Papers by Nicholas G Zaorsky
International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 2014
Purpose: To determine the precision of our institution's current immobilization devices for spine... more Purpose: To determine the precision of our institution's current immobilization devices for spine SBRT, ultimately leading to recommendations for appropriate planning margins. Methods: We identified 12 patients (25 treatments) with spinal metastasis treated with spine Stereotactic Body Radiation Therapy (SBRT). The Body-FIX system was used as immobilization device for thoracic (T) and lumbar (L) spine lesions. The head and shoulder mask system was used as immobilization device for cervical (C) spine lesions. Initial patient setup used the infrared positioning system with body markers. Stereotactic X-ray imaging was then performed and correction was made if the initial setup error exceeded predetermined institutional tolerances, 1.5 mm for translation and 2˚ for rotation. Three additional sets of verification X-rays were obtained pre-, mid-, and post-treatment for all treatments. Results: Intrafraction motion regardless of immobilization technique was found to be 1.28 ± 0.57 mm. The mean and standard deviation of the variances along each direction were as follows: Superior-inferior, 0.56 ± 0.39 mm and 0.77 ± 0.52 mm, (p = 0.25); Anterior-posterior, 0.57 ± 0.43 mm and 1.14 ± 0.61 mm, (p = 0.01); Left-right, 0.48 ± 0.34 mm and 0.74 ± 0.40 mm, (p = 0.09) respectively. There was a significantly greater difference in the average 3D variance of the BodyFIX as compared to the head and shoulder mask immobilization system, 1.04 ± 0.46 mm and 1.71 ± 0.52 mm; (p = 0.003) respectively. Conclusions: Overall, our institution's image guidance system using stereotactic X-ray imaging verification provides acceptable localization accuracy as previously defined in the literature. We observed a greater intrafraction motion for the head and shoulder mask as compared with the BodyFIX immobilization system, which may be a result of greater C-spine mobility and/or the suboptimal mask immobilization. Thus, better immobilization techniques for C-spine SBRT are needed to reduce setup error and intrafraction motion. We are currently exploring alternative C-spine immobilization techniques to improve set up accuracy and decrease intrafraction motion during treatment.
Brachytherapy, 2014
PURPOSE: Prostate volume greater than 50 cc is traditionally a relative contraindication to prost... more PURPOSE: Prostate volume greater than 50 cc is traditionally a relative contraindication to prostate seed implantation (PSI), but there is little consensus regarding prostate size and clinical outcomes. We report biochemical control and toxicity after low-dose-rate PSI and compare outcomes according to the prostate size. METHODS AND MATERIALS: A total of 429 men who underwent low-dose-rate PSI between 1998 and 2009 were evaluated. Median followup was 38.7 months. Patients were classified by prostate volume into small, medium, and large subgroups. Differences were analyzed using the Man-neWhitney and Pearson's c 2 tests for continuous and categorical variables, respectively. Cox proportional hazards regression models were used to evaluate effect of prostate size on outcomes. RESULTS: Patient pretreatment factors were balanced between groups except for age ( p 5 0.001). The 10-year actuarial freedom from biochemical failure for all patients treated with PSI was 96.3% with no statistically significant difference between large vs. small/medium prostate size (90% vs. 96.6%, p 5 0.47). In a multivariate analysis, plan type (hazard ratio [HR] 5 0.25, p 5 0.03), dose to 90% of the gland (D 90 : HR 5 0.98, p 5 0.02), volume receiving 200 Gy (V 200 : HR 5 0.98, p 5 0.026), and biologic effective dose (HR 5 0.99, p 5 0.045), but not prostate size (HR 5 2.27, p 5 0.17) were significantly associated with freedom from biochemical failure. Prostate size was not significantly associated with time to maximum American Urologic Association score. CONCLUSION: In men with large prostates, the PSI provides biochemical control and temporal changes in genitourinary toxicity that are comparable with men having smaller glands. Accurate dose optimization and delivery of PSI provides the best clinical outcomes regardless of gland size. Published by Elsevier Inc. on behalf of American Brachytherapy Society.
International Journal of Radiation Oncology*Biology*Physics, 2013
Brachytherapy, 2013
ABSTRACT PURPOSE: Low dose rate brachytherapy (LDR-BT) is a popular treatment for localized prost... more ABSTRACT PURPOSE: Low dose rate brachytherapy (LDR-BT) is a popular treatment for localized prostate cancer, but long-term data have only recently been published. We investigate the efficacy and toxicity of LDR-BT for localized prostate cancer. MATERIALS AND METHODS: Between 1991 and 2012, 388 men were treated at Thomas Jefferson University Hospital with LDR-BT for localized prostate cancer. Outcomes analyzed included overall survival (OS); freedom from biochemical failure (FFBF); and acute and late RTOG genitourinary (GU), gastrointestinal (GI), skin, and hematologic toxicities. Fisher's exact chi-squared test was used to compare number of deaths per stage and Kaplan-Meier estimation was used for survival analysis. RESULTS: The average age of patients was 64 years. Based on the 7th edition of the American Joint Committee on Cancer, 72% of patients were Stage I; 25%, Stage IIA; 2.3%, Stage IIB; 0.5%, Stage III. Eleven percent of patients received androgen deprivation therapy. The mean dose BT was 140 Gy. At a median follow-up time of 9.3 years, the 10-year OS was 94% and FFBF was 84% for all patients [Figure 1]. There was no significant difference in 10-year OS between Stage I and Stage II patients (97% vs. 94%, p = 0.18). There was no significant difference in 10-year FFBF between Stage I and Stage II patients (89% vs. 73%, p = 0.4). The overall incidences of acute RTOG Grade 0, 1, 2, and 3 GU toxicities were 37%, 1.3%, 2.0%, and 0.83%; late GU toxicities, 38%, 5.5%, 2.4%, 0.3%. The overall incidences of acute RTOG Grade 0, 1, 2, and 3 GI toxicities were 58%, 1.4%, 4.4%, and 0%; late GI toxicities, 55%, 1.3%, 6.9%, 0.28%. The overall incidences of acute RTOG Grade 0, 1, 2, and 3 skin toxicities were 99%, 0.5%, 0.2%, and 0%. No patients had late skin toxicity; none had acute or late hematological toxicities. CONCLUSIONS: LDR-BT is an efficacious treatment modality for localized prostate cancer, with a 94% OS rate and 84% FFBF rate at 10 years among our patients, which is comparable to published studies. Less than 10% of patients experienced Grade 1 or 2 GI or GU toxicity. Future studies will aim to identify patients at high risk of toxicity and evaluate other measures of quality of life.
Nature Reviews Urology
Conventional treatment options for clinically localized, low-risk prostate cancer include radical... more Conventional treatment options for clinically localized, low-risk prostate cancer include radical prostatectomy, external-beam radiotherapy (EBRT) and low-dose-rate brachytherapy. Advances in image-guided radiotherapy (IGRT) since the 1980s, the development of intensity-modulated radiotherapy (IMRT) during the 1990s and evidence from radiobiological models-which support the use of high doses per fraction-have developed alongside novel advanced radiotherapy modalities that include high-dose-rate brachytherapy (HDR-BT), stereotactic body radiotherapy (SBRT) and proton beam therapy. The relationship between the outcomes of and toxicities experienced by patients with prostate cancer treated with HDR-BT, SBRT and particle-beam therapy should provide urologists and oncologists an understanding of the continually evolving technology in prostate radiotherapy. On the basis of published evidence, conventionally fractionated EBRT with IMRT is considered the standard of care over conventional 3...
Future Oncology
Approximately a third of men with localized prostate cancer who are treated with external beam ra... more Approximately a third of men with localized prostate cancer who are treated with external beam radiation therapy (EBRT) or radical prostatectomy (RP) develop biochemical failure (BF). Presumably, BF will progress to distant metastasis and prostate cancer-specific mortality in some patients over subsequent years. Accurate detection of recurrent disease is important because it allows for appropriate treatment selection (e.g., local vs systemic therapy) and early delivery of therapy (e.g., salvage EBRT), which affect patient outcome. In this article, we discuss the paradigm shift in imaging technology in the detection of recurrent prostate cancer. First, we discuss the commonly used morphological and anatomical imaging modalities and their role in the post-RP and post-EBRT settings of BF. Second, we discuss the accuracy of functional and molecular imaging techniques, many of which are under investigation. Further studies are needed to establish the role of imaging techniques for detect...
Nature Reviews Urology, 2012
| In general, patients with prostate cancer are able to maintain a relatively high quality of lif... more | In general, patients with prostate cancer are able to maintain a relatively high quality of life (QOL), commonly reporting improvements in physical, emotional, and social functioning within 1 year of treatment. However, certain subpopulations of patients are susceptible to significant reductions in QOL during the course of their treatment. Data suggest that ethnic background and sexual preference both have significant effects on QOL for patients with prostate cancer. These parameters are often poorly documented and addressed by medical practitioners. Greater attention is needed to identify patients who are at increased risk of QOL reduction as a result of these factors.
American journal of cancer research, 2014
Inhibitors of apoptosis (IAPs) limit the effectiveness of radiation in non-small cell lung cancer... more Inhibitors of apoptosis (IAPs) limit the effectiveness of radiation in non-small cell lung cancer (NSCLC). Debio 1143 (D1143) is an antagonist of IAPs. The purpose of this study was to investigate the potential of D1143 as a radiosensitizer in NSCLC. MTS assays were performed in two NSCLC cell lines: HCC193 and H460. Extent of apoptotic cell death was characterized by Annexin V assay and Western blot for cleaved caspase-3, -8, and IAPs. TNF-α release was determined by ELISA. Radiosensitivities were compared with dose enhancement ratios (DERs). HCC193 cells D1143 IC50 was 1 μM. HCC193 cells demonstrated noticeable cleaved caspase-3, -8, and a decrease in IAP levels with 2.5 μM D1143; H460 cells, with 10 μM; both in a time-dependent manner. Additionally, HCC193 cells exhibited an increase in TNF-α. D1143 radiosensitized cells: HCC193, 2.5 μM D1143, 24 h incubation, DER of 2.19, p = 0.001; H460 cells, 10 μM D1143, 48 h incubation, DER of 1.29, p = 0.082. Treatment of H460 cells with ra...
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 28, 2015
To determine if increasing the biologically equivalent dose (BED) via various radiation fractiona... more To determine if increasing the biologically equivalent dose (BED) via various radiation fractionation regimens is correlated with clinical outcomes or toxicities for prostate cancer. We performed a meta-analysis that included 12,756 prostate cancer patients from 55 studies published from 2003 to 2013 who were treated with non-dose-escalated conventionally fractionated external beam radiation therapy (non-DE-CFRT), DE-CFRT, hypofractionated RT, and high dose rate brachytherapy (HDR-BT; either mono or boost) with ⩾5-year actuarial follow-up. BEDs were calculated based on the following formula: (nd[1+d/(α/β)]), where n is the number of fractions, and d is dose per fraction; assuming an α/β of 1.5 for prostate cancer and 3.0 for late toxicities. Mixed effects meta-regression models were used to estimate weighted linear relationships between BED and the observed percentages of patients experiencing late toxicities or 5-year freedom from biochemical failure (FFBF). Increases in 10Gy incre...
Molecular Cancer Therapeutics, 2013
Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that h... more Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC). While in clinical trials, PF02341066 has shown a significant therapeutic benefit as a single agent; the effectiveness of combining it with other therapeutic modalities including ionizing radiation remains unknown. To further elucidate the role of PF02341066 in tumor inhibition, we examined its effects alone and in combination with radiation on downstream signaling, apoptosis, and radiosensitivity in two NSCLC cell lines in vitro: H3122, which harbors the EML4-ALK fusion, and H460, which does not. We also examined the in vivo effects of PF02341066 in H3122 mouse xenografts. In the H3122 cell line, PF02341066 inhibited phosphorylation of ALK and its downstream effectors: AKT, ERK, and STAT3. H3122 cells treated with a combination of PF02341066 and radiation showed an increase in cellular apoptosis and were sensitized to radiation therapy (dose enhancement ratio, 1.43; P < 0.0001). Moreover, in an H3122 xenograft model, the combined treatment resulted in greater tumor growth inhibition than either treatment alone (P < 0.05). None of these effects was observed in the EML4-ALK-negative H460 cells. Our findings indicate that PF02341066 acts as a radiation sensitizer in cells harboring the EML4-ALK fusion, providing a rationale for a clinical trial combining ALK inhibitor with radiation in the NSCLCs expressing ALK.
International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 2014
Purpose: To determine the precision of our institution's current immobilization devices for spine... more Purpose: To determine the precision of our institution's current immobilization devices for spine SBRT, ultimately leading to recommendations for appropriate planning margins. Methods: We identified 12 patients (25 treatments) with spinal metastasis treated with spine Stereotactic Body Radiation Therapy (SBRT). The Body-FIX system was used as immobilization device for thoracic (T) and lumbar (L) spine lesions. The head and shoulder mask system was used as immobilization device for cervical (C) spine lesions. Initial patient setup used the infrared positioning system with body markers. Stereotactic X-ray imaging was then performed and correction was made if the initial setup error exceeded predetermined institutional tolerances, 1.5 mm for translation and 2˚ for rotation. Three additional sets of verification X-rays were obtained pre-, mid-, and post-treatment for all treatments. Results: Intrafraction motion regardless of immobilization technique was found to be 1.28 ± 0.57 mm. The mean and standard deviation of the variances along each direction were as follows: Superior-inferior, 0.56 ± 0.39 mm and 0.77 ± 0.52 mm, (p = 0.25); Anterior-posterior, 0.57 ± 0.43 mm and 1.14 ± 0.61 mm, (p = 0.01); Left-right, 0.48 ± 0.34 mm and 0.74 ± 0.40 mm, (p = 0.09) respectively. There was a significantly greater difference in the average 3D variance of the BodyFIX as compared to the head and shoulder mask immobilization system, 1.04 ± 0.46 mm and 1.71 ± 0.52 mm; (p = 0.003) respectively. Conclusions: Overall, our institution's image guidance system using stereotactic X-ray imaging verification provides acceptable localization accuracy as previously defined in the literature. We observed a greater intrafraction motion for the head and shoulder mask as compared with the BodyFIX immobilization system, which may be a result of greater C-spine mobility and/or the suboptimal mask immobilization. Thus, better immobilization techniques for C-spine SBRT are needed to reduce setup error and intrafraction motion. We are currently exploring alternative C-spine immobilization techniques to improve set up accuracy and decrease intrafraction motion during treatment.
With an emphasis on multidisciplinary collaboration and decision-making, this practical resource ... more With an emphasis on multidisciplinary collaboration and decision-making, this practical resource reflects the extraordinary advances in the treatment of prostate cancer during the past five years. Approximately thirty international, leading-edge investigators describe the most current evidence-based approaches to prostate cancer treatment. The book provides a comprehensive view of the entire spectrum of prostate cancer management from initial screening through novel and experimental treatments that have the potential for a major impact on practice. The book first reviews fundamental issues including epidemiology, screening, risk reduction, diagnosis and pathologic characterization, staging, and imaging. This includes strategies for improving the accuracy of PSA screening and an update on controversies surrounding the ISUP Modified Gleason Score. The book covers novel molecular and genotype profiling in prostate cancer, including morphometric and systems pathology. Detailed informati...
International Journal of Radiation Oncology*Biology*Physics, 2011
Background: Skull base meningiomas commonly present with cranial neuropathies. Fractionated stere... more Background: Skull base meningiomas commonly present with cranial neuropathies. Fractionated stereotactic radiation therapy (FSRT) has been used to treat these tumors with excellent local control, but rates of improvement in cranial neuropathies have not been well defined. We review the experience at Thomas Jefferson University using FSRT in the management of these patients with a focus on symptom outcomes. Methods: We identified 225 cases of skull base meningiomas treated with FSRT at Thomas Jefferson University from 1994 through 2009. The target volume was the enhancing tumor, treated to a standard prescription dose of 54 Gy. Symptoms at the time of RT were classified based on the cranial nerve affected. Logistic regression was performed to determine predictors of symptom improvement after FSRT.
Cancer Biology & Therapy, 2013
Journal of thoracic disease, 2014
The elucidation of driver mutations involved in the molecular pathogenesis of cancer has led to a... more The elucidation of driver mutations involved in the molecular pathogenesis of cancer has led to a surge in the application of novel targeted therapeutics in lung cancer. Novel oncologic research continues to lead investigators towards targeting personalized tumor characteristics rather than applying targeted therapy to broad patient populations. Several driver genes, in particular epidermal growth factor receptor (EGFR) and ALK fusions, are the earliest to have made their way into clinical trials. The avant-garde role of genomic profiling has led to important clinical challenges when adapting current standard treatments to personalized oncologic care. This new frontier of medicine requires newer biomarkers for toxicity that will identify patients at risk, as well as, new molecular markers to predict and assess clinical outcomes. Thus far, several signature genes have been developed to predict outcome as well as genetic factors related to inflammation to predict toxicity.
Practical Radiation Oncology, 2014
Purpose: Sparing the hippocampus during whole brain radiation therapy (WBRT) offers potential neu... more Purpose: Sparing the hippocampus during whole brain radiation therapy (WBRT) offers potential neurocognitive benefits. However, previously reported intensity modulated radiation therapy (IMRT) plans use multiple noncoplanar beams for treatment delivery. An optimized coplanar IMRT template for hippocampal-sparing WBRT would assist in clinical workflow and minimize resource utilization. In this study, we sought to determine the optimal patient position to facilitate coplanar treatment planning and delivery of hippocampal-sparing WBRT using IMRT. Methods and materials: A variable angle, inclined board was utilized for patient positioning. An anthropomorphic phantom underwent computed tomography simulation at various head angles. The IMRT goals were designed to achieve target coverage of the brain while maintaining hippocampal dose-volume constraints designed to conform to the Radiation Therapy Oncology Group 0933 protocol. Optimal head angle was then verified using data from 8 patients comparing coplanar and noncoplanar WBRT IMRT plans. Results: Hippocampal, hippocampal avoidance region, and whole brain mean volumes were 1.1 cm 3 , 12.5 cm 3 , and 1185.1 cm 3 , respectively. The hippocampal avoidance region occupied 1.1% of the whole brain planning volume. For the 30-degree head angle, a 7-field coplanar IMRT plan was generated, sparing the hippocampus to a maximum dose of 14.7 Gy; D100% of the hippocampus was 7.4 Gy and mean hippocampal dose was 9.3 Gy. In comparison, for flat head positioning the hippocampal Dmax was 22.9 Gy with a D100% of 9.2 Gy and mean dose of 11.7 Gy. Target coverage and dose homogeneity was comparable with previously published noncoplanar IMRT plans. Conclusions: Compared with conventional supine positioning, an inclined head board at 30 degrees optimizes coplanar whole brain IMRT treatment planning. Clinically acceptable hippocampal-sparing WBRT dosimetry can be obtained using a simplified coplanar plan at a 30-degree head angle, thus obviating the need for complex and time consuming noncoplanar IMRT plans.
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Papers by Nicholas G Zaorsky