Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma, therefore often misdiagnosed and has no available standard treatment. Here, we report 3 cases of metastatic GNET with variable clinical courses. Our small case series as well as extensive literature review, further support that GNET is a spectrum of diseases with variable inherent biology and prognosis. Surgical management in the setting of recurrent/metastatic disease may be appropriate for GNET with indolent nature. Response to systemic treatments including chemotherapy and targeted treatments is variable, likely related to heterogenous biology as well. Furthermore, we retrospectively identified 20 additional GNET cases from Foundation Medicine’s genomic database and expanded on their clinicopathological and genomic features. Comprehensive genomic profiling (CGP) with DNA and RNA sequencing of this cohort, in the course of clinical care, demonstrated recurrent EWSR1 chromosomal rearrangements and a sparsity of additional recurrent or driver genomic alterations. All cases had low tumor mutational burden (TMB) and were microsatellite stable.

Introduction: Fulvestrant has demonstrated efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC), both in first-and second-line settings. In clinical practice, however, fulvestrant has been used as a later-line therapy. This study assessed the efficacy of fulvestrant in women with mBC in early-versus later-line therapy. Methods: This retrospective cohort study assessed Saskatchewan women with HR+ mBC who received fulvestrant between 2003–2019. A multivariate Cox proportional survival analysis was performed. Results: One hundred and eighty-six women with a median age of 63.5 years were identified—178 (95.6%) had hormone-resistant mBC, 57.5% had visceral disease, and 43.0% had received chemotherapy before fulvestrant. 102 (54.8%) women received ≤2-line-therapy, and 84 (45.2%) received ≥3 line-therapy before fulvestrant. The median time to progression (TTP) was 12 months in the early-treatment vs. 6 months in the later-treatment group, p = 0.015. Overall survival (OS) from the start of fulvestrant was 26 months in the early-treatment group vs. 16 months in the later-treatment group, p = 0.067. On multivariate analysis, absence of visceral metastasis, HR: 0.70 (0.50–0.99), was significantly correlated with better TTP, whereas post-fulvestrant chemotherapy, HR: 0.32 (0.23–0.47), clinical benefit from fulvestrant, HR: 0.44 (0.30–0.65), and absence of visceral metastasis, HR: 0.70 (0.50–0.97), were correlated with better OS. Conclusions: Fulvestrant has demonstrated efficacy as both early-and later-line therapy in hormone-resistant mBC. Our results show that women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease, had better survival.

Background: The current study aimed to determine the association between timing and completion of adjuvant chemotherapy and outcomes in real-world patients with early-stage pancreatic cancer. Methods: In this multi-center cohort study patients with early-stage pancreatic cancer who were diagnosed from 2007–2017 and underwent complete resection in the province of Saskatchewan were examined. Cox proportional multivariate analyses were performed for correlation with recurrence and survival. Results: Of 168 patients, 71 eligible patients with median age of 69 years and M:F of 37:34 were identified. Median time to the start of adjuvant therapy from surgery was 73 days. Of all patients, 49 (69%) patients completed adjuvant chemotherapy and 22 (31%) required early treatment discontinuation. Median recurrence-free survival of patients who completed treatment was 22 months (95%CI:15.8–28.2) vs. 9 months (3.3–14.7) if treatment was discontinued early (P<0.001). Median overall survival of those who completed treatment was 33 (17.5–48.5) vs. 16 months (17.5–48.5) with early treatment discontinuation (P<0.001). In the multivariate analysis, treatment discontinuation was significantly correlated with recurrent disease, hazard ratio (HR), 2.57 (1.41–4.68), P = 0.002 and inferior survival, HR, 2.55 (1.39–4.68), P = 0.003. No correlation between treatment timing and survival was noted. Conclusions: Early discontinuation but not the timing of adjuvant chemotherapy correlates with inferior outcomes.

Background: Small intestine adenocarcinoma is a rare cancer. The current study aims to determine the outcomes of patients with small intestine adenocarcinoma in a Canadian province. Methods: This retrospective population-based cohort study assessed patients with small intestine adenocarcinoma who were diagnosed from 2008 to 2017 in Saskatchewan. A Cox proportional multivariate regression analysis was performed to determine the correlation between survival and exploratory factors. Results: 112 eligible patients with a median age of 73 years and M:F of 47:53 were identified. Overall, 75% had a comorbid illness, and 45% had a WHO performance status >1. Of the 112 patients, 51 (46%) had early-stage disease and 61 (54%) had advanced-stage disease. The median overall survival (mOS) was as follows: stage one, 59 months; stage two, 30 months; stage three, 20 months; and stage four, 3 months (p < 0.001). The median disease-free survival of patients with stage three disease who received adjuvant chemotherapy was 26 months (95% CI:23.1–28.9) vs. 4 months (0.0–9.1) with observation (p = 0.04). Patients who received chemotherapy for advanced disease had a mOS of 10 months (3.5–16.5) vs. 2 months (0.45–3.6) without chemotherapy (p < 0.001). In the multivariate analysis, stage four disease, hazard ratio (HR), 3.20 (1.84–5.40); WHO performance status >1, HR, 2.22 (1.42–3.45); lack of surgery, HR, 2.10 (1.25–3.50); and a neutrophil:lymphocyte ratio of >4.5, HR, 1.72 (1.10–2.71) were significantly correlated with inferior survival. Conclusions: Most patients with small intestine adenocarcinoma were diagnosed with advanced-stage disease. Advanced-stage disease, poor performance status, lack of surgery and a baseline neutrophil:lymphocyte ratio >4.5 were correlated with inferior survival.

Background: Breast cancer is rare in men. This population-based study aimed to determine outcomes of male breast cancer in relation to residence and other variables. Methods: In this retrospective cohort study, men diagnosed with breast cancer in Saskatchewan during 2000–2019 were evaluated. Cox proportional multivariable regression analyses were performed to determine the correlation between survival and clinicopathological and contextual factors. Results: One hundred-eight eligible patients with a median age of 69 years were identified. Of them, 16% had WHO performance status ≥ 2 and 61% were rural residents. The stage at diagnosis was as follows: stage 0, 7%; I, 31%; II, 42%; III, 11%; IV, 8%. Ninety-eight percent had hormone receptor-positive breast cancer. The median disease-free survival of urban patients was 97 (95% CI: 50–143) vs. 64 (46–82) months of rural patients (p = 0.29). The median OS of urban patients was 127 (94–159) vs. 93 (32–153) months for rural patients (p = 0.27). On multivariable analysis, performance status ≥ 2, hazard ratio (HR) 2.82 (1.14–6.94), lack of adjuvant systemic therapy, HR 2.47 (1.03–5.92), and node-positive disease, HR 2.32 (1.22–4.40) were significantly correlated with inferior disease-free survival in early-stage invasive breast cancer. Whereas stage IV disease, HR 7.8 (3.1–19.5), performance status ≥ 2, HR 3.25 (1.57–6.71), and age ≥ 65 years, HR 2.37 (1.13–5.0) were correlated with inferior overall survival in all stages. Conclusions: Although residence was not significantly correlated with outcomes, rural men had numerically inferior survival. Poor performance status, node-positive disease, and lack of adjuvant systemic therapy were correlated with inferior disease-free survival.

Background: The standard approaches for resectable stomach cancer are postoperative chemoradiotherapy (PCR) or perioperative chemotherapy (PC). Limited evidence is available regarding the superiority of one of the two approaches. We aimed to compare the survival of patients with operable stomach cancer who were treated with PC or PCR. Methods: In this retrospective cohort study, patients with operable stomach cancer diagnosed between 2005–2015 in the province of Saskatchewan were identified and, based on type of treatment, were placed into PCR and PC groups. A Cox proportional multivariate analysis was performed to assess independent prognostic variables, including survival advantage of PC over PCR. Results: A total of 88 eligible patients with a median age of 66 (56–71) and a male to female ratio of 1:0.44 were identified. Seventy-three (83%) patients had pathologically node positive disease. Sixty-seven (76%) patients received PCR, while 21 (24%) patients received PC. The median overall survival of the whole group was 34 months, with 38 months (95% CI 24.6–51.3) in the PCR group vs. 30 months (14.3–45.7) in the PC group (p = 0.29). Median relapse-free survival was 34 months (20.7–47.3) in the PCR group vs. 23 months (6.7–39.3) in the PC group (p = 0.20). Toxicities were comparable. On multivariate analysis, T ≥ 3 tumor (HR, 3.57 (1.39–8.56)), neutrophil to lymphocyte ratio (LNR) > 2.8 (HR, 1.85 (1.05–3.25)), and positive resection margins (HR, 1.89 (1.06–3.37)) were independently correlated with inferior survival. Conclusions: This well-designed population based cohort study suggests a lack of survival benefit of PC over PCR. Both treatment options remain viable approaches for resectable stomach cancer.