Tom Baker Cancer Center
Tom Baker Cancer Center
Ghatage P.,Tom Baker Cancer Center |
Sabagh H.,Tom Baker Cancer Center
Expert Opinion on Drug Metabolism and Toxicology | Year: 2012
Introduction: Cervical cancer is the second-most common malignancy in women worldwide. Cisplatin was introduced as a radiosensitizer in 1999 to improve chances of survival. Tumor cell hypoxia, however, remains a major limiting factor in the treatment of solid tumors with chemotherapy and radiation. There has since been significant interest in the use of bioreductive agents to overcome the hypoxia and improve survival. The addition of tirapazamine (TPZ) to conventional chemoradiation protocols in the management of cervical cancer held promise in the initial Phase I and II clinical trials in delaying recurrence and improving survival. However, GOG recently announced early closure of the Phase III trial of tirapazamine in cervical cancer due to a lack of increased survival. Areas covered: This article covers the definition of hypoxic tumor cells, the markers of tumor hypoxia, methods for measuring hypoxia as well as the pharmacologic action of tirapazamine in hypoxic media. Furthermore, it critically evaluates TPZ's role in cervical cancer treatment and the drawbacks to the GOG study. The authors review all clinical trials published to date with special emphasis on cervical cancer. A systematic review of the literature was also undertaken with PubMed and Ovid. Expert opinion: Despite the promising results from early clinical trials, it has been shown that the addition of tirapazamine appears to confer no benefits on progression-free or overall survival in patients with cervical cancer. Success in the future will require smaller randomized trials with biologic targets that have acceptable toxicity and efficacy. © 2012 Informa UK, Ltd.
Banerjee R.,Tom Baker Cancer Center |
Kamrava M.,University of California at Los Angeles
International Journal of Women's Health | Year: 2014
Dramatic advances have been made in brachytherapy for cervical cancer. Radiation treatment planning has evolved from two-dimensional to three-dimensional, incorporating magnetic resonance imaging and/or computed tomography into the treatment paradigm. This allows for better delineation and coverage of the tumor, as well as improved avoidance of surrounding organs. Consequently, advanced brachytherapy can achieve very high rates of local control with a reduction in morbidity, compared with historic approaches. This review provides an overview of state-of-the-art gynecologic brachytherapy, with a focus on recent advances and their implications for women with cervical cancer. © 2014 Banerjee and Kamrava.
Robson E.J.D.,Amgen |
Ghatage P.,Tom Baker Cancer Center
Expert Opinion on Investigational Drugs | Year: 2011
Introduction: Ovarian cancer is the second most common gynecologic malignancy in the world with the majority of women presenting with advanced disease; whilst chemotherapeutic advances have improved progression-free survival, the increases in overall survival have been marginal. Novel biologic agents, including those designed to disrupt tumor angiogenesis, have demonstrated promising antitumor activity. Areas covered: This review evaluates AMG 386, a novel investigational angiopoietin antagonist peptide-Fc fusion protein (peptibody), which potently and selectively inhibits angiopoietin-1 and angiopoietin-2 binding to the Tie2 tyrosine kinase receptor. Preclinical and clinical studies for AMG 386 are summarized, highlighting data pertaining to ovarian cancer. The role of angiopoietins in regulating physiologic and tumorigenic angiogenesis is addressed, as well as a brief discussion of non-angiopoietin anti-angiogenic strategies, followed by a review of preclinical, Phase I and II data and ongoing clinical studies for AMG 386, all in the context of ovarian cancer. Expert opinion: AMG 386 has clinical activity and an acceptable safety profile both as monotherapy and in combination with chemotherapy. Of note, as the toxicity profiles of AMG 386 and inhibitors of the VEGF axis do not substantially overlap, AMG 386 could potentially be combined with other anti-angiogenic compounds to maximize disruption of malignant vascularization in ovarian cancer and other solid tumors. © 2011 Informa UK, Ltd.
Walker L.M.,Tom Baker Cancer Center |
Wassersug R.J.,University of British Columbia |
Robinson J.W.,Tom Baker Cancer Center
Nature Reviews Urology | Year: 2015
Many therapies for erectile dysfunction (ED) after prostate cancer treatment improve erectile firmness, yet, most couples stop using aids within 1-2 years. Patients and partners who expect immediate and complete success with their first ED treatment can be demoralized when they experience treatment failure, which contributes to reticence to explore other ED aids. Comprehensive patient education should improve sustainability and satisfaction with ED treatments. Pre-emptive and realistic information should be provided to couples about the probability of recovering natural erections. Beginning intervention early and using a couple-based approach is ideal. Recommendations are provided about the timing of ED treatment, the order of aid introduction, and combination therapies. Renegotiation of sexual activity is an essential part of sexual adaptation. From the outset of therapy, couples should be encouraged to broaden their sexual repertoire, incorporate erection-independent sexual activities, and continue to be sexual despite ED and reduced libido.
Walker L.M.,University of Calgary |
Robinson J.W.,Tom Baker Cancer Center
Qualitative Health Research | Year: 2012
More than half of all men with prostate cancer will be treated with androgen deprivation therapy (ADT) at some point during their lives. Though an effective treatment for prostate cancer, ADT results in profound changes in the man's sense of masculinity and sexuality (e.g., erectile dysfunction, loss of libido, genital atrophy and severe genital shrinkage, hot flashes, loss of muscle mass, fatigue, bodily feminization). These changes usually result in the cessation of all sexual activity. Surprisingly, some couples do find ways of continuing to have satisfying sex despite the man's castrate level of testosterone. Herein, we describe the sexual struggles that couples encounter when attempting to adapt sexually to ADT. A grounded theory methodology was used to analyze interview data. The successful strategies that couples used to overcome struggles, as well as those which seemed to exacerbate struggles, are documented. Couples adjusting to ADT might benefit from knowing which strategies are most likely to result in positive adjustment and which are not. © 2012 SAGE Publications.
Dunscombe P.,Tom Baker Cancer Center
Frontiers in Oncology | Year: 2012
Radiotherapy, with close to a million courses delivered per year in North America, is a very safe and effective intervention for a devastating disease. However, although rare, several deeply regrettable incidents have occurred in radiotherapy and have rightly been the subject of considerable public interest. Partly in response to reports of these incidents a variety of authoritative organizations across the globe has harnessed the expertise amongst their members in attempts to identify the measures that will make radiotherapy safer. While the intentions of all these organizations are clearly good it is challenging for the health care providers in the clinic to know where to start with so much advice coming from so many directions. Through a mapping exercise we have identified commonalities between recommendations made in seven authoritative documents and identified those issues most frequently cited. The documents reviewed contain a total of 117 recommendations. Using the 37 recommendations in "Towards Safer Radiotherapy" as the initial base layer, recommendations in the other documents were mapped, adding to the base layer to accommodate all the recommendations from the additional six documents as necessary. This mapping exercise resulted in the distillation of the original 117 recommendations down to 61 unique recommendations. Twelve topics were identified in three or more of the documents as being pertinent to the improvement of patient safety in radiotherapy. They are, in order of most to least cited: training, staffing, documentation, incident learning, communication, check lists, quality control and preventive maintenance, dosimetric audit, accreditation, minimizing interruptions, prospective risk assessment, and safety culture. This analysis provides guidance for the selection of those activities most likely to enhance safety and quality in radiotherapy based on the frequency of citation in selected recent authoritative literature. © 2012 Dunscombe.
Nelson G.,Tom Baker Cancer Center |
Kalogera E.,Rochester College |
Dowdy S.C.,Rochester College
Gynecologic Oncology | Year: 2014
Objective. Many commonplace perioperative practices are lacking in scientific evidence and may interfere with the goal of optimizing patient recovery. Individual components of perioperative care have therefore been scrutinized, resulting in the creation of so-called "enhanced recovery" pathways (ERP), with the goal of hastening surgical recovery through attenuation of the stress response. In this review we examine the evidence for ERP in gynecologic oncology using data from our specialty and general surgery. Methods. We performed a systematic literature search on ERP in gynecologic oncology in June 2014 using PubMed/MEDLINE, EMBASE, and The Cochrane Library. All study types were included. References were hand reviewed to ensure completeness. The Enhanced Recovery After Surgery (ERAS) Society was contacted to identify any unpublished protocols. Results. Seven investigations were identified that examined the role of ERP in gynecologic oncology. Common interventions included allowing oral intake of fluids up to 2 hours before induction of anesthesia, solids up to 6 hours before anesthesia, carbohydrate supplementation, intra- and postoperative euvolemia, aggressive nausea/vomiting prophylaxis, and oral nutrition and ambulation the day of surgery. In addition, bowel preparations, the NPO after midnight rule, nasogastric tubes, and intravenous opioids were discontinued. While no randomized data are available in gynecologic oncology, significant improvements in patient satisfaction, length of stay (up to 4 days), and cost (up to $7600 in savings per patient) were observed in ERP cohorts compared to historical controls. Morbidity, mortality, and readmission rates were no different between groups. Conclusion. Enhanced recovery is a safe perioperative management strategy for patients undergoing surgery for gynecologic malignancies, reduces length of stay and cost, and is considered standard of care at a growing number of institutions. Our specialty would benefit from a formalized ERP such as ERAS which audits compliance to protocol care elements to optimize patient outcomes and value. © 2014 Elsevier Inc. All rights reserved.
Molina A.M.,Sloan Kettering Cancer Center |
Motzer R.J.,Sloan Kettering Cancer Center |
Heng D.Y.,Tom Baker Cancer Center
Seminars in Oncology | Year: 2013
The introduction of therapy targeting vascular endothelial growth factor (VEGF) and the mammalian target of rapomycin (mTOR) has significantly improved the outcome of patients with metastatic renal cancer. In this article a comprehensive overview of treatment choices for previously untreated patients with metastatic disease is given. Both established and emerging therapeutic options are discussed, as are prognostic factors predicting outcome. © 2013 Elsevier Inc.
Vassiliev O.N.,Tom Baker Cancer Center
Physics in Medicine and Biology | Year: 2012
Recently, a very low energy extension was added to the Monte Carlo simulation toolkit Geant4. It is intended for radiobiological modeling and is referred to as Geant4-DNA. Its performance, however, has not been systematically benchmarked in terms of transport characteristics. This study reports on the electron slowing-down spectra and mean energy per ion pair, the W-value, in water for monoenergetic electron and photon sources calculated with Geant4-DNA. These quantities depend on electron energy, but not on spatial or angular variables which makes them a good choice for testing the model of energy transfer processes. The spectra also have a scientific value for radiobiological modeling as they describe the energy distribution of electrons entering small volumes, such as the cell nucleus. Comparisons of Geant4-DNA results with previous studies showed overall good agreement. Some differences in slowing-down spectra between Geant4-DNA and previous studies were found at 100 eV and at approximately 500 eV that were attributed to approximations in models of vibrational excitations and atomic de-excitation after ionization by electron impact. We also found that the high-energy part of the Geant4-DNA spectrum for a 1 keV electron source was higher, and the asymptotic high-energy W-value was lower than previous studies reported. © 2012 Institute of Physics and Engineering in Medicine.
Vassiliev O.N.,Tom Baker Cancer Center
International Journal of Radiation Oncology Biology Physics | Year: 2012
Purpose: We proposed a formulation of the multi-hit single-target model in which the Poisson distribution of hits was replaced by a combination of two distributions: one for the number of particles entering the target and one for the number of hits a particle entering the target produces. Such an approach reflects the fact that radiation damage is a result of two different random processes: particle emission by a radiation source and interaction of particles with matter inside the target. Methods and Materials: Poisson distribution is well justified for the first of the two processes. The second distribution depends on how a hit is defined. To test our approach, we assumed that the second distribution was also a Poisson distribution. The two distributions combined resulted in a non-Poisson distribution. We tested the proposed model by comparing it with previously reported data for DNA single- and double-strand breaks induced by protons and electrons, for survival of a range of cell lines, and variation of the initial slopes of survival curves with radiation quality for heavy-ion beams. Results: Analysis of cell survival equations for this new model showed that they had realistic properties overall, such as the initial and high-dose slopes of survival curves, the shoulder, and relative biological effectiveness (RBE) In most cases tested, a better fit of survival curves was achieved with the new model than with the linear-quadratic model. The results also suggested that the proposed approach may extend the multi-hit model beyond its traditional role in analysis of survival curves to predicting effects of radiation quality and analysis of DNA strand breaks. Conclusions: Our model, although conceptually simple, performed well in all tests. The model was able to consistently fit data for both cell survival and DNA single- and double-strand breaks. It correctly predicted the dependence of radiation effects on parameters of radiation quality. © 2012 Elsevier Inc.