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BACKGROUND The COVID-19 pandemic led to the rapid implementation of remote work, but few studies have examined the impact. We evaluated clinical staff experience with working remotely at a large, urban comprehensive cancer center in Toronto, Canada. METHODS An electronic survey was disseminated between June 2021, and August 2021, via e-mail to staff who had completed at least some remote work during the COVID-19 pandemic. Factors associated with a negative experience were examined with binary logistic regression. Barriers were derived from a thematic analysis of open-text fields. RESULTS Most respondents (N = 333; response rate, 33.2%) were age 40-69 years (46.2%), female (61.3%), and physicians (24.6%). Although the majority of respondents wished to continue remote work (85.6%), relative to administrative staff (admin), physicians (odds ratio [OR], 16.6; 95% CI, 1.45 to 190.14) and pharmacists (OR, 12.6; 95% CI, 1.0 to 158.9) were more likely to want to return on-site. Physicians were approximately eight times more likely to report dissatisfaction with remote work (OR, 8.4; 95% CI, 1.4 to 51.6) and 24 times more likely to report that remote work negatively affected efficiency (OR, 24.0; 95% CI, 2.7 to 213.0); nurses were approximately seven times more likely to report the need for additional resources (OR, 6.5; 95% CI, 1.71 to 24.48) and/or training (OR, 7.02; 95% CI, 1.78 to 27.62). The most common barriers were the absence of fair processes for allocation of remote work, poor integration of digital applications and connectivity, and poor role clarity. CONCLUSION Although overall satisfaction with working remotely was high, work is needed to overcome barriers to implementation of remote and hybrid work models in the health care setting.

We report herein an exploratory biomarker analysis of refractory tumors collected from pediatric patients before atezolizumab therapy (iMATRIX-atezolizumab, NCT02541604). Elevated levels of CD8+ T cells and PD-L1 were associated with progression-free survival and a diverse baseline infiltrating T-cell receptor repertoire was prognostic. Differential gene expression analysis revealed elevated expression of CALCA (preprocalcitonin) and CCDC183 (highly expressed in testes) in patients who experienced clinical activity, suggesting that tumor neoantigens from these genes may contribute to immune response. In patients who experienced partial response or stable disease, elevated Igα2 expression correlated with T- and B-cell infiltration, suggesting that tertiary lymphoid structures existed in these patients’ tumors. Consensus gene co-expression network analysis identified core cellular pathways that may play a role in antitumor immunity. Our study uncovers features associated with response to immune-checkpoint inhibition in pediatric patients with cancer and provides biological and translational insights to guide prospective biomarker profiling in future clinical trials.

4057 Background: While several clinical scoring systems exist to aid prognostication and patient (pt) selection for clinical trials in oncology, none are standardly used. We compared the ability of four prognostic scores to predict overall survival (OS) in pts with advanced gastric and esophageal (GE) cancer. Methods: Pts with advanced (unresectable or metastatic) GE cancer receiving first-line palliative-intent systemic therapy at the Princess Margaret Cancer Centre from 2007 to 2020 were included. High prognostic risk pts were identified using four scoring systems: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune Score (GRIm-S) and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) score. OS was estimated using the Kaplan-Meier method and compared between risk groups (high vs. not-high) for each scoring system using the log-rank test. Cox proportional hazards models were used to analyze the association between each prognostic score and OS, adjusting for baseline clinical factors. Harrell’s c-index was used to evaluate predictive discrimination of the models. Time-dependent AUCs were used to measure predictive ability for early death (within 90 days). Results: In total, 451 pts with advanced GE cancer were included. The median age was 59 years, 68% were male, 51% had ECOG status 0-1, 63% presented with de novo metastatic disease. The proportion of pts categorized as high risk was: RMH 25% (N=113), MDACC 13% (N=95), GRIm-S 24% (N=109), MDA-ICI 26% (N=117). In all scoring systems, high risk pts had significantly shorter OS (median OS 7.9 versus 12.2 months for RMH high vs. low risk, p

Background Lung cancer is the leading cause of cancer mortality globally. Early detection through risk-based screening can markedly improve prognosis. However, most risk models were developed in North American cohorts of smokers, whereas less is known about risk profiles for never-smokers, which represent a growing proportion of lung cancers, particularly in Asian populations. Methods Based on the China Kadoorie Biobank, a population-based prospective cohort of 512 639 adults with up to 12 years of follow-up, we built Asian Lung Cancer Absolute Risk Models (ALARM) for lung cancer mortality using flexible parametric survival models, separately for never and ever-smokers, accounting for competing risks of mortality. Model performance was evaluated in a 25% hold-out test set using the time-dependent area under the curve and by comparing model-predicted and observed risks for calibration. Results Predictors assessed in the never-smoker lung cancer mortality model were demographics, body mass index, lung function, history of emphysema or bronchitis, personal or family history of cancer, passive smoking, and indoor air pollution. The ever-smoker model additionally assessed smoking history. The 5-year areas under the curve in the test set were 0.77 (95% confidence interval = 0.73 to 0.80) and 0.81 (95% confidence interval = 0.79 to 0.84) for ALARM-never-smokers and ALARM-ever smokers, respectively. The maximum 5-year risk for never and ever-smokers was 2.6% and 12.7%, respectively. Conclusions This study is among the first to develop risk models specifically for Asian populations separately for never and ever-smokers. Our models accurately identify Asians at high risk of lung cancer death and may identify those with risks exceeding common eligibility thresholds who may benefit from screening.

Case-control studies have shown that patients with Crohn's disease (CD) have a microbial composition different from healthy individuals. Although the causes of CD are unknown, epidemiologic studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. We hypothesized that long-term dietary clusters (DCs) are associated with gut microbiome compositions and gut inflammation. Our objectives were to identify dietary patterns and assess whether they are associated with alterations in specific gut microbial compositions and subclinical levels of gut inflammation in a cohort of healthy first-degree relatives (FDRs) of patients with CD.As part of the Genetic, Environmental, Microbial (GEM) Project, we recruited a cohort of 2289 healthy FDRs of patients with CD. Individuals provided stool samples and answered a validated food frequency questionnaire reflecting their habitual diet during the year before sample collection. Unsupervised analysis identified 3 dietary and 3 microbial composition clusters.DC3, resembling the Mediterranean diet, was strongly associated with a defined microbial composition, with an increased abundance of fiber-degrading bacteria, such as Ruminococcus, as well as taxa such as Faecalibacterium. The DC3 diet was also significantly associated with lower levels of subclinical gut inflammation, defined by fecal calprotectin, compared with other dietary patterns. No significant associations were found between individual food items and fecal calprotectin, suggesting that long-term dietary patterns rather than individual food items contribute to subclinical gut inflammation. Additionally, mediation analysis demonstrated that DC3 had a direct effect on subclinical inflammation that was partially mediated by the microbiota.Overall, these results indicated that Mediterranean-like dietary patterns are associated with microbiome and lower intestinal inflammation. This study will help guide future dietary strategies that affect microbial composition and host gut inflammation to prevent diseases.

Background Surgical resection following neoadjuvant therapy with either chemotherapy or chemoradiotherapy remains the cornerstone of curative management of oesophageal cancer. In spite of this, there remains uncertainty regarding the optimal radicality of lymphadenectomy, and whether increasing lymph node yields confer a true survival benefit. This study aims to assess the impact of lymph node yield and lymph node ratio on survival following surgery for oesophageal cancer, in addition to identifying factors that may influence lymph node yield and radicality of resection. Methods Patients in a single centre undergoing oesophagectomy with curative intent from January 1, 2010 to December 31, 2020 were reviewed. Clinical and pathological variables were assessed, with univariable, multivariable, regression and survival analyses performed as appropriate. Regression with cut-point analysis was used to determine the optimal cut-off for lymph node ratio and for minimum number of nodes resected. Results Three hundred and ninety-seven patients underwent oesophagectomy in the study period, with 288 of these having a minimally invasive operation (MIE). Stage (stage 3 HR: 1.64 (1.02–2.62), p=0.04, stage 4 HR: 2.50 (1.43–5.01), p=0.001), positive margin status (HR: 2.62 (1.57–4.36), p Conclusions Lymphadenectomy is a cornerstone of resection of oesophageal cancer. Low lymph node yield and high lymph node ratio are associated with reduced overall survival. A lymph node ratio of

Germline variants might predict cancer progression. Bevacizumab improves overall survival (OS) in patients with advanced cancers. No biomarkers are available to identify patients that benefit from bevacizumab. A meta-analysis of genome-wide association studies (GWAS) was conducted in 1,520 patients from Phase III trials (CALGB 80303, 40503, 80405 and ICON7), where bevacizumab was randomized to treatment without bevacizumab. We aimed to identify genes and single nucleotide polymorphisms (SNPs) associated with survival independently of bevacizumab treatment or through interaction with bevacizumab. A cause-specific Cox model was used to test the SNP-OS association in both arms combined (prognostic), and the effect of SNPs-bevacizumab interaction on OS (predictive) in each study. The SNP effects across studies were combined using inverse variance. Findings were tested for replication in advanced colorectal and ovarian cancer patients from The Cancer Genome Atlas (TGCA). In the GWAS meta-analysis, patients with rs680949 in PRUNE2 experienced shorter OS compared to patients without it (P = 1.02 × 10-7 , hazard ratio [HR] = 1.57, 95% confidence interval [CI] 1.33-1.86), as well as in TCGA (P = .0219, HR = 1.58, 95% CI 1.07-2.35). In the GWAS meta-analysis, patients with rs16852804 in BARD1 experienced shorter OS compared to patients without it (P = 1.40 × 10-5 , HR = 1.51, 95% CI 1.25-1.82) as well as in TCGA (P = 1.39 × 10-4 , HR = 3.09, 95% CI 1.73-5.51). Patients with rs3795897 in AGAP1 experienced shorter OS in the bevacizumab arm compared to the nonbevacizumab arm (P = 1.43 × 10-5 ). The largest GWAS meta-analysis of bevacizumab treated patients identified PRUNE2 and BARD1 (tumor suppressor genes) as prognostic genes of colorectal and ovarian cancer, respectively, and AGAP1 as a potentially predictive gene that interacts with bevacizumab with respect to patient survival.

Surgical resection following neoadjuvant therapy remains the cornerstone of curative management of esophageal cancer. In spite of this, there remains uncertainty regarding the optimal radicality of lymphadenectomy, and whether increasing lymph node yields confer a true survival benefit. This study aims to assess the impact of lymph node (LN) yield and LN ratio on survival following surgery for esophageal cancer, in addition to identifying factors that may influence LN yield and radicality of resection. All patients undergoing esophagectomy with curative intent from January 1, 2010 to December 31, 2020 were reviewed. Clinical and pathological variables were assessed, with univariable, multivariable, regression and survival analyses performed as appropriate. Cutpoint analysis was used to determine the optimal lymph node ratio. 397 patients underwent esophagectomy, with 288 having a minimally invasive operation (MIE). Stage (stage 3 HR: 1.64 (1.02–2.62), p = 0.04, stage 4 HR: 2.50 (1.43–5.01), p = 0.001), margin status (HR: 2.62 (1.57–4.36), p Lymphadenectomy is a cornerstone of resection of esophageal cancer. Low LN yield and high LN ratio are associated with reduced overall survival. Maintaining a LN yield >15 should remain a key quality metric. A LN ratio of

MRI quantification of liver iron concentration (LIC) using R2 or R2* relaxometry requires offline post-processing causing reporting delays, administrative overhead, and added costs. A prototype 3D multi-gradient-echo pulse sequence, with inline post-processing, allows immediate calculation of LIC from an R2* map (inline R2*-LIC) without offline processing. We compared inline R2*-LIC to FerriScan and offline R2* calibration methods. Forty patients (25 women, 15 men; age 18–82 years), prospectively underwent FerriScan and the prototype sequence, which produces two R2* maps, with and without fat modeling, as well as an inline R2*-LIC map derived from the R2* map with fat modeling, with informed consent. For each map, the following contours were drawn: ROIs, whole-axial-liver contour, and an exact copy of contour utilized by FerriScan. LIC values from the FerriScan report and those calculated using an alternative R2 calibration were the reference standards. Results were compared using Pearson and interclass correlation coefficients (PCC, ICC), linear regression, Bland-Altman analysis, and estimation of area under the receiver operator curve (ROC-AUC). Inline R2*-LIC demonstrated good agreement with the reference standards. Compared to FerriScan, inline R2*-LIC with whole-axial-liver contour, ROIs, and FerriScan contour demonstrated PCC of 94.8%, 94.8%, and 92%; ICC 93%, 92.7%, and 90.2%; regression slopes 1.004, 0.974, and 1.031; mean bias 5.54%, 10.91%, and 0.36%; and ROC-AUC estimates 0.903, 0.906, and 0.890 respectively. Agreement was maintained when adjusted for sex, age, diagnosis, liver fat content, and fat-water swap. Inline R2*-LIC provides robust and comparable quantification of LIC compared to FerriScan, without the need for offline post-processing. • In patients being treated for iron overload with chelation therapy, liver iron concentration (LIC) is regularly assessed in order to monitor and adjust therapy. • Magnetic resonance imaging (MRI) is commonly used to quantify LIC. Several R 2 and R 2 * methods are available, all of which require offline post-processing. • A novel R 2 * MRI method allows for immediate calculation of LIC and provides comparable quantification of LIC to the FerriScan and recently published alternative R 2 * methods.

OBJECTIVE. The purpose of the present study was to compare the diagnostic performance of an abbreviated MR enterography (MRE) protocol consisting of balanced steady-state free-precession (b-SSFP) imaging only versus standard full-protocol MRE for the evaluation of Crohn disease activity. MATERIALS AND METHODS. This single-center retrospective study included 112 patients with Crohn disease (66 women and 46 men; age range, 18-84 years) who underwent MRE between January 2017 and March 2018. Utilizing binary and 5-point Likert confidence scales, two blinded readers independently interpreted and scored disease activity on b-SSFP sequences only and on full-protocol MRE images. Interreader and intrareader agreement on confidence regarding disease activity were calculated using weighted kappa indexes. Correlation between MRE findings of Crohn disease and the Harvey-Bradshaw index was also performed. RESULTS. Perfect intrareader agreement and strong interreader agreement on disease activity were observed (intrareader agreement: κ = 0.97, 0.96, and 0.96 for reader A, reader B, and both readers combined; interreader agreement: κ = 0.82 for b-SSFP imaging only and κ = 0.81 for MRE). For detecting active Crohn disease, b-SSFP sequences had a sensitivity and specificity of 97% and 100%, respectively, for reader A and 98% and 86%, respectively, for reader B. Strong-to-perfect intrareader agreement was achieved between b-SSFP imaging only and MRE for identification of penetrating disease (κ = 0.80 and 0.97) and stenosing disease (κ = 0.87 and 0.95). Perfect intrareader agreement was also obtained between b-SSFP imaging only and MRE for detecting abnormal bowel segments (κ = 0.91 for reader A; κ = 0.98 for reader B). Weak agreement was noted between both b-SSFP imaging only and MRE versus the Harvey-Bradshaw index (κ = 0.08 of reader A; κ = 0.04 for reader B). CONCLUSION. Robust agreement was observed between b-SSFP imaging only and full-protocol MRE for the assessment of Crohn disease activity and complications. An abbreviated MRE protocol that exclusively uses b-SSFP sequences appears feasible and has significant implications for health care resources.

Background Malnutrition and sarcopenia are poor prognostic factors in many cancers. Studies in gastric and esophageal (GE) cancer have focused on curative intent patients. This study aims to evaluate the prognostic utility of malnutrition and sarcopenia in de novo metastatic GE adenocarcinoma. Methods Patients with de novo metastatic GE adenocarcinoma seen at the Princess Margaret Cancer Centre from 2010 to 2016 with an available pre‐treatment abdominal computed tomography (CT) were included. Malnutrition was defined as nutritional risk index (NRI), In de novo metastatic gastric and esophageal adenocarcinoma patients, ECOG, pre‐treatment nutritional risk index (NRI) and change in NRI during treatment were significant prognostic factors for overall survival while sarcopenia was not. Use of NRI at baseline and during treatment can provide useful prognostic information.

BackgroundLung cancer is the leading cause of cancer mortality globally. Early detection through screening can markedly improve prognosis and prediction models can identify high-risk individuals for risk-based screening. However, most models have been developed in North American cohorts of smokers and much less is known about risk factors for never-smokers, which represent a growing proportion of lung cancers, particularly for Asian populations.MethodsBased on the China Kadoorie Biobank, a population-based prospective cohort study of 512,639 adults age 30-79 recruited between 2004-2008 with up to 12 years of follow-up, we built an Asian Lung Cancer Absolute Risk Model (ALARM) for lung cancer mortality using flexible parametric survival models, separately for ever- and never-smokers, accounting for competing risks of all-other-cause mortality. Model performance was evaluated in a 25% hold-out test set using the time-dependent area under the receiver operating characteristic curve (AUC) and by comparing the model-predicted and observed risks for model calibration.ResultsPredictors assessed in the never-smoker lung cancer mortality model were age, sex, household income, lung function, history of emphysema/bronchitis, family history of cancer, personal cancer history, BMI, passive smoking, and indoor air pollution. The ever-smoker model additionally assessed smoking status (former vs. current), duration, and intensity. The 5-year AUC based on the hold-out test set for the never and ever-smoker models were 0.77 (95% CI: 0.73-0.80) and 0.81 (95% CI: 0.79-0.84), respectively. The maximum 5-year risk for never and ever smokers were 2.6% and 12.7%, respectively.ConclusionsThis study is among the first to develop and test risk models specifically for Asian populations, separately for never (ALARM-NS) and ever-smokers (ALARM-ES). Our models identify Asian never- and ever-smokers at high-risk of death due to lung cancer with a high degree of accuracy and may identify those with risks exceeding common eligibility thresholds who would likely benefit from lung cancer screening.

Introduction: Metastatic gastroesophageal adenocarcinoma (GEA) is a heterogeneous disease with an overall poor prognosis. The impact of sites of metastatic dissemination on survival is not well characterized. This study aimed to evaluate whether certain sites of metastatic disease impacts survival. Methods: A retrospective analysis of 375 patients with metastatic GEA treated at the Princess Margaret Cancer Centre from 2006 to 2016 was performed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association between sites of metastases and OS adjusting for baseline patient characteristics. Results: Median duration of follow-up was 47.8 months. Median OS in this cohort was 11.8 months (95% CI: 10.2–12.9 months). Patients with lymph node only disease, compared to those with other sites of metastases, had the longest median OS (20.4 vs. 10.6 months; p < 0.001) and PFS (11.4 vs. 6.3 months; p < 0.001). On multivariable analysis adjusting for relevant clinical factors including age, sex, and Eastern Cooperative Oncology Group performance status, the presence of lung (HR 1.67, 95% CI: 1.23–2.26; p < 0.001) or bone metastases (HR 1.84, 95% CI: 1.31–2.59; p < 0.001) were independently associated with shorter OS. The majority of patients (68%) were treated with palliative intent first-line platinum-based chemotherapy. Discussion/Conclusion: Patients with metastatic GEA have an overall poor prognosis. The presence of lung or bone metastases is an independent risk factor for decreased survival. Prognostic models incorporating sites of metastasis should be considered in the clinical evaluation of metastatic GEA.

To determine whether EORTC QLQ-C30/QLQ-OG25 and FACT-E compared longitudinally provide similar reflections of health-related quality of life (HRQOL). Eighty-six esophageal cancer patients treated with curative intent, scheduled to complete both questionnaires at baseline and post-treatment time points until 36 months. A generalized estimating equation model utilizing a Gaussian family compared instruments longitudinally. The two-one-sided-test (TOST) method assessed equivalence between the instruments. Trajectories for social domain and overall quality of life differed significantly between instruments. Also, FACT-G’s functional well-being post-treatment returns to baseline 3–6 months earlier than the EORTC QLQ-C30’s role functioning subscale, suggesting measurement of different components. Trajectories for physical and esophageal symptom subscales are similar and are deemed equivalent. Emotional domains are comparable and bear little resemblance to the physical domain trajectories indicating reflection of emotional experience rather than a physical proxy. EORTC QLQ-C30 subscales have a trajectory similar to its physical functioning scale except for the emotional and esophageal symptoms scales. Overall HRQOL in both instruments showed a consistent return to baseline/pre-treatment levels by 6 months post-treatment. Overall HRQOL recovers earlier after curative-intent treatment than previously reported despite persistence of physical symptoms, with a consistent return to pre-treatment levels by 6 months after treatment. This supports the concept that HRQOL is not primarily defined by physical function. Based on this longitudinal comparison, FACT-E provides a more multidimensional assessment of HRQOL. Curative intent treatment for esophageal cancer has adverse effects on HRQOL but despite intense treatment, overall HRQOL recovers within 6 months.

Background: Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. Methods: A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. Results: Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (n = 67; 72%) or dCRT (n = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; p = 0.001; HR 3.1; 95% CI: 1.2–7.7) and DFS (0 vs. 41%; p = 0.004; HR 3.6; 95% CI: 1.4–8.9) on multivariable and IPTW sensitivity analyses. Conclusions: TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.

BACKGROUND: A microscopically positive (R1) resection margin following resection for gastric and esophageal cancers has been documented to be a poor prognostic factor. The optimal strategy and impact of different modalities of adjuvant treatment for an R1 resection margin remain unclear. METHODS: A retrospective analysis was performed for patients with gastric and esophageal adenocarcinoma treated at the Princess Margaret Cancer Centre (PMCC) from 2006–2016. Electronic medical records of all patients with an R1 resection margin were reviewed. Kaplan-Meier and Cox proportional hazards methods were used to analyze recurrence free survival (RFS) and overall survival (OS) with stage and neoadjuvant treatment as covariates in the multivariate analysis. RESULTS: We identified 69 gastric and esophageal adenocarcinoma patients with a R1 resection. Neoadjuvant chemoradiation was used in 13% of patients, neoadjuvant chemotherapy in 12%, surgery alone in 75%. Margins involved included proximal in 30%, distal in 14%, radial in 52% and multiple margins in 3% of patients. Pathological staging showed 3% with stage I disease, 20% stage II and 74% stage III. Adjuvant therapy was given in 52% of R1 pts (28% CRT, 20% chemotherapy alone, 3% radiation alone, 1% reoperation). Median RFS was 14.1 months [95% confidence interval (CI), 11.1–17.2]. The site of first recurrence was 72% distant, 12% mixed, 16% locoregional alone. Median OS was 34.5 months (95% CI, 23.3–57.9) for all patients. There was no significant difference in RFS (adjusted P=0.26) or OS (adjusted P=0.83) comparing modality of adjuvant therapy. CONCLUSIONS: Most patients with positive margins after resection for gastric and esophageal cancer had advanced pathologic stage and prognosis was poor. Our study did not find improved RFS or OS with adjuvant treatment and only one patient had reresection. The main failure pattern was distant recurrence, suggesting that patients being considered for adjuvant radiotherapy (RT) should be carefully selected. Further studies are required to determine factors to select patients with good prognosis despite a positive margin, or those who may benefit from adjuvant treatment.

Background The goal of surveillance testing is to enable curative salvage therapy through early disease detection, however supporting evidence in gastroesophageal adenocarcinoma is limited. We evaluated frequency of successful salvage therapy and outcomes in patients who underwent surveillance. Methods A single‐site, retrospective cohort study was conducted to identify all patients who received curative resection for gastroesophageal adenocarcinoma. Surveillance testing were those investigations not triggered by abnormal symptoms, physical examination, or blood tests. Successful salvage therapy was any potentially curative therapy for disease recurrence which resulted in postrecurrence disease‐free survival ≥2 years. Time‐to‐event data were analyzed using the Kaplan‐Meier method and log rank tests. Results Between 2011 and 2016, 210 consecutive patients were reviewed. Esophageal (14%), gastroesophageal junction (40%), and gastric adenocarcinomas (45%) were treated with surgery alone (29%) or multimodality therapy (71%). Adjuvant therapy was administered in 35%. At median follow‐up of 38.3 months, 5‐year overall survival (OS) rate was 56%. Among 97 recurrences, 53% were surveillance‐detected, and 46% were symptomatic. None was detected by surveillance endoscopy. Median time‐to‐recurrence (TTR) was 14.8 months. Recurrences included locoregional only (4%), distant (86%), and both (10%). Salvage therapy was attempted in 15 patients, 4 were successful. Compared to symptomatic recurrences, patients with surveillance‐detected recurrences had longer median OS (36.2 vs 23.7 months, P = .004) and postrecurrence survival (PRS, 16.5 vs 4.6 months, P, For resected gastroesophageal adenocarcinoma treated at our institution, routine surveillance testing rarely enabled successful salvage therapy, did not detect recurrence earlier, and did not extend duration of palliative chemotherapy. Further prospected data is warranted to establish the role of surveillance testing in gastroesophageal adenocarcinoma.

Purpose Intestinal stem cell markers play a significant role in esophageal adenocarcinoma carcinogenesis via Barrett's esophagus; however, its utility as a prognostic biomarker has not been established. Methods We analyzed the immunohistochemical expression of intestinal stem cell markers, ASCL2 and LGR5, using whole slides (35 cases) and tissue microarray (TMA; 64 cases). On TMA slides, adjacent normal squamous epithelium, metaplastic glandular epithelium (Barrett's esophagus), and dysplastic glandular epithelium were inserted when applicable. Two pathologists semi-quantitatively scored stained slides independently, and the results were correlated with clinicopathologic factors and outcomes. Results In whole slides, 51% and 57% expressed high ASCL2 and high LGR5; in TMA, 69% and 88% expressed high ASCL2 and high LGR5, respectively. In TMA, high ASCL2 and low LGR5 expression significantly correlated to a higher number of involved lymph nodes (p=0.027 and p=0.0039), and LGR5 expression significantly correlated to the pathological stage (p=0.0032). Kaplan-Meier analysis showed a negative impact of high ASCL2 expression on overall survival (OS; WS p=0.0168, TMA p=0.0276) as well as progression-free survival (PFS; WS p=0.000638, TMA p=0.0466) but not LGR5. Multivariate Cox regression analysis revealed that ASCL2 expression is an independent prognostic factor for esophageal adenocarcinoma (OS; WS p=0.25, TMA p=0.011. PFS; WS p=0.012, TMA p=0.038). Analysis of the TCGA dataset showed that ASCL2 mRNA levels were correlated to nodal status but not overall survival. Conclusion High expression of the intestinal stem cell marker ASCL2 may predict unfavorable outcomes in surgically resected esophageal adenocarcinoma.

ObjectiveThe measure of serum proteome in the preclinical state of Crohn’s disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.DesignIn a nested case–control study within the Crohn’s and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay.ResultsWe identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (qConclusionWe identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.

302 Background: The majority of esophageal and gastric cancers are diagnosed at an advanced stage with poor overall survival (OS), leading some to propose screening, even in countries with a low incidence. Whether diagnostic delay from symptom onset has any impact on OS is unclear. We investigated this question in the peri-COVID19 pandemic era. Methods: We retrospectively analyzed a cohort of 308 patients with esophageal, gastroesophageal junction, or gastric carcinoma treated with curative intent at the Princess Margaret Cancer Centre from January 2017 to December 2021. Clinical details pertaining to the initial presentation were determined through a retrospective chart review. OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association between pre-diagnostic interval with OS adjusting for baseline patient characteristics. Results: The median interval from symptom onset to diagnosis was 98 days (IQR 47-169 days). Using a cox proportional hazard model, prolonged pre-diagnostic interval was not associated with worse OS (HR 1.00, P=0.62). Comparing patients diagnosed before and during the COVID19 pandemic, there was a notable increase in diagnostic delay with median pre-diagnostic interval increasing from 92 to 126 days (P=0.007). Median age at time of diagnosis was 69.6 during the pandemic vs 64.7 before the pandemic. Linear regression showed squamous cell histology was significantly associated with increasing time to initial diagnosis (P=0.04). Looking at other delay metrics, there were no changes in time interval from diagnosis to treatment during versus before the pandemic (median = 1.7 weeks for both), and there was no change in time from diagnosis to resection in those patients who underwent surgery. Conclusions: The COVID19 pandemic caused significant diagnostic delay for patients presenting with curative esophageal and gastric cancer. We found no evidence of pandemic-related health system delays in treatment, once a diagnosis was made. The lack of correlation of pre-diagnostic interval with OS may reflect underlying tumour biology as the driving force that determines prognosis.