No abstract

No abstract

Objective: We aimed to explore possible drivers for urban-rural disparities in colon cancer outcomes in a single-payer health care system where all patients had access to universal health care coverage. Methods: Patients diagnosed with stage II/III colon cancer between 2004 and 2015 in Alberta, Canada were reviewed. On the basis of postal code, patients were categorized as living in urban, rural, or suburban areas based on travel distance to the cancer center. Kaplan-Meier methods and Cox regression models assessed the associations among the area of residence, receipt of treatment, and overall survival (OS). Results: Of 6163 patients identified, there were 3691, 1779, and 693 from urban, rural, and suburban areas, respectively. There was a larger proportion of younger patients (P=0.033) and left-sided colon cancers (P=0.042) in urban areas. Urban patients experienced shorter times from diagnosis to surgery (P<0.001), but longer delays from surgery to adjuvant chemotherapy (P=0.001). A significant difference in outcomes was identified among urban, rural, and suburban populations where median OS were 104, 94, and 83 months, respectively (P<0.001). In multivariate analysis, the location of residence continued to predict for worse OS in suburban (hazard ratio=1.60, 95% confidence interval: 1.24-2.07, P<0.001) and rural areas (hazard ratio=1.24, 95% confidence interval: 1.02-1.50, P=0.042), when compared with urban areas. Conclusions: In this population-based study, urban-rural differences in colon cancer survival persist, even in settings with universal health care coverage. These findings may be partly driven by a younger population with more left-sided colon cancers as well as expedited surgical intervention in urban populations, but these factors do not fully explain the disparities.

694 Background: The impact of primary tumour sidedness has recently been demonstrated in patients with metastatic colorectal cancer (mCRC). Differences in right (R) versus left (L) sided mCRC may be due to differences in consensus molecular subtyping. Clinically predictive mutations in ras, ( kras, nras and braf) may also help drive some of the differences in outcome. However, patients with mCRC who undergo surgical resection of CRLM often have a good prognosis. The aim of this study was to assess the impact of tumour sidedness on OS after resection of CRLM. Methods: Patients who underwent resection of CRLM in the province of Alberta, Canada were identified from 2004-2016. Tumour sidedness was determined by chart review, with R from the cecum to transverse and L from splenic flexure to sigmoid. Where available, ras mutational status was collected. OS was measured from the time of CRLM resection to death or last follow-up using the Kaplan-meier method. R and L were compared using the log-rank test and a Cox regression model. Results: 471 patients were identified who underwent resection of CRLM for mCRC, including 204 R and 267 L. Median age was 65, 63% male, with 54% synchronous metastatic disease, and 67% with a Charleson comorbidity index of 0. All ras wildtype was present in 22% of cases, any ras mutation was detected in 21% and 57% were unknown at the time of analysis. The median OS of R was 45 months, compared to 72 months for L, log-rank p = 0.01. After adjusting for potential confounders with a Cox-proportional hazard model, R compared to L remained significant, with a HR of 1.4 (95% CI 1.0-1.9, p = 0.02). ras mutational status was also significant for ras mutant, HR 2.4 (95% CI 1.7-3.3) and ras unknown HR 2.2 (95% CI 1.5-3.1) compared to ras wildtype p < 0.01. Conclusions: Primary tumour sidedness continues to have an impact on OS in mCRC, even when disease is managed surgically with resection of CRLM. Though limited by numbers, the impact remained significant even after controlling for potential confounders, including ras mutational status. Additional ras testing is underway. Further molecular classification may provide a biologic rationale for the observed differences.

Background Cognitive impairment is commonly reported in patients receiving chemotherapy, but the acuity of onset is not known. This study utilized the psychomotor vigilance test (PVT) and trail-making test B (TMT-B) to assess cognitive impairment immediately post-chemotherapy. Methods Patients aged 18–80 years receiving first-line intravenous chemotherapy for any stage of breast or colorectal cancer were eligible. Patient symptoms, peripheral neuropathy and Stanford Sleepiness Scale were assessed. A five-minute PVT and TMT-B were completed on a tablet computer pre-chemotherapy and immediately post-chemotherapy. Using a mixed linear regression model, changes in reciprocal transformed PVT reaction time (mean 1/RT) were assessed. A priori, an increase in median PVT reaction times by > 20 ms (approximating PVT changes with blood alcohol concentrations of 0.04–0.05 g%) was considered clinically relevant. Results One hundred forty-two cancer patients (73 breast, 69 colorectal, median age 55.5 years) were tested. Post-chemotherapy, mean 1/RT values were significantly slowed compared to pre-chemotherapy baseline ( p = 0.01). This corresponded to a median PVT reaction time slowed by an average of 12.4 ms. Changes in PVT reaction times were not correlated with age, sex, cancer type, treatment setting, or use of supportive medications. Median post-chemotherapy PVT reaction time slowed by an average of 22.5 ms in breast cancer patients and by 1.6 ms in colorectal cancer patients. Post-chemotherapy median PVT times slowed by > 20 ms in 57 patients (40.1%). Exploratory analyses found no statistically significant association between the primary outcome and self-reported anxiety, fatigue or depression. TMT-B completion speed improved significantly post-chemotherapy ( p = 0.03), likely due to test-retest phenomenon. Conclusions PVT reaction time slowed significantly immediately post-chemotherapy compared to a pre-chemotherapy baseline, and levels of impairment similar to effects of alcohol consumption in other studies was seen in 40% of patients. Further studies assessing functional impact of cognitive impairment on patients immediately after chemotherapy are warranted. Electronic supplementary material The online version of this article (10.1186/s12885-019-5349-2) contains supplementary material, which is available to authorized users.

Bone is a common site for metastatic colonization in patients with breast cancer, hence the importance of identifying new treatments for this disease. Preclinical studies of bone metastases have commonly employed MDA-MB-231 cells that possess an activated KRAS allele. While activating RAS mutations are relatively rare in human breast cancer, increased RAS-RAF-MEK pathwayactivity is common in high-grade breast cancers. To study the consequences of MEK inhibition on bone metastases stemming from the intra-cardiac injection of luciferase-expressing MDA-MB-231 cells in mice, we used the MEK inhibitor AZD6244 (Selumetinib). We found that AZD6244 treatment caused decreased tumor bioluminescence that was associated with cavitation of the bone metastases, owing to apoptosis of cells specifically within the central region of the bone lesions. Hypothesizing that the latter effect was due to the increased sensitivity of poorly perfused regions to pro-apoptotic stimuli, we found that the combination of serum deprivation and AZD6244 led to dramatic induction pf MDA-MB-231 apoptosis in vitro. Our results suggest that MEK inhibition may be a strategy for triggering cell death within the hypoperfused, oxygen and nutrient poor regions of tumors with activated RAS alleles.

146 Background: The acute impact of chemotherapy on cognition is unknown. This study utilized performance on the psychomotor vigilance task (PVT) and trail-making test B (TMT) to assess CRCI immediately following chemotherapy administration. Methods: Patients aged 18-80 years receiving first-line IV chemotherapy for any stage of breast or colorectal cancer were eligible. Patients with brain metastases, neurologic disorders or allergic reactions to chemotherapy were excluded. Patient symptoms, peripheral neuropathy and Stanford Sleepiness Scale were assessed. A five-minute PVT and TMT were completed on a tablet computer pre-chemotherapy and immediately post-chemotherapy. Paired Wilcoxon Rank Sum tests were used to assess changes in median PVT reaction time, TMT completion time, TMT errors and PVT lapses. A priori, increases of 20 ms or over in median PVT reaction times (approximating reaction time changes with blood alcohol concentrations of 0.04 to 0.05 g%) were considered clinically relevant. Results: 144 patients (74 breast, 70 colorectal, median age 55.5 years) were tested. Post-chemotherapy, median PVT reaction time slowed by an average of 12.4 ms (p = 0.01). Post-chemotherapy median PVT times slowed by over 20 ms in 59 patients (40.9%). TMT completion post-chemotherapy was faster by an average of 6.1 seconds (p < 0.001). No differences were seen in TMT errors (p = 0.417) or PVT lapses (p = 0.845). Change in median PVT reaction time was not associated with age, gender, number of prior chemotherapy cycles, use of paclitaxel (which contains alcohol), peripheral neuropathy grade, or self-reported anxiety, fatigue or depression. Conclusions: Median PVT reaction time was significantly slower immediately after chemotherapy compared to a pre-chemotherapy baseline, and impairment correlating to effects of alcohol was seen in 41% of patients. This effect appears independent of age, self-reported symptoms or prior chemotherapy cycles. Further studies assessing the functional implications of immediate-term CRCI are warranted.

The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer.