Adjuvant platinum-based chemotherapy in non-small cell lung cancer: The role of relative dose-intensity and treatment delay.

BACKGROUND: The study investigated the association of the relative dose-intensity (RDI) of cisplatin and timing of adjuvant platinum-based chemotherapy (APC) with survival for stage I-III non-small cell lung cancer (NSCLC) patients. MATERIAL AND METHODS: Real-life data of patients treated with APC (four cycles of cisplatin and vinorelbine) between 2007 and 2014 was included to analyse the association between disease-free survival (DFS) and overall survival (OS) with RDI (ratio of received to planned dose-intensity). High RDI was defined as cisplatin RDI of > 75% and low RDI ≤ 75%. RESULTS: Out of 198 patients, 166 were eligible. Low RDI was administered to 72 (43%) patients. In multivariate analysis, those patients had a significantly higher risk of recurrence (HR: 1.87, 95%CI 1.13-3.09, p = 0.01) and death (HR: 1.91, 95%CI 1.32-3.23, p = 0.01) versus patients in the high RDI group. The risk of death was significantly higher in patients with PS 1 treated with low versus high RDI (HR: 2.72, 95%CI: 1.22-6.09, p = 0.014). The risk of recurrence was higher for patients with squamous cell carcinoma of low versus high RDI (HR: 3.82, 95%CI: 1.01-14.4, p = 0.048). No impact of delayed APC beyond six weeks from surgery on neither DFS (HR: 0.78, 95%CI: 0.46-1.33, p = 0.36) nor OS (HR 0.67, 95%CI: 0.40-1.15, p = 0.15) was observed. CONCLUSION: Low cisplatin RDI ≤ 75% of APC, but not extended time from surgery to APC onset > six weeks, was associated with significantly shorter survival in NSCLC patients.

The established and future biomarkers of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an asbestos-related cancer with a median survival of 12months. The MPM incidence is 1-6/100,000 and is increasing as a result of historic asbestos exposure in industrialized countries and continued use of asbestos in developing countries. Lack of accurate biomarkers makes diagnosis, prognostication and treatment prediction of MPM challenging. The aim of this review is to identify the front line of MPM biomarkers with current or potential clinical impact. Literature search using the PubMed and PLoS One databases, the related-articles function of PubMed and the reference lists of associated publications until April 26th 2015 revealed a plethora of candidate biomarkers. The current gold standard of MPM diagnosis is a combination of two positive and two negative immunohistochemical markers in the epithelioid and biphasic type, but sarcomatous type do not have specific markers, making diagnosis more difficult. Mesothelin in serum and pleural fluid may serve as adjuvant diagnostic with high specificity but low sensitivity. Circulating proteomic and microRNA signatures, fibulin-3, tumor cell gene-ratio test, transcriptomic, lncRNA, glycopeptides, pleural fluid FISH assay, hyaluronate/N-ERC mesothelin and deformability cytometry may be important future markers. Putative predictive markers for pemetrexed-platinum are tumor TS and TYMS, for vinorelbine the ERCC1, beta-tubuline class III and BRCA1. Mutations of the BAP1 gene are potential markers of MPM susceptibility. In conclusion, the current status of MPM biomarkers is not satisfactory but encouraging as more sensitive and specific non-invasive markers are emerging. However, prospective validation is needed before clinical application.

Fine needle aspiration cytology of nodular thyroid lesions: a 2-year experience of the Bethesda system for reporting thyroid cytopathology in a large regional and a university hospital, with histological correlation.

OBJECTIVE: Thyroid fine needle aspiration (FNA) contributes to the appropriate management of nodular thyroid lesions. The introduced categories in the Bethesda system for reporting thyroid cytopathology (TBSRTC) are associated with an implied cancer risk, providing a clinical management guideline. This study aims to evaluate the reproducibility of this implied risk and to compare the results from two different cytopathology departments. METHODS: Five hundred histologically confirmed FNAs, studied since the introduction of TBSRTC, were obtained from 4208 and 3587 FNAs performed in a large regional hospital in Herakleion, Crete (group A) and a university hospital in Athens (group B), respectively. Reports were issued according to TBSRTC. Aspirates were prepared with ThinPrep(®) and evaluated by two experienced cytopathologists. The reproducibility and accuracy were evaluated. RESULTS: The proportion test for suspicious for malignancy (SFM) and malignant (M) cytology reports (P < 0.0001), and the number of malignancies on histology (P < 0.0001), were significantly higher in group A than in group B, consistent with a higher incidence of thyroid carcinomas in southern Greece. Although the malignancy rates were higher in group A than in group B for all categories, except M (A, 99.3%; B, 100%), the difference was only significant for benign aspirates (P = 0.0303). Malignancy rates for all categories in group A were above the TBSRTC recommended range, but were consistent with an increased prevalence of malignancy in that centre, differences in reporting practice and the variable ranges reported in the literature. There was lower sensitivity (P = 0.019) and overall accuracy (P = 0.003) in group A relative to group B, but no difference in specificity. CONCLUSIONS: TBSRTC provides valuable information for the appropriate management of nodular thyroid lesions, both in a university and a large regional hospital.

Molecular epidemiology of HPV infection using a clinical array methodology in 2952 women in Greece.

The molecular epidemiology of human papillomavirus (HPV) infection in a sample of Greek women (n = 2952, mean age 42.2 ± 13.3 years) was examined. HPV prevalence was 50.7% (95% confidence interval, 48.8-52.6). The most frequent HPV types were HPV 53, 51 and 66 (10.2%, 9.4% and 9.3%, respectively). HPV positivity was associated with age, age of sexual debut, number of sexual partners and duration of sexual relationship, while marriage or multiparity protected against infection (all p <0.001). Follow-up of this cohort will assist in predicting the effect of vaccination with the new HPV vaccines on future screening with HPV-based tests for cervical cancer.