Curr. Oncol., Volume 20, Issue 5 (October 2013) – 22 articles

Drug-induced lupus erythematosus (DILE) syndromes are documented complications of chemotherapeutic agents, including paclitaxel. Subacute cutaneous lupus erythematosus (SCLE) is a distinct DILE syndrome presenting with characteristic annular or papulosquamous skin lesions in a photosensitive distribution with associated high anti-SSA titres. Previously, DILE syndromes complicating paclitaxel therapy have been attributed to polyethoxylated castor oil (Kolliphor EL: BASF, Ludwigshafen, Germany), the biologic solvent included in the drug’s original formulation (Taxol: Bristol–Myers Squibb, Montreal, QC), rather than the parent chemotherapy molecule. Here, we report a characteristic case of drug-induced SCLE complicating treatment with nanoparticle albumin bound (nab)–paclitaxel (Abraxane: Celgene, Summit, NJ, U.S.A.), a solvent-free taxane formulation. The pertinent English-language literature is also discussed. This case report is the first to link solvent-free paclitaxel with SCLE, and it suggests that the parent molecule is responsible for the reaction. Full article

The burden of cancer for Canadian citizens and society is large. New technologies have the potential to increase the use of genetic information in clinical decision-making, furthering prevention, surveillance, and safer, more effective drug therapies for cancer patients. Personalized medicine can have different meanings to different people. The context for personalized medicine in the present paper is genetic testing, which offers the promise of refining treatment decisions for those diagnosed with chronic and life-threatening illnesses. Personalized medicine and genetic characterization of tumours can also give direction to the development of novel drugs. Genetic testing will increasingly become an essential part of clinical decision-making. In Canada, provinces are responsible for health care, and most have unique policies and programs in place to address cancer control. The result is inconsistency in access to and delivery of therapies and other interventions, beyond the differences expected because of demographic factors and clinical education. Inconsistencies arising from differences in resources, policy, and application of evidence-informed personalized cancer medicine exacerbate patient access to appropriate testing and quality care. Geographic variations in cancer incidence and mortality rates in Canada—with the Atlantic provinces and Quebec having higher rates, and British Columbia having the lowest rates—are well documented. Our purpose here is to provide an understanding of current and future applications of personalized medicine in oncology, to highlight the benefits of personalized medicine for patients, and to describe issues and opportunities for improvement in the coordination of personalized medicine in Canada. Efficient and more rapid adoption of personalized medicine in oncology in Canada could help over-come those issues and improve cancer prevention and care. That taks mignth benefit from the creation of a National Genetics Advisory Panel that would review research and provide recommendations on tests for funding or reimbursement, guidelines, service delivery models, laboratory quality assurance, education, and communication. More has to be known about the current state of personalized cancer medicine in Canada, and strategies have to be developed to inform and improve understanding and appropriate coordination and delivery. Our hope is that the perspectives emphasized in this paper will stimulate discussion and further research to create a more informed response. Full article

Background: Cancer can be a devastating diagnosis. In particular, malignancy and its indicated treatments have profoundly negative effects on the fertility of young cancer patients. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. In Canada, these fertility issues are often inadequately addressed despite the availability of resources. The goal of this four-part series is to facilitate systemic improvements in fertility preservation for adolescent and young adult Canadians with a new diagnosis of cancer. Methods: Here, we describe the services currently available in Canada and the challenges associated with their utilization. Finally, we outline strategies to help maximize and facilitate fertility preservation in the young cancer patient. Results: Despite an existing infrastructure to the oncofertility system in Canada, the ability of that system’s components to function together and to coordinate patient care is a challenge. Areas of weakness include poor access and referral to fertility services, a lack of readily available education for patients and health care providers, and inconsistent interdisciplinary coordination in patient care. Conclusions: The implementation of a framework for multidisciplinary resource allocation, education, patient referral, and established lines of communication may facilitate a functional oncofertility system in Canada. Full article

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20–22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage ii colon cancer. Full article

Questions: Does chemotherapy—that is, gemcitabine, gemcitabine plus docetaxel, doxorubicin, or trabectedin—improve clinical outcomes in women with inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma (lms)? Is there a difference in the tumour response rate to chemotherapy between recurrent pelvic disease and extrapelvic metastases in the target patients? Methods: This guideline was developed by Cancer Care Ontario’s Program in Evidence-Based Care, the Sarcoma Disease Site Group (dsg), and the Gynecologic Cancer dsg. The core methodology was the systematic review. The medline and embase databases (2004 to June 2011), the Cochrane Library, main guideline Web sites, and relevant annual meeting abstracts (2005–2010) were searched. Internal and external reviews were conducted, with final approval by the dsgs and the Program in Evidence-Based Care. Clinical Practice Guideline: Based on currently available evidence from the medical literature (four single-arm phase ii studies, one arm of a randomized controlled trial, and one abstract), doxorubicin alone, gemcitabine alone, or gemcitabine plus docetaxel may be treatment options in first- or second-line therapy (or both) for women with inoperable, locally advanced, recurrent, or metastatic uterine lms. Hematologic toxicity is common and should be monitored, and granulocyte colony–stimulating factor should be considered when gemcitabine plus docetaxel is used. Other toxicities, such as neurotoxicity, pulmonary toxicity, and cardiovascular toxicity should be monitored. No recommendation is made for or against the use of trabectedin in the targeted patients. No data were available concerning differences in response in recurrent pelvic disease or extrapelvic metastases, or concerning quality of life. Full article

Giant cell tumour of bone (GCTB) is one type of giant-cell-rich bone lesion characterized by the presence of numerous multinucleated osteoclast-type giant cells. Giant cells are known to express RANKL (receptor activator of nuclear factor κB ligand) and are responsible for the aggressive osteolytic nature of the tumour. No available treatment option is definitively effective in curing this disease, especially in surgically unsalvageable cases. In recent years, several studies of denosumab in patients with advanced or unresectable GCTB have shown objective changes in tumour composition, reduced bony destruction, and clinical benefit. Denosumab is a fully human monoclonal antibody that targets and binds with high affinity and specificity to RANKL. Several large phase III studies have shown that denosumab is more effective than bisphosphonates in reducing skeletal morbidity arising from a wide range of tumours and that it can delay bone metastasis. The relevant articles are reviewed here. The controversies related to the future use of denosumab in the treatment of GCTB are discussed. Full article

Purpose: Surgical resection of the primary tumour in patients with advanced colorectal cancer (CRC) remains controversial. This review compares survival in patients with advanced crc who underwent surgical resection of the primary tumour with that in patients not undergoing resection, and determines rates of post-operative mortality and nonfatal complications, the primary tumour complication rate, the non-resection surgical procedures rate, and quality of life (QOL). Methods: Reports in the CENTRAL, MEDLINE, and EMBASE databases were searched for relevant studies, which were selected using pre-specified eligibility criteria. The search was also restricted to publication dates from 1980 onward, the English language, and studies involving human subjects. Screening, evaluation of relevant articles, and data abstraction were performed in duplicate, and agreement between the abstractors was assessed. Articles that met the inclusion criteria were assessed for quality using the Newcastle–Ottawa Scale. Data were collected and synthesized per protocol. Results: From among the 3379 reports located, fifteen retrospective observational studies were selected. Of the 12,416 patients in the selected studies, 8620 (69%) underwent surgery. Median survival was 15.2 months (range: 10–30.7 months) in the resection group and 11.4 months (range: 3–22 months) in the non-resection group. Hazard ratio for survival was 0.69 [95% confidence interval (CI): 0.61 to 0.79] favouring surgical resection. Mean rates of postoperative mortality and nonfatal complications were 4.9% (95% CI: 0% to 9.7%) and 25.9% (95% CI: 20.1% to 31.6%) respectively. The mean primary tumour complication rate was 29.7% (95% CI: 18.5% to 41.0%), and the non-resection surgical procedures rate in the non-resection group was 27.6% (95 CI: 15.4% to 39.9%). No study provided QOL data. Conclusions: Although this review supports primary tumour resection in advanced CRC, the results have significant biases. Randomized trials are warranted to confirm the findings. Full article

Recurrent nasopharyngeal carcinoma, which represents a small proportion of head-and-neck cancers, has a unique set of patho-clinical characteristics. The management of recurrent nasopharyngeal carcinoma remains a challenging clinical problem. Traditional treatments offer limited local control and survival benefits; more seriously, they frequently induce severe late complications. Recently, novel treatment techniques and strategies—including precision radiotherapy, endoscopic surgery or transoral robotic resection, third-generation chemotherapy regimens, and targeted therapies and immunotherapy—have provided new hope for patients with recurrent nasopharyngeal carcinoma. Some of these patients can potentially be cured with modern treatments. However, a lack of adequate evidence makes it difficult for clinicians to apply these powerful techniques and strategies. Individualized management guidelines, full evaluation of quality of life in these patients, and a further understanding of the mechanisms underlying recurrence are future directions for research into recurrent nasopharyngeal carcinoma. Full article

Objective: We examined whether patterns of practice in the prescription of palliative radiation therapy for bone metastases had changed over time in the Rapid Response Radiotherapy Program (RRRP). Methods: After reviewing data from August 1, 2005, to April 30, 2012, we analyzed patient demographics, diseases, organizational factors, and possible reasons for the prescription of various radiotherapy fractionation schedules. The chi-square test was used to detect differences in proportions between unordered categorical variables. Univariate logistic regression analysis and the simple Fisher exact test were also used to determine the factors most significant to choice of dose–fractionation schedule. Results: During the study period, 2549 courses of radiation therapy were prescribed. In 65% of cases, a single fraction of radiation therapy was prescribed, and in 35% of cases, multiple fractions were prescribed. A single fraction of radiation therapy was more frequently prescribed when patients were older, had a prior history of radiation, or had a prostate primary, and when the radiation oncologist had qualified before 1990. Conclusions: For patients with bone metastasis, a single fraction of radiation therapy was prescribed with significantly greater frequency. Full article

Background: Recent studies have suggested a controversial role of Helicobacter pylori infection in gastric cancer prognosis. The aim of the present study was to investigate the potential impact of H. pylori status on the prognosis of patients with gastric cancer in a Chinese prospective cohort. Methods: Between 2007 and 2009, 261 patients with curatively resected gastric cancer were enrolled in the study. H. pylori status was defined by means of immunohistochemical staining in tumour and non-neoplastic tissues. Treatment prognosis was measured in terms of cancer-specific survival and disease-free survival (DFS). Univariate and multivariate Cox regression models were used to assess the association between H. pylori status and patient prognosis. Results: Positivity for H. pylori infection was observed in 188 of the 261 patients (72.0%). In patients positive for H. pylori, mean cancer-specific survival was 55.2 months [95% confidence interval (CI): 53.4 to 56.9 months] and mean DFS was 53.9 months (95% CI: 51.8 to 56.0 months); the same survivals were, respectively, 45.1 months (95% CI: 42.2 to 47.9 months) and 43.7 months (95% CI: 40.4 to 47.0 months) in patients negative for H. pylori. In univariate analysis, positive H. pylori status was associated with better cancer-specific survival [hazard ratio (HR): 0.486; 95% CI: 0.271 to 0.870; p = 0.015] and DFS (HR: 0.540; 95% CI: 0.307 to 0.950; p = 0.033). In multivariate analysis, H. pylori was an independent prognostic factor for cancer-specific survival (HR: 0.485; 95% CI: 0.265 to 0.889; p = 0.019). Conclusions: Our study demonstrates that positive H. pylori status is a beneficial prognostic indicator in patients with gastric cancer and might suggest possible therapeutic approaches for gastric cancer. Further research is required to better understand inflammation mechanisms and cancer progression. Full article

Background: The cost-effectiveness of first-line treatment with lapatinib plus letrozole for postmenopausal women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (mBC) has not been assessed from the Canadian health care system and societal perspectives. Methods: A partitioned survival analysis model with 3 health states (alive, pre-progression; alive, post-progression; dead) was developed to estimate direct and indirect costs and quality-adjusted life years (QALYS) with lapatinib–letrozole, letrozole, anastrozole, or trastuzumab–anastrozole as first-line treatment. Clinical inputs for lapatinib–letrozole and letrozole were taken from the EGF30008 trial (NCT00073528). Clinical inputs for anastrozole and trastuzumab–anastrozole were taken from a network meta-analysis of published studies. Drug costs were obtained from the manufacturer’s price list, the Quebec list of medications, and imsBrogan. Other costs were taken from the Ontario Health Insurance Plan’s Schedule of Benefits and Fees and published studies. A 10-year time horizon was used. Costs and QALYS were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the effects of changes in model parameters. Results: Quality-adjusted life years gained with lapatinib–letrozole were 0.236 compared with trastuzumab–anastrozole, 0.440 compared with letrozole, and 0.568 compared with anastrozole. Assuming a health care system perspective, incremental costs were $5,805, $67,029, and $67,472 respectively. Given a cost per QALY threshold of $100,000, the probability that lapatinib–letrozole is preferred was 21% compared with letrozole, 36% compared with anastrozole, and 68% compared with trastuzumab–anastrozole. Results from the societal perspective were similar. Conclusions: In postmenopausal women with HR+/HRR2+ mbc receiving first-line treatment, lapatinib–letrozole may not be cost-effective compared with letrozole or anastrozole, but may be cost-effective compared with trastuzumab–anastrozole. Full article

Objectives: Data on how to identify cancer survivors (CSS) at the greatest risk for cardiovascular conditions are limited. We aimed to characterize the clinical factors associated with ischemic heart disease (IHD) and congestive heart failure (CHF) in CSS and to develop a stratification schema for predicting the risk of cardiovascular comorbidities in CSS. Methods: Cancer survivors and non-cancer controls (NCCS) were identified from the U.S. National Health and Nutrition Examination Survey. Independent factors associated with increased relative risk (RR) for cardiovascular conditions were determined. A risk stratification schema was devised that correlated risk score with the prevalence of cardiovascular comorbidities in CS. Results: Baseline characteristics were similar for the 1869 CSS and 24,337 NCCS included in the study. Compared with NCCS, CSS were more likely to report IHD (13.7% vs. 5.2%), CHF (7.9% vs. 2.1%), or both (4.2% vs. 1.2%; all p < 0.01). Based on multivariate analyses, risk factors for cardiovascular problems included ages 40–60 years RR: 3.66; 95% CI: 1.87 to 7.17), 60–80 years RR: 14.18; 95% CI: 7.65 to 26.30), and 80 years or older RR: 25.34; 95% CI: 13.16 to 48.78); male sex RR: 2.25; 95% CI: 1.72 to 2.94); U.S. citizenship RR: 2.10; 95% CI: 1.08 to 4.08); annual incomes of $20,000–$45,000 RR: 1.81; 95% CI: 1.21 to 2.70) and less than $20,000 RR: 3.05; 95% CI: 1.81 to 5.14); comorbid diabetes mellitus RR: 2.97; 95% CI: 2.05 to 4.32); and physical inactivity RR: 1.98; 95% CI: 1.41 to 2.79). Conclusions: Independent risk factors for IHD and CHF in CSS were identified. The risk stratification schema presented here may be helpful in developing a risk-based approach to preventive cardiovascular strategies for CSS. Full article

At a consensus meeting held in Montreal, October 28, 2011, a multidisciplinary group of Canadian experts in the fields of genetics, gastroenterology, surgery, oncology, pathology, and health care services participated in presentation and discussion sessions for the purpose of developing consensus statements pertaining to the development and maintenance of hereditary colorectal cancer registries in Canada. Five statements were approved by all participants. Full article

Background: Downsizing strategies are often attempted for patients with hepatocellular carcinoma (HCC) before liver transplantation (LT). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (TACE) before LT for HCC outside the Milan criteria, so as to better select candidates for this strategy. Methods: In this retrospective study, patients with HCC tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based TACE treatments. Exclusion criteria for TACE included Child–Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after TACE underwent LT. Results: Of 160 HCC patients who received liver grafts between 1997 and 2010, 35 were treated with TACE preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8–8.5 cm), which decreased with TACE to 5.0 cm (range: 3.3–7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αFP) was a positive predictor (p = 0.0051) and the time from last TACE treatment to transplantation was a negative predictor (p < 0.0001) for overall survival. Conclusions: The percentage drop in αFP and a shorter time from the final TACE treatment to transplantation significantly predicted improved overall survival after LT for HCC downsized with TACE. As a serum marker, αFP should be followed when TACE is used as a strategy to stabilize or downsize HCC lesions before LT. Full article

Background: Small-cell carcinomas (sccs) of the genitourinary (gu) tract are rare systemic diseases, and there is no standard treatment strategy for patients with this malignancy. The objectives of the present study were to report the management and outcome of patients with scc of the gu tract treated at a tertiary-care institution from 1982 to 2009. Methods: In a chart review of all patients diagnosed with scc of the gu tract between 1982 and 2009, data on demographics, clinical and pathologic characteristics, treatment, and patient outcomes were collected. Results: The 58 patients identified had scc in the following primary sites: urinary bladder (n = 35), prostate (n = 17), and upper urinary tract (n = 6). In 38 patients (66%), the scc was of pure histology; in the remainder, histology was mixed. Overall, 28 patients had limited-stage disease; 24 had extensive-stage disease; and staging was unknown in 6 patients. Median survival for the entire cohort was 7.5 months, with extensive-stage disease being identified as a poor prognostic factor (survival was 22.0 months for limited-stage patients and 4.1 months for extensive-stage patients, p < 0.001). Based on site, prostate patients fared worst, with a median survival of only 5.1 months. Compared with best supportive care, treatment was associated with better outcomes (median survival: 12.3 months vs. 2.3 months, p < 0.0001). Conclusions: Small-cell cancer of the gu tract is an aggressive cancer, with a poor prognosis overall. Although there is no standard of care, patients should be treated using a multimodality approach analogous to that used in the treatment of small-cell lung cancer. Full article

Background: Early implementation of programmatic colorectal cancer (CRC) screening for average-risk individuals 50–74 years of age in Canada has used fecal occult blood tests [FTS (guaiac or immunochemical)] and colonoscopy for follow-up of abnormal FTS. This paper presents results of an evaluation of this CRC screening. Methods: Five Canadian provincial programs provided aggregated data for individuals with a first-round FT processed between January 1, 2009, and December 31, 2011. Results: The 104,750 people who successfully completed a first round of screening represented 16.1% of those who had access to the programs between January 1, 2009, and December 31, 2011 (mean age: 61.2 years; men: 61.4 years; women: 61.1 years). Of those participants, 4661 had an abnormal FT (4.4%). Uptake of colonoscopy within 180 days after an abnormal FT was 80.5%, ranging from 67.8% to 89.5% by program. The positive predictive value (PPV) for adenoma was 35.9% for guaiac FT and 50.6% for immunochemical FT. Adenoma and CRC detection rates were, respectively, 16.9 and 1.8 per 1000 screened. Of invasive crcs detected, 64.6% were stage I or II. Conclusions: Considering the variation in characteristics and stage of implementation of each provincial program, the collaboration of the provinces leading to this report on the early performance of CRC screening in Canada is a major milestone. Targets are met or nearly met for significant indicators such as PPV for adenoma and cancer detection rate. Participation is expected to increase as programs are fully implemented in the provinces. Additional effort may be needed to improve timely access to follow-up colonoscopy. Full article

Background: Before its regulatory approval in Canada, bevacizumab to treat patients with colorectal cancer (CRC) was accessed through the Bevacizumab Expanded Access Trial and a special-access program at the Jewish General Hospital. We retrospectively evaluated patient outcomes in that large cohort. Methods: All patients (n = 196) had metastatic CRC, were bevacizumab-naïve, and received bevacizumab in combination with chemotherapy at the Jewish General Hospital between 2004 and 2009. We collected patient demographics and clinical characteristics; relevant medical history, disease stage and tumour pathology at diagnosis; type, duration, and line of therapy; grades 3 and 4 adverse events (AES), time to disease progression (TTP), and overall survival (OS) from diagnosis. Results: Median follow-up was 36.0 months. Median TTP was 8.0 months [95% confidence interval (CI): 7.0 to 9.0 months). Median OS was 41.0 months (95% CI: 36.0 to 47.0 months). Of the 40 grades 3 and 4 bevacizumabrelated AES experienced by 38 patients (19.4%), the most common were thrombocytopenia (n = 17), deep-vein thrombosis (n = 6), pulmonary embolism (n = 4), and hypertension (n = 3). Conclusions: In an expanded access setting, our data reflect the efficacy and safety of bevacizumab-based therapy in the controlled post-registration clinical trial setting. Full article