Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups?
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ABSTRACT:
SUBMITTER: Pinero F
PROVIDER: S-EPMC8240059 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPatients with cancer history are usually excluded from hepatocellular carcinoma (HCC) clinical trials. However, whether previous malignancy affects the oncological outcomes of HCC patients has not been fully assessed. This study aimed to evaluate whether prior cancer compromised the survival of HCC patients.MethodsPatients with HCC were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2015, and then they were classified into groups with and without prior cancer. The Kaplan-Meier and multivariate Cox regression analysis were adopted to evaluate whether prior cancer impacted clinical outcomes after propensity score matching (PSM) adjusting baseline differences. Validation was performed in the cohort from our institution.ResultsWe identified 2642 HCC patients with prior cancer. After PSM, the median overall survival (OS) time were 14.5 and 12.0 months respectively for groups with and without prior cancer. Prior cancer did not compromise prognosis in patients with HCC (p = 0.49). The same tendency was found in subgroups stratified by tumor stages and cancer interval period: OS was similar between groups with and without prior cancer (both p values> 0.1). In the multivariate Cox regression model, prior cancer did not adversely impact patients' survival (HR: 1.024; 95% CI: 0.961-1.092). In the validation cohort from our institution, prior cancer had no significant association with worse outcomes (p = 0.48).ConclusionFor HCC patients, prior cancer did not compromise their survival, regardless of tumor stage and cancer interval period. Exclusion criteria for HCC clinical trials could be reconsidered.
| S-EPMC7871582 | biostudies-literature
Project description:BACKGROUND AND AIMS:The Barcelona Clinic Liver Cancer (BCLC) stage C (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population for which sorafeninb is one of the recommended therapies. We aim to evaluate the real world clinical treatment and survival of BCLC stage C patients in an Asian cohort. METHODS:This is a retrospective cohort study that enrolled 427 consecutive BCLC stage C patients diagnosed between 2011 and 2017 by using the HCC registry data for our hospital. All patients were managed via a multidisciplinary team (MDT) approach. RESULTS:Hepatitis B surface antigen positive was noted in 50.6% of the patients. The patients were classified as performance status (PS)1 alone (n = 83; 19.4%), PS2 alone (n = 23; 5.4%), or macrovascular invasion (MVI) or extrahepatic spread (EHS) (n = 321; 75.2%). The median overall survival (OS) was 11.0 months in the whole cohort. The most frequent treatments were transcatheter arterial embolization (TAE) in the PS1 (45.8%) and PS2 patients (52.2%) and sorafenib (32.4%) in the MVI or EHS patients. The independent prognostic factors were the PS, Child-Pugh class, MVI or EHS, alpha fetoprotein levels, and treatment type. CONCLUSIONS:We reported the real world management in BCLC stage C patients in an Asian cohort through the use of personalized management via a MDT approach.
| S-EPMC7067409 | biostudies-literature
Project description:BackgroundTo investigate maximum tolerated dose (MTD) of axitinib, a selective vascular endothelial growth factor receptor 1-3 inhibitor, in combination with radiotherapy (RT) for advanced hepatocellular carcinoma (HCC).MethodsThis phase I study followed the rule of traditional 3?+?3 design. Major eligibility included: (1) patients with advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization, or who failed after prior local-regional treatment; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT. The secondary endpoints included overall response rate (ORR), RT in-field response rate, acute and late toxicities, overall survival (OS) and progression free survival (PFS).ResultsTotal nine eligible patients received axitinib dose levels of 1 mg twice daily (n?=?3), 2 mg twice daily (n?=?3) and 3 mg twice daily (n?=?3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months.ConclusionsAxitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort. Trial registration ClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02814461.
| S-EPMC7819176 | biostudies-literature
Project description:Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child-Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49-1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45-1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51-1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.
| S-EPMC7825785 | biostudies-literature
Project description:Well-designed randomized trials provide the highest level of scientific evidence to guide clinical decision making. In chemoradiotherapy of locally advanced squamous cell carcinoma of the head and neck (SCCHN), data support the use of three cycles of 100 mg/m2 cisplatin given every 3 weeks concurrently with conventionally fractionated external beam radiotherapy, although a full compliance with all three cycles is reserved to only about two thirds of initially eligible cases. On an individual patient level, practicing oncologists have to determine whether the patient is a suitable candidate for this treatment or whether contraindications exist. In the latter case, an adequate alternative has to be offered. In this regard, to facilitate triaging of medical information, we reviewed available publications on this topic and prepared practice-oriented recommendations for systemic treatment concurrent to definitive and post-operative radiotherapy. Even if no contraindications for the standard-of-care cisplatin apply, clinicians may opt for alternative regimens by adjusting the peak dose, cumulative dose, or timing of cisplatin. Relative contraindications pose the major issue in clinical practice, as very limited data is available in the literature and final decisions are usually based on an expert opinion or retrospective cohort studies. In the case of absolute interdiction of cisplatin, several alternative regimens incorporating carboplatin, 5-fluorouracil, cetuximab, and docetaxel are available. At the same time, it should be kept in mind that radiotherapy alone represents a viable option with hyperfractionation being particularly beneficial in the definitive management of limited nodal disease. Ideally, all treatment propositions should be discussed within multidisciplinary tumor boards taking into account the patient- and disease-related characteristics as well as local logistics and reimbursement policies.
| S-EPMC6579895 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome.
| S-EPMC4568488 | biostudies-literature
Project description:AimTo assess real-world management of patients diagnosed with hepatocellular carcinoma (HCC) within an integrated delivery network.Materials & methodsA retrospective cohort analysis of adults newly diagnosed with HCC from January 2014 to March 2019. Overall survival and treatment journey were assessed over the entire available follow-up period per patient.ResultsOf the 462 patients, 85% had ≥1 treatment. The 24-month overall survival rate (95% CI) from first treatment was 77% (72-82%). Majority of Child-Pugh class A (71%) and B (60%) patients received locoregional therapy first. Half (53.6%) of the patients with liver transplantation first were Child-Pugh class C patients. Sorafenib was the predominant systemic therapy.ConclusionThis integrated delivery network data analysis offers a comprehensive insight into the real-world management of HCC.
| S-EPMC10064261 | biostudies-literature
Project description:Background:The prognosis for advanced hepatocellular carcinoma (HCC) remains clinically unsatisfying. Apatinib has proven to be a very effective treatment for advanced HCC in our previous retrospective study. Our aim in this study was to evaluate the efficacy, safety, and toxicity of apatinib in patients with advanced HCC. Methods:This single-arm, open-label phase II clinical trial enrolled patients with advanced HCC. These patients received apatinib, 500 mg once daily, until disease progression, unacceptable toxicity, consent withdrawal, or death. One treatment cycle consisted of 4 weeks of apatinib treatment. The response evaluation criteria in solid tumors (RECIST) was used to assess tumor response every 1-2 cycles. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and toxicity. Results:Between December 2016 and June 2018, 23 patients were enrolled in the study, 22 of whom were available for response evaluation. The cutoff date was August 10, 2018. The overall ORR and DCR were 30.4% and 65.2%, respectively. The median OS and PFS were 13.8 (95% CI: 5.3-22.3) and 8.7 (95% CI: 5.9-11.1) months, respectively. The most common treatment-related adverse events were proteinuria (39.1%), hypertension (34.8%), and hand-foot-skin reaction (34.8%). Conclusions:Apatinib showed robust clinical activity in patients with advanced HCC. Moreover, apatinib was safe to use, well tolerated, and had acceptable toxicity. (NCT03046979).
| S-EPMC7576000 | biostudies-literature
Project description:BackgroundIn the context of liver transplantation for hepatocellular carcinoma (HCC), traditional transplant criteria appear restrictive. The objective of the current study was to determine risk factors for recurrence and improve transplant eligibility in patients with HCC.Materials and methodsThis was a retrospective study of patients who underwent living donor liver transplant (LDLT) for HCC (n = 219). Largest tumor diameter, tumor number, AFP and neutrophil to lymphocyte ratio were assessed. Multivariate analysis was performed to develop risk scores. The new model was compared with seven previously published transplant criteria using receiver operator curves.ResultsLargest tumor size >3.7 cm [HR:2.6, P = 0.02], and AFP > 600 ng/ml [HR:4.7, P = 0.001] were independent predictors of recurrence. Patients with risk scores of 0, 1-3, 4-6 and 7-9 had recurrence rate of 5.9%, 12.5%, 25% and 58.4% respectively. When compared with Milan criteria, Metro ticket 2.0, AFP model and Samsung criteria; transplant eligibility increased by 31.5%, 22.9%, 8.7%, and 7% respectively. Recurrence rate with the current model was 16/199 (8%) (P < 0.0001) and was comparable with other transplant criteria (6.9-9.1%). On ROC analysis, only Milan criteria (AUC = 0.7, P = 0.001) and the current model (AUC = 0.66, P = 0.01) showed significance for recurrence. All patients with high risk scores within Milan criteria had recurred at 3 years (P = 0.03).ConclusionsLow AFP can be used to select patients for LDLT outside traditional criteria for HCC, with comparable recurrence rates.
| S-EPMC8281598 | biostudies-literature
Project description:In oncologic practice, treatment guidelines provide appropriate treatment strategies based on evidence. Currently, many guidelines are used, including those of the European Association for the Study of the Liver and European Organization for Research and Treatment of Cancer (EASL-EORTC), National Comprehensive Cancer Network (NCCN), Asia-Pacific Primary Liver Cancer Expert (APPLE), and Korean Liver Cancer Study Group and National Cancer Centre (KLCSG-NCC). Although radiotherapy is commonly used in clinical practice, some guidelines do not accept it as a standard treatment modality. In this review, we will investigate the clinical practice guidelines currently used, and discuss the application of radiotherapy.
| S-EPMC5066447 | biostudies-literature