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Qingsong Pang,
Qingyi Wei,
Ting Xu,
Xianglin Yuan,
Jose Luis Lopez Guerra,
Lawrence B Levy,
Zhensheng Liu,
Daniel R Gomez, Yan Zhuang,
Li-E Wang,
Radhe Mohan,
Ritsuko Komaki,
Zhongxing Liao
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ABSTRACT: PURPOSE: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. RESULTS: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. CONCLUSIONS: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.
International journal of radiation oncology, biology, physics 01/2013; · 4.59 Impact Factor
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ABSTRACT: PURPOSE: We investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor β1 (TGFβ1) gene and the risk of radiation-induced esophageal toxicity (RE) in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Ninety-seven NSCLC patients with available genomic DNA samples and mostly treated with intensity modulated radio(chemo)therapy from 2003 to 2006 were used as a test dataset and 101 NSCLC patients treated with 3-dimensional conformal radio(chemo)therapy from 1998 to 2002 were used as a validation set. We genotyped three SNPs of the TGFβ1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: In the test dataset, the CT/TT genotypes of TGFβ1 rs1800469:C-509T were associated with a statistically significant higher risk of RE grade⩾3 in univariate (P=0.026) and multivariate analysis (P=0.045) when compared with the CC genotype. These results were again observed in both univariate (P=0.045) and multivariate (P=0.023) analysis in the validation dataset. CONCLUSION: We found and validated that the TGFβ1 rs1800469:C-509T genotype is associated with severe RE. This response marker may be used for guiding therapy intensity in an individual patient, which would further the goal of individualized therapy.
Radiotherapy and Oncology 09/2012; · 5.58 Impact Factor
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ABSTRACT: Scoring of radiation pneumonitis (RP), a dose-limiting toxicity after thoracic radiochemotherapy, is subjective and thus inconsistent among studies. Here we investigated whether the extent of change in diffusing capacity of the lung for carbon monoxide (DLCO) after radiation therapy (RT) for non-small-cell lung cancer (NSCLC) could be used as an objective means of quantifying RP.
We analyzed potential correlations between DLCO and RP in 140 patients who received definitive RT (≥ 60 Gy) with or without chemotherapy for primary NSCLC. All underwent DLCO analysis before and after RT. Post-RT DLCO values within 1 week of the RP diagnosis (Grade 0, 1, 2, or 3) were selected and compared with that individual's preradiation values. Percent reductions in DLCO and RP grade were compared by point biserial correlation in the entire patient group and in subgroups stratified according to various clinical factors.
Patients experiencing Grade 0, 1, 2, or 3 RP had median percentage changes in DLCO after RT of 10.7%, 13%, 22.1%, or 35.2%. Percent reduction in DLCO correlated with RP Grade ≤ 1 vs. ≥ 2 (p = 0.0004). This association held for the following subgroups: age ≥ 65 years, advanced stage, smokers, use of chemotherapy, volume of normal lung receiving at least 20 Gy ≥ 30%, and baseline DLCO or forced expiratory volume in 1 second ≥ 60%.
By correlating percent change in DLCO from pretreatment values at the time of diagnosis of RP with RP grade, we were able to identify categories of RP based on the change in DLCO. These criteria provide a basis for an objective scoring system for RP based on change in DLCO.
International journal of radiation oncology, biology, physics 08/2012; 83(5):1573-9. · 4.59 Impact Factor
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Ting Xu,
Qingyi Wei,
Jose Luis Lopez Guerra,
Li-E Wang,
Zhensheng Liu,
Daniel Gomez,
Michael O'Reilly,
Steven Hsesheng Lin, Yan Zhuang,
Lawrence B Levy,
Radhe Mohan,
Honghao Zhou,
Zhongxing Liao
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ABSTRACT: We investigated potential associations between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall survival in US patients with non-small cell lung cancer (NSCLC).
Using available genomic DNA samples from 224 patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative probability and Cox proportional hazards analyses to evaluate the effect of HSPB1 genotypes on survival.
Our cohort consisted of 117 men and 107 women, mostly white (79.5%), with a median age of 70 years. The median radiation dose was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC (61%). Univariate and multivariate analyses showed that this genotype was associated with poorer survival than CG and GG genotypes (univariate hazard ratio [HR] = 1.39, 95% confidence interval [CI], 1.02-1.90; P=.037; multivariate HR = 1.39; 95% CI, 1.01-1.92; P=.045).
Our results showed that the CC genotype of HSPB1 rs2868371 was associated with poorer overall survival in patients with NSCLC after radio(chemo)therapy, findings that contradict those of a previous study of Chinese patients. Validation of our findings with larger numbers of similar patients is needed, as are mechanical and clinical studies to determine the mechanism underlying these associations.
International journal of radiation oncology, biology, physics 05/2012; 84(2):e229-35. · 4.59 Impact Factor
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ABSTRACT: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis.
From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy (≥45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses.
Univariate Cox proportional hazard analysis revealed better overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume ≤124 cm³ (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately.
Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.
International journal of radiation oncology, biology, physics 04/2012; 84(1):e61-7. · 4.59 Impact Factor
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ABSTRACT: To investigate the extent of change in pulmonary function over time after definitive radiotherapy for non-small-cell lung cancer (NSCLC) with modern techniques and to identify predictors of changes in pulmonary function according to patient, tumor, and treatment characteristics.
We analyzed 250 patients who had received ≥ 60 Gy radio(chemo)therapy for primary NSCLC in 1998-2010 and had undergone pulmonary function tests before and within 1 year after treatment. Ninety-three patients were treated with three-dimensional conformal radiotherapy, 97 with intensity-modulated radiotherapy, and 60 with proton beam therapy. Postradiation pulmonary function test values were evaluated among individual patients compared with the same patient's preradiation value at the following time intervals: 0-4 (T1), 5-8 (T2), and 9-12 (T3) months.
Lung diffusing capacity for carbon monoxide (DLCO) was reduced in the majority of patients along the three time periods after radiation, whereas the forced expiratory volume in 1 s per unit of vital capacity (FEV1/VC) showed an increase and decrease after radiation in a similar percentage of patients. There were baseline differences (stage, radiotherapy dose, concurrent chemotherapy) among the radiation technology groups. On multivariate analysis, the following features were associated with larger posttreatment declines in DLCO: pretreatment DLCO, gross tumor volume, lung and heart dosimetric data, and total radiation dose. Only pretreatment DLCO was associated with larger posttreatment declines in FEV1/VC.
Lung diffusing capacity for carbon monoxide is reduced in the majority of patients after radiotherapy with modern techniques. Multiple factors, including gross tumor volume, preradiation lung function, and dosimetric parameters, are associated with the DLCO decline. Prospective studies are needed to better understand whether new radiation technology, such as proton beam therapy or intensity-modulated radiotherapy, may decrease the pulmonary impairment through greater lung sparing.
International journal of radiation oncology, biology, physics 03/2012; 83(4):e537-43. · 4.59 Impact Factor
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Zhi-Qin Jiang,
Kunyu Yang,
Ritsuko Komaki,
Xiong Wei,
Susan L Tucker, Yan Zhuang,
Mary K Martel,
Sastray Vedam,
Peter Balter,
Guangying Zhu,
Daniel Gomez,
Charles Lu,
Radhe Mohan,
James D Cox,
Zhongxing Liao
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ABSTRACT: In 2007, we published our initial experience in treating inoperable non-small-cell lung cancer (NSCLC) with intensity-modulated radiation therapy (IMRT). The current report is an update of that experience with long-term follow-up.
Patients in this retrospective review were 165 patients who began definitive radiotherapy, with or without chemotherapy, for newly diagnosed, pathologically confirmed NSCLC to a dose of ≥60 Gy from 2005 to 2006. Early and late toxicities assessed included treatment-related pneumonitis (TRP), pulmonary fibrosis, esophagitis, and esophageal stricture, scored mainly according to the Common Terminology Criteria for Adverse Events 3.0. Other variables monitored were radiation-associated dermatitis and changes in body weight and Karnofsky performance status. The Kaplan-Meier method was used to compute survival and freedom from radiation-related acute and late toxicities as a function of time.
Most patients (89%) had Stage III to IV disease. The median radiation dose was 66 Gy given in 33 fractions (range, 60-76 Gy, 1.8-2.3 Gy per fraction). Median overall survival time was 1.8 years; the 2-year and 3-year overall survival rates were 46% and 30%. Rates of Grade ≥3 maximum TRP (TRP(max)) were 11% at 6 months and 14% at 12 months. At 18 months, 86% of patients had developed Grade ≥1 maximum pulmonary fibrosis (pulmonary fibrosis(max)) and 7% Grade ≥2 pulmonary fibrosis(max). The median times to maximum esophagitis (esophagitis(max)) were 3 weeks (range, 1-13 weeks) for Grade 2 and 6 weeks (range, 3-13 weeks) for Grade 3. A higher percentage of patients who experienced Grade 3 esophagitis(max) later developed Grade 2 to 3 esophageal stricture.
In our experience, using IMRT to treat NSCLC leads to low rates of pulmonary and esophageal toxicity, and favorable clinical outcomes in terms of survival.
International journal of radiation oncology, biology, physics 11/2011; 83(1):332-9. · 4.59 Impact Factor
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Jose Luis Lopez Guerra,
Qingyi Wei,
Xianglin Yuan,
Daniel Gomez,
Zhensheng Liu, Yan Zhuang,
Ming Yin,
Minghuan Li,
Li-E Wang,
James D Cox,
Zhongxing Liao
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ABSTRACT: We investigated the association between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and the risk of radiation-induced esophageal toxicity (RIET) in patients with non-small-cell lung cancer (NSCLC).
The experimental dataset comprised 120 NSCLC patients who were treated with radio(chemo)therapy between 2005 and 2009, when novel radiation techniques were implemented at MD Anderson. The validation dataset comprised 181 NSCLC patients treated between 1998 and 2004. We genotyped two SNPs of the HSPB1 gene (rs2868370 and rs2868371) by TaqMan assay.
Univariate and multivariate analyses of the experimental dataset showed that the CG/GG genotypes of HSPB1 rs2868371 were associated with significantly lower risk of grade ⩾3 RIET than the CC genotype (univariate hazard ratio [HR] 0.30; 95% confidence interval [CI], 0.10-0.91; P=0.033; multivariate HR 0.29; 95% CI, 0.09-0.97; P=0.045). This difference in risk was replicated in the validation cohort despite the different radiation techniques used during that period.
The CG/GG genotypes of HSPB1 rs2868371 were associated with lower risk of RIET, compared with the CC genotype in patients with NSCLC treated with radio(chemo)therapy. This finding should be validated in large multi-institutional prospective trials.
Radiotherapy and Oncology 09/2011; 101(2):271-7. · 5.58 Impact Factor
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ABSTRACT: The purpose of this study is to assess predictive value of the positron emission tomography (PET) with 18F-fluoro-deoxyglucose (FDG) for recurrence and survival after radiotherapy (RT) for non-small cell lung cancer (NSCLC). One hundred forty-nine patients underwent pretreatment PET (n = 67) or PET/computed tomography (CT) (n = 82) and definitive RT for NSCLC. We evaluated the relationship between the maximum-pixel standardized uptake value (SUV(max)) and clinical tumor features. Univariate Cox proportional hazard analysis (UVA) was used to quantify the risk for local-regional recurrence, distant metastases, and death. Multivariate Cox proportional hazard analysis (MVA) was used to assess the potential independent effect of SUV(max). In the PET group, T1 tumors showed significantly lower SUV(max) than T2, T3, and T4 tumors; in the PET/CT group, T1 tumors showed significantly lower SUV(max) than T3 and T4 tumors. A high SUV(max )was a negative factor for local-regional control (LRC) (p < 0.001), distant metastasis-free survival (DMFS) (p = 0.02), and overall survival (OS) (p = 0.001) on UVA in the PET group. However, the significance decreased to 0.05 for LRC, 0.04 for DMFS, and 0.04 for OS by MVA when tumor size was included in the analysis. A high SUV(max) was not a negative factor for LRC, DMFS, or OS on UVA and MVA in the PET/CT group. In conclusion, assessment of predictive value of SUV(max) for NSCLC requires consideration of primary tumor size, and the evidence is not sufficient to suggest that FDG uptake in a primary NSCLC provides prognostic information.
Journal of Radiation Research 01/2010; 51(4):465-71. · 1.68 Impact Factor
