Curr. Oncol., Volume 25, Issue 5 (October 2018) – 25 articles

Therapy for breast cancer involves a complex interplay of three main treatment modalities: surgery, systemic therapy, and radiation therapy. The Canadian Consortium for Locally Advanced Breast Cancer (LABC) was established with the goal to convene a strong multidisciplinary team of breast oncology clinicians and scientists who are dedicated to the advancement of LABC research and treatment, with a vision to drive progress through increased collaboration across disciplines and throughout Canada. The most recent meeting in May 2017 highlighted the latest evidence and literature about the optimal use of neoadjuvant systemic therapy in breast cancer. There is a need for increased clinical and scientific collaboration and the development of guidelines for the use of emerging treatment strategies. The interactive meeting sessions fostered unique opportunities for academic debate and nurtured collaboration between the attendees. Full article

Medical assistance in dying (MAID) is a new medical service in Canada. Access to maid for patients with advanced cancer can be daunting during periods of declining health near the end of life. In this report, we describe a collaborative approach between the centralized coordination service and a regional cancer centre as an effective strategy for enabling interdisciplinary care delivery and enhancing patient-centred care at the end of the patient’s cancer journey. Full article

Palliative care (pc) is part of the recommended standard of care for patients with advanced cancer. Nevertheless, delivery of pc is inconsistent. Patients who could benefit from pc services are often referred late—or not at all. In planning for improvements to oncology pc practice in our health care system, we sought to identify barriers to the provision of earlier pc, as perceived by health care providers managing patients with metastatic colorectal cancer (mcrc). We used the Michie Theoretical Domains Framework (tdf) and Behaviour Change Wheel (bcw), together with knowledge of previously identified barriers, to develop a 31-question survey. The survey was distributed by e-mail to mcrc health care providers, including physicians, nurses, and allied staff. Responses were obtained from 57 providers (40% response rate). The most frequently cited barriers were opportunity-related—specifically, lack of time, of clinic space for consultations, and of access to specialist pc staff or services. Qualitative responses revealed that resource limitations varied by cancer centre location. In urban centres, time and space were key barriers. In rural areas, access to specialist pc was the main limiter. Self-perceived capability to manage pc needs was a barrier for 40% of physicians and 30% of nurses. Motivation was the greatest facilitator, with 89% of clinicians perceiving that patients benefit from pc. Based on the Michie tdf and bcw model, interventions that best address the identified barriers are enablement and environmental restructuring. Those findings are informing the development of an intervention plan to improve oncology pc practices in a publicly funded health care system. Full article

Background Physical function is important for defining treatment strategies in patients with cancer and can be estimated using patient-reported outcomes (pros). Although pros are subjective, physical activity and fitness can be tested objectively with adequate, but more labour-intensive methods that are rarely used in daily clinical practice. To determine whether pros for physical function (pro-pf) accurately predict physical function, we studied their interrelationships with objective measures of physical activity and fitness in patients with cancer who had completed cancer treatment, including adjuvant or neoadjuvant chemotherapy or autologous stem-cell transplantation. Methods Baseline data from the react (Resistance and Endurance Exercise After Chemotherapy) and exist (Exercise Intervention After Stem-Cell Transplantation) studies were evaluated. In those studies, the effects of an exercise intervention on physical fitness, fatigue, and health-related quality of life in patients with cancer shortly after completion of chemotherapy or stem-cell transplantation were studied. Interrelationships between pro-pf (physical function subscale of the European Organisation for Research and Treatment of Cancer 30-question core Quality of Life Questionnaire), physical activity (accelerometer), and cardiorespiratory fitness (peak oxygen uptake) were assessed using univariable and multivariable multilevel linear mixed-model analyses. Results After adjustment for age, sex, and body mass index, the pro-pf was significantly associated with physical activity (β = 1.75; 95% confidence interval: 1.08 to 2.42) and cardiorespiratory fitness (β = 0.10; 95% confidence interval: 0.06 to 0.13). Standardized coefficients were 0.28 and 0.26 respectively, indicating a weak association. Conclusions The pro-pf is only weakly associated with objective physical activity and fitness evaluation in patients after curative treatment for cancer. The pro-pf cannot, therefore, be used in clinical practice as a substitute for objective measures of physical function. Full article

Chronic lymphocytic leukemia (cll) is the most common adult leukemia in North America. In Canada, no unified national guideline exists for the front-line treatment of cll; provincial guidelines vary and are largely based on funding. A group of clinical experts from across Canada developed a national evidence-based treatment guideline to provide health care professionals with clear guidance on the first-line management of cll. Consensus recommendations based on available evidence are presented for the first-line treatment of cll. Full article

Background: Radiation therapy (RT) is a longstanding treatment modality for cancer. In addition, immune checkpoint blockade has been a significant development in the field of immunotherapy, modifying key immunosuppressive pathways of cancer cells. Methods: The aim of the present work was to review current concepts of RT and immunotherapy synergism, the abscopal effect, and the molecular effects of RT in the tumour microenvironment, its influence on immune stimulation, and potential clinical outcomes that might evolve from ongoing studies. We also discuss potential predictors of clinical response. Results: Up-to-date literature concerning the mechanisms, interactions, and latest knowledge about RT and immunotherapy was reviewed and summarized, and is presented here. Conclusions: The possibility of using hyperfractionated RT to combine an abscopal effect with the enhanced effect of immune treatment using checkpoint blockade is a very promising method for future tumour treatments. Full article

Background: Although surgical resection remains the standard of care for localized kidney cancers, a significant proportion of patients experience systemic recurrence after surgery and hence might benefit from effective adjuvant therapy. So far, several treatment options have been evaluated in adjuvant clinical trials, but only a few have provided promising results. Nevertheless, with the recent development of targeted therapy and immunomodulatory therapy, a series of clinical trials are in progress to evaluate the potential of those novel agents in the adjuvant setting. In this paper, we provide a narrative review of the progress in this field, and we summarize the results from recent adjuvant trials that have been completed. Methods: A literature search was conducted. The primary search strategy at the medline, Cochrane reviews, and http://ClinicalTrials.gov/databases included the keywords “adjuvant therapy,” “renal cell carcinoma,” and “targeted therapy or/and immunotherapy.” Conclusions: Data from the S-TRAC study indicated that, in the “highest risk for recurrence” patient population, disease-free survival was increased with the use of adjuvant sunitinib compared with placebo. The assure trial showed no benefit for adjuvant sunitinib or sorafenib in the “intermediate- to high-risk” patient population. The ARISER (adjuvant girentuximab) and PROTECT (adjuvant pazopanib) trials indicated no survival benefit, but subgroup analyses in both trials recommended further investigation. The inconsistency in some of the current results can be attributed to a variety of factors pertaining to the lack of standardization across the trials. Nevertheless, patients in the “high risk of recurrence” category after surgery for their disease would benefit from a discussion about the potential benefits of adjuvant treatment and enrolment in ongoing adjuvant trials. Full article

Background: Gastrectomy with negative resection margins and adequate lymph node dissection is the cornerstone of curative treatment for gastric cancer (GC). However, gastrectomy is a complex and invasive operation with significant morbidity and mortality. Little is known about surgical practice patterns or short- and long-term outcomes in earlystage GC in Canada. Methods: We undertook a population-based retrospective cohort study of patients with GC diagnosed between 1 April 2005 and 31 March 2008. Chart review provided clinical and operative details such as disease stage, primary tumour location, surgical approach, operation, lymph nodes, and resection margins. Administrative data provided patient demographics, geography, and vital status. Variations in treatment and outcomes were compared for 14 local health integration networks. Descriptive statistics and log-rank tests were used to examine geographic variation. Results: We identified 722 patients with nonmetastatic resected GC. We documented significant provincial variation in case mix, including primary tumour location, stage at diagnosis, and tumour grade. Short-term surgical outcomes varied across the province. The percentage of patients with 15 or fewer lymph nodes removed and examined varied from 41.8% to 73.8% (p = 0.02), and the rate of positive surgical margins ranged from 15.2% to 50.0% (p = 0.002). The 30-day surgical mortality rates did not vary statistically significantly across the province (p = 0.13); however, rates ranged from 0% to 16.7%. Overall 5-year survival was 44% and ranged from 31% to 55% across the province. Conclusions: This cohort of patients with resected stages I–III GC is the largest analyzed in Canada, providing important historical information about treatment outcomes. Understanding the causes of regional variation will support interventions aiming to improve GC operative outcomes in the cancer system.
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Background: In 2010, a multicentre randomized controlled trial reported increased postoperative complications in pancreaticoduodenectomy (PDE) patients undergoing preoperative biliary decompression (PBD). We evaluated the effect of that publication on rates of PBD at the population level. Methods: This retrospective observational cohort study identified patients undergoing PDE for malignancy, 2005–2013, linking them with administrative health care databases covering medical services for a population of 13.5 million. Patients undergoing PBD within 6 weeks before their surgery were identified using physician billing codes and were divided into those undergoing PDE before and after article publication, with a 6-month washout period. Chi-square tests were used to compare rates of PBD. Results: Of 1997 PDE patients identified, 963 underwent surgery before article publication, and 911, after (123 during the washout period). The rate of PBD was 47.5% before publication, and 41.6% after (p = 0.01). The lowest PBD rates occurred immediately after publication, in 2010 and 2011. Similar results were observed when the cohort was restricted to patients seen preoperatively by a gastroenterologist (n = 1412). Conclusions: Rates of PBD have declined a small, but significant, amount after randomized trial publication. Persistence of PBD might relate to suboptimal knowledge translation, the role of PBD in diagnosis of periampullary malignancy, and treatment of complications (cholangitis, severe hyperbilirubinemia) or anticipation of delay from diagnosis to surgery. The nadir in PBD rates after article publication and the subsequent rise suggest an element of transience in the effect of article publication on clinical practice. Further investigation into the reasons for persistent PBD is needed. Full article

Objective: We compared failure patterns and survival after elective nodal irradiation (eni) or involved-field irradiation (ifi) in patients with thoracic esophageal squamous cell carcinoma (escc), clinical stage T2–4N0M0, to determine whether ifi is feasible for such patients. Methods: Between 2005 and 2015, 126 patients with clinical stage T2–4N0M0 thoracic escc who received definitive concurrent chemoradiotherapy in Shandong Cancer Hospital and Institute and who had complete data, were analyzed retrospectively. Of those patients, 49 received ifi, and 77 received eni. In the ifi group, the radiation field included the primary tumour, with a 3-cm to 4-cm margin in the craniocaudal direction, and the elective irradiation was delivered to the adjacent regional lymphatics according to the location of the primary tumour. Patterns of failure were classified using the first site of failure, which included primary tumour failure, regional lymph node failure, and distant metastasis. Results: Median progression-free survival was 20 months [95% confidence interval (ci): 7.87 months to 39.2 months] in the ifi group and 30 months (95% ci: 17.4 months to 44.6 months) in the eni group (p = 0.580). Median overall survival (os) was 36 months (95% ci: 21.9 months to 50.1 months) in the ifi group and 38 months (95% ci: 26.1 months to 49.9 months) in the eni group (p = 0.761). The estimated 1-year, 3-year, and 5-year os rates were, respectively, 87.8%, 49.4%, and 32.3% for the ifi patients and 92.2%, 52.0%, and 28.9% for the eni patients. Disease persistence and primary lesion recurrence after complete remission (cr) were the most frequent causes of treatment failure in the patients overall (83 of 124, 66.9%). Of the 66 patients achieving a clinical cr, 25 experienced recurrence of the primary lesion, 12 experienced distant relapse, 10 experienced regional nodal failure, and 2 experienced an isolated recurrence. No significant differences in the pattern of failure or in the incidences of grade 3 or greater treatmentrelated myelosuppression or esophagitis were found between the ifi and eni groups. Conclusions: In patients with thoracic escc clinical stage T2–4N0M0 receiving definitive chemoradiotherapy, failure patterns and os were similar with either eni or ifi. Large prospective randomized studies are needed to further investigate and verify those results in this subgroup of patients. Full article

Background: Malnutrition is a common and critical problem that influences outcome in cancer patients. Body composition reflects a patient’s metabolic profile and physiologic reserves, which might be the true determinant of prognosis. In the present study, which aimed to identify valuable new prognostic indicators, we investigated the association between computed tomography–quantified body composition and short-term outcomes after gastrectomy for gastric cancer. Methods: Skeletal muscle index, mean muscle attenuation, and ratio of visceral-to-subcutaneous adipose tissue area (VSR) were calculated from preoperative computed tomography images. Low skeletal muscle index, low mean muscle attenuation, and high VSR were respectively termed “sarcopenia,” “myosteatosis,” and “visceral obesity.” The association of body composition with postoperative complications and serum markers of nutrition and inflammation after radical gastrectomy were analyzed. Results: The overall complication rate was significantly higher in the sarcopenia (62.5% vs. 27.3%, p = 0.001) and myosteatosis groups (38.2% vs. 4%, p = 0.002). Patients with visceral obesity had a higher incidence of inflammatory complications (20.3% vs. 6.5%, p = 0.01). Multivariate logistic regression analysis demonstrated that sarcopenia (p = 0.013), myosteatosis (p = 0.017), and low serum retinol-binding protein (p = 0.019) were independent risk factors for overall complications. Compared with control subjects, patients with sarcopenia had lower postoperative levels of serum retinol-binding protein (p = 0.007), and patients with visceral obesity had higher levels of C-reactive protein (p = 0.026). Conclusions: Sarcopenia, myosteatosis, and visceral obesity were significantly associated with increased rates of postoperative complications and affected the postoperative nutrition and inflammation status of patients with gastric cancer. Full article

Purpose: We aimed to elucidate predictive factors for the development of immune-related adverse events (iraes) in patients receiving immunotherapies for the management of advanced solid cancers. Methods: This retrospective study involved all patients with histologically confirmed metastatic or inoperable melanoma, non-small-cell lung cancer, or renal cell carcinoma receiving immunotherapy at the Cancer Centre of Southeastern Ontario. The type and severity of iraes, as well as potential protective and exacerbating factors, were collected from patient charts. Results: The study included 78 patients receiving ipilimumab (32%), nivolumab (33%), or pembrolizumab (35%). Melanoma, non-small-cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the cancers in the study population. In 41 patients (53%) iraes developed, with multiple iraes developing in 12 patients (15%). In most patients (70%), the iraes were of severity grade 1 or 2. Female sex [adjusted odds ratio (or_adj): 0.094; 95% confidence interval (ci): 0.021 to 0.415; p = 0.002] and corticosteroid use before immunotherapy (or_adj: 0.143; 95% ci: 0.036 to 0.562; p = 0.005) were found to be associated with a protective effect against iraes. In contrast, a history of autoimmune disease (or_adj: 9.55; 95% ci: 1.34 to 68.22; p = 0.025), use of ctla-4 inhibitors (or_adj: 6.25; 95% ci: 1.61 to 24.25; p = 0.008), and poor kidney function of grade 3 or greater (or_adj: 10.66; 95% ci: 2.41 to 47.12; p = 0.025) were associated with a higher risk of developing iraes. A Hosmer–Lemeshow goodness-of-fit test demonstrated that the logistic regression model was effective at predicting the development of iraes (chi-square: 1.596; df = 7; p = 0.979). Conclusions: Our study highlights several factors that affect the development of iraes in patients receiving immunotherapy. Although future studies are needed to validate the resulting model, findings from the study can help to guide risk stratification, monitoring, and management of iraes in patients given immunotherapy for advanced cancer. Full article

Background: Mutations in BRAF are rare oncogene mutations, found in 2% of non-small-cell lung cancers (NSCLCS). Little information is available about the management of patients with BRAF-mutated nsclc, except for those included in clinical trials. We undertook the present study to assess the clinical characteristics, management, and outcomes of those patients in a real-life setting. Methods: This retrospective multicentre observational study included all patients with BRAF-mutated nsclc diagnosed between January 2012 and December 2014. Results: Patients (n = 59) from 24 centres were included: 57.6% men; mean age: 64.5 ± 14.5 years; 82% with a performance status of 0–1 at diagnosis; smoking status: 40.3% current, 32.6% former; 93% with adenocarcinoma histology; 75% stage iv; 78% with V600E mutations; 2 with EGFR and 2 with ALK co-mutations. Of the stage iv patients, 79% received first-line therapy (14.2% anti-BRAF), and 48% received second-line treatment (23.8% anti-BRAF). Response rate and progression-free survival were, respectively, 51.7% and 8.7 months [95% confidence interval (CI): 6.4 months to 15.2 months] for first-line therapy and 35.3% and 4.1 months (95% CI: 2 months to 10.9 months) for second-line treatments. The 2-year overall survival was 58.5% (95% CI: 45.8% to 74.8%). Outcomes in patients with stage iv nsclc harbouring BRAF V600E mutations (n = 32) did not differ significantly from those of patients with other BRAF mutations. Conclusions: In this real-world analysis, most nsclc patients with a BRAF mutation were men and current or former smokers. Survival appears to be better in these BRAF-mutated patients than in nsclc patients without an oncogenic driver. Full article

Background: Myelodysplastic syndrome (MDS) is characterized by peripheral blood cytopenias, with most patients developing significant anemia and dependence on red blood cell (RBC) transfusion. In paroxysmal nocturnal hemoglobinuria (PNH), mutations in the PIGA gene lead to lack of cell-surface glycosylphosphatidylinositol, allowing complement-mediated lysis to occur. Paroxysmal nocturnal hemoglobinuria results in direct antiglobulin test–negative hemolysis and cytopenias, and up to 50% of patients with MDS test positive for PNH cells. We wanted to determine whether PNH is considered to be a contributor to anemia in MDS. Methods: Patients with a diagnosis of MDS confirmed by bone-marrow biopsy since 2009 were reviewed. Highresolution PNH testing by flow cytometry examined FLAER (fluorescein-labeled proaerolysin) binding and expression of CD14, CD15, CD24, CD45, CD59, CD64, and CD235 on neutrophils, monocytes, and RBCS. Results: In 152 patients with MDS diagnosed in 2009 or later, the MDS diagnosis included subtypes associated with PNH positivity (refractory anemia, n = 7, and hypoplastic MDS, n = 4). Of 11 patients who underwent PNH testing, 1 was positive (9.0%). Reasons for PNH testing were anemia (n = 3), new MDS diagnosis (n = 2), hypoplastic MDS (n = 2), decreased haptoglobin (n = 1), increased RBC transfusion requirement (n = 1), and unexplained iron deficiency (n = 1). Conclusions: Testing for PNH was infrequent in MDS patients, and the criteria for testing were heterogeneous. Clinical indicators prompted PNH testing in 6 of 11 patients. Given that effective treatment is now available for PNH and that patients with PNH-positive MDS can respond to immunosuppressive therapy, PNH testing in MDS should be considered. Prospective analyses to clarify the clinical significance of PNH positivity in MDS are warranted. Full article

Background: Afatinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), is approved for first-line therapy in advanced EGFR mutation–positive non-small-cell lung cancer (NSCLC) and has previously demonstrated activity after failure of chemotherapy and reversible EGFR TKI, with improved response and progression-free survival, compared with placebo. Outcomes in pretreated patients with advanced NSCLC receiving afatinib through a Canadian special access program (sap) are reported here. Methods: Patients with NSCLC progressing after at least 1 line of chemotherapy and an EGFR TKI were eligible to enrol in the sap. Characteristics of patients from the two largest accruing Canadian centres were retrospectively reviewed, including demographics, disease and treatment data, and patient outcomes. Results: The 53 patients who received afatinib (57% women, 51% never-smokers, 26% of East Asian ethnicity, and 66% with adenocarcinoma) had a median age of 59 years. EGFR mutations were documented in 25%, and EGFR wildtype in 8%. All patients had received prior EGFR TKI treatment, with 42% achieving a response. Patients took afatinib for a median of 2 months (range: 0–26 months); 17% required 1 or more dose reductions. Of 47 evaluable patients receiving afatinib, 10 experienced tumour shrinkage, and 11, stable disease. Median survival from afatinib initiation was 5 months (95% confidence interval: 2 months to 8 months). Grade 3 or greater diarrhea, rash, paronychia, and stomatitis were seen in 9%, 11%, 6%, and 4% of patients respectively. Conclusions: In an unselected population of pretreated patients with advanced NSCLC after TKI failure, median survival with afatinib therapy was 5 months. Through a sap, afatinib demonstrated activity in clinical practice, with manageable toxicity. Full article

Immunotherapy has emerged as a new standard of care, showing survival benefit for solid tumours in multiple disease sites and indications. The survival improvements seen in diseases that were highly resistant to traditional therapies, with a poor prognosis, are unprecedented. Although the benefits observed in clinical trials are undeniable, not all patients derive those benefits, leading to emerging combination strategies and an ongoing quest for biomarker selection. Here, we summarize the current evidence for immunotherapy in the treatment of solid tumours, and we discuss emerging strategies at the forefront of research. We discuss future challenges that will be encountered as experience and knowledge continue to expand in this rapidly emerging field. Full article

Background: Up to 90% of breast cancer survivors report low levels of physical activity (PA) and spend approximately 70% of the day in sedentary behaviour. Survivors might not be receiving information about the health benefits of PA and the consequences of sedentary behaviour in the context of their cancer. The primary purpose of the present study was to evaluate cancer centres for PA and sedentary behaviour information and infrastructure. A secondary aim was to evaluate the quality of the information that is accessible to breast cancer survivors in cancer centres. Methods: A built-environment scan of the 14 regional cancer centres in Ontario and an evaluation of the text materials about PA available at the cancer centres were completed. Data analyses included descriptive statistics, proportions, and inter-rater reliability. Results: The infrastructure of the cancer centres provided few opportunities for dissemination of information related to PA through signs and printed notices. Televisions were present in all waiting rooms, which could provide a unique opportunity for dissemination of information about PA and sedentary behaviour. Text materials were rated as trustworthy, used some behaviour change techniques (for example, information about the consequences of lack of PA, barrier identification, and setting graded tasks), and were aesthetically pleasing. These findings represent areas for knowledge dissemination both for the centre and for resources that could be further improved. Full article

Introduction: Neuroendocrine tumours (NETS) are a poorly understood malignancy lacking standardized care. Differences in socioeconomic status (SES) might worsen the effect of non-standardized care. We examined the effect of SES on NET peri-diagnostic care patterns and outcomes. Methods: In this population-based cohort study, NET cases identified from a provincial cancer registry (1994–2009) were divided into low (1st and 2nd income quintiles) and high (3rd, 4th, and 5th quintiles) SES groups. We compared peri-diagnostic health care utilization (–2 years to +6 months), metastatic recurrence, and overall survival (os) between the groups. Results: Of 4966 NET patients, 38.3% had a low SES. Neither the primary NET sites (p = 0.15), nor the metastatic presentation (p = 0.31) differed. Patients with low SES had a higher mean number of physician visits (20.1 ± 19.9 vs. 18.1 ± 16.5, p = 0.001) and imaging studies (56 ± 50 vs. 52 ± 44, p = 0.009) leading to the NET diagnosis. Rates of primary tumour resection (p = 0.14), hepatectomy (p = 0.45), systemic therapy (p = 0.38), and liver embolization (p = 0.13) did not differ with SES. In the low-SES group, metastatic recurrence was more likely (41.1% vs. 37.6%, p = 0.01) during a median follow-up of 61.7 months, and the 10-year os was inferior (47.1% vs. 52.2%, p < 0.01). Low SES was associated with worse os (hazard ratio: 1.16; 95% confidence interval: 1.06 to 1.26) after adjustment for age, sex, comorbidity burden, primary NET site, and rural living. Conclusions: Low SES was associated with more physician visits and imaging before a NET diagnosis, but not with more advanced stage at presentation nor with an effect on the pattern of therapy. Long-term outcomes were inferior in the low-SES group. These data can help to inform the design of health care delivery for NETS. Full article

Immune checkpoint inhibitors (ICIS) such as inhibitors of CTLA-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (irAES) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality. Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities. The CTLA-4 and PD-1/PD-L1 inhibitors odulate T-cell response differently, resulting in distinct toxicity patterns, toxicity kinetics, and dose–toxicity relationships. Using individualized patient education, screening, and assessment for the early identification of iraes is key to proactive management and is therefore key to improving outcomes and prolonging therapy. Management of irAES is guided by appropriate grading, which sets the stage for the treatment setting (outpatient vs. inpatient), ICI treatment course (delay vs. discontinuation), supportive care, corticosteroid use, organ specialist consultation, and additional immunosuppression. Health care professionals in oncology must work collaboratively with emergency and community colleagues to facilitate an understanding of irAES in an effort to optimize seamless care. Full article

Background: Cancer research is essential in evaluating the safety and effectiveness of emerging cancer treatments, which in turn can lead to ground-breaking advancements in cancer care. Given limited research funding, allocating resources in alignment with societal burden is essential. However, evidence shows that such alignment does not typically occur. The objective of the present study was to provide an updated overview of site-specific cancer research investment in Canada and to explore potential discrepancies between the site-specific burden and the level of research investment. Methods: The 10 cancer sites with the highest mortality in 2015—which included brain, female breast, colorectal, leukemia, lung, non-Hodgkin lymphoma, ovary, pancreas, prostate, and uterus—were selected for the analysis. Information about site-specific research investment and cancer burden (raw incidence and mortality) was obtained from the Canadian Cancer Research Survey and Statistics Canada’s cansim (the Canadian Socio-Economic Information Management System) respectively. The ratio of site-specific research investment to site-specific burden was used as an indicator of overfunding (ratio > 1) or underfunding (ratio < 1). Results: The 3 cancer sites with the highest research investments were leukemia, prostate, and breast, which together represented 51.3% of 2015 cancer research funding. Conversely, the 3 cancer sites with the lowest investments were uterus, pancreas, and ovary, which together represented 7.8% of 2015 research funding. Relative to site-specific cancer burden, the lung, uterus, and colorectal sites were consistently the most underfunded. Conclusions: Observed discrepancies between cancer burden and research investment indicate that some cancer sites (such as lung, colorectal, and uterus) seem to be underfunded when site-specific incidence and mortality are taken into consideration. Full article

Management of anticoagulant therapy for the treatment of venous thromboembolism (VTE) in cancer patients is complex because of an increased risk of recurrent VTE and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent VTE and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental VTE, to prevent recurrent VTE, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug–drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient’s cancer status and management change over time. Full article

Background: Inhibition of the anaplastic lymphoma kinase (ALK) oncogenic driver in advanced non-small-cell lung carcinoma (NSCLS) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the ALK inhibitor crizotinib in the first line. New scientific literature warrants a consensus update. Methods: Clinical trials of ALK inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with ALK-positive NSCLS. Results: Randomized phase III trials have demonstrated clinical benefit for single-agent alectinib and ceritinib used in treatment-naïve patients and as second-line therapy after crizotinib. Phase II trials have demonstrated activity for single-agent brigatinib and lorlatinib in further lines of therapy. Improved responses in brain metastases were observed for all second- and next/third-generation ALK tyrosine kinase inhibitors in patients progressing on crizotinib. Canadian recommendations are therefore revised as follows: (1) Patients with advanced nonsquamous NSCLS have to be tested for the presence of an ALK rearrangement. (2) Treatment-naïve patients with ALK-positive disease should initially be offered single-agent alectinib or ceritinib, or both sequentially. (3) Crizotinib-refractory patients should be treated with single-agent alectinib or ceritinib, or both sequentially. (4) Further treatments could include single-agent brigatinib or lorlatinib, or both sequentially. (5) Patients progressing on ALK tyrosine kinase inhibitors should be considered for pemetrexed-based chemotherapy. (6) Other systemic therapies should be exhausted before immunotherapy is considered. Summary: Multiple lines of ALK inhibition are now recommended for patients with advanced NSCLS with an ALK rearrangement. Full article

Introduction: Patients with cancer of unknown primary (CUP) have pathologically confirmed metastatic tumours with unidentifiable primary tumours. Currently, very little is known about the relationship between the treatment of patients with CUP and their survival outcomes. Thus, we compared oncologic treatment and survival outcomes for patients in Ontario with CUP against those for a cohort of patients with metastatic cancer of known primary site. Methods: Using the Ontario Cancer Registry and the Same-Day Surgery and Discharge Abstract databases maintained by the Canadian Institute for Health Information, we identified all Ontario patients diagnosed with metastatic cancer between 1 January 2000 and 31 December 2005. Ontario Health Insurance Plan treatment records were linked to identify codes for surgery, chemotherapy, or therapeutic radiation related to oncology. Multivariable Cox regression models were constructed, adjusting for histology, age, sex, and comorbidities. Results: In 45,347 patients (96.3%), the primary tumour site was identifiable, and in 1743 patients (3.7%), CUP was diagnosed. Among the main tumour sites, CUP ranked as the 6th largest. The mean Charlson score was significantly higher (p < 0.0001) in patients with CUP (1.88) than in those with a known primary (1.42). Overall median survival was 1.9 months for patients with CUP compared with 11.9 months for all patients with a known-primary cancer. Receipt of treatment was more likely for patients with a known primary site (n = 35,012, 77.2%) than for those with CUP (n = 891, 51.1%). Among patients with a known primary site, median survival was significantly higher for treated than for untreated patients (19.0 months vs. 2.2 months, p < 0.0001). Among patients with CUP, median survival was also higher for treated than for untreated patients (3.6 months vs. 1.1 months, p < 0.0001). Conclusions: In Ontario, patients with CUP experience significantly lower survival than do patients with metastatic cancer of a known primary site. Treatment is associated with significantly increased survival both for patients with CUP and for those with metastatic cancer of a known primary site. Full article

Background: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy. Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) constitute 55% of new nhl cases and are initially treated with rituximab-based chemoimmunotherapy. Relative to intravenous (IV) rituximab, a subcutaneous (SC) formulation approved in 2016 has comparable pharmacokinetics, efficacy, and safety, and a greatly reduced administration time; it is also preferred by patients. The objective of the present study was to estimate the effect (on systemic therapy suite time and on the costs of drug acquisition and administration) of implementing SC rituximab in the initial chemoimmunotherapy for FL and DLBCL over 3 years in the Canadian market. Methods: An Excel (Microsoft Corporation, Redmond, WA, U.S.A.)–based model was created with a population size based on epidemiologic data and current rituximab use, duration of use considering initial therapy, time savings for SC rituximab administration from published studies, costs from standard Canadian sources, and assumed uptake in implementing provinces of 65%, 75%, and 80% over 3 years. Key parameters and sensitivity analysis values were validated by clinical experts located in various Canadian jurisdictions. Costs are reported in 2017 Canadian dollars from the perspective of the health care system. Results: More than 3 years after implementation of SC rituximab, we estimated that 5762 Canadians would be receiving SC rituximab, resulting in savings of 128,715 hours in systemic therapy suite time and approximately $40 million in drug and administration costs. Sensitivity analyses suggest that the model is most sensitive to SC market uptake, number of induction therapy cycles, and eligible patients. Conclusions: Subcutaneous administration of rituximab can significantly reduce systemic therapy suite time and achieve substantial savings in drug and administration costs. Full article