Gastrointestinal Cancer Outcomes Research Articles

Association between different patterns of obesity and the short-term outcomes of gastric cancer surgery.

Previous studies have shown that general and central obesity are each linked to adverse outcomes in gastrointestinal cancers. However, their combined effect on gastrointestinal cancers surgery outcomes were less understood. This study aims to integrate both general and central obesity to examine the outcomes of gastric cancer surgery in different obesity patterns. We retrospectively analyzed 248 patients who underwent gastric cancer surgery between 2021 and 2023 in a single institute. The Inbody720 body composition analyzer measured body composition. We evaluated the relationship between obesity patterns - combining BMI with central obesity measures (waist circumference, waist-to-hip ratio, visceral fat area) - and postoperative complications and 30-day readmission. Central-only obesity were more likely to induce fistula (P = 0.025), while non-obesity was more likely to develop postoperative abdominal effusion (P = 0.049) and bleeding (P = 0.042). Central-only obesity was significantly associated with severe postoperative complications after adjustment for hypertension, diabetes, abdominal surgery history, preoperative albumin levels, age, sex, and surgical types. This remains significant even after adjusting for muscle mass. However, we did not find the same results for significant complications. Regarding 30-day readmission, there are no differences between different patterns of obesity. Central-only obesity is an independent risk factor for severe postoperative complications in gastric cancer, while a high BMI appears to be associated with a lower risk compared to non-obese patients, but not significant postoperative complications. The likelihood of readmission within 30 days post-surgery may not be related to the patient's pattern of obesity.

Tissue-Resident Memory T Cells in Gastrointestinal Cancers: Prognostic Significance and Therapeutic Implications.

Gastrointestinal cancers, which include a variety of esophageal and colorectal malignancies, present a global health challenge and require effective treatment strategies. In the evolving field of cancer immunotherapy, tissue-resident memory T cells (Trm cells) have emerged as important players in the immune response within nonlymphoid tissues. In this review, we summarize the characteristics and functions of Trm cells and discuss their profound implications for patient outcomes in gastrointestinal cancers. Positioned strategically in peripheral tissues, Trm cells have functions beyond immune surveillance, affecting tumor progression, prognosis, and response to immunotherapy. Studies indicate that Trm cells are prognostic markers and correlate positively with enhanced survival. Their presence in the tumor microenvironment has sparked interest in their therapeutic potential, particularly with respect to immune checkpoint inhibitors, which may improve cancer treatment. Understanding how Trm cells work will not only help to prevent cancer spread through effective treatment but will also contribute to disease prevention at early stages as well as vaccine development. The role of Trm cells goes beyond just cancer, and they have potential applications in infectious and autoimmune diseases. This review provides a thorough analysis of Trm cells in gastrointestinal cancers, which may lead to personalized and effective cancer therapies.

The associations of food environment with gastrointestinal cancer outcomes in the United States.

Social conditions and dietary behaviors have been implicated in the rising burden of gastrointestinal cancers (GIC). The "food environment" reflects influences on a community level relative to food availability, nutritional assistance, and social determinants of health. Using the US Department of Agriculture-Food Environment Atlas (FEA), we sought to characterize the association of food environment on GIC presenting stage and long-term survival. Patients diagnosed with GIC between 2013 and 2017 were identified using the SEER database. FEA-scores were based on 282 county-level food security variables, store-restaurant availability, SNAP/WIC enrollment, pricing/taxes, and producer vicinity adjusted-for factors of socioeconomic status, race-ethnicity, transportation access, and comorbidities. Relative FEA rankings across US counties were averaged into a composite score and assigned to patients by county-of-residence. The association of FEA, cancer stage, and survival were analyzed using multiple logistic regression and cox-proportional hazard models relative to White/non-White race/ethnicity. Among 287,148 patients, the most common GIC-sites were colon (n = 97,942, 34%), pancreas (n = 49,785, 17.3%), liver (n = 31,098, 11.0%) and esophagus (n = 16,271, 5.7%). A worse food environment was independently associated with increased odds of late-stage diagnosis (esophageal odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05; hepatic OR: 1.06, 95% CI: 1.03-1.08; pancreatic OR: 1.04, 95% CI: 1.01-1.06) among all patients; in contrast, food environment was associated with colorectal cancer stage among non-White patients only (OR: 1.04, 95% CI: 1.03-1.06). Worse food environment was associated with worse 3-year survival (colon OR: 1.03, 95% CI: 1.01-1.04; hepatic OR: 1.12, 95% CI: 1.08-1.17; gastric OR: 1.07, 95% CI: 1.01-1.13). Similar associations were noted relative to overall survival among the entire cohort (biliary tract hazard ratio [HR]: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.02, 95% CI: 1.01-1.04; hepatic HR: 1.07, 95% CI: 1.06-1.09; pancreatic HR: 1.04, 95% CI: 1.02-1.05; rectum HR: 1.03, 95% CI: 1.01-1.04; gastric HR: 1.05, 95% CI: 1.03-1.07), as well as among non-White patients (biliary HR: 1.04, 95% CI: 1.01-1.07; colon HR: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.05, 95% CI: 1.02-1.08; hepatic HR: 1.08, 95% CI: 1.06-1.10) (all p < 0.003). Food environment was independently associated with late-stage tumor presentation and worse 3-year and overall survival among GIC patients. Interventions to address inequities across communities relative to food environments are needed to alleviate disparities in cancer care.

Commitment Complex Splicing Factors in Cancers of the Gastrointestinal Tract-An In Silico Study.

The initial step in pre-mRNA splicing involves formation of a spliceosome commitment complex (CC) or E-complex by factors that serve to bind and mark the exon-intron boundaries that will undergo splicing. The CC component U1 snRNP assembles at the 5'-splice site (ss), whereas SF1, U2AF2, and U2AF1 define the 3'-ss of the intron. A PRP40 protein bridges U1 snRNP with factors at the 3'-ss. To determine how defects in CC components impact cancers, we analyzed human gastrointestinal (GI) cancer patient tissue and clinical data from cBioPortal. cBioPortal datasets were analyzed for CC factor alterations and patient outcomes in GI cancers (bowel, stomach, esophagus, pancreas, and liver). In addition, co-expression datasets were used to determine the splicing targets of the CC. Our analysis found that frequency of genetic changes was low (1%-13%), but when combined with changes in expression levels, there was an overall surprisingly high incidence of CC component (>30%) alterations in GI cancers. Colon cancer patients carrying BRAF driver gene mutations had high incidences of CC alterations (19%-61%), whereas patients with APC, KRAS, or TP53 gene mutations had low (<5%) incidences of CC alterations. Most significantly, patients with mutations in CC genes exhibited a consistent trend of favorable survival rates, indicating that mutations that impair or lower CC component expression favor patient survival. Conversely, patients with high CC expression had worse survival. Pathway analysis indicates that the CC regulates specific metabolic and tumor suppressor pathways. Metabolic pathways involved in cell survival, nutrition, biosynthesis, autophagy, cellular movement (invasion), or immune surveillance pathways correlated with CC factor upregulation, whereas tumor suppressor pathways, which regulate cell proliferation and apoptosis, were inversely correlated with CC factor upregulation. This study demonstrates the versatility of in silico analysis to determine molecular function of large macromolecular complexes such as the spliceosome CC. Furthermore, our analysis indicates that therapeutic lowering of CC levels in colon cancer patients may enhance patient survival.

Absence of association between CT-assessed skeletal muscle mass and long-term oncological outcomes after curative therapy for colorectal liver metastasis.

Sarcopenia is associated with impaired short- and long-term outcomes in gastrointestinal cancers. Whether sarcopenia is associated with impaired survival after local therapy of Colorectal Cancer Liver Metastases (CRLM) remains controversial. This study aimed to determine the influence of sarcopenia on long-term outcomes after curative-intent therapy for CRLM. Patients undergoing local therapy for CRLM between 2003 and 2019 were retrospectively analyzed using the skeletal muscle index at the level of the third lumbar vertebra as an indicator of sarcopenia. Factors associated with overall (OS) and disease-free (DFS) survival were analyzed using univariable and multivariable cox regression. In total 213/465 patients (46%) were considered sarcopenic. Sarcopenic patients had no impaired 5-year OS or DFS compared to non-sarcopenic patients, 38% vs 44% (p=0.153) and 19 vs 23% (p=0.339) respectively. Sarcopenia was not associated with impaired OS (HR=1.11, 95%CI=0.85-1.46, p=0.43) or DFS (HR=0.99, 95%CI=0.77-1.28, p=0.96) in multivariable analysis. There were no significant differences in postoperative complications (p=0.47), the incidence (p=0.65) and treatment (p=0.37) of recurrent metastases. Five-year OS after resection for recurrences was 14% (sarcopenic) and 22% (non-sarcopenic) p 0.716. Sarcopenia assessed by computed tomography was not associated with impaired survival outcomes in the group of CRLM patients overall.

ANK2 mutation as an indicator stratified patients benefit from immune checkpoint inhibitors in NSCLC.

e21080 Background: Immune checkpoint inhibitors (ICIs), targeting the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have demonstrated impressive anti-tumor efficacy in multiple cancers, in particular with non-small cell lung cancer (NSCLC). However, only a minority of patients could benefit from ICIs. Therefore, investigating predictive biomarkers of ICIs is important to identify the target population that derives the best therapeutic benefit. ANK2 encodes ankyrin-2, which plays a crucial role in cell development. Studies have shown a significant correlation between ANK2 expression levels and clinical outcomes in gastrointestinal cancers and pancreatic cancer. However, its role in lung cancer immunotherapy remains unknown. Here we aimed to demonstrate the association between ANK2 and ICIs. Methods: 165 patients from three public immunotherapy cohorts (Hellmann 2018, Miao 2018, and Rizvi 2015 cohort) were included to analyze the association between ANK2 gene mutation and efficacy of ICI therapy. Genomic, survival and mRNA data of NSCLC patients from the Cancer Genome Atlas (TCGA) database was used to explore the potential mechanisms of anti-tumor immunity. Results: Patients with ANK2 mutation were significantly associated with better PFS (HR = 0.28; 95% CI, 0.15-0.53; P &lt; 0.001), objective response rate (ORR, 69.0% vs 24.3%; P &lt; 0.001) and durable clinical benefit (DCB, 72.4% vs 41.9%; P = 0.003) compared with those with wide-type in NSCLC. ANK2 mutation were associated with increased TMB (P &lt; 0.001). In the multivariable Cox proportional hazards regression model adjusted by the smoking status, PD-L1 expression and TMB, the association between ANK2 mutation and PFS remained significant (HR = 0.28; 95% CI, 0.20-0.82; P = 0.012).In TCGA, no association between ANK2 mutation and OS (LUAD: P =0.27 ; LUSC: P = 0.39) or PFS (LUAD: P = 0.21; LUSC: P = 0.63) was observed, suggesting that ANK2 mutation may be a predictive but not a prognostic factor in ICI treatment for NSCLC patients. Based on CIBERSORT-inferred tumor infiltrating lymphocytes from TCGA, ANK2mutation was significantly associated with higher CD8+ T cells, higher M1 macrophage, and lower M2 macrophage. Moreover, ANK2 mutation was associated with increased TMB (P &lt; 0.001) and neoantigen load (P &lt; 0.001) in TCGA. In addition, GSEA analysis revealed that ANK2 mutation was correlated with upregulated DNA damage repair (DDR) signaling pathway in LUAD. Conclusions: Our results demonstrated that ANK2 mutation is an independent classifier that could stratify patients with NSCLC for ICIs. The role of ANK2 in immunotherapy is needed to be further studied.

Impact of pathological response after neoadjuvant chemotherapy on adjuvant therapy decisions and patient outcomes in gastrointestinal cancers.

BackgroundNeoadjuvant chemotherapy (NAC) is frequently used in gastrointestinal cancers (GIC), and pathological, radiological, and tumor marker responses are assessed during and after NAC.AimTo evaluate the relationship between pathologic, radiologic, tumor marker responses and recurrence‐free survival (RFS), overall survival (OS), adjuvant chemotherapy (AC) decisions, and the impact of changing to a different AC regimen after poor response to NAC.Methods and resultsMedical records of GIC patients treated with NAC at Mount Sinai between 1/2012 and 12/2018 were reviewed. One hundred fifty‐six patients (58.3% male, mean age 63 years) were identified. Primary tumor sites were: 43 (27.7%) pancreas, 62 (39.7%) gastroesophageal, and 51 (32.7%) colorectal. After NAC, 31 (19.9%) patients had favorable pathologic response (FPR; defined as College of American Pathologists [CAP] score 0–1). Of 107 patients with radiological data, 59 (55.1%) had an objective response, and of 113 patients with tumor marker data, 61 (54.0%) had a ≥50% reduction post NAC. FPR, but not radiographic or serological responses, was associated with improved RFS (HR 0.28; 95% CI 0.11–0.72) and OS (HR 0.13; 95% CI 0.2–0.94). Changing to a different AC regimen from initial NAC, among all patients and specifically among those with unfavorable pathological response (UPR; defined as CAP score 2–3) after NAC, was not associated with improved RFS or OS.ConclusionsGIC patients with FPR after NAC experienced significant improvements in RFS and OS. Patients with UPR did not benefit from changing AC. Prospective studies to better understand the role of pathological response in AC decisions and outcomes in GIC patients are needed.

Proton Pump Inhibitor Use and the Efficacy of Chemotherapy in Metastatic Colorectal Cancer: A Post Hoc Analysis of a Randomized Phase III Trial (AXEPT)

Concomitant use of proton pump inhibitors (PPIs) with capecitabine was suggested to be associated with poor outcomes in gastrointestinal cancers. We analyzed the differential impact of PPI use on capecitabine and fluorouracil using the data set from the AXEPT trial, a phase III randomized trial that demonstrated the noninferiority of mXELIRI (modified XELIRI: capecitabine plus irinotecan) to FOLFIRI (leucovorin, fluorouracil, and irinotecan), either with or without bevacizumab in patients with metastatic colorectal cancer. Out of the per-protocol set (n = 620), patients with information on concomitant medications (n = 482) were included in this post hoc analysis. PPI use was defined as concomitant exposure of capecitabine and the use of any PPI for 20% or more of the study period. The treatment-by-PPI-use interaction was examined after adjusting for stratification factors. Of the 482 patients, 49 (10.1%) used PPI. Among the PPI users, the mXELIRI group tended to have poorer overall survival compared with the FOLFIRI group. In contrast, among the nonusers, the overall survival of the mXELIRI group was significantly better than that of the FOLFIRI group. Similarly, a trend of worse progression-free survival with mXELIRI compared with FOLFIRI was observed in PPI users but not in nonusers. Treatment-by-PPI-use interaction was significant for overall survival and progression-free survival. The significant interaction between PPI use and the type of fluoropyrimidine in terms of overall and progression-free survival suggests that fluorouracil could be a more favorable option than capecitabine for patients with metastatic colorectal cancer using PPIs. This study showed a significant interaction between the use of proton pump inhibitors (PPIs) and the type of fluoropyrimidines. This interaction mainly comes from the positive impact of PPIs in the survival outcomes in the fluorouracil arm rather than a negative impact of PPIs in the capecitabine arm. The possible drug-drug interaction shown in this study suggests that fluorouracil, rather than capecitabine, could be a more appropriate choice of fluoropyrimidine for patients who are taking PPIs in the treatment of metastatic colorectal cancer.

Understanding Racial Disparities in Gastrointestinal Cancer Outcomes: Lack of Surgery Contributes to Lower Survival in African American Patients.

Race/ethnicity-related differences in rates of cancer surgery and cancer mortality have been observed for gastrointestinal (GI) cancers. This study aims to estimate the extent to which differences in receipt of surgery explain racial/ethnic disparities in cancer survival. The National Cancer Database was used to obtain data for patients diagnosed with stage I-III mid-esophageal, distal esophagus/gastric cardia (DEGC), noncardia gastric, pancreatic, and colorectal cancer in years 2004-2015. Mediation analysis was used to identify variables influencing the relationship between race/ethnicity and mortality, including surgery. A total of 600,063 patients were included in the study: 3.5% mid-esophageal, 12.4% DEGC, 4.9% noncardia gastric, 17.0% pancreatic, 40.1% colon, and 22.0% rectal cancers. The operative rates for Black patients were low relative to White patients, with absolute differences of 21.0%, 19.9%, 2.3%, 8.3%, 1.6%, and 7.7%. Adjustment for age, stage, and comorbidities revealed even lower odds of receiving surgery for Black patients compared with White patients. The observed HRs for Black patients compared with White patients ranged from 1.01 to 1.42. Mediation analysis showed that receipt of surgery and socioeconomic factors had greatest influence on the survival disparity. The results of this study indicate that Black patients appear to be undertreated compared with White patients for GI cancers. The disproportionately low operative rates contribute to the known survival disparity between Black and White patients. Interventions to reduce barriers to surgery for Black patients should be promoted to reduce disparities in GI cancer outcomes.See related commentary by Hébert, p. 438.

Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor.

Identifying valid biomarkers for patient selection impressively promotes the success of anti-PD-1 therapy. However, the unmet need for biomarkers in gastrointestinal (GI) cancers remains significant. We aimed to explore the predictive value of the circulating T-cell receptor (TCR) repertoire for clinical outcomes in GI cancers who received anti-PD-1 therapy. 137 pre- and 79 post-treated peripheral blood samples were included. The TCR repertoire was evaluated by sequencing of complementarity-determining region 3 (CDR3) in the TRB gene. The Shannon index was used to measure the diversity of the TCR repertoire, and Morisita's overlap index was used to determine TCR repertoire similarities between pre- and post-treated samples. Among all enrolled patients, 76 received anti-PD-1 monotherapy and 61 received anti-PD-1 combination therapy. In the anti-PD-1 monotherapy cohort, patients with higher baseline TCR diversity exhibited a significantly higher disease control rate (77.8% vs. 47.2%; hazard ratio [HR] 3.92; 95% confidence interval [CI] 1.14-13.48; P = 0.030) and a longer progression-free survival (PFS) (median: 6.47months vs. 2.77months; HR 2.10; 95% CI 1.16-3.79; P = 0.014) and overall survival (OS) (median: NA vs. 8.97months; HR 3.53; 95% CI 1.49-8.38; P = 0.004) than those with lower diversity. Moreover, patients with a higher TCR repertoire similarity still showed a superior PFS (4.43months vs. 1.84months; HR 13.98; 95% CI 4.37-44.68; P < 0.001) and OS (13.40months vs. 6.12months; HR 2.93; 95% CI 1.22-7.03; P = 0.016) even in the cohort with lower baseline diversity. However, neither biomarker showed predictive value in the anti-PD-1 combination therapy cohort. Interestingly, the combination of TCR diversity and PD-L1 expression can facilitate patient stratification in a pooled cohort. The circulating TCR repertoire can serve as a predictor of clinical outcomes in anti-PD-1 therapy in GI cancers.

2011P The impact of pathological response (PR) on adjuvant chemotherapy (AC) decisions and patient outcomes in gastrointestinal cancers (GIC)

2011P The impact of pathological response (PR) on adjuvant chemotherapy (AC) decisions and patient outcomes in gastrointestinal cancers (GIC)

Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers.

Radiotherapy is used in the treatment of approximately 50% of all malignancies including gastrointestinal cancers. Radiation can be given prior to surgery (neoadjuvant radiotherapy) to shrink the tumour or after surgery to kill any remaining cancer cells. Radiotherapy aims to maximize damage to cancer cells, while minimizing damage to healthy cells. However, only 10-30% of patients with rectal cancer or oesophageal cancer have a pathological complete response to neoadjuvant chemoradiation therapy, with the rest suffering the negative consequences of toxicities and delays to surgery with no clinical benefit. Furthermore, in pancreatic cancer, neoadjuvant chemoradiation therapy results in a pathological complete response in only 4% of patients and a partial pathological response in only 31%. Resistance to radiation therapy is polymodal and associated with a number of biological alterations both within the tumour itself and in the surrounding microenvironment including the following: altered cell cycle; repopulation by cancer stem cells; hypoxia; altered management of oxidative stress; evasion of apoptosis; altered DNA damage response and enhanced DNA repair; inflammation; and altered mitochondrial function and cellular energetics. Radiosensitizers are needed to improve treatment response to radiation, which will directly influence patient outcomes in gastrointestinal cancers. This article reviews the literature to identify strategies - including DNA-targeting agents, antimetabolic agents, antiangiogenics and novel immunotherapies - being used to enhance radiosensitivity in gastrointestinal cancers according to the hallmarks of cancer. Evidence from radiosensitizers from in vitro and in vivo models is documented and the action of radiosensitizers through clinical trial data is assessed.

Comprehensive Genetic Profiling and Clinical Outcomes in Gastrointestinal Cancers Treated with Radiotherapy

The clinical significance of many genetic mutations in gastrointestinal cancers is not well characterized. As next-generation sequencing (NGS) has become more commercially available, there is opportunity to better establish the role of mutations in DNA damage and repair (DDR), tumor suppressor (TS), cell cycle (CC) and immune checkpoint (IC) genes. This information may be used to better predict local control (LC), distant metastasis (DM) or overall survival (OS). Commercially available DNA sequencing was conducted on patients with gastrointestinal (GI) cancers to identify significant genetic mutations. A total of 86 solid tumor biopsy specimens from GI cancers were submitted for molecular profiling with NGS. Clinical outcomes were measured from time of radiotherapy (RT) to time of progression or last follow-up and included RT to primary lesions and distant metastases. DDR genes included MGMT, MSH 2/6, and ERCC1. CC genes included cMET, EGFR, ERBB2 and KRAS. TS genes included APC, PTEN, and TP53. IC genes included PD-1 and PDL-1. Patients with locally controlled versus progressive disease were compared with regards to prevalence of genetic mutations in order to identify predictors of LC and OS. Patients were treated locally or distantly for colorectal (CRC, n = 36), gastroesophageal (GE, n = 5), liver and bile duct (LBD, n = 14), pancreatic (PC, n = 26) and other (OC, n = 5) GI cancers. Overall, patients had at least one mutation in DDR (46.3%), CC (55.2%), TS (65.5%), or IC (25.3%). DDR and CC mutations were most common in PC (57.7% and 69.2%, respectively), TS mutations were most common in CRC (80.6%), and IC was most common in CE (80.0%). Patients with at least one mutation in DDR, CC, or IC did not have any difference in LC following RT compared to patients without mutations. Mutations in TS genes were associated with improved local control following RT versus those without mutations in TS genes (p = 0.035). Mutations in TS, DDR, CC, and IC were not significantly associated with overall survival. Genetic mutations may be used to predict better response to local radiotherapy in patients with gastrointestinal cancer. In our analysis, patients with mutations in tumor suppressor genes including APC, PTEN, and TP53 had better local control following radiotherapy than patients without mutations in tumor suppressor genes. This information may be useful in future studies to identify patients at increased risk of local failure.

Prognostic effect of sidedness in early stage versus advanced colon cancer.

Background and AimsThe prognostic effect of sidedness in colorectal cancer has been evaluated in numerous prospective and retrospective cohorts. Most of these have reported overall survival data; there is scant relapse‐free survival data in early stage disease. This study aimed to determine the effect of tumor sidedness in survival in early stage and relapsed colon cancer.MethodsPatients with stage I‐III colorectal cancer were identified from the BC Cancer Agency Gastrointestinal Cancer Outcomes Unit. Survival analysis by stage and sidedness was compared with the log‐rank test. Baseline characteristics were controlled by multivariate Cox‐proportional hazard models. In relapsed patients, bevacizumab and EGFR inhibitor (EGFRI) treatments were included and tested for interaction.ResultsAmong 5378 patients with stage I‐III colon cancer, patients with right‐sided stage II tumors experienced better relapse‐free survival compared with those with left‐sided tumors; right‐sidedness was not prognostic for RFS in stage III disease. When survival was considered in patients who relapsed, right‐sided tumors had inferior survival after relapse in both stage II and stage III tumors. At relapse, right‐sided outcomes were inferior regardless of biologic therapy. An interaction test revealed a significant association between sidedness and survival with EGFRIs.ConclusionsIn this large, population‐based study, right‐sided presentation has a significant prognostic impact: in early stage, right‐sidedness is favorably prognostic among stage II tumors and not prognostic in stage III disease. After relapse, right‐ sidedness is associated with an inferior prognosis, regardless of initial stage of presentation. Colon tumor sidedness is independently prognostic and may be considered in treatment assignment for both early stage and advanced disease.

Can Total Psoas Area Predict Toxicity After Stereotactic Body Radiation Therapy in Borderline Resectable and Locally Advanced Pancreatic Cancers?

455Background: Total Psoas Area (TPA), a marker of sarcopenia, found clinical utility as an independent predictor of clinical outcomes in gastrointestinal cancers as a proxy for nutritional status. Our study evaluated the relationship of TPA and other proxies of nutrition like Body Mass Index (BMI) and Body Surface Area (BSA) with outcomes in Borderline Resectable Pancreatic Cancer (BRPC) and Locally Advanced Pancreatic Cancer (LAPC) patients receiving Stereotactic Body Radiation Therapy (SBRT). Methods: In retrospective analysis of an IRB approved database, 183 BRPC and LAPC patients treated with SBRT from 2009-2016 met our selection criteria. Patients underwent gemcitabine based or FOLFIRINOX chemotherapy for 3 months prior to SBRT. Eligible patients were those with pre-SBRT planning CT imaging on Pinnacle, a treatment planning system, and an identifiable L4 vertebra. Bilateral psoas muscles were manually contoured at the L4 vertebral level. This area was normalized by patient height (median = 876.505 m...

Can total psoas area predict toxicity after stereotactic body radiation therapy in borderline resectable and locally advanced pancreatic cancers?

455 Background: Total Psoas Area (TPA), a marker of sarcopenia, found clinical utility as an independent predictor of clinical outcomes in gastrointestinal cancers as a proxy for nutritional status. Our study evaluated the relationship of TPA and other proxies of nutrition like Body Mass Index (BMI) and Body Surface Area (BSA) with outcomes in Borderline Resectable Pancreatic Cancer (BRPC) and Locally Advanced Pancreatic Cancer (LAPC) patients receiving Stereotactic Body Radiation Therapy (SBRT). Methods: In retrospective analysis of an IRB approved database, 183 BRPC and LAPC patients treated with SBRT from 2009-2016 met our selection criteria. Patients underwent gemcitabine based or FOLFIRINOX chemotherapy for 3 months prior to SBRT. Eligible patients were those with pre-SBRT planning CT imaging on Pinnacle, a treatment planning system, and an identifiable L4 vertebra. Bilateral psoas muscles were manually contoured at the L4 vertebral level. This area was normalized by patient height (median = 876.505 mm2/m). ROC curves were created for TPA, BMI and BSA. Toxicities were evaluated by binomial logistic regression; survival functions were evaluated by Kaplan-Meier. Significance was set at p &lt; 0.05. Results: Low TPA (OR = 1.903, p = 0.036) and BSA (OR = 1.836 p = 0.048) were predictive of acute toxicities but only TPA was predictive of Grade 3+ acute toxicities (OR = 10.24, p = 0.040). Both findings were independent of tumor resectability. No association was found between TPA/BMI/BSA and late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median = 21.98 months) than their LAPC (median = 16.2 months) counterparts (p = 0.002), independent of nutritional status. Conclusions: Pre-SBRT TPA measurement is readily available and more specific than BMI or BSA as a predictor of serious acute radiotoxic complications following SBRT in BRPC/LAPC patients. However, tumor resectability remains as the only predictor of overall survival in this cohort. Whether initial pre-chemo TPA may predict acute toxicity related to chemotherapy and guide individualization of systemic regimen warrants further investigation.

Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract.

Obesity is an increasingly common problem worldwide and a risk factor for a variety of gastrointestinal (GI) diseases, both non-neoplastic (e.g. gastro-oesophageal reflux and Barrett's oesophagus) and neoplastic (e.g. oesophageal adenocarcinoma, colorectal carcinoma, and gallbladder cancer). Furthermore, obesity is associated with worse GI cancer outcomes. Body mass index is a commonly used measure of fat accumulation, although specific patterns such as abdominal/central obesity and visceral fat quantity sometimes predict disease risk more accurately. Metabolic syndrome (MS) is a related condition characterized by central adiposity and insulin resistance. The reasons for the associations with neoplasia are diverse. Established cancer-related conditions that have a higher prevalence in overweight subjects include Barrett's oesophagus and gallstones. Preneoplastic lesions such as colorectal adenoma, colorectal serrated lesions and pancreatic intraepithelial neoplasia are also associated with obesity/MS. At the cellular level, adipocytes can release carcinogens such as adipokines, insulin-like growth factor, and vascular endothelial growth factor. Inflammatory cells constitute a further potential source of carcinogens; in obese subjects, their numbers are increased systemically and in adipose tissue. Animal studies have contributed additional information. For example, mice with a genetic predisposition to develop colorectal carcinoma given a high-fat diet have larger and more numerous intestinal adenomas than controls, and there may be demonstrably higher levels of mucosal oncogenic factors. The associations between obesity and GI disease are of variable strength, and the underlying mechanisms are incompletely understood, but it is clear that obesity and MS have a significant, potentially avoidable and often under-recognized impact on the population burden of GI disease.

Plasma N-acetyl-glucosaminidase in advanced gastro-intestinal adenocarcinoma correlates with age, stage and outcome.

N-acetyl-glucosaminidase (NAG) is a potential marker of genotoxicity. We retrospectively analyzed plasma NAG and clinico-pathologic features in advanced gastrointestinal adenocarcinoma patients. Plasma from 118 patients and 51 healthy volunteers was analyzed for associations between NAG levels and age, disease presence, stage, treatment responses and survival. Pretreatment NAG correlated with age but was independently increased in metastatic versus locally advanced disease, particularly in gastric/esophageal patients. NAG was also associated with reduced overall survival. In subgroup analysis, increased NAG activity between day 1 and 2 of chemotherapy cycle 1 correlated with treatment response. We demonstrated that NAG correlates with gastrointestinal cancer outcomes. Further studies are required to determine if plasma markers of genotoxicity can be useful for disease monitoring.

Natural history of venous thromboembolism in gastrointestinal cancers.

593 Background: Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer. Characterisation of VTE in cancer will guide prophylactic anti-coagulation of high risk populations. Methods: We performed a retrospective analysis using electronic patient records, of 910 upper GI (UGI) cancer and 1,299 colorectal cancer (CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its relationship to chemotherapy and impact on survival. VTE risk scores were calculated using the Khorana index (Khorana AA et al. Blood 2008 May 15;111(10):4902-7). Results: VTE were identified in 88/910 (9.7%) patients with UGI cancer (oesophageal 37%, gastro-oesophageal 24%, gastric 39%), comprising 50 deep vein thromboses (DVT) and 43 pulmonary emboli (PE). 52% were stage I-III and 48% stage IV. 56% of patients received chemotherapy up to 4 weeks before VTE. Median time to VTE from cancer diagnosis was 5.3 months (range -3 to 31.2). No difference in survival was seen for patients with VTE compared to a stage matched control group without VTE (median OS 12.5 v 9.4 months, log rank p=0.2). VTE (DVT:PE, 69:49) affected 115/1299 (8.9%) patients with CRC (25% stage I-III, 75% stage IV). Median time to VTE from CRC diagnosis was 5.4 months (range -4.3 to 54.5) for stage I-III and 8.6 months (range -4.3 to 77) for stage IV CRC. Chemotherapy was received by 41% (stage I-III) and 78% (stage IV) of patients within 4 weeks before VTE. Data to perform VTE risk score were available for 72/115 CRC patients with VTE, which classified 61.1% as low-risk (stage I-III 81.2% (13/16); stage IV 55.3% (31/56)). Again, no difference in survival was seen for patients with VTE compared to a control group without VTE matched for stage and performance status (median OS for stage I-III, 40 vs. 50.3 months p=0.41; stage IV, 20.7 vs. 18.8 months, p=0.52). Conclusions: VTE affects nearly 1 in 10 patients with GI cancer receiving chemotherapy. The peak incidence is in the first 6 months following diagnosis. Most patients have DVT and 36% are asymptomatic. No adverse impact on survival was seen for patients with VTE compared to stage matched controls implying VTE is not a prognosticator of poor outcomes in gastrointestinal cancers. Mature data will be presented at the meeting.

Outcomes of laparoscopic colon cancer surgery in a population-based cohort in British Columbia: are they as good as the clinical trials?

BackgroundRandomized controlled trials have shown equivalent outcomes for laparoscopic-assisted colectomy (LAC) and open colectomy (OC) when performed by well-trained surgeons experienced in both techniques. Our goal was to evaluate the outcomes of LAC at a population level. MethodsUsing the prospectively collected Gastrointestinal Cancer Outcomes Unit database from the British Columbia Cancer Agency, short- and long-term outcomes in patients with colon cancer treated with LAC and OC were compared from 2003 to 2008 inclusive. ResultsThere was a statistically significant increase in the proportion of LAC from 2003 to 2008 (P < .001). LAC was more likely to be performed in the elective setting (P < .001) and for smaller tumors (P < .001). A similar proportion of patients had a minimum of 12 lymph nodes identified by pathology (58% vs 60%, P = not significant). Disease-free survival was similar for the 2 groups after adjusting for stage, emergency presentation, and adjuvant chemotherapy. There was no difference in overall survival. ConclusionsThe introduction of LAC for colon cancer in British Columbia outside of optimized clinical trial conditions appears to be effective and safe.