Voxel-based dosimetry predicting treatment response and related toxicity in HCC patients treated with resin-based Y90 radioembolization: a prospective, single-arm study.

BACKGROUND: There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC). PURPOSE: To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization. MATERIALS AND METHODS: This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs. RESULTS: N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively. CONCLUSION: In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes. CLINICAL TRIAL NUMBER: NCT04172714.

Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial.

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 (90Y) (scout90Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic 90Y (Rx90Y) dose for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout90Y. Rx90Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout90Y were compared with those by Rx90Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout90Y and MAA with that of Rx90Y. The safety of scout90Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout90Y. RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx90Y. Scout90Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx90Y. Furthermore, the TNR and LSF of scout90Y had a stronger agreement with those of Rx90Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx90Y, whereas scout90Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout90Y had a strong linear correlation with the TD and NTLD of Rx90Y. CONCLUSIONS: Compared with MAA, scout90Y is a more accurate surrogate for Rx90Y biodistribution for nonsegmental therapies.

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

PURPOSE: To 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 METHODS: Retrospectively, 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). RESULTS: The 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). CONCLUSIONS: The TNR attained from Y90-Brem SPECT/CT is often underestimated, positively correlated, and less variable than that attained from MAA SPECT/CT.

Contemporary Cardiac SPECT Imaging-Innovations and Best Practices: An Information Statement from the American Society of Nuclear Cardiology.

This information statement from the American Society of Nuclear Cardiology highlights advances in cardiac SPECT imaging and supports the incorporation of new technology and techniques in laboratories performing nuclear cardiology procedures. The document focuses on the application of the latest imaging protocols and the utilization of newer hardware and software options to perform high quality, state-of-the-art SPECT nuclear cardiology procedures. Recommendations for best practices of cardiac SPECT imaging are discussed, highlighting what imaging laboratories should be doing as the standard of care in 2018 to achieve optimal results (based on the ASNC 2018 SPECT guideline [Dorbala et al., J Nucl Cardiol. 2018. https://doi.org/10.1007/s12350-018-1283-y ]).

Is There a Role for PET/CT Parameters to Characterize Benign, Malignant, and Metastatic Parotid Tumors?

OBJECTIVE: Assessment of benign and malignant lesions of the parotid gland, including metastatic lesions, is challenging with current imaging methods. Fluorine-18 FDG PET/CT is a noninvasive imaging modality that provides both anatomic and metabolic information. Semiquantitative data obtained from PET/CT, also known as PET/CT parameters, are maximum, mean, or peak standardized uptake values (SUVs); metabolic tumor volume; total lesion glycolysis; standardized added metabolic activity; and normalized standardized added metabolic activity. Our aim was to determine whether FDG PET/CT parameters can differentiate benign, malignant, and metastatic parotid tumors. MATERIALS AND METHODS: Thirty-four patients with parotid neoplasms underwent PET/CT before parotidectomy; maximum SUV, mean SUV, peak SUV, total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity were calculated on a dedicated workstation. Univariate analyses were performed. A ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven benign, malignant, and metastatic parotid gland neoplasms. RESULTS: Fourteen patients had a benign or malignant primary parotid tumor. Twenty had metastases to the parotid gland. When the specificity was set to at least 85% for each parameter to identify cut points, the corresponding sensitivities ranged from 15% to 40%. Assessment of benign versus malignant lesions of parotid tumors, as well as metastasis from squamous cell carcinoma versus other metastatic causes, revealed that none of the PET/CT parameters has enough power to differentiate among these groups. CONCLUSION: PET/CT parameters, including total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity, are not able to differentiate benign from malignant parotid tumors, primary parotid tumors from metastasis, or metastasis from squamous cell carcinoma and nonsquamous cell carcinoma metastasis.

(90)Y Radioembolization: Multimodality Imaging Pattern Approach with Angiographic Correlation for Optimized Target Therapy Delivery.

Primary and metastatic liver cancers are responsible for considerable morbidity and mortality, and many patients are not curable at presentation. Therefore, new therapies such as radioembolization with yttrium 90 ((90)Y)-labeled microspheres are an alternative method to treat patients with unresectable primary or secondary liver tumors. Patient selection, treatment technique, and early recognition of potential complications are the keys for successful patient outcomes. The activity of administered (90)Y microspheres depends on multiple variables, including the tumor burden, the volume of the liver lobe to be treated, the type of (90)Y microspheres, and the hepatopulmonary shunt fraction. Preprocedural planning relies on the results of cross-sectional imaging to determine the extent of disease, tumoral and nontumoral liver volumes, patency of the portal vein, and the degree of extrahepatic disease. A multidisciplinary approach that combines expertise in cross-sectional imaging, nuclear medicine, and flow dynamics is critical to adequately target malignant tissue. Preprocedural multimodality imaging, particularly combined single photon emission computed tomography (SPECT) and computed tomography (CT) imaging (SPECT/CT), may be used to identify nontarget imaging patterns that, if recognized, can potentially be corrected with either branch vessel embolization or catheter repositioning. Postprocedural multimodality imaging is also useful to confirm the appropriate delivery of (90)Y microspheres, enabling early identification of potential complications and the adequacy of microsphere distribution, thereby optimizing planning for subsequent therapies.

Quantitative dosimetry for yttrium-90 radionuclide therapy: tumor dose predicts fluorodeoxyglucose positron emission tomography response in hepatic metastatic melanoma.

PURPOSE: To assess a new method for generating patient-specific volumetric dose calculations and analyze the relationship between tumor dose and positron emission tomography (PET) response after radioembolization of hepatic melanoma metastases. METHODS AND MATERIALS: Yttrium-90 ((90)Y) bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) acquired after (90)Y radioembolization was convolved with published (90)Y Monte Carlo estimated dose deposition kernels to create a three-dimensional dose distribution. Dose-volume histograms were calculated for tumor volumes manually defined from magnetic resonance imaging or PET/CT imaging. Tumor response was assessed by absolute reduction in maximum standardized uptake value (SUV(max)) and total lesion glycolysis (TLG). RESULTS: Seven patients with 30 tumors treated with (90)Y for hepatic metastatic melanoma with available (90)Y SPECT/CT and PET/CT before and after treatment were identified for analysis. The median (range) for minimum, mean, and maximum dose per tumor volume was 16.9 Gy (5.7-43.5 Gy), 28.6 Gy (13.8-65.6 Gy) and 36.6 Gy (20-124 Gy), respectively. Response was assessed by fluorodeoxyglucose PET/CT at a median time after treatment of 2.8 months (range, 1.2-7.9 months). Mean tumor dose (P = .03) and the percentage of tumor volume receiving ≥ 50 Gy (P < .01) significantly predicted for decrease in tumor SUV(max), whereas maximum tumor dose predicted for decrease in tumor TLG (P < .01). CONCLUSIONS: Volumetric dose calculations showed a statistically significant association with metabolic tumor response. The significant dose-response relationship points to the clinical utility of patient-specific absorbed dose calculations for radionuclide therapy.

A simple method for estimating dose delivered to hepatocellular carcinoma after yttrium-90 glass-based radioembolization therapy: preliminary results of a proof of concept study.

PURPOSE: To investigate a simple semiquantitative method to estimate yttrium-90 ((90)Y) dose delivered with radioembolization to infiltrative hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In a prospective study, patients with infiltrative HCC and portal vein thrombosis (PVT) underwent glass-based (90)Y radioembolization including technetium-99m macroaggregated albumin ((99m)Tc-MAA) hepatopulmonary shunt study before therapy and bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) after (90)Y radioembolization. Baseline magnetic resonance imaging was coregistered with (99m)Tc-MAA and bremsstrahlung SPECT/CT imaging separately. Unit tumor activity ((90)Y radioactivity delivered to each cubic centimeter of tumor) was estimated based on a lobar infusion approach. Correlation between proportions of (99m)Tc-MAA and (90)Y delivered to the tumor was investigated. Survival analysis was performed using Kaplan-Meier estimations. RESULTS: (90)Y therapy was administered in 18 consecutive patients (median age, 55.3 y; mean tumor volume, 588 cm(3)). Higher intratumoral (90)Y dose predicted prolonged survival, with 13.2-month median survival in patients with HCC and mean (90)Y dose of ≥ 100 Gy versus 4.6-month median survival for other patients (P < .001). Of administered (90)Y dose, 51.9% was delivered to the targeted tumors compared with 74.1% of (99m)Tc-MAA with linear correlation between biodistribution of (99m)Tc-MAA and (90)Y observed (Pearson r = 0.774, P < .001). CONCLUSIONS: The findings in this study suggest that approximately 50% of administered (90)Y dose is taken up by targeted infiltrative HCC with PVT. Intratumoral (90)Y dose ≥ 100 Gy in unresectable infiltrative HCC via a lobar intraarterial approach is a positive prognostic factor for survival.

Diagnostic performance of low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT using the 530c CZT camera: quantitative vs visual analysis.

BACKGROUND: We set out to develop normal databases and prospectively validate abnormality criteria for a low-dose Tc-99m tetrofosmin myocardial perfusion SPECT protocol using the 530c CZT camera. METHODS: All patients received 6 mCi rest/20 mCi stress doses of Tc-99m tetrofosmin. Rest and stress images were obtained over 7-9 and 5-7 minutes according to the chest size. Low-dose CT of the chest was obtained on a standalone CT scanner. Forty patients with very low likelihood (LLK) of coronary artery disease (CAD) were used to define the normal count distributions. The abnormality criteria were prospectively validated in 55 patients who had coronary angiography and in 40 patients with LLK of CAD. RESULTS: The results for quantitative non-attenuation-corrected (AC) and AC analysis and visual analysis were as follows: sensitivity of 79%, 85%, and 92% (P = NS) and specificity of 44%, 75%, and 56% (P = NS), respectively. The normalcy rates for quantitative non-AC and AC analyses and visual analysis were 95%, 98%, and 98% (P = NS). CONCLUSIONS: We have developed non-AC and AC normal databases for low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT protocol using the 530c CZT camera. The per-patient diagnostic performance of quantitative analyses is not significantly different from visual analysis by an experienced reader.

Resin-Based 90 Y Tumor Dose as a Predictor of Duration of Response and Survival in Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study.

BACKGROUND: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization. PATIENTS AND METHODS: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival. FINDINGS: Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR. INTERPRETATION: For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes.

Myocardial perfusion imaging-derived left ventricular strain: Regional abnormalities associated with transthyretin cardiac amyloidosis.

Background: Transthyretin (ATTR) cardiac amyloidosis is associated with an apical-sparing strain pattern on TTE. We hypothesize that strain indices derived from myocardial perfusion imaging (MPI) can identify this abnormality. Methods: A group with ATTR amyloidosis was compared to age-matched controls with LVH but without amyloidosis who underwent PET or SPECT MPI. Strain values were used to calculate the apical strain index (ASI), apex-to-base ratio (ABR), and ejection fraction to global strain ratio in multiple planes. Results: A direct comparison using Welch's t-tests reveals 6 statistically significant metrics. After regression analysis, the circumferential ASI and ABR at rest remain significantly greater in the ATTR group compared to controls. Conclusion: MPI-derived strain from the circumferential plane at rest may distinguish cardiac amyloidosis from other forms of LVH. If these findings are confirmed with validation studies, routine MPI-derived strain analysis could identify patients with subclinical amyloidosis who may benefit from further testing.

CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent.

BACKGROUND: the objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow-derived CD34(+) cells after ST elevation myocardial infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells. METHODS: patients were randomized to bone marrow harvest (n = 16) or control (n = 15). At a median of 8.3 days after coronary stenting for STEMI, CD34(+) cells were infused via the IRA at 3 dose levels (5, 10, and 15 × 10(6)) in cohorts of 5 patients each. Baseline and follow-up imaging and ex vivo CD34(+) cell mobility were performed. RESULTS: Cell harvest and infusion were safe. Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the ≥ 10 million cohorts compared with controls (-256 vs +14, P = .02). There was a trend toward improved ejection fraction at 6 months (+4.5%) in the ≥ 10 million cohorts compared with no change in the controls and 5 million cohort (+0.7%). Improved perfusion and infarct size reduction correlated with the quantity and mobility of the infused CD34(+) cells. CONCLUSIONS: the effects of CD34(+) cell IRA infusion during the repair phase after STEMI are dose dependent and, at a threshold dose of 10 million CD34(+) cells, associated with a significant improvement in perfusion that may limit deterioration in cardiac function (IRA infusion of CD34(+) cells in patients with acute myocardial infarction [AMR-01] NCT00313339).

Characterization of mechanical dyssynchrony measured by gated single photon emission computed tomography phase analysis after acute ST-elevation myocardial infarction.

BACKGROUND: Left ventricular dyssynchrony is an adverse consequence of ST-elevation myocardial infarction (STEMI) and bears an unfavorable prognosis. Mechanical dyssynchrony as measured by phase analysis from gated single photon emission computed tomography (GSPECT) correlates well with other imaging methods of assessing dyssynchrony but has not been studied in STEMI. We hypothesized that systolic dyssynchrony as measured by GSPECT would correlate with adverse remodeling after STEMI. METHODS: In 28 subjects suffering STEMI, GSPECT with technetium-99m sestamibi was performed immediately after presentation (day 5) and remotely (6 months). Parameters of left ventricular dyssynchrony (QRS width, histogram bandwidth (HBW) and phase standard deviation (PSD)) were measured from GSPECT using the Emory Cardiac Toolbox. Left ventricular volumes, ejection fraction (LVEF) and infarct size were also assessed. RESULTS: After successful primary percutaneous coronary intervention to the infarct-related artery, subjects had an LVEF of 46.4% ± 11% and a resting perfusion defect of 27.4% ± 16% at baseline. Baseline QRS width was normal (91.5 ± 17.5 ms). Subjects with STEMI had dyssynchrony compared with a cohort of 22 normal subjects (age 57.2 ± 10.6 years, <5% perfusion defect) by both HBW (100.3° ± 70.7° vs 26.5° ± 5.3°, P < .0001) and PSD (35.3° ± 16.9° vs 7.9° ± 2.1°, P < .0001). Baseline HBW correlated with resting perfusion defect size (r = 0.67, P < .001), end-systolic volume (r = 0.72, P < .001), end-diastolic volume (r = 0.63, P = .001), and inversely with LVEF (r = -0.74, P < .001). HBW and PSD improved over the follow-up period (-24.1 ± 35.9 degrees, P = .003 and -8.7° ± 14.6°, P = .006, respectively), and improvement in HBW correlated with reduction in LV end-systolic volumes (r = 0.43, P = .034). Baseline HBW and PSD, however, did not independently predict LVEF at 6 months follow-up. CONCLUSIONS: After STEMI, subjects exhibit mechanical dyssynchrony as measured by GSPECT phase analysis without evidence of electrical dyssynchrony. Improvement in mechanical dyssynchrony correlates with beneficial ventricular remodeling. The full predictive value of this measure in post-infarct patients warrants further study.

Determination of Tumor Dose Response Thresholds in Patients with Chemorefractory Intrahepatic Cholangiocarcinoma Treated with Resin and Glass-based Y90 Radioembolization.

PURPOSE: To compare the efficacies of glass and resin-based Yttrium-90 microspheres by comparing absorbed tumor dose (TD) with both tumor response (TR) and overall survival (OS) in patients with chemorefractory intrahepatic cholangiocarcinoma (ICC). METHODS: Post-Y90 treatment bremsstrahlung SPECT/CT of 38 consecutive patients receiving 45 treatments (21 resin microspheres, 24 glass microspheres) were analyzed retrospectively. MIM software v6.9.4 (MIM Software Inc, Cleveland, OH) was used to calculate targeted tumors' dose volume histogram. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response 3 months post-treatment. Kaplan Meier estimation was used for survival analysis. T-test was used to compare the devices on various dosimetric parameters. RESULTS: Thresholds for TD to predict TR with ≥ 80% specificity were as follows: mean TD (Resin: 78.9 Gy; Glass: 254.7 Gy), maximum TD (Resin: 162.9 Gy; Glass: 591 Gy), minimum TD (Resin: 53.7 Gy; Glass: 149.1 Gy). Microsphere type had no effect on survival from first Y90 (Resin: 11.2 mo; Glass 10.9 mo [p = 0.548]). In patients receiving resin microspheres, mean TD ≥ 75 Gy or maximum TD ≥ 150 Gy was associated with median OS of 20.2 mo compared to 6.5 mo for those receiving less (p = 0.001, 0.002, respectively). For patients treated with glass microspheres, those receiving a mean TD ≥ 150 Gy had a median OS of 14.6 mo vs. 2.6 mo for those receiving less (p = 0.031). CONCLUSION: TD thresholds predictive of TR and OS differ significantly between glass and resin microspheres. However, microsphere type has no impact on survival in patients with chemorefractory ICC. LEVEL OF EVIDENCE: Level 3, Retrospective Study.