Curr. Oncol., Volume 25, Issue 2 (April 2018) – 19 articles

Patient-reported outcomes measures (PROMS) are an important component of the shift from disease-centred to person-centred care. In oncology, PROMS describe the effects of cancer and its treatment from the patient perspective and ideally enable patients to communicate to their providers the physical symptoms and psychosocial concerns that are most relevant to them. The Edmonton Symptom Assessment System–revised (ESAS-r) is a commonly used and validated tool in Canada to assess symptoms related to cancer. Here, we describe the extent to which patientreported outcome programs have been implemented in Canada and the severity of symptoms causing distress for patients with cancer. As of April 2017, 8 of 10 provinces had implemented the ESAS-r to assess patient-reported outcomes. Data capture methods, the proportion of cancer treatment sites that have implemented the ESAS-r, and the time and frequency of screening vary from province to province. From October 2016 to March 2017 in the 8 reporting provinces, 88.0% of cancer patients were screened for symptoms. Of patients who reported having symptoms, 44.3% reported depression, with 15.5% reporting moderate-to-high levels; 50.0% reported pain, with 18.6% reporting moderate-to-high levels; 56.2% reported anxiety, with 20.4% reporting moderate-to-high levels; and 75.1% reported fatigue, with 34.4% reporting moderate-to-high levels. There are some notable areas in which the implementation of PROMS could be improved in Canada. Findings point to a need to increase the number of cancer treatment sites that screen all patients for symptoms; to standardize when and how frequently patients are screened across the country; to screen patients for symptoms during all phases of their cancer journey, not just during treatment; and to assess whether giving cancer care providers real-time patient-reported outcomes data has led to appropriate interventions that reduce the symptom burden and improve patient outcomes. Continued measurement and reporting at the system level will allow for a better understanding of progress in PROMS activity over time and of the areas in which targeted quality improvement efforts could ensure that patient symptoms and concerns are being addressed. Full article

Background: Despite the fact that heterozygosity for a pathogenic ATM variant is present in 1%–2% of the adult population, clinical guidelines to inform physicians and genetic counsellors about optimal management in that population are lacking. Methods: In this narrative review, we describe the challenges and controversies in the management of women who are heterozygous for a pathogenic ATM variant with respect to screening for breast and other malignancies, to choices for systemic therapy, and to decisions about radiation therapy. Results: Given that the lifetime risk for breast cancer in women who are heterozygous for a pathogenic ATM variant is likely greater than 25%, those women should undergo annual mammographic screening starting at least by 40 years of age. For women in this group who have a strong family history of breast cancer, earlier screening with both magnetic resonance imaging and mammography should be considered. High-quality data to inform the management of established breast cancer in carriers of pathogenic ATM variants are lacking. Although deficiency in the ATM gene product might confer sensitivity to DNA-damaging pharmaceuticals such as inhibitors of poly (ADP–ribose) polymerase or platinum agents, prospective clinical trials have not been conducted in the relevant patient population. Furthermore, the evidence with respect to radiation therapy is mixed; some data suggest increased toxicity, and other data suggest improved clinical benefit from radiation in women who are carriers of a pathogenic ATM variant. Conclusions: As in the 2017 U.S. National Comprehensive Cancer Network guidelines, we recommend high-risk imaging for women in Ontario who are heterozygous for a pathogenic ATM variant. Currently, ATM carrier status should not influence decisions about systemic or radiation therapy in the setting of an established breast cancer diagnosis. Full article

Three groups of men are at high risk of developing prostate cancer: men with a strong family history of prostate cancer, men of West African or Caribbean ancestry, and men with a germline pathogenic variant in a prostate cancer–associated gene. Despite the fact that those men constitute a significant portion of the male population in North America, few recommendations for prostate cancer screening specific to them have been developed. For men at general population risk for prostate cancer, screening based on prostate-specific antigen (PSA) has remained controversial despite the abundance of literature on the topic. As a result, recommendations made by major screening authorities are inconsistent (ranging from no psa screening to baseline PSA screening at age 45), allowing physicians to pick and choose how to screen their patients. The Male Oncology Research and Education (more) program is an observational research program that serves as an academic platform for multiple research foci. For its participants, serum and dna are biobanked, medical information is collected, and contact for relevant research-related opportunities is maintained. This research program is paired with a specialized clinic called the more clinic, where men at high risk are regularly screened for prostate cancer in a standard approach that includes physical examination and serum psa measurement. In this article, we describe the goals, participant accrual to date, and projects specific to this unique program. Full article

Approximately 11% of patients with breast cancer (BCA) are diagnosed before menopause, and because in most of those patients the tumour expresses a hormone receptor, treatment with endocrine interventions can be applied in any setting of disease (early or advanced). In the past, hormonal treatment consisted only of the estrogen receptor modulator tamoxifen, associated with luteinizing hormone–releasing hormone (LHRH); more recently, aromatase inhibitors (AIS) have come into widespread use. The AIS interfere with the last enzymatic step of estrogen synthesis in which androgens are converted into estrogens. Initially, the AIS were used alone in postmenopausal patients to prevent disease recurrence, but together with LHRH analogs, they can be used in premenopausal patients to produce better estrogen suppression than can be achieved with tamoxifen plus a LHRH analog. Using a systematic review of the scientific literature (prospective and retrospective studies), we set out to assess the efficacy of AIS compared with other endocrine therapy in various disease settings (neoadjuvant, adjuvant, metastatic). Full article

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIS) are recommended as first-line systemic therapy for patients with non-small-cell lung cancer (NSCLC) having mutations in the EGFR gene. Resistance to TKIS eventually occurs in all nsclc patients treated with such drugs. In patients with resistance to TKIS caused by the EGFR T790M mutation, the third-generation TKI osimertinib is now the standard of care. For optimal patient management, accurate EGFR T790M testing is required. A multidisciplinary working group of pathologists, laboratory medicine specialists, medical oncologists, a respirologist, and a thoracic radiologist from across Canada was convened to discuss best practices for EGFR T790M mutation testing in Canada. The group made recommendations in the areas of the testing algorithm and the pre-analytic, analytic, and post-analytic aspects of clinical testing for both tissue testing and liquid biopsy circulating tumour DNA testing. The recommendations aim to improve EGFR T790M testing in Canada and to thereby improve patient care. Full article

Background: Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (HSCT). Methods: For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, CINAHL, and PsychINFO for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of HSCT. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models. Results: In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins (n = 31), stimulants (n = 19), L-carnitine (n = 6), corticosteroids (n = 5), antidepressants (n = 5), appetite stimulants (n = 3), and other agents (n = 48). Fatigue was significantly reduced with erythropoietin [standardized mean difference (SMD): −0.52; 95% confidence interval (ci): −0.89 to −0.14] and with methylphenidate (SMD: −0.36; 95% CI: −0.56 to −0.15); modafinil (or armodafinil) and corticosteroids were not effective. Conclusions: Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of HSCT. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects. Full article

Recent guidelines concerning exercise for people with cancer provide evidence-based direction for exercise assessment and prescription for clinicians and their patients. Although the guidelines promote exercise integration into clinical care for people with cancer, they do not support strategies for bridging the guidelines with related resources or programs. Exercise program accessibility remains a challenge in implementing the guidelines, but that challenge might be mitigated with conceptual frameworks (“pathways”) that connect patients with exercise-related resources. In the present paper, we describe a pathway model and related resources that were developed by an expert panel of practitioners and researchers in the field of exercise and rehabilitation in oncology and that support the transition from health care practitioner to exercise programs or services for people with cancer. The model acknowledges the nuanced distinctions between research and exercise programming, as well as physical activity promotion, that, depending on the available programming in the local community or region, might influence practitioner use. Furthermore, the pathway identifies and provides examples of processes for referral, screening, medical clearance, and programming for people after a cancer diagnosis. The pathway supports the implementation of exercise guidelines and should serve as a model of enhanced care delivery to increase the health and well-being of people with cancer. Full article

Background: Radiation therapy (RT) after mastectomy for breast cancer can improve survival outcomes, but has been associated with inferior cosmesis after breast reconstruction. In the literature, RT dose and fractionation schedules are inconsistently reported. We sought to determine the pattern of RT prescribing practices in a provincial RT program for patients treated with mastectomy and reconstruction. Methods: Women diagnosed with stages 0–III breast cancer between January 2012 and December 2013 and treated with curative-intent rt were identified from a clinicopathology database. Patient demographic, tumour, and treatment information were extracted. Of the identified patients, those undergoing mastectomy were the focus of the present analysis. Results: Of 4016 patients identified, 1143 (28%) underwent mastectomy. The patients treated with mastectomy had a median age of 57 years, and 37% of them underwent reconstruction. Treatment with more than 16 fractions of rt was associated with autologous reconstruction [odds ratio (OR): 37.2; 95% confidence interval (CI): 11.2 to 123.7; p < 0.001], implant reconstruction (OR: 93.3; 95% CI: 45.3 to 192.2; p < 0.001), and treating centre. Hypofractionated treatment was associated with older age (OR: 0.94; 95% CI: 0.92 to 0.96; p < 0.001), and living more than 400 km from a treatment centre (OR: 0.37; 95% CI: 0.16 to 0.86; p = 0.02). Conclusions: Prescribing practices in breast cancer patients undergoing mastectomy are influenced by reconstruction intent, age, nodal status, and distance from the treatment centre. Those factors should be considered when making treatment decisions. Full article

Background: A twice-weekly galactomannan (GM) screening protocol was implemented in high-risk hematology inpatients. Study objectives were to determine adherence to the protocol, use of selected resources, and patient outcomes. Methods: This retrospective cohort study compared outcomes of interest before and after implementation of GM screening. Adults undergoing matched related allogeneic hematopoietic stem-cell transplantation or induction chemotherapy for acute leukemia were eligible. Patients could be enrolled more than once and were evaluated as episodes. Adherence to the GM protocol was assessed in post-implementation episodes. Use of broad-spectrum antifungals (BSAFS), consultations (infectious diseases, respirology), and diagnostic procedures (computed tomography imaging, bronchoalveolar lavage) were compared between phases, as were the patient outcomes of all-cause mortality and clinical success (alive and not taking a BSAF). Results: Of 182 episodes consecutively screened, 70 per phase were enrolled. Clinical characteristics and duration of assessment were similar for the phases. Full or partial adherence to the protocol was observed in 61 post-implementation episodes (87%), with full adherence in 40 episodes (57%). More episodes in the pre-implementation phase than in the post-implementation phase involved receipt of BSAFS, consultations, and diagnostics (27% vs. 7%, p = 0.02; 46% vs. 26%, p = 0.014; and 46% vs. 31%, p = 0.083 respectively). Although mortality was similar in the two phases, clinical success at the final assessment was observed in fewer pre-implementation than post-implementation episodes (79% vs. 98%, p < 0.001). Conclusions: Implementation of a GM screening protocol was feasible and associated with significantly fewer episodes involving receipt of BSAFS and consultations, and with significantly more episodes showing clinical success. Full article

This article reviews intravenous vitamin C (IV C) in cancer care and offers a rational approach to enable medical oncologists and integrative practitioners to safely provide IV C combined with oral vitamin C to patients. The use of IV C is a safe supportive intervention to decrease inflammation in the patient and to improve symptoms related to antioxidant deficiency, disease processes, and side effects of standard cancer treatments. A proposed rationale, together with relevant clinical safety considerations for the application of IV C in oncologic supportive care, is provided. Full article

Purpose: The mainstay of treatment for ductal carcinoma in situ (DCIS) involves surgery in the form of mastectomy or lumpectomy. Inconsistency in the use of endocrine therapy (ET) for DCIS is evident worldwide. We sought to assess the variation in ET prescribing for patients with DCIS across a population-based radiotherapy (RT) program and to identify variables that predict its use. Methods: Data from a breast cancer database were obtained for women diagnosed with DCIS in British Columbia from 2009 to 2014. Associations between ET use and patient characteristics were assessed by chi-square test and multilevel multivariate logistic regression. The Kaplan–Meier method, with propensity score matching and Cox regression analysis, was used to assess the effects of ET on overall survival (OS) and relapse-free survival (RFS). Results: For the 2336 dcis patients included in the study, ET use was 13% in dcis patients overall, and 17% in patients with estrogen receptor–positive (ER+) tumours treated with breast-conserving surgery and RT. Significant variation in ET use by treatment centre was observed (range: 8–23%; p < 0.001), and prescription of et by individual oncologists varied in the range 0–40%. After controlling for confounding factors, age less than 50 years [odds ratio (OR): 1.72; p = 0.01], treatment centre, er+ status (OR: 5.33; p < 0.001), and RT use (or: 1.77; p < 0.001) were significant predictors of ET use. No difference in OS or RFS with the use of et was observed. Conclusions: In this population-based analysis, 13% of patients with dcis in British Columbia received ET, with variation by treatment centre (8–23%) and individual oncologist (0–40%). Age less than 50 years, ER+ status, and rt use were most associated with ET use. Full article

Background: We aimed to develop a new EGFR mutation–predictive scoring system to use in screening for EGFR-mutated lung adenocarcinomas (LACS). Methods: The study enrolled 279 patients with LAC, including 121 patients with EGFR wild-type tumours and 158 with EGFR-mutated tumours. The Student t-test, chi-square test, or Fisher exact test was applied to discriminate clinical and computed tomography (CT) features between the two groups. Using a principal component analysis (PCA) model, we derived predictive coefficients for the presence of EGFR mutation in LAC. Results: The EGFR mutation–predictive score includes sex, smoking history, homogeneity, ground-glass opacity (GGO) on imaging, and the presence of pericardial effusion. The PCA predictive model took this form: sex × 16 + smoking history × 15 + GGO × 12 + pericardial effusion × 10 + emphysema × 11. Model scores ranged from 79 to 147. The area under the receiver operating characteristic curve was 0.752 [95% confidence interval (ci): 0.697 to 0.801] in the LAC population at the optimal cut-off value of 109, and the sensitivity and specificity were 68.4% (95% CI: 60.5% to 75.5%) and 74.4% (95% CI: 65.6% to 81.9%) respectively. Conclusions: The EGFR mutation risk scoring system based on clinical data and CT features is noninvasive and user-friendly. The model appears to frame a positive predictive value and was able to determine the value of repeating a biopsy if tissue is limited. Full article

Background: Overuse of surveillance imaging in patients after curative treatment for early breast cancer (EBC) was recently identified as one of the Choosing Wisely Canada initiatives to improve the quality of cancer care. We undertook a population-level examination of imaging practices in Ontario as they existed before the launch of that initiative. Methods: Patients diagnosed with ebc between 2006 and 2010 in Ontario were identified from the Ontario Cancer Registry. Records were linked deterministically to provincial health care databases to obtain comprehensive follow-up. We identified all advanced imaging exams [aies: computed tomography (CT), bone scan, positron-emission tomography] and basic imaging exams (bies: ultrasonography, chest radiography) occurring within the first 2 years after curative treatment. Poisson regression was used to assess associations between patient or provider characteristics and the rate of AIES. Results: Of 30,006 women with ebc, 58.6% received at least 1 BIE, and 30.6% received at least 1 AIE in year 1 after treatment. In year 2, 52.7% received at least 1 BIE, and 25.7% received at least 1 AIE. The most common AIES were chest CTS and bone scans. The rate of AIES increased with older age, higher disease stage, comorbidity, chemotherapy exposure, and prior staging investigations (p < 0.001). Imaging was ordered mainly by medical oncologists (38%), followed by primary care physicians (23%), surgeons (13%), and emergency room physicians (7%). Conclusions: Despite recommendations against its use, imaging is common in EBC survivors. Understanding the factors associated with aie use helps to identify areas for further research and is required to lower imaging rates and to improve survivorship care. Full article

Background: The actual practices of routine follow-up after curative treatment for head-and-neck cancer are unknown, and existing guidelines are not evidence-based. Methods: This retrospective population-based study used administrative data to describe 5 years of routine follow-up care in 3975 head-and-neck cancer patients diagnosed between 2007 and 2012 in Ontario. Results: The mean number of visits per year declined during the follow-up period (from 7.8 to 1.9, p < 0.001). The proportion of patients receiving visits in concordance with guidelines ranged from 80% to 45% depending on the follow-up year. In at least 50% of patients, 1 head, neck, or chest imaging test was performed in the first follow-up year; that proportion subsequently declined (p < 0.001). Factors associated with follow-up practices included comorbidity, tumour site, treatment, geographic region, and physician specialty (p < 0.05). Conclusions: Given current practice variation and the absence of an evidence-based standard, the challenge in identifying a single optimal follow-up strategy might be better addressed with a harmonized approach to providing individualized follow-up care. Full article

Background: Clinical trials are vital for evidence-based cancer care. Oncologist engagement in clinical trials has an effect on patient recruitment, which in turn can affect trial success. Identifying barriers to clinical trial participation might enable interventions that could help to increase physician participation. Methods: To assess factors affecting physician engagement in oncology trials, a national survey was conducted using the online SurveyMonkey tool (SurveyMonkey, San Mateo, CA, U.S.A.; http://www.surveymonkey.com). Physicians associated with the Canadian Cancer Clinical Trials Network and the Canadian Cancer Trials Group were asked about their specialty, years of experience, barriers to participation, and motivating interventions, which included an open-ended question inviting survey takers to suggest interventions. Results: The survey collected 207 anonymous responses. Respondents were predominantly medical oncologists (46.4%), followed by radiation oncologists (24.6%). Almost 70% of the respondents had more than 10 years of experience. Significant time constraints included extra paperwork (77%), patient education (54%), and extended follow-up or clinic visits (53%). Timing of events within trials was also a barrier to participation (55%). Most respondents favoured clinical work credits (72%), academic credits (67%), a clinical trial alert system (75%), a regular meeting to review trial protocols (65%), and a screening log to aid in patient accrual (67%) as motivational strategies. Suggested interventions included increased support staff, streamlined regulatory burden, and provision of greater funding for trials and easier access to ancillary services. Conclusions: The present study confirms that Canadian oncologists are willing to participate in clinical research, but face multiple barriers to trial participation. Those barriers could be mitigated by the implementation of several interventions identified in the study. Full article

Background: The neutrophil–lymphocyte ratio (NLR) has been reported to correlate with patient outcome in several cancers, including breast cancer. We evaluated whether the NLR can be a predictive factor for pathologic complete response (PCR) after neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer (TNBC). Methods: We analyzed the correlation between response to NAC and various factors, including the NLR, in 87 patients with TNBC who underwent NAC. In addition, we analyzed the association between the NLR and recurrence-free survival (RFS) in patients with TNBC. Results: Of the 87 patients, 25 (28.7%) achieved a PCR. A high Ki-67 index and a low NLR were significantly associated with PCR. The PCR rate was higher in patients having a high Ki-67 index (≥15%) than in those having a low Ki-67 index (35.7% vs. 0%, p = 0.002) and higher in patients having a low NLR (≤1.7) than in those having a high NLR (42.1% vs. 18.4%, p = 0.018). In multiple logistic analysis, a low NLR remained the only predictive factor for PCR (odds ratio: 4.274; p = 0.008). In the survival analysis, the RFS was significantly higher in the low NLR group than in the high NLR group (5-year RFS rate: 83.7% vs. 66.9%; log-rank p = 0.016). Conclusions: Our findings that the NLR is a predictor of PCR to NAC and also a prognosticator of recurrence suggest an association between response to chemotherapy and inflammation in patients with TNBC. The pretreatment NLR can be a useful predictive and prognostic marker in patients with TNBC scheduled for NAC. Full article