Curr. Oncol., Volume 26, Issue 6 (December 2019) – 19 articles

The sixth International African–Caribbean Cancer Consortium (AC3) Conference was held 6–9 October 2017 in Miami, Florida, U.S.A. The conference was open to all researchers, trainees, clinical and public health professionals, and community members, and served as an international hub for the United States, the Caribbean, and Africa. Sessions included AC3 collaboration meetings, cancer surveillance and research skills training workshops, and a community cancer prevention conference. Full article

The 20th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, 28–29 September 2018. This interactive multidisciplinary conference is attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancers. In addition, invited speakers from other provinces participate. Surgical, medical, and radiation oncologists, and allied health care professionals participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancers. Full article

Introduction: Retroperitoneal sarcoma (rps) encompasses a heterogeneous group of malignancies with a high recurrence rate after resection. Neoadjuvant radiotherapy (nrt) is often used in the hope of sterilizing margins and decreasing local recurrence after excision. We set out to compare local recurrence-free survival (lrfs) and overall survival (os) in patients treated with or without nrt before resection. Methods: Patients diagnosed with rps from February 1990 to October 2014 were identified in the Alberta Cancer Registry. Patients with complete gross resection of rps and no distant disease were included. Patient, tumour, treatment, and outcomes data were abstracted in a primary chart review. Baseline characteristics were compared using the Wilcoxon nonparametric test for continuous data and the Fisher exact test for dichotomous and categorical data. Survival was analyzed using Kaplan–Meier curves with log-rank test. Cox regression was performed to control for age, sex, tumour size, tumour grade, date of diagnosis, multivisceral resection, and intraoperative rupture. Results: Resection alone was performed in 62 patients, and resection after nrt, in 40. Use of nrt was associated with multivisceral resection and negative microscopic margins. On univariate analysis, nrt was associated with superior median lrfs (89.3 months vs. 28.4 months, p = 0.04) and os (119.4 months vs. 75.9 months, p = 0.04). On multivariate analysis, nrt, younger age, and lower tumour grade predicted improved lrfs and os; sex, tumour size, date of diagnosis, multivisceral resection, and tumour rupture did not. Conclusions: In this population-based study, nrt was associated with superior lrfs and os on both univariate and multivariate analysis. When feasible, nrt should be considered until a randomized controlled trial is completed. Full article

Background: Past research suggests that patients with early- and late-stage melanoma will endure adverse events and inconvenient treatment regimens for improved survival. Evidence about the preferences of Canadian patients and physicians for novel adjuvant treatments for melanoma is unavailable. Methods: Patient and physician preferences for adjuvant treatments for melanoma were assessed in an online discrete choice experiment (dce). Treatment alternatives were characterized by 8 attributes with respect to dosing regimen, efficacy, and toxicities, with levels corresponding to those for dabrafenib–trametinib, nivolumab, pembrolizumab, and interferon. For patients, the effects of melanoma on quality of life and ability to work and perform activities of daily living were also assessed. Patients were recruited by Canadian melanoma patient advocacy groups through e-mail and social media. Physicians were recruited by e-mail. Results: Of 94 patients who started the survey, 51 completed 1 or more dce questions. Of 166 physicians sent the e-mail invitation, 18 completed 1 or more dce questions. For patients, an increased probability of remaining cancer-free over 21 months was the most important attribute. For physicians, an increased chance of the patient’s remaining alive over 36 months was the most important attribute. Patients and physicians chose active treatment over no treatment 85% and 86% of the time respectively and a treatment with attributes consistent with dabrafenib–trametinib 71% and 67% of the time respectively. A substantial proportion of patients reported worrying about future diagnostic tests and their cancer coming back. Conclusions: Canadian patients and physicians are generally concordant in their preferences for adjuvant melanoma treatments, preferring active treatment to no treatment and dabrafenib–trametinib to other options. Full article

Background: Selection and sequencing of treatment regimens for individual patients with metastatic colorectal cancer (mcrc) is driven by maintaining reasonable quality of life and extending survival, as well as by access to and cost of therapies. The objectives of the present study were to describe, for patients with mcrc, attrition across lines of systemic therapy, patterns of therapy and their timing, and KRAS status. Methods: A retrospective chart review at 6 Canadian academic centres included sequential patients who were diagnosed with mcrc from 1 January 2009 onward and who initiated first-line systemic treatment for mcrc between 1 January and 31 December 2009. Death was included as a competing risk in the analysis. Results: The analysis included 200 patients who started first-line therapy. The proportions of patients who started second-, third-, and fourth-line systemic therapy were 70%, 30%, and 15% respectively. Chemotherapy plus bevacizumab was the most common first-line combination (66%). The most common first-line regimen was folfiri plus bevacizumab. KRAS testing was performed in 103 patients (52%), and 38 of 68 patients (56%, 19% overall) with confirmed KRAS wild-type tumours received an epidermal growth factor receptor inhibitor (egfri), which was more common in later lines. Most KRAS testing occurred after initiation of second-line therapy. Conclusions: In the modern treatment era, a high proportion of patients receive at least two lines of therapy for mcrc, but only 19% receive egfri therapy. Earlier KRAS testing and therapy with an egfri might allow a greater proportion of patients to access all 5 active treatment agents. Full article

Background: Of hospitalized patients in Canada, 7.5% experience an adverse event (AE). Physicians whose patients experience AES often become second victims of the incident. The present study is the first to evaluate how physicians in Canada cope with aes occurring in their patients. Methods: Survey participants included oncologists, surgeons, and trainees at the Foothills Medical Centre, Calgary, AB. The surveys were administered through REDCap (Research Electronic Data Capture, version 9.0: REDCap Consortium, Vanderbilt University, Nashville, TN, U.S.A.). The Brief COPE (Coping Orientation to Problems Experienced) Inventory, the IES-R (Impact of Event Scale–Revised), the Causal Dimension Scale, and the Institutional Punitive Response scale were used to evaluate coping strategies, prevalence of post-traumatic stress, and institutional culture with respect to AES. Results: Of 51 responses used for the analysis, 30 (58.8%) came from surgeons and 21 (41.2%) came from medical specialists. On the IES-R, 54.9% of respondents scored 24 or higher, which has been correlated with clinically concerning post-traumatic stress. Individuals with a score of 24 or higher were more likely to report self-blame (p = 0.00026) and venting (p = 0.042). Physicians who perceive institutional support to be poor reported significant post-traumatic stress (p = 0.023). On multivariable logistic regression modelling, self-blame was associated with an IES-R score of 24 or higher (p = 0.0031). No significant differences in IES-R scores of 24 or higher were observed between surgeons and non-surgeons (p = 0.15). The implications of AES for physicians, patients, and the health care system are enormous. More than 50% of our respondents showed emotional pathology related to an AE. Higher levels of self-blame, venting, and perception of inadequate institutional support were factors predicting increased post-traumatic stress after a patient AE. Conclusions: Our study identifies a desperate need to establish effective institutional supports to help health care professionals recognize and deal with the emotional toll resulting from AES. Full article

Background: We assessed whether the presence and severity of common cancer symptoms are associated with the health utility score (HUS) generated from the EQ-5D (EuroQol Research Foundation, Rotterdam, Netherlands) in patients with cancer and evaluated whether it is possible pragmatically to integrate routine hus and symptom evaluation in our cancer population. Methods: Adult outpatients at Princess Margaret Cancer Centre with any cancer were surveyed cross-sectionally using the Edmonton Symptom Assessment System (ESAS) and the EQ-5D-3L, and results were compared using Spearman correlation coefficients and regression analyses. Results: Of 764 patients analyzed, 27% had incurable disease. We observed mild-to-moderate correlations between each ESAS symptom score and the HUS (Spearman coefficients: −0.204 to −0.416; p < 0.0001 for each comparison), with the strongest associations being those for pain (R = −0.416), tiredness (R = −0.387), and depression (R =−0.354). Multivariable analyses identified pain and depression as highly associated (both p < 0.0001) and tiredness as associated (p = 0.03) with the HUS. The ability of the ESAS to predict the HUS was low, at 0.25. However, by mapping ESAS pain, anxiety, and depression scores to the corresponding EQ-5D questions, we could derive the HUS using partial ESAS data, with Spearman correlations of 0.83–0.91 in comparisons with direct EQ-5D measurement of the HUS. Conclusions: The HUS derived from the EQ-5D-3L is associated with all major cancer symptoms as captured by the ESAS. The ESAS scores alone could not predict EQ-5D scores with high accuracy. However, ESAS-derived questions assessing the same domains as the EQ-5D-3L questions could be mapped to their corresponding EQ-5D questions to generate the HUS, with high correlation to the directly measured HUS. That finding suggests a potential approach to integrating routine symptom and HUS evaluations after confirmatory studies. Full article

Background: A pilot inter-laboratory proficiency scheme for 5 Ontario clinical laboratories testing tumour samples for the Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) study was undertaken to assess proficiency in the identification and reporting of next-generation sequencing (NGS) test results in solid tumour testing from archival formalin-fixed, paraffin-embedded (FFPE) tissue. Methods: One laboratory served as the reference centre and provided samples to 4 participating laboratories. An analyte-based approach was applied: each participating laboratory received 10 FFPE tissue specimens profiled at the reference centre, with tumour site and histology provided. Laboratories performed testing per their standard NGS tumour test protocols. Items returned for assessment included genes and variants that would be typically reported in routine clinical testing and variant call format (VCF) files to allow for assessment of NGS technical quality. Results: Two main aspects were assessed: (1) Technical quality and accuracy of identification of exonic variants; (2) Site-specific reporting practices. Technical assessment included evaluation of exonic variant identification, quality assessment of the VCF files to evaluate base calling, variant allele frequency, and depth of coverage for all exonic variants. Concordance at 100% was observed from all sites in the technical identification of 98 exonic variants across the 10 cases. Variability between laboratories in the choice of variants considered clinically reportable was significant. Of the 38 variants reported as clinically relevant by at least 1 site, only 3 variants were concordantly reported by all participating centres as clinically relevant. Conclusions: Although excellent technical concordance for ngs tumour profiling was observed across participating institutions, differences in the reporting of clinically relevant variants were observed, highlighting reporting as a gap where consensus on the part of Ontario laboratories is needed. Full article

In the initially published manuscript, the article stated (about the BEACON clinical trial) that “Interestingly, the triplet did not appear more active than the combination of encorafenib and binimetinib (mos: 9.0 months vs. 8.4 months; HR: 0.79; 95% CI: 0.59 to 1.06).” [...] Full article

Background: Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. However, that interaction remains unclear in clinical practice. Methods: We performed a systematic review in medline to determine (1) whether antibiotics affect ici efficacy, (2) whether baseline gm composition and ici efficacy show any correlations, (3) whether baseline gm composition and emergence of immune-related adverse events (iraes) show any correlations, and (4) whether gm manipulation can alleviate the iraes. Included publications had to be written in English or French and had to describe a quantifiable link between gm composition or its modification and the response to icis or the occurrence of iraes, or both. Results: Of 1451 articles published before December 2018, 13 publications met the inclusion criteria. Five full-text articles and two abstracts highlighted a negative effect of antibiotics on ici efficacy. The composition of the gm was associated with ici efficacy in five full-text articles and one abstract, and with iraes in two full-text articles. In 2 cases, fecal microbiota transplantation was reported to reduce immune colitis. Conclusions: If possible, antibiotics should be avoided before ici treatment because of their negative effect on ici anticancer efficacy. No specific commensal bacterium was associated with ici efficacy, but an intact gm with high bacterial diversity and a good ratio of “responder-associated” bacteria to “non-responder-associated” bacteria seem to be correlated with better patient outcomes. Fecal microbiota transplantation is a promising technique for reducing ici-associated colitis. Full article

Medullary thyroid cancer is a rare type of neuroendocrine tumour that arises from the parafollicular cells (C cells) of the thyroid gland. It accounts for 3%–5% of thyroid cancer cases. Close to 25% of cases are familial, and 75% are considered sporadic. Familial cases are associated with a germline RET mutation; 43%–65% of sporadic cases harbour a somatic event in the gene. Germline RET mutations are associated with the autosomal-dominant inherited multiple endocrine neoplasia (MEN) 2A and 2B syndromes and the isolated familial medullary thyroid cancer syndrome. More than 100 RET codon mutations have been reported to date, with genotype–phenotype correlations that include the extent and aggressiveness of the medullary thyroid cancer and the presence of other features of the MEN2 syndromes. The latter include pheochromocytoma–paraganglioma, hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung disease. In this narrative review, we focus on RET proto-oncogene physiology and pathogenesis induced by germline and somatic RET mutations, the genotype–phenotype correlation, and the management and follow-up of patients with germline-mutated medullary thyroid cancer. Full article

Background: Breast-conserving surgery (BCS) and radiation therapy (RT) are the standard of care for early breast cancer; studies have demonstrated that adjuvant RT confers a protective effect with respect to recurrence, although no randomized trials have shown a survival benefit. Methods: This retrospective cohort study used Ontario data linked through ICES to examine patients treated for breast cancer between 1 April 2007 and 31 March 2014. The primary outcome was death or recurrence. Outcomes were compared between patients who did and did not receive RT. Results: The total cohort size was 26,279. The hazard ratios (HRS) for various outcomes were significantly higher for patients who did not receive RT than for patients who did: recurrence or death combined [HR: 2.49; 95% confidence interval (CI): 2.25 to 2.75], recurrence (HR: 2.33; 95% CI: 1.91 to 2.84), and death (HR: 2.28; 95% CI: 2.03 to 2.56). The HR for death was 1.81 (95% CI: 1.65 to 1.99) for patients having stage II cancer compared with those having stage I disease. The HR for death was 1.97 (95% CI: 1.74 to 2.22) for patients having high comorbidity compared with those having little comorbidity. Conclusions: Adjuvant RT carries a protective effect with respect to recurrence and survival in patients with early-stage breast cancer. That survival benefit has not been appreciated in previous randomized trials and underscores the importance of rt as a component of breast cancer treatment. Full article

Background: Shared decision-making at end of life (EOL) requires discussions about goals of care and prioritization of length of life compared with quality of life. The purpose of the present study was to describe patient and oncologist discordance with respect to goals of care and to explore possible predictors of discordance. Methods: Patients with metastatic cancer and their oncologists completed an interview at study enrolment and every 3 months thereafter until the death of the patient or the end of the study period (15 months). All interviewees used a 100-point visual analog scale to represent their current goals of care, with quality of life (scored as 0) and survival (scored as 100) serving as anchors. Discordance was defined as an absolute difference between patient and oncologist goals of care of 40 points or more. Results: The study enrolled 378 patients and 11 oncologists. At baseline, 24% discordance was observed, and for patients who survived, discordance was 24% at their last interview. For patients who died, discordance was 28% at the last interview before death, with discordance having been 70% at enrolment. Dissatisfaction with EOL care was reported by 23% of the caregivers for patients with discordance at baseline and by 8% of the caregivers for patients who had no discordance (p = 0.049; φ = 0.20). Conclusions: The data indicate the presence of significant ongoing oncologist–patient discordance with respect to goals of care. Early use of a simple visual analog scale to assess goals of care can inform the oncologist about the patient’s goals and lead to delivery of care that is aligned with patient goals. Full article

Background: Quitting smoking after a cancer diagnosis maximizes treatment-related effects, improves prognosis, and enhances quality of life. However, smoking cessation (SC) services are not routinely integrated into cancer care. The Princess Margaret Cancer Centre implemented a digitally-based sc program in oncology, leveraging an e-referral system (CEASE) to screen all new ambulatory patients, provide tailored education and advice on quitting, and facilitate referrals. Methods: We adopted the Framework for Managing eHealth Change to guide implementation of the sc program by integrating 6 key elements: governance and leadership, stakeholder engagement, communication, workflow analysis and integration, monitoring and evaluation, and training and education. Results: Incorporating elements of the Framework, we used extensive stakeholder engagement and strategic partnerships to establish a sc program with organizational and provincial accountability. Existing electronic patient-reported assessments were changed to integrate cease. Clinic audits and staff engagement allowed for analysis of workflow, ongoing monitoring and evaluation that aided in establishing a communication strategy, and development of cancer-specific education for patients and health care providers. From April 2016 to March 2018, 22,137 new patients were eligible for screening. Among those new patients, 13,617 (62%) were screened, with 1382 (10%) being current smokers and 532 (4%) having recently quit (within 6 months). Of the current smokers and those who had recently quit, all were advised to quit or to stay smoke-free, and 380 (20%) accepted referral to a sc counselling service. Conclusions: Here, we provide a comprehensive practice blueprint for the implementation of digitally based sc programs as a standard of care within comprehensive cancer centres with high patient volumes. Full article

Background: Practices in somatic variant interpretation and classification vary between Canadian clinical molecular diagnostic laboratories, and understanding of current practices and perspectives is limited. To define gaps and future directions, including consensus guideline development, the Somatic Curation and Interpretation Across Laboratories (SOCIAL) project examined the present state of somatic variant interpretation in Canadian molecular laboratories, including testing volumes and methods, data sources and evidence criteria, and application of published classification guidelines. Methods: Individuals who perform somatic variant interpretation in Canadian centres were invited to participate in an online survey. Invitees included laboratory directors (certified as Fellows of the Canadian College of Medical Geneticists or the American College of Medical Geneticists), MD or MD and PhD molecular pathologists, and other PhD experts, including PhD specialists in variant annotation or bioinformatics. Current testing methods, volumes, and platforms in next-generation sequencing, use of variant annotation resources and evidence criteria, and preference for variant classification schemes were evaluated. Results: Responses were received from 37 participants in 8 provinces. A somatic variant classification scheme jointly supported by the Association for Molecular Pathology (AMP), the American Society of Clinical Oncology (ASCO), and the College of American Pathologists (CAP) was used by 47% of respondents; an alternative guideline or a combination of published guidelines was used by 35% of respondents. The remaining 18% did not use a published scheme. Only 41% of respondents used a published scheme without alteration. Although all respondents indicated that there is a need for Canadian laboratories to adopt a somatic variant classification guideline, only 38% of respondents felt that it should be mandatory to adopt the AMP/ASCO/CAP–endorsed guideline. Conclusions: Data from the SOCIAL project identified high variability in current practice, yet strong support for standardization of solid-tumour somatic variant interpretation across Canadian institutions. Aligning classification methods will reduce variation in cross-institutional classification and reporting practices, aiding in consistent practice nationwide. Full article