The impact of ZTE-based MR attenuation correction compared to CT-AC in 18F-FBPA PET before boron neutron capture therapy.

Tumor-to-normal ratio (T/N) measurement of 18F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (- 5.18 ± 9.52%; p < 0.05). The T/N difference between ZTE-AC and AB-AC was also significant (4.71 ± 5.80%; p < 0.01). Our findings suggested PET/MRI imaging using ZTE-AC provided superior quantification on 18F-FBPA-PET compared to atlas-based AC. Using ZTE-AC on 18F-FBPA-PET /MRI might be crucial for BNCT pre-treatment planning.

Prognostic assessment of 18F-boronophenylalanine positron emission tomography (BPA-PET) in salvage boron neutron capture therapy for malignant brain tumors.

Background: Boron neutron capture therapy (BNCT) stands out as a propitious anti-cancer modality. 18F-boronophenylalanine positron emission tomography (BPA-PET) holds the potential to ascertain the concentration of BPA within the tumor, enabling meticulous treatment planning and outcome evaluation. However, no studies have been conducted on comparing the outcomes of those treated with BNCT to those who did not undergo this therapy. This study endeavors to analyze the correlation between BPA-PET and BNCT in the context of malignant brain tumors, and assess the survival outcomes following BNCT. Methods: A cohort study was performed on patients who underwent BPA-PET between February 2017 and April 2022 in our hospital. Patients were stratified into two groups: those subjected to BNCT (Group 1) and those not (Group 2). The tumor to normal tissue (T/N) ratio derived from BPA-PET was set at 2.5. The findings were scrutinized based on clinical follow-up. Student's t-test and Chi-squared test were employed to discern differences between the groups. A cumulative survival curve was constructed employing the Kaplan-Meier method. Differences were considered statistically significant at P<0.05. Results: In total, 116 patients with T/N ratios obtained from BPA-PET were enrolled. BNCT was administered to 58 patients, while mortality was observed in 100 patients. The median overall survival (OS) for the two groups was 8.5 and 6.0 months, respectively. The cumulative OS exhibited no significant discrepancy between the two groups, nor in their T/N ratios. Within Group 1, 44 out of 58 (75.9%) patients exhibited T/N ratios exceeding 2.5. Excluding 3 patients who expired within 3 months, 55 out of 58 patients were evaluated for response after BNCT. The objective response rate (ORR) was 30.9%. Patients achieving ORR displayed substantially higher survival rates compared to those without (median OS 13.5 vs. 8.3 months, P=0.0021), particularly when T/N ratio exceeded 2.5 (median OS 14.8 vs. 9.0 months, P=0.0199). Conclusions: BNCT does not appear indispensable for prolonging the survival of patients afflicted with malignant brain tumors. Nevertheless, it proves advantageous when ORR is attained, a condition closely linked to the values of T/N ratio derived from BPA-PET.

Survival outcomes of radium-223 therapy for metastatic castration-resistant prostate cancer following national health insurance reimbursement in Taiwan.

BACKGROUND: Radium-223 dichloride (Ra-223) prolongs overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases. However, there is considerable variation in outcomes among individuals. We aimed to evaluate the prognostic determinants associated with patient survival following National Health Insurance (NHI) reimbursement for Ra-223 therapy in Taiwan. METHODS: Patients with mCRPC who underwent Ra-223 treatment at Taipei Veterans General Hospital were retrospectively enrolled. Each intravenous Ra-223 dose was administered at 55 kBq/kg at 4-week intervals. Clinical outcomes were obtained from medical records; potential prognostic factors for survival were assessed. Kaplan-Meier analysis was used to generate cumulative survival curves; between-group differences were evaluated using the Chi-squared test. Statistical significance was set at p < 0.05. RESULTS: Seventy-six patients underwent Ra-223 therapy; 62 patients received NHI reimbursement and the remainder self-paid. Fifty patients (65.8%) completed six cycles of treatment; 26 (34.2%) received 1 to 5 cycles. Mortality occurred in 47 patients. Factors significantly associated with survival included ≤five bone metastases ( p = 0.0018), baseline prostate-specific antigen (PSA) ≤36 ng/mL ( p = 0.0004), baseline alkaline phosphate (ALP) <115 U/L ( p = 0.0007), and baseline hemoglobin (Hb) >12 g/dL ( p = 0.0029). Patients who completed six cycles of treatment achieved significantly higher OS compared to those who did not ( p < 0.0001). There has been a 4.4-fold increase in the number of patients since reimbursement began; there was no significant difference in OS between patients who received NHI reimbursement and those who self-paid. CONCLUSION: Administration of Ra-223 demonstrates considerable potential to extend the survival of patients with mCRPC. Survival outcomes may be influenced by various prognostic factors. However, no significant difference in OS was observed subsequent to reimbursement of Ra-223 therapy for mCRPC through the NHI system in Taiwan.

Boron Neutron Capture Therapy Followed by Image-Guided Intensity-Modulated Radiotherapy for Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

BACKGROUND: This trial investigated the efficacy and safety of salvage boron neutron capture therapy (BNCT) combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for recurrent head and neck cancer after prior radiotherapy (RT). METHODS: BNCT was administered using an intravenous boronophenylalanine-fructose complex (500 mg/kg) in a single fraction; multifractionated IG-IMRT was administered 28 days after BNCT. For BNCT, the mucosa served as the dose-limiting organ. For IG-IMRT, the clinical target volume (CTV) and the planning target volume (PTV) were generated according to the post-BNCT gross tumor volume (GTV) with chosen margins. RESULTS: This trial enrolled 14 patients, and 12 patients received combined treatment. The median BNCT average dose for the GTV was 21.6 Gy-Eq, and the median IG-IMRT dose for the PTV was 46.8 Gy/26 fractions. After a median (range) follow-up period of 11.8 (3.6 to 53.2) months, five patients had a complete response and four had a partial response. One patient had grade 4 laryngeal edema; another patient had a grade 4 hemorrhage. Most tumor progression occurred within or adjacent to the CTV. The 1-year overall survival and local progression-free survival rates were 56% and 21%, respectively. CONCLUSION: Despite the high response rate (64%) of this trial, there was a high incidence of in-field and marginal failure with this approach. Future studies combining BNCT with modalities other than radiation may be tried.

SPECT and CT misregistration reduction in [99mTc]Tc-MAA SPECT/CT for precision liver radioembolization treatment planning.

PURPOSE: Respiration and body movement induce misregistration between static [99mTc]Tc-MAA SPECT and CT, causing lung shunting fraction (LSF) and tumor-to-normal liver ratio (TNR) errors for 90Y radioembolization planning. We aim to alleviate the misregistration between [99mTc]Tc-MAA SPECT and CT using two registration schemes on simulation and clinical data. METHODS: In the simulation study, 70 XCAT phantoms were modeled. The SIMIND Monte Carlo program and OS-EM algorithm were used for projection generation and reconstruction, respectively. Low-dose CT (LDCT) at end-inspiration was simulated for attenuation correction (AC), lungs and liver segmentation, while contrast-enhanced CT (CECT) was simulated for tumor and perfused liver segmentation. In the clinical study, 16 patient data including [99mTc]Tc-MAA SPECT/LDCT and CECT with observed SPECT and CT mismatch were analyzed. Two liver-based registration schemes were studied: SPECT registered to LDCT/CECT and vice versa. Mean count density (MCD) of different volumes-of-interest (VOIs), normalized mutual information (NMI), LSF, TNR, and maximum injected activity (MIA) based on the partition model before and after registration were compared. Wilcoxon signed-rank test was performed. RESULTS: In the simulation study, compared to before registration, registrations significantly reduced estimation errors of MCD of all VOIs, LSF (Scheme 1: - 100.28%, Scheme 2: - 101.59%), and TNR (Scheme 1: - 7.00%, Scheme 2: - 5.67%), as well as MIA (Scheme 1: - 3.22%, Scheme 2: - 2.40%). In the clinical study, Scheme 1 reduced 33.68% LSF and increased 14.75% TNR, while Scheme 2 reduced 38.88% LSF and increased 6.28% TNR compared to before registration. One patient may change from 90Y radioembolization untreatable to treatable and other patients may change the MIA up to 25% after registration. NMI between SPECT and CT was significantly increased after registrations in both studies. CONCLUSION: Registration between static [99mTc]Tc-MAA SPECT and corresponding CTs is feasible to reduce their spatial mismatch and improve dosimetric estimation. The improvement of LSF is larger than TNR. Our method can potentially improve patient selection and personalized treatment planning for liver radioembolization.

Voxel-S-Value based 3D treatment planning methods for Y-90 microspheres radioembolization based on Tc-99m-macroaggregated albumin SPECT/CT.

Partition model (PM) for Y-90 microsphere radioembolization is limited in providing 3D dosimetrics. Voxel-S-Values (VSV) method has good agreement with Monte Carlo (MC) simulations for 3D absorbed dose conversion. We propose a new VSV method and compare its performance along with PM, MC and other VSV methods for Y-90 RE treatment planning based on Tc-99m MAA SPECT/CT. Twenty Tc-99m-MAA SPECT/CT patient data are retrospectively analyzed. Seven VSV methods are implemented: (1) local energy deposition; (2) liver kernel; (3) liver kernel and lung kernel; (4) liver kernel with density correction (LiKD); (5) liver kernel with center voxel scaling (LiCK); (6) liver kernel and lung kernel with density correction (LiLuKD); (7) proposed liver kernel with center voxel scaling and lung kernel with density correction (LiCKLuKD). Mean absorbed dose and maximum injected activity (MIA) obtained by PM and VSV are evaluated against MC results, and 3D dosimetrics generated by VSV are compared with MC. LiKD, LiCK, LiLuKD and LiCKLuKD have the smallest deviation in normal liver and tumors. LiLuKD and LiCKLuKD have the best performance in lungs. MIAs are similar by all methods. LiCKLuKD could provide MIA consistent with PM, and precise 3D dosimetrics for Y-90 RE treatment planning.

Advances in Boron Neutron Capture Therapy (BNCT) for Recurrent Intracranial Meningioma.

Meningiomas are the most frequently diagnosed primary intracranial tumors in adults. Surgical resection is preferred if the meningioma is accessible; for those that are not suitable for surgical resection, radiotherapy should be considered to improve local tumor control. However, recurrent meningiomas are challenging to treat, as the recurrent tumor might be located in the previously irradiated area. Boron Neutron Capture Therapy (BNCT) is a highly selective radiotherapy modality in which the cytotoxic effect focuses mainly on cells with increased uptake of boron-containing drugs. In this article, we describe four patients with recurrent meningiomas treated with BNCT in Taiwan. The mean boron-containing drug tumor-to-normal tissue uptake ratio was 4.125, and the tumor mean dose was 29.414 GyE, received via BNCT. The treatment response showed two stable diseases, one partial response, and one complete response. We also introduce and support the effectiveness and safety of BNCT as an alternative salvage treatment for recurrent meningiomas.

Very-Low-Dose Radiation and Clinical Molecular Nuclear Medicine.

Emerging molecular and precision medicine makes nuclear medicine a de facto choice of imaging, especially in the era of target-oriented medical care. Nuclear medicine is minimally invasive, four-dimensional (space and time or dynamic space), and functional imaging using radioactive biochemical tracers in evaluating human diseases on an anatomically configured image. Many radiopharmaceuticals are also used in therapies. However, there have been concerns over the emission of radiation from the radionuclides, resulting in wrongly neglecting the potential benefits against little or any risks at all of imaging to the patients. The sound concepts of radiation and radiation protection are critical for promoting the optimal use of radiopharmaceuticals to patients, and alleviating concerns from caregivers, nuclear medicine staff, medical colleagues, and the public alike.

Compassionate Treatment of Brainstem Tumors with Boron Neutron Capture Therapy: A Case Series.

Brainstem tumors are heterogenous and cancerous glioma tumors arising from the midbrain, pons, and the medulla that are relatively common in children, accounting for 10% to 20% of all pediatric brain tumors. However, the prognosis of aggressive brainstem gliomas remains extremely poor despite aggressive treatment with chemotherapy and radiotherapy. That means there are many life-threatening patients who have exhausted all available treatment options and are beginning to face end-of-life stage. Therefore, the unique properties of highly selective heavy particle irradiation with boron neutron capture therapy (BNCT) may be well suited to prolong the lives of patients with end-stage brainstem gliomas. Herein, we report a case series of life-threatening patients with end-stage brainstem glioma who eligible for Emergency and Compassionate Use, in whom we performed a scheduled two fractions of salvage BNCT strategy with low treatment dosage each time. No patients experienced acute or late adverse events related to BNCT. There were 3 patients who relapsed after two fractionated BNCT treatment, characterized by younger age, lower T/N ratio, and receiving lower treatment dose. Therefore, two fractionated low-dose BNCT may be a promising treatment for end-stage brainstem tumors. For younger patients with low T/N ratios, more fractionated low-dose BNCT should be considered.

Salvage Boron Neutron Capture Therapy for Malignant Brain Tumor Patients in Compliance with Emergency and Compassionate Use: Evaluation of 34 Cases in Taiwan.

Although boron neutron capture therapy (BNCT) is a promising treatment option for malignant brain tumors, the optimal BNCT parameters for patients with immediately life-threatening, end-stage brain tumors remain unclear. We performed BNCT on 34 patients with life-threatening, end-stage brain tumors and analyzed the relationship between survival outcomes and BNCT parameters. Before BNCT, MRI and 18F-BPA-PET analyses were conducted to identify the tumor location/distribution and the tumor-to-normal tissue uptake ratio (T/N ratio) of 18F-BPA. No severe adverse events were observed (grade ≥ 3). The objective response rate and disease control rate were 50.0% and 85.3%, respectively. The mean overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) times were 7.25, 7.80, and 4.18 months, respectively. Remarkably, the mean OS, CSS, and RFS of patients who achieved a complete response were 17.66, 22.5, and 7.50 months, respectively. Kaplan-Meier analysis identified the optimal BNCT parameters and tumor characteristics of these patients, including a T/N ratio ≥ 4, tumor volume < 20 mL, mean tumor dose ≥ 25 Gy-E, MIB-1 ≤ 40, and a lower recursive partitioning analysis (RPA) class. In conclusion, for malignant brain tumor patients who have exhausted all available treatment options and who are in an immediately life-threatening condition, BNCT may be considered as a therapeutic approach to prolong survival.

Predicting aggressive histopathological features in esophageal cancer with positron emission tomography using a deep convolutional neural network.

BACKGROUND: The presence of lymphovascular invasion (LVI) and perineural invasion (PNI) are of great prognostic importance in esophageal squamous cell carcinoma. Currently, positron emission tomography (PET) scans are the only means of functional assessment prior to treatment. We aimed to predict the presence of LVI and PNI in esophageal squamous cell carcinoma using PET imaging data by training a three-dimensional convolution neural network (3D-CNN). METHODS: Seven hundred and ninety-eight PET scans of patients with esophageal squamous cell carcinoma and 309 PET scans of patients with stage I lung cancer were collected. In the first part of this study, we built a 3D-CNN based on a residual network, ResNet, for a task to classify the scans into esophageal cancer or lung cancer. In the second stage, we collected the PET scans of 278 patients undergoing esophagectomy for a task to classify and predict the presence of LVI/PNI. RESULTS: In the first part, the model performance attained an area under the receiver operating characteristic curve (AUC) of 0.860. In the second part, we randomly split 80%, 10%, and 10% of our dataset into training set, validation set and testing set, respectively, for a task to classify the scans into the presence of LVI/PNI and evaluated the model performance on the testing set. Our 3D-CNN model attained an AUC of 0.668 in the testing set, which shows a better discriminative ability than random guessing. CONCLUSIONS: A 3D-CNN can be trained, using PET imaging datasets, to predict LNV/PNI in esophageal cancer with acceptable accuracy.

The importance of optimal ROIs delineation for FBPA-PET before BNCT.

One of the eligible criteria for patients to receive boron neutron capture therapy (BNCT) is based on the tumour-to-normal ratio (T/N) measured by FBPA-PET. However, there is no standard protocol for normal region-of-interested delineation. With comparison of contralateral cerebrum, our study revealed the consistency (p < 0.05) and high feasibility using the cerebellum as an alternative normal tissue baseline because of its homogeneous uptake. Following RECIST version 1.1, the standard-operating-procedure (SOP) for the BNCT fulfilled the expected tumour response and tumour shrinkage rate (p < 0.05). Our modified procedure can provide more precise information for BNCT within a reasonable time.

Using salvage Boron Neutron Capture Therapy (BNCT) for recurrent malignant brain tumors in Taiwan.

Radiation therapy has an irreplaceable role in modern oncologic therapy, thanks to the advanced radiation techniques developed in recent decades. However, photon-resistant cases are sometimes encountered. Boron Neutron Capture Therapy (BNCT) is a highly selective radiotherapy technique due to the high tumor to tissue ratio of boronophenylalanine (BPA), the unique medication used for the BNCT treatment reaction. In this study, we report on three special patients with malignant brain tumors treated with BNCT.

BIGDOSE: software for 3D personalized targeted radionuclide therapy dosimetry.

BACKGROUND: Advance 3D quantitative radionuclide imaging techniques boost the accuracy of targeted radionuclide therapy (TRT) dosimetry to voxel level. The goal of this work is to develop a comprehensive 3D dosimetric software, BIGDOSE, with new features of image registration and virtual CT for patient-specific dosimetry. METHODS: BIGDOSE includes a portable graphical user interface written in Python, integrating (I) input of sequential ECT/CT images; (II) segmentation; (III) non-rigid image registration; (IV) curve fitting and voxel-based integration; (V) dose conversion and (VI) 3D dose analysis. The accuracy of the software was evaluated using a simulation study with 9 XCAT phantoms. We simulated SPECT/CT acquisitions at 1, 12, 24, 72 and 144-hrs post In-111 Zevalin injection with inter-scans misalignments using an analytical projector for medium energy general purpose (MEGP) collimator, modeling attenuation, scatter and collimator-detector response. The SPECT data were reconstructed using quantitative OS-EM method. A CT organ-based registration was performed before the dose calculation. Organ absorbed doses for the corresponding Y-90 therapeutic agent were calculated on target organs and compared with those obtained from OLINDA/EXM, using dose measured from GATE as the gold standard. One patient with In-111 DTPAOC injection as well as two patients with Y-90 microsphere embolization were used to demonstrate the clinical effectiveness of our software. RESULTS: In the simulation, the organ dose errors of BIGDOSE were -9.59%±9.06%, -8.36±5.82%, -23.41%±6.67%, -6.05%±2.06% for liver, spleen, kidneys and lungs, while they were -25.72%±12.52%, -14.93%±10.91%, -28.63%±12.97% and -45.30%±5.84% for OLINDA/EXM. Cumulative dose volume histograms, dose maps and iso-dose contours provided 3D dose distribution information on the simulated and patient data. CONCLUSIONS: BIGDOSE provides a one-stop platform for voxel-based dose estimation with enhanced functions. It is a promising tool to streamline the current clinical TRT dosimetric practice with high accuracy, incorporating 3D personalized imaging information for improved treatment outcome.

Simultaneous Time-of-Flight PET/MR Identifies the Hepatic 90Y-Resin Distribution After Radioembolization.

A 61-year-old woman with multiple hepatic metastases from uterus cervical cancer received Y radioembolization. The simultaneous time-of-flight (TOF) PET/MR clearly identified the untreated tumor parts on the posttherapeutic Y internal pair-production imaging. After another boosted Y injection, the metastatic hepatic tumors were well covered. The follow-up PET/MR revealed tumor shrinkage. The one-stop-shop TOF PET/MR provided useful follow-up information in patients receiving Y radioembolization.

Deep Convolutional Neural Network-Based Positron Emission Tomography Analysis Predicts Esophageal Cancer Outcome.

In esophageal cancer, few prediction tools can be confidently used in current clinical practice. We developed a deep convolutional neural network (CNN) with 798 positron emission tomography (PET) scans of esophageal squamous cell carcinoma and 309 PET scans of stage I lung cancer. In the first stage, we pretrained a 3D-CNN with all PET scans for a task to classify the scans into esophageal cancer or lung cancer. Overall, 548 of 798 PET scans of esophageal cancer patients were included in the second stage with an aim to classify patients who expired within or survived more than one year after diagnosis. The area under the receiver operating characteristic curve (AUC) was used to evaluate model performance. In the pretrain model, the deep CNN attained an AUC of 0.738 in identifying patients who expired within one year after diagnosis. In the survival analysis, patients who were predicted to be expired but were alive at one year after diagnosis had a 5-year survival rate of 32.6%, which was significantly worse than the 5-year survival rate of the patients who were predicted to survive and were alive at one year after diagnosis (50.5%, p < 0.001). These results suggest that the prediction model could identify tumors with more aggressive behavior. In the multivariable analysis, the prediction result remained an independent prognostic factor (hazard ratio: 2.830; 95% confidence interval: 2.252-3.555, p < 0.001). We conclude that a 3D-CNN can be trained with PET image datasets to predict esophageal cancer outcome with acceptable accuracy.

Nuclear Theranostics in Taiwan.

Boron neutron capture therapy and Y-90 radioembolization are emerging therapeutic methods for uncontrolled brain cancers and hepatic cancers, respectively. These advanced radiation therapies are heavily relied on theranostic nuclear medicine imaging before the therapy for the eligibility of patients and the prescribed-dose simulation, as well as the post-therapy scanning for assessing the treatment efficacy. In Taiwan, the Taipei Veterans General Hospital is the only institute performing the BNCT and also the leading institute performing Y-90 radioembolization. In this article, we present our single institute experiences and associated theranostic nuclear medicine approaches for these therapies.

A practical background correction method for an immediately repeated first-pass radionuclide angiography.

BACKGROUND: A satisfactory bolus injection is essential for a successful first-pass radionuclide angiography (FPRNA). Rescheduling the FPRNA study is usually needed due to high background interference caused by an unsatisfactory bolus injection. We developed a protocol to correct the pre-existing background activity subsequent to immediately repeating the study. METHODS: Seventy-four consecutive patients who had their bone scan and FPRNA scheduled on the same day were included for analysis. The initial 51 cases constituted the "validation-only" group. In the other 23 cases, the "validation plus clearance constants" group, a 5-min dynamic acquisition was performed during the 5-min equilibrium to obtain the background clearance curve and the clearance constants. For all included 74 cases ejection fraction (EF) analysis was proceeded using the images from the first injection, second injection, and second injection with the corrected background to yield EF1, EF2, and EF2', respectively. EF2 and EF2' were then compared to the ejection fraction without background interference, the EF1. RESULTS: For the LV, the mean difference between the EF1 and the uncorrected EF2 (|LVEF1-LVEF2| in mean ± SD) was 3.1 ± 2.0% and the difference between the EF1 and the corrected EF2' (|LVEF1-LVEF2'|) was 1.6 ± 2.1%, while the mean differences for RV are 2.2 ± 1.9% and 1.8 ± 1.8%, respectively. A significant difference (p < 0.05) was observed between the uncorrected and the corrected data for both the LV and RV. CONCLUSION: In FPRNA, when a bolus injection is immediately readministered, both LVEF and RVEF can be underestimated. With our correction method, the results are superior to those without correction.

Combined Yttrium-90 microsphere selective internal radiation therapy and external beam radiotherapy in patients with hepatocellular carcinoma: From clinical aspects to dosimetry.

PURPOSE: Selective internal radiation therapy (SIRT) is an effective treatment strategy for unresectable hepatocellular carcinoma (HCC) patients. However, the prognoses of patients with portal vein thrombosis, extra-hepatic metastases, or residual tumors remain poor when treated with SIRT alone. In these patients, sequential external beam radiotherapy (EBRT) may offer a chance of salvage. Here, we reported the clinical outcomes and the detailed dosimetry analysis of 22 patients treated with combination therapy. METHODS: Between October 2011 and May 2015, 22 consecutive patients who underwent EBRT after yttrium-90 (90Y) SIRT were included in this study. The post-SIRT 90Y bremsstrahlung SPECT/CT of each patient was transferred to dose distribution by adopting the local deposition hypothesis. The patient-specific 3-dimensional biological effective dose distribution of combined SIRT and EBRT was generated. The overall survival and safety were evaluated. The relationship between dosimetric parameters and liver toxicity was analyzed. RESULTS: The mean administered activity of SIRT was 1.50 GBq (range: 0.5-2.8). The mean prescribed dose of EBRT was 42.3 Gy (range: 15-63) in 14 fractions (range: 5-15) and was targeted to the residual liver tumor in 12 patients (55%), portal vein thrombosis in 11 patients (50%), and perihilar lymphadenopathies in 4 patients (18%). The overall 1-, 2-, and 3-year survival rates were 59.8%, 47.9%, and 47.9%, respectively. Overall, 8 patients (36%) developed > grade 2 liver toxicities, and the Child-Pugh score prior to EBRT strongly affected the toxicity risk. A dosimetry analysis restricted to 18 Child-Pugh A/B patients showed that the V100 (The fraction of normal liver exposed to more than 100 Gy) to V140 significance differed between patients who did or did not experience hepatotoxicity. The V110 was the strongest predictor of hepatotoxicity (18.6±11.6% vs 29.5±5.8%; P = 0.030). CONCLUSION: Combined therapy is feasible and safe if patients are carefully selected. Specifically, 3-dimensional dosimetry is crucial for the evaluation of efficacy and toxicity. The normal liver V100 to V140 values of the combined dose should be as low as possible to minimize the risk of liver toxicity.