Role of 18F-choline and 18F-fluorodeoxyglucose positron emission tomography in combination with magnetic resonance imaging in brachytherapy planning for locally advanced cervical cancer: A pilot study.

Background and purpose: This pilot study aims to describe the advantages of combining metabolic and anatomic imaging modalities in brachytherapy (BT) planning for locally advanced cervical cancer (LACC) and to evaluate the supplementary value of Fluoro(F)-Choline positron emission tomography/computed tomography (PET/CT) in comparison to 18F-fluorodeoxyglucose (FDG) in this setting. Materials and methods: A prospective cohort of six patients with LACC was included in this study. Each patient underwent BT planning CT scan, magnetic resonance imaging (MRI), and both FDG and F-Choline PET/CT scans on the same day, with BT applicators in place. Patients were treated according to the standard of care. Metabolic target volumes (TV) were generated retrospectively and compared with the anatomic volumes using Dice coefficients and absolute volume comparison. Results: The threshold at which the metabolic and anatomic volumes were the most concordant was found to be 35% maximum standardized uptake value (SUV max) for both PET/CT scans. Amongst the six patients in this cohort, three in the FDG cohort and four in the F-Choline cohort were found to have more than ten percent ratio of excess (increase) in their MRI gross tumor volumes (GTV) when incorporating the metabolic information from the PET/CT scans. However, no significant changes were needed in the high risk-clinical target volumes (CTVHR) for both PET tracers. Conclusions: FDG and F-Choline PET/CT scans can substantially modify the BT GTV on MRI, without affecting the CTVHR. F-Choline is potentially more informative than FDG in assessing residual TV, particularly in cases with significant post-radiation inflammatory changes.

Validation of MRI to TRUS registration for high-dose-rate prostate brachytherapy.

PURPOSE: The objective of this study was to develop and validate an open-source module for MRI to transrectal ultrasound (TRUS) registration to support tumor-targeted prostate brachytherapy. METHODS AND MATERIALS: In this study, 15 patients with prostate cancer lesions visible on multiparametric MRI were selected for the validation. T2-weighted images with 1-mm isotropic voxel size and diffusion weighted images were acquired on a 1.5T Siemens imager. Three-dimensional (3D) TRUS images with 0.5-mm slice thickness were acquired. The investigated registration module was incorporated in the open-source 3D Slicer platform, which can compute rigid and deformable transformations. An extension of 3D Slicer, SlicerRT, allows import of and export to DICOM-RT formats. For validation, similarity indices, prostate volumes, and centroid positions were determined in addition to registration errors for common 3D points identified by an experienced radiation oncologist. RESULTS: The average time to compute the registration was 35 ± 3 s. For the rigid and deformable registration, respectively, Dice similarity coefficients were 0.87 ± 0.05 and 0.93 ± 0.01 while the 95% Hausdorff distances were 4.2 ± 1.0 and 2.2 ± 0.3 mm. MRI volumes obtained after the rigid and deformable registration were not statistically different (p > 0.05) from reference TRUS volumes. For the rigid and deformable registration, respectively, 3D distance errors between reference and registered centroid positions were 2.1 ± 1.0 and 0.4 ± 0.1 mm while registration errors between common points were 3.5 ± 3.2 and 2.3 ± 1.1 mm. Deformable registration was found significantly better (p < 0.05) than rigid registration for all parameters. CONCLUSIONS: An open-source MRI to TRUS registration platform was validated for integration in the brachytherapy workflow.

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy.

PURPOSE: This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). METHOD: 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. RESULTS: Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. CONCLUSIONS: DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.

Stereotactic Body Radiotherapy for Inoperable Liver Tumors: Results of a Single Institutional Experience.

OBJECTIVES: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumors unsuitable for ablation or surgery. We report our experience with SBRT in the treatment of liver tumors. MATERIALS AND METHODS: Patients with primary or secondary liver cancer were identified in our local SBRT database. Patients were included irrespective of prior liver-directed therapies. The primary endpoint of our review was in-field local control (LC). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: From 2009 to 2015, a total of 71 liver lesions in 68 patients were treated with SBRT (three patients had two liver lesions treated). The median age was 71 years (27-89 years). Hepatocellular carcinoma (HCC) was the diagnosis in 23 patients (34%), with the grade of Child-Pugh A (52%), B (39%), or C (nine percent) cirrhosis. Six patients (nine percent) had intrahepatic cholangiocarcinoma (IHC). The remaining 39 patients (57%) had metastatic liver lesions. Colorectal adenocarcinoma was the most common primary tumor type (81%). The median size for HCC, IHC, and metastatic lesions was 5 cm (2-9 cm), 3.6 cm (2-4.9 cm), and 4 cm (1-8 cm), respectively. The median prescribed dose was 45 Gy (16-50 Gy). Median follow-up was 11.5 months (1-45 months). Actuarial one-year in-field LC for HCC and metastatic lesions was 85% and 64% respectively (p= 0.66). At one year, the actuarial rate of new liver lesions was 40% and 26%, respectively, (p=0.58) for HCC and metastases. Only six patients with IHC were treated with SBRT in this study - in these patients, one-year LC was 78% with new liver lesions in 53%. The SBRT treatments were well tolerated. The side effects included common criteria for adverse events (CTCAE) v4 grade 1 acute gastrointestinal toxicity in three patients, grade 3 nausea in one patient, and grade 3 acute dermatitis in another patient. Two patients had grade 5 toxicity. Radiation pneumonitis was observed in one patient two months post-SBRT treatment, and another patient was suspected to have had radio-induced liver disease (RILD) two months after SBRT. No late toxicity was seen. CONCLUSION: SBRT is a well-tolerated and effective alternative treatment option for selected patients with primary and metastatic liver tumors.

Accuracy of Breath-hold CT in Treatment Planning for Lung Stereotactic Ablative Radiotherapy.

PURPOSE: The objectives of this study are (1) to measure concordance of tumor position on breath-hold (BH) computed tomography (CT) scans relative to the natural tumor path during free breathing (FB) and (2) to evaluate the benefits of the breathing monitoring device Abches (Apex Medical, Tokyo) for stereotactic ablative radiotherapy (SABR) treatment planning. METHODS: In 53 lung cancer patients treated with CyberKnife™ robotic radiosurgery system, FB four-dimensional computerized tomography (4DCT) and end-expiration (EE) BH CT images were obtained. Extent of natural tumor motion was assessed with rigid registration derived from end-inspiration (EI) and EE phases of the 4DCT. Tumor displacement in BH scans relative to the natural tumor path was measured relative to the EE 4DCT phase. RESULTS: Mean tumor motion (+/- 1 SD) during natural FB was 1 ± 1 mm, 2 ± 2 mm, and 6 ± 6 mm in medio-lateral, anterior-posterior, and cranio-caudal directions, respectively. Tumor position on BH CT scan was closer to EE than EI 4DCT phase for 35/53 patients (66%). Difference of BH tumor position vs. EE state was 4 ± 3 mm. Gross tumor displacements perpendicular to natural tumor path were as great as 11 mm (anterior-posterior) and were seen with or without the breathing monitoring device. CONCLUSION: Tumor position during BH CT may not accurately correspond to positions observed on FB 4DCT. Hence, accurate and custom 4D analysis for each individual patient is recommended for treatment planning, especially those involving BH acquisitions.