Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib

Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline

The impact of multidisciplinary team management on outcome of hepatic resection in liver-limited colorectal metastases

Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88–1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p < 0.0001). The median duration of chemotherapy was lower in MDT patients (8 vs 10 cycles; p < 0.001). Post-operative morbidity was lower in the MDT cohort (6.2 vs 21.5%; p < 0.001). One hundred and ninety-seven patients in each group were matched by propensity score and no significant difference was observed between the two groups in terms of OS and DFS. Our study does not demonstrate a survival benefit from MDT management, but it allows surgery to patients with a more advanced disease. MDT assessment reduces the median duration of chemotherapy and post-operative morbidities

advanced intrahepatic cholangiocarcinoma icca treated with arterial directed therapies adt outcomes and safety from a multicenter italian experience

n/

The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib

Background and aims The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). Results A PNI cut-off value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12–76.3) and 6.8 months (95% CI 2.7–24.6) for patients with a high (>31.3) and low (<31.3) PNI, respectively. At both the univariate and the multivariate analysis, low PNI value (p = 0.0004), a 1-unit increase of aspartate aminotransferase (p = 0.0001), and age > 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI <31.3 versus >31.3 was found to be an independent prognostic factor for predicting OS in all the three validation cohorts. Conclusions PNI represents a prognostic tool in advanced HCC treated with first-line Sorafenib. It is readily available and low-cost, and it could be implemented in clinical practice in patients with HCC

The secretory senescence in otorhinolaryngology: Principles of treatment

Atrophy or hypofunction of the salivary gland because of aging, radiotherapy or disease causes hyposalivation and impairs the quality of life of patients by compromising mastication, swallowing and speech and by leading to a loss of taste. Moreover, hyposalivation exacerbates dental caries and induces periodontal disease, and oral candidiasis. Currently, no satisfactory therapies have been established to solve salivary hypofunction. Current treatment options for atrophy or hypofunction of the salivary glands in clinical practice are only symptomatic and include saliva substitutes and parasympathetic agonists, such as pilocarpine, to stimulate salivary flow. However, parasympathomimetics have systemic side effects, so different treatment options are necessary, and research has recently focused on this. The main strategies that have been proposed to restore salivary gland atrophy and hypofunction are gene therapy by gene activation/silencing during stem cell differentiation and by the use of viral vectors, such as adenoviruses; cell-based therapy with salivary gland cells, stem cells and non-salivary gland and/ or non-epithelial cells to regenerate damaged salivary gland cells; replacement with tissue bioengineering in which organoids from pluripotent stem cells are used in the development of organ replacement regenerative therapy. Remarkable progression in this research field has been made in the last decade, but a definitive therapy for salivary gland hypofunction has not been developed due to intrinsic challenges that come with each approach. However, with research efforts in the future, a range of precision medicine therapies may become available individualized to each patient

Validation and refinement of PROSASH model using the neutrophil‐to‐lymphocyte ratio in patients with HCC receiving sorafenib

AbstractThe recently developed PROSASH model is proving to be a useful tool in risk‐group discrimination in hepatocellular carcinoma (HCC) patients treated with sorafenib. Several studies highlighted that the neutrophil‐to‐lymphocyte ratio (NLR) is one of the most important predictors of survival in HCC patients treated with sorafenib. The aims of the present study were to validate the PROSASH model and determine whether the incorporation of inflammatory markers can improve risk stratification. This study included 438 patients. According to the four categories of the PROSASH model, median overall survival (OS) was 20.0, 14.9, 8.5 and 3.0 months respectively (P < .001). The Harrell's c for this categorized model was 0.621. NLR (cut‐off 3) stratified OS in each of the PROSASH categories. After reclassification, median OS was 21.0, 15.1, 8.2 and 4.1 months (P < .001). The Harrell's c increased from 0.621 to 0.673 (P = .001). Integrating NLR into the PROSASH model allowed a more accurate classification of the patients in the risk groups

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

Introduction: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated. Methods: We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy. Results: Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) &gt; 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) &gt;400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4-14.8) and 5.1 (3.3-6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3-4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS &gt; 0, and AFP &gt;400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes. Conclusions: In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

Background & Aims: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH‐2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha‐fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post‐hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). Methods: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH‐2. Kaplan‐Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression‐free survival (PFS), time to progression (TTP) and patient‐reported outcomes (Functional Hepatobiliary System Index‐8 [FHSI‐8] score). Results: A total of 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581‐0.975), ≥65 to <75 years (0.602; 0.419‐0.866) and ≥75 years (0.709; 0.420‐1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI‐8 with ramucirumab was observed in all subgroups. Conclusions: In this post‐hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75 years

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

Background &amp; Aims: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400&nbsp;ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP&nbsp;≥&nbsp;400&nbsp;ng/mL by three prespecified age subgroups (&lt;65, ≥65 to &lt;75 and ≥75&nbsp;years). Methods: Individual patient data were pooled from REACH (baseline AFP ≥400&nbsp;ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). Results: A total of 542 patients (&lt;65&nbsp;years: n&nbsp;=&nbsp;302; ≥65 to &lt;75&nbsp;years: n&nbsp;=&nbsp;160; ≥75&nbsp;years: n&nbsp;=&nbsp;80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the &lt;65&nbsp;years subgroup. Ramucirumab prolonged OS in patients &lt;65&nbsp;years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to &lt;75&nbsp;years (0.602; 0.419-0.866) and ≥75&nbsp;years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. Conclusions: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75&nbsp;years

Ocular and cervical vestibular-evoked myogenic potentials in idiopathic sudden sensorineural hearing loss (ISSHL) without vertigo: VEMPs in ISSHL

Purpose: Idiopathic sudden sensorineural hearing loss (ISSHL) is a hearing impairment greater than 30&nbsp;dB at three consecutive frequencies developing in less than 3&nbsp;days. The aim of this study was to evaluate VEMPs and caloric testing in patients affected by ISSHL without vertigo. Methods: We retrospectively evaluated 35 subjects affected by ISSHL. The audio-vestibular investigation consisted of pure-tone and speech audiometry, impedance, bithermal caloric testing, oVEMPs and cVEMPs. Results: VEMPS were abnormal in 21 patients (60%): cVEMPs in 12 (34.2%) and oVEMPs in 19 (54.2%). 10 patients (28.5%) presented with both c-and oVEMPs altered. Subjects without vestibular involvement showed a significant lower PTA in the affected ear both at admission and at discharge. Recovery rate was significantly higher in group without vestibular involvement. Conclusion: The evaluation of the vestibular system can be useful for predicting the auditory recovery in patients without vertigo also