Selectivity of Exhaled Breath Biomarkers of Lung Cancer in Relation to Cancer of Other Localizations.

Lung cancer is a leading cause of death worldwide, mostly due to diagnostics in the advanced stage. Therefore, the development of a quick, simple, and non-invasive diagnostic tool to identify cancer is essential. However, the creation of a reliable diagnostic tool is possible only in case of selectivity to other diseases, particularly, cancer of other localizations. This paper is devoted to the study of the variability of exhaled breath samples among patients with lung cancer and cancer of other localizations, such as esophageal, breast, colorectal, kidney, stomach, prostate, cervix, and skin. For this, gas chromatography-mass spectrometry (GC-MS) was used. Two classification models were built. The first model separated patients with lung cancer and cancer of other localizations. The second model classified patients with lung, esophageal, breast, colorectal, and kidney cancer. Mann-Whitney U tests and Kruskal-Wallis H tests were applied to identify differences in investigated groups. Discriminant analysis (DA), gradient-boosted decision trees (GBDT), and artificial neural networks (ANN) were applied to create the models. In the case of classifying lung cancer and cancer of other localizations, average sensitivity and specificity were 68% and 69%, respectively. However, the accuracy of classifying groups of patients with lung, esophageal, breast, colorectal, and kidney cancer was poor.

Non-Invasive Lung Cancer Diagnostics through Metabolites in Exhaled Breath: Influence of the Disease Variability and Comorbidities.

Non-invasive, simple, and fast tests for lung cancer diagnostics are one of the urgent needs for clinical practice. The work describes the results of exhaled breath analysis of 112 lung cancer patients and 120 healthy individuals using gas chromatography-mass spectrometry (GC-MS). Volatile organic compound (VOC) peak areas and their ratios were considered for data analysis. VOC profiles of patients with various histological types, tumor localization, TNM stage, and treatment status were considered. The effect of non-pulmonary comorbidities (chronic heart failure, hypertension, anemia, acute cerebrovascular accident, obesity, diabetes) on exhaled breath composition of lung cancer patients was studied for the first time. Significant correlations between some VOC peak areas and their ratios and these factors were found. Diagnostic models were created using gradient boosted decision trees (GBDT) and artificial neural network (ANN). The performance of developed models was compared. ANN model was the most accurate: 82-88% sensitivity and 80-86% specificity on the test data.

Detection of EGFR mutations and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides.

BACKGROUND: Although the molecular analysis of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in archived lung cancer tissues is relatively well established, the genetic testing of cytological material has not yet become a routine. METHODS: The current study used cell samples that were obtained by bronchial brushing, transthoracic needle aspiration, or biopsy imprint preparation between 1993 and 2008. Islets of malignant cells were visually located on the archived cytological slides, lysed in situ by a drop of sodium dodecyl sulfate-containing buffer, and subjected to the standard DNA and RNA extraction. Examination of paraffin-embedded tissue blocks (resection specimens or biopsy material) from the same patients was performed in parallel. RESULTS: A total of 75 cytological/histological lung adenocarcinoma sample pairs underwent polymerase chain reaction analysis for the EGFR mutation. Two cytological samples and 1 morphological sample failed to produce DNA. Concordance for the wild-type and mutation status was observed in 54 of 72 and 14 of 72 informative pairs, respectively; 3 pairs and 1 pair, respectively, had mutation only in the cytological or histological material. The discrepancies could be explained by the failure to ensure a high percentage of lung cancer cells in the analyzed samples or, alternatively, by the genuine intratumoral molecular heterogeneity of some neoplasms. RNA extraction followed by reverse transcriptase-polymerase chain reaction analysis for the EML4-ALK translocation was performed for 44 EGFR mutation-negative sample pairs; failures were observed for 2 cytological and 6 histological specimens. All informative pairs were concordant either for the norm (32 of 36 pairs) or for the presence of EML4-ALK gene fusion (4 of 36 pairs). CONCLUSIONS: Archived cytological slides appear to be well suited both for EGFR and ALK analysis.

Distribution of coding apoptotic gene polymorphisms in women with extreme phenotypes of breast cancer predisposition and tolerance.

AIMS AND BACKGROUND: Comparison of subjects with extreme phenotypes of cancer susceptibility and tolerance allows to detect low-penetrance gene-disease interactions with a relatively small study size. METHODS AND STUDY DESIGN: We analyzed the distribution of 19 coding apoptotic gene polymorphisms (Bid Gly10Ser; Casp2 Leu141Val; Casp5 Ala90Thr and Val318Leu; Casp7 Glu255Asp; Casp8 His302Asp; Casp9 Val28Ala, His173Arg and Arg221Gln; Casp10 Ile479Leu; Faim Thr117Ala and Ser127Leu; DR4 Arg141His, Thr209Arg, Ala228Glu and Lys441Arg; Survivin Lys129Glu; TNFR1 Gln121Arg; XIAP Pro423Gln) in 121 breast cancer patients with clinical features of a hereditary predisposition (family history and/or early onset and/or bilaterality) and 142 elderly tumor-free women. RESULTS: None of the individual single nucleotide polymorphisms (SNPs) demonstrated an association with breast cancer risk. The analysis of gene interactions revealed that the combination of XIAP Pro423Gln (rs5956583) AA genotype with Casp7 Glu255Asp (rs2227310) CG genotype appeared to prevail in "supercases" relative to "supercontrols" (25/121 [21%] vs 11/142 [8%], P = 0.002). We attempted to validate this association in the second round of case-control analysis, which involved 519 randomly selected breast cancer patients and 509 age-matched healthy women, but no difference was detected upon this comparison. CONCLUSIONS: Coding apoptotic gene polymorphisms do not play a major role in BC predisposition. The results of this investigation may be considered while designing future studies on breast cancer-associated candidate SNPs.

Phase II study of picoplatin as second-line therapy for patients with small-cell lung cancer.

PURPOSE: This study was designed to confirm the efficacy and safety of picoplatin, a cisplatin analog designed to overcome platinum resistance, in patients with small-cell lung cancer (SCLC) with platinum-refractory/-resistant disease. PATIENTS AND METHODS: All patients received intravenous picoplatin 150 mg/m(2) every 3 weeks. Tumor response, progression-free survival, and overall survival were evaluated. Adverse events were assessed for frequency, severity, and relationship to treatment. Quality of life was assessed with the Lung Cancer Symptom Scale instrument. RESULTS: Seventy-seven patients were treated with picoplatin (median number of cycles, two; range one to 10). Three patients (4%) had a partial response, 33 (43%) had stable disease (four of these were unconfirmed partial responses), 36 (47%) had progressive disease, and five were not assessable for response. Median progression-free survival was 9.1 weeks (95% CI, 7.0 to 12.1 weeks). Median overall survival was 26.9 weeks (95% CI, 21.1 to 33.4). The most common grade 3 and 4 toxicities were thrombocytopenia (48%), neutropenia (25%), and anemia (20%). The most commonly reported adverse events of any severity included thrombocytopenia (64%), anemia (49%), neutropenia (39%), nausea (27%), fatigue (16%), and dyspnea (16%). No severe neurotoxicity or nephrotoxicity were observed. There were no treatment-related deaths. CONCLUSION: Picoplatin demonstrated clinical efficacy in platinum-refractory SCLC. The major toxicity was hematologic. These results warrant further evaluation in this patient population.