Oncology care providers' perceptions and anticipated barriers regarding the use of geriatric assessment in routine clinic practice: A mixed-methods study.

INTRODUCTION: Geriatric assessment (GA) is currently not a standard of cancer care across Canada. In the Canadian province of Saskatchewan, there are no known formal geriatric teams in outpatient oncology settings. Therefore, it is not known whether, how, and to what extent GA is performed in oncology clinics, or what supports are needed to carry out a GA. The objective of this study was to explore Saskatchewan oncology care providers' knowledge, perceptions, and practices regarding GA, and their perceived barriers to implementing formal GA. MATERIALS AND METHODS: In this mixed-methods study, oncology physicians and nurses within the Saskatchewan Cancer Agency (SCA) were invited to participate in an anonymous survey and individual open-ended interview. Quantitative survey data were analyzed using descriptive statistics; free-text responses provided in the survey were summarized. Data from interviews were analyzed using thematic analysis. RESULTS: A total of 19 physicians and 30 clinic nurses participated in the survey (response rate: 24% [physicians] and 38.0% [nurses]). In terms of cancer treatment and management, the majority (74% of physicians and 62% of nurses) stated considerations for older adults are different than younger patients. More than half (53% of physicians and 58% of nurses) reported making treatment and management decisions primarily based on judgement versus validated tools. For physicians whose practices involve prescribing chemotherapy (16/19), 75% rarely or never use validated tools (e.g., CARG, CRASH) to assess risk of chemotoxicity for older patients. Lack of time and supporting staff and feeling unsure as to where to refer older patients for help or follow-up were the most commonly voiced anticipated barriers to implementing GA. Two physicians and six nurses (n = 8) participated in the open-ended interviews. Main themes included: (1) tension between knowing the importance of GA versus capacity and (2) buy-in. DISCUSSION: Our findings review barriers and opportunities for implementing GA in oncology care in Saskatchewan and provides foundational knowledge to inform efforts to promote personalized medicine and to optimize cancer care for older adults with cancer in this region.

Outcomes of Rural Men with Breast Cancer: A Multicenter Population Based Retrospective Cohort Study.

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.

Patient and Physician Satisfaction with Telemedicine in Cancer Care in Saskatchewan: A Cross-Sectional Study.

Background: Telemedicine is a useful tool that connects patients to their care team remotely and improves access to medical care for rural residents. This study aimed to determine the telemedicine experience of both rural patients with cancer and their physicians, and to explore factors associated with a positive patient experience. Methods: In this cross-sectional study, cancer patients and physicians in Saskatchewan completed a paper-based survey composed of 32 items or an electronic survey of 18 items, respectively. Logistic regression analysis was performed to assess patient satisfaction in relation to various sociodemographic and cancer-related factors. Results: Overall, 25 physicians and 165 patients participated in the study. Among the physicians, 94% were confident in their telemedicine assessment, 58% agreed that telemedicine improved clinical efficiency, and 73% agreed that doctor−patient rapport was unimpaired with telemedicine. Of 165 patients, 61% had used telemedicine for the first time, 81% felt that their needs were met, 83% were satisfied with the quality of their care, and 88% had a positive experience. Overall, 83% patients vs. 45% physicians preferred telemedicine to a face-to-face clinic visit (p = 0.005). On univariate analysis, patients ≥ 65 years old had a greater positive telemedicine experience compared to patients < 65 years old (odds ratio 4.1 [1.2−13.8], p = 0.02). Conclusion: Both patients and physicians have a high rate of positive experiences with telemedicine. However, patients have a higher preference for telemedicine over face-to-face visits compared to physicians. In addition, elderly patients have more positive telemedicine experiences compared to younger patients.

Outcomes of Patients with Small Intestine Adenocarcinoma in a Canadian Province: A Retrospective Multi-Center Population-Based Cohort Study.

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.

Early discontinuation of adjuvant chemotherapy in patients with early-stage pancreatic cancer correlates with inferior survival: A multicenter population-based cohort study.

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.

Efficacy of adjuvant trastuzumab in women with HER2-positive T1a or bN0M0 breast cancer: a population-based cohort study.

Adjuvant trastuzumab has been associated with superior survival in women with ≥ T1c or node-positive HER2-positive early-stage breast cancer; however, there is a lack of phase III trials in women with T1a/bN0 disease. Our study aimed to assess the outcomes of women with HER2-positive T1a/bN0 breast cancer who received adjuvant trastuzumab in Saskatchewan, Canada. We evaluated all women diagnosed with HER2-positive T1a/bN0 breast cancer in Saskatchewan between 2008 and 2017. We performed Cox proportional multivariable analysis to determine factors correlated with survival. In addition, inverse probability treatment weighting (IPTW) using propensity score was performed to assess benefit of adjuvant trastuzumab. Ninety-one eligible women with a median age of 61 years (range 30-89) were identified. Thirty-nine (43%) women received adjuvant trastuzumab. Women who received trastuzumab were younger and had a higher rate of T1b disease. Overall, 3% of women who received trastuzumab compared to 12% of women who did not receive trastuzumab developed breast cancer recurrence (p = 0.23). Five-year disease-free survival (DFS) of women who received adjuvant trastuzumab was 94.8% compared to 82.7% of women who did not receive trastuzumab (p = 0.22). Five-year overall survival was 100% of women who received trastuzumab compared to 90.4% of women who did not receive adjuvant trastuzumab (p = 0.038). In the multivariable analysis, grade III tumors were correlated with inferior DFS (hazard ratio [HR] 5.5, 95% CI [1.7-17.7]). The propensity score using the inverse probability of treatment weighting showed that lack of adjuvant trastuzumab was correlated inferior DFS, with an HR of 4 (95% CI 1.05-15.5). Women with HER2-positive T1a/bN0 breast cancer had overall low recurrence of breast cancer. However, the results of this exploratory analysis indicate that women who received adjuvant trastuzumab had better survival.

Early Single-Center Experience With Irreversible Electroporation for Stage 2, 3, and 4 Pancreatic Adenocarcinomas.

OBJECTIVES: Irreversible electroporation (IRE) is an ablation technology that uses electrical energy delivered between electrodes. If the electrodes are placed atraumatically, there is little to no risk of collateral injury, making IRE appealing for the treatment of pancreatic tumors. METHODS: We report on 20 patients with pancreatic adenocarcinoma (PAC) who underwent 21 IRE in our center. There were 6 IRE for stage 2 PAC, 11 for stage 3 PAC, 1 for stage 4 PAC, and 2 patients treated with IRE for recurrence after pancreaticoduodenectomy. One patient had local progression 18 months after IRE and received a second IRE treatment. Using propensity score matching (age, sex, stage, tumor size, and chemotherapy), cases were matched 2 to 1 with patients from the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 7 cases experienced 8 complications; 4 complications were mild, and 4 were severe. Significant survival benefit was seen for patients with stage 3 PAC (27.5 vs 14.6 months for the matched group, P = 0.003); for stage 2, median survival was 15 months, and the single stage 4 patient survived 9 months after IRE treatment. CONCLUSIONS: Pancreatic cancers were safely and effectively treated with image-guided IRE in our medium-sized center.

Rate of Curative Surgery in Real-world Patients with Unresectable Metastatic Colorectal Cancer Treated with FOLFOXIRI ± Bevacizumab: A Western Canadian Province Experience.

BACKGROUND: Recent evidence from randomized trials suggests that FOLFOXIRI (fluorouracil, oxaliplatin, and irinotecan) ± bevacizumab is associated with higher response rates, with the potential for conversion of unresectable to resectable disease in metastatic colorectal cancer (mCRC). However, limited evidence is available on the efficacy and safety of this regimen in real-world patients with mCRC. The current study aims to evaluate the conversion rate and safety of FOLFOXIRI ± bevacizumab in real-world patients with unresectable mCRC. METHODS: In this retrospective multicenter population-based cohort study, patients who were diagnosed with unresectable mCRC between January 2015 and December 2018 in Saskatchewan and received FOLFOXIRI ± bevacizumab were assessed. Kaplan-Meier survival methods and the log-rank test were performed. RESULTS: A total of 28 eligible patients with a median age of 51 years (interquartile range 39-60) and a male:female ratio of 11:17 were identified; 39% had rectal cancer, 46% had extrahepatic disease, and 46% had bilobar liver metastases. Overall, 63% of the patients had a positive response to FOLFOXIRI ± bevacizumab and 53% underwent metastasectomy. Of all patients 60% had grade 3/4 toxicity and 32% required hospital admission. No treatment-related mortality was noted. After 4 years, 50% of the patients were alive. Median progression-free survival of patients who underwent surgery was 18 months (95% CI 11.3-24.7) versus 11 months (4-18.1) without surgery (p = 0.28). Median overall survival of patients with surgery was 33 months (17.5-48.5) versus 16 months (8.3-23.7) without surgery (p = 0.03). CONCLUSION: The current study suggests that FOLFOXIRI ± bevacizumab therapy in real-world patients with mCRC is associated with a high rate of conversion from unresectable to resectable metastatic disease. Patients with metastasectomy had better survival.

Feasibility of a Remotely Delivered Strength and Balance Training Program for Older Adults with Cancer.

Falls are a major issue among older adults with cancer and lead to interruptions in cancer treatment. Resistance and balance training can prevent falls in older adults, but minimal evidence is available regarding the older cancer population, who often have unique risk factors. We used a pre-post design to assess the feasibility of a remotely delivered exercise program that progressed in difficulty and its efficacy on lower body strength, balance, and falls in older adults with cancer who had prior in-person exercise experience. Twenty-six older adults with cancer completed the intervention. Attendance rate for the virtual component was 97.6% and for the independent component was 84.7%. Participants perceived the program as rewarding and enjoyable (100%), felt this program prepared them to exercise on their own (92%), were confident to continue exercising on their own (81%), and would recommend the program to other patients (100%). The median balance score at baseline and end-of-study was 4 (IQR = 0). The median chair-stand time decreased from 9.2 s (IQR = 3.13) to 7.7 s (IQR = 4.6). A statistically significant difference in lower body strength (r = 0.68, p = 0.001) was detected post-intervention. The findings from this study can inform the design of a larger randomized trial.

Oncology clinic nurses' attitudes and perceptions regarding implementation of routine fall assessment and fall risk screening: A survey study.

Falls in older adults with cancer are often under-recognized and under-reported. The objective of this study was to explore oncology clinic nurses' willingness and perceived barriers to implement routine falls assessment and falls screening in their practice. Nurses working in outpatient oncology clinics were invited to complete an online survey. Data were analyzed using descriptive statistics and sorted into thematic categories. The majority of respondents indicated willingness to routinely ask older patients about falls (85.7%) and screen for fall risks (73.5%). The main reasons for unwillingness included: belief that patients report falls on their own, lack of time, and lack of support staff. Findings from this study show many oncology nurses believe in the importance of routine fall assessment and screening and are willing to implement them routinely, although falls are not routinely asked about or assessed. Future work should explore strategies to address barriers nurses face given the implications of falls amongst this vulnerable population.

Efficacy of Fulvestrant in Women with Hormone-Resistant Metastatic Breast Cancer (mBC): A Canadian Province Experience.

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.

Outcomes of Patients with Borderline Resectable Pancreatic Cancer Treated with Combination Chemotherapy.

BACKGROUND: Patients with borderline resectable pancreatic cancer are at high risk of incomplete resection with upfront surgery. Currently, no standard induction chemotherapy regimen exists for these patients. Both FOLFIRINOX (5-FU, irinotecan, & oxaliplatin) and gemcitabine plus nab-paclitaxel (GnP) have shown better efficacy than gemcitabine alone in advanced pancreatic cancer. The current study aims to assess outcomes of real-world patients with borderline resectable pancreatic cancer who received induction FOLFIRINOX or GnP. METHODS: In this population-based multicenter retrospective cohort study, patients with biopsy-proven borderline resectable pancreatic cancer diagnosed from 2011 to 2017, in the province of Saskatchewan, Canada, who received FOLFIRINOX or GnP were assessed. Kaplan Meier methods and log rank tests were performed for survival analyses. RESULTS: Of 161 patients with pancreatic cancer who received FOLFIRINOX or GnP during the study period, 20 eligible patients with borderline resectable pancreatic cancer were identified. Ten patients each received FOLFIRINOX or GnP. Eleven patients had partial response (5, FOLFIRINOX; 6, GnP); 3 progressed during treatment. Five patients (4, FOLFIRINOX; 1, GnP; p = NS) underwent curative surgery. The median progression-free survival was 17 months in FOLFIRINOX (95% CI, 5.3-28.6) vs. 9 months (95% CI, 3.0-15) in GnP groups (p = 0.27). Overall, 80% patients in GnP vs. 40% in FOLFIRINOX died from progressive disease. The median overall survival has not been reached in FOLFIRINOX group versus 16 months (95% CI, 9.3-22.7) in GnP group (p = 0.15). CONCLUSION: The current study suggests that patients with borderline resectable pancreatic cancer who received FOLFIRINOX tend to have better outcomes. Future studies are warranted to establish a preferred systemic therapy for patients with borderline resectable pancreatic cancer.

Second-line Chemotherapy Prolongs Survival in Real World Patients With Advanced Biliary Tract and Gallbladder Cancers: A Multicenter Retrospective Population-based Cohort Study.

BACKGROUND: Limited evidence is available regarding the survival benefit of second-line therapy in real world patients with advanced biliary tract and gallbladder cancer. Until very recently, there was a lack of randomized clinical trials to address this important question. In this multicenter population-based cohort study, the authors evaluated whether second-line therapy improves the survival of real world patients with advanced biliary tract and gallbladder cancer. METHODS: Patients with biopsy-proven advanced biliary tract and gallbladder cancer who were diagnosed during the period of 2006 to 2015 and had received first-line chemotherapy were assessed. Cox proportional multivariate analysis was performed to determine the survival benefit of second-line therapy. RESULTS: One hundred thirty-six eligible patients with a median age of 66 years and male:female ratio of 1:1.34 were identified. Sixty-eight percent of patients had metastatic disease. Primary tumor sites were as follows: gallbladder 31%, intrahepatic cholangiocarcinoma 36%, extrahepatic bile duct 23%, and ampullary cancer 10%. Overall, 37% of patients received second-line therapy. The median overall survival of the treatment group was 17 months (95% confidence interval [CI]: 12.5-21.5) compared with 7 months (95% CI: 5.3-8.7) in the control (P<0.0001). Patients who received combination chemotherapy had a median overall survival of 20 months (14.0-26.1) compared with 17 months (13.5-20.5) if they received single-agent second-line therapy (P=0.73). Multivariate analysis of second-line therapy, hazard ratio: 0.55 (95% CI: 0.36-0.83) and neutrophil to lymphocyte ratio >2, HR: 1.10 (1.05-1.15) showed a significant correlation with survival. CONCLUSIONS: This well-designed population-based retrospective cohort study suggests that second-line chemotherapy improves survival of real world patients with advanced biliary tract and gallbladder cancers and should be offered to the patients who are potential candidates for chemotherapy.

Comparisons of Outcomes of Real-World Patients With Advanced Pancreatic Cancer Treated With FOLFIRINOX Versus Gemcitabine and Nab-Paclitaxel: A Population-Based Cohort Study.

OBJECTIVES: The aim of this study was to compare the efficacy and safety of FOLFIRINOX (5-FU/leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel (GnP) in patients with advanced pancreatic cancer. METHODS: Patients with newly diagnosed advanced pancreatic cancer in Saskatchewan, Canada, from 2011 to 2016, who received FOLFIRINOX or GnP were assessed. A Cox proportional multivariate analysis was performed to evaluate prognostic variables. RESULTS: One hundred nineteen eligible patients with median age of 61 years and male/female ratio of 70:49 were identified. Seventy-seven percent had metastatic disease. Of 119 patients, 86 (72%) received FOLFIRINOX and 33 (28%) were treated with GnP. Median progression-free survival of the FOLFIRINOX group was 6.0 months [95% confidence interval (CI), 4.5-7.5] versus 4.0 months (95% CI, 2.9-5.1) with GnP (P = 0.39). The median overall survival of the FOLFIRINOX group was 9.0 months (95% CI, 7-11) compared with 9.0 months (95% CI, 4.2-13.8) with GnP (P = 0.88). On multivariate analysis, albumin [hazard ratio (HR), 0.63; 95% CI, 0.41-0.97], male sex (HR, 0.65; 95% CI, 0.43-0.97), and second-line therapy (HR, 0.50; 95% CI, 0.28-0.86) were correlated with survival. CONCLUSIONS: Our results showed that real-world patients with advanced pancreatic cancer treated with FOLFIIRNOX or GnP had comparable survival with different safety profile.

Effects of Social and Contextual Factors Including Marital Status and Children on the Use of Palliative Chemotherapy in Metastatic Colorectal Cancer.

BACKGROUND: There is evidence that social and contextual factors such as living alone are associated with outcomes in cancer patients. However, little is known about their influence on the use of palliative chemotherapy in metastatic colorectal cancer (mCRC). In this study, we examined social and contextual factors, including marital status, having children, and distance to a cancer center, for their association with the use of chemotherapy in patients with mCRC. METHODS: A cohort of patients with mCRC diagnosed from 2006 to 2010 in Saskatchewan was evaluated. Logistic regression analyses were performed to assess the relationship between the variables and use of chemotherapy. RESULTS: Of 569 patients, 326 (57%) received chemotherapy significant differences were noted between the chemotherapy versus no chemotherapy groups with respect to age (62 vs. 76 y), poor performance status (18% vs. 58%), comorbid illness (24% vs. 63%), low albumin (61% vs. 89%), anemia (61% vs. 87%), elevated alkaline phosphatase (53% vs. 84%), elevated creatinine (6% vs. 11%), hyponatremia (20% vs. 14%), primary tumor resection (61% vs. 47%), metastasectomy (21% vs. 9%), mean distance to cancer center (98.7±113.6 vs. 127.8±124.6 km), married/partnered (67% vs. 33%), and having children (64% vs. 36%). On multivariate logistic regression analysis, low performance status (odds ratio [OR], 5.1; 95% confidence interval [CI]: 3.1-8.1), not having children (OR, 3.3; 95% CI: 1.78-6.2), hyponatremia (OR, 2.9; 95% CI: 1.6-5.1), elevated alkaline phosphatase (OR, 2.9; 95% CI: 1.8-4.8), and low albumin (OR, 2.2; 95% CI: 1.2-3.8) were correlated with low rates of chemotherapy use. CONCLUSIONS: Our results showed that the use of chemotherapy in patients with mCRC significantly varies between those with and without children.

A Randomized Phase II Study of FOLFOX6/Bevacizumab With or Without Pelareorep in Patients With Metastatic Colorectal Cancer: IND.210, a Canadian Cancer Trials Group Trial.

BACKGROUND: Oncolytic reovirus pelareorep might preferentially infect and destroy rat sarcoma (RAS)-activated cells, and has preclinical and early clinical activity against colorectal cancer (CRC). PATIENTS AND METHODS: After a 6-patient safety run-in, 103 patients with metastatic CRC were randomly assigned to standard first-line leucovorin/5-FU/oxaliplatin (FOLFOX6)/bevacizumab (FOLFOX/BEV) every 2 weeks with (n = 51) or without (n = 52) pelareorep 3 × 1010 tissue culture infective dose 50 on days 1 to 5 (cycles 1, 2, 4, and alternate cycles thereafter). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life, and correlative analyses. RESULTS: At 13 months' median follow-up, PFS was inferior in the pelareorep arm (median 7 vs. 9 months; hazard ratio [HR], 1.59 [80% confidence interval (CI), 1.18-2.15]; P = .046). There was no statistical difference in OS (median, 19.2 vs. 20.1 months; HR, 1.22; P = .38). An increased ORR was observed with pelareorep (adjusted odds ratio, 2.52 [80% CI, 1.44-4.41]; P = .03), but with a shorter median duration of response (5 vs. 9 months; P = .028). Pelareorep patients experienced more hypertension and proteinuria, and were more likely to omit bevacizumab before progression. A trend to lower dose intensity and shorter oxaliplatin and bevacizumab treatment duration was observed with pelareorep. CONCLUSION: Combination pelareorep with FOLFOX/BEV was tolerable with an increased ORR, but PFS was inferior. Subgroup analysis of baseline variables including Kirsten rat sarcoma oncogene did not identify subgroups with PFS benefit. Decreased treatment intensity with standard agents likely contributed to the lack of benefit with pelareorep. Future studies might consider alternate pelareorep/chemotherapy strategies or combination therapy with novel agents.

Primary Tumor Location and Survival in the General Population With Metastatic Colorectal Cancer.

BACKGROUND: Recent evidence from clinical trials suggests that primary tumor location in patients with metastatic colorectal cancer correlates with differential outcomes, and patients with tumors originating in the right side of the colon have inferior survival. We conducted a large population-based cohort study using individual patient data to confirm the prognostic importance of primary tumor location in the general population with metastatic colorectal cancer. METHODS: A cohort of 1947 patients who were diagnosed with metastatic colorectal cancer from 1992 to 2010 was studied. Ascending and transverse colon cancers were defined as right-sided tumors. Cox proportional multivariate analyses were done to determine prognostic significance of primary tumor location. RESULTS: The median age was 70 years (interquartile range, 60-78 years), and the male to female ratio was 1.3:1. Twenty-nine percent had World Health Organization performance status of > 1. Seven-hundred and seventy (39%) patients had right-sided tumors, and 908 (47%) received chemotherapy. The median overall survival of patients with right-sided tumors was 14 months (95% confidence interval [CI], 12.7-15.3 months) compared with 20.5 months (95% CI, 18.5-22.5 months) of patients with left-sided tumors (P < .001). On multivariate analysis, right-sided tumors (hazard ratio [HR], 1.40; 95% CI, 1.20-1.60), no metastasectomy (HR, 2.40; 95% CI, 1.90-2.90), intact primary tumor (HR, 1.60; 95% CI, 1.32-1.90), an elevated carcinoembryonic antigen level (HR, 1.54; 95% CI, 1.30-1.90), lack of combination chemotherapy (HR, 1.52; 95% CI, 1.31-1.80), stage IVb disease (HR, 1.50; 95% CI, 1.17-1.86), leukocytosis (HR, 1.44; 95% CI, 1.28-1.73), and World Health Organization performance status > 1 (HR, 1.30; 95% CI, 1.10-1.55) were correlated with inferior survival. CONCLUSIONS: Our results confirm that individuals with metastatic colorectal cancer and right-sided tumors who received chemotherapy have inferior survival independent of other known prognostic variables. Future studies are required to understand the underlying pathophysiology.

Impact of travel distance on access to treatment and survival in patients with metastatic colorectal cancer prescribed bevacizumab plus chemotherapy.

INTRODUCTION: Given Saskatchewan's size and low population density outside of city centres, many rural and remote residents have issues accessing regional oncology services. We performed a study to determine whether travel distance to cancer treatment centres affects first-line treatment accessibility and survival in patients with metastatic colorectal adenocarcinoma. METHODS: Retrospective chart review of patients with stage IV metastatic colorectal adenocarcinoma collected by the Saskatchewan Cancer Agency registry between June 1, 2009, and June 30, 2013. Patients were categorized as living within 100 km of or more than 100 km from the nearest cancer treatment centre offering bevacizumab plus first-line chemotherapy. Main outcome measures were differences in first-line treatment accessibility and overall survival estimates (calculated via the Kaplan-Meier method) between cohorts. RESULTS: Of the 252 included patients, 91 (36.1%) resided more than 100 km from a cancer treatment centre. Accessibility of standard single-agent and combination chemotherapy in the first-line setting, when not prescribed in conjunction with bevacizumab, was comparable between cohorts. Patients living within 100 km of a treatment centre and those living more than 100 km from a treatment centre had comparable access to bevacizumab in conjunction with first-line chemotherapy (57 [62.6%] v. 116 [72.0%] patients; p = 0.1) and similar median overall survival (18.1 v. 25.0 mo; p = 0.2). CONCLUSION: Neither access to bevacizumab treatment nor survival times for metastatic colorectal adenocarcinoma were significantly different between the cohorts. This suggests that health care providers in Saskatchewan may be doing well in arranging timely access to advanced oncology centres. Future studies with a larger sample, different tumour types or changes to the definition of remoteness are indicated.

INTRODUCTION: Compte tenu de la taille de la Saskatchewan et de la faible densité de sa population hors des centres urbains, beaucoup de personnes en régions rurales et éloignées ont de la difficulté à obtenir des services d'oncologie régionaux. Nous avons mené une étude pour déterminer si la distance à parcourir pour se rendre aux centres de traitement du cancer a des répercussions sur l'accès aux traitements de première intention et sur la survie des patients atteints d'adénocarcinome colorectal métastasique. METHODS: Nous avons procédé à un examen rétrospectif des dossiers du registre de la Saskatchewan Cancer Agency portant sur les patients atteints d'adénocarcinome colorectal métastasique de stade IV, pour la période du 1er juin 2009 au 30 juin 2013. Nous avons réparti les patients selon 2 catégories : ceux vivant à moins de 100 km et ceux vivant à plus de 100 km du centre de traitement du cancer le plus près offrant le bévacizumab et la chimiothérapie de première intention. Nous avons utilisé comme principaux indicateurs de résultats les différences entre les cohortes au niveau de l'accès au traitement de première intention et du taux de survie global estimé (calculés d'après la méthode Kaplan­Meier). RESULTS: Sur les 252 patients de l'étude, 91 (36,1 %) habitaient à plus de 100 km d'un centre de traitement du cancer. L'accès à une monothérapie standard et à une chimiothérapie combinée en première intention, lorsque non prescrite en même temps que le bévacizumab, était comparable entre les cohortes. Les patients vivant à moins de 100 km d'un centre de traitement et ceux vivant à plus de 100 km d'un centre de traitement avaient un accès comparable au bévacizumab associé à la chimiothérapie de première intention (57 [62,6 %] c. 116 [72,0 %] patients; p = 0,1) et un taux de survie global médian similaire (18,1 c. 25,0 mois; p = 0,2). CONCLUSION: Il n'y avait aucune différence sur le plan statistique entre les cohortes pour ce qui est de l'accès au traitement de bévacizumab et de la durée de survie pour l'adénocarcinome colorectal métastasique. Ces résultats suggèrent que les professionnels de la santé de la Saskatchewan réussissent bien à prévoir l'accès rapide aux centres de traitement avancé en oncologie. D'autres études sont nécessaires au moyen d'un échantillon plus important, sur d'autres types de tumeurs ou en modifiant la définition de l'éloignement.

Effects of metformin versus placebo on vitamin B12 metabolism in non-diabetic breast cancer patients in CCTG MA.32.

BACKGROUND: Metformin is associated with low levels of vitamin B12 (VitB12) in patients with diabetes. The CCTG/MA.32 trial investigates the effects of metformin vs placebo on breast cancer (BC) outcomes in non-diabetic high-risk BC patients. We analyzed VitB12 at baseline and after 6 months of metformin (versus placebo) in the first 492 patients with paired blood samples. METHODS: VitB12 was analyzed centrally in baseline and 6-month fasting plasma. Levels <181 pmol/L were considered deficient, 181-221 pmol/L borderline, and ≥222 pmol/L sufficient. Methylmalonic acid (MMA) and homocysteine (HC) were assayed in those with VitB12 levels <222 pmol/L. Statistical analyses used Spearman's rank correlation coefficients and Wilcoxon signed-rank test for continuous variables and Chi-square test for categorical variables. RESULTS: 237 patients received metformin and 255 received placebo; median (inter quartile range) baseline VitB12 levels were 390 (290, 552) and 370 (290, 552) pmol/L in the metformin and placebo arms, respectively (p = 0.97). At 6 months, the median levels were 320 (244, 419) in the metformin versus 380 (286, 546) pmol/L in the placebo arm (p = 0.0001). At baseline, 15 patients (11 metformin and 4 placebo) had VitB12 <181 pmol/L, and at 6 months, 18 patients (15 metformin and 3 placebo) (p = 0.004). Median hemoglobin was similar at baseline, metformin, 130 g/L (124-137), and placebo arms, 131 g/L (124-137) (p = 0.38), and at 6 months, metformin, 131 g/L (91-162), and 131 g/L (106-169) in placebo group (p = 0.11). Of the 74 subjects with vitamin B12 <222 pmol/L at either time point (45 metformin, 29 placebo), at baseline MMA was normal in all patients and two had elevated HC (>15µmol/L). At 6 months, one patient (metformin) had MMA >0.4µmol/L and 3 (2 metformin, 1 placebo) had HC > 15µmol/L. CONCLUSIONS: There was an increased rate of biochemical VitB12 deficiency after 6 months of metformin; this was not associated with anemia. Further research will investigate VitB12 levels in all subjects at baseline and at 6 and 60 months.