Development and validation of a novel online calculator for estimating survival benefit of adjuvant transcatheter arterial chemoembolization in patients undergoing surgery for hepatocellular carcinoma

Background and aims Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. Methods From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. Results A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child–Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. Conclusions Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.

Clinical Relevance of Gastroesophageal Cancer Associated SNPs for Oncologic Outcome After Curative Surgery

Background Gastric and esophageal cancers are malignant diseases with rising importance in Western countries. To improve oncologic outcome after surgery, it is essential to understand the relevance of germline mutations. The aim of the study was to identify and distinguish clinically relevant single-nucleotide polymorphisms (SNPs). Patients and Methods In total, 190 patients with curative oncological resections of gastric and distal esophageal adenocarcinomas at Heidelberg University Hospital were eligible for this study. Outcome differences were determined for each SNP by analysis of clinical variables, survival, and mRNA expression levels. Results Significant survival differences were found on univariate analysis for usual prognostic variables (such as pTNM) and for six SNPs. On multivariate survival analysis, the SNPs rs12268840 (intron variant of MGMT, p = 0.045) and rs9972882 (intron variant of STARD3 and eQTL of PGAP3, p = 0.030) were independent and significant survival predictors along with R status and pT/pN category. Group TT of rs12268840 had the highest rate of second primary carcinoma (30.4%, p = 0.0003), lowest expression of MGMT based on cis-eQTL analysis in normal gastroesophageal tissue (p = 1.99 × 10−17), and worst oncologic outcome. Group AA of rs9972882 had the highest rate of distant metastases pM1 (42.9%, p = 0.0117), highest expression of PGAP3 (p = 1.29 × 10−15), and worst oncologic outcome. Conclusions Two intron variant SNPs of MGMT and STARD3 were identified that were significant survival predictors and may influence tumor biology. The data indicate that DNA methylation (MGMT) and malfunction of GPI anchoring (PGAP3) are distinct mechanisms that are relevant for tumor progression and relapse.

Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS)

Purpose 177Lu-Dotatate is an emerging treatment modality for patients with unresectable or metastatic well-differentiated NETs. This study examines survival predictors in patients who received 177Lu-Dotatate. Methods A retrospective single-center review was conducted, examining 47 individuals with progressive well-differentiated NETs treated with 177Lu-Dotatate (four induction cycles of 5.5 GBq at 10-week intervals followed by eight maintenance cycles of 3.7 GBq at 6-month intervals). Results Median follow-up was 63.1 months with a median progression-free survival (PFS) of 34.1 months. However, median overall survival (OS) was not reached at the time of analysis. The presence of ≥ 5 bone metastases (hazard ratio HR 4.33; p = 0.015), non-gastroenteropancreatic (non-GEP) NETs (HR 3.22; p = 0.025) and development of interim ascites (HR 3.15; p = 0.047) independently predicted a worse OS. Patients with chromogranin A of ≥ 4 × upper limit of normal (ULN) had shorter OS (p < 0.001) and PFS (p = 0.004). Similarly, those with pre-existing ascites demonstrated a worse OS (p = 0.009) and PFS (p = 0.026). Liver metastases involving greater than 50% liver volume and the existence of unusual metastatic locations had a negative impact on OS (p = 0.033) and PFS (p = 0.026), respectively. Conclusion High burden of skeletal and hepatic metastases, non-GEP-NETs, chromogranin A of ≥ 4 × ULN, unusual metastatic sites, pre-existing and interim ascites are predictors of poor outcomes in patients treated with 177Lu-Dotatate. These common indicators can be used for the risk stratification and identification of patients most likely to benefit from PRRT. Trial registration ClinicalTrials.gov identifier: NCT02236910, Retrospectively registered on September, 2014.

Pacemaker lead-associated tricuspid regurgitation in patients with or without pre-existing right ventricular dilatation

Background Transcatheter tricuspid valve intervention became an option for pacemaker lead-associated tricuspid regurgitation. This study investigated the progression of tricuspid regurgitation (TR) in patients with or without pre-existing right ventricular dilatation (RVD) undergoing pacemaker implantation. Methods Patients were included if they had implantation of transtricuspid pacemaker lead and completed echocardiography before and after implantation. The cohort was divided in patients with and without RVD (cut-off basal RV diameter ≥ 42 mm). TR was graded in none/mild, moderate, and severe. Worsening of one grade was defined as progression. Survival analyses were plotted for 10 years. Results In total, 990 patients were analyzed (24.5% with RVD). Progression of TR occurred in 46.1% of patients with RVD and in 25.6% of patients without RVD (P < 0.001). Predictors for TR progression were RV dilatation (OR 2.04; 95% CI 1.27–3.29; P = 0.003), pre-existing TR (OR 4.30; 95% CI 2.51–7.38; P < 0.001), female sex (OR 1.68; 95% CI 1.16–2.43; P = 0.006), single RV lead (OR 1.67; 95% CI 1.09–2.56; P = 0.018), mitral regurgitation (OR 2.08; 95% CI 1.42–3.05; P < 0.001), and enlarged left atrium (OR 1.98; 95% CI 1.07–3.67; P = 0.03). Survival-predictors were pacemaker lead-associated TR (HR 1.38; 95% CI 1.04–1.84; P = 0.028), mitral regurgitation (HR 1.34; 95% CI 1.02–1.77; P = 0.034), heart failure (HR 1.75; 95% CI 1.31–2.33; P < 0.001), kidney disease (HR 1.62; 95% CI 1.25–2.11; P < 0.001), and age ≥ 80 years (HR 2.84; 95% CI 2.17–3.71; P < 0.001). Conclusions Patients with RVD receiving pacemaker suffered from increased TR progression, leading to decreased survival. Graphic abstract

Survival Predictors of Heart Rate Variability After Myocardial Infarction With and Without Low Left Ventricular Ejection Fraction

BackgroundHeart rate variability (HRV) and heart rate (HR) dynamics are used to predict the survival probability of patients after acute myocardial infarction (AMI), but the association has been established in patients with mixed levels of left ventricular ejection fraction (LVEF).ObjectiveWe investigated whether the survival predictors of HRV and HR dynamics depend on LVEF after AMI.MethodsWe studied 687 post-AMI patients including 147 with LVEF ≤35% and 540 with LVEF &gt;35%, of which 23 (16%) and 22 (4%) died during the 25 month follow-up period, respectively. None had an implanted cardioverter-defibrillator. From baseline 24 h ECG, the standard deviation (SDNN), root mean square of successive difference (rMSSD), percentage of successive difference &gt;50 ms (pNN50) of normal-to-normal R-R interval, ultra-low (ULF), very-low (VLF), low (LF), and high (HF) frequency power, deceleration capacity (DC), short-term scaling exponent (α1), non-Gaussianity index (λ25s), and the amplitude of cyclic variation of HR (Acv) were calculated.ResultsThe predictors were categorized into three clusters; DC, SDNN, α1, ULF, VLF, LF, and Acv as Cluster 1, λ25s independently as Cluster 2, and rMSSD, pNN50, and HF as Cluster 3. In univariate analyses, mortality was best predicted by indices belonging to Cluster 1 regardless of LVEF. In multivariate analyses, however, mortality in patients with low LVEF was best predicted by the combinations of Cluster 1 predictors or Cluster 1 and 3 predictors, whereas in patients without low LVEF, it was best predicted by the combinations of Cluster 1 and 2 predictors.ConclusionThe mortality risk in post-AMI patients with low LVEF is predicted by indices reflecting decreased HRV or HR responsiveness and cardiac parasympathetic dysfunction, whereas in patients without low LVEF, the risk is predicted by a combination of indices that reflect decreased HRV or HR responsiveness and indicator that reflects abrupt large HR changes suggesting sympathetic involvement.

Survival Predictors of Metastatic Adrenocortical Carcinoma: a SEER-based Retrospective Study

Background: Metastatic adrenocortical carcinomas (MAC) have a poor prognosis. Advanced adrenocortical carcinoma often metastasizes to lung and liver. Prognostic factors of MAC have been rarely reported. This study aims to identify the association between specific metastasis and overall survival (OS) in MAC and determine the survival predictors for MAC patients.Methods: MAC patients' data was obtained from Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Survival differences were analyzed by Kaplan–Meier analysis and log-rank tests. Cox proportional hazard model was used to identify the prognostic factors associated with overall survival.Results: A total of 152 MAC patients were selected, among whom 77 patients (50.7%) were diagnosed with one metastatic site, 75 (49.3%) diagnosed with more than one distant metastasis. For the whole MAC cohort, multivariable analysis showed that year of diagnosis between 2013 and 2016, without liver metastasis, surgery and chemotherapy were significantly favorable predictors of OS. For patients with one metastatic site, lung metastases had a better survival outcome than liver metastases(p=0.037). Besides, compared with patients who didn’t received surgery, patients underwent surgery were correlated with longer OS (p=0.004). For patients with more than one site of distant metastases, married status, surgery, and chemotherapy predicted a better OS. Radiotherapy did not improve overall survival outcomes in the three cohort.Conclusion: Liver metastasis has a poor prognosis. Year of diagnosis, metastatic sites, surgery and chemotherapy were significant prognostic factors for OS in MAC patients. For patients with single metastasis, surgery was a favorable prognostic factor, while married patients, surgery and chemotherapy predicted a better survival outcome in patients with more than one metastasis. Based on the collective findings, surgery can be regarded as the preferred treatment option for all MAC patients. Besides, chemotherapy is also a good choice for patients with multiple metastases.