Chia-Lin Tseng

Salvage Stereotactic Body Radiotherapy (SBRT) Following In-Field Failure of Initial SBRT for Spinal Metastases

PURPOSE We report our experience in salvaging spinal metastases initially irradiated with stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression, and were re-irradiated with a salvage second SBRT course to the same level. METHODS AND MATERIALS From a prospective database, 56 metastatic spinal segments in 40 patients were identified as having been irradiated with a salvage second SBRT course to the same level. In addition, 24 of 56 (42.9%) segments had initially been irradiated with conventional external beam radiation therapy before the first course of SBRT. Local control (LC) was defined as no progression on magnetic resonance imaging at the treated segment, and calculated according to the competing risk model. Overall survival (OS) was evaluated for each patient treated by use of the Kaplan-Meier method. RESULTS The median salvage second SBRT total dose and number of fractions was 30 Gy in 4 fractions (range, 20-35 Gy in 2-5 fractions), and for the first course of SBRT was 24 Gy in 2 fractions (range, 20-35 Gy in 1-5 fractions). The median follow-up time after salvage second SBRT was 6.8 months (range, 0.9-39 months), the median OS was 10.0 months, and the 1-year OS rate was 48%. A longer time interval between the first and second SBRT courses predicted for better OS (P=.02). The crude LC was 77% (43/56), the 1-year LC rate was 81%, and the median time to local failure was 3.0 months (range, 2.7-16.7 months). Of the 13 local failures, 85% (11/13) and 46% (6/13) showed progression within the epidural space and paraspinal soft tissues, respectively. Absence of baseline paraspinal disease predicted for better LC (P<.01). No radiation-induced vertebral compression fractures or cases of myelopathy were observed. CONCLUSION A second course of spine SBRT, most often with 30 Gy in 4 fractions, for spinal metastases that failed initial SBRT is a feasible and efficacious salvage treatment option.

Spine Stereotactic Body Radiotherapy: Indications, Outcomes, and Points of Caution:

Study Design: A broad narrative review. Objectives: The objective of this article is to provide a technical review of spine stereotactic body radiotherapy (SBRT) planning and delivery, indications for treatment, outcomes, complications, and the challenges of response assessment. The surgical approach to spinal metastases is discussed with an overview of emerging minimally invasive techniques. Methods: A comprehensive review of the literature was conducted on the techniques, outcomes, and developments in SBRT and surgery for spinal metastases. Results: The optimal management of patients with spinal metastases is complex and requires multidisciplinary assessment from an oncologic team that is familiar with the shifting paradigm as a consequence of evolving techniques in surgery and stereotactic radiation, as well as new developments in systemic agents. The Spinal Instability Neoplastic Score and the epidural spinal cord compression (Bilsky) grading system are useful tools that facilitate communication among oncologic team members and can direct management by providing a baseline assessment of risks prior to therapy. The combined multimodality approach with “separation surgery” followed by postoperative spine SBRT achieves thecal sac decompression, improves tumor control, and avoids complications that may be associated with more extensive surgery. Conclusion: Spine SBRT is a highly effective treatment that is capable of delivering ablative doses to the target while sparing the critical organs-at-risk, chiefly the critical neural tissues, within a short and manageable schedule. At the same time, surgery occupies an important role in select patients, particularly with the expanding availability and expertise in minimally invasive techniques. With rapid adoption of spine SBRT in centers outside of the academic setting, it is imperative for the practicing oncologist to understand the relevance and application of these evolving concepts.

Re-irradiation of Vertebral Body Metastases: Treatment in the Radiosurgery Era

Vertebral bodies remain one of the most common sites of metastases. In cases where surgical intervention is not indicated or appropriate, conventional external radiation therapy (cEBRT) has been the standard treatment modality. Unfortunately, cEBRT is typically limited, with low complete response and poor local control rates. Disappointing results with re-irradiation using cEBRT highlight the need for innovative salvage therapeutic strategies, such as stereotactic body radiotherapy. A detailed description of this complex treatment strategy is outlined, as is a systematic review of current literature. Although data are limited to single institution series, re-irradiation has consistently been found to be effective with respect to local control (1 year rates range from 66 to 90%) and pain response. Importantly, the treatment is shown to be safe, with the crude rate of radiation myelopathy <1% and a rate of vertebral compression fracture of 12%. As further research and technologic advances continue to refine therapy, stereotactic body radiotherapy is now a recommended option for the treatment of previously irradiated vertebral body metastases.

Dosimetric feasibility of the hybrid Magnetic Resonance Imaging (MRI)-linac System (MRL) for brain metastases: The impact of the magnetic field

BACKGROUND AND PURPOSE We aimed to investigate the suitability of treating patients with single brain metastases using stereotactic radiosurgery (SRS) with the MRL and to characterize the dosimetric impact at tissue-air interfaces resulting primarily from the electron return effect (ERE). MATERIAL AND METHODS 24 patients treated for intact single brain metastases were analyzed. Three radiotherapy plans with the same prescribed dose were generated for each case: (1) noncoplanar volumetric modulated arc therapy (VMAT), (2) coplanar step-and-shoot intensity modulated radiotherapy (IMRT) on the MRL in the absence (MRLB=0), and (3) in the presence of the transverse magnetic field (MRLB=1.5). The plans were evaluated using cumulative dose-volume histograms and by calculation of Paddick conformity index (CI), V100%, V12Gy minus gross tumor volume (V12Gy - GTV), and V2Gy. At tissue-air boundaries, the dosimetric impact of the magnetic field was quantified using a 5 mm rim of tissue. RESULTS All plans met the target coverage and organs-at-risk planning objectives. Differences between all investigated dosimetric parameters significantly favored the VMAT plans as compared to the MRLB=0 and MRLB=1.5 plans, except for V2Gy. The mean V12Gy - GTV and V2Gy marginally favored the MRLB=0 plans compared to the MRLB=1.5 plans (mean difference: 0.45 cm3, p = 0.0019 and 16.46 cm3, p < 0.0001, respectively). The presence of the magnetic field resulted in a statistically significant but small increase in mean dose and D2cc in the skin (0.08 Gy, p < 0.0001 and 0.6 Gy, p < 0.0001, respectively) and around air cavities (0.07 Gy, p = 0.0092 and 0.3 Gy, p = 0.0004, respectively). CONCLUSIONS It is feasible to generate stereotactic radiation plans that satisfy clinical requirements using the MRL in the setting of single brain metastases. The dosimetric impact of the magnetic field including the ERE at tissue-air boundaries is minor and does not negatively impact target conformity or dose gradient.

Inter-observer agreement in GTV delineation of bone metastases on CT and impact of MR imaging: A multicenter study

BACKGROUND AND PURPOSE The use of Stereotactic Body Radiotherapy (SBRT) for bone metastases is increasing rapidly. Therefore, knowledge of the inter-observer differences in tumor volume delineation is essential to guarantee precise dose delivery. The aim of this study is to compare inter-observer agreement in bone metastases delineated on different imaging modalities. MATERIAL AND METHODS Twenty consecutive patients with bone metastases treated with SBRT were selected. All patients received CT and MR imaging in treatment position prior to SBRT. Five observers from three institutions independently delineated gross tumor volume (GTV) on CT alone, CT with co-registered MRI and MRI alone. Four contours per imaging modality per patient were available, as one set of contours was shared by 2 observers. Inter-observer agreement, expressed in generalized conformity index [CIgen], volumes of contours and contours center of mass (COM) were calculated per patient and imaging modality. RESULTS Mean GTV delineated on MR (45.9±52.0cm3) was significantly larger compared to CT-MR (40.2±49.4cm3) and CT (34.8±41.8cm3). A considerable variation in CIgen was found on CT (mean 0.46, range 0.15-0.75) and CT-MRI (mean 0.54, range 0.17-0.71). The highest agreement was found on MRI (mean 0.56, range 0.20-0.77). The largest variations of COM were found in anterior-posterior direction for all imaging modalities. CONCLUSIONS Large inter-observer variation in GTV delineation exists for CT, CT-MRI and MRI. MRI-based GTV delineation resulted in larger volumes and highest consistency between observers.

Impact of Magnetic Resonance Imaging on Gross Tumor Volume Delineation in Non-spine Bony Metastasis Treated With Stereotactic Body Radiation Therapy

PURPOSE This study investigates the inter-observer variability of contouring non-spine bone metastases using the planning CT alone vs. the addition of MRI T1 and T2 imaging sequences. METHODS AND MATERIALS 10 cases of non-spine bone metastases treated with SBRT at our institution were selected. The gross tumor volume (GTV) for each case was delineated by six SBRT radiation oncologists (RO) and one diagnostic radiologist (DR) on the treatment planning CT. After a minimum of three months, each case was re-contoured on the CT fused with a MRI T1 sequence followed by a MRI T2 sequence. STAPLE consensus contours were created from the RO volumes and inter-observer variability was measured using both κ agreement and the Dice coefficient (DSC). RESULTS In total, 180 RO contours were analyzed within three datasets (CT, CT + MRI T1 and CT + MRI T1 + MRI T2). The mean GTV was 16.95 cm3 (range, 0.12-269.6 cm3). The RO κ agreement was 0.6129 based on CT alone, and significantly increased to 0.7045 in the CT + MRI T1 (P = .042) dataset and 0.7017 in the CT + MRI T1 + MRI T2 dataset (P = .048). The mean DSC in the CT alone dataset was 0.7047, and significantly increased to 0.7628 in the CT + MRI T1 dataset (P < .001) and 0.7544 in the CT + MRI T1 + MRI T2 dataset (P = .001). There were no statistical differences in RO κ agreement (P = .948) or mean DSC (P = .573) when comparing the CT + MRI T1 and CT + MRI T1 + MRI T2 datasets. The DSC agreement between DR and RO volumes was lowest (0.6887) in the CT alone dataset and significantly increased to 0.7398 in the CT + MRI T1 dataset (P = .003) and 0.7342 in the CT + MRI T1 + MRI T2 dataset (P = .008). CONCLUSIONS The fusion of MRI T1 images to CT significantly reduced inter-observer variability amongst ROs in delineating non-spine bone metastases, and improved agreement between GTVs delineated by the RO to the DR.

Hospitalizations in elderly glioblastoma patients

BACKGROUND Elderly glioblastoma (GB) patients are at risk of hospitalizations due to the morbidity of the disease and possible treatment toxicity. METHODS In this observational cohort study, 255 newly diagnosed GB patients age 65 years and older were included. Survival, emergency room visits and admissions to an acute care hospital were determined. Mean and median total health care costs were calculated. Risk factors for Emergency room visits and acute care hospital admissions were determined. RESULTS Median overall survival was 6 months. The majority of patients (68%) had at least one visit to the emergency department and 77% had at least one admission to acute care. The mean and median total costs (hospital, ambulatory, physician billing, other health care costs) per patient were

SU-G-JeP2-01: A New Approach for MR-Only Treatment Planning: Tissue Segmentation-Based Pseudo-CT Generation Using T1-Weighted MRI.

162,479.78 (CAN) and

Magnetic Resonance Imaging Assessment of Spinal Cord and Cauda Equina Motion in Supine Patients With Spinal Metastases Planned for Spine Stereotactic Body Radiation Therapy

125,511.00 (CAN), respectively. Treatment with radiation or treatment with radio-chemotherapy was associated with a relative risk (RR) of 2.31 (95% CI: 1.44-3.7; P=0.0005) and 2.19 (95% CI: 1.28-3.74; P=0.004), respectively for emergency department visits as compared to patients who were managed with comfort measures only. Patients with a baseline ECOG 0 had a RR of 1.71 (95% CI: 1.06-2.77; P=0.0289) and patients with baseline ECOG 1 had a RR of 1.49 (0.98-2.26; P=0.0623) for hospital admission as compared to patients with ECOG 4. CONCLUSIONS A large proportion of elderly GB patients (particularly those with good baseline performance status who underwent active treatment) presented to the emergency department and had at least one admission to acute care.

Dosimetric Feasibility of the Hybrid Magnetic Resonance Imaging (MRI)-Linear Accelerator System for Brain Metastases: The Impact of the Magnetic Field

PURPOSE To evaluate MR-only treatment planning for brain Stereotactic Ablative Radiotherapy (SABR) based on pseudo-CT (pCT) generation using one set of T1-weighted MRI. METHODS T1-weighted MR and CT images from 12 patients who were eligible for brain SABR were retrospectively acquired for this study. MR-based pCT was generated by using a newly in-house developed algorithm based on MR tissue segmentation and voxel-based electron density (ED) assignment (pCTv). pCTs using bulk density assignment (pCTb where bone and soft tissue were assigned 800HU and 0HU,respectively), and water density assignment (pCTw where all tissues were assigned 0HU) were generated for comparison of ED assignment techniques. The pCTs were registered with CTs and contours of radiation targets and Organs-at-Risk (OARs) from clinical CT-based plans were copied to co-registered pCTs. Volumetric-Modulated-Arc-Therapy(VMAT) plans were independently created for pCTv and CT using the same optimization settings and a prescription (50Gy/10 fractions) to planning-target-volume (PTV) mean dose. pCTv-based plans and CT-based plans were compared with dosimetry parameters and monitor units (MUs). Beam fluence maps of CT-based plans were transferred to co-registered pCTs, and dose was recalculated on pCTs. Dose distribution agreement between pCTs and CT plans were quantified using Gamma analysis (2%/2mm, 1%/1mm with a 10% cut-off threshold) in axial, coronal and sagittal planes across PTV. RESULTS The average differences of PTV mean and maximum doses, and monitor units between independently created pCTv-based and CT-based plans were 0.5%, 1.5% and 1.1%, respectively. Gamma analysis of dose distributions of the pCTs and the CT calculated using the same fluence map resulted in average agreements of 92.6%/79.1%/52.6% with 1%/1mm criterion, and 98.7%/97.4%/71.5% with 2%/2mm criterion, for pCTv/CT, pCTb/CT and pCTw/CT, respectively. CONCLUSION Plans produced on Voxel-based pCT is dosimetrically more similar to CT plans than bulk assignment-based pCTs. MR-only treatment planning using voxel-based pCT generated from T1-wieghted MRI may be feasible.