A retrospective study for prognostic significance of type II diabetes mellitus and hemoglobin A1c levels in non-small cell lung cancer patients treated with pembrolizumab

Background: Diabetes mellitus (DM) is common and recognized as a risk factor for developing non-small cell lung cancer (NSCLC) while the prognostic evaluation is still controversial. As immunotherapy is widely used in clinical practice, its efficacy and survival should be investigated in patients with DM. Methods: We retrospectively recruited 266 locally advanced and metastatic NSCLC patients who received pembrolizumab alone or in combination with chemotherapy. Patients\u27 clinicopathological data, including age, history of DM, hemoglobin A1c (HbA1c), genetic tumor profiling, and survival data were collected. Associations between clinical characteristics and survival were evaluated by univariate and multivariate analyses. Results: In this cohort, 15.04 % (40/266) of the patients had a history of DM. Fifty-nine (22.2 %) patients had a HbA1c level ≥ 6.5 %. A total of 169 (63.5 %) patients received 1st-line therapy, and 97 (36.5 %) received 2nd- or subsequent-line therapy. Patients with high ( ≥ 6.5 %) HbA1c and lower ( \u3c 35 g/L) albumin levels at baseline had worse survivals, and epidermal growth factor receptor (EGFR) mutants significantly associated with worse outcomes at normal HbA1c ( \u3c 6.5%) levels (all P \u3c 0.05). Among the 1st-line therapy patients, a higher HbA1c level ( ≥ 6.5 %) at baseline indicated a worse overall survival (OS) (2-year survival rate: 31.25 % vs. 27.03 %, P = 0.045), tumor protein p53 (TP53) alternations and high programmed death-ligand 1 (PD-L1) expression ( ≥ 50 %) were significantly associated with better outcomes (P \u3c 0.05). For 2nd- or subsequent-line patients, EGFR mutants and non-squamous carcinomas (non-SCs) indicated worse survivals, and the normal peripheral blood markers of the carcinoembryonic antigen (CEA), C-reactive protein (CRP), albumin levels were favorable prognostic factors for survivals. In non-SCs, Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, high PD-L1 expression, and normal alkaline phosphatase (ALP) levels favored better progression-free survival (PFS), while EGFR mutants indicated poor PFS (P \u3c 0.05). Conclusions: Among patients treated with 1st-line immunotherapy, a higher HbA1c level ( ≥ 6.5 %) indicated dismal OS, while history of DM, baseline blood glucose levels, and glucose changes during the treatment process were not significantly associated with any of the outcomes

Efficacy and safety of anlotinib combined with PD‐1/PD‐L1 inhibitors as second‐line and subsequent therapy in advanced small‐cell lung cancer

Abstract Objectives Treatments for advanced small‐cell lung cancer (SCLC) patients who are resistant to first‐line chemotherapy are limited. Given that antiangiogenic agents and immune‐checkpoint inhibitors (ICIs) can confer synergistic therapeutic benefits, combination therapy should be considered. We explored the efficacy and safety of combination therapy with anlotinib and programmed cell death protein 1 (PD‐1)/programmed cell death‐ligand 1 (PD‐L1) inhibitors as second‐line and subsequent therapy for advanced SCLC. Materials and Methods We reviewed advanced SCLC patients at Shanghai Chest Hospital who had received anlotinib in combination with ICIs from November 2016 to November 2020 as second‐ and subsequent‐line treatment. Patients with advanced SCLC who had received paclitaxel monotherapy as second‐line treatment were included as the control group. Results A total of 141 patients were included in the final analysis (40 in the combination therapy group and 101 in the paclitaxel monotherapy group). The median progression‐free survival (PFS) times for the combination therapy and paclitaxel monotherapy groups were 3.40 and 2.83 months (p = 0.022), respectively, while the median overall survival (OS) times for the combination therapy and paclitaxel monotherapy groups were 8.20 and 5.87 months (p = 0.048), respectively. Hypertension and hepatic dysfunction were the most pronounced adverse events of combination therapy and two patients changed regimens due to severe fatigue and anorexia. Conclusion The combination of anlotinib and PD‐1/PD‐L1 blockade has promising efficacy and safety as a second‐line or subsequent therapy for SCLC

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in the Diagnosis of Intrathoracic Metastasis from Extrapulmonary Malignancy

Background and objective Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has been widely applied in diagnosing mediastinal and hilar adenopathy. This study is further to evaluate value and safety of EBUS-TBNA in diagnosing intrathoracic metastasis from extrapulmonary malignancy. Methods Prospectively analysis of 41 patients suspected intrathoracic metastasis from previous diagnosed/concurrent extrapulmonary malignancies in Shanghai Chest Hospital, with radiologic findings showing mediastinal/hilar lymph node enlargement or intrapulmonary lesion requiring EBUS-TBNA examination for pathological diagnosis. Results 41 candidate patients enrolled, and 67 mediastinal/hilar lymph nodes and 5 intrapulmonary lesions were aspirated. 14 intrathoracic metastasis, 10 primary lung cancer, 9 reactive lymphadenitis, 4 sarcoid-like reactions, and 1 tuberculosis was diagnosed by EBUS-TBNA. Sensitivity and accuracy of EBUS-TBNA in diagnosing intrathoracic metastasis was 87.50% and 95.12%, respectively. Immunohistochemistry (IHC) was performed in 18 malignant tumors to obtain definite type or origin, twelve intrathoracic metastasis and 6 primary lung cancer were further confirmed. Conclusion EBUS-TBNA is a safe, effective method for the diagnosis of intrathoracic metastasis from extrapulmonary malignancy. IHC can provide additional evidence for distinguishing extrapulmonary malignancy from primary lung cancer

Detection of Genetic Mutations by Next-Generation Sequencing for Predicting Prognosis of Extensive-Stage Small-Cell Lung Cancer

Some studies have revealed that specific genetic mutations could be associated with chemotherapy response or even survival in small-cell lung cancer (SCLC). Our retrospective study aimed to identify the correlation between genetic mutations and progression-free survival (PFS) in extensive-stage SCLC after first-line chemotherapy. A total of 75 patients with extensive-stage SCLC confirmed by histopathology from February 2018 to February 2019 were retrospectively analyzed. The biopsy specimens of all patients were analyzed by Next-Generation Sequencing (NGS). All patients received first-line chemotherapy and follow-up at Shanghai Chest Hospital. Eleven genes were mutated in, at least, 10% of the 75 patients, including TP53 (96%), RB1 (77%), SMAD4 (32%), NOTCH1 (21%), PTEN (16%), FGFR1 (16%), KDR (15%), PIK3CA (15%), ROS1 (15%), BRCA2 (13%), and ERBB4 (10%). The median number of mutated genes among all patients was 5. Patients with more than 5 mutated genes (PFS = 6.7 months, P=0.004), mutant TP53 (PFS = 5.0 months, P=0.011), and mutant BRCA2 (PFS = 6.7 months, P=0.046) had better PFS after first-line chemotherapy than other patients. Multivariate Cox regression analysis showed that patients who achieved a PR (HR 3.729, 95% CI 2.038–6.822), had more than 5 mutated genes (HR 1.929, 95% CI 1.096–3.396), had BRCA2 mutations (HR 4.581, 95% CI 1.721–12.195), and had no liver metastasis (HR 0.415, 95% CI 0.181–0.951) showed improvements in PFS after first-line chemotherapy. In conclusion, the number of mutated genes and BRCA2 mutation status in extensive-stage SCLC were significantly related to PFS after first-line chemotherapy

The Clinical Analysis of 21 Patients with Lymphoepithelioma-like Carcinoma after Operation

Background and objective Lung lymphoepithelioma-like carcinoma is a rare subtype of large cell carcinomas of the lung. The aim of this study is to retrospectively analyze the clinical characteristics, surgical methods, laboratory inspection, chemotherapy, radiotherapy and prognosis of LELC. Methods From 2004 to 2008, clinical data were collected from 21 patients who were treated in Shanghai Chest Hospital. The correlation between clinicopathological characteristics and prognosis was evaluated. Results Of the 21 patients, 15 patients had lobectomy; 4 patients had wedge resection; 1 patient had pneumonectomy and 1 patient had sleeve resection. 12 patients received chemotherapy and 3 patients received radiotherapy after operation. Until 2009-4-31, 4 patients died, and the median survival time (MST) was 49 months. Conclusion Lymphoepitheliomalike carcinoma of the lung is a very rare and unique subtype of large cell carcinomas of the lung, which has a better prognosis with surgical, chemotherapy and radiotherapy

Rationale and design of a multicenter, randomized phase II trial of durvalumab with or without multitarget tyrosine kinase inhibitor as maintenance treatment in extensive‐stage small‐cell lung cancer patients (DURABLE study)

Abstract Introduction Durvalumab is a check‐point inhibitor against programmed death ligand‐1 (PD‐L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs. However, it is unclear that whether this combination is effective when initiated as maintenance treatment in ES‐SCLC patients. Methods This is a multicenter, randomized, phase II study. A total of 64 eligible patients who do not experience disease progression after four cycles platinum‐based chemotherapy combined with durvalumab will be randomized to durvalumab with anlotinib or durvalumab alone until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is PFS (from randomization); secondary endpoint was OS and PFS (from diagnosis), objective response rate (ORR); disease control rate (DCR) and duration of response (DOR), safety and tolerability assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Discussion We conduct a phase II study to investigate the safety and efficacy of durvalumab combined with anlotinib as maintenance treatment in ES‐SCLC patients

Prediction of lymph node status in completely resected IIIa/N2 small cell lung cancer: importance of subcarinal station metastases

Abstract Background The aim of this study was to determine the prognostic value of lymph node status in patients with pathologic N2 (pN2) stage IIIA small cell lung cancer (SCLC). Methods A total of 163 consecutive pN2 stage IIIA SCLC patients who underwent pulmonary resections and systematic lymphadenectomies at Shanghai Chest Hospital between January 2006 and June 2014 were enrolled. We retrospectively analyzed the potential clinicopathologic factors that influenced survival, including the node levels (single or multiple-station) and the node-spreading patterns (skip N2 or non-skip N2). The prognostic significance was examined by Cox regression analysis. Results The median overall survival (OS) was 23.7 months. Multiple-station lymph node metastasis indicated a poorer prognosis than single-station involvement (p = 0.003). Skip metastasis did not appear to influence survival (p = 0.099). With respect to the station of lymph node metastasis, the OS was only related to the involvement of the subcarinal node, regardless of tumor location (p < 0.05). Multivariate analysis showed two statistically significant risk factors for survival, including multiple-station lymph node and subcarinal node metastasis (hazard ratio [HR] = 1.76, 95% confidence interval [CI]:1.11–2.78, p = 0.015; HR = 1.61, 95% CI: 1.03–2.50, p = 0.036, respectively). Conclusions Multiple-station N2 metastasis and involvement of the subcarinal node predicted poor prognosis in pN2 stage IIIA SCLC patients, which may profoundly influence therapeutic decisions