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.

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.

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

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 cm(3) (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.

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 cm(3) 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.

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-[(18)F] fluoro-2-deoxy-ᴅ-glucose ((18)F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less. In this article, we describe new radiation plans for the treatment of moving lung tumors.

Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner.

PURPOSE: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. METHODS: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system--MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was "printed" using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. RESULTS: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A passing rate of 99% was measured in areas of above 40% of the prescription dose. The final inverse treatment plan was comprised of 43 beams ranging from 5 to 12.5 mm in diameter (2.5 mm size increments are available up to 15 mm in diameter collimation). Using the Xsight Spine Tracking module, the CyberKnife system could not reliably identify and track the tiny mouse spine; however, the CyberKnife system could identify and track the fiducial markers on the 3D mold.In vivo positional accuracy analysis using the 3D mold generated a mean error of 1.41 mm ± 0.73 mm when fiducial markers were used for position tracking. Analysis of the dissected brain confirmed the ability to target the correct brain volume. CONCLUSIONS: With the use of a stereotactic body mold with fiducial markers, microCT imaging, and resolution down-sampling, the CyberKnife system can successfully perform small-animal radiotherapy studies.

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.

18FDG-PET/CT Definition of Clinical Target Volume for Robotic Stereotactic Body Radiosurgery Treatment of Metastatic Gynecologic Malignancies.

The objective of the current article was to evaluate 2-[18F]fluoro-2-deoxy-D-glucose 18F-FDG) as measured by positron emission tomography for delineation of abdominopelvic gross tumor volumes (GTV) for stereotactic body radiosurgery treatment (SBRT) of metastatic gynecologic cancers. A retrospective review of SBRT was conducted in 27 women with stage IV gynecologic cancers recurring in para-aortic lymph nodes. Robotic SBRT involved 2400 cGy in 3 consecutive 800 cGy daily fractions prescribed to a 3.0 mm expanded planning tumor volume (PTV) defined by both CT-based and 18F-FDG-based GTVs. In this study, 18F-FDG-based GTVs led to significantly larger PTVs in all 27 women, than if they had been based on CT GTVs alone (P < 0.001). Enlarged PTVs may have resulted from the breathing-induced target motion during the time of 18F-FDG image acquisition smearing 18F-FDG signal over a greater anatomic dimension. Ultimately, SBRT-target local control, based on the RECIST 1.1 criteria, was 96% (26 of 27), and associated with minor reversible toxicity. The use of 18F-FDG to define SBRT target volumes warrants further interrogation in SBRT clinical trials.