Medicine and Health Sciences Commons^™

Spaceoar To Improve Dosimetric Outcomes For Monotherapy High-Dose-Rate Prostate Implantation In A Patient With Ulcerative Colitis., Michael Trager, Benjamin Greenberger, Amy S. Harrison, James Keller, Robert B. Den

Department of Radiation Oncology Faculty Papers

High-dose-rate (HDR) brachytherapy is an attractive option for patients receiving definitive radiation therapy for prostate cancer with decreased overall dose to the pelvis. However, ulcerative colitis increases rectal toxicity risk and may be a contraindication. A synthetic hydrogel, SpaceOAR (Augmentix Inc., Waltham, MA, USA), can facilitate the use of HDR brachytherapy for patients where rectal toxicity is a limiting factor. SpaceOAR gel (13.19 cc) was utilized in a monotherapy HDR prostate treatment with Ir-192 under transrectal ultrasound guidance, with the intention of decreasing rectal dose. SpaceOAR gel was inserted transperineally into the patient 18 days prior to the procedure. The …

Effect Of Differences In Metabolic Activity Of Melanoma Models On Response To Lonidamine Plus Doxorubicin., Kavindra Nath, Jeffrey Roman, David S. Nelson, Lili Guo, Seung-Cheol Lee, Stepan Orlovskiy, Kevin Muriuki, Daniel F. Heitjan, Stephen Pickup, Dennis B. Leeper, Ian A. Blair, Mary E. Putt, Jerry D. Glickson

Department of Radiation Oncology Faculty Papers

Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than WM983B in vitro. ³¹P magnetic resonance spectroscopy (MRS) indicates that LND (100 mg/kg, i.p.) induces similar selective acidification and de-energization of WM983B xenografts in immunosuppressed mice. Over three hours, intracellular pH (pHi) of WM983B decreased from 6.91 ± 0.03 to 6.59 ± 0.10 (p …

Evaluation Of Hybrid Arc And Volumetric-Modulated Arc Therapy Treatment Plans For Fractionated Stereotactic Intracranial Radiotherapy., Jun Li, David To, Vickie Gunn, Wenyin Shi, Yan Yu, Haisong Lui

Department of Radiation Oncology Faculty Papers

PURPOSE: The study was aimed to compare hybrid arc and volumetric-modulated arc therapy treatment plans for fractionated stereotactic radiotherapy of brain tumors.

METHODS: Treatment plans of 22 patients were studied. Hybrid arc and volumetric-modulated arc therapy plans were generated using Brainlab iPlanDose and Varian Eclipse treatment planning systems, respectively, with 6 MV photon beams on a Varian TrueBeam STx linear accelerator (Palo Alto, CA). Prescription dose was 54 Gy. The fractionation was 1.8 Gy per fraction and 30 fractions in total, or 2 Gy per fraction and 27 fractions in total. Planning target volume ranged from 2.4 to 28.6 cm …

Development And Validation Of A Prostate Cancer Genomic Signature That Predicts Early Adt Treatment Response Following Radical Prostatectomy., R. Jeffrey Karnes, Vidit Sharma, Voleak Choeurng, Hussam Al-Deen Ashab, Nicholas Erho, Mohammed Alshalalfa, Bruce Trock, Ashley Ross, Kasra Yousefi, Harrison Tsai, Shuang G. Zhao, Jeffrey J. Tosoian, Zaid Haddad, Mandeep Takhar, S. Laura Chang, Daniel E. Spratt, Firas Abdollah, Robert B. Jenkins, Eric A. Klein, Paul L. Nguyen, Adam P. Dicker, Robert B. Den, Elai Davicioni, Felix Y. Feng, Tamara L. Lotan, Edward M. Schaeffer

Department of Radiation Oncology Faculty Papers

Purpose: Currently, no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy for high-risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT.

Experimental Design: A training set consisting of 284 radical prostatectomy patients was established after 1:1 propensity score matching metastasis between adjuvant-ADT (a-ADT)-treated and no ADT–treated groups. An ADT Response Signature (ADT-RS) was identified from neuroendocrine and AR signaling–related genes. Two independent cohorts were used to form three separate data sets for validation (set I, n = 232; set II, …

Impact Of The Spop Mutant Subtype On The Interpretation Of Clinical Parameters In Prostate Cancer., Deli Liu, Mandeep Takhar, Mohammed Alshalalfa, Nicholas Erho, Jonathan Shoag, Robert B. Jenkins, R. Jeffrey Karnes, Ashley E. Ross, Edward M. Schaeffer, Mark A. Rubin, Bruce Trock, Eric A. Klein, Robert B. Den, Scott A. Tomlins, Daniel E. Spratt, Elai Davicioni, Andrea Sboner, Christopher E. Barbieri

Department of Radiation Oncology Faculty Papers

Purpose: Molecular characterization of prostate cancer, including The Cancer Genome Atlas, has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes, SPOP (speckle-type POZ protein) mutant prostate cancer, has previously only been identifiable via DNA sequencing, which has made the impact on prognosis and routinely used risk stratification parameters unclear.

Methods: We have developed a novel gene expression signature, classifier (Subclass Predictor Based on Transcriptional Data), and decision tree to predict the SPOP mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate …

Development And Validation Of A 28-Gene Hypoxia-Related Prognostic Signature For Localized Prostate Cancer., Lingjian Yang, Darren Roberts, Mandeep Takhar, Nicholas Erho, Becky A.S. Bibby, Niluja Thiruthaneeswaran, Vinayak Bhandari, Wei-Chen Cheng, Syed Haider, Amy M.B. Mccorry, Darragh Mcart, Suneil Jain, Mohammed Alshalalfa, Ashley Ross, Edward Schaffer, Robert Den, R. Jeffrey Karnes, Eric Klein, Peter J. Hoskin, Stephen J. Freedland, Alastair D. Lamb, David E. Neal, Francesca M. Buffa, Robert G. Bristow, Paul C. Boutros, Elai Davicioni, Ananya Choudhury, Catharine M.L. West

Department of Radiation Oncology Faculty Papers

BACKGROUND: Hypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer.

METHOD: Hypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON).

RESULTS: A 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients …

Analysis Of Clinical Data To Determine The Minimum Number Of Sensors Required For Adequate Skin Temperature Monitoring Of Superficial Hyperthermia Treatments., Akke Bakker, Rebecca Holman, Dario B. Rodrigues, Hana Dobšíček Trefná, Paul R. Stauffer, Geertjan Van Tienhoven, Coen R.N. Rasch, Hans Crezee

Department of Radiation Oncology Faculty Papers

PURPOSE: Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients.

METHODS: Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm²). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset …

Beyond Concurrent Chemoradiation: The Emerging Role Of Pd-1/Pd-L1 Inhibitors In Stage Iii Lung Cancer., Neal S. Mccall, Adam P. Dicker, Bo Lu

Department of Radiation Oncology Faculty Papers

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non-small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials …

Therapeutic Challenge With A Cdk 4/6 Inhibitor Induces An Rb-Dependent Smac-Mediated Apoptotic Response In Non-Small Cell Lung Cancer., Thangavel Chellappagounder, Boopathi Ettickan, Yi Liu, Christopher Mcnair, Alex Haber, Maryna Perepelyuk, Anshul Bhardwaj, Sankar Addya, Adam Ertel, Sunday Shoyele, Ruth Birbe, Joseph M. Salvino, Adam P. Dicker, Karen E. Knudsen, Robert B. Den

Department of Radiation Oncology Faculty Papers

Purpose: The retinoblastoma tumor suppressor (RB), a key regulator of cell-cycle progression and proliferation, is functionally suppressed in up to 50% of non-small cell lung cancer (NSCLC). RB function is exquisitely controlled by a series of proteins, including the CyclinD-CDK4/6 complex. In this study, we interrogated the capacity of a CDK4/6 inhibitor, palbociclib, to activate RB function.

Experimental Design and Results: We employed multiple isogenic RB-proficient and -deficient NSCLC lines to interrogate the cytostatic and cytotoxic capacity of CDK 4/6 inhibition in vitro and in vivo We demonstrate that while short-term exposure to palbociclib induces cellular senescence, prolonged exposure results …

Dosimetric Impact Of A Tumor Treating Fields Device For Glioblastoma Patients Undergoing Simultaneous Radiation Therapy, Taoran Li, Gaurav Shukla, Cheng Peng, Virginia Lockamy, Haisong Lui, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Purpose: A recent randomized phase III clinical trial in patients with glioblastoma demonstrated the efficacy of tumor treating fields (TTFields), in which alternating electric fields are applied via transducer arrays to a patient's scalp. This treatment, when added to standard of care therapy, was shown to increase overall survival from 16 to 20.9 months. These results have generated significant interest in incorporating the use of TTFields during postoperative concurrent chemoradiation. However, the dosimetric impact of high-density electrodes on the scalp, within the radiation field, is unknown. Methods: The dosimetric impact of TTFields electrodes in the radiation field was quantified in …