We established and validated a novel nomogram that can provide individual prediction of OS for patients with resected NSCLC. This practical prognostic model may help clinicians in decision making and design of clinical studies.
Summary Background The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. Methods A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I–III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). Findings Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5–80·0) in low-risk, 58·3% (48·9–66·6) in intermediate-risk, and 49·2% (42·2–55·8) in high-risk patients (ptrend=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0–80·6) in low-risk, 57·4% (48·3–65·5) in intermediate-risk, and 44·6% (40·2–48·9) in high-risk patients (ptrend<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. Interpretation Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. Funding UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
Superspreading events were pivotal in the global spread of severe acute respiratory syndrome (SARS). We investigated superspreading in one transmission chain early in Beijing’s epidemic. Superspreading was defined as transmission of SARS to at least eight contacts. An index patient with onset of SARS 2 months after hospital admission was the source of four generations of transmission to 76 case-patients, including 12 healthcare workers and several hospital visitors. Four (5%) case circumstances met the superspreading definition. Superspreading appeared to be associated with older age (mean 56 vs. 44 years), case fatality (75% vs. 16%, p = 0.02, Fisher exact test), number of close contacts (36 vs. 0.37) and attack rate among close contacts (43% vs. 18.5%, p < 0.025). Delayed recognition of SARS in a hospitalized patient permitted transmission to patients, visitors, and healthcare workers. Older age and number of contacts merit investigation in future studies of superspreading.
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