Radiology Commons^™

Comparative Effectiveness Of Intensity Modulated Radiation Therapy To 3-Dimensional Conformal Radiation In Locally Advanced Lung Cancer: Pathological And Clinical Outcomes., Sarit Appel, Jair Bar, Alon Ben-Nun, Marina Perelman, Dror Alezra, Damien Urban, Maoz Ben-Ayun, Nir Honig, Efrat Ofek, Tamar Katzman, Amir Onn, Sumit Chatterji, Sergey Dubinski, Lev Tsvang, Shira Felder, Judith Kraitman, Ory Haisraely, Tatiana Rabin Alezra, Sivan Lieberman, Edith M. Marom, Nir Golan, David Simansky, Zvi Symon, Yaacov Richard Lawrence

Department of Radiation Oncology Faculty Papers

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy.

METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) …

Top2a And Ezh2 Provide Early Detection Of An Aggressive Prostate Cancer Subgroup., David P. Labbé, Christopher J. Sweeney, Myles Brown, Phillip Galbo, Spencer Rosario, Kristine M. Wadosky, Sheng-Yu Ku, Martin Sjöström, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, R. Jeffrey Karnes, Edward M. Schaeffer, Robert B. Jenkins, Robert B. Den, Ashley E. Ross, Michaela Bowden, Ying Huang, Kathryn P. Gray, Felix Y. Feng, Daniel E. Spratt, David W. Goodrich, Kevin H. Eng, Leigh Ellis

Department of Radiation Oncology Faculty Papers

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess …

Hematologic Toxicity Of Concurrent Administration Of Radium-223 And Next-Generation Antiandrogen Therapies., Tu Dan, Harriet B. Eldredge-Hindy, Jean Hoffman-Censits, Jianqing Lin, William K. Kelly, Leonard G. Gomella, Costas D. Lallas, Edouard J. Trabulsi, Mark D. Hurwitz, Adam P. Dicker, Robert B. Den

Department of Radiation Oncology Faculty Papers

PURPOSE/OBJECTIVES: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving …

Nrg Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From A Phase 2 Study Of Repeat Breast-Preserving Surgery And 3-Dimensional Conformal Partial-Breast Reirradiation For In-Breast Recurrence., Douglas W. Arthur, Kathryn A. Winter, Henry M. Kuerer, Bruce G. Haffty, Laurie W. Cuttino, Dorin A. Todor, Nicole L. Simone, Shelly B. Hayes, Wendy A. Woodward, Beryl Mccormick, Randi J. Cohen, Walter M. Sahijdak, Daniel J. Canaday, Doris R. Brown, Adam D. Currey, Christine M. Fisher, Reshma Jagsi, Julia White

Department of Radiation Oncology Faculty Papers

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation.

METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, <3 >cm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was …

Adjuvant Radiation Therapy, Androgen Deprivation, And Docetaxel For High-Risk Prostate Cancer Postprostatectomy: Results Of Nrg Oncology/Rtog Study 0621., Mark D. Hurwitz, Jonathan Harris, Oliver Sartor, Ying Xiao, Bobby Shayegan, Paul W. Sperduto, Kasra R. Badiozamani, Colleen A.F. Lawton, Eric M. Horwitz, Jeff M. Michalski, Kevin Roof, David C. Beyer, Qiang Zhang, Howard M. Sandler

Department of Radiation Oncology Faculty Papers

BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined.

METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The …

Cogstate Computerized Memory Tests In Patients With Brain Metastases: Secondary Endpoint Results Of Nrg Oncology Rtog 0933., Chip Caine, Snehal Deshmukh, Vinai Gondi, Minesh Mehta, Wolfgang Tomé, Benjamin W. Corn, Andrew Kanner, Howard Rowley, Vijayananda Kundapur, Albert Denittis, Jeffrey Noah Greenspoon, Andre A. Konski, Glenn S. Bauman, Adam Raben, Wenyin Shi, Merideth Wendland, Lisa Kachnic

Department of Radiation Oncology Faculty Papers

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning …

Quantifying Unnecessary Normal Tissue Complication Risks Due To Suboptimal Planning: A Secondary Study Of Rtog 0126., Kevin L. Moore, Rachel Schmidt, Vitali Moiseenko, Lindsey A. Olsen, Jun Tan, Ying Xiao, James Galvin, Stephanie Pugh, Michael J Seider, Adam P. Dicker, Walter Bosch, Jeff Michalski, Sasa Mutic

Department of Radiation Oncology Faculty Papers

PURPOSE: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol.

METHODS AND MATERIALS: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative …

Focused Ultrasound For Treatment Of Bone Tumours., Dario B. Rodrigues, Paul R. Stauffer, David Vrba, Mark Hurwitz, Md

Department of Radiation Oncology Faculty Papers

PURPOSE: Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions.

METHODS: A comprehensive literature search and review of abstracts presented at the recently completed …

On Voxel-By-Voxel Accumulated Dose For Prostate Radiation Therapy Using Deformable Image Registration., Jialu Yu, Nicholas Hardcastle, Kyoungkeun Jeong, Edward T. Bender, Mark A. Ritter, Wolfgang A. Tomé

Department of Radiation Oncology Faculty Papers

Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using …

African American Men With Low-Grade Prostate Cancer Have Increased Disease Recurrence After Prostatectomy Compared With Caucasian Men., Kosj Yamoah, Curtiland Deville, Neha Vapiwala, Elaine Spangler, Charnita M. Zeigler-Johnson, Bruce Malkowicz, David I Lee, Michael Kattan, Adam P. Dicker, Timothy R. Rebbeck

Department of Radiation Oncology Faculty Papers

PURPOSE: To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP).

METHODS: The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and …

Hyperthermia, Radiation And Chemotherapy: The Role Of Heat In Multidisciplinary Cancer Care., Mark Hurwitz, Md, Paul R. Stauffer

Department of Radiation Oncology Faculty Papers

The compelling biologic basis for combining hyperthermia with modern cancer therapies including radiation and chemotherapy was first appreciated nearly half a century ago. Hyperthermia complements radiation as conditions contributing to radio-resistance generally enhance sensitivity to heat and sensitizing effects occur through increased perfusion/tumor oxygenation and alteration of cellular death pathways. Chemosensitization with hyperthermia is dependent on the particular mechanism of effect for each agent with synergistic effects noted for several commonly used agents. Clinically, randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in treatment of a wide range of malignancies. Improvements in …

Thermal Dosimetry Characteristics Of Deep Regional Heating Of Non-Muscle Invasive Bladder Cancer., Titania Juang, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Yu Yuan, Shiva K Das, Mark W Dewhirst, Brant A Inman, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: The aim of this paper is to report thermal dosimetry characteristics of external deep regional pelvic hyperthermia combined with intravesical mitomycin C (MMC) for treating bladder cancer following transurethral resection of bladder tumour, and to use thermal data to evaluate reliability of delivering the prescribed hyperthermia dose to bladder tissue.

MATERIALS AND METHODS: A total of 14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma Ellipse or Sigma 60). The hyperthermia objective was 42° ± 2 °C to bladder tissue for ≥40 min per treatment. Temperatures were monitored with thermistor probes and recorded values were used …

A Pilot Clinical Trial Of Intravesical Mitomycin-C And External Deep Pelvic Hyperthermia For Non-Muscle-Invasive Bladder Cancer., Brant A Inman, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Mark W Dewhirst, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC).

MATERIALS AND METHODS: We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured.

RESULTS: Fifteen patients were …

A Randomized Trial Of Bevacizumab For Newly Diagnosed Glioblastoma., Mark R Gilbert, James J Dignam, Terri S Armstrong, Jeffrey S Wefel, Deborah T Blumenthal, Michael A Vogelbaum, Howard Colman, Arnab Chakravarti, Stephanie Pugh, Minhee Won, Robert Jeraj, Paul D Brown, Kurt A Jaeckle, David Schiff, Volker W Stieber, David G Brachman, Maria Werner-Wasik, Ivo W Tremont-Lukats, Erik P Sulman, Kenneth D Aldape, Walter J Curran, Minesh P Mehta

Department of Radiation Oncology Faculty Papers

BACKGROUND: Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known.

METHODS: In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. …

Multiple Courses Of Stereotactic Re-Irradiation In Recurrent Oligodendroglioma: A Case Report., Shannon Fogh, Charles Glass, David W Andrews, Maria Werner-Wasik

Department of Radiation Oncology Faculty Papers

INTRODUCTION: High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit.

CASE PRESENTATION: In this report, we describe a 37-year-old Caucasian male initially diagnosed with a grade IV oligodendroglioma, who received multiple courses of re-irradiation and experienced a survival of 10 …

Phase I Study Of 'Dose-Dense' Pemetrexed Plus Carboplatin/Radiotherapy For Locally Advanced Non-Small Cell Lung Carcinoma., Xinglei Shen, Albert Denittis, Maria Werner-Wasik, Rita Axelrod, Paul Gilman, Thomas Meyer, Joseph Treat, Walter J Curran, Mitchell Machtay

Department of Radiation Oncology Faculty Papers

BACKGROUND: This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC).

METHODS: Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level …

Differential Regulation Of P53 Function By The N-Terminal Δnp53 And Δ113p53 Isoforms In Zebrafish Embryos., William R Davidson, Csaba Kari, Qing Ren, Borbala Daroczi, Adam P Dicker, Ulrich Rodeck

Department of Radiation Oncology Faculty Papers

BACKGROUND: The p53 protein family coordinates stress responses of cells and organisms. Alternative promoter usage and/or splicing of p53 mRNA gives rise to at least nine mammalian p53 proteins with distinct N- and C-termini which are differentially expressed in normal and malignant cells. The human N-terminal p53 variants contain either the full-length (FL), or a truncated (ΔN/Δ40) or no transactivation domain (Δ133) altogether. The functional consequences of coexpression of the different p53 isoforms are poorly defined. Here we investigated functional aspects of the zebrafish ΔNp53 ortholog in the context of FLp53 and the zebrafish Δ133p53 ortholog (Δ113p53) coexpressed in the …

Splenic Infarction: An Update On William Osler's Observations., Yaacov R Lawrence, Ma Mbbs Mrcp, Russell Pokroy, Mb Bch, Daniel Berlowitz, Mb Bch, Dvora Aharoni, Md, Daniel Hain, Md, Gabriel S Breuer, Md

Department of Radiation Oncology Faculty Papers

BACKGROUND: Osler taught that splenic infarction presents with left upper abdominal quadrant pain, tenderness and swelling accompanied by a peritoneal friction rub. Splenic infarction is classically associated with bacterial endocarditis and sickle cell disease.

OBJECTIVES: To describe the contemporary experience of splenic infarction.

METHODS: We conducted a chart review of inpatients diagnosed with splenic infarction in a Jerusalem hospital between 1990 and 2003.

RESULTS: We identified 26 cases with a mean age of 52 years. Common causes were hematologic malignancy (six cases) and intracardiac thrombus (five cases). Only three cases were associated with bacterial endocarditis. In 21 cases the splenic …

Combination Of Vandetanib, Radiotherapy, And Irinotecan In The Lovo Human Colorectal Cancer Xenograft Model., Phyllis Wachsberger, Randy Burd, Anderson Ryan, Constantine Daskalakis, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

PURPOSE: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. METHODS AND MATERIALS: LoVo cells were injected subcutaneously into the right hind limb (5 x 10(6) cells in 100 microL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm(3) before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3 x 3 Gy) …

Dosimetric Evaluation Of Heterogeneity Corrections For Rtog 0236: Stereotactic Body Radiotherapy Of Inoperable Stage I-Ii Non-Small-Cell Lung Cancer., Ying Xiao, Lech Papiez, Rebecca Paulus, Robert Timmerman, William L. Straube, Walter R. Bosch, Jeff Michalski, James M. Galvin

Department of Radiation Oncology Faculty Papers

PURPOSE: Using a retrospective analysis of treatment plans submitted from multiple institutions accruing patients to the Radiation Therapy Oncology Group (RTOG) 0236 non-small-cell stereotactic body radiotherapy protocol, the present study determined the dose prescription and critical structure constraints for future stereotactic body radiotherapy lung protocols that mandate density-corrected dose calculations.

METHOD AND MATERIALS: A subset of 20 patients from four institutions participating in the RTOG 0236 protocol and using superposition/convolution algorithms were compared. The RTOG 0236 protocol required a prescription dose of 60 Gy delivered in three fractions to cover 95% of the planning target volume. Additional requirements were specified …

Recent Trends In Soft-Tissue Infection Imaging., Nicholas Petruzzi, Md, Nylla Shanthly, Mbbs, Drm, Mathew L. Thakur, Phd

Department of Radiation Oncology Faculty Papers

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, central nervous system, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection-specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory tract infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to …

Increasing Tumor Volume Is Predictive Of Poor Overall And Progression-Free Survival: Secondary Analysis Of The Radiation Therapy Oncology Group 93-11 Phase I-Ii Radiation Dose-Escalation Study In Patients With Inoperable Non-Small-Cell Lung Cancer, Maria Werner-Wasik, R. Suzanne Swann, Jeffrey Bradley, Mary Graham, Bahman Emami, James Purdy, William Sause

Department of Radiation Oncology Faculty Papers

PURPOSE: Patients with non-small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels. We investigated the effect of the gross tumor volume (GTV) on the outcome.

METHODS AND MATERIALS: The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (< or =45 cm(3)) vs. larger (>45 cm(3)) tumors.

RESULTS: The distribution of …

Department Of Radiation Oncology And Kimmel Cancer Center, Thomas Jefferson University, The Intronic G13964c Variant In P53 Is Not A High-Risk Mutation In Familial Breast Cancer In Australia., Anna Marsh, Amanda B Spurdle, Bruce C Turner, Sian Fereday, Heather Thorne, Gulietta M Pupo, Graham J Mann, John L Hopper, Joseph F Sambrook, Georgia Chenevix-Trench

Department of Radiation Oncology Faculty Papers

BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in …