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Title: PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response

Abstract

PurposeThe purpose of our study is to determine if there is a relationship between dose deposition measured by PET/MRI and individual lesion response to yttrium-90 ({sup 90}Y) microsphere radioembolization.Materials and Methods26 patients undergoing lobar treatment with {sup 90}Y microspheres underwent PET/MRI within 66 h of treatment and had follow-up imaging available. Adequate visualization of tumor was available in 24 patients, and contours were drawn on simultaneously acquired PET/MRI data. Dose volume histograms (DVHs) were extracted from dose maps, which were generated using a voxelized dose kernel. Similar contours to capture dimensional and volumetric change of tumors were drawn on follow-up imaging. Response was analyzed using both RECIST and volumetric RECIST (vRECIST) criteria.ResultsA total of 8 hepatocellular carcinoma (HCC), 4 neuroendocrine tumor (NET), 9 colorectal metastases (CRC) patients, and 3 patients with other metastatic disease met inclusion criteria. Average dose was useful in predicting response between responders and non-responders for all lesion types and for CRC lesions alone using both response criteria (p < 0.05). D70 (minimum dose to 70 % of volume) was also useful in predicting response when using vRECIST. No significant trend was seen in the other tumor types. For CRC lesions, an average dose of 29.8 Gy offered 76.9 % sensitivity and 75.9 %more » specificity for response.ConclusionsPET/MRI of {sup 90}Y microsphere distribution showed significantly higher DVH values for responders than non-responders in patients with CRC. DVH analysis of {sup 90}Y microsphere distribution following treatment may be an important predictor of response and could be used to guide future adaptive therapy trials.« less

Authors:
 [1];  [2];  [3];  [1];  [3]; ; ;  [4]
  1. Washington University, Department of Radiology (United States)
  2. Washington University, Department of Biomedical Engineering (United States)
  3. Washington University, Department of Nuclear Medicine (United States)
  4. Washington University, Department of Radiation Oncology (United States)
Publication Date:
OSTI Identifier:
22642510
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cardiovascular and Interventional Radiology; Journal Volume: 39; Journal Issue: 6; Other Information: Copyright (c) 2016 Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE); Article Copyright (c) 2015 The Author(s); http://www.springer-ny.com; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOMEDICAL RADIOGRAPHY; HEPATOMAS; LIVER; METASTASES; MICROSPHERES; NMR IMAGING; PATIENTS; POSITRON COMPUTED TOMOGRAPHY; RADIATION DOSES; RADIOEMBOLIZATION; YTTRIUM 90

Citation Formats

Fowler, Kathryn J., Maughan, Nichole M., Laforest, Richard, Saad, Nael E., Sharma, Akash, Olsen, Jeffrey, Speirs, Christina K., and Parikh, Parag J., E-mail: parikh@wustl.edu. PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response. United States: N. p., 2016. Web. doi:10.1007/S00270-015-1285-Y.
Fowler, Kathryn J., Maughan, Nichole M., Laforest, Richard, Saad, Nael E., Sharma, Akash, Olsen, Jeffrey, Speirs, Christina K., & Parikh, Parag J., E-mail: parikh@wustl.edu. PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response. United States. doi:10.1007/S00270-015-1285-Y.
Fowler, Kathryn J., Maughan, Nichole M., Laforest, Richard, Saad, Nael E., Sharma, Akash, Olsen, Jeffrey, Speirs, Christina K., and Parikh, Parag J., E-mail: parikh@wustl.edu. 2016. "PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response". United States. doi:10.1007/S00270-015-1285-Y.
@article{osti_22642510,
title = {PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response},
author = {Fowler, Kathryn J. and Maughan, Nichole M. and Laforest, Richard and Saad, Nael E. and Sharma, Akash and Olsen, Jeffrey and Speirs, Christina K. and Parikh, Parag J., E-mail: parikh@wustl.edu},
abstractNote = {PurposeThe purpose of our study is to determine if there is a relationship between dose deposition measured by PET/MRI and individual lesion response to yttrium-90 ({sup 90}Y) microsphere radioembolization.Materials and Methods26 patients undergoing lobar treatment with {sup 90}Y microspheres underwent PET/MRI within 66 h of treatment and had follow-up imaging available. Adequate visualization of tumor was available in 24 patients, and contours were drawn on simultaneously acquired PET/MRI data. Dose volume histograms (DVHs) were extracted from dose maps, which were generated using a voxelized dose kernel. Similar contours to capture dimensional and volumetric change of tumors were drawn on follow-up imaging. Response was analyzed using both RECIST and volumetric RECIST (vRECIST) criteria.ResultsA total of 8 hepatocellular carcinoma (HCC), 4 neuroendocrine tumor (NET), 9 colorectal metastases (CRC) patients, and 3 patients with other metastatic disease met inclusion criteria. Average dose was useful in predicting response between responders and non-responders for all lesion types and for CRC lesions alone using both response criteria (p < 0.05). D70 (minimum dose to 70 % of volume) was also useful in predicting response when using vRECIST. No significant trend was seen in the other tumor types. For CRC lesions, an average dose of 29.8 Gy offered 76.9 % sensitivity and 75.9 % specificity for response.ConclusionsPET/MRI of {sup 90}Y microsphere distribution showed significantly higher DVH values for responders than non-responders in patients with CRC. DVH analysis of {sup 90}Y microsphere distribution following treatment may be an important predictor of response and could be used to guide future adaptive therapy trials.},
doi = {10.1007/S00270-015-1285-Y},
journal = {Cardiovascular and Interventional Radiology},
number = 6,
volume = 39,
place = {United States},
year = 2016,
month = 6
}
  • Sixteen patients with metastatic disease to the liver (12 colorectal and four unknown primary tumors) were treated in a pilot study of hepatic irradiation (2500-3000 rads in 10-12 fractions) delivered concomitantly with continuous short-term intraarterial infusion of 5-fluorouracil (1 g/d) or FUDR (0.5 mg/kg/d) via a percutaneously placed hepatic artery catheter. Abnormal liver function tests, including SGOT, LDH, and alkaline phosphatase, decreased in all patients by day 7-10 of treatment, and other metabolic factors, including serum cholesterol, calcium, albumin, phosphorous, and uric acid, also decreased, often to subnormal levels by termination of treatment (day 15-20). These chemical alterations did notmore » correlate with tumor response in that the identical pattern was observed in responders (ten patients) as well as nonresponders (six patients). Objective determinants of response were assessed by serial monitoring of the plasma carcinoembryonic antigen (CEA) and liver scan. In 14 patients with elevated CEA levels, tumor response (nine patients), nonresponse (four patients), and relapse (five patients) was predicted and confirmed by sequential monitoring of CEA. In one patient, a paradoxical decrease in plasma CEA was associated with progressive disease. The liver scan identified all responding patients but was difficult to quantitate and was delayed for months following subjective clinical response and changes in plasma CEA levels.« less
  • Sixteen patients with metastatic disease to the liver (12 colorectal and four unknown primary tumors) were treated in a pilot study of hepatic irradiation (2500-3000 rads in 10-12 fractions) delivered concomitantly with continuous short-term intraarterial infusion of 5-fluorouracil (1 g/d) or FUDR (0.5 mg/kg/d) via a percutaneously placed hepatic artery catheter. Abnormal liver function tests, including SGOT, LDH, and alkaline phosphatase, decreased in all patients by day 7-10 of treatment, and other metabolic factors, including serum cholesterol, calcium, albumin, phosphorous, and uric acid, also decreased, often to subnormal levels by termination of treatment (day 15-20). These chemical alterations did notmore » correlate with tumor response in that the identical pattern was observed in responders (ten patients) as well as nonresponders (six patients). Objective determinants of response were assessed by serial monitoring of plasma carcinoembryonic antigen (CEA) and liver scan. In 14 patients with elevated CEA levels, tumor response (nine patients), nonresponse (four patients), and relapse (five patients) was predicted and confirmed by sequential monitoring of CEA. In one patient, a paradoxical decrease in plasma CEA was associated with progressive disease. The liver scan identified all responding patients but was difficult to quantitate and was delayed for months following subjective clinical response and changes in plasma CEA levels.« less
  • Purpose: The primary purpose of this study was to demonstrate intraobserver/interobserver reproducibility for novel semiautomated measurements of hepatic volume used for Yttrium-90 dose calculations as well as whole-liver and necrotic-liver (hypodense/nonenhancing) tumor volume after radioembolization. The secondary aim was to provide initial comparisons of tumor volumetric measurements with linear measurements, as defined by Response Evaluation Criteria in Solid Tumors criteria, and survival outcomes. Methods: Between 2006 and 2009, 23 consecutive radioembolization procedures were performed for 14 cases of hepatocellular carcinoma and 9 cases of hepatic metastases. Baseline and follow-up computed tomography obtained 1 month after treatment were retrospectively analyzed. Threemore » observers measured liver, whole-tumor, and tumor-necrosis volumes twice using semiautomated software. Results: Good intraobserver/interobserver reproducibility was demonstrated (intraclass correlation [ICC] > 0.9) for tumor and liver volumes. Semiautomated measurements of liver volumes were statistically similar to those obtained with manual tracing (ICC = 0.868), but they required significantly less time to perform (p < 0.0001, ICC = 0.088). There was a positive association between change in linear tumor measurements and whole-tumor volume (p < 0.0001). However, linear measurements did not correlate with volume of necrosis (p > 0.05). Dose, change in tumor diameters, tumor volume, and necrotic volume did not correlate with survival (p > 0.05 in all instances). However, Kaplan-Meier curves suggest that a >10% increase in necrotic volume correlated with survival (p = 0.0472). Conclusion: Semiautomated volumetric analysis of liver, whole-tumor, and tumor-necrosis volume can be performed with good intraobserver/interobserver reproducibility. In this small retrospective study, measurements of tumor necrosis were suggested to correlate with survival.« less
  • Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearingmore » mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-κB activity in CD4 + T cells.« less
  • Purpose: To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. Methods: FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function ofmore » pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. Results: Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. Conclusion: Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.« less