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Background: 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., Methods: 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)., Results: 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., Conclusions: 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., (Published by Oxford University Press 2024.)

Purpose: High-grade appendiceal adenocarcinomas (HGAA) with peritoneal metastases (PMs) are associated with poor survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a novel treatment approach for unresectable HGAA-PM. However, its influence on immunogenomic profiles has not yet been fully explored., Materials and Methods: We obtained 79 samples of metastatic peritoneal tumor deposits from patients diagnosed with HGAA and performed whole-exome sequencing, RNA sequencing, and immunoprofiling before and after HIPEC. Tumor biopsies were subjected to immunogenomic profiling to detect mutational signatures and immune populations associated with oncologic outcomes., Results: Fifteen patients with HGAA-PMs were included in the study. The median progression-free survival (PFS) was 6.7 months (2.7-25.3) and the median overall survival was 11.4 months (4.7-42). Mucin-associated genes ( MUC16 , MUC3A , and MUC5AC ) and titin ( TTN ) had the highest mutation frequencies. Mutational signatures such as single-base substitution 29 and doublet-base substitution 11 were present in >50% of single-base and double-base mutations. Higher PD-L1 coexpression on CD8 + T cells demonstrated a higher PFS both intratumorally ( P = .019) and at the margin ( P = .025)., Conclusion: HIPEC-associated mutational signatures were identified in HGAA-PMs. Elevated PD-L1+ cytotoxic T-cell populations after HIPEC had better PFS, offering valuable insights for prognostication in the context of HIPEC treatment.

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

Despite our increased understanding of the biological and molecular aspects of gastro-oesophageal tumourigenesis, the identification of prognostic or predictive factors remains challenging. Patients with resectable gastric and oesophageal adenocarcinoma are often treated similarly after surgical resection, regardless of their tumour biology, clinical characteristics, and histological treatment response. Substantial progress has been made in the past 5 years in managing patients with gastric or oesophageal adenocarcinoma, including the use of immune checkpoint inhibitors and new targeted therapies, leading to substantial improvements in clinical outcomes. These advancements have primarily been established in advanced and metastatic disease, while the management framework for local and locoregional disease is just beginning to shift. We provide an overview of existing data on biomarkers and tumour-related and host-related factors that are relevant to stratify patients into low-risk and high-risk recurrence groups, both before and after surgery, paving the way for more personalised treatment approaches., Competing Interests: Declaration of interests TV reports consulting fees from Bristol-Myers Squibb; advisory boards for Bristol-Myers Squibb; and honoraria for presentations for Baxter and Bristol-Myers Squibb. TA reports attending advisory board meetings, and, or, receiving consulting fees from AbbVie, Astellas, Aptitude Health, Bristol-Myers Squibb, Gritstone Oncology, Gilead, GlaxoSmithKline, Merck & Co, Nordic Oncology, Seagen, Servier, and Takeda; reports honoraria for lectures, presentations, or speakers bureaus from Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co, Merck Serono, Pierre Fabre, Roche, Sanofi, Seagen, Servier, and Takeda; reports research grants from GlaxoSmithKline and Bristol-Myers Squibb; reports support for meetings from Merck & Co; reports a DMC member role for Inspirna. CDLF reports research grants from Servier, Pierre Fabre Oncology, MSD, and Agenus; reports advisory boards for Bristol-Myers Squibb, Amgen, Servier, Pierre Fabre Oncology, Eisai, MSD, Ipsen, Roche, Eli Lilly, Daichi-Sankyo, Astellas Pharma, and Takeda; and reports travel, accommodations, and expenses from Amgen, Pierre Fabre Oncology, MSD, Roche, and Servier. MS reports consulting fees from Amgen, Astellas, Owkin, MSD, and Servier and reports travel, accommodations, and expenses from Astellas and MSD. ECS reports grants and personal fees from Bristol-Myers Squibb and AstraZeneca; reports personal fees from Amgen, Daiichi Sankyo, Merck, Viracta, Astellas, Novartis, Pfizer, Zymeworks, T-Cypher Bio, and Beigene; reports personal fees and non-financial support from Mirati; is the chair of the European Organization for Research and Treatment GI Trials Group (2024–27); is a trustee for the UK and Ireland Oesophagogastric Cancer Group; and is supported by the National Institute for Health and Care Research Biomedical Research Centre at Oxford., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To investigate the association between household income and overall survival (OS) of patients with cervical adenocarcinoma., Methods: We conducted a retrospective cohort study involving participants selected from the Surveillance, Epidemiology, and End Results (SEER) database. Data were collected on various variables, including demographic variables such as median household income and clinicopathological characteristics for all participants. Cox regression analysis was utilized to examine the association between household income and OS. Subgroup analysis, sensitivity analysis, and E-value were used to further confirm the association., Results: A total of 2217 patients were included in the study. Compared with low-income (<$35,000-$54,999), middle-income (55,000-$69,999) or high-income (≥$70,000) was significantly associated with a higher 5-year OS (70.8 %, 58.7 % vs 50 %) in patients with cervical adenocarcinoma. The HR was 0.49, 95 % CI 0.41-0.58, p < 0.001 and 0.66 (0.55-0.78), p < 0.001 respectively, in the unadjusted model. After adjustment for potential confounders, the results were similar (adjusted HR 0.54 (0.45-0.65), p < 0.001) and 0.79 (0.66-0.94), p = 0.01), respectively. This significant association was also present in the various adjusted models. Subgroup and sensitivity analyses suggested that the relationship remained robust and reliable. The E-value analysis indicated robustness to unmeasured confounding. There was evidence of an interaction between age at diagnosis, race, primary site, tumor grade, T, N, M, or Scope Reg LN Sur, and household income on increasing the 5-year OS of cervical adenocarcinoma., Conclusions: Our study found that middle or high household income was significantly associated with a better 5-year OS compared with low household income in patients with cervical adenocarcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Total neoadjuvant therapy (TNT) in the management of locally advanced rectal cancer (LARC) did not show survival benefit over the standard long course chemoradiotherapy. Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features., Methodology: In this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma who were treated with chemoradiotherapy followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for patients in Manitoba between January 2007 and December 2019., Results: The cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year overall survival (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (P = .001) and in the N2 sub-cohort (P = 003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR., Conclusions: Achieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Immunochemotherapy with PD-1 blockade has been established as the current standard first-line therapy for patients with mGEA. Reviewing the history of clinical trials offers valuable insight into the evolution of immune oncology in mGEA, paving the way for future advancements in this field., Areas Covered: This review summarizes the findings of previous clinical trials related to immunotherapy for patients with GEA in the metastatic and locally advanced setting. We also introduce ongoing clinical trials to address the current challenging issues in clinical practice., Expert Opinion: In general, GEA exhibits intermediate immunogenic characteristics with heterogeneous expressions, and responders to anti-PD-(L)1 therapy are mostly enriched to patients with specific genomic profiles such as MSI-H, high PD-L1 expression, high TMB, and EBV-associated type. Co-administration with anti-angiogenic agents or simultaneous blockade of immune checkpoint molecules is being explored to offer benefit of immunotherapy for more patients. We hope that CLDN18.2 and upcoming targets like FGFR2b will complement the treatment niche of immunotherapy in the field of mGEA. Bispecific antibodies, antibody drug conjugates, CAR-T, and vaccine are anticipated to enhance efficacy and expand the scope of immunotherapy.

Background: Non‑intestinal adenocarcinoma of the nasal cavity and paranasal sinuses (non‑ITAC) is a heterogeneous tumour that has rarely been reported in previous studies. We compared and analysed the symptoms, radiographic and pathological features, treatment methods, and prognosis of patients with low-grade (G1) and high-grade (G3) tumours., Methods: This was a retrospective study included 22 patients with pathologically confirmed non-ITAC of the nasal cavity and paranasal sinuses who were treated between January 2008 and December 2021 at a single centre. Of these, 11 patients had G1 tumours, and 11 patients had G3 tumours. Clinicopathological features, treatment methods, and survival outcomes were analysed., Results: The median follow-up period was 48.5 months. Nasal congestion was the most common initial symptom, and the nasal cavity was the most frequently involved site. For G1 tumours, the main treatment was simple surgery, 1 and 3‑year overall survival (OS) rates were 100 and 88.9%, while the 1 and 3‑year local control (LC) rates were 100 and 100%, respectively. For G3 tumours, the main treatments were surgery combined with radiotherapy and/or chemotherapy,1 and 3‑year OS rates were 72.7 and 72.7%, while the 1 and 3‑year LC rates were 100 and 90.91%, respectively. G3 tumours was associated with significantly shorter overall survival than G1 tumours (P = 0.035). Patients with stage III-IV showed shorter overall survival compared to stage I-II patients (P = 0.035)., Conclusions: Non-ITAC of the nasal cavity and paranasal sinuses may frequently occur in the nasal cavity. The main treatment modality is surgery, supplemented by radiotherapy and chemotherapy. Pathological grade and tumour stage were poor prognostic factors for the disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW., Methods: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR)., Results: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns)., Conclusions: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81)., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The detection rates of early gastric cancer (GC) in China are approximately 20%; upon diagnosis, the majority of patients with GC are identified as having advanced stage disease, and in some cases, even metastatic advanced GC. Currently, the optimal treatment strategy for peritoneal metastasis (PM) in GC remains uncertain, and pathological complete response (pCR) is rare following conversion therapy., Case Presentation: This case report details the management of a 66-year-old patient diagnosed with advanced stage IVB (T4N2M1c) adenocarcinomas of the gastric cardia with PM who received multimodal therapy comprised of hyperthermic intraperitoneal chemotherapy (HIPEC), XELOX chemotherapy, and anti-programmed cell death-1 (PD-1) therapy followed by radical gastrectomy. Through the multimodal management, the patient attained PCR and experienced long-term survival., Conclusion: The conversion therapy protocol combined with HIPEC, XELOX chemotherapy, and anti-PD-1 therapy and our scientific, accurate, full-course management strategy may be propagable for potentially curing patients with advanced GC with PM., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: The purpose of this review is to analyze the diagnosis and treatments of the sinonasal malignant tumors throw systematic reviewed literature. The systematic review of the literature was performed according to PRISMA guidelines., Recent Findings: Total 11,653 cases of five article were analyzed. The cohort of 3824 cases received appropriate treatment. The most frequent histotype of the group of sinonasal malignancies was squamous cell carcinoma. Squamous cell carcinoma was represented by 54%. The other histopathological subtypes were esthesioneuroblastoma with 9,9%, melanoma 9,8%, adenocarcinoma 7,5%, sarcoma 7,3%, adeno cystic carcinoma 7,1%, sinonasal undifferentiated carcinoma 3,9%, sinonasal neuroendocrine carcinoma 2,8% respectively. All 772 cases of total 3824 were treated only surgically. All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT. The other 2990 cases of total 3824 were treated with multimodality treatment. The diagnosis and treatment of sinonasal cancers require a interdisciplinary approach and multimodality treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Carrilizumab, a PD-1 inhibitor, has shown therapeutic effectiveness in patients with late-stage or metastatic solid tumors exhibiting DNA mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). dMMR/MSI-H cancer patients are known to be responsive to PD-1 inhibitors. However, the use of carrilizumab for preoperative immunotherapy in early, unresectable MSI-H/dMMR primary colon cancer lesions is relatively underexplored. We present the case of a 46-year-old male who sought medical attention at our institution due to a history of hematochezia for two weeks, right-sided abdominal pain for one week, and loose stools. Imaging indicated duodenal involvement, and a biopsy confirmed ascending colon adenocarcinoma with MSI-H status. Given that the patient's family exhibited a history of more than three confirmed cases of colorectal cancer spanning two generations, Lynch syndrome was considered. After four cycles of PD-1 antagonist immunotherapy with carrilizumab, the patient's symptoms resolved, and physical examination revealed no abdominal tenderness or palpable masses. Following radical colectomy, the primary tumor exhibited a pathological complete response. This case highlights the potential of preoperative neoadjuvant immunotherapy to improve staging accuracy and increase surgical resection rates in T4b MSI-H colon cancer patients without distant metastasis, suggesting a need for reconsideration of the treatment approach., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: This study evaluated the perioperative outcomes for patients who had locally advanced esophageal adenocarcinoma (EAC) treated with neoadjuvant immunotherapy (IO) and chemotherapy versus a matched cohort of patients who received neoadjuvant chemotherapy (NAC) alone., Methods: A single-center non-randomized phase 2 trial was undertaken with locally advanced (cT3-4 and/or N+) EAC, and 49 patients completed neoadjuvant avelumab + docetaxel, cisplatin, 5FU (DCF) and esophagectomy between February 2018 and February 2020. These patients were matched with contemporary patients (January 2018 to June 2020) who met the inclusion criteria but received neoadjuvant chemotherapy alone (NAC) with a comparable docetaxel-based therapy. The postoperative outcomes then were compared between the two groups., Results: For this study, 99 patients with locally advanced EAC underwent esophagectomy and met the enrolment criteria. Of these patients, 50 received NAC alone and 49 received IO + NAC. Baseline characteristics such as age, gender, and clinical stage were comparable between the two groups. Operative approach and rate of minimally invasive esophagectomy (~ 60%) were similar in the two groups. For the NAC-alone and IO + NAC groups, the respective overall and major complication rates were similar between the two groups (50% vs. 51% [p = 0.91] and 20% vs. 26% [p = 0.44], respectively), with concordant rates for anastomotic leak (6 [12%] vs. 6 [12%]; p = 0.86) and respiratory complications (13 [26%] vs. 11 [22%]; p = 0.68). The two groups did not differ significantly in terms of hospital length of stay or 30- and 90-day mortality rates., Conclusion: The addition of immunotherapy to neoadjuvant chemotherapy for locally advanced esophageal adenocarcinoma does not appear to alter perioperative short-term outcomes significantly after esophagectomy., (© 2024. Society of Surgical Oncology.)

Background: A large proportion of patients with foregut cancers do not receive guideline-concordant treatment (GCT). This study sought to understand underlying barriers to GCT through a root cause analysis approach., Methods: A single-institution retrospective review of 498 patients with foregut (gastric, pancreatic, and hepatobiliary) adenocarcinoma from 2018 to 2022 was performed. Guideline-concordant treatment was defined based on National Comprehensive Cancer Network guidelines. The Ishikawa cause and effect model was used to establish main contributing factors to non-GCT., Results: Overall, 34% did not receive GCT. Root causes of non-GCT included Patient, Physician, Institutional Environment and Broader System-related factors. In decreasing order of frequency, the following contributed to non-GCT: receipt of incomplete therapy (N = 28, 16.5%), deconditioning on chemotherapy (N = 26, 15.3%), delays in care because of patient resource constraints followed by loss to follow-up (N = 19, 11.2%), physician factors (N = 19, 11.2%), no documentation of treatment plan after referral to oncologic expertise (N = 19, 11.2%), loss to follow-up before oncology referral (N = 17, 10%), nonreferral to medical oncologic expertise (N = 16, 9.4%), nonreferral to surgical oncology in patients with resectable disease (N = 15, 8.8%), and complications preventing completion of treatment (N = 11, 6.5%). Non-GCT often was a function of multiple intersecting patient, physician, and institutional factors., Conclusions: A substantial percentage of patients with foregut cancer do not receive GCT. Solutions that may improve receipt of GCT include development of automated systems to improve patient follow-up; institutional prioritization of resources to enhance staffing; financial counseling and assistance programs; and development and integration of structured prehabilitation programs into cancer treatment pathways., (© 2024. The Author(s).)

Background: There has been an increase in the elderly patient population seeking care for pancreatic ductal adenocarcinoma (PDAC). This study aimed to delineate the effectiveness of therapeutic options in nonagenarians (aged 90-99 years) diagnosed with resectable PDAC., Methods: This study used the National Cancer Database to identify patients with nonmetastatic PDAC (stage I-III) from 2004 to 2021. The study compared median overall survival (mOS) using Kaplan-Meier curves among 5 treatment categories: surgery, surgery along with chemoradiation, chemotherapy alone, radiotherapy alone, and chemoradiation alone. Cox proportional hazards regression was used in multivariate analyses., Results: Of 459,174 patients, 793 aged ≥ 90 years had nonmetastatic PDAC. Of 793 patients, 245 (30.9 %) underwent chemotherapy alone, 296 (37.3 %) underwent radiotherapy alone, 162 (20.4 %) underwent chemoradiation alone, 58 (7.3 %) underwent curative-intent resection, and 32 (4.0 %) underwent surgery combined with chemoradiation. The mOS estimates in different treatment modalities were 9.5 months (95 % CI, 6.7-14.5) for surgery alone, 19.1 months (95 % CI, 2.4-64.3) for surgery combined with chemoradiation, 8.2 months (95 % CI, 7.2-9.2) for chemotherapy alone, 8.4 months (95 % CI, 7.6-9.6) for radiotherapy alone, and 11.2 months (95 % CI, 8.7-12.9) for chemoradiation alone (P < .001). In multivariate analysis, the odds of survival were better for patients who underwent surgery alone than for those who underwent chemotherapy alone, although the odds of survival did not significantly differ between patients who underwent radiotherapy alone and those who underwent chemoradiation alone. Nonetheless, surgery combined with chemoradiation was associated with decreased mortality risk compared with surgery alone (hazard ratio, 0.46; 95 % CI, 0.25-0.87; P = .02). Operative 30-day mortality rate was 8.8 %, and 90-day mortality rate was 17.8 %., Conclusion: Surgery combined with chemoradiation improved the survival of nonagenarians with PDAC compared with other therapies. However, only 1 in 25 patients received all 3 treatment components. Moreover, our study highlights a very high operative mortality rate in nonagenarians., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Comprehensive information on genetic alterations in salivary gland cancer (SGC) is limited. This study aimed to elucidate the genetic and clinical characteristics of patients with SGC using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, a Japanese national genomic database. We analyzed data of 776 patients with SGC registered in the C-CAT database between June 1, 2019, and June 30, 2023. Adenoid cystic carcinoma was the most common histologic type, followed by salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified. Genetic data of 681 patients receiving FoundationOne® CDx were analyzed. We identified specific features of the combination of TP53 and CDKN2A alterations among the histological types. Specific LYN amplification was mainly detected in carcinoma ex pleomorphic adenoma and myoepithelial carcinoma. For SDC, the frequency of ERBB2 and BRAF alterations were higher in cases with metastatic lesions than in those with primary lesions. Although 28.6% patients were offered recommended treatment options, only 6.8% received the recommended treatments. This study highlights the differences in genetic alterations among the histological types of SGC, with comprehensive genomic profiling tests revealing lower drug accessibility. These findings could contribute to the development of personalized treatment for patients with SGC., (© 2024 UICC.)

Peritoneal involvement represents one of the major difficulties that arise during the treatment of pancreatic adenocarcinoma. In fact, currently, there is a growing interest in the administration of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) as an adjunct to surgical pancreatic resection, both with prophylactic or therapeutic intent. With this video, we report a case of pancreatic body adenocarcinoma treated with fully laparoscopic distal splenic pancreatectomy with intraoperative HIPEC with gemcitabine, administered initially with a prophylactic intent, based on a preliminary negative peritoneal washing cytology result. In our case, the association of HIPEC and surgical resection did not affect the postoperative recovery, and after 15 months of follow-up, the patient remains alive and has no signs of disease recurrence., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Extracellular vesicles play an important role in the progression of pancreatic adenocarcinoma (PAAD) through the transfer of proteins, mRNAs, and long noncoding RNAs (lncRNAs). However, the intricate interplay between extracellular vesicles-related lncRNAs and the tumor microenvironment (TME) remains poorly elucidated. Consequently, our investigation aimed to delineate the association between extracellular vesicles-related lncRNAs and the PAAD microenvironment. Initially, we identified differentially expressed lncRNAs (DELs) from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project datasets. Subsequently, we validated the expression of these DELs within extracellular vesicles and assessed their prognostic implications in PAAD using the GSE133684 and TCGA datasets. Multiomics data were analyzed comprehensively, including genomic landscape, functional annotation, immune profiles, and therapeutic responses. Differential expression of selected lncRNAs in both cellular and exosomal fractions of PAAD was further confirmed through quantitative polymerase chain reaction (qPCR). Eight DELs were identified from TCGA and GTEx datasets, and two exosomal lncRNAs exhibited a significant correlation with overall survival, warranting further investigation. Specifically, elevated expression of LINC00996 correlated positively with immune infiltration and enhanced response to immunotherapy. Conversely, heightened expression of TRHED-AS1 was associated with compromised immune cell infiltration and diminished responsiveness to immunotherapy. Our study establishes a compelling link between two extracellular vesicles-related gene signatures, prognosis, and immune infiltration in PAAD. Notably, these signatures serve as robust prognostic indicators for PAAD patients, offering valuable insights for the strategic selection of immunotherapeutic interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflicts of interest., (Copyright © 2024 Kai Nan et al.)

Pancreatic adenocarcinoma represents one of the most challenging malignancies to treat, with dismal survival rates despite advances in therapeutic modalities. Immunotherapy, particularly vaccines, has emerged as a promising strategy to harness the body's immune system in combating this aggressive cancer. This abstract reviews the trials and tribulations encountered in the development of vaccines targeting pancreatic adenocarcinoma. Key challenges include the immunosuppressive tumor microenvironment, the heterogeneity of tumor antigens, and a limited understanding of immune evasion mechanisms employed by pancreatic cancer cells. Various vaccine platforms, including peptide-based, dendritic cell-based, and viral vector-based vaccines, have been explored in preclinical and clinical settings. However, translating promising results from preclinical models to clinical efficacy has proven elusive. In recent years, mRNA vaccines have emerged as a promising immunotherapeutic strategy in the fight against various cancers, including pancreatic adenocarcinoma. We will discuss the potential applications, opportunities, and challenges associated with mRNA vaccines in pancreatic cancer treatment.

Background: Neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC). Mucinous adenocarcinoma (MAC) is a potential poor prognosis subgroup of rectal cancer. However, the predictive value of MAC in NCRT treatment of LARC is controversial., Methods: A comprehensive literature search of PubMed, Embase, and the Cochrane Library was performed. All studies examining the effect of MAC on CRT response in LARC were included. Outcomes of MAC were compared with non-specific adenocarcinoma (AC) by using random-effects methods. Data were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The main outcomes were the rates of pathological complete response (pCR), tumor and nodal down-staging, positive resection margin rate, local recurrence, and overall mortality., Results: Fifteen studies containing comparative data on outcomes in a total of 9,238 patients receiving NCRT for LARC were eligible for inclusion. MAC had a reduced rate of pCR (OR, 0.38; 95% CI, 0.18-0.78) and tumor down-staging (OR, 0.31; 95% CI, 0.22-0.44) following NCRT compared with AC. MAC did not significantly affect nodal down-staging (OR, 0.42; 95% CI, 0.16-1.12) after NCRT., Conclusion: MAC of LARC was found to be a negative predictor of response to NCRT with lower rates of pCR and tumor down-staging for LARC. The nodal down-staging of MAC was relatively lower than that of AC, although the differences were not statistically significant., (© 2024. The Author(s).)

Introduction: Sepsis often leads to acute kidney injury (AKI), presenting significant challenges in fluid management. This study explores the potential of analyzing intrarenal venous flow (IRVF) patterns to guide tailored fluid therapy, aiming to improve patient outcomes., Patient Concerns: A patient was admitted to the intensive care unit with symptoms of septic shock, including fever, severe hypotension, and altered mental status, secondary to a perforated ascending colon adenocarcinoma., Diagnosis: The patient was diagnosed with perforated ascending colon adenocarcinoma, septic shock, and AKI. Clinical findings included elevated inflammatory markers and impaired renal function., Interventions: The primary therapeutic interventions included surgical resection of the perforated colon, administration of broad-spectrum antibiotics, and fluid resuscitation. Fluid management was guided by continuous monitoring of IRVF, which facilitated precise adjustments to optimize fluid balance and renal perfusion., Outcomes: By utilizing IRVF patterns to guide fluid therapy, the patient's circulatory status and renal function significantly improved. The individualized fluid management approach contributed to better stabilization of the patient's condition., Lessons: This case underscores the potential utility of IRVF patterns in guiding fluid management strategies for patients with sepsis and AKI. The main is the benefit of IRVF-guided fluid therapy in improving patient outcomes. Further research is warranted to validate the efficacy and safety of this approach, with the aim of enhancing clinical outcomes in critically ill patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: High-grade non-intestinal-type sinonasal adenocarcinoma (non-ITAC) is a rare and aggressive form of adenocarcinoma with poor prognosis. The current standard treatment approach involves surgery combined with radiation therapy. However, there is a need for exploring additional treatment modalities to improve patient outcomes., Case Presentation: We present a case of a 65-year-old male patient who presented with pain in the right maxillary sinus and was diagnosed with high-grade non-ITAC following surgery. Postoperative pathology revealed tumor invasion into bone tissue and vascular invasion, necessitating further treatment. The patient underwent radiation therapy, followed by immunotherapy with carilizumab combined with chemotherapy. During the maintenance immunotherapy period, tumor progression was observed, and genetic testing identified EGFR and TP53 mutations. Consequently, the patient was treated with gefitinib, a targeted therapy drug. Notably, the patient's lung metastases showed a gradual reduction in size, indicating a favorable treatment response. The patient is currently undergoing oral treatment with gefitinib., Conclusions: This case report highlights the potential benefit of combining immunotherapy and targeted therapy in the treatment of high-grade non-ITAC. Despite the rarity of this cancer type, this approach may offer an alternative treatment strategy for patients with this aggressive disease. We hope that this case can contribute to a deeper understanding of high-grade non-ITAC and promote the application of immunotherapy and targeted therapy in improving survival rates for patients with this condition., (© 2024. The Author(s).)

Letter to the Editor Regarding 'Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia', published in Neoplasma 2024; 71: 201-208. https://doi.org/10.4149/neo&#95;2024&#95;231209N633.

Objective: To determine the demographic and clinical characteristics of individuals diagnosed with colorectal cancer., Methods: A retrospective study was conducted on 650 patients diagnosed with colorectal cancer in West Kazakhstan from 2019 to 2023. Statistical analysis was performed to explore the relationships between various factors and outcomes, using significance tests and regression techniques., Results: The study included 650 colorectal cancer patients, with 59.7% males and 40.3% females. Age distribution showed 63.1% between 24-65 years and 36.9% over 65, with no gender-based age differences. Nationality significantly influenced patient composition (63.8% Kazakh, 36.2% Russian, P=0.03). KRAS mutations (76.0% negative) and tumor morphology (40% adenocarcinoma, P=0.02) displayed varied associations. Univariate logistic regression revealed links between demographic/clinical factors and cancer outcomes. Multivariate analysis emphasized age, stage of cancer, expansion, involvement of lymphatic and metastasis in cancer progression. Nomogram predictive modeling incorporated gender, tumor form, stage, and infiltration. Evaluation in a validation cohort showed good differentiation (AUC=0.6293) and calibration. The findings provide insights into colorectal cancer demographics, progression, treatment, and mortality, aiding personalized interventions., Conclusion: this study reveals critical insights into demographics, treatment, and prognosis. Emphasizing the complexity of CRC, the study highlights age, gender, and tumor characteristics' impact on progression and mortality. A developed nomogram model offers clinicians a practical tool for personalized treatment decisions, enhancing prognosis discussions with patients.

Purpose: To evaluate the diagnostic performance of Golden-Angle Radial Sparse Parallel (GRASP) MRI in identifying pathological stage T0-1 (ypT0-1) after neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer, compared to T2-weighted imaging (T2WI) combined with Diffusion Weighted Imaging (DWI)., Methods: In this retrospective study, 168 patients were carefully selected based on inclusion criteria that targeted individuals with biopsy-confirmed primary rectal adenocarcinoma, identified via MRI as having locally advanced disease (≥ T3 and/or positive lymph node results) prior to nCRT. Post-nCRT, all MRI images obtained after nCRT were assessed by two observers independently. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying ypT0-1 based on GRASP and T2 + DWI were calculated. Multivariable regression analysis was used to explore the factors independently associated with ypT0-1 tumor., Results: 45 patients out of these cases were ypT0-1, and the accuracy, sensitivity, specificity, PPV, and NPV of GRASP were higher than the T2 + DWI (88% vs 74%, 93% vs 71%, 86% vs 75%, 71% vs 52% and 97% vs 88%), the AUC in identifying ypT0-1 tumor based on GRASP was 0.90 (95% CI:0.84, 0.94), which was better than the T2 + DWI (0.73; 95% CI: 0.66, 0.80). Multivariable logistic regression analysis showed that the yT stage on GRASP scans was the only factor independently associated with ypT0-1 tumor (P < 0.001)., Conclusion: The GRASP helped distinguish ypT0-1 tumor after nCRT and can select patients who may be suitable for local excision., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background Neoadjuvant chemotherapy (NCT) is gaining acceptance for the management of locally advanced rectal cancer (LARC) in patients without negative prognostic factors. However, the value of MRI in evaluating tumor response after NCT remains unclear. Purpose To investigate the accuracy of MRI in assessing pathologic complete response in participants with LARC who underwent surgery after NCT without radiation. Materials and Methods A retrospective imaging substudy was conducted within two consecutive prospective clinical trials: the expanded phase II trial (from December 2017 to May 2021) and the COPEC trial (comparison of tumor response to two or four cycles of neoadjuvant chemotherapy alone, ongoing from August 2021). All included participants received four cycles of capecitabine combined with oxaliplatin (or CAPOX) before surgery. Three radiologists who were blinded to the clinicopathologic data independently evaluated the tumor response using five methods, namely, MR tumor regression grade (MR-TRG) alone, diffusion-weighted imaging (DWI) alone, DWI-modified MR-TRG (DWImodMR-TRG), MRI complete response, and radiologic neoadjuvant response score. With pathologic assessment serving as the reference standard, the positive and negative predictive values, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined to evaluate the accuracy and performance of these models. The AUCs of the models were compared using the DeLong test. Results A total of 224 participants were included, comprising 119 from the expanded phase II trial (median age, 61 years [IQR, 53-67]; 89 male) and 105 from the COPEC trial (median age, 59 years [IQR, 53-67]; 65 male). MR-TRG, DWI, DWImodMR-TRG, MRI complete response, and the radiologic neoadjuvant response score were associated with pathologic complete response. DWImodMR-TRG achieved the highest AUC of 0.90 (95% CI: 0.85, 0.95), with a specificity of 89% (162 of 182) and a negative predictive value of 93% (162 of 174). Conclusion MRI-based models were accurate for determining pathologic complete response in participants with LARC following NCT. DWI improved the predictive performance of MRI-based assessment. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Santiago and Shur in this issue.

Background: There is a paucity of evidence supporting the use of adjuvant radiation therapy in resected biliary cancer. Supporting evidence for use comes mainly from the small SWOG S0809 trial, which demonstrated an overall median survival of 35 months. We aimed to use a large national database to evaluate the use of adjuvant chemoradiation in resected extrahepatic bile duct and gallbladder cancer., Methods: Using the National Cancer Database, we selected patients from 2004 to 2017 with pT2-4, pN0-1, M0 extrahepatic bile duct or gallbladder adenocarcinoma with either R0 or R1 resection margins, and examined factors associated with overall survival (OS). We examined OS in a cohort of patients mimicking the SWOG S0809 protocol as a large validation cohort. Lastly, we compared patients who received chemotherapy only with patients who received adjuvant chemotherapy and radiation using entropy balancing propensity score matching., Results: Overall, 4997 patients with gallbladder or extrahepatic bile duct adenocarcinoma with available survival information meeting the SWOG S0809 criteria were selected, 469 of whom received both adjuvant chemotherapy and radiotherapy. Median OS in patients undergoing chemoradiation was 36.9 months, and was not different between primary sites (p = 0.841). In a propensity score matched cohort, receipt of adjuvant chemoradiation had a survival benefit compared with adjuvant chemotherapy only (hazard ratio 0.86, 95% confidence interval 0.77-0.95; p = 0.004)., Conclusion: Using a large national database, we support the findings of SWOG S0809 with a similar median OS in patients receiving chemoradiation. These data further support the consideration of adjuvant multimodal therapy in resected biliary cancers., (© 2024. The Author(s).)

Objectives: To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo., Methods: Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether-filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI-based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings., Results: The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images., Conclusion: Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background and Objectives: Given increased utilization of neoadjuvant therapy (NAT) for gastric adenocarcinoma, practice patterns deviating from standard of care (upfront resection) remain unknown. We sought to identify factors associated with NAT use and survival outcomes among early-stage gastric cancers., Methods: The National Cancer Database identified patients with early-stage (T1N0M0) gastric cancer (2010-2020). Multivariable logistic regression assessed characteristics associated with NAT utilization compared to upfront surgery. After 1:1 propensity score matching, Kaplan-Meier methods and Cox regression assessed overall survival (OS)., Results: Of 6452 patients with early-stage gastric cancer, 626 (9.7%) received NAT. Patients who received NAT were more likely treated at community hospitals, had moderate to poorly differentiated disease, and tumors located in the cardia (all p < 0.05). After propensity score matching, 1,248 patients remained. Median OS for NAT was 37.1 months (IQR 20.2-64.0) versus 45.6 months (IQR 22.5-72.8) for resection (p < 0.001). Treatment with NAT remained independently predictive of worse OS on Cox regression (hazard ratio 1.19; 95% confidence interval 1.05-1.34)., Conclusions: Although patients who received NAT had more aggressive prognostic features, NAT was associated with worse OS despite accounting for this selection bias. These results highlight the importance of adhering to guidelines, regardless of differing disease characteristics, which has significant implications on outcomes., (© 2024 Wiley Periodicals LLC.)

Background & Aims: Accumulating data has shown the rising incidence and poor prognosis of early-onset gastrointestinal cancers, but few data exist on biliary tract cancers (BTC). We aimed to analyse the clinico-pathological, molecular, therapeutic characteristics and prognosis of patients with early onset BTC (EOBTC, age ≤50 years at diagnosis), versus olders., Methods: We analysed patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma between 1 January 2003 and 30 June 2021. Baseline characteristics and treatment were described in each group and compared. Progression-free survival, overall survival and disease-free survival were estimated in each group using the Kaplan-Meier method., Results: Overall, 1256 patients were included, 188 (15%) with EOBTC. Patients with EOBTC demonstrated fewer comorbidities (63.5% vs. 84.5%, p < .0001), higher tumour stage (cT3-4: 50.0% vs. 32.3%, p = .0162), bilobar liver involvement (47.8% vs. 32.1%, p = .0002), and metastatic disease (67.6% vs. 57.5%, p = .0097) compared to older. Patients with EOBTC received second-line therapy more frequently (89.5% vs. 81.0% non-EOBTC, p = .0224). For unresectable patients with BTC, median overall survival was 17.0 vs. 16.2 months (p = .0876), and median progression-free survival was 5.8 vs. 6.0 months (p = .8293), in EOBTC vs. older. In advanced stages, fewer actionable alterations were found in EOBTC (e.g., IDH1 mutations [7.8% vs. 16.6%]; FGFR2-fusion [11.7% vs. 8.9%]; p = .029)., Conclusions: Patients with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage but show similar survival. A distinctive molecular profile enriched for FGRF2 fusions was found., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting., Methods: This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup., Results: Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors., Conclusion: After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors., (© 2024. Society of Surgical Oncology.)

Purpose: To describe the global landscape of clinical research into interventions for gastroesophageal cancers (GECs), with examination of trial characteristics, geographic distribution of trial sites, and factors associated with trial termination., Methods: We queried ClinicalTrials.gov to identify all completed or terminated phase III interventional studies investigating GECs (esophageal squamous cell carcinoma [ESCC], esophageal adenocarcinoma [EAC], gastroesophageal junctional [GEJ], and gastric adenocarcinoma). Data on all reported trial characteristics were extracted. Pearson's chi-square and Fisher's exact tests were used to compare differences in completed and terminated trials. Multivariate logistic regression evaluated predictors of termination., Results: A total of 179 trials were identified; of these, 90% were therapeutic. Most included sites in Asia (61%) and Europe (32%); few included sites in Africa (4%). Thirty percent included sites in low- and middle-income countries (LMICs). Most (70%) focused on gastric or GEJ adenocarcinoma, 13% on EAC and ESCC, and 9% on ESCC alone. Sixteen percent (n = 29) of trials terminated prematurely. In multivariate analysis, study site number, location of recruitment sites, and patient population emerged as predictors of termination. Trials recruiting from US-based sites were more likely to terminate (odds ratio [OR], 7.22 [95% CI, 1.59 to 32.69]). Trials conducted exclusively in LMICs were less likely to terminate (OR, 0.04 [95% CI, 0.01 to 0.59] v conducted in high-income countries [HICs] alone). Studies on ESCC were more likely to terminate (OR, 17.74 [95% CI, 1.49 to 210.69])., Conclusion: Although 80% of GECs occur in LMICs, trial activity disproportionately occurs in HICs. Few trials focus on EAC/ESCC despite being highly fatal, highlighting an unmet need. Overall, this study highlights (1) a missed opportunity to recruit patients from high-incidence regions globally; and (2) a pressing need for increasing funding, infrastructure, and support for GEC trials in LMICs.

Background: Neoadjuvant therapy regimens have significantly improved the prognosis of GEJ (gastroesophageal junction) cancer; however, there are a significant percentage of patients who benefit from earlier resection or adapted therapy regimens, and the true response rate can only be determined histopathologically. Methods that allow preoperative assessment of response are lacking., Purpose: The purpose of this retrospective study is to assess the potential of pretherapeutic and posttherapeutic spectral CT iodine density (IoD) in predicting histopathological response to neoadjuvant chemotherapy in patients diagnosed with adenocarcinoma of the GEJ., Methods: In this retrospective cohort study, a total of 62 patients with GEJ carcinoma were studied. Patients received a multiphasic CT scan at diagnosis and preoperatively. Iodine-density maps were generated based on spectral CT data. All tumors were histopathologically analyzed, and the tumor regression grade (TRG) according to Becker et al ( Cancer . 2003;98:1521-1530) was determined. Two experienced radiologists blindly placed 5 defined ROIs in the tumor region of highest density, and the maximum value was used for further analysis. Iodine density was normalized to the aortic iodine uptake. In addition, tumor response was assessed according to standard RECIST measurement. After assessing interrater reliability, the correlation of IoD values with treatment response and with histopathologic TRG was evaluated., Results: The normalized ΔIoD (IoD at diagnosis - IoD after neoadjuvant treatment) and the normalized IoD after neoadjuvant treatment correlated significantly with the TRG. For the detection of responders and nonresponders, the receiver operating characteristic (ROC) curve for normalized ΔIoD yielded the highest area under the curve of 0.95 and achieved a sensitivity and specificity of 92.3% and 92.1%, respectively. Iodine density after neoadjuvant treatment achieved an area under the curve of 0.88 and a sensitivity and specificity of 86.8% and 84.6%, respectively (cutoff, 0.266). Iodine density at diagnosis and RECIST did not provide information to distinguish responders from nonresponders. Using the cutoff value for IoD after neoadjuvant treatment, a reliable classification of responders and nonresponders was achieved for both readers in a test set of 11 patients. Intraclass correlation coefficient revealed excellent interrater reliability (intraclass correlation coefficient, >0.9). Lastly, using the cutoff value for normalized ΔIoD as a definition for treatment response, a significantly longer survival of responders was shown., Conclusions: Changes in IoD after neoadjuvant treatment of GEJ cancer may be a potential surrogate for therapy response., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer; however, their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes., Methods: This prospective, multicenter, observational study investigated the outcomes of patients with clinical stage II-III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of 2 years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at 3 years., Results: Of the 178 patients enrolled in 16 centers, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6-45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall survival, disease-free survival, local recurrence-free survival, and distant recurrence-free survival was 80.6% (95% CI 73.9-85.8), 97.6% (95% CI 93.6-99.1), 90.0% (95% CI 84.3-93.7), 94.7% (95% CI 90.1-97.2), and 94.6% (95% CI 89.9-97.2), respectively. The 3-year stoma-free survival was 95.0% (95% CI 89.5-97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95% CI 59.9-81.2)., Conclusions: In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromising the outcomes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The standard treatment of T2-T3 rectal adenocarcinoma is radical proctectomy by total mesorectal excision often combined with some neoadjuvant treatment. To reduce morbidity of this surgery, organ preservation strategy using various combination of radiotherapy, chemotherapy and local excision is gaining interest. Some randomized trials have proven the feasibility of such approaches. The OPERA trial demonstrated, for T2 T3<5cm diameter low-middle rectum, that a contact X-ray brachytherapy boost of 90Gy in three fractions over 4 weeks was able to achieve a planned organ preservation in 81% of patients at 3years with 97% success for tumour smaller than 3cm treated with contact X-ray brachytherapy boost first. To try to expand organ preservation to larger tumours we set up a feasibility trial in T2-T3 tumours using total neoadjuvant treatment and a contact X-ray brachytherapy boost., Material and Method: The trial was approved by the institutional review board of Nice. Inclusion criteria were operable patients, 75years or less, adenocarcinoma of the low-middle rectum staged T2c-T3N0 larger than 3.5cm and less than 6cm in diameter or T2-T3N1 less than 6cm in diameter. Treatment started in all cases with neoadjuvant chemotherapy associating 5-fluoro-uracile, irinotecan and oxaliplatin ('folfirinox' regimen, four to six cycles). In case of good tumour response after four cycles, a contact X-ray brachytherapy boost (delivering 90Gy in three fractions) was given followed by chemoradiotherapy (external beam radiotherapy delivering 50Gy, with concurrent capecitabine). After six cycles if only a partial response (tumour still larger than 3cm) was seen, chemoradiotherapy was given and contact X-ray brachytherapy boost was delivered after that. At the end of this total neoadjuvant treatment a watch and wait strategy was decided in case of clinical complete response or radical proctectomy by total mesorectal excision for partial response., Results: Between July 2019 and October 2022, 14 patients were included; median age was 66years (range: 51-77years), there were nine male and five female, two T2 N1 tumours, seven T3N0, and five T3N1, all were M0. Median tumour diameter was 40mm (range: 11-50mm); three tumours had a circumferential extension greater than 50%. Seven patients received four folfirinox cycles and seven had six cycles. Contact X-ray brachytherapy boost was given during folfirinox chemotherapy before chemoradiotherapy in 11 patients (and after in three). The tolerance was good, with no grade 4-5 toxicity. The main grade 3 early toxicity was in relation with the folfirinox regimen. A clinical complete response was seen in 12 patients at the end of the total neoadjuvant treatment (85%). All these patients are alive and have preserved their rectum with a mean follow-up time of 17.8months (range: 6-48months) and a good bowel function (low anterior rectal resection syndrome score below 30). The main contact X-ray brachytherapy boost toxicity was radiation ulceration in three patients that usually healed within 6 months, sometimes necessitating hyperbaric oxygen., Conclusion: The preliminary results of this feasibility study show that early tolerance of these intensive total neoadjuvant treatment is compatible with an acceptable toxicity. The high rate of organ preservation in this intermediate group of T2-T3 tumours is encouraging and is a good argument to start the next randomized TRESOR trial that will aim at achieving a 65% of 3-year survival with organ preservation in this intermediate tumour group., (Copyright © 2024 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Preoperative neoadjuvant therapy followed by resection is the mainstay treatment for locally advanced esophageal adenocarcinoma. We recently observed the histology shift from predominant esophageal adenocarcinoma in the biopsy to neuroendocrine neoplasm with or without adenocarcinoma in the post-treatment resection. The underlying mechanism of this finding is uncertain, and there is limited information in the literature. A total of 11 patients were identified: 10 patients received presurgical chemoradiation and 1 with chemotherapy. All biopsies were diagnosed with adenocarcinoma. When neuroendocrine immunomarkers were retrospectively performed on 5 biopsies, 2 showed focal positivity, although the classic neuroendocrine morphology was not readily appreciated. All resections contained neuroendocrine neoplasm, including 8 of well-differentiated type and 3 of neuroendocrine carcinomas. Two post-treatment esophagectomies consisted of neuroendocrine neoplasm only without residual adenocarcinoma. Upon follow-up, 8 patients died of the disease (median survival = 26 months), and 3 patients were alive after a median follow-up of 14 months. The overall median survival time was better than the reported esophageal neuroendocrine carcinoma (15 months). The 5-year observed survival rate was 11.3%, which was lower than the Surveillance, Epidemiology, and End Results 5-year survival rate of adenocarcinoma (21.8%). We reported a small series of esophageal adenocarcinoma that showed histology shift between biopsy and esophagectomy after neoadjuvant therapy. Our limited data suggest that prognosis of this group is different than the conventional adenocarcinoma. Awareness of this morphological change reminds pathologists to examine the biopsy specimens thoroughly, because recognition of neuroendocrine neoplasm, especially high-grade neuroendocrine component, might potentially affect pre- and post-surgical regimens., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone., Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes., Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023., Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach., Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality., Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00])., Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

Background: Neoadjuvant chemotherapy (NAC) use for pancreatic ductal adenocarcinoma (PDAC) has increased, but some patients never get resection following NAC., Methods: Data from January 2012 to December 2019 for all clinically resectable patients across two health networks were utilized, as well as data from the ACS NCDB registry. Univariate testing, multivariable logistic regression, and survival analyses were employed to evaluate failure to resection after neo-adjuvant chemotherapy., Results: Of the 10 007 registry patients eligible for resection, the resected group was younger (64.6 vs. 69.5 years; p < 0.001) and had a slightly lower mean comorbidity index (0.41 vs. 0.45; p < 0.001) than the nonsurgical group. The nonsurgical group was composed of a higher percentage of Black and Hispanic patients (17.5 vs. 13.1%; p < 0.001). After adjusting for age and comorbidities, the factors associated with decreased probability of resection after NAC were evaluation at a community hospital (OR 2.4), Black or Hispanic race (OR 1.6), areas of increased high school drop-out rates (OR 1.4), and lack of private health insurance (OR 1.3). The median overall survival for nonsurgery was markedly worse than the surgical cohort (10.6 vs. 26.6 months; p < 0.001). The most frequent reasons for a lack of definitive resection were operative upstaging to unresectable (39.6%), patient preference (14.5%), progression on NAC (13.2%), deconditioning or comorbidity severity (12.5%), and nonreferral to a surgeon (8.8%)., Conclusions: Racial, economic, and educational disparities have a considerable influence on the successful completion of a neoadjuvant approach for resectable PDAC. A comprehensive closed or highly collaborative/communicative multidisciplinary neoadjuvant program is optimal for treatment success and completion., (© 2024 Wiley Periodicals LLC.)

Background and Aims: Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry., Methods: This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (Steris, Mentor, Ohio, USA) (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma. Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated., Results: Among 138 subjects with low-grade dysplasia (24%), high-grade dysplasia (49%), and intramucosal adenocarcinoma (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after 2 years and 67% and 92% after 3 years. In RFA-naïve patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (per centimeter: adjusted hazard ratio, 0.90; 95% confidence interval, 0.83-0.96) and prior treatment with RFA (adjusted hazard ratio, 0.39; 95% confidence interval, 0.22-0.69) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n = 6) at a mean follow-up of 2.5 years after CEIM., Conclusion: In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for the treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort, approximately 50% attained CEIM at 3 years., Competing Interests: Disclosure The following authors disclosed financial relationships: V. Kaul: Ad hoc consultant for Steris. B. Greenwald: consultant for Steris Endoscopy. N. J. Shaheen: grant support from Steris, Lucid, Pentax, Interpace, and CDx Medical. Consultant for Exact Sciences. All other authors disclosed no financial relationships. This study was supported by grants from CSA Medical, Steris, and National Institutes of Health award number K23DK121338 (to S. Eluri)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: According to current international guidelines, stage cT2N0M0 gastric adenocarcinoma warrants preoperative chemotherapy followed by surgery. However, upfront surgery is often preferred in clinical practice, depending on patient clinical status and local treatment preferences., Objective: The aim of the present study was to assess the impact of neoadjuvant chemotherapy in overall survival (OS) and disease-free survival (DFS) of cT2N0M0 patients., Methods: A retrospective analysis was performed among 32 centers, including gastric adenocarcinoma patients operated between January 2007 and December 2017. Patients with cT2N0M0 stage were divided into upfront surgery (S) and neoadjuvant chemotherapy followed by surgery (CS) groups. Inverse probability of treatment weighting (IPTW) was used to compensate for baseline differences between the groups., Results: Among the 202 patients diagnosed with cT2N0M0 stage, 68 (33.7%) were in the CS group and 134 (66.3%) were in the S group. CS patients were younger (mean age 62.7 ± 12.8 vs. 69.8 ± 12.1 years for S patients; p < 0.001) and had a better health status (World Health Organization performance status = 0 in 60.3% of CS patients vs. 34.5% of S patients; p = 0.006). During follow-up, recurrence occurred in 27.2% and 19.6% of CS and S patients, respectively, after IPTW (p = 0.32). Five-year OS was similar between CS and S patients (78.9% vs. 68.3%; p = 0.42), as was 5-year DFS (70.4% vs. 68.5%; p = 0.96). Neoadjuvant chemotherapy was associated with neither OS nor DFS in multivariable analysis after IPTW., Conclusions: Patients with cT2N0M0 gastric adenocarcinoma did not present a survival or recurrence benefit if treated with perioperative chemotherapy followed by surgery as opposed to surgery alone., (© 2024. The Author(s).)

Objective: This study aimed to determine whether the combined use of bevacizumab could improve overall survival (OS) in patients with brain metastasis (BM), epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) undergoing cerebral radiotherapy., Materials and Methods: A total of 237 patients with EGFR-mutant lung adenocarcinoma and BM met the inclusion criteria for this retrospective study, including 102 patients in the bevacizumab treatment group and 135 in the non-bevacizumab group. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to identify EGFR-mutated BM prognostic factors for these patients., Results: At the end of the last follow-up period, 176 patients (74.3%) had died, and the median overall survival (OS) was 34.2 months. We observed a significant difference in the median OS between the bevacizumab and non-bevacizumab groups (45.8 months vs 30.0 months, P < 0.0001). Among the 178 (75.1%) patients who received cerebral radiotherapy, the median OS of patients in the bevacizumab + cerebral radiotherapy group was 45.8 months versus 32.0 months in the non-bevacizumab + cerebral radiotherapy group, respectively (P = 0.0007). Patients treated with bevacizumab after cerebral radiotherapy had a longer median OS than patients treated with bevacizumab before cerebral radiotherapy (59.4 months vs 33.7 months, P = 0.0198). In the univariate analysis, smoking status, Lung-molGPA scores, and bevacizumab therapy showed correlations (HR = 1.450, P = 0.045; HR = 0.700, P = 0.023; HR = 0.499, P < 0.001). Multivariate analysis showed that bevacizumab therapy alone (hazard ratio [HR] = 0.514; P < 0.001) was independently associated with improved OS., Conclusion: In patients with BM from EGFR-mutated NSCLC, cerebral radiotherapy with bevacizumab markedly improved OS. This improvement was more evident after cerebral radiotherapy., (© 2024. The Author(s).)

Background: The preoperative diagnosis of salivary gland cancer (SGC) is crucial for the application of appropriate treatment, particularly involving the extension of the resection., Methods: Retrospective search of medical database identified 116 patients treated surgically with malignant tumors of salivary gland between 2010 and 2020. Analysis included the demographical data, clinical course, type of surgical and adjuvant treatment, histology type and margin status, perivascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LN). Facial nerve function, recurrence-free and overall survival were evaluated. Adequate statistics were used for data analysis., Results: The final cohort included 63 SGC patients, with adenoid cystic carcinoma the most common pathological type (27%, n = 17), followed by adenocarcinoma (17.4% n = 11). T1 and T2 patients accounted for majority cases (n = 46). The lymph node metastases were confirmed with the histopathology in 31.7% (n = 20). Distant metastases were observed in 4.8% of cases (n = 3). 38% (n = 24) of SGC were treated selectively with surgery, 49.2% (n = 31) had postoperative radiotherapy and 15.9% (n = 10)-radio-chemotherapy. The final facial nerve function was impaired in 38% of patients. Mean overall survival (OS) for all patients was 108.7 (± 132.1) months, and was the most favorable for acinar cell carcinoma (118.9 ± 45.4) and the poorest for squamous cell carcinoma (44 ± 32). Cox regression analysis of disease-free survival and OS identified significant association only with patients' age over 65 years, the hazard ratio of 7.955 and 6.486, respectively., Conclusions: The efficacy of treatment modalities for SGC should be verified with regard to the histopathological type, but also the patients' age should be taken into account., (© 2024. The Author(s).)

Rare hepatoid adenocarcinomas are highly heterogeneous. In this case, hepatoid adenocarcinoma occurred in both the esophagus and thyroid, and the combination of chemotherapy and immunotherapy may be a promising therapeutic tool for rare tumors. Laryngoscope, 134:3673-3676, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: We aimed to summarize survival data from RCTs in patients with GO adenocarcinoma; estimate and explain worst-, typical-, and best-case-scenarios of survival time; and determine if simple multiples of median overall survival (mOS) could estimate these percentiles., Methods: We systematically searched RCTs of systemic therapies for GO adenocarcinoma published 2000-2022. The following key percentiles were extracted from overall survival curves: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We tested if these percentiles could be estimated by simple multiples of mOS: 0.25 of the median for the 90 th percentile, 0.5 for the 75 th , 2 for the 25 th , and 3 for the 10 th ., Results: We identified 44 trials (22,447 participants). For first line chemotherapy and immunotherapy combined (CI) trials ( n  = 3) worst-to-best case survival time ranged from 4 months to not reached, compared to 3-30 months for other trials ( n  = 27) and 1-23 months for subsequent lines ( n  = 14). Simple multiples of mOS accurately estimated the following survival percentiles: 90 th ( n  = 3/3 trials), 75 th ( n  = 3/3), and 25 th ( n  = 2/3) in first line CI trials. In other first line trials, the mOS accurately estimated the 90 th survival percentile in n  = 22/27 trials, 75 th percentile in n  = 26/27, 25 th percentile in 27/27 trials, and 10 th percentile in 22/27 trials. Simple multiples of the mOS accurately predicted the 90 th , 75 th , 25 th , and 10 th survival percentiles in the majority of trials of second and subsequent lines apart from chemotherapy and immunotherapy only trials., Conclusion: We provide realistic, evidence-based prognostic information as scenarios for survival time which can inform clinical decision-making. Simple multiples of the mOS accurately estimated the percentiles for most groups.

To assess adjuvant treatment patterns on survival in patients with pT3N0M0 esophageal cancer who underwent esophagectomy without neoadjuvant chemoradiotherapy. Stage pT3N0M0 esophageal cancer patients were assessed between 2000 and 2020 from the Surveillance, Epidemiology, and End Results databases. Kaplan-Meier analysis was used to compare overall survival (OS) among various treatment patterns. We identified 445 patients: 252 (56.6%) received surgery alone, 85 (19.1%) received surgery+chemoradiotherapy, 80 (18.0%) underwent surgery+chemotherapy, and 28 (6.3%) received surgery+ radiotherapy. For squamous cell carcinoma, surgery+chemoradiotherapy ([hazard ratio] HR = 1.04, 95% confidence interval (CI): 0.65-1.66; P = 0.873), surgery+chemotherapy (HR = 0.72, 95% CI: 0.42-1.22; P = 0.221), and surgery+radiotherapy (HR = 1.33, 95% CI: 0.74-2.39; P = 0.341) had similar OS compared to surgery alone. For adenocarcinoma, surgery+chemoradiotherapy (HR = 0.51, 95% CI: 0.36-0.74; P < 0.001) and surgery+chemotherapy (HR = 0.61, 95% CI: 0.42-0.87; P = 0.006) had better OS compared to surgery alone. However, surgery+radiotherapy had a comparable OS (HR = 0.81, 95% CI: 0.44-1.49; P = 0.495).Adjuvant treatments did not improve survival in stage pT3N0M0 esophageal squamous cell carcinoma patients. In contrast, adjuvant chemoradiotherapy and chemotherapy were recommended for esophageal adenocarcinoma patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)