Tharakeswara Bathala

Clinical Outcomes for Patients with Metastatic Renal Cell Carcinoma Treated with Alternative Sunitinib Schedules

PURPOSE We identified sunitinib alternative schedules that maintained dose intensity while decreasing adverse events in patients with metastatic renal cell cancer. We also determined the impact of alternative schedules on clinical outcomes. MATERIALS AND METHODS We retrospectively reviewed the records of patients 18 years old or older with clear cell metastatic renal cell cancer who received first line sunitinib between January 26, 2006 and March 1, 2011 at our major comprehensive cancer center. A subset of patients was switched at the first intolerable adverse event from the traditional schedule of 28 days on and 14 days off to a schedule of 14 days on and 7 days off or other alternative schedules. A control group underwent standard dose reduction. We estimated progression-free and overall survival by the Kaplan-Meier method. Predictors of progression-free and overall survival were analyzed using Cox regression. RESULTS A total of 187 patients were included in analysis, of whom 87% were on the traditional schedule at baseline. During treatment 53% of patients continued on the traditional schedule and 47% began or were transitioned to alternative schedules. Baseline characteristics were similar. Adverse events prompting schedule modification included fatigue in 64% of cases, hand-foot syndrome in 38% and diarrhea in 32%. Median time to alternative schedules was 5.6 months. Median overall survival was 17.7 months (95% CI 10.8-22.2) on the traditional schedule compared to 33.0 months (95% CI 29.3-not estimable) on alternative schedules (p <0.0001). On multivariable analysis poor Eastern Cooperative Oncology Group (ECOG) performance status, increased lactate dehydrogenase, decreased albumin, unfavorable Heng criteria and the traditional schedule were associated with decreased overall survival (p <0.05). CONCLUSIONS Sunitinib administered on alternative schedules may mitigate adverse events while achieving outcomes comparable to those of the traditional schedule in patients with metastatic renal cell cancer. Prospective investigations of alternate dosing schemas are warranted.

Adult UrologyOncology: Adrenal/Renal/Upper Tract/BladderClinical Outcomes for Patients with Metastatic Renal Cell Carcinoma Treated with Alternative Sunitinib Schedules

PURPOSE We identified sunitinib alternative schedules that maintained dose intensity while decreasing adverse events in patients with metastatic renal cell cancer. We also determined the impact of alternative schedules on clinical outcomes. MATERIALS AND METHODS We retrospectively reviewed the records of patients 18 years old or older with clear cell metastatic renal cell cancer who received first line sunitinib between January 26, 2006 and March 1, 2011 at our major comprehensive cancer center. A subset of patients was switched at the first intolerable adverse event from the traditional schedule of 28 days on and 14 days off to a schedule of 14 days on and 7 days off or other alternative schedules. A control group underwent standard dose reduction. We estimated progression-free and overall survival by the Kaplan-Meier method. Predictors of progression-free and overall survival were analyzed using Cox regression. RESULTS A total of 187 patients were included in analysis, of whom 87% were on the traditional schedule at baseline. During treatment 53% of patients continued on the traditional schedule and 47% began or were transitioned to alternative schedules. Baseline characteristics were similar. Adverse events prompting schedule modification included fatigue in 64% of cases, hand-foot syndrome in 38% and diarrhea in 32%. Median time to alternative schedules was 5.6 months. Median overall survival was 17.7 months (95% CI 10.8-22.2) on the traditional schedule compared to 33.0 months (95% CI 29.3-not estimable) on alternative schedules (p <0.0001). On multivariable analysis poor Eastern Cooperative Oncology Group (ECOG) performance status, increased lactate dehydrogenase, decreased albumin, unfavorable Heng criteria and the traditional schedule were associated with decreased overall survival (p <0.05). CONCLUSIONS Sunitinib administered on alternative schedules may mitigate adverse events while achieving outcomes comparable to those of the traditional schedule in patients with metastatic renal cell cancer. Prospective investigations of alternate dosing schemas are warranted.

Development of a magnetic resonance imaging protocol to visualize encapsulated contrast agent markers in prostate brachytherapy recipients: initial patient experience

Purpose Computed tomography (CT)-based prostate post-implant dosimetry allows for definitive seed localization but is associated with high interobserver variation in prostate contouring. Currently, magnetic resonance imaging (MRI)-based post-implant dosimetry allows for accurate anatomical delineation but is limited due to inconsistent seed localization. Encapsulated contrast agent markers were previously proposed to overcome the seed localization limitation on MRI images by placing hyperintense markers adjacent to hypointense seeds. The aim of this study was to assess the appearance of these markers in prostatic tissue, and develop an MRI protocol to enable marker visualization. Material and methods We acquired MRI scans in prostate implant patients (n = 10) on day 0 (day of implant) and day 30 (month after implant). Before implantation of the markers, the routine post-implant MRI protocol included a 3D T2-weighted fast-spin-echo (FSE) sequence with which markers and seeds could not be clearly visualized. To visualize the MRI markers, a 3D fast radiofrequency-spoiled gradient-recalled echo (FSPGR) sequence was evaluated for marker and seed visibility, as well as prostate boundary definitions. Results The 3D FSPGR sequence allowed for the visualization of markers in the prostate, enabling the distinction of signal voids as seeds versus needle tracks. The updated post-implant MRI protocol consists of this 3D FSPGR scan and an optional 3D T2-weighted FSE scan. The optional 3D T2-weighted FSE sequence may be employed to better visualize intraprostatic detail. We also described the observed image artifacts, including seed susceptibility, marker chemical shift, partial volume averaging, motion, and wraparound artifacts. Conclusions We have demonstrated an MRI protocol for use with hyperintense encapsulated contrast agent markers to assist in the identification of hypointense seeds.

Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors: a single institution experience

To explore the efficacy and safety of pazopanib in a ‘real‐world’ setting in unselected patients, as data regarding unselected patients with metastatic clear‐cell renal cell carcinoma (ccRCC) treated with first‐line pazopanib are limited.

Pulse sequence considerations for simulation and postimplant dosimetry of prostate brachytherapy

PURPOSE The purpose of this work is to present a brief review of MRI physics principles pertinent to prostate brachytherapy, and a summary of our experience in optimizing protocols for prostate brachytherapy applications. METHODS AND MATERIALS We summarized essential MR imaging characteristics and their interplays that need to be considered for prostate brachytherapy applications. These include spatial resolution, signal-to-noise ratio, image contrast, artifacts, geometric distortion, specific absorption rate, and total scan time. We further described the optimization of the protocols for three pulse sequences: three-dimensional (3D) fast-spoiled gradient echo sequence for T1-weighted imaging, 3D fast-spin echo sequence for T2-weighted imaging, and 3D fast imaging in steady-state precession sequence for combined T1 and T2-weighed imaging. The utilization of an endorectal coil was also described. RESULTS Using the optimized protocols, we acquired high-quality images of the entire prostate within 3-5 minutes for each sequence. These images display the desired image contrasts and a spatial resolution that is equal to or better than 0.59 mm × 0.73 mm × 1.2 mm. While 3D fast-spoiled gradient echo sequence and 3D fast-spin echo sequence depict radioactive seed markers and anatomic structures separately, 3D fast imaging in steady-state precession sequence demonstrates great promise for imaging both seed markers and prostate anatomy simultaneously in a single acquisition. CONCLUSIONS We have optimized current MRI protocols and demonstrated that the anatomic structures and positive contrast radioactive seed markers for prostate post-implant dosimetry can be adequately imaged either separately or simultaneously using different pulse sequences within a total scan time of 3-5 minutes each.

Parallel imaging compressed sensing for accelerated imaging and improved signal-to-noise ratio in MRI-based postimplant dosimetry of prostate brachytherapy

PURPOSE To investigate the feasibility of using parallel imaging compressed sensing (PICS) to reduce scan time and improve signal-to-noise ratio (SNR) in MRI-based postimplant dosimetry of prostate brachytherapy. METHODS AND MATERIALS Ten patients underwent low-dose-rate prostate brachytherapy with radioactive seeds stranded with positive magnetic resonance-signal seed markers and were scanned on a Siemens 1.5T Aera. MRI comprised a fully balanced steady-state free precession sequence with two 18-channel external pelvic array coils with and without a rigid two-channel endorectal coil. The fully sampled data sets were retrospectively subsampled with increasing acceleration factors and reconstructed with parallel imaging and compressed sensing algorithms. The images were assessed in a blinded reader study by board-certified care providers. Rating scores were compared for statistically significant differences between reconstruction types. RESULTS Images reconstructed from subsampling up to an acceleration factor of 4 with PICS demonstrated consistently sufficient quality for dosimetry with no apparent loss of SNR, anatomy depiction, or seed/marker conspicuity when compared to the fully sampled images. Images obtained with acceleration factors of 5 or 6 revealed reduced spatial resolution and seed marker contrast. Nevertheless, the reader study revealed that images obtained with an acceleration factor of up to 5 and reconstructed with PICS were adequate-to-good for postimplant dosimetry. CONCLUSIONS Combined parallel imaging and compressed sensing can substantially reduce scan time in fully balanced steady-state free precession imaging of the prostate while maintaining adequate-to-good image quality for postimplant dosimetry. The saved scan time can be used for multiple signal averages and improved SNR, potentially obviating the need for an endorectal coil in MRI-based postimplant dosimetry.

SU‐E‐J‐214: MR Protocol Development to Visualize Sirius MRI Markers in Prostate Brachytherapy Patients for MR‐Based Post‐Implant Dosimetry

Purpose: The current CT-based post-implant dosimetry allows precise seed localization but limited anatomical delineation. Switching to MR-based post-implant dosimetry is confounded by imprecise seed localization. One approach is to place positive-contrast markers (Sirius) adjacent to the negative-contrast seeds. This patient study aims to assess the utility of a 3D fast spoiled gradient-recalled echo (FSPGR) sequence to visualize Sirius markers for post-implant dosimetry. Methods: MRI images were acquired in prostate implant patients (n=10) on Day 0 (day-of-implant) and Day 30. The post-implant MR protocol consisted of 3D T2-weighted fast-spin-echo (FSE), T2-weighted 2D-FSE (axial) and T1-weighted 2D-FSE (axial/sagittal/coronal). We incorporated a 3D-FSPGR sequence into the post-implant MR protocol to visualize the Sirius markers. Patients were scanned with different number-of-excitations (6, 8, 10), field-of-view (10cm, 14cm, 18cm), slice thickness (1mm, 0.8mm), flip angle (14 degrees, 20 degrees), bandwidth (122.070 Hz/pixel, 325.508 Hz/pixel, 390.625 Hz/pixel), phase encoding steps (160, 192, 224, 256), frequency-encoding direction (right/left, anterior/posterior), echo-time type (minimum-full, out-of-phase), field strength (1.5T, 3T), contrast (with, without), scanner vendor (Siemens, GE), coil (endorectal-coil only, endorectal-and-torso-coil, torsocoil only), endorectal-coil filling (30cc, 50cc) and endorectal-coil filling type (air, perfluorocarbon [PFC]). For post-implant dosimetric evaluation with greater anatomical detail, 3D-FSE images were fused with 3D-FSPGR images. For comparison with CT-based post-implant dosimetry, CT images were fused with 3D-FSPGR images. Results: The 3D-FSPGR sequence facilitated visualization of markers in patients. Marker visualization helped distinguish signal voids as seeds versus needle tracks for more definitive MR-based post-implant dosimetry. On the CT-MR fused images, the distance between the seed on CT to MR images was 3.2±1.6mm in patients with no endorectal coil, 2.3±0.8mm in patients with 30cc-PFC-filled endorectal-coil and 5.0±1.8mm in patients with 50cc-PFC-filled endorectal-coil. Conclusion: An MR protocol to visualize positive-contrast Sirius markers to assist in the identification of negative-contrast seeds was demonstrated. S Frank is a co-founder of C4 Imaging LLC, the manufacturer of the MRI markers.

SU-C-17A-02: Sirius MRI Markers for Prostate Post-Implant Assessment: MR Protocol Development

PURPOSE Currently, CT is used to visualize prostate brachytherapy sources, at the expense of accurate structure contouring. MRI is superior to CT for anatomical delineation, but the sources appear as voids on MRI images. Previously we have developed Sirius MRI markers (C4 Imaging) to replace spacers to assist source localization on MRI images. Here we develop an MRI pulse sequence protocol that enhances the signal of these markers to enable MRI-only post-implant prostate dosimetric analysis. METHODS To simulate a clinical scenario, a CIRS multi-modality prostate phantom was implanted with 66 markers and 86 sources. The implanted phantom was imaged on both 1.5T and 3.0T GE scanners under various conditions, different pulse sequences (2D fast spin echo [FSE], 3D balanced steadystate free precession [bSSFP] and 3D fast spoiled gradient echo [FSPGR]), as well as varying amount of padding to simulate various patient sizes and associated signal fall-off from the surface coil elements. Standard FSE sequences from the current clinical protocols were also evaluated. Marker visibility, marker size, intra-marker distance, total scan time and artifacts were evaluated for various combinations of echo time, repetition time, flip angle, number of excitations, bandwidth, slice thickness and spacing, fieldof- view, frequency/phase encoding steps and frequency direction. RESULTS We have developed a 3D FSPGR pulse sequence that enhances marker signal and ensures the integrity of the marker shape while maintaining reasonable scan time. For patients contraindicated for 3.0T, we have also developed a similar sequence for 1.5T scanners. Signal fall-off with distance from prostate to coil can be compensated mainly by decreasing bandwidth. The markers are not visible using standard FSE sequences. FSPGR sequences are more robust for consistent marker visualization as compared to bSSFP sequences. CONCLUSION The developed MRI pulse sequence protocol for Sirius MRI markers assists source localization to enable MRIonly post-implant prostate dosimetric analysis. S.J. Frank is a co-founder of C4 Imaging (manufactures the MRI markers).