Curr. Oncol., Volume 18, Issue 6 (December 2011) – 17 articles

Introduction: In non-small-cell lung cancer (nsclc), invasive mediastinal staging is typically used to guide treatment decision-making. Here, we present clinical practice guideline recommendations for invasive mediastinal staging in nsclc patients who have been staged T1–4, N0–3, with no distant metastases. Draft recommendations were formulated based on the best available evidence gathered by a systematic review and a consensus of expert opinion. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline. In general, most clinical experts agreed with the guideline, approving it for methodologic rigour. More than 80% of the surveyed practitioners gave it a high quality rating. The expert reviewers also provided written comments, with some of the suggested changes being incorporated into the final version of the guideline. In the clinical practice guideline, invasive mediastinal staging of nsclc is recommended in all cases except those involving patients with normal-sized lymph nodes, negative combine positron-emission tomography and computed tomography, and peripheral clinical stage 1A tumour. When performing mediastinoscopy, 5 nodal stations (2R/L, 4R/L, and 7) should routinely be examined. Full article

In recent years, significant advances have been made in the management of metastatic colorectal cancer. Traditionally, an improvement in overall survival has been considered the “gold standard”—the most convincing measure of efficacy. However, overall survival requires larger patient numbers and longer follow-up and may often be confounded by other factors, including subsequent therapies and crossover. Given the number of active therapies for potential investigation, demand for rapid evaluation and early availability of new therapies is growing. Progression-free survival is regarded as an important measure of treatment benefit and, compared with overall survival, can be evaluated earlier, with fewer patients and no confounding by subsequent lines of therapy. The present paper reviews the advantages, limitations, and relevance of progression-free survival as a primary endpoint in randomized trials of metastatic colorectal cancer. Full article

Background: Systemic treatment options in hepatocellular carcinoma (hcc) are limited. Sorafenib, a multikinase inhibitor, has been shown to improve survival in patients with advanced hcc and adequate hepatic reserve. Currently, the proportion of referred patients with hcc that would be eligible for sorafenib therapy is unclear. We reviewed patterns in the presentation and management of referred patients with hcc at the BC Cancer Agency (bcca) before the availability of sorafenib. Methods: Records of patients with hcc referred to the bcca from January 1, 2003, to December 31, 2007, were reviewed. Distributions were analyzed using frequency statistics. Results: Of 518 patients reviewed, 77% were men and 45% were of Asian ethnicity; median age was 64 years. Histology confirmation was available in only 34% of the patients; 64% had an elevated level of alpha-fetoprotein at diagnosis. The Child–Pugh score at presentation could not be determined in 56%; the most common missing variable was albumin (44%). Among the 226 evaluable patients, the Child–Pugh classification was A in 140 (62%), B in 64 (28%), and C in 22 (10%). Eastern Cooperative Oncology Group performance status was not documented in 40% of patients. The TNM staging was recorded per agency protocol; however, it was incompletely documented in most patients. Distant metastases were recorded in 12% of patients, and 75 patients (15%) underwent hepatic resection before referral. After bcca referral, no further therapy was offered to 287 patients (54%), regional therapy was offered to 170 (33%), and chemotherapy was offered to 67 (13%). Conclusions: In this era of targeted therapies, characterizing the proportion of patients with hcc that would be eligible for such therapies is important. In our experience, referred patients are commonly Asian men with an acceptable hepatic reserve by Child–Pugh score, who have been diagnosed by clinical criteria alone. Most patients were offered no further therapy. Moving forward, accurate and systematic documentation of staging, performance status, and Child–Pugh score per the Barcelona Clinic Liver Cancer staging protocol will be imperative to best identify patients who may benefit most from sorafenib or available clinical trials, and to subsequently evaluate the population-based impact of the introduction of such therapies in patients with advanced hcc. Full article

The inaugural Canadian Cardiac Oncology Network conference was held at the Ottawa Convention Centre, Ottawa, Ontario, May 13, 2011. The learning objectives of the meeting were to: 1. understand and appreciate the importance of cardiac toxicity in the treatment of cancer patients; 2 review current guidelines, recommendations, and ways to prevent and treat cardiac toxicity in cancer patients; 3 develop potential research initiatives and collaboration across Canada. Although the cardiac toxicities associated with conventional systemic therapy agents are well established, the short- and long-term cardiac toxicities associated with targeted agents are less understood. In addition, the effects of exposing patients to multiple targeted therapies, and potentially compounding multiple cardiac toxicities, are unknown. This meeting report includes highlights from presentations at the conference. Full article

Purpose: The adoption of a chemotherapeutic regimen in oncologic practice is a function of both its clinical and its economic impacts on cancer management. For breast cancer, U.S. Oncology trial 9735 reported significant improvements in disease-free and overall survival favoring adjuvant tc (docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles) compared with ac (doxorubicin 60 mg/ m2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles). We carried out an economic evaluation to examine the cost–utility of adjuvant tc relative to ac, in terms of cost per quality-adjusted life year (qaly) gained, given the improved breast cancer outcomes and higher costs associated with the tc regimen. Methods: A Markov model was developed to calculate the cumulative costs and qalys gained over a 10-year horizon for hypothetical cohorts of women with breast cancer treated with ac or with tc. Event rates, costs, and utilities were derived from the literature and local resources. Efficacy and adverse events were based on results reported from U.S. Oncology trial 9735. The model takes a third-party direct payer perspective and reports its results in 2008 Canadian dollars. Costs and benefits were both discounted at 3%. Results: At a 10-year horizon, tc was associated with $3,960 incremental costs and a 0.24 qaly gain compared with ac, for a favorable cost–utility of $16,753 per qaly gained. Results were robust to model assumptions and input parameters. Conclusions: Relative to ac, tc is a cost-effective adjuvant chemotherapy regimen, with a cost-effectiveness ratio well below commonly applied thresholds. Full article

Background: Although arthralgia is a known adverse effect of aromatase inhibitor (ai) treatment in postmenopausal breast cancer patients, few studies have carried out a comprehensive evaluation of the nature, onset, and incidence of musculoskeletal (msk) pain in these patients. We therefore used a pilot study to identify conditions or markers predictive of pain. Methods: For 24 weeks, we monitored 30 eligible postmenopausal women starting ai therapy. Pre-existing and incident msk conditions and pain were assessed clinically and with ultrasonography of the hands and wrists. In addition, patient questionnaires were used to assess pain before and during ai therapy. Biochemical markers were measured at baseline and at regular intervals after anastrozole therapy began. Gene profiling studies were carried out before and 48 h after the initial ai administration. Results: Over the 24-week study period, 20 participants (67%) showed no pain symptoms; 5 (17%) experienced low or moderate pain at baseline, which did not increase with ai treatment; and during therapy, 5 (17%) showed exacerbation of pain attributable to osteoarthritis of the hand and to finger flexor tenosynovitis. Although all 30 participants had some degree of msk conditions before anastrozole therapy started, the pre-existing conditions did not necessarily predispose the women to increased pain during anastrozole treatment. Higher levels of urinary N-telopeptides of type i collagen were associated with the groups presenting pain, suggesting a higher extent of pre-existing bone resorption, without significant evolution over the 24-week treatment period. Slightly higher levels of 1,25(OH)2 vitamin D₃ were observed at baseline in patients with pain increase, but did not significantly change during treatment; however, average levels of 25(OH) vitamin D₃ increased, likely because of supplementation. Although biochemical markers did not discriminate efficiently between pain groups, a signature of 166 genes in peripheral blood mononuclear cells was identified that could stratify patients into the various groups observed in this pilot study. The gene signature was enriched in components of inflammatory signalling and chemokine expression, of antitumoural immunity pathways, and of metabolic response to hormones and xenobiotics, although no clinically significant association could be made in the present study, considering the small number of patients. Nevertheless, the observed trend suggests the feasibility of developing surrogate predictive markers of msk pain. Patient compliance was high in this study and was not affected by pain exacerbation. Conclusions: Baseline msk assessment showed pre-existing causes for pain in most of the study patients before initiation of the ai. Exacerbation of existing osteoarthritis pain and tenosynovial symptoms was the primary cause of pain increase. Musculoskeletal pain assessment at baseline and prompt treatment of pain symptoms may help to optimize adherence to ai therapy. The value of routinely assessing inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate was not supported by our pilot study. Gene expression profiles in peripheral blood mononuclear cells may be further explored in larger-scale studies as stratification markers to identify patients at risk of developing arthralgia. Full article

Introduction: The primary objective of this pilot study was to examine the inter-rater reliability in scoring the computed tomography (ct) imaging features of spinal metastases in patients referred for radiotherapy (rt) for bone pain. Methods: In a retrospective review, 3 musculoskeletal radiologists and 2 orthopedic spinal surgeons independently evaluated ct imaging features for 41 patients with spinal metastases treated with rt in an outpatient radiation clinic from January 2007 to October 2008. The evaluation used spinal assessment criteria that had been developed in-house, with reference to: osseous and soft tissue tumour extent; presence of a pathologic fracture; severity of vertebral height loss, and; presence of kyphosis. The Cohen kappa coefficient between the two specialties was calculated. Results: Mean patient age was 69.2 years (30 men, 11 women). The mean total daily oral morphine equivalent was 73.4 mg. Treatment dose–fractionation schedules included 8 Gy/1 (n = 28), 20 Gy/5 (n = 12), and 20 Gy/8 (n = 1). Areas of moderate agreement in identifying the ct imaging appearance of spinal metastasis included extent of vertebral body involvement (κ = 0.48) and soft-tissue component (κ = 0.59). Areas of fair agreement included extent of pedicle involvement (κ = 0.28), extent of lamina involvement (κ = 0.35), and presence of pathologic fracture (κ = 0.20). Areas of poor agreement included nerve-root compression (κ = 0.14) and vertebral body height loss (κ = 0.19). Conclusions: The range of agreement between musculoskeletal radiologists and orthopedic surgeons for most spinal assessment criteria is moderate to poor. A consensus for managing challenging vertebral injuries secondary to spinal metastases needs to be established so as to best triage patients to the most appropriate therapeutic modality. Full article

Objectives: Febrile neutropenia is considered an oncologic emergency, for which prompt initiation of antibiotics is essential. Methods: We conducted a retrospective cohort study for the 2006 calendar year involving all adult oncology patients presenting with febrile neutropenia to a regional health authority’s emergency departments. The objective was to determine the time from triage to antibiotic administration and its impact on patient outcomes. Results: We identified 68 patients presenting with febrile neutropenia, most of whom (76%) were seen in tertiary care centers. Of those patients, 65% were triaged to be seen within 15 minutes of arrival in the emergency room; however, the median time to reassessment was 57 minutes. The median time from triage to antibiotic administration was 5 hours (range: 1.23–22.8 hours). No increased risk of death or increased length of hospital stay was associated with delayed antibiotic administration. Older patients and patients without caregiver support were more likely to experience delayed antibiotic administration (odds ratio: 3.8 and 12.7 respectively). Conclusions: We were not able to show a deleterious effect of delay in antibiotic administration, but our analysis identified several points at which patient flow through the emergency room could be improved. Full article

Objective: Nationally, efforts to implement an innovation in cancer surgery—a Web-based synoptic reporting tool—are ongoing in five provinces. The objective of the present study was to identify the key multilevel factors influencing implementation and early use of this innovation for breast and colorectal cancer surgery at two academic hospitals in Halifax, Nova Scotia. Methods: We used case-study methodology to examine the implementation of surgical synoptic reporting. Methods included semi-structured interviews with key informants (surgeons, implementation team members, and report end users; n = 9), nonparticipant observation, and document analysis. A thematic analysis was conducted separately for each method, followed by explanation-building to integrate the evidence and to identify the key multilevel factors influencing implementation. An audit was performed to determine use. Results: Key factors influencing implementation were these: 1. Innovation–values fit; 2. Flexibility with the innovation and implementation; 3. The innovation is not flawless; 4. Strengthening the climate for implementation; 5. Resource needs and availability; 6. Partner engagement; 7. Surgeon champions and involvement. In a 6-month period after implementation, 91.2% and 58.0% respectively of eligible breast and colorectal cancer surgeries were reported using the new tool. Conclusions: An improved understanding of the multilevel factors influencing the implementation of innovations is critical to planning effective change interventions in health care. Further study is needed to explore differences in the use of the innovation between breast and colorectal cancer surgeons. Findings will inform the study of additional cases of synoptic reporting implementation, enabling cross-case analyses and identification of higher-level themes that may be applied in similar settings or contexts. Full article

Objective: Our goal was to develop evidence-based recommendations for the organization and structure of cancer survivorship services, and best-care practices to optimize the health and well-being of post–primary treatment survivors. This review sought to determine the optimal organization and care delivery structure for cancer survivorship services, and the specific clinical practices and interventions that would improve or maximize the psychosocial health and overall well-being of adult cancer survivors. Data Sources: We conducted a systematic search of the Inventory of Cancer Guidelines at the Canadian Partnership Against Cancer, the U.S. National Guideline Clearinghouse, the Canadian Medical Association InfoBase, medline (ovid: 1999 through November 2009), embase (ovid: 1999 through November 2009), Psychinfo (ovid: 1999 through November 2009), the Cochrane Library (ovid; Issue 1, 2009), and cinahl (ebsco: 1999 through December 2009). Reference lists of related papers and recent review articles were scanned for additional citations. Methods: Articles were selected for inclusion as evidence in the systematic review if they reported on organizational system components for survivors of cancer, or on psychosocial or supportive care interventions HOWELL et al. designed for survivors of cancer. Articles were excluded from the systematic review if they focused only on pediatric cancer survivor populations or on populations that transitioned from pediatric cancer to adult services; if they addressed only pharmacologic interventions or diagnostic testing and follow-up of cancer survivors; if they were systematic reviews with inadequately described methods; if they were qualitative or descriptive studies; and if they were opinion papers, letters, or editorials. Data Extraction and Synthesis: Evidence was selected and reviewed by three members of the Cancer Journey Survivorship Expert Panel (SM, TC, TKO). The resulting summary of the evidence was guided further and reviewed by the members of Cancer Journey Survivorship Expert Panel. Fourteen practice guidelines, eight systematic reviews, and sixty-thee randomized controlled trials form the evidence base for this guidance document. These publications demonstrate that survivors benefit from coordinated post-treatment care, including interventions to address specific psychosocial, supportive care, and rehabilitative concerns. Conclusions: Ongoing high-quality research is essential to optimize services for cancer survivors. Interventions that promote healthy lifestyle behaviours or that address psychosocial concerns and distress appear to improve physical functioning, psychosocial well-being, and quality of life for survivors. Full article

Objective: The aim of this study was to gather data from Canadian stakeholders to help construct a national strategy and agenda for lymphedema management. Methods: The Canadian Lymphedema Framework, a collaboration of medical academics, lymphedema therapists, patient advocates, and others, used participatory action research and Open Space Technology to identify issues and build consensus at a national meeting of lymphedema stakeholders. Proceedings were videotaped and underwent content analysis. Existing Canadian documentation on lymphedema services was analyzed. Using those data sources, the Canadian Lymphedema Framework drafted a development strategy. Results: Of 320 invited stakeholders (patients, therapists, physicians, industry representatives, and health policymakers), 108 participated in a day-long videotaped meeting discussing strategies to improve the management of lymphedema and related disorders in Canada. Participants identified barriers, challenges, and issues related to the need to raise awareness about lymphedema with patients, physicians, and the public. Five priority areas for development were articulated: education, standards, research, reimbursement and access to treatment, and advocacy. The main barrier to development was identified as the lack of clear responsibility within the health care system for lymphedema care. Conclusions: Data from stakeholders was obtained to solidly define priority areas for lymphedema development at a national level. The Canadian Lymphedema Framework has created a working plan, an advisory board, and working groups to implement the strategy. Full article