Development and validation of AI-assisted transcriptomic signatures to personalize adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: After surgical resection of pancreatic ductal adenocarcinoma (PDAC), patients are predominantly treated with adjuvant chemotherapy, commonly consisting of gemcitabine-based regimens or the modified FOLFIRINOX regimen (mFFX). While mFFX has been shown to be more effective than gemcitabine-based regimens, it is also associated with higher toxicity. Current treatment decisions are based on patient performance status rather than on the molecular characteristics of the tumor. To address this gap, the goal of this study was to develop drug-specific transcriptomic signatures for personalized chemotherapy treatment. PATIENTS AND METHODS: We used PDAC datasets from preclinical models, encompassing chemotherapy response profiles for the mFFX-regimen components. From them we identified specific gene transcripts associated with chemotherapy response. Three transcriptomic AI-signatures were obtained by combining Independent Component Analysis, Least Absolute Shrinkage and the Selection Operator-Random Forest approach. We integrated a previously developed gemcitabine signature with three newly developed ones. The machine learning strategy employed to enhance these signatures incorporates transcriptomic features from the tumor microenvironment, leading to the development of the Pancreas-View tool ultimately clinically validated in a cohort of 343 patients from the PRODIGE-24/CCTG PA6 trial. RESULTS: Patients who were predicted to be sensitive to the administered drugs (n=164; 47.8%) had longer disease-free survival (DFS) than the other patients. The median DFS in the mFFX sensitive group treated with mFFX was 50.0 months (stratified HR: 0.31; 95% CI, 0.21-0.44; p<0.001) and 33.7 months (stratified HR: 0.40; 95% CI, 0.17-0.59; p<0.001) in the gemcitabine sensitive group when treated with gemcitabine. Comparatively patients with signature predictions unmatched with the treatments (n=86; 25.1%) or those resistant to all drugs (n=93; 27.1%) had shorter DFS (10.6 and 10.8 months, respectively). CONCLUSIONS: This study presents a transcriptome-based tool that was developed using preclinical models and machine learning to accurately predict sensitivity to mFFX and gemcitabine.

Comparative Effectiveness of FOLFIRINOX Versus Gemcitabine and Nab-paclitaxel in Initially Unresectable Locally Advanced Pancreatic Cancer: A Population-based Study to Assess Subsequent Surgical Resection and Overall Survival.

AIMS: First-line FOLFIRINOX (FOLinic acid, Fluorouracil, IRINotecan, and OXaliplatin) and gemcitabine plus nab-paclitaxel (GnP) have been publicly funded for patients with unresectable locally advanced pancreatic cancer (uLAPC) in Ontario, Canada. We examined the overall survival and surgical resection rate after first-line FOLFIRINOX or GnP and determined the association between resection and overall survival in patients with uLAPC. MATERIALS AND METHODS: We conducted a retrospective population-based study including patients with uLAPC who received first-line treatment FOLFIRINOX or GnP from April 2015 to March 2019. The cohort was linked to administrative databases to ascertain demographic and clinical characteristics. Propensity score methods were used to balance differences between FOLFIRINOX and GnP. The Kaplan-Meier method was used to calculate overall survival. Cox regression was used to determine the association between receipt of treatment and overall survival, adjusting for time-dependent surgical resections. RESULTS: We identified 723 patients with uLAPC (mean age = 65.8, 43.5% female) who received FOLFIRINOX (55.2%) or GnP (44.8%). The median overall survival and 1-year overall survival probability were higher for FOLFIRINOX (13.7 months, 54.6%) than for GnP (8.7 months, 34.0%). Post-chemotherapy surgical resection occurred in 89 (12.3%) patients (FOLFIRINOX: 74 [18.5%] versus GnP: 15 [4.6%]), with no difference in survival since surgery between FOLFIRINOX and GnP (P = 0.29). After adjusting time-dependent post-treatment surgical resection, FOLFIRINOX (inverse probability treatment weighting hazard ratio 0.72, 95% confidence interval 0.61, 0.84) was independently associated with improved overall survival. CONCLUSIONS: In this real-world population-based study of patients with uLAPC, FOLFIRINOX was associated with improved survival and higher resection rates. FOLFIRINOX was associated with improved survival in patients with uLAPC after accounting for the effect of post-chemotherapy surgical resection, suggesting the benefit of FOLFIRINOX was not solely due to improving resectability.

Outcomes Following Treatment with FOLFOX for Patients with Resectable or Potentially Resectable Metastatic Colorectal Cancer: A Population-based Cohort Study.

AIMS: To evaluate the safety and effectiveness of oxaliplatin-based combination chemotherapy for patients with metastatic colorectal cancer (mCRC) to extrahepatic sites. MATERIALS AND METHODS: We conducted a population-based retrospective study examining the safety and effectiveness of perioperative oxaliplatin for resectable or potentially resectable colorectal metastases in Ontario, Canada. Outcomes were also compared with patients with liver-only metastases. Patients received oxaliplatin for mCRC between 1 January 2013 and 30 June 2020. RESULTS: In total, 192 patients had extrahepatic metastases. Seventy per cent had R0 metastasectomy. The 3-year disease-free survival and overall survival were 62% and 79%, respectively; <4% of patients died within 60 days of metastasectomy and 74-90% of patients received treatment according to recommendations from a multidisciplinary setting. Compared with liver-only controls (n = 1306), patients had mCRC to the lung only (n = 115), lung and liver (n = 55) and liver with non-pulmonary site (n = 22). Extrahepatic metastases were more likely to be found for patients whose primary colorectal resection had positive margins (14% versus 7%, P = 0.005) and primary tumours located in the rectum [odds ratio 4.01 (2.31-6.97)]. After adjustment, there was no difference in overall survival between liver-only controls and patients with lung-only [hazard ratio 0.82 (0.59-1.15)] or liver and lung metastases [hazard ratio 1.26 (0.85-1.87)] (P = 0.24). In total, 79/115 (69%) of patients with lung-only metastases had a metastasectomy compared with 645/1306 (49%) and 15/55 (27%) of patients with liver-only and liver and lung metastases, respectively. Hospital visits were similar between patients with liver-only and extrahepatic metastases. CONCLUSION: Oxaliplatin-based chemotherapy for patients with resectable or potentially resectable mCRC with extrahepatic metastases was safe and resulted in similar outcomes in appropriately selected patients when compared with patients with liver-only metastases.

Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a clinical practice guideline.

Objective: The purpose of the present review was to provide evidence-based guidance about the provision of cytoreductive surgery (crs) with hyperthermic intraperitoneal chemotherapy (hipec) in the treatment of peritoneal cancers. Methods: The guideline was developed by the Program in Evidence-Based Care together with the Surgical Oncology Program at Ontario Health (Cancer Care Ontario) through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews. Results: Recommendation 1a: For patients with newly diagnosed stage iii primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, hipec should be considered for those with at least stable disease after neoadjuvant chemotherapy at the time that interval crs (if complete) or optimal cytoreduction is achieved. Recommendation 1b: There is insufficient evidence to recommend the addition of hipec when primary crs is performed for patients with newly diagnosed advanced primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, outside of a clinical trial. Recommendation 2: There is insufficient evidence to recommend hipec with crs in patients with recurrent ovarian cancer outside the context of a clinical trial. Recommendation 3: There is insufficient evidence to recommend hipec with crs in patients with peritoneal colorectal carcinomatosis outside the context of a clinical trial. Recommendation 4: There is insufficient evidence to recommend hipec with crs for the prevention of peritoneal carcinomatosis in colorectal cancer outside the context of a clinical trial; however, hipec using oxaliplatin is not recommended. Recommendation 5: There is insufficient evidence to recommend hipec with crs for the treatment of gastric peritoneal carcinomatosis outside the context of a clinical trial. Recommendation 6: There is insufficient evidence to recommend hipec with crs for the prevention of gastric peritoneal carcinomatosis outside the context of a clinical trial. Recommendation 7: There is insufficient evidence to recommend hipec with crs as a standard of care in patients with malignant peritoneal mesothelioma; however, patients should be referred to hipec specialty centres for assessment for treatment as part of an ongoing research protocol. Recommendation 8: There is insufficient evidence to recommend hipec with crs as a standard of care in patients with disseminated mucinous neoplasm in the appendix; however, patients should be referred to hipec specialty centres for assessment for treatment as part of an ongoing research protocol.

Eastern Canadian Colorectal Cancer Consensus Conference 2017.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

Medical oncology workload in Canada: infrastructure, supports, and delivery of clinical care.

Background: In 2000, a Canadian task force recommended that medical oncologists (mos) meet a target of 160-175 new patient consultations per year. Here, we report the Canadian results of a global survey of mo workload compared with mo workload in other high-income countries (hics). Methods: Using a snowball method, an online survey was distributed by national oncology societies to chemotherapy-prescribing physicians in 22 hics (World Bank criteria). The survey was distributed within Canada to all members of the Canadian Association of Medical Oncologists. Workload was measured as the annual number of new cancer patient consults per oncologist. Results: The survey was completed by 782 oncologists from hics, including 58 from Canada. Median annual consults per mo were 175 in Canada compared with 125 in other hics. The proportions of mos having 100 or fewer consults or more than 300 consults per year were 3% (2/58) and 5% (3/58) in Canada compared with 31% (222/724) and 16% (116/724) in other hics (p < 0.001 and p = 0.023 respectively). The median number of patients seen in a full-day clinic was 15 in Canada and 25 in other hics (p = 0.220). Canadian mos reported spending a median of 55 minutes per new consultation; new consultations of 35 minutes were reported in other hics (p < 0.001). Median hours worked per week was 55 in Canada and 45 in other hics (p = 0.200). Conclusions: Although the median annual clinical volume for Canadian mos aligns with recommended targets, half the respondents exceeded that level of activity. Health policymakers and educators have to consider mo workforce supply and alternative models of care in preparation for the anticipated surge in cancer incidence in the coming decade.

Uptake and Effectiveness of FOLFIRINOX for Advanced Pancreatic Cancer: a Population-based Study.

AIMS: Although FOLFIRINOX is a standard treatment option for advanced pancreas cancer, there are few data describing utilisation and effectiveness in routine clinical practice. Here we report practice patterns and outcomes in the general population of Ontario, Canada. MATERIALS AND METHODS: Using the Ontario Cancer Registry and New Drug Funding Program, we identified all patients with pancreas cancer treated with palliative intent gemcitabine or FOLFIRINOX in Ontario during 2006-2014. FOLFIRINOX became available in Ontario's single-payer health system in November 2011. Gemcitabine cases were classified as pre-FOLFIRINOX era (2006-2010) or post-FOLFIRINOX era (2011-2014). Cases treated with perioperative chemotherapy were excluded. Comparisons of proportions between study groups were made using the chi-square test. Overall survival was measured from the date of chemotherapy initiation. RESULTS: During 2006-2014, 3826 patients in Ontario were treated with gemcitabine (n = 3042) or FOLFIRINOX (n = 784) chemotherapy for advanced pancreas cancer. Uptake of FOLFIRINOX increased from 41% (206/505) of treated cases in 2012 to 56% (274/486) of treated cases in 2014. The median overall survival of patients treated with gemcitabine was 5.0 months in 2006-2010 and 4.8 months in 2011-2014. The median overall survival of FOLFIRINOX patients treated in 2011-2014 was 8.2 months. CONCLUSION: The use of FOLFIRINOX in the general population has increased since 2011. Survival outcomes show a substantial efficacy-effectiveness gap between the pivotal Prodige 4/ACCORD 11 clinical trial and routine practice.

The predictive effect of primary tumour location in the treatment of metastatic colorectal cancer: a Canadian consensus statement.

In recently published data, the predictive value of primary tumour location for the treatment of metastatic colorectal cancer with available biologic therapies has been explored. Recognizing the potential effect of those data on clinical practice, we convened a meeting of Canadian experts who treat metastatic colorectal cancer to develop a set of national, evidence-based treatment guidelines based on primary tumour location. This report summarizes the relevant evidence and presents the consensus recommendations of those experts.

Shifting practice in definitive chemoradiation for localized esophageal cancer.

BACKGROUND: The efficacy of carboplatin-paclitaxel in the trimodality setting was demonstrated in the cross trial. Because of better tolerance, that regimen has been adopted as an alternative for patients receiving definitive chemoradiation (dcrt). The purpose of our study was to compare outcomes in patients with localized esophageal and gastroesophageal junction (gej) cancer who received dcrt using either platinum-5-fluorouracil (5fu) or carboplatin-paclitaxel. METHODS: Medical records and outcomes for all patients diagnosed with localized carcinoma of the esophagus and gej at our centre between 2008 and 2015 were reviewed. All patients who underwent dcrt using cisplatin-5fu, carboplatin-5fu, or carboplatin-paclitaxel were included. RESULTS: The 73 identified patients (34 cisplatin-5fu, 13 carboplatin-5fu, 26 carboplatin-paclitaxel) were all prescribed concomitant radiotherapy of 50 Gy in 25 daily fractions. The diagnosis was adenocarcinoma in 64% and squamous cell carcinoma in 36%. Median overall survival (os) duration for the cisplatin-5fu group was 28 months [95% confidence interval (ci): 19 to 41 months], with a 3-year os rate of 44%, in contrast to the 15 months (95% ci: 11 to 17 months) and 15% in the carboplatin-paclitaxel group (log-rank p = 0.0047). Median os duration for the carboplatin-5fu group was 17 months (95% ci: 11 to 68 months) with a 3-year os rate of 31%. Adjusting for patient and disease factors, better os durations and rates were associated with cisplatin-5fu (hazard ratio: 0.34; p = 0.0016) and carboplatin-5fu (hazard ratio: 0.55; p = 0.20) than with carboplatin-paclitaxel. CONCLUSIONS: In a dcrt regimen, a better os is associated with cisplatin-5fu than with carboplatin-paclitaxel. Clinical trials to determine optimal chemotherapy regimens are warranted for patients who are not suitable for surgery.

Phase I/II trial of dose-reduced capecitabine in elderly patients with advanced colorectal cancer.

BACKGROUND: Combination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (acrc). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial. METHODS: A multicentre phase i/ii trial of reduced-dose capecitabine (2000 mg/m2, days 1-14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54). Based on phase i results, patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity. RESULTS: Median age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0-50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand-foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (pfs) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh). CONCLUSIONS: Toxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and pfs appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m2, or even 750 mg/m2, twice daily is an appropriate dose in elderly or frail patients with acrc.

Adjuvant Chemotherapy for Stage II Colon Cancer: Practice Patterns and Effectiveness in the General Population.

AIMS: Although guidelines do not recommend adjuvant chemotherapy (ACT) for stage II colon cancer, many state that ACT may be considered in high-risk disease. Here we describe practice patterns and outcomes associated with ACT in the general population. MATERIALS AND METHODS: All cases of colon cancer diagnosed in Ontario 2002-2008 were identified using the Ontario Cancer Registry, which was linked to electronic treatment records. Pathology reports were obtained for a 25% random sample of cases. High-risk disease was defined as: T4 tumours, <12 lymph nodes, poorly differentiated histology, lymphovascular invasion. Modified Poisson regression was used to evaluate factors associated with ACT. The Cox proportional hazards model was used to explore the association between ACT and cancer-specific (CSS) and overall survival. RESULTS: The study population included 2488 patients with stage II colon cancer; 1175 (47%) with high-risk disease. ACT was delivered to 18% of all patients and 24% of patients with high-risk disease. ACT rates were higher among younger patients (51% age 20-49 years versus 16% age 70-79, P < 0.001) and varied considerably across geographic regions (range 10-39%, P < 0.001). Among all patients with stage II colon cancer, ACT was not associated with improved CSS (hazard ratio 1.41, 95% confidence interval 1.09-1.82) or overall survival (hazard ratio 1.16, 95% confidence interval 0.94-1.42). Stratified survival analysis for patients with high-risk disease did not show benefit to ACT (CSS hazard ratio 1.14, 95% confidence interval 0.84-1.55; overall survival hazard ratio 1.02, 95% confidence interval 0.79-1.31). CONCLUSION: ACT use varies across age groups and geographic regions. ACT is not associated with improved survival among patients with stage II colon cancer including those with high-risk disease.

Chemotherapy delivery for resected colorectal cancer liver metastases: Management and outcomes in routine clinical practice.

BACKGROUND: International guidelines recommend peri-operative chemotherapy for patients with resectable colorectal cancer liver metastases (CRCLM). Chemotherapy delivery in routine practice is not well described. METHODS: All cases of CRC who underwent resection of LM in 2002-2009 were identified using the population-based Ontario Cancer Registry. Electronic treatment records identified chemotherapy delivered within 16 weeks before or after hepatectomy. All pathology reports were reviewed to describe extent of LM. Modified Poisson regression was used to evaluate factors associated with chemotherapy delivery. Cox proportional hazards model and propensity score analysis were used to explore the association between post-operative chemotherapy and cancer-specific (CSS) and overall (OS) survival. RESULTS: We identified 1310 patients. Sixty-two percent of cases (815/1310) received peri-operative chemotherapy; 25% (200/815) pre-operative, 45% (366/815) post-operative, and 31% (249/815) pre- and post-operative. Utilization of chemotherapy increased over time from 51% in 2002 (57/112) to 73% in 2009 (157/216, p < 0.001). Fifty-four percent of patients received FOLFOX, 41% FOLFIRI, and 10% 5-FU monotherapy. Factors that were independently associated with greater utilization of post-operative chemotherapy included younger age (p < 0.001), female sex (p = 0.050), shorter disease-free interval (p = 0.006), and no prior adjuvant chemotherapy (p < 0.001). Utilization of chemotherapy varied substantially across geographic regions (from 24% to 71%, p = 0.001). Post-operative chemotherapy was associated with improved CSS (HR 0.58, 95%CI 0.44-0.76) and OS (HR 0.49, 95%CI 0.38-0.61); results were consistent in propensity score analysis. CONCLUSION: Utilization of chemotherapy for resected CRCLM in routine practice has evolved with emerging evidence. Post-operative chemotherapy is associated with improved survival in the general population.

Corrigendum: Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014.

[This corrects the article DOI: 10.3747/co.22.2603.].

Research output and the public health burden of cancer: is there any relationship?

PURPOSE: The relative distribution of research output across cancer sites is not well described. Here, we evaluate whether the volume of published research is proportional to the public health burden of individual cancers. We also explore whether research output is proportional to research funding. METHODS: Statistics from the Canadian and American cancer societies were used to identify the top ten causes of cancer death in 2013. All journal articles and clinical trials published in 2013 by Canadian or U.S. authors for those cancers were identified. Total research funding in Canada by cancer site was obtained from the Canadian Cancer Research Alliance. Descriptive statistics and Pearson correlation coefficients were used to describe the relationship between research output, cancer mortality, and research funding. RESULTS: We identified 19,361 publications and 2661 clinical trials. The proportion of publications and clinical trials was substantially lower than the proportion of deaths for lung (41% deaths, 15% publications, 16% clinical trials), colorectal (14%, 7%, 6%), pancreatic (10%, 7%, 5%), and gastroesophageal (7%, 5%, 3%) cancers. Conversely, research output was substantially greater than the proportion of deaths for breast cancer (10% deaths, 29% publications, 30% clinical trials) and prostate cancer (8%, 15%, 17%). We observed a stronger correlation between research output and funding (publications r = 0.894, p < 0.001; clinical trials r = 0.923, p < 0.001) than between research output and cancer mortality (r = 0.363, p = 0.303; r = 0.340, p = 0.337). CONCLUSIONS: Research output is not well correlated with the public health burden of individual cancers, but is correlated with the relative level of research funding.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

Surgical resection and peri-operative chemotherapy for colorectal cancer liver metastases: A population-based study.

BACKGROUND: Most literature describing surgery for colorectal cancer (CRC) liver metastases (LM) comes from high volume centres. Here, we report management and outcomes achieved in routine clinical practice. METHODS: All cases of CRC in Ontario who underwent resection of LM in 1994-2009 were identified using the population-based Ontario Cancer Registry. Electronic treatment records identified chemotherapy delivery. Temporal trends are described for 3 periods: 1994-1999, 2000-2004, 2005-2009. We describe volume of resected CRCLM as a ratio of incident cases per CRCLM resection. Overall (OS) and cancer-specific survival (CSS) are measured from time of LM resection. RESULTS: 2717 patients underwent resection of CRCLM. Between 1994 and 2009 there was a 78% increase in case volume; from one resection for every 48 incident cases to one resection for every 27 incident cases, p < 0.001. Use of peri-operative chemotherapy increased over study periods from 44% (306/700), to 52% (429/830), to 65% (777/1187, p < 0.001). Chemotherapy utilization rates varied across geographic regions (range 43%-69%, p < 0.001). Post-operative mortality rates at 30 and 90 days were 2.5% and 4.3% respectively. Five year OS during the study periods was 36% (95% CI 32-39%), 40% (95% CI 36-43%), and 46% (95% CI 43-49%) (p < 0.001); CSS was 38% (95% CI 35-42%), 42% (95% CI 38-45%), 49% (95% CI 44-53%) (p < 0.001). The temporal improvement in OS/CSS persisted on adjusted analyses. CONCLUSIONS: Outcomes of patients with resected CRCLM in routine practice is comparable to those reported from high volume centres. Survival improved over the study period despite a greater proportion of patients with CRC undergoing liver resection.

Management and outcomes of localized esophageal and gastroesophageal junction cancer in older patients.

BACKGROUND: Older patients are commonly excluded from clinical trials in esophageal and gastroesophageal junction (gej) cancer. High-level evidence to guide management in this group is lacking. In the present study, we compared outcomes and described tolerance for curative- and noncurative-intent treatments among patients 70 years of age and older. METHODS: We retrospectively reviewed all patients 70 years of age and older diagnosed with localized esophageal and gej cancer at our centre between 2005 and 2012. RESULTS: The 74 patients identified had a median age of 77 years. Of those patients, 62% received curative-intent treatment, consisting mostly of concomitant chemoradiation therapy (n = 43, 93%). Median overall survival for patients receiving curative-intent treatment was 18.6 months [95% confidence interval (ci): 13.0 to 28.0 months], with 23% being long-term survivors (95% ci: 11.3% to 36.7%). In contrast, patients receiving noncurative-intent treatment had a median overall survival of 8.8 months (95% ci: 6.7 to 11.9 months), with none being long-term survivors (p < 0.0001). Improvement of dysphagia was seen after curative (81%) or palliative radiotherapy (78%) in symptomatic patients, and toxicities were manageable. The odds of not receiving curative treatment was higher by a factor of 8.5 among patients 80 years of age or older compared with those 70-79 years of age (95% ci: 2.5 to 28.7). CONCLUSIONS: In managing older patients with esophageal and gej cancer, curative-intent treatment (compared with noncurative-intent treatment) leads to a significant survival benefit with a reasonable toxicity profile. Informed counselling of patients and their families about a curative treatment approach and efforts to increase awareness among oncology care providers are suggested.

The optimal organization of gynecologic oncology services: a systematic review.

BACKGROUND: A system-level organizational guideline for gynecologic oncology was identified by a provincial cancer agency as a key priority based on input from stakeholders, data showing more limited availability of multidisciplinary or specialist care in lower-volume than in higher-volume hospitals in the relevant jurisdiction, and variable rates of staging for ovarian and endometrial cancer patients. METHODS: A systematic review assessed the relationship of the organization of gynecologic oncology services with patient survival and surgical outcomes. The electronic databases medline and embase (ovid: 1996 through 9 January 2015) were searched using terms related to gynecologic malignancies combined with organization of services, patterns of care, and various facility and physician characteristics. Outcomes of interest included overall or disease-specific survival, short-term survival, adequate staging, and degree of cytoreduction or optimal cytoreduction (or both) for ovarian cancer patients by hospital or physician type, and rate of discrepancy in initial diagnoses and intraoperative consultation between non-specialist pathologists and gyne-oncology-specialist pathologists. RESULTS: One systematic review and sixteen additional primary studies met the inclusion criteria. The evidence base as a whole was judged to be of lower quality; however, a trend toward improved outcomes with centralization of gynecologic oncology was found, particularly with respect to the gynecologic oncology care of patients with advanced-stage ovarian cancer. CONCLUSIONS: Improvements in outcomes with centralization of gynecologic oncology services can be attributed to a number of factors, including access to specialist care and multidisciplinary team management. Findings of this systematic review should be used with caution because of the limitations of the evidence base; however, an expert consensus process made it possible to create recommendations for implementation.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2014.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23-25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer.