Arnold W. Malcolm

Impact of inhomogeneity corrections on dose coverage in the treatment of lung cancer using stereotactic body radiation therapy.

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.

Comparison of manual and automatic segmentation methods for brain structures in the presence of space-occupying lesions: a multi-expert study

The purpose of this work was to characterize expert variation in segmentation of intracranial structures pertinent to radiation therapy, and to assess a registration-driven atlas-based segmentation algorithm in that context. Eight experts were recruited to segment the brainstem, optic chiasm, optic nerves, and eyes, of 20 patients who underwent therapy for large space-occupying tumors. Performance variability was assessed through three geometric measures: volume, Dice similarity coefficient, and Euclidean distance. In addition, two simulated ground truth segmentations were calculated via the simultaneous truth and performance level estimation algorithm and a novel application of probability maps. The experts and automatic system were found to generate structures of similar volume, though the experts exhibited higher variation with respect to tubular structures. No difference was found between the mean Dice similarity coefficient (DSC) of the automatic and expert delineations as a group at a 5% significance level over all cases and organs. The larger structures of the brainstem and eyes exhibited mean DSC of approximately 0.8-0.9, whereas the tubular chiasm and nerves were lower, approximately 0.4-0.5. Similarly low DSCs have been reported previously without the context of several experts and patient volumes. This study, however, provides evidence that experts are similarly challenged. The average maximum distances (maximum inside, maximum outside) from a simulated ground truth ranged from (-4.3, +5.4) mm for the automatic system to (-3.9, +7.5) mm for the experts considered as a group. Over all the structures in a rank of true positive rates at a 2 mm threshold from the simulated ground truth, the automatic system ranked second of the nine raters. This work underscores the need for large scale studies utilizing statistically robust numbers of patients and experts in evaluating quality of automatic algorithms.

Reducing radiation exposure to patients from kV-CBCT imaging

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.

REDUCTION OF DOSE DELIVERED TO ORGANS AT RISK IN PROSTATE CANCER PATIENTS VIA IMAGE-GUIDED RADIATION THERAPY

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.

An optically stimulated luminescence dosimeter for measuring patient exposure from imaging guidance procedures

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 patients 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 patients 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.

Neoadjuvant cisplatin plus vinblastine chemotherapy in locally advanced non-small cell lung cancer

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 (< 1000/μl). 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.

Glutathione pool size affects cell survival after hyperthermic treatment.

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.

Acid modification of thermal damage and its relationship to nutrient availability

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 degrees or 43 degrees C) and/or irradiated in either McCoys 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.

Chemotherapy and Radiation Therapy of Non-Small Cell Lung Carcinoma

Carcinoma of the lung remains the leading cause of death due to malignant disease in the United States, and is rapidly becoming the leading cause of cancer death in women [1]. Although surgical therapy of non-small cell lung cancers has improved during the past two decades, the overall results remain discouraging. The limited efficacy of surgical therapy has led to exploration of other treatment modalities such as radiation or chemotherapy either alone or in combination with surgery, particularly for the two thirds of the patients who present with advanced disease and for those in whom the presence of associated disease renders resection too hazardous. This chapter will attempt to review the present limitations and usefulness of radiation therapy and chemotherapy in the treatment of non-small cell lung cancer.

SU‐E‐T‐63: The Unintended Dose to Normal Tissues Resulting from Incorrect Jaw Settings Using Cones in Stereotactic Radiosrurgery (SRS)

Purpose: To report changes of cone beam properties when opened jaw field sizes were incorrectly set larger than the cone beam limiting device and to show the unintended dose to normal tissues resulting from the error in Linac‐based non‐coplanar arc treatment. Methods: The Monte Carlo code, BEAMnrc, was used to simulate the entire Linac head and circular cone beam limiting device accessory of a 6 MV beam. In addition to the correct jaw size of 5cm×5cm, two incorrect jaw sizes, 10cm×10cm and 20cm×20cm are simulated. The simulated beams were stored in phase‐space files and were analyzed to obtain the beam properties. The beams were then used to calculate dose to patient based on CTimages resulting from non‐coplanar arcs. For the same circular cones, the dose to both target and the normal tissues were compared between using correct jaw settings and incorrect ones. Results: When the jaw sizes are larger than the cone beam limiting device, significant photon fluence at off‐axis distances greater than 5cm was confirmed using film measurements. Monte Carlo dose calculations for a representative patient using a 10 mm BrainLab cone arc plan resulted in a small dose increase within the regions of less than 5cm radius and a large dose increase (20% of dose to the target) for the regions at distance greater than 5cm up to the field size of 20cm×20cm set by jaws. For 20 Gy tumor dose, this jaw size error may result in 4 Gy of unintended dose to normal tissues at distance greater than 5 cm away from the isocenter. Conclusions: The unintended doses to normal tissues are significant due to jaw setting errors. The point dose QA measurement performed at isocenter may not detect the error in jaw setting. A more robust QA protocol is warranted.