Medicine and Health Sciences Commons^™

A Measure Of Srs/Srt Plan Quality: Quantitative Limits For Intermediate Dose Spill (R50%) In Linac-Based Delivery, Dharmin D. Desai, Ivan L. Cordrey, Ellis L. Johnson

Radiation Medicine Faculty Publications

Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) of multiple cranial targets using a single isocenter on conventional C-arm linear accelerators are rapidly developing clinical techniques. However, no universal guidelines for acceptable intermediate dose spill limits are currently available or widely accepted. In this work, we propose an intermediate dose spill guidance range for cranial SRS/SRT delivered on C-arm linacs with MLC collimation for single PTV plans and single isocenter multiple target plans with PTV volumes in the range 0.02–57.9 cm³. We quantify intermediate dose spill with the R50% metric (R50% = volume of 50% of prescription isodose cloud …

Feasibility Of Using Ring-Mounted Halcyon Linac For Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy, Damodar Pokhrel, Aaron Webster, Richard Mallory, Justin Visak, Mark E. Bernard, Ronald C. Mcgarry, Mahesh Kudrimoti

Radiation Medicine Faculty Publications

PURPOSE: To demonstrate the plan quality and delivery efficiency of volumetric-modulated arc therapy (VMAT) with the Halcyon Linac ring delivery system (RDS) in the treatment of single-isocenter/two-lesion lung stereotactic body radiation therapy (SBRT).

MATERIALS/METHODS: Sixteen previously treated non-coplanar VMAT single-isocenter/two-lesion lung SBRT plans delivered with SBRT-dedicated C-arm TrueBeam Linac were selected. Prescribed dose was 50 Gy to each lesion over five fractions with treatment delivery every other day and AcurosXB algorithm as the final dose calculation algorithm. TrueBeam single-isocenter plans were reoptimized for Halcyon Linac with coplanar geometry. Both TrueBeam and Halcyon plans were normalized for identical combined target coverage …

Fast Generation Of Lung Sbrt Plans With A Knowledge-Based Planning Model On Ring-Mounted Halcyon Linac, Justin Visak, Aaron Webster, Mark E. Bernard, Mahesh R. Kudrimoti, Marcus E. Randall, Ronald C. Mcgarry, Damodar Pokhrel

Radiation Medicine Faculty Publications

PURPOSE: To demonstrate fast treatment planning feasibility of stereotactic body radiation therapy (SBRT) for centrally located lung tumors on Halcyon Linac via a previously validated knowledge-based planning (KBP) model to support offline adaptive radiotherapy.

MATERIALS/METHODS: Twenty previously treated non-coplanar volumetric-modulated arc therapy (VMAT) lung SBRT plans (c-Truebeam) on SBRT-dedicated C-arm Truebeam Linac were selected. Patients received 50 Gy in five fractions. c-Truebeam plans were re-optimized for Halcyon manually (m-Halcyon) and with KBP model (k-Halcyon). Both m-Halcyon and k-Halcyon plans were normalized for identical or better target coverage than clinical c-Truebeam …

Predicting The Effect Of Indirect Cell Kill In The Treatment Of Multiple Brain Metastases Via Single-Isocenter/Multitarget Volumetric Modulated Arc Therapy Stereotactic Radiosurgery, Allison N. Palmiero, Denise Fabian, Marcus E. Randall, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

PURPOSE: Due to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m-bm) when using single-isocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT-VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty …

Gamma Knife Radiosurgery To Four Brainstem Lesions After Whole Brain Radiation Therapy, Mark E. Bernard, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Our patient was a 58-year-old female with a history of extensive stage small cell lung cancer initially diagnosed in November 2018. She received palliative radiation to the right hip and whole brain in December of 2018 and then received chemotherapy. Unfortunately, in October 2019, the repeat brain magnetic resonance imaging (MRI) showed recurrent lesions and she was referred for Gamma Knife Radiosurgery (GKRS). At the time of the treatment, she was found to have four brainstem lesions as well as a left frontal lobe and a right frontal lobe lesion. She completed GKRS to all six lesions without any neurological …

Computer Automation For Physics Chart Check Should Be Adopted In Clinic To Replace Manual Chart Checking For Radiotherapy, Edward L. Clouser, Quan Chen, Yi Rong

Radiation Medicine Faculty Publications

No abstract provided.

Radiation‐Induced Oral Mucositis Hamster Model Using A Linear Accelerator Enhances Clinical Relevance Of Preclinical Studies For Treatment Strategy Investigation, Carolyn T. Jordan, Emily M. Bradford, Dennis C. Cheek, Mahesh R. Kudrimoti, Craig S. Miller, Molly H. Smith, J. Zach Hilt, Thomas D. Dziubla

Radiation Medicine Faculty Publications

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory‐initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation‐induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, …

An Analytical Expression For R50% Dependent On Ptv Surface Area And Volume: A Cranial Srs Comparison, Dharmin D. Desai, Ellis Lee Johnson, Ivan L. Cordrey

Radiation Medicine Faculty Publications

The intermediate dose spill for a stereotactic radiosurgery (SRS) plan can be quantified with the metric R50%, defined as the 50% isodose cloud volume (V_IDC50%) divided by the volume of the planning target volume (PTV). By coupling sound physical principles with the basic definition of R50%, we derive an analytical expression for R50% for a spherical PTV. Our analytical expression depends on three quantities: the surface area of PTV (SA_PTV), the volume of PTV (V_PTV), and the distance of dose drop-off to 50% (Δr). The value of ∆r was obtained from a simple set …

A Novel And Clinically Useful Dynamic Conformal Arc (Dca)-Based Vmat Planning Technique For Lung Sbrt, Damodar Pokhrel, Justin Visak, Lana Sanford

Radiation Medicine Faculty Publications

PURPOSE: Volumetric modulated arc therapy (VMAT) is gaining popularity for stereotactic treatment of lung lesions for medically inoperable patients. Due to multiple beamlets in delivery of highly modulated VMAT plans, there are dose delivery uncertainties associated with small-field dosimetry error and interplay effects with small lesions. We describe and compare a clinically useful dynamic conformal arc (DCA)-based VMAT (d-VMAT) technique for lung SBRT using flattening filter free (FFF) beams to minimize these effects.

MATERIALS AND METHODS: Ten solitary early-stage I-II non-small-cell lung cancer (NSCLC) patients were treated with a single dose of 30 Gy using 3-6 non-coplanar VMAT arcs (clinical …

A Transfer Learning Approach For Malignant Prostate Lesion Detection On Multiparametric Mri, Quan Chen, Shiliang Hu, Peiran Long, Fang Lu, Yujie Shi, Yunpeng Li

Radiation Medicine Faculty Publications

Purpose: In prostate focal therapy, it is important to accurately localize malignant lesions in order to increase biological effect of the tumor region while achieving a reduction in dose to noncancerous tissue. In this work, we proposed a transfer learning–based deep learning approach, for classification of prostate lesions in multiparametric magnetic resonance imaging images. Methods: Magnetic resonance imaging images were preprocessed to remove bias artifact and normalize the data. Two state-of-the-art deep convolutional neural network models, InceptionV3 and VGG-16, were pretrained on ImageNet data set and retuned on the multiparametric magnetic resonance imaging data set. As lesion appearances differ by …

Potential Reduction Of Lung Dose Via Vmat With Jaw Tracking In The Treatment Of Single-Isocenter/Two-Lesion Lung Sbrt, Damodar Pokhrel, Lana Sanford, Matthew Halfman, Janelle A. Molloy

Radiation Medicine Faculty Publications

Purpose/objectives: Due to higher radiosensitivity, non‐target normal tissue dose is a major concern in stereotactic body radiation therapy (SBRT) treatment. The aim of this report was to estimate the dosimetric impact, specifically the reduction of normal lung dose in the treatment of single‐isocenter/two‐lesion lung SBRT via volumetric modulated arc therapy with jaw tracking (JT‐VMAT).

Materials/methods: Twelve patients with two peripherally located early‐stage non‐small‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal non‐coplanar JT‐VMAT SBRT treatment in our institution. The mean isocenter to tumors distance was 5.6 ± 1.9 (range 4.3–9.5) cm. The mean combined planning target volume (PTV) was 38.7 …

Initial Results Of A Prospective Study Of Adjuvant Pancreatic Stereotactic Body Radiation Therapy For Close Or Positive Margins, Mark E. Bernard, Philip A. Sutera, Nicholas A. Iarrobino, Kimmen Quan, Steven A. Burton, Nathan Bahary, Melissa Hogg, Amer Zureikat, Dwight E. Heron

Radiation Medicine Faculty Publications

Purpose: Patients with close or positive margins after surgery for pancreatic carcinoma are at a high risk for recurrence. Stereotactic body radiation therapy (SBRT) allows for safe dose escalation with great conformity and short duration of treatment. Herein, we report the initial results of a prospective observational study that evaluated the efficacy and safety of this treatment option.

Methods and Materials: Patients eligible for the study had pathologically proven T1-4N0-1M0 pancreatic adenocarcinoma with a positive margin (≤ 1 mm) or a close margin defined as < 2.5 mm. Patients were treated with either neoadjuvant or adjuvant chemotherapy, if eligible for systemic therapy. All patients received 36 Gy in 3 fractions to the close or positive margin site.

Results: From February 2013 to January 2018, 50 patients were enrolled with 49 patients treated …

Excluding Ptv From Lung Volume May Better Predict Radiation Pneumonitis For Intensity Modulated Radiation Therapy In Lung Cancer Patients, Yinnan Meng, Haihua Yang, Wei Wang, Xingni Tang, Caiping Jiang, Yichao Shen, Wei Luo

Radiation Medicine Faculty Publications

Background: Lung dose-volume histogram (DVH) in radiotherapy could be calculated from multiple normal lung definitions. The lung dosimetric parameters generated from various approaches are significantly different. However, limited evidence shows which definition should be used to more accurately predict radiation pneumonitis (RP). We aimed to compare the RP prediction accuracy of dosimetric parameters from three lung volume methods in lung cancer patients treated with Intensity-Modulated Radiation Therapy (IMRT).

Methods: We retrospectively reviewed 183 consecutive lung cancer patients treated with IMRT from January 2014 to October 2017. The normal lungs were defined by total bilateral lung volume (Total Lung), excluding PTV …

Evaluation Of Plan Quality And Treatment Efficiency For Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy, Lana Sanford, Janelle A. Molloy, Sameera S. Kumar, Marcus Randall, Ronald C. Mcgarry, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose/objectives: To evaluate the plan quality and treatment delivery efficiency of single‐isocenter/two‐lesions volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT).

Materials/methods: Eight consecutive patients with two peripherally located early stage nonsmall‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal noncoplanar VMAT SBRT treatment in our institution. A single‐isocenter was placed between the two lesions. Doses were 54 or 50 Gy in 3 and 5 fractions respectively. Patients were treated every other day. Plans were calculated in Eclipse with AcurosXB algorithm and normalized to at least 95% of the planning target volume (PTV) receiving 100% of the prescribed …

The Pervasive Crisis Of Diminishing Radiation Therapy Access For Vulnerable Populations In The United States—Part 4: Appalachian Patients, Shearwood Mcclelland Iii, Tasneem Kaleem, Mark E. Bernard, Hiba Z. Ahmed, Terence T. Sio, Robert C. Miller

Radiation Medicine Faculty Publications

Purpose: Compared with the rest of the United States, the population of Appalachia has lower education levels, higher rates of poverty, and limited access to health care. The presence of disparities in radiation therapy (RT) access for Appalachian patients with cancer has rarely been examined.

Methods and materials: The National Cancer Institute initiatives toward addressing disparities in treatment access for rural populations were examined. An extensive literature search was undertaken for studies investigating RT access disparities in Appalachian patients, beginning with the most common cancers in these patients (lung, colorectal, and cervical).

Results: Although the literature investigating RT access disparities …

The Impact Of Serum Glucose, Anti-Diabetic Agents, And Statin Usage In Non-Small Cell Lung Cancer Patients Treated With Definitive Chemoradiation, Nick A. Iarrobino, Beant S. Gill, Mark E. Bernard, Rainer J. Klement, Maria Werner-Wasik, Colin E. Champ

Radiation Medicine Faculty Publications

Introduction: Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation.

Method and Materials: In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values (n …

Prognostic Factors For Elderly Patients Treated With Stereotactic Body Radiation Therapy For Pancreatic Adenocarcinoma, Philip A. Sutera, Mark E. Bernard, Hong Wang, Dwight E. Heron

Radiation Medicine Faculty Publications

Introduction: Pancreatic ductal adenocarcinoma (PDAC) commonly presents later in life with a median age at diagnosis of 70 years. Unfortunately, elderly patients are significantly underrepresented in clinical trials. Stereotactic body radiation therapy (SBRT) is a promising treatment modality in this population as it has demonstrated excellent local control with minimal toxicity. We aimed to determine prognostic factors associated with outcomes in elderly patients treated with SBRT.

Materials and Methods: Elderly patients older than 70 treated with SBRT for PDAC at our institution, from 2004 to 2014 were included. Our primary endpoints included overall survival (OS) and local-progression-free survival (LPFS). Secondary …

A Dose Falloff Gradient Study In Rapidarc Planning Of Lung Stereotactic Body Radiation Therapy, Ganesh Narayanasamy, Dharmin Desai, Sanjay Maraboyina, Jose Penagaricano, Robert Zwicker, Ellis Lee Johnson

Radiation Medicine Faculty Publications

Introduction: Radiation Therapy Oncology Group (RTOG) report #0813 and 0915 recommends using D_2cm and R_50% as plan quality metrics for evaluation of normal tissue sparing in stereotactic body radiation therapy (SBRT) of lung lesion. This study introduces dose falloff gradient (DFG) as a tool for analyzing the dose beyond the planning target volume (PTV) extending into normal tissue structures. In ascertaining the impact of PTV size and SBRT planning techniques in DFG, this study questions the independence of the RTOG recommended metrics. Materials and Methods: In this retrospective study, 41 RapidArc lung SBRT plans with 2 or 3 …

Stereotactic Body Radiation Therapy For Locally Progressive And Recurrent Pancreatic Cancer After Prior Radiation, Philip Sutera, Mark E. Bernard, Hong Wang, Nathan Bahary, Steven Burton, Herbert Zeh, Dwight E. Heron

Radiation Medicine Faculty Publications

Introduction: Pancreatic adenocarcinoma is an aggressive malignancy that has consistently demonstrated poor outcomes despite aggressive treatments. Despite multimodal treatment, local disease progression and local recurrence are common. Management of recurrent or progressive pancreatic carcinomas proves a further challenge. In patients previously treated with radiation therapy, stereotactic body radiation therapy (SBRT) is a promising modality capable of delivering high dose to the tumor while limiting dose to critical structures. We aimed to determine the feasibility and tolerability of SBRT for recurrent or local pancreatic cancer in patients previously treated with external beam radiation therapy (EBRT).

Materials and methods: Patients treated with …

Volumetric Modulated Arc Therapy Treatment Planning Of Thoracic Vertebral Metastases Using Stereotactic Body Radiotherapy, Matthew Mallory, Damodar Pokhrel, Rajeev Badkul, Hongyu Jiang, Christopher Lominska, Fen Wang

Radiation Medicine Faculty Publications

Purpose/Objectives: To retrospectively evaluate the plan quality, treatment efficiency, and accuracy of volumetric modulated arc therapy (VMAT) plans for thoracic spine metastases using stereotactic body radiotherapy (SBRT).

Materials/Methods: Seven patients with thoracic vertebral metastases treated with noncoplanar hybrid arcs (NCHA) (1 to 2 3D-conformal partial arcs +7 to 9 IMRT beams) were re-optimized with VMAT plans using three coplanar arcs. Tumors were located between T2 and T7 and PTVs ranged between 24.3 and 240.1 cc (median 48.1 cc). All prescriptions were 30 Gy in 5 fractions with 6 MV beams treated using the Novalis Tx linac equipped with high definition …

Development And Validation Of Nomograms Predictive Of Overall And Progression-Free Survival In Patients With Oropharyngeal Cancer, Carol Fakhry, Qiang Zhang, Phuc Felix Nguyen-Tân, David I. Rosenthal, Randal S. Weber, Louise Lambert, Andy M. Trotti Iii, William L. Barrett, Wade L. Thorstad, Christopher U. Jones, Sue S. Yom, Stuart J. Wong, John A. Ridge, Shyam S. D. Rao, James A. Bonner, Eric Vigneault, David Raben, Mahesh R. Kudrimoti, Jonathan Harris, Quynh-Thu Le, Maura L. Gillison

Radiation Medicine Faculty Publications

Purpose

Treatment of oropharyngeal squamous cell carcinoma (OPSCC) is evolving toward risk-based modification of therapeutic intensity, which requires patient-specific estimates of overall survival (OS) and progression-free survival (PFS).

Methods

To develop and validate nomograms for OS and PFS, we used a derivation cohort of 493 patients with OPSCC with known p16 tumor status (surrogate of human papillomavirus) and cigarette smoking history (pack-years) randomly assigned to clinical trials using platinum-based chemoradiotherapy (NRG Oncology Radiation Therapy Oncology Group [RTOG] 0129 and 0522). Nomograms were created from Cox models and internally validated by use of bootstrap and cross-validation. Model discrimination was measured by …

One- Vs. Three-Fraction Pancreatic Stereotactic Body Radiation Therapy For Pancreatic Carcinoma: Single Institution Retrospective Review, Philip Anthony Sutera, Mark E. Bernard, Beant S. Gill, Kamran K. Harper, Kimmen Quan, Nathan Bahary, Steven A. Burton, Herbert Zeh, Dwight E. Heron

Radiation Medicine Faculty Publications

Background/introduction: Early reports of stereotactic body radiation therapy (SBRT) for pancreatic ductal adenocarcinoma (PDAC) used single fraction, but eventually shifted to multifraction regimens. We conducted a single institution review of our patients treated with single- or multifraction SBRT to determine whether any outcome differences existed.

Methods and materials: Patients treated with SBRT in any setting for PDAC at our facility were included, from 2004 to 2014. Overall survival (OS), local control (LC), regional control (RC), distant metastasis (DM), and late grade 3 or greater radiation toxicities from the time of SBRT were calculated using Kaplan–Meier estimation to either the date …

Randomized Phase Ii Study Comparing Prophylactic Cranial Irradiation Alone To Prophylactic Cranial Irradiation And Consolidative Extracranial Irradiation For Extensive-Disease Small Cell Lung Cancer (Ed Sclc): Nrg Oncology Rtog 0937, Elizabeth M. Gore, Chen Hu, Alexander Y. Sun, Daniel F. Grimm, Suresh S. Ramalingam, Neal E. Dunlap, Kristin A. Higgins, Maria Werner-Wasik, Aaron M. Allen, Puneeth Iyengar, Gregory M. M. Videtic, Russell K. Hales, Ronald C. Mcgarry, James J. Urbanic, Anthony T. Pu, Candice A. Johnstone, Volker W. Stieber, Rebecca Paulus, Jeffrey D. Bradley

Radiation Medicine Faculty Publications

Introduction—RTOG-0937 is a randomized phase-II trial evaluating 1-year OS with PCI or PCI plus consolidative radiation therapy (cRT) to intra-thoracic disease and extracranial metastases for ED-SCLC.

Methods—Patients with 1–4 extracranial metastases were eligible after CR or PR to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included PR vs CR after chemotherapy and 1 vs 2–4 metastases; age < 65 vs ≥ 65 was added after an observed imbalance. PCI was 25GY/10 fractions. cRT was 45GY/15 fractions. To detect an OS improvement from 30% to 45% with a 34% hazard reduction (HR=0·66) under a 0.1 type-1 error (1-sided) and 80% power, 154 patients were required.

Results—Ninety-seven patients were randomized between March, 2010 and February, 2015. Eleven patients were ineligible (nine PCI, two PCI+cRT), leaving 42 randomized to PCI and 44 to PCI+cRT. At planned interim analysis the study …

Emerging Therapies For Stage Iii Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy And Immunotherapy, Sameera S. Kumar, Kristin A. Higgins, Ronald C. Mcgarry

Radiation Medicine Faculty Publications

The current standard of care for locally advanced non-small cell lung cancer (NSCLC) includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT) has shown …

Dusquetide: Reduction In Oral Mucositis Associated With Enduring Ancillary Benefits In Tumor Resolution And Decreased Mortality In Head And Neck Cancer Patients, Mahesh Kudrimoti, Amarinthia Curtis, Samar Azawi, Francis Worden, Sanford Katz, Douglas Adkins, Marcelo Bonomi, Zack Scott, Jenna Elder, Stephen T. Sonis, Richard Straube, Oreola Donini

Radiation Medicine Faculty Publications

Innate immunity is a key component in the pathogenesis of oral mucositis, a universal toxicity of chemoradiation therapy (CRT). Dusquetide, a novel Innate Defense Regulator, has demonstrated both nonclinical and clinical efficacy in ameliorating severe oral mucositis (SOM). Long term follow-up studies from the Phase 2 clinical study evaluating dusquetide as a treatment for SOM in head and neck cancer (HNC) patients receiving CRT have now been completed. Extended analysis indicates that dusquetide therapy was well-tolerated and did not contribute to increased infection, tumor growth or mortality. Potential ancillary benefits of duquetide therapy were also identified.

A Naturally Generated Decoy Of The Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance In Tumors, Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S. J. Elenitoba-Johnson, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 proapoptotic function. Conversely, PAF, which contains this VASA …

Prostate Brachytherapy Seed Migration To The Heart Seen On Cardiovascular Computed Tomographic Angiography, Shilpa Sachdeva, Nneka S. Udechukwu, Hossam Elbelasi, Kevin P. Landwehr, William H. St. Clair, Michael A. Winkler

Radiation Medicine Faculty Publications

Brachytherapy consists of placing radioactive sources into or adjacent to tumors, to deliver conformal radiation treatment. The technique is used for treatment of primary malignancies and for salvage in recurrent disease. Permanent prostate brachytherapy seeds are small metal implants containing radioactive sources of I-125, Pd-103, or Cs-131 encased in a titanium shell. They can embolize through the venous system to the lungs or heart and subsequently be detected by cardiovascular computed tomography. Cardiovascular imagers should be aware of the appearance of migrated seeds, as their presence in the chest is generally benign, so that unnecessary worry and testing are avoided. …

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings …

Plant-Derived Sac Domain Of Par-4 (Prostate Apoptosis Response 4) Exhibits Growth Inhibitory Effects In Prostate Cancer Cells, Shayan Sarkar, Sumeet Jain, Vineeta Rai, Dipak K. Sahoo, Sumita Raha, Sujit Suklabaidya, Shantibhusan Senapati, Vivek M. Rangnekar, Indu B. Maiti, Nrisingha Dey

Radiation Medicine Faculty Publications

The gene Par-4 (Prostate Apoptosis Response 4) was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4) selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. …

Radiobiological Evaluation Of Intensity Modulated Radiation Therapy Treatments Of Patients With Head And Neck Cancer: A Dual-Institutional Study, G. Narayanasamy, A. P. Pyakuryal, S. Pandit, J. Vincent, C. Lee, P. Mavroidis, N. Papanikolaou, Mahesh Kudrimoti, T. T. Sio

Radiation Medicine Faculty Publications

In clinical practice, evaluation of clinical efficacy of treatment planning stems from the radiation oncologist's experience in accurately targeting tumors, while keeping minimal toxicity to various organs at risk (OAR) involved. A more objective, quantitative method may be raised by using radiobiological models. The purpose of this work is to evaluate the potential correlation of OAR-related toxicities to its radiobiologically estimated parameters in simultaneously integrated boost (SIB) intensity modulated radiation therapy (IMRT) plans of patients with head and neck tumors at two institutions. Lyman model for normal tissue complication probability (NTCP) and the Poisson model for tumor control probability (TCP) …