Jeffrey Fabien

Multicenter results of stereotactic body radiotherapy (SBRT) for non-resectable primary liver tumors

Abstract Background. An excess of 100 000 individuals are diagnosed with primary liver tumors every year in USA but less than 20% of those patients are amenable to definitive surgical management due to advanced local disease or comorbidities. Local therapies to arrest tumor growth have limited response and have shown no improvement on patient survival. Stereotactic body radiotherapy (SBRT) has emerged as an alternative local ablative therapy. The purpose of this study was to evaluate the tumor response to SBRT in a combined multicenter database. Study design. Patients with advanced hepatocellular carcinoma (HCC, n = 21) or intrahepatic cholangiocarcinoma (ICC, n = 11) treated with SBRT from four Academic Medical Centers were entered into a common database. Statistical analyses were performed for freedom from local progression (FFLP) and patient survival. Results. The overall FFLP for advanced HCC was 63% at a median follow-up of 12.9 months. Median tumor volume decreased from 334.2 to 135 cm3 (p < 0.004). The median time to local progression was 6.3 months. The 1- and 2-years overall survival rates were 87% and 55%, respectively. Patients with ICC had an overall FFLP of 55.5% at a median follow-up of 7.8 months. The median time to local progression was 4.2 months and the six-month and one-year overall survival rates were 75% and 45%, respectively. The incidence of grade 1–2 toxicities, mostly nausea and fatigue, was 39.5%. Grade 3 and 4 toxicities were present in two and one patients, respectively. Conclusion. Higher rates of FFLP were achieved by SBRT in the treatment of primary liver malignancies with low toxicity.

Multicentre results of stereotactic body radiotherapy for secondary liver tumours

BACKGROUND Surgical resection is the standard treatment for liver metastases, although for the majority of patients this is not possible. Stereotactic body radiotherapy (SBRT) is an alternative local-regional therapy. The purpose of this study was to evaluate the results of SBRT for secondary liver tumours from a combined multicentre database. METHODS Variables from patients treated with SBRT from four Academic Medical Centres were entered into a common database. Local tumour control and 1-year survival rates were calculated. RESULTS In total, 153 patients (91 women) 59 ± 8.4 years old with 363 metastatic liver lesions were treated with SBRT. The underlying primary tumour arose from gastrointestinal (GI), retroperitoneal and from extra-abdominal primaries in 56%, 8% and 36% of patients, respectively. Metastases, with a gross tumour volume (GTV) of 138.5 ± 126.8 cm(3) , were treated with a total radiation dose of 37.5 ± 8.2 Gy in 5 ± 3 fractions. The 1-year overall survival was 51% with an overall local control rate of 62% at a mean follow-up of 25.2 ± 5.9 months. A complete tumour response was observed in 32% of patients. Grade 3-5 adverse events were noted in 3% of patients. CONCLUSION Secondary liver tumours treated with SBRT had a high rate of local control with a low incidence of adverse events.

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.

Comparison of Ray Tracing and Monte Carlo Calculation Algorithms for Thoracic Spine Lesions Treated With CyberKnife-Based Stereotactic Body Radiation Therapy.

Stereotactic body radiation therapy (SBRT) is an emerging technology for the treatment of spinal metastases, although the dosimetric impact of the calculation method on spinal dose distribution is unknown. This study attempts to determine whether CyberKnife (CK)-based SBRT using a Ray Tracing (RyTc) algorithm is comparable dosimetrically to that of Monte Carlo (MC) for thoracic spinal lesions. Our institutional CK-based SBRT database for thoracic spinal lesions was queried and a cohort was generated. Patients were planned using RyTc and MC algorithms using the same beam angles and monitor units. Dose–volume histograms of the planning target volume (PTV), spinal cord, esophagus, and skin were generated, and dosimetric parameters were compared. There were 37 patients in the cohort. The average percentage volume of PTV covered by the prescribed dose with RyTc and MC algorithms was 91.1% and 80.4%, respectively (P < .001). The difference in average maximum spinal cord dose between RyTc and MC plans was significant (1126 vs 1084 cGy, P = .004), with the MC dose ranging from 18.7% below to 13.8% above the corresponding RyTc dose. A small reduction in maximum skin dose was also noted (P = .017), although no difference was seen in maximum esophageal dose (P = .15). Only PTVs smaller than 27 cm3 were found to correlate with large (>10%) changes in dose to 90% of the volume (P = .014), while no correlates with the average percentage volume of PTV covered by the prescribed dose were demonstrated. For thoracic spinal CK-based SBRT, RyTc computation may overestimate the MC calculated average percentage volume of PTV covered by the prescribed dose and have unpredictable effects on doses to organs at risk, particularly the spinal cord. In this setting, use of RyTc optimization should be limited and always verified with MC.

Acute gastrointestinal toxicity after robotic stereotactic ablative radiotherapy for treatment of metastatic gynecological malignancies

AIMS The aim of this study was to assess acute and subacacute gastrointestinal toxicity after fractionated stereotactic ablative radiotherapy (SABR) in women having recurrent gynecological cancers in the upper abdomen. MATERIALS & METHODS In total, 34 women underwent upper abdominal SABR (24 Gy/three divided 8 Gy consecutive daily doses) using a robotic Cyberknife® (Accuray, CA, USA) platform. Volumes of the duodenum receiving 10% increments of the prescription dose were associated to post-therapy gastrointestinal toxicities using binary logistic regression analyses. RESULTS Median clinical follow-up was 10 months. In total, 14 (41%) of the 34 women manifested grade 2 or higher post-therapy gastrointestinal adverse events. The duodenal volume, receiving 80% of a 24-Gy dose, was significantly associated with gastrointestinal toxicity (p = 0.03). However, in a multivariate analysis, only patient age at SABR adjusted the odds of experiencing gastrointestinal toxicity (p = 0.02). CONCLUSION The duodenal volume receiving 80% of 24 Gy dose may be associated with gastrointestinal toxicity from upper abdominal SABR.

Hybrid Arc Stereotactic Ablative Body Radiation Therapy for Pelvic Relapse of Gynecologic Malignancies

Relapsed gynecologic cancers are difficult to control in the pelvis, especially when surgery, chemotherapy and radiation treatments have already been administered. For this clinical scenario, stereotactic body radiation therapy has emerged as a meaningful treatment strategy. The new Vero stereotactic body radiation therapy system uses coplanar and noncoplanar radiation treatment beams with submillimeter precision to treat cancer targets. This study describes the initial clinical experience with Vero hybrid arc stereotactic ablative body radiation therapy to treat relapsed gynecologic cancers detected in the pelvis.

Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time ±4 cm pan-and-tilt action. Robot-driven ±60° pivots of an integrated ±185° rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[18F] fluoro-2-deoxy-ᴅ-glucose (18F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less1. In this article, we describe new radiation plans for the treatment of moving lung tumors.

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.