Radioembolization For Hepatocellular Carcinoma Research Articles

Abstract No. LBA1 Route90 US IDE Pivotal Study Early Results in Radioembolization of Hepatocellular Carcinoma (HCC) with Imageable Y90 Microspheres

Abstract No. LBA1 Route90 US IDE Pivotal Study Early Results in Radioembolization of Hepatocellular Carcinoma (HCC) with Imageable Y90 Microspheres

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.

Yttrium-90 transarterial radioembolization and capecitabine in hepatocellular carcinoma with portal vein involvement.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombus is considered an advanced stage disease. Non-surgical local and systemic therapies are the only treatment options available. To analyze the survival and toxicity outcomes of systemic treatment concurrent with yttrium-90 transarterial radioembolization in HCC with liver-limited disease and portal vein involvement with Child-Pugh B liver reserve. The medical records of 22 patients who underwent yttrium-90 transarterial radioembolization concomitant with capecitabine chemotherapy as first-line treatment between 2014 and 2019 were retrospectively reviewed. Twenty-two patients were included in the study. Grade 3 to 4 side effects were evaluated, and hepatic encephalopathy developed in 1 patient after yttrium-90 transarterial radioembolization. In the fourth month of radiological evaluation, 11 patients had a partial response (50%), 5 patients had stable disease (22.7%), and 6 patients (27.3%) developed progressive disease. The median survival time was 21 months. Combined treatment with yttrium-90 transarterial radioembolization and capecitabine may be an effective and safe treatment option. Treatment was associated with a median overall survival of 21 months and a disease control rate of 72.7% at 4 months in patients with inoperable HCC.

Long-term outcome analysis of Y90 radioembolization in hepatocellular carcinoma.

Yttrium-90 (Y90) radioembolization is a catheter-based therapy for hepatocellular carcinoma (HCC). Multiple trials have evaluated the efficacy of Y90 in HCC; however, few have assessed long-term hepatic function. This study aimed to evaluate a clinical real-world experience of Y90 effectiveness and long-term impact on hepatic function. A single-center retrospective chart review was performed for patients with Child-Pugh (CP) class A or B who received Y90 for primary HCC between 2008 and 2016. Model for end-stage liver disease (MELD) and CP scores were calculated on the day of treatment and 1, 3, 6, 12, and 24 months post-procedure. Of the 134 patients included, the mean age was 60 years old and median overall survival (OS) from date of diagnosis was 28 months [95% confidence interval (CI): 22.21-38.05]. Patients with CP class A (85%) had a median progression-free survival (PFS) of 3 months (95% CI: 2.99-5.55) and median OS of 17 months (95% CI: 9.59-23.10) from date of Y90 treatment compared to a median PFS of 4 months (95% CI: 2.07-8.28) and OS of 8 months (95% CI: 4.60-15.64) for patients with CP class B. MELD scores were significantly higher post-treatment than pre-treatment, with significant recovery at 24 months. No significant differences were seen between cancer stage and OS, while PFS and cancer stage did show difference between cancer stage 1 and 3 with longer median PFS seen in stage 1. While our study supports the literature for OS in Y90-treated patients, we found a shorter PFS in this population. This may reflect the differences between the utilization of RECIST in clinical trials and clinical radiology practice in determining progression. Significant factors associated with OS were age, MELD, CP scores and portal vein thrombosis (PVT). For PFS, CP score and stage at diagnosis were significant. Increasing MELD scores over time likely reflected a combination of radioembolization-induced liver disease, liver decompensation or progression of HCC. The downtrend at 24 months is likely due to long term survivors with significant benefit from therapy with no long-term complications from Y90.

Accuracy and reproducibility of a cone beam CT-based virtual parenchymal perfusion algorithm in the prediction of SPECT/CT anatomical and volumetric results during the planification of radioembolization for HCC.

To evaluate anatomical and volumetric predictability of a cone beam computed tomography (CBCT)-based virtual parenchymal perfusion (VPP) software for the single-photon-emission computed tomography (SPECT)/CT imaging results during the work-up for transarterial radioembolization (TARE) procedure in patients with hepatocellular carcinoma (HCC). VPP was evaluated retrospectively on CBCT data of patients treated by TARE for HCC. 99mTc macroaggregated albumin particles (99mTc-MAA) uptake territories on work-up SPECT/CT was used as ground truth for the evaluation. Semi-quantitative evaluation consisted of the ranking of visual consistency of the parenchymal enhancement and portal vein tumoral involvement on VPP and 99mTc-MAA SPECT/CT, using a three-rank scale and two-rank scale, respectively. Inter-reader agreement was evaluated using a kappa coefficient. Quantitative evaluation included absolute volume error calculation and Pearson correlation between volumes enhanced territories on VPP and 99mTc-MAA SPECT/CT. Fifty-two CBCTs were performed in 33 included patients. Semi-quantitative evaluation showed a good concordance between actual 99mTc-MAA uptake and the virtual enhanced territories in 73% and 75% of cases; a mild concordance in 12% and 10% and a poor concordance in 15%, for the two readers. Kappa coefficient was 0.86. Portal vein involvement evaluation showed a good concordance in 58.3% and 66.7% for the two readers, respectively, with a kappa coefficient of 0.82. Quantitative evaluation showed a volume error of 0.46 ± 0.78mL [0.01-3.55], and Pearson R2 factor at 0.75 with a p value < 0.01. CBCT-based VPP software is accurate and reliable to predict 99mTc-MAA SPECT/CT anatomical and volumetric results in HCC patients during TARE. • Virtual parenchymal perfusion (VPP) software is accurate and reliable in the prediction of 99mTc-MAA SPECT volumetric and targeting results in HCC patients during transarterial radioembolization (TARE). • VPP software may be used per-operatively to optimize the microcatheter position for 90Y infusion allowing precise tumor targeting while preserving non-tumoral parenchyma. • Post-operatively, VPP software may allow an accurate estimation of the perfused volume by each arterial branch and, thus, a precise 90Y dosimetry for TARE procedures.

Prior ablation and progression of disease correlate with higher tumor-to-normal liver 99mTc-MAA uptake ratio in hepatocellular carcinoma.

Factors affecting tumor-to-normal tissue ratio (T:N) have implications for patient selection, dosimetry, and outcomes when considering radioembolization for HCC. This study sought to evaluate patient, disease specific, and technical parameters that predict T:N as measured on planning pre-90Y radioembolization 99mTc-MAA scintigraphy for hepatocellular carcinoma (HCC). 99mTc-MAA hepatic angiography procedures with SPECT/CT over a 4-year period were reviewed. Data recorded included patient demographics, details of underlying liver disease, tumor size, history of prior treatments for HCC and technical parameters from angiography. Anatomic-based segmentation was performed in 93 cases for measurement of tumor and perfused liver volumes and SPECT counts. T:N were calculated and correlated with collected variables. Mean calculated T:N was 2.52. History of prior ablation was significantly correlated with higher T:N (mean 3.39 vs 2.24, p = 0.003). Cases in which mapping was being performed for treatment of disease progression was significantly correlated with higher T:N (mean 3.35 vs 2.14, p = 0.001). Larger tumor size trended toward lower T:N (p = 0.052). Patients with history of ablation and those undergoing treatment for disease progression have higher T:N and, therefore, could be considered for radioembolization preferentially over alternative treatments.

Clinical factors associated with early disease progression after radioembolization for hepatocellular carcinoma and feasibility of post‐progression systemic therapy

Background and Aims Radioembolization (RE) for unresectable hepatocellular carcinoma (HCC) can provide clinical benefit for well-selected patients, whilst in others, rapid disease progression is observed. As an alternative for this patient population, new potent systemic treatment options are emerging. We aimed to identify the clinical factors associated with rapid progression following RE and assess the feasibility of starting a systemic treatment after progression. Methods A retrospective cohort study of patients with unresectable HCC undergoing RE at a single referral centre between January 2009 and December 2018. Progression-free and overall survival times were calculated. Uni- and multivariate cox regression analysis was used to assess factors associated with poor outcomes. Charts were reviewed for post-progression treatment strategies. Results Overall, 116 patients with unresectable HCC were included. Median PFS after RE was 6.7 months (95% CI 3.97–9.37), which varied significantly (P < .001) with Eastern Cooperative Oncology Group Performance Status (EGOC PS) (ECOG 0, 20.9 months [95% CI 8.6–33.2]; ECOG 1, 7.7 months [95% CI 3.1–12.1]; ECOG 2, 4.4 months [95% CI 1.7–7]). This association remained significant after multivariate testing, together with the number of HCC lesions (P = .017) and α-FP (P = .050). Progressive disease after RE occurred in 82 patients, of whom only 40 received subsequent systemic treatment. Again, ECOG PS at the time of progression was significantly better for patients who did receive systemic treatment versus those who did not (P = .002). Conclusion Patients with unresectable HCC, impaired general condition and multinodular disease have inferior outcomes after radioembolization. After RE, close monitoring of patient performance status, liver function and cancer control is warranted to allow timely initiation of systemic treatment when indicated.

Abstract No. 199 Machine learning for tumor enhancement and morphometry after Y-90 radioembolization of hepatocellular carcinoma: implications for optimal assessment of treatment response

Existing imaging criteria do not adequately predict tumor response after radioembolization. This study aimed to assess the utility of tumor enhancement and morphometry in predicting hepatocellular carcinoma (HCC) recurrence after Y-90.

Abstract No. 195 Tumor size is an independent risk factor for mortality after yttrium-90 radioembolization for HCC

Tumor size impacts patient eligibility for surgical interventions, staging, and locoregional approaches to treatment. The purpose of this study was to evaluate tumor size as a prognosticator for long-term overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with yttrium-90 radioembolization (Y-90). The hypothesis was tumor size would stratify long-term OS after Y-90.

Optimization of the Clinical Effectiveness of Radioembolization in Hepatocellular Carcinoma with Dosimetry and Patient-Selection Criteria.

Selective internal radiation therapy (SIRT) is part of the treatment strategy for hepatocellular carcinoma (HCC). Strong clinical data demonstrated the effectiveness of this therapy in HCC with a significant improvement in patient outcomes. Recent studies demonstrated a strong correlation between the tumor response and the patient outcome when the tumor-absorbed dose was assessed by nuclear medicine imaging. Dosimetry plays a key role in predicting the clinical response and can be optimized using a personalized method of activity planning (multi-compartmental dosimetry). This paper reviews the main clinical results of SIRT in HCC and emphasizes the central role of dosimetry for improving it effectiveness. Moreover, some patient and tumor characteristics predict a worse outcome, and toxicity related to SIRT treatment of advanced HCC patient selection based on the performance status, liver function, tumor characteristics, and tumor targeting using technetium-99m macro-aggregated albumin scintigraphy can significantly improve the clinical performance of SIRT.

Radioembolization for Hepatocellular Carcinoma: The Effects of Arterioportal Shunts on Nontargeted Liver Hypertrophy

PurposeTo determine whether arterioportal shunting to the contralateral lobe attenuates liver function and hypertrophy of the nontargeted liver after radioembolization in patients with hepatocellular carcinoma (HCC). Materials and MethodsThe current retrospective study included 46 patients who received radioembolization for HCC contained within the right lobe between 2012 and 2020. The patients were divided into the following groups on the basis of the presence and extent of arterioportal shunting: patients with retrograde arterioportal shunting to the left lobe (contralateral group) and patients with arterioportal shunt limited to the right lobe or no arterioportal shunt (control group). Safety profiles, including adverse events, tumor response, and overall survival, were compared. With the volume of the left lateral segment used as a surrogate marker for nontarget liver, the degree of hypertrophy was compared between the 2 groups at 3 and 6 months. ResultsLiver function significantly deteriorated in the contralateral group in a month (P ≤ .05). Tumor response and overall survival did not significantly differ between the 2 groups. The degree of hypertrophy was significantly higher in the control group than in the contralateral group at 3 months (10.6% vs 3.5%; P = .008) and 6 months (20.7% vs 2.4%; P < .001). ConclusionsIn patients with arterioportal shunting to the contralateral lobe, hypertrophy of the nontarget liver may not occur and the liver function may be worsened.

Radioembolization for hepatocellular carcinoma: what clinicians need to know.

Transarterial radioembolization (TARE) with yttrium 90 (90Y) has been used in the management of hepatocellular carcinoma (HCC) for more than 10 years in Korea. There are two types of 90Y radioactive microspheres available, namely, glass and resin microspheres, with comparable clinical outcomes. In general, TARE outperforms transarterial chemoembolization regarding post-embolization syndrome, time to progression, tumor downsizing for liver transplantation, and hospitalization stay. Although TARE is commonly recommended for patients with unresectable large HCCs, it can be an alternative to or performed in combination with ablation, surgical resection, and systemic treatment. This review aimed to address 90Y radioactive microspheres, patient selection, clinical outcomes, simulation tests, radioembolization procedures, follow-up imaging, and complications.

Radioembolization of Hepatocellular Carcinoma with 90Y Glass Microspheres: No Advantage of Voxel Dosimetry with Respect to Mean Dose in Dose-Response Analysis with Two Radiological Methods.

Simple SummaryWe confirmed that the non-uniformity of an intra-lesion dose distribution, which was introduced in calculations as voxel dosimetry, did not significantly improve the AUC values of the dose–response relationship with respect to the mean dose. This was probably derived from the strong correlations (all p < 0.0001) among all voxel-based dosimetric variables (minimum Spearman correlation coefficient: 0.67) caused by the limited spatial resolution of nuclear medicine images. Responses were assessed with mRECIST and with an experimental densitometric method with a response threshold optimized at 20% HU variation. Significant dose–response agreement was obtained only with the densitometric method and only with post-therapy 90Y-PET data. More unexpectedly, the injection of Theraspheres™ on day 8 from the reference date rather than on day 4 worsened the dose–response correlation and reduced the efficacy at high doses. This may be explained by the increased non-uniformity following the non-linear mega-clustering effect triggered by the higher number of microspheres/GBq injected on day 8.In this confirmatory study, we tested if a calculation that included the non-uniformity of dose deposition through a voxel-based dosimetric variable Ψ was able to improve the dose–response agreement with respect to the mean absorbed dose D. We performed dosimetry with 99mTc-MAA SPECT/CT and 90Y-PET/CT in 86 patients treated 8 instead of 4 days after the reference date with 2.8 times more 90Y glass microspheres/GBq than in our previous study. The lesion-by-lesion response was assessed with the mRECIST method and with an experimental densitometric criterion. A total of 106 lesions were studied. Considering Ψ as a prognostic response marker, having no Ψ provided a significantly higher AUC than D. The correlation, t-test, and AUC values were statistically significant only with the densitometric method and only with post-therapy dosimetry. In comparison with our previous study, the dose–response correlation and AUC values were poorer (maximum r = 0.43, R2 = 0.14, maximal AUC = 0.71), and the efficacy at a high dose did not reach 100%. The expected advantages of voxel dosimetry were nullified by the correlation between any Ψ and D due to the limited image spatial resolution. The lower AUC and efficacy may be explained by the mega-clustering effect triggered by the higher number of microspheres/GBq injected on day 8.

Facile preparation of 177Lu-microspheres for hepatocellular carcinoma radioisotope therapy

As one of the most common cancers in the world, hepatocellular carcinoma (HCC) has become a major threat to human health. Radioembolization is a first-line option for the treatment of HCC, especially when other conventional treatments fail or there exist some relative contraindications. Herein, we developed a facile and efficient method for preparing 177Lu-microspheres potentially useful for precise radioembolization therapy of HCC. The radiolabeling efficiency of 177Lu-microspheres was as high as 96.8% ± 0.5%, and the radiolabeling process did not alter the morphology of the mother microspheres. The SPECT/CT studies enabled by the unique emissions of 177Lu suggested that almost no 177Lu ion loaded by the microspheres was released over more than 32 d in vivo, which led to remarkable inhibition effect on the growth of HepG2 tumors subcutaneously transplanted in mice. The current approach may thus offer promising 177Lu-microspheres for clinical radioembolization of HCC.

Deceased Donor Liver Transplantation After Radioembolization for Hepatocellular Carcinoma and Portal Vein Tumoral Thrombosis: A Pilot Study.

Hepatocellular carcinoma (HCC) with portal vein tumoral thrombosis (PVTT) represents a major concern especially in the field of deceased donor liver transplantation (DDLT). However, when receiving transarterial radioembolization (TARE), a considerable percentage of such patients are able to achieve a radiologic complete response with adequate survival rates. In this pilot prospective study, we evaluated the effect of TARE in downstaging HCC patients with PVTT to meet criteria for DDLT. Between May 2013 and November 2016, patients were evaluated to be enrolled into our “Superdownstaging” protocol. Patients received yttrium‐90 TARE and were enlisted for DDLT in case of complete and sustained (6 months) radiological response. Patients with tumor thrombus in the main trunk and/or in the contralateral portal vein branch were excluded. TARE was effective in downstaging and receiving DDLT in 5/17 patients (29.4%). The 5‐year overall survival was significantly higher in patients who underwent DDLT compared with those who were not transplanted (60.0% versus 0.0%, P = 0.03). Three out of 5 patients developed recurrence within 1 year after LT. The current series showed a clear survival gain in those patients who were able to receive DDLT after TARE but careful selection for DDLT is however advised.

Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences

Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3–6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time–intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (–38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.

Abstract No. 152 Aspartate aminotransferase-lymphocyte ratio: utility in hepatocellular carcinoma patients undergoing radioembolization

The aspartate aminotransferase-lymphocyte ratio (ALRI) has been found to be a general predictor of outcomes in patients with Hepatocellular Carcinoma (HCC). However, data on its utility in those undergoing radioembolization is lacking. The purpose of this study was to evaluate the usefulness of ALRI in the prediction of radiologic response and overall survival (OS) following radioembolization for hepatocellular carcinoma (HCC). A total of 159 patients who underwent radioembolization for the treatment of HCC were reviewed. The patient’s electronic medical records were evaluated for pre and post procedural laboratory values as well as radiologic response according to the European Association for the Study of the Liver (EASL) criteria. Overall radiologic response (ORR) was defined as those who showed a partial or complete response. Survival was measured from the initial radioembolization to time of death and patients were censored for transplant. Patients were separated into cohorts utilizing an ALRI of 100. The average pretreatment ALRI was 99.9 ± 195.3. When comparing those who had an ORR to those who did not the ALRI was not significantly different (93.2 ± 215.7 vs 111.2 ± 156.3, P = 0.28). When looking at those with an ALRI< 100 and ≥100 there was no significant difference in the OS (1.04 ± 0.99 vs 0.85 ± 0.7 years, P = 0.17). The percentage of patients with ALRI < 100 who had an ORR was 83.7% (77/92) and with those >100 it was 71.9% (23/32) (P = 0.14). Of those patients with both pre and post TACE ALRI values, those that demonstrated a decrease in ALRI did not differ in OS from those who did not have an increase in ALRI (1.02 ± 0.99 vs 1.13 ± 0.64 years, P = 0.39). Similarly, there was no significant difference in the ORR in those who did (68/86, 79.1%) and those who did not (18/22, 81.8%) have an increase in their ALRI following treatment (P = 0.77). ALRI does not appear to have predictive value in HCC patients undergoing treatment with radioembolization, an interesting finding as it departs from its value in patients being treated with other locoregional therapies for the same disease.

Abstract No. 153 Neutrophil-to-lymphocyte ratio may predict survival and radiologic response in those undergoing radioembolization for hepatocellular carcinoma

While neutrophil-to-lymphocyte ratio (NLR) has been found to be predictive of outcomes in some locoregional therapies utilized for hepatocellular carcinoma (HCC) therapy, data on its utility in patients treated with radioembolization (RE) is limited. The purpose of this study was to evaluate the usefulness of NLR for the prediction of radiologic response and overall survival (OS) following RE for HCC. Between January 1, 2014, and December 31, 2019, a total of a 156 patients who underwent RE for the treatment of HCC were reviewed. The patients’ electronic medical records were evaluated for pre and post procedural laboratory values as well as radiologic response according to the European Association for the Study of the Liver (EASL) criteria. Overall radiologic response (ORR) was defined as those who showed a partial or complete response. Survival was measured from the initial radioembolization to time of death and patients were censored for transplant. Patients were separated into cohorts utilizing an NLR of 4. The average age of the patients was 63.8 ± 10.3 years and the cohort consisted of 79.5% (124/156) men and 20.5% (32/156) women. The average pretreatment NLR was 5.5 ± 15.7. When dividing patients by NLR, those who had a NLR < 4 were significantly more likely to have an ORR (86/103 83.5% vs 14/23 60.9%, P = 0.02). During an average follow up of 2.92 years, 66 patients died. When looking at those with an NLR < 4 the OS was 1.1 ± 1 years, which was significantly longer than those with an NLR >4 (0.6 ± 0.5 years) (P = 0.03). Furthermore, the NLR was significantly higher in those patients who lived less than 2 years as compared to those that lived longer than 2 years (32.7 ± 24.9 vs 3.2 ± 1.4, P = 0.05). Of those who had a post treatment NLR there was no significant difference in those who demonstrated an increased NLR after treatment (0.92 ± 0.76 years) and those who did not (1.05 ± 1.15 years) in terms of OS (P = 0.29). Pretreatment NLR may predict those patients with HCC who are likely to respond to RE, furthermore lower NLR may be predictive of survival.

Prediction of tumor response and patient outcome after radioembolization of hepatocellular carcinoma using 90Y-PET-computed tomography dosimetry.

90Y-radioembolization using glass or resin microspheres is increasingly used for the treatment of hepatocellular carcinoma (HCC). The aim of this retrospective study is to determine the prognostic relevance of dosimetric parameters defined with 90Y-PET-CT obtained immediately after radioembolization. Forty-five HCC patients, mostly with multiple lesions, were treated by radioembolization between 2011 and 2017. After treatment, all underwent a 90Y PET-CT with time of flight reconstruction (90Y-TOF-PET-CT). Tumor absorbed dose and cumulative tumor dose-volume histogram were calculated using a dose point Kernel convolution algorithm. The radiological tumor response was assessed using modified (m)-RECIST criteria. Progression-free-survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression analysis. Twenty-six patients were treated with glass microspheres (73 lesions) and nineteen with resin microspheres (60 lesions). Thresholds of 118 and 61 Gy for glass and resin microspheres respectively correlate well with radiological response with a positive predictive value (PPV) of 98 and 80% and discriminate patient outcome with regard to PFS (P = 0.03 and 0.005) and OS (P = 0.003 and 0.007). Using dose volume histogram, a minimal absorbed dose of 40 Gy in 66% of the tumor volume (defined as D66) was highly predictive of radiological response (PPV = 94%), PFS (P < 0.001) and OS (P = 0. 008), for either device. Dosimetric parameters obtained using 90Y-PET-CT are predictive of tumor response, PFS and OS. In clinical practice, a systematic dosimetric evaluation using 90Y PET should be implemented to help predicting patient outcomes.

Prognostic Significance of Neutrophil to Lymphocyte Ratio Dynamics in Patients with Hepatocellular Carcinoma Treated with Radioembolization Using Glass Microspheres.

To study the prognostic significance of neutrophil and lymphocyte dynamics in patients with hepatocellular carcinoma (HCC) treated with radioembolization. A retrospective, single-center review of clinical records and treatment parameters (liver volume treated, administered activity, and radiation dose) in consecutive patients who received radioembolization for HCC was performed between August 20, 2015, and May 24, 2019. Neutrophil and lymphocyte variables associated with overall survival (OS) were determined by Barcelona Clinic Liver Cancer (BCLC) stage and were correlated with radioembolization treatment parameters. Statistical methods included Wilcoxon signed-rank test, univariate, and multivariate Cox regression analysis; receiver operating characteristic analysis; and the Kaplan-Meier method. One hundred sixty-three patients with a median 67.0 years of age were included for analysis. Eighty-one percent of patients received segmental radioembolization with a median treatment dose of 358 Gray (interquartile range 256-497). The post-treatment lymphocyte count decreased significantly in 94.5 % (p < 0.001) of patients but was not predictive of OS (p = 0.248). The pre-procedure neutrophil to lymphocyte ratio (NLRpre) was not predictive of OS (p = 0.891), and the 1-month post-procedure NLR was a borderline independent predictor of OS (p = 0.05). The NLR ratio (NLRR = NLRpost-procedure/NLRpre) (Hazard ratio [HR], 1.31; 95% Cl, 1.04-1.66) and change in NLR (ΔNLR= NLRpost-procedure - NLRpre) (HR, 1.09; 95% CI, 1.02-1.15) were associated with worse OS in BCLC C patients. NLRR (> 3.17) and ΔNLR (> 3.74) were independent predictors when adjusted for tumor presentation, treatment parameters, and liver function. Volume of liver treated and administered activity positively correlated with NLRR and ΔNLR (p < 0.001). A decrease in lymphocyte count is common after radioembolization, but of little clinical impact. Neither pre-treatment or post-treatment NLR was a predictor of survival in our study population. NLRR and ΔNLR were independent predictors of survival in BCLC stage C disease and had positive correlations with volume of liver tissue treated and administered activity.