchemotherapy and/or radiation therapy (RT) have thus evolved as ways to reduce the rates of diseaserecurrence and improve survival outcomes. This review article provides a comprehensive literaturereview on the role of preoperative RT for resectable gastric and GEJ cancer. A literature review on the role of preoperative RT for resectable gastric and GEJ cancer wasconducted. Preoperative RT has the potential to facilitate tumor downstaging and improved R0 resection,allowing for better locoregional control and thereby survival. For resectable locally advanced GEJ cancer,preoperative chemoradiotherapy (CRT) is currently a standard of care option along with perioperativechemotherapy, based on evidence from randomized trials. In resectable gastric cancer, however, therole of preoperative CRT is less defined with no randomized data to date, although phase II single-armstudies have shown promising results. Current standard of care for gastric cancer remains perioperativechemotherapy, with consideration for preoperative CRT in select cases. Results from ongoing and future randomized controlled trials are expected to help definethe role of preoperative CRT compared to perioperative chemotherapy alone as well as postoperativeCRT for gastric and GEJ cancer.

Association between fibrosis around the tumor and postoperative infectious complication in patients with esophageal cancer who underwent preoperative therapy.

Multidisciplinary treatment combining chemotherapy, chemo radiation therapy (CRT), and surgery has been utilized for advanced esophageal cancer. However, preoperative treatment could cause postoperative inflammation and complications. We hypothesized that fibrosis surrounding tumor tissue caused by preoperative treatment could inducepostoperative systemic inflammation and influence postoperative complications. Surgical specimens from patients with thoracic esophageal cancer who underwent preoperative CRT (38 cases) or chemotherapy (77 cases) and those who received no preoperative treatment (49 cases) were evaluated to measure the fibrotic area adjacent to the tumor (10mm from the tumor edge) by applying Azan staining. Pleural effusion and peripheral blood serum interleukin-6 levels were analyzed to evaluate local and systemic postoperative inflammation in 37 patients. The fibrotic areas around the tumors were significantly larger in patients who underwent preoperative CRT than in patients who underwent chemotherapy (p<0.001) or who had received no preoperative therapy (p<0.001). Infectious complications were higher in patients who underwent preoperative CRT than chemotherapy (p=0.047) or surgery alone (p<0.001). The patients with larger fibrotic areas had more infectious complications (p=0.028). Multivariate analysis showed that both a large fibrotic area and preoperative CRT were correlated with infectious complications, but not significantly. Pleural effusion interleukin-6 was significantly higher in patients who underwent preoperative CRT than in patients who received no preoperative therapy (p=0.013). A large fibrotic peritumoral esophageal tissue area after preoperative treatment could cause postoperative inflammatory response and infectious complications.

Preoperative chemoradiotherapy vs. chemotherapy for adenocarcinoma of the esophagus and esophagogastric junction (AEG): systematic review with individual patient data (IPD) network meta-analysis (NMA)

Preoperative chemoradiotherapy vs. chemotherapy for adenocarcinoma of the esophagus and esophagogastric junction (AEG): systematic review with individual patient data (IPD) network meta-analysis (NMA)

Updated German guideline on diagnosis and treatment of squamous cell carcinoma and adenocarcinoma of the esophagus.

Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline "Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poorwith surgery alone, multimodality therapy is recommended. In locally advancedadenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.

Efficacy and Safety of Preoperative Transcatheter Rectal Arterial Chemoembolisation in Patients with Locally Advanced Rectal Cancer: Results from a Prospective, Phase II PCAR Trial

AimsThe PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC). Materials and methodsThis was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0–1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4–8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4–6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events. ResultsIn total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45–74.45) and 74.80% (95% confidence interval 65.05–86.01), respectively. Grade 3–4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101–8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058–5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347–7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664–10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290–13.306, P = 0.0344) were independent predictors for overall survival. ConclusionThe current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.

Mucin 5 AC (MUC5AC) to predict pathologic treatment response (TR) to neoadjuvant chemotherapy (NAT) in resected-pancreatic ductal adenocarcinoma (R-PDA).

690 Background: MUC5AC is a gel-forming glycoprotein that exists in two major glycoforms in PDA. We studied the differential expression and predictive value of heavily glycosylated mature MUC5AC (MM) detected in the apical (Ap) and/or extracellular region (EC) and less-glycosylated immature MUC5AC (IM) detected only in the cytoplasm (Cy) in R-PDA. Methods: R-PDA formalin-fixed paraffin-embedded tissue blocks from January 2010 to June 2021 were obtained from the Ohio State University biorepository. Immunohistochemistry was performed to study the expression for MM and IM using monoclonal antibodies 45M1 and CLH2, respectively, and H-scores were calculated. Analysis of variance (ANOVA), t-tests, and Wilcoxon tests were used for statistical analysis. Results: Tissue samples from 100 R-PDA (43 received NAT and 57 had upfront surgery (UpS)) were available for testing. The median age of diagnosis was 65 years, and 50% were females. MM and IM were positive in 96% R-PDA (MM-95% Ap and 72% EC).In the NAT group, 89% (n=38) had 5-fluorouracil (5FU) based (36 FOLFIRINOX and 2 FOLFOX), and the rest received gemcitabine (Gem)-based therapy; patients received a median of 6 cycles of NAT; 37% (16) had preoperative chemoradiation (CRT) after NAT; 63% (27) had adjuvant systemic therapy (AST); pathologic objective response (OR = near complete or partial) and no response (NR) to NAT was reported in 63% (27) and 37% (16), respectively. In UpS group, 92% and 4% had AST (48 Gem-based, 4 5FU-based) and adjuvant CRT, respectively. The median time to recurrence (mTTR) and overall survival of the group was 15 and 33 months (m), respectively. NAT group had significantly (p&lt;0.05) lower EC-positive MM (mean H-score 108 vs. 151), IM (mean H-score 122 vs. 162), and mTTR (11 vs 15 m) than UpS group. IM levels were directly proportional to the response (near complete (mean H-score 98) &lt; partial (105) &lt; NR (152) &lt; UpS (162), p=0.04). Other TR results are discussed in the table. Conclusions: MUC5AC (IM &gt; MM) is a potential predictive marker for TR among PDA patients, specifically among those receiving FOLFIRINOX. These associations must be validated in further prospective studies.[Table: see text]

Phase I trial of short-course chemoradiotherapy followed by chemotherapy as total neoadjuvant therapy for patients with potentially resectable gastric cancer.

362 Background: The purpose of this phase I trial was to evaluate the safety and toxicity of preoperative short-course chemoradiotherapy (CXRT) in patients with potentially resectable gastric or gastroesophageal adenocarcinoma as part of a total neoadjuvant therapy (TNT) approach. Methods: Patients with potentially resectable gastric or gastroesophageal adenocarcinoma received CXRT consisting of 30 Gy in 10 fractions with concurrent capecitabine or fluorouracil, followed by systemic therapy for 2 months and then surgery. The primary objective was safety of CXRT with secondary endpoints of pathologic complete response, perioperative complications, and overall survival (OS). Results: A total of 24 patients were treated between March 2021 and December 2022. Ten patients (42%) presented with bleeding and 3 (13%) presented with gastric outlet obstruction. Two patients (8%) had cirrhosis. Clinical nodal involvement was reported in 12 patients (50%). Twenty patients (83%) had poorly differentiated tumors, and 13 (54%) had signet ring cell histology. All patients completed CXRT. CXRT treatment-related toxic effects included grade 3 lymphopenia in 7 patients (29%), grade 4 lymphopenia in 1 (4%), and grade 3 anemia in 1 (4%). After CXRT, 22 patients (92%) completed 2 months of chemotherapy, 1 patient (4%) with a microsatellite-high tumor completed immunotherapy, and 1 patient (4%) underwent resection without systemic therapy. All patients underwent attempted resection, and gastrectomy was performed in 20 (83%). R0 resection rate was 95%. Pathologic complete response was observed in 2 patients (8%), and ≤ 1% viability was observed in an additional 4 (17%). Three patients had surgical complications (grade I in 1 patient [4%], grade IIIb in 1 [4%], and grade IVa in 1 [4%]); there were no deaths within 90 days. The median follow-up time was 20 months, and median OS was not reached. One- and 3-year OS rates from the date of diagnosis were 96% and 80%, respectively. Conclusions: Short-course CXRT (30 Gy in 10 fractions) may be safely used as part of a planned TNT approach. Rates of treatment completion, pathologic response, and survival were promising, supporting further research into TNT for gastric cancer. Clinical trial information: NCT04523818 .