To frame or not to frame? Cone-beam CT-based analysis of head immobilization devices specific to linac-based stereotactic radiosurgery and radiotherapy.

PURPOSE: Noninvasive frameless systems are increasingly being utilized for head immobilization in stereotactic radiosurgery (SRS). Knowing the head positioning reproducibility of frameless systems and their respective ability to limit intrafractional head motion is important in order to safely perform SRS. The purpose of this study was to evaluate and compare the intrafractional head motion of an invasive frame and a series of frameless systems for single fraction SRS and fractionated/hypofractionated stereotactic radiotherapy (FSRT/HF-SRT). METHODS: The noninvasive PinPoint system was used on 15 HF-SRT and 21 SRS patients. Intrafractional motion for these patients was compared to 15 SRS patients immobilized with Cosman-Roberts-Wells (CRW) frame, and a FSRT population that respectively included 23, 32, and 15 patients immobilized using Gill-Thomas-Cosman (GTC) frame, Uniframe, and Orfit. All HF-SRT and FSRT patients were treated using intensity-modulated radiation therapy on a linear accelerator equipped with cone-beam CT (CBCT) and a robotic couch. SRS patients were treated using gantry-mounted stereotactic cones. The CBCT image-guidance protocol included initial setup, pretreatment and post-treatment verification images. The residual error determined from the post-treatment CBCT was used as a surrogate for intrafractional head motion during treatment. RESULTS: The mean intrafractional motion over all fractions with PinPoint was 0.62 ± 0.33 mm and 0.45 ± 0.33 mm, respectively, for the HF-SRT and SRS cohort of patients (P-value = 0.266). For CRW, GTC, Orfit, and Uniframe, the mean intrafractional motions were 0.30 ± 0.21 mm, 0.54 ± 0.76 mm, 0.73 ± 0.49 mm, and 0.76 ± 0.51 mm, respectively. For CRW, PinPoint, GTC, Orfit, and Uniframe, intrafractional motion exceeded 1.5 mm in 0%, 0%, 5%, 6%, and 8% of all fractions treated, respectively. CONCLUSIONS: The noninvasive PinPoint system and the invasive CRW frame stringently limit cranial intrafractional motion, while the latter provides superior immobilization. Based on the results of this study, our clinical practice for malignant tumors has evolved to apply an invasive CRW frame only for metastases in eloquent locations to minimize normal tissue exposure.

Investigation of Dose Falloff for Intact Brain Metastases and Surgical Cavities Using Hypofractionated Volumetric Modulated Arc Radiotherapy.

INTRODUCTION: Intact brain metastases tend to be small and spherical compared to postsurgery brain cavities, which tend to be large and irregular shaped and, as a result, a challenge with respect to treatment planning. The purpose of the present study is to develop guidelines for normal brain tissue dose and to investigate whether there is a dependence on target type for patients treated with hypofractionated volumetric modulated arc radiotherapy (HF-VMAT). METHODS: Treatment plans from a total of 100 patients and 136 targets (55 cavity and 81 intact) were retrospectively reviewed. All targets were treated with HF-VMAT with total doses ranging between 20 and 30 gray (Gy) in 5 fractions. All plans met institutional objectives for organ-at-risk constraints and were clinically delivered. Dose falloff was quantified using gradient index (GI) and distance between the 100% and 50% isodose lines (R50). Additionally, the dose to normal brain tissue (brain contour excluding all gross tumor or clinical target volumes) was assessed using volume receiving specific doses (Vx) where x ranged from 5 to 30 Gy. Best-fit curves using power law relationships of the form y = ax(b) were generated for GI, R50, and Vx (normal brain tissue) versus target volume. RESULTS: There was a statistically significant difference in planning target volume (PTV) for cavities versus intact metastases with mean volumes of 37.8 cm(3) and 9.5 cm(3), respectively (P < .0001). The GI and R50 were statistically different: 3.4 and 9.8 mm for cavities versus 4.6 and 8.3 mm for intact metastases (P < .0001). The R50 increased with PTV with power law coefficients (a, b) = (6.3, 0.12) and (5.9, 0.15) for cavities and intact, respectively. GI decreased with PTV with coefficients (a, b) = (5.9, -0.18) and (5.7, -0.14) for cavities and intact, respectively. The normal brain tissue Vx also exhibited power law relationships with PTV for x = 20 to 28.8 Gy. In conclusion, target volume is the main predictor of dose falloff. The results of the present study can be used for determining target volume-based thresholds for dose falloff and normal brain tissue dose-volume constraints.

Spine stereotactic body radiotherapy for renal cell cancer spinal metastases: analysis of outcomes and risk of vertebral compression fracture.

OBJECT: The aim of this study was to evaluate local control (LC) and the risk of vertebral compression fracture (VCF) after stereotactic body radiotherapy (SBRT) in patients with renal cell cancer spinal metastases. METHODS: Prospectively collected data on 71 spinal segments treated with SBRT in 37 patients were reviewed. The median follow-up was 12.3 months (range 1.2-55.4 months). The LC rate was assessed based on each spinal segment treated and overall survival (OS) according to each patient treated. Sixty of 71 segments (85%) were radiation naive, 11 of 71 (15%) were previously irradiated, and 10 of 71 (14%) were treated with postoperative SBRT. The median SBRT total dose and number of fractions were 24 Gy and 2, respectively. The VCF analysis also included evaluation of the Spinal Instability Neoplastic Score criteria. RESULTS: The 1-year OS and LC rates were 64% and 83%, respectively. Multivariate analysis identified oligometastatic disease (13 of 37 patients) as a positive prognostic factor (p = 0.018) for OS. Of 61 non-postoperative spinal segments treated, 10 (16%) developed VCFs; 3 of 10 were de novo VCFs and 7 of 10 occurred as progression of an existing VCF. The 1-year VCF-free probability rate was 82%. Multivariate analysis identified single-fraction SBRT and baseline VCF as significant predictors of SBRT-induced VCF (p = 0.028 and p = 0.012, respectively). CONCLUSIONS: Spine SBRT yields high rates of local tumor control in patients with renal cell cancer. Baseline VCF and 18-24 Gy delivered in a single fraction were predictive of further collapse. Patients with oligometastatic disease may benefit most from such aggressive local therapy, given the prolonged survival observed.

Lung stereotactic body radiation therapy (SBRT) delivered over 4 or 11 days: a comparison of acute toxicity and quality of life.

PURPOSE: The optimal duration over which lung SBRT should be delivered is unknown. We conducted a randomized pilot study in patients treated with four fractions of lung SBRT delivered over 4 or over 11 days. METHODS: Patients with a peripheral solitary lung tumor (NSCLC or pulmonary metastasis) ≤ 5 cm were eligible. For NSCLC lung tumors ≤ 3 cm, a dose of 48 Gy in 4 fractions was used, otherwise 52 Gy in 4 fractions was delivered. Patients were randomized to receive treatment over 4 consecutive days or over 11 days. The primary end-point was acute grade ≥ 2 toxicity. Secondary end-points included quality of life (QOL) assessed using the EORTC QLQ-C30 and QLQ-LC13 questionnaires. RESULTS: Fifty four patients were enrolled. More patients in the 11 day group had respiratory symptoms at baseline. 55.6% patients treated over 4 days and 33.3% of patients treated over 11 days experienced acute grade ≥ 2 toxicity (p=0.085). Dyspnea, fatigue and coughing domains were worse in the 11 day group at baseline. At 1 and 4 months, more patients in the 4 day group experienced a clinically meaningful worsening in the dyspnea QOL domain compared to the 11 day group (44.5% vs 15.4%, p=0.02; 38.5% vs 12.0%, p=0.03, respectively). However, raw QOL scores were not different at these time-points between treatment groups. CONCLUSIONS: Grade 2 or higher acute toxicity was more common in the 4 day group, approaching statistical significance. More patients treated on 4 consecutive days reported a clinically meaningful increase in dyspnea, although interpretation of these results is challenging due to baseline imbalance between treatment groups. Larger studies are required to validate these results.

Pain flare is a common adverse event in steroid-naïve patients after spine stereotactic body radiation therapy: a prospective clinical trial.

PURPOSE: To determine the incidence of pain flare after spine stereotactic body radiation therapy (SBRT) in steroid-naïve patients and identify predictive factors. METHODS AND MATERIALS: Forty-one patients were treated with spine SBRT between February 2010 and April 2012. All patients had their pain assessed at baseline, during, and for 10 days after SBRT using the Brief Pain Inventory. All pain medications were recorded daily and narcotics converted to an oral morphine equivalent dose. Pain flare was defined as a 2-point increase in worst pain score as compared with baseline with no decrease in analgesic intake, a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score, or if corticosteroids were initiated at any point during or after SBRT because of pain. RESULTS: The median age and Karnofsky performance status were 57.5 years (range, 27-80 years) and 80 (range, 50-100), respectively. Eighteen patients were treated with 20-24 Gy in a single fraction, whereas 23 patients were treated with 24-35 Gy in 2-5 fractions. Pain flare was observed in 68.3% of patients (28 of 41), most commonly on day 1 after SBRT (29%, 8 of 28). Multivariate analysis identified a higher Karnofsky performance status (P=.02) and cervical (P=.049) or lumbar (P=.02) locations as significant predictors of pain flare. In those rescued with dexamethasone, a significant decrease in pain scores over time was subsequently observed (P<.0001). CONCLUSIONS: Pain flare is a common adverse event after spine SBRT and occurs most commonly the day after treatment completion. Patients should be appropriately consented for this adverse event.

Vertebral compression fracture (VCF) after spine stereotactic body radiation therapy (SBRT): analysis of predictive factors.

PURPOSE: Vertebral compression fractures (VCFs) are increasingly observed after spine stereotactic body radiation therapy (SBRT). The aim of this study was to determine the risk of VCF after spine SBRT and identify clinical and dosimetric factors predictive for VCF. The analysis incorporated the recently described Spinal Instability Neoplastic Score (SINS) criteria. METHODS AND MATERIALS: The primary endpoint of this study was the development of a de novo VCF (ie, new endplate fracture or collapse deformity) or fracture progression based on an existing fracture at the site of treatment after SBRT. We retrospectively scored 167 spinal segments in 90 patients treated with spine SBRT according to each of the 6 SINS criteria. We also evaluated the presence of paraspinal extension, prior radiation, various dosimetric parameters including dose per fraction (≥20 Gy vs <20 Gy), age, and histology. RESULTS: The median follow-up was 7.4 months. We identified 19 fractures (11%): 12 de novo fractures (63%) and 7 cases of fracture progression (37%). The mean time to fracture after SBRT was 3.3 months (range, 0.5-21.6 months). The 1-year fracture-free probability was 87.3%. Multivariate analysis confirmed that alignment (P=.0003), lytic lesions (P=.007), lung (P=.03) and hepatocellular (P<.0001) primary histologies, and dose per fraction of 20 Gy or greater (P=.004) were significant predictors of VCF. CONCLUSIONS: The presence of kyphotic/scoliotic deformity and the presence of lytic tumor were the only predictive factors of VCF based on the original 6 SINS criteria. We also report that patients with lung and hepatocellular tumors and treatment with SBRT of 20 Gy or greater in a single fraction are at a higher risk of VCF.

Cone beam CT (CBCT) evaluation of inter- and intra-fraction motion for patients undergoing brain radiotherapy immobilized using a commercial thermoplastic mask on a robotic couch.

Patients receiving fractionated intensity-modulated radiation therapy (IMRT) for brain tumors are often immobilized with a thermoplastic mask; however, masks do not perfectly re-orient the patient due to factors including the maximum pressure which can be applied to the face, deformations of the mask assembly, patient compliance, etc. Consequently, ~3-5mm PTV margins (beyond the CTV) are often recommended. We aimed to determine if smaller PTV margins are feasible using mask immobilization coupled with 1) a gantry mounted CBCT image guidance system and 2) position corrections provided by a full six-degree of freedom (6-DOF) robotic couch. A cohort of 34 brain tumor patients was treated with fractionated IMRT. After the mask set-up, an initial CBCT was obtained and registered to the planning CT. The robotic couch corrected the misalignments in all 6-DOF and a pre-treatment verification CBCT was then obtained. The results indicated a repositioning alignment within our threshold of 1.5 mm (3D). Treatment was subsequently delivered. A post-treatment CBCT was obtained to quantify intra-fraction motion. Initial, pre-treatment and post-treatment CBCT image data was analyzed. A total of 505 radiation fractions were delivered to the 34 patients resulting in ~1800 CBCT scans. The initial median 3D (magnitude) set-up positioning error was 2.60 mm. Robotic couch corrections reduced the 3D median error to 0.53 mm prior to treatment. Intra-fraction movement was responsible for increasing the median 3D positioning error to 0.86 mm, with 8% of fractions having a 3D positioning error greater than 2 mm. Clearly CBCT image guidance coupled with a robotic 6-DOF couch dramatically improved the positioning accuracy for patients immobilized in a thermoplastic mask system; however, such intra-fraction motion would be too large for single fraction radiosurgery.

Spine stereotactic body radiotherapy utilizing cone-beam CT image-guidance with a robotic couch: intrafraction motion analysis accounting for all six degrees of freedom.

PURPOSE: To evaluate the residual setup error and intrafraction motion following kilovoltage cone-beam CT (CBCT) image guidance, for immobilized spine stereotactic body radiotherapy (SBRT) patients, with positioning corrected for in all six degrees of freedom. METHODS AND MATERIALS: Analysis is based on 42 consecutive patients (48 thoracic and/or lumbar metastases) treated with a total of 106 fractions and 307 image registrations. Following initial setup, a CBCT was acquired for patient alignment and a pretreatment CBCT taken to verify shifts and determine the residual setup error, followed by a midtreatment and posttreatment CBCT image. For 13 single-fraction SBRT patients, two midtreatment CBCT images were obtained. Initially, a 1.5-mm and 1° tolerance was used to reposition the patient following couch shifts which was subsequently reduced to 1 mm and 1° degree after the first 10 patients. RESULTS: Small positioning errors after the initial CBCT setup were observed, with 90% occurring within 1 mm and 97% within 1°. In analyzing the impact of the time interval for verification imaging (10 ± 3 min) and subsequent image acquisitions (17 ± 4 min), the residual setup error was not significantly different (p > 0.05). A significant difference (p = 0.04) in the average three-dimensional intrafraction positional deviations favoring a more strict tolerance in translation (1 mm vs. 1.5 mm) was observed. The absolute intrafraction motion averaged over all patients and all directions along x, y, and z axis (± SD) were 0.7 ± 0.5 mm and 0.5 ± 0.4 mm for the 1.5 mm and 1 mm tolerance, respectively. Based on a 1-mm and 1° correction threshold, the target was localized to within 1.2 mm and 0.9° with 95% confidence. CONCLUSION: Near-rigid body immobilization, intrafraction CBCT imaging approximately every 15-20 min, and strict repositioning thresholds in six degrees of freedom yields minimal intrafraction motion allowing for safe spine SBRT delivery.

A comparison of two immobilization systems for stereotactic body radiation therapy of lung tumors.

PURPOSE: This study aims to compare the efficacy, efficiency and comfort level of two immobilization systems commonly used in lung stereotactic body radiation therapy (SBRT): the Bodyfix and the abdominal compression plate (ACP). MATERIALS AND METHODS: Twenty-four patients undergoing SBRT for medically inoperable stage I lung cancer or pulmonary metastases were entered on this prospective randomized study. All underwent 4DCT simulation with free breathing, the Bodyfix, and the ACP to assess respiratory tumor motion. After CT simulation, patients were randomly assigned to immobilization with either the Bodyfix or the ACP for the actual SBRT treatment. Cone beam CTs (CBCTs) were acquired before and after each treatment to assess intrafraction tumor motion. Setup time and patient comfort were recorded. RESULTS: There were 16 upper lobe, two middle lobe and seven lower-lobe lesions. Both the Bodyfix and the ACP significantly reduced the superior-inferior (SI) and overall respiratory tumor motion compared to free breathing (4.6 and 4.0 vs 5.3mm; 5.3 and 4.7 vs 6.1mm, respectively, p<0.05). The ACP further reduced the SI and overall respiratory tumor motion compared to the Bodyfix (p<0.05). The mean overall intrafraction tumor motion was 2.3mm with the Bodyfix and 2.0mm with the ACP (p>0.05). The ACP was faster to set up and rated more comfortable by patients than the Bodyfix (p<0.05). CONCLUSIONS: While there is no significant difference between the Bodyfix and ACP in reducing intrafraction tumor motion, the ACP is more comfortable, faster to set up, and superior to the Bodyfix in reducing SI and overall respiratory tumor motion.