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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: Gender differences may contribute to variations in disease presentations and health outcomes. To explore the gender difference in pain and patient reported outcomes in cancer patients with bone metastases undergoing palliative radiotherapy on the National Cancer Institute of Canada (NCIC) SC.23 randomized trial. Methods: Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) bone metastases module (QLQ-BM22) and EORTC QOL Core-15-Palliative (QLQ-C15-PAL) before treatment and at days 10 and 42 after a single 8 Gy radiation treatment. Patient demographics, performance status, analgesic consumption, BM22 and C15 were compared between males and females using the 2-sample t-test for continuous variables or the Chi-squared test for categorical variables. Multiple linear regression models were used to check the difference between gender groups adjusting for the baseline demographics and primary disease sites. Results: There were 298 patients (170 male, 128 female) with median age of 69 years. The most common primary cancer sites were lung, prostate and breast. At baseline, there were no differences in BM22 and C15 scores, except a worse nausea and vomiting score (P=0.03) in females on the C15. In patients with moderate baseline worst pain scores (WPS), females reported worse scores in painful sites of BM22. At day 42, there was no significant difference in response to radiotherapy. Among the responders, females reported better improvement in emotional aspect. Conclusions: In cancer patients with bone metastases undergoing palliative radiotherapy, the majority of symptom presentations, patient reported outcomes, and response to radiation was not significantly different between genders. Trial registration: NCT01248585.

Palliative radiotherapy (RT) is effective in patients with painful bone metastases. Genetic factors may identify subgroup of patients who responded to RT. To identify DNA biomarkers associated with response to palliative RT.Patients who received a single 8 Gy dose of RT for painful bone metastases were categorised into responders (n=36), non-responders (NR) (n=71). Saliva samples were sequenced to identify single-nucleotide variants (SNVs) in genes with known disease-causing variants from inflammation, radiation response, and DNA damage pathways. In univariate analysis, Cochran-Armitage trend tests were used to identify SNVs that associated with pain response (P0.005), and the Penalized LASSO method with minimum Bayesian Information Criterion was used to identify multi-SNVs that jointly predict pain response to RT. The corresponding estimated effect of the multi-SNVs were used to drive the prognostic score for each patient. Based on it, patients were divided into 3 equal size risk groups.Forty-one significant variants were identified in univariate analysis. Multivariable analysis selected 14 variants to generate prognostic scores, adjusting for gender and primary cancer site. Eighty-nine percent of patients in the high prognostic group responded to palliative radiation therapy (P=0.0001). Estimated effect sizes of the variants ranged from 0.108-2.551. The most statistically significant variant was a deletion at position 111992032 in the ataxin gene ATXN2 (P=0.0001). Five variants were non-synonymous, including AOAH rs7986 (P=0.0017), ZAN rs539445 (P=0.00078) and rs542137 (P=0.00078), RAG1 rs3740955 (P=0.0014), and GBGT1 rs75765336 (P=0.0026).SNVs involved in mechanisms including DNA repair, inflammation, cellular adhesion, and cell signalling have significant associations with radiation response. SNVs with predictive power may stratify patient populations according to likelihood of responding to treatment, therefore enabling more efficient identification of beneficial strategies for pain management and improved resource utilisation.

Background: Functional Assessment of Cancer Therapy-Esophagus (FACT-E) is a health-related quality of life (HRQOL) instrument validated in patients with esophageal cancer. It is made up of both a general component and an esophageal cancer subscale (ECS). Our objective was to explore the relationship between baseline FACT-E, ECS and clinically determined T-stage in patients with stage II–IV cancer of the gastroesophageal junction or thoracic esophagus. Methods: Data from four prospective studies in Canadian academic hospitals were combined. These were consecutive and eligible patients treated between 1996 and 2014 with clinical stage II–IV cancer of the gastroesophageal junction or thoracic esophagus. All patients completed pre-treatment FACT-E. Parametric (ANOVA) and non-parametric (Kruskal-Wallis) analyses were performed. Results: Of the 135 patients that were deemed eligible, the T-stage distribution determined clinically was: 10 (7.4%) T1, 33 (24.4%) T2, 79 (58.5%) T3 and 13 (9.6%) T4. Parametric analysis showed no significant association between FACT-E & T-stage, although there was a trend towards significance (P=0.08). Non-parametric analysis showed a significant association between FACT-E and T-stage (P=0.05). Post-hoc tests identified that the most significant differences in FACT-E scores were between T1 and T3 patients. Both parametric (P=0.002) and non-parametric (P=0.003) analyses showed an association between ECS & T-stage. Post-hoc analyses showed significant differences in ECS scores between T1 and higher T-stages (P Conclusions: Patient-reported HRQOL scores appear to be significantly different in patients with clinical T1 esophageal cancer as compared to those with higher clinical T stages. Since distinguishing T1 from T2/T3 lesions is important in guiding the most appropriate treatment modality and since EUS appears to have difficulties reliably making such T-stage distinctions, FACT-E and ECS scores may be helpful as an adjunct to guide decision-making.