James Brindle

Stereotactic Body Radiation Therapy for Nonresectable Tumors of the Pancreas

BACKGROUND Stereotactic body radiation therapy (SBRT) has emerged as a potential treatment option for local tumor control of primary malignancies of the pancreas. We report on our experience with SBRT in patients with pancreatic adenocarcinoma who were found not to be candidates for surgical resection. METHODS The prospective database of the first 20 consecutive patients receiving SBRT for unresectable pancreatic adenocarcinomas and a neuroendocrine tumor under an IRB approved protocol was reviewed. Prior to SBRT, cylindrical solid gold fiducial markers were placed within or around the tumor endoscopically (n = 13), surgically (n = 4), or percutaneously under computerized tomography (CT)-guidance (n = 3) to allow for tracking of tumor during therapy. Mean radiation dose was 25 Gray (Gy) (range 22-30 Gy) delivered over 1-3 fractions. Chemotherapy was given to 68% of patients in various schedules/timing. RESULTS Patients had a mean gross tumor volume of 57.2 cm(3) (range 10.1-118 cm(3)) before SBRT. The mean total gross tumor volume reduction at 3 and 6 mo after SBRT were 21% and 38%, respectively (P < 0.05). Median follow-up was 14.57 mo (range 5-23 mo). The overall rate of freedom from local progression at 6 and 12 mo were 88% and 65%. The probability of overall survival at 6 and 12 mo were 89% and 56%. No patient had a complication related to fiducial markers placement regardless of modality. The rate of radiation-induced adverse events was: grade 1-2 (11%) and grade 3 (16%). There were no grade 4/5 adverse events seen. CONCLUSION Our preliminary results showed SBRT as a safe and likely effective local treatment modality for pancreatic primary malignancy with acceptable rate of adverse events.

Stereotactic Body Radiosurgery for Pelvic Relapse of Gynecologic Malignancies

Clinical management of pelvic relapses from gynecologic malignancies remains challenging. Bulky pelvic relapses often lead to symptomatic cancer-related complications and poor clinical outcomes. Options may be limited by prior surgical, chemotherapeutic, and radiation treatment. Stereotactic body radiosurgery is a novel treatment modality which allows high radiation dose delivery in a non-coplanar fashion with sub-millimeter precision utilizing a linear accelerator mounted on a robotic arm. This study details our clinical experience with stereotactic body radiosurgery for treatment of patients with pelvic relapses of gynecologic malignancies after prior pelvic radiation.

Cyberknife Radiosurgery for Squamous Cell Carcinoma of Vulva after Prior Pelvic Radiation Therapy

Limited options exist for patients experiencing a local recurrence of vulvar malignancies after surgery and pelvic radiation. These recurrences often are associated with cancer-related skin desquamation and poor clinical outcomes. A new radiotherapeutic treatment modality for the previously irradiated patient is cyberknife radiosurgery, which uses a linear accelerator mounted on an industrial robotic arm to allow non-coplanar radiation therapy delivery with sub-millimeter precision. This study describes the first reported use of cyberknife radiosurgery for the treatment of recurrent vulvar cancer in three women.

Hematological toxicity after robotic stereotactic body radiosurgery for treatment of metastatic gynecologic malignancies.

PURPOSE To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. METHODS AND MATERIALS A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile, 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. RESULTS In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. CONCLUSIONS Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.

Investigation of Nonuniform Dose Voxel Geometry in Monte Carlo Calculations

The purpose of this work is to investigate the efficacy of using multi-resolution nonuniform dose voxel geometry in Monte Carlo (MC) simulations. An in-house MC code based on the dose planning method MC code was developed in C++ to accommodate the nonuniform dose voxel geometry package since general purpose MC codes use their own coupled geometry packages. We devised the package in a manner that the entire calculation volume was first divided into a coarse mesh and then the coarse mesh was subdivided into nonuniform voxels with variable voxel sizes based on density difference. We name this approach as multi-resolution subdivision (MRS). It generates larger voxels in small density gradient regions and smaller voxels in large density gradient regions. To take into account the large dose gradients due to the beam penumbra, the nonuniform voxels can be further split using ray tracing starting from the beam edges. The accuracy of the implementation of the algorithm was verified by comparing with the data published by Rogers and Mohan. The discrepancy was found to be 1% to 2%, with a maximum of 3% at the interfaces. Two clinical cases were used to investigate the efficacy of nonuniform voxel geometry in the MC code. Applying our MRS approach, we started with the initial voxel size of 5 × 5 × 3 mm3, which was further divided into smaller voxels. The smallest voxel size was 1.25 × 1.25 × 3 mm3. We found that the simulation time per history for the nonuniform voxels is about 30% to 40% faster than the uniform fine voxels (1.25 × 1.25 × 3 mm3) while maintaining similar accuracy.

Retrospective Prostate Treatment Plan Comparison for Proton, Tomotherapy, and Cyberknife Therapy

Abstract Background: Twenty-eight cases from patients previously treated for prostate cancer using helical tomotherapy (22 patients) or Cyberknife (6 patients; Accuray, Sunnyvale, California) linear accelerators were selected chronologically between 2009 and 2011 and were replanned using parallel-opposed beam geometry for proton therapy (PT). Methods: Proton data used an IBA (Louvain-La-Neuve, Belgium) beam model that was made available from the Philips Radiation Oncology System (Fitchburg, Wisconsin) as a pre-510(k)–approved Pinnacle treatment planning system. Comparison for the coverage of the planned target volume (expanded clinical target volume) and doses to bladder, rectum, and femoral heads were used to evaluate the plans. Radiation Therapy Oncology Group (RTOG, Philadelphia, Pennsylvania) trial 0815, a prostate intensity-modulated radiation therapy protocol, and trial 0938, a prostate stereotactic radiation therapy protocol, were used as an independent “benchmark” for plan robustness. Results: In ...

SU‐E‐T‐432: Dosimetric Computation of Cyberknife SBRT Plans for Treatment of Kidney and Adrenal Gland

PURPOSE It is well-accepted that Monte Carlo algorithm (MCA) methods are superior to Ray-Tracing algorithm (RTA), i.e., effective path length (EPL), methods for computing radiation dose, especially for structures with heterogeneous tissue compositions. In this study, the differences of dose distribution in target volumes (kidneys and adrenal glands) and adjacent organs at risk (OARs) were evaluated while the treatment plans were computed using MCA and RTA for Cyberknife™ stereotactic body radiotherapy (SBRT). METHODS A total of 14 renal tumor (10 kidney and 4 adrenal gland) patients who had prescriptions in the range of 24Gy-48Gy (mean=42Gy) were selected. Treatment plans were computed using RTA and MCA in Cyberknife MultiPlan™ (version-3.5.2). First, dose was calculated using RTA and then was recomputed using MCA, keeping total MU the same. Liver, heart, stomach, spleen, bowel, and contralateral kidney were considered as OARs. Dosimetric parameters considered for the target and OARs were minimum dose, mean dose, and maximum point dose. Additionally, dose delivered to 95% and 5% of the target volumes were evaluated. Dose computed with two algorithms were compared and statistically analyzed using two-tailed t-tests. RESULTS This study revealed that differences (average) in mean dose (0.79Gy), maximum dose (2.02Gy), 95% (0.76Gy) and 5% (0.83Gy) of target coverage dose were not statistically significant (p-value>0.05). Differences in minimum dose (average=0.04-3.75Gy) to OARs exhibited significance (p-value< 0.05), though differences in minimum dose to target volumes (average=1.14Gy) showed no significant difference (p-value>0.05). CONCLUSION Although Monte-Carlo is more accurate compared to Ray-Tracing for dosimetric computation, especially tumors in heterogeneous tissue composition, dose computation and delivery using MCA are quite involved due to additional computational time and associated patient-specific quality assurance. This study indicated that both RTA and MCA are almost equally effective as dosimetric computation methods for renal tumors, and RTA can be used without compromising dosimetric accuracy.

SU‐D‐105‐01: Patient‐Specific Quality Assurance for Monte Carlo‐Calculated Lung SBRT On Cyberknife ‐ Is It Necessary?

PURPOSE In transitioning from ray-tracing (RT) to Monte Carlo (MC) dose computation algorithm for Cyberknife lung stereotactic body radiotherapy (SBRT), we realized large differences (10-20%) in PTV coverage to heterogeneous target regions which required dosimetric confirmation. Currently, our practice requires an independent second calculation for all plans. MuCheck software (Oncology Data Systems) is used in lieu of physical measurements for RT plans; however, there exists no commercial software for verifying MC plans. We determined all lung SBRT plans should utilize the MC algorithm and initially be confirmed by direct measurements. METHODS Lung treatment plans were first optimized with RT then recalculated using MC for final optimization and high-resolution dose computation. The MC plan was superimposed on a heterogeneous thorax phantom CT (Standard Imaging 91230) using the phantom overlay tool of the MultiPlan 3.5.2 software. Isodose distributions were manually shifted to place the ion chamber (0.053cc Exradin-A1SL) in a suitably homogeneous region within the CTV. The plan was then delivered to the thorax phantom with the ion chamber placed in the mediastinum insert location. RESULTS This methodology was used for 33 consecutive lung patients receiving Cyberknife SBRT with PTVs ranging from 10.7-185.9cm3. The mean deviation between measured and MC calculated doses was -2.31%±1.66%. The maximum deviation was -4.69%. Acceptable tolerance for patient-specific QA was considered ±5%. CONCLUSION The MC algorithm provides improved accuracy over RT for heterogeneous dose calculation, confirmed by direct point measurements. Patient-specific QA using a heterogeneous lung phantom provided an acceptable anthropomorphic approximation of patient plans calculated with MC. Since the QA results establish satisfactory delivery of MC doses, patient-specific plans calculated on a homogeneous phantom comparing RT and MC algorithms may provide a suitable second check without direct measurement. Conversely, many users may continue direct measurement as a second check until commercial MC verification software becomes available.

SU‐C‐211‐02: A Fast Monte Carlo Dose Algorithm for Radiotherapy Treatment Planning Based on Hybrid Adaptive Meshes

Purpose:Monte Carlo methods are considered to be the most accurate dose algorithm for radiotherapy. Variance reduction techniques such as history repetition, Russian roulette and photon splitting are employed to improve the calculation efficiency. Generally, it takes a large portion of the simulation time for two inevitable tasks, that is, voxel‐to‐voxel boundary crossing and energy deposition. The purpose of this work is to investigate the potential for additional speedup achieved by reducing the number of boundary crossing based on hybrid adaptive meshes. Method and Materials: A Monte Carlo code was developed to simulate the coupled photon‐electron transport for radiation therapy using a hybrid adaptive mesh. Photontransport was modeled in an analog fashion. The Compton scattering, photoelectric ionization and pair production were considered. For electron transport, a condensed history method was used in which the hard interactions such as inelastic collision and bremsstrahlung were simulated explicitly. The formulation by Kawrakow and Bielajew was used for electron multiple scattering. Photons and electrons were tracked on a hybrid adaptive mesh, which was generated from an initial uniform coarse mesh. The coarse uniform mesh was divided voxel‐by‐voxel into an unstructured finer mesh depending on the splitting criterion such as the density gradient. The resulting adaptive mesh contains larger voxels in smooth density areas and smaller voxels used for density regions with large gradient to retain the accuracy. Results: The speed up observed by varying the splitting level is proportional to N1/3, where N is the total number of the voxels. For the test cases, 30% of the calculation time was saved by using the adaptive meshes starting with 10mm spacing and reduced to 1.25mm voxels for high gradient regions comparing with the 1.25mm uniform meshes. Conclusions: The Monte Carlo simulations can be further accelerated based on these hybrid adaptive meshes.

SU‐E‐T‐644: Software Tool Used in Setting Optimization Control Points for Hypofractionated CyberKnife Treatment Planning

Purpose: Normal tissuedose tolerance for hypofractionated radiotherapy is under active investigation. Previous radiation increases the complexity of determining the dose limits. We developed a software tool to optimize CyberKnife treatment planning for patient specific dose tolerances using the linear quadratic (LQ) model to derive biologically effective doses (BED) and to correlate these findings with observed toxicities. Methods: A program was written in Visual Basic using LQ model to estimate the normal organ BED tolerance for hypofractionated radiotherapy. Total tolerance BED was derived from the literature on conventional fractionated radiotherapy. For patients who previously received radiation from other modalities and fractionation schemes, prior doses were converted to equivalent BED and subtracted. Based on these calculations, physicians set dose constraints for organs at risk (OAR) to optimize the treatment plan. Plan re‐optimization was required until the plan dose was less than 90% of the dose constraint for each OAR. 259 consecutive patients treated with CyberKnife radiosurgery at our institution since 2007 to 2010 were retrospectively reviewed. Treatment related toxicities were evaluated according to CTCAE for 208 out of 259 patients who had available follow‐up data. Results: Guided by this software tool, plan re‐optimizations were routinely performed for most patients (193/208 patients or 93%). 60 patients (29%) received previous radiation treatment. High grade early toxicities were observed in 4 patients (4 or 1.9% in grade 3, no grade 4 or 5). All high grade toxicities were related to the OAR identified in the planning process. Conclusions: This software provides an essential tool to appropriately optimize hypofractionated radiotherapy. The LQ model and BED dose evaluations appear to be a safe method to obtain normal tissue tolerances for these patients, with toxicity rates comparable to conventional fractionation. The BED subtraction method properly set the optimization objectives for patients treated with different fractionation schemes.