Dosimetric Evaluation and Reproducibility of Breath-hold Plans in Intensity Modulated Proton Therapy: An Initial Clinical Experience.

Purpose: Breath-hold (BH) technique can mitigate target motion, minimize target margins, reduce normal tissue doses, and lower the effect of interplay effects with intensity-modulated proton therapy (IMPT). This study presents dosimetric comparisons between BH and nonbreath-hold (non-BH) IMPT plans and investigates the reproducibility of BH plans using frequent quality assurance (QA) computed tomography scans (CT). Methods and Materials: Data from 77 consecutive patients with liver (n = 32), mediastinal/lung (n = 21), nonliver upper abdomen (n = 20), and malignancies in the gastroesophageal junction (n = 4), that were treated with a BH spirometry system (SDX) were evaluated. All patients underwent both BH CT and 4-dimensional CT simulations. Clinically acceptable BH and non-BH plans were generated on each scan, and dose-volume histograms of the 2 plans were compared. Reproducibility of the BH plans for 30 consecutive patients was assessed using 1 to 3 QA CTs per patient and variations in dose-volume histograms for deformed target and organs at risk (OARs) volumes were compared with the initial CT plan. Results: Use of BH scans reduced initial and boost target volumes to 72% ± 20% and 70% ± 17% of non-BH volumes, respectively. Additionally, mean dose to liver, stomach, kidney, esophagus, heart, and lung V20 were each reduced to 71% to 79% with the BH technique. Similarly, small and large bowels, heart, and spinal cord maximum doses were each lowered to 68% to 84%. Analysis of 62 QA CT scans demonstrated that mean target and OAR doses using BH scans were reproducible to within 5% of their nominal plan values. Conclusions: The BH technique reduces the irradiated volume, leading to clinically significant reductions in OAR doses. By mitigating tumor motion, the BH technique leads to reproducible target coverage and OAR doses. Its use can reduce motion-related uncertainties that are normally associated with the treatment of thoracic and abdominal tumors and, therefore, optimize IMPT delivery.

A novel deformable lung phantom with programably variable external and internal correlation.

PURPOSE: Lung motion phantoms used to validate radiotherapy motion management strategies have fairly simplistic designs that do not adequately capture complex phenomena observed in human respiration such as external and internal deformation, variable hysteresis and variable correlation between different parts of the thoracic anatomy. These limitations make reliable evaluation of sophisticated motion management techniques quite challenging. In this work, we present the design and implementation of a programmable, externally and internally deformable lung motion phantom that allows for a reproducible change in external-internal and internal-internal correlation of embedded markers. METHODS: An in-house-designed lung module, made from natural latex foam was inserted inside the outer shell of a commercially available lung phantom (RSD, Long Beach, CA, USA). Radiopaque markers were placed on the external surface and embedded into the lung module. Two independently programmable high-precision linear motion actuators were used to generate primarily anterior-posterior (AP) and primarily superior-inferior (SI) motion in a reproducible fashion in order to enable (a) variable correlation between the displacement of interior volume and the exterior surface, (b) independent changes in the amplitude of the AP and SI motions, and (c) variable hysteresis. The ability of the phantom to produce complex and variable motion accurately and reproducibly was evaluated by programming the two actuators with mathematical and patient-recorded lung tumor motion traces, and recording the trajectories of various markers using kV fluoroscopy. As an example application, the phantom was used to evaluate the performance of lung motion models constructed from kV fluoroscopy and 4DCT images. RESULTS: The phantom exhibited a high degree of reproducibility and marker motion ranges were reproducible to within 0.5 mm. Variable correlation was observed between the displacements of internal-internal and internal-external markers. The SI and AP components of motion of a specific marker had a correlation parameter that varied from -11 to 17. Monitoring a region of interest on the phantom's surface to estimate internal marker motion led to considerably lower uncertainties than when a single point was monitored. CONCLUSIONS: We successfully designed and implemented a programmable, externally and internally deformable lung motion phantom that allows for a reproducible change in external-internal and internal-internal correlation of embedded markers.

Mild hyperthermia as a localized radiosensitizer for deep-seated tumors: investigation in an orthotopic prostate cancer model in mice.

OBJECTIVE:: Non-ablative or mild hyperthermia (HT) has been shown in preclinical (and clinical) studies as a localized radiosensitizer that enhances the tumoricidal effects of radiation. Most preclinical in vivo HT studies use subcutaneous tumor models which do not adequately represent clinical conditions (e.g. proximity of normal/critical organs) or replicate the tumor microenvironment-both of which are important factors for eventual clinical translation. The purpose of this work is to demonstrate proof-of-concept of locoregional radiosensitization with superficially applied, radiofrequency (RF)-induced HT in an orthotopic mouse model of prostate cancer. METHODS:: In a 4-arm study, 40 athymic male nude mice were inoculated in the prostate with luciferase-transfected human prostate cancer cells (PC3). Tumor volumes were allowed to reach 150-250 mm3 (as measured by ultrasound) following which, mice were randomized into (i) control (no intervention); (ii) HT alone; (iii) RT alone; and (iv) HT + RT. RF-induced HT was administered (Groups ii and iv) using the Oncotherm LAB EHY-100 device to achieve a target temperature of 41 °C in the prostate. RT was administered ~30 min following HT, using an image-guided small animal radiotherapy research platform. In each case, a dual arc plan was used to deliver 12 Gy to the target in a single fraction. One animal from each cohort was euthanized on Day 10 or 11 after treatment for caspase-9 and caspase-3 Western blot analysis. RESULTS:: The inoculation success rate was 89%. Mean tumor size at randomization (~16 days post-inoculation) was ~189 mm3 . Following the administration of RT and HT, mean tumor doubling times in days were: control = 4.2; HT = 4.5; RT = 30.4; and HT + RT = 33.4. A significant difference (p = 0.036) was noted between normalized nadir volumes for the RT alone (0.76) and the HT + RT (0.40) groups. Increased caspase-3 expression was seen in the combination treatment group compared to the other treatment groups. CONCLUSION:: These early results demonstrate the successful use of external mild HT as a localized radiosensitizer for deep-seated tumors. ADVANCES IN KNOWLEDGE:: We successfully demonstrated the feasibility of administering external mild HT in an orthotopic tumor model and demonstrated preclinical proof-of-concept of HT-based localized radiosensitization in prostate cancer radiotherapy.