Consensus clustering methodology to improve molecular stratification of non-small cell lung cancer.

Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

Prognostic role of the PET parameter maximum standardized uptake value in non small cell lung cancer: analysis in tumour of diameter ≥ and <25 mm.

AIM: The aim of this study was to evaluate whether the primary tumour maximum standardized uptake value (SUV(max)) plays an independent prognostic role in patients with non small cell lung cancer (NSCLC) and whether this role is limited by partial volume effect (PVE) and motion artefacts. METHODS: One hundred and fifty-three consecutive patients underwent PET exam, surgery (R0 resection) and follow-up (mean 20.3; range 6-44.8 months). Correlation with Disease Free and Overall Survival (DFS, OS) was evaluated in the entire population for: SUV(max), clinical and histopathological features and pathological stage. To evaluate the PVE and motion artefacts' interferences on SUV calculation, the correlation between SUV(max) and DFS/OS was also calculated in the groups of patients with tumour diameter ≥ and < than 25 mm (group A and B, respectively). RESULTS: In the entire population only TNM and SUV(max) resulted correlated with DFS/OS. However, SUV(max) was significantly correlated with DFS/OS in group A but not in group B. Furthermore, only in the group of patients with primary tumour diameter ≥ 25 mm (group A), tumour diameter, tumour histotype, and tumour necrosis resulted significantly related with SUV(max) at both uni and multivariate analysis. CONCLUSION: TNM together with SUV(max) could be useful in giving a better prognostic stratification of patients with NSCLC; however technical limitations in the SUV calculation must be taken into account in patients with tumour diameter <25 mm.

CT-guided percutaneous transthoracic biopsy in the diagnosis of mediastinal masses: evaluation of 73 procedures.

PURPOSE: This study was performed to evaluate the factors affecting the diagnostic accuracy and rate of complications of CT-guided percutaneous transthoracic needle biopsy of mediastinal masses. MATERIALS AND METHODS: We reviewed 73 consecutive mediastinal biopsies in 70 patients. Final diagnoses were based on a retrospective analysis of surgical outcomes, results of repeat biopsies or findings of imaging and clinical follow-up lasting at least 4 months. Benign and malignant biopsy findings were compared with the final outcomes to determine the diagnostic accuracy of the method. Finally, we analysed the complications. RESULTS: CT-guided percutaneous transthoracic needle biopsy provided adequate samples in 61/73 cases, with a total sample rate of 83.6%. Of these 61 biopsies, 51 yielded a correct diagnosis with specific histological typing, mainly in the case of thymoma and metastasis. Lymphomas were less reliably diagnosed. The overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy values were 83.6%, 100%, 100%, 35.3% and 83.6%, respectively. Pneumothorax was the most common complication (5.5%). CONCLUSIONS: CT-guided percutaneous transthoracic needle biopsy is an easy, reliable and safe procedure that obviates the need for exploratory surgery in medically treatable or unresectable cases. It should be the first invasive procedure in the diagnostic workup of mediastinal masses.

Accuracy of CT-guided transthoracic needle biopsy of lung lesions: factors affecting diagnostic yield.

PURPOSE: This study was performed to analyse the variables affecting the diagnostic accuracy of computed tomography (CT)-guided transthoracic needle biopsy of pulmonary lesions. MATERIALS AND METHODS: A retrospective study of 612 consecutive procedures with confirmed final diagnoses was undertaken. Benign and malignant needle biopsy results were compared with final outcomes to determine diagnostic accuracy. A statistical analysis of factors related to patient characteristics, lung lesions and biopsy technique was performed to determine possible influences on diagnostic yield. A p value less than 0.05 was interpreted as statistically significant. RESULTS: There were 508 (83%) malignant and 104 (17%) benign lesions. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for a diagnosis of malignancy were 90.2%, 99.0%, 99.8%, 67.3% and 91.7%, respectively. Overall diagnostic accuracy was 83.3%. Variables affecting diagnostic accuracy were the final diagnosis (benign 67%, malignant 92%; p<0.001) and lesion size (lesions<1.5 cm 68%, lesions 1.5-5.0 cm 87%, lesions>5 cm 78%; p<0.05). CONCLUSIONS: In CT-guided transthoracic needle biopsy, the final diagnosis and lesion size affect diagnostic accuracy: benign lung lesions and lesions smaller than 1.5 cm or larger than 5.0 cm in diameter provide lower diagnostic yield.