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Malignant small bowel obstruction (mSBO) is a common consequence of advanced malignancies. Surgical consultation is common, however data on the outcomes following an operation are lacking. We investigated a specific operative approach-intestinal bypass-to determine the outcomes associated with this intervention.Patients with a preoperative diagnosis of mSBO who underwent intestinal bypass between 2015 and 2021 were included. Isolated colonic obstruction was excluded as was gastric outlet obstruction. Perioperative and postoperative outcomes were measured, including complications, overall survival, return to oral intake, and return to intended oncologic therapy. Patients were additionally grouped as to whether the operation was performed as elective or as inpatient.Overall, 55 patients were identified, with a mean age of 61.2 ± 14 years. The most common primary malignancy was colorectal cancer (65.5%) and 80% of patients had a preoperative diagnosis of metastatic disease. Small bowel to colon was the most common bypass procedure (51%). Severe complications occurred in 25.5% of patients with three in-hospital mortalities (5.5%). Survival rates at 30, 90, and 180 days were 91%, 80%, and 62%, respectively. The majority of patients were discharged to home (85.5%) and were tolerating an oral diet (74.6%). Twenty-seven patients (49.1%) returned to some form of oncologic treatment.Patients with mSBO face a potentially terminal condition. In this study, approximately 75% of patients who underwent intestinal bypass were able to regain the ability to eat, and 49% returned to oncologic therapy. Although retrospective, these data suggest the approach is efficacious for palliation of this difficult sequela of advanced cancer.

Macrophages are an abundant inflammatory cell type in the tumor microenvironment that can contribute to tumor growth and metastasis. Macrophage recruitment into tumors is mediated by multiple cytokines, including vascular endothelial growth factor (VEGF), which is thought to function primarily through VEGF receptor (VEGFR) 1 expressed on macrophages. Macrophage infiltration is affected by VEGF inhibition. We show that selective inhibition of VEGFR2 reduced macrophage infiltration into orthotopic pancreatic tumors. Our studies show that tumor-associated macrophages express VEGFR2. Furthermore, peritoneal macrophages from tumor-bearing animals express VEGFR2, whereas peritoneal macrophages from non–tumor-bearing animals do not. To our knowledge, this is the first time that tumor-associated macrophages have been shown to express VEGFR2. Additionally, we found that the cytokine pleiotrophin is sufficient to induce VEGFR2 expression on macrophages. Pleiotrophin has previously been shown to induce expression of endothelial cell markers on macrophages and was present in the microenvironment of orthotopic pancreatic tumors. Finally, we show that VEGFR2, when expressed by macrophages, is essential for VEGF-stimulated migration of tumor-associated macrophages. In summary, tumor-associated macrophages express VEGFR2, and selective inhibition of VEGFR2 reduces recruitment of macrophages into orthotopic pancreatic tumors. Our results show an underappreciated mechanism of action that may directly contribute to the antitumor activity of angiogenesis inhibitors that block the VEGFR2 pathway. [Cancer Res 2008;68(11):4340–6]

Supplementary Figure 1 from Vascular Endothelial Growth Factor Receptor 2 Mediates Macrophage Infiltration into Orthotopic Pancreatic Tumors in Mice

Supplementary Tables S1-S2. Metastatic events in preclinical models of PDA (S1); Warfarin enhances the activity of gemcitabine in an Axl-dependent manner (S2).

Supplementary Figures S1-S6. Axl is required for the growth of Mia PaCa-2 tumors (S1); Characterization of 10C9 (S2); Warfarin inhibits autocrine activation of Axl in pancreatic tumor cells (S3); In vivo warfarin effects (S4); Maintenance of mesenchymal phenotype is Axl dependent and inhibited by warfarin (S5); Acquisition of Axl expression sensitizes Capan-EMT cells to warfarin (S6).

Repurposing “old” drugs can facilitate rapid clinical translation but necessitates novel mechanistic insight. Warfarin, a vitamin K “antagonist” used clinically for the prevention of thrombosis for more than 50 years, has been shown to have anticancer effects. We hypothesized that the molecular mechanism underlying its antitumor activity is unrelated to its effect on coagulation, but is due to inhibition of the Axl receptor tyrosine kinase on tumor cells. Activation of Axl by its ligand Gas6, a vitamin K-dependent protein, is inhibited at doses of warfarin that do not affect coagulation. Here, we show that inhibiting Gas6-dependent Axl activation with low-dose warfarin, or with other tumor-specific Axl-targeting agents, blocks the progression and spread of pancreatic cancer. Warfarin also inhibited Axl-dependent tumor cell migration, invasiveness, and proliferation while increasing apoptosis and sensitivity to chemotherapy. We conclude that Gas6-induced Axl signaling is a critical driver of pancreatic cancer progression and its inhibition with low-dose warfarin or other Axl-targeting agents may improve outcome in patients with Axl-expressing tumors. Cancer Res; 75(18); 3699–705. ©2015 AACR.

Supplementary Figures 1-2, Tables 1-2 from Smac Mimetic Increases Chemotherapy Response and Improves Survival in Mice with Pancreatic Cancer

Supplementary Figure 2 from Vascular Endothelial Growth Factor Receptor 2 Mediates Macrophage Infiltration into Orthotopic Pancreatic Tumors in Mice

Supplementary Methods and References. Description of additional methods and procedures used in the study. Also includes Supplementary References.

Tumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Using a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. zTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. Elevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population.

Background The COVID crisis hit during the interview season for the Complex General Surgical Oncology (CGSO) fellowship. With minimal time to adapt, all programs transitioned to virtual interviews. Here we describe the experience of both program directors (PDs) and candidates with virtual interviews, and provide guidelines for implementation based on the results. Methods Surveys regarding interview day specifics and perceptions were created for CGSO fellowship PDs and candidates. They were distributed at the conclusion of the season, prior to match. Results Thirty (94%) PDs and 64 (79%) candidates responded. Eighty-three% of PDs and 79% of candidates agreed or strongly agreed that they felt comfortable creating a rank list. If given the choice, 60% of PDs and 45% of candidates would choose virtual interviews over in-person interviews. The majority of candidates found PD overviews, fellows only sessions and pre-interview materials helpful. Conclusion Overall, the majority of PDs and candidates felt comfortable creating a rank list; however, more PDs preferred virtual interviews for the future. Our results also confirm key components of a virtual interview day.

Gastric cancer (GC) is a common cancer worldwide, with patients developing isolated peritoneal metastases (PM) in approximately 30% of cases. In patients with PM, prognosis is quite poor, and long-term survival is almost zero. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been demonstrated to be an effective treatment in many peritoneal malignancies, including appendiceal and ovarian cancers and in peritoneal mesothelioma. In this educational review, we summarize many of the seminal studies addressing the potential benefit of CRS/HIPEC for patients with gastric cancer and peritoneal metastases (GC/PM).

Perioperative management entails the multiple substeps in the performance of major abdominal surgery that are considered relevant for an optimal outcome. The PG/CME symposium of the SSAT 2018 provided a set of key talks that the authors subsequently summarized in the respective subsections of this summary article. Highlights topics included oral antibiotics and mechanical bowel prep, surgical site infections, DVT prophylaxis, enhanced recovery after surgery (ERAS), and narcotic-sparing pain management.

Cytoreductive surgery (CRS) is one of the most complex operations in surgical oncology with significant morbidity, and improved risk prediction tools are critically needed. Machine learning models can potentially overcome the limitations of traditional multiple logistic regression (MLR) models and provide accurate risk estimates.To develop and validate an explainable machine learning model for predicting major postoperative complications in patients undergoing CRS.This prognostic study used patient data from tertiary care hospitals with expertise in CRS included in the US Hyperthermic Intraperitoneal Chemotherapy Collaborative Database between 1998 and 2018. Information from 147 variables was extracted to predict the risk of a major complication. An ensemble-based machine learning (gradient-boosting) model was optimized on 80% of the sample with subsequent validation on a 20% holdout data set. The machine learning model was compared with traditional MLR models. The artificial intelligence SHAP (Shapley additive explanations) method was used for interpretation of patient- and cohort-level risk estimates and interactions to define novel surgical risk phenotypes. Data were analyzed between November 2019 and August 2021.Cytoreductive surgery.Area under the receiver operating characteristics (AUROC); area under the precision recall curve (AUPRC).Data from a total 2372 patients were included in model development (mean age, 55 years [range, 11-95 years]; 1366 [57.6%] women). The optimized machine learning model achieved high discrimination (AUROC: mean cross-validation, 0.75 [range, 0.73-0.81]; test, 0.74) and precision (AUPRC: mean cross-validation, 0.50 [range, 0.46-0.58]; test, 0.42). Compared with the optimized machine learning model, the published MLR model performed worse (test AUROC and AUPRC: 0.54 and 0.18, respectively). Higher volume of estimated blood loss, having pelvic peritonectomy, and longer operative time were the top 3 contributors to the high likelihood of major complications. SHAP dependence plots demonstrated insightful nonlinear interactive associations between predictors and major complications. For instance, high estimated blood loss (ie, above 500 mL) was only detrimental when operative time exceeded 9 hours. Unsupervised clustering of patients based on similarity of sources of risk allowed identification of 6 distinct surgical risk phenotypes.In this prognostic study using data from patients undergoing CRS, an optimized machine learning model demonstrated a superior ability to predict individual- and cohort-level risk of major complications vs traditional methods. Using the SHAP method, 6 distinct surgical phenotypes were identified based on sources of risk of major complications.

Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients.Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD.The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P 0.001).Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). The US HIPEC collaborative database (2000–2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. A total of 174 patients were identified. Median PCI was 16 (3–39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59–4.74; MOR-2+ : HR 0.77, 95% CI 0.22–2.69). MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.

The impact of adjuvant chemotherapy (AT) on resected colon adenocarcinoma based on histologic subtype is poorly defined and extrapolated from patients with advanced disease. We evaluated the receipt and effect of AT on overall survival stratified by histologic subtype—mucinous, non-mucinous, and signet ring adenocarcinomas. A retrospective cohort study from 2004 to 2015 was conducted using the National Cancer Database. Patients with colon adenocarcinoma who underwent curative resection with pathologic stage III were included. Appendiceal and rectal tumors were excluded. The predictor variable was histologic subtype, and outcome variables were overall survival and receipt of AT. Absolute survival was increased for mucinous, non-mucinous, and signet ring tumors with receipt of AT (88.1, 108.9, and 38.1 months, respectively). In multivariable analysis, there was no difference in overall survival for mucinous patients relative to non-mucinous patients. In subgroup analysis, a modest survival advantage for non-mucinous patients relative to the mucinous patients was observed (HR, 0.92; 95% CI, 0.89–0.95). In multivariable modeling, non-mucinous and signet ring adenocarcinoma had decreased odds of receipt of AT relative to mucinous adenocarcinoma patients. Histologic subtype is an important prognostic factor for overall survival for stage III colon adenocarcinoma. Although the magnitude of the benefit of AT may vary in stage III curatively resected patients, it has a substantial survival benefit across all histologic subtypes. Based on these observations, there is no indication that patients with stage III mucinous adenocarcinoma of the colon should not receive AT. All patients with resected stage III colon cancer should be referred for AT regardless of histologic subtype.

Robotic-assisted gastrectomy is increasingly utilized for the treatment of gastric malignancies. However, the benefits of robotic surgery have been questioned. This study describes short-term outcomes in the establishment of a comprehensive robotic program for gastric malignancies.Patients who underwent robotic-assisted gastric resections between 2013 and 2018 were studied. Preoperative measures and surgical outcomes were analyzed. Finally we studied and analyzed robotic and open gastrectomy for the management of gastric adenocarcinoma (GC) at the same institution between 2000 and 2018 for quality benchmarking.Forty six patients (pts.) underwent robotic-assisted gastric resections. 26 (56.5%) were male, with a median age of 62 y (range: 29-87). Pathology included GC, gastrointestinal stromal tumors, neuroendocrine tumors, metastatic lesions, and benign processes. 19 pts. underwent total gastrectomy, 16 distal gastrectomy, four subtotal gastrectomy, and seven wedge resection. Pts. undergoing distal gastrectomy and wedge resection experienced shorter operative times and length of stay than total gastrectomy (P 0.01; P 0.01). Four operations (8.8%) were converted to open and 13 pts (28.3%) had postoperative complications, including an 8.7% readmission rate. Median lymph nodes retrieved during total, subtotal, and distal gastrectomy were 20 (13-46), 12.5 (0-26), and 16.5 (0-34), respectively. All pts. underwent margin negative resection. Median follow-up for GC was 21 mo, and 60% of pts. received adjuvant therapy at a median of 59d (range: 23-106).Robotic gastrectomy is a feasible alternative to open gastrectomy. Our results will help establish benchmarks to improve perioperative outcomes, especially length of stay and time to initiation of therapy.

BACKGROUND. Patient age is a significant factor in preoperative selection for major abdominal surgery. The association of age, tumor biology, and postoperative outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains ill-defined. METHODS. Retrospective analysis was performed for patients who underwent a CCR0/1 CRS/HIPEC from the US HIPEC Collaborative Database (2000–2017). Age was categorized into < 65 or ≥ 65 years. Primary outcome was postoperative major complications. Secondary outcomes were non-home discharge (NHD) and readmission. Analysis was stratified by disease histology: non-invasive (appendiceal LAMN/HAMN), and invasive (appendiceal/colorectal adenocarcinoma). RESULTS. Of 1090 patients identified, 22% were ≥ 65 (n = 240), 59% were female (n = 646), 25% had non-invasive (n = 276) and 51% had invasive (n = 555) histology. Median PCI was 13 (IQR 7–20). Patients ≥ 65 had a higher rate of major complications (37 vs 26%, p = 0.02), NHD (12 vs 5%, p < 0.01), and readmission (28 vs 22%, p = 0.05), compared to those < 65. For non-invasive histology, age ≥ 65 was not associated with major complications or NHD on multivariable analysis. For invasive histology, when accounting for PCI and CCR, age ≥ 65 was associated with major complications (OR 2.04, 95% CI 1.16–3.59, p = 0.01). When accounting for major complications, age ≥ 65 was associated with NHD (OR 2.54, 95% CI 1.08–5.98, p = 0.03). Age ≥ 65 was not predictive of readmission for any histology when accounting for major complications. CONCLUSIONS. Age ≥ 65 years is an independent predictor for postoperative major complications and non-home discharge for invasive histology, but not non-invasive histology. These data inform preoperative counseling, risk stratification, and early discharge planning.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is offered to select patients with peritoneal metastases. In instances of recurrence/progression, a repeat CRS/HIPEC may be considered. The perioperative morbidity and the potential oncologic benefits are not well described. We performed a retrospective analysis of a multiinstitutional database to assess the perioperative outcomes following repeat CRS/HIPEC (repeat). Kaplan–Meier and Cox estimates were used to assess survival. In the entire cohort, 2157 patients were analyzed, with 158 (7.3%) in the repeat cohort. The rate of complete cytoreduction was 89.8% versus 83.0% in initial versus repeat groups. The overall incidence of major complications was similar (26.3% vs. 30.7%); however, reoperation was more common in the repeat group. Perioperative outcomes such as length of stay and nonhome discharge were not significantly different. For the entire cohort, 5-year overall survival (OS) was 56.0% in the initial group and 59.5% in the repeat group. In patients with only appendiceal cancer, we observed a 5-year OS of 64.0% in the initial group compared with 67.3% in the repeat cohort. For patients with appendiceal cancer who developed a recurrence/progression, median OS was 36 months in the no repeat operation group compared with 73 months for those that did. Multivariable regression demonstrated that completeness of cytoreduction and tumor grade were associated with OS, but repeat operation was not. Repeat CRS/HIPEC is not associated with prohibitive risk. Survival is possibly improved, and therefore, repeat operation should be considered in selected patients with recurrent or progressive disease.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of desmoplastic small round cell tumor, breast, and gastrointestinal stromal tumor specifically related to peritoneal surface malignancy. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for palliative care specifically related to peritoneal surface malignancies. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, gynecologic oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of neuroendocrine tumors specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

Radiographic prediction of peritoneal carcinomatosis index (PCI) can improve patient selection for cytoreductive surgery. We aimed to determine the correlation of computed tomography (CT)-predicted PCI (CT-PCI) and magnetic resonance imaging (MRI)-predicted PCI (MRI-PCI) with intraoperative-PCI, and if a preoperative-PCI cutoff is associated with incomplete cytoreduction.Patients from the US HIPEC Collaborative (2000-2017) with appendiceal, colorectal, or peritoneal mesothelioma (PM) histology who underwent cytoreductive surgery were included. Pearson correlation coefficients were used to determine correlation between preoperative and intraoperative-PCI values. Fisher r-to-z transformation was used to compare correlations.A total of 488 patients were included. Of these, 34% had noninvasive appendiceal, 30% invasive appendiceal, 28% colorectal, and 8% PM histology. CT-PCI was correlated with intraoperative-PCI for patients with noninvasive and invasive appendiceal and colorectal histologies (r = 0.689, 0.554, and 0.571; all P .001), but not PM (r = 0.188; P = .295). MRI-PCI was correlated with intraoperative-PCI for all histologies (non-invasive appendiceal: r = 0.591; P = .002; invasive appendiceal: r = 0.848; P .001; colorectal: r = 0.729; P .001; PM: r = 0.890; P = .007). Comparing CT and MRI, correlations were similar in noninvasive appendiceal and colorectal histologies; MRI was better for invasive appendiceal and PM (P = .005 and P = .021, respectively). Twenty-eight (6%) patients underwent an incomplete cytoreduction (cytoreduction score, 2-3). PCI greater than 15 was associated with cytoreduction score of 2 to 3 for both CT and MRI (CT-PCI: odds ratio, 3.0; P = .033; MRI-PCI: odds ratio, 7.6; P = .071).In this multi-institutional cohort, CT and MRI-PCI correlate well with intraoperative-PCI. MRI appears to be superior for invasive appendiceal and peritoneal mesothelioma. External validation in a larger population is needed.

Background Gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ) are molecularly diverse. TP53 is the most frequently altered gene with approximately 50% of patients harboring mutations. This qualitative study describes the distinct genomic alterations in GCs and GEJs stratified by TP53 mutation status. Patients and Methods Tumor DNA sequencing results of 324 genes from 3741 patients with GC and GEJ were obtained from Foundation Medicine. Association between gene mutation frequency and TP53 mutation status was examined using Fisher’s exact test. Functional gene groupings representing molecular pathways suggested to be differentially mutated in TP53 wild-type (TP53WT) and TP53 mutant (TP53MUT) tumors were identified. The association of the frequency of tumors containing a gene mutation in the molecular pathways of interest and TP53 mutation status was assessed using Fisher’s exact test with a P-value of Results TP53 mutations were noted in 61.6% of 2946 GCs and 81.4% of 795 GEJs (P < .001). Forty-nine genes had statistically different mutation frequencies in TP53WT vs. TP53MUT patients. TP53WT tumors more likely had mutations related to DNA mismatch repair, homologous recombination repair, DNA and histone methylation, Wnt/B-catenin, PI3K/Akt/mTOR, and chromatin remodeling complexes. TP53MUT tumors more likely had mutations related to fibroblast growth factor, epidermal growth factor receptor, other receptor tyrosine kinases, and cyclin and cyclin-dependent kinases. Conclusion The mutational profiles of GCs and GEJs varied according to TP53 mutation status. These mutational differences can be used when designing future studies assessing the predictive ability of TP53 mutation status when targeting differentially affected molecular pathways.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.

Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood.Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula).Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p 0.01), higher complication rate (90% vs 59%; p 0.01), higher reoperation rate (41% vs 9%; p 0.01), more 30-day readmissions (59% vs 22%; p 0.01), greater 30-day mortality (9% vs 1%; p 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p 0.01).Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC.The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed.Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA.While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for patients with low-grade mucinous adenocarcinoma (LGMA) is most effective when complete cytoreduction is achieved. We externally validated two radiographic scoring systems to predict resectability and assessed radiographic response to systemic chemotherapy (SCT). Patients with LGMA who received preoperative SCT followed by CRS/HIPEC from 2013 to 2016 were identified. CT scans were graded by six physicians using the simplified radiologic score (SRS) and simplified preoperative assessment of appendiceal tumor (SPAAT) systems. Positive and negative predictive values (PPV, NPV) were calculated by comparing to completeness of cytoreduction. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC). Twenty-four patients had preoperative SCT followed by CRS/HIPEC. Thirteen patients underwent incomplete CRS and 11 patients complete CRS. Scoring of the preoperative CT had a PPV of complete cytoreduction of 75% and 66.7% for SRS and SPAAT, respectively. NPV was 83.4% and 88.9% for SRS and SPAAT, respectively. ICC for the preoperative SRS and SPAAT score was 0.826 (95% confidence interval [CI]: 0.720–0.910] and 0.788 [0.667–0.888). Comparison of CT scans before and after SCT recorded an increase in calculated scores in 45.8% (SRS) and 50% (SPAAT) of patients. External validation of two radiographic scoring systems to predict complete cytoreduction showed that inter-rater agreement for both systems was good. Both scoring systems predicted incomplete cytoreduction. Applying a systematic approach to preoperative imaging review is recommended to improve treatment selection by minimizing morbidity associated with incomplete CRS and help to set patient expectations.

The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6–15.3) versus 13.1 months (95% CI 9.5–16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5–36.6) versus 45.4 months (95% CI 35.9–54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19–2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09–2.73; p = 0.020). Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.

OBJECTIVE We compare neoadjuvant chemotherapy (CT) to neoadjuvant chemotherapy plus chemoradiation (CRT) for patients with gastric adenocarcinoma (GA). SUMMARY OF BACKGROUND DATA The optimal neoadjuvant therapy regimen for resectable GA is not defined. METHODS Utilizing data from 2 high-volume cancer centers, we analyzed patients who underwent surgery for localized GA from 1/1/2000-12/31/2017. Standard CT regimens were used according to treatment period. We compared propensity matched cohorts based on age, sex, race, histology, and clinical stage. RESULTS Four-hundred five patients (age 62 ± 12 year, 58% male, 56% White) were analyzed. 231 (57%) received CRT and 174 (43%) received CT. Groups differed based on histopathologic characteristics including preoperative stage (p = 0.013). To control for these differences, propensity matched cohorts of 113 CT and 113 CRT patients were compared. CRT had similar frequencies of microscopically negative resections to CT (93% vs 91%, p = 0.81), but higher rates of complete pathologic response (15% vs 4%, p = 0.003) and lower pathologic stage (p = 0.002). Completion of intended perioperative therapy occurred in 63% of CT and 91% of CRT patients (p < 0.001). Median DFS was 45mo (95%CI: 20-70) in the CT group and 113mo (95%CI: 75-151) in the CRT group (p = 0.018). Median OS was 53mo (95%CI: 30-77) versus 120mo (95%CI: 101-138); p = 0.015. CONCLUSIONS In this multi-institutional comparison of neoadjuvant CT and CRT for resectable GA, CRT is associated with higher rates of completed perioperative therapy, higher rates of complete pathologic response, lower pathologic stage, and improved survival.Level of Evidence: Level III.

Background The impact of socioeconomic status (SES) has been described for screening and accessing treatment for colon cancer. However, little is known about the “downstream” effect in patients who receive guideline‐concordant treatment. This study assessed the impact of SES on cancer‐specific survival (CSS) and overall survival (OS) for stage III colon cancer patients. Methods The SEER Census Tract‐Level SES Dataset from 2004 to 2015 was used to identify stage III colon adenocarcinoma patients who received curative‐intent surgery and adjuvant chemotherapy. The predictor variable was census tract SES. SES was analyzed as quintiles. The outcome variables were OR and CSS. Statistical analysis included chi square tests for association, Kaplan–Meier, Cox, Fine and Gray regression for survival analysis. Results In total, 27,222 patients met inclusion criteria. Lower SES was associated with younger age, Black or Hispanic race/ethnicity, Medicaid/uninsured, higher T stage, and lower grade tumors. CSS at the 25th percentile was 54 months for the lowest SES quintile and 80 for the highest. Median OS was 113 months for the lowest SES quintile and not reached for highest. The 5‐year CSS rate was 72.4% for the lowest SES quintile compared to 78.9% in the highest (p, This is the first study to evaluate CSS and OS in a national cohort of stage III colon cancer patients using a granular, standardized measure of SES. We showed that despite receipt of guideline‐based treatment, socioeconomic status is associated with disparities in overall and cancer specific survival. These findings suggest opportunities to improve colon cancer outcomes farther down the cancer care continuum.

BackgroundPostoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on thesurvivalof patients withappendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown.MethodsThe US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS).ResultsOf the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p

Objective To evaluate perioperative and oncologic outcomes in our RAMIE cohort and compare outcomes with contemporary OE controls. Summary of background data RAMIE has emerged as an alternative to traditional open or laparoscopic approaches. Described in all esophagectomy techniques, rapid adoption has been attributed to both enhanced visualization and technical dexterity. Methods We retrospectively reviewed patients who underwent RAMIE for malignancy. Patient characteristics, perioperative outcomes, and survival were evaluated. For perioperative and oncologic outcome comparison, contemporary OE controls were propensity-score matched from NSQIP and NCDB databases. Results We identified 350 patients who underwent RAMIE between 2010 and 2019. Median body mass index was 27.4, 32% demonstrated a Charlson Comorbidity Index ≥4. Nodal disease was identified in 50% of patients and 74% received neoadjuvant chemoradiotherapy. Mean operative time and blood loss were 425 minutes and 232 mL, respectively. Anastomotic leak occurred in 16% of patients, 2% required reoperation. Median LOS was 9 days, and 30-day mortality was 3%. A median of 21 nodes were dissected with 96% achieving an R0 resection. Median survival was 67.4 months. 222 RAMIE were matched 1:1 to the NSQIP OE control. RAMIE demonstrated decreased LOS (9 vs 10 days, P = 0.010) and reoperative rates (2.3 vs 12.2%, P = 0.001), longer operative time (427 vs 311 minutes, P = 0.001), and increased rate of pulmonary embolism (5.4% vs 0.9%, P = 0.007) in comparison to NSQIP cohort. There was no difference in leak rate or mortality. Three hundred forty-three RAMIE were matched to OE cohort from NCDB with no difference in median overall survival (63 vs 53 months; P = 0.130). Conclusion In this largest reported institutional series, we demonstrate that RAMIE can be performed safely with excellent oncologic outcomes and decreased hospital stay when compared to the open approach.

The impact of adjuvant chemotherapy (AT) on resected colon adenocarcinoma based on histologic subtype is poorly defined and extrapolated from patients with advanced disease. We evaluated the receipt and effect of AT on overall survival stratified by histologic subtype-mucinous, non-mucinous, and signet ring adenocarcinomas.A retrospective cohort study from 2004 to 2015 was conducted using the National Cancer Database. Patients with colon adenocarcinoma who underwent curative resection with pathologic stage III were included. Appendiceal and rectal tumors were excluded. The predictor variable was histologic subtype, and outcome variables were overall survival and receipt of AT.Absolute survival was increased for mucinous, non-mucinous, and signet ring tumors with receipt of AT (88.1, 108.9, and 38.1 months, respectively). In multivariable analysis, there was no difference in overall survival for mucinous patients relative to non-mucinous patients. In subgroup analysis, a modest survival advantage for non-mucinous patients relative to the mucinous patients was observed (HR, 0.92; 95% CI, 0.89-0.95). In multivariable modeling, non-mucinous and signet ring adenocarcinoma had decreased odds of receipt of AT relative to mucinous adenocarcinoma patients.Histologic subtype is an important prognostic factor for overall survival for stage III colon adenocarcinoma. Although the magnitude of the benefit of AT may vary in stage III curatively resected patients, it has a substantial survival benefit across all histologic subtypes. Based on these observations, there is no indication that patients with stage III mucinous adenocarcinoma of the colon should not receive AT. All patients with resected stage III colon cancer should be referred for AT regardless of histologic subtype.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major operation frequently necessitating red blood cell transfusion. Using multi-institutional data from the U.S. HIPEC Collaborative, this study sought to determine the association of perioperative allogenic blood transfusion (PABT) with perioperative outcomes after CRS/HIPEC. This retrospective cohort study analyzed patients who underwent CRS/HIPEC for peritoneal surface malignancy between 2000 and 2017. Propensity score-matching was performed to mitigate bias. Univariate analysis was used to compare demographic, preoperative, intraoperative, and postoperative variables. Factors independently associated with PABT were identified using multivariate analysis. The inclusion criteria were met by 1717 patients, 510 (29.7%) of whom required PABT. The mean Peritoneal Cancer Index (PCI) of our cohort was 14.8 ± 9.3. Propensity score-matching showed an independent association between PABT and postoperative risk of pleural effusion, hemorrhage, pulmonary embolism, enteric fistula formation, Clavien-Dindo grades 3 and 4 morbidity, longer hospital stay, and reoperation (all P

Prognostication based on preoperative clinical factors is lacking in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study aims to determine the value of preoperative tumor markers as predictors of progression-free survival (PFS) and overall survival (OS) for patients with peritoneal carcinomatosis from a primary mucinous adenocarcinoma of the appendix (MACA). We queried the United States HIPEC Collaborative, a database of patients with peritoneal carcinomatosis treated with CRS/HIPEC at twelve institutions between 2000 and 2017, identifying 409 patients with MACA. Multivariate analysis was used to identify independent predictors of disease progression. Subgroup analysis was conducted to evaluate the impact of tumor grade on the predictive value of tumor markers. CA19-9 [HR 2.44, CI 1.2–3.4] emerged as an independent predictor of PFS while CEA [HR 4.98, CI 1.06–23.46] was independently predictive of OS (p

While recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM).All patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay75th percentile, and non-home discharge.Among 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p 0.01).Among patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.

BackgroundWhile parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC.MethodsPatients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS).ResultsA total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p

BACKGROUND Variations in care have been demonstrated both within and among institutions in many clinical settings. By standardizing perioperative practices, Enhanced Recovery After Surgery (ERAS) pathways reduce variation in perioperative care. We sought to characterize the variation in cytoreductive surgery (CRS)/heated intraperitoneal chemotherapy (HIPEC) perioperative practices among experienced US medical centers. METHODS Data from the US HIPEC Collaborative represents a retrospective multi-institutional cohort study of CRS and CRS/HIPEC procedures performed from 12 major academic institutions. Patient characteristics and perioperative practices were reported and compared. Institutional variation was analyzed using hierarchical mixed-effects linear (continuous outcomes) or logistic (binary outcomes) regression models. RESULTS A total of 2372 operations were included. CRS/HIPEC was performed most commonly for appendiceal histologies (64.2%). The rate of complications (overall 56.3%, range: 31.8-70.9) and readmissions (overall 20.6%, range: 8.9-33.3) varied by institution (P

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000&ndash, 2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

355 Background: Perioperative chemotherapy is the standard of care for locoregional gastric cancers in western populations. However, the impact of response to therapy as a biomarker of cancer survival has not been fully defined. This study focuses on the pathological response to neoadjuvant chemotherapy, as measured by tumor regression grade (TRG), for gastric cancer and its impact on patient outcomes, primarily overall survival. Methods: Patients undergoing gastrectomy for nonmetastatic invasive gastric adenocarcinoma following perioperative chemotherapy (clinical T2+/N+cM0) were identified from an institutional database (2000-2021). Demographics, clinical staging including histologic grade, surgical factors and survival outcomes were included. The association between TRG and overall survival from time of surgery was assessed. OS was estimated using the Kaplan Meier method with adjustment for covariates using Cox regression. Results: One hundred seventeen patients were identified. Median age was 65 years (IQR 57–73). The majority of the patients were male (n = 64, 55%). Seventy-six patients underwent total gastrectomy, 22 subtotal gastrectomy, and 19 distal gastrectomy. Six patients (5.1%) had a TRG of 0, 18 patients (15.4%) had a TRG of 1, 25 patients (21.4%) had a TRG of 2, and 68 patients (58.1%) had a TRG of 3. Median survival overall was 40.9 months (95% CI 28.7–66.4). TRG status was not significantly different between chemotherapy regimens (doublet vs triplet, p = 0.96). Median survival was longest in the TRG 0 group (86.9 months), followed sequentially by TRG 1 (74.5 months), TRG 2 (51.5 months), and lastly, TRG 3 group with 27.0 months. Increased tumor regression (lower TRG) was significantly associated with prolonged survival (p < 0.01 by log-rank for trend). After adjustment for clinical patient factors and tumor factors, TRG remained significantly associated with overall survival (Table; TRG hazard ratio 1.62, p = 0.007). In addition to TRG status, clinical T4 tumors and diffuse histology were associated with poor survival (cT4 hazard ratio 2.09, p = 0.039, diffuse histology hazard ratio 1.82 (p = 0.071). Conclusions: In patients receiving perioperative chemotherapy for treatment of gastric cancer, response to therapy as defined by TRG is independently prognostic of survival.[Table: see text]