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Title: WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments

Abstract

Purpose: Selective-internal-radiation-therapy (SIRT) and transarterial-chemoembolization (TACE) are commonly used for treatment of liver tumors. The use of TACE, which is macroembolic, prior to SIRT may cause hemodynamic changes in tumor vasculature that impair yttrium-90 (90Y) microsphere delivery to the targeted lesions. This work aims to quantify dosimetric tumor coverage using 90Y positron emission tomography (PET) dosimetry after SIRT alone compared to TACE followed by SIRT. Methods: A total of 40 consecutive hepatocellular carcinoma (HCC) SIRT patients who had a post-SIRT 90Y PET/CT scan were evaluated. The patient-specific-3D-dose was reconstructed from the PET images. Patients were categorized into two groups: patients received TACE prior SIRT procedure (n=18) and patient received SIRT alone (n=22). The lesions and liver were delineated by a senior radiologist. We evaluated both the lesion-specific dose-volume-histogram (DVH) and the selectivity index (SI) defined as the ratio of the average dose inside the total lesion(s) and the average dose of the normal liver. The SI values of patients were compared based on whether TACE was previously used. Results: A wide spectrum was observed in the lesion-specific DVH-evaluation and SI appeared to be suitable of evaluating the quality of each SIRT infusion. The average SI of the entire patient groupmore » was 3.0, i.e. targeted lesion receiving three times higher dose than normal liver. The average SI was 1.8 for patients who had prior TACE and 3.9 for patients who did not have prior TACE (p=0.008). 85% of the patients with prior TACE demonstrated poor 90Y-microsphere delivery (SI <2) while none demonstrated excellent delivery (SI >4). On the other hand, the incidence SI >4 among patients with no prior TACE was 37%. Conclusion: 3D dose evaluation using post-SIRT PET suggests that 90Y microsphere delivery to liver tumors is impaired among patients who received prior TACE compared to those who receive SIRT alone.« less

Authors:
 [1];  [2]
  1. The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)
  2. University of Maryland School of Medicine, Baltimore, MD (United States)
Publication Date:
OSTI Identifier:
22654095
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; DELIVERY; HEPATOMAS; IMAGE PROCESSING; LIVER; MICROSPHERES; PATIENTS; POSITRON COMPUTED TOMOGRAPHY; RADIATION DOSES; YTTRIUM 90

Citation Formats

Lin, M, and Saboury, B. WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments. United States: N. p., 2016. Web. doi:10.1118/1.4957734.
Lin, M, & Saboury, B. WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments. United States. doi:10.1118/1.4957734.
Lin, M, and Saboury, B. Wed . "WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments". United States. doi:10.1118/1.4957734.
@article{osti_22654095,
title = {WE-AB-BRA-05: PET-Guided Delivery Quality Evaluation of Yttrium-90 Microsphere Radioembolizaton for Hepatocellular Carcinoma Patients: The Optimal Sequence of Radioembolizaton and Chemoembolization Treatments},
author = {Lin, M and Saboury, B},
abstractNote = {Purpose: Selective-internal-radiation-therapy (SIRT) and transarterial-chemoembolization (TACE) are commonly used for treatment of liver tumors. The use of TACE, which is macroembolic, prior to SIRT may cause hemodynamic changes in tumor vasculature that impair yttrium-90 (90Y) microsphere delivery to the targeted lesions. This work aims to quantify dosimetric tumor coverage using 90Y positron emission tomography (PET) dosimetry after SIRT alone compared to TACE followed by SIRT. Methods: A total of 40 consecutive hepatocellular carcinoma (HCC) SIRT patients who had a post-SIRT 90Y PET/CT scan were evaluated. The patient-specific-3D-dose was reconstructed from the PET images. Patients were categorized into two groups: patients received TACE prior SIRT procedure (n=18) and patient received SIRT alone (n=22). The lesions and liver were delineated by a senior radiologist. We evaluated both the lesion-specific dose-volume-histogram (DVH) and the selectivity index (SI) defined as the ratio of the average dose inside the total lesion(s) and the average dose of the normal liver. The SI values of patients were compared based on whether TACE was previously used. Results: A wide spectrum was observed in the lesion-specific DVH-evaluation and SI appeared to be suitable of evaluating the quality of each SIRT infusion. The average SI of the entire patient group was 3.0, i.e. targeted lesion receiving three times higher dose than normal liver. The average SI was 1.8 for patients who had prior TACE and 3.9 for patients who did not have prior TACE (p=0.008). 85% of the patients with prior TACE demonstrated poor 90Y-microsphere delivery (SI <2) while none demonstrated excellent delivery (SI >4). On the other hand, the incidence SI >4 among patients with no prior TACE was 37%. Conclusion: 3D dose evaluation using post-SIRT PET suggests that 90Y microsphere delivery to liver tumors is impaired among patients who received prior TACE compared to those who receive SIRT alone.},
doi = {10.1118/1.4957734},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}
  • Purpose: To evaluate weather the current radiobiological models can predict the normal liver complications of radioactive Yttrium-90 ({sup 90}Y) selective-internal-radiation-treatment (SIRT) for metastatic liver lesions based on the post-infusion {sup 90}Y PET images. Methods: A total of 20 patients with metastatic liver tumors treated with SIRT that received a post-infusion {sup 90}Y-PET/CT scan were analyzed in this work. The 3D activity distribution of the PET images was converted into a 3D dose distribution via a kernel convolution process. The physical dose distribution was converted into the equivalent dose (EQ2) delivered at 2 Gy based on the linear-quadratic (LQ) model consideringmore » the dose rate effect. The biological endpoint of this work was radiation-induce liver disease (RILD). The NTCPs were calculated with four different repair-times (T1/2-Liver-Repair= 0,0.5,1.0,2.0 hr) and three published NTCP models (Lyman-external-RT, Lyman 90Y-HCC-SIRT, parallel model) were compared to the incidence of RILD of the recruited patients to evaluate their ability of outcome prediction. Results: The mean normal liver physical dose (avg. 51.9 Gy, range 31.9–69.8 Gy) is higher than the suggested liver dose constraint for external beam treatment (∼30 Gy). However, none of the patients in our study developed RILD after the SIRT. The estimated probability of ‘no patient developing RILD’ obtained from the two Lyman models are 46.3% to 48.3% (T1/2-Liver-Repair= 0hr) and <1% for all other repair times. For the parallel model, the estimated probability is 97.3% (0hr), 51.7% (0.5hr), 2.0% (1.0hr) and <1% (2.0hr). Conclusion: Molecular-images providing the distribution of {sup 90}Y enable the dose-volume based dose/outcome analysis for SIRT. Current NTCP models fail to predict RILD complications in our patient population, unless a very short repair-time for the liver is assumed. The discrepancy between the Lyman {sup 90}Y-HCC-SIRT model predicted and the clinically observed outcomes further demonstrates the need of an NTCP model specific to the metastatic liver SIRT.« less
  • Purpose. To elucidate the local therapeutic results of computed tomography (CT)-guided transcatheter arterial chemoembolization (TACE) as initial treatment for hepatocellular carcinoma (HCC), and to verify factors which affect local therapeutic results. Methods. From 1992 to 2002, 265 tumors of 79 HCC patients were treated by 139 sessions of CT-guided TACE as initial treatment. Among these 265 tumors, 182 constituted multiple new lesions, and the remaining 83 tumors were single new lesions. Local recurrence was retrospectively ascertained on follow-up CT images obtained after TACE. Results. The overall local recurrence-free rates (LR-FRs) after a single TACE session at 6, 12, and 36more » months were 67%, 49%, and 28%; those of the single new lesions were 80%, 66%, and 32%; and those of tumors with complete lipiodol accumulation were 82%, 68%, and 41%, respectively. LR-FRs of tumors of the single new lesions, and those of tumors with complete lipiodol accumulation, were significantly higher than the LR-FRs of multiple new lesions and tumors with incomplete lipiodol accumulation, respectively. For single new lesions {<=}4 cm and the tumors that were one of multiple new lesions, there were no significant differences in the LR-FRs regarding the number of TACE sessions on the basis of patient, tumor location, or tumor size. Conclusion. Local therapeutic results of single new lesions were better than those of multiple new lesions, and the local therapeutic effect of TACE was not affected by the number of treatments on the basis of patient, tumor location, or tumor size.« less
  • Purpose: The short- and long-term effects of {sup 90}Yttrium microspheres therapy for hepatocellular carcinoma (HCC) on peripheral blood lymphocytes are unknown and were therefore examined. Methods and Materials: Ninety-two HCC patients were enrolled in a {sup 90}Yttrium therapy study and routine blood counts were examined as part of standard clinical monitoring. Results: We found an early, profound, and prolonged lymphopenia. In a subsequent cohort of 25 additional HCC patients, prospective flow cytometric immune-monitoring analysis was performed to identify specific changes on distinct lymphocyte subsets (i.e., CD3, CD4, CD8 T, and CD19 B lymphocytes) and NK cells absolute numbers, in additionmore » to the granulocytes and platelets subsets. We found that the pretreatment lymphocyte subset absolute numbers (with the exception of NK cells) had a tendency to be lower compared with healthy control values, but no significant differences were detected between groups. Posttherapy follow-up revealed that overall, all lymphocyte subsets, except for NK cells, were significantly (>50% from pretherapy values), promptly (as early as 24 h) and persistently (up to 30 months) depleted post-{sup 90}Yttrium microspheres therapy. In contrast, granulocytes increased rapidly (24 h) to compensate for lymphocyte depletion, and remained increased at 1-year after therapy. We further stratified patients into two groups, according to survival at 1 year. We found that lack of recovery of CD19, CD3, CD8, and especially CD4 T cells was linked to poor patient survival. No fungal or bacterial infections were noted during the 30-month follow-up period. Conclusions: The results show that lymphocytes (and not granulocytes, platelets, or NK cells) are sensitive to hepatic arterial {sup 90}Yttrium without associated clinical toxicity, and lack of lymphocyte recovery (possibly leading to dysregulation of adaptive cellular immunity) posttherapy indicates poor survival.« less
  • Purpose: PET/CT guidance is used for biopsies of metabolically active lesions, which are not well seen on CT alone or to target the metabolically active tissue in tumor ablations. It has also been shown that PET/CT guided biopsies provide an opportunity to verify the location of the lesion border at the place of needle insertion. However the error in needle placement with respect to the metabolically active region may be affected by motion between the PET/CT scan performed at the start of the procedure and the CT scan performed with the needle in place and this error has not beenmore » previously quantified. Methods: Specimens from 31 PET/CT guided biopsies were investigated and correlated to the intraoperative PET scan under an IRB approved HIPAA compliant protocol. For 4 of the cases in which larger motion was suspected a second PET scan was obtained with the needle in place. The CT and the PET images obtained before and after the needle insertion were used to calculate the displacement of the voxels along the needle path. CTpost was registered to CTpre using a free form deformable registration and then fused with PETpre. The shifts between the PET image contours (42% of SUVmax) for PETpre and PETpost were obtained at the needle position. Results: For these extreme cases the displacement of the CT voxels along the needle path ranged from 2.9 to 8 mm with a mean of 5 mm. The shift of the PET image segmentation contours (42% of SUVmax) at the needle position ranged from 2.3 to 7 mm between the two scans. Conclusion: Evaluation of the mis-registration between the CT with the needle in place and the pre-biopsy PET can be obtained using deformable registration of the respective CT scans and can be used to indicate the need of a second PET in real-time. This work is supported in part by a grant from Biospace Lab, S.A.« less
  • Purpose: 2D-2D kV image guided radiation therapy (IGRT) credentialing evaluation for clinical trial qualification was historically qualitative through submitting screen captures of the fusion process. However, as quantitative DICOM 2D-2D and 2D-3D image registration tools are implemented in clinical practice for better precision, especially in centers that treat patients with protons, better IGRT credentialing techniques are needed. The aim of this work is to establish methodologies for quantitatively reviewing IGRT submissions based on DICOM 2D-2D and 2D-3D image registration and to test the methodologies in reviewing 2D-2D and 2D-3D IGRT submissions for RTOG/NRG Oncology clinical trials qualifications. Methods: DICOM 2D-2Dmore » and 2D-3D automated and manual image registration have been tested using the Harmony tool in MIM software. 2D kV orthogonal portal images are fused with the reference digital reconstructed radiographs (DRR) in the 2D-2D registration while the 2D portal images are fused with DICOM planning CT image in the 2D-3D registration. The Harmony tool allows alignment of the two images used in the registration process and also calculates the required shifts. Shifts calculated using MIM are compared with those submitted by institutions for IGRT credentialing. Reported shifts are considered to be acceptable if differences are less than 3mm. Results: Several tests have been performed on the 2D-2D and 2D-3D registration. The results indicated good agreement between submitted and calculated shifts. A workflow for reviewing these IGRT submissions has been developed and will eventually be used to review IGRT submissions. Conclusion: The IROC Philadelphia RTQA center has developed and tested a new workflow for reviewing DICOM 2D-2D and 2D-3D IGRT credentialing submissions made by different cancer clinical centers, especially proton centers. NRG Center for Innovation in Radiation Oncology (CIRO) and IROC RTQA center continue their collaborative efforts to enhance quality assurance services and to be consistently adaptive to the new advances in radiation therapy. This project was supported by NCI grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less