Classification of lung adenocarcinoma according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification correlated with 5-year survival. These relationships persisted after controlling for known prognostic patient and tumor characteristics. The new classification has advantages not only for individual patient care but also for better selection and stratification for clinical trials and molecular studies.
Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.
Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up.
Control of local disease at each site and long-term survival after lung resection and resection of either synchronous or metachronous brain METASTASIS and whole brain irradiation is readily achievable. We believe this should continue as the standard of care for this presentation.
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