Prognostic impact of micropapillary and solid histological subtype on patients undergoing curative resection for stage I lung adenocarcinoma according to the extent of pulmonary resection and lymph node assessment.

BACKGROUND: We aimed to evaluate the impact of micropapillary and/or solid (MPSOL) components on survival and recurrence of patients with resected stage I lung adenocarcinoma (LUAD) according to the extent of surgery and completeness of lymph node assessment (LNA). METHODS: We retrospectively reviewed 1886 consecutive patients who underwent surgical resection for pathologic stage I LUAD between 2009 and 2014. The patients were classified by the presence (≥1%) of MPSOL into the MPSOL(+) (n = 489) and MPSOL(-) (n = 1397) group.We analyzed the outcomes according to the extent of surgery (sublobar resection [SR] vs. lobectomy) and the LNA (complete vs. incomplete). Complete LNA was defined as systematic LN dissection according to European Society of Thoracic Surgeons guideline. RESULTS: In the MPSOL(+) patients, there was no significant difference in adjusted overall survival (OS), recurrence-free survival (RFS), and recurrence pattern between the lobectomy and SR group. Of note, patients with complete LNA had higher adjusted OS and RFS than those with incomplete LNA (aOS, 86.3% vs. 78%, p = 0.002; aRFS, 70% vs 63.1%, p = 0.06). In the MPSOL(-) patients, adjusted RFS of the SR group was better than the lobectomy group (95% vs. 90.5%, p = 0.021), although there was no difference in survival regarding to the LNA. Complete LNA was a favorable prognostic factor for RFS in the MPSOL(+) patients (HR = 0.463, 95% CI: 0.227-0.944, p = 0.034). CONCLUSIONS: In MPSOL(+) patients, complete LN assessment affects the OS and RFS rather than the extent of lung resection. In patients with solid tumor or tumor>2 cm, a complete LN assessment would be required, even if sublobar resection is unavoidable.

Volume-Based Assessment With 18F-FDG PET/CT Improves Outcome Prediction for Patients With Stage IIIA-N2 Non-Small Cell Lung Cancer.

OBJECTIVE: We evaluated the prognostic impact of volume-based assessment by pretreatment (18)F-FDG PET/CT in patients who had clinical stage IIIA-N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection. MATERIALS AND METHODS: We reviewed 161 consecutive patients who had stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery. In all cases, N2 disease was pathologically confirmed by mediastinoscopic biopsy, endobronchial ultrasound-guided transbronchial needle aspiration, or video-assisted thoracoscopic surgery. We measured the total metabolic tumor volume (total MTV) and the maximum standardized uptake value (SUVmax), including a primary tumor and metastatic nodes on the pretreatment scan. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. The association of PET parameters with OS and DFS was determined by univariable and multivariable analyses performed using the Cox regression model. RESULTS: A higher total MTV was significantly associated with poor DFS (hazard ratio [HR], 1.82; p = 0.036) and OS (HR = 2.97; p = 0.012) in the multivariable analysis. In contrast, a higher SUVmax was not significantly associated with poor DFS and OS. Patients with a high total MTV (> 22 cm(3)) had a median survival time that was significantly shorter than that of patients with a low total MTV (median DFS, 11.3 vs 42.0 months, respectively [p < 0.001]; median OS, 38.3 months vs not reached [p < 0.001]). Kaplan-Meier curves showed significant differences on the basis of total MTV in patients with or without mediastinal downstaging after CCRT. Patients with a high total MTV had significantly worse DFS when they had post-neoadjuvant pathologic (yp) stage 0-II disease (p = 0.020) or yp stage III disease (p = 0.036). Higher total MTV was also associated with worse OS in patients with yp stage 0-II disease (p = 0.013) or yp stage III disease (p = 0.007). CONCLUSION: A higher pretreatment total MTV is associated with worse outcome, independent of yp stage, in patients with stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery.

Assessment of intratumoral heterogeneity of oncogenic driver mutations in surgically-resected lung adenocarcinoma: implications of percutaneous biopsy-based molecular assay for target-directed therapy.

AIM: The present study investigated whether there is intratumoral heterogeneity of oncogenic driver mutations within surgically-resected tumors and between surgical specimens and percutaneous biopsy samples. PATIENTS AND METHODS: Thirty-four patients who underwent surgery for lung adenocarcinoma were studied. We obtained four to five snap-frozen samples from each surgical specimen. Mutational analyses of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit-alpha (PIK3CA) genes were performed and then compared in multiple surgical specimens and between surgical and percutaneous biopsy samples. RESULTS: EGFR and KRAS mutations were detected in 19 and 2 patients, respectively. Multiple surgical samples from different areas of the tumor had the same mutation genotype in all cases except for one. The 14 biopsy specimens had the same mutational profiles as the corresponding surgical specimens. CONCLUSION: Heterogeneous distributions of oncogenic driver mutations were not found in surgically-resected lung adenocarcinoma. Small tumor specimens obtained with percutaneous biopsy were suitable for EGFR analyses, thus providing critical information for personalized therapy.

Employment status and work-related difficulties in lung cancer survivors compared with the general population.

OBJECTIVE: To investigate the employment status of lung cancer survivors and the work-related problems they face. BACKGROUND: Although the number of lung cancer survivors is increasing, little is known about their employment and work-related issues. METHODS: We enrolled 830 lung cancer survivors 12 months after lung cancer curative surgery (median time after diagnosis, 4.11 years) and 1000 volunteers from the general population. All participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30-item and a questionnaire that included items relating to their jobs. We used logistic regression analysis to identify independent predictors of unemployment. RESULTS: The employment rate of lung cancer survivors decreased from 68.6% at the time of diagnosis to 38.8% after treatment, which was significantly lower than the employment rate of the general population (63.5%; adjusted odds ratio = 2.31, 95% confidence interval: 1.66-3.22). The posttreatment unemployment rate was higher for women than for men. Among survivors, employment was inversely associated with older age, household income, number of comorbidities, and poor social functioning. Fatigue (78.6%) was the most common work-related problem reported by survivors. CONCLUSIONS: Lung cancer survivors experienced more difficulties in employment than did the general population. Age, monthly household income, number of comorbidities, and social functioning appear to be important factors influencing employment status. These findings suggest that lung cancer survivors need support to cope with the financial impact of cancer.

Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer.

PURPOSE: We evaluated the prognostic impact of volume-based assessment by (18)F-FDG PET/CT in patients with stage III non-small-cell lung cancer (NSCLC). METHODS: We reviewed 194 consecutive patients with stage IIIA NSCLC treated with surgical resection (surgical group) and 115 patients treated with nonsurgical therapy (nonsurgical group: 50 stage IIIA, 65 stage IIIB). Metabolic tumour volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) of primary tumours were measured using pretreatment (18)F-FDG PET/CT. Overall survival was assessed using the Kaplan-Meier method. The prognostic significance of PET parameters and other clinical variables was assessed using Cox proportional hazards regression analyses. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used. RESULTS: In the Cox proportional hazards models, MTV (HR=1.27 for a doubling of MTV, P=0.008) and TLG (HR=1.22 for a doubling of TLG, P=0.035) were significantly associated with an increased risk of death after adjusting for age, gender, histological cell type, T stage, N stage, and treatment variables in the surgical group. SUVmax was not a significant prognostic factor in either the surgical or nonsurgical group. In the time-dependent ROC curve analysis, volume-based PET parameters predicted survival better than SUVmax. CONCLUSION: The volume-based PET parameters (MTV and TLG) are significant prognostic factors for survival independent of tumour stage and better prognostic imaging biomarkers than SUVmax in patients with stage IIIA NSCLC after surgical resection.

Repeated resection of colorectal cancer pulmonary oligometastases: pooled analysis and prognostic assessment.

BACKGROUND: Repeated resection of colorectal cancer pulmonary metastasis is associated with long-term survival. Nevertheless, very limited data addressing the best candidates for repeated pulmonary resection is available. PATIENTS AND METHODS: We searched the PubMed database for retrospective studies evaluating lung metastasectomy for metastatic colorectal cancer (CRC). We included studies with available data about repeated pulmonary metastasectomy. Potential prognostic factors were analyzed for possible impact on survival following the second metastasectomy through univariate and multivariate analysis. RESULTS: Between 1983 and 2008, 944 lung metastasectomies were carried out on 759 patients. Of those, 148 patients had a second metastasectomy. The 5-year survival rate was 52 % for patients who had 1 metastasectomy and 57.9 % from the second metastasectomy for patients who had repeated resection. More than 2 metastatic pulmonary nodules and maximum diameter of largest pulmonary nodule ≥3 cm were the only independent factors associated with inferior survival following repeated pulmonary resection. CONCLUSIONS: In selected patients with metastatic CRC, repeated pulmonary metastasectomy offers an excellent chance for long-term survival and is associated with a quite low operative mortality. Patients with more than 2 metastatic nodules and a maximum diameter of the largest metastatic lung nodule of ≥3 cm have a significantly inferior survival.