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.

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.

Same day yttrium-90 radioembolization with single photon emission computed tomography/computed tomography: An opportunity to improve care during the COVID-19 pandemic and beyond.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has made it more challenging for patients to undergo yttrium-90 (Y-90) radioembolization (RE). Same day Y-90 RE provides an opportunity to minimize logistical challenges and infection risk associated with COVID-19, thus improving patient access. AIM: To describe the use of same day Y-90 RE with routine single photon emission computed tomography/computed tomography (SPECT/CT) in order to optimize therapy. METHODS: All patients were selected for Y-90 RE through a multidisciplinary tumor board, and were screened and tested for COVID-19 infection per institutional protocol. A same day procedure was developed, consisting of angiography, imaging, and Y-90 resin particle delivery. Routine SPECT/CT after technetium-99m macroaggregated albumin (Tc-99m MAA) administration was performed for assessment of arterial supply, personalized dosimetry, and extrahepatic activity. Post-treatment Y-90 bremsstrahlung SPECT/CT was performed for confirmation of particle delivery, by utilization of energy windowing to limit signal from previously administered Tc-99m MAA particles. RESULTS: A total of 14 patients underwent same day Y-90 RE between March and June 2020. Mean lung shunt fraction was 6.13% (range 3.5%-13.1%). Y-90 RE was performed for a single lesion in 7 patients, while the remaining 7 patients had treatment of multifocal lesions. The largest lesion measured 8.3 cm. All patients tolerated the procedure well and were discharged the same day. CONCLUSION: Same day Y-90 RE with resin-based microspheres is feasible, and provides an opportunity to mitigate infection risk and logistical challenges associated with the COVID-19 pandemic and beyond. We recommend consideration of SPECT/CT, especially among patients with complex malignancies, for the potential to improve outcomes and eligibility of patients to undergo same day Y-90 RE.

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.

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.

Yttrium-90 dosimetry and implications on tumour response and survival after radioembolisation of chemo-refractory hepatic metastases from breast cancer.

PURPOSE: The aim of the study was to evaluate the effects of tumour dose on tumour response and overall survival (OS) in patients with chemo-refractory metastatic breast cancer (MBC) to the liver undergoing yttrium-90 radioembolisation (Y90 RE). MATERIALS AND METHODS: In 20 consecutive patients with chemo-refractory MBC to the liver undergoing 33 total Y90 RE resin treatments, volumes of interest were drawn around the five largest tumours of the targeted liver lobe on post-Y90 RE Bremsstrahlung single-photon emission computed tomography/computed tomography using MIM software v.6.9 (MIM Software, Cleveland, Ohio, USA) and dose-volume histograms were calculated. Response Evaluation Criteria in Solid Tumours (RECIST) was used to determine tumour response at 3 months. Receiver operating characteristics (ROC) curves were used to determine thresholds for various dosimetry parameters. Kaplan-Meier estimation was used to determine OS. RESULTS: Overall, 11 of 33 (33%) Y90 RE treatments resulted in complete or partial response according to RECIST criteria with a median OS of 20.97 months compared to 11.73 months for nonresponders (P = 0.003). Mean tumour dose, defined as the aggregate tumour dose of up to the five largest tumours in the targeted lobe, was the most predictive of tumour response with the highest area under the ROC curve of 0.967. Mean tumour dose >70 Gy had 91% sensitivity and 100% specificity for predicting tumour response. Patients with mean tumour dose >70 Gy experienced a median OS of 16.1 months vs. 12.8 months for those who did not (P = 0.008). CONCLUSION: For patients with chemo-refractory breast cancer with liver metastases, achieving a mean tumour dose >70 Gy is a significant predictor of tumour response and prolonged OS.

Comparison of Tc-99m MAA Planar Versus SPECT/CT Imaging for Lung Shunt Fraction Evaluation Prior to Y-90 Radioembolization: Are We Overestimating Lung Shunt Fraction?

PURPOSE: To compare lung shunt fraction (LSF) prior to Y-90 radioembolization calculated using planar imaging versus SPECT/CT in patients with hepatocellular carcinoma (HCC). METHODS: A single institution retrospective analysis of technetium-99m macroaggregated albumin (Tc-99m MAA) LSF studies for 293 consecutive patients with HCC between 2013 and 2018 was performed. LSF using planar imaging (PLSF) was compared to retrospectively calculated LSF using SPECT/CT (SLSF) via semiautomated segmentation using MIM v.6.9. Sub-analyses of patients were performed based on PLSF range, tumor size, BCLC stage, and Child-Pugh (C-P) score. Mean LSF absolute discrepancy between sub-groups was analyzed. Comparisons were performed using paired t tests and linear regression analysis. RESULTS: Mean PLSF, 8.27%, was greater than mean SLSF, 3.27% (p < 0.001). When categorizing patients by PLSF ranges of < 10%, 10-19.9%, and ≥ 20%, PLSF remained greater than SLSF in all subgroups (p's < 0.001). Patients with PLSF ≥ 20% had a greater absolute discrepancy with SLSF (13.31%) compared to patients with PLSF < 20% (4.74%; p < 0.0001). LSF absolute discrepancy was greater for patients with a maximum liver tumor size ≥ 5.0 cm (5.59%) compared to a liver tumor size < 5.0 cm (4.40%; p = 0.0076). For all BCLC grades and C-P scores, PLSF was greater than SLSF. A greater LSF discrepancy existed for patients with a worse C-P score (C-P A: 4.78%, C-P B/C: 6.12%; p = 0.0081), but not BCLC stage (0/A/B: 4.87%, C: 4.56%; p = 0.5993). CONCLUSION: In patients with HCC, SLSF is significantly lower compared to PLSF, with a greater discrepancy among patients with a PLSF ≥ 20%, tumor size ≥ 5 cm, and worse C-P score. LEVEL OF EVIDENCE: Level 3, Retrospective Study.

Incidence of Radioembolization-Induced Liver Disease and Liver Toxicity Following Repeat 90Y-Radioembolization: Outcomes at a Large Tertiary Care Center.

PURPOSE: The complication profile following repeat Y-radioembolization (RE) is not well understood, and repeat RE is sometimes avoided because of concerns for RE-induced liver disease (REILD) and liver toxicity. The purpose of this study was to examine the incidence of REILD and liver toxicity following repeat Y-RE and to identify potential risk factors. METHODS: A retrospective analysis of patients undergoing repeat RE to the same hepatic lobe between 2013 and 2018 was performed. Baseline factors were evaluated as predictors of liver toxicity, mortality, and REILD, which was defined as the presence symptomatic ascites or jaundice in the absence of biliary obstruction within 8 weeks following RE. Post-RE complications were graded according to the Common Terminology Criteria for Adverse Events version 5. RESULTS: A total of 39 patients underwent repeat RE with 14 (35.9%) experiencing Common Terminology Criteria for Adverse Events toxicity of grade 2 or greater, 3 (10.3%) grade 3, and no grade 4 or greater. A Model for End Stage Liver Disease score of 8 or greater was associated with grade 2 toxicity or greater (26.7% vs 75%; P = 0.013). Only 3 patients (7.7%) experienced REILD due to symptomatic ascites without jaundice. Greater than 2 REs were associated with a greater rate of 6-month mortality (12% vs 58.3%, P = 0.003), 12-month mortality (28% vs 75%, P = 0.007), and REILD (0% vs 21.4%, P = 0.016). Age, sex, microsphere type, cirrhosis, Child-Pugh, and Eastern Cooperative Oncology Group status were not significantly associated with complications, REILD, or survival. CONCLUSIONS: Repeat Y-RE appears to be well tolerated with a low rate of high-grade adverse events and REILD.

Gastric Emptying Scintigraphy Before Gastric per Oral Endoscopic Myotomy: Imaging May Inform Treatment.

Gastric emptying scintigraphy (GES) helps to diagnose gastroparesis and is typically only used for whole stomach retention patterns. However, it may provide significantly more information when looking specifically at proximal and distal retention patterns. This article reviews global GES changes following gastric per oral endoscopic myotomy; how global, proximal, and distal GES measurements correlate to gastroparesis symptoms; and how proximal and distal GES may serve as proxies for the various mechanisms involved in gastroparesis. The authors' data on how GES may be used to select which patients will have success from G-POEM is also reviewed.

Radionuclide Therapies in Molecular Imaging and Precision Medicine.

This article reviews recent advances and applications of radionuclide therapy. Individualized precision medicine, new treatments, and the evolving role of radionuclide therapy are discussed.

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.

Is there a role for PET/CT parameters to differentiate thyroid cartilage invasion from penetration?

BACKGROUND: Assessment of thyroid cartilage invasion (tumor extension through inner cortex) and thyroid cartilage penetration (tumor involving both the inner and outer cortices of thyroid cartilage) may be challenging with CT (Computed Tomography) and MR imaging (Magnetic Resonance Imaging). Positron Emission Tomography/Computed Tomography (PET/CT) is a non invasive imaging modality that provides both anatomic and metabolic information. Quantitative data obtained from PET/CT, also known as PET/CT parameters, include maximum, mean or peak standardized uptake values (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized added metabolic activity (SAM) and normalized standardized added metabolic activity (NSAM). Our aim was to examine if FDG PET/CT parameters could differentiate thyroid cartilage invasion from penetration. METHODS: 50 patients who underwent PET/CT before laryngectomy for squamous cell carcinoma of the larynx, had SUVmax, SUVmean, SUVpeak, TLG, MTV, SAM and NSAM calculated on a dedicated workstation. Univariate and multivariate analysis was performed. ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven thyroid cartilage invasion or penetration. RESULTS: Of the 50 patients, 50% (25/50 patients) had history of prior radiation therapy. Among the previously irradiated group, 24% had thyroid cartilage invasion and penetration. 8% of the patients in this group had thyroid cartilage invasion only. Among the non-irradiated group, 76% had thyroid cartilage invasion and penetration, 8% had thyroid cartilage invasion without penetration. ROC analysis revealed that none of the PET/CT parameters had enough power to predict thyroid cartilage penetration, but TLG, MTV and SAM had enough power to predict thyroid cartilage invasion in non-irradiated patients. TLG, MTV, SAM and NSAM had enough power to predict thyroid cartilage invasion and penetration in irradiated group. CONCLUSION: TLG, MTV and SAM have enough power to predict thyroid cartilage invasion and penetration in irradiated patients. PET/CT parameters do not have enough potential to differentiate thyroid cartilage invasion from penetration.

Standardized Added Metabolic Activity Predicts Survival After Intra-arterial Resin-Based 90Y Radioembolization Therapy in Unresectable Chemorefractory Metastatic Colorectal Cancer to the Liver.

PURPOSE: Standardized added metabolic (SAM) activity is a functional objective measurement of the total tumoral metabolic activity that avoids partial volume effect and thresholding, which limit conventional PET parameters. The purpose of this study is to investigate the role of SAM in predicting survival in unresectable, chemorefractory colorectal hepatic metastatic disease treated with resin-based Y radioembolization. MATERIALS AND METHODS: This is a prospective correlative study of patients with unresectable, chemorefractory colorectal liver metastasis who underwent F-FDG PET/CT and CT/MRI before and after Y. Target RECIST, PERCIST, change in total glycolytic activity (ΔTGA), and ΔSAM treatment response were assessed. Percentage changes in diameter, SUVpeak, TGA, and SAM were calculated pre- and post-Y therapy and objective response was defined as >30% change (responders). Survival analysis by Kaplan-Meier, log-rank, and Cox proportional hazard models were performed and significance was set at <0.05. RESULTS: Sixteen patients (mean age of 61.6) were enrolled and performed a total of 20 Y therapies. After Y, target ΔSAM showed an objective response rate of 40% vs. 35%, 30%, and 22.2% based on target ΔTGA, PERCIST, and RECIST criteria, respectively. Median overall survival (OS) of the cohort after Y was 9.2 months (CI 95% 2.2-16.2). Patients demonstrating objective response based on ΔSAM had a median OS of 22.7 months (CI 95% 12.4-33.0) vs. 6.7 (CI 95% 4.2-9.2) in non-responders (P = 0.007). On multivariate analysis, hazard ratios for the objective response group based on target ΔSAM were 0.01 (P = 0.03) vs. 0.05 (P = 0.08), 0.20 (P = 0.29), and 0.91 (P = 0.98) based on target ΔTGA, PERCIST, and RECIST criteria, respectively. CONCLUSIONS: In unresectable colorectal liver metastatic disease refractory to standard chemotherapy, ΔSAM predicted OS for assessment of response following Y radioembolization therapy, whereas RECIST, PERCIST, and ΔTGA did not.

(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.

18F-FDG-PET/CT parameters as imaging biomarkers in oral cavity squamous cell carcinoma, is visual analysis of PET and contrast enhanced CT better than the numbers?

PURPOSE: This study was designed to seek associations between positron emission tomography/computed tomography (PET/CT) parameters, contrast enhanced neck computed tomography (CECT) and pathological findings, and to determine the potential prognostic value of PET/CT and CECT parameters in oral cavity squamous cell carcinoma (OCSCC). MATERIALS AND METHOD: 36 OCSCC patients underwent staging PET/CT and 30/36 of patients had CECT. PET/CT parameters were measured for the primary tumor and the hottest involved node, including maximum, mean, and peak standardized uptake values (SUV max, SUV mean, and SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized added metabolic activity (SAM), and normalized standardized added metabolic activity (N SAM). Qualitative assessment of PET/CT and CECT were also performed. Pathological outcomes included: perineural invasion, lymphovascular invasion, nodal extracapsular spread, grade, pathologic T and N stages. Multivariable logistic regression models were fit for each parameter and outcome adjusting for potentially confounding variables. Multivariable Cox proportional hazards models were used for progression free survival (PFS), locoregional recurrence free survival (LRFS), overall survival (OS) and distant metastasis free survival (DMFS). RESULTS: In multivariable analysis, patients with high (≥ median) tumor SUV max (OR 6.3), SUV mean (OR 6.3), MTV (OR 19.0), TLG (OR 19.0), SAM (OR 11.7) and N SAM (OR 19.0) had high pathological T-stage (T3/T4) (p<0.05). Ring/heterogeneous pattern on CECT qualitative assessment was associated with worse DMFS and OS. CONCLUSION: High PET/CT parameters were associated with pathologically advanced T stage (T3/T4). Qualitative assessment of CECT has prognostic value. PET/CT parameters did not predict clinical outcome.

Do 18F-FDG PET/CT parameters in oropharyngeal and oral cavity squamous cell carcinomas indicate HPV status?

OBJECTIVE: The aim of this study was to explore the relationship of PET/CT parameters with human papillomavirus (HPV) status of oropharyngeal (OP) and oral cavity (OC) squamous cell carcinomas (SCCs). PATIENTS AND METHODS: We retrospectively reviewed 39 patients with OC and OP-SCC who underwent staging 18F-FDG PET/CT. PET/CT parameters were measured for the primary tumor and the hottest involved node, including SUV max, SUV mean, SUV peak, metabolic tumor volume, total lesion glycolysis, standardized added metabolic activity (SAM), and normalized SAM. Patient characteristics were compared between HPV positive (HPV+) and negative (HPV-) groups. Receiver operating characteristic analysis was used to dichotomize PET/CT parameters into high and low. Logistic regression models predicting HPV status were fit for each PET/CT parameter. RESULTS: The HPV+ group was composed of 18 patients all with OP-SCC; the HPV- group consisted of 21 patients, 4 OP cancer patients and 17 OC cancer patients. The HPV+ group had a higher proportion of N2 stage (94% vs 43%; P < 0.001). Nodal PET/CT parameters were higher in the HPV+ group (P < 0.01); this difference was not present for the primary lesion. After adjusting for sex and age, the association of higher nodal SUV max (odds ratio [OR], 9.67), SUV mean (OR, 10.48), SUV peak (OR 9.67), metabolic tumor volume (OR, 14.52), total lesion glycolysis (OR, 11.84), and SAM, normalized SAM (OR, 16.21) with HPV+ status remained statistically significant (P < 0.05). CONCLUSIONS: Nodal PET/CT parameters predict HPV status. High nodal FDG uptake should raise suspicion for positive HPV status in the evaluation of the primary lesion.

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.

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.