Curr. Oncol., Volume 22, Issue 2 (April 2015) – 21 articles

Patients with myelodysplastic syndrome (MDS) experience clinical complications related to progressive marrow failure and have an increased risk of developing acute myeloid leukemia. Frequent red blood cell transfusion can lead to clinical iron overload and is associated with decreased survival in MDS patients. Iron chelation therapy reduces markers of iron overload and prevents end-organ damage. Here, we present the case of a patient with lowrisk MDS with transfusional iron overload. He was treated for 2 years with an oral iron chelator, deferasirox, and after 12 months of treatment, he experienced a hemoglobin increase of more than 50 g/L, becoming transfusion-independent. He has remained transfusion-independent, with a normal hemoglobin level, for more than 2 years since stopping chelation therapy. Hematologic and erythroid responses have previously been reported in MDS patients treated with iron chelation. The durability of our patient’s response suggests that iron chelation might alter the natural history of MDS in some patients. Full article

Background: Aromatase inhibitor (ai) therapy has been subjected to numerous cost-effectiveness analyses. However, with most ais having reached the end of patent protection and with maturation of the clinical trials data, a re-analysis of ai cost-effectiveness and a consideration of ai use as part of sequential therapy is desirable. Our objective was to assess the cost-effectiveness of the 5-year upfront and sequential tamoxifen (tam) and ai hormonal strategies currently used for treating patients with estrogen receptor (er)–positive early breast cancer. Methods: The cost-effectiveness analysis used a Markov model that took a Canadian health system perspective with a lifetime time horizon. The base case involved 65-year-old women with tam-positive early breast cancer. Probabilistic sensitivity analyses were used to incorporate parameter uncertainties. An expected-value-of-perfect-information test was performed to identify future research directions. Outcomes were quality-adjusted life-years (qalys) and costs. Results: The sequential tam–ai strategy was less costly than the other strategies, but less effective than upfront ai and more effective than upfront tam. Upfront ai was more effective and less costly than upfront tam because of less breast cancer recurrence and differences in adverse events. In an exploratory analysis that included a sequential ai–tam strategy, ai–tam dominated based on small numerical differences unlikely to be clinically significant; that strategy was thus not used in the base-case analysis. Conclusions: In postmenopausal women with er-positive early breast cancer, strategies using ais appear to provide more benefit than strategies using tam alone. Among the ai-containing strategies, sequential strategies using tam and an ai appear to provide benefits similar to those provided by upfront ai, but at a lower cost. Full article

To meet the needs of patients, Canadian surgical and medical oncology leaders in the treatment of peritoneal surface malignancies (PSMS), together with patient representatives, formed the Canadian HIPEC Collaborative Group (CHICG). The group is dedicated to standardizing and improving the treatment of PSM in Canada so that access to treatment and, ultimately, the prognosis of Canadian patients with PSM are improved. Patients with resectable PSM arising from colorectal or appendiceal neoplasms should be reviewed by a multidisciplinary team including surgeons and medical oncologists with experience in treating patients with PSM. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should be offered to appropriately selected patients and performed at experienced centres. The aim of this publication is to present guidelines that we recommend be applied across the country for the treatment of PSM. Full article

Background: Clinical practice guidelines (cpgs) are systematically developed statements designed to assist practitioners and patients in making decisions about appropriate heath care interventions. Clinical practice guidelines are expensive and time-consuming to create. A cpg on concurrent chemotherapy with radiation therapy (ccrt) was developed in Ontario at a time when treatment approaches for head-and-neck cancer were changing significantly. Methods: An assessment of treatments and outcomes based on electronic and chart data obtained from a population-based study of 571 patients with oropharynx cancer treated in Ontario (2003–2004) was combined with a review of relevant knowledge transfer (publications and presentations at major meetings) to understand variation in adherence to a cpg. Results: In 9 Ontario cancer treatment centres, ccrt was used for 55% of all patients with oropharyngeal cancer; however, at the centres individually, that proportion ranged from 82% to 39%. Furthermore, there was no agreement on the chemotherapy regimen: 2–4 years later (a period during which newer regimens were emerging), only 4 of 9 centres were following the guideline for most patients. When outcomes of treated patients were compared for centres with “higher” and “lower” use of ccrt, no difference in survival was observed (p = 0.64). Conclusions: At a time of treatment evolution, the new guideline was controversial, and there are many reasons for the mixed adherence. An estimation of adherence should be included during both development and review of guidelines. Full article

Across Canada, introduction of the Pap test for cervical cancer screening, followed by mammography for breast cancer screening and, more recently, the fecal occult blood test for colorectal cancer screening, has contributed to a reduction in cancer mortality. However, another contribution of screening has been disparities in cancer mortality between certain populations. Here, we explore the disparities associated with breast and cervical cancer screening and preliminary data concerning disparities in colorectal cancer screening. Although some disparities in screening utilization have been successfully reduced over time (for example, mammography and Pap test screening in rural and remote populations), screening utilization data for other populations (for example, low-income groups) clearly indicate that disparities have existed and continue to exist across Canada. Organized screening programs in Canada have been able to successfully engage 80% of women for regular cervical cancer screening and 70% of women for regular mammography screening, but of the women who remain to be reached or engaged in regular screening, those with the least resources, those who are the most isolated, and those who are least culturally integrated into Canadian society as a whole are overrepresented. Population differences are also observed for utilization of colorectal cancer screening services. The research literature on interventions to promote screening utilization provides some evidence about what can be done to increase participation in organized screening by vulnerable populations. Adaption and adoption of evidence-based screening promotion interventions can increase the utilization of available screening services by populations that have experienced the greatest burden of disease with the least access to screening services. Full article

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended. Full article

Treatment with an epidermal growth factor receptor inhibitor (EGFRI) in patients having non-small-cell lung cancer can cause frequent and diverse skin toxicities, an acneiform rash being one of the commonest. Although the exact pathophysiology of this rash and its development mechanisms remain unknown, investigators have noted that egfri-induced skin toxicity might be partly associated with sebaceous gland function. Sebum is composed mainly of the lipids squalene (SQ), wax ester (WE), triglyceride, free fatty acid, and cholesterol, which are secreted mostly from the sebaceous glands and by keratinocytes. We therefore investigated the lipid composition of sebum before and after administration of egfri and whether sebum composition was associated with the development of acneiform rash. To investigate any associated changes in sebum gland activity, we focused especially on alterations in the amounts of SQ and WE , which are secreted solely from the sebaceous glands. In contrast to our expectations, we observed no substantial changes in the lipid composition of sebum before and after administration of egfri. Composition varies with the individual; however, the proportion of SQ and WE derived from the sebaceous glands was significantly lower in regions that did not develop acneiform rash than in regions that did. Our results suggest that development of an acneiform rash after administration of EGFRI could be related to sebaceous gland activity. Measurement of the lipid composition of sebum before therapy with EGFRI might predict which patients will be prone to acneiform rash. Full article

Targeting the epidermal growth factor receptor (EGFR) pathway has become standard practice for the treatment of advanced non-small-cell lung cancer. Compared with chemotherapy, EGFR tyrosine kinase inhibitors (TKIS) have been associated with improved efficacy in patients with an EGFR mutation. Together with the increase in efficacy comes an adverse event (AE) profile different from that of chemotherapy. That profile includes three of the most commonly occurring dermatologic AES: acneiform rash, stomatitis, and paronychia. Currently, no randomized clinical trials have evaluated the treatments for the dermatologic AES that patients experience when taking EGFR TKIS. Based on the expert opinion of the authors, some basic strategies have been developed to manage those key dermatologic AES. Those strategies have the potential to improve patient quality of life and compliance and to prevent inappropriate dose reductions. Full article

The 16th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, September 4–5, 2014. The Consensus Conference is an interactive, multidisciplinary event attended by health care professionals from across western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer. Full article

Background: Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the genetics and causes of pdac and other periampullary tumours (pats) that are also rare and underrepresented in research studies. Methods: Patients diagnosed with pdac or pat were introduced to the study at their initial clinical encounter, with a strategy to enrol participants within 2 weeks of diagnosis. Patient self-referrals and referrals of unaffected individuals with an increased risk of pdac were also accepted. Family histories, epidemiologic and clinical data, and biospecimens were collected. Additional relatives were enrolled in families at increased genetic risk. Results: The first 346 completed referrals led to 306 probands being enrolled, including 190 probands affected with pdac, who represent the population focus of the qpcs. Participation rates were 88.4% for all referrals and 89.2% for pdac referrals. Family history, epidemiologic and clinical data, and biospecimens were ascertained from 91.9%, 54.6%, and 97.5% respectively of patients with pdac. Although demographics and trends in risk factors in our patients were consistent with published statistics for patients with pdac, the qpcs is enriched for families with French-Canadian ancestry (37.4%), a population with recurrent germ-line mutations in hereditary diseases. Conclusions: Using rapid ascertainment, a pdac and pat research registry with high participation rates can be established. The qpcs is a valuable research resource and its enrichment with patients of French-Canadian ancestry provides a unique opportunity for studies of heredity in these diseases. Full article

Background: This study set out to identify patterns in the causes of waits and wait-related satisfaction. Methods: We conducted qualitative interviews with urban, semi-urban, and rural patients (n = 60) to explore their perceptions of the waits they experienced in the detection and treatment of their breast, prostate, lung, or colorectal cancer. We asked participants to describe their experiences from the onset of symptoms to the start of treatment at the cancer clinic and their satisfaction with waits at various intervals. Interview transcripts were coded using a thematic approach. Results: Patients identified five groups of wait-time causes: (1) Patient-related (beliefs, preferences, and non-cancer health issues); (2) Treatment-related (natural consequences of treatment); (3) System-related (the organization or functioning of groups, workforce, institution, or infrastructure in the health care system); (4) Physician-related (a single physician responsible for a specific element in the patient’s care); (5) Other causes (disruptions to normal operations of a city or community as a whole). With the limited exception of physician-related absences, the nature of the cause was not linked to overall satisfaction or dissatisfaction with waits. Conclusions: Causes in themselves do not explain wait-related satisfaction. Further work is needed to explore the underlying reasons for wait-related satisfaction or dissatisfaction. Although our findings shed light on patient experiences with the health system and identify where interventions could help to inform the expectations of patients and the public with respect to wait time, more research is needed to understand wait-related satisfaction among cancer patients. Full article

Background: Breast cancer stage at diagnosis is an important predictor of survival. Our goal was to compare breast cancer stage at diagnosis (by American Joint Committee on Cancer criteria) in Chinese and South Asian women with stage at diagnosis in the remaining general population in Ontario. Methods: We used the Ontario population-based cancer registry to identify all women diagnosed with breast cancer during 2005–2010, and we applied a validated surname algorithm to identify South Asian and Chinese women. We used logistic regression to compare, for Chinese or South Asian women and for the remaining general population, the frequency of diagnoses at stage II compared with stage I and stages II–IV compared with stage I. Results: The registry search identified 1304 Chinese women, 705 South Asian women, and 39,287 women in the remaining general population. The Chinese and South Asian populations were younger than the remaining population (mean: 54, 57, and 61 years respectively). Adjusted for age, South Asian women were more often diagnosed with breast cancer at stage II than at stage I [odds ratio (OR): 1.28; 95% confidence interval (CI): 1.08 to 1.51] or at stages II–IV than at stage I (OR: 1.27; 95% CI: 1.08 to 1.48); Chinese women were less likely to be diagnosed at stage II than at stage I (OR: 0.82; 95% CI: 0.72 to 0.92) or at stages II–IV than at stage I (OR: 0.73; 95% CI: 0.65 to 0.82). Conclusions: Breast cancers were diagnosed at a later stage in South Asian women and at an earlier stage in Chinese women than in the remaining population. A more detailed analysis of ethnocultural factors influencing breast screening uptake, retention, and care-seeking behavior might be needed to help inform and evaluate tailored health promotion activities. Full article

Background: Recent reports suggest a decline over time in the survival of patients newly diagnosed with laryngeal cancer in spite of developments in treatment practices. Our study set out to determine whether the survival of patients with laryngeal cancer in Ontario has changed over time. Methods: This population-based cohort study of patients diagnosed with laryngeal cancer in the province of Ontario between 1995 and 2007 used data extracted from linked provincial administrative and registry databases. Its main outcomes were overall survival, laryngectomy-free survival, and survival ratio relative to an age- and sex-matched general population. Results: The 4298 patients newly diagnosed with laryngeal cancer during the period of interest were predominantly men (n = 3615, 84.1%) with glottic cancer (n = 2787, 64.8%); mean age in the group was 66 years (interquartile range: 59–74 years). Patient demographics did not significantly change over time. Overall, 5-year survival was 57.4%; laryngectomy-free survival was 45.4%. Comparing patients from three eras (1995–1998, 1999–2003, 2004–2007) and adjusting for age, sex, and comorbidity status, we observed no differences in overall survival or laryngectomy-free survival over time. The 5-year relative survival ratio for patients with laryngeal cancer compared with an age- and sex-matched group from the general population was 81.1% for glottic cancer and 44.5% for supraglottic cancer. Conclusions: In patients with a new diagnosis of laryngeal cancer, overall and laryngectomy-free survival have remained unchanged since the mid-1990s. New methods to improve survival and the rate of laryngeal preservation in this patient population are needed. Full article

Almost 25 years ago, prominent health researcher Margaret Whitehead, in conjunction with the World Health Organization, developed a definition of the term “health inequities,” which has since become widely used in the international health literature. While health inequality is quite simply a difference in health between groups, health inequity is a normative concept [...] Full article

Background: Dose-escalated hypofractionated radiotherapy (hfrt) using intensity-modulated radiotherapy (imrt), with inclusion of the pelvic lymph nodes (plns), plus androgen suppression therapy (ast) in high-risk prostate cancer patients should improve patient outcomes, but acute toxicity could limit its feasibility. Methods: Our single-centre phase ii prospective study enrolled 40 high-risk prostate cancer patients. All patients received hfrt using imrt with daily mega-voltage computed tomography imaging guidance, with 95% of planning target volumes (ptv68 and ptv50) receiving 68 Gy and 50 Gy (respectively) in 25 daily fractions. The boost volume was targeted to the involved imrt and the prostate (minus the urethra plus 3 mm and minus 3 mm from adjacent rectal wall) and totalled up to 75 Gy in 25 fractions. Acute toxicity scores were recorded weekly during and 3 months after radiotherapy (rt) administration. Results: For the 37 patients who completed rt and the 3-month follow-up, median age was 65.5 years (range: 50–76 years). Disease was organ-confined (T1c–T2c) in 23 patients (62.1%), and node-positive in 5 patients (13.5%). All patients received long-term ast. Maximum acute genitourinary (gu) and gastrointestinal (gi) toxicity peaked at grade 2 in 6 of 36 evaluated patients (16.6%) and in 4 of 31 evaluated patients (12.9%) respectively. Diarrhea and urinary frequency were the chief complaints. Dose–volume parameters demonstrated no correlation with toxicity. The ptv treatment objectives were met in 36 of the 37 patients. Conclusions: This hfrt dose-escalation trial in high-risk prostate cancer has demonstrated the feasibility of administering 75 Gy in 25 fractions with minimal acute gi and gu toxicities. Further follow-up will report late toxicities and outcomes. Full article

Background: To enhance cancer symptom management for residents of Sudbury–Manitoulin District, an ambulatory palliative clinic (pac) was established at the Northeast Cancer Centre of Health Sciences North. The pac is accessed from a medical or radiation oncology consultation. The primary purpose of the present population-based retrospective study was to estimate the percentage of cancer patients who died without ever having a medical or radiation oncology consultation. A secondary purpose was to determine factors associated with never having received one of those specialized consultations. Methods: Administrative data was obtained through the Ontario Cancer Data Linkage Project. For each index case, we constructed a timeline, in days, of all Ontario Health Insurance Plan billing codes and associated service dates starting with the primary cancer diagnosis and ending with death. Results: Within the 5-year study period (2004–2008), 6683 people in the area of interest with a valid record of primary cancer diagnosis died from any cause. Most (n = 5988, 89.6%) had 1 primary cancer diagnosis. For that subgroup, excluding those with a disease duration of 0 days (n = 67), about 18.4% (n = 1088) never had a consultation with a medical or radiation oncologist throughout their disease trajectory. Patients who were older or who resided in a rural area were significantly less likely to have had a consultation. Conclusions: Specific strategies directed toward older and rural patients might help to address this important access-to-care issue. Full article

Objective: During clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca. Methods: A panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab. Results: The subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training. Conclusions: This expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease. Full article

Background: Several screening methods for colorectal cancer (CRC) are available, and some have been shown by randomized trials to be effective. In the present study, we used a well-developed population health simulation model to compare the risks and benefits of a variety of screening scenarios. Tests considered were the fecal occult blood test (FOBT), the fecal immunochemical test (FIT), flexible sigmoidoscopy, and colonoscopy. Outcomes considered included years of life gained, CRC cases and deaths prevented, and direct health system costs. Methods: A natural history model of CRC was implemented and calibrated to specified targets within the framework of the Cancer Risk Management Model (CRMM) from the Canadian Partnership Against Cancer. The CRMM-CRC permits users to enter their own parameter values or to use program-specified base values. For each of 23 screening scenarios, we used the CRMM-CRC to run 10 million replicate simulations. Results: Using base parameter values and some user-specified values in the CRMM-CRC, and comparing our screening scenarios with no screening, all screening scenarios were found to reduce the incidence of and mortality from CRC. The fobt was the least effective test; it was not associated with lower net cost. Colonoscopy screening was the most effective test; it had net costs comparable to those for several other strategies considered, but required more than 3 times the colonoscopy resources needed by other approaches. After colonoscopy, strategies based on the FIT were predicted to be the most effective. In sensitivity analyses performed for the FOBT and FIT screening strategies, FOBT parameter values associated with high-sensitivity formulations were associated with a substantial increase in test effectiveness. The FIT was more cost-effective at the 50 ng/mL threshold than at the 100 ng/mL threshold. Conclusions: The CRMM-CRC provides a sophisticated and flexible environment in which to evaluate CRC control options. All screening scenarios considered in this study effectively reduced CRC mortality, although sensitivity analyses demonstrated some uncertainty in the magnitude of the improvements. Where possible, local data should be used to reduce uncertainty in the parameters. Full article