Lobar Treatment Research Articles

Anatomical Quantitative Volumetric Evaluation of Liver Segments in Hepatocellular Carcinoma Patients Treated with Selective Internal Radiation Therapy: Key Parameters Influencing Untreated Liver Hypertrophy

Background: Factors affecting morphological changes in the liver following selective internal radiation therapy (SIRT) are unclear, and the available literature focuses on non-anatomical volumetric assessment techniques in a lobar treatment setting. This study aimed to investigate quantitative changes in the liver post-SIRT using an anatomical volumetric approach in hepatocellular carcinoma (HCC) patients with different levels of treatment selectivity and evaluate the parameters affecting those changes. This retrospective, single-institution, IRB-approved study included 88 HCC patients. Whole liver, liver segments, tumor burden, and spleen volumes were quantified on MRI at baseline and 3/6/12 months post-SIRT using a segmentation-based 3D software relying on liver vascular anatomy. Treatment characteristics, longitudinal clinical/laboratory, and imaging data were analyzed. The Student’s t-test and Wilcoxon test evaluated volumetric parameters evolution. Spearman correlation was used to assess the association between variables. Uni/multivariate analyses investigated factors influencing untreated liver volume (uLV) increase. Results: Most patients were cirrhotic (92%) men (86%) with Child–Pugh A (84%). Absolute and relative uLV kept increasing at 3/6/12 months post-SIRT vs. baseline (all, p ≤ 0.005) and was maximal during the first 6 months. Absolute uLV increase was greater in Child–Pugh A5/A6 vs. ≥B7 at 3 months (A5, p = 0.004; A6, p = 0.007) and 6 months (A5, p = 0.072; A6, p = 0.031) vs. baseline. When the Child–Pugh class worsened at 3 or 6 months post-SIRT, uLV did not change significantly, whereas it increased at 3/6/12 months vs. baseline (all p ≤ 0.015) when liver function remained stable. The Child–Pugh score was inversely correlated with absolute and relative uLV increase at 3 months (rho = −0.21, p = 0.047; rho = −0.229, p = 0.048). In multivariate analysis, uLV increase was influenced at 3 months by younger age (p = 0.013), administered 90Y activity (p = 0.003), and baseline spleen volume (p = 0.023). At 6 months, uLV increase was impacted by younger age (p = 0.006), whereas treatment with glass microspheres (vs. resin) demonstrated a clear trend towards better hypertrophy (f = 3.833, p = 0.058). The amount (percentage) of treated liver strongly impacted the relative uLV increase at 3/6/12 months (all f ≥ 8.407, p ≤ 0.01). Conclusion: Liver function (preserved baseline and stable post-SIRT) favored uLV hypertrophy. Younger patients, smaller baseline spleen volume, higher administered 90Y activity, and a larger amount of treated liver were associated with a higher degree of untreated liver hypertrophy. These factors should be considered in surgical candidates undergoing neoadjuvant SIRT.

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.

Quantitative differences in volumetric calculations for radiation dosimetry in segmental Y90 treatment planning using hybrid angiography-CT compared with anatomic segmentation.

To compare treatment volumes reconstructed from hybrid Angio-CT catheter-directed infusion imaging and Couinaud anatomic model as well as the implied differences in Y-90 radiation dosimetry. Patients who underwent transarterial radioembolization (TARE) using Y-90 glass microspheres with pretreatment CT or MRI imaging as well as intraprocedural angiography-CT (Angio-CT) were analysed. Treatment volumes were delineated using both tumoural angiosomes (derived from Angio-CT) and Couinaud anatomic landmarks. Segmental and lobar treatment volumes were calculated via semi-automated contouring software. Volume and dose differences were compared by the two-tailed Student t test or Wilcoxon signed-rank test. Factors affecting volume and dose differences were assessed via simple and/or multiple variable linear regression analysis. From September 2018 to March 2021, 44 patients underwent 45 lobar treatments and 38 patients received 56 segmental treatments. All target liver lobes and all tumours were completely included within the field-of-view by Angio-CT. Tumour sizes ranged between 1.1 and 19.5 cm in diameter. Segmental volumes and treatment doses were significantly different between the Couinaud and Angio-CT volumetry methods (316 vs 404 mL, P < .0001 and 253 vs 212 Gy, P < .01, respectively). Watershed tumours were significantly correlated with underestimated volumes by the Couinaud anatomic model (P < .001). There was a significant linear relationship between tumour diameter and percent volume difference (R2 = 0.44, P < .0001). The Couinaud model overestimated volumes for large tumours that exhibited central hypovascularity/necrosis and for superselected peripheral tumours. Angio-CT may confer advantages over the Couinaud anatomic model and enable more accurate, personalized dosimetry for TARE. Angio-CT may confer advantages over traditional cross-sectional and cone-beam CT imaging for selective internal radiation therapy planning.

For Hepatocellular Carcinoma Treated with Yttrium-90 Microspheres, Dose Volumetrics on Post-Treatment Bremsstrahlung SPECT/CT Predict Clinical Outcomes.

In transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) with Yttrium-90 (Y-90) microspheres, recent studies correlate dosimetry from bremsstrahlung single photon emission tomography (SPECT/CT) with treatment outcomes; however, these studies focus on measures of central tendency rather than volumetric coverage metrics commonly used in radiation oncology. We hypothesized that three-dimensional (3D) isodose coverage of gross tumor volume (GTV) is the driving factor in HCC treatment response to TARE and is best assessed using advanced dosimetry techniques applied to nuclear imaging of actual Y-90 biodistribution. We reviewed 51 lobar TARE Y-90 treatments of 43 HCC patients. Dose prescriptions were 120 Gy for TheraSpheres and 85 Gy for SIR-Spheres. All patients underwent post-TARE Y-90 bremsstrahlung SPECT/CT imaging. Commercial software was used to contour gross tumor volume (GTV) and liver on post-TARE SPECT/CT. Y-90 dose distributions were calculated using the Local Deposition Model based on post-TARE SPECT/CT activity maps. Median gross tumor volume (GTV) dose; GTV receiving less than 100 Gy, 70 Gy and 50 Gy; minimum dose covering the hottest 70%, 95%, and 98% of the GTV (D70, D95, D98); mean dose to nontumorous liver, and disease burden (GTV/liver volume) were obtained. Clinical outcomes were collected for all patients by chart and imaging review. HCC treatment response was assessed according to the modified response criteria in solid tumors (mRECIST) guidelines. Kaplan-Meier (KM) survival estimates and multivariate regression analyses (MVA) were performed using STATA. Median survival was 22.5 months for patients achieving objective response (OR) in targeted lesions (complete response (CR) or partial response (PR) per mRECIST) vs. 7.6 months for non-responders (NR, stable disease or disease progression per mRECIST). On MVA, the volume of underdosed tumor (GTV receiving less than 100 Gy) was the only significant dosimetric predictor for CR (p = 0.0004) and overall survival (OS, p = 0.003). All targets with less than CR (n = 39) had more than 20 cc of underdosed tumor. D70 (p = 0.038) correlated with OR, with mean D70 of 95 Gy for responders and 60 Gy for non-responders (p = 0.042). On MVA, mean dose to nontumorous liver trended toward significant association with grade 3+ toxicity (p = 0.09) and correlated with delivered activity (p < 0.001) and burden of disease (p = 0.05). Dosimetric models supplied area under the curve estimates of > 0.80 predicting CR, OR, and ≥grade 3 acute toxicity. Dosimetric parameters derived from the retrospective analysis of post-TARE Y-90 bremsstrahlung SPECT/CT after lobar treatment of HCC suggest that volumetric coverage of GTV, not a high mean or median dose, is the driving factor in treatment response and that this is best assessed through the analysis of actual Y-90 biodistribution.

Overall Survival after Y-90 Selective Internal Radiotherapy of Liver Metastases in Oligometastatic Patients

<h3>Purpose/Objective(s)</h3> Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for patients with inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients, hypothesizing that local failure after SIRT would be correlated with lower OS. <h3>Materials/Methods</h3> A retrospective, single-institution, IRB-approved study selected oligometastatic patients defined as 5 or fewer total non-CNS metastases at the time of unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. Patients were staged with CT and/or MRI. The primary endpoint was OS defined from Y-90 SIRT completion to date of death or last follow-up. Local failure was classified as progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. Failure was defined by imaging or if salvage locoregional therapy was performed. OS outcomes were calculated using the Kaplan-Meier method, and correlations with clinical variables were evaluated using log-rank testing. <h3>Results</h3> Twenty-three oligometastatic patients, with a total of 57 liver lesions, completed SIRT. The cohort was comprised of patients with colorectal adenocarcinoma (n=15), pancreatic adenocarcinoma (n=6), thymic carcinoma (n=1), and uveal melanoma (n=1). Fifteen patients (65%) received bilateral lobar SIRT and 8 (35%) received unilateral lobar treatment. Median follow up was 15.6 months (range 2.7-54.3). Twenty patients were treated with resin Y-90 microspheres and 3 received glass microspheres. On volumetric analysis of liver tumor burden, the range of liver involvement was 0.03% to 18.2%. The range of liver metastases was 1 to 5 with a median of 3. Of the 57 individual lesions treated, 19 (33%) failed. Fourteen patients (61%) failed in a treated lesion, including 9 as the first site of failure. Seven patients received salvage liver-directed therapy following intrahepatic failure; six received repeat SIRT. Seven patients did not receive post-SIRT chemotherapy, of which 5 experienced intralesional failure. Median OS (mOS) was 20.1 months, and 12-month OS was 68.6%. Metachronous versus synchronous metastasis at presentation was not found to be prognostic of OS (21.7 months vs 17.9 months (p<0.96)). Those with tumor involving <5% of the liver (n=17) had a mOS of 21.7 months vs 15.1 months for those with >5% (n=6) (p<0.12). Intralesional failure was associated with worse mOS (15.1 months vs. not reached, p<0.03). <h3>Conclusion</h3> These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low metastatic burden patients. Percentage of liver involvement may be predictive of local failure after SIRT. Larger prospective studies examining oligometastatic patients treated with SIRT are needed for further patient risk stratification.

Conventional Hepatic Volumetry May Lead to Inaccurate Segmental Yttrium-90 Radiation Dosimetry.

To compare radioembolization treatment zone volumes from mapping cone beam CT (CBCT) versus planning CT/MRI and to model their impact on dosimetry. Y90 cases were retrospectively identified in which intra-procedural CBCT angiograms were performed. Segmental and lobar treatment zone volumes were calculated with semi-automated contouring using Couinaud venous anatomy (planning CT/MRI) or tumor angiosome enhancement (CBCT). Differences were compared with a Wilcoxon signed-rank test. Treatment zone-specific differences in segmental volumes by volumetric method were also calculated and used to model differences indelivered dose using medical internal radiation dosimetry (MIRD) at 200 and 120Gy targets. Anatomic, pathologic, and technical factors likely affecting segmental volumes by volumetric method were evaluated. Forty segmental and 48 lobar CBCT angiograms and corresponding planning CT/MRI scans were included. Median Couinaud- and CBCT-derived segmental volumes were 281 and 243mL, respectively (p = 0.005). Differences between Couinaud and CBCT lobar volumes (right, left) were not significant (p = 0.24, p = 0.07). Couinaud overestimated segmental volumes in 28 cases by a median of 98mL (83%) and underestimated in 12 cases by median 69mL (20%). At a 200Gy dose target, Couinaud estimates produced median delivered doses of 367 and 160Gy in these 28 and 12 cases. At a 120Gy target, Couinaud produced doses of 220 and 96Gy. Proximal vs. distal microcatheter positioning, variant arterial anatomy, and tumor location on or near segmental watersheds were leading factors linked to volumetric differences. Use of CBCT-based volumetry may allow more accurate, personalized dosimetry for segmental Y90 radioembolization.

Tumor-to-Normal Ratio Relationship between Planning Technetium-99 Macroaggregated Albumin and Posttherapy Yttrium-90 Bremsstrahlung SPECT/CT

PurposeTo quantify the relationship of the tumor-to-normal ratio (TNR) attained from the technetium-99m macroaggregated albumin (MAA) and posttreatment yttrium-90 bremsstrahlung (Y90-Brem) single-photon emission computerized tomography (SPECT)/computer tomography (CT) studies in patients with hepatocellular carcinoma (HCC) treated with glass microspheres. Materials and MethodsRetrospectively, a total of 190 consecutive patients with HCC who underwent 204 MAA and Y90-Brem SPECT/CT for glass microsphere Y90 radiation segmentectomy (Y90-RS) or lobar treatment (Y90-RLT) between 2013 and 2018 were included. Semi-automated regions-of-interests were drawn around the targeted tumor and nontumoral liver tissue on the SPECT/CT studies. TNR values from MAA and Y90-Brem SPECT/CT were compared using paired t-tests, Pearson correlation, and median with interquartile ranges (IQR). ResultsThe mean TNR for MAA and Y90-Brem SPECT/CT was 2.96 ± 1.86 (median, 2.64; IQR, 2.50) and 2.29 ± 1.10 (median, 2.06; IQR, 1.05), respectively (P < .0001). The mean Y90-RLT TNR was 2.88 ± 1.67 (median, 2.59; IQR, 0.83) and 2.17 ± 0.89 (median, 1.98; IQR, 0.81) for MAA and Y90-Brem SPECT/CT, respectively (P < .0001). The mean Y90-RS TNR was 3.02 ± 2.01 (median, 2.87; IQR, 3.01) and 2.39 ± 1.25 (median, 2.11; IQR, 1.28) for MAA and Y90-Brem SPECT/CT, respectively (P = .0003). TNR attained from MAA and Y90 SPECT/CT studies showed a moderate correlation in a positive linear fashion for the overall (r = 0.54; P < .001), Y90-RLT (r = 0.66, P < .001), and Y90-RS cohorts (r = 0.48, P < .001). ConclusionsThe TNR attained from Y90-Brem SPECT/CT is often underestimated, positively correlated, and less variable than that attained from MAA SPECT/CT.

4:21 PM Abstract No. 246 Transarterial Y90 radioembolization of liver metastases from breast cancer

To evaluate safety and efficacy of transarterial hepatic Y90 radioembolization in patients with breast cancer liver metastases. From September 2011 to May 2018, 22 female patients with liver metastases from breast cancer and median age of 63 years (range, 31-71 years), were treated with transarterial hepatic Yttrium-90 glass microsphere radioembolization. Retrospective review of medical records and imaging studies was performed to evaluate toxicities, progression free survival, and overall survival. All patients had received prior systemic chemotherapy. The median follow-up period from radioembolization was 393 days (range, 113-1340 days). 15 patients had right lobar treatment, 4 had left lobar, 2 had segmental and 1 patient had whole-liver treatment. Survival data was analyzed by Kaplan-Meyer method. Multivariate analysis was used to compare Albumin-Bilirubin (ALBI) score, Model for end-stage liver disease (MELD) score, total bilirubin, serum albumin, alkaline phosphatase, and Ca15-3 before and at 1-month post radioembolization. Log-rank test was used to compare outcomes by factors. Common Terminology Criteria for Adverse Events (CTCAE) was used to report and grade adverse events. From the date of radioembolization, median overall survival was 13 months (95%CI, 8.6 -17.5 months), median hepatic progression free survival was 7-months (95%CI, 4.4-9.7 months) and median overall progression free survival was 3 months (95%CI, 0.7-5 months). There was no significant change in ALBI score (P = 0.74), MELD score (P = 0.619), total bilirubin (P = 0.891), serum albumin (P = 0.678), alkaline phosphatase (P = 0.928) and Ca15-3 (P = 0.222) at 1 month posttreatment. Overall survival was higher for patients with right lobar treatment (13 months) than left lobar (6 months) treatment (P = 0.08). Only 2 patients had a CTCAE of 3 after the procedure, and 20 patients had a CTCAE < 3. Transarterial Y90 radioembolization of liver metastases from breast cancer is a safe procedure with an efficacy comparable to the efficacy of transarterial chemoembolization found in literature. Limitations of the study include its retrospective nature and the low patient number.

3:45 PM Abstract No. 142 Safety and efficacy of repeat Y90 radioembolization to the same hepatic arterial territory

To investigate the safety and efficacy of repeat transarterial radioembolization (TARE) to the same hepatic territory for the treatment of residual or recurrent hepatocellular carcinoma (HCC). Between March 2011 and April 2019, 27 patients underwent TARE with Y90 glass microspheres to treat residual or recurrent HCC in the same hepatic arterial segment or lobe. Baseline demographics in addition to treatment indication, tumor distribution, Child Pugh score, and BCLC were recorded. Tumor response was documented according to modified RECIST criteria. Adverse events were graded by standardized criteria using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Kaplan-Meier survival analysis was used to analyze overall survival of repeat procedures. Mean cumulative dose after the 1st treatment was 2.53 GBq (SD: 1.04; range, 0.61-4.93) and 2nd treatment was 2.29 GBq (SD, 1.01; range, 0.92-5.46). Mean interval between treatments was 9.6 months (range, 1-53 months). Tumor responses were complete, partial, or progression in 74%, 22%, and 4% of patients respectively. Treatment administration was segmental in 48% of patients and in this group 69% had complete response, 23% had partial, and 8% had tumor progression. The remaining 52% of patients received lobar treatment with 79% showing complete response and 21% showing partial response. The incidence of radiation induced liver disease was 0%. Toxicity after 1st and 2nd treatment was seen in 22% and 11% patients respectively and were all of CTCAE grade 2. The toxicities included fever, nausea, and pain. Kaplan-Meier survival analysis in retreatment patients showed a median survival of 15.0 months (95% CI¬ 8.8-21.1). Repeat TARE with glass microspheres was a safe and effective treatment strategy for disease control in patients with recurrent or residual HCC to the same hepatic arterial territory and did not result in any instances of radiation induced liver disease. The findings of this study contradict previous literature that cites a higher risk of liver injury due to cumulative radiation to the same hepatic lobe or segment.Tabled 1Patient #Child-Pugh Score (CPS)BCLCAdverse Events After First Procedure (CTCAE Grade)Adverse Events after Second Procedure (CTCAE Grade)IndicationTumor LobeSegmental or LobarFirst Dose (GBq)Second Dose (GBq)Modified RECIST Response15 (A)BNoneNoneHCCRLobar3.043.57Partial27 (B)BNoneNoneHCCLLobar2.471.78Complete35 (A)CNoneNoneHCCLLobar2.062.22Partial47 (B)ANoneNoneHCCRSegmental2.152.12Partial56 (A)ANoneNoneHCCRSegmental2.21.7Complete65 (A)BPain to right shoulder (2), chest pain (2)Nausea and Abdominal pain (2)METRSegmental3.293.09Complete75 (A)AAbdominal Pain (2)NoneHCCRSegmental3.063.15Complete85 (A)CFevers (2)NoneHCCRSegmental4.935.46Complete95 (A)CNoneNoneHCCRLobar4.562.87Complete105 (A)ANoneNoneHCCRSegmental2.451.22Complete116 (A)ANoneNoneHCCRSegmental3.411.21Complete126 (A)ANoneNoneHCCRLobar2.863.12Complete137 (A)AAbdominal Pain (2)NoneHCCRLobar1.692.4Complete145 (A)ANoneAbdominal Pain and nausea (2)HCCRSegmental2.853.08Partial155 (A)BNoneNoneHCCLSegmental2.770.92Progression165 (A)ANoneNoneHCCRSegmental0.611.11Complete176 (A)ANoneAbdominal Pain and nausea (2)HCCRLobar0.992.85Complete186 (A)ANoneNoneHCCRSegmental1.073.29Complete195 (A)ANoneNoneCholangiocarcinomaRLobar1.641.32Complete207 (A)AFevers (2)NoneHCCRSegmental3.632.16Complete215 (A)BNoneNoneHCCRLobar1.952.26Complete225 (A)CAbdominal Pain (2)NoneHCCRSegmental2.52.61Partial235 (A)ANoneNoneHCCRLobar3.572.59Complete245 (A)ANoneNoneHCCRLobar1.280.94Complete256 (A)BNoneNoneHCCRLobar1.781.35Partial265 (A)ANoneNoneHCCRLobar2.031.63Complete275 (A)BNoneNoneHCCRLobar Open table in a new tab

Quantifying the effects of absorbed dose from radioembolisation on healthy liver function with [99mTc]TcMebrofenin.

To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9Gy) and those that decreased their functional burden (35Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.

Intra arterial treatment of hepatocellular carcinoma: Comparison of MELD score variations between radio-embolization and chemo-embolization

PurposeThe purpose of this study was to assess liver function deterioration, as assessed using the model for end-stage liver disease (MELD) score variations, following transarterial chemo-embolization (TACE) versus selective internal radiation therapy (SIRT) in patients with unresectable unilobar hepatocellular carcinomas (HCC). Patients and methodsWe retrospectively evaluated all patients who underwent a single conventional TACE or SIRT procedure in our department from May 2013 to May 2018 for unilobar unresectable HCC. A total of 86 patients (76 men, 20 women; mean age, 65.5 years) were included. There were 63 patients in the TACE group [56 men, 7 women; mean age, 65.1±9.6 (SD) years] and 23 patients in the SIRT group [20 men, 3 women; mean age, 70±9.2 (SD) years]. Delta MELD, defined as post treatment minus pre-treatment MELD score, was considered for liver function deterioration and compared between patients who underwent single lobar treatment of SIRT versus TACE. ResultsPatients in SIRT group had significant higher tumor burden, alpha-fetoprotein serum level, and rates of macroscopic vessel invasion. Mean pre-treatment MELD scores did not differ between TACE [mean, 8.41±1.71 (SD); range: 7.24–9.24] and SIRT groups [mean, 8.36±1.74 (SD); range: 7.07–9.21] (P=0.896) as well as Child-Pugh class and albumin-bilirubin (ALBI) grade distribution. However, following treatment, mean DeltaMELD was greater in TACE group (mean, 0.83±1.83 [SD]; range: −0.30–−1.31) than in SIRT group (mean, −0.13±1.06 [SD]; range: −0.49–0.32) (P=0.021). At multivariate analysis, SIRT treatment was independently associated with a lower DeltaMELD score than TACE (R=−0.955 [−1.68; −0.406]; P=0.017;). ConclusionWhereas performed in patients with higher tumor burden, SIRT resulted in lower degrees of liver function worsening as assessed using MELD score variations.

Predictors of Response to Endobronchial Coil Therapy in Patients With Advanced Emphysema

The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment. The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy. Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response. In total, 125 patients underwent coil treatment and had evaluable 12-month follow-up results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]+), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVM+ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200%predicted, emphysema score > 20%low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean ± SE improvement in FEV1 (15.2 ± 3.1%), St. George's Respiratory Questionnaire (-12 ± 2points), and residual volume (-0.57 ± 0.13 L). This post hoc analysis found that both significant hyperinflation (residual volume≥ 200%predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (< 20%low attenuation area), whereas visual assessment identifies patients with signs of airway disease associated with worse outcomes. ClinicalTrials.gov; No.: NCT01608490; URL: www.clinicaltrials.gov.

3:27 PM Abstract No. 264 PI3K pathway mutations predict response on PET/CT after radioembolization as salvage therapy for heavily pretreated patients with breast cancer liver metastases

Transarterial radioembolization (RE) is an emerging treatment for patients with hepatic metastasis due to breast cancer. This single-center retrospective review was conducted to identify factors predicting favorable outcomes and survival after RE. Thirty-one heavily pretreated female patients underwent RE between January 2011 and September 2017 (9 with glass and 22 with resin microspheres). Of these, 24 also underwent next-generation genetic sequencing with MSK-IMPACT or Sequenom, and 26 had PET/CTs available to document imaging response performed on average 38 ± 35 before and 80 ± 33 days after RE. Response was categorized as complete response when the SUVmax in the targeted liver segments decreased by >80%, partial response when SUVmax decreased by 30-80%, stable disease when a change in by normalized SUVmax between -30% and 30%, and progressive disease when normalized SUVmax increased by more than 30%. Kaplan-Meier survival analysis demonstrated a median survival after RE of 10.8 months. Complete or partial response was achieved in 18/26 (69%). PI3K pathway mutations were associated with imaging response (p = 0.006) but not survival (p = 0.58). Imaging response predicted longer survival (p = 0.005). Trends for lower bilirubin levels (p = 0.15), lower preprocedure neutrophil-to-lymphocyte ratio (p = 0.06), younger age (p = 0.15), and lower total bilirubin level (p = 0.06) to predict improved survival were not significant. Mutations in TP53, the MAPK-ERK pathway, hormonal status, and preradioembolization imaging variables (lung shunt fraction, arterial enhancement fraction, or tumor burden) did not correlate with imaging response (p>0.05). Three (9.6%) patients had major adverse events after resin microsphere-radioembolization, including two with gastric ulcers managed conservatively and one with liver failure and death 26 days after the first lobar treatment. These preliminary observations confirm the prognostic relevance of early interval follow-up imaging after RE to survival. Furthermore, these data suggest that genomic profiling may help predict which metastatic breast cancer patients could benefit most from RE.

Abstract No. 278 - Radioembolization for recurrent hepatocellular carcinoma after surgical resection: safety and long-term outcomes

The aim of this study is to assess safety/efficacy of yttrium-90 radioembolization (Y90) in patients with recurrent hepatocellular carcinoma (HCC) who have previously undergone surgical resection. With IRB approval, we searched our prospectively acquired database for consecutive patients with recurrent HCC following surgical resection that subsequently underwent Y90. Baseline characteristics and bilirubin toxicities (CTCAE v 4.0) following Y90 were evaluated. Intention to treat survival following date of first Y90 was calculated using Kaplan-Meier analysis. 39 patients met study inclusion criteria; median time from HCC surgical resection to first radioembolization was 19 months (95% CI: 13-37). The mean number of Y90 treatment sessions was 1.8 (range: 1-5). 9 patients received lobar treatment while 30 patients received selective (≤2 hepatic segments) treatment. Grade 1/2/3/4 bilirubin toxicity was seen in 7(17.9%)/4(10.2%)/5(12.8%)/1(2.5%) patients following Y90. No statistically significant differences in grade 1/2/3/4 bilirubin toxicities was identified when lobar [4(44%)/3(33%)/1(11%)/0] or selective [3(10%)/1(3%)/4(13%)/1(3%)] approach was utilized (P = 0.27). Two patients (5%) had biliary-enteric anastomoses during surgical resection. No post-Y90 infectious complications were identified. The median survival of the cohort is 30.3 months (CI: 12.2-46.7). Four patients went on to undergo liver transplantation. Radioembolization is a safe and effective method to treat recurrent HCC following surgical resection. No statistically significant difference in bilirubin toxicity was identified between patients who received lobar or selective treatments.

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres.

Yttrium-90 (90Y)-resin microspheres can prolong intrahepatic disease control and improve overall survival (OS) in patients with metastatic colorectal cancer (CRC). Prognostic factors for improved outcomes in patients undergoing selective internal radiation therapy (SIRT) have been studied, but the relationship between pre-SIRT liver tumor volume and outcomes has not well described. We retrospectively reviewed the records of patients with metastatic CRC who were treated at our institution with 90Y-resin microspheres. Each patient underwent either MR or CT imaging of the liver with intravenous (IV) contrast before and within ~2-3 months after SIRT. Imaging data were transferred into our treatment planning system. Each metastatic liver lesion was contoured, and the volume of each lesion was summed to determine the total liver tumor volume at a given time point. We evaluated whether pretreatment liver tumor volume was related to OS. We also evaluated the relationship between pre-SIRT tumor volume and radiographic treatment response by either unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) or three-dimensional volumetric criteria. We included 60 patients with a median age of 59 years (range, 38-97 years); 60% of patients received sequential lobar treatment. The median number of chemotherapy cycles received prior to SIRT was 2. Median follow-up from first SIRT was 8.9 months. Pre- and post-SIRT tumor volumes were primarily calculated on CT (87%). The median pre-SIRT tumor volume was 77 cc (range, 4.5-2,170.4 cc). The median intervals between the first SIRT and the first, second, and third follow-up scans were 2.2, 4.4, and 7.7 months, respectively. No patient experienced a radiographic complete response. Pretreatment volume was a significant predictor for estimating the odds of a patient having stable disease or partial response using volumetric response criteria at first (P=0.016), second (P=0.023), and third (P=0.015) follow-ups. For each unit increase in log volume, a patient's odds of having a stable or partial response were 0.57, 0.63, and 0.61 times as likely at first, second, and third follow-up, respectively. OS was not significantly associated with pretreatment tumor volume. Patients with metastatic CRC with larger overall pretreatment liver tumor volumes, regardless of number of individual liver lesions, are less likely to have radiographic evidence of stable disease or partial response following SIRT using volumetric response criteria. However, pretreatment volume was not significantly associated with OS, and thus SIRT should be considered for patients with larger pretreatment volumetric tumor burden.

Safety, Efficacy, and Prognostic Factors After Radioembolization of Hepatic Metastases from Breast Cancer: A Large Single-Center Experience in 81 Patients.

The present study evaluated safety, efficacy, and prognostic factors for (90)Y-yttrium microsphere radioembolization of unresectable liver metastases from breast cancer. Eighty-one patients were treated with radioembolization. Acute toxicity was monitored through daily physical examination and serum tests until 3 d after radioembolization; late toxicity was evaluated until 12 wk after radioembolization. Overall survival and response according to (18)F-FDG PET (>30% decrease of tracer uptake) and CA15-3 serum level (any decline) were recorded. Pretherapeutic characteristics, including pretreatment history, liver function tests, and PET/CT parameters, were assessed by univariate and subsequent multivariate Cox regression for predicting patient survival. A toxicity grade of 3 or more based on clinical symptoms, bilirubin, ulcer, pancreatitis, ascites, or radioembolization-induced liver disease occurred in 10% or less of patients. Two patients eventually died from radioembolization-induced liver disease. Sequential lobar treatment and absence of prior angiosuppressive therapy were both associated with a lower rate of serious adverse events. On the basis of PET/CA15-3 criteria, 52/61% of patients responded to treatment. Median overall survival after radioembolization was 35 wk (interquartile range, 41 wk). Pretherapeutic tumor burden of the liver greater than 50% or more (P< 0.001; hazard ratio, 5.67; 95% confidence interval, 2.41-13.34) and a transaminase toxicity grade of 2 or more (P= 0.009; hazard ratio, 2.15; 95% confidence interval, 1.21-3.80) independently predicted short survival. Radioembolization for breast cancer liver metastases shows encouraging local response rates with low incidence of serious adverse events, especially in those patients with sequential lobar treatment or without prior angiosuppressive therapy. High hepatic tumor burden and liver transaminase levels at baseline indicate poor outcome.

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

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

Double-Blinded, Randomized Phase II Study Using Embolization with or without Granulocyte–Macrophage Colony-Stimulating Factor in Uveal Melanoma with Hepatic Metastases

PurposeTo investigate the effects of immunoembolization with granulocyte–macrophage colony-stimulating factor (GM-CSF) in patients with uveal melanoma (UM) with liver-only metastasis. Materials and MethodsIn this double-blind phase II clinical trial, patients were randomized to undergo immunoembolization or bland embolization (BE). Lobar treatment was performed with GM-CSF or normal saline solution mixed with ethiodized oil followed by embolization with gelatin sponge emulsified with iodinated contrast medium. Fifty-two patients (immunoembolization, n = 25; BE, n = 27) were enrolled. Response was assessed after every two treatments. The primary endpoint was overall response rate (ORR) of liver metastases. Progression-free survival (PFS), overall survival (OS), and immunologic responses were secondary endpoints. ResultsThere were five partial responses in the immunoembolization group (ORR, 21.2%; 90% confidence interval [CI], 10.3%–30.5%) and three in the BE group (ORR, 16.7%; 90% CI, 6.3%–26.9%). Stable disease was seen in 12 patients in the immunoembolization group and 19 in the BE group. OS times were 21.5 months (95% CI, 18.5–24.8 mo) with immunoembolization and 17.2 months (95% CI, 11.9–22.4 mo) with BE. The degree of proinflammatory cytokine production was more robust after immunoembolization and correlated with time to “systemic” extrahepatic progression. In the immunoembolization group, interleukin (IL)-6 levels at 1 hour (P = .001) and IL-8 levels at 18 hours after the procedure (P < .001) were significant predictors of longer systemic PFS. Moreover, a dose–response pattern was evident between posttreatment serum cytokine concentrations and systemic PFS. ConclusionsImmunoembolization induced more robust inflammatory responses, which correlated with the delayed progression of extrahepatic systemic metastases.

Defeating the pores of Kohn

In the treatment of emphysema with an endobronchial valve, entire lobar treatment is important in achieving adequate atelectasis. This case illustrates that without treatment of the entire lobe, it can fail to collapse even after several years, leading to treatment failure. Intralobar collateral ventilation through the pores of Kohn is demonstrated in this case, as endobronchial valve blockage of the remaining patent anterior segment resulted in the desired atelectasis and significant improvements in pulmonary function.

Splenomegaly-Associated Thrombocytopenia After Hepatic Yttrium-90 Radioembolization

Thrombocytopenia is often observed after yttrium-90 radioembolization (RE). Possible mechanisms include radiation toxicity to the bone marrow, consumption in the liver due to local radiation effects, and sequestration in the spleen. We sought to identify the causative factors. Patients with complete baseline and 3-month post-RE imaging and laboratory data were included in this retrospective analysis. Univariate and multivariate regression analyses were performed on clinical, procedural, and imaging data. A total of 116 patients were identified (65 male, 51 female; median age 64years). Forty-six patients were treated for primary and 70 for metastatic liver malignancy. Of these, 86 were treated with resin and 30 with glass microspheres; median activity was 1.85GBq. Eighty-three patients underwent whole-liver treatment. Maximum individual change in platelet count was -20.2% leading to new or increased grade of thrombocytopenia in 48 patients (41.4%) by National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.02 criteria. Independent risk factors for decreased platelet count included change in spleen volume (median change +17.5%; p=0.001) and whole-liver (rather than lobar or segmental) treatment (p=0.025). Administered activity and absorbed dose were not associated with change in platelet count. The change in spleen volume itself was associated with previous epidermal growth factor receptor-inhibitor treatment (p=0.002), whole-liver absorbed dose (p=0.027), and multiple-line chemotherapy (0.012) for whole-liver treatments only. Post-RE treatment increase of spleen volume is correlated with decreased peripheral platelet count suggesting a mechanism of increased portal hypertension and hypersplenism being responsible.