Curr. Oncol., Volume 21, Issue 2 (April 2014) – 30 articles

Objectives: It is estimated that 1–2% of individuals of Ashkenazi Jewish (AJ) ancestry carry one of three pathogenic founder mutations in BRCA1 and BRCA2. Targeted testing for these mutations (BRCA1 187delAG and 5385insC, and BRCA2 6174delT) is therefore recommended for all AJ breast and ovarian cancer patients, regardless of age of diagnosis or family history. Comprehensive analysis of both genes is recommended for a subset of AJ patients in whom founder mutations are not identified, but estimates of the yield from comprehensive analysis in this population vary widely. Methods: We sought to establish the proportion of non-founder mutations in AJ patients undergoing clinical testing in our laboratory from January 2006 through August 2013. Analysis included AJ patients for whom: (1) comprehensive testing was ordered as the initial test, or (2) founder mutation testing was ordered with instructions to “reflex” to comprehensive analysis if negative. The latter group was limited to cases where the reflex testing was ordered on the original test request form, and not cancelled for any reason other than the detection of a founder mutation. Results: The percentage of non-founder mutations detected in these groups was 13% (104/802) and 7.2% (198/2769) respectively. We detected 189 unique non-founder mutations, 76 in BRCA1 and 113 in BRCA2. BRCA2 4075delGT was detected in 15 patients. The next most common mutations, found in 7 patients each, were BRCA1 5055delG, BRCA2 1982delA, and BRCA2 R3128X. Conclusions: Non-founder mutations make up between 13% and 7.2% of BRCA1 and BRCA2 mutations in patients reporting AJ ancestry. These numbers may represent underestimates if some patients were ascertained for testing based on the identification of a founder mutation in a relative. These numbers suggest that the prevalence of non-founder mutations in AJ individuals may be comparable to the prevalence of BRCA1/2 mutations in non-AJ individuals. Full article

Because of common risk factors, synchronous squamous cell carcinomas of the esophagus and head and neck are common, and their concurrent presence can significantly complicate disease eradication and survival. Here, we report the case of a patient with a history of extensive tobacco and alcohol use who was diagnosed with a localized thoracic esophageal squamous cell carcinoma, and in whom positron-emission tomography–computed tomography discovered a nearby asymptomatic localized hypopharyngeal focus that was confirmed by biopsy to also be malignant. He was treated with definitive concurrent chemoradiotherapy in a single unified radiotherapy plan, with surgery reserved for salvage treatment. He currently remains in remission without a need for surgical salvage. However, significant concern remains for both treatment failure and development of another primary because of “field cancerization.” Full article

Li–Fraumeni syndrome is an autosomal dominant disorder characterized by germline TP53 mutation and increased susceptibility to cancer. Despite certain in vitro findings and a theoretical rationale for patients with TP53 mutation to be more radiosensitive and more prone to developing radiotherapy (RT)–induced secondary malignancies, corresponding clinical data remain elusive. Here, we report the case of a woman with TP53 mutation who was treated with adjuvant pelvic RT for stage ib uterine leiomyosarcoma in 2000, with radioactive iodine for papillary thyroid cancer in 2001, and with palliative RT to the humerus in 2010 for metastatic uterine leiomyosarcoma. She has not developed any acute or late RT-related toxicity, nor any secondary malignancies, since her first RT treatment. The literature review describes the potential risks and benefits of using irradiation in patients with TP53 mutation. Full article

Patients with neurofibromatosis type 1 (NF1) are at increased risk for both benign and malignant tumours, and distinguishing the malignant potential of an individual tumour is a common clinical problem in these patients. Here, we review two cases of uncommon malignancies (Hodgkin lymphoma and mediastinal germ-cell tumour) in patients with nf1. Although ¹⁸F-fluorodeoxyglucose positron-emission tomography (FDG-PET) has been used to differentiate benign neurofibromas from malignant peripheral nerve sheath tumours, FDG-PET characteristics for more rare tumours have been poorly described in children with NF1. Here, we report the role of PET imaging in clinical decision-making in each case. In NF1, FDG-PET might be useful in the clinical management of unusual tumour presentations and might help to provide information about the malignant potential of uncommon tumours. Full article

Hepatocellular carcinoma (hcc) is a leading cause of cancer mortality, and its incidence is increasing in developed countries. Risk factors include cirrhosis from viral hepatitis or alcohol abuse. Metabolic syndrome is a newly recognized, but important, risk factor that is likely contributing to the increased incidence of hcc. Surgery is the therapy of choice for hcc, but local therapies are often contraindicated, usually because of advanced disease or comorbid conditions such as cardiac disease (which is associated with metabolic syndrome). Current radiation therapy techniques such as stereotactic body radiotherapy allow for treatment plans that highly conform to the target and provide excellent sparing of normal structures. Radiation therapy is emerging as a viable option in patients not eligible for surgery or other locoregional therapies. Here, we report a case of a large hcc presenting in a patient with metabolic syndrome without significant alcohol history or biochemical liver dysfunction. The patient was not a candidate for locoregional therapies because of cardiac and renal comorbidities typical of patients experiencing the long-term sequelae of metabolic syndrome. Treatment using an arc-based volumetric-modulated arc therapy technique allowed for the highest dose of radiation to be delivered to the tumour while the peripheral radiation dose was minimized. A complete local response was confirmed by computed tomography imaging 21 months after treatment completion. Full article

Patients undergoing myeloablative conditioning regimens and autologous stem-cell transplantation (ASCT) are at high risk of malnutrition. This randomized study aimed to determine if early nutrition support (commenced when oral intake is less than 80% of estimated requirements) compared with usual care (commenced when oral intake is less than 50% of estimated requirements) reduces weight loss in wellnourished patients undergoing high-nutritional-risk conditioning chemotherapy and ASCT. In the 50 well-nourished patients who were randomized, the outcomes evaluated included changes in weight and lean body mass (mid-upper arm circumference), length of stay, time to hemopoietic engraftment, and quality of life (Memorial Symptom Assessment Scale – Short Form). On secondary analysis, after exclusion of a single extreme outlier, both groups demonstrated significant weight loss over time (p = 0.0005). Weight loss was less in the early nutrition support group at time of discharge (mean: –0.4% ± 2.9% vs. –3.4% ± 2.6% in the usual care group, p = 0.001). This difference in weight was no longer observed at 6 months after discharge (mean: –1.0% ± 6.8% vs. 1.4% ± 6.1%, p = 0.29). In practice, an early start to nutrition support proved difficult because of patient resistance and physician preference, with 8 patients (33%) in the control group and 4 (15%) in the intervention group not commencing nutrition support when stipulated by the study protocol. No significant differences between the groups were found for other outcomes. In wellnourished patients receiving ASCT, early nutrition support maintained weight during admission, but did not affect other outcomes. Interpretation of results should take into consideration the difficulties encountered with intervention implementation. Full article

Distress has been declared the 6th vital sign in Canadian cancer care. Accordingly, health care professionals in Canada are expected to screen for distress in patients with cancer, for which a toolkit has been developed. Identifying patients who may be in need of further resources has the potential to improve quality of care because those patients are more likely to have their existing distress identified and to be referred for appropriate follow-up services. The present article briefly reviews the background literature and the validation of the measures in the toolkit, and highlights future directions for methodologic validation of the toolkit for use according to the protocol. Full article

Predictive factors of recurrence were examined in 448 non-melanoma skin cancers (72% basal cell carcinoma, 28% squamous cell carcinoma) treated with radiotherapy. The overall recurrence rate was 15.8% at a median follow-up of 18.4 months. In multivariate analysis, significant factors for recurrence were age (p = 0.0197), tumour size 2 cm or greater (p = 0.0095), immunosuppression (p = 0.0082), and treatment modality (p = 0.0009). Full article

Adult Philadelphia chromosome–positive (Ph+) or BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (ALL) is an acute leukemia previously associated with a high relapse rate, short disease-free survival, and poor overall survival. In adults, allogeneic hematopoietic cell transplant in first remission remains the only proven curative strategy for transplant-eligible patients. The introduction of tyrosine kinase inhibitors (TKIS) in the treatment of patients with Ph+ or BCR-ABL+ ALL has significantly improved the depth and duration of complete remission, allowing more patients to proceed to transplantation. Although tkis are now considered a standard of care in this setting, few randomized trials have examined the optimal use of TKIS in patients with Ph+ ALL. Questions of major importance remain, including the best way to administer these medications, the choice of tki to administer, and the schedule and the duration to use. We present the results of a systematic review of the literature with consensus recommendations based on the available evidence. Full article

Since the early 1950s, Papanicolaou (“Pap”) cytology screening has dramatically reduced cervical cancer mortality in most high-income settings. Currently, human papillomavirus (hpv) vaccination has the greatest potential to reduce the global burden of cervical cancer and precancerous lesions. However, as the prevalence of precancerous lesions declines, maintaining cytology as the primary screening test in settings with established programs might become less efficient. A reduction in test performance (sensitivity, specificity, and positive predictive value) would lead to an increase in unnecessary colposcopy referrals. Fortunately, hpv dna testing has emerged as a suitable candidate to replace cytology. Compared with the Pap test, hpv testing is less specific but much more sensitive in detecting high-grade precancerous lesions, less prone to human error, and more reproducible across settings. Linkage of hpv vaccination and screening registries could serve the added role of monitoring vaccine efficacy. As a triage test, cytology is expected to perform with sufficient accuracy because most hpv-positive smears would contain relevant abnormalities. This approach and others—for example, hpv testing followed by genotyping—are being evaluated in large population studies and have already been recommended in some settings. Other specific biomarkers that might perform well for screening and triage include hpv E6/ E7 messenger rna testing, methylation of host or viral genes, and p16^INK4a staining. Considering the rapid pace of major discoveries and the anticipated arrival of a nonavalent hpv vaccine (currently in phase iii trials), the evidence base in this field has become an elusive target and will continue to be an obstacle for policymakers. Full article

Backgroud: We set out to determine the rate, time-trend, and defining factors associated with publication of abstracts presented at two annual scientific meetings of the Canadian Association of Radiation Oncology (caro). Methods: All abstracts accepted for oral presentation in 2007 and 2010 were obtained from the caro program archives and searched using the PubMed database. Variables in the dataset included the year of presentation at caro and of publication in a scientific journal, time to publication (in months), publishing journal, impact factor of publishing journal, abstract research type (clinical, technical, or basic science) and disease site, country of origin, and university of the first author. Results: Overall, 88 of 172 abstracts from the 2007 (n = 102) and 2010 (n = 70) caro meetings were published in peer-reviewed journals (publication rate: 51.2%). Mean time to publication was 18.5 months. Among research types, clinical research (62.5%) and, among disease sites, prostate cancer (40.4%) were most likely to be published. Of all the abstracts, 50.1% were contributed by only 2 universities, a proportion that resembles the overall abstract publication rate of 51.2%. The conversion rate for those 2 universities (51.1%) is very similar to that for all abstracts presented at the two meetings. Conclusions: Half the abstracts presented at the 2007 and 2010 caro meetings were ultimately published in journals indexed in PubMed by about 1.5 years after presentation. Half the abstracts and publications came from just 2 universities; more must to be done to close the gap. Full article

Background: We used an interview-assisted survey of patients with chronic myeloid leukemia (cml) at a single tertiary care centre to explore patient reactions to and preferences for, and the risk-acceptability of, stopping tyrosine kinase inhibitor (tki) treatment. Methods: The study included patients with confirmed cml currently being treated with a tki. The survey was conducted by structured interview using a standard form. Patient preferences were explored in a casebased scenario using 0%–100% visual analog scales and 5-point Likert scales. Data were analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables. Results: Of 63 patients approached, 56 completed the survey. Participant responses suggest that the idea of stopping tki use is appealing to many patients if there is a chance of long-term stable disease and a high probability of response upon restarting a tki. Participants were more likely to stop their tki as the risk of relapse decreased. Participants reported loss of disease control and failure of disease to respond to treatment as important concerns if they chose to stop their tki. Conclusions: Given the current 60% estimated rate of relapse after discontinuation of tki therapy, most patients with cml chose to continue with tki. However, at the lower relapse rates reported with second-generation tkis, participants were more undecided, demonstrating a basic understanding of risk. Contrary to our hypothesis, neither compliance nor occurrence of side effects significantly affected patient willingness to stop their tki. Full article

Background: Data on real-life utilization of granulocyte colony– stimulating factors (g-csfs) in Canada are limited. The objective of the present study was to describe the reasons for, and the patterns of, g-csf use in selected outpatient oncology clinics in Ontario and Quebec. Methods: In a retrospective longitudinal cohort study, a review of medical records from 9 Canadian oncology clinics identified patients being prescribed filgrastim (fil) and pegfilgrastim (peg). Patient characteristics, reasons for g-csf use, and treatment patterns were descriptively analyzed. Results: Medical records of 395 patients initiating g-csf therapy between January 2008 and January 2009 were included. Of this population, 80% were women, and breast cancer was the predominant diagnosis (59%). The most commonly prescribed g-csf was fil (56% in Ontario and 98% in Quebec). The most frequent reason for g-csf use was primary prophylaxis (42% for both fil and peg), followed by secondary prophylaxis (37% fil, 41% peg). Those proportions varied by tumour type and chemotherapy regimen. Delayed g-csf administration (more than 1 day after the end of chemotherapy) was frequently observed for fil, but rarely reported for peg, and that finding was consistent across tumours and concurrent chemotherapy regimens. Conclusions: The use of g-csf varies with the malignancy type and the provincial health care setting. The most commonly prescribed g-csf agent was fil, and most first g-csf prescriptions were for primary prophylaxis. Delays were frequently observed for patients receiving fil, but were rarely reported for those receiving peg. Full article

Backgroud: Computerized physician order entry (cpoe) systems allow for medical order management in a clinical setting. Use of a cpoe has been shown to significantly improve chemotherapy safety by reducing the number of prescribing errors. Usability of these systems has been identified as a critical factor in their successful adoption. However, there is a paucity of literature investigating the usability of cpoe for chemotherapy and describing the experiences of cancer care providers in implementing and using a cpoe system. Methods: A mixed-methods study, including a national survey and a workshop, was conducted to determine the current status of cpoe adoption in Canadian oncology institutions, to identify and prioritize knowledge gaps in cpoe usability and adoption, and to establish a research agenda to bridge those gaps. Survey respondents were representatives of cancer care providers from each Canadian province. The workshop participants were oncology clinicians, human factors engineers, patient safety researchers, policymakers, and hospital administrators from across Canada, with participation from the United States. Results: A variety of issues related to implementing and using a cpoe for chemotherapy were identified. The major issues concerned the need for better understanding of current practices of chemotherapy ordering, preparation, and administration; a lack of system selection and procurement guidance; a lack of implementation and maintenance guidance; poor cpoe usability and workflow support; and other cpoe system design issues. An additional three research themes for addressing the existing challenges and advancing successful adoption of cpoe for chemotherapy were identified: The need to investigate variances in workflows and practices in chemotherapy ordering and administration. The need to develop best-practice cpoe procurement and implementation guidance specifically for chemotherapy. The need to measure the effects of cpoe implementation in medical oncology. Conclusions: Addressing the existing challenges in cpoe usability and adoption for chemotherapy, and accelerating successful migration to cpoe by cancer care providers requires future research focusing on workflow variations, chemotherapy-specific cpoe procurement needs, and implementation guidance needs. Full article

Background: Cancer survivors (css) are frequently exposed to polypharmacy, which might increase their risk of drug interactions. Our study aimed to determine the relative prevalence of potential drug interactions (pdis) among css compared with non-cancer respondents (ncrs). Methods: Self-reported prescription data from 4975 patients were extracted from the U.S. National Health and Nutrition Examination Survey and screened for pdis using iFacts: Drug Interaction Facts (Facts and Comparisons, St. Louis, MO, U.S.A.). The clinical significance of each pdi was graded on a 5-point scale based on the severity of the interaction and the level of evidence documenting the interaction. Summary statistics and logistic regression models were used to assess the impact of cancer history on the risk of pdis. Results: Of patients eligible for the analyses, the css (n = 302) indicated using 4.4 ± 0.22 prescriptions on average, and the ncrs (n = 908), 3.8 ± 0.09. Nearly half of both cohorts (40% of css, 43% of ncrs) had at least 1 pdi. In both cohorts, 12% were at risk for fatal or permanently debilitating effects. In multivariate analyses, css were significantly less likely than ncrs to be at risk for any pdis (odds ratio: 0.65; 95% confidence interval: 0.46 to 0.92; p = 0.02). Advanced age and low household income were associated with pdis among css. Medications most commonly prescribed to css with a pdi included metoprolol (15.6%), levothyroxine (13.6%), and furosemide (11.9%). Conclusions: Although css appear to be less susceptible than ncrs to pdis, the prevalence of pdis among css remains suboptimal. Specific subgroups of css may be particularly prone to pdis, underscoring the importance of increased vigilance. Full article

Introduction: Determining the likely benefit of adjuvant chemotherapy for early-stage breast cancer patients depends on estimating baseline recurrence risk. Gene expression profile (gep) testing of tumours informs risk prediction, but evidence of its clinical utility is limited. We explored patient perceptions of gep testing and the impact of those perceptions on chemotherapy decisions. Methods: We conducted one focus group (n = 4) and individual interviews (n = 24) with patients who used gep testing, recruited through clinics at two hospitals in Ontario. Data were analyzed using content analysis and constant comparison techniques. Results: Patients’ understanding of gep testing was variable, and misapprehensions were common. Patients valued the test because it provided them with certainty amidst confusion, with options and a sense of empowerment, and with personalized, authoritative information. They commonly believed that the test was better and fundamentally different from other clinical tests, attributing to it unique power and truth-value. This kind of “magical thinking” was derived from an amplified perception of the test’s validity and patients’ need for reassurance about their treatment choices. Despite misperceptions or magical thinking, gep was widely considered to be the deciding factor in treatment decisions. Conclusions: Patients tend to overestimate the truth-value of gep testing based on misperceptions of its validity. Our results identify a need to better support patient understanding of the test and its limitations. Findings illustrate the deep emotional investment patients make in gep test results and the impact of that investment on their treatment decisions. Full article

Background: Surgery is a cornerstone of cancer treatment, but significant differences in the quality of surgery have been reported. Surgical process improvement tools (spits) modify the processes of care as a means to quality improvement (qi). We were interested in developing spits in the area of gastrointestinal (gi) cancer surgery. We report the recommendations of an expert panel held to define quality gaps and establish priority areas that would benefit from spits. Methods: The present study used the knowledge-to-action cycle was as a framework. Canadian experts in qi and in gi cancer surgery were assembled in a nominal group workshop. Participants evaluated the merits of spits, described gaps in current knowledge, and identified and ranked processes of care that would benefit from qi. A qualitative analysis of the workshop deliberations using modified grounded theory methods identified major themes. Results: The expert panel consisted of 22 participants. Experts confirmed that spits were an important strategy for qi. The top-rated spits included clinical pathways, electronic information technology, and patient safety tools. The preferred settings for use of spits included preoperative and intraoperative settings and multidisciplinary contexts. Outcomes of interest were cancer-related outcomes, process, and the technical quality of surgery measures. Conclusions: Surgical process improvement tools were confirmed as an important strategy. Expert panel recommendations will be used to guide future research efforts for spits in gi cancer surgery. Full article

Background: Reliable and valid assessment of the disease burden across all forms of cancer is critical to the evaluation of treatment effectiveness and patient progress. The Edmonton Symptom Assessment System (esas) is used for routine evaluation of people attending for cancer care. In the present study, we used Rasch analysis to explore the measurement properties of the esas and to determine the effect of using Raschproposed interval-level esas scoring compared with traditional scoring when evaluating the effects of an exercise program for cancer survivors. Methods: Polytomous Rasch analysis (Andrich’s rating-scale model) was applied to data from 26,645 esas questionnaires completed at the Juravinski Cancer Centre. The fit of the esas to the polytomous Rasch model was investigated, including evaluations of differential item functioning for sex, age, and disease group. The research implication was investigated by comparing the results of an observational research study previously analysed using a traditional approach with the results obtained by Rasch-proposed interval-level esas scoring. Results: The Rasch reliability index was 0.73, falling short of the desired 0.80–0.90 level. However, the esas was found to fit the Rasch model, including the criteria for uni-dimensional data. The analysis suggests that the current esas scoring system of 0–10 could be collapsed to a 6-point scale. Use of the Rasch-proposed interval-level scoring yielded results that were different from those calculated using summarized ordinallevel esas scores. Differential item functioning was not found for sex, age, or diagnosis groups. Conclusions: The esas is a moderately reliable uni-dimensional measure of cancer disease burden and can provide interval-level scaling with Rasch-based scoring. Further, our study indicates that, compared with the traditional scoring metric, Rasch-based scoring could result in substantive changes to conclusions. Full article

Background: The unmet needs of cancer survivors in rural, remote, and aboriginal communities are largely unexplored. We explored potential differences between rural survivors (rss) in 4 general population (gp) and 4 First Nations (fn) communities. Methods: We approached 4 gp and 4 fn rs communities to participate in a mixed-methods project. Participants completed the Hospital Anxiety and Depression Scale (hads) and the Survivor Unmet Needs Survey (suns) and provided demographic information. Each question on the suns can be scored from 0 to 4, with 0 representing “no unmet need” and 4 representing “very high unmet need.” A directed approach to content analysis of focus group and interview data was used to triangulate the hads and suns results. Results: We prospectively accrued 23 fn rss and 56 gp rss for this study. More fn rss had borderline or abnormal anxiety (5% vs. 21%, p = 0.02). Compared with gp rss, fn rss had higher unmet needs scores in all categories: Information (2.29 vs. 0.8, p < 0.001), Work and Financial (1.66 vs. 0.5, p < 0.001), Access and Continuity of Health Care (1.83 vs. 0.44, p < 0.001), Coping and Sharing (2.22 vs. 0.62, p < 0.001), and Emotional (2.12 vs. 0.63, p < 0.001). The qualitative findings provided examples and insight into the unmet needs experienced by rss. Conclusions: First Nations rss had significantly higher anxiety and unmet needs compared with their gp rs counterparts. In addition, different qualitative themes were identified in the groups. Our findings support the development of tailored approaches to survivorship for these populations. Full article

Background: Palliative sedation (ps), the continuous use of sedating doses of medication to intentionally reduce consciousness and relieve refractory symptoms at end of life, is ethically acceptable if administered according to standards of best practice. Procedural guidelines outlining the appropriate use of ps and the need for rigorous documentation have been developed. As a quality improvement strategy, we audited the practice and documentation of ps on our palliative care unit (pcu). Methods: A pharmacy database search of admissions in 2008 identified, for a subsequent chart review, patients who had received either a continuous infusion of midazolam (≥10 mg/24 h), regular parenteral dosing of methotrimeprazine (≥75 mg daily), or regular phenobarbital. Documentation of the decision-making process, consent, and medication use was collected using a data extraction form based on current international ps standards. Results: Interpretation and comparison of data were difficult because of an apparent lack of a consistent operational definition of ps. Patient records had no specific documentation in relation to ps initiation, to clearly identified refractory symptoms, and to informed consent in 60 (64.5%), 43 (46.2%), and 38 (40.9%) charts respectively. Variation in the medications used was marked: 54 patients (58%) were started on a single agent and 39 (42%), on multiple agents. The 40 patients (43%) started on midazolam alone received a mean daily dose of 21.4 mg (standard deviation: 24.6 mg). Conclusions: The lack of documentation and standardized practice of ps on our pcu has resulted in a quality improvement program to address those gaps. They also highlight the importance of conducting research and developing clinical guidelines in this area. Full article

Repair of radiation-induced dna double-strand breaks is a key mechanism in cancer cell radioresistance. The synthesized compound NU7026 specifically inhibits dna-dependent protein kinase (dna-pk) within the non-homologous end-joining repair mechanism. Earlier studies demonstrated increased radiosensitivity in dna-pk deficient cells compared with wild-type cells. In chronic leukemia cells, NU7026 appears to enhance the cytotoxic effect of chlorambucil. The radio-modifying effects of NU7026 on cell survival, cell cycle, apoptosis, and dna double-strand break repair have yet to be studied in gastric cancer cells. Methods: The gastric cancer cell line N87 was treated with 0 Gy or 4 Gy in the presence of NU7026 at a dose range of 0–20 μmol/L. Clonogenic assays were used to assess cell survival after treatment. Cell-cycle distribution was analyzed using propidium iodide with fluorescence-activated cell sorting. Apoptosis was detected using annexin-V and propidium iodide with fluorescence-activated cell sorting. The γH2AX assay was used to measure dna doublestrand breaks. Results: Statistically significant increases in G2/M arrest were observed in N87 cells treated with radiation and NU7026 compared with those treated with radiation alone (p = 0.0004). Combined treatment also led to an increase in apoptosis (p = 0.01). At 24 hours, the γH2AX analysis revealed more dna double-strand breaks in N87 cells treated with radiation and NU7026 than in those treated with radiation alone (p = 0.04). Clonogenic assays demonstrated declining cell survival as both the radiation and the NU7026 dose increased. The dose enhancement factor at 0.1 survival fraction was 1.28 when N87 cells were treated with 4 Gy radiation and 5 μmol/L NU7026. Conclusions: In gastric cancer cells, NU7026 appears to enhance the cytotoxic effect of irradiation as assessed by clonogenic assays. This increased cytotoxicity might be the result of an increase in dna double-strand breaks resulting in G2/M cell arrest and possibly higher levels of apoptosis. Full article

Background: Prediction of prognosis is important for patients so that they can make the most of the rest of their lives. Oncologists could predict survival, but the accuracy of such predictions is unclear. Methods: In this observational prospective cohort study, 14 oncologists treating 9 major adult solid malignancies were asked to complete questionnaires predicting survival based on performance status, oral intake, and other clinical factors when patients experienced progressive disease after standard chemotherapies. Clinically predicted survival (cps) was calculated by the oncologists from the date of progressive disease to the predicted date of death. Actual survival (as) was compared with cps using Kaplan–Meier survival curves, and factors affecting inaccurate prediction were determined by logistic regression analysis. The prediction of survival time was considered accurate when the cps/as ratio was between 0.67 and 1.33. Results: The study cohort consisted of 75 patients. Median cps was 120 days (interquartile range: 60–180 days), and median as was 121 days (interquartile range: 40–234 days). The participating oncologists accurately predicted as within a 33% range 36% of the time; the survival time was overestimated 36% of time and underestimated 28% of the time. The factors affecting the accuracy of the survival estimate were the experience of the oncologist, patient age, and information given about the palliative care unit. Conclusions: Prediction of cps was accurate for just slightly more than one third of all patients in this study. Additional investigation of putative prognostic factors with a larger sample size is warranted. Full article

Background: In 2006, perioperative epirubicin, cisplatin, and 5-fluorouracil (ECF), compared with surgery alone, demonstrated a significant survival benefit in resectable gastroesophageal cancers. We report the results of our experience with that protocol. Methods: The BC Cancer Agency (BCAA) is a multicentre institution that treats most oncology patients for the province. Characteristics of the 83 bcca patients with localized gastric, gastroesophageal junction, or lower esophageal cancer who initiated perioperative chemotherapy either ecf or epirubicin, cisplatin, and capecitabine (ECX) from 2008 to 2011 were abstracted to an anonymous database and analyzed. Results: Of the 83 patients in the cohort [66 men; median age: 62 years (range: 37–79 years)], 87.9% completed 3 cycles of perioperative chemotherapy, and 93.9% (n = 78) underwent an attempt at surgery (2 patients died of chemotherapy toxicities, 1 refused surgery, and 2 developed disease progression before surgery). In 11 of the surgeries (14.1%), tumours could not be resected because of unresectability (n = 1), liver metastasis (n = 1), and peritoneal carcinomatosis (n = 9). One patient died of surgical complications. The 6 patients (7.2%) who achieved a pathologic complete response are all alive and recurrence-free. Of 46 patients (55.4%) who subsequently began postoperative chemotherapy, 44.5% completed 3 cycles. Estimated median survival was 40.3 months. Weight loss was the only significant prognostic factor for worse overall survival. Conclusions: Our multicentre experience confirmed the feasibility of the MAGIC protocol in a real-world scenario and showed that ECX is also an adequate regimen in the perioperative setting. Weight loss was the only significant prognostic factor for worse overall survival. All patients who achieved a pathologic complete response are recurrence-free after a median followup of 40.3 months. Full article

(1) Objective: Our aim was to determine the extent to which comprehensive navigation augments the provincial health system for meeting the needs of newly-diagnosed cancer patients (clients). We also assessed reactions of attending physicians to comprehensive navigation. (2) Methods: Clients who completed navigation as an employee benefit or through membership in an insurance organization were polled to determine whether they needed help beyond that provided by the provincial health system and the extent to which that help was provided by navigation. Exit interviews were analyzed for perceptions of the clients about reactions by their attending physicians to navigation. (3) Results: Of eligible clients, 72% responded. They reported needing help beyond that which the provincial system could provide in 64%–98% of specified areas. Navigation provided help in more than 90% of those cases. Almost all respondents (98%) appreciated having a designated oncology nurse navigator. Family doctors were perceived to be positive or neutral about navigation in 100% of exit interviews. Oncologists were positive or neutral in 92% (p < 0.001 for difference from family doctors). (4) Conclusions: In many areas, cancer patients need additional help beyond that which the provincial health system can provide. Comprehensive cancer navigation provides that help to a considerable extent. Clients perceived the reactions of attending physicians to comprehensive navigation to be generally supportive or neutral. Full article

Background: The risk of breast cancer in carriers of BRCA1 and BRCA2 mutations is influenced by factors other than the genetic mutation itself. Modifying factors include a woman’s reproductive history and family history of cancer. Risk factors are more likely to be present in women with breast cancer than in women without breast cancer, and therefore the risk of cancer in the two breasts should not be independent. It is not clear to what extent modifying factors influence the risk of a first primary or a contralateral breast cancer in BRCA carriers. Methods: We conducted a matched case–control study of breast cancer among 3920 BRCA1 or BRCA2 mutation carriers. We asked whether a past history of breast cancer in the contralateral breast was a risk factor for breast cancer. Results: After adjustment for age, country of residence, and cancer treatment, a previous cancer of the right breast was found to be a significant risk factor for cancer of the left breast among BRCA1 or BRCA2 carriers (relative risk: 2.1; 95% confidence interval: 1.4 to 3.0; p < 0.0001). Conclusions: In a woman with a BRCA1 or BRCA2 mutation who is diagnosed with breast cancer, the risk of cancer in the contralateral breast depends on the first diagnosis. That observation supports the hypothesis that there are important genetic or non-genetic modifiers of cancer risk in BRCA carriers. Discovering risk modifiers might lead to greater personalization of risk assessment and management recommendations for BRCA-positive patients. Full article