Accurate knowledge of ionizing radiation dose from cone-beam CT (CBCT) imaging in radiotherapy is important to allow concomitant risks to be estimated and for justification of imaging exposures. This study uses a Monte Carlo CBCT model to calculate imaging dose for a wide range of imaging protocols for male and female patients. The Elekta XVI CBCT system was modeled using GATE and simulated doses were validated against measurements in a water tank and thorax phantom. Imaging dose was simulated in the male and female ICRP voxel phantoms for a variety of anatomical sites and imager settings (different collimators, filters, full and partial rotation). The resulting dose distributions were used to calculate effective doses for each scan protocol. The Monte Carlo simulated doses agree with validation measurements within 5% and 10% for water tank and thorax phantom respectively. Effective dose for head CBCT scans was generally lower for scans centred on the pituitary than the larynx (0.03 mSv versus 0.06 mSv for male ICRP phantom). Pelvis CBCT scan effective dose was higher for the female than male phantom (5.11 mSv versus 2.80 mSv for M15 collimator scan), principally due to the higher dose received by gonads for the female scan. Medium field of view thorax scan effective doses ranged from 1.38–3.19 mSv depending on scan length and phantom sex. Effective dose for half rotation thorax scans with offset isocentre varied by almost a factor of three depending on laterality of the isocentre, patient sex and imaged field length. The CBCT imaging doses simulated here reveal large variations in dose depending on imaging isocentre T E Marchant and K D Joshi Monte Carlo study of CBCT dose Printed in the UK 13 JRPREA © 2016 IOP Publishing Ltd 37 J. Radiol. Prot.

There is a growing interest in patient exposure resulting from an x-ray imaging procedure used in image-guided radiation therapy. This study explores a feasibility to use a commercially available optically stimulated luminescence (OSL) dosimeter, nanoDot, for estimating imaging radiation exposure to patients. The kilovoltage x-ray sources used for kV-cone-beam CT (CBCT) imaging acquisition procedures were from a Varian on-board imager (OBI) image system. An ionization chamber was used to determine the energy response of nanoDot dosimeters. The chamber calibration factors for x-ray beam quality specified by half-value layer were obtained from an Accredited Dosimetry Calibration Laboratory. The Monte Carlo calculated dose distributions were used to validate the dose distributions measured by using the nanoDot dosimeters in phantom and in vivo. The range of the energy correction factors for the nanoDot as a function of photon energy and bow-tie filters was found to be 0.88-1.13 for different kVp and bow-tie filters. Measurement uncertainties of nanoDot were approximately 2-4% after applying the energy correction factors. The tests of nanoDot placed on a RANDO phantom and on patient's skin showed consistent results. The nanoDot is suitable dosimeter for in vivo dosimetry due to its small size and manageable energy dependence. The dosimeter placed on a patient's skin has potential to serve as an experimental method to monitor and to estimate patient exposure resulting from a kilovoltage x-ray imaging procedure. Due to its large variation in energy response, nanoDot is not suitable to measure radiation doses resulting from mixed beams of megavoltage therapeutic and kilovoltage imaging radiations.

The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer. This report highlights notable recent updates. Radium-223 dichloride is a first-in-class radiopharmaceutical that recently received approval for the treatment of patients with symptomatic bone metastases and no known visceral disease. It received a category 1 recommendation as both a first-line and second-line option. The NCCN Prostate Cancer Panel also revised recommendations on the choice of intermittent or continuous androgen deprivation therapy based on recent phase III clinical data comparing the 2 strategies in the nonmetastatic and metastatic settings.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.

BACKGROUND AND PURPOSE:This study explores methods to reduce dose due to kV-CBCT imaging for patients undergoing radiation therapy. MATERIAL AND METHODS:Doses resulting from kV-CBCT scans were calculated using Monte Carlo techniques and were analyzed using dose-volume histograms. Patients were modeled as were CBCT acquisitions using both 360° and 200° gantry rotations. The effects of using the half fan bow-tie and the full fan bow-tie filters were examined. RESULTS:Doses for OBI 1.3 are 15 times (head), 5 times (thorax) and 2 times (Pelvis) larger than the current OBI 1.4. When using 200° scans, the doses to eyes and cord are 0.2 (or 0.65) cGy and 0.35 (or 0.2) cGy when rotating the X-ray source underneath (or above) the patient, respectively. The 360° Pelvis scan dose is 1-2 cGy. The rectum dose is 1.1 (or 2.8) cGy when rotating the source above (or below) the patient with the 200° Pelvis scan. The dose increases up to two times as the patient size decreases. CONCLUSIONS:The dose can be minimized by reducing the scan length, the exposure settings, by selecting the gantry rotation angles, and by using the full fan bow-tie whenever possible.

PURPOSE:To determine whether image guidance can improve the dose delivered to target organs and organs at risk (OARs) for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS:Eight prostate cancer patients were treated with IMRT to 76 Gy at 2 Gy per fraction. Daily target localization was performed via alignment of three intraprostatic fiducials and weekly kV-cone beam computed tomography (CBCT) scans. The prostate and OARs were manually contoured on each CBCT by a single physician. Daily patient setup shifts were obtained by comparing alignment of skin tattoos with the treatment position based on fiducials. Treatment fields were retrospectively applied to CBCT scans. The dose distributions were calculated using actual treatment plans (an 8-mm PTV margin everywhere except for 6-mm posteriorly) with and without image guidance shifts. Furthermore, the feasibility of margin reduction was evaluated by reducing planning margins to 4 mm everywhere except for 3 mm posteriorly. RESULTS:For the eight treatment plans on the 56 CBCT scans, the average doses to 98% of the prostate (D98) were 102% (range, 99-104%) and 99% (range, 45-104%) with and without image guidance, respectively. Using margin reduction, the average D98s were 100% (range, 84-104%) and 92% (range, 40-104%) with and without image guidance, respectively. CONCLUSIONS:Currently, margins used in IMRT plans are adequate to deliver a dose to the prostate with conventional patient positioning using skin tattoos or bony anatomy. The use of image guidance may facilitate significant reduction of planning margins. Future studies to assess the efficacy of decreasing margins and improvement of treatment-related toxicities are warranted.

The purpose of this study is to assess the real target dose coverage when radiation treatments were delivered to lung cancer patients based on treatment planning according to the RTOG-0236 Protocol. We compare calculated dosimetric results between the more accurate anisotropic analytical algorithm (AAA) and the pencil beam algorithm for stereotactic body radiation therapy treatment planning in lung cancer. Ten patients with non-small cell lung cancer were given 60 Gy in three fractions using 6 and 10 MV beams with 8-10 fields. The patients were chosen in accordance with the lung RTOG-0236 protocol. The dose calculations were performed using the pencil beam algorithm with no heterogeneity corrections (PB-NC) and then recalculated with the pencil beam with modified Batho heterogeneity corrections (PB-MB) and the AAA using an identical beam setup and monitor units. The differences in calculated dose to 95% or 99% of the PTV, between using the PB-NC and the AAA, were within 10% of prescribed dose (60 Gy). However, the minimum dose to 95% and 99% of PTV calculated using the PB-MB were consistently overestimated by up to 40% and 36% of the prescribed dose, respectively, compared to that calculated by the AAA. Using the AAA as reference, the calculated maximum doses were underestimated by up to 27% using the PB-NC and overestimated by 19% using the PB-MB. The calculations of dose to lung from PB-NC generally agree with that of AAA except in the small high-dose region where PB-NC underestimates. The calculated dose distributions near the interface using the AAA agree with those from Monte Carlo calculations as well as measured values. This study indicates that the real minimum PTV dose coverage cannot be guaranteed when the PB-NC is used to calculate the monitor unit settings in dose prescriptions.

Background and purpose: Changes in tumor size during the course of radiotherapy warrant performing adaptive radiotherapy (ART). This work investigates the feasibility and usefulness of acquiring on-board cone-beam CT (CBCT) for ART for patients with bulky head and neck tumors treated with IMRT and for prostate patients with potentially significant target position variations during the treatment course. Materials and methods: A phantom designed for CT quality assurance was used to compare the dosimetric and geometric accuracy between conventional CT and CBCT from a linear accelerator's on-board imager. Patient planning CT and CBCT images were acquired before treatment and at mid-course. The IMRT plans made on the CT were applied to the CBCT and dose-volume histograms were calculated. Results: In both phantom and patient studies, the dose-volume histograms (DVHs) based on CBCT images were in excellent agreement with DVHs based on planning CT images. Minimum, maximum and mean doses agreed very well. In a patient study, doses for targets and normal tissues from the same IMRT plans calculated on CBCT images agreed within 1-3% with those calculated on planning CT images. Conclusions: CBCT images can be used to accurately predict dosimetric results. It is feasible to use CBCT to determine dosimetric consequences resulting from tumor shrinkage and patient geometry changes. An additional planning CT may be necessary to perform IMRT re-planning at present in order to accurately delineate tumor and organs. The CBCT has potential to become a very useful tool for on-line ART. (c) 2007 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 85 (2007) 116-125.

We report our initial experience with deep-inspiration breath-hold (DIBH) cone-beam CT (CBCT) on the treatment table, using the kilovoltage imager integrated into our linear accelerator, for setting up patients for DIBH stereotactic body radiation therapy (SBRT) for lung tumors. Nine patients with non-small cell lung cancer (seven stage I), were given 60Gy in three fractions. All nine patients could perform a DIBH for 35s. For each patient we used a diagnostic reference CT volume image acquired during a DIBH to design an SBRT plan consisting of 7-10 noncoplanar conformal beams. Four patients were setup by registering DIBH kilovoltage projection radiographs or megavoltage portal images on the treatment table to digitally reconstructed radiographs from the reference CT. Each of the last 14 fractions out of a total of 27 was setup by acquiring a CBCT volume image on the treatment table in three breath-holds. The CBCT and reference CT volume images were directly registered and the shift was calculated from the registration. The CBCT volume images contained excellent detail on soft tissue and bony anatomy for matching to the reference CT. Most importantly, the tumor was always clearly visible in the CBCT images, even when it was difficult or impossible to see in the radiographs or portal images. The accuracy of the CBCT method was confirmed by DIBH megavoltage portal imaging and each treatment beam was delivered during a DIBH. CBCT acquisition typically required five more minutes than radiograph acquisition but the overall setup time was often shorter using CBCT because repeat imaging was minimized. We conclude that for setting up SBRT treatments of lung tumors, DIBH CBCT is feasible, fast and may result in less variation among observers than using bony anatomy in orthogonal radiographs.

784 Background: Randomized studies and academic centers have demonstrated favorable outcomes after BCT for early stage breast cancer. There are few modern reports of BCT in community settings, validating its generalizability. We, as a large community practice, retrospectively reviewed our experience in treating early-stage breast cancer with BCT to determine outcomes and clinical, pathologic, and treatment risk factors. Methods: Tumor registry was used to identify breast cancer cases diagnosed between 1/1/87 and 12/31/94 and treated at Providence St Joseph's Hospital, a 455-bed, non-profit hospital in southern California, and 1 free-standing affiliate. Of the 1746 breast cancer cases, 744 were pathologic T1–2, N0 and had ≥ 8 years of potential follow up. Of these, 521 (70%) received BCT and are the topic of this review. We calculated crude rates of first failure at 8 years, classified as local failure (LF), distant or regional node failure (DNF), dead without failure (DWF), or alive without failure (AWF)....

The current study documented the implementation of three‐dimensional conformal radiotherapy and assessed the tumor control and toxicity of such treatment in a large, multisite community practice.

Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.

Forty‐one patients with marginally resectable stage III M0 non‐small cell lung cancer (NSCLC) were entered into a study evaluating neoadjuvant cyclophosphamide, adriamycin, and cisplatin chemotherapy (CAP) followed by radiotherapy and subsequent resection. Postoperative radiotherapy and additional CAP were also administered. The objective disease regression rate prior to surgery was 72% (2 complete, 12 partial, and 7 minimal responses). Thoracotomy was carried out in 37 patients (90%), with resection of all gross disease in 36 patients (97%). Relapse occurred in 22 (61%) of the resected patients, involving chest only (four patients), chest and extra thoracic (nine patients), and extra thoracic only (nine patients). Subsequent CNS relapse developed in 9 (25%) of 36 postop patients in association with other sites of relapse (five patients) or as a solitary location (four patients). Only one of seven patients receiving prophylactic cranial irradiation (PCI) developed CNS relapse compared with 7 (26%) of 27 patients not receiving PCI. The median long‐term follow‐up for 14 living patients is 53 + months, with a range of 38 + to 71 + months. Median survival for all patients is 32 months, with 1‐year survival being 75%. The survival curve shows a plateau of 31% from 3 to 5 + years. Using a log rank test, no prognostic subgroups could be identified that significantly affected response rate, disease‐free survival, or overall survival. While neoadjuvant CAP followed by radiotherapy appears to improve survival, more effective chemotherapy along with randomized studies are needed to determine the role of initial chemotherapy in marginally resectable NSCLC.

Intracellular glutathione (GSH) concentrations were titrated in Chinese hamster ovary cells by exposure to various concentrations of diethylmaleate (DEM). The various steady state levels of GSH obtained were maintained throughout the experimental time course. Cells were incubated at 42° after DEM addition in order to produce thermal dose response curves using colony formation as the end point. The slope of the dose response curve was subsequently determined and compared to the intracellular GSH concentration. This comparison indicated Chinese hamster ovary cells contain multiple reservoirs of GSH which in turn regulate thermal toxicity in a stepwise manner. Removal of 50% or less of the GSH did not affect thermal sensitivity. A small increase in sensitivity occured when 50 to 80% of the GSH was removed. Removal of greater than 80% of the GSH increased thermal toxicity significantly. The facts that 10 and 20 µM DEM produce extensive GSH depletion and only small changes in survival imply that a threshold concentration of GSH must be removed before thermal toxicity is affected.

The purpose of this present investigation was to determine if the presence of exogenous nutrients constitutes a prerequisite for acid modification of thermal damage and to determine if thermal cytotoxicity is affected by nutrient availability under acid conditions. To this end, Chinese hamster ovary cells (CHO) were heated (42° or 43°C) and/ or irradiated in either McCoy's medium containing 10% fetal bovine serum or glucose free Hanks Balanced Salt Solution (HBSS). Both thermal sensitivity and thermal radiosensitization were increased when CHO cells were treated under acid conditions (e.g., pH 6.8) compared to alkaline conditions (e.g., pH 7.2), independent of the media used. Furthermore, decreasing nutrient availability increased thermal cytotoxicity, but the increase was greatest at pH 7.2 compared to pH 6.8. This study indicates that thermal sensitivity is more dependent upon pH than upon nutrient availability.

A chemotherapy combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) was administered to 30 patients with stage III M0 or M1 (supraclavicular nodes) unresectable non-small cell lung cancer before and after radiotherapy. All patients had mediastinal metastases and most had T2 or T3 primary lesions. The response rate (complete plus partial) after two cycles of CAP was 47%, which increased to 66% (24% complete response rate) following radiotherapy. The overall median survival from initiation of chemotherapy was 9 months. CNS relapse occurred in five (26%) of 19 responding patients who did not receive prophylactic cranial irradiation in the early part of the study.

Seventeen patients with advanced ovarian carcinoma who had minimal residual intraabdominal disease after six months of combination chemotherapy were treated with abdominopelvic irradiation. All 17 patients had residual intraabdominal tumor nodules with a cross-sectional diameter of less than 2 cm. Eleven had only microscopic residual disease at the time of irradiation. Fourteen have relapsed at a median of eight months after the completion of radiotherapy. All but two had intraabdominal recurrences. Myelosuppression was common and severe, causing marked delays or discontinuation of radiotherapy in ten of 17 patients. Patients receiving the entire planned dose of radiotherapy had longer disease-free survival (14 months median) than did patients receiving only partial doses (seven months median). However, six of seven patients receiving full dose irradiation have relapsed. Abdominopelvic irradiation in the schedule employed here is poorly tolerated and is not an effective salvage treatment in patients with limited or microscopic residual tumor following initial combination chemotherapy.