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BACKGROUND: Overall Survival (OS) and Progression-Free Survival (PFS) analyses are crucial metrics for evaluating the efficacy and impact of treatment. This study evaluated the role of clinical biomarkers and dosimetry parameters on survival outcomes of patients undergoing 90Y selective internal radiation therapy (SIRT). MATERIALS/METHODS: This preliminary and retrospective analysis included 17 patients with hepatocellular carcinoma (HCC) treated with 90Y SIRT. The patients underwent personalized treatment planning and voxel-wise dosimetry. After the procedure, the OS and PFS were evaluated. Three structures were delineated including tumoral liver (TL), normal perfused liver (NPL), and whole normal liver (WNL). 289 dose-volume constraints (DVCs) were extracted from dose-volume histograms of physical and biological effective dose (BED) maps calculated on 99mTc-MAA and 90Y SPECT/CT images. Subsequently, the DVCs and 16 clinical biomarkers were used as features for univariate and multivariate analysis. Cox proportional hazard ratio (HR) was employed for univariate analysis. HR and the concordance index (C-Index) were calculated for each feature. Using eight different strategies, a cross-combination of various models and feature selection (FS) methods was applied for multivariate analysis. The performance of each model was assessed using an averaged C-Index on a three-fold nested cross-validation framework. The Kaplan-Meier (KM) curve was employed for univariate and machine learning (ML) model performance assessment. RESULTS: The median OS was 11 months [95% CI: 8.5, 13.09], whereas the PFS was seven months [95% CI: 5.6, 10.98]. Univariate analysis demonstrated the presence of Ascites (HR: 9.2[1.8,47]) and the aim of SIRT (segmentectomy, lobectomy, palliative) (HR: 0.066 [0.0057, 0.78]), Aspartate aminotransferase (AST) level (HR:0.1 [0.012-0.86]), and MAA-Dose-V205(%)-TL (HR:8.5[1,72]) as predictors for OS. 90Y-derived parameters were associated with PFS but not with OS. MAA-Dose-V205(%)-WNL, MAA-BED-V400(%)-WNL with (HR:13 [1.5-120]) and 90Y-Dose-mean-TL, 90Y-D50-TL-Gy, 90Y-Dose-V205(%)-TL, 90Y-Dose- D50-TL-Gy, and 90Y-BED-V400(%)-TL (HR:15 [1.8-120]) were highly associated with PFS among dosimetry parameters. The highest C-index observed in multivariate analysis using ML was 0.94 ± 0.13 obtained from Variable Hunting-variable-importance (VH.VIMP) FS and Cox Proportional Hazard model predicting OS, using clinical features. However, the combination of VH. VIMP FS method with a Generalized Linear Model Network model predicting OS using Therapy strategy features outperformed the other models in terms of both C-index and stratification of KM curves (C-Index: 0.93 ± 0.14 and log-rank p-value of 0.023 for KM curve stratification). CONCLUSION: This preliminary study confirmed the role played by baseline clinical biomarkers and dosimetry parameters in predicting the treatment outcome, paving the way for the establishment of a dose-effect relationship. In addition, the feasibility of using ML along with these features was demonstrated as a helpful tool in the clinical management of patients, both prior to and following 90Y-SIRT.
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BACKGROUND: Selective internal radiation therapy with 90Y radioembolization aims to selectively irradiate liver tumours by administering radioactive microspheres under the theragnostic assumption that the pre-therapy injection of 99mTc labelled macroaggregated albumin (99mTc-MAA) provides an estimation of the 90Y microspheres biodistribution, which is not always the case. Due to the growing interest in theragnostic dosimetry for personalized radionuclide therapy, a robust relationship between the delivered and pre-treatment radiation absorbed doses is required. In this work, we aim to investigate the predictive value of absorbed dose metrics calculated from 99mTc-MAA (simulation) compared to those obtained from 90Y post-therapy SPECT/CT. RESULTS: A total of 79 patients were analysed. Pre- and post-therapy 3D-voxel dosimetry was calculated on 99mTc-MAA and 90Y SPECT/CT, respectively, based on Local Deposition Method. Mean absorbed dose, tumour-to-normal ratio, and absorbed dose distribution in terms of dose-volume histogram (DVH) metrics were obtained and compared for each volume of interest (VOI). Mann-Whitney U-test and Pearson's correlation coefficient were used to assess the correlation between both methods. The effect of the tumoral liver volume on the absorbed dose metrics was also investigated. Strong correlation was found between simulation and therapy mean absorbed doses for all VOIs, although simulation tended to overestimate tumour absorbed doses by 26%. DVH metrics showed good correlation too, but significant differences were found for several metrics, mostly on non-tumoral liver. It was observed that the tumoral liver volume does not significantly affect the differences between simulation and therapy absorbed dose metrics. CONCLUSION: This study supports the strong correlation between absorbed dose metrics from simulation and therapy dosimetry based on 90Y SPECT/CT, highlighting the predictive ability of 99mTc-MAA, not only in terms of mean absorbed dose but also of the dose distribution.
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RATIONALE: Currently, the estimated absorbed radiation dose to the lung in 90Y radioembolization therapy is calculated using an assumed 1 kg lung mass for all patients. The aim of this study was to evaluate whether using a patient-specific lung mass measurement for each patient rather than a generic, assumed 1 kg lung mass would change the estimated lung absorbed dose. METHODS: A retrospective analysis was performed on 68 patients who had undergone 90Y radioembolization therapy at our institution. Individualized lung volumes were measured manually on CT scans for each patient, and these volumes were used to calculate personalized lung masses. The personalized lung masses were used to recalculate the estimated lung absorbed dose from the 90Y therapy, and this dose was compared to the estimated lung absorbed dose calculated using an assumed 1 kg lung mass. RESULTS: Patient-specific lung masses were significantly different from the generic 1 kg when compared individually for each patient (p < 0.0001). Median individualized lung mass was 0.71 (IQR: 0.59, 1.02) kg overall and was significantly different from the generic 1 kg lung mass for female patients [0.59 (0.50, 0.68) kg, (p < 0.0001)] but not for male patients [0.99 (0.71, 1.14) kg, (p = 0.24)]. Median estimated lung absorbed dose was 4.48 (2.38, 11.71) Gy using a patient-specific lung mass and 3.45 (1.81, 6.68) Gy when assuming a 1 kg lung mass for all patients. The estimated lung absorbed dose was significantly different using a patient-specific versus generic 1 kg lung mass when comparing the doses individually for each patient (p < 0.0001). The difference in the estimated lung absorbed dose between the patient-specific and generic 1 kg lung mass method was significant for female patients as a subgroup but not for male patients. CONCLUSIONS: The current method of assuming a 1 kg lung mass for all patients inaccurately estimates the lung absorbed dose in 90Y radioembolization therapy. Using patient-specific lung masses resulted in estimated lung absorbed doses that were significantly different from those calculated using an assumed 1 kg lung mass for all patients. A personalized dosimetry method that includes individualized lung masses is necessary and can warrant a 90Y dose reduction in some patients with lung masses smaller than 1 kg. LEVEL OF EVIDENCE: Level 3, Retrospective Study.
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Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Masculino , Femenino , Radioisótopos de Itrio/uso terapéutico , Estudios Retrospectivos , Itrio , Radiometría , Pulmón/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Embolización Terapéutica/métodos , MicroesferasRESUMEN
PURPOSE: To investigate the accuracy and biases of predicted lung shunt fraction (LSF) and lung dose (LD) calculations via 99m Tc-macro-aggregated albumin (99m Tc-MAA) planar imaging for treatment planning of 90 Y-microsphere radioembolization. METHODS AND MATERIALS: LSFs in 52 planning and LDs in 44 treatment procedures were retrospectively calculated, in consecutive radioembolization patients over a 2 year interval, using 99m Tc-MAA planar and SPECT/CT imaging. For each procedure, multiple planar LSFs and LDs were calculated using different: (1) contours, (2) views, (3) liver 99m Tc-MAA shine-through compensations, and (4) lung mass estimations. The accuracy of each planar-based LSF and LD methodology was determined by calculating the median (range) absolute difference from SPECT/CT-based LSF and LD values, which have been demonstrated in phantom and patient studies to more accurately and reliably quantify the true LSF and LD values. RESULTS: Standard-of-care LSF using geometric mean of lung and liver contours had median (range) absolute over-estimation of 4.4 percentage points (pp) (0.9 to 11.9 pp) from SPECT/CT LSF. Using anterior views only decreased LSF errors (2.4 pp median, -1.1 to +5.7 pp range). Planar LD over-estimations decreased when using single-view versus geometric-mean LSF (1.3 vs. 2.6 Gy median and 7.2 vs. 18.5 Gy maximum using 1000 g lung mass) but increased when using patient-specific versus standard-man lung mass (2.4 vs. 1.3 Gy median and 11.8 vs. 7.2 Gy maximum using single-view LSF). CONCLUSIONS: Calculating planar LSF from lung and liver contours of a single view and planar LD using that same LSF and 1000 g lung mass was found to improve accuracy and minimize bias in planar lung dosimetry.
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Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Estudios Retrospectivos , Radioisótopos de Itrio/uso terapéutico , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Pulmón/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Embolización Terapéutica/métodos , MicroesferasRESUMEN
Radiation pneumonitis is a rare but possibly fatal side effect of 90Y radioembolization. It may occur 1-6 mo after therapy, if a significant part of the 90Y microspheres shunts to the lungs. In current clinical practice, a predicted lung dose greater than 30 Gy is considered a criterion to exclude patients from treatment. However, contrasting findings regarding the occurrence of radiation pneumonitis and lung dose were previously reported in the literature. In this study, the relationship between the lung dose and the eventual occurrence of radiation pneumonitis after 90Y radioembolization was investigated. Methods: We retrospectively analyzed 317 90Y liver radioembolization procedures performed during an 8-y period (February 2012 to September 2020). We calculated the predicted lung mean dose (LMD) using 99mTc-MAA planar scintigraphy (LMDMAA) acquired during the planning phase and left LMD (LMDY-90) using the 90Y PET/CT acquired after the treatment. For the lung dose computation, we used the left lung as the representative lung volume, to compensate for scatter from the liver moving in the craniocaudal direction because of breathing and mainly affecting the right lung. Results: In total, 272 patients underwent 90Y procedures, of which 63% were performed with glass microspheres and 37% with resin microspheres. The median injected activity was 1,974 MBq (range, 242-9,538 MBq). The median LMDMAA was 3.5 Gy (range, 0.2-89.0 Gy). For 14 procedures, LMDMAA was more than 30 Gy. Median LMDY-90 was 1 Gy (range, 0.0-22.1 Gy). No patients had an LMDY-90 of more than 30 Gy. Of the 3 patients with an LMDY-90 of more than 12 Gy, 2 patients (one with an LMDY-90 of 22.1 Gy and an LMDMAA of 89 Gy; the other with an LMDY-90 of 17.7 Gy and an LMDMAA of 34.1 Gy) developed radiation pneumonitis and consequently died. The third patient, with an LMDY-90 of 18.4 Gy (LMDMAA, 29.1 Gy), died 2 mo after treatment, before the imaging evaluation, because of progressive disease. Conclusion: The occurrence of radiation pneumonitis as a consequence of a lung shunt after 90Y radioembolization is rare (<1%). No radiation pneumonitis developed in patients with a measured LMDY-90 lower than 12 Gy.
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Embolización Terapéutica , Neoplasias Hepáticas , Neumonía , Neumonitis por Radiación , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Humanos , Incidencia , Neoplasias Hepáticas/terapia , Pulmón/diagnóstico por imagen , Microesferas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neumonitis por Radiación/diagnóstico por imagen , Neumonitis por Radiación/epidemiología , Neumonitis por Radiación/etiología , Estudios Retrospectivos , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Radioisótopos de Itrio/efectos adversosRESUMEN
BACKGROUND: Metastatic colorectal cancer (mCRC) is associated with different molecular biology, clinical characteristics, and outcome depending on the primary tumor localization. We aimed to evaluate the effectiveness of 90Y-radioembolization (RE) for therapy of colorectal liver metastases depending on the primary tumor side. METHODS: We performed a retrospective analysis of n = 73 patients with mCRC and RE in our university liver center between 2009 and 2018. Patients were stratified according to the primary tumor side (left vs. right hemicolon), treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) at follow-up after 3 months. Kaplan-Meier analysis was performed to analyze survival followed by Cox regression to determine independent prognostic factors for survival. RESULTS: Prior to RE, all patients had received systemic therapy, with either stable or progressive disease, but no partial or complete response. In n = 22/73 (30.1%) patients, the primary tumor side was in the right colon; in n = 51/73 (69.9%) patients, in the left colon. Hepatic tumor burden was ≤25% in n = 36/73 (49.3%) patients and >25% in n = 37/73 (50.7%) patients. At 3 months, n = 21 (33.8%) patients showed treatment response (n = 2 [3.2%]; complete response, n = 19 [30.6%]; partial response), n = 13 (21.0%) stable disease, and n = 28 (45.2%) progressive disease after RE. The median survival in case of primary tumor side in the left colon was significantly higher than for primary tumors in the right colon (8.7 vs. 6.0 months, p = 0.033). The median survival for a hepatic tumor burden ≤25% was significantly higher than that of >25% (13.9 vs. 4.3 months, p < 0.001). The median overall survival was 6.1 months. CONCLUSION: The median survival after RE in hepatic-mCRC depends on the primary tumor side and the preprocedural hepatic tumor burden.
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Neoplasias Colorrectales/terapia , Embolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Embolización Terapéutica/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Carga TumoralRESUMEN
90Y radioembolization is a safe and efficacious treatment option for many patients with unresectable hepatocellular carcinoma. Potential candidates for radioembolization, based on clinical criteria, undergo 99mTc-labeled macroaggregated albumin imaging to determine the extent of hepatopulmonary shunting. Dose selection is based on results from shunt imaging and can exclude patients from radioembolization therapy. We present a case of miscalculated lung shunt fraction and the circumstances that led to the critical error.
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Embolización Terapéutica , Pulmón/efectos de la radiación , Errores Médicos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Radioisótopos de Itrio/uso terapéuticoRESUMEN
PURPOSE: Current treatment planning for 90 Y radioembolization estimates lung mean dose (LMD) by measuring the lung shunt fraction (LSF) from 99m Tc-macroaggregated albumin (MAA) planar imaging and assuming a 1-kg lung mass. This methodology, however, overestimates LSF and LMD and could therefore unnecessarily limit the dose to target volume(s). We propose an improved LMD calculation that derives LSF from 99m Tc-MAA SPECT/CT and the patient-specific lung mass from diagnostic chest CT. Furthermore, we investigated the errors in lung mass, LSF, and LMD arising from contour variability in patient data in order to estimate the precision of our proposed methodology. METHODS: Our proposed LMD (LMDnew ) calculation consisted of the following steps: (a) estimate liver counts from the MAA SPECT/CT liver contour; (b) estimate total lung counts by multiplying density (counts/g) from the MAA SPECT/CT left-lung contour by the total lung mass (g) from the diagnostic CT lung contours; (c) compute LSFnew from liver and lung counts; (d) calculate LMDnew using LSFnew and the total lung mass from the diagnostic CT (Mnew ). LMDnew , LSFnew , and Mnew estimates were compared to standard model values (LMDclin , LSFclin , and 1 kg, respectively) in 52 consecutive patients with hepatocellular carcinoma who underwent radioembolization using 90 Y glass microspheres. The precision of our methodology was quantified by varying lung and liver contours in the same patient population and calculating the resulting relative errors in the liver count, lung count, and lung mass measurements. RESULTS: The median Mnew was 839 g (range, 550-1178 g) for men and 731 g (range, 548-869 g) for women. The median LSFnew was 0.02 (range, 0.01-0.11), while the median LMDnew was 4.9 Gy (range, 0.3-25.5 Gy). Mnew , LSFnew , and LMDnew were significantly lower than Mclin , LSFclin , and LMDclin , with respective relative mean (±SD) differences of -20% (±16%) for Mnew , -63% (±15%) for LSFnew , and -53% (±23%) for LMDnew . The estimated 1-sigma uncertainties in Mnew , LSFnew , and LMDnew were 9%, 10%, and 13%, respectively. CONCLUSIONS: We derived a method to calculate lung mass and LSF using routinely available diagnostic chest CT and 99m Tc-MAA SPECT/CT. More importantly, we systematically quantified the errors in our measurements to establish the precision of the estimated lung dose (13%). The proposed methodology provides a more accurate LMD and an estimate of its precision, which will improve treatment and retreatment planning for 90 Y radioembolizations.
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Embolización Terapéutica , Pulmón/efectos de la radiación , Dosis de Radiación , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Tórax/diagnóstico por imagen , Radioisótopos de Itrio/uso terapéutico , Humanos , Pulmón/diagnóstico por imagen , Errores Médicos , Microesferas , Planificación de la Radioterapia Asistida por Computador , Radioisótopos de Itrio/químicaRESUMEN
90Y radioembolization is an increasingly used treatment for both primary and metastatic malignancy in the liver. Understanding the biophysical properties, dosing concerns, and imaging appearance of this treatment is important for interventional radiologists and nuclear medicine physicians to provide important therapy. 90Y radioembolization is efficacious and safe, although the possibility of complications does exist. This article provides a comprehensive in-depth discussion about the indications for 90Y radioembolization, reviews the role of preprocedural angiography and 99mTc-macroaggregated albumin scans, illustrates different dosing techniques, compares and contrasts resin and glass microspheres, and describes potential complications.
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Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Medicina Nuclear/métodos , Angiografía/métodos , Carcinoma Hepatocelular/diagnóstico por imagen , Educación Médica Continua , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Microesferas , Medicina Nuclear/educación , Radiofármacos/uso terapéutico , Dosificación Radioterapéutica , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Imagen de Cuerpo Entero/métodos , Radioisótopos de Itrio/uso terapéuticoRESUMEN
We report survival outcomes for patients with advanced-stage hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) treated with 90Y radioembolization. Methods: With institutional review board approval, we searched our prospectively acquired database for 90Y patients treated between 2003 and 2017. Inclusion criteria were patients who had HCC with tumor PVT. Patients with metastases were excluded. Laboratory data were collected at baseline and 1 mo after 90Y radioembolization. Toxicity grades were reported according to the Common Terminology Criteria for Adverse Events, version 4.0, and long-term survival outcomes were reported and stratified by Child-Pugh class (CP). Overall survival was calculated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. A subanalysis for patients with a high level of α-fetoprotein (AFP) (>100 ng/dL) was conducted. Results: In total, 185 patients with HCC PVT underwent 90Y radioembolization. Seventy-four (40%) were CP-A, 51 (28%) were CP-B7, and 60 (32%) were ≥CP-B8. New albumin, bilirubin, and alkaline phosphatase grade 3/4 toxicities were, respectively, 3%, 10%, and 0% for CP-A; 14%, 12%, and 6% for CP-B7; and 23%, 32%, and 3% for ≥CP-B8. Median overall survival for CP-A patients was 13.3 mo (95% confidence interval [CI], 8.7-15.7 mo). CP-B7 and ≥CP-B8 patients exhibited median overall survival of 6.9 mo (95% CI, 5.3-10.1 mo) and 3.9 mo (95% CI, 2.9-5.0 mo), respectively. Significant overall survival prognosticators on univariate analysis were albumin, bilirubin, ascites, tumor size 5 cm or smaller, focality, distribution, infiltration, Eastern Cooperative Oncology Group status, AFP level, and PVT extent. Multivariate analysis showed the prognosticators of overall survival to be bilirubin, no ascites, tumor size 5 cm or smaller, solitary lesion, baseline AFP level lower than 100 ng/dL, and Eastern Cooperative Oncology Group status. Of 123 patients with a high AFP level (>100 ng/dL), 12 patients achieved restored normal AFP levels (<13 ng/dL) and exhibited median overall survival of 23.9 mo (95% CI, 20.1-124.1 mo). AFP responders at 1 mo had better overall survival than nonresponders, at 8.5 mo versus 4.8 mo (P = 0.018); AFP responders at 3 mo had overall survival of 13.3 mo, versus 6.9 mo for nonresponders (P = 0.021). Conclusion:90Y radioembolization can serve as a safe and effective treatment for advanced-stage HCC patients with tumor PVT. Overall survival outcomes are affected by baseline liver function, tumor size, and AFP level.
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Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/radioterapia , Embolización Terapéutica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/radioterapia , Trombosis de la Vena/complicaciones , Radioisótopos de Itrio/uso terapéutico , Anciano , Carcinoma Hepatocelular/complicaciones , Estudios de Cohortes , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Vena Porta , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
90Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment 99mTc-macroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of 99mTc-MAA SPECT/CT and posttreatment dosimetry based on 90Y time-of-flight (TOF) PET/CT. METHODS: We compared the 99mTc-MAA SPECT/CT results for 27 treatment sessions (25 HCC patients, 41 tumors) with 90Y SIRT (7 glass spheres, 20 resin spheres) and the posttreatment 90Y TOF PET/CT results. Three-dimensional voxelized dose maps were computed from the 99mTc-MAA SPECT/CT and 90Y TOF PET/CT data. Mean absorbed dose ([Formula: see text]) was evaluated to compute the predicted-to-actual dose ratio ([Formula: see text]) in tumor volumes (TVs) and nontumor volumes (NTVs) for glass and resin spheres. The Lin concordance ([Formula: see text]) was used to measure accuracy ([Formula: see text]) and precision (ρ). RESULTS: Administered activity ranged from 0.8 to 1.9 GBq for glass spheres and from 0.6 to 3.4 GBq for resin spheres, and the respective TVs ranged from 2 to 125 mL and from 6 to 1,828 mL. The mean dose [Formula: see text] was 240 Gy for glass and 122 Gy for resin in TVs and 72 Gy for glass and 47 Gy for resin in NTVs. [Formula: see text] was 1.46 ± 0.58 (0.65-2.53) for glass and 1.16 ± 0.41 (0.54-2.54) for resin, and the respective values for [Formula: see text] were 0.88 ± 0.15 (0.56-1.00) and 0.86 ± 0.2 (0.58-1.35). DR variability was substantially lower in NTVs than in TVs. The Lin concordance between [Formula: see text] and [Formula: see text] (resin) was significantly better for tumors larger than 150 mL than for tumors 150 mL or smaller ([Formula: see text] = 0.93 and [Formula: see text] = 0.95 vs. [Formula: see text] = 0.57 and [Formula: see text] = 0.93; P < 0.05). CONCLUSION: In 90Y radioembolization of HCC, predictive dosimetry based on 99mTc-MAA SPECT/CT provided good estimates of absorbed doses calculated from posttreatment 90Y TOF PET/CT for tumor and nontumor tissues. The low variability of [Formula: see text] demonstrates that pretreatment dosimetry is particularly suitable for minimizing radiation-induced hepatotoxicity.
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Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Radioisótopos de Itrio , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Protección Radiológica/métodos , Radiometría/métodos , Dosificación Radioterapéutica , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The management of unresectable HCC and hepatic metastases from various solid tumors is a clinical dilemma. There is paucity of data on the treatment of unresectable HCC and hepatic metastases with yttrium-90 (90Y) radioembolization. METHODS: Thirty patients (mean age; 55.2 years; range 43-82 years) comprising 21 patients with HCC (12 patients have cirrhosis of which 3 patients belong to Child-Pugh class A and 9 patients belong to Child-Pugh class B), 7 patients with metastasis from colorectal cancer, 1 patient with metastasis from melanoma, and 1 patient with metastasis from ovarian carcinoma underwent resin-based 90Y radioembolization between 2013 and 2015 in our study. In all the patients, after embolization of non-target vasculature, SPECT and planar scintigraphy were done with the injection of 5-6 mCi (185-222 MBq) of 99mTc-labeled macroaggregated albumin (MAA) into the hepatic artery. Then, lung shunt fraction was assessed and dose was calculated based on body surface area (BSA) method for SIR-Spheres. Post therapeutic 90Y bremsstrahlung SPECT and 90Y PET was performed within 30 hours following therapy to see the hepatic and extrahepatic distribution of spheres. Side effects following therapy were noted in all the patients. All patients were followed up with triphasic CT liver 3 months following therapy. Therapeutic response was evaluated with necrosis criteria used for therapy response assessment in solid tumors. RESULTS: On follow up, 14 patients (46 %) developed minor side effects following treatment and resolved without active intervention. The most common side effects include mild abdominal pain in 11 patients (36 %), nausea in 8 patients (26 %), and fatigue in 6 patients (20 %). On follow up imaging at 3 months following treatment, a complete response was observed in two patients (7 %), partial response in seven patients (23 %), stable disease in 15 patients (50 %), and progressive disease in six patients (20 %). CONCLUSION: This study provides supportive evidence of the safety and efficacy on 90Y radioembolization for the treatment of unresectable HCC and hepatic metastases from various solid tumors. 90Y PET is a better radionuclide technique for assessing the hepatic and extrahepatic distribution of spheres following therapy compared to 90Y Bremsstrahlung SPECT. Thus, 90Y radioembolization is proving to be promising treatment with average disease control rates around 80 % and should be widely utilized.
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Carcinoma Hepatocelular/radioterapia , Embolización Terapéutica/métodos , Neoplasias Hepáticas/radioterapia , Radiofármacos/uso terapéutico , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/secundario , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: We investigated the prognostic role of (68)Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing (90)Y radioembolization ((90)Y-RE). METHODS: A group of 15 consecutive patients with unresectable NET liver metastases underwent (68)Ga-DOTANOC PET at baseline and 6 weeks after (90)Y-RE. Molecular response was defined as a reduction of >50% in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50% and nonresponders with ΔT/S <50%) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following (90)Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). RESULTS: A decrease in T/S ratio was seen in all patients on (68)Ga-DOTANOC PET scans performed after (90)Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. CONCLUSION: Molecular response assessed with (68)Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with (90)Y-RE.
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Radioisótopos de Galio/química , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Compuestos Organometálicos/química , Itrio/química , Anciano , Biomarcadores de Tumor , Estudios de Cohortes , Supervivencia sin Enfermedad , Embolización Terapéutica , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Microesferas , Persona de Mediana Edad , Imagen Multimodal , Metástasis de la Neoplasia , Octreótido/análogos & derivados , Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos/uso terapéutico , Resultado del TratamientoRESUMEN
To assess the prognostic role of total lesion glycolysis (TLG) in patients with breast cancer liver metastases (BCLM) after sequential lobar (90)Y-radioembolization ((90)Y-RE). Seventeen patients with bilobar BCLM underwent FDG PET/CT and TLG calculation before (90)Y-RE. The hepatic lobe with the highest TLG was treated in the first session. PET was performed 6 weeks postprocedure and decrease in TLG (ΔTLG) in the treated lobe was calculated before the second (90)Y administration. Subjects were divided in two groups (group 1: ΔTLG >50%, group 2: ΔTLG <50%). After the two consecutive (90)Y-therapies, patients underwent follow-up until death. Statistical analysis was performed to identify prognostic factors on overall survival (OS). After the first (90)Y administration, 10 cases showed a ΔTLG >50% and seven had a ΔTLG value <50%. After the two consecutive procedures, the mean OS for all patients was 13.5 ± 0.8 months. Subjects with a ΔTLG >50% and ΔTLG <50% had a mean OS of 16.4 ± 0.6 and 10.3 ± 0.4 months, respectively (p < 0.001). Cox regression analysis demonstrated hepatic tumor load (p = 0.048) and ΔTLG as the only significant (p = 0.005) predictors of survival. ΔTLG after the first (90)Y administration agrees with final outcome in BCLM patients after separate sequential lobar (90)Y-RE.
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Neoplasias de la Mama/metabolismo , Embolización Terapéutica , Glucólisis , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Embolización Terapéutica/efectos adversos , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Carga Tumoral , Radioisótopos de Itrio/efectos adversosRESUMEN
PURPOSE: We analyzed overall survival (OS) following radioembolization according to macroscopic growth pattern (nodular vs infiltrative) and vascular invasion in intermediate-advanced hepatocellular carcinoma (HCC). METHODS: Between September 2005 and November 2013, 104 patients (50.0% portal vein thrombosis [PVT], 29.8% infiltrative morphology) were treated. RESULTS: Median OS differed significantly between patients with segmental and lobar or main PVT (p = 0.031), but was 17 months in both those with patent vessels and segmental PVT. Median OS did not differ for infiltrative and nodular HCC. Median OS was prolonged in patients with a treatment response at 3 months (p = 0.023). Prior TACE was also a significant predictor of improved OS. CONCLUSION: A further indication for radioembolization might be infiltrative HCC, since OS was similar to nodular types.
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Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Radiofármacos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Vena Porta/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga Tumoral , Trombosis de la Vena/etiología , Trombosis de la Vena/patología , Adulto Joven , Radioisótopos de Itrio/administración & dosificaciónRESUMEN
OBJECTIVE: The practice guideline of the American Association for the Study of Liver Diseases currently recommends transarterial chemoembolization (TACE) for the treatment of intermediate-stage hepatocellular carcinoma (HCC). The use of transarterial radioembolization (TARE) using (90)Y microspheres is not formally recommended. This article discusses the current clinical applications of TACE and TARE and compares the clinical utility of these techniques for various subpopulations of patients with HCC. CONCLUSION: For most clinical scenarios, the efficacy and safety of TACE and TARE are probably equivalent. However, TARE appears to have an advantage over TACE in the facilitation of surgical resection by resulting in compensatory hypertrophy of the future liver remnant and possibly in the treatment of patients with portal vein tumor thrombus. On the contrary, TACE is the transarterial treatment of choice for patients with marginal hepatic reserve (i.e., hyperbilirubinemia, ascites) who may be candidates for transplant.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Microesferas , Radioisótopos de Itrio/administración & dosificación , Carcinoma Hepatocelular/patología , Arteria Hepática , Humanos , Neoplasias Hepáticas/patologíaRESUMEN
UNLABELLED: This study analyzed the predictive value of (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) SPECT for (90)Y-labeled resin microsphere therapy (radioembolization) by comparing uptake on pretherapeutic (99m)Tc-MAA SPECT with uptake on posttherapeutic (90)Y-bremsstrahlung SPECT. METHODS: We included 502 patients (55% male; mean age ± SD, 62 ± 11 y) who underwent radioembolization between 2005 and 2013 because of primary or secondary liver malignancies (colorectal cancer [n = 195, 38.8%], neuroendocrine tumors [n = 77, 15.3%], breast cancer [n = 68, 13.5%], hepatocellular carcinoma [n = 59, 11.8%], cholangiocellular carcinoma [n = 40, 8.0%], or urologic tumors [n = 14, 2.8%]). Manually drawn regions of interest around tumors and adjacent healthy liver tissue for up to 3 lesions per patient on (99m)Tc-MAA and (90)Y-bremsstrahlung scans were used to quantify mean counts per pixel and evaluate the mean tumor-to-background ratio (TBR). Data were given as mean ± SD. Additionally, uptake in lesions on (99m)Tc-MAA and (90)Y-bremsstrahlung scans was graded visually as homogeneously higher than (grade 1), heterogeneously higher than (grade 2), equal to (grade 3), or lower than (grade 4) uptake in normal liver tissue. The Mann-Whitney U test and Spearman correlation were used to evaluate statistically significant differences between (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT. RESULTS: In total, 1,008 lesions were analyzed. Of the 23% (230/1,008) of lesions that had grade 1 uptake on (99m)Tc-MAA SPECT, 81% (186/230) remained grade 1 after radioembolization whereas 16% (37/230) were grade 2. Of the lesions with grade 2 uptake on (99m)Tc-MAA SPECT, 16% had grade 1 uptake and 82% grade 2 uptake after radioembolization. Of the lesions with grade 3 uptake, however, 27% had grade 1 uptake and 47% grade 2 uptake after radioembolization. Even among the lesions with grade 4 uptake on (99m)Tc-MAA SPECT, 21% had grade 1 uptake and 46% grade 2 uptake after radioembolization. The mean TBR on (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT showed a significant, though low, correlation in the total population (r = 0.26; P < 0.001) and in hepatocellular carcinoma (r = 0.4; P < 0.001), cholangiocellular carcinoma (r = 0.3; P < 0.05), breast cancer (r = 0.3; P < 0.001), colorectal cancer (r = 0.2; P < 0.001), and neuroendocrine tumors (r = 0.2; P < 0.01). CONCLUSION: Although significant for most lesions, the correlation between (99m)Tc-MAA and (90)Y-microsphere mean TBR was low. Classifying uptake into 4 grades revealed that lesions with high uptake on (99m)Tc-MAA SPECT maintain high uptake within radioembolization. More than 60% of lesions with a pretherapeutically lower uptake than in healthy liver tissue, however, showed high uptake within radioembolization. Patients with low tumor uptake on pretherapeutic (99m)Tc-MAA imaging should not be excluded from radioembolization.
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Embolización Terapéutica/métodos , Neoplasias Hepáticas/radioterapia , Radiofármacos , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón Único/métodos , Radioisótopos de Itrio , Adulto , Anciano , Anciano de 80 o más Años , Angiografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Neoplasias Hepáticas/secundario , Masculino , Microesferas , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Radiofármacos/farmacocinética , Agregado de Albúmina Marcado con Tecnecio Tc 99m/farmacocinética , Distribución Tisular , Radioisótopos de Itrio/farmacocinéticaRESUMEN
In the last years, radioembolization (RE) has emerged as a novel technique for the treatment of malignant hepatic lesions using (90)Y embedded in spheres, which are infused directly into the hepatic arterial circulation. (90)Y-spheres, once implanted in liver, can release a significant radiation burden to neoplastic cells with a relative low dose to normal parenchyma. (90)Y RE results as a combination of embolization and radiation therapy, thus the standard radiologic follow up modalities may be not sufficiently accurate to assess tumor response to treatment. (18)Fluoro-deoxyglucose Positron Emission Tomography ((18)F-FDG PET) detects glucose uptake and metabolic activity in tumor cells. (18)F-FDG PET has become a well established diagnostic tool in many oncological scenarios. Furthermore, PET response criteria (PERCIST) have been recently introduced to categorize the metabolic response to therapy of cancer patients. Several semiquantitative parameters, such as SUVmax and its changes, the Functional Tumor Volume and the Total Lesion Glycolysis can be useful to accurately assess tumor changes after therapy. The purpose of this article is to present the literature on the role of (18)F-FDG PET in the evaluation of patients with primary and secondary liver tumors treated with (90)Y RE.
RESUMEN
BACKGROUND: The safety and efficacy of yttrium 90 ((90) Y) therapy for unresectable infiltrative hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) requires further evaluation. METHODS: A prospective, single-center safety and feasibility study recruited patients with unresectable (Barcelona Clinic Liver Cancer stage C) infiltrative HCC with PVT. Safety was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Overall survival (OS) and time to progression (TTP) were measured from the first (90) Y therapy. Survival analysis was performed with Kaplan-Meier estimation. Prognostic factors were tested with a log-rank test and Cox proportional regression analysis. RESULTS: Overall, 45 patients were recruited, and 30 patients who met the study's inclusion criteria underwent glass-based (90) Y therapy. Four patients (13%) had transient hepatobiliary toxicity (grade ≥ 2). Ten patients (33%) had related emergency department visits, with 5 patients (17%) requiring short-term hospitalization. No radiation pneumonitis, gastrointestinal ulceration, or procedure-related mortality occurred. The median OS was 13 months (95% confidence interval, 4.4-22 months) with a TTP of 9 months (95% confidence interval, 6.2-13.1 months). Absence of ascites, an international normalized ratio < 1.2, an Eastern Cooperative Oncology Group (ECOG) performance status of 0, Child-Pugh class A, a macroaggregated albumin lung shunt fraction (LSF) < 10%, and no hepatobiliary toxicity were significant predictors of prolonged OS according to a univariate analysis (P < .05). A multivariate analysis found an ECOG performance status of 0, Child-Pugh class A, an LSF < 10%, and lack of transient hepatobiliary toxicity (grade ≥ 2) to be independent predictors of prolonged OS (P < .05). An ECOG performance status of 0, Child-Pugh class A, and an LSF < 10% were also predictors of prolonged TTP according to the multivariate analysis (P < .05). CONCLUSIONS: In patients with unresectable infiltrative HCC and PVT, (90) Y therapy appears to be a safe and viable therapy.
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Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Embolización Terapéutica/métodos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Trombosis de la Vena/patología , Trombosis de la Vena/terapia , Radioisótopos de Itrio/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/radioterapia , Progresión de la Enfermedad , Embolización Terapéutica/efectos adversos , Femenino , Humanos , Neoplasias Hepáticas/radioterapia , Masculino , Persona de Mediana Edad , Vena Porta/patología , Pronóstico , Estudios Prospectivos , Resultado del Tratamiento , Trombosis de la Vena/radioterapia , Radioisótopos de Itrio/efectos adversosRESUMEN
INTRODUCTION: Our aim was to assess the prognostic value of post-treatment decrease in total lesion glycolysis (ΔTLG) assessed by 2-[(18)F]-fluorodeoxyglucose ([(18)F] FDG) PET-CT performed 6weeks after (90)Y radioembolization ((90)Y RE) in patients affected by intrahepatic cholangiocarcinoma (ICC). METHODS: A total of 18 patients were accepted into our department for (90)Y RE. Before the procedure, all patients underwent [(18)F] FDG PET-CT, and total lesion glycolysis was calculated. Six weeks after (90)Y administration, PET scan was performed, and ΔTLG was determined. Patients underwent follow up by imaging and laboratory at quarterly intervals until death or for at least 24 months from (90)Y RE. Furthermore, subjects were divided in 2 groups (group 1: 6 weeks ΔTLG>50%, group 2: ΔTLG<50%). Kaplan-Meier method was used to achieve time to progression (TTP) and overall survival (OS) curves for each group. TTP and OS curves were compared to demonstrate eventual relevant differences between the 2 groups. RESULTS: Seventeen patients underwent (90)Y RE, and one subject was considered ineligible. According to PET Response Criteria in Solid Tumors, partial response was found in 14 patients (82.4%), stable disease in 3 (17.6%). No patient showed complete metabolic response. The mean OS for all patients was 64.5±5.0 weeks. Subjects with a ΔTLG>50% and ΔTLG<50% had a mean OS of 79.6±3.6 and 43.1±2.0 weeks, respectively (p<0.001). TTP resulted of 28.9±3.8 weeks for the whole cohort. Patients with ΔTLG>50% had a significantly longer TTP (mean 36.9±3.6 weeks) than those with ΔTLG<50% (mean 13.7±1.7 weeks, p=0.001). CONCLUSION: Our results indicate that (90)Y RE can be an effective and safe therapy for ICC. ΔTLG calculated on post-treatment [(18)F] FDG PET-CT agrees with patients' final outcome.