Dose volume histogram‐based optimization of image reconstruction parameters for quantitative 90Y‐PET imaging

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147185/1/mp13269.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147185/2/mp13269_am.pd

Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry

Purpose: Dosimetry for 90Y microsphere therapies (YMT) with Standard (SM) and Partition (PM) models provide only uniform dose estimates to tumor and liver. Our objective is to calculate tumor dose heterogeneity, known to effect response, using voxel-based dosimetry and investigate the limitations of SM and PM.Methods: Voxel-based dosimetry was performed on 17 YMT patients using Monte Carlo DOSXYZnrc. 90Y activity and tissue/density distributions were based on quantitative 90Y bremsstrahlung SPECT/CT. Tumors (n=31), liver, and treatment lobe/segments were segmented on diagnostic CT or MR. Dose volume histograms (DVH) were created for tumors and normal liver. Bland-Altman analysis compared voxel-based mean absorbed doses to tumor and liver with SM and PM. Tumor and normal liver absorbed dose heterogeneity were investigated through metrics: integral uniformity (IU), D10/D90, COV. Correlations of heterogeneity with voxel-based mean doses and volumes were evaluated.Results: Heterogeneity metrics (mean ± 1σ) for tumor dose were COV = 0.48 ± 0.28, D10/D90 = 4.7 ± 3.9, and IU = 0.8 ± 0.18. Heterogeneity metrics correlated with tumor volume (r > 0.58) but not tumor mean doses (r < 0.20). Voxel-based tumor mean doses correlated with PM (r = 0.84) but not SM (r = 0.08). Both yielded poor limits of agreement with of 83 ± 174 and -28 ± 181 Gy, respectively. Normal liver heterogeneity metrics (mean ± 1σ) were COV = 0.83 ± 0.29, D10/D90 = 12 ± 15, and IU = 0.97 ± 0.03. Only D10/D90 (r = 0.49) correlated with mean normal liver absorbed dose. Voxel-based normal liver/lobe mean doses correlated with PM (r = 0.96), but had poor limits of agreement (26 ± 29 Gy).Conclusion: Tumor doses have high levels of heterogeneity that increase with volume but are independent of dose. Voxel-based DVH and dose heterogeneity metrics will promote accurate characterization of tumor response following YMT.--------------------------------------Cite this article as: Mikell J, Mourtada F, Mahvash A, Kappadath SC. Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry. Int J Cancer Ther Oncol 2014; 2(2):020228. DOI: 10.14319/ijcto.0202.2

Detection of Canonical Hedgehog Signaling in Breast Cancer by 131-Iodine-Labeled Derivatives of the Sonic Hedgehog Protein

Activation of hedgehog (HH) pathway signaling is observed in many tumors. Due to a feedback loop, the HH receptor Patched (PTCH-1) is overexpressed in tumors with activated HH signaling. Therefore, we sought to radiolabel the PTCH-1 ligand sonic (SHH) for detection of cancer cells with canonical HH activity. Receptor binding of 131I-SHH was increased in cell lines with high HH pathway activation. Our findings also show that PTCH-1 receptor expression is decreased upon treatment with HH signaling inhibitors, and receptor binding of 131I-SHH is significantly decreased following treatment with cyclopamine. In vivo imaging and biodistribution studies revealed significant accumulation of 131I-SHH within tumor tissue as compared to normal organs. Tumor-to-muscle ratios were approximately 8 : 1 at 5 hours, while tumor to blood and tumor to bone were 2 : 1 and 5 : 1, respectively. Significant uptake was also observed in liver and gastrointestinal tissue. These studies show that 131I-SHH is capable of in vivo detection of breast tumors with high HH signaling. We further demonstrate that the hedgehog receptor PTCH-1 is downregulated upon treatment with hedgehog inhibitors. Our data suggests that radiolabeled SHH derivatives may provide a method to determine response to SHH-targeted therapies

2017 American Brachytherapy Society’s Annual Meeting Report

The American Brachytherapy Society (ABS) and its membership seeks to benefit patients by promoting the highest possible standard for brachytherapy practice, support health care professionals through the encouragement of state of the art technology and education, promote clinical and laboratory research, and advocate for the socioeconomic aspects of brachytherapy. The 2017 ABS Annual Meeting took place is Boston, Massachusetts, United States from April 20–22, 2017. The theme “The Value of Brachytherapy in Multidisciplinary Cancer Care” drew a multitude of national and international speakers to present data and debate clinical indications, advancements in practice and the value of brachytherapy. With a focus on the advancement of brachytherapy for prostate cancer and the socioeconomic benefits of brachytherapy, the globally focused program hosted 93 speakers, 506 attendees, and exhibitors from 15 countries and featured 251 abstracts for presentation and display. The ABS Annual Meeting left attendees with initial data on timely and relevant topics such as outcomes following brachytherapy for recurrent prostate cancer following external beam radiotherapy, findings of prototype algorithms capable of rapidly generating prostate brachytherapy pre-operative treatment plans and results on the socioeconomic disparities impacting the utilization of brachytherapy for common malignancies. These novel findings, among many other thoughtful and thought-provoking presentations, gave meeting attendees knowledge of the current state of brachytherapy and future directions of the specialty

Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry

Purpose: Dosimetry for 90Y microsphere therapies (YMT) with Standard (SM) and Partition (PM) models provide only uniform dose estimates to tumor and liver. Our objective is to calculate tumor dose heterogeneity, known to effect response, using voxel-based dosimetry and investigate the limitations of SM and PM.Methods: Voxel-based dosimetry was performed on 17 YMT patients using Monte Carlo DOSXYZnrc. 90Y activity and tissue/density distributions were based on quantitative 90Y bremsstrahlung SPECT/CT. Tumors (n=31), liver, and treatment lobe/segments were segmented on diagnostic CT or MR. Dose volume histograms (DVH) were created for tumors and normal liver. Bland-Altman analysis compared voxel-based mean absorbed doses to tumor and liver with SM and PM. Tumor and normal liver absorbed dose heterogeneity were investigated through metrics: integral uniformity (IU), D10/D90, COV. Correlations of heterogeneity with voxel-based mean doses and volumes were evaluated.Results: Heterogeneity metrics (mean ± 1σ) for tumor dose were COV = 0.48 ± 0.28, D10/D90 = 4.7 ± 3.9, and IU = 0.8 ± 0.18. Heterogeneity metrics correlated with tumor volume (r &gt; 0.58) but not tumor mean doses (r &lt; 0.20). Voxel-based tumor mean doses correlated with PM (r = 0.84) but not SM (r = 0.08). Both yielded poor limits of agreement with of 83 ± 174 and -28 ± 181 Gy, respectively. Normal liver heterogeneity metrics (mean ± 1σ) were COV = 0.83 ± 0.29, D10/D90 = 12 ± 15, and IU = 0.97 ± 0.03. Only D10/D90 (r = 0.49) correlated with mean normal liver absorbed dose. Voxel-based normal liver/lobe mean doses correlated with PM (r = 0.96), but had poor limits of agreement (26 ± 29 Gy).Conclusion: Tumor doses have high levels of heterogeneity that increase with volume but are independent of dose. Voxel-based DVH and dose heterogeneity metrics will promote accurate characterization of tumor response following YMT.--------------------------------------Cite this article as: Mikell J, Mourtada F, Mahvash A, Kappadath SC. Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry. Int J Cancer Ther Oncol 2014; 2(2):020228. DOI: 10.14319/ijcto.0202.28</p