Serum Biomarkers May Prognosticate Recurrence in Node-Negative, Non-Small Cell Lung Cancers Less Than 4 Centimeters

摘要

Background A significant proportion of patients who undergo lung resection for less than 4 cm non-small cell lung cancer (NSCLC) will die of disease recurrence within 5 years. The ability to identify patients at greatest risk for recurrence may help individualize treatment and surveillance regimens and improve outcomes. We hypothesized that a serum-based biomarker panel could help risk stratify patients with node-negative NSCLC less than 4 cm for recurrence after lung resection.;Methods An institutional biorepository of more than 1,800 cases was used to identify patients with resected, node-negative NSCLC less than 4 cm in size. Clinical and radiographic data were collected. Preoperative serum specimens were evaluated in a blinded manner for 47 biomarkers that sampled biological processes associated with metastatic progression, including angiogenesis, energy metabolism, apoptosis, and inflammation. Receiver-operating characteristics curves and log rank tests were used to evaluate individual biomarkers with respect to?recurrence, followed by random forest analysis to generate and cross validate a multiple-analyte panel to risk stratify patients for recurrence.;Results The cohort included 123 patients with a median follow-up of 58.2 months; 23 patients had recurrences. A seven-analyte panel consisting of human epididymis protein 4, insulinlike growth factor–binding protein 1, beta-human chorionic gonadotropin, follistatin, prolactin, angiopoietin-2, and hepatocyte growth factor optimally identified patients with disease recurrence with a cross-validated specificity of 91%, sensitivity of 22%, negative predictive value of 83%, positive predictive value of 36%, and accuracy of 78%, providing an area under the receiver-operating characteristics curve of 0.70.;Conclusions Serum-based biomarkers may be useful for risk stratifying patients with node-negative NSCLC less than 4 cm for recurrence after lung resection.;;The Annals of Thoracic Surgery CME Program is located online at http://www.annalsthoracicsurgery.org/cme/home. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.;The Supplemental TablesSupplemental Tables can be viewed in the?online?version of this article [http://dx.doi.org/10.1016/j.athoracsur.2017.06.036] on http://www.annalsthoracicsurgery.org.;Jump to SectionPatients and MethodsPatient CohortsMeasurement of Serum Biomarker ConcentrationsStatistical MethodsResultsClinical CharacteristicsUnivariate Analysis of Biomarker and Clinical Characteristic Ability to Risk Stratify for RecurrenceMulti-Analyte Panel to Predict Early RecurrenceCommentDiscussionSupplementary DataReferences;Between 2004 and 2015, serum and tissue specimens from more than 1,800 patients who underwent pulmonary resection for suspected lung cancer at Rush University Medical Center were collected in an institutional lung tumor biorepository. Inclusion criteria for the current study included patients with pathologically proven, node-negative NSCLC less than 4 cm with serum available in the Rush University Cancer Center Biorepository. Patients with tumors 2 cm to 3.9 cm were included if they underwent lobectomy or pneumonectomy with mediastinal lymph node dissection or sampling, whereas patients with tumors less than 2 cm were included if they received lobar or sublobar resection with mediastinal lymph node dissection or sampling. Exclusion criteria included age less than 18 years, neuroendocrine histology, absence of mediastinal lymph node dissection, lack of an R0 resection, administration of neaodjuvant or adjuvant chemotherapy or radiotherapy, or survival less than 30 days.Computed tomography scans and positron emission tomography–computed tomography scans were routinely used in the clinical staging of lung cancer patients during the study period. Endobronchial ultrasound-guided fine needle aspiration and mediastinoscopy were selectively used, as clinically indic