Relationship with programmed cell death ligand 1 (PD-L1) and DTI features in brain metastases of non-small cell lung cancer; Preliminary study

2021 ◽  
Vol 17 ◽  
Author(s):  
Temel Fatih Yilmaz ◽  
İsmail Yurtsever ◽  
Hacı Mehmet Turk ◽  
Mehmet Ali Gultekin ◽  
Mehmet Besiroglu ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Metastases ◽  
Small Cell ◽  
Peritumoral Edema ◽  
Small Cell Lung ◽  
Protein Status ◽  
Adc Values ◽  
Group 2 ◽  
L1 Protein ◽  
Group 1

Objectives: The purpose of the study was to determine DTI properties of brain metastases in subjects with non-small cell lung carcinoma (NSCLC), to evaluate whether there was a correlation between DTI findings and programmed cell death ligand-1 (PD-L1). Methods: The study population (n:22) was assigned to PD-L1 negative (Group 1: PD-L1 expression<%50) (n=11) or positive (Group 2: PD-L1 expression ≥%50) (n=11). We compared ADC and FA values measured from the enhanced solid metastases and peritumoral edema area with PD-L1 protein status. Results: The mean ADC values were lower in group 2 compared to group 1. The peritumoral ADC values were higher in group 2 compared to group 1. Mean peritumoral edema FA values are lower in group 2 compared to group 1. The peritumoral edema nADC values were higher in group 2 compared to group 1. As PD-L1 expression frequency increased, ADC values in the peritumoral edema area increased and FA values decreased. Conclusions: We thought that the existence of PD-L1 protein doesn’t affect ADC and FA values of brain metastasis (BM) originating from NSCLC. DTI characteristics of the peritumoral edema area could be a guide in determining PD-L1 protein status of brain metastases of NSCLC. The relationship between PD-L1 expression status and DTI features in BM from NSCLC could help us to have an idea in response to immunotherapy.

scholarly journals Best Supportive Care Versus Whole-Brain Irradiation, Chemotherapy Alone, or WBRT Plus Chemotherapy in Patients With Brain Metastases From Small-Cell Lung Cancer: A Case-Controlled Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hongwei Li ◽  
Ruiqi Xue ◽  
Xiaotang Yang ◽  
Songye Han ◽  
Weihua Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Best Supportive Care ◽  
Small Cell ◽  
The Other ◽  
Small Cell Lung ◽  
Group 2 ◽  
Group 1

BackgroundWBRT and systemic chemotherapy are the mainstay treatments for small-cell lung cancer (SCLC) brain metastases (BM). However, current recommendations are mainly based on evidence from retrospective analyses. A recent randomized trial found no benefits from WBRT compared with best supportive care (BSC) in patients with more than three BM from non-small-cell lung cancer (NSCLC). Herein, we aimed to evaluate the roles of WBRT and chemotherapy further in the management of BM from SCLC.Materials and MethodsThere were 698 patients with BM from SCLC included. Of these, 580 received anti cancer treatment (Group 1), including 178 who received WBRT only (Group 1a), 129 who received chemotherapy only (Group 1b), and 273 who received WBRT plus chemotherapy (Group 1c). The other 118 received BSC (Group 2). Propensity score matching (PSM) analysis was used to compare Group 2 with each of the other groups.ResultsAfter PSM, compared with Group 2 (n = 118), patients in Group 1 (n = 440) had a prolonged overall survival (OS) in both univariate and multivariate tests, with a median survival time of 10 months (95% CI = 9−11) in Group 1 and 3.5 months (95% CI = 2−7) in Group 2 (p &lt; 0.001). In subgroup analyses, patients who received WBRT plus chemotherapy were more likely to benefit from treatment (p &lt; 0.001). Chemotherapy alone or WBRT alone did not show survival benefits.ConclusionWBRT plus chemotherapy improved OS in patients with BM from SCLC as compared to BSC. Chemotherapy alone and WBRT alone did not show survival benefits. This retrospective study suggests that SCLC patients with BM who receive WBRT combined with chemotherapy have a better outcome than those receiving BSC alone.

scholarly journals Efficiency and safety of video-assisted mediastinal lymphadenectomy in the treatment of non-small cell lung cancer

2021 ◽  
Vol 179 (6) ◽  
pp. 24-33
Author(s):  
A. A. Skorokhod ◽  
A. S. Petrov ◽  
A. R. Kozak ◽  
M. A. Atyukov ◽  
A. O. Nefedov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Nodes ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lung Resection ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mediastinal Lymphadenectomy ◽  
Group 2 ◽  
Group 1

INTRODUCTION. A number of studies demonstrate the advantage of bilateral mediastinal lymphadenectomy in surgery of non-small cell lung cancer (nSCLC). For surgical approach to the opposite mediastinum for many years there were proposed sternotomy, video-thoracoscopy, and transcervical video-assisted interventions. In our practice, we use videoassisted mediastinal lymphadenectomy (VAMLA).The OBJECTIVE was to learn the efficiency and safety of VAMLA in surgery of NSCLC.METHODS AND MATERIALS. The study included the materials of examination and treatment of 102 patients with NSCLC. 102 patients were divided into 2 groups. In the 1st group (54 patients), VAMLA and lung resection were performed. In the 2nd group (48 patients): anatomical lung resection and systematic ipsilateral lymphadenectomy (SLD) were performed.RESULTS. The average number of remote lymph node stations in group 1 was (7.8±1.7); in group 2 – (4.5±1.2) (p<0.05). The average number of lymph nodes was 26±8.6 compared to (14.3±6) in both groups, respectively (p<0.05). «Occult» pN2-N3 metastasis was detected in 20 % (7/34) of patients of the group 1 and 6.5 % (2/31) of patients of the group 2 (p<0.05). The level of postoperative complications in both groups was 33.4 vs. 29.2 %, respectively (p>0.05). The duration of the postoperative day ((12.7±4.9) vs. (13.7±6.5)) and the duration of pleural drainage ((5.5±4.2) vs. (5.8±4.4)) did not differ in both groups (p>0.05).CONCLUSION. VAMLA is an effective and safe method for evaluating the pN stage of NSCLC. Performing VAMLA in left-sided NSCLC allows removing significantly more lymph nodes and stations in comparison with SLD available in VATS and thoracotomy, which increases the accuracy of postoperative N-staging. The use of the VAMLA in minimally invasive surgery of right-sided NSCLC may be promising in cases of high risk of «occult» pN3 lesion, but requires further study of the role of contralateral lymphatic dissection.

scholarly journals Subtyping Lung Cancer Using DNA Methylation in Liquid Biopsies

2019 ◽  
Vol 8 (9) ◽  
pp. 1500 ◽  
Author(s):  
Nunes ◽  
Diniz ◽  
Moreira-Barbosa ◽  
Constâncio ◽  
Silva ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Independent Study ◽  
Study Group ◽  
Small Cell Lung ◽  
Group 2 ◽  
Group 1

Background: Lung cancer (LCa) is the most frequently diagnosed and lethal cancer worldwide. Histopathological subtyping, which has important therapeutic and prognostic implications, requires material collection through invasive procedures, which might be insufficient to enable definitive diagnosis. Aberrant DNA methylation is an early event in carcinogenesis, detectable in circulating cell-free DNA (ccfDNA). Herein, we aimed to assess methylation of selected genes in ccfDNA from LCa patients and determine its accuracy for tumor subtyping. Methods: Methylation levels of APC, HOXA9, RARβ2, and RASSF1A were assessed in three independent study groups (study group #1: 152 tissue samples; study group #2: 129 plasma samples; study group #3: 28 benign lesions of lung) using quantitative methylation-specific PCR. Associations between gene promoter methylation levels and LCa subtypes were evaluated using non-parametric tests. Receiver operating characteristic (ROC) curve analysis was performed. Results: In study group #2, HOXA9 and RASSF1A displayed higher methylation levels in small-cell lung cancer (SCLC) than in non-small-cell lung cancer (NSCLC). HOXA9 displayed high sensitivity (63.8%), whereas RASSF1A disclosed high specificity (96.2%) for SCLC detection in ccfDNA. Furthermore, HOXA9 methylation levels showed to be higher in squamous cell carcinoma in comparison with adenocarcinoma in study group #1. Conclusions: Methylation level assessments in ccfDNA may provide a minimally invasive procedure for LCa subtyping, complementing standard diagnostic procedures.

scholarly journals Poor efficacy of anti‐programmed cell death‐1/ligand 1 monotherapy for non‐small cell lung cancer patients with active brain metastases

2020 ◽  
Vol 11 (9) ◽  
pp. 2465-2472
Author(s):  
Takehiro Tozuka ◽  
Satoru Kitazono ◽  
Hiroaki Sakamoto ◽  
Hiroshi Yoshida ◽  
Yoshiaki Amino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Programmed Cell Death 1 ◽  
Poor Efficacy

Role of Radiation Therapy in the Combined-Modality Treatment of Patients With Extensive Disease Small-Cell Lung Cancer: A Randomized Study

1999 ◽  
Vol 17 (7) ◽  
pp. 2092-2092 ◽  
Author(s):  
Branislav Jeremic ◽  
Yuta Shibamoto ◽  
Nebojsa Nikolic ◽  
Biljana Milicic ◽  
Slobodan Milisavljevic ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Extensive Disease ◽  
Group 2 ◽  
Group 1

PURPOSE: To investigate the efficacy and toxicity of cisplatin/etoposide (PE) chemotherapy (CHT) with or without accelerated hyperfractionated radiation therapy (ACC HFX RT) and concurrent daily carboplatin/etoposide (CE) in patients with extensive-disease small-cell lung cancer. PATIENTS AND METHODS: A total of 210 patients were treated with three cycles of standard PE. Patients with a complete response (CR) at both the local and distant levels (CR/CR) or a partial response (PR) at the local level and CR at the distant level (PR/CR) received either thoracic ACC HFX RT with 54 Gy in 36 fractions over 18 treatment days in combination with CE followed by two cycles of PE (group 1, n = 55) or an additional four cycles of PE (group 2, n = 54). Patients who experienced less response were treated nonrandomly (groups 3, 4, and 5). All patients with a CR at the distant level received prophylactic cranial irradiation. RESULTS: For 206 assessable patients, the median survival time (MST) was 9 months and the 5-year survival rate was 3.4%. Patients in group 1 had significantly better survival rates than those in group 2 (MST, 17 v 11 months; 5-year survival rate, 9.1% v 3.7%, respectively; P = .041). Local control was also better in group 1, but the difference was only marginally not significant (P = .062). There was no difference in distant metastasis-free survival between groups 1 and 2. Acute high-grade toxicity was higher in group 2 than in group 1. CONCLUSION: The addition of ACC HFX RT to the treatment of the most favorable subset of patients led to improved survival over that obtained with CHT alone.

Megestrol Acetate for Cachexia and Anorexia in Advanced Non-small Cell Lung Cancer: A Randomized Study Comparing Two Different Doses

2002 ◽  
Vol 88 (4) ◽  
pp. 277-280 ◽  
Author(s):  
H Cüneyt Ulutin ◽  
Fikret Arpaci ◽  
Yücel Pak
Keyword(s):  
Lung Cancer ◽  
Weight Gain ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Megestrol Acetate ◽  
Small Cell Lung ◽  
Group 2 ◽  
Dose Levels ◽  
Group 1

Background The primary aim of the study was to compare two different dose levels of megestrol acetate, administered for cancer-related anorexia and cachexia for 3 months. Methods From August 1996 to December 2000, 119 patients with advanced non-small cell lung cancer were randomized to take 160 mg/day or 320 mg/day of megestrol acetate for 3 months at the Gülhane Military Medicine Academy of Ankara, Turkey. Patients were controlled at biweekly periods. Results There were 59 patients in the single dose arm (group 1) and 60 patients in the twice a day dose arm (group 2). The mean percentages of weight loss were 16.9% and 16.7% in group 1 and 2, respectively. In the first and the second month of weight gain, there were no significant differences in the two groups (P = 0.23 and P = 0.11). In the third month, weight gain was significantly higher in group 2 than in group 1 (P = 0.038). Toxicity was similar for both dose levels. Conclusions Megestrol acetate can be safely and effectively given to patients with advanced non-small cell lung cancer. Although lower doses of megestrol acetate can be effective for anorexia and cachexia, the higher dose level seems to be more efficient.

Comparative proteomic analysis of radiation induced changes in non small cell lung cancer patients with or without radiation induced lung toxicity

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22146-e22146
Author(s):  
X. Cai ◽  
K. Shedden ◽  
X. Ao ◽  
T. S. Lawrence ◽  
D. M. Lubman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Factor H ◽  
Complement Factor ◽  
Small Cell Lung ◽  
Factor I ◽  
Radiation Induced ◽  
Group 2 ◽  
Group 1

e22146 Background: Radiation-induced lung toxicity (RILT) is dose limiting in the treatment of non small cell lung cancer (NSCLC). Early prediction of RILT would allow physicians to individualize treatment. This work aims to study if radiation induces differential changes in plasma proteomics in patients with and without RILT. Methods: 20 Patients with NSCLC in 3 stage- matched groups and treated with radiation therapy (RT) or chemoradiation were included in this analysis: 6 grade 0 (group 0), 8 grade 1 (group 1), and 6 grade ≥ 2 RILT (group 2). Platelet poor plasma was obtained pre-RT, at 2-, 4-, 6-week during-RT, and 1-, 3-month post-RT. The plasma proteomic characterizations from patients with and without RILT were compared using a multiplexed quantitative proteomics approach involving ExacTag labeling, reverse-phase high-performance liquid chromatography (RP-HPLC), and nano-LC electrospray tandem mass spectrometry (LC-ESI-MS/MS). ANOVA model was applied for significance test. Results: 23 common proteins were detected in all 20 patients, 9 of them, Ceruloplasmin, Prothrombin, Complement C3, Beta-2-glycoprotein (β2GP1) 1, Vitronectin, Complement factor I, Complement factor H, Complement C4-A, Complement C7, had significant difference among 3 groups. At baseline (Pre-RT), the levels of Vitronectin and C4-A in group 2 were both significantly higher than that in group 0 (p=0.008 and 0.021, respectively). At 2-week during RT, the levels of Ceruloplasmin, Prothrombin and β2GP1 in group 1 were significantly higher than that in group 0 (p=0.017, 0.011 and 0.013, respectively). At 4-week during RT, the levels of β2GP1 in group 1 and group 2 were significantly higher than that in group 0 (p=0.005 and 0.014). At 6-weeks during RT, Prothrombin, C3, Complement factor H, C7 and Complement factor I also had some significant changes among three groups. Conclusions: Plasma proteins related to inflammation, coagulation and fibrosis, such as β2GP1, change differently during RT in patients with and without RILT. This proteomic approach may identify new markers during treatment to predict RILT for adapting treatment to patient. Fundings: ASCO career developmental award, grant from Pardee foundation, and RTOG translational research program. No significant financial relationships to disclose.

Efficacy of anti-programmed cell death-1/ligand 1 monotherapy for non-small cell lung cancer patients with active brain metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14511-e14511
Author(s):  
Takehiro Tozuka ◽  
Satoru Kitazono ◽  
Hiroaki Sakamoto ◽  
Hiroshi Yoshida ◽  
Yoshiaki Amino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Factors Associated ◽  
Programmed Cell Death 1 ◽  
Significant Factors

e14511 Background: The efficacy of anti-programmed cell death-1/ligand 1 (anti-PD-(L)1) for active brain metastases (BMs) is not established, because most clinical trials excluded patients (pts) with active BMs such as untreated, symptomatic, or unstable BMs. The aim of this study was to evaluate the efficacy of anti-PD-(L)1 monotherapy in non-small cell lung cancer (NSCLC) pts with active BMs. Methods: This retrospective study included NSCLC pts who had received anti-PD-(L)1 monotherapy in 2nd or later line between December 2015 and August 2019. Pts who had not evaluated BMs by CT/MRI before anti-PD-(L)1 were excluded. Pts were classified into those with or without active BMs which were defined as untreated or symptomatic BMs or BMs requiring systemic steroids. Progression free survival (PFS) and overall survival (OS) of pts with or without active BMs were compared. Intra-cranial and extra-cranial tumor responses were evaluated in pts with active BMs. Results: In this study, 242 pts who had received anti-PD-(L)1 monotherapy were identified and 197 pts were analyzed. Twenty-four pts were classified to pts with active BMs. Among pts without active BMs, 145 pts had no BMs and 28 pts had treated asymptomatic BMs. PFS of pts with active BMs was significantly shorter than that of pts without active BMs (1.3 versus 2.7 months; p < 0.001). OS of pts with active BMs was significantly shorter than that of pts without active BMs (4.5 vs 16.3 months; p = 0.001). Intracranial response rate (RR) was 13.3% (2/15) and extracranial RR was 26.7% (4/15) in pts with active BMs. In multivariate Cox regression analysis, active BM, poor PS and EGFR/ALK(+) were selected as significant factors associated with poor PFS. Active BM and poor PS were selected as significant factors associated with poor OS. Conclusions: Anti-PD-(L)1 monotherapy is not recommend for pts with active BMs.

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