Purpose: One of the main challenges of lung cancer research is identifying patients at high risk for recurrence after surgical resection. Simple, accurate, and reproducible methods of evaluating individual risks of recurrence are needed. Experimental Design: Based on a combined analysis of time-to-recurrence data, censoring information, and microarray data from a set of 138 patients, we selected statistically significant genes thought to be predictive of disease recurrence. The number of genes was further reduced by eliminating those whose expression levels were not reproducible by real-time quantitative PCR. Within these variables, a recurrence prediction model was constructed using Cox proportional hazard regression and validated via two independent cohorts (n = 56 and n = 59). Results: After performing a log-rank test of the microarray data and successively selecting genes based on real-time quantitative PCR analysis, the most significant 18 genes had P values of <0.05.After subsequent stepwise variable selection based on gene expression information and clinical variables, the recurrence prediction model consisted of six genes (CALB1, MMP7, SLC1A7, GSTA1, CCL19, and IFI44). Two pathologic variables, pStage and cellular differentiation, were developed. Validation by two independent cohorts confirmed that the proposed model is significantly accurate (P = 0.0314 and 0.0305, respectively). The predicted median recurrence-free survival times for each patient correlated well with the actual data. Conclusions: We have developed an accurate, technically simple, and reproducible method for predicting individual recurrence risks. This model would potentially be useful in developing customized strategies for managing lung cancer.
A B S T R A C T PurposeLung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients.
Patients and MethodsWe performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.
ResultsThis cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC.
ConclusionThese findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.
MTV, a volumetric parameter of (18)F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with esophageal carcinoma.
FDG PET is more sensitive than CT for depicting nodal metastases in patients with squamous cell carcinoma of the esophagus. FDG PET is slightly less specific than CT for depicting metastases, but the difference in specificity between the two modalities is statistically significant. Both FDG PET and CT have low sensitivity for depicting nodal metastasis. The relatively low specificity of FDG PET for depiction of nodal metastasis compared with that of CT is caused mainly by a high rate of false-positive hilar node interpretations.
The prethoracotomy CEA level and the number of metastases were independent prognostic factors. Resection of pulmonary metastasis from colorectal cancer may result in improved survival or even healing in selected patients. Pulmonary resection of colorectal cancer is regarded as a safe and effective treatment with low morbidity and mortality rates.
Early aggressive treatment comprising at least 4 effective drugs and surgical resection, when indicated, may improve the outcome for patients with MDR TB or XDR TB.
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