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.

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.

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.

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.

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.

scholarly journals Circulating Endothelial-Derived Activated Microparticle: A Useful Biomarker for Predicting One-Year Mortality in Patients with Advanced Non-Small Cell Lung Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Chin-Chou Wang ◽  
Chia-Cheng Tseng ◽  
Chang-Chun Hsiao ◽  
Huang-Chih Chang ◽  
Li-Teh Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Flow Cytometry ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Male Gender ◽  
Small Cell Lung ◽  
Group 2 ◽  
One Year ◽  
Group 1

Background. This study tested the hypothesis that circulating microparticles (MPs) are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC).Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1) platelet-derived activated MPs (PDAc-MPs), (2) platelet-derived apoptotic MPs (PDAp-MPs), (3) endothelial-derived activated MPs (EDAc-MPs), and (4) endothelial-derived apoptotic MPs (EDAp-MPs), were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1(n=56)(one-year survivors) and patients who survived less than one year were categorized into group 2(n=51)(one-year nonsurvivors). Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (allP<0.05). Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1(P=0.006). Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (allP<0.035).Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.

Low level of complement factor H increases the risk of cancer-related death in patients with small-cell lung cancer

2021 ◽  
pp. postgradmedj-2021-141186
Author(s):  
Mengqi Xiang ◽  
Huachuan Zhang ◽  
Lingna Kou ◽  
Jing Chen ◽  
Zhihua Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Factor H ◽  
Complement Factor H ◽  
Prognostic Impact ◽  
Complement Factor ◽  
Small Cell Lung ◽  
Risk Of Death

IntroductionPulmonary cancer is a kind of deeply invasive tumour which is difficult to treat, and its mortality rate is high. Previous research has shown that activation of complement could contribute to the progression of non-small-cell lung cancer (SCLC). However, little research has been done on SCLC.MethodsComplement factor H (CFH), complements C3 as well as C4 were measured in patients, and the prognostic impact of different parameters was assessed by log-rank function analysis and Cox multifactor models. Besides, we constructed a predictive model based on complement fractions and validated the accuracy of the model.ResultsAmong these 242 patients, 200 (82.6%) died. The median survival time was 18.3 months. We found by multifactorial analysis that high levels of CFH decreased the risk of death (HR 0.23, 95% CI 0.10 to 0.57, p<0.001), while elevated complement C4 displayed poor prognosis (HR 2.28, 95% CI 1.66 to 3.13, p<0.001). We screened variables by Cox models and constructed CFH-based prediction models to plot a nomogram by internal validation. The nomogram showed excellent accuracy in assessing the probability of death, yielding an adjusted C-statistics of 0.905.ConclusionsCFH can be recognised as a biomarker to predict the risk of death in SCLC. The prediction model established based on CFH, C3 and C4 levels has good accuracy in patients’ prognostic assessment.

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