Monte Carlo based continuous aperture optimization for VMAT on conventional and MR-linacs: A proof of concept.

BACKGROUND: Currently, the commercial treatment planning systems for magnetic-resonance guided linear accelerators (MR-linacs) only support step-and-shoot intensity-modulated radiation therapy (IMRT). However, recent studies have shown the feasibility of delivering arc therapy on MR-linacs, which is expected to improve dose distributions and delivery speed. By accurately accounting for the electron return effect in the presence of a magnetic field, a Monte Carlo (MC) algorithm is ideally suited for the inverse treatment planning of this technique. PURPOSE: We propose a novel MC-based continuous aperture optimization (MCCAO) algorithm for volumetric modulated arc therapy (VMAT), including applications to VMAT on MR-linacs and trajectory-based VMAT. A unique feature of MCCAO is that the continuous character of gantry rotation and multileaf collimator (MLC) motion is accounted for at every stage of the optimization. METHODS: The optimization process uses a multistage simulation of 4D dose distribution. A phase space is scored at the top surface of the MLC and the energy deposition of each particle history is mapped to its position in this phase space. A progressive sampling method is used, where both MLC leaf positions and monitor unit (MU) weights are randomly changed, while respecting the linac mechanical limits. Due to the continuous nature of the leaf motion, such changes affect not only a single control point, but propagate to the adjacent ones as well, and the corresponding dose distribution changes are accounted for. A dose-volume cost function is used, which includes the MC statistical uncertainty. RESULTS: We applied our optimization technique to various treatment sites, using standard and flattening-filter-free (FFF) 6 MV beam models, with and without a 1.5 T magnetic field. MCCAO generates deliverable plans, whose dose distributions are in good agreement with measurements on ArcCHECK and stereotactic radiosurgery End-To-End Phantom. CONCLUSIONS: We show that the novel MCCAO method generates VMAT plans that meet clinical objectives for both conventional and MR-linacs.

Lung cancer epidermal growth factor receptor mutations and radiotherapy response: A multicentre clinical study.

PURPOSE: To examine the impact of epidermal growth factor receptor (EGFR) mutations on objective response to palliative lung radiotherapy in patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A multicentre retrospective study was conducted of patients with metastatic NSCLC diagnosed between March 2010 and June 2012 who received palliative radiotherapy to the chest. Patients included for study had baseline imaging and follow-up imaging 1-3 months after radiotherapy. The primary endpoint was 1-3 month local objective imaging response by the Response Evaluation Criteria in Solid Tumours (RECIST). Patients were divided into EGFR mutation positive (EGFR+) and EGFR wild type (WT) cohorts for analysis. RESULTS: There were 121 patients for study inclusion: 89 (74%) were EGFR WT and 32 (26%) were EGFR+. The response rate between EGFR WT and EGFR+ cohorts was not significantly different (49 vs. 63%, p = 0.21). On multivariate analysis, initiation of a tyrosine kinase inhibitor (TKI) after radiotherapy was associated with a higher rate of response (OR: 5.07, 95%CI: 1.08-23.69, p = 0.039) but EGFR mutation status was not. For the EGFR+ cohort, patients with disease progression after initial management on a TKI had a worse response rate compared to patients who were TKI-naïve before starting radiotherapy (30 vs. 77%, p = 0.018). Local control was not statistically different between the EGFR cohorts. CONCLUSION: The EGFR mutation status alone was not an independent predictor of objective radiographic response to palliative thoracic radiotherapy. Acquired resistance to TKI therapy may be associated with disease cross-resistance to palliative radiotherapy.

Technical Note: Development of a phantom for dosimetric comparison of murine micro-CT protocols with optically stimulated luminescent dosimeters.

PURPOSE: This work aims to evaluate the utility and accuracy of a mouse-like phantom and optically stimulated luminescent dosimeters (OSLDs) in measuring dose delivered to the body and lung of mice undergoing micro-CT imaging. METHODS: A phantom with two cavities for NanoDot OSLDs (Landauer, Inc., Greenwood, IL) was designed and constructed using acrylic to model the mouse body and polyurethane foam to obtain an approximate lung tissue dose. The OSLD dose was compared to ion chamber measurements for the same imaging protocols delivered by a Siemens Inveon micro-CT (Siemens Medical Solutions USA, Inc., Hoffman Estates, IL, USA). A whole body scan, using 80 kV, 0.5 mA and 0.5 mm of aluminum filter, was used to compare results to previously published data. Additionally, dose was measured for the whole body scan without the aluminum filter and two chest protocols (full and half rotation). RESULTS: OSLD dose results agree with chamber measurements within 3%. Average OSLD measurements for the whole body scan without filter were 10.7 ± 0.7 cGy in the abdomen and 11.2 ± 0.7 cGy in the lung. For the full rotation chest protocol, the average dose measured in the lung was 65.8 ± 4.3 cGy and 60.2 ± 3.9 cGy in the abdomen. Average doses were 41.1 ± 2.7 cGy in the lung and 38.2 ± 2.5 cGy in the abdomen for the half rotation chest protocol. The OSLD measurements showed a coefficient of variation under 1.4%. A maximum rotational geometry under-response of 0.86% with respect to exposure at normal incidence to the OSLD was measured. CONCLUSIONS: The doses measured were found to be comparable to other studies for the scanner configuration and protocols chosen. The phantom built for this study was found to give reproducible dose measurements with 4% uncertainty. In this way, a robust and convenient method is established for future dose assessment of micro-CT protocols and interinstitutional comparisons.

Monte Carlo validation of the TrueBeam 10XFFF phase-space files for applications in lung SABR.

PURPOSE: To establish the clinical acceptability of universal Monte Carlo phase-space data for the 10XFFF (flattening filter free) photon beam on the Varian TrueBeam Linac, including previously unreported data for small fields, output factors, and inhomogeneous media. The study was particularly aimed at confirming the suitability for use in simulations of lung stereotactic ablative radiotherapy treatment plans. METHODS: Monte Carlo calculated percent depth doses (PDDs), transverse profiles, and output factors for the TrueBeam 10 MV FFF beam using generic phase-space data that have been released by the Varian MC research team were compared with in-house measurements and published data from multiple institutions (ten Linacs from eight different institutions). BEAMnrc was used to create field size specific phase-spaces located underneath the jaws. Doses were calculated with DOSXYZnrc in a water phantom for fields ranging from 1 × 1 to 40 × 40 cm(2). Particular attention was paid to small fields (down to 1 × 1 cm(2)) and dose per pulse effects on dosimeter response for high dose rate 10XFFF beams. Ion chamber measurements were corrected for changes in ion collection efficiency (P(ion)) with increasing dose per pulse. MC and ECLIPSE ANISOTROPIC ANALYTICAL ALGORITHM (AAA) calculated PDDs were compared to Gafchromic film measurement in inhomogeneous media (water, bone, lung). RESULTS: Measured data from all machines agreed with Monte Carlo simulations within 1.0% and 1.5% for PDDs and in-field transverse profiles, respectively, for field sizes >1 × 1 cm(2) in a homogeneous water phantom. Agreements in the 80%-20% penumbra widths were better than 2 mm for all the fields that were compared. For all the field sizes considered, the agreement between their measured and calculated output factors was within 1.1%. Monte Carlo results for dose to water at water/bone, bone/lung, and lung/water interfaces as well as within lung agree with film measurements to within 2.8% for 10 × 10 and 3 × 3 cm(2) field sizes. This represents a significant improvement over the performance of the ECLIPSE AAA. CONCLUSIONS: The 10XFFF phase-space data offered by the Varian Monte Carlo research team have been validated for clinical use using measured, interinstitutional beam data in water and with film dosimetry in inhomogeneous media.