Positron emission tomography/computed tomography and endobronchial ultrasound-guided transbronchial needle aspiration to evaluate the status of N2 in preoperative non-small cell lung cancer: a diagnostic test.

Background: As a minimally invasive method, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was more accurate than non-invasive methods such as positron emission tomography (PET) and computed tomography (CT) to evaluate the lymph nodes in preoperative non-small cell lung cancer (NSCLC). PET/CT has more anatomical advantages than PET scanning and is more accurate in lung cancer staging. However, no relevant studies have comparatively evaluated PET/CT and EBUS-TBNA for NSCLC patients. Methods: A total of 112 patients were included in this retrospective analysis. The golden diagnosis of N2 status was postoperative pathological results. In EBUS-TBNA puncture specimens, if clear malignant tumor cells could be seen, the results were taken as positive. In PET/CT image analysis, the CT values, short diameter, and maximum standardized uptake value (SUVmax) of each lymph node were recorded to evaluate N2 status. The results of PET/CT and EBUS-TBNA were compared with the final pathological results, and respective sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. - Then, the patients were divided into adenocarcinoma group and squamous cell carcinoma group -and the results were calculated and compared with the above method. Results: The results showed that EBUS-TBNA had a higher diagnostic value for mediastinal lymph nodes than PET/CT, and the difference was statistically significant (P<0.001). In NSCLC patients, the results showed that the sensitivity (P=0.013), specificity (P<0.001), PPV (P<0.001), NPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than that of PET/CT (AUC =0.954 and 0.636, respectively). In adenocarcinoma cases, specificity (P<0.001), PPV (P<0.001), NPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than that of PET/CT (AUC =0.957 and 0.596, respectively).In cases with squamous cell carcinoma, specificity (P=0.003), PPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than PET/CT (AUC =0.952 and 0.657, respectively). Conclusions: For preoperative diagnosis of mediastinal lymph node metastases in NSCLC, EBUS-TBNA is more accurate than PET/CT. For those patients with suspected mediastinal lymph node metastasis, EBUS-TBNA should be preferred method to evaluate the status of mediastinal lymph nodes.

The role of ERBB4 mutations in the prognosis of advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have witnessed the achievements of convincing clinical benefits that feature the significantly prolonged overall survival (OS) of patients suffering from advanced non-small cell lung cancer (NSCLC), according to reports recently. Sensitivity to immunotherapy is related to several biomarkers, such as PD-L1 expression, TMB level, MSI-H and MMR. However, a further investigation into the novel biomarkers of the prognosis on ICIs treatment is required. In addition, there is an urgent demand for the establishment of a systematic hazard model to assess the efficacy of ICIs therapy for advanced NSCLC patients. METHODS: In this study, the gene mutation and clinical data of NSCLC patients was obtained from the TCGA database, followed by the analysis of the detailed clinical information and mutational data relating to two advanced NSCLC cohorts receiving the ICIs treatment from the cBioPortal of Cancer Genomics. The Kaplan-Meier plot method was used to perform survival analyses, while selected variables were adopted to develop a systematic nomogram. The prognostic significance of ERBB4 in pan-cancer was analyzed by another cohort from the cBioPortal of Cancer Genomics. RESULTS: The mutation frequencies of TP53 and ERBB4 were 54% and 8% in NSCLC, respectively. The mutual exclusive analysis in cBioPortal has indicated that ERBB4 does show co-occurencing mutations with TP53. Patients with ERBB4 mutations were confirmed to have better prognosis for ICIs treatment, compared to those seeing ERBB4 wild type (PFS: exact p = 0.017; OS: exact p < 0.01) and only TP53 mutations (OS: p = 0.021). The mutation status of ERBB4 and TP53 was tightly linked to DCB of ICIs treatment, PD-L1 expression, TMB value, and TIICs. Finally, a novel nomogram was built to evaluate the efficacy of ICIs therapy. CONCLUSION: ERBB4 mutations could serve as a predictive biomarker for the prognosis of ICIs treatment. The systematic nomogram was proven to have the great potential for evaluating the efficacy of ICIs therapy for advanced NSCLC patients.