Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions / 医学前沿

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

Analysis of the Efficacy of Pemetrexed Maintenance Therapy in Patients with Malignant Pleural Mesothelioma / 中国肺癌杂志

BACKGROUND@#Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM.@*METHODS@#A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT.@*RESULTS@#The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%).@*CONCLUSIONS@#Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.

Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2020 Version) / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Individualized treatment recommendations for lung cancer patients at different stages of treatment during the outbreak of 2019 novel coronavirus disease epidemic / 中华肿瘤杂志

In order to achieve the overall victory of the 2019 novel coronavirus disease epidemic in this 'war’, especially to prevent the disease recurrence from rebounding during the resumption of labor, the government has not loosened any control of personnel mobility, which has obviously affected the normal examination and treatment of lung cancer patients under the influence of this epidemic. During the epidemic period, cancer patients with low immunity levels face the double ordeals of disease and epidemic situation. Compared with the general population, they are more likely to be infected with the new coronavirus. Among the infected cancer patients, lung cancer is the most common type. It is necessary to provide more appropriate individualized treatment recommendations for patients with lung cancer based on the epidemic situation of the patient's location and in combination with the patient's own condition. Through active prevention of infection, timely conversion of treatment strategies, online and offline joint control, and positive psychological counseling, we significantly hope to help patients with lung cancer to survive this difficult period.

The clinical application of laparoscopic common bile duct stone removal / 中华肝胆外科杂志

Cholecystolithiasis with choledocholithiasis (CCL) is a common disease.The removal of common bile stone is a challenge for the surgery.This paper discussed the clinical application of three stone removal techniques including direct stone removal,irrigation and stone extraction by basket under cholangioscopy in order to take the stones effectively and safely,shorten the procedure time,avoid the injuries of common bile duct wall caused by the repetition of a single method such as biliary endoscopic stone extraction,reduce the difficulty of taking stone and enhance recovery of patients.

An ingenious method to suture laparoscopic puncture holes / 中华肝胆外科杂志

Objective To study the ingenious method to suture laparoscopic puncture holes.Methods A curved needle and a hook-like needle were used in 650 patients during biliary tract surgery.Results The curved needle was used in 200 patients and the hook-like needle was used in 450 patients.All patients had good wound healing except for one patient who developed puncture hole seroma under the xiphoid.The patient was treated with drainage and improved rapidly.No other complications such as puncture hole hemorrhage,infection and puncture hole hernia occurred.Conclusion Suturing using a curved needle and a hook-like needle was easy and effective,and avoided complications.

An analysis of the curative effect of 1 and 2 ureters anastomosis in modified sigma operation / 中华泌尿外科杂志

Objective To make a comparison of curative effect of 1 and 2 ureters anastomosis in modified sigma operation. Methods Modified sigma operation was used after radical cystectomy in 14 cases of bladder transitional cell carcinoma and 1 case of adenocarcinoma of the bladder.We used a folded suture of 25 cm from the sigmoid colon to make the U-shaped urinary reservoirs to anastomose with the ureters in study group.Among study group,1 ureter was anastomosed with urinary reservoir in 5 cases.In the other 10 cases,1.5-2 cm of the terminal parts of 2 ureters were sutured tI am not sure what the authors mean by big diamogether and then anastomosed with the urinary reservoir.Results 15 cases obtained good voiding control and no obvious water-electrolyte disturbance occurred.All the patients were cured and discharged within 15 to 22 days.Thirteen cases were followed-up in 8 to 24 month time period.Anastonmtic stenosis and moderate-severe hydronephrosis occurred in 4 cases with 1 ureter anastomosis.No hydronephrosis occurred in the 9 cases with 2 ureters anastomosis.Conclusions Modified sigma operation has the advantages of less injury and fewer complications.The patients can obtain self-control urination by anal sphincter without urine bags or intermittent catheterization,so the life quality of the patients is improved.Modified sigma operation with 2 ureters anastomosis has big diameter and there was a lower incidence of serious complications such as anastomotic stenosis.

Target therapy of non-small cell lung cancer directed by biomarkers / 肿瘤研究与临床

Lung cancer is one of the most frequent malignant tumors. Target therapy is a milestone of non-small cell lung cancer (NSCLC) treatment in the 21st century. Biomarker detections have provided a solid foundation for individualized treatment. This review mainly focused on significance of EGFR mutation detection in EGFR tyrosine kinase inhibitors (EGFR-TKIs) as first line, second line and maintenance therapy in NSCLC. Simultaneously, this review introduced predicting significance of EGFR FISH test for the response of TKI treatment, and analyzed potential predictive biomarkers for antiangiogenic agents and status of antiEGFR monoclonal antibody in NSCLC individual therapy.

Prognostic analysis of intrapulmonary metastasis for patients with non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>It is well known that more than 40% patients were initially diagnosed with advanced non-small cell lung cancer (NSCLC) with intrapulmonary or/and distant metastasis. However, up to now, the reports about effects of different metastatic sites on survival were limited. The aim of this study is to investigate the clinicopathologic and survival difference by retrospective analysis among sole intrapulmonary metastasis, sole extrathoracic distant metastasis and simultaneous metastasis of lung and other extrathoracic organs for the patients with advanced NSCLC, and to analyze the prognosis-related factors of NSCLC with intrapulmonary metastasis.</p><p><b>METHODS</b>Of the 425 patients with stage IV NSCLC diagnosed by pathology and through staging evaluation and treated at Beijing Cancer Hospital with long follow-up during Oct. 1995 to Dec. 2003, 81 cases had sole intrapulmonary metastasis, 98 cases had sole extrathoracic distant metastasis and 68 cases presented simultaneous lung metastasis and extrathoracic spread. Kaplan-Meier survival curve was performed to estimate the survival of patients with different metastasis, Log-Rank test was used to compare their survival difference, and univariate analysis was used to find prognostic related factors.</p><p><b>RESULTS</b>Median survival time (MST) and 1-, 2-, 3-year survival rate (SR) for patients with sole intrapulmonary metastasis were 13 months (95% CI: 11-15), 57%, 21%, 7%, respectively; MST was 22 months (95% CI: 18-26) for patients with N1 and/or N2 and 10 months (95%CI: 7-13) for patients with N3 (P=0.001). Among the patients with ipsilateral, contralateral and bilateral intrapulmonary metastasis, difference of MST and 1-, 2-, 3-year SR had no statistical significance (P > 0.05); Survival of patients with sole intrapulmonary metastasis was not significantly different from that of patients with sole brain or bone metastasis (P > 0.05), but was longer than that of patients with simultaneous lung and extrathoracic spread (P=0.021). One way analysis of variance showed that no significant association were found among age, pathologic subtype, differentiation degree or response of first-line chemotherapy and survival of the patients with sole intrapulmonary metastasis (P > 0.05), but sex and invasive status of lymph node (N1/N2 vs N3) were found to influence the survival of the patients (P= 0.018, P=0.001). Further stratified analysis by age showed that invasion of lymph node was independent prognostic factor (P=0.002); whereas for the patients with simultaneous metastasis of lung and distant organs, metastatic numbers (2 vs ≥3) of organ were independent prognostic factor (P=0.013).</p><p><b>CONCLUSIONS</b>No statistical difference is found among survival of NSCLC patients with sole intrapulmonary metastasis and with sole brain, bone metastasis. Invasive status of lymph node and metastatic number of organ are important prognostic factors for patients with sole intrapulmonary metastasis and simultaneous metastasis of lung and extrathoracic organs, respectively.</p>