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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 -
Radiology. Artificial Intelligence Sep 2019Some patients with hepatocellular carcinoma (HCC) are more likely to experience disease progression despite transcatheter arterial chemoembolization (TACE) treatment,...
PURPOSE
Some patients with hepatocellular carcinoma (HCC) are more likely to experience disease progression despite transcatheter arterial chemoembolization (TACE) treatment, and thus would benefit from early switching to other therapeutic regimens. We sought to evaluate a fully automated machine learning algorithm that uses pre-therapeutic quantitative computed tomography (CT) image features and clinical factors to predict HCC response to TACE.
MATERIALS AND METHODS
Outcome information from 105 patients receiving first-line treatment with TACE was evaluated retrospectively. The primary clinical endpoint was time to progression (TTP) based on follow-up CT radiological criteria (mRECIST). A 14-week cutoff was used to classify patients as TACE-susceptible (TTP ≥14 weeks) or TACE-refractory (TTP <14 weeks). Response to TACE was predicted using a random forest classifier with the Barcelona Clinic Liver Cancer (BCLC) stage and quantitative image features as input as well as the BCLC stage alone as a control.
RESULTS
The model's response prediction accuracy rate was 74.2% (95% CI=64%-82%) using a combination of the BCLC stage plus quantitative image features versus 62.9% (95% CI= 52%-72%) using the BCLC stage alone. Shape image features of the tumor and background liver were the dominant features correlated to the TTP as selected by the Boruta method and were used to predict the outcome.
CONCLUSION
This preliminary study demonstrates that quantitative image features obtained prior to therapy can improve the accuracy of predicting response of HCC to TACE. This approach is likely to provide useful information for aiding HCC patient selection for TACE.
PubMed: 31858078
DOI: 10.1148/ryai.2019180021 -
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 -
Molecular Genetics and Metabolism... Dec 2018Glucagon receptor (GCGR) defect (Mahvash disease) is an autosomal recessive hereditary pancreatic neuroendocrine tumor (PNET) syndrome that has only been reported in...
Glucagon receptor (GCGR) defect (Mahvash disease) is an autosomal recessive hereditary pancreatic neuroendocrine tumor (PNET) syndrome that has only been reported in adults with pancreatic α cell hyperplasia and PNETs. We describe a 7-year-old girl with persistent hyperaminoacidemia, notable for elevations of glutamine (normal ammonia), alanine (normal lactate), dibasic amino acids (arginine, lysine and ornithine), threonine and serine. She initially was brought to medical attention by an elevated arginine on newborn screening (NBS) and treated for presumed arginase deficiency with a low protein diet, essential amino acids formula and an ammonia scavenger drug. This treatment normalized plasma amino acids. She had intermittent emesis and anorexia, but was intellectually normal. Arginase enzyme assay and sequencing and deletion/duplication analysis were normal. Treatments were stopped, but similar pattern of hyperaminoacidemia recurred. She also had hypercholesterolemia type IIa, with only elevated LDL cholesterol, despite an extremely lean body habitus. Exome sequencing was initially non-diagnostic. Through a literature search, we recognized the pattern of hyperaminoacidemia was strikingly similar to that reported in the knockout mice. Subsequently the patient was found to have an extremely elevated plasma glucagon and a novel, homozygous c.958_960del (p.Phe320del) variant in . Functional studies confirmed the pathogenicity of this variant. This case expands the clinical phenotype of GCGR defect in children and emphasizes the clinical utility of plasma amino acids in screening, diagnosis and monitoring glucagon signaling interruption. Early identification of a GCGR defect may provide an opportunity for potential beneficial treatment for an adult onset tumor predisposition disease.
PubMed: 30294546
DOI: 10.1016/j.ymgmr.2018.09.006 -
Journal of Vascular Surgery. Venous and... Sep 2017Our primary purpose was to assess the impact of an inferior vena cava filter retrieval algorithm in a cancer population. Because cancer patients are at persistently...
OBJECTIVE
Our primary purpose was to assess the impact of an inferior vena cava filter retrieval algorithm in a cancer population. Because cancer patients are at persistently elevated risk for development of venous thromboembolism (VTE), our secondary purpose was to assess the incidence of recurrent VTE in patients who underwent filter retrieval.
METHODS
Patients with malignant disease who had retrievable filters placed at a tertiary care cancer hospital from August 2010 to July 2014 were retrospectively studied. A filter retrieval algorithm was established in August 2012. Patients and referring physicians were contacted in the postintervention period when review of the medical record indicated that filter retrieval was clinically appropriate. Patients were classified into preintervention (August 2010-July 2012) and postintervention (August 2012-July 2014) study cohorts. Retrieval rates and clinical pathologic records were reviewed.
RESULTS
Filter retrieval was attempted in 34 (17.4%) of 195 patients in the preintervention cohort and 66 (32.8%) of 201 patients in the postintervention cohort (P < .01). The median time to filter retrieval in the preintervention and postintervention cohorts was 60 days (range, 20-428 days) and 107 days (range, 9-600 days), respectively (P = .16). In the preintervention cohort, 49 of 195 (25.1%) patients were lost to follow-up compared with 24 of 201 (11.9%) patients in the postintervention cohort (P < .01). Survival was calculated from the date of filter placement to death, when available. The overall survival for patients whose filters were retrieved was longer compared with the overall survival for patients whose filters were not retrieved (P < .0001). Of the 80 patients who underwent successful filter retrieval, two patients (2.5%) suffered from recurrent VTE (n = 1 nonfatal pulmonary embolism; n = 1 deep venous thrombosis). Both patients were treated with anticoagulation without filter replacement.
CONCLUSIONS
Inferior vena cava filter retrieval rates can be significantly increased in patients with malignant disease with a low rate (2.5%) of recurrent VTE after filter retrieval.
Topics: Adult; Aged; Aged, 80 and over; Algorithms; Female; Follow-Up Studies; Hospitals, University; Humans; Incidence; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Retrospective Studies; Survival Rate; Treatment Outcome; United States; Vena Cava Filters; Venous Thromboembolism
PubMed: 28818223
DOI: 10.1016/j.jvsv.2017.05.017 -
Oncology 2017Hepatocellular carcinoma (HCC) prognosis depends on clinicopathological features in addition to the treatment provided. We aimed to assess the natural history of TNM...
BACKGROUND
Hepatocellular carcinoma (HCC) prognosis depends on clinicopathological features in addition to the treatment provided. We aimed to assess the natural history of TNM stage I HCC tumors which received different treatment over a period of 20 years.
METHODS
Between 1992 and 2011, a total of 397 stage I HCC patients were included. Detailed information was retrieved from MD Anderson Cancer Center patients' medical records. The Kaplan-Meier method was used to calculate patients' overall survival (OS). Cox regression analysis was used to calculate the estimated hazard ratio and 95% confidence interval of different prognostic factors.
RESULTS
Out of 397 patients, 67.5% were males, 42.8% had hepatitis-related HCC, and 59.7% had underlying cirrhosis. After adjustment for confounding factors, we found that all therapeutic modalities were associated with a significant mortality rate reduction with an OS of 63, 42.03, 34.3, and 22.1 months among patients treated with surgery, ablation, local, and systemic therapy, respectively. A restricted analysis of cirrhotic and noncirrhotic patients showed that ablative and local therapy were significantly associated with a longer OS compared to systemic therapy.
CONCLUSION
TNM stage I HCC patients have a favorable prognosis regardless of the type of treatment. Notably, ablative and local therapy significantly improved OS compared to systemic therapy.
Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Catheter Ablation; Chemoembolization, Therapeutic; Disease-Free Survival; Female; Hepatectomy; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Niacinamide; Phenylurea Compounds; Prognosis; Retrospective Studies; Sorafenib; Treatment Outcome; United States
PubMed: 28683459
DOI: 10.1159/000455957 -
The Lancet. Oncology Apr 2017Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for...
BACKGROUND
Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA.
METHODS
We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169.
RESULTS
We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported.
INTERPRETATION
To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.
FUNDING
National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.
Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Anus Neoplasms; Carcinoma, Squamous Cell; Case-Control Studies; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Nivolumab; Prognosis; Prospective Studies; Response Evaluation Criteria in Solid Tumors; Salvage Therapy; Survival Rate
PubMed: 28223062
DOI: 10.1016/S1470-2045(17)30104-3 -
Journal of Hepatocellular Carcinoma 2016Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic... (Review)
Review
Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic liver disease, which affects management decisions. Image-guided percutaneous ablative or transarterial therapies have acquired wide acceptance in HCC management as a single treatment modality or combined with other treatment options in patients who are not amenable for surgery. Recently, such treatment modalities have also been used for bridging or downsizing before definitive treatment (ie, surgical resection or liver transplantation). This review focuses on the use of minimally invasive image-guided locoregional therapies for HCC. Additionally, it highlights recent advancements in imaging and catheter technology, embolic materials, chemotherapeutic agents, and delivery techniques; all lead to improved patient outcomes, thereby increasing the interest in these invasive techniques.
PubMed: 27785450
DOI: 10.2147/JHC.S92732 -
Journal of Hepatocellular Carcinoma 2016The safety and efficacy of the combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS) to treat advanced hepatocellular carcinoma (HCC) is not well...
PURPOSE
The safety and efficacy of the combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS) to treat advanced hepatocellular carcinoma (HCC) is not well established. We determined the incidence of adverse events with this combination therapy in patients with advanced HCC at our institution and analyzed the treatment and survival outcomes.
MATERIALS AND METHODS
We reviewed the records of 19 patients with Barcelona Clinic Liver Cancer class B or C HCC who underwent treatment with Y90 RMS (for 21 sessions) while receiving full or reduced doses of sorafenib between January 2008 and May 2010. Therapy response was evaluated using Response Evaluation Criteria in Solid Tumors. We evaluated median overall survival (OS) and progression-free survival (PFS) as well as hepatic and extrahepatic disease PFS and incidence of adverse events.
RESULTS
The median patient age was 67 years, and portal or hepatic venous invasion was present in eight patients (42%). Ten patients received reduced doses of sorafenib. The median Y90 radiation activity delivered was 41.2 mCi. The partial response of Response Evaluation Criteria in Solid Tumors was observed in four patients (19%). The median hepatic disease PFS was 7.82 months, extrahepatic disease PFS was 8.94 months, OS was 19.52 months, and PFS was 6.63 months. Ninety days after treatment with Y90 RMS, five patients (26%) had grade II adverse events and four patients (21%) had grade III adverse events.
CONCLUSION
OS and PFS outcomes were superior to those observed in prior studies evaluating sorafenib alone in patients with a similar disease status, warranting further study of this treatment combination.
PubMed: 27574586
DOI: 10.2147/JHC.S62261