Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study.

BACKGROUND: Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. METHODS: Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). RESULTS: Among 129 patients with RET-rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation (n = 15) had shorter overall survival than those without (n = 30; median, 18.4 months [95% CI, 8.6-39.1] vs 24.8 months [95% CI, 11.7-52.8]; P < 0.05). Patients with lower peripheral blood TCR diversity (n = 5) had superior overall survival compared with those with higher diversity (n = 6; median, 18.4 months [95% CI, 16.9-19.9] vs 4.8 months [95% CI, 4.5-5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). CONCLUSIONS: RET-rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal.

Clinical analysis of postoperative venous thromboembolism risk factors in lung cancer patients.

BACKGROUND AND OBJECTIVES: The objective of this study is to explore clinical risk factors for venous thromboembolism (VTE) in postoperative lung cancer patients in order to provide a basis for the prevention and treatment of postoperative VTE. METHODS: A total of 1,001 lung cancer patients were retrospectively analyzed. Each patient was confirmed with surgical pathology diagnosis and had a complete clinical and follow-up record. VTE was identified in a combination of spiral computed tomography (CT), pulmonary angiography, and color Doppler ultrasound. We used life table method to create an occurrence frequency curve of thrombosis. We also searched for high risk factors for postoperative VTE with Cox multivariate regression model and created frequency curves of thrombosis against different risk factors using Kaplan-Meier method. RESULTS: As of July 31, 2011, the median follow-up time is 25.73 ± 0.11 months (19.23-31.37). The cumulative frequency of VTE among 1,001 lung cancer patients is 2%, 3%, 4%, 5%, and 5.3% over 1, 3, 6, 12, and 30 months after the surgery. COX regression analysis showed that the hazard ratio of VTE occurrence in patients with incomplete resection relative to ones with complete resection is 9.867 (95% CI: 5.275-18.459, P = 0.000). And the hazard ratio of VTE occurrence is 3.472 (95% CI: 1.761-6.845, P = 0.000) in patients with anti-angiogenesis treatment compared to patients without such treatment. The hazard ratio of VTE occurrence is 2.808 (95% CI: 1.439-5.479, P = 0.002) in patients with EGFR-TKI treatment relative to patients without the treatment, and 7.520 (95% CI: 3.968-14.250, P = 0.000) in patients with an increase in D-dimer level relative to normal ones CONCLUSIONS: The highest incidence of VTE is within 1 month after lung cancer surgery. High risk factors for VTE include incomplete surgical resection, postoperative use of anti-angiogenesis drugs, EGFR-TKI application and an increase in preoperative D-dimer level.

Establishment of a biomarker model for predicting bone metastasis in resected stage III non-small cell lung cancer.

BACKGROUND: This study was designed to establish a biomarker risk model for predicting bone metastasis in stage III non-small cell lung cancer (NSCLC). METHODS: The model consists of 105 cases of stage III NSCLC, who were treated and followed up. The patients were divided into bone metastasis group (n = 45) and non-bone metastasis group (other visceral metastasis and those without recurrence) (n = 60). Tissue microarrays were constructed for immunohistochemical study of 10 molecular markers associated with bone metastasis, based on which a model was established via logistic regression analysis for predicting the risk of bone metastases. The model was prospectively validated in another 40 patients with stage III NSCLC. RESULTS: The molecular model for predicting bone metastasis was logit (P) = - 2.538 + 2.808 CXCR4 +1.629 BSP +0.846 OPN-2.939 BMP4. ROC test showed that when P ≥ 0.408, the sensitivity was up to 71% and specificity of 70%. Model validation in the 40 cases in clinical trial (NCT 01124253) demonstrated that the prediction sensitivity of the model was 85.7%, specificity 66.7%, Kappa: 0.618, with a high degree of consistency. CONCLUSION: The molecular model combining CXCR4, BSP, OPN and BMP4 could help predict the risk of bone metastasis in stage IIIa and IIIb resected NSCLC.