Cardiac Progenitor Cells and Adipocyte Stem Cells from Same Patients Exhibit In Vitro Functional Differences.

Cardiac progenitor cells (CPCs) and adipocyte stem cells (ASCs) are widely tested for their efficacy in repairing the diseased heart with varying results. However, no study has directly compared the functional efficacy of CPCs and ASCs collected from the same patient. CPCs and ASCs were isolated from the right atrial appendage and epicardial adipose tissue of the same patients, using explant culture. The flow cytometry analysis confirmed that both the cell types express common mesenchymal stem cells markers CD90 and CD105. ASCs, in addition, expressed CD29 and CD73. The wound-healing assay demonstrated that CPCs migrate faster to cover the wound area. Both cell types were resistant to hypoxia-induced cell death when exposed to hypoxia and serum deprivation; however, the ASCs showed increased proliferation. Conditioned medium (CM) collected after culturing serum-deprived CPCs and ASCs showed differential secretion patterns, with ASC CM showing an increased IGF-1 level, while CPC CM showed an increased FGF level. Only CPC CM reduced hypoxia-induced apoptosis in AC-16 human ventricular cardiomyocytes, while vascular network formation by endothelial cells was comparable between CPC and ASC CM. In conclusion, ASCs and CPCs exhibit differential characteristics within the same patient, and in vitro studies showed that CPCs have marginally superior functional efficacy.

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma.

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial.

BACKGROUND: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients. METHODS: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy. DISCUSSION: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010.

National Cancer Centre Singapore Consensus Guidelines for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26(th) September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data.

Gender, Race, and Age at Diagnosis as Risk Factors for Metastasis or Recurrence among 1,657 Thyroid Cancer Patients Treated with Radioiodine across 40 Years in Singapore.

BACKGROUND: To obtain descriptive data on Singaporean thyroid cancer patients treated with radioiodine and to assess gender, race, and age at diagnosis as risk factors for metastasis or recurrence. METHODS: This is a retrospective study of all thyroid cancer patients treated with radioiodine of any prescribed activity at our institution. Data collected included: age at diagnosis, gender, race, histopathological type, duration of follow-up, and metastasis at diagnosis (locoregional or distant) or recurrence at any time. Gender, race, and age at diagnosis were analyzed for possible associations with metastasis or recurrence. RESULTS: A total of 1,657 thyroid cancer patients were treated with radioiodine across a 40-year period; mean follow-up 6.4 ± 6.9 years (median 4.2 years). 656 (39.6%) patients had metastasis or recurrence over the duration of their follow-up. Male gender (odds ratio (OR) 1.38; p = 0.006), Malay race (OR 1.71; p < 0.0001), and age at diagnosis of > 46 years (OR 1.31; p = 0.007) were significantly associated with metastasis or recurrence. CONCLUSION: Male gender, Malay race, and age at diagnosis of > 46 years were significant risk factors for metastasis or recurrence in Singaporean thyroid cancer patients treated with radioiodine.

Personalized predictive lung dosimetry by technetium-99m macroaggregated albumin SPECT/CT for yttrium-90 radioembolization.

BACKGROUND: For yttrium-90 ((90)Y) radioembolization, the common practice of assuming a standard 1,000-g lung mass for predictive dosimetry is fundamentally incongruent with the modern philosophy of personalized medicine. We recently developed a technique of personalized predictive lung dosimetry using technetium-99m ((99m)Tc) macroaggregated albumin (MAA) single photon emission computed tomography with integrated CT (SPECT/CT) of the lung as part of our routine dosimetric protocol for (90)Y radioembolization. Its rationales are the technical superiority of SPECT/CT over planar scintigraphy, ease and convenience of lung auto-segmentation CT densitovolumetry, and dosimetric advantage of patient-specific lung parenchyma masses. METHODS: This is a retrospective study of our pulmonary clinical outcomes and comparison of lung dosimetric accuracy and precision by (99m)Tc MAA SPECT/CT versus conventional planar methodology. (90)Y resin microspheres (SIR-Spheres) were used for radioembolization. Diagnostic CT densitovolumetry was used as a reference for lung parenchyma mass. Pulmonary outcomes were based on follow-up diagnostic CT chest or X-ray. RESULTS: Thirty patients were analyzed. The mean lung parenchyma mass of our Southeast Asian cohort was 822 ± 103 g standard deviation (95% confidence interval 785 to 859 g). Patient-specific lung parenchyma mass estimation by CT densitovolumetry on (99m)Tc MAA SPECT/CT is accurate (bias -21.7 g) and moderately precise (95% limits of agreement -194.6 to +151.2 g). Lung mean radiation absorbed doses calculated by (99m)Tc MAA SPECT/CT and planar methodology are both accurate (bias <0.5 Gy), but (99m)Tc MAA SPECT/CT offers better precision over planar methodology (95% limits of agreement -1.76 to +2.40 Gy versus -3.48 to +3.31 Gy, respectively). None developed radiomicrosphere pneumonitis when treated up to a lung mean radiation absorbed dose of 18 Gy at a median follow-up of 4.4 months. CONCLUSIONS: Personalized predictive lung dosimetry by (99m)Tc MAA SPECT/CT is clinically feasible, safe, and more precise than conventional planar methodology for (90)Y radioembolization radiation planning.

Underlying liver disease influences volumetric changes in the spared hemiliver after selective internal radiation therapy with 90Y in patients with hepatocellular carcinoma.

OBJECTIVE: Hypertrophy of the contralateral liver lobe after treatment with yttrium-90 ((90)Y) microspheres has recently been reported. This study aimed to quantify left hepatic lobe hypertrophy after right-sided radioembolization for hepatocellular carcinoma (HCC) and to identify pretreatment predictive factors of hypertrophy in an Asian population. METHODS: A retrospective review of patients with inoperable HCC undergoing selective internal radiation treatment (SIRT) with (90)Y microspheres at a single institution from January 2008 to January 2012 was performed. Only patients who had treatment delivered via the right hepatic artery alone were included. RESULTS: In all, 17 patients fulfilling the study criteria were identified. The mean percentage of left-lobe hypertrophy was 34.2% ± 34.9% (range 19.0-106.5%) during a median of 5-month follow-up. Patients with hepatitis B were found to experience a significantly greater degree of hypertrophy than those with hepatitis C or alcoholic liver cirrhosis. There were no cases of acute liver failure after the administration of SIRT in this study and none of the patients developed disease in the contralateral lobe over the study period. CONCLUSIONS: Administration of unilobar SIRT to the right liver lobe in patients with HCC resulted in a significant degree of contralateral left lobe hypertrophy. Patients with hepatitis B experienced a greater degree of hypertrophy than those with hepatitis C or alcoholic liver cirrhosis.

Post-thyroidectomy neck ultrasonography in patients with thyroid cancer and a review of the literature.

The importance of routine neck ultrasonography for the detection of unsuspected local or nodal recurrence of thyroid cancer following thyroidectomy (with or without neck dissection) is well documented in many journal articles and international guidelines. Herein, we present a pictorial summary of the sonographic features of benign and malignant central neck compartment nodules and cervical lymph nodes via a series of high-quality ultrasonographic images, with a review of the literature.

Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma.

BACKGROUND: The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. METHODS: Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). RESULTS: Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. CONCLUSIONS: This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712790.

Non-Target Activity Detection by Post-Radioembolization Yttrium-90 PET/CT: Image Assessment Technique and Case Examples.

High resolution yttrium-90 ((90)Y) imaging of post-radioembolization microsphere biodistribution may be achieved by conventional positron emission tomography with integrated computed tomography (PET/CT) scanners that have time-of-flight capability. However, reconstructed (90)Y PET/CT images have high background noise, making non-target activity detection technically challenging. This educational article describes our image assessment technique for non-target activity detection by (90)Y PET/CT, which qualitatively overcomes the problem of background noise. We present selected case examples of non-target activity in untargeted liver, stomach, gallbladder, chest wall, and kidney, supported by angiography and (90)Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) or technetium-99m macroaggregated albumin SPECT/CT.

Survival and pattern of tumor progression with yttrium-90 microsphere radioembolization in predominantly hepatitis B Asian patients with hepatocellular carcinoma.

PURPOSE: Intra-arterial yttrium-90 ((90)Y) microsphere radioembolization (RE) is an emerging treatment option with good outcomes reported predominantly in hepatitis C Western populations with hepatocellular carcinoma (HCC). We report outcomes in predominantly hepatitis B Asian patients treated with (90)Y-RE focusing on overall survival (OS), time to progression (TTP), tumor response, pattern of tumor recurrence and adverse events. Prognostic factors for survival were also identified. METHODS: A retrospective cohort study was conducted in a single tertiary institution. All non-trial patients treated with (90)Y-RE at our institution from 1 January 2008 to 30 June 2012 were included. RESULTS: Data from 103 consecutive patients were analyzed. The majority of patients were Child-Pugh class A (59.2 %) and Barcelona Clinic Liver Cancer (BCLC) stage C (68.9 %). Median OS was 14.4 months (95 % CI 11.0-22.2), which varied by disease stage: Child-Pugh A, 21.7 months; Child-Pugh B, 7.1 months; BCLC B, 23.8 months; BCLC C, 11.8 months. Response and disease control rates by RECIST 1.1 were 21.2 and 59.6 %, respectively, while disease control for index lesions treated with (90)Y-RE was 100 %. Development of new intrahepatic lesions was the main reason for eventual disease progression. Median overall TTP was 5.3 months (95 % CI 4.1-10.0). Pretreatment vascular invasion, low serum albumin and elevated total bilirubin levels predicted poorer survival. CONCLUSIONS: Survival outcomes in hepatitis B Asian patients treated with (90)Y-RE for HCC are comparable to hepatitis C Western populations. While disease control for lesions treated with (90)Y-RE is excellent, the development of new lesions suggests a role for concomitant systemic therapy.

Stress myocardial perfusion imaging for the evaluation and triage of chest pain in the emergency department: a randomized controlled trial.

BACKGROUND: Patients with acute coronary syndrome (ACS) often present atypically. In a randomized controlled trial, we studied whether adding stress myocardial perfusion imaging (SMPI) to an evaluation strategy for emergency department (ED) patients presenting with chest pain more effectively identifies patients with ACS. METHODS: Participants were randomized to standard ED chest pain protocol (clinical assessment) or standard protocol supplemented with SMPI results. During 6 hours of electrocardiogram (ECG) monitoring and serial cardiac markers (creatine kinase-MB isoenzyme, troponin), participants developing ST segment changes or elevated cardiac markers were admitted. Those with a negative observation period underwent SMPI (N = 1,004) or clinical assessment (N = 504) based on randomization, and admitted if their SMPI scan was abnormal or senior clinicians found a high or intermediate risk for ACS. RESULTS: SMPI participants had a significantly lower admission rate than clinical assessment participants (10.16% vs 18.45%), with no significant between-group differences in risk of cardiac events (CEs) after 30 days (0.40% vs 0.79%) or 1 year (0.70% vs 0.99%). CONCLUSIONS: When added to a standard triage strategy incorporating clinical evaluation, serial ECGs, and cardiac markers, SMPI improved clinical decision making for chest pain patients, significantly reducing the need for hospitalization without an increase in adverse CE rates at 30 days or 1 year.

Post-radioembolization yttrium-90 PET/CT - part 1: diagnostic reporting.

BACKGROUND: Yttrium-90 (90Y) positron emission tomography with integrated computed tomography (PET/CT) represents a technological leap from 90Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) by coincidence imaging of low abundance internal pair production. Encouraged by favorable early experiences, we implemented post-radioembolization 90Y PET/CT as an adjunct to 90Y bremsstrahlung SPECT/CT in diagnostic reporting. METHODS: This is a retrospective review of all paired 90Y PET/CT and 90Y bremsstrahlung SPECT/CT scans over a 1-year period. We compared image resolution, ability to confirm technical success, detection of non-target activity, and providing conclusive information about 90Y activity within targeted tumor vascular thrombosis. 90Y resin microspheres were used. 90Y PET/CT was performed on a conventional time-of-flight lutetium-yttrium-oxyorthosilicate scanner with minor modifications to acquisition and reconstruction parameters. Specific findings on 90Y PET/CT were corroborated by 90Y bremsstrahlung SPECT/CT, 99mTc macroaggregated albumin SPECT/CT, follow-up diagnostic imaging or review of clinical records. RESULTS: Diagnostic reporting recommendations were developed from our collective experience across 44 paired scans. Emphasis on the continuity of care improved overall diagnostic accuracy and reporting confidence of the operator. With proper technique, the presence of background noise did not pose a problem for diagnostic reporting. A counter-intuitive but effective technique of detecting non-target activity is proposed, based on the pattern of activity and its relation to underlying anatomy, instead of its visual intensity. In a sub-analysis of 23 patients with a median follow-up of 5.4 months, 90Y PET/CT consistently outperformed 90Y bremsstrahlung SPECT/CT in all aspects of qualitative analysis, including assessment for non-target activity and tumor vascular thrombosis. Parts of viscera closely adjacent to the liver remain challenging for non-target activity detection, compounded by a tendency for mis-registration. CONCLUSIONS: Adherence to proper diagnostic reporting technique and emphasis on continuity of care are vital to the clinical utility of post-radioembolization 90Y PET/CT. 90Y PET/CT is superior to 90Y bremsstrahlung SPECT/CT for the assessment of target and non-target activity.

Post-radioembolization yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres.

BACKGROUND: Coincidence imaging of low-abundance yttrium-90 (90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry. METHODS: Retrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET. RESULTS: Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D70 > 100 Gy (D70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D70 < 100 Gy; smaller tumors (<80 cm3) achieved D70 > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy (V20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those by 90Y PET, with a low median relative error of +3.8% (95% confidence interval, -1.2% to +13.2%). CONCLUSIONS: Tumor and non-target tissue absorbed dose quantification by 90Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor 99mTc MAA SPECT/CT predictive dosimetry is feasible. 90Y DVHs may guide future techniques in predictive dosimetry.

Radioembolization with infusion of yttrium-90 microspheres into a right inferior phrenic artery with hepatic tumor supply is feasible and safe.

PURPOSE: To evaluate the feasibility and safety of yttrium-90 ((90)Y) radioembolization through the inferior phrenic arteries (IPAs). MATERIALS AND METHODS: Retrospective analysis of 108 patients referred for radioembolization to treat primary (n = 103) or secondary (n = 5) liver malignancy was performed. Five patients had malignant hepatic tumors supplied by the IPA and met criteria for infusion of (90)Y spheres into the IPA. Digital subtraction angiography (DSA), catheter-directed computed tomographic (CT) angiography, and technetium-99m ((99m)Tc) macroaggregated albumin (MAA) single photon emission CT (SPECT)/CT were used to plan treatment. Bremsstrahlung SPECT/CT was performed 1 day after radioembolization. Follow-up included clinical and biochemical tests and cross-sectional CT or magnetic resonance imaging. RESULTS: Parasitized extrahepatic arteries were detected in 37% of patients (n = 40). Of these, 62.5% (n = 25) had tumor supply through an IPA. Of the patients with IPA supply, 20% (n = 5) underwent infusion of (90)Y into the right IPA. Reasons for disqualifying patients from infusion into the IPA were less than 10% tumor supply (n = 11), failed catheterization of IPA (n = 3), arterioportovenous shunt (n = 2), failed identification of IPA on pretreatment angiography (n = 1), and gastric or esophageal enhancement on catheter-directed CT angiography (n = 3). In all five patients, technical success was demonstrated on (90)Y imaging, with no significant extrahepatic radionuclide activity. No adverse events related to IPA radioembolization occurred at mean follow-up of 4.5 months (range, 2.2-10.1 mo). CONCLUSIONS: Delivery of (90)Y microspheres through the right IPA is feasible and safe with the use of catheter-directed CT angiography in addition to DSA and (99m)Tc MAA SPECT/CT in patients with tumors with greater than 10% IPA supply.

Radioembolization after portal vein embolization in a patient with multifocal hepatocellular carcinoma.

Radioembolization is an effective locoregional therapy for patients with intermediate or advanced stage hepatocellular carcinoma (HCC). It has been shown that radioembolization is safe in patients with portal vein thrombosis. This case report describes safe radioembolization after portal vein embolization in a patient with multifocal HCC.

Image-guided personalized predictive dosimetry by artery-specific SPECT/CT partition modeling for safe and effective 90Y radioembolization.

UNLABELLED: Compliance with radiobiologic principles of radionuclide internal dosimetry is fundamental to the success of (90)Y radioembolization. The artery-specific SPECT/CT partition model is an image-guided personalized predictive dosimetric technique developed by our institution, integrating catheter-directed CT hepatic angiography (CTHA), (99m)Tc-macroaggregated albumin SPECT/CT, and partition modeling for unified dosimetry. Catheter-directed CTHA accurately delineates planning target volumes. SPECT/CT tomographically evaluates (99m)Tc-macroaggregated albumin hepatic biodistribution. The partition model is validated for (90)Y resin microspheres based on MIRD macrodosimetry. METHODS: This was a retrospective analysis of our early clinical outcomes for inoperable hepatocellular carcinoma. Mapping hepatic angiography was performed according to standard technique with the addition of catheter-directed CTHA. (99m)Tc-MAA planar scintigraphy was used for liver-to-lung shunt estimation, and SPECT/CT was used for liver dosimetry. Artery-specific SPECT/CT partition modeling was planned by experienced nuclear medicine physicians. RESULTS: From January to May 2011, 20 arterial territories were treated in 10 hepatocellular carcinoma patients. Median follow-up was 21 wk (95% confidence interval [CI], 12-50 wk). When analyzed strictly as brachytherapy, (90)Y radioembolization planned by predictive dosimetry achieved index tumor regression in 8 of 8 patients, with a median size decrease of 58% (95% CI, 40%-72%). Tumor thrombosis regressed or remained stable in 3 of 4 patients with baseline involvement. The best α-fetoprotein reduction ranged from 32% to 95%. Clinical success was achieved in 7 of 8 patients, including 2 by sublesional dosimetry, in 1 of whom there was radioembolization lobectomy intent. Median predicted mean radiation absorbed doses were 106 Gy (95% CI, 105-146 Gy) to tumor, 27 Gy (95% CI, 22-33 Gy) to nontumorous liver, and 2 Gy (95% CI, 1.3-7.3 Gy) to lungs. Across all patients, tumor, nontumorous liver, and lungs received predicted ≥91 Gy, ≤51 Gy, and ≤16 Gy, respectively, via at least 1 target arterial territory. No patients developed significant toxicities within 3 mo after radioembolization. The median time to best imaging response was 76 d (95% CI, 55-114 d). Median time to progression and overall survival were not reached. SPECT/CT-derived mean tumor-to-normal liver ratios varied widely across all planning target volumes (median, 5.4; 95% CI, 4.1-6.7), even within the same patient. CONCLUSION: Image-guided personalized predictive dosimetry by artery-specific SPECT/CT partition modeling achieves high clinical success rates for safe and effective (90)Y radioembolization.

Dosimetric considerations in radioimmunotherapy and systemic radionuclide therapies: a review.

Radiopharmaceutical therapy, once touted as the "magic bullet" in radiation oncology, is increasingly being used in the treatment of a variety of malignancies; albeit in later disease stages. With ever-increasing public and medical awareness of radiation effects, radiation dosimetry is becoming more important. Dosimetry allows administration of the maximum tolerated radiation dose to the tumor/organ to be treated but limiting radiation to critical organs. Traditional tumor dosimetry involved acquiring pretherapy planar scans and plasma estimates with a diagnostic dose of intended radiopharmaceuticals. New advancements in single photon emission computed tomography and positron emission tomography systems allow semi-quantitative measurements of radiation dosimetry thus allowing treatments tailored to each individual patient.