Curr. Oncol., Volume 19, Issue 2 (April 2012) – 14 articles

The use of systemic therapy before surgery (“neoadjuvant therapy”) is the standard of care for the treatment of locally advanced and nonoperable breast cancer. The advantages of neoadjuvant therapy include improved rates of breast-conserving surgery, the possibility of early measurement of response, and potentially improved outcomes for certain subgroups of high-risk patients. The use of neoadjuvant therapy in operable breast cancer is increasing, although there are no clear guidelines in Canada to help guide patient selection and management. Multidisciplinary experts in the diagnosis and treatment of locally advanced breast cancer (labc) converged at the fourth annual meeting of the Canadian Consortium for LABC (colab) to further their goals of improved standards for neoadjuvant care and clinical research through education and collaboration. Canadian clinical researchers were joined by Dr. Michael Untch of the Helios Hospital Berlin–Buch—representing the German neoadjuvant treatment groups German Gynecologic Oncology Working Group (Arbeitsgemeinschaft Gynakologische Onkologie) and German Breast Group—to discuss the advancement of research in the neoadjuvant setting and important issues of clinical care and investigator-led research. The group reached a consensus on the importance of multidisciplinary collaboration, the use of clips to mark tumour location, and core biopsy testing for the estrogen and progesterone receptors and the human epidermal growth factor receptor 2 at the time of diagnosis. Other initiatives—including creation of a prospective database, inception of the colab Neoadjuvant Network, and development of a clinical survey to evaluate current practice—continue to further the colab mandate of transforming the neoadjuvant treatment landscape in Canada. Full article

This article provides an overview of recent advances in chemotherapy that may be used for the treatment of patients with locally advanced or metastatic breast cancer (mbc). Key phase ii and iii trial data for eribulin mesylate, ixabepilone, and nab-paclitaxel, published since 2006, are discussed on the basis of recency, depth, and quality. Eribulin mesylate is the first monotherapy to significantly increase overall survival in patients with pretreated mbc, but nab-paclitaxel offers a novel and safer mode of delivery in comparison with standard taxanes. By contrast, the use of ixabepilone will be limited for now, until the associated neurotoxicity can be better managed. Alongside a brief overview of the other major chemotherapies currently in use, we have aimed to provide a Canadian context for how these novel agents may be integrated into clinical practice. Full article

Background: Nearly 15% of DNA tests for BRCA1/2 results in the identification of an unclassified variant (UV). In DNA diagnostic laboratories in The Netherlands, a 4-group classification system (class I to IV) is in use (Bell et al.). Aim of this study was to investigate whether the UVs in different classes showed a significant difference in their in silico characteristics and would justify current differences in protocols for counselling with respect to communication to the counselees. Methods: Missense UVs in BRCA1/2 identified between 2002 and 2010 (n = 88) were analyzed. In silico analysis of UVs was performed using SIFT– analysis Grantham score and AGVGD for the predicted severity of amino acid substitutions. Each UV was classified to one of the four classes. Results: More than half of the UVs (n = 50) were predicted to be tolerated using SIFT-analysis. Accordingly, all these variants are scored as neutral (C0) by AGVGD. Of the remaining 38 UVs not tolerated using SIFT-analysis, 19 were scored as C0 (neutral), 8 were scored C15–C25 (intermediate) and 11 were scored C35 or higher (likely to be pathogenic). Although class III UVs more frequently show in silico parameter outcomes that are suspicious for a pathogenic effect, the observed differences are not absolute. Seven UVs classified in class II had similar in silico profiles with 7 UVs in class III. Conclusion: This study showed that, in general, in silico analysis is consistently applied and proved to be able to discriminate between the different classes of UVs. However, additional analyses will be required to classify the UVs with more accuracy. In order to reduce psychological distress in families in which a UV is identified, we propose that communication of a UV should not primarily depend on its class, but also on the possibility to perform additional research in the family. Full article

Lung cancer is one of the most commonly diagnosed malignancies and the leading cause of cancer-related mortality in Canada. The heterogeneity of nsclc and the importance of linking new targeted agents to the appropriate disease subtype require an individualized approach to treatment. In patients with EGFR (epidermal growth factor receptor gene) mutations, egfr tyrosine kinase inhibitors (tkis) provide a highly effective treatment option, with improved toxicity compared with standard chemotherapy. However, the identification of mutation-positive patients is limited by a lack of funding for testing. The length of time required to receive test results and insufficient tissue from biopsies are additional limitations. In Canada, the use of egfr-tkis varies based on differences in provincial funding for both testing and treatment. With improvements in testing and access to funding for treatment, targeted use of egfr-tkis may greatly improve outcomes in nsclc. Full article

Background: This phase II clinical trial examined the activity of a metronomic dosing schedule of docetaxel and capecitabine chemotherapy in patients with advanced breast cancer. Patients also received daily oral celecoxib in an effort to improve outcome measures and to ameliorate some of the common side effects of chemotherapy. Methods: Patients received docetaxel at a starting dose of 15 mg/m² weekly, oral capecitabine 1250 mg/m² once daily, and oral celecoxib 200 mg twice daily. The primary endpoint was clinical benefit: percentage of patients experiencing either an objective response or stable disease (SD) for more than 6 months. In the absence of significant neutropenia, the dose of docetaxel was escalated after 4 and 8 weeks of treatment. Therapy was given until disease progression or development of unacceptable toxicity. The level of thymidine phosphorylase expression in peripheral white blood cells of patients was measured before and during treatment to determine the effect on this capecitabine-activating enzyme. Results: Of 47 patients enrolled, 38 (81%) completed treatment to a disease endpoint. No complete responses were achieved, but 13 of the 38 patients (34%) experienced a partial response, and another 3 patients (8%) experienced SD for more than 6 months. The clinical benefit rate was therefore 42% (95% confidence interval: 27% to 57%). The median time to disease progression for all evaluable patients was 3.6 months (range: 0.9–21.7 months). The most common nonhematologic toxicities were diarrhea, plantar– palmar erythrodysesthesia, fatigue, mucositis, and vomiting. Most patients (89%) received combination chemotherapy until disease progression. Conclusions: The present study demonstrates that metronomic docetaxel–capecitabine chemotherapy with daily celecoxib can produce significant anticancer activity, with predictable toxicity. Efficacy fell short of expectations, with outcome measures being similar to those obtained when the study agents are given in conventional dosing. Furthermore, there is mounting evidence to indicate that a low dose of taxanes fails to induce thymidine phosphorylase expression, an effect believed to be important in achieving therapeutic synergism when taxanes are given concurrently with capecitabine. Full article

Background: In 2006, the federal government committed funding of $250 million over 5 years for the Canadian Partnership Against Cancer Corporation to begin implementation of the Canadian Strategy for Cancer Control (cscc). The Partnership was established as a not-for-profit corporation designed to work actively with a broad range of stakeholders and organizations that had been engaged in the development of the cscc and with the public more broadly. A policy experiment unto itself, the Partnership was the first disease-based organization funded at the federal level outside of government. It was charged with a mandate to enable transfer of knowledge and to catalyze coordinated and accelerated action across the country to reduce the burden of cancer. Implementation: Implementation has involved establishing shared goals, objectives, and plans with participating partners. Knowledge management—incorporating pan-Canadian approaches to the identification of content, processes, technology, and culture change—was used to enable that work across the federated health care delivery system. Evaluation of the organization through independent review, the ability to achieve initiative-level targets by 2012, and progress measured using indicators of system performance was used to examine the effectiveness of the strategy and approach overall. Discussion and Conclusions: Evaluation findings support the conclusions that Canada has made progress in achieving immediate outcomes (achievable in 25 years) impact on cancer. The mechanism of funding the Partnership to develop collaboration among stakeholders in cancer control to achieve coordinated action has been possible and has been enabled through the Partnership’s knowledge-to-action mandate. Opportunities are available to further engage and clarify the roles of stakeholders in action, to clearly define outcomes, and to further quantify the economic benefits that have resulted from a coordinated approach. With the ongoing funding commitment to support coordinated action within a federated environment of health care delivery, there is opportunity to reduce the impact that cancer may have in the long term in Canada. Full article

Background: Non-small-cell lung cancer (NSCLC) tumours with activating mutations of the epidermal growth factor receptor (EFGR) tyrosine kinase are highly sensitized to the effects of oral tyrosine kinase inhibitors such as gefitinib and erlotinib, suggesting the possibility of targeted treatment of NSCLC based on EFGR mutation status. However, no standardized method exists for assessing the EGFR mutation status of tumours. Also, it is not known if available methods are feasible for routine screening. To address that question, we conducted a validation study of methods used for detecting EGFR mutations in exons 19 and 21 at molecular laboratories located in five specialized Canadian cancer centres. Methods: The screening methods were first optimized using cell lines harbouring the mutations in question. A validation phase using anonymized patient samples followed. Results: The methods used at the sites were highly specific and sensitive in detecting both mutations in cell-line DNA (specificity of 100% and sensitivity of at least 1% across all centres). In the validation phase, we observed excellent concordance between the laboratories for detecting mutations in the patient samples. Concordant results were obtained in 26 of 30 samples (approximately 87%). In general, the samples for which results were discordant were also less optimal, containing small amounts of tumour. Conclusions: Our results suggest that currently available methods are capable of reliably detecting exon 19 and exon 21 mutations of EFGR in tumour samples (provided that sufficient tumour material is available) and that routine screening for those mutations is feasible in clinical practice. Full article

Background: Of all mastectomy patients, 90% will use an external prosthesis where the standard of care uses a stock prosthesis that is purchased “off the shelf.” Our objectives were to determine patient demand for and perceived value of a custom breast prosthesis. The information obtained will influence future research and program direction. Methods: We asked 65 women who had undergone lumpectomy or mastectomy to participate before exploring rehabilitation options. The quantitative outcome measures were the European Organisation for Research and Treatment of Cancer QLQ-C30 general and -BR23 breast cancer–specific quality of life questionnaires, and the Ambulatory Oncology Patients Satisfaction Tool. The QLQ results were analyzed using the Mann–Whitney U-test. Results of the satisfaction tool were compared using the Fisher exact and chi-square tests. A descriptive qualitative approach—involving in-depth interviews exploring the experiences of the women—was used to establish the perceived value of the services to the patients. The analysis of the interview transcripts was conducted using a standardized content method to describe the experiences of the women. Results: All the women had had previous experiences with a conventional prosthesis, and they reported that wearing a custom prosthesis was more satisfying for them. They reported comfort and ease in wearing it, coupled with a sense of feeling less like a victim. Comparison of the qlq and patient satisfaction scores showed no significant difference between the women wearing the conventional prosthesis and those wearing the custom prosthesis. Conclusions: The willingness of women to pay for a prosthesis and the qualitative results from the present study demonstrate that there is demand for a custom approach to treatment. However, if a mixed-methods approach had not been applied during this initial exploration of women’s experiences with custom breast prostheses, the essence of the perceived value of the custom prosthesis would have been lost. Quantitative measures suggest that there is no difference between custom and conventional breast prostheses, but the qualitative data captured in the study provide a sense of aspects of care that a standardized outcome measure cannot capture. Further research with a larger sample size is needed to determine if real differences from a quantitative perspective are possible. Suggestions for improvements in the device and in program operations were gathered and will influence the future development and implementation of a breast prosthesis service, but financial assistance will most likely be needed to make such a service universally accessible. Full article

Although orthodox medicine trains general medical practitioners to comprehensively treat the whole patient and to refer to specialists only when patients present ailments exceeding the knowledge and skills of the practitioner, specialists continually face challenges in ensuring that their specialty careers are mutually interdependent and intertwined with total patient care. [...] Full article

Background: The palliation of dysphagia in metastatic esophageal cancer remains a challenge, and the optimal approach for this difficult clinical scenario is not clear. We therefore sought to define and determine the efficacy of various treatment options used at our institution for this condition. Methods: We reviewed a prospective database for all patients managed in an esophageal cancer referral centre over a 5-year period. All patients receiving palliation of malignant dysphagia were reviewed for demographics, palliative treatment modalities, complications, and dysphagia scores (0 = none to 4 = complete). The Wilcoxon signed rank test was used to determine significance (p < 0.05). Results: During 2004–2009, 63 patients with inoperable esophageal cancer were treated for palliation of dysphagia. The primary treatment was radiotherapy in 79% (brachytherapy in 18 of 50; external-beam in 10 of 50; both types in 22 of 50), and stenting in 21%. Mean wait time from diagnosis to treatment was 22 days in the stent group and 54 days in the radiotherapy group (p = 0.003). Mean duration of treatment was 1 day in the stent group and 40 days in the radiotherapy group (p = 0.001). In patients treated initially by stenting, dysphagia improved within 2 weeks of treatment in 85% of patients (dysphagia score of 0 or 1). However, 20% of patients presented with recurrence of dysphagia at 10 weeks of treatment. In the radiotherapy group, the onset of palliation was slower, with only 50% of patients palliated at 2 weeks (dysphagia score of 0 or 1). However, long-term palliation was more satisfactory, with 90% of patients remaining palliated after 10 weeks of treatment. Full article

Context: The delineation of populations of cancer patients with complex symptoms can inform the planning and delivery of supportive care services. Objectives: We explored the physical, psychosocial, and practical concerns experienced by patients attending an ambulatory oncology symptom control clinic. Methods: Patients attending a Pain Clinic at a large tertiary cancer centre were invited to complete screening measures assessing distress, pain, fatigue, anxiety, depression, and practical and psychosocial problems. A matched sample of patients who did not attend the Pain Clinic were selected as a comparison group. Results: Of all eligible Pain Clinic patients, 46 (77%) completed the measures; so did 46 comparison group patients. The percentages of patients reporting distress (78.3%), pain (93.5%), and fatigue (93.5%) were higher among Pain Clinic patients than among the comparison patients. A higher percentage of Pain Clinic patients also reported multiple, severe, concurrent symptoms: 87% scored 7 or higher in at least one of the pain, fatigue, or distress scales, and 30.4% of the patients scored 7 or higher on all three. The most common problem areas were feeling a burden to others, trouble talking with friends and family, spirituality, and sleep difficulties. Conclusions: Higher levels of multiple, concurrent symptoms and psychosocial problems were found in Pain Clinic patients than in a group of patients who did not attend the Pain Clinic. Routine screening and triaging of cancer patients using a comprehensive and standardized panel of questions can facilitate symptom assessment and management, and can inform program planning. Full article

Background: Of all mastectomy patients, 90% will use an external prosthesis where the standard of care uses a stock prosthesis that is purchased “off the shelf.” Our objectives were to determine patient demand for and perceived value of a custom breast prosthesis. The information obtained will influence future research and program direction. Methods: We asked 65 women who had undergone lumpectomy or mastectomy to participate before exploring rehabilitation options. The quantitative outcome measures were the European Organisation for Research and Treatment of Cancer qlq-C30 general and -BR23 breast cancer–specific quality of life questionnaires, and the Ambulatory Oncology Patients Satisfaction Tool. The QLQ results were analyzed using the Mann–Whitney U-test. Results of the satisfaction tool were compared using the Fisher exact and chi-square tests. A descriptive qualitative approach—involving in-depth interviews exploring the experiences of the women—was used to establish the perceived value of the services to the patients. The analysis of the interview transcripts was conducted using a standardized content method to describe the experiences of the women. Results: All the women had had previous experiences with a conventional prosthesis, and they reported that wearing a custom prosthesis was more satisfying for them. They reported comfort and ease in wearing it, coupled with a sense of feeling less like a victim. Comparison of the QLQ and patient satisfaction scores showed no significant difference between the women wearing the conventional prosthesis and those wearing the custom prosthesis. Conclusions: The qualitative data provide a strong case in support of the new device. Patient demand, perceived benefit, and experience wearing the prosthesis were documented. Suggestions for improvements in the device and in the program operations were gathered and will influence future development of this service. Full article