Curr. Oncol., Volume 22, Issue 1 (February 2015) – 15 articles

Background: We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy. Methods: We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3–4N0–3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70–80 Gy), the lymph node–positive area (60–70 Gy), and the lymph node–negative area (50–60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan–Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis. Results: During the median follow-up of 3.9 years (range: 1–5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp; the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55; p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years. Conclusions: Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy. Full article

Background: Evidence shows that wait times before bladder cancer surgery have been increasing, and wait time can negatively affect survival. We aimed to determine if a long delay caused by an indirect referral before a first urologist visit affects the survival of patients undergoing radical cystectomy for bladder cancer. Methods: We analyzed data from 1271 patients who underwent surgery for bladder cancer during the decade 2000–2009. The cohort was obtained by linking two administrative databases in the province of Quebec. Patients were considered to have been directly referred to a urologist if they had 5 or fewer visits with a general practitioner before their first urologist visit; otherwise, they were considered to have been indirectly referred. The effect on survival after surgery of a longer delay before a first urologist visit was assessed using Cox regression models. Results: Median referral delay for the study population was 30 days (56 days for women, 23 days for men; p < 0.0001). Indirect referral was observed for 49% of women and 33% of men. Compared with patients who were directly referred, those who were indirectly referred after first symptoms of bladder cancer experienced poorer survival (hazard ratio: 1.29; 95% confidence interval: 1.10 to 1.52). Women who were indirectly referred had a significant 47% greater risk of death after radical cystectomy. Men who were indirectly referred also experienced decreased survival (adjusted hazard ratio: 1.25; 95% confidence interval: 1.03 to 1.51). Conclusions: Patients indirectly referred to a urologist had an increased risk of mortality after surgery. Compared with men, women had longer wait times and poorer survival. Full article

Metastatic castration-resistant prostate cancer is now commonly treated with abiraterone, an orally administered chronic medication. Although abiraterone has certain advantages over docetaxel-based therapy, patients are now responsible for ensuring optimal adherence to their medication. To our knowledge, adherence to abiraterone in a real-world setting has never been described. The objective of the present study was to measure adherence to abiraterone among the first patients to receive the drug in Saskatchewan. Electronic pharmacy claims were obtained from the Saskatchewan Cancer Agency after removal of patient names and identifiers. All patients with at least 1 dispensation for abiraterone between August 2011 and October 2013 were eligible. The primary endpoint was the percentage of patients achieving optimal adherence at 6 months, defined as a medication possession ratio (mpr) of 80% or better. During the study period, 141 patients received abiraterone, among whom 86 could be followed for at least 6 months. Optimal adherence was achieved in 82.6% of patients (71 of 86) at 6 months, with 79.1% achieving a mpr of at least 90%. Of patients with available follow-up to 1 year, 81.6% (31 of 38) maintained optimal adherence during the entire period. Full article

Background: Depending on interest, knowledge, and skills, oncologists are adapting clinical behaviour to include integrative approaches, supporting patients to make informed complementary care decisions. The present study sought to improve the knowledge base in three ways: (1) Test the acceptability of a self-reported online survey for oncologists. (2) Provide preliminary data collection concerning knowledge, attitudes, beliefs, and current referral practices among oncologists with respect to yoga in adult cancer. (3) List the perceived benefits of and barriers to yoga intervention from a clinical perspective. Methods: A 38-item self-report questionnaire was administered online to medical, radiation, and surgical oncologists in British Columbia. Results: Some of the 29 oncologists who completed the survey (n = 10) reported having recommended yoga to patients to improve physical activity, fatigue, stress, insomnia, and muscle or joint stiffness. Other responding oncologists were hesitant or unlikely to suggest yoga for their patients because they had no knowledge of yoga as a therapy (n = 15) or believed that scientific evidence to support its use is lacking (n = 11). All 29 respondents would recommend that their patients participate in a clinical trial to test the efficacy of yoga. In qualitative findings, oncologists compared yoga with exercise and suggested that it might have similar psychological and physical health benefits that would improve patient capacity to endure treatment. Barriers to and limitations of yoga in adult cancer are also discussed. Conclusions: An online self-report survey is feasible, but has response rate limitations. A small number of oncologists are currently recommending yoga to improve health-related outcomes in adult cancer. Respondents would support clinical yoga interventions to improve the evidence base in cancer patients, including men and women in all tumour groups. Full article

Several randomized controlled trials have demonstrated that the preventive use of an antiestrogen agent such as tamoxifen, raloxifene, anastrozole, or exemestane will reduce the incidence of estrogen receptor (er)–positive breast cancers by 50% or more. The reduction in risk becomes apparent shortly after tamoxifen initiation. However, no mortality benefit has yet been demonstrated with tamoxifen or any other agent, an effect that might be statistical: that is, the statistical power to detect a difference in mortality could be lacking because deaths from breast cancer are far fewer in number than cases of breast cancer, and because the average time to cancer is much shorter than the time to death. In other words, it could be too early to see an effect. However, the lack of an observed survival benefit might also be a result of chemoprevention agents preferentially preventing cancers that would rarely lead to death. That paradigm extends the (controversial) concepts of overdiagnosis and of the potential for spontaneous regression of some lowgrade breast cancers [...] Full article

Background: We aimed to characterize the localization and prognostic significance of tumour-associated macrophages (tams) in pancreatic ductal adenocarcinoma (pdac). Methods: Tumour specimens from 70 patients with pdac and inflammatory specimens from 13 patients with chronic pancreatitis were collected and analyzed for tam and M2 macrophage counts by immunohistochemistry. Correlations between tam distributions and clinicopathologic features were determined. Results: Immunohistochemical analysis showed that tam and M2 macrophage counts were higher in tissues from pdac than from chronic pancreatitis. The tams and M2 macrophages both infiltrated more into peritumour. Both macrophage types were positively associated with lymph node metastasis (p = 0.041 for tams in peritumour, p = 0.013 for M2 macrophages in introtumour, p = 0.006 for M2 macrophage in peritumour). In addition, abdominal pain was significantly more frequent in pdac patients with a greater tams count. The survival rate was much lower in patients having high infiltration by M2 macrophages than in those having low infiltration. Conclusions: The tam count might be associated with neural invasion in pdac, and M2 macrophages might play an important role in lymph node metastasis. Higher counts of either macrophage type were associated with increased risk of lymph node metastasis, and the M2 macrophage count could potentially be a marker for evaluating prognosis. Full article

Venous thromboembolism is a common complication in cancer patients, and thromboembolism is the second most common cause of death after cancer progression. A number of clinical practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, the guidelines lack recommendations covering commonly encountered clinical challenges (for example, thrombocytopenia, recurrent venous thromboembolism, etc.) for which little or no evidence exists. Accordingly, recommendations were developed to provide expert guidance to medical oncologists and other health care professionals caring for patients with cancer-associated thrombosis. The current expert consensus was developed by a team of 21 clinical experts. For each identified clinical challenge, the literature in MEDLINE, EMBASE, and Evidence Based Medicine Reviews was systematically reviewed. The quality of the evidence was assessed, summarized, and graded. Consensus statements were generated, and the experts voted anonymously using a modified Delphi process on their level of agreement with the various statements. Statements were progressively revised through separate voting iterations and were then finalized. Clinicians using these recommendations and suggestions should tailor patient management according to the risks and benefits of the treatment options, patient values and preferences, and local cost and resource allocations. Full article

Long-term survival for adult patients with solid tumours continues to increase. For some cancers, the possibility of recurrence after a number of years is extremely low, and the risk of death becomes similar to that of the general population of the same sex and age. During the Fifth European Conference on Survivors and Chronic Cancer Patients held in Siracusa, Italy, June 2014, oncologists, general practitioners, epidemiologists, cancer patients and survivors, and patient advocates joined to discuss the possible use of the term “cured” in reference to some adult patients with solid tumours. The specific focus was the appropriateness of using the term in communicating with cancer patients, survivors, and their families. Initial results of the discussion, in concert with a review of the published literature on the subject, were later further discussed by all participants through electronic communication. The resulting final statement aims to suggest appropriate ways to use the word “cured” in the clinical and communicative setting, to highlight the potential impact of the word on patients, and to open a critical discussion concerning this timely and delicate matter. Full article

The PI3K/Akt/mTOR (phosphatidylinositol 3 kinase/ Akt/mammalian target of rapamycin) signalling pathway is an established driver of oncogenic activity in human malignancies. Therapeutic targeting of this pathway holds significant promise as a treatment strategy. Everolimus, an mtor inhibitor, is the first of this class of agents approved for the treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer. Everolimus has been associated with significant improvements in progression-free survival; however, it is also associated with increased toxicity related to its specific mechanism of action. Methods: A comprehensive review of the literature conducted using a focused medline search was combined with a search of current trials at http://ClinicalTrials.gov/. Summary tables of the toxicities of the various classes of PI3K/Akt/mTOR inhibitors were created. A broad group of Canadian health care professionals was assembled to review the data and to produce expert opinion and summary recommendations for possible best practices in managing the adverse events associated with these pathway inhibitors. Results: Differing toxicities are associated with the various classes of PI3K/Akt/mTOR pathway inhibitors. The most common unique adverse events observed in everolimus clinical trials in breast cancer include stomatitis (all grades: approximately 60%), noninfectious pneumonitis (15%), rash (40%), hyperglycemia (15%), and immunosuppression (40%). To minimize grades 3 and 4 toxicities and to attempt to attain optimal outcomes, effective management of those adverse events is critical. Management should be interdisciplinary and should use approaches that include education, early recognition, active intervention, and potentially prophylactic strategies. Discussion: Everolimus likely represents the first of many complex oral targeted therapies for the treatment of breast cancer. Using this agent as a template, it is essential to establish best practices involving and integrating multiple disciplines for the management of future PI3K/Akt/mTOR signalling pathway inhibitors. Full article

Background: This evidence-based practice guideline was developed to update and address new issues in the handling of cytotoxics, including the use of oral cytotoxics; the selection and use of personal protective equipment; and treatment in diverse settings, including the home setting. Methods: The guideline was developed primarily from an adaptation and endorsement of an existing guideline and from three systematic reviews. Before publication, the guideline underwent a series of peer and external reviews to gather feedback. All comments were addressed, and the guideline was amended when required. The guideline applies to health care workers who could come into contact with cytotoxic drugs at any point in the medication circuit. The intended users are hospital administrators, educators, and managers; occupational health and safety services; and pharmacy and health care workers. Results: The recommendations represent a reasonable and practical set of procedures that the intended users of this guideline should implement to minimize opportunities for accidental exposure. They are not limited to just the point of care; they cover the entire chain of cytotoxics handling from the time such agents enter the institution until they leave in the patient or as waste. Conclusions: Reducing the likelihood of accidental exposure to cytotoxic agents within the medication circuit is the main objective of this evidenced-based guideline. The recommendations differ slightly from earlier guidelines because of the availability of new evidence. Full article

Background: In cases of locally advanced breast cancer (labc), preoperative (“neoadjuvant”) therapy was traditionally reserved to render the patient operable. More recently, neoadjuvant therapy, particularly chemotherapy, is being used in patients with operable disease to increase the opportunity for breast conservation. Despite the increasing use of preoperative chemotherapy, rates of pathologic complete response, a surrogate marker for disease-free survival, remain modest in patients with locally advanced disease and particularly so when the tumour is estrogen or progesterone receptor–positive and her2-negative. A new paradigm for labc patients is needed. In other solid tumours (for example, rectal, esophageal, and lung cancers), concurrent chemoradiotherapy (ccrt) is routinely used in neoadjuvant and adjuvant treatment protocols alike. Results: The literature suggests that ccrt in labc patients with inoperable disease is associated with response rates higher than would be anticipated with systemic therapy alone. Conclusions: Ongoing trials in this field are eagerly awaited to determine if ccrt should become the new paradigm. Full article