Curr. Oncol., Volume 21, Issue 6 (December 2014) – 19 articles

In the first paragraph of the article, the author mentions that “Pamela Fayerman received a grant of $20,000 from the Canadian Institutes of Health Research in 2012 to pursue health journalism research” as part of his introduction to the hypotheses of B.C. pathologist Dr. David Huntsman concerning preventive salpingectomy in women at risk of ovarian cancer. [...] Full article

The second Systemic Treatment Safety Symposium, which took place February 21, 2014, in Toronto, aimed to identify opportunities for improving the delivery of systemic cancer treatment in Ontario based on regional needs, while providing a venue for collaboration and knowledgesharing. The agenda included a series of panel sessions followed by discussions, presentations of regional improvement projects and results, and breakout sessions. Based on the discussion that took place at the symposium, a provincial goal of zero handwritten or verbal oral chemotherapy orders by June 30, 2015, has now been established, and regions will be provided with funding for safe prescribing initiatives to support achievement of that aim. Building on the lessons learned from the 2014 System Treatment Safety Symposium, a common measurement strategy will be identified, and Cancer Care Ontario (cco) will also support the work by identifying the recommended key elements of a safe oral chemotherapy prescription. Additionally, cco will identify areas for improving systemic treatment computerized prescriber order entry systems to better enable prescribing of oral agents within such systems. Among the most prominent of the lessons learned during the symposium was the importance of having a focused topic (such as oral chemotherapy) while maintaining a province-wide scope. Another significant takeaway was that attendees appreciate the opportunity to hear from colleagues across the province about the work underway in various regions. Future safety symposia will also explore opportunities for enhanced engagement with participants through greater use of technology. Full article

Background: Children with high-grade glioma still have a poor prognosis despite the use of multimodal therapy including surgery, radiotherapy, and chemotherapy. New therapeutic strategies and methods evaluating such therapies are needed. Observation: Here we describe a child with anaplastic oligodendroglioma of the spinal cord who was unable to tolerate standard chemoradiotherapy and who had still-vital residual tumour during therapy. A good response was obtained with low-dose metronomic treatment containing vinblastine. The treatment was guided according to gradual response assessed using various positron-emission tomography tracers. Conclusions: Metronomic treatment guided by positron-emission tomography could be a reasonable option in some high-risk pediatric tumours. Full article

Angiosarcoma is a rare and aggressive type of sarcoma, and primary angiosarcoma of the ovary is extremely rare. We report the case of a 29-year-old woman who was diagnosed with ovarian angiosarcoma and possible bone metastases. We treated this patient with a gemcitabine-based regimen as postoperative adjuvant chemotherapy, after which she achieved at least 7 years of progression-free survival, an extremely long duration given the aggressive features of this tumour. We retrospectively performed immunohistochemical analyses and fluorescence in situ hybridization to make a pathology diagnosis and to investigate the tumour features. MYC amplification and c-Myc protein overexpression were positively detected. It might be possible to correlate the effectiveness of the gemcitabine-based chemotherapeutic regimen with MYC gene amplification and c-Myc protein overexpression. Full article

Glioblastoma is the most common form of primary brain cancer. Its treatment involves surgery, radiotherapy, and chemotherapy with temozolomide (TMZ), which is an oral alkylating agent. To the best of our knowledge, few dermatologic side effects of TMZ have been described. We report two cases of cutaneous drug eruption caused by TMZ during and after radiochemotherapy treatment. In the first case, all tests were negative, but the clinical history and the time of onset supported an allergy to TMZ. In the second case, an allergy to TMZ was proved by a positive lymphocyte activation test. In this context, our study is one of a very few trying to determine dermatologic side effects by applicable tests used in routine practice. Full article

Follicular dendritic cell sarcoma (FDCS) is a rare entity, often presenting a diagnostic challenge for both the pathologist and the clinician. It accounts for only 0.4% of soft-tissue sarcomas, and its underlying causes are largely unknown. Most of these tumours occur in lymph nodes, and extranodal involvement is uncommon. In the gastrointestinal tract, FDCS is extremely rare. Here, we report a case of primary FDCS originating in the stomach. Upon review of the literature, we identified only 2 additional cases of FDCS presenting as a primary stomach tumour. Given the rarity of this tumour in gastrointestinal sites and the lack of consensus on treatment, evaluation of this entity must continue. Full article

Background: Combined positron-emission tomography and computed tomography (PET-CT) reduces futile thoracotomy (FT) rates in patients with non-small-cell lung cancer (NSCLC). We sought to identify preoperative risk factors for FT in patients staged with PET-CT. Methods: We retrospectively reviewed all patients referred to the BC Cancer Agency during 2009–2010 who underwent PET-CT and thoracotomy for NSCLC. Patients with clinical N2 disease were excluded. An FT was defined as any of a benign lesion; an exploratory thoracotomy; pathologic N2 or N3, stage IIIB or IV, or inoperable T3 or T4 disease; and recurrence or death within 1 year of surgery. Results: Of the 108 patients who met the inclusion criteria, FT occurred in 27. The main reason for FT was recurrence within 1 year (14 patients) and pathologic N2 disease (10 patients). On multivariate analysis, an Eastern Cooperative Oncology Group performance status greater than 1, a PET-CT positive N1 status, a primary tumour larger than 3 cm, and a period of more than 16 weeks from PET-CT to surgery were associated with FT. N2 disease that had been negative on PET-CT occurred in 21% of patients with a PET-CT positive N1 status and in 20% of patients with tumours larger than 3 cm and non-biopsy mediastinal staging only. The combination of PET-CT positive N1 status and a primary larger than 3 cm had 85% specificity, and the presence of either risk factor had 100% sensitivity, for FT attributable to N2 disease. Conclusions: To reduce FT attributable to N2 disease, tissue biopsy for mediastinal staging should be considered for patients with PET-CT positive N1 status and with tumours larger than 3 cm even with a PET-CT negative mediastinum. Full article

Purpose: We evaluated the novel combination of aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting (RINV) among patients receiving moderately-emetogenic radiotherapy for thoracolumbar bone metastases. Methods: In this single-centre two-arm nonrandomized prospective pilot study, patients undergoing single-fraction radiotherapy (8 Gy) received aprepitant 125 mg and granisetron 2 mg on the day of radiotherapy and aprepitant 80 mg on each of the first 2 days after the day of radiotherapy. Patients undergoing multiple-fraction radiotherapy (20 Gy in 5 fractions) received aprepitant 125 mg on day 1 of radiotherapy, aprepitant 80 mg on days 3 and 5 of radiotherapy, and granisetron 2 mg on every day of radiotherapy. Symptoms and total medication intake were recorded daily during the acute phase (day 1 of radiotherapy until the first day after the last day of radiotherapy), and the delayed phase (days 2–10 after the last day of radiotherapy). Control of vomiting, retching, and nausea was defined as no symptoms and no use of rescue medication. Results: Control rates for single-fraction patients (n = 13) were 100% for acute nausea, 62% for delayed nausea, 100% for acute vomiting and retching, and 85% for delayed vomiting and retching. Control rates for multiple-fraction patients (n = 6) were 67% for acute nausea, 83% for delayed nausea, 67% for acute vomiting and retching, and 83% for delayed vomiting and retching. No grade 3 or 4 toxicities attributable to the study intervention were observed. Conclusions: The combination of aprepitant and granisetron was safe and efficacious for the prophylaxis of RINV after both single- and multiple-fraction moderately emetogenic radiotherapy for thoracolumbar bone metastases. Our results require confirmation in a larger population. Full article

(1) Background: In the phase iii palette trial of pazopanib compared with placebo in patients with advanced or metastatic soft-tissue sarcoma (sts) who had received prior chemotherapy, pazopanib treatment was associated with improved progression-free survival (pfs). We used an economic model and data from palette and other sources to evaluate the cost-effectiveness of pazopanib in patients with advanced sts who had already received chemotherapy. (2) Methods: We developed a multistate model to estimate expected pfs, overall survival (os), lifetime sts treatment costs, and quality-adjusted life-years (qalys) for patients receiving pazopanib or placebo as second-line therapy for advanced sts. Cost-effectiveness was calculated alternatively from the health care system and societal perspectives for the province of Quebec. Estimated pfs, os, incidence of adverse events, and utilities values for pazopanib and placebo were derived from the palette trial. Costs were obtained from published sources. (3) Results: Compared with placebo, pazopanib is estimated to increase qalys by 0.128. The incremental cost of pazopanib compared with placebo is CA$20,840 from the health care system perspective and CA$15,821 from the societal perspective. The cost per qaly gained with pazopanib in that comparison is CA$163,336 from the health care system perspective and CA$124,001 from the societal perspective. (4) Conclusions: Compared with placebo, pazopanib might be cost-effective from the Canadian health care system and societal perspectives depending on the threshold value used by reimbursement authorities to assess novel cancer therapies. Given the unmet need for effective treatments for advanced sts, pazopanib might nevertheless be an appropriate alternative to currently used treatments. Full article

Purpose: We investigated correlations of somatic BRAF V600E mutation and RET/PTC1 rearrangement with recurrent disease in Chinese patients with papillary thyroid carcinoma (PTC). Methods: This prospective study included 214 patients with PTC histologically confirmed between November 2009 and May 2011 at a single institute. Results: We found somatic BRAF V600E mutation in 68.7% and RET/PTC1 rearrangement in 25.7% of the patients. Although BRAF mutation was not significantly associated with clinicopathologic features such as patient sex or age, multicentric disease, thyroid capsule invasion, tumour stage, or nodal metastasis, it was significantly associated with recurrent disease. Multivariate analysis revealed that BRAF mutation and tumour size were independent risk factors associated with recurrent disease, with odds ratios of 9.072 and 2.387 respectively. The area under the receiver operating characteristic curve increased 8.3% when BRAF mutation was added to the traditional prognostic factors, but that effect was statistically nonsignificant (0.663 vs. 0.746, p = 0.124). RET/PTC1 rearrangement and nodal metastasis were significantly associated in all patients (p = 0.042), marginally associated in PTC patients (p = 0.051), but not associated in microPTC patients (p = 0.700). RET/PTC1 rearrangement was not significantly associated with recurrent disease. Conclusions: BRAF positivity is an independent predictor of recurrent disease in PTC. Full article

Treatment for non-small-cell lung cancer (nsclc) is moving away from traditional chemotherapy toward personalized medicine. The reversible tyrosine kinase inhibitors (tkis) erlotinib and gefitinib were developed to target the epidermal growth factor receptor (egfr). Afatinib, an irreversible ErbB family blocker, was developed to block egfr (ErbB1), human epidermal growth factor receptor 2 (ErbB2), and ErbB4 signalling, and transphosphorylation of ErbB3. All of the foregoing agents are efficacious in treating nsclc, and their adverse event profile is different from that of chemotherapy. Two of the most common adverse events with egfr tkis are rash and diarrhea. Here, we focus on diarrhea. The key to successful management of diarrhea is to treat early and aggressively using patient education, diet, and antidiarrheal medications such as loperamide. We also present strategies for the effective assessment and management of egfr tki–induced diarrhea. Full article

Background: Before the emergence of first-line combination chemotherapy, the standard of care for unresectable metastatic colorectal cancer (mCRC) was first-line monotherapy with modulated 5-fluorouracil. Several large phase III randomized controlled trials, now completed, have assessed whether a planned sequential chemotherapy strategy—beginning with fluoropyrimidine monotherapy until treatment failure, followed by another regimen (either monotherapy or combination chemotherapy) until treatment failure—could result in the same survival benefit produced with an upfront combination chemotherapy strategy, but with less toxicity for patients. Methods: The MEDLINE and EMBASE databases, and abstracts from meetings of the American Society for Clinical Oncology and the European Society for Medical Oncology, were searched for reports comparing a sequential strategy of chemotherapy with an upfront combination chemotherapy in adult patients with mcrc. Publications that reported efficacy or toxicity data (or both) were included. Results: The five eligible trials that were identified included 4532 patients. A meta-analysis of those trials demonstrates a statistically significant survival advantage for combination chemotherapy (hazard ratio: 0.92; 95% confidence interval: 0.86 to 0.99). However, the median survival advantage (3–6 weeks in most trials) is small and of questionable clinical significance. Three trials reported first-line toxicities. Upfront combination chemotherapy results in significantly more neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, nausea, vomiting, and sensory neuropathy. Sequential chemotherapy results in significantly more hand–foot syndrome. Conclusions: Given the small survival advantage associated with upfront combination chemotherapy, planned sequential chemotherapy and upfront combination chemotherapy can both be considered treatment strategies. Treatment should be chosen on an individual basis considering patient and tumour characteristics, toxicity of each strategy, and patient preference. Full article

Molecular strategies to improve outcomes for patients with pancreatic neuroendocrine tumours (nets) have focused on targeting vascular endothelial growth factor, platelet-derived growth factor, and mtor (the mammalian target of rapamycin). This approach has led to the regulatory approval of two molecularly targeted agents for advanced pancreatic nets: sunitinib, a multi-targeted tyrosine kinase inhibitor, and everolimus, an mtor inhibitor. Initial experience with sunitinib in advanced pancreatic net was gained from the phase iii registration trial, which used a continuous daily dosing (cdd) schedule instead of daily drug administration for 4 consecutive weeks every 6 weeks (schedule 4/2), the approved schedule for advanced renal cell carcinoma (rcc) and gastrointestinal stromal tumour (gist). Clinical experience gained with schedule 4/2 in rcc and gist shows that, using a therapy management approach, patients can start and be maintained on the recommended dose and schedule, thus optimizing treatment outcomes. Here, we discuss challenges that can potentially be faced by physicians who use sunitinib on the cdd schedule, and we use clinical data and real-life clinical experience to present therapy management approaches that support cdd in advanced pancreatic net. Full article

Background: Activating mutations of the epidermal growth factor receptor (EGFR) gene are known to drive a proportion of non-small-cell lung cancers. Identification of lung cancers harbouring such mutations can lead to effective treatment using one of the agents that targets and blocks EGFR-mediated signalling. Methods: All specimens received at the BC Cancer Agency (Vancouver) for EGFR testing were prospectively identified and catalogued, together with clinical information and EGFR status, over a 14-month period. Results: Specimens from 586 patients were received for EGFR testing, and EGFR status was reported for 509 patients. No relationship between specimen type or site of origin and EGFR test failure rate was identified. Concurrent immunohistochemical (IHC) status for thyroid transcription factor 1 (TTF1) was available for 309 patients. The negative predictive value of TTF1-negative status by IHC was 94.2% for predicting negative EGFR status. Conclusions: In patients with limited tissue available for testing, a surrogate for EGFR status would aid in timely management. Immunohistochemistry for TTF1 is readily available and correlates highly with EGFR status. In conjunction with genetic assays, TTF1 could be used to optimize an EGFR testing strategy. Full article

Background: Cervical cancer (cca) is largely a preventable disease if women receive regular screening, which allows for the detection and treatment of preinvasive lesions before they become invasive. Having been inadequately screened is a common finding among women who develop cca. Our primary objective was to determine the Pap screening histories of women diagnosed with cca in Montreal, Quebec. Secondary objectives were to determine the characteristics of women at greatest risk of cca and to characterize the level of physician contact those women had before developing cca. Methods: The Invasive Cervical Cancer Study, a population-based case–control study, consisted of Greater Montreal residents diagnosed with histologically confirmed cca between 1998 and 2004. Respondents to the 2003 Canadian Community Health Survey and a sample of women without cca obtained from Quebec medical billing records served as controls. Results: During the period of interest, 568 women were diagnosed with cca. Immigrants and women speaking neither French nor English were at greatest risk of cca. Most of the women in the case group had been screened at least once during their lifetime (84.8%–90.4%), but they were less likely to have been screened within 3 years of diagnosis. Having received care from a family physician or a medical specialist other than a gynecologist within the 5 years before diagnosis was associated with a greater risk of cca development. Conclusions: Our findings provide evidence of the need for an organized population-based screening program. They also underscore the need for provider education to prevent missed opportunities for cca screening when at-risk women seek medical attention. Full article

Objective: The objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (BCa) patients by disease stage. Methods: Incident cases of female invasive BCa (2005–2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of BCa patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars. Results: This cohort study involved 39,655 patients with BCa and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most BCa patients were classified as either stage I (34.4%) or stage II (31.8%). Of the BCa cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per BCa case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: I, $29,938; II, $46,893; III, $65,369; and IV, $66,627. The attributable cost of BCa was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. Conclusions: Costs of care increased by stage of BCa. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources. Full article