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Academic Radiology Nov 2022
Topics: Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Pancreas; Abdomen; Syndrome
PubMed: 36075823
DOI: 10.1016/j.acra.2022.08.003 -
JAMA Oncology Jun 2022Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent... (Clinical Trial)
Clinical Trial
IMPORTANCE
Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single-agent programmed cell death 1 inhibitors in NET have been disappointing.
OBJECTIVE
To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs.
DESIGN, SETTING, AND PARTICIPANTS
This single-arm, open-label nonrandomized clinical study in patients with rare cancers included 40 patients with advanced, progressive grade 1 to 2 NETs (20 with pancreatic NETs [pNETs] and 20 with extrapancreatic NETs [epNETs]) treated at a tertiary care referral cancer center between March 31, 2017, and February 19, 2019. Data were analyzed from June to September 2021.
INTERVENTIONS
Patients received intravenous bevacizumab and atezolizumab at standard doses every 3 weeks until progression, death, or withdrawal.
MAIN OUTCOMES AND MEASURES
The primary end point was objective radiographic response using Response Evaluation Criteria in Solid Tumors, version 1.1, with progression-free survival (PFS) as a key secondary end point.
RESULTS
Following treatment of the 40 study patients with bevacizumab and atezolizumab, objective response was observed in 4 patients with pNETs (20%; 95% CI, 5.7%-43.7%) and 3 patients with epNETs (15%; 95% CI, 3.2%-37.9%). The PFS was 14.9 (95% CI, 4.4-32.0) months and 14.2 (95% CI, 10.2-19.6) months in these cohorts, respectively.
CONCLUSIONS AND RELEVANCE
In this nonrandomized clinical trial, findings suggest that clinical responses in patients with NET may follow treatment with the combination of bevacizumab and atezolizumab, with a PFS consistent with effective therapies.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03074513.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Humans; Neuroectodermal Tumors, Primitive; Neuroendocrine Tumors; Prospective Studies; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 35389428
DOI: 10.1001/jamaoncol.2022.0212 -
Academic Radiology Nov 2022
Topics: Humans; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Abdomen; Syndrome
PubMed: 36180326
DOI: 10.1016/j.acra.2022.08.004 -
Frontiers in Cardiovascular Medicine 2022Carcinoid heart disease (CnHD) is a frequent cause of morbidity and mortality in patients with neuroendocrine tumors and carcinoid syndrome. Although valve replacement...
BACKGROUND
Carcinoid heart disease (CnHD) is a frequent cause of morbidity and mortality in patients with neuroendocrine tumors and carcinoid syndrome. Although valve replacement surgery appears to decrease all-cause mortality in patients with advanced CnHD, few studies have investigated the outcomes of patients after valve replacement.
METHODS
We conducted a multi-institution retrospective registry of patients who received both tricuspid and pulmonic bioprosthetic valve (TV/PV) replacements for advanced CnHD from November 2005 to March 2021. Patients were followed post-operatively with echocardiographic studies every 3 months. Carcinoid valvular heart disease scores were used to monitor valve degeneration. Neuroendocrine tumor treatment, their administration times, and associations with echocardiographic findings were recorded.
RESULTS
Of 87 patients with CnHD, 22 patients underwent simultaneous surgical TV and PV replacement. In 6 patients (27.3%), increased PV V was the first echocardiographic manifestation of valve degeneration in the setting of occult neurohormonal release. Post-operative telotristat ethyl and peptide receptor radionuclide therapy appeared to stabilize PV V. The PV V showed consistent elevation in the entire patient population when compared to baseline, while bioprosthetic TV echocardiographic parameters were relatively unchanged throughout. Post-operative warfarin therapy did not affect the rate of PV degeneration, and no major bleeding was recorded during or after post-operative anticoagulation therapy.
CONCLUSION
Bioprosthetic valve degeneration is common in CnHD. Monitoring with echocardiographic studies every 3 months, focusing on PV velocities, could identify patients with occult disease that very likely promotes valve degeneration. Novel neuroendocrine tumor therapies may have a beneficial impact on valve degeneration.
PubMed: 36712267
DOI: 10.3389/fcvm.2022.1072890 -
Cardiovascular and Interventional... Feb 2020Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on...
PURPOSE
Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT.
METHODS
Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected.
RESULTS
Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3-4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8-5.1 years] after radioembolization for the entire study population was found.
CONCLUSION
Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare.
LEVEL OF EVIDENCE
4, case series.
Topics: Adult; Aged; Aged, 80 and over; Brachytherapy; Female; Humans; Liver Neoplasms; Male; Microspheres; Middle Aged; Neuroendocrine Tumors; Receptors, Peptide; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Treatment Outcome; Yttrium Radioisotopes
PubMed: 31646375
DOI: 10.1007/s00270-019-02350-2 -
Journal of Gastrointestinal Surgery :... Sep 2023To evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression...
PURPOSE
To evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression following radiotherapy.
METHODS
This single-institution retrospective analysis included consecutive HCC patients having intrahepatic tumor progression following radiotherapy during 2015-2019. Overall survival (OS) was calculated from the date of intrahepatic tumor progression after initial radiotherapy by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariable and multivariable analyses. An inverse probability weighting was used to estimate treatment effect of salvage-LT considering confounding factors.
RESULTS
A total of 123 patients (mean age ± SD, 70 years ± 10; 97 men) were evaluated. Among those, 35 patients underwent 59 sessions of salvage-LT, including transarterial embolization/chemoembolization (n = 33), ablation (n = 11), selective internal radiotherapy (n = 7), and external beam radiotherapy (n = 8). At a median follow-up of 15.1 months (range, 3.4-54.5 months), the median OS was 23.3 months in patients who received salvage-LT and 6.6 months who did not. At multivariate analysis, ECOG performance status, Child-Pugh class, albumin-bilirubin grade, extrahepatic disease, and lack of salvage-LT were independent predictors of worse OS. After inverse probability weighting, salvage-LT was associated with a survival benefit of 8.9 months (95% CI: 1.1, 16.7 months; p = 0.03).
CONCLUSIONS
Salvage locoregional therapy is associated with increased survival in HCC patients suffering from intrahepatic tumor progression following initial radiotherapy.
Topics: Male; Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Chemoembolization, Therapeutic; Combined Modality Therapy; Salvage Therapy; Treatment Outcome
PubMed: 37268830
DOI: 10.1007/s11605-023-05712-x -
Journal of Hepatocellular Carcinoma 2020To assess the overall survival (OS) and progression-free survival (PFS) of unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass-microsphere...
PURPOSE
To assess the overall survival (OS) and progression-free survival (PFS) of unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass-microsphere transarterial radioembolization (TARE) with and without concurrent sorafenib.
METHODS
OS and PFS were analyzed in 55 patients with an intrahepatic tumor (IHT) ≤50% without advanced or aggressive disease features (ADFs), which was referred to presence of infiltrative/ill-defined HCC, macrovascular invasion, or extrahepatic disease treated with only TARE (TARE_alone) and in 74 patients with IHT ≤50% with ADFs or IHT >50% treated with TARE and sorafenib (TARE_sorafenib). Prognostic factors for OS and PFS were identified using univariate and multivariate analyses.
RESULTS
Median OS and PFS of TARE_alone patients were 21.6 (95% CI 6.1-37.1) and 9.1(95% CI 5.2-13.0) months, respectively, and for TARE_sorafenib patients 12.4 (95% CI 9.1-15.6) and 5.1 (95% CI 2.6-7.5) months, respectively. Better OS was associated with serum AFP <400 (HR 0.27, =0.02) in TARE_alone, and IHT ≤50% (HR 0.39, =0.004) and AFP <400 (HR 0.5, =0.027) in TARE_sorafenib. Unilobar involvement (HR 0.43, =0.029) and AFP <400 ng/mL (HR 0.52, =0.015) correlated with better PFS in TARE_alone and TARE_sorafenib, respectively. Adverse events (AEs) were more frequent in TARE_sorafenib than TARE_alone (92.4 vs 80.3%), but only 9.3% were grade 3 or higher AEs.
CONCLUSION
TARE_alone provided the most prominent survival benefit in IHT ≤50%-without ADF patients who had unilobar HCC and serum AFP <400 ng/mL. TARE and sorafenib yielded the best outcomes in patients with IHT ≤50% and serum AFP <400 ng/mL, with some additional grade 1-2 AEs compared to TARE only.
PubMed: 32984089
DOI: 10.2147/JHC.S248314 -
Cancer Discovery Nov 2021Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint...
Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum-pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTv1.1 by independent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1-64.0] with median response duration of 12.8 months. Six (75%) responses lasted for >10 months. Progression-free and overall survival at one year were 61% (95% CI, 35-80) and 85% (95% CI, 60-95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial-mesenchymal transition gene expression correlated with therapeutic resistance/response ( = 0.80; = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease. SIGNIFICANCE: Efficacy of atezolizumab and bevacizumab vis-à-vis response rates and survival in advanced peritoneal mesothelioma previously treated with chemotherapy surpassed outcomes expected with conventional therapies. Biomarker analyses uncovered epithelial-mesenchymal transition phenotype as an important resistance mechanism and showcase the value and feasibility of performing translationally driven clinical trials in rare tumors...
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Bevacizumab; Biomarkers, Tumor; Humans; Mesothelioma; Vascular Endothelial Growth Factor A
PubMed: 34261675
DOI: 10.1158/2159-8290.CD-21-0331 -
Journal of Hepatocellular Carcinoma 2021The most common cause of death in advanced/metastatic hepatocellular carcinoma (HCC) is liver failure due to tumor progression. While retrospective studies and...
PURPOSE
The most common cause of death in advanced/metastatic hepatocellular carcinoma (HCC) is liver failure due to tumor progression. While retrospective studies and meta-analyses of systemic therapy combined with liver-directed therapy have been performed, prospective studies of safety/efficacy of antiangiogenesis followed by intra-arterial therapies are lacking. We tested our hypothesis that sorafenib followed by yttrium 90 glass microspheres (Y GMs) is safe and that survival outcomes may improve by controlling hepatic tumors.
METHODS
We enrolled 38 Child-Pugh A patients with advanced/metastatic HCC. In sum, 34 received sorafenib, followed after 4 weeks by Y GMs. Analysis of safety and survival outcomes was performed to assess adverse events, median progression-free survival, and overall survival.
RESULTS
A total of 34 patients were evaluable: 14 (41.2%) with chronic hepatitis, nine (26.5%) with vascular invasion, and eleven (32.4%) with extrahepatic diseases. Safety analysis revealed that the combination therapy was well tolerated. Grade III-IV adverse events comprised fatigue (n=3), diarrhea (n=2), nausea (n=1), vomiting (n=2), hypertension (n=4), thrombocytopenia (n=1), hyperbilirubinemia (n=1), proteinuria (n=1), hyponatremia (n=1), and elevated alanine or aspartate aminotransferase (n=5). Median progression-free and overall survival were 10.4 months (95% CI 5.8-14.4) and 13.2 months (95% CI 7.9-18.9), respectively. Twelve patients (35.3%) achieved partial responses and 16 (47.0%) stable disease. Median duration of sorafenib was 20 (3-90) weeks, and average dose was 622 (466-800) mg daily. Dosimetry showed similar mean doses between planned and delivered calculations to normal liver and tumor:normal liver uptake ratio, with no significant correlation with adverse events at 3 and 6 months post-Y treatment.
CONCLUSION
This is the first prospective study to evaluate sorafenib followed by Y in patients with advanced HCC. The study validated our hypothesis of safety with encouraging efficacy signals of the sequencing treatment, and provides proof of concept for future combination modalities for patients with advanced or metastatic HCC.
CLINICAL TRIAL REGISTRATION NUMBER
NCT01900002.
PubMed: 34527608
DOI: 10.2147/JHC.S318865 -
European Radiology Experimental Jan 2023To evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE)...
A novel method for predicting hepatocellular carcinoma response to chemoembolization using an intraprocedural CT hepatic arteriography-based enhancement mapping: a proof-of-concept analysis.
BACKGROUND
To evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE) using computed tomography hepatic arteriography enhancement mapping (CTHA-EM) method.
METHODS
This three-institution retrospective study included 29 patients with 46 HCCs treated with DEB-TACE between 2017 and 2020. Pre- and posttreatment CTHA-EM images were generated using a prototype deformable registration and subtraction software. Relative tumor enhancement (T) defined as the ratio of tumor enhancement to normal liver tissue was calculated to categorize tumor response as residual (T > 1) versus non-residual (T ≤ 1) enhancement, which was blinded compared to the response assessment on first follow-up imaging using modified RECIST criteria. Additionally, for tumors with residual enhancement, CTHA-EM was evaluated to identify its potential feeding arteries.
RESULTS
CTHA-EM showed residual enhancement in 18/46 (39.1%) and non-residual enhancement in 28/46 (60.9%) HCCs, with significant differences on T (3.05 ± 2.4 versus 0.48 ± 0.23, respectively; p < 0.001). The first follow-up imaging showed non-complete response (partial response or stable disease) in 19/46 (41.3%) and complete response in 27/46 (58.7%) HCCs. CTHA-EM had a response prediction sensitivity of 94.7% (95% CI, 74.0-99.9) and specificity of 100% (95% CI, 87.2-100). Feeding arteries to the residual enhancement areas were demonstrated in all 18 HCCs (20 arteries where DEB-TACE was delivered, 2 newly developed collaterals following DEB-TACE).
CONCLUSION
CTHA-EM method was highly accurate in predicting initial HCC response to DEB-TACE and identifying feeding arteries to the areas of residual arterial enhancement.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Treatment Outcome; Chemoembolization, Therapeutic; Tomography, X-Ray Computed; Angiography
PubMed: 36717474
DOI: 10.1186/s41747-022-00315-8