Resin-Based 90Y 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 90Y 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 90Y radioembolization. PATIENTS AND METHODS: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90Y versus 99mTc-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 90Y 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 90Y 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 90Y 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 90Y, 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.

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.

Correlation of Non-tumoral Liver Dose with Treatment-Related Adverse Events in Patients with Hepatocellular Carcinoma Treated with Glass-Based Yttrium-90 Radioembolization.

PURPOSE: To evaluate the relationship between non-tumor liver (NTL) dose and adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with glass-based Yttrium-90 radioembolization (Y90-RE). MATERIALS AND METHODS: A retrospective analysis of patients with HCC treated with Y90-RE between 2013 and 2018 was performed. Baseline characteristics including demographics and Y90-RE treatment approach were captured. Common Terminology Criteria for Adverse Events v5 was assessed at months 3 and 6 post-treatment. Using voxel-based dosimetry with MIM Software V. 6.9, dose-volume histograms of treated area of liver were created. Receiver operator characteristic curve was used to determine NTL dose threshold predicting AEs. Multivariate analysis was used to determine independent clinical factors of predicting severe AEs. Chi-square analysis was used to compare proportions. RESULTS: Two hundred and twenty-nine consecutive patients (115(50.2%) lobar and 114(49.8%) segmental) were included. At 3 months, there was a lower rate of any grade AE (55(46%) segmental and 36(31%) lobar, p = 0.009) and increased rate of severe AEs for lobar compared to segmental (2(2%) segmental and 9(8%) lobar, p = 0.029). At 6 months, severe AEs were greater for lobar than segmental (1(1%) segmental vs 10(9%) lobar, p = 0.005). For lobar Y90-RE, mean NTL dose of 112 Gy predicted severe AE (89% sensitivity and 91% specificity (AUC = 0.95, p = < 0.0001) at 3 and 6 months. For the segmental group, no significant association was found between NTL dose and severe treatment-related AE at 3 and 6 months. CONCLUSION: In patients with HCC undergoing glass-based lobar Y90-RE, NTL dose of > 112 Gy is associated with severe treatment-related AEs at 3-6 months.

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.

Role of Resin Microsphere Y90 Dosimetry in Predicting Objective Tumor Response, Survival and Treatment Related Toxicity in Surgically Unresectable Colorectal Liver Metastasis: A Retrospective Single Institution Study.

PURPOSE: To Evaluate the correlation between tumor dosimetric parameters with objective tumor response (OR) and overall survival (OS) in patients with surgically unresectable colorectal liver metastasis (CRLM) undergoing resin-based Ytrrium-90 selective internal radiation therapy (Y90 SIRT). MATERIALS AND METHODS: 45 consecutive patients with CRLM underwent resin-based Y90 SIRT in one or both hepatic lobes (66 treated lobes total). Dose volume histograms were created with MIM Sureplan® v.6.9 using post-treatment SPECT/CT. Dosimetry analyses were based on the cumulative volume of the five largest tumors in each treatment session and non-tumoral liver (NTL) dose. Receiver operating characteristic (ROC) curve was used to evaluate tumor dosimetric factors in predicting OR by Response Evaluation Criteria for Solid Tumors at 3 months post-Y90. Additionally, ROC curve was used to evaluate non-tumoral liver dose as a predictor of grade ≥ 3 liver toxicity and radioembolization induced liver disease (REILD) 3 months post Y90. To minimize for potential confounding demographic and clinical factors, univariate and multivariate analysis of survival with mean tumor dose as one of the factors were also performed. Kaplan-Meier estimation was used for OS analysis from initial Y90 SIRT. RESULTS: 26 out of 45 patients had OR with a median OS of 17.2 months versus 6.8 months for patients without OR (p < 0.001). Mean tumor dose (TD) of the five largest tumors was the strongest predictor of OR with an area under the curve of 0.73 (p < 0.001). Minimum TD, and TD to 30%, 50%, and 70% of tumor volume also predicted OR (p's < 0.05). Mean TD ≥ 100 Gy predicted a significantly prolonged median OS of 19 vs. 11 months for those receiving TD < 100 Gy (p = 0.016). On univariate analysis, mean TD < 100 Gy, presence of any genomic mutation, presence of MAPK pathway mutation, bilobar hepatic metastases and diffuse metastatic disease (>10 lesions per liver lobe) were found to be predictors of shorter median OS. On multivariate analysis, mean TD < 100 Gy, presence of any genomic mutation, and diffuse hepatic metastatic disease were found to be independent predictors of shorter OS. Overall, six (13.3%) patients developed grade ≥ 3 liver toxicity post Y90 of whom two (4.4%) patients developed REILD. No dose threshold predicting grade ≥ 3 liver toxicity or REILD was identified. CONCLUSIONS: Mean TD ≥ 100 Gy in patients with unresectable CRLM undergoing resin-based Y90 SIRT predicts OR and prolonged OS.

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 tumour dose response threshold and implication on survival in patients with HCC treated with Y90 radiation segmentectomy: a simple semi-quantitative analysis.

PURPOSE: To evaluate the relationship between Yttrium-90 (Y90) tumour dose and response rate in patients with hepatocellular carcinoma (HCC) who undergo Y90 radiation segmentectomy (Y90-RS) and to determine implication on overall survival (OS). MATERIALS AND METHODS: Post Y90-RS Bremsstrahlung single-photon emission computed tomography/CT of 105 HCC patients with 110 treatments performed with glass microspheres was retrospectively analysed. The dose-volume histogram of the targeted tumour was determined with commercially available dosimetry software. Tumour response at 3 months was evaluated using modified Response Evaluation Criteria in Solid Tumours. Tumour dose thresholds associated with the objective response with 80% specificity were then used to evaluate implication on OS using Kaplan-Meier estimation and log-rank analysis. RESULTS: Tumour dose thresholds to predict objective response with 80% specificity were the following: maximum tumour dose (748 Gy), mean tumour dose (568 Gy), minimum tumour dose of 30% tumour volume (608 Gy), minimum tumour dose of 50% tumour volume (565 Gy), minimum tumour dose of 70% tumour volume (464 Gy) and minimum tumour dose of 100% tumour volume (213 Gy). These parameters all significantly predicted tumour response with areas under the ROC curve of >0.6. Mean tumour dose of ≥250 Gy predicted median OS of 43.67 vs. 17.87 months for others (P = 0.026). Minimum dose ≥180 Gy to 100% of tumour volume predicted median OS of 44.93 vs. 35.87 months for others (P = 0.043). CONCLUSION: In patients with HCC undergoing Y90-RS, mean tumour dose ≥250 Gy and minimum tumour dose of ≥180 Gy to 100% of tumour volume are both significantly correlated with higher objective tumour response and prolonged survival.

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.

Outcomes and Predictive Value of Post-adjuvant Therapy PET/CT for Locally Advanced Oral Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: For locally advanced oral squamous cell carcinoma (OSCC) treated by surgery and adjuvant therapy, consensus has yet to be reached on whether the optimal time to initiate surveillance positron emission tomography/computed tomography (PET/CT) scan is before or after adjuvant therapy. In this study, we characterize the utility of PET/CT scans obtained 3 months after adjuvant therapy. STUDY DESIGN: PET/CT scans were obtained for 220 patients with stage III, IVA, or IVB OSCC who underwent resection followed by adjuvant radiotherapy or chemoradiotherapy. METHODS: Using the Neck Imaging Reporting and Data System, PET/CT scans were dichotomized as suspicious (primary or neck category ≥3, or distant lesion present) versus nonsuspicious. We then computed differences in locoregional progression, distant progression, and overall survival; positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity; and success rate of salvage. RESULTS: Sixty-seven patients (30%) had suspicious PET/CT scans, which were significantly associated with local failure (hazard ratio [HR] 14.0, 95% confidence interval [CI] 7.3-26.6), distant failure (HR 18.4, 95% CI 9.6-35.3), and poorer overall survival (HR 9.5, 95% CI 5.0-17.9). Overall PPV, locoregional PPV, NPV, sensitivity, and specificity were 85%, 79%, 73%, 58%, and 92%, respectively. Among those with biopsy-confirmed progression, 37 patients (65%) underwent salvage therapy; four (11%) were without evidence of disease at last follow-up. CONCLUSIONS: For locally advanced OSCC, PET/CT scan 3 months after adjuvant therapy is strongly predictive of disease recurrence and survival, demonstrating improved performance over postoperative imaging in previous studies. Following a suspicious post-adjuvant therapy PET/CT scan, cure of locoregional recurrence is possible but unlikely. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

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.

Chronic Q Fever with Vascular Involvement: Progressive Abdominal Pain in a Patient with Aortic Aneurysm Repair in the United States.

Q fever is a zoonotic bacterial infection caused by Coxiella burnetii. Chronic Q fever comprises less than five percent of all Q fever cases and, of those, endocarditis is the most common presentation (up to 78% of cases), followed by vascular involvement. Risk factors for chronic Q fever with vascular involvement include previous vascular surgery, preexisting valvular defects, aneurysms, and vascular prostheses. The most common symptoms of chronic Q fever with vascular involvement are nonspecific, including weight loss, fatigue, and abdominal pain. Criteria for diagnosis of chronic Q fever include clinical evidence of infection and laboratory criteria (antibody detection, detection of Coxiella burnetii DNA, or growth in culture). Treatment of chronic Q fever with vascular involvement includes a prolonged course of doxycycline and hydroxychloroquine (≥18 months) as well as early surgical intervention, which has been shown to improve survival. Mortality is high in untreated chronic Q fever. We report a case of chronic Q fever with vascular involvement in a 77-year-old man with prior infrarenal aortic aneurysm repair, who lived near a livestock farm in the southeastern United States.

Head and neck PET/CT therapy response interpretation criteria (Hopkins criteria) - external validation study.

Qualitative assessment of PET/CT results in post therapy is very important to provide a reproducible and systemic reporting. A recently introduced response criteria, known as the Hopkins criteria showed promising results. Our aim is to externally validate the Hopkins interpretation system to assess therapy response in head and neck squamous cell cancer (HNSCC). The study included 69 biopsy proven HNSCC patients who underwent post therapy PET/CT between 5-24 weeks after completion of therapy. PET/CT images were interpreted by one nuclear medicine physician and one nuclear radiologist, independently. The studies were scored according to the Hopkins criteria for right neck, left neck, primary tumor site, and overall assessment. Scores 1, 2, 3 were considered as negative and scores 4 and 5 were considered as positive for tumors. Inter-reader variability was assessed using percent agreement and Kappa statistics. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and analyzed using Cox proportional hazards regression. Of the 69 patients, 59 (85.5%) were males, with a mean age of 62.8 years. The percent agreement between readers for overall, right neck, left neck, and primary tumor site were 91.3%, 97.6%, 97.6%, 91.3% respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the overall therapy assessment were 66.7%, 87.3%, 33%, 96.5% respectively. Cox univariate regression analysis showed positive primary tumor site scores and overall scores were associated with a higher risk of progression (p<0.05). External validation of Hopkins criteria showed excellent inter-reader agreement and prediction of PFS in HNSCC patients.

Characteristics and Limitations of FDG PET/CT for Imaging of Squamous Cell Carcinoma of the Head and Neck: A Comprehensive Review of Anatomy, Metastatic Pathways, and Image Findings.

OBJECTIVE: This image-based article illustrates the anatomic regions of squamous cell carcinomas of the head and neck and describes the metastatic pathways in and TNM staging for each region. Both the role and limitations of FDG PET/CT in imaging such cancers are discussed, and cases exemplifying these issues are reported. Also included is a discussion of the use of FDG PET/CT to monitor the response of squamous cell carcinomas of the head and neck to therapy, in addition to a brief comparison of PET/CT with such traditional imaging modalities as CT, MRI, and ultrasound. CONCLUSION: Understanding the characteristics of squamous cell carcinoma of the head and neck, as imaged by FDG PET/CT, is crucial for determining treatment strategy, because it helps to avoid incorrect staging and also provides an accurate assessment of treatment response.

The role of single-photon emission computed tomography and SPECT/computed tomography in oncologic imaging.

Single-photon emission computed tomography (SPECT) and hybrid SPECT/computed tomography (SPECT/CT) cameras have emerged as a dominant technology providing invaluable tools in the diagnosis, staging, therapy planning, and treatment monitoring of multiple cancers over the past decade. In the same way that positron emission tomography (PET) benefited from the addition of CT, functional SPECT and anatomic CT data obtained as a single study have shown improvements in diagnostic imaging sensitivity and specificity by improving lesion conspicuity, reducing false positives, and clarifying indeterminate lesions. Furthermore, the anatomic imaging better localizes the functional data, which can be critical in surgical and therapy planning. As more disease-specific imaging agents become available, the role of SPECT/CT in the new paradigms of molecular imaging for personalized medicine will expand. Established and emerging uses of SPECT/CT in a wide variety of oncologic diseases, as well as radiation exposure issues, are reviewed.

Meta-analysis: comparison of F-18 Fluorodeoxyglucose-positron emission tomography and bone scintigraphy in the detection of bone metastases in patients with breast cancer.

PURPOSE: To evaluate the diagnostic properties of FDG-PET and bone scintigraphy in the detection of osseous metastases in patients with breast cancer. MATERIALS AND METHODS: Studies evaluating the diagnostic accuracy of FDG-PET and bone scintigraphy in the diagnosis of osseous metastasis were systematically searched for in the MEDLINE, CINAHL, and EBM Review databases from January 1995 to November 2006. Two reviewers independently abstracted data including research design, sample size, imaging technique and technical characteristics, reference standard, method of image interpretation, and totals of true positives, false positives, true negatives, and false negatives. Per-patient and per-lesion pooled sensitivity and specificity, and area under summary receiver operating characteristic curves were calculated using Meta-Test software. RESULTS: The pooled patient-based sensitivity for FDG-PET was 81% (95% CI: 70%-89%), specificity was 93% (95% CI: 84%-97%), and the area under the curve (AUC) was 0.08. The pooled sensitivity of bone scan was 78% (95% CI: 67%-86%), specificity was 79% (95% CI: 40%-95%), and the AUC was 0.43. The pooled lesion-based sensitivity for FDG-PET was 69% (95% CI: 28%-93%), specificity was 98% (95% CI: 87%-100%), and the AUC was 0.09. The pooled sensitivity for bone scan was 88% (95% CI: 82%-92%), specificity was 87% (95% CI: 29%-99%), and the AUC was 0.81. CONCLUSIONS: It remains inconclusive whether FDG-PET or bone scintigraphy is superior in detecting osseous metastasis from breast cancer. However, FDG-PET does have a higher specificity and may better serve as a confirmatory test than bone scintigraphy and used to monitor response to therapy.

Release of protein-bound residues of thiabendazole from liver.

Tissue-bound residues of thiabendazole (TBZ), a veterinary anthelmintic and postharvest fungicide, are formed when this compound is incubated with rabbit hepatocytes or administered to mice or pigs. Several pretreatment steps were investigated for removing free TBZ and metabolites prior to the release of bound residues, and three procedures were evaluated for the release of bound residues from solvent-extracted rabbit hepatocytes: incubation under acidic conditions, enzymatic action using cystathionine beta-lyase, and Raney nickel desulfurization. Immunoaffinity chromatography utilizes monoclonal antibodies capable of binding TBZ or its 5-hydroxy metabolite enabled isolation of crossreactive residue fractions. Residues released from incurred pig liver and isolated by immunoaffinity included TBZ, as determined by HPLC with photodiode array detection. The methodology described should facilitate food safety assessments of TBZ.

Immunoassays of soy proteins.

Proteins of soybeans (Glycine max) are widely used in animal and human nutrition. In addition to the bulk of the seed storage proteins, which are classified as albumins and globulins, approximately 6% of soybean proteins are classified as inhibitors of trypsin and chymotrypsin and approximately 0.5% are sugar-binding lectins. The two major classes of inhibitors are the Kunitz trypsin inhibitor, which inhibits trypsin, and the Bowman-Birk inhibitor (BBI), which inhibits both trypsin and chymotrypsin. Unless removed or inactivated, these inhibitors and lectins can impair the nutritional quality and safety of soy-based diets. On the other hand, several studies suggest that BBI can also function as an anticarcinogen, possibly through interaction with a cellular serine protease. Good-quality soybean proteins contribute to the nutritional value of many specialty foods including infant soy formulas and milk replacers for calves, and provide texture to many processed foods. However, they may also induce occasional allergic responses in humans. This paper outlines immunoassays developed to analyze for soy proteins in different soybean lines, in processed foods, and in nonsoy foods fortified with soy proteins. An assessment of the current status of immunoassays, especially of enzyme-linked immunosorbent assays for soybean inhibitors of digestive enzymes, soy globulins, and soy lectins, demonstrates the usefulness of these methods in plant and food sciences and in medicine.