Curr. Oncol., Volume 26, Issue 2 (April 2019) – 35 articles

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung carcinoma with a poor prognosis and poor response to chemotherapy and radiotherapy. A previous study reported that psc expresses high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumours. We report 2 cases of patients with a lung sarcomatoid carcinoma. Both patients initially underwent curative lung resection, but developed early recurrent disease. Because PD-L1 was highly expressed in the tumour cells, we initiated therapy with nivolumab, which showed good efficacy, almost complete radiologic tumour remission, and a remarkable improvement in the condition of those patients. Immune checkpoint inhibitors targeting PD-1 might be a valuable therapy option for PSCS. Full article

Charcot–Marie–Tooth (CMT) disease is the most common form of inherited neuropathy. Core features include peripheral neuropathy and secondary axonal degeneration, with a noted distal predominance of limb-muscle wasting, weakness, and sensory loss. Given the significant prevalence of CMT, superimposed neoplastic disease can be encountered within this patient population. Malignancies that are treated with vincristine (a microtubule-targeting agent), even at low doses as part of standard treatment, pose a significant challenge for patients with CMT. Here, we present the case of a child with CMT who was successfully treated for medulloblastoma without vincristine, a standard drug used for treatment of that disease, to avoid the risk of severe debilitating neuropathy. This report is the first of a patient successfully treated for medulloblastoma without vincristine. Full article

Introduction: Patients with urothelial carcinoma (uc) have a poor prognosis after progression on first-line cisplatinbased chemotherapy. Real-world data about second-line cytotoxic therapies are limited. We sought to characterize patients with metastatic uc who receive more than 1 line of systemic therapy and to describe their treatments and outcomes. Methods: Using BC Cancer’s pharmacy database, we identified patients with documented metastatic uc who had received more than 1 line of systemic therapy. A retrospective chart review was then performed to collect clinicopathologic, treatment, and outcomes data. Results: The 51 included patients, of whom 42 were men (82%), had a median age of 65 years (range: 38–81 years). Sites of metastasis included lymph nodes (n = 30), bone (n = 7), lung (n = 9), and peritoneum (n = 2). Second-line chemotherapy regimens included gemcitabine–cisplatin [gc (n = 14)], paclitaxel (n = 24), docetaxel (n = 12), and an oral topoisomerase i inhibitor (n = 1). Median time to progression (ttp) and overall survival (os) were 2.0 and 6.83 months respectively. Compared with patients who received a different agent, patients who had experienced a prior response to first-line gc and who were re-challenged with second-line gc had a better median ttp (11.0 months vs. 6.0 months, p = 0.02) and survived longer (4.0 months vs. 1.0 months, p = 0.02). No differences in os between non-gc regimens were evident. Conclusions: In patients with metastatic uc, overall outcomes remain poor, but compared with patients receiving other agents, the subgroup of patients re-challenged with second-line gc demonstrated improved ttp. Conventional chemotherapy regimens provide only modest benefits in the second-line setting and have largely been replaced with immunotherapy. Full article

Assessment of the clinical benefit of cancer treatments can be highly subjective, influenced by both perspective and context. Such assessments are required in regulatory and policy decision-making, but consistency between jurisdictions is often lacking. Clear and consistent standards for determining when a treatment offers a meaningful benefit, relative to the current standard of care, can help to address issues of equity and transparency in health technology assessment. For metastatic colorectal cancer (MCRC), no standardized Canadian definition of clinically meaningful benefit has yet been proposed. Colorectal Cancer Canada therefore convened a group of medical oncologists expert in colorectal cancer to review the literature about clinical significance. The resulting consensus is intended to apply to any therapeutic agent being considered in the setting of chemotherapy-refractory MCRC. It was agreed that overall survival is the appropriate measure of clinical efficacy in chemorefractory MCRC. As quantitative targets for efficacy, an improvement of 2 months or more in median overall survival or a hazard ratio for survival of 0.75 or lower (or both) are proposed as the threshold for clinically meaningful benefit. That threshold could be influenced by a treatment’s effect on quality of life. Treatment toxicity is also relevant to the assessment of clinical benefit in this setting, specifically when significant differences in treatment tolerability are evident. Full article

Rapid advancements in next-generation sequencing (NGS) technology have created an unprecedented opportunity to decipher the molecular profile of tumours to more effectively prevent, diagnose, and treat cancer. Oncologists now have the option to order molecular tests that can guide treatment decisions. However, to date, most oncologists have received limited training in genomics, and they are now faced with the challenge of understanding how such tests and their interpretation align with patient management. Guidance on how to effectively use NGS technology is therefore needed to aid oncologists in applying the results of genomic tests. The Canadian guideline presented here describes best practices and unmet needs related to ngs-based testing for somatic variants in oncology, including clinical application, assay and sample selection, bioinformatics and interpretation of reports performed by laboratories, patient communication, and clinical trials. Full article

Mantle cell lymphoma (MCL) is a rare subtype of aggressive B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. Patients typically require multiple lines of therapy, and those with relapsed or refractory (R/R) disease have a very poor prognosis. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has proven to be an effective agent for patients with R/R MCL. Although usually well tolerated, ibrutinib can be associated with unique toxicities, requiring discontinuation in some patients. Effective and well-tolerated alternatives to ibrutinib for patients with R/R MCL are therefore needed. Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib. Data from single-arm clinical trials suggest that, compared with ibrutinib, second-generation btk inhibitors have comparable efficacy and might have a more favourable toxicity profile. Those newer btk inhibitors might therefore provide a viable treatment option for patients with R/R MCL. Full article

Background: Data showing the value of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in the management of advanced-stage serous endometrial carcinoma (ECA) are limited; the aim of the present study was to expand the knowledge about that treatment strategy in patients with advanced ECA, including endometrioid ECA. Methods: Data were collected retrospectively from all patients with advanced-stage eca treated with NACT between 2005 and 2014 at 3 oncology referral centres. Primary outcomes were the radiologic response to nact and achievement of optimal or complete IDS. Secondary outcomes were recurrence rate and progression-free and overall survival. Results: Of 102 ECA cases included, a complete radiologic response was achieved in only 4 cases, with a partial response being achieved in 72% (64% of endometrioid cases, 80% of serous cases). Complete IDS was achieved in 62% of the endometrioid cases and in 56% of the serous ECA cases, with optimal IDS achieved in 31% and 28% of those cases respectively. Survival rates were calculated for all patients with complete and optimal IDS; recurrence was observed in 56% and 67% of the cases respectively, and progression-free survival was 18 months and 13 months respectively. Median survival duration was 24 months for endometrioid ECA and 28 months for serous ECA. Conclusions: For patients with advanced ECA who are not suitable for primary debulking, NACT followed by IDS can be considered regardless of histologic subtype. The treatment options for this group of patients are limited and have to be explored. Full article

Background: The rate of mastectomy is much higher in Newfoundland and Labrador than in any other province in Canada, even for women diagnosed at an early stage. In this paper, we present qualitative data from women who have made a decision for surgical treatment and from breast surgeons in an effort to better explicate factors influencing breast cancer (BCA) surgical decision-making. Methods: The study’s descriptive, qualitative design involved holding interviews with breast surgeons and holding focus groups and interviews with women who were offered the choice of breast-conserving surgery (BCS) or mastectomy (MT). Results: Participants included 35 women and 13 surgeons. High interest in MT and increasing requests for prophylactic contralateral MT were evident. A host of factors—clinical, demographic, psychosocial, education-related, and cultural—influenced the decisions. A key factor for women was fear of recurrence and a need to “just get rid of it,” but the experiences of others also influenced the decisions. Life stage and family considerations also factored prominently into women’s decisions. Conclusions: Women with early-stage BCA more often chose MT and often demanded prophylactic removal of the healthy breast. Findings highlight the importance of ensuring that women at average risk are appropriately counselled about the low likelihood of a subsequent contralateral BCA and the lack of survival benefit associated with prophylactic contralateral MT. Findings also revealed other areas of presurgical discussion that might help women think through their personal circumstances and values so as to encourage informed surgical decisions. Full article

Background: Two ongoing prospective randomized trials are evaluating whether omitting axillary lymph node dissection (alnd) in patients with breast cancer (bca) and sentinel lymph node (sln) macrometastases undergoing mastectomy is safe. Determining predictive risk factors for non-sln metastases and developing a model to predict the probability of those patients having non-sln metastases is also important. Methods: This retrospective study enrolled 396 patients with bca and 1–2 slns with macrometastases who underwent alnd and mastectomy between January 2012 and December 2016. Factors influencing the non-sln metastases were determined, and a predictive nomogram was formulated. Performance of the nomogram was evaluated by its area under the curve (auc). Results: We developed a predictive nomogram with an auc of 0.81 (cross-validation 95% confidence interval: 0.75 to 0.86) that included 4 factors (tumour size, histologic grade, and number of negative slns and axillary lymph nodes on imaging). Conclusions: Our predictive nomogram assesses the risk of non-sln metastases in patients with bca and 1–2 sln macrometastases undergoing mastectomy. Full article

Background: The role of splenectomy in proximal gastric cancer is still debated. The objective of the present meta-analysis was to provide more-robust evidence about the effect of spleen-preserving total gastrectomy on postoperative infectious complications, overall morbidity, and 5-year overall survival (OS). Methods: PubMed, EMBASE, and the Web of Science were consulted. Pooled effect measures were calculated using an inverse-variance weighted or Mantel–Haenszel in random effects meta-analysis. Heterogeneity was evaluated using I² index and Cochran Q-test. Results: Three randomized controlled trials published between 2000 and 2018 were included. Overall, 451 patients (50.1%) underwent open total gastrectomy with spleen preservation and 448 (49.9%) underwent open total gastrectomy with splenectomy. The patients ranged in age from 24 to 78 years. No differences were found in the number of harvested lymph nodes (p = 0.317), the reoperation rate (p = 0.871), or hospital length of stay (p = 0.347). The estimated pooled risk ratios for infectious complications, overall morbidity, and mortality were 1.53 [95% confidence interval (CI): 1.09 to 2.14; p = 0.016], 1.51 (95% CI: 1.11 to 2.05; p = 0.008), and 1.23 (95% CI: 0.40 to 3.71; p = 0.719) respectively. The estimated pooled hazard ratio for 5-year OS was 1.06 (95% CI: 0.78 to 1.45; p = 0.707). Conclusions: Spleen-preserving total gastrectomy should be considered in patients with curable gastric cancer because it is significantly associated with decreased postoperative infectious complications and overall morbidity, with no difference in the 5-year OS. Those observations appear worthwhile for establishing better evidence-based treatment for gastric cancer. Full article

Background: Preoperative breast magnetic resonance imaging (mri) is commonly requested by surgeons in the initial workup of women with breast cancer; however, its use is controversial. We performed a survey of breast cancer surgeons across Canada to investigate current knowledge about, attitudes to, and self-reported use of preoperative breast mri in a publicly funded health care system in light of the limited evidence to support it. Methods: All identified general surgeons in Canada were mailed a survey instrument designed to probe current practice and knowledge of published trials. Results: Of 403 responding surgeons, 233 (58%) indicated that they performed breast cancer surgery. Of those 233, 218 (94%) had access to breast mri and completed the entire survey. Overall, 54.6% of responding surgeons felt that breast mri was useful in surgical planning, and more than half (58.3%) indicated that their frequency of use was likely to increase over the next 5 years. Surgeons found preoperative mri most useful in detecting mammographically occult disease (71.5% of respondents) and in planning for breast-conserving surgery (57.3%). The main limitations reported were timely access to mri (51%) and false positives (36.7%). Responses suggest a knowledge gap in awareness of published trials in breast mri. Conclusions: Our study found that, in early-stage breast cancer, self-reported use of mri by breast cancer surgeons in Canada varied widely. Reported indications did not align with published data, and significant gaps in self-reported knowledge of the data were evident. Our results would support the development and dissemination of guidelines to optimize use of mri. Full article

Background: Patients with cancer experience various levels of loss of dignity. Exploring levels of loss of dignity and the factors that influence such losses for patients with cancer is rare, but important in palliative care in China. Methods: Participants were cancer patients with early and advanced cancer recruited from a tertiary cancer hospital in North China. Patients were surveyed to assess their level of loss of dignity and potentially relevant factors. Data were collected using the Patient Dignity Inventory, the MD Anderson Symptom Inventory–Chinese, the distress thermometer, the Hospital Anxiety and Depression Scale, and the 30-question core Quality of Life Questionnaire from the European Organisation for Research and Treatment of Cancer, and were analyzed using quantitative methods. Results: The study included 202 cancer patients, 143 of whom experienced mild loss of dignity (71%); 37, moderate loss of dignity (18%); and 10, severe loss of dignity (5%). The problems with dignity were slightly different in patients with early-stage disease than in those with advanced-stage disease. Loss of dignity in the patients was significantly correlated with psychological distress, symptom burden, and quality of life (p < 0.05). Logistic regression showed that age, Karnofsky performance status, anxiety, and symptom burden were significant predictors of loss of dignity. Conclusions: Most patients with early and advanced cancer experienced some level of loss of dignity. Loss of dignity was more likely for patients of younger age, high Karnofsky performance status, high symptom burden, and anxiety. Understanding the dignity of cancer patients and potentially relevant factors is of great value for implementing comprehensive palliative care in China. Full article

Background: Variations in treatment choice, or late stage at first diagnosis, mean that, despite guideline recommendations, not all patients with hormone receptor (hr)–positive locally advanced or metastatic breast cancer (la/mbca) will have received endocrine therapy before disease progression. In the present study, we aimed to estimate the proportion of women with postmenopausal hr-positive la/mbca in the United States who are endocrine therapy-naïve. Methods: Women in the Optum Electronic Health Record (ehr) database with a breast cancer (bca) diagnosis (January 2008–March 2015) were included. Patient and malignancy characteristics were identified using structured data fields and natural-language processing of free-text clinical notes. The proportion of women with postmenopausal hr-positive, human epidermal growth factor 2 (her2)–negative (or unknown) la/mbca who had not received prior endocrine therapy was determined. Results were extrapolated to the entire U.S. population using the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Results are presented descriptively. Results: In the ehr database, 11,831 women with bca had discernible information on postmenopausal status, hr status, and disease stage. Of those women, 1923 (16.3%) had postmenopausal hr-positive, her2-negative (or unknown) la/mbca, and 70.7% of those 1923 patients (n = 1360) had not received prior endocrine therapy, accounting for 11.5% of the overall population. Extrapolating those estimates nationally suggests an annual incidence of 14,784 cases, and a 5-year limited duration prevalence of 50,638 cases. Conclusions: A substantial proportion of women with postmenopausal hr-positive la/mbca in the United States could be endocrine therapy–naïve. Full article

Objectives: In the present study, we explored the real-world efficacy of the immuno-oncology checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib in the second-line setting. Methods: Using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) dataset, a retrospective analysis of patients with metastatic renal cell carcinoma (MRCC) treated with nivolumab or cabozantinib in the second line after prior therapy targeted to the vascular endothelial growth factor receptor (VEGFR) was performed. Baseline characteristics and imdc risk factors were collected. Overall survival (OS) and time to treatment failure (TTF) were calculated using Kaplan–Meier curves. Overall response rates (ORRS) were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences between cabozantinib and nivolumab treatment. Results: The analysis included 225 patients treated with nivolumab and 53 treated with cabozantinib. No significant difference in median OS was observed: 22.10 months [95% confidence interval (CI): 17.18 months to not reached] with nivolumab and 23.70 months (95% CI: 15.52 months to not reached) with cabozantinib (p = 0.61). The TTF was also similar at 6.90 months (95% CI: 4.60 months to 9.20 months) with nivolumab and 7.39 months (95% CI: 5.52 months to 12.85 months) with cabozantinib (p = 0.20). The adjusted hazard ratio (HR) for nivolumab compared with cabozantinib was 1.30 (95% CI: 0.73 to 2.3), p = 0.38. When adjusted by IMDC criteria and age, the HR was 1.32 (95% CI: 0.74 to 2.38), p = 0.35. Conclusions: Real-world IMDC data indicate comparable OS and TTF for nivolumab and cabozantinib. Both agents are reasonable therapeutic options for patients progressing after initial first-line VEGFR-targeted therapy. Full article

Background: In the present study, we examined real-world treatment patterns for squamous cell carcinoma of the head and neck (scchn) in Canada, which are largely unknown. Methods: Oncologists across Canada provided data for disease history, characteristics, and treatment patterns during May–July 2016 for 6–8 consecutive patients receiving first-line or second-line drug treatment for scchn (including locally advanced and recurrent or metastatic disease). Results: Information from 16 physicians for 109 patients receiving drug treatment for scchn was provided; 1 patient was excluded from the treatment-pattern analysis. Median age in the cohort was 63 years [interquartile range (iqr): 57–68 years], and 24% were current smokers, with a mean exposure of 26.2 ± 12.7 pack–years. The most common tumour site was the oropharynx (48%). Most patients (84%) received platinum-based regimens as first-line treatment (44% received cisplatin monotherapy). Use of cetuximab-based regimens as first-line treatment was limited (17%). Of 53 patients receiving second-line treatment, 87% received a first-line platinum-based regimen. Median time between first-line treatment with a platinum-based regimen and initiation of second-line treatment was 55 days (iqr: 20–146 days). The most common second-line regimen was cetuximab monotherapy (43%); platinum-based regimens were markedly infrequent (13%). Conclusions: Our analysis provides real-world insight into scchn clinical practice patterns in Canada, which could inform reimbursement decision-making. High use of platinum-based regimens in first-line drug treatment was generally reflective of treatment guidelines; cetuximab use in the second-line was higher than anticipated. Additional real-world studies are needed to understand the effect of novel therapies such as immuno-oncology agents on clinical practice and outcomes, particularly for recurrent or metastatic scchn. Full article

Background: The optimal management of hypomagnesemia (hMg) induced by epidermal growth factor receptor inhibitors (EGFRIS) for advanced colorectal cancer is unclear. We surveyed gastrointestinal medical oncologists in Canada to determine practice patterns for the management of EGFRI-induced hMg. Methods: Based on distribution lists from the Eastern Canadian Colorectal Cancer Consensus Conference and the Western Canadian Gastrointestinal Cancer Consensus Conference, medical oncologists were invited to participate in an online questionnaire between November 2013 and February 2014. Results: From the 104 eligible physicians, 40 responses were obtained (38.5%). Panitumumab was more commonly prescribed than cetuximab by 70% of respondents, with 25% prescribing cetuximab and panitumumab equally. Most respondents obtain a serum magnesium level before initiating a patient on an EGFRI (92.5%) and before every treatment (90%). Most use a reactive strategy for magnesium supplementation (90%) and, when using supplementation, favour intravenous (IV) alone (40%) or IV and oral (45%) dosing. Magnesium sulfate was used for IV replacement, and the most common oral strategies were magnesium oxide (36.4%) and magnesium rougier (18.2%). Under the reactive strategy, intervention occurred at hMg grade 1 (70.3%) or grade 2 (27%). Of the survey respondents, 45% felt that 1–5 of their patients have ever developed symptoms attributable to hMg, and 35% have had to interrupt EGFRI therapy because of this toxicity, most commonly at grade 3 (30%) or grade 4 (45%) hMg. The most important question about EGFRI-induced hMg was its relevance to clinical outcomes (45%) and its symptoms (37.5%). Conclusions: In Canada, various strategies are used in the management of EGFRI-induced hMg, including prophylactic and reactive approaches that incorporate IV, oral, or a combination of IV and oral supplementation. Clinicians are concerned about the effect of hMg on clinical outcomes and about the symptoms that patients experience as a result of this toxicity. Full article

Background: In Canada, requests for public reimbursement of cancer drugs are predominately initiated by pharmaceutical manufacturers. Clinician-led submissions provide a mechanism to initiate the drug funding process when industry does not submit a request for funding consideration. Although such requests are resource-intensive to produce, Cancer Care Ontario (CCO) has the capacity to facilitate clinician-led submissions. In 2014, CCO began developing a cancer drug prioritization framework that allocates resources to systematically address a growing number of clinician-identified funding gaps with clinician-led submissions. Methods: Cancer site–specific drug advisory committees established by CCO consist of health care practitioners whose roles include identifying and prioritizing funding gaps. The committees submit their identified gaps to a cross-cancer-site prioritization exercise in which the requests are ranked based on a set of guiding principles derived from health technology assessment. The requests are then sequentially allocated the resources needed to meet submission requirements. Whether the funding gap is of provincial or pan-Canadian relevance determines where the submission is filed for assessment. Results: Since its inception, the CCO framework has identified 17 funding gaps in 9 cancer sites. In 4 prioritizations, the framework supported 6 submissions. As of June 2018, the framework had contributed to the eventual funding of more than 9 new drug–indication pairs, with more awaiting funding consideration. Conclusions: The CCO prioritization framework has enabled clinicians to effectively and systematically identify, prioritize, and fill funding gaps not addressed by industry. Ultimately, the framework helps to ensure that patients can access evidence-informed and cost-effective therapies. The framework will continue to evolve as it encounters new challenges, including funding requests for rare indications. Full article

Background: Improved treatments resulting in a rising number of survivors of breast cancer (bca) calls for optimization of current specialist-based follow-up care. In the present study, we evaluated well survivors of bca with respect to their supportive care needs and attitudes toward follow-up with various care providers, in varying settings, or mediated by technology (for example, videoconference or e-mail). Methods: A cross-sectional paper survey of well survivors of early-stage pT1–2N0 bca undergoing posttreatment follow-up was completed. Descriptive and univariable logistic regression analyses were performed to examine associations between survivor characteristics, supportive care needs, and perceived satisfaction with follow-up options. Qualitative responses were analyzed using conventional content analysis. Results: The 190 well survivors of bca who participated (79% response rate) had an average age of 63 ± 10 years. Median time since first follow-up was 21 months. Most had high perceived satisfaction with in-person specialist care (96%, 177 of 185). The second most accepted model was shared care involving specialist and primary care provider follow-up (54%, 102 of 190). Other models received less than 50% perceived satisfaction. Factors associated with higher perceived satisfaction with non-specialist care or virtual follow-up by a specialist included less formal education (p < 0.01) and more met supportive care needs (p < 0.05). Concerns with virtual follow-up included the perceived impersonal nature of virtual care, potential for inadequate care, and confidentiality. Conclusions: Well survivors of bca want specialists involved in their follow-up care. Compared with virtual followup, in-person follow-up is perceived as more reassuring. Certain survivor characteristics (for example, met supportive care needs) might signal survivor readiness for virtual or non-specialist follow-up. Future work should examine multi-stakeholder perspectives about barriers to and facilitators of shared multimodal follow-up care. Full article

Background: Rates of contralateral prophylactic mastectomy (CPM) continue to rise internationally despite evidence-based guidance strongly discouraging its use in most women with unilateral breast cancer. The purpose of the present study was to develop and assess the feasibility of a knowledge translation tool [a patient decision aid (DA)] designed to enhance evidence-informed shared decision-making about CPM. Methods: A consultation DA was developed using the Ottawa Patient Decision Aid Development eTraining in consultation with clinicians and knowledge translation experts. The final DA was then assessed for feasibility with health care professionals and patients across Canada. The assessment involved a survey completed online (health care professionals) or by telephone (patients). Survey data were analyzed using descriptive statistics for closed-ended questions and qualitative content analysis for open-ended questions. Results: The 51 participants who completed the survey included 39 health care professionals and 12 patients. The DA was acceptable; 88% of participants viewed it as having the right amount of information or slightly more or less information than they would like. Almost all participants (98%) felt that the DA would prepare patients to make better decisions. The aid was perceived to be usable, with 73% of participants stating that they would be willing to use or share the DA. Conclusions: The CPM patient DA developed for the present study was viewed by health care professionals and patients across Canada to be acceptable and usable during the clinical consultation. It holds promise as a knowledge translation tool to be used by clinicians in consultation with women who have unilateral breast cancer to enhance evidence-informed and shared decision-making with respect to undergoing CPM. Full article

Background: Participation in colorectal screening remains low even in countries with universal health coverage. Area-level determinants of low screening participation in Canada remain poorly understood. Methods: We assessed the association between area-level income and two indicators of colorectal screening (having never been screened, having not been screened recently) by linking census-derived local area-level income data with self-reported screening data from urban-dwelling respondents to the Canadian Community Health Survey (50–75 years of age, cycles 2005 and 2007, n = 18,362) who reported no known risk factors for colorectal cancer. Generalized estimating equation Poisson models estimated the prevalence ratios and differences for having never been screened and having not been screened recently, adjusting for individual-level income, education, marital status, having a regular physician, age, and sex. Results: About 53% of the study population had never been screened. Among individuals who had ever been screened, 35% had been screened recently. Adjusting for covariates, lower area-level income was associated with having never been screened [covariate-adjusted prevalence ratios: 1.24 for quartile 1; 95% confidence limits (cl): 1.16, 1.34; 1.25 for quartile 2; 95% cl: 1.15, 1.33; 1.15 for quartile 3; 95% cl: 1.08, 1.23]. Among individuals who had been screened in their lifetime, area-level income was not associated with having not been screened recently. Conclusions: Lower area-level income is associated with having never been screened for colorectal cancer even after adjusting for individual socioeconomic factors. Those findings highlight the potential importance of socioeconomic contexts for colorectal screening initiation and merit attention in both future research and surveillance efforts. Full article

Background: Patient education materials (PEMS) are frequently used to help patients make cancer screening decisions. However, because PEM are typically developed by experts, they might inadequately address patient barriers to screening. We co-created, with patients, a prostate cancer (pca) screening PEM, and we compared how the co-created PEM and a PEM developed by experts affected decisional conflict and screening intention in patients. Methods: We identified and used patient barriers to pca screening to co-create a pca screening PEM with patients, clinicians, and researchers. We then conducted a parallel-group randomized controlled trial with men 40 years of age and older in Ontario to compare decisional conflict and intention about pca screening after those men had viewed the co-created PEM (intervention) or an expert-created PEM (control). Participants were randomized using dynamic block randomization, and the study team was blinded to the allocation. Results: Of 287 participants randomized to exposure to the co-created PEM, 230 were analyzed, and of 287 randomized to exposure to the expert-created PEM, 223 were analyzed. After PEM exposure, intervention and control participants did not differ significantly in Decisional Conflict Scale scores [mean difference: 0.37 ± 1.23; 95% confidence interval (CI): −2.05 to 2.79]; in sure (Sure of myself, Understand information, Risk–benefit ratio, or Encouragement) scores (odds ratio: 0.75; 95% CI: 0.52 to 1.08); or in screening intention (mean difference: 0.09 ± 0.08; 95% CI: −0.06 to 0.24]). Conclusions: The effectiveness of the co-created PEM did not differ from that of the PEM developed by experts. Thus, PEM developers should choose the method that best fits their goals and resources. Full article

Background: Epithelial–mesenchymal transition (EMT) refers to the biologic process in which epithelial cells are transformed into interstitial phenotypes by specific pathways. This transition plays an important biologic role in the process by which epithelium-derived malignant tumour cells acquire the ability to migrate and invade. We explored the relationship between EMT-associated molecules and patient-related clinical factors to determine whether any clinical characteristics could be used as biomarkers for EMT-related protein alterations in lung cancer—especially lung adenocarcinoma. Methods: Tumour specimens were collected from 80 patients with lung adenocarcinoma who underwent surgery or lung biopsy, with 4 patients being evaluated a 2nd time after re-biopsy. Expression of EMT-related proteins, including E-cadherin and vimentin, was evaluated by immunohistochemistry. We analyzed the relationship between clinicopathologic characteristics and expression level of the EMT markers. Results: Positive expression of E-cadherin was observed in 63 patients (79%), and vimentin, in 46 patients (57.5%). No significant relationships between E-cadherin or vimentin expression and smoking history, sex, age, driving gene mutations, or cell differentiation were identified. A significant correlation was observed between vimentin expression and pathologic stage. Of the 4 patients who were evaluated a 2nd time after re-biopsy, 3 showed the same emt-related protein expression status as in the first analysis. In the remaining patient, E-cadherin had changed completely. Conclusions: Clinicopathologic factors in cancer patients did not help to diagnose emt status in lung adenocarcinoma; however, TNM stage might be associated with vimentin expression. Full article

Oropharyngeal cancer (OPC) has become the leading site for human papillomavirus (HPV)–associated cancers in humans. It is an epidemic that remains relatively unfamiliar to most physicians, potentially delaying diagnosis and treatment. Traditionally, cancers involving the head and neck have occurred in smokers and in those with a significant alcohol history. Typically, HPV-positive opc presents in a younger, healthier population with a different set of risk factors and good prognosis for survival. However, many head-and-neck cancer patients, including those with HPV-positive disease, develop lifelong disabilities because of the morbid nature of their treatments, and those patients have the highest level of unmet needs in studies spanning cancer sites. Knowledge of this epidemic, a high index of suspicion, and an understanding of how the tumours present in clinical practice can help physicians to make an early diagnosis, thus sparing the patient significant morbidity from treatments associated with more advanced disease stages. Furthermore, recognizing that these patients have distinct psychosocial needs and implementing a collaborative team approach is critical to providing optimal care and improving quality of life in the survivorship period. Full article

Introduction: Given the high occurrence and morbidity of non-melanoma skin cancer (NMSC), its economic burden on the Canadian health care system is a cause for concern. Despite that relevance, few studies have used patient-level data to calculate the cost of NMSC. The objective of the present study was to use physician billing data to describe the health care costs and service utilization associated with NMSC in Saskatchewan. Methods: The Saskatchewan Cancer Agency’s cancer registry was used to identify patients diagnosed with NMSC between 2004 and 2008. Treatment services and costs were based on physician billing claims, which detail physician services performed in an outpatient setting. Total and annual outpatient costs for nmsc and mean outpatient cost per person were calculated by skin cell type, lesion site, and geographic location. Service utilization and costs by physician specialty were also explored. Results: Total outpatient costs grew 12.08% annually, to $845,954.98 in 2008 from $527,458.76 in 2004. The mean outpatient cost per person was estimated at $397.86. Differences in the cost-per-person estimates were observed when results were stratified by skin cell type ($403.41 for basal cell carcinoma vs. $377.85 for squamous cell carcinoma), lesion site ($425.27 for the face vs. $317.80 for an upper limb), and geographic location ($415.07 urban vs. $363.48 rural). Investigation of service utilization found that 92.14% of treatment was delivered by general practice and plastic surgery/otolaryngology physicians; dermatology delivered only 6.33% of services. Conclusions: Our results underestimate the direct costs of NMSC because inpatient services and non-physician costs were not included in the calculations. The present research represents a first step in understanding the cost burden of NMSC in Saskatchewan. Full article

Introduction: Diffuse large B-cell lymphoma (DLBCL) accounts for 30%–40% of all non-Hodgkin lymphomas. Approximately 60% of patients are cured with standard treatment. Targeted treatments are being investigated and might improve disease outcomes; however, their effect on cancer drug budgets will be significant. For the present study, we conducted an analysis of real-world costs for dlbcl patients treated in British Columbia, useful for health care system planning. Methods: Patient records from a retrospective cohort of patients diagnosed with dlbcl in British Columbia during 2004–2013 were anonymously linked across multiple administrative data sources: systemic therapy, radiotherapy, hospitalizations, oncologist services, outpatient medications, and fee-for-service physician services. Using generalized linear modelling regression, time-dependent costs (in 2015 Canadian dollars) were estimated in 6-month intervals over a 5-year period. The inverse probability weighting method was applied to account for censored observations. Nonparametric bootstrapping was used to estimate standard errors for the mean cost at each time interval. Results: The cohort consisted of 678 patients (5-year overall survival: 67%). Mean age at diagnosis was 64 ± 14 years; median follow-up was 3.2 years. Mean total cost of care was highest in the first 6 months after diagnosis ($29,120; 95% confidence interval: $28,986 to $29,170) and after disease progression ($18,480; 95% confidence interval: $15,187 to $24,772). Systemic therapy and hospitalization costs were the largest cost drivers. At each time interval, costs were observed to be positively skewed. Conclusions: Our results depict real-world costs for the treatment of dlbcl patients with standard chop-r therapy. Cost-model parameters are also provided for economic modelling of dlbcl interventions. Full article

Background: With recent advances in the treatment of non-small-cell lung cancer (NSCLC) and current fiscal constraints within publicly funded health care systems, understanding the real-world economic effect of lung cancer management has become important. The objective of the present study was to determine the costs and resources used in the management of nsclc cohorts in Ontario. Methods: Patients diagnosed between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry and linked to provincial administrative databases, capturing resources such as hospitalizations, cancer clinic visits, physician services, and systemic therapies or radiotherapy. A cost-of-illness analysis using a bottom-up approach and the GETCOST macro available at ices determined the overall total and mean costs in 2017 Canadian dollars. Resource utilization results were analyzed according to the total number of encounters per resource, the number of patients using each resource, and the number of encounters per patient. A separate cost-and-resource analysis was conducted for radiotherapy. Results: The 24,729 NSCLC patients identified included 4542 with stage iii unresectable disease and 10,103 with stage iv nonsquamous disease. The overall total cost for all nsclc patients was $1.9 billion, with inpatient hospitalizations ($635.2 million), cancer clinic visits ($323.7 million), and physician services ($301.4 million) being the top cost contributors. The mean cost per patient was $76,816. The total cost of radiotherapy was $38.5 million. Conclusions: Real-world costs for the management of nsclc during the 5-year period examined were substantial, despite the fact that median survival was poor and treatment information was limited. Full article

Introduction: This paper describes the funding rates established in Ontario to reflect best practices in hospital-based care delivery for these endoscopic procedures: colonoscopy, colonoscopy biopsy, gastroscopy, gastroscopy biopsy, and colonoscopy combined with gastroscopy. Methods: The funding rates are based on direct costs and were established using a micro-costing approach after receipt of inputs from 3 working groups and a review of the administrative data and literature, where applicable. The first group advised on nursing activities, time, and staffing ratios along the patient pathway for each of the procedures. The second group provided recommendations about the duration for each procedure, and the third group provided information about supplies and equipment, their use, and costs. Results: The resulting funding rates are $161.18 for colonoscopy and $151.08 for gastroscopy (without accompanying interventions), $16.06 for colonoscopy biopsy and $8.22 for gastroscopy biopsy (added to the respective procedures), and $207.26 for combined colonoscopy and gastroscopy. Detailed costs for each component embedded in the rates are also provided. Conclusions: The rates came into effect in April 2018. The process and outcomes described here allowed for a transparent pricing mechanism in which funding follows the patient, clinical expert consensus is the basis for practice, and providers and payers both understand the components. Full article

Introduction: Costs associated with cancer care are increasing. Cancer costs in the context of other common non-cancer diagnoses have not been extensively studied at the population level. Knowledge from such analyses can inform health care resource allocation and highlight strategies to reduce overall costs. Methods: Using cross-sectional data from publicly available population-level administrative data sources (health insurance claims, physician billing, and hospital discharge abstracts), we calculated incidence-adjusted health care costs (in 2014 Canadian dollars) for cancers and common non-cancer diagnoses in the adult population in a large Canadian province. Subgroup analyses were also performed for various provincial health administrative regions. Results: Total costs related to cancer care amounted to $495 million for the province, of which at least $67 million (14%) was attributable to radiation and chemotherapy. Of the various cancer subtypes, hematologic malignancies were most costly at $70 million, accounting for 14% of the total cancer budget. Colon cancer followed at $51 million (10%), and lung cancer, at $44 million (9%). Cancer costs (with and without costs for radiation and chemotherapy) exceeded those for cardiovascular disease, diabetes mellitus, mental health, and trauma (p < 0.001). In addition, the costs of specific cancer subtypes varied by region, but hematologic and lung cancers were typically the most costly no matter the health region. Conclusions: Using provincial administrative data to establish cost trends can help to inform health care allocation and budget decisions, and can facilitate comparisons between provinces. Full article

Background: Economic evaluations are an integral component of many clinical trials. Costs used in those analyses are based on the prices of branded drugs when they first enter the market. The effect of genericization on the cost-effectiveness (CE) or cost–utility (CU) of an intervention is unknown because economic analyses are rarely updated using the costs of generic drugs. Methods: We re-examined the CE or CU of regimens previously evaluated in Canadian Cancer Trials Group (CCTG) studies that included prospective economic evaluations and where genericization has occurred or is anticipated in Canada. We incorporated the new costs of generic drugs to characterize changes in CE or CU. We also determined acceptable cost levels of generic drugs that would make regimens reimbursable in a publicly funded health care system. Results: The four randomized controlled trials included (representing 1979 patients) were CCTG BR.10 (early lung cancer, adjuvant vinorelbine–cisplatin vs. observation, n = 172), CCTG BR.21 (metastatic lung cancer, erlotinib vs. placebo, n = 731), CCTG CO.17 (metastatic colon cancer, cetuximab vs. best supportive care, n = 557), and CCTG LY.12 (relapsed or refractory lymphoma, gemcitabine–dexamethasone–cisplatin vs. cytarabine–dexamethasone–cisplatin, n = 619). Since the initial publication of those trials, the genericization of vinorelbine, erlotinib, cetuximab, and cisplatin has taken place or is expected in Canada. Costs of generics improved the ces and cus of treatment significantly. For example, genericization of erlotinib ($1460.25 per 30 days) resulted in an incremental cost-effectiveness ratio (ICER) of $45,746 per life-year gained compared with $94,638 for branded erlotinib. Likewise, genericization of cetuximab ($275.80 per 100 mg) produced an icer of $261,126 per quality-adjusted life-year (QALY) gained compared with $299,613 for branded cetuximab. Decreases in the cost of generic cetuximab to $129.39 and $63.51 would further improve the icer to $150,000 and $100,000 per QALY respectively. Conclusions: Genericization of a costly oncology drug can modify the CE and CU of a regimen significantly. Failure to revisit economic analyses with the costs of generics could be a missed opportunity for funding bodies to optimize value-based allocation of health care resources. At current levels, the costs of generics might not be sufficiently low to sustain publicly funded health care systems. Full article