scholarly journals Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors

Author(s):  
Da Hyun Kang ◽  
Chaeuk Chung ◽  
Pureum Sun ◽  
Da Hye Lee ◽  
Song-I Lee ◽  
...  

Abstract Background Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. Methods This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. Results The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). Conclusion Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Hsin Lee ◽  
Tsung-Ying Yang ◽  
Kun-Chieh Chen ◽  
Yen-Hsiang Huang ◽  
Jeng-Sen Tseng ◽  
...  

AbstractPleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.


2018 ◽  
Vol 4 (3) ◽  
pp. 00001-2018 ◽  
Author(s):  
Tanel Laisaar ◽  
Bruno Sarana ◽  
Indrek Benno ◽  
Kaja-Triin Laisaar

Since publication of the National Lung Cancer Screening Trial (NLST) results early lung cancer detection has been widely studied, targeting individuals based on smoking history and age. However, over recent decades several changes in lung cancer epidemiology, including risk factors, have taken place. The aim of the current study was to explore smoking prevalence among lung cancer patients who had been treated surgically or undergone a diagnostic operation and whether these patients would have met the NLST inclusion criteria.All patients operated on for lung cancer in a university hospital in Estonia between 2009 and 2015 were included. Data were collected from hospital records.426 patients were operated on for lung cancer, with smoking history properly documented in 327 patients (87 females; median age 67 years). 170 (52%) patients were smokers, 97 (30%) patients were ex-smokers and 60 (18%) patients were nonsmokers. The proportion of females among smokers was 15%, among ex-smokers was 9% and among nonsmokers was 87%. 107 of our patients would not have met the NLST age criteria and 128 of our patients would not have met the NLST smoking criteria. In total, 183 patients (56% (79% of females and 48% of males)) would not have met the NLST inclusion criteria.Only half of surgically treated lung cancer patients were current smokers and more than half did not meet the NLST inclusion criteria.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yanning Wang ◽  
Qianning Zhang ◽  
Chuansheng Chen ◽  
Yuxuan Hu ◽  
Liyun Miao ◽  
...  

BackgroundIn pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases.MethodsSystematic searches of PubMed, Embase, Cochrane database, and conference proceedings up to Aug 6, 2020 without year and language restrictions. The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios.ResultsNine eligible randomized controlled trials involving 6241 patients (682 [11%] with brain metastases and 5559 [89%] without brain metastases) were included in the analysis. A survival benefit of immunotherapy was observed for both patients with brain metastases (HR, 0.75; 95%CI, 0.53-0.97; P = .026) and patients without brain metastases (HR, 0.75; 95%CI, 0.67-0.83; P &lt;.001). However, patients without brain metastases benefit more from immunotherapy than patients with brain metastases (HR, 1.37; 95%CI, 1.15-1.63; P = .001). Additionally, subgroup analyses indicated that tumor type affect the efficacy of immunotherapy in patients with brain metastases (HR, 1.04 vs 1.54; interaction, P = .041).ConclusionsImmunotherapy can significantly improve overall survival for advanced lung cancer patients with asymptomatic brain metastases, especially in patients with non-small-cell lung cancer, but the magnitude of benefit is brain metastases dependent.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206597.


2021 ◽  
Author(s):  
Arno Mohr ◽  
Mia Kloos ◽  
Christian Schulz ◽  
Michael Pfeifer ◽  
Bernd Salzberger ◽  
...  

Abstract IntroductionThe aim of this study was to investigate the adherence to vaccinations, especially pneumococcal vaccinations, in lung cancer patients.MethodsThe study was performed at the University Hospital Regensburg, Germany. All patients with a regular appointment scheduled between December 1, 2020, and April 29, 2021, and who provided informed consent were included. Available medical records, vaccination certificates and a questionnaire were analyzed.Results136 lung cancer patients (NSCLC n = 113, 83.1%, SCLC n = 23, 16.9%) were included. A correct pneumococcal vaccination according to national recommendations was performed in 9.4% (12/127) of patients.A correct vaccination was performed for tetanus in 50.4% (6/131), diphtheria in 34.4% (44/128), poliomyelitis in 25.8% (33/128), tick-borne encephalitis in 40.7% (24/59), hepatitis A in 45.5% (7/11), hepatitis B in 38.5% (5/13), shingles in 3.0% (3/101), measles in 50.0% (3/6), pertussis in 47.7% (62/130), influenza in 54.4% (74/136) and meningococcal meningitis in 0% (0/2).ConclusionAdherence to pneumococcal vaccinations, as well as other vaccinations, is rather low in lung cancer patients.


2012 ◽  
Vol 7 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Miep A. van der Drift ◽  
Henrike E. Karim-Kos ◽  
Sabine Siesling ◽  
Harry J.M. Groen ◽  
Michel W.J.M. Wouters ◽  
...  

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