Inoperable Advanced Lung Cancer Research Articles

Precise medicine of programmed cell death-1/programmed cell death 1 ligand 1 inhibitor immunotherapy combined radiotherapy for inoperable advanced lung cancer: A protocol for systematic review and meta-analysis.

Background:Programmed cell death-1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibitors are a group of immune checkpoint inhibitors immunotherapy for cancer treatment. These immune checkpoint inhibitors are becoming first-line treatments for several types of cancer. Radiotherapy for cancer is a traditional treatment and the therapeutic effect is not satisfactory due to the side effect of chemotherapeutic drugs. This study aims to evaluate the efficacy and safety of PD1/PD-L1 inhibitor immunotherapy combined chemotherapy for inoperable advanced lung cancer.Methods:We will utilize PubMed, PubMed Central, EMbase, Medline, CNKI, WAN FANG Database, and Web of Science to screen eligible studies published from January 1, 2015 to December 30, 2020. Two reviewers will extract data and evaluate the risk of bias independently. The quality of the included studies will be evaluated using the RevMan 5.3 software for data analysis.Results:This review will summarize high-quality evidence of trials to evaluate the precise medicine efficacy and safety of PD1/PD-L1 inhibitor combined radiotherapy for inoperable advanced lung cancer.Conclusions:The findings of the systematic review will provide scientific evidence of the efficacy and safety of PD1/PD-L1 inhibitor combined radiotherapy for inoperable advanced lung cancer to guide the clinician's drug use.Ethics and dissemination:Not applicable.INPLASY registration number:INPLASY202140123.

Abstract 744: Effective use of MDK/Midkine and MEK inhibitor to treat KRas mutated pulmonary adenocarcinoma cells

Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Although a platinum-doublet regimen has become the standard of care, the benefit is modest and the 5-year survival rate has remained essentially unchanged over the past 3 decades. Recently, several molecular alterations have been defined as “driver mutations,“ such as mutations in epidermal growth factor receptor (EGFR), KRas, chimeric tyrosine kinases involving ALK, RET, ROS1. And molecular targeting therapies for lung adenocarcinoma, targeting mutant EGFR or ALK, RET and ROS1 fusions, limit non-tumor toxicity and extend survival time compared to the conventional chemotherapies. However, there is no effective molecularly targeted therapy for mutant KRas-driven lung adenocarcinoma, the most frequent type of lung adenocarcinoma in the Caucasian population. Therefore, specific therapies that target various lung tumor types are desperately needed. Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many malignant tumors, including lung cancers. We have previously reported that a MDK inhibitor: iMDK suppresses non-small cell lung cancer expressing MDK in vitro and in vivo without harming normal cells. Importantly, iMDK inhibits the PI3 kinase / Akt pathway and induces apoptosis in MDK expressing non-small cell lung cancer cells. In the present study, we have investigated the combination effect of iMDK and a mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD0325901. The combination treatment of iMDK and PD0325901 more effectively suppressed cell viability and colony formation, increased caspase-3 activity and induced apoptosis than those of single use in H441 and H2009 pulmonary adenocarcinoma cells harboring a G12 KRas mutation. Here, we describe the efficacy of the use of iMDK and PD0325901 for patients with inoperable advanced lung cancer including pulmonary adenocarcinoma harboring KRas mutations. Citation Format: Takuya Fukazawa, Yutaka Maeda, Naomasa Ishida, Tomoki Yamatsuji, Munenori Takaoka, Minoru Haisa, Nagio Takigawa, Jeffery Whitsett, Yoshio Naomoto. Effective use of MDK/Midkine and MEK inhibitor to treat KRas mutated pulmonary adenocarcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 744. doi:10.1158/1538-7445.AM2014-744

The role of airway stent placement in the management of tracheobronchial stenosis caused by inoperable advanced lung cancer

To our knowledge there is no in-depth report on the benefits of airway stenting, which focuses specifically on patients with inoperable advanced lung cancer causing severe central airway obstruction. We evaluated the role of airway stenting as one aspect of the multidisciplinary management of advanced lung cancer. We performed airway stenting in 40 lung cancer patients, placing a total of 58 stents. Stenting was done as a final modality in 22 patients with terminal-stage lung cancer (group A). The other 18 patients received additional therapy after stenting (group B), 12 (66.7%) of whom were treatment-naïve on admission. The performance status (PS) and Hugh-Jones classification (H-J) scores improved in both groups after stenting: from 3.56 to 2.48 (P = 0.001) and 4.29 to 3.20 (P = 0.004) in group A, and from 3.15 to 1.25 (P < 0.001) and 4.10 to 2.10 (P < 0.001) in group B, respectively. The median survival time and 1-year survival rate after stenting were 1.6 months and 5.1%, respectively, in group A, and 5.6 months and 25.0%, respectively, in group B. Airway stenting followed by adjuvant therapy may improve the survival of treatment-naïve patients with severe symptomatic airway obstruction caused by advanced lung cancer.

Restaging by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in Patients with Inoperable Advanced Lung Cancer

We present two cases of inoperable advanced lung cancer in which the main lesions were mediastinal lymph nodes detected with positive positron emission tomography (PET). Drug therapy was very effective, and post-treatment PET results were negative. Restaging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed on the mediastinal lymph nodes with a short axis < or = 10 mm measured by computed tomography (CT). Cancer cells were detected, which helped determine the therapeutic strategy. Re-evaluation of mediastinal lymph nodes using EBUS-TBNA appears to be useful, even among patients with inoperable advanced lung cancer.

Clinical Benefits and Complications of Cryotherapy in Advanced Lung Cancer with Central Airway Obstruction

Background: The efficacy of the use of the interventional bronchoscope for palliation of patients with central airway obstruction has been established. In the palliative setting to alleviate central airway obstruction, the use of laser resection, electrocautery, argon plasma coagulation, photodynamic therapy and cryotherapy can provide relief of an airway obstruction. Cryotherapy is the therapeutic application of extreme cold for the local destruction of living tissue. Recently, this technique has been used for endoscopic management of central airway obstructions in Korea. We report the role and complications of the use of cryotherapy for airway obstructions in patients with advanced lung cancer. Methods: We used a flexible cryoprobe for cryotherapy using nitrous oxide as a cryogen. The cryoprobe was applied through the working channel of a flexible fiberoptic bronchoscope. The temperature of the tip was approxi- mately −89 o C, and the icing time was 5∼20 seconds. Results: Four patients with a central airway obstruction from advanced lung cancer were treated with cryotherapy. Three of the four patients were treated successfully and the airway obstruction was improved after the cryotherapy procedure. Dyspnea, hypoxia and atelectais were improved in three cases. Two patients experienced compli- cations-one patient experienced pneumomediastinum and the other patient experienced massive hemoptysis during the cryotherapy procedure. However, these complications resolved and did not influence mortality. Conclusion: This technique is effective and relatively safe for palliation of inoperable advanced lung cancer with a central airway obstruction. (Tuberc Respir Dis 2008;64:272-277)

C4-02: The role of airway stent placement in the management of tracheobronchial stenosis due to inoperable advanced lung cancer

C4-02: The role of airway stent placement in the management of tracheobronchial stenosis due to inoperable advanced lung cancer

Clinical Experience of Photodynamic Therapy in Five Patients with Advanced Lung Cancer

Background : A tracheobronchial obstruction in lung cancer is associated with significant morbidity and mortality due to dyspnea, cough, hemoptysis, and recurrent respiratory infection. It is well known that one of standard treatments is photodynamic therapy (PDT) in tracheobronchial obstruction after radiotherapy, chemotherapy, and/or surgery. We reported here the role of PDT in airway obstruction in patients advanced lung cancer. Method : Pre-treatment protocol consisted of clinical, radiologic, and bronchoscopic examination, pulmonary function test, and assessment of Karnofsky performance status. A 2 mg/kg of porfimer sodium was injected intravenously, and then followed by cylindrical and/or interstitial irradiation with 630 nm of laser after 48 hours. The repeated bronchoscopy for debridement of necrotic tissue and re-illumination was performed after 48 hours. Result : Improved airway obstruction and selective tumor necrosis were achieved by photodynamic therapy in all cases. Dyspnea and performance status were improved in three cases. A purulent sputum, fever and hemoptysis were improved in one of five cases. After PDT, all patients showed temporarily aggravation of dyspnea, two of five showed febrile reaction for a few days and nobody presented photosensitivity reaction, hemoptysis and respiratory failure. Conclusion : Our experiences of PDT are effective in palliation of inoperable advanced lung cancer in terms of tracheobronchial obstruction. (Tuberc Respir Dis 2004; 57:72-77)

The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: experience of 100 cases1

The objectives of the study were: (1) to evaluate effectiveness of photodynamic therapy (PDT) for symptom palliation in patients with inoperable lung cancer; (2) to determine survival benefit in a subset of patients. One hundred patients, 68 male, 32 female, aged 44-81 years (mean 62.5) with advanced inoperable bronchogenic cancer and endobronchial luminal obstruction were prospectively studied. Eighty-two percent had previous chemo/radiotherapy. The pre-treatment protocol consisted of: clinical, radiological and bronchoscopic examination, pulmonary function testing, assessment of WHO performance status and clinical staging. Treatment protocol was: intravenous injection of 2 mg/kg body weight of photofrin/polyhaematoporphyrin and interstitial illumination using 630 nm laser light 24-72 h later. Follow-up was at 6-8 weeks for 1 year. Then every 3-6 months if applicable. Repeat PDT as necessary. All patients were stage IIIa-IV. The histology of the tumour was: non small cell in 90 and small cell in 10. There was no treatment related mortality. Mean endoluminal obstruction fell from 85.8% to 17.5%, mean forced vital capacity (FVC) and forced expiratory volume in 1s (FEVI) improvement was 430 ml and 280 ml, respectively. Ninety patients died from 6 weeks to 37 months, mean and median survival: 9 months and 5 months, respectively. Ten patients are alive from 13 to 72 months, mean 36 months, median 29 months. Overall 2-year survival was 19%. Multivariant analysis indicated that age, sex, histology and stage of disease did not influence survival significantly but performance status did. Patients with WHO < 2 had mean and median survival of 17.8 and 14 months versus WHO > 2, 6.9 mean and 4 months median survival (log-rank P < 0.0001). (1) PDT is effective in palliation of inoperable advanced lung cancer. (2) Subset of patients with a better performance status have added survival benefit.