Curr. Oncol., Volume 16, Issue 5 (September 2009) – 16 articles

Please be advised that there is an error in Table I of “The Role of HER2-targeted Therapies in Women with HER2-Overexpressing Metastatic Breast Cancer” by Dent et al. which appeared in Current Oncology Volume 16, Number 4 on page 236 in print, and page 26 online [...] Full article

The 4th annual Ontario Thoracic Cancer Conference at Niagara-on-the-Lake focused on the themes of innovations in the management of lung cancer, controversies in the management of esophageal cancer, and molecular targeted therapies in lung cancer. This conference summary highlights the presentations and provides clinicians with a referenced update on these topics. Full article

Background: Germline mutation screening of BRCA1 and BRCA2 genes is performed in suspected familial breast cancer cases, but a causative mutation is found in only 30% of patients. The development of additional methods to identify good candidates for BRCA1 and BRCA2 analysis would therefore increase the efficacy of diagnostic mutation screening. With this in mind, we developed a study to determine molecular signatures of BRCA1—or BRCA2—mutated breast cancers. Materials and Methods: Array-cgh (comparative genomic hybridization) and transcriptomic analysis were performed on a series of 103 familial breast cancers. The series included 7 breast cancers with a BRCA1 mutation and 5 breast cancers with a BRCA2 mutation. The remaining 91 cases were obtained from 73 families selected on the basis of at least 3 affected first-degree relatives or at least 2 affected first-degree relatives with breast cancer at an average age of 45 years. Array-cgh analyses were performed on a 4407 BAC-array (CIT-V8) manufactured by IntegraGen. Transcriptomic analyses were performed using an Affymetrix Human Genome U133 Plus 2.0 chip. Results: Using supervised clustering analyses we identified two transcriptomic signatures: one for BRCA1-mutated breast cancers consisting of 600 probe sets and another for BRCA2-mutated breast cancers also consisting of 600 probes sets. We also defined cgh-array signatures, based on the presence of specific genomic rearrangements, one for BRCA1-mutated breast cancers and one for BRCA2-mutated breast cancers. Conclusions: This study identified molecular signatures of breast cancers with BRCA1 or BRCA2 germline mutations. Genes present in these signatures could be exploited to find new markers for such breast cancers. We also identified specific genomic rearrangements in these breast cancers, which could be screened for in a diagnostic setting using fluorescence in situ hybridization, thus improving patient selection for BRCA1 and BRCA2 molecular genetic analysis. Full article

Oncogenic osteomalacia is a rare metabolic bone disease characterized by phosphate leakage from the kidney and subsequent hypophosphatemia. It is caused by a phosphaturic factor produced by certain tumours. Removal of such tumours can completely cure the condition. Here, we report the case of a patient who was crippled with oncogenic osteomalacia. Extensive study revealed a tumour deeply located in the pelvis; removal of the tumour resulted in complete recovery. The tumour was identified as a mesenchymal tumour (mixed connective-tissue variant). The diagnostic evaluation, differential diagnosis, and treatment are discussed. Full article

Bevacizumab is currently approved in association with first- and second-line 5-fluorouracil–based chemotherapy regimens for patients with metastatic colorectal cancer. Few data about the usefulness of bevacizumab in third-line settings are available. We describe a patient refractory to folfiri and folfox chemotherapy regimens who showed a dramatic and durable response to bevacizumab and folfiri. We also review and discuss the available literature. Full article

Extramammary Paget disease is a rare intraepithelial neoplasm of the vulvar, penoscrotal, or perianal skin. No effective therapies for metastatic disease have been reported, and prognosis for metastatic disease is poor. Here, we report the case of an Asian man who was initially diagnosed with extramammary Paget disease of the scrotum. Three years later, the patient presented to hospital with pancytopenia and back pain. After an extensive work-up, biopsies of liver and bone marrow revealed adenocarcinoma with signet cells and immunohistochemical staining positive for keratin 7, carcinoembryonic antigen, and prolactininduced protein, but negative for keratin 20, S100, and prostate markers, consistent with his previous biopsyproven Paget disease of the scrotum. The patient was treated with 5-fluorouracil–based therapy in addition to palliative radiotherapy to selected spine levels. A promising palliative response was demonstrated following 5-fluorouracil chemotherapy. A review of the literature on the pathogenesis, diagnosis, treatment options, and outcomes for metastatic extramammary Paget disease is presented. Full article

Treatment of patients with metastatic colorectal cancer has changed in recent years, with many patients now being offered intent-to-treat regimens. In this context, a multidisciplinary approach to the metastatic disease may lead to individualized treatment for any patient. Stereotactic body radiotherapy (sbrt) is not the most common treatment. Here, we present the clinical case of a patient with a solitary liver metastasis initially treated with sbrt that was rescued with surgery when a local recurrence was detected. Full article

This integrative review critically examines quantitative and qualitative evidence concerning factors influencing the participation of Canadian women in mammography. Empirical studies published between 1980 and 2006 were identified and retrieved by searching electronic databases and references listed in published studies. Among the 1461 citations identified and screened, 52 studies met the inclusion criteria and were independently appraised by two researchers. Extracted data were categorized, summarized, compared, and interpreted within and across studies. The presentation of barriers and facilitators to mammography was guided by the Pender Health Promotion Model. Findings from this review showed that no published studies were specific to settings in Saskatchewan, Nova Scotia, Prince Edward Island, Newfoundland and Labrador, and the three Canadian territories. The most common barriers to screening were membership in an ethnic minority and concerns about pain, radiation, and embarrassment. The recommendation of a health care provider for mammography was found to be the most common facilitator for the engagement of women in this health behaviour. The targeting of specific strategies aimed at overcoming identified barriers and the enhancement of facilitators are essential to improving mammography participation rates throughout Canada. Full article

Introduction: Our study examined the wait time from ready-to-treat to radiation therapy for cohorts of breast cancer patients requiring adjuvant radiation therapy in 2001 and in 2005 after the implementation of strategies to reduce wait times for radiation treatment. We also examined the overall time from diagnosis to radiation treatment and whether distance from the cancer treatment centre or month of referral had an effect on wait times. Methods: This population-based retrospective study looked at representative samples of women newly diagnosed with breast cancer in 2001 and 2005. Patients who required radiation treatment to the breast or chest wall were followed from first contact to the start of radiation treatment. Results: Time from ready-to-treat to first radiation treatment was significantly reduced for patients in 2005 as compared with 2001, regardless of whether chemotherapy was administered before radiation treatment. Time from diagnosis to radiation treatment was not different by year for those who received radiation only. Time from diagnosis to chemotherapy was significantly longer in 2005. No effect of month of diagnosis on wait times was observed. Interpretation: A significant improvement in the median wait time from ready-to-treat to first radiation treatment was noted from 2001 to 2005. This improvement may be attributable to measures taken to reduce such waits. However, we observed an increase in the median time from diagnosis to referral and from referral to consultation with medical or radiation oncology (or both), so that the overall time from diagnosis to radiation treatment was not different. Although specific intervals related to radiation treatment delivery were improved, the entire trajectory of breast cancer care experienced by patients needs to be considered. Full article

Women receiving neoadjuvant systemic therapy for primary operable or inoperable breast cancer can potentially benefit in a number of ways, but the main advantage, which has been consistently demonstrated, is improved tumour resectability. Given the improvement in outcomes with the adjuvant use of trastuzumab in patients with early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2), questions have been raised about the use of trastuzumab in the neoadjuvant setting. The present paper reviews the currently available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other her2-targeted agents in the neoadjuvant setting. The panel focussed on (1) the use of trastuzumab and other her2-targeted agents as neoadjuvant therapy in primary operable, locally advanced, and inflammatory breast cancer; and (2) possible choices of chemotherapeutic regimens with trastuzumab. The suggestions described here will continue to evolve as data from current and future trials with trastuzumab and other her2-targeted agents emerge. Full article

Radioimmunoconjugates are radioisotope-bound monoclonal antibodies that target radiation specifically to sites of lymphoma involvement. Initial studies of ¹³¹I–tositumomab in non-Hodgkin lymphoma (nhl) have suggested benefit in patients with relapsed or refractory indolent disease. However, the routine adoption of this agent is tempered by concerns about associated toxicities and unclear long-term benefit. Based on a comprehensive search for studies on ¹³¹I–tositumomab use in lymphoma, this systematic review summarizes and evaluates the evidence on (1) the benefits and risks of this novel therapy, (2) the predictors for response and toxicity, and (3) the role of dosimetry and imaging studies before treatment. We identified 18 trials investigating the use of ¹³¹I–tositumomab for the treatment of adult patients with nhl. In trials of patients with relapsed or refractory indolent nhl, overall response rates ranged from 67% to 83%. In patients with follicular nhl refractory to the monoclonal antibody rituximab, response rates remained high (65%–72%). However, in rituximabnaïve patients with relapsed or refractory indolent or transformed nhl, improvements in time to progression or survival have not been clearly established. ¹³¹I–Tositumomab is an active agent in relapsed and refractory non-Hodgkin lymphoma that should be considered in selected patients. Full article

Background: Standard treatment for differentiated thyroid cancer is thyroidectomy followed in selected cases by radioiodine ablation (ra). Recombinant humanized thyroid-stimulating hormone (rhtsh) is an exogenous source of tsh that can be administered to obviate the need for hormone withdrawal. In this systematic review, we analysed the evidence for the therapeutic use of rhtsh for ra preparation. Method: A systematic review of the medline and embase databases from 1996 through January 2008 selected articles reporting randomized controlled trials, cohort studies, and retrospective studies published in English that compared ra using rhtsh with standard hormone withdrawal. Results and Interpretation: Stimulation by rhtsh is equivalent to thyroid hormone withdrawal in achieving ablation while avoiding detrimental symptoms of hypothyroidism and significantly lowering the whole-body radiation dose. Furthermore, rhtsh may be the only option for patients who either cannot raise endogenous tsh or who would be at risk from the morbidity of hypothyroidism. Based on the results of validated instruments of physical and mental performance, there is agreement that rhtsh maintains a better quality of life. Studies of cost-effectiveness found that rhtsh-prepared patients lost less time from work and required fewer encounters with health care providers. Full article

Objective: The aim of the present study was to survey human resources personnel about how their northeastern Ontario workplaces assist employees with cancer. Study Design and Setting: This cross-sectional study was conducted from December 2007 to April 2008. Surveys were sent to 255 workplaces in northeastern Ontario with 25 or more employees, and 101 workplaces responded (39.6% response rate). Logistic regression modelling was used to identify factors associated with more or less workplace support. More or less workplace support was defined by provision of paid time to employees with medical appointments and an offer of a return-to-work meeting and reduced hours for employees with cancer. Factors considered in the model included organization size, geographic location (urban, rural), and workplace type (private sector, public sector). Results: Most of the human resources staff who completed the surveys were women (67.4%), and respondents ranged in age from 25 to 70 years (mean: 45.30 ± 8.10 years). Respondents reported working for organizations that ranged in size from 25 to more than 9000 employees. In the logistic regression model, large organization size [odds ratio (or): 6.97; 95% confidence interval (ci): 1.34 to 36.2] and public sector (or: 4.98; 95% ci: 1.16 to 21.3) were associated with employer assistance. Public sector employers provided assistance at a rate 5 times that of private sector employers, and large organizations (>50 employees) provided assistance at a rate 7 times that of smaller organizations. Conclusions: In the population studied, employees with cancer benefit from working in larger and public sector organizations. The data suggest a need for further support for employees with cancer in some other organizations. Full article

Background: The BC Cancer Agency Gastro-intestinal Tumor Group supports one standard of care (soc) chemotherapy regimen for metastatic esophagogastric adenocarcinoma—specifically, weekly cisplatin and 5-fluorouracil (5fu) infusion. All other regimens require Compassionate Access Program (cap) approval for public funding. Objectives: We examined response, toxicity, and survival after first-line cap chemotherapy (cap1), or soc and second-line cap chemotherapy (cap2). Patients and Methods: We searched cap records for December 1999 to April 2006, abstracted charts, constructed a database, and undertook survival analyses. Treatment response, serious toxicities, and hospitalizations were recorded. Results: We identified 32 esophageal (10 gastroesophageal junction) and 53 gastric cancer (62%) patients, 55 of whom were stage M1 at diagnosis. Prior therapy consisted of chemoradiotherapy (n = 14), adjuvant chemotherapy (n = 3), and radical surgery (n = 34). Of these 85 patients, 50 received cap1, and 35 received soc, then cap2. Docetaxel and irinotecan regimens accounted for 34% and 36%, 5% and 55%, 16% and 32% respectively of first-, second-, and third-line cap requests. Partial responses were documented with soc (11/35, 31%) and cap1 (6/50, 12%). Grade 3+ toxicity rates were 19/50 (38%) and 6/35 (17%) with cap1 and soc chemotherapy. With cap chemotherapy, 20 hospitalizations occurred, and with soc chemotherapy, 2 hospitalizations. For all patients, median follow-up and survival times were 8.9 months and 9.7 months respectively. Limitations: This is a retrospective analysis of patients deemed suitable to receive non-soc chemotherapy regimens or unsuitable to receive soc chemotherapy. Conclusions: Toxicities in cap chemotherapy regimens were substantial. Survival times were consistent with results of international phase ii and iii trials in esophagogastric cancer. Full article