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.

Current Role of Immunotherapy in Gastric, Esophageal and Gastro-Esophageal Junction Cancers-A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference.

Gastric, esophageal and gastro-esophageal junction cancers are associated with inferior outcomes. For early-stage disease, perioperative chemotherapy or chemoradiation followed by surgery is the standard treatment. For most patients with advanced upper gastrointestinal tract cancers, platinum-based chemotherapy remains a standard treatment. Recently, several randomized clinical trials have demonstrated the benefit of immunotherapy involving checkpoint inhibitors alone or in combination with chemotherapy in patients with gastro-esophageal cancer and have changed the treatment landscape. The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC), involving experts from four Western Canadian provinces, convened virtually on 16 June 2021 and developed the recommendations on the role of immunotherapy in patients with gastro-esophageal cancer.

Systemic Therapy and Its Surgical Implications in Patients with Resectable Liver Colorectal Cancer Metastases. A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference.

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.

Report from the Western Canadian Gastrointestinal Consensus Cancer Conference-Management of Total Neoadjuvant Therapy in Rectal Cancer.

An educational session related to the Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held virtually on 14 October 2020. The WCGCCC is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba), who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists, radiologists, and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of total neoadjuvant therapy in rectal cancer.

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.

Current progress in systemic therapy for biliary tract cancers.

BACKGROUND: Biliary tract cancers (BTCs) are heterogeneous cancers that include cancers of the bile duct and gallbladder. Although they are relatively uncommon, most patients with BTC are diagnosed at advanced-stage disease with high mortality rates. Recently, systemic therapy options for patients with BTC have evolved. This paper reviews recent advancements in systemic therapy and the results of key clinical trials in BTC. METHODS: A literature search in PubMed and Google Scholar was performed using keywords related to BTC and systemic therapy. Studies that were presented in major international cancer research conferences were also included. RESULTS: The evidence shows that adjuvant capecitabine has been associated with a lower relapse rate in early-stage BTC. In unselected patients with advanced BTC, combination chemotherapy is a standard treatment option. However, with a better understanding of the molecular profile of BTC, there has been a shift toward targeted agents in BTC that have shown promising responses. The evolving data also support the evolving role of immunotherapy in patients with deficient DNA mismatch repair or PD-L1-positive BTC. DISCUSSION: Systemic treatment options for BTC have improved. The future identification of new targets, novel compounds, and predictive markers is a key step toward the use of personalized medicine in BTC.

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.

Report from the Western Canadian Gastrointestinal Cancer Consensus Conference Virtual Education Series-Transition from Local to System Therapy and Optimal Sequencing of Systemic Therapy for HCC.

The Western Canadian Gastrointestinal Cancer Consensus Conference (WC-5) convened virtually on 10 February 2021. The WC-5 is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular cancer (HCC). Recommendations have been made for the transition from local to systemic therapy and the optimal sequencing of systemic regimens in the management of HCC.

Report from the 21st Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Calgary, Alberta; 20-21 September 2019.

The 21st annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Calgary, Alberta, 20-21 September 2019. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists, pathologists, radiologists, and allied health care professionals such as dietitians and nurses participated in presentation and discussion sessions to develop the recommendations presented here. This consensus statement addresses current issues in the management of hepato-pancreato-biliary (HPB) cancers.

Comparison of Perioperative Chemotherapy versus Postoperative Chemoradiotherapy for Operable Stomach Cancer: A Western Canadian Province Experience.

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.

Mining the plasma-proteome associated genes in patients with gastro-esophageal cancers for biomarker discovery.

Gastro-esophageal (GE) cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of GE cancers, to yield predictive response to the available therapies. Our study aims to identify leading genes that are differentially regulated in patients with these cancers. We explored the expression data for those genes whose protein products can be detected in the plasma using the Cancer Genome Atlas to identify leading genes that are differentially regulated in patients with GE cancers. Our work predicted several candidates as potential biomarkers for distinct stages of GE cancers, including previously identified CST1, INHBA, STMN1, whose expression correlated with cancer recurrence, or resistance to adjuvant therapies or surgery. To define the predictive accuracy of these genes as possible biomarkers, we constructed a co-expression network and performed complex network analysis to measure the importance of the genes in terms of a ratio of closeness centrality (RCC). Furthermore, to measure the significance of these differentially regulated genes, we constructed an SVM classifier using machine learning approach and verified these genes by using receiver operator characteristic (ROC) curve as an evaluation metric. The area under the curve measure was > 0.9 for both the overexpressed and downregulated genes suggesting the potential use and reliability of these candidates as biomarkers. In summary, we identified leading differentially expressed genes in GE cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted treatment.

Prevalence of Hormone-Related Cancers (HRCs) at Two-Time Points in Rural Saskatchewan: The Saskatchewan Rural Health Study (SRHS).

OBJECTIVE: This study aimed to determine the prevalence of hormone-related cancers (HRCs) among Saskatchewan rural dwellers and explore associated risk factors. METHODS: Data were analyzed from the Saskatchewan Rural Health Study (SRHS), which was a prospective cohort (2010 to 2014). Completed questionnaires were obtained from 4624 (2797) households, with information about 8261 (4867) individuals more than or equal to 18 years at baseline (follow-up). The crude prevalence of HRCs was calculated using appropriate formulae. Adjusted prevalence was calculated using logistic regression based on the generalized estimating equation (GEE). RESULTS: Crude prevalence of HRCs was 3.0% at the baseline. Variables significantly associated with HRCs were: exposure to radiation comprising ultraviolet radiation from sunlight as well as ionizing radiation (odds ratio [OR] 3.39; 95% confidence interval [CI]: 2.23, 4.84), previous history of cancer in sibling (OR = 1.51, 95% CI: 1.11, 2.07) and in father (OR = 1.37; 95% CI = 1.01, 1.86). CONCLUSIONS: The study informs the Saskatchewan Health Region for health care resource allocation.

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.

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.

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.

Warming of Irrigation Fluids for Prevention of Perioperative Hypothermia During Arthroscopy: A Systematic Review and Meta-analysis.

PURPOSE: To determine whether warming of irrigation fluids (32°C-40°C) compared with using room-temperature irrigation fluids (20°C-22°C) decreases the risk of perioperative hypothermia (<36°C) for patients undergoing shoulder, hip, or knee arthroscopy. METHODS: One reviewer, with the assistance of a medical librarian, searched the following databases: PubMed, Embase, Cochrane Central, SPORTDiscus, Web of Science, and CINAHL (Cumulative Index to Nursing and Allied Health Literature). Level I and II studies involving shoulder, hip, or knee arthroscopy were included. Two reviewers screened the abstracts and titles. Two reviewers assessed the risk of bias of selected studies using The Cochrane Collaboration tool. Meta-analyses were conducted on the following outcomes: hypothermia, lowest temperature, maximum temperature drop, and shivering. RESULTS: Seven studies of patients undergoing arthroscopy were included in the qualitative synthesis (5 shoulder studies, 1 hip study, and 1 knee study; 501 patients). The study involving knee arthroscopy was excluded from the meta-analyses because of insufficient data and high clinical heterogeneity (surgical site distal to the core, not involving extravasation of large amounts of fluid). The remaining 6 studies were included in 1 or more meta-analyses: hypothermia (5 shoulder and 1 hip study), lowest temperature (3 shoulder and 1 hip study), maximum temperature drop (2 shoulder and 1 hip study), and shivering (5 shoulder and 1 hip study). Warming of irrigation fluids for shoulder or hip arthroscopy significantly decreased the risk of hypothermia (odds ratio, 0.15; 95% confidence interval [CI], 0.06-0.40; P = .0001), increased the lowest mean temperature (mean difference, 0.46°C; 95% CI, 0.11°C-0.81°C; P = .01), decreased the maximum temperature drop (mean difference, -0.64°C; 95% CI, -0.94°C to -0.35°C; P < .0001), and decreased the risk of shivering (odds ratio, 0.25; 95% CI, 0.07-0.86; P = .03). CONCLUSIONS: When irrigation fluids are warmed for shoulder and hip arthroscopy, the risk of hypothermia is less, the drop in intraoperative temperature is less, the lowest body temperature is higher, and the risk of postoperative shivering is reduced. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

Regional Lymph Nodes Status and Ratio of Metastatic to Examined Lymph Nodes Correlate with Survival in Stage IV Colorectal Cancer.

BACKGROUND: Although lymph nodes status and the ratio of metastatic to examined lymph node (LNR) are important prognostic factors in early-stage colorectal cancer (CRC), their significance in patients with metastatic disease remains unknown. The study aims to determine prognostic importance of nodal status and LNR in patients with stage IV CRC. METHODS: A cohort of 1109 eligible patients who were diagnosed with synchronous metastatic CRC in Saskatchewan during 1992-2010 and underwent primary tumor resection was evaluated. We conducted the Cox proportional multivariate analyses to determine the prognostic significance of nodal status and LNR. RESULTS: Median age was 70 years (22-98) and M:F was 1.2:1. Rectal cancer was found in 26 % of patients; 96 % had T3/T4 tumor, and 82 % had node positive disease. The median LNR was 0.36 (0-1.0). Fifty-four percent received chemotherapy. Median overall survival of patients who had LNR of <0.36 and received chemotherapy was 29.7 months (95 % CI 26.6-32.9) compared with 15.6 months (95 % CI 13.6-17.6) with LNR of ≥0.36 (P < .001). On multivariate analyses, no chemotherapy (HR 2.36 [2.0-2.79]), not having metastasectomy (HR 1.94 [1.63-2.32]), LNR ≥0.36 (HR 1.59 [1.38-1.84]). nodal status (HR 1.34 [1.14-1.59]), and T status (HR 1.23 [1.07-1.40]) were correlated with survival. Test for interaction was positive for LNR and high-grade cancer (HR 1.51 [1.10-2.10]). CONCLUSIONS: Our results suggest that nodal status and LNR are important prognostic factors independent of chemotherapy and metastasectomy in stage IV CRC patients.

Surgical Resection of Primary Tumor in Asymptomatic or Minimally Symptomatic Patients With Stage IV Colorectal Cancer: A Canadian Province Experience.

BACKGROUND: Surgical resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Survival benefit reported in the literature has been attributed to the selection of younger and healthier patients with good performance status. We have recently reported that resection of the primary tumor improved survival of patients with stage IV CRC. In this study we examined survival benefit of surgery in patients with asymptomatic or minimally symptomatic primary tumor. PATIENTS AND METHODS: A cohort of patients with stage IV CRC and asymptomatic or minimally symptomatic primary tumor, who were diagnosed during the period of 1992 to 2005, in the province of Saskatchewan Canada, was evaluated. The Kaplan-Meier method was used to determine survival. A multivariate Cox proportional hazard regression analysis was performed to determine prognostic importance of resection of primary tumor. A test for interaction was performed for resection of primary tumor and other important clinicopathological variables. RESULTS: A total of 834 patients with a median age of 70 years (range, 22-93) and male:female ratio of 58:42 were identified. Among them 521 (63%) patients underwent surgery and 361 (43.3%) received chemotherapy. Patients who underwent surgery and received any chemotherapy had a median overall survival of 19.7 months (95% confidence interval [CI], 16.9-22.6) compared with 8.4 months (95% CI, 6.9-10.0) if they did not have surgery (P < .0001). In multivariate analysis, 5-fluorouracil-based chemotherapy (hazard ratio [HR], 0.43; 95% CI, 0.36-0.53), surgical resection of the primary tumor (HR, 0.47; 95% CI, 0.39-0.57), metastasectomy (HR, 0.48; 95% CI, 0.38-0.62), and second-line chemotherapy (HR, 0.72; 95% CI, 0.58-0.92) were correlated with superior survival. A test for interaction between ≥ 1 metastatic sites and surgery was significant, which suggests a larger benefit of surgery in patients with stage IVA disease. CONCLUSION: Results of this large population-based cohort study suggest that resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV CRC improved survival independent of other prognostic variables. The benefit was more pronounced in stage IVA disease.

Predictive Factors of the Use of Systemic Therapy in Stage IV Colorectal Cancer: Who Gets Chemotherapy?

BACKGROUND: Chemotherapy improves survival in patients with stage IV colorectal cancer (CRC). Although in a clinical trial setting, strict eligibility criteria are used for chemotherapy, little is known about the use of chemotherapy in the general population. The study aims to assess clinicopathological variables that correlate with the use of chemotherapy in patients with stage IV CRC. METHODS: A retrospective cohort study involving patients with stage IV CRC, diagnosed between 1992 and 2005, in the province of Saskatchewan was carried out. A logistic regression analysis was performed to assess the correlation of various clinicopathological factors with the use of chemotherapy. RESULTS: A total of 1,237 eligible patients were identified. Their median age was 70 years (range: 22-98) and the male:female ratio was 1.3:1. 23.8% had an ECOG performance status (PS) of ≥2 and 61.8% of the patients had a comorbid illness. 46.8% of the patients received chemotherapy. The multivariate logistic regression analysis revealed that an age of <65 years [odds ratio (OR) 3.82, 95% CI: 2.59-5.63], metastasectomy (OR 3.60, 95% CI: 1.82-7.10), normal albumin (OR 3.26, 95% CI: 2.44-4.36), no comorbid illness (OR 2.87, 95% CI: 1.34-6.16), ECOG PS of <2 (OR 2.72, 95% CI: 1.94-3.82), normal blood urea nitrogen (OR 2.24, 95% CI: 1.40-3.59), palliative radiation (OR 2.03, 95% CI: 1.38-2.99), primary tumor resection (OR 2.00, 95% CI: 1.47-2.73), and the time period (OR 1.85, 95% CI: 1.41-2.42) were significantly correlated with the use of chemotherapy. CONCLUSIONS: The use of chemotherapy appears to be increasing in stage IV CRC. Patients treated with curative intention or who underwent primary tumor resection were more likely to receive chemotherapy. Despite a known benefit of chemotherapy in elderly patients, a differential use of chemotherapy was noted in this population.