Background: In recent years, the tumor-stroma ratio (TSR) has been considered to a new and independent predictive variable for the prognosis of some kinds of neoplasms. The objective of this study was to assess the prognostic significance of the TSR in non-small cell lung cancer (NSCLC). Methods: A cohort of 261 NSCLC patients who underwent radical surgery of lung cancer were included in the present study. Two independent observers visually estimated the TSR on hematoxylin-eosin (H&E) stained tissue pathological slices. According to the proportion of stroma ≥50% or <50%, We separate the patients into two groups: those with stroma-poor and those with stroma-rich tumors. Results: Both univariate and multivariate analyses disclosed that the TSR was associated with overall survival (OS) [hazard ratio (HR), 1.741; 95% confidence intervals (CI), 1.040–2.913 and HR, 1.904; 95% CI, 1.132–3.202, respectively]. The HR values for disease-free survival (DFS) were 1.795 (95% CI, 1.073–3.005) and 2.034 (95% CI, 1.210–3.420). The OS and DFS of patients with stroma-poor tumors were better than those with stroma-rich tumors. Conclusions: These results demonstrated that the TSR is a new prognostic factor for NSCLC. Stroma-poor tumors were associated with longer disease-free period and better prognosis than were stroma-rich tumors in NSCLC patients. The TSR may contribute to the development of individualized treatment for NSCLC in the future.

High-level tissue tumor mutational burden (tTMB) or blood TMB (bTMB) are associated with better response of immunotherapy in non-small cell lung cancer (NSCLC) patients. However, the correlations of single-region tTMB, multi-region tTMB and bTMB remain to be determined. Moreover, whether intratumor heterogeneity (ITH) has impact on TMB should be clarified. We collected multi-region tumor tissues with matched blood from 32 operative NSCLC and evaluated single-region tTMB, multi-region tTMB and bTMB through a 1021-gene panel sequencing. TMB of > 9 mutations/Mb was classified as high. Besides, we used tTMB fold-change to evaluate the influence of the enrolled region number on tTMB. We found both of single-region tTMB and bTMB showed strong correlations with multi-region tTMB, while the former correlated better (Pearson r = 0.94, P = 2E-84; Pearson r = 0.47, P = 0.0067). It showed extremely high specificity (100%) but low sensitivity (43%) when using bTMB to define TMB-high patients, while most false-negative predictions were in early-stage patients. Compared to single region, we found significantly enhanced tTMB fold-change if taking multi-regions for consideration. However, it showed insignificant tTMB fold-change increase if the included regions’ number more than three. Moreover, ITH-high patients had significantly higher tTMB fold-change compared with ITH-low patients (2.32 vs. 1.02, P = 8.879e-05). The conversion rate of tTMB level (tTMB-low to tTMB-high) was numerically higher in ITH-high group than that in ITH-low group (16.67% vs. 3.84%). In summary, single-region tTMB has stronger correlation with multi-region tTMB compared with bTMB. ITH has an impact on tTMB, especially in high-level ITH patients.

OBJECTIVES: Video-assisted thoracoscopic sublobar resection of ultra-small, non-visible and non-palpable pulmonary lesions is challenging. The purpose of this study was to explore an alternative and efficient method for the localization of pulmonary lesions using electromagnetic navigation bronchoscopy (ENB). METHODS: Between May 2015 and April 2016, 24 consecutive patients with 30 pulmonary peripheral lesions underwent video-assisted thoracoscopic surgery for sublobar resection in our hospital. ENB was performed before surgery to guide a catheter adjacent to the target lesion, and fibrin sealant mixed with methylene blue was injected. RESULTS: All patients underwent ENB with pleural dye marking followed immediately by surgery. No surgical complications occurred. The median size of the nodules was 11.0 mm (range, 6–19 mm). The median navigation time was 18.0 min (range, 13 to 120 min), and the average interval between dye marking and thoracic surgery was 22.1 min (range, 15–40 min). In all cases, the target pulmonary parenchyma was stained and had tactile sense with few complications. All lesions were fully excised, and pathological examination confirmed the accuracy of the dye staining. CONCLUSIONS: Fibrin sealant mixed with methylene blue injection with ENB guidance is a new effective approach to localize even ultra-small and non-palpable pulmonary lesions. The visible staining and tactile sensation of this method may allow more rapid intraoperative identification of lesions.

Plenty of studies have confirmed the prognostic values of inflammation-based prognostic scores in many malignant tumors. In present study, we aim to explore whether these indexes has same prognostic values in patients with stage T1N0 esophageal squamous cell carcinoma (ESCC). The clinicopathological data of 160 consecutive patients with pathological stage T1N0 ESCC from January 2005 to December 2012 were collected retrospectively. As prognostic factors, the inflammation-based prognostic scores, including C-reactive protein (CRP), Glasgow prognostic score (GPS), prognostic index (PI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and CRP to albumin ratio (CAR), were evaluated. The best cut-off values were determined by the receiver operating characteristic (ROC) curves. The median follow-up time was 71.8 months. During the follow-up period, 34 (21.3%) patients occurred postoperative recurrence and 30 (18.8%) tumor-related deaths were recorded. The best cut-off values of CRP, NLR, PLR and CAR were 1.090, 1.976, 103.200 and 0.023, respectively. After multivariate analysis, the GPS and CAR were identified as independently prognostic factors for overall survival (OS) (p=0.017 and 0.040, respectively). Of all 160 individuals, there were 86 (53.8%) and 85 (53.1%) patients classified into high GPS group (1-2) and elevated CAR group (>0.023), respectively. In addition, the GPS were positively associated with PI (p<0.000) and the levels of serum CRP (p<0.000), NLR (p=0.004), PLR (p=0.029) and CAR (p<0.000) and the above correlations were also observed between the CAR and other inflammation-based prognostic scores (all p<0.050, except for p=0.054 for PLR levels). The preoperative GPS and CAR were simple, inexpensive, readily available predictor for long-term survival in stage T1N0 ESCC patients who underwent esophagectomy.

High expression of fibrinogen and platelets are often observed in non-small cell lung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months; P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

We proposed to identify the efficacy of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) using whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS)/surgery in brain metastases from patients with non-small cell lung cancer (NSCLC) and clarify the association between treatment outcome and EGFR gene mutation status. A total of 282 patients with NSCLC brain metastases who underwent WBRT/SRS/surgery alone or in combination with TKI were enrolled in our study from 2003–2013. Amplification mutation refractory system technology was used to determine the EGFR mutation status in 109 tissue samples. EGFR mutation detection was performed in 109 patients with tumor tissues. The EGFR positive rate was 50 % (55/109), including 26 exon 19 deletions and 24 L858R mutations. The median follow-up time was 28 months. The median overall survival, median progression-free survival of intracranial disease, and median progression-free survival of extracranial disease was significantly longer for patients with TKI treatment (31.9 vs 17.0 months, P < 0.0001; 19.8 vs 12.0 months, P < 0.0001; and 19.6 vs 12.3 months, P < 0.0001; respectively). In subgroup analysis within the TKI group, patients harboring EGFR mutations had better extracranial disease control (20.4 vs 14.1 months, P = 0.032). Administration of TKI agents with conventional therapy compared with conventional therapy alone might be beneficial for overall survival, progression-free survival of intracranial disease and progression-free survival of extracranial disease in patients with brain metastases from NSCLC independent of EGFR mutations.