Curr. Oncol., Volume 23, Issue 3 (June 2016) – 31 articles

Nurse navigation is a developing facet of oncology care. The concept of patient navigation was originally created in 1990 at the Harlem Hospital Center in New York City as a strategy to assist vulnerable and socially disadvantaged populations with timely access to breast cancer care. Since the mid-1990s, navigation programs have expanded to include many patient populations that require specialized management and prompt access to diagnostic and clinical resources. Advanced non-small-cell lung cancer is ideally suited for navigation to facilitate efficient assessment in this fragile patient population and to ensure timely results of molecular tests for first-line therapy with appropriately targeted agents. At the BC Cancer Agency, nurse navigator involvement with thoracic oncology triage has been demonstrated to increase the proportion of patients receiving systemic treatment, to shorten the time to delivery of systemic treatment, and to increase the rate of molecular testing and the number of patients with molecular testing results available at time of initial consultation. Insights gained through the start-up process are briefly discussed, and a framework for implementation at other institutions is outlined. Full article

Introduction: The accrual rate to clinical trials in oncology remains low. In this exploratory pilot study, we prospectively assessed the role that engaging a referring surgeon plays in enhancing nonsurgical oncologic clinical trial accrual. Methods: Newly diagnosed breast cancer patients were seen by a surgeon who actively introduced specific patient-and physician-centred strategies to increase clinical trial accrual. Patient-centred strategies included providing patients, before their oncology appointment, with information about specific clinical trials for which they might be eligible, as evaluated by the surgeon. The attitudes of the patients about clinical trials and the interventions used to improve accrual were assessed at the end of the study. The primary outcome was the clinical trial accrual rate during the study period. Results: Overall clinical trial enrolment during the study period among the 34 participating patients was 15% (5 of 34), which is greater than the institution’s historical average of 7%. All patients found the information delivered by the surgeon before the oncology appointment to be very helpful. Almost three quarters of the patients (73%) were informed about clinical trials by their oncologist. The top reasons for nonparticipation reported by the patients who did not participate in clinical trials included lack of interest (35%), failure of the oncologist to mention clinical trials (33%), and inconvenience (19%). Conclusions: Accrual of patients to clinical trials is a complex multistep process with multiple potential barriers. The findings of this exploratory pilot study demonstrate a potential role for the referring surgeon in enhancing nonsurgical clinical trial accrual. Full article

Peritoneal carcinomatosis (PTC) represents advanced malignant disease and has generally been associated with a grim prognosis. Peritoneal surface malignancy is often the major source of morbidity and mortality; it is of major concern in cancer management. Although PTC is categorized as metastatic disease, it represents a special disease pattern considered to be a locoregional disease limited to the abdominal cavity. The combination of cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has successfully been used as locoregional treatment for selected patients with PTC from gastric, colorectal, and ovarian cancer; with mesothelioma; and with pseudomyxoma peritonei. In the prophylactic setting, HIPEC can also be used to prevent PTC in high-risk patients, and the first results of the “second-look” approach are promising. Patient selection—in which the risks of perioperative morbidity and mortality, which are analogous to those for any other major gastrointestinal surgery, are assessed—is of utmost importance. Those risks have to be weighed against the anticipated survival benefit, which depends mainly on tumour biology, extent of disease, and probability of achieving complete CRS. The present review discusses the principles of CRS and HIPEC, the most significant recent clinical data, and current perspectives concerning the application of this treatment modality in various malignancies. Ongoing trials and future directions are noted. It appears that the combination of CRS and HIPEC is an indispensable tool in the oncologist’s armamentarium. Full article

Background: Metronomic chemotherapy (mCTX) combined with radiation therapy (RT) is an emerging anticancer strategy. The aim of the present study was to assess the efficacy of mCTX combined with RT as salvage treatment in children with refractory or relapsed solid malignancies. Methods: This prospective study enrolled patients with refractory or relapsed pediatric solid tumours from January 2013 to January 2015. Treatment consisted of 3–12 courses of mCTX in all patients, followed by RT in patients who experienced local recurrence, distant metastases, or both. Each course of mCTX consisted of oral celecoxib 100–400 mg twice daily (days 1–42), intravenous vinblastine 3 mg/m² weekly (weeks 1–6), oral cyclophosphamide 2.5 mg/m² daily (days 1–21), and oral methotrexate 15 mg/m² twice weekly (days 21–42). Statistical methods used were the log-rank test and binary logistic regression. Results: A favourable disease response (partial response or stable disease) was seen in 49 of 64 patients (76.6%), with mild acute toxicity occurring in 41 (64%). After a median follow-up of 14 months, 1-year overall survival was 62%. Pattern of disease relapse (p < 0.0001), time from initial treatment to relapse (p = 0.0002), and response to treatment (p < 0.0001) significantly affected survival. Age was the only factor that significantly correlated with treatment toxicity (p = 0.002; hazard ratio: 3.37; 95% confidence interval: 1.53 to 7.35). Conclusions: Combining mCTX with RT resulted in a favourable response rate, minimal toxicity, and 62% 1-year overall survival in patients with heavily pretreated recurrent disease. Patients with localized late recurrence or disease progression are the most likely to benefit from this regimen. Full article

Background: Gastric cancer is the 2nd leading cause of cancer death worldwide. Malignant bowel obstruction (mbo) is a common complication in advanced gastric cancer because of peritoneal dissemination. A multicentre prospective study reported that patients with peritoneal dissemination of gastric origin survive for a median of 3.1 months. The aim of the present study was therefore to evaluate the efficacy and safety of metronomic combination chemotherapy with 5-fluorouracil and cisplatin in inoperable mbo from peritoneal dissemination in gastric cancer. Methods: Gastric cancer patients diagnosed with inoperable mbo because of peritoneal dissemination were treated with infusional 5-fluorouracil 300 mg/m2 daily on days 1–5 and 8–12, and cisplatin 5 mg/m2 daily on days 1–4 and 8–11 every 3 weeks. The primary endpoint was symptom control (remission of obstruction); the secondary endpoint was symptom control time and survival; the tertiary endpoint was adverse effects. Results: Between January 2013 and December 2014, 26 patients received the study treatment. Before treatment, 18 patients (69.2%) were nil per os, and 8 (30.8%) could consume liquids. After a mean of 3.3 cycles of the study treatment, just 4 patients (15.4%) was still nil per os. Of the remaining 22 patients, 3 (11.5%) could consume liquids, 7 (26.9%) could consume soft solids, and 12 (46.2%) ate a full diet. The improved ability to eat was statistically significant (p < 0.0001). Median duration of remission from mbo was 105 days. Median survival was 182 days. The 3-month survival rate was 69.2%, and the 6-month survival rate was 53.8%. Treatment was well tolerated, with grade iii toxicities consisting of thrombocytopenia in 1 patient (3.84%) and mucositis in 2 patients (7.7%). No abnormalities in serum creatinine were observed. Conclusions: Metronomic combination chemotherapy with 5-fluorouracil and cisplatin is well tolerated and shows activity in inoperable mbo because of peritoneal dissemination in gastric cancer. Metronomic combination chemotherapy with 5-fluorouracil and cisplatin provides a rationale for exploring this medical problem in the future. Full article

Purpose: We evaluated the feasibility, reliability, and validity of the Brain Metastases Symptom Checklist (BMSC), a novel self-report measure of common symptoms experienced by patients with brain metastases. Methods: Patients with first-presentation symptomatic brain metastases (n = 137) referred for whole-brain radiotherapy (WBRT) completed the BMSC at time points before and after treatment. Their caregivers (n = 48) provided proxy ratings twice on the day of consultation to assess reliability, and at week 4 after WBRT to assess responsiveness to change. Correlations with 4 other validated assessment tools were evaluated. Results: The symptoms reported on the BMSC were largely mild to moderate, with tiredness (71%) and difficulties with balance (61%) reported most commonly at baseline. Test–retest reliability for individual symptoms had a median intraclass correlation of 0.59 (range: 0.23–0.85). Caregiver proxy and patient responses had a median intraclass correlation of 0.52. Correlation of absolute scores on the BMSC and other symptom assessment tools was low, but consistency in the direction of symptom change was observed. At week 4, change in symptoms was variable, with improvements in weight gain and sleep of 42% and 41% respectively, and worsening of tiredness and drowsiness of 62% and 59% respectively. Conclusions: The BMSC captures a wide range of symptoms experienced by patients with brain metastases, and it is sensitive to change. It demonstrated adequate test–retest reliability and face validity in terms of its responsiveness to change. Future research is needed to determine whether modifications to the BMSC itself or correlation with more symptom-specific measures will enhance validity. Full article

Background: Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario. Methods: An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt. Results: From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated. Conclusions: Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption. Full article

Background: The Enhanced Recovery After Surgery (ERAS) colorectal guideline has been implemented widely across Alberta. Our study examined the clinical and cost impacts of ERAS on colon cancer patients across the province. Methods: We first used both summary statistics and multivariate regression methods to compare, before and after guideline implementation, clinical outcomes (length of stay, complications, readmissions) in consecutive elective colorectal patients 18 or more years of age and in colon cancer and non-cancer patients treated at the Peter Lougheed Centre and the Grey Nuns Hospital between February 2013 and December 2014. We then used the differences in clinical outcomes for colon cancer patients, together with the average cost per hospital day, to estimate cost impacts. Results: The analysis considered 790 patients (398 cancer and 392 non-cancer patients). Mean guideline compliance increased to 60% in cancer patients and 57% in non-cancer patients after ERAS implementation from 37% overall before ERAS implementation. From pre- to post-ERAS, mean length of stay declined to 8.4 ± 5 days from 9.5 ± 7 days in cancer patients, and to 6.4 ± 4 days from 8.8 ± 5.5 days in non-cancer patients (p = 0.0012 and p = 0.0041 respectively). Complications declined significantly in the renal, hepatic, pancreatic, and gastrointestinal groups (difference in proportions: 13% in cancer patients; p < 0.05). No significant change in the risk of readmission was observed. The net cost savings attributable to ERAS implementation ranged from $1,096 to $2,771 per cancer patient and from $3,388 to $7,103 per non-cancer patient. Conclusions: Implementation of ERAS not only resulted in clinical outcome improvements, but also had a significant beneficial impact on scarce health system resources. The effect for cancer patients was different from that for non-cancer patients, representing an opportunity for further refinement and study. Full article

Each February, the Canadian Lung Cancer Conference brings together lung cancer researchers, clinicians, and care professionals who are united in their commitment to improve the care of patients with lung cancer. This year’s meeting, held 11–12 February, featured a resident education session, a welcome dinner, networking sessions, lectures, breakout sessions, debates, and a satellite symposium. Key themes from this year’s meeting included innovations across the care spectrum and results of recent clinical trials with targeted agents, immuno-oncology agents, and novel drug combinations. Full article

Adolescents and young adults (AYAS) with cancer in active treatment face a number of barriers to optimal care. In the present article, we focus on the 3 critical domains of care for ayas—medical, psychosocial, and research—and how changes to the system could overcome barriers. We summarize the current literature, outline recommended principles of care, raise awareness of barriers to optimal care, and suggest specific changes to the system to overcome those barriers in the Canadian context. Many of the recommendations can nevertheless be applied universally. These recommendations are endorsed by the Canadian Task Force on Adolescents and Young Adults with Cancer and build on outcomes from two international workshops held by that group. Full article

Evidence shows that continued smoking by cancer patients leads to adverse treatment outcomes and affects survival. Smoking diminishes treatment effectiveness, exacerbates side effects, and increases the risk of developing additional complications. Patients who continue to smoke also have a higher risk of developing a second primary cancer or experiencing a cancer recurrence, both of which ultimately contribute to poorer quality of life and poorer survival. Here, we present a snapshot of smoking behaviours of current cancer patients compared with the non-cancer patient population in Canada. Minimal differences in smoking behaviours were noted between current cancer patients and the rest of the population. Based on 2011–2014 data from the Canadian Community Health Survey, 1 in 5 current cancer patients (20.1%) reported daily or occasional smoking. That estimate is comparable to findings in the surveyed non-cancer patient population, of whom 19.3% reported smoking daily or occasionally. Slightly more male cancer patients than female cancer patients identified as current smokers. A similar distribution was observed in the non-cancer patient population. There is an urgent need across Canada to better support cancer patients in quitting smoking. As a result, the quality of patient care will improve, as will cancer treatment and survival outcomes, and quality of life for these patients. Full article

Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered. Full article

Background: The incidence of hepatocellular carcinoma (HCC) and the complexity of its diagnosis and treatment are increasing. We estimated trends in net health care utilization, costs of care attributable to HCC in Ontario, and rate ratios of resource use at various stages of care. Methods: This population-based retrospective cohort study identified HCC patients and non-cancer control subjects, and health care resource utilization between 2002 and 2009. Generalized estimating equations were then used to estimate net health care utilization (HCC patients vs. the matched control subjects) and net costs of care attributable to HCC. Generalized linear models were used to analyze rate ratios of resource use. Results: We identified 2832 HCC patients and 2808 matched control subjects. In comparison with the control subjects, HCC patients generally used a greater number of health care services. Overall, the mean net cost of care per 30 patient–days (2013 Canadian dollars) attributable to outpatient visits and hospitalizations was highest in the pre-diagnosis (1 year before diagnosis), initial (1st year after diagnosis), and end-of-life (last 6 months before death, short-term survivors) phases. Mean net homecare costs were highest in the end-of-life phase (long-term survivors). In the end-of-life phase (short-term survivors), mean net costs attributable to outpatient visits and total services significantly increased to $14,220 from $1,547 and to $33,121 from $14,450 (2008–2009 and 2002–2003 respectively). Conclusions: In HCC, our study found increasing resource use and net costs of care, particularly in the end-of-life phase among short-term survivors. Our findings offer a basis for resource allocation decisions in the area of cancer prevention and control. Full article

Objective: Traditional Chinese Medicine (TCM) is used in China as part of the treatment for non-small-cell lung cancer (NSCLC) and often includes prescription of herbal therapy based on syndrome differentiation. Studies of various Astragalus-based Chinese medicines combined with platinum-based chemotherapy in the treatment of lung cancer are popular in East Asia, particularly in China. The aim of the present study was to perform a systematic review and meta-analysis comparing platinum-based chemotherapy alone with platinum-based chemotherapy plus Astragalus-based Chinese botanicals, with and without prescription based on syndrome differentiation, as first-line treatment for advanced NSCLC. Methods: We searched the Chinese Biomedical Literature database, the China National Knowledge Internet, the VIP Chinese Science and Technology Periodicals Database, PubMed, EMBASE, the Cochrane databases, and abstracts presented at meetings of the American Society of Clinical Oncology, the World Conference on Lung Cancer, the European Society for Medical Oncology, and the Chinese Society of Clinical Oncology for all eligible studies. Endpoints were overall survival; 1-year, 2-year, and 3-year survival rates; performance status; overall response rate; and grade 3 or 4 adverse events. Subgroup analyses based on herbal formulae individualized using syndrome differentiation or on oral or injection patent medicines were performed using the Stata software application (version 11.0: StataCorp LP, College Station, TX, U.S.A.) and a fixed-effects or random-effects model in case of heterogeneity. Results are expressed as a hazard ratio (HR) or relative risk (RR), with corresponding 95% confidence intervals (CIs). Results: Seventeen randomized studies with scores on the Jadad quality scale of 2 or more, representing 1552 patients, met the inclusion criteria. Compared with platinum-based chemotherapy alone, the addition of Astragalus-based TCM to chemotherapy was associated with significantly increased overall survival (HR: 0.61; 95% CI: 0.42 to 0.89; p = 0.011); 1-year (RR: 0.73; 95% CI: 0.65 to 0.82; p < 0.001), 2-year (RR: 0.3344; 95% CI: 0.237 to 0.4773; p < 0.001), and 3-year survival rates (RR: 0.30; 95% CI: 0.17 to 0.53; p < 0.001); performance status (RR: 0.43; 95% CI: 0.34 to 0.55; p < 0.001); and tumour overall response rate (RR: 0.7982; 95% CI: 0.715 to 0.89; p < 0.001). Subgroup analyses indicated that Astragalus herbal formulae given based on syndrome differentiation were more effective than Astragalus-based oral and injection patent medicines. Side effects—including anemia, neutropenia, thrombocytopenia, fatigue, poor appetite, nausea, and vomiting—were significantly more frequent with platinum-based chemotherapy alone than when platinum-based chemotherapy was combined with Astragalus-based TCM. Conclusions: Astragalus-based Chinese botanical therapy, especially when based on syndrome differentiation, is associated with increased efficacy of platinum-based chemotherapy and decreased platinum-derived toxicities for patients with advanced NSCLC. Full article

Background: The management of small-cell lung cancer (SCLC) with radiotherapy (RT) varies, with many treatment regimens having been described in the literature. We created a survey to assess patterns of practice and clinical decision-making in the management of SCLC by Canadian radiation oncologists (ROS). Methods: A 35-item survey was sent by e-mail to Canadian ROS. The questions investigated the role of RT, the dose and timing of RT, target delineation, and use of prophylactic cranial irradiation (PCI) in limited-stage (LS) and extensive-stage (ES) SCLC. Results: Responses were received from 52 eligible ROS. For LS-SCLC, staging (98%) and simulation or dosimetric (96%) computed tomography imaging were key determinants of RT suitability. The most common dose and fractionation schedule was 40–45 Gy in 15 once-daily fractions (40%), with elective nodal irradiation performed by 31% of ROS. Preferred management of clinical T1/2aN0 SCLC favoured primary chemoradiotherapy (64%). For ES-SCLC, consolidative thoracic RT was frequently offered (88%), with a preferred dose and fractionation schedule of 30 Gy in 10 once-daily fractions (70%). Extrathoracic consolidative RT would not be offered by 23 ROS (44%). Prophylactic cranial irradiation was generally offered in LS-SCLC (100%) and ES-SCLC (98%) after response to initial treatment. Performance status, baseline cognition, and pre-PCI brain imaging were important patient factors assessed before an offer of PCI. Conclusions: Canadian ROS show practice variation in SCLC management. Future clinical trials and national treatment guidelines might reduce variability in the treatment of early-stage disease, optimization of dose and targeting in LS-SCLC, and definition of suitability for PCI or consolidative RT. Full article

Background: Low-dose computed tomography (LDCT) screening has been shown to reduce mortality from lung cancer; however, the optimal screening duration and “at risk” population are not known. Methods: The Cancer Risk Management Model developed by Statistics Canada for the Canadian Partnership Against Cancer includes a lung screening module based on data from the U.S. National Lung Screening Trial (NLST). The base-case scenario reproduces NLST outcomes with high fidelity. The impact in Canada of annual screening on the number of incident cases and life-years gained, with a wider range of age and smoking history eligibility criteria and varied participation rates, was modelled to show the magnitude of clinical benefit nationally and by province. Life-years gained, costs (discounted and undiscounted), and resource requirements were also estimated. Results: In 2014, 1.4 million Canadians were eligible for screening according to NLST criteria. Over 10 years, screening would detect 12,500 more lung cancers than the expected 268,300 and would gain 9200 life-years. The computed tomography imaging requirement of 24,000–30,000 at program initiation would rise to between 87,000 and 113,000 by the 5th year of an annual NLST-like screening program. Costs would increase from approximately $75 million to $128 million at 10 years, and the cumulative cost nationally over 10 years would approach $1 billion, partially offset by a reduction in the costs of managing advanced lung cancer. Conclusions: Modelling various ways in which LDCT might be implemented provides decision-makers with estimates of the effect on clinical benefit and on resource needs that clinical trial results are unable to provide. Full article

Background: Despite its importance for patient outcomes, biomarker testing for lung cancer is not uniformly integrated into the Canadian health care system. To better understand current practice patterns for lung cancer biomarker testing, we assessed physician perspectives by specialty and region. Methods: A national survey of Canadian lung cancer specialists was conducted to understand their perspectives on biomarker testing in lung cancer. The 11-item survey assessed the current practice and challenges of testing. The survey was sent to 375 specialists. Results: The overall response rate for the survey was 36%. Nearly all specialists reported that knowing tumour genotyping results affects patient outcome and influences the treatment decision. Medical oncologists most commonly initiated molecular testing; however, most respondents suggested a shared model involving medical oncologists and pathologists. More than half of all responding specialists had the perception that fewer than 25% of test results are available for first-line treatment decisions. Identified barriers to routine testing for all lung cancer patients included cost, lack of funding, tissue availability, and sample quality. Conclusions: There was clear agreement that biomarker testing is important in determining appropriate treatment for patients. There is a need for general consensus on who should initiate molecular testing. Clear clinical guidance for pathologists has to be established for molecular testing, including defining the population to be tested, the timing of testing, and the tests to be performed. Testing could be facilitated by including more information on diagnostic sample requisitions, such as clinical suspicion of primary lung cancer, cancer history, and other samples already collected. Full article

Background: Despite lack of a true comparative study, the folfox (5-fluorouracil–leucovorin–oxaliplatin) and capox (capecitabine–oxaliplatin) regimens are believed to be similar in their efficacy and tolerability in the treatment of stage III colorectal cancer. However, that belief has been disputed, because real-life data suggest that the capox regimen is more toxic, leading to more frequent reductions in the delivered dose intensity—thus raising questions about the effect of dose intensity on clinical outcomes. Methods: A retrospective data review for two Canadian institutions, the Segal Cancer Centre and the Tom Baker Cancer Centre, considered patients diagnosed with stage iii colorectal cancer during 2006–2013. Primary endpoints were dose intensity and toxicity, with a secondary endpoint of disease-free survival. Results: The study enrolled 180 eligible patients (80 at the Segal Cancer Centre, 100 at the Tom Baker Cancer Centre). Of those 180 patients, 75 received capox, and 105 received mfolfox6. In the capox group, a significant dose reduction was identified for capecitabine compared with 5-fluorouracil in mfolfox6 group (p = 0.0014). Similarly, a significant dose reduction was observed for oxaliplatin in mfolfox6 compared with oxaliplatin in capox (p = 0.0001). Compared with the patients receiving capox, those receiving mfolfox6 were twice as likely to experience a treatment delay of more than 1 cycle-length (p = 0.03855). Toxicity was more frequent in patients receiving mfolfox6 (nausea: 30% vs. 18%; diarrhea: 47% vs. 24%; peripheral sensory neuropathy: 32% vs. 3%). At a median follow-up of 40 months, preliminary data showed no difference in disease-free survival (p = 0.598). Pooled data from both institutions were also separately analyzed, and no significant differences were found. Conclusions: Our results support the use of capox despite a lack of head-to-head randomized trial data. Full article

Background: Epithelial cell adhesion molecule (epcam) is a multifunctional transmembrane glycoprotein expressed on both normal epithelium and epithelial neoplasms such as gastric, breast, and renal carcinomas. Recent studies have proposed that the proteolytic cleavage of the intracellular domain of epcam (epcam-icd) can trigger signalling cascades leading to aggressive tumour behavior. The expression profile of epcam-icd has not been elucidated for primary colorectal carcinoma. In the present study, we examined epcam-icd immunohistochemical staining in a large cohort of patients with primary colorectal adenocarcinoma and assessed its performance as a potential prognostic marker. Methods: Immunohistochemical staining for epcam-icd was assessed on tissue microarrays consisting of 137 primary colorectal adenocarcinoma samples. Intensity of staining for each core was scored by 3 independent pathologists. The membranous epcam-icd staining score was calculated as a weighted average from 3 core samples per tumour. Univariate analysis of the average scores and clinical outcome measures was performed. Results: The level of membranous epcam-icd staining was positively associated with well-differentiated tumours (p = 0.01); low preoperative carcinoembryonic antigen (p = 0.001); and several measures of survival, including 2-year (p = 0.02) and 5-year survival (p = 0.05), and length of time post-diagnosis (p = 0.03). A number of other variables—including stage, grade, and lymph node status—showed correlations with epcam staining and markers of poor outcome, but did not reach statistical significance. Conclusions: Low membranous epcam-icd staining might be a useful marker to identify tumours with aggressive clinical behavior and potential poor prognosis and might help to select candidates who could potentially benefit from treatment targeting epcam. Full article

Background: Unlike cytotoxic agents, novel antineoplastic drugs can variably affect thyroid function and so impair patient outcomes. However, the widely used standard thyroid tests have demonstrated low sensitivity for detecting early thyroid damage that leads to dysfunction of the gland. To find a more reliable thyroid marker, we assessed the presence of antibodies binding thyroid hormones (thAbs) in a cancer population undergoing potentially thyrotoxic treatment. Methods: From April 2010 to September 2013, 82 patients with hematologic malignancies treated with tyrosine kinase inhibitors or immunoregulatory drugs were recruited. Healthy volunteers (n = 104) served as control subjects. Thyroid function, autoimmunity tests, thAbs, and thyroid sonography were assessed once during treatment. Results: Overall, thAb positivity was recorded in 13% of the entire cohort. In most cases, the thAbs were of a single type, with a predominance of T3 immunoglobulin G. More specifically, thAbs were detected in 11 cancer patients; and abnormal levels of thyroid-stimulating hormone, thyroglobulin antibody, and thyroperoxidase antibody were detected in 6 (p = 0.05), 0 (p = 0.0006), and 2 cancer patients (p = 0.001) respectively. Ultrasonographic alterations of the thyroid were observed in 12 cancer patients. In contrast, of the 104 healthy control subjects, only 1 was positive for thAbs (1%). Conclusions: We have demonstrated for the first time that thAbs are a reliable marker of early thyroid dysfunction when compared with the widely used standard thyroid tests. A confirmatory prospective trial aiming at evaluating thAbs at various time points during treatment could clarify the incidence and timing of antibody appearance. Full article

Purpose: We compared the efficacy, toxicity, and use of granulocyte colony–stimulating factor (g-csf) with tac (docetaxel–doxorubicin–cyclophosphamide) and fec-d (5-fluorouracil–epirubicin–cyclophosphamide followed by docetaxel) in women less than 50 years of age. Methods: The study included all women more than 18 years but less than 50 years of age with her2-negative, node-positive, stage ii or iii breast cancer diagnosed in Alberta between 2008 and 2012 who received tac (n = 198) or fec-d (n = 274). Results: The patient groups were well-balanced, except that radiotherapy use was higher in the tac group (91.9% vs. 79.9%, p < 0.001). At a median follow-up of 49.6 months, disease-free survival was 91.4% for tac and 92.0% for fec-d (p = 0.76). Overall survival (os) was 96% with tac and 95.3% with fec-d (p = 0.86).The incidences of grades 3 and 4 toxicities were similar in the two groups (all p > 0.05). Overall, febrile neutropenia (fn) was reported in 11.6% of tac patients and 15.7% of fec-d patients (p = 0.26). However, use of g-csf was higher in the tac group than in the fec-d group (96.4% vs. 71.5%, p < 0.001). Hospitalization for fn was required in 10.5% of tac patients and 13.0% of fec-d patients (p = 0.41). In g-csf–supported and –unsupported patients receiving tac, fn occurred at rates of 11.1% and 33.3% respectively (p = 0.08); in patients receiving the fec portion of fec-d, those proportions were 2.9% and 8.1% respectively (p = 0.24); and in patients receiving docetaxel after fec, the proportions were 4.1% and 17.6% respectively (p < 0.001). Conclusions: In women less than 50 years of age receiving adjuvant tac or fec-d, we observed no differences in efficacy or other nonhematologic toxicities. Based on the timing and rates of fn, use of prophylactic g-csf should be routine for the docetaxel-containing portion of treatment; however, prophylactic g-csf could potentially be avoided during the fec portion of fec-d treatment. Full article

Background: Concerns have been raised about the potential influence of political pressures on drug funding decisions. We evaluated the temporal relationship between cancer drug funding and provincial elections in 9 Canadian provinces. Methods: New indications for cancer drugs between January 2003 and December 2012 were identified, and the dates of official provincial funding dates and election dates between 1 January 2003 and 31 December 2014 were retrieved. The probability of drug funding announcements in the 60-day period preceding a provincial election was evaluated using binomial probability distribution analysis. Results: Data from 9 provinces (all Canadian provinces except Quebec) were available. During the period of interest, 69 new indications for 39 individual drugs were identified. Variation in the availability of funding dates was identified. At the time of data collection, 2 provinces did not have data available for all 69 indications. For the 9 provinces, the number of funded indications during the 60-day period preceding an election ranged from 0 to 3; however, no differences in the proportion of indications funded pre-election were identified. Additional analyses also failed to demonstrate any significant associations with the 90-day period before an election, or the 60- and 90-day periods after an election. Conclusions: We observed no clear temporal relationship between provincial election dates and funding decisions in this recent Canadian sample of new indications for cancer drugs. Full article

Background: Colorectal cancer (crc) has a median diagnostic age of 68 years. Despite significant progress in chemotherapy (ctx) options, few data on outcomes or toxicity from ctx in patients 80 years of age and older are available. We investigated ctx in such patients with metastatic crc (mcrc), hypothesizing high rates of hospitalization and toxicity. Methods: A retrospective chart review identified patients 80 years of age and older with mcrc who initiated ctx between 2005–2010 at our institution. Patient demographics and ctx data were collected. Endpoints included rates of hospitalization, ctx discontinuation because of toxicity, and overall survival. Results: In 60 patients, ctx was initiated on 88 occasions. Median age in the cohort was 83 years; 52% were men; 72% lived with family; 53% had a modified Charlson comorbidity index of 2 or greater; and 31% were taking 6 or more prescription medications at baseline. At baseline, 33% of the patients were anemic (hemoglobin < 100 g/L), 36% had leukocytosis (white blood cells > 11×109/L), and 48% had renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m2). In 53%, ctx was given as first-line treatment. The initial ctx dose was adjusted in 67%, and capecitabine was the most common chemotherapeutic agent (45%). In 19 instances (22%), the patient was hospitalized during or within 30 days of ctx; in 26 instances (30%), the ctx was discontinued because of toxicity, and in 48 instances (55%), the patient required at least 1 dose reduction, omission, or delay. Median overall survival was 17.8 months (95% confidence interval: 14.3 to 20.8 months). Conclusions: In the population 80 years of age and older, ctx for mcrc is feasible; however, most recipients will require dose adjustments, and a significant proportion will be hospitalized or stop ctx because of toxicity. Prospective research incorporating geriatric assessment tools is required to better select these older patients for ctx. Full article