W. Chu

Tumor Response After Stereotactic Body Radiation Therapy to Nonspine Bone Metastases: An Evaluation of Response Criteria

PURPOSEnTo evaluate the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and University of Texas MD Anderson (MDA) Cancer Center criteria in the setting of stereotactic body radiation therapy (SBRT) to nonspine bone metastases.nnnMETHODSnPatients who were treated with SBRT to nonspine bone metastases were identified by retrospective chart review. An independent musculoskeletal radiologist evaluated response to treatment using computed tomography (CT) scans.nnnRESULTSnThirty-three patients were treated to 42 nonspine bone metastases. The most common primary cancer cites were renal cell carcinoma (RCC) (33.3%), lung (24.2%), and prostate (18.2%). Bone metastases were either mainly lytic (57.1%), mainly sclerotic (28.6%), or mixed (14.3%). When lytic and sclerotic lesions were evaluated according to RECIST 1.1, local control (LC) was 83%, 85%, 88%, and 80% for those with CT imaging between months 1 to 3, 4 to 6, 7 to 9, and 10 to 12, respectively. When evaluated by the MDA criteria by density, LC within each time period was slightly greater. Overall LC decreased considerably when evaluated by MDA in terms of size.nnnCONCLUSIONSnConsensus definitions of response are required as they have implications on clinical trials and disease management. Without consistent response criteria, outcomes from clinical trials cannot be compared and treatment efficacy remains undetermined.

Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation

PURPOSEnTo evaluate the feasibility of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU.nnnMETHODS AND MATERIALSnMild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2xa0seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60xa0minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor.nnnRESULTSnIn pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion.nnnCONCLUSIONSnIn pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30xa0minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.

Magnetic Resonance–Guided High-Intensity- Focused Ultrasound for Palliation of Painful Skeletal Metastases A Pilot Study

Background: Bone is one of the most common sites of metastases, with bone metastases-related pain representing a significant source of morbidity among patients with cancer. Magnetic resonance–guided focused ultrasound is a noninvasive, outpatient modality with the potential for treating painful bone metastases. The aim of this study is to report our initial experience with magnetic resonance–guided focused ultrasound in the treatment of bone metastases and our preliminary analysis of urinary cytokine levels after therapy. Methods: This was a single-center pilot study of 10 patients with metastatic cancer to investigate the feasibility of magnetic resonance–guided focused ultrasound for primary pain control in device-accessible skeletal metastases. Treatments were performed on a clinical magnetic resonance–guided focused ultrasound system using a volumetric ablation technique. Primary efficacy was assessed using Brief Pain Inventory scores and morphine equivalent daily dose intake at 3 time points: before, day 14, and day 30 after the magnetic resonance–guided focused ultrasound treatment. Urine cytokines were measured 3 days before treatment and 2 days after the treatment. Results: Of the 10 patients, 8 were followed up 14 days and 6 were followed up 30 days after the treatment. At day 14, 3 patients (37.5%) exhibited partial pain response and 4 patients (50%) exhibited an indeterminate response, and at day 30 after the treatment, 5 patients (83%) exhibited partial pain response. No treatment-related adverse events were recorded. Of the urine cytokines measured, only Transforming growth factor alpha (TGFα) demonstrated an overall decrease, with a trend toward statistical significance (P = .078). Conclusion: Our study corroborates magnetic resonance–guided focused ultrasound as a feasible and safe modality as a primary, palliative treatment for painful bone metastases and contributes to the limited body of literature using magnetic resonance–guided focused ultrasound for this clinical indication.

Computed Tomography Evaluation of Density Following Stereotactic Body Radiation Therapy of Nonspine Bone Metastases.

Introduction: Stereotactic body radiation therapy allows for the precise delivery of high-dose radiation to disease sites and is becoming increasingly used to treat nonspine bone metastases. Previous studies have shown that remineralization of lytic bone metastases follows after conventional radiotherapy. The objective of this study was to investigate changes in bone density in nonspine bone metastases following stereotactic body radiation therapy. Methods: A retrospective review was conducted for all patients treated with stereotactic body radiation therapy to nonspine bone metastases between May 2011 and April 2014. A minimum of 1 pretreatment and 1 posttreatment computed tomography scan was required. An independent musculoskeletal radiologist contoured the lesions on the most representative computed tomography slices. Density was measured in Hounsfield units and analyzed using pretreatment and posttreatment ratios. Results: Forty sites were treated (55% lytic, 30% sclerotic, and 15% mixed). The median follow-up duration was 7 months. Lytic osseous metastases from renal cell carcinoma progressed during initial follow-up imaging and then returned to baseline. Of 9 lytic lesions not from renal cell carcinoma, 6 showed an immediate increase in density and 2 remained stable. Six of 7 sclerotic lesions from prostate cancer showed decreased density throughout all follow-ups. Conclusion: Stereotactic body radiation therapy is efficacious in the remineralization of lytic and demineralization of sclerotic nonspine bone metastases.

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

PURPOSEnThis 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.nnnMETHODS AND MATERIALSn10 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).nnnRESULTSnIn 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).nnnCONCLUSIONSnThe 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.