scholarly journals Single Nucleotide Polymorphism at rs1982073:T869C of the TGFβ1 Gene Is Associated With the Risk of Radiation Pneumonitis in Patients With Non–Small-Cell Lung Cancer Treated With Definitive Radiotherapy

2009 ◽  
Vol 27 (20) ◽  
pp. 3370-3378 ◽  
Author(s):  
Xianglin Yuan ◽  
Zhongxing Liao ◽  
Zhensheng Liu ◽  
Li-E Wang ◽  
Susan L. Tucker ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lower Risk ◽  
Radiation Pneumonitis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Nucleotide ◽  
Platinum Based Chemotherapy ◽  
Grade 3

Purpose In search of reliable biologic markers to predict the risk of normal tissue damage by radio(chemo)therapy before treatment, we investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor 1 (TGFβ1) gene and risk of radiation pneumonitis (RP) in patients with non–small-cell lung cancer (NSCLC). Patients and Methods Using 164 available genomic DNA samples from patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped three SNPs of the TGFβ1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by polymerase chain reaction restriction fragment length polymorphism method. We used Kaplan-Meier cumulative probability to assess the risk of grade ≥ 3 RP and Cox proportional hazards analyses to evaluate the effect of TGFβ1 genotypes on such risk. Results There were 90 men and 74 women in the study, with median age of 63 years. Radiation doses ranging from 60 to 70 Gy (median = 63 Gy) in 30 to 58 fractions were given to 158 patients (96.3%) and platinum-based chemotherapy to 147 (89.6%). Grade ≥ 2 and grade ≥ 3 RP were observed in 74 (45.1%) and 36 patients (22.0%), respectively. Multivariate analysis found CT/CC genotypes of TGFβ1 rs1982073:T869C to be associated with a statistically significantly lower risk of RP grades ≥ 2 (hazard ratio [HR] = 0.489; 95% CI, 0.227 to 0.861; P = .013) and grades ≥ 3 (HR = 0.390; 95% CI, 0.197 to .774; P = 0.007), respectively, compared with the TT genotype, after adjustment for Karnofsky performance status, smoking status, pulmonary function, and dosimetric parameters. Conclusion Our results showed that CT/CC genotypes of TGFβ1 rs1982073:T869C gene were associated with lower risk of RP in patients with NSCLC treated with definitive radio(chemo)therapy and thus may serve as a reliable predictor of RP.

Radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent radiotherapy and gemcitabine after induction with gemcitabine and carboplatin

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e18504-e18504
Author(s):  
R. M. Michel ◽  
D. Gallardo-Rincon ◽  
C. Villarreal-Garza ◽  
A. Astorga-Ramos ◽  
J. Zamora ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Radiation Pneumonitis ◽  
Locally Advanced ◽  
Disease Patient ◽  
Small Cell ◽  
Small Cell Lung ◽  
Thoracic Radiation ◽  
Grade 3

e18504 Background: The combination of chemotherapy (CT) and thoracic radiation (RT) is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). The most favorable CT regime, timing of full-dose CT and the best way to combine CT with RT to maximize systemic and radiosensitizing effects remain to be determined. The aim of this study was to assess the efficacy, safety and tolerability of gemcitabine concurrent with RT after induction CT (gemcitabine + carboplatin) in locally advanced NSCLC. Methods: Patients with histologically proven NSCLC IIIA and IIIB received carboplatin (AUC of 2.5) and gemcitabine (800 mg/m2) on day 1 and 8, every 21 days (two cycles), followed by conventional fractioned RT (60Gy) with concomitant weekly gemcitabine 200 mg/m2 and by consolidation CT. Survival was analyzed with Kaplan-Meier. Results: Median follow-up was of 11.9 months, 11 patients (57.9%) had stage IIIB disease. Patient inclusion was discontinued due to high grade 3/4 radiation pneumonitis events (5/19 patients, 26.3%). One treatment-related death from radiation pneumonitis occurred. The most common hematological side effects grade 3/4 were anemia and neutropenia 3/19 (15.8%) each and thrombocytopenia 4/19 (21.1%) during induction CT. Partial response was observed in 11 patients (57.9%) following induction. After concurrent chemo-radiotherapy, overall response was 68.4%. Four patients underwent surgical resection. Median progression-free survival was 12 ± 1 months (95% CI, 9.8 -14.1). Overall survival was of 21 ± 3.5 months (95% CI, 14–27.9). Conclusions: Concurrent RT with gemcitabine after induction CT with gemcitabine and carboplatin showed a high response rate. However, it is associated with excessive pulmonary toxicity. Adjustments in gemcitabine dosage during RT or changes in RT planning could reduce toxicity. No significant financial relationships to disclose.

scholarly journals The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19059-e19059
Author(s):  
Zhou Fei
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
P Value ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy ◽  
Cox 2 ◽  
Grade 3

e19059 Background: Overexpression of COX-2 is thought to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis, and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers of survival and toxicity outcomes for platinum treatment. This study aimed to investigate the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non–small cell lung cancer patients treated with platinum-based chemotherapy. Methods: Two hundred and twelve patients with inoperable stage IIIB-IV receiving first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP) methods. Results: The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 −1195G/A (rs689466) polymorphism compared to wild-type homozygotes AA (P value = 0.013; odds ratio, 2.30; 95% confidence internal, 1.20-4.42) and still significant after a Bonferroni correction. More statistically significant difference was found in grade 3 or 4 leukocytopenia (P value = 0.010; OR=2.28; 95%CI=1.28-6.05). No other significant association between genotype and toxicity was observed in the study. The haplotype analysis showed the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic toxicity (P value= 0.015; OR= 0.61; 95%CI =0.41-0.91) while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic toxicity (P value=0.008; OR=1.71; 95%CI=1.15-2.54), global X2= 6.9825, df =2, P = 0.030. Conclusions: This investigation, for the first time, suggests that polymorphism in COX-2 −1195G/A may be a useful bio-marker to predict severe hematologic toxicity in NSCLC patients after platinum-based chemotherapy.

Prognostic value of the TGFβ1 rs4803455 single nucleotide polymorphism in small cell lung cancer

2020 ◽  
pp. 030089162094684 ◽  
Author(s):  
Pablo Ayala de Miguel ◽  
María Valle Enguix-Riego ◽  
Jon Cacicedo ◽  
Blas David Delgado ◽  
Marco Perez ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Transforming Growth Factor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Nucleotide ◽  
Potential Biomarker ◽  
Platinum Based Chemotherapy ◽  
Thoracic Radiation

Background: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein β1 (HSPB1) and transforming growth factor β1 (TGFβ1) and survival have been investigated. Methods: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFβ1 gene and 5 of HSPB1 gene) variables were analyzed. Results: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFβ1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19–8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37–10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98–3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS ( p < 0.001) and DFS ( p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. Conclusions: Genetic analysis showed the CA genotype of TGFβ1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.

scholarly journals Study of The Predictors for Radiation Pneumonitis in Patient With Non-Small Cell Lung Cancer Received Radiotherapy After Pneumonectomy

2020 ◽  
Author(s):  
Jia-Hua Yu ◽  
Chang-Lu Wang ◽  
Yuan Liu ◽  
Jia-Ming Wang ◽  
Chang Xing Lv ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Radiation Pneumonitis ◽  
Descriptive Analysis ◽  
Univariate Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cutoff Values ◽  
Grade 3

Abstract Background: To identify the valuable predictors of grade≥2 radiation pneumonitis (RP) in patient treated with radiotherapy after pneumonectomy for non-small cell lung cancer (NSCLC); and to construct a nomogram predicting the incidence of grade≥2 RP in such patients.Methods: We reviewed 74 patients with NSCLC received radiotherapy after pneumonectomy from 2008 to 2018. The endpoint was grade≥2 RP. Univariate and multivariate regression analysis were conducted to evaluate significant factors of grade ≥2 RP. Receiver operating characteristic (ROC) curve was used to establish optimal cutoff values and the nomogram was built to make the predictive model visualized. Descriptive analysis was performed on 5 patients with grade 3 RP. Results: A total of 25(33.8%) patients developed grade≥2 RP and 5(6.8%) patients were grade 3 RP. V5, V10, V20, V30, MLD, PTV, and PTV/TLV were associated with the occurrence of grade≥2 RP in univariate analysis, while none of the clinical factors was significant; V5(OR,1.195;95%CI,1.082-1.319; P<0.001) and V20(OR,1.412;95%CI,1.161-1.717; P=0.001) were the independent significant predictors by multivariate analysis and were included in the nomogram. The ROC analysis for the cutoff values for predicting grade≥2 RP were V5>22%(AUC=0.816, sensitivity:0.712, specificity:0.837) and V20>8%(AUC=0.822, sensitivity:0.681, specificity:0.828). Additionally, grade≥3 RP did not occur when V5<30%, V20<13% and MLD<751.2cGy, respectively.Conclusions: Our study showed that V5 and V20 were independent predictors for grade≥2 RP in NSCLC patients receiving radiotherapy after pneumonectomy. Grade 3 RP did not occur whenV5<30%, V20<13% and MLD<751.2cGy, respectively. In addition, patient underwent right pneumonectomy may have a lower tolerance to radiation compared to left pneumonectomy.

scholarly journals Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Katrina Kildey ◽  
Neha S. Gandhi ◽  
Katherine B. Sahin ◽  
Esha T. Shah ◽  
Eric Boittier ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genome Instability ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Levels ◽  
Platinum Based Chemotherapy ◽  
Platinum Agents

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.

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