Yttrium-90 Research Articles

CTNI-69. A FIRST-IN-HUMAN FEASIBILITY STUDY TO EVALUATE THE SAFETY OF SELECTIVE YTTRIUM-90 ENDOVASCULAR RADIOTHERAPY IN PATIENTS WITH RECURRENT GBM: INTERIM RESULTS FROM THE FRONTIER TRIAL

Abstract BACKGROUND Yttrium-90 (Y90) microsphere treatment is an FDA-approved endovascular radiotherapy for Hepatocellular Carcinoma; however, extra-hepatic experience is limited. The FRONTIER trial (NCT05303467) is a first-in-human study conducted under an IDE from the FDA evaluating the safety and feasibility of intra-arterial Y90 endovascular radiotherapy in patients with recurrent glioblastoma (rGBM). METHODS The primary endpoint is the incidence of treatment-related limiting toxicities through 30 days, in 12 patients with rGBM. Eight subjects (50% male) with non-dominant hemisphere rGBM have been enrolled to date, with 6 patients reported herein. The treatment region, encompassing the recurrent lesion, excluding eloquent regions, and defined using cerebral angiography-MRI fusion, was selectively targeted with 40±4Gy. Immediate post-treatment imaging included MRI to evaluate acute treatment-related effects and Y90-PET to evaluate the absorbed dose distribution. Neurological assessments were performed pre- and post-treatment. Analysis of post-contrast T1w enhancing tissue volume (T1wvol) inside and outside the treated region was performed longitudinally. RESULTS All patients tolerated the procedure well and were discharged the following day. No decrease in neurological function and no limiting toxicities were reported through 30 days. Post-treatment MRI revealed no device-related acute ischemia or hemorrhage. Mean absorbed dose to the treatment region was 42.1±2.4Gy, within 3% of the targeted value, suggesting technical feasibility. Mean tumor absorbed dose within the treatment region was 65.1±22.6Gy most likely due to increased tumor perfusion in the treatment region. A reduction in T1wvol at 2m was observed in 4/6 patients, with the remaining 2 patients showing increased T1wvol. Disease progression by T1wvol occurred more rapidly outside the treatment region than within. All patients received subsequent therapy, with 2 patients receiving surgery 82 and 120 days post Y90 treatment. CONCLUSION Interim results in this first-in-human feasibility study demonstrated technical feasibility and no limiting toxicities through 30 days. Enrollment is ongoing. These data warrant additional investigation.

7040 Embolization Of Hepatic Metastases Is Effective For Palliative Management Of Severe Cushing Syndrome

Abstract Disclosure: S. Zhang: None. C. Musonza: None. A. Pillai: None. M. Ramos-Roman: None. J. Abramowitz: None. S. Mirfakhraee: None. P. Polanco: None. A.P. Dackiw: None. S. Al Mutar: None. A. Mallik: None. L. Jia: None. O. Hamidi: None. Background: Cushing syndrome (CS) due to metastatic endocrine neoplasms poses substantial treatment challenges. Arterial embolization and Yttrium-90 (Y-90) radioembolization for hepatic metastases are effective in the management of metastases due to neuroendocrine tumors (NETs). However, data are scarce on the role of embolization of liver metastases in patients with CS. Here, we report two cases of severe CS due to bulky hepatic metastases treated with embolization techniques. Case 1 A 49-year-old woman presented with severe ectopic CS and a 15-cm hepatic metastatic conglomerate. Liver biopsy showed NET of unknown primary. Treatment with subcutaneous octreotide and metyrapone (total daily dose 3000mg) resulted in modest improvement of serum cortisol from 89.8 to 45.8 mcg/dL. She was not a candidate for bilateral adrenalectomy or hepatectomy due to bulky hepatic metastases and subsequently underwent bland embolization to the hepatic conglomerate. Cortisol decreased from 63.9 mcg/dL to 13.8 mcg/dL after the initial procedure, but then rebounded to 35.8 mcg/dL. Serum cortisol decreased to 19.4 mcg/dL following additional embolization, and she was discharged on metyrapone 500mg three times daily. CS remained controlled 12 weeks after the procedure. Interval imaging showed a decrease in size of the dominant hepatic mass (9.7 cm). The patient is currently undergoing chemotherapy with carboplatin and etoposide. Case 2: A 40-year-old man presented to an outside institution with CS due to a 6.9 cm right adrenal mass and underwent adrenalectomy. Pathology showed oncocytic neoplasm of uncertain malignant potential. A year later, he presented to our hospital with recurrent CS and was found to have a 10.2 cm liver lesion, confirming stage IV adrenocortical carcinoma. FDG PET/CT did not show additional lesions. He was treated with osilodrostat and mitotane but his hypercortisolism remained uncontrolled. Mitotane was discontinued after a few doses due to side effects. Metastasectomy was attempted but halted due to extensive peritoneal carcinomatosis noted in the operating room. He was subsequently treated with Y-90 radioembolization to the liver metastasis. Afterwards, osilodrostat was held and serum cortisol decreased from 49.6 to 6.9 mcg/dL on day 14 post-procedure. Hydrocortisone was initiated for treatment of adrenal insufficiency. He received cisplatin, doxorubicin, and etoposide, but stopped after the first cycle due to side effects. Recent imaging showed a decrease in the hepatic lesion to 6.5 cm. Presently, the patient continues to have persistent adrenal insufficiency confirming remission of CS. Conclusion: These cases illustrate the potential efficacy of bland embolization and Y-90 radioembolization for palliative treatment of severe CS in patients with hepatic metastases. Presentation: 6/2/2024

The Impact of Radiation Dose and Tumour Burden on Outcomes in Hepatocellular Carcinoma: 11-Year Experience in a 413-Patient Cohort Treated with Yttrium-90 Resin Microsphere Radioembolisation

Introduction: Transarterial radioembolisation (RE) using yttrium-90 (Y-90) microspheres is a widely used locoregional therapy for a broad spectrum of hepatocellular carcinoma (HCC) given its favourable safety profile. We evaluated the real-world outcomes of unresectable HCC treated with resin Y-90 RE and the relationship between tumour absorbed dose and subsequent curative therapy with survival. Methods: Included were consecutive patients treated with Y-90 resin microspheres RE for unresectable HCC between January 2008 and May 2019 at the National Cancer Centre Singapore/Singapore General Hospital. The outcomes were stratified by tumour burden, distribution, presence of portal vein invasion (PVI) and liver function to improve prognostication. Results: The median overall survival (OS) evaluated on 413 included patients was 20.9 months (95% CI: 18.2–24.0). More than half of the patients (214/413, 51.8%) had HCC beyond up-to-seven criteria, and 37.3% had portal vein invasion (154/413, 37.3%). Majority (71.7%) had dosimetry calculated based on the partition model. Patients who received ≥150 Gy to tumour had significantly better outcomes (OS 32.2 months, 95% CI: 18.3–46.4) than those who did not (OS 17.5 months, 95% CI: 13.7–22.7, p < 0.001). Seventy patients (17%) received curative therapies after tumour was downstaged by Y-90 RE and had better OS of 79.7 months (95% CI: 40.4 – NE) compared to those who did not receive curative therapies (OS 17.1 months; 95% CI: 13.5–20.4, p < 0.001). RE-induced liver injury was observed in 5.08% of the patients while 3.2% of the patients had possible radiation pneumonitis but none developed Grade 3–4 toxicity. For HCC without PVI, OS differed significantly with performance status, albumin-bilirubin grade, tumour distribution, and radiation dose; for HCC with PVI, Child-Pugh class and AFP were significant predictors of survival. Conclusions: Treatment outcomes for unresectable HCC using Y-90 RE were favourable. Incorporating tumour burden and distribution improved prognostication. Patients who received tumour absorbed dose above 150 Gy had better OS. Patients who subsequently received curative therapies after being downstaged by Y-90 RE had remarkable clinical outcomes.

Use of selective internal radiation therapy with yttrium-90 as a bridge to liver resection: a 5-year single-center experience

Selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) has been historically reserved for unresectable liver malignancy. Evidence is emerging for the use of SIRT to increase future liver remnant (FLR), allowing for the resection of previously inoperable disease. This was a 5-year retrospective review of all patients undergoing SIRT with Y-90 at a tertiary institute. Patient demographics, clinicopathologic data, surgical details, and postoperative outcomes were reviewed. The primary outcome, safety of liver resection after SIRT, was evaluated with 90-day morbidity and mortality. A total of 134 SIRT procedures were performed on 113 patients. Post-SIRT complications occurred in 18 patients (15.9%), with a single 30-day mortality. In addition, 17 patients underwent SIRT with the intent to augment FLR for liver resection. After SIRT, mean hepatic mebrofenin extraction and FLR increased from 2.5%/min/m2 and 30.5% to 4.2%/min/m2 and 52.5% (P=.01 and P<.0001, respectively). Ten patients underwent resection, and there were 2 intraoperative complications. The median time from SIRT to resection was 5.2 months. The 90-day postoperative morbidity was 20% (n=2), and complications were analyzed according to the Clavien-Dindo II classification scale. There was no 30-day or 90-day postoperative mortality. Post-SIRT liver resection is a challenging procedure with low postoperative mortality and morbidity.

Determining beta radiation doses from Y-90 microsphere for the treatment of hepatic tumors by using Monte Carlo and analytical methods

The very short range of beta radiation is a potential radiation treatment for tumor, which can preserve sensitive structures. However, due to the limited range of beta radiation, practical dosimetry of beta sources may be a point of concern, and theoretical dosimetry methods play an important role. A resin microsphere loaded with the Yttrium-90 (Y-90) radionuclide can be applied in the radioembolization of hepatic tumors. In this work, we present initial calculations of dose rates around a microsphere loaded with the Y-90 radionuclide uniformly distributed on its exterior surface. Two approaches were used to carry out the estimations: the first one by means of Monte Carlo simulations using the PENELOPE code and the second one by means of the beta-point dose function formalism. A Fortran code was developed to handle with the various quantities necessary to perform the numerical integration of the beta-point dose function. A comparison between results obtained by means of both methods indicated a maximum difference of ~5% up to the 0.3 cm distance from the center of the sphere.

Arterial hypoperfusion as a negative predictive marker for primary hepatic malignancies treated with Y-90 glass microsphere transarterial radioembolization.

Radioembolization with yttrium-90 (Y-90) is utilized to treat primary liver malignancies. The efficacy of this intra-arterial therapy in arterially hypoperfused tumors is not known. We reviewed data of patients with primary liver tumors treated with Y-90 prescription doses of at least 150 Gy. Baseline patient characteristics, treatment history, imaging-based tumor response assessments, and clinical outcome metrics were recorded. Tumors were classified as arterially hyperperfused versus hypoperfused on post-TARE Y-90 SPECT/CTs or pre-TARE hepatic perfusion SPECT/CTs. Perfusion status was correlated with tumor response assessments and clinical outcomes. Cox proportional hazards models were utilized to compare survival and progression-free survival. Inverse probability weighting was utilized to account for clinical factors and adjusted multivariable proportional hazards analyses to examine the relationship of quantitative perfusion and cancer outcomes. Of 400 Y-90 treatments, 88 patients received a prescribed dose of at least 150 Gy and had pre- or post-treatment SPECT/CT images. 11 and 77 patients had arterially hypoperfused and hyperperfused lesions, respectively. On dedicated liver MRI or CT at 3 months after Y-90, the complete response rates were 5.6% and 16.5% in the hypoperfused and hyperperfused cohort, respectively (P = 0.60). When controlling for various clinical features, including tumor histology, patients with arterially hypoperfused tumors had significantly shorter progression-free survival (HR 1.87, 95% CI - 1.03 - 3.37, P = 0.039) and greater elsewhere liver (HR 3.36, 95% CI = 1.23 - 9.20, P = 0.019) and distant failure (HR 7.64 (2.71 - 21.54, P < 0.001). In inverse probability weighted analysis, patients with arterially hypoperfused tumors had worse overall survival (P = 0.032). In the quantitative analysis, lower levels of lesion perfusion were also associated with worse clinical outcomes, again controlling for tumor histology. Compared to arterially hyperperfused tumors, hypoperfused primary liver tumors treated with Y-90 may have worse clinical outcomes.

Y90 Radiation Segmentectomy versus Microwave Ablation for Hepatocellular Carcinoma in Locations Suboptimal for Percutaneous Ablation

Abstract Purpose The purpose of our study was to evaluate outcomes following percutaneous microwave ablation (MWA) versus yttrium-90 (Y90) radiation segmentectomy (RS) for tumors in suboptimal locations for ablation. Materials and Methods Retrospective review (January 2014–July 2019) was performed on patients who underwent Y90-RS or MWA (with or without prior transarterial chemoembolization [TACE]) with curative intent for early-stage hepatocellular carcinoma (HCC) lesions in suboptimal locations for percutaneous ablation, defined as locations in which needle placement is within 5 mm of critical structures (liver dome, liver capsule, gallbladder, and hilum). The primary endpoints were treatment response as per the modified Response Evaluation Criteria in Solid Tumors criteria and complications. Statistical Analysis Fischer's exact test was performed for categorical variables, and Student's t-tests for nominal variables. Results Twenty-three lesions in 20 patients (13 male, 67 ± 8.8 years) and 30 lesions in 30 patients (18 male, 62.5 ± 10.6 years) were treated with Y90-RS and MWA (19 with prior TACE), respectively. There were no differences in demographics (p &gt; 0.05). Mean tumor diameter was 2.9 ± 1.0 in those treated with Y90-RS and 2.3 ± 0.9 for MWA (p &lt; 0.05). Lesions were located adjacent to the following structures: dome (n = 22), capsule (n = 16), hilum (n = 9), and gallbladder (n = 6). All patients were Eastern Cooperative Oncology Group performance status 0 to 1. Of the MWA cohort, 19 were Child-Pugh class A, 5 were B, and 6 were C and the mean pretreatment laboratory values were as follows: Model for End-stage Liver Disease sodium (MELD-Na) 12.7 ± 4.6, alpha-fetoprotein (AFP) 848 ± 3168.0, aspartate aminotransferase (AST) 71.9 ± 49.1, alanine aminotransferase (ALT) 48.0 ± 32.4, and total bilirubin 2.4 ± 2.7. Of the Y90-RS cohort, 15 were Child-Pugh class A, 4 were B, and 1 was C and pretreatment laboratory values were as follows: MELD-Na 10.5 ± 3.3 (Y90-RS), AFP 762.2 ± 1793.8 (Y90), AST 50.3 ± 30.5 (Y90), ALT 30.1 ± 16.9 (Y90), and total bilirubin 1.6 ± 1.1 (Y90). Complete response rate following Y90 was 96 versus 76% for MWA, with no disease progression after Y90-RS within the follow-up period. Three (13%) lesions demonstrated progression of disease (time to progression 6.3 months) after MWA. No grade &gt; 2 toxicities or procedure-related complications were noted following Y90-RS. There were 7 major (arterioportal fistula with hemoperitoneum, pneumothorax, liver infarction, and capsular burn) and 3 minor complications following MWA. Conclusion Y90-RS is a valuable alternative to percutaneous MWA as a first-line therapy for early-stage HCC for tumors in suboptimal locations for ablation, offering a favorable treatment response and safety profile.

Radioembolization of HCC and secondary hepatic tumors: a comprehensive review.

Transarterial radioembolization (TARE), also called Selective Internal Radiation Therapy (SIRT), has emerged as an effective locoregional therapy for primary and secondary hepatic tumors, utilizing yttrium-90 (Y90) microspheres and other agents such as holmium-166 and rhenium-188. TARE has various applications in the management of HCC across different BCLC stages. Radiation segmentectomy, which involves administering high doses of Y90 (>190 Gy), can be both curative and ablative, achieving complete necrosis of the tumor. In contrast, radiation lobectomy involves administering a lower dose of Y90 (80-120 Gy) as a neoadjuvant treatment modality to improve local control and induce future liver remnant (FLR) hypertrophy in patients who are planned to undergo surgery but have insufficient FLR. Modified radiation lobectomy combines both techniques and offers several advantages over portal vein embolization (PVE). Y90 is also used in downstaging HCC patients outside liver transplantation criteria, as well as bridging those awaiting liver transplantation (LT). Multiple studies and combined analyses were described to highlight the outcomes of TARE and compare it with other treatment modalities, including TACE and sorafenib. Additionally, the review delves into the efficacy and safety of radioembolization in managing metastatic colorectal cancer and other metastatic tumors to the liver. Recent studies have emphasized the role of personalized dosimetry for improved outcomes, and thus we described the different methods used for this purpose. Pretherapy imaging, estimating lung shunt, selection of therapeutic radionuclides, adverse effects, and cost-effectiveness were all discussed as well.

Advancements in Interventional Radiology for Managing Hepatic Encephalopathy: A Comprehensive Review.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome resulting from liver dysfunction, leading to cognitive, behavioral, and motor impairments. The management of HE has traditionally relied on pharmacological treatments, dietary modifications, and liver transplantation. However, recent advancements in interventional radiology (IR) have introduced minimally invasive procedures that offer promising alternatives. This comprehensive review explores the latest IR techniques, including transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), portal vein embolization (PVE), and Yttrium-90 (Y90) radioembolization. The efficacy, clinical outcomes, and potential complications of these techniques are examined through an analysis of current studies and trials. The review highlights the benefits of IR in reducing portal hypertension and improving hepatic blood flow, ultimately alleviating HE symptoms. Additionally, it underscores the importance of multidisciplinary collaboration, ongoing research, and the development of clear patient selection criteria to optimize the use of IR in HE management. By integrating these advancements into clinical practice, healthcare providers can enhance the quality of care and improve outcomes for patients with HE.

The safety and short-term efficacy of selective internal radiation therapy combined with systemic treatment for unresectable malignant hepatic tumors in Chinese patients.

e16247 Background: There are many systemic treatment options for patients with unresectable malignant hepatic tumors. In China, selective internal radiation therapy (SIRT) with yttrium-90 (Y90) resin microspheres was approved until 2022. The aim of this retrospective study was to investigate the safety and short-term efficacy of SIRT with Y90 resin microspheres followed by systemic treatment in Chinese patients. Methods: The study analyzed patients who received SIRT with Y90 combined with systemic treatment at our center between June 2022 and October 2023. The study's primary endpoint was to determine the objective response rate (ORR), while safety was the secondary endpoint. Response was measured based on modified Response Evaluation Criteria in Solid Tumors criteria (mRECIST) up to 90 days after the initial therapy. Safety was evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Results: 21 patients wereincluded, of whom 22 times of SIRT were performed. 18 patients had HCC, and 3 had mCRC.The baseline characteristics of the patients are shown in Table. The median age was 54 years (IQR, 48-59 years) and 90.5% of patients were male. According to Eastern Cooperative Oncology Group performance status, grade 0 and grade 1 were 81% and 19%, respectively, whereas Child-Pugh A represented 90.5% of cases. The proportion of patients with hepatitis B virus infection was 95.2%. Thirteen (61.9%) patients received different treatments before SIRT. The median number of tumors was 2.5 (IQR, 1-4.3), whereas the median diameter of the largest lesion was 100.4 mm (IQR, 68.3-127.7 mm). PVTT was classified as follows: Vp1 (n = 3), Vp2 (n = 2), Vp3 (n = 2) and Vp4 (n = 1). Median AFP was 33.2 ng/mL (IQR, 5.9-401 ng/mL). The median total radiation activity administered was 1.4 GBq (IQR, 0.9-2.7 GBq) and the median target tissue dose was 205 Gy (IQR, 155-242 Gy). Nine (43%) patients were downstaged to surgery. Four (19%) patients had a complete response, fifteen (71.4%) had a partial response and two (9.5%) had a progressive disease. ORR and disease control rate were 90.5% and 90.5%, respectively. None of the patients experienced grade 3 and higher adverse events. The most common treatment-related adverse events were fever and abdominal pain, which required no special treatment. Conclusions: SIRT with Y90 resin microspheres combined with systemic treatment is safe and effective in patients with unresectable malignant hepatic tumors, which resulted in encouraging ORR (90.5%) and a downstaging rate (43%). Clinical trial information: ChiCTR2300077524. [Table: see text]

Implications of lung shunt fraction calculation discrepancy in Y-90 radioembolization treatment from 2D planar vs 3D SPECT imaging

Abstract The safety and efficacy of Yttrium-90 (Y-90) radio-embolization therapy is partly dependent on the lung shunt fraction (LSF). There may be a notable disparity between LSF when calculated using 2D planar imaging vs 3D SPECT; this can affect the total allowable Y-90 dose delivered and therefore change the effectiveness of the procedure. The case presented demonstrates an 81% decrease in LSF when calculated by SPECT as compared to 2D planar imaging. This case highlights the importance of considering the imaging technique and the potential discrepancies that can arise between planar and SPECT imaging in LSF assessment.

Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis.

This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

Techniques to Optimize Radioembolization Tumor Coverage.

Yttrium-90 (Y90) radioembolization has become a major locoregional treatment option for several primary and secondary liver cancers. Understanding the various factors that contribute to optimal tumor coverage including sphere count, embolization techniques, and catheter choice is important for all interventional radiologists while planning Y90 dosimetry and delivery. Here, we review these factors and the evidence supporting current practice paradigms.

Safety and efficacy of external beam radiotherapy in hepatocellular carcinoma patients previously treated with yttrium-90 radioembolization.

523 Background: Data on the safety and efficacy of external beam radiation (EBRT) after Yttrium-90 (Y-90) radioembolization for hepatocellular carcinoma (HCC) is limited. We report our experience using EBRT to treat HCC patients who were previously treated with Y-90. Methods: We analyzed 31 HCC patients who received EBRT following Y-90 treatment. Eighteen were treated with photon therapy (40-50 Gy in 5 fractions), and thirteen with proton therapy (42-67.5 Gy in 15 fractions). Twenty-four patients underwent Y-90 segmentectomies, while seven received Y-90 lobar treatment. The median administered Y-90 activity was 44.4 mCi (range 8.3-114.4). Results: Patients had received 1 (n=14), 2 (n=7), or ≥3 (n=10) prior Y-90 treatments. EBRT was administered for various reasons: poor Y-90 response in two patients, technical limitations in 25 patients, and other reasons in four patients. Ten patients had previously received Y-90 within the EBRT area, thirteen outside the EBRT area, and eight in both regions. The median tumor size was 3.8 cm (range 1.6-19.4). Twenty-seven patients had Child-Pugh (CP)-A score, three had CP-B, and one had CP-C baseline liver function. With a median follow-up of 21 months, the 2-year progression-free survival, and overall survival rates were 28%, and 43%, respectively. The 2-year cumulative incidence of local failure was 7%. CP+2 progression was observed in five patients (16%): three had Y-90 delivered outside the EBRT area and two within the EBRT area. Three patients had possible RILD-related deaths. Grade 3+ biliary complications occurred in three patients (10%): one biloma, one liver abscess, and one biliary stricture which resulted in a possible treatment-related death. All three patients had received at least two prior Y-90 treatment overlapping with the area treated with EBRT and had tumors located near the porta hepatis. Conclusions: EBRT for HCC patients previously treated with Y-90 is feasible and offers excellent local control. Hepatic function and biliary toxicities are potential complications and should be weighed against the clinical benefits.

Liver-Directed Therapy and Systemic Chemotherapy for Pancreatic Adenocarcinoma with Liver Metastases: Experience of 12-years

Background Pancreatic adenocarcinoma with liver metastases (PCLM) has a poor prognosis with a median survival of ≤6-months. Treatment options are limited as only a few patients can undergo curative surgery, therefore locoregional therapies such as liver-directed therapy (LDT) may offer an adjunct to systemic therapies. The purpose of this retrospective study is to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with Yttrium-90 (Y90), trans-arterial chemoembolization (TACE), and radiofrequency ablation (RFA) with systemic chemotherapy in the treatment of PCLM. Methods We retrospectively evaluated 42 patients, with data available on 39 patients, with PCLM who underwent LDT between February 2007 and March 2019. Patient outcomes were assessed using response evaluation criteria in solid tumors (RECIST), Version 1.1 treatment-related adverse events were assessed using common terminology criteria for adverse events (CTCAE), version 5.0. Results Of 39 patients, 56% underwent TARE, 36% RFA, and 7.8% TACE. The median overall survival (mOS) was 5-months (range 4 to 5.5-months) from the application of LDT and the one-year mOS was 7.8-months (6.5 to 9.5-months). Overall and liver-specific disease response included complete response in 2.5%, partial response in 59%, stable disease in 21%, and progression of disease in 18% of patients. Grade 3 toxicities included abdominal pain in 13%, hyperbilirubinemia in 7.7%, fever in 7.7%, abscess in 2.6%, and thrombocytopenia in 5.1% of patients. Conclusion LDT can be safely combined with systemic chemotherapy for the treatment of PCLM. LDT may be the treatment opportunity for PCLM. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings.

SBRT vs. Y90: HCC Treatment Outcomes and Costs.

Stereotactic Body Radiotherapy (SBRT) and Yttrium-90 (Y90) are among the ablative therapies used as treatment options for localized hepatocellular carcinoma (HCC). To date, direct comparisons of the 2 modalities' outcomes and costs are lacking. This study aimed to analyze demographic, treatment, and cost information for patients with HCC treated with SBRT and Y90. Patients with HCC treated with SBRT or Y90 radioembolization between January 2018 and January 2020 at one institution were retrospectively reviewed. Demographic and treatment data were compared utilizing χ 2 tests. Kaplan-Meier curves and log-rank tests were applied to compare overall survival and progression-free survival in different treatment groups. Cox proportional hazard models were applied to analyze the unadjusted and adjusted survival differences. Ten SBRT and 10 Y90 patients were randomly selected for Medicare cost analysis. Sixty-three patients received Y90, and 21 received SBRT. On univariable and multivariable analysis, there was no significant difference in overall survival or progression-free survival between the Y90 and SBRT cohorts. SBRT patients had higher American Joint Committee on Cancer staging ( P =0.039), greater tumor size (4.07 vs. 2.96cm, P =0.013), and greater rates of prior liver-directed therapy (71.4% SBRT vs. 12.7% Y90, P <0.001). The average cost for SBRT was $15,148, and Y90 was $41,360. SBRT and Y90 are effective therapies in the treatment of HCC, specifically having similar overall survival and progression-free survival. Y90 was found to have a significantly higher cost than SBRT. This study demonstrates the need for prospective studies to assess these modalities in treating HCC.

Optimization of Y-90 Radioembolization Imaging for Post-Treatment Dosimetry on a Long Axial Field-of-View PET/CT Scanner.

PET imaging after yttrium-90 (Y-90) radioembolization is challenging because of the low positron fraction of Y-90 (32 × 10-6). The resulting low number of events can be compensated by the high sensitivity of long axial field-of-view (LAFOV) PET/CT scanners. Nevertheless, the reduced event statistics require optimization of the imaging protocol to achieve high image quality (IQ) and quantification accuracy sufficient for post-treatment dosimetry. Two phantoms (NEMA IEC and AbdoMan phantoms, mimicking human liver) filled with Y-90 and a 4:1 sphere (tumor)-to-background ratio were scanned for 24 h with the Biograph Vision Quadra (Siemens Healthineers). Eight patients were scanned after Y-90 radioembolization (1.3-4.7 GBq) using the optimized protocol (obtained by phantom studies). The IQ, contrast recovery coefficients (CRCs) and noise were evaluated for their limited and full acceptance angles, different rebinned scan durations, numbers of iterations and post-reconstruction filters. The s-value-based absorbed doses were calculated to assess their suitability for dosimetry. The phantom studies demonstrate that two iterations, five subsets and a 4 mm Gaussian filter provide a reasonable compromise between a high CRC and low noise. For a 20 min scan duration, an adequate CRC of 56% (vs. 24 h: 62%, 20 mm sphere) was obtained, and the noise was reduced by a factor of 1.4, from 40% to 29%, using the full acceptance angle. The patient scan results were consistent with those from the phantom studies, and the impacts on the absorbed doses were negligible for all of the studied parameter sets, as the maximum percentage difference was -3.89%. With 2i5s, a 4 mm filter and a scan duration of 20 min, IQ and quantification accuracy that are suitable for post-treatment dosimetry of Y-90 radioembolization can be achieved.

Predictive Value of Day of Treatment SPECT/CT Radiomics in Lobar Y90 Radioembolization of Hepatocellular Carcinoma: A Pilot Study

Transarterial Radioembolization (TARE) with Yttrium-90 (Y90) microspheres is a well-tolerated liver-directed therapy for patients with inoperable hepatocellular carcinoma (HCC). Y90 TARE uses pretreatment and post-treatment single photon emission computed tomography (SPECT)/CT for assessment of microsphere biodistribution within tumor. Patients who develop disease progression (PD) after lobar TARE have poor overall survival (OS). Conventional radiography can require several months follow-up to assess tumor response per modified RECIST (mRECIST), resulting in treatment delays for patients with PD. Predictive models capable of identifying patients at high risk for PD could prompt close surveillance and rapid initiation of salvage therapies, enhancing disease control (DC). Predictive models in various cancers have incorporated radiomics, an analytic technique that extracts digital patterns from medical imaging. We hypothesized that radiomics of immediate post-treatment SPECT/CT can predict objective response (OR) to Y90 TARE. A total of 38 lobar TARE treatments were assessed retrospectively. For all treatments, the prescribed dose was 120 Gy. SPECT/CT obtained immediately after TARE underwent radiomics analysis. A total of 75 features related to gray-level (GL) co-occurrence matrices (COM), dependency matrices (DM), run length matrices (RLM), zone size matrices (ZSM), and neighborhood difference matrices (NDM) were examined and balanced between cohorts with and without OR by aid of Gaussian noise up-sampling. Top features were chosen for a weighted k-nearest neighbors (KNN) classifier based on rank as determined by the RELIEF-F algorithm. Performance of the developed classifier was evaluated by receiver operating characteristic (ROC) curve analysis. Most patients (76%) were Child-Pugh A cirrhotic, while Barcelona Clinic Liver Cancer (BCLC) stage was evenly distributed A to C. On radiographic review, 22 treatments (58%) achieved OR. The selected top features consisted of two from CT (GLNDM-based coarseness; GLDM-based small dependence low gray level emphasis) and two from SPECT (GLNDM-based coarseness; GLZSM-based zone entropy). The weighted KNN classifier built using the selected features demonstrated a relatively strong power for predicting OR, with a ROC area under curve (AUC) of 0.83. In lobar TARE Y90 of inoperable HCC, a predictive model using texture features extracted from day of treatment SPECT/CT distinguished responders from non-responders with high accuracy. Limitations of this study include its retrospective nature and the absence of toxicity analysis. These findings suggest that predictive modeling incorporating SPECT/CT radiomics could enhance the therapeutic ratio for vulnerable HCC patients and merits further investigation in prospective clinical trials of Y90 TARE.

Deep-Learning Based Auto-Segmentation for Liver Yttrium-90 Selective Internal Radiation Therapy

In resin Yttrium-90 (Y-90) selective internal radiation therapy (SIRT), liver volume sizes are needed for Y-90 activity calculations using the body-surface-area method, which are obtained from contours that are manually delineated in 3D images. The aim was to apply a deep-learning based auto-segmentation method for liver delineation for Y-90 SIRT. A deep-learning-based liver segmentation method was applied using the U-Net3D architecture, which is a 3D convolutional neural network (CNN) extended from the original 2D U-Net architecture for 3D objects in medical imaging. The segmentation model was trained on the Liver Tumor Segmentation (LiTS) dataset. The training data set contained 130 CT scans, and the test data set contained 70 CT scans. The model was deployed in the clinic using DICOM communication. Auto-segmentation of liver in the CT images of 18 SIRT patients was studied. The CT images were exported from clinical database to the segmentation model's DICOM location, where a monitoring software detected the incoming data and automatically ran the liver segmentation. The results were then returned to the original DICOM location where the CT images were stored. Auto-segmented liver contours were compared with physician manually-delineated contours. Dice similarity coefficient (DSC), mean distance to agreement (MDA), ratio of volume (RV), and ratio of activity (RA, ratio of activity calculated using an auto-segmented liver contour to the accurate activity calculated using a manually-delineated contour), were assessed. DSC, MDA, and RV are 0.942±0.014 (range: 0.908-0.959), 1.902±0.503 mm (range: 1.043-2.956 mm), and 0.988±0.039 (range: 0.901-1.045), respectively. RA is 1.001±0.003 (range: 0.993-1.007), which indicates that the activities calculated using the auto-segmented liver contours are close to the accurate activities. The segmentation model was able to successfully identify and segment livers in the CT images, and provide accurate and reliable results. The proposed method is beneficial for clinical use as it can process large amounts of data quickly and efficiently, and can be easily deployed in a clinical environment using DICOM communication.

Combination of transarterial radioembolization with atezolizumab and bevacizumab for intermediate and advanced staged hepatocellular carcinoma: A preliminary report of safety and feasibility

PurposeThe IMbrave150 Phase III trial demonstrated the superiority of atezolizumab and bevacizumab (Atezo/Bev) over sorafenib for unresectable hepatocellular carcinoma (HCC). The present study aims to evaluate the feasibility of TARE in combination with Atezo/Bev for the treatment of intermediate and advanced staged HCC. MethodsA retrospective review at a single institution was performed between May 2021 and December 2022. Patients who received TARE using yttrium-90 (Y90) with concomitant or sequential Atezo/Bev systemic treatment were included. The following outcomes were retrieved: overall survival (OS), radiologic tumor response, progression-free survival, technical adverse events related to TARE, and toxicity based on the National Cancer Institute–Common Terminology Criteria for Adverse Events version 5.0. ResultsTen consecutive patients with intermediate (n ​= ​4) and advanced stage HCC (n ​= ​6) were treated with TARE and sequential/concomitant Atezo/Bev. Tumor control was achieved in all TARE-treated target lesions (100%). Overall disease progression occurred in 4 patients with PFS of 78.8% and 66.7% at 6- and 12- months, respectively. Two patients died at follow-up, with 6-month and 12-month OS rates of 90.0% and 77.1%, respectively. Three (75%) patients with intermediate stage disease were downstaged into Milan criteria. One patient developed grade 3 transaminitis and hypoglobulinemia, while Atezo/Bev was switched to Lenvatinib in another patient due to immunotherapy related myositis. ConclusionThis study demonstrates the initial safety and feasibility of combined TARE with Atezo/Bev for intermediate/advanced stage HCC. Further prospective studies with larger sample sizes are warranted.