No abstract

Background: Adjuvant chemotherapy after resection of colorectal cancer (CRC) lung metastases may reduce recurrences and improve survival. The choice of best candidates for adjuvant chemotherapy in this setting is controversial, especially when a single lung metastases (SLM) is resected. The aim of this study is to evaluate the risk of recurrence after radical resection for single lung metastasis from CRC. Patients and methods: Demographic, clinical, and pathological data were retrospectively collected for patients radically operated on for single pulmonary metastasis from CRC in 4 centers. Survival was computed by Kaplan-Meyer methods. Chi-square, log-rank test, and for multivariate analysis, Cox-regression and binary logistic regression were used when indicated. Results: The sample consisted of 344 patients, mean age 65 yrs. Overall 5 yrs survival was 61.9%. Recurrence occurred in 113 pts (32.8%). At univariate analysis, age > 70 ( p = 0.046) and tumor size > 2 cm ( p = 0.038) were predictive of the worst survival chance, while synchronous lung metastasis ( p = 0.039), previous resection of extrathoracic metastasis ( p = 0.017), uptake at FDG-PET scan ( p = 0.006) and short (<12 months) disease-free interval (DFI) prior to lung metastasectomy ( p = 0.048) were risk factors for recurrence. At multivariate analysis, only high CEA (>4 ng/mL) was associated with worst survival (HR: 4.3, p = 0.014), while prior abdominal surgery (HR: 3, p = 0.033), PET positivity (HR: 2.7, p = 0.041), and DFI > 12 months (HR: 0.14, p < 0.001) confirmed to predict recurrence of disease. Conclusions: Surgical resection of solitary lung metastases from CRC is associated with prolonged survival. High value of CEA, PET positivity, previous extrathoracic resected metastasis, and short (<12 months) DFI were found to be predictive of death or disease recurrence and might identify in this scenario patients at higher risk which could potential benefit of chemotherapy.

No abstract

Malignant Pleural Mesothelioma (MPM) is a heterogeneous disease. Morphologically, three different phenotypes are distinguishable: epithelioid (e-), sarcomatoid (s-) and biphasic (biph-) MPM, the latest, being a mixture of e- and s-MPM cells. Being an intermediate entity, management of biph-MPM, remains debatable and controversial, with different guidelines recommending distinct approaches. Identification of biph-MPM associated genetic alterations, through deep sequencing analysis, may provide useful tools to understand these lesions. A retrospective cohort of 69 surgically resected MPMs, 39 biph-MPMs (56.5%) and 30 e-MPMs (43.5%) was selected. A separate set of 16 biph-MPM was used as validation set. Deep sequencing analysis on an MPM-specific custom panel (MPM_geneset) comprising 1041 amplicons spanning 34 genes was performed. A total of 588 variants and 5309 mutational events were detected. In total, 91.3% of MPMs showed at least one mutation and 76.8% showed co-occurrence of more than one alteration. Mutations in MXRA5 (p = 0.05) and NOD2 (p = 0.018) were significantly associated with biph-MPM both in the training and validation cohort and correlated with the extent of the sarcomatoid component. Mutations in NOD2 and XRCC6 correlated with patients’ survival. We demonstrated that biph-MPM are associated with a specific mutation set, and that genetic analysis at diagnosis may improve patients’ risk stratification.