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Purpose: The purpose of the present review was to determine which antineoplastic systemic therapy is most effective in improving clinical outcomes for patients with incurable gastroenteropancreatic neuroendocrine tumours (NETs). Methods: A systematic search (2008-2016) of the literature in the medline and embase databases and the Cochrane Database of Systematic Reviews was conducted; abstracts from the American Society of Clinical Oncology, the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, the European Society for Medical Oncology, the European Cancer Congress, the European Neuroendocrine Tumor Society, and the North American Neuroendocrine Tumor Society were reviewed. Draft recommendations were created, and a comprehensive review process was undertaken. Outcomes--including progression-free survival (PFS), overall survival, objective response rate, adverse events, and quality of life--were extracted from each of the studies. Results: Eleven randomized controlled trials (RCTs), sixteen nonrandomized prospective studies, and thirteen retrospective studies met the inclusion criteria. Conclusions: Patients with well- or moderately-differentiated pancreatic NETs (PNETs) should receive targeted therapy (that is, everolimus or sunitinib), and patients with non-PNETs should be offered either targeted therapy (that is, everolimus) or somatostatin analogues (ssas--that is, octreotide long-acting release or lanreotide). Evidence from two phase iii trials demonstrated a significant pfs benefit for patients with PNETs. For patients with non-PNETs, the evidence comes from subgroup analyses of rcts, as well as from a planned interim analysis. Although the evidence has limitations, the rarity of the disease, coupled with the difficulty of conducting methodologically sound trials in the affected population, means that treatment decisions have to make use of the best available evidence. Because of insufficient evidence for both PNETs and non-pnets, no evidence-based recommendation can be made for or against other types of targeted therapy, other SSAs, chemotherapy, or combination therapy. [ABSTRACT FROM AUTHOR]

Background: Various tyrosine kinase signalling pathways affect the development and progression of colorectal cancer (CRC). In clinical trials, regorafenib has been associated with a survival benefit in metastatic CRC (mCRC). We assessed the safety and efficacy of regorafenib in real-world patients. Methods: In a retrospective review of patients with mcrc treated with regorafenib at our institution from 2013 to 2015, patient demographics, treatment, and survival data were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: In total, 48 patients were offered regorafenib, and 35 (73%) started treatment. Of the patients who started regorafenib, 57% were men. Median age in the cohort was 61 years, and all patients had a performance status in the range 0-2. Time from diagnosis of mcrc to regorafenib treatment was more than 18 months in 71% of patients. Starting dose was 160 mg in 54% of the patients, 120 mg in 40%, and 80 mg in 6%. Dose reductions occurred in 34% of the patients, and interruptions, in 29%. Best response was progressive disease (60%) and stable disease (17%); response in the rest of the patients was unknown. The most common adverse events on regorafenib (any grade) were fatigue (57%), hyperbilirubinemia (43%), thrombocytopenia (37%), anorexia (31%), and hypertension (31%). The most common grade 3 or 4 adverse events were fatigue (29%), hypophosphatemia (17%), weight loss (11%), and hyperbilirubinemia (9%). Common reasons for discontinuing regorafenib included progressive disease (51%) and toxicity (26%). In patients treated with regorafenib, pfs was 2.4 months (95% confidence interval: 1.8 to 3.3 months) and os was 5.6 months (95% confidence interval: 3.7 to 8.9 months). No factors were associated with survival in univariate or multivariate analysis. Conclusions: In a real-world setting, regorafenib is associated with survival similar to that reported in the randomized controlled trials, but at the expense of toxicity leading to discontinuation in many patients. Future studies of regorafenib should focus on identifying the patients most likely to benefit and on minimizing toxicity. [ABSTRACT FROM AUTHOR]

The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m2) + Cisplatin (30 mg/m2) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50 Gy/25 fractions) on weeks 4-8. Sunitinib was commenced 4-13 weeks after surgery and continued for one year. Sixty-one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12-month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2-year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy (n = 43), median survival was 36 months, with a 2-year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer. [ABSTRACT FROM AUTHOR]

The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m2) + Cisplatin (30 mg/m2) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50 Gy/25 fractions) on weeks 4-8. Sunitinib was commenced 4-13 weeks after surgery and continued for one year. Sixty-one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12-month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2-year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy ( n = 43), median survival was 36 months, with a 2-year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer (CRC) has a median diagnostic age of 68 years. Despite significant progress in chemotherapy (CTX) options, few data on outcomes or toxicity from CTX in patients 80 years of age and older are available. We investigated ctx in such patients with metastatic crc (MCRC), hypothesizing high rates of hospitalization and toxicity. Methods A retrospective chart review identified patients 80 years of age and older with mcrc who initiated ctx between 2005-2010 at our institution. Patient demographics and CTX data were collected. Endpoints included rates of hospitalization, ctx discontinuation because of toxicity, and overall survival. Results In 60 patients, ctx was initiated on 88 occasions. Median age in the cohort was 83 years; 52% were men; 72% lived with family; 53% had a modified Charlson comorbidity index of 2 or greater; and 31% were taking 6 or more prescription medications at baseline. At baseline, 33% of the patients were anemic (hemoglobin < 100 g/L), 36% had leukocytosis (white blood cells > 11×109/L), and 48% had renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m2). In 53%, ctx was given as first-line treatment. The initial ctx dose was adjusted in 67%, and capecitabine was the most common chemotherapeutic agent (45%). In 19 instances (22%), the patient was hospitalized during or within 30 days of CTX; in 26 instances (30%), the ctx was discontinued because of toxicity, and in 48 instances (55%), the patient required at least 1 dose reduction, omission, or delay. Median overall survival was 17.8 months (95% confidence interval: 14.3 to 20.8 months). Conclusions In the population 80 years of age and older, ctx for mcrc is feasible; however, most recipients will require dose adjustments, and a significant proportion will be hospitalized or stop ctx because of toxicity. Prospective research incorporating geriatric assessment tools is required to better select these older patients for CTX. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Cancer is a health concern in Inuit populations. Unique cultural, dietary, and genetic factors and geographic isolation influence cancer epidemiology in this group. Inuit-specific data about oncology treatments and survival outcomes in Canadian Inuit referred to urban treatment centres are lacking. Methods A retrospective chart review of Inuit patients referred to The Ottawa Hospital Cancer Centre (TOHCC) from the Baffin region of Nunavut between 2000 and 2010 was conducted. Nunavut cancer registry data were used to establish the percentage of cancer cases referred and their survival outcomes. Results Of 307 cancer patients registered among Baffin-region Inuit, 216 [70% (63 men, 153 women)] were referred to tohcc for chemotherapy (CT) and radiation therapy (RT). Mean age in the referred group was 59.3 years (range: 25-89 years), and current smokers constituted half the group (52%). The cancers most commonly leading to referral in men were lung (55%), colorectal (19%), and nasopharyngeal (11%) cancers; in women, they were lung (46%), colorectal (24%), breast (10%), nasopharyngeal (6%), and cervical (5%) cancers. Of the 216 referred patients, 82 (38%) had already undergone surgery, and 18 (8%) received chemoradiation or RT only, all given with curative intent. Among the surgical patients referred, 33 (40%) and 23 (28%) went on to receive adjuvant CT and adjuvant RT respectively. Among 116 patients referred for palliative care, 64 (55%) received CT, 76 (66%) received RT, 43 (37%) received both CT and RT, and 19 (16%) received neither treatment. Median all-stage overall survival was 10 months for patients with lung cancer [95% confidence interval: 6.1 to 13.9 months] and 37 months for patients with colorectal cancer [95% confidence interval: 14.8 to 59.2 months]. Conclusions High uptake of palliative and adjuvant CT and RT was observed in the Inuit patients referred to TOHCC. Lung cancer was the most common cancer in referred Inuit men and women. The survival rates for Inuit lung cancer patients referred to TOHCC were comparable to those in the rest of Canada. Further research is required to understand reasons for non-referral of Canadian Inuit to TOHCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Anal cancer is uncommon. We reviewed the treatment and outcomes of anal cancer patients in a population referred to the Ottawa Hospital Cancer Centre (TOHCC) over a 12-year period. Methods A chart review was conducted with patient data collected from hospital records, including: demographic, treatment and outcome information. Outcomes of interest included: overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS). Results 180 patients were included in the study population. 72% (n = 130) female and 28% (n = 50) male. 6.7% (n = 12 males) of patients were HIV positive – all were on anti-retroviral therapy. 60% (n = 108) of patients were ever-smokers, mean patient age was 62 [range 35–90] years. The most frequent presenting symptoms were blood per rectum and anal pain. Treatment intent was curative in 87%. Treatment included radiotherapy (94%), brachytherapy (26%), chemotherapy (73%). Among patients treated with curative-intent, 72% had a complete response, 31% had local/regional recurrence, 16% required salvage surgery and 21% had distant recurrence. The colostomy rate was 23%. 5 year overall survival (OS) was not significantly different for patients by HIV status. Survival was superior if MMC-FU was used first vs. CIS-FU; OS HR 0.47 (0.24–0.94), p < 0.033. Conclusions The outcomes of patients in this large retrospective cohort study are similar to the outcomes of patients in highly selective clinical trials. Five year overall survival and colostomy free survival are encouraging. MMC-FU was found to be superior to CIS-FU. [ABSTRACT FROM AUTHOR]

Background Before the emergence of first-line combination chemotherapy, the standard of care for unresectable metastatic colorectal cancer (mCRC) was first-line monotherapy with modulated 5-fluorouracil. Several large phase III randomized controlled trials, now completed, have assessed whether a planned sequential chemotherapy strategy—beginning with fluoropyrimidine monotherapy until treatment failure, followed by another regimen (either monotherapy or combination chemotherapy) until treatment failure—could result in the same survival benefit produced with an upfront combination chemotherapy strategy, but with less toxicity for patients. Methods The MEDLINE and EMBASE databases, and abstracts from meetings of the American Society for Clinical Oncology and the European Society for Medical Oncology, were searched for reports comparing a sequential strategy of chemotherapy with an upfront combination chemotherapy in adult patients with mCRC. Publications that reported efficacy or toxicity data (or both) were included. Results The five eligible trials that were identified included 4532 patients. A meta-analysis of those trials demonstrates a statistically significant survival advantage for combination chemotherapy (hazard ratio: 0.92; 95% confidence interval: 0.86 to 0.99). However, the median survival advantage (3–6 weeks in most trials) is small and of questionable clinical significance. Three trials reported first-line toxicities. Upfront combination chemotherapy results in significantly more neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, nausea, vomiting, and sensory neuropathy. Sequential chemotherapy results in significantly more hand-foot syndrome. Conclusions Given the small survival advantage associated with upfront combination chemotherapy, planned sequential chemotherapy and upfront combination chemotherapy can both be considered treatment strategies. Treatment should be chosen on an individual basis considering patient and tumour characteristics, toxicity of each strategy, and patient preference. [ABSTRACT FROM AUTHOR]

Background: Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind VEGF receptors 1 and 2 (VEGFR-1 and -2), respectively. This randomized phase II study evaluated the antitumor activity and safety of icrucumab and ramucirumab each in combination with mFOLFOX-6 in patients with metastatic colorectal cancer after disease progression on first-line therapy with a fluoropyrimidine and irinotecan. Patients and methods: Eligible patients were randomly assigned to receive mFOLFOX-6 alone (mFOLFOX-6) or in combination with ramucirumab 8 mg/kg IV (RAM+mFOLFOX-6) or icrucumab 15 mg/kg IV (ICR+mFOLFOX-6) every 2 weeks. Randomization was stratified by prior bevacizumab therapy. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, safety, and PK. Results: In total, 158 patients were randomized, but only 153 received treatment (49 on mFOLFOX-6, 52 on RAM+mFOLFOX-6, and 52 on ICR+mFOLFOX-6). Median PFS was 18.4 weeks on mFOLFOX-6, 21.4 weeks on RAM+mFOLFOX-6, and 15.9 weeks on ICR+mFOLFOX-6 (RAM+mFOLFOX-6 versus mFOLFOX-6, stratified hazard ratio [HR] 1.116 [95% CI 0.713-1.745], P = 0.623; ICR+mFOLFOX-6 versus mFOLFOX-6, stratified HR 1.603 [95% CI 1.011- 2.543], P = 0.044). Median survival was 53.6 weeks on mFOLFOX-6, 41.7 weeks on RAM+mFOLFOX-6, and 42.0 weeks on ICR+mFOLFOX-6. The most frequent adverse events reported on the ramucirumab arm (RAM+mFOLFOX-6) were fatigue, nausea, and peripheral sensory neuropathy; those on the icrucumab arm (ICR+mFOLFOX-6) were fatigue, diarrhea, and peripheral sensory neuropathy. Grade ≥3 serious adverse events occurred at comparable frequency across arms. Conclusions: In this study population, combining ramucirumab or icrucumab with mFOLFOX-6 did not achieve the predetermined improvement in PFS. [ABSTRACT FROM AUTHOR]

Background: Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels., Methods: In this phase 2, randomized, double-blind, 12-week trial, we assigned patients with cancer cachexia and an elevated serum GDF-15 level (≥1500 pg per milliliter) in a 1:1:1:1 ratio to receive ponsegromab at a dose of 100 mg, 200 mg, or 400 mg or to receive placebo, administered subcutaneously every 4 weeks for three doses. The primary end point was the change from baseline in body weight at 12 weeks. Key secondary end points were appetite and cachexia symptoms, digital measures of physical activity, and safety., Results: A total of 187 patients underwent randomization. Of these patients, 40% had non-small-cell lung cancer, 32% had pancreatic cancer, and 29% had colorectal cancer. At 12 weeks, patients in the ponsegromab groups had significantly greater weight gain than those in the placebo group, with a median between-group difference of 1.22 kg (95% credible interval, 0.37 to 2.25) in the 100-mg group, 1.92 (95% credible interval, 0.92 to 2.97) in the 200-mg group, and 2.81 (95% credible interval, 1.55 to 4.08) in the 400-mg group. Improvements were observed across measures of appetite and cachexia symptoms, along with physical activity, in the 400-mg ponsegromab group relative to placebo. Adverse events of any cause were reported in 70% of the patients in the ponsegromab group and in 80% of those in the placebo group., Conclusions: Among patients with cancer cachexia and elevated GDF-15 levels, the inhibition of GDF-15 with ponsegromab resulted in increased weight gain and overall activity level and reduced cachexia symptoms, findings that confirmed the role of GDF-15 as a driver of cachexia. (Funded by Pfizer; ClinicalTrials.gov number, NCT05546476.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC., Materials and Methods: Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site., Results: A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2., Conclusion: The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The COVID-19 pandemic resulted in an unprecedent shift towards virtual cancer care, including the care of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The aim of this study was to evaluate the use of virtual care for GEP-NETs during the COVID-19 pandemic at a high-volume academic cancer center., Methods: This retrospective, observational study performed at the Ottawa Hospital Cancer Center in Canada evaluated adult patients with GEP-NETs seen in consultation by medical oncology between 1 June 2019 and 31 December 2022. Demographic, clinicopathologic, cancer treatment and visit data were collected. Univariable and multivariable analyses assessed the relationship between patient characteristics and virtual care use., Results: A total of 103 patients with well-differentiated GEP-NETS were included. Overall, 18/103 (17.5%) consults and 594/781 (76.1%) follow-ups were performed virtually. All consultation visits returned to in-person assessment by 2022, while 67.0% and 41.4% follow-ups remained virtual in 2022 and 2023, respectively. The year of follow-up, sex, employment and Charlston comorbidity index were associated with virtual follow-up use in the multivariable analysis., Discussion: Virtual care remained a predominant method of GEP-NET patient assessment in the peri-pandemic period. These results highlight an opportunity to improve access to subspecialty neuroendocrine cancer care through the continued use of virtual care.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023 was held in Quebec City, Quebec 2-4 February 2023. The purpose of the conference was to develop consensus statements on emerging and evolving treatment paradigms. Participants included Canadian medical oncologists, radiation oncologists, pathologists and surgical oncologists from across Ontario, Quebec, and the Atlantic provinces. Consensus statements were developed following rapid review presentations and discussion of available literature. The recommendations proposed here represent the consensus opinions of physicians involved in the care of patients with gastrointestinal malignancies who participated in this meeting.

(1) Aim: The prevalence and incidence of small bowel NETs have increased significantly over the past two decades. This study aims to report the 10-year experience of SB-NET management at a regional cancer center in Canada. (2) Materials and methods: We conducted a retrospective study of the clinical and pathological data of patients diagnosed with biopsy-proven SB-NET at The Ottawa Hospital (TOH), Ottawa, Canada between 2011 and 2021. We report the clinicopathological characteristics of these patients, as well as their outcomes data, including survival rates. (3) Results: Between 2011 and 2021, a total of 177 SB-NET cases were identified with 51% ( n = 91) of cases being males. The most common sites of the tumors were the ileum 53% ( n = 94), followed by the duodenum 9% ( n = 16) and jejunum 7% ( n = 12). Approximately 24% ( n = 42) of the patients had symptoms for over six months prior to diagnosis and 18% ( n = 32) had functioning SB-NET during the course of the disease. The majority of patients had locally advanced or metastatic disease at the time of presentation with stage III, and stage IV representing 42% ( n = 75), and 41% ( n = 73) respectively. The majority of patients 84% ( n = 148) had well-differentiated histology. One hundred twenty patients underwent surgical resection of the primary tumor including 28 patients (16%) with limited metastatic disease. A total of 21 patients (18%) had recurrence after curative surgery. A total of 62 patients (35%) received first-line somatostatin analog (SSA) therapy for unresectable disease and seven patients had PRRT after progression on SSA. Five years OS was 100%, 91%, 97%, and 73% for stages I, II, III, and IV respectively. In univariate analysis, carcinoid symptoms, T stage, and differentiation were significant predictors for worse overall survival, but not RFS. (4) Conclusions: Compared to published historical controls, our study suggests improvement in the 5-year survival rate of SB-NETs over the last 10 years.

High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.

Background: Treatment for metastatic neuroendocrine tumors (NETs) is often with somatostatin analogues (SSA) such as lanreotide in the first-line setting. Real world use of lanreotide in Canada is not well studied., Methods: We performed a retrospective chart review of 69 patients to study real world use of lanreotide at our centre., Results: Lanreotide was the first-line of systemic treatment in 60 patients. Watch-and-wait was a common strategy and was seen in 31 patients. SSA switch strategy was seldom applied. Majority of patients on lanreotide had low-grade NETs. Standard starting dose of lanreotide 120 mg every 28 days was used in 66 patients. Dose escalation to 120 mg every 21 days occurred in 7 patients. The primary intention for treatment was tumor control in 32 patients, and both tumor and symptom control in 34 patients. Median time on treatment was 21.6 months., Conclusions: Overall, our findings were in keeping with current guidelines. It will be interesting to assess how clinical practice evolves in the future and to determine the role of dose escalation for disease control., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-1182/coif). TA is a consultant for Ipsen and involved in enrolling patients in clinical trials. MV is a consultant for Amgen, a speaker for Merck and is involved in enrolling patients in clinical trials. RG is a member of advisory board for Ipsen, Pfizer, Eisai, Roche, Bayer, AAA and Apobiologix. She is a speaker for Merck, Viatris, Pfizer and Amgen. She received independent educational grants from Pfizer and Eisai and Apobiologix. She is also involved in enrolling patients in clinical trials. The other authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

(1) Background: Small bowel adenocarcinoma (SBA) is one of the predominant primary small bowel cancers that has a dismal outcome. We aim to report 10 years of experience in SBA management at a regional cancer centre in Canada.; (2) Methods: We retrospectively analysed clinical and pathological data of patients diagnosed with an SBA between 2011 and 2021 at the Ottawa Hospital (TOH), Ottawa, Canada. We describe the clinicopathological features and outcomes, including survival. Potential prognostic factors were analysed using the Cox proportional hazard model for multivariate analysis.; (3) Results: We identified 115 patients with SBA. The duodenum was the most common SBA location representing 61% (70) of the total patients, followed by the jejunum (17%) and ileum (10%). Around 24% (27) of cases presented with bowel obstructions. The majority of patients (56%, 64) had stage IV disease on presentation. Seven patients had MSI-high tumours, while 24% (27) were MS-stable. In terms of management, 48 patients underwent curative surgical resection, 17 of whom received adjuvant chemotherapy. On the other hand, 57 patients (49.5%) with the advanced disease received palliative systemic therapy, and 18 patients (16%) had supportive care only. Over a median follow-up of 21.5 months (range 0-122), the median overall survival was 94, 61, and 34 months for stages II, III, and IV, respectively ( p < 0.05). The median recurrence-free survival was 93 and 23 months for stages II and III, respectively. However, there was no statistically significant difference between TNM stages in RFS, p = 0.069. Multivariate Cox regression analysis showed only poor performance status at diagnosis as a predictor for shorter overall survival ( p < 0.05). The univariate analysis didn't show any significant correlation between RFS and covariants.; (4) Conclusions: SBA remains one of the most aggressive tumours with a dismal prognosis even after surgical resection. The optimal chemotherapy regimen has not been established. Further studies are needed to explore the role of adjuvant chemotherapy for stages I-III SBA., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

(1) Background: The management of gastrointestinal stromal tumors (GIST) has significantly evolved over the last two decades, with the introduction of tyrosine kinase inhibitors (TKI). We aim to report 10 years of experience of GIST management at a regional cancer center in Canada. (2) Methods: We retrospectively analyzed the records of 248 consecutive patients diagnosed with GIST between 2011 and 2021. We describe the clinical and pathological data, management, and outcome, including survival. (3) Results: The most common GIST sites were the stomach 63% (156), followed by the small bowel 29% (73). At diagnosis, 83% (206) of patients had localized disease (stage I-III). According to the modified National Institutes of Health consensus criteria (NIH) for GIST, around 45% (90) had intermediate or high-risk disease. Most patients, 86% (213), underwent curative surgical resection. Forty-nine patients received adjuvant imatinib, while forty-three patients had advanced disease and received at least one line of TKI. With a median follow-up of 47 months, the 5-year recurrence-free survival (RFS) rates for very low and low risk were 100% and 94%, respectively, while those for intermediate and high risk were 84% and 51%, respectively. The 5-year overall survival (OS) rates for very low and low risk were 100% and 94%, while intermediate, high risk, and advanced were 91%, 88%, and 65%, respectively. Using the Kaplan-Meier method, there were statistically significant differences in RFS and OS between NIH risk groups, p < 0.0005. In univariate analysis, ECOG, site, mitosis, secondary malignancy, and size were predictors for OS. High mitosis and large size (>5 cm) were associated with worse RFS. (4) Conclusions: Curative surgical resection remains the gold standard management of GIST. Our results are comparable to the reported literature. Further research is needed to explore histology's role in risk stratification and initiating adjuvant TKI.

Objective: To determine the efficacy and safety of extended duration perioperative thromboprophylaxis by low molecular weight heparin when assessing disease-free survival in patients undergoing resection for colorectal cancer., Design: Multicentre, open label, randomised controlled trial., Settings: 12 hospitals in Quebec and Ontario, Canada, between 25 October 2011 and 31 December 2020., Participants: 614 adults (age ≥18 years) were eligible with pathologically confirmed invasive adenocarcinoma of the colon or rectum, no evidence of metastatic disease, a haemoglobin concentration of ≥8 g/dL, and were scheduled to undergo surgical resection., Interventions: Random assignment to extended duration thromboprophylaxis using daily subcutaneous tinzaparin at 4500 IU, beginning at decision to operate and continuing for 56 days postoperatively, compared with in-patient postoperative thromboprophylaxis only., Main Outcome Measures: Primary outcome was disease-free survival at three years, defined as survival without locoregional recurrence, distant metastases, second primary (same cancer), second primary (other cancer), or death. Secondary outcomes included venous thromboembolism, postoperative major bleeding complications, and five year overall survival. Analyses were done in the intention-to-treat population., Results: The trial stopped recruitment prematurely after the interim analysis for futility. The primary outcome occurred in 235 (77%) of 307 patients in the extended duration group and in 243 (79%) of 307 patients in the in-hospital thromboprophylaxis group (hazard ratio 1.1, 95% confidence interval 0.90 to 1.33; P=0.4). Postoperative venous thromboembolism occurred in five patients (2%) in the extended duration group and in four patients (1%) in the in-hospital thromboprophylaxis group (P=0.8). Major surgery related bleeding in the first postoperative week was reported in one person (<1%) in the extended duration and in six people (2%) in the in-hospital thromboprophylaxis group (P=0.1). No difference was noted for overall survival at five years in 272 (89%) patients in the extended duration group and 280 (91%) patients in the in-hospital thromboprophylaxis group (hazard ratio 1.12; 95% confidence interval 0.72 to 1.76; P=0.1)., Conclusions: Extended duration to perioperative anticoagulation with tinzaparin did not improve disease-free survival or overall survival in patients with colorectal cancer undergoing surgical resection compared with in-patient postoperative thromboprophylaxis alone. The incidences of venous thromboembolism and postoperative major bleeding were low and similar between groups., Trial Registration: ClinicalTrials.gov NCT01455831., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Canadian Institute of Health Research, Ottawa Hospital Academic Medical Organisation, and Leo Pharma, as well as through generous patient donations through the Ottawa Hospital Foundation for the submitted work. MC has received research funding from BMS, Pfizer, and Leo Pharma, and honorariums from Bayer, Pfizer, BMS, Servier, and Leo Pharma. VT received consulting honorariums from Pfizer-BMS and Daiichi-Sankyo and has received research funding from Sanofi. MB received consulting honorariums from Johnson and Johnson. ACM received consulting honorariums from Johnson and Johnson. MO received consulting honorariums from Johnson and Johnson Ethicon. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Inuit are the Indigenous Arctic peoples and residents of the Canadian territory of Nunavut who have the highest global rate of lung cancer. Given lung cancer's mortality, histological and genomic characterization was undertaken to better understand the disease biology. We retrospectively studied all Inuit cases from Nunavut's Qikiqtani (Baffin) region, referred to the Ottawa Hospital Cancer Center between 2001 and 2011. Demographics were compiled from medical records and tumor samples underwent pathologic/histologic confirmation. Tumors were analyzed by next generation sequencing (NGS) with a cancer hotspot mutation panel. Of 98 patients, the median age was 66 years and 61% were male. Tobacco use was reported in 87%, and 69% had a history of lung disease (tuberculosis or other). Histological types were: non-small cell lung carcinoma (NSCLC), 81%; small cell lung carcinoma, 16%. Squamous cell carcinoma (SCC) represented 65% of NSCLC. NGS on 55 samples demonstrated mutation rates similar to public lung cancer datasets. In SCC, the STK11 F354L mutation was observed at higher frequency than previously reported. This is the first study to characterize the histologic/genomic profiles of lung cancer in this population. A high incidence of SCC, and an elevated rate of STK11 mutations distinguishes this group from the North American population.

Objective: To provide recommendations for a surveillance regimen that leads to the largest overall survival benefit for patients after curative treatment for Stage I-IV colon and rectal cancer., Methods: Consistent with the Program in Evidence-Based Care's standard approach, guideline databases, i.e., MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO, were systematically searched. Then, we drafted recommendations and methodology experts performed an internal review of the resulting draft recommendations, which was followed by an external review by targeted experts and intended users., Results: Four systematic reviews and two randomized controlled trials were identified that provided evidence for recommendations., Conclusions: For patients with stage I-III colon cancer, a medical history and physical examination should be performed every six months for three years; computed tomography (CT) of the chest-abdomen-pelvis (CT CAP) should be performed at one and three years, or one CT CAP could be performed at 18 months; the use of carcinoembryonic antigen (CEA) is optional if CT imaging is being performed; and surveillance colonoscopy should be performed one year after the initial surgery. The frequency of subsequent surveillance colonoscopy should be dictated by previous findings, but generally, colonoscopies should be performed every five years if the findings are normal. There was insufficient evidence to support these recommendations for patients with rectal cancer, Stage IV colon cancer, and patients over the age of 75 years. Patients should be informed of current recommendations and the treating physician should discuss the specific risks and benefits of each recommendation with their patients.

Objective: To provide recommendations for preferred models of follow-up care for stage I-IV colorectal (CRC) cancer survivors in Ontario; to identify signs and symptoms of potential recurrence and when to investigate; and to evaluate patient information and support needs during the post-treatment survivorship period., Methods: Consistent with the Program in Evidence-Based Medicine's standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO databases were systematically searched. The authors drafted recommendations and revised them based on the comments from internal and external reviewers., Results: Four guidelines, three systematic reviews, three randomized controlled trials, and three cohort studies provided evidence to develop recommendations., Conclusions: Colorectal cancer follow-up care is complex and requires multidisciplinary, coordinated care delivered by the cancer specialist, primary care provider, and allied health professionals. While there is limited evidence to support a shared care model for follow-up, this approach is deemed to be best suited to meet patient needs; however, the roles and responsibilities of care providers need to be clearly defined, and patients need to know when and how to contact them. Although there is insufficient evidence to recommend any individual or combination of signs or symptoms as strong predictor(s) of recurrence, patients should be educated about these and know which care provider to contact if they develop any new or concerning symptoms. Psychosocial support and empathetic, effective, and coordinated communication are most valued by patients for their post-treatment follow-up care. Continuing professional education should emphasize the importance of communication skills and coordination of communication between the patient, family, and healthcare providers.

Background: Signal Transducer and Activator of Transcription-3 (STAT3) mediates cellular functions. We assessed the IHC expression of phosphorylated STAT3 (pSTAT3) in paired primary tumors and liver metastases in patients with advanced stage colorectal cancer (CRC)., Methods: We included patients with tissue blocks available from both the primary CRC and a surgically resected liver metastasis. The IHC pSTAT3 expression agreement was measured using Cohen's kappa statistic., Results: The study included 103 patients, 55% male, median age was 64. 43% tumors originated in rectum, and 63% of the primary tumors were synchronous. Expression of pSTAT3 was 76% in liver metastases and 71% in primary tumors. A difference in pSTAT3 staining between the primary tumor and liver metastases was noted in 64%. There was lost expression of pSTAT3 in the liver metastases in 28% and gained expression in 36% of cases compared to the primary. The kappa statistic comparing agreement between staining patterns of the primary tumors and liver metastases was a "less-than-chance", at -0.02. Median survival was 4.9 years, with no difference in survival outcomes by pSTAT3 expression in the primary tumor or liver metastases., Discussion: STAT3 is not a prognostic marker in the selective setting of metastatic CRC to liver, but it may remain a potential therapeutic target given most liver metastases expressed pSTAT3. Discordant pSTAT3 expression in between primary tumors and paired liver metastases suggests that use of this class of drug to treat liver predominant metastatic colorectal cancer in a biomarker-driven approach may require confirmatory liver tumor biopsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Drug resistance is one of the most important factors limiting the success of systemic anticancer therapy in achieving cure or prolonged overall survival. In clinical practice, resistant disease describes cancer that is found to have progressed since the time of treatment initiation. The term "drug resistant" is often used synonymously with "progressive disease" when referring to a treated tumour. Stopping a treatment at the time of disease progression is the current dominant approach of clinical trial conduct; therefore, available data from clinical trials are routinely not able to provide any information that could challenge this concept of permanent drug resistance. However, drug rechallenge and treatment continuation beyond progression have emerged as potential strategies in the past decade, especially for molecularly targeted agents and immunotherapy. In this review we focussed on rechallenge strategies for chemotherapy, immune therapy and targeted therapy in the main types of cancer., (© 2020 S. Karger AG, Basel.)

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20-22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology 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 pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including ■ surgical management of pancreatic adenocarcinoma,■ adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma,■ the role of radiotherapy in the management of pancreatic adenocarcinoma,■ systemic therapy in pancreatic neuroendocrine tumours,■ updates in systemic therapy for patients with advanced hepatocellular carcinoma,■ optimum duration of adjuvant systemic therapy for colorectal cancer, and■ sequence of therapy in oligometastatic colorectal cancer., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conf licts of interest, and we declare the following interests: DA is a member of advisory boards for Bristol–Myers Squibb, Sanofi, and Shire, and has received grants or honoraria from Celgene and Amgen; TA is a member of advisory boards for Amgen, Apobiologix, Bayer, Eisai, Novartis, Ipsen, Celgene, and Shire, and has received grants or honoraria from Novartis and Ipsen; SB (Berry) is a member of advisory boards for Amgen, Bayer, Servier, and Taiho, and has received grants or honoraria from Amgen; DB has received grants or honoraria from Amgen, AbbVie, AstraZeneca, Bristol–Myers Squibb, Ipsen, and Pfizer; BC is a member of advisory boards for Amgen, Eli Lilly, Taiho, Shire, Celgene, Merck, and Novartis; EC is a member of advisory boards for Taiho and Eisai, and is listed as co-investigator for trials at an institution that has received funding from AstraZeneca, Bristol–Myers Squibb, Boston Biomedical, Merck, and Seattle Genetics; RG (Goodwin) is a member of advisory boards for Ipsen, Novartis, Taiho, and Celgene, and has received funding from Novartis, Ipson, and Pfizer in an unrestricted grant for a tumour bank; SG is a member of advisory boards for Amgen, Ipsen, Merck, Pfizer, and Sanofi, and has received funding from Janssen and Sanofi as honoraria for a talk; PK is a member of advisory boards for Sanofi and is listed as a co-investigator for trials at an institution that has received for grants or honoraria from Baxter and Sanofi; NL is a member of advisory boards for Amgen, Celgene, Genomic Health, Bristol–Myers Squibb, Novartis, and Eisai, and is a member of speaker’s bureaus for Amgen, AstraZeneca, Astellas, Roche, Eisai, Novartis, Celgene, and Bristol–Myers Squibb; JM is a member of advisory boards for Amgen and has received grants or honoraria from Bristol–Myers Squibb for a talk; EP is a member of advisory boards for Amgen and Pfizer and has received grants or honoraria from Roche for travel to a symposium; RR is a member of advisory boards for Celgene, Servier, Eisai, Merck, Bayer, and Eli Lilly, is a member of the speaker’s bureaus for Celgene, Servier, Novartis, and Eli Lilly, and is listed as co-investigator for trials at an institution that has received funding from Merck, Bristol–Myers Squibb, AstraZeneca, and Macrogenetics, and has received grants or honoraria from Essai and Celgene; WS has received grants or honoraria from Genomic Health for a conference presentation; SS is a member of advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Merck, Roche, Novartis, Shire, Amgen, and Lilly, is listed as coinvestigator for trials at an institution that has received funding from Bristol–Myers Squibb, Novartis, Merck, and AbbVie, and has received grants or honoraria from Amgen and Taiho for travel; MT (Tehfé) is a member of advisory boards for Bristol–Myers Squibb, AstraZeneca, Merck, Eisai, Takeda Celgene, and Taiho, and has received grants or honoraria from Celgene for research; MT (Thirlwell) is a member of an advisory board for Taiho; KV is a member of an advisory board for Amgen and has received grants or honoraria from Roche for travel to European Society for Medical Oncology meetings; SW is a member of an advisory board for Amgen and has received grants or honoraria from Amgen and Ipsen for invited talks. The remaining authors have no conflicts to disclose., (2019 Multimed Inc.)

Background: There is a paucity of data about effective interventions to improve happiness and reduce burnout in oncologists. Benjamin Franklin developed a 13-week program of "necessary activities" or "virtues" (temperance, silence, order, resolution, frugality, industry, sincerity, justice, moderation, cleanliness, tranquility, chastity, and humility) to follow, in his attempt at self-improvement. In this pilot study, we explored whether using a modified version of this was associated with any discernable impact on physician happiness, burnout, or compliance with each of the virtues., Methods: Self-reported happiness (Oxford happiness scores) and burnout (Abbreviated Maslach Burnout Inventory) were completed at baseline (pre-study), week 13, and 1 month after completion of the program. Each day during the 13-week program, oncologists were emailed a list of virtues to focus on and scored how they felt they were complying with them. The oncologist's spouses also assessed how they felt the oncologist was complying with the virtues., Results: Thirteen physicians completed the baseline scores, 11 completed Maslach/Oxford scores at the end of the study, and 8 the 1-month post-study assessment. No significant improvements in happiness and burnout (emotional exhaustion, depersonalization, personal accomplishment) scores were observed. Statistically significant changes in self-rated virtue scores were observed for temperance (p = 0.046), order (p = 0.049), and resolution (p = 0.014). Additionally, although not reaching statistical significance, 11 of 13 virtues (excepting sincerity and chastity) assessed by spouses indicated a positive change over time., Conclusion: In this hypothesis generating study, daily reflection on personal virtues was not associated with any statistically significant change in happiness or burnout scores. Alternative strategies should be considered.

Background: Use of complementary therapies is high among people with cancer despite research gaps. The Thoracic Peri-Operative Integrative Surgical Care Evaluation (POISE) Trial will evaluate the impact of an integrative care intervention delivered by naturopathic doctors (NDs) in conjunction with usual care for patients undergoing surgery for lung, gastric, and esophageal cancer., Objectives: To describe the multistep, multidisciplinary process of defining the integrative care intervention to be used in the Thoracic POISE trial using a principle-based approach that is pragmatic, holistic, safe, feasible, evidence driven, and consensus based., Methods: An Intervention Development Committee (IDC) made up of a multidisciplinary team of health care providers (NDs, surgeons, oncologists, nurses, dietitians, physiotherapists, pharmacists, and psychologists), researchers, and patients was established to oversee the process. Potential intervention components were identified through a clinical practice survey and expert opinion. Systematic literature reviews were conducted and scores assigned based on the following criteria: usage, safety, goals, feasibility/scalability, and evidence. The IDC selected an intervention to be piloted that consists of a standard palette including core and optional components. Safety, known risks, and interactions with pharmaceuticals were evaluated using industry and professional monographs, a scoping literature review, and consultations with hospital pharmacists., Results: The clinical practice survey and expert opinion identified 28 components for consideration. Following literature reviews, scoring, consensus from the IDC, and safety and interaction considerations, an intervention palette consisting of core and optional components was defined. The intervention options vary based on the patient's phase of treatment and symptom-specific needs. The intervention includes supplements, physical recommendations (exercise), nutritional counseling, and psychological support (audio scripts)., Conclusion: Through a multistep, multidisciplinary process an integrative care intervention was developed for the Thoracic POISE trial. The intervention will be piloted in a single-arm feasibility study, followed by a single-center randomized controlled trial (RCT), and finally a multicenter RCT.

Background: According to the IDEA trial, 6-month adjuvant chemotherapy should remain the treatment standard in stage III T4 or N2 colon cancer. The relatively poor survival in this high-risk subgroup-a 3-year disease-free survival (DFS) rate of 65%-and the potential synergistic efficacy of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan suggest that FOLFIRINOX may be a regimen of particular interest in this setting., Patients and Methods: This multicenter international phase 3 trial (ClinicalTrials.gov NCT02967289) being conducted in 49 centers in France and Canada plans to randomize (1:1; minimization method) 640 patients aged 18 to 70 years with Eastern Cooperative Oncology Group performance status ≤ 1. Randomization occurs within 42 days (with treatment initiated within 56 days) after curative-intent R0 surgical resection of a pT4N1 or pT1-4N2 colon adenocarcinoma. Patients will be randomized to receive adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 , irinotecan 180 mg/m 2 , and 5-FU 2.4 g/m 2 over 46 hours) or modified FOLFOX6 (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 , 5-FU bolus 400 mg/m 2 , then 2.4 g/m 2 over 46 hours) every 2 weeks for 24 weeks (12 cycles). Patients will be followed for 5 years after the end of adjuvant chemotherapy. A gain of 9% in 3-year DFS (primary end point) is expected (74% in the experimental arm vs. 65% in the control arm; α, 5% [2-sided log-rank test]; 1-β, 80%). Secondary end points of this study include 2-year DFS, overall survival, and toxicity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

There is no consensus on optimal follow-up for completely resected gastroenteropancreatic neuroendocrine tumors. Published guidelines for follow-up are complex and emphasize closer surveillance in the first 3 years after resection. Neuroendocrine tumors have a different pattern and timescale of recurrence, and thus require more practical and tailored follow-up. The Commonwealth Neuroendocrine Tumour Collaboration convened an international multidisciplinary expert panel, in collaboration with the North American Neuroendocrine Tumor Society, to create patient-centered follow-up recommendations for completely resected gastroenteropancreatic neuroendocrine tumors. This panel used the RAND/UCLA (University of California, Los Angeles) Appropriateness Method to generate recommendations. A large international survey was conducted outlining current the surveillance practice of neuroendocrine tumor practitioners and shortcomings of the current guidelines. A systematic review of available data to date was supplemented by recurrence data from 2 large patient series. The resultant guidelines suggest follow-up for at least 10 years for fully resected small-bowel and pancreatic neuroendocrine tumors and also identify clinical situations in which no follow-up is required. These recommendations stratify follow-up strategies based on evidence-based prognostic factors that allow for a more individualized patient-centered approach to this complex and heterogeneous malignant neoplasm.

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 × 10 10 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Background: The objective of the present phase I study was to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of irinotecan, capecitabine, and oxaliplatin given in combination (IXO regimen) to patients with previously untreated, unresectable advanced or metastatic colorectal cancer (CRC)., Patients and Methods: Patients received oxaliplatin followed by irinotecan as intravenous infusions on day 1, with oral capecitabine taken twice daily (BID) on days 2 to 15 of a 3-week cycle. The dose ranges were explored as follows: oxaliplatin, 75 to 120 mg/m 2 ; irinotecan, 160 to 230 mg/m 2 ; capecitabine, 750 to 1000 mg/m 2 BID. Dose escalation was performed individually for each drug at each dose level according to the type and severity of toxicity encountered in the previous cohort., Results: A total of 39 patients were enrolled at 7 dose levels and the MTD. The recommended doses for phase II evaluation were oxaliplatin 100 mg/m 2 , irinotecan 160 mg/m 2 , and capecitabine 950 mg/m 2 BID. Diarrhea and febrile neutropenia were DLTs. Of the 39 enrolled patients, 26 (67%) had confirmed objective responses. The median progression-free survival was 11 months, and the median overall survival was 25 months. The survival rate at 5 years was 23%., Conclusion: The IXO regimen has a manageable toxicity profile with promising antitumor activity as first-line treatment of advanced and metastatic CRC., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)