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BACKGROUND: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. METHODS: Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. RESULTS: The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (Nâ =â 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEAâ ≥â 35 ng/mL from both treatment arms; subgroup B (Nâ =â 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (Nâ =â 143) demonstrated superior outcomes vs Chemo (Nâ =â 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided Pâ =â .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided Pâ <â .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided Pâ =â .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided Pâ <â .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. CONCLUSIONS: Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027).
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Neoplasias Colorrectales , Neoplasias Hepáticas , Calidad de Vida , Radioisótopos de Itrio , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/terapia , Radioisótopos de Itrio/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Selección de Paciente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , VidrioRESUMEN
The dosimetry evaluation for the selective internal radiation therapy is currently performed assuming a uniform activity distribution, which is in contrast with literature findings. A 2D microscopic model of the perfused liver was developed to evaluate the effect of two different 90Y microspheres distributions: i) homogeneous partitioning with the microspheres equally distributed in the perfused liver, and ii) tumor-clustered partitioning where the microspheres distribution is inferred from the patient specific images. METHODS: Two subjects diagnosed with liver cancer were included in this study. For each subject, abdominal CT scans acquired prior to the SIRT and post-treatment 90Y positron emission tomography were considered. Two microspheres partitionings were simulated namely homogeneous and tumor-clustered partitioning. The homogeneous and tumor-clustered partitionings were derived starting from CT images. The microspheres radiation is simulated by means of Russell's law. RESULTS: In homogenous simulations, the dose delivery is uniform in the whole liver while in the tumor-clustered simulations a heterogeneous distribution of the delivered dose is visible with higher values in the tumor regions. In addition, in the tumor-clustered simulation, the delivered dose is higher in the viable tumor than in the necrotic tumor, for all patients. In the tumor-clustered case, the dose delivered in the non-tumoral tissue (NTT) was considerably lower than in the perfused liver. CONCLUSIONS: The model proposed here represents a proof-of-concept for personalized dosimetry assessment based on preoperative CT images.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Microesferas , Dosificación Radioterapéutica , Radioisótopos de Itrio , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagen , Humanos , Radioisótopos de Itrio/uso terapéutico , Modelos Biológicos , Tomografía Computarizada por Rayos X , Dosis de Radiación , MicroscopíaRESUMEN
Interim analysis of the DOSISPHERE-01 study demonstrated a strong improvement in response and overall survival (OS) on using 90Y-loaded glass microspheres with personalized dosimetry compared with standard dosimetry in patients with nonoperable locally advanced hepatocellular carcinoma. This report sought to provide a long-term analysis of OS. Methods: In this phase II study (ClinicalTrials.gov identifier NCT02582034), treatment was randomly assigned (1:1) with the goal to deliver either at least 205 Gy (if possible >250-300 Gy) to the index lesion in the personalized dosimetry approach (PDA) or 120 ± 20 Gy to the treated volume in the standard dosimetry approach (SDA). The 3-mo response of the index lesion was the primary endpoint, with OS being one of the secondary endpoints. This report is a post hoc long-term analysis of OS. Results: Overall, 60 hepatocellular carcinoma patients with at least 1 lesion larger than 7 cm and more than 30% of hepatic reserve were randomized (intent-to-treat population: PDA, n = 31; SDA, n = 29), with 56 actually treated (modified intent-to-treat population: n = 28 in each arm). The median follow-up for long-term analysis was 65.8 mo (range, 2.1-73.1 mo). Median OS was 24.8 mo and 10.7 mo (hazard ratio [HR], 0.51; 95% CI, 0.29-0.9; P = 0.02) for PDA and SDA, respectively, in the modified intent-to-treat population. Median OS was 22.9 mo for patients with a tumor dose of at least 205 Gy, versus 10.3 mo for those with a tumor dose of less than 205 Gy (HR, 0.42; 95% CI, 0.22-0.81; P = 0.0095), and was 22.9 mo for patients with a perfused liver dose of 150 Gy or higher, versus 10.3 mo for those with a perfused liver dose of less than 150 Gy (HR, 0.42; 95% CI, 0.23-0.75; P = 0.0033). Lastly, median OS was not reached in patients who were secondarily resected (n = 11, 10 in the PDA group and 1 in the SDA group), versus 10.8 mo in those without secondary resection (n = 45) (HR, 0.17; 95% CI, 0.065-0.43; P = 0.0002). Only resected patients displayed favorable long-term OS rates, meaning an OS of more than 50% at 5 y. Conclusion: After longer follow-up, personalized dosimetry sustained a meaningful improvement in OS, which was dramatically improved for patients who were accurately downstaged toward resection, including most portal vein thrombosis patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombosis de la Vena , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/patología , Radiometría , Trombosis de la Vena/complicaciones , Radioisótopos de Itrio/uso terapéutico , MicroesferasRESUMEN
BACKGOUND AND AIMS: In advanced, liver-only intrahepatic cholangiocarcinoma (iCCA), selective internal radiation therapy (SIRT) has been suggested as promising in nonrandomized studies. We aimed to compare data from patients with advanced, liver-only iCCA treated in the first line in clinical trials with either chemotherapy alone or the combination with SIRT. APPROACH AND RESULTS: We collected individual patients' data from the ABC-01, ABC-02, ABC-03, BINGO, AMEBICA, and MISPHEC prospective trials. Data from patients with liver-only iCCA treated in chemotherapy-only arms of the first 5 trials were compared with data from patients treated with SIRT and chemotherapy in MISPHEC. Emulated target trial paradigm and Inverse Probability of Treatment Weighting (IPTW methods) using the propensity score were used to minimize biases. We compared 41 patients treated with the combination with 73 patients treated with chemotherapy alone, the main analysis being in 43 patients treated with cisplatin-gemcitabine or gemcitabine-oxaliplatin. After weighting, overall survival was significantly higher in patients treated with SIRT: median 21.7 months (95% CI: 14.1; not reached) versus 15.9 months(95% CI: 9.8; 18.9), HR = 0.59 (95% CI: 0.34; 0.99), p = 0.049. Progression-free survival was significantly improved: median 14.3 months (95% CI: 7.8; not reached) versus 8.4 months (95% CI: 5.9; 12.1), HR = 0.52 (95% CI: 0.31; 0.89), p < 0.001. Results were confirmed in most sensitivity analyses. CONCLUSIONS: This analysis derived from prospective clinical trials suggests that SIRT combined with chemotherapy might improve outcomes over chemotherapy alone in patients with advanced, liver-only iCCA. Randomized controlled evidence is needed to confirm these findings.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Gemcitabina , Estudios Prospectivos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/radioterapiaRESUMEN
PURPOSE: Investigate reproducibility of two segmentation methods for multicompartment dosimetry, including normal tissue absorbed dose (NTAD) and tumour absorbed dose (TAD), in hepatocellular carcinoma patients treated with yttrium-90 (90Y) glass microspheres. METHODS: TARGET was a retrospective investigation in 209 patients with < 10 tumours per lobe and at least one tumour ≥ 3 cm ± portal vein thrombosis. Dosimetry was compared using two distinct segmentation methods: anatomic (CT/MRI-based) and count threshold-based on pre-procedural 99mTc-MAA SPECT. In a round robin substudy in 20 patients with ≤ 5 unilobar tumours, the inter-observer reproducibility of eight reviewers was evaluated by computing reproducibility coefficient (RDC) of volume and absorbed dose for whole liver, whole liver normal tissue, perfused normal tissue, perfused liver, total perfused tumour, and target lesion. Intra-observer reproducibility was based on second assessments in 10 patients ≥ 2 weeks later. RESULTS: 99mTc-MAA segmentation calculated higher absorbed doses compared to anatomic segmentation (n = 209), 43.9% higher for TAD (95% limits of agreement [LoA]: - 49.0%, 306.2%) and 21.3% for NTAD (95% LoA: - 67.6%, 354.0%). For the round robin substudy (n = 20), inter-observer reproducibility was better for anatomic (RDC range: 1.17 to 3.53) than 99mTc-MAA SPECT segmentation (1.29 to 7.00) and similar between anatomic imaging modalities (CT: 1.09 to 3.56; MRI: 1.24 to 3.50). Inter-observer reproducibility was better for larger volumes. Perfused normal tissue volume RDC was 1.95 by anatomic and 3.19 by 99mTc-MAA SPECT, with corresponding absorbed dose RDC 1.46 and 1.75. Total perfused tumour volume RDC was higher, 2.92 for anatomic and 7.0 by 99mTc-MAA SPECT with corresponding absorbed dose RDC of 1.84 and 2.78. Intra-observer variability was lower for perfused NTAD (range: 14.3 to 19.7 Gy) than total perfused TAD (range: 42.8 to 121.4 Gy). CONCLUSION: Anatomic segmentation-based dosimetry, versus 99mTc-MAA segmentation, results in lower absorbed doses with superior reproducibility. Higher volume compartments, such as normal tissue versus tumour, exhibit improved reproducibility. TRIAL REGISTRATION: NCT03295006.
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Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamiento farmacológico , Estudios Retrospectivos , Reproducibilidad de los Resultados , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón Único , Radioisótopos de Itrio/uso terapéutico , Microesferas , Embolización Terapéutica/efectos adversosRESUMEN
OBJECTIVE: The aim of this study was to evaluate the efficacy of yttrium-90 transarterial radioembolization (TARE) to convert to resection initially unresectable, single, large (≥5 cm) hepatocellular carcinoma (HCC). BACKGROUND: TARE can downsize cholangiocarcinoma to resection but its role in HCC resectability remains debatable. METHODS: All consecutive patients with a single large HCC treated between 2015 and 2020 in a single tertiary center were reviewed. When indicated, patients were either readily resected (upfront surgery) or underwent TARE. TARE patients were converted to resection (TARE surgery) or not (TARE-only). To further assess the effect of TARE on the long-term and short-term outcomes, a propensity score matching analysis was performed. RESULTS: Among 216 patients, 144 (66.7%) underwent upfront surgery. Among 72 TARE patients, 20 (27.7%) were converted to resection. TARE-surgery patients received a higher mean yttrium-90 dose that the 52 remaining TARE-only patients (211.89±107.98 vs 128.7±36.52 Gy, P <0.001). Postoperative outcomes between upfront-surgery and TARE-surgery patients were similar. In the unmatched population, overall survival at 1, 3, and 5 years was similar between upfront-surgery and TARE-surgery patients (83.0%, 60.0%, 47% vs 94.0%, 86.0%, 55.0%, P =0.43) and compared favorably with TARE-only patients (61.0%, 16.0% and 9.0%, P <0.0001). After propensity score matching, TARE-surgery patients had significantly better overall survival than upfront-surgery patients ( P =0.021), while disease-free survival was similar ( P =0.29). CONCLUSION: TARE may be a useful downstaging treatment for unresectable localized single large HCC providing comparable short-term and long-term outcomes with readily resectable tumors.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Radioisótopos de Itrio/uso terapéuticoRESUMEN
BACKGROUND: Despite the wide development of 90Y-loaded microspheres, 188Re-labeled lipiodol is still being used for radioembolization of hepatocellular carcinoma (HCC). However, the use of this latter compound is limited by in vivo instability. This study sought to evaluate the safety, bio-distribution, and response to 188Re-SSS lipiodol, a new and more stable compound. METHOD: Lip-Re-01 was an activity-escalation Phase 1 study involving HCC patients progressing after sorafenib. The primary endpoint was safety based on Common Terminology Criteria for Adverse Events (AEs) of Grade ≥3 within 2 months. Secondary endpoints included bio-distribution assessed by scintigraphy quantification from 1 to 72 h, tumor to non-tumor uptake ratio (T/NT), as well as blood, urine and feces collection over 72 h, dosimetry, and response evaluation (mRECIST). RESULTS: Overall, 14 heavily pre-treated HCC patients were treated using a whole liver approach. The mean injected activity was 1.5 ± 0.4 GBq for activity Level 1 (n = 6), 3.6 ± 0.3 GBq for Level 2 (n = 6), and 5.0 ± 0.4 GBq for Level 3 (n = 2). Safety was acceptable with only 1/6 of Level 1 and 1/6 of Level 2 patients experiencing limiting toxicity (one liver failure; one lung disease). The study was prematurely discontinued unrelated to clinical outcomes. Uptake occurred in the tumor, liver, and lungs, and only sometimes in the bladder. The T/NT ratio was high with a mean of 24.9 ± 23.4. Cumulative urinary elimination and fecal eliminations at 72 h were very low, 4.8 ± 3.2% and 0.7 ± 0.8%, respectively. Partial response occurred in 21% of patients (0% in the first activity level; 37.5% in the others). CONCLUSION: The high in vivo stability of 188Re-SSS lipiodol was confirmed, resulting in encouraging responses for a Phase 1 study. As the 3.6 GBq activity proved to be safe, it will be used in a future Phase 2 study.
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PURPOSE: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). METHODS: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. RESULTS: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. CONCLUSION: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.
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Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Radioisótopos de Itrio/uso terapéutico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamiento farmacológico , Microesferas , Radiofármacos/uso terapéutico , Embolización Terapéutica/métodos , VidrioRESUMEN
BACKGROUND: A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the "ideal" intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. METHODS: This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. RESULTS: A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73%) responded, including 23 interventional radiologists (79%), three nuclear medicine physicians (10%), two hepatologists, and one oncologist, from 11 countries spanning three continents. The final TO consisted 11 parameters across six domains ("pre-intervention workup," "tumor targeting and dosimetry," "intervention," "post-90Y imaging," "length of hospital stay," and "complications"). Of these, all but one were applied in the institutions of > 80% of experts. CONCLUSIONS: This multidimensional indicator is a comprehensive standardization tool, suitable for routine care, clinical round, and research.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamiento farmacológico , Radiometría , Radioisótopos de Itrio/uso terapéuticoRESUMEN
In cirrhotic patients with hepatocellular carcinoma (HCC), right-sided radioembolization (RE) with Yttrium-90-loaded microspheres is an established palliative therapy and can be considered a "curative intention" treatment when aiming for sequential tumor resection. To become surgical candidate, hypertrophy of the left liver lobe to > 40% (future liver remnant, FLR) is mandatory, which can develop after RE. The amount of radiation-induced shrinkage of the right lobe and compensatory hypertrophy of the left lobe is difficult for clinicians to predict. This study aimed to utilize machine learning to predict left lobe liver hypertrophy in patients with HCC and cirrhosis scheduled for right lobe RE, with external validation. The results revealed that machine learning can accurately predict relative and absolute volume changes of the left liver lobe after right lobe RE. This prediction algorithm could help to estimate the chances of conversion from palliative RE to curative major hepatectomy following significant FLR hypertrophy.
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Braquiterapia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , HipertrofiaRESUMEN
Trans-arterial radioembolization is currently performed using 90Y-loaded glass or resin microspheres and also using 166Ho-loaded microspheres. The goal of this review is to present dosimetry and radiobiology concepts, the different dosimetry approaches available (simulation-based dosimetry and post-treatment dosimetry), main confounding factors as main clinical dosimetry results provided during the last decade for both hepatocellular carcinoma (HCC) and metastases of colorectal carcinoma (mCRC). Based on the different number of microspheres or different isotope used, radiobiology of the three devices is different, meaning that tumouricidal doses and maximal tolerated doses are different. Tumouricidal doses described for HCCs were 100-120 grays (Gy) with 90Y resin microspheres and 205 Gy with 90Y glass microspheres. For mCRC, it is 39-60 with 90Y resin microspheres, 139 Gy with 90Y glass microspheres and 90 Gy with 166Ho microspheres. An impact of tumoural doses with overall survival has also been reported. Personalised dosimetry has been developed and is now recommended by several international expert groups. Level-one evidence of the major impact of personalised dosimetry on response and overall survival in HCC is now available, bringing a new standard approach for TARE in clinical practice as well as for trial design.
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Braquiterapia , Carcinoma Hepatocelular , Neoplasias Colorrectales , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Embolización Terapéutica/métodos , Radiometría , Microesferas , Neoplasias Colorrectales/patología , Radioisótopos de Itrio/uso terapéuticoRESUMEN
PURPOSE: To investigate the relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and clinical outcomes in hepatocellular carcinoma (HCC) treated with yttrium-90 glass microspheres. METHODS: TARGET was a retrospective investigation in 13 centers across eight countries. Key inclusion criteria: liver-dominant HCC with or without portal vein thrombosis, < 10 tumors per lobe (at least one ≥ 3 cm), Child-Pugh stage A/B7, BCLC stages A-C, and no prior intra-arterial treatment. Multi-compartment pre-treatment dosimetry was performed retrospectively. Primary endpoint was the relationship between ≥ grade 3 hyperbilirubinemia (such that > 15% of patients experienced an event) without disease progression and NTAD. Secondary endpoints included relationships between (1) objective response (OR) and TAD, (2) overall survival (OS) and TAD, and (3) alpha fetoprotein (AFP) and TAD. RESULTS: No relationship was found between NTAD and ≥ grade 3 hyperbilirubinemia, which occurred in 4.8% of the 209 patients. The mRECIST OR rate over all lesions was 61.7%; for the target (largest) lesion, 70.8%. Responders and non-responders had geometric mean total perfused TADs of 225.5 Gy and 188.3 Gy (p = 0.048). Probability of OR was higher with increasing TAD (p = 0.044). Higher TAD was associated with longer OS (HR per 100 Gy increase = 0.83, 95% CI: 0.71-0.95; p = 0.009). Increased TAD was associated with higher probability of AFP response (p = 0.046 for baseline AFP ≥ 200 ng/mL). CONCLUSION: Real-world data confirmed a significant association between TAD and OR, TAD and OS, and TAD and AFP response. No association was found between ≥ grade 3 hyperbilirubinemia and NTAD. TRIAL REGISTRATION NUMBER: NCT03295006.
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Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/radioterapia , Embolización Terapéutica/efectos adversos , Humanos , Hiperbilirrubinemia/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/radioterapia , Microesferas , Estudios Retrospectivos , Resultado del Tratamiento , Radioisótopos de Itrio/uso terapéutico , alfa-FetoproteínasRESUMEN
The Barcelona Clinic Liver Cancer (BCLC) system is the most commonly used staging system for hepatocellular carcinoma (HCC) in Western countries. BCLC aims to categorize patients into five stages with different prognoses and to allocate treatment according to these stages based on the best possible contemporary evidence. Transarterial radioembolization (TARE) has recently entered at the left of the BCLC algorithm (i.e., BCLC 0-A), mainly because of negative phase III trials in BCLC C stage. TARE has shown a steady increase in nationwide studies over the past 20 years and has even been adopted in some tertiary centers as the primary HCC treatment across all BCLC stages. We aimed to review the history of TARE in HCC, starting from advanced HCC and gradually expanding to earlier stages at the left of the BCLC system.
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Braquiterapia , Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Radioisótopos de Itrio , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
PRIMARY OBJECTIVE: Recently, selective internal radiation therapy using yttrium-90 (Y90) glass microspheres (TheraSphere™) was approved for reimbursement by health authorities in France. The PROACTIF study aims to gather data on effectiveness, patient quality of life, and safety with use of Y90 glass microspheres in real-world clinical settings in France. INCLUSION CRITERIA: Patient with a diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCC), and/or metastatic colorectal cancer (mCRC) who was treated with a dose of Y90 glass microspheres that has been reimbursed in France and who do not oppose use of their personal medical data. EXCLUSION CRITERIA: If data collection is opposed, treatment is reimbursed but not administered, or treatment is administered but not reimbursed. OUTCOME MEASURES: Primary outcome measures include overall survival from time of Y90 glass microsphere treatment and quality of life, as assessed using the Functional Assessment of Cancer Therapy- Hepatobiliary questionnaire. ESTIMATED NUMBER OF PATIENTS TO BE INCLUDED: This is an open study and there is no set number of patients; 115 have already been enrolled. PLANNED SUBGROUP ANALYSES: Analyses will be stratified by disease state (HCC, iCC, or mCRC). Subgroups to be analyzed include age group, unilobar/bilobar disease at baseline, Eastern Cooperative Oncology Group (ECOG) status at baseline, liver tumor burden at baseline, target lesion size, and standard versus multi-compartment personalized dosimetry treatment. PLANNED RECRUITMENT AND OBSERVATION PERIOD: Recruitment includes patients who are prescribed and treated with a commercial vial of Y90 glass microspheres between 01 January 2019 and 31 December 2024. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069468.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Colorrectales , Embolización Terapéutica , Neoplasias Hepáticas , Conductos Biliares Intrahepáticos , Carcinoma Hepatocelular/radioterapia , Colangiocarcinoma/radioterapia , Ensayos Clínicos Fase IV como Asunto , Neoplasias Colorrectales/radioterapia , Humanos , Neoplasias Hepáticas/radioterapia , Microesferas , Estudios Prospectivos , Calidad de Vida , Sistema de Registros , Resultado del Tratamiento , Radioisótopos de Itrio/uso terapéuticoRESUMEN
BACKGROUND: Selective internal radiation therapy (SIRT) is applied to hepatocellular carcinoma (HCC), a disease with increased incidence in the elderly. However, SIRT has rarely been specifically studied in elderly population. The aim of this study was to investigate efficacy and safety of SIRT in elderly HCC patients. METHODS: We studied retrospectively data from patients treated with SIRT for HCC. Clinical and laboratory data were retrieved. We used 70-years old as threshold between younger and elderly populations, to compare outcomes. RESULTS: A total of 222 patients treated with SIRT for HCC were studied, of which 134 patients were younger and 88 older. Median overall survival (OS) was not significantly different between younger and elderly group: 15.6 months (95% CI, 11.7-19.5) and 14.8 months (95% CI, 9.4-20.3) (P = 0.86). Age was not associated with OS in multivariable analysis, with a Hazard ratio of 1.09 (95% CI, 0.82-1.45, P = 0.55). Results of progression-free survival and responses were also similar in both groups. Toxicities were similar between the two groups, including the occurrence of radioembolization-induced liver disease (11.5 vs. 11.4%, P = 0.97). CONCLUSION: SIRT appears to be a well-tolerated treatment with the same efficacy in elderly compared to younger patients in HCC. Our study is the first to study its impact with glass microspheres. This warrants confirmation in large prospective studies.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Anciano , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Microesferas , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Radioisótopos de Itrio/efectos adversosRESUMEN
BACKGROUND: In the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) single-arm phase 2 trial, concomitant chemotherapy and selective internal radiotherapy (SIRT) showed antitumor activity as a first-line treatment of unresectable intrahepatic cholangiocarcinomas (ICCs). In this sub-analysis, we aimed to evaluate one of the secondary endpoints, the health-related quality of life (QoL), evaluated with an EORTC QLQ-C30 instrument at the baseline and during treatment. METHODS: The MISPHEC trial included treatment-naïve patients with an unresectable ICC between November 2013 and June 2016. Patients received concomitant first-line chemotherapy with cisplatin and gemcitabine for 8 cycles; SIRT was administered during cycle 1 (for patients with unilobar disease) or cycles 1 and 3 (for patients with bilobar disease) using glass Yttrium-90 microspheres. We evaluated the QoL-measured by the QLQ-C30 questionnaire-at the baseline, every 8 weeks during chemotherapy and follow-up, between 12 and 15 weeks after embolization and every 12 weeks after a liver resection if applicable. RESULTS: A total of 41 patients were included, of which 34 completed questionnaires at the baseline. No clinically significant changes in the global health score or the sub-scales of the QLQ-C30 were observed during follow-up. The physical, social and role function mean score worsened during treatment and fatigue, nausea and pain scores increased although the differences were not clinically significant. In patients undergoing subsequent surgery, the QoL was not impaired. CONCLUSIONS: A combination of SIRT and chemotherapy with gemcitabine and cisplatin as the first-line treatment of unresectable ICCs was found to maintain the QoL.
Asunto(s)
Neoplasias de los Conductos Biliares , Braquiterapia , Colangiocarcinoma , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares Intrahepáticos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/radioterapia , Humanos , Calidad de VidaRESUMEN
PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS: Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION: The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/mortalidad , Neoplasias Colorrectales/terapia , Embolización Terapéutica/mortalidad , Neoplasias Hepáticas/terapia , Radioisótopos de Itrio/uso terapéutico , Bevacizumab/administración & dosificación , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Irinotecán/administración & dosificación , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Selective internal radiation therapy (SIRT) is an innovative treatment of hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI) score was designed to better evaluate liver functions in HCC. METHODS: We studied, retrospectively, data from patients treated with SIRT for HCC. The primary endpoint was the occurrence of radioembolization-induced liver disease (REILD). The secondary endpoint was overall survival (OS). RESULTS: 222 patients were studied. The ALBI grade 1 patients had significantly less REILD (3.4%) after the first SIRT than ALBI grade 2 or 3 patients (16.8%, p = 0.002). Of the 207 patients with data, 77 (37.2%) had a worsening of ALBI grade after one SIRT. The baseline ALBI grade was significantly associated with OS (p = 0.001), also in the multivariable analysis. The ALBI grade after the first SIRT was significantly associated with OS (p ≤ 0.001), with median OS of 26.4 months (CI 95% 18.2-34.7) for ALBI grade 1 patients (n = 48) versus 17.3 months (CI 95% 12.9-21.8) for ALBI grade 2 patients (n = 123) and 8.1 months (CI 95% 4.1-12.1) for ALBI grade 3 patients (n = 36). CONCLUSIONS: The baseline ALBI grade is a strong predictor of REILD. The baseline ALBI score and variations of ALBI are prognostic after SIRT.