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Mohindra P.,University of Wisconsin - Madison | Sinha R.N.,Western Radiation Oncology | Andrews R.J.,NASA | Khuntia D.,Western Radiation Oncology
Current Cancer Drug Targets | Year: 2012

Brain tumors, primary and metastatic, are a cause of significant mortality and morbidity. Radiotherapy (RT) forms an integral part of the treatment of brain tumors. Intrinsic relative tumor radio-resistance, normal tissue tolerance and impact on neurocognitive function, all limits the efficacy of RT. Radiosensitizers can potentially increase efficacy on tumors while maintaining normal tissue toxicity, with or without inherent cytotoxicity. This article reviews the evolution of evidence with use of non-cytotoxic radiosensitizers in brain radiotherapy and their status at the end of the first decade of this millennium. Considering, the era of development and mechanism of action, these agents are classified as first, second and third-generation non-cytotoxic radiosensitizers. The last millennium involved elaboration of first-generation compounds including halogenated pyrimidines, hypoxic cell sensitizers (e.g. imidazoles) and glycolytic inhibitors (e.g. lonidamine). The first decade of this millennium has highlighted redox modulators like motexafin gadolinium and newer hypoxic cell sensitizers like efaproxiral, which have shown promise. However, phase III trials and meta-analyses have not identified a clear winner though the second-generation has shown some rays of hope. Recent research has focused on expanding the horizon by studying modulation of newer molecular pathways like DNA repair, microtubule stabilization, cytokine function and nuclear factor-kappa beta (NF-KB) in order to increase RT efficacy. The review concludes by summarizing the class of evidence and the level of recommendation available for use of non-cytotoxic radiosensitizers in brain RT. © 2012 Bentham Science Publishers.


Thomadsen B.R.,University of Wisconsin - Madison | Erickson B.A.,Medical College of Wisconsin | Eifel P.J.,University of Houston | Hsu I.-C.,University of California at San Francisco | And 4 more authors.
Practical Radiation Oncology | Year: 2014

This white paper was commissioned by the American Society for Radiation Oncology (ASTRO) Board of Directors to evaluate the status of safety and practice guidance for high-dose-rate (HDR) brachytherapy. Given the maturity of HDR brachytherapy technology, this white paper considers, from a safety point of view, the adequacy of general physics and quality assurance guidance, as well as clinical guidance documents available for the most common treatment sites. The rate of medical events in HDR brachytherapy procedures in the United States in 2009 and 2010 was 0.02%, corresponding to 5-sigma performance. The events were not due to lack of guidance documents but failures to follow those recommendations or human failures in the performance of tasks. The white paper summarized by this Executive Summary reviews current guidance documents and offers recommendations regarding their application to delivery of HDR brachytherapy. It also suggests topics where additional research and guidance is needed. © 2014 American Society for Radiation Oncology.


Taira Al.V.,Western Radiation Oncology | Merrick G.S.,Wheeling Jesuit University | Galbreath R.W.,Wheeling Jesuit University | Butler W.M.,Wheeling Jesuit University | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size (≤20 cm 3) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate size for the entire cohort was 32.7 cm 3. For the 167 men with small prostates, median prostate size was 17.4 cm 3. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size. © 2012 Elsevier Inc.


Taira A.V.,Western Radiation Oncology | Merrick G.S.,Wheeling Jesuit University | Galbreath R.W.,Wheeling Jesuit University | Butler W.M.,Wheeling Jesuit University | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase ≥25%, 23% of men experienced a decrease ≥25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response does not seem related to temporal testosterone changes. Copyright © 2012 Elsevier Inc. Printed in the USA. All rights reserved.


Daniel E.S.,Colorectal Unit | Gibbs P.,Royal Melbourne Hospital | Guerrieri M.,Western Radiation Oncology | Faragher I.,Colorectal Unit
Colorectal Disease | Year: 2014

Aim: Neoadjuvant chemoradiotherapy is the standard of care for locally advanced rectal cancer, with diagnostic work-up routinely including a biopsy confirming invasive carcinoma. For the occasional patient where initial biopsies reveal only dysplasia, or even normal epithelium, repeat biopsy is currently advised, but this may delay therapy and repeat biopsy has potential adverse effects. The study aimed to determine, in the setting of clinical findings and imaging demonstrating locally advanced rectal cancer, whether the absence of a tissue diagnosis prior to commencing chemoradiation compromises patient outcome. Method: A review was conducted of our database, including comprehensive treatment and outcome details, in which consecutive patients with colorectal cancer have been enrolled since 1997 at a single institution. All records for patients who received neoadjuvant chemoradiotherapy for locally advanced rectal cancer were reviewed to identify patients for whom treatment was initiated before a tissue diagnosis was obtained, and to assess any consequences of this. Results: Of 254 patients who had received neoadjuvant treatment for rectal cancer, 16 (6.3%) were found to have had neoadjuvant therapy without a tissue diagnosis of invasive cancer. Compared with cases where a tissue diagnosis had been obtained, median age (59 vs 63 years, P = 0.497), sex (75% vs 71.3% male, P = 0.955) and tumour location (56.3% vs 73.5% < 8 cm, P = 0.230) were similar. Of these, 14 (87.5%) had adenocarcinoma identified on histopathology review of the surgical specimen. Three patients were considered to have had complete pathological responses with mucin lakes within the muscularis propria (n = 2) or lymph nodes (n = 1) or fibrosis (n = 3). One of these had no mucin evident and only fibrosis; thus final pathological proof of invasive cancer was present in 15 (93.5%) patients. There were no local recurrences, but three of the 16 (18.8%) cases developed distant recurrence. Conclusion: For the small number of cases without a confirmatory tissue diagnosis before chemoradiation, no adverse consequences were identified. In particular the initial diagnosis was confirmed in 15 out of 16 cases following pathological examination of the operative specimen. We would suggest that, where clinical and radiological features support a diagnosis of locally advanced rectal cancer, proceeding directly to neoadjuvant chemoradiotherapy in the absence of a biopsy demonstrating invasive cancer may not be unreasonable, particularly where repeat biopsy would delay the commencement of treatment. © 2014 The Association of Coloproctology of Great Britain and Ireland.

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