Curr. Oncol., Volume 18, Issue 3 (June 2011) – 15 articles

Rosai–Dorfman disease is a rare lymphoproliferative disorder that can have nodal and extranodal manifestations. In the absence of established guidelines for the management of this condition, various therapeutic modalities are used, including radiotherapy. Radiation dosages and fractionation schedules have not been reported in all instances. We present a case in which glottic and subglottic Rosai–Dorfman lesions causing airway obstruction in a frail steroid-refractory patient were put into complete remission using radiotherapy. The lesions responded transiently to a course of prednisone, but responded completely to external-beam radiation, with minimal side effects to the patient. Full article

With the recent approval by the U.S. Food and Drug Administration of the first therapeutic vaccine for cancer, the long-awaited goal of harnessing a patient’s immune system to attack cancer through this modality is finally realized. However, as researchers in the field of cancer immunotherapy continue to perform randomized definitive studies, much remains to be learned about potential surrogate endpoints and appropriate patient populations for therapeutic vaccines. The present review addresses available data from clinical trials of immunotherapeutic agents relevant to the selection of appropriate patient populations. We believe that the weight of evidence supports the use of immunotherapy earlier in the disease course and in patients with less aggressive disease, and that the relevant findings have important implications for the design of clinical trials with therapeutic vaccines. Full article

The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11–12, 2010. The meeting focused on current and future directions in labc treatment and research, the specific benefits of labc as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in labc research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference. Full article

Aims: Distributed delivery models for cancer care have been introduced to bring care closer to home and to provide better access to cancer patients needing radiotherapy. Very little work has been done to demonstrate the elements critical for success in a non-centralized approach. The present study set out to identify the elements that are important for implementing radiotherapy away from large cities. Methods and Results: This qualitative research project consisted of two separate components. In the first component, structured interviews were conducted with 5 external experts. Input on the expert responses was then sought from internal leaders in medical physics, radiation therapy, and radiation oncology. Those interviews were used to develop a proposed template of the elements needed in a small-city department. We tested the validity of all elements by surveying staff members from the radiation treatment program in Calgary, leading to a definition of the resources needed for the proposed department in Lethbridge. Seventy-five staff members contributed to the survey. Conclusions: Qualitative research methods allowed us to define important elements for a small-city radiotherapy department and to validate those elements with a large cohort of staff working in a tertiary centre. This work has influenced the planning of a small-city department in Lethbridge, emphasizing the importance of the elements identified to the service planners. We await the completion of the construction project and the opening of the centre so that we can re-evaluate the importance of the identified elements in actual practice. We recommend such an approach to jurisdictions that are considering devolved radiotherapy. Full article

Non-small-cell lung cancer (nsclc) has the highest prevalence of all types of lung cancer, which is the second most common cancer and the leading cause of cancer-related mortality in Canada. The need for more effective and less toxic treatment options for nsclc has led to the development of agents targeting the epidermal growth factor receptor (egfr)–mediated signalling pathway, such as egfr tyrosine kinase inhibitors (egfr-tkis). Although egfr-tkis are less toxic than traditional anti-neoplastic agents, they are commonly associated with acneiform-like rash and diarrhea. This review summarizes the clinical presentation and causes of egfr-tki–induced rash and diarrhea, and presents strategies for effective assessment, monitoring, and treatment of these adverse effects. Strategies to improve the management of egfr-tki–related adverse events should improve clinical outcomes, compliance, and quality of life in patients with advanced nsclc. Full article

Recommendation 1: Multidisciplinary Approach: To optimize treatment outcomes, the management of patients with recurrent glioblastoma should be individualized and should involve a multidisciplinary team approach, including neurosurgery, neuropathology, radiation oncology, neuro-oncology, and allied health professions. Recommendation 2: Imaging: The standard imaging modality for assessment of recurrent glioblastoma is Gd-enhanced magnetic resonance imaging (MRI). Tumour recurrence should be assessed according to the criteria set out by the Response Assessment in Neuro-Oncology Working Group. The optimal timing and frequency of MRI after chemoradiation and adjunctive therapy have not been established. Recommendation 3: Pseudo-progression: Progression observed by MRI after chemoradiation can be pseudo-progression. Accordingly, treated patients should not be classified as having progressive disease by Gd-enhancing MRI within the first 12 weeks after the end of radiotherapy unless new enhancement is observed outside the radiotherapy field or viable tumour is confirmed by pathology at the time of a required re-operation. Adjuvant temozolomide should be continued and follow-up imaging obtained. Recommendation 4: Repeat Surgery: Surgery can play a role in providing symptom relief and confirming tumour recurrence, pseudo-progression, or radiation necrosis. However, before surgical intervention, it is essential to clearly define treatment goals and the expected impact on prognosis and the patient’s quality of life. In the absence of level 1 evidence, the decision to re-operate should be made according to individual circumstances, in consultation with the multidisciplinary team and the patient. Recommendation 5: Re-irradiation: Re-irradiation is seldom recommended, but can be considered in carefully selected cases of recurrent glioblastoma. Recommendation 6: Systemic Therapy: Clinical trials, when available, should be offered to all eligible patients. In the absence of a trial, systemic therapy, including temozolomide rechallenge or antiangiogenic therapy, may be considered. Combination therapy is still experimental; optimal drug combinations and sequencing have not been established. Full article

It has been 21 years since the first successful use of umbilical cord blood as a source of donor cells for hematopoietic stem cell transplantation (HSCT). Over those years, cord blood transplantation (CBT) has shown marked success as an effective modality in the treatment of children and adults with hematologic malignancies, marrow failure, immunodeficiency, hemoglobinopathy, and inherited metabolic diseases. Furthermore, transplantation without full human leukocyte antigen (HLA) matching is possible and, despite a lower incidence of graft-versus-host disease, graft-versus-leukemia effect is preserved. More than 20,000 cbts have been performed worldwide. Ontario is the most populated province in Canada, and its CBT numbers have increased dramatically in recent years, but most of the umbilical cord blood units are purchased from unrelated international registries. There is no public cord bank in Ontario, but there is a private cord banking option, and notably, Ontario has the largest number of live births in Canada [approximately 40% of all Canadian live births per year occur in Ontario (Statistics Canada, 2007)]. In this brief review, the pros and cons of private and public cord banking and the feasibility of starting an Ontario public cord bank are discussed. Full article

Background: The efficacy of adjuvant chemotherapy with FEC-D (5-fluorouracil–epirubicin–cyclophosphamide followed by docetaxel) is superior to that with FEC-100 alone in women with early-stage breast cancer. As the use of FEC-D increased in clinical practice, health care providers anecdotally noted higher-than-expected toxicity rates and frequent early treatment discontinuations because of toxicity. In the present study, we compared the rates of serious adverse events in patients who received adjuvant FEC-D chemotherapy in routine clinical practice with the rates reported in the PACS-01 trial. Methods: We retrospectively reviewed all patients prescribed adjuvant FEC-D for early-stage breast cancer at 4 regional cancer centres in Ontario. Information was collected from electronic and paper charts by a physician investigator from each centre. Data were analyzed using chi-square tests, independent samples t-tests, one-way analysis of variance, and univariate regression. Results: The 671 electronic and paper patient records reviewed showed a median patient age of 52.2 years, 229 patients (34.1%) with N0 disease, 508 patients (75.7%) with estrogen or progesterone receptor–positive disease (or both), and 113 patients (26%) with HER2/neu–overexpressing breast cancer. Febrile neutropenia occurred in 152 patients (22.7%), most frequently at cycle 4, coincident with the initiation of docetaxel [78/152 (51.3%)]. Conclusions: Primary prophylaxis with hematopoietic growth factor support was used in 235 patients (35%), and the rate of febrile neutropenia was significantly lower in those who received prophylaxis than in those who did not [15/235 (6.4%) vs. 137/436 (31.4%); p < 0.001; risk ratio: 0.20]. In routine clinical practice, treatment with FEC-D is associated with a higher-than-expected rate of febrile neutropenia, in light of which, primary prophylaxis with growth factor should be considered, per international guidelines. Adoption based on clinical trial reports of new therapies into mainstream practice must be done carefully and with scrutiny. Full article

O. Harold Warwick graduated in medicine from McGill University as a gold medalist and Rhodes Scholar in 1940. After World War II, he started postgraduate training in Montreal, and in 1946, he began studying the newly described drug treatment of cancer in London, England. There he carried out the first study of nitrogen mustard in a group of adult patients with a non-hematologic solid tumour, lung cancer. After a brief period of practice in Montreal, he moved in 1948 to Toronto, where he became executive director of the Canadian Cancer Society and the National Cancer Institute of Canada. Simultaneously, he joined the staff of Toronto General Hospital and its Radiotherapy Institute, where he became the first physician–oncologist to provide medical care and administer anticancer drugs in a Canadian cancer centre. In 1958, the new Princess Margaret Hospital opened in Toronto; Warwick became its first chief physician, responsible for clinical drug trials. Here he carried out his best known clinical study—the use of vinblastine sulphate in patients with Hodgkin lymphoma. From 1961 to 1971, he served as dean and then vice-president Health Sciences at the University of Western Ontario. He returned to the practice of medical oncology from 1972 to 1980 at the London Cancer Clinic, after which he had a long and productive retirement. He died in October 2009. Although the specialty was not named until the latter years of his career, Harold Warwick satisfied all the criteria for and was undoubtedly Canada’s first medical oncologist. Full article

Background: Despite the positive conclusions of several randomized controlled trials and the publication of national recommendations on colorectal cancer (crc) screening, uptake remained low. The inauguration of the National Colorectal Cancer Screening Network in 2007, the same year that the first screening program was announced in Canada, provided an opportunity for integrated knowledge translation to accelerate the processes of program implementation and screening uptake. Aim: Two primary aims were identified. The first focused on means to monitor the effects of various implementation plans in delivering high-quality population-based crc screening. The second focused on identifying and addressing knowledge gaps that may impair screening participation. Method: The methods used are described in the context of the knowledge-to-action cycle and demonstrate that the initiative itself dictates the point in the cycle at which to start. Results: The identified need to monitor various implementation plans resulted in the shared development of a quality determinants document. All programs committed to designing data collection so that core components could be measured and compared; 6 operating programs have conducted the first data collection, which will allow for monitoring and for new knowledge creation as the process develops further. The knowledge gap identification project started with new knowledge creation, which identified a higher-than-expected willingness of Canadians to discuss crc screening with physicians, but a low level of understanding of screening as a wellness-related behaviour. Knowledge translation interventions have been developed with the stakeholders to address those gaps, and ongoing surveys to be carried out later in 2011 will help to gauge progress in the understanding and acceptance of crc screening by the population. Conclusions: A national network that engaged all programs, policymakers, experts, and lay representatives successfully used knowledge translation principles to enhance the trajectory of crc screening in Canada. Full article

Background: Cancer pain is highly prevalent, and existing treatments are often insufficient to provide adequate relief. Objectives: We assessed the long-term safety and efficacy of subcutaneous tetrodotoxin treatment in reducing the intensity of chronic cancer-related pain. Methods: In this multicentre open-label longitudinal trial, 30 μg tetrodotoxin was administered subcutaneously twice daily for 4 days in a heterogeneous cohort of patients with persistent pain despite opioids and other analgesics. “Responder” was defined as a mean reduction of 30% or more in pain intensity from baseline; and “clinical responder” as some pain reduction, but less than 30%, plus agreement on the part of both the patient and the physician that a meaningful analgesic response to treatment had occurred. Results: Of 45 patients who entered the longitudinal trial, 41 had sufficient data for analysis. Of all 45 patients, 21 (47%) met the criteria for “responder” [16 patients (36%)] or “clinical responder” [5 patients (11%)]. Onset of pain relief was typically cumulative over days, and after administration ended, the analgesic effect subsided over the course of a few weeks. No evidence of loss of analgesic effect was observed during subsequent treatments (2526 patient–days in total and a maximum of 400 days in 1 patient). One patient withdrew from the study because of adverse events. Toxicity was usually mild (82%) or moderate (13%), and remained so through subsequent treatment cycles, with no evidence of cumulative toxicity or tolerance. Conclusions: Long-term treatment with tetrodotoxin is associated with acceptable toxicity and, in a substantial minority of patients, resulted in a sustained analgesic effect. Further study of tetrodotoxin for moderate-to-severe cancer pain is warranted. Full article