Wood T.J.,McMaster University |
Racano A.,McMaster University |
Yeung H.,McMaster University |
Farrokhyar F.,McMaster University |
And 3 more authors.
Annals of Surgical Oncology | Year: 2014
Background: Surgical management of metastatic bone disease (MBD) is typically reserved for lesions with the highest risk of fracture. However, the high risk of perioperative complications associated with surgery may outweigh the benefits of improved pain and/or function. The goal of this study was to (1) assess the quality of current evidence in this domain; (2) confirm that surgical management of metastases to the long bones and pelvis/acetabulum provides pain relief and improved function; and (3) assess perioperative morbidity and mortality rates.Methods: We conducted a systematic review of the literature for clinical studies that reported pain relief and function outcomes, as well as perioperative complications and mortality, in patients with MBD to the long bones and/or pelvis/acetabulum treated surgically. Multiple databases were searched up to January 2012. Pooled weighted proportions are reported.Results: Forty-five studies were included in the final analysis, with 807 patients. All included studies were level IV with ‘moderate’ overall quality of evidence using the Methodological Index for Non-Randomized Studies scale. Pain relief following surgical management of metastases was 93, 91, and 93 % in the humerus, femur, and pelvis/acetabulum, respectively. Maintained or improved function after surgery was seen in 94, 89, and 94 % in the humerus, femur, and pelvis/acetabulum, respectively. Perioperative complications and mortality were 17 and 4 %, respectively.Conclusions: Despite the inherent limitations of the current evidence, a benefit for the surgical management of bone metastases to the long bones and pelvis/acetabulum is evident; however, there is still substantial risk of perioperative morbidity and mortality that should be considered. © 2014, Society of Surgical Oncology.
McWilliams A.,Vancouver General Hospital |
McWilliams A.,British Columbia Cancer Agency |
Tammemagi M.C.,Brock University |
Mayo J.R.,Vancouver General Hospital |
And 31 more authors.
New England Journal of Medicine | Year: 2013
Background: Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a populationbased prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. Methods: We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. Results: In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. Conclusions: Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. Copyright © 2013 Massachusetts Medical Society.
Bormanis J.,The Ottawa Hospital Regional Cancer Center |
Quirt I.,University of Toronto |
Chang J.,ughlin Durham Regional Cancer Center |
Kouroukis C.T.,Juravinski Hospital and Cancer Center |
And 4 more authors.
Critical Reviews in Oncology/Hematology | Year: 2013
Purpose: Anemia in cancer patients can be a result of the underlying cancer or related to treatment. Erythropoiesis-stimulating agents (ESAs) are an important option for many patients with chemotherapy-induced anemia, but are immersed in controversy. This article aims to reconcile conflicting opinions and provide expert guidance for appropriate ESA use. Methods: Teleconference, email, and a face-to-face meeting were used to assess ESA therapy "interpretive" data, which included two current meta-analyses, expert guidelines, and regulatory approved indications from Canada, Europe, and the USA. Results: Risks and benefits are associated with both red blood cell transfusions and ESA therapy, including improvements in hemoglobin levels and quality of life. ESAs have been associated with concerns regarding survival and progression of cancer, particularly when used in patients with cancer-related anemia. Conclusion: Although safety concerns do exist, ESA therapy can be considered for use in patients with chemotherapy-induced anemia in accordance with Health Canada labeling. © 2013 Elsevier Ireland Ltd.
Hallett R.M.,McMaster University |
Pond G.,Juravinski Hospital and Cancer Center |
Hassell J.A.,McMaster University
BMC Medical Genomics | Year: 2012
Background: The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available. Methods: We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Results: Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol. Conclusions: Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients. © 2012 Hallet et al.; licensee BioMed Central Ltd.
Leber B.,Juravinski Hospital and Cancer Center
Current Oncology | Year: 2011
Chronic myeloid leukemia (CML) is a model disease in oncology: it is the first human cancer linked to a distinct chromosomal abnormality, ultimately causing constitutive overactivity of a known oncogenic tyrosine kinase that represents a drug target. The introduction of the tyrosine kinase inhibitor imatinib into clinical practice has far exceeded expectations and resurrected hope that the fundamental insights from the "war on cancer" can lead to significant therapeutic advances. Nevertheless,the current perception among clinicians is that imatinib and its newer more potent cousins offer superb long-term disease control for most patients, but that cure without transplantation has remained elusive. However, several important laboratory-based observations over the last few years have changed those perceptions. Several of those developments are discussed here, including direct manipulation of the apoptosis pathway in cancer cells and prevention of disease progression with the use of antioxidants. Intriguing results from a French study indicate that, if disease progression is halted, a small but significant group of patients may be able to stop imatinib therapy without disease recurrence. And for patients whose disease, because of resistant stem cells,needs a more direct attack than tyrosine kinase inhibitors alone, several approaches investigated in laboratory and animal models seem promising, and some are ripe for clinical testing, including inhibitors of Smoothened and 5-lipoxygenase, and suppression of autophagy. Thus,there is realistic hope that true cure of cml, without transplantation, may be a feasible goal in the near future.©2011 Multimed Inc.
Westdorp H.,Radboud University Nijmegen |
Skold A.E.,Radboud University Nijmegen |
Snijer B.A.,Radboud University Nijmegen |
Franik S.,Radboud University Nijmegen |
And 5 more authors.
Frontiers in Immunology | Year: 2014
Prostate cancer (PCa) is the most common cancer in men and the second most common cause of cancer-related death in men. In recent years, novel therapeutic options for PCa have been developed and studied extensively in clinical trials. Sipuleucel-T is the first cell-based immunotherapeutic vaccine for treatment of cancer. This vaccine consists of autologous mononuclear cells stimulated and loaded with an immunostimulatory fusion protein containing the prostate tumor antigen prostate acid posphatase. The choice of antigen might be key for the efficiency of cell-based immunotherapy. Depending on the treatment strategy, target antigens should be immunogenic, abundantly expressed by tumor cells, and preferably functionally important for the tumor to prevent loss of antigen expression. Autoimmune responses have been reported against several antigens expressed in the prostate, indicating that PCa is a suitable target for immunotherapy. In this review, we will discuss PCa antigens that exhibit immunogenic features and/or have been targeted in immunotherapeutic settings with promising results, and we highlight the hurdles and opportunities for cancer immunotherapy. © 2014 Westdorp, Sköld, Snijer, Franik, Mulder, Major, Foley, Gerritsen and de Vries.
Hay A.E.,Queen's University |
Meyer R.M.,Juravinski Hospital and Cancer Center
Hematology/Oncology Clinics of North America | Year: 2014
Because long-term survival of patients with nonbulky stage IA to IIA Hodgkin lymphoma is dependent on disease control and avoidance of late toxic effects associated with the treatment received, the initial choice of treatment can be associated with trade-offs that balance optimum disease control with avoidance of these late effect risks. Health professionals and patients face the dilemma of making treatment decisions without the benefit of completely understanding the risk-benefit balances associated with how current treatments affect all outcomes of interest. Optimum management of these patients requires careful multidisciplinary evaluation and communication strategies that account for patient preferences. © 2014 Elsevier Inc.
Coroneos C.J.,McMaster University |
Heller A.M.,McMaster University |
Voineskos S.H.,McMaster University |
Avram R.,McMaster University |
Avram R.,Juravinski Hospital and Cancer Center
Plastic and Reconstructive Surgery | Year: 2015
Background: The authors analyzed arterial complications in patients undergoing breast reconstruction with superficial inferior epigastric artery (SIEA) flaps compared with deep inferior epigastric artery perforator (DIEP) flaps. The variability, caliber, and angiosome of the SIEA are cited as limitations. Experts currently limit SIEA reconstruction to cases with favorable arterial anatomy on preoperative imaging. Methods: In this retrospective cohort study, consecutive flaps for breast reconstruction from the initial 7 years of a single microsurgeon's practice (2007 to 2013) were reviewed. Preoperative imaging was not used. Consistent intraoperative criteria for SIEA flap selection were used. All complications were abstracted independently in duplicate using a standardized form and a priori criteria. Results: One hundred sixty-nine free flaps (SIEA, n = 44; DIEP, n = 125) were performed on 112 patients for unilateral or bilateral breast reconstruction. Significantly more SIEA flaps required reexploration versus DIEP flaps (20 percent versus 7 percent; p = 0.03). Arterial insufficiency was significantly higher among SIEA flaps (14 percent versus 1 percent; p = 0.001). There was no difference in venous insufficiency (p = 0.92). Significantly more SIEA flaps had necrosis requiring intervention (p = 0.03). Ultimately, significantly more SIEA flaps failed completely (14 percent versus 2 percent; p < 0.01). All SIEA flap failures were attributable to arterial thrombosis. Conclusions: Compared with DIEP flaps, SIEA flaps had significantly higher proportions of reexploration, arterial complication, necrosis, and failure. No difference in venous complications was found. DIEP outcomes agree with existing literature from specialized centers. Complications and failures in SIEA flaps were attributed to arterial thrombosis. Given the authors' practice setting, SIEA flaps are no longer performed. © 2015 by the American Society of Plastic Surgeons.
Kavsak P.A.,McMaster University |
Kavsak P.A.,Juravinski Hospital and Cancer Center |
Worster A.,McMaster University
Expert Review of Cardiovascular Therapy | Year: 2012
Evaluation of: Collinson P, Goodacre S, Gaze D et al. Very early diagnosis of chest pain by point-of-care testing: comparison of the diagnostic efficiency of a panel of cardiac biomarkers compared with troponin measurement alone in the RATPAC trial. Heart 98(4), 312-318 (2012). An early diagnosis of myocardial infarction in the emergency setting would be advantageous for both patients and the physicians treating these patients. Guidelines currently recommend serial samples that are drawn at presentation and 6-9 h later to be measured for cardiac troponin to aid in this diagnosis. However, much effort has been directed to decrease the time to make a diagnosis in this setting, and there has been renewed interest in shortening the time between serial measurements as well as the turnaround time for reporting the results. By eliminating the blood sample transit time to the central laboratory, point-of-care testing or near-patient testing can reduce the turnaround time for reporting the results, however this is possibly at the cost of decreased diagnostic performance. In this article, we discuss the recent results from the RATPAC study, which evaluated whether the combination of myoglobin, the MB isoenzyme of creatine kinase (CKMB) and a sensitive troponin assay would be superior to troponin alone. © 2012 Expert Reviews Ltd.
Mahe E.,McMaster University |
Tang S.,McMaster University |
Deb P.,McMaster University |
Sur M.,McMaster University |
And 4 more authors.
International Journal of Gynecological Pathology | Year: 2013
Studies have suggested serous tubal intraepithelial carcinoma (STIC) of the fallopian tube to be a putative precursor to ovarian and peritoneal serous carcinoma. It has been recommended that resected fallopian tube specimens should be rigorously examined for STIC, especially in women at high risk of serous carcinoma, such as those with BRCA mutations or with a strong family history. The SEE-FIM protocol allows for the greatest surface area of the tube to be histologically assessed. There have been suggestions that multiple deeper sections should be examined if the initial hematoxylin and eosin (H&E) sections are negative; however, whether this identifies more cases of STIC has not rigorously examined. We examined deeper sections from 56 cases of pelvic carcinoma in which the initial H&E sections of the fallopian tubes were negative for STIC. All initial and deeper sections underwent consensus review by panel of experts in gynecologic pathology. These cases are part of a larger study in which we had examined 300 consecutive bilateral salpingectomies using the SEE-FIM protocol and a single-H&E section per block and had identified 68 cases of pelvic serous carcinoma, of which 12 were associated with STIC. We calculated the sensitivity of a single-H&E section to detect STIC, as compared with examination of multiple deeper sections, and reevaluated the clinicopathologic data of the parent study in light of the additional cases of STIC. In the 56 cases initially negative for STIC, 4 cases of STIC were identified after examination of multiple deeper sections of the fallopian tubes. The single-H&E section SEE-FIM approach therefore detected only 75% (95% confidence interval, 51%-90%) of STIC that was present. Three of these new cases were associated with primary ovarian serous carcinoma and 1 with primary peritoneal serous carcinoma. All 3 new cases associated with ovarian carcinoma were noted in women without neoadjuvant chemotherapy. In considering the data from the parent study, we calculated a statistically significant lower incidence of STIC in women with ovarian serous carcinoma who received neoadjuvant chemotherapy as compared with those who did not (P=0.042). Our study demonstrated that additional cases of STIC can be detected if deeper sections are examined. These additional cases also highlighted a statistically significant difference in the incidence of STIC associated with ovarian serous carcinoma who received neoadjuvant chemotherapy relative to those who did not. Consideration to this should be given in future studies of the prevalence of STIC and to routine examination of salpingectomy specimens from women at high risk for pelvic serous carcinoma. © 2013 International Society of Gynecological Pathologists.