BackgroundCentral nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC.MethodsIn a prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage. They received standard chemotherapy. CEA was measured prior to treatment; EGFR and HER2 were evaluated by immunohistochemistry. BM development was confirmed by MRI in symptomatic patients.ResultsBM developed in 27, and 32% of patients at 1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002–29; p = 0.05) and CEA ≥ 40 ng/mL (RR 11.4; 95% CI, 1.7–74; p < 0.01) as independent associated factors. EGFR and HER2 were not statistically significant. Masculine gender (RR 1.4; 95% CI, 1.002–1.9; p = 0.048), poor performance status (RR 1.8; 95% CI, 1.5–2.3; p = 0.002), advanced clinical stage (RR 1.44; 95% CI, 1.02–2; p = 0.04), CEA ≥ 40 ng/mL (RR 1.5; 95% CI, 1.09–2.2; p = 0.014) and EGFR expression (RR 1.6; 95% CI, 1.4–1.9; p = 0.012) were independent associated factors to worse OS.ConclusionHigh CEA serum level is a risk factor for BM development and is associated with poor prognosis in patients with advanced NSCLC. Surface expression of CEA in tumor cells could be the physiopathological mechanism for invasion to CNS.
Objective:To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapyinduced peripheral neuropathy in an experimental animal model and in a randomized, doubleblinded, controlled trial in patients with non-small-cell lung cancer (NSCLC). Methods:Forty male Wistar rats were randomized in 5 groups: group A, control; groups B and C, treated with cisplatin; and groups D and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days in groups C and E. We evaluated neuropathy and nerve regenerationrelated morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)-␣ and RAR- expression. In addition, 95 patients with NSCLC under chemotherapy treatment were randomized to either ATRA (20 mg/m 2 /d) or placebo. Serum NGF, neurophysiologic tests, and clinical neurotoxicity were assessed. Results:The experimental animals developed neuropathy and axonal degeneration, associated with decreased NGF levels in peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve morphology; this was associated with increased NGF levels and RAR- expression. Patients treated with chemotherapy had clinical neuropathy and axonal loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA reduced axonal degeneration demonstrated by nerve conduction velocity and clinical manifestations of neuropathy grades Ն2.Conclusions: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR- expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations. Classification of evidence:This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy. Neurology ® 2011;77:987-995 GLOSSARY ATRA ϭ all-trans retinoic acid; CI ϭ confidence interval; CIPN ϭ chemotherapy-induced peripheral neuropathy; CP ϭ cisplatin/paclitaxel; DM ϭ diabetes mellitus; NGF ϭ nerve growth factor; NSCLC ϭ non-small-cell lung cancer; OR ϭ odds ratio; QOL ϭ quality of life; qRT-PCR ϭ quantitative reverse transcriptase and real-time PCR; RAR ϭ retinoic acid receptor; RT ϭ radiation therapy.Platinum-based chemotherapy is the first-line therapy for non-small-cell lung cancer (NSCLC) and improves both survival and disease-related symptomatology. 1 However, chemotherapyinduced peripheral neuropathy is common and decreases quality of life (QOL) and may limit chemotherapy doses.2 Cisplatin promotes the formation of free radicals, while paclitaxel blocks axonal transport within peripheral nerves. As many as 38% of patients with NSCLC treated with these drugs develop a disabling sensory neuropathy. 3,4 Retinoids play a critical role in a variety of biological functions, particularly in epithelial and neural differentiation.5 Different types of retinoids possess variable selectivity to retinoidFrom the Laboratorio de Oncología Experimental (Ó ....
A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. In 2001, we started a protocol for LDLT in Child A-B patients with HCC fulfilling a set of criteria-the Barcelona Clinic Liver Cancer (BCLC) expanded criteria-that expanded the conventional indications of transplantation: 1 tumor ≤ 7 cm, 5 tumors ≤ 3 cm, and 3 tumors ≤ 5 cm without macrovascular invasion or downstaging to Milan after locoregional therapies. We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (n = 17) or downstaging (n = 5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age, 57 years old; males/female, n = 20/2; Child-Pugh A/B, n = 16/6; and alpha fetoprotein < 100 ng/mL, n = 21. Twelve patients received neoadjuvant locoregional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow-up of 81 months, the 1-, 3-, 5-, and 10-year survival was 95.5%, 86.4%, 80.2%, and 66.8%, respectively. Overall, 7 patients recurred (range, 9-108 months), and the 5-year and 10-year actuarial recurrence rates were 23.8% and 44.4%, respectively. In conclusion, a proper selection of candidates for extended indications of LDLT for HCC patients provide survival outcomes comparable to those obtained within the Milan criteria, but these results need confirmation. Liver Transplantation 24 369-379 2018 AASLD.
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