Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial.

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, Setting, And Participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion.

A comparison of two methodologies for radiotherapy treatment plan optimization and QA for clinical trials.

Background And Purpose: The efficacy of clinical trials and the outcome of patient treatment are dependent on the quality assurance (QA) of radiation therapy (RT) plans. There are two widely utilized approaches that include plan optimization guidance created based on patient-specific anatomy. This study examined these two techniques for dose-volume histogram predictions, RT plan optimizations, and prospective QA processes, namely the knowledge-based planning (KBP) technique and another first principle (FP) technique.

Monte Carlo Simulations of Neutron Ambient Dose Equivalent in a Novel Proton Therapy Facility Design.

Purpose: The neutron shielding properties of the concrete structures of a proposed proton therapy facility were evaluated with help of the Monte Carlo technique. The planned facility's design omits the typical maze-structured entrances to the treatment rooms to facilitate more efficient access and, instead, proposes the use of massive concrete/steel doors. Furthermore, straight conduits in the treatment room walls were used in the design of the facility, necessitating a detailed investigation of the neutron radiation outside the rooms to determine if the design can be applied without violating existing radiation protection regulations.

Evaluation of the high definition field of view option of a large-bore computed tomography scanner for radiation therapy simulation.

Background And Purpose: Computed tomography (CT) scanning is the basis for radiation treatment planning, but the 50-cm standard scanning field of view (sFOV) may be too small for imaging larger patients. We evaluated the 65-cm high-definition (HD) FOV of a large-bore CT scanner for CT number accuracy, geometric distortion, image quality degradation, and dosimetric accuracy of photon treatment plans.

Materials And Methods: CT number accuracy was tested by placing two 16-cm acrylic phantoms on either side of a 40-cm phantom to simulate a large patient extending beyond the 50-cm-diameter standard scanning FOV.

Results of the NRG Oncology/RTOG 0848 Adjuvant Chemotherapy Question-Erlotinib+Gemcitabine for Resected Cancer of the Pancreatic Head: A Phase II Randomized Clinical Trial.

Purpose: NRG/RTOG 0848 was designed to determine whether adjuvant radiation with fluoropyrimidine sensitization improved survival following gemcitabine-based adjuvant chemotherapy for patients with resected pancreatic head adenocarcinoma. In step 1 of this protocol, patients were randomized to adjuvant gemcitabine versus the combination of gemcitabine and erlotinib. This manuscript reports the final analysis of these step 1 data.

Statistical evaluation of worst-case robust optimization intensity-modulated proton therapy plans using an exhaustive sampling approach.

Purpose: To assess the worst-case robust optimization IMPT plans with setup and range uncertainties and to test the hypothesis that the worst-case robust optimization strategies could cover most possible setup and range uncertainties in the real scenarios.

Methods: We analyzed the nominal and worst-case robust optimization IMPT plans of seven patients with head and neck cancer patients. To take uncertainties into account for the dose calculation, we performed a comprehensive simulation in which the dose was recalculated 625 times per given plan using Gaussian systematic setup and proton range uncertainties.

Characterization of a new physical phantom for testing rigid and deformable image registration.

The purpose of this study was to describe a new user-friendly, low-cost phantom that was developed to test the accuracy of rigid and deformable image registration (DIR) systems and to demonstrate the functional efficacy of the new phantom. The phantom was constructed out of acrylic and includes a variety of inserts that simulate different tissue shapes and properties. It can simulate deformations and location changes in patient anatomy by changing the rotations of both the phantom and the inserts.

Proton versus photon radiation-induced cell death in head and neck cancer cells.

Background: Photon (X-ray) radiotherapy (XRT) kills cells via DNA damage, however, how proton radiotherapy (PRT) causes cell death in head and neck squamous cell carcinoma (HNSCC) is unclear. We investigated mechanisms of HNSCC cell death after XRT versus PRT.

Methods: We assessed type of death in 2 human papillomavirus (HPV)-positive and two HPV-negative cell lines: necrosis and apoptosis (Annexin-V fluorescein isothiocyanate [FITC]); senescence (β-galactosidase); and mitotic catastrophe (γ-tubulin and diamidino-phenylindole [DAPI]).

3D treatment planning system-Varian Eclipse for proton therapy planning.

The capabilities of the Eclipse treatment planning system (TPS) (Varian Medical Systems, Palo Alto, CA) for proton therapy treatment planning are described. Various steps involved in the planning process to produce a 3-dimensional (3D) dose distribution both for the passive scattering and pencil beam scanning proton beam therapy are outlined. Mitigation of range and setup uncertainties through robust optimization is discussed.

Synchrotron-Based Pencil Beam Scanning Nozzle with an Integrated Mini-Ridge Filter: A Dosimetric Study to Optimize Treatment Delivery.

A mini-ridge filter is often used to widen the Bragg peak in the longitudinal direction at low energies but not high energies. To facilitate the clinical use of a mini-ridge filter, we performed a planning study for the feasibility of a mini-ridge filter as an integral part of the synchrotron nozzle (IMRF). Dose models with and without IMRF were commissioned in a commercial Treatment planning system (TPS).

Technical Note: Dosimetric characteristics of the ocular beam line and commissioning data for an ocular proton therapy planning system at the Proton Therapy Center Houston.

Purpose: To systematically analyze and present the properties of a small-field, double-scattering proton beam line intended to be used for the treatment of ocular cancer, and to provide configuration data for commission of the Eclipse Ocular Proton Planning System.

Methods: Measurements were made using ionization chambers, diodes, and films to determine dose profiles and output factors of the proton beams of the beam line at the Proton Therapy Center Houston. In parallel, Monte Carlo simulations were performed to validate the measured data and to provide additional insight into detailed beam parameters that are hard to measure, such as field size factors and a comparison of output factors as a function of circular and rectangular fields.

Intensity-Modulated Proton Therapy Adaptive Planning for Patients with Oropharyngeal Cancer.

Purpose: The authors aimed to illustrate the potential dose differences to clinical target volumes (CTVs) and organs-at-risk (OARs) volumes after proton adaptive treatment planning was used.

Patients And Methods: The records of 10 patients with oropharyngeal cancer were retrospectively reviewed. Each patient's treatment plan was generated by using the Eclipse treatment planning system.

Reirradiation of thoracic cancers with intensity modulated proton therapy.

Purpose: Reirradiation of thoracic malignancies is a treatment challenge, with concerns for toxicity and the inability to deliver definitive doses. Intensity modulated proton therapy (IMPT) may allow safe delivery of a higher dose of radiation to the tumor while minimizing toxicities.

Methods And Materials: Between 2011 and 2016, 27 patients who received IMPT for reirradiation of thoracic malignancies with definitive intent were retrospectively analyzed.

Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer.

Purpose: The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC).

Patients And Methods: From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.

Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells.

Background: Human papillomavirus (HPV)-positive oropharyngeal carcinomas response better to X-ray therapy (XRT) than HPV-negative disease. Whether HPV status influences the sensitivity of head and neck cancer cells to proton therapy or the relative biological effectiveness (RBE) of protons versus XRT is unknown.

Methods: Clonogenic survival was used to calculate the RBE; immunocytochemical analysis and neutral comet assay were used to evaluate unrepaired DNA double-strand breaks.

Robust Optimization for Intensity Modulated Proton Therapy Plans with Multi-Isocenter Large Fields.

We have developed a robust optimization approach for intensity modulated proton therapy treatment plans with multi-isocenter large fields. The method creates a low-gradient field dose in the junction regions to mitigate the impact caused by misalignment errors and is more efficient than the conventional junction shifting technique.

Spot scanning proton therapy minimizes neutron dose in the setting of radiation therapy administered during pregnancy.

This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination.

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy.

Purpose: To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center.

Methods: At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents.

Novel Hybrid Scattering- and Scanning-Beam Proton Therapy Approach.

Purpose: To determine whether a hybrid intensity-modulated proton therapy (IMPT) and passive scattered proton therapy (PSPT) technique, termed HimpsPT, could be adopted as an alternative delivery method for patients demanding scanning beam proton therapy.

Patients And Methods: We identified 3 representative clinical cases-an oropharyngeal cancer, skull base chordoma, and stage III non-small-cell lung cancer-that had been treated with IMPT at our center. We retrospectively redesigned these cases using HimpsPT.

Proton Beam Therapy for Localized Prostate Cancer: Results from a Prospective Quality-of-Life Trial.

Purpose: To report prostate cancer outcomes, toxicity, and quality of life (QOL) in men treated with proton beam therapy (PBT).

Patients And Methods: Patients were enrolled in a prospective trial. All participants received 75.

Establishing the feasibility of the dosimetric compliance criteria of RTOG 1308: phase III randomized trial comparing overall survival after photon versus proton radiochemotherapy for inoperable stage II-IIIB NSCLC.

Background: To establish the feasibility of the dosimetric compliance criteria of the RTOG 1308 trial through testing against Intensity Modulation Radiation Therapy (IMRT) and Passive Scattering Proton Therapy (PSPT) plans.

Methods: Twenty-six lung IMRT and 26 proton PSPT plans were included in the study. Dose Volume Histograms (DVHs) for targets and normal structures were analyzed.

Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma.

Purpose: A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer.

Methods And Materials: Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration.

Motion-robust intensity-modulated proton therapy for distal esophageal cancer.

Purpose: To develop methods for evaluation and mitigation of dosimetric impact due to respiratory and diaphragmatic motion during free breathing in treatment of distal esophageal cancers using intensity-modulated proton therapy (IMPT).

Methods: This was a retrospective study on 11 patients with distal esophageal cancer. For each patient, four-dimensional computed tomography (4D CT) data were acquired, and a nominal dose was calculated on the average phase of the 4D CT.

Dosimetric Characteristics of a Two-Dimensional Diode Array Detector Irradiated with Passively Scattered Proton Beams.

Purpose: To evaluate the dosimetric characteristics of a two-dimensional (2D) diode array detector irradiated with passively scattered proton beams.

Materials And Methods: A diode array detector, MapCHECK (Model 1175, Sun Nuclear, Melbourne, FL, USA) was characterized in passive-scattered proton beams. The relative sensitivity of the diodes and absolute dose calibration were determined using a 250 MeV beam.

Selective robust optimization: A new intensity-modulated proton therapy optimization strategy.

Purpose: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications.

Methods: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy.