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Fengming Spring Kong - One of the best experts on this subject based on the ideXlab platform.
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plasma levels of il 8 and tgf β1 predict radiation induced Lung Toxicity in non small cell Lung cancer a validation study
International Journal of Radiation Oncology Biology Physics, 2017Co-Authors: S Wang, Fengming Spring Kong, Randall Ten K Haken, M M Matuszak, Matthew H Stenmark, Jeff Campbell, Jing Zhao, Paul E StantonAbstract:Purpose and Objectives We previously reported that the combination of mean Lung dose (MLD) and inflammatory cytokines interleukin-8 (IL-8) and transforming growth factor-β1 (TGF-β1) may provide a more accurate model for radiation-induced Lung Toxicity (RILT) prediction in 58 patients with non-small cell Lung cancer (NSCLC). This study is to validate the previous findings with new patients and to explore new models with more cytokines. Methods and Materials One hundred forty-two patients with stage I-III NSCLC treated with definitive radiation therapy (RT) from prospective studies were included. Sixty-five new patients were used to validate previous findings, and all 142 patients were used to explore new models. Thirty inflammatory cytokines were measured in plasma samples before RT and 2 weeks and 4 weeks during RT (pre, 2w, 4w). Grade ≥2 RILT was defined as grade 2, and higher radiation pneumonitis or symptomatic pulmonary fibrosis was the primary endpoint. Logistic regression was performed to evaluate the risk factors of RILT. The area under the curve (AUC) for the receiver operating characteristic curves was used for model assessment. Results Sixteen of 65 patients (24.6%) experienced RILT2. Lower pre IL-8 and higher TGF-β1 2w/pre ratio were associated with higher risk of RILT2. The AUC increased to 0.73 by combining MLD, pre IL-8, and TGF-β1 2w/pre ratio compared with 0.61 by MLD alone to predict RILT. In all 142 patients, 29 patients (20.4%) experienced grade ≥2 RILT. Among the 30 cytokines measured, only IL-8 and TGF-β1 were significantly associated with the risk of RILT2. MLD, pre IL-8 level, and TGF-β1 2w/pre ratio were included in the final predictive model. The AUC increased to 0.76 by combining MLD, pre IL-8, and TGF-β1 2w/pre ratio compared with 0.62 by MLD alone. Conclusions We validated that a combination of mean Lung dose, pre IL-8 level, and TGF-β1 2w/pre ratio provided a more accurate model to predict the risk of RILT2 compared with MLD alone.
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nondosimetric risk factors for radiation induced Lung Toxicity
Seminars in Radiation Oncology, 2015Co-Authors: Fengming Spring Kong, Shulian WangAbstract:The decision to administer a radical course of radiotherapy (RT) is largely influenced by the dose-volume metrics of the treatment plan, but what are the patient-related and other factors that may independently increase the risk of radiation Lung Toxicity? Poor pulmonary function has been regarded as a risk factor and a relative contraindication for patients undergoing radical RT, but recent evidence suggests that patients with poor spirometry results may tolerate conventional or high-dose RT as well as, if not better than, patients with normal function. However, caution may need to be exercised in patients with underlying interstitial pulmonary fibrosis. Furthermore, there is emerging evidence of molecular markers of increased risk of Toxicity. This review discusses patient-related risk factors other than dosimetry for radiation Lung Toxicity.
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combining physical and biologic parameters to predict radiation induced Lung Toxicity in patients with non small cell Lung cancer treated with definitive radiation therapy
International Journal of Radiation Oncology Biology Physics, 2012Co-Authors: Matthew H Stenmark, James A Hayman, Theodore S Lawrence, Shuanghu Yuan, Randall Ten K Haken, Xuwei Cai, Kerby Shedden, Timothy Ritter, Fengming Spring KongAbstract:Purpose To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1β), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) to ascertain their value in predicting radiation-induced Lung Toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III Lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-s1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-s1, and mean Lung dose into a single model yielded an improved predictive ability ( P Conclusions Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.
Feng Ming Kong - One of the best experts on this subject based on the ideXlab platform.
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elevation of plasma tgf β1 during radiation therapy predicts radiation induced Lung Toxicity in patients with non small cell Lung cancer a combined analysis from beijing and michigan
International Journal of Radiation Oncology Biology Physics, 2009Co-Authors: Lujun Zhao, James A Hayman, Gregory P Kalemkerian, Theodore S Lawrence, Luhua Wang, Xiaozhen Wang, Xiangzhi Zhu, Weizhi Yang, Dean E Brenner, Feng Ming KongAbstract:Purpose To test whether radiation-induced elevations of transforming growth factor-β1 (TGF-β1) during radiation therapy (RT) correlate with radiation-induced Lung Toxicity (RILT) in patients with non-small-cell Lung cancer (NSCLC) and to evaluate the ability of mean Lung dose (MLD) to improve the predictive power. Methods and Materials Eligible patients included those with Stage I–III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4–5 weeks (40–50 Gy) during RT. TGF-β1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was ≥ Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. Results A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-β1 ratio > 1 vs. 7.9% in patients with a TGF-β1 ratio ≤ 1 ( p 20 Gy vs. 17.4% if MLD ≤ 20 Gy ( p = 0.024). The incidence was 4.3% in patients with a TGF-β1 ratio ≤ 1 and MLD ≤ 20 Gy, 47.4% in those with a TGF-β1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-β1 ratio >1 and MLD > 20 Gy ( p Conclusions Radiation-induced elevation of plasma TGF-β1 level during RT is predictive of RILT. The combination of TGF- β1 and MLD may help stratify the patients for their risk of RILT.
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the use of blood biomarkers to predict radiation Lung Toxicity a potential strategy to individualize thoracic radiation therapy
Cancer Control, 2008Co-Authors: Feng Ming Kong, Li Wang, Theodore S LawrenceAbstract:BackgroundRadiation-induced Lung Toxicity (RILT) is an important dose-limiting Toxicity during thoracic radiotherapy. Early prediction of radiation Lung Toxicity will allow physicians to determine ...
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final Toxicity results of a radiation dose escalation study in patients with non small cell Lung cancer nsclc predictors for radiation pneumonitis and fibrosis
International Journal of Radiation Oncology Biology Physics, 2006Co-Authors: Feng Ming Kong, James A Hayman, Kent A Griffith, Gregory P Kalemkerian, Douglas A Arenberg, Susan E Lyons, Andrew T Turrisi, Allen S Lichter, Benedick A FraassAbstract:Purpose: We aimed to report the final Toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non–small-cell Lung cancer (NSCLC) by quantifying the dose–volume Toxicity relationship of the Lung. Methods and Materials: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-Lung Toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. Results: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 Lung Toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly ( p Conclusions: With long-term follow-up for Toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative Lung dose–volume Toxicity–based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients.
Roger W Byhardt - One of the best experts on this subject based on the ideXlab platform.
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acute esophagitis and late Lung Toxicity in concurrent chemoradiotherapy trials in patients with locally advanced non small cell Lung cancer analysis of the radiation therapy oncology group rtog database
Clinical Lung Cancer, 2011Co-Authors: Maria Wernerwasik, Rebecca Paulus, Walter J Curran, Roger W ByhardtAbstract:Abstract Background We analyzed time course and factors associated with acute esophagitis (ES) and late Lung Toxicity (PN), as well as any association between ES and PN in patients (pts) with non–small-cell Lung cancer (NSCLC) treated with concurrent chemoradiation (chemo-RT) on the Radiation Therapy Oncology Group (RTOG) trials. Materials and Methods Multivariable analysis was used to investigate factors associated with ES or PN. Results Patients (n = 528) received standard fractionated (SFX; 63 Gy) or hyperfractionated (HFX; 69.6 Gy) radiation therapy (RT) with cisplatin-based chemotherapy. Grade > 2 ES developed in 75% of pts; Grade > 3 ES, in 34%. Nineteen percent of pts developed ES by the first, 32% by the second, and 33% by the third month (and for Grade > 3 PN, 9% by 6 months, 15% by year 1, and 18% by year 2). Any PN developed in 59% of pts; Grade > 2, in 39%; Grade > 3, in 18%; and lethal PN, in 2%. Grade > 2 PN was associated with increasing RT dose and Grade > 3 PN, with HFX RT. No association was seen with ES. Grade > 3 ES was less likely to occur in non-whites and more likely, in pts treated with HFX RT. Conclusion Most (95%) pts developed ES, and 33% had severe ES, peaking within the first or second month of RT. PN developed in 57% of pts, with 18% experiencing Grade > 3 PN, with most diagnosed by 1 year from RT. No relationship was observed between 1 Toxicity (ES or PN) as predictor of the other. HFX RT was associated with more severe PN or ES.
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the influence of field size and other treatment factors on pulmonary Toxicity following hyperfractionated irradiation for inoperable non small cell Lung cancer nsclc analysis of a radiation therapy oncology group rtog protocol
International Journal of Radiation Oncology Biology Physics, 1993Co-Authors: Roger W Byhardt, Linda Martin, Thomas F Pajak, Kyu H Shin, Bahman Emami, James D CoxAbstract:Abstract Purpose : The risk of pulmonary Toxicity, observed in an Radiation Therapy Oncology Group Phase I/II randomized dose escalation trial of hyperfractioned irradiation for nonsmall cell Lung cancer, was analyzed with regard to custom vs.hand blocking and compliance to protocol specified treatment field parameters. Materials and Methods : There were 832 evaluable cases analyzed. The protocol required field margins 2 cm beyond primary tumor and involved nodes. In 674, the field margins were considered “per protocol” or as having minor protocol variations. In 94, margins exceeded protocol specification (“excessive margin” group). In this group, the area (cm2) of the effective (blocked) field and the portion including Lung was measured from simulator films with a computer scanning device. Based on size and location of the primary and nodal disease, “per protocol” fields were constructed and the area (cm2) of Lung included beyond these margins was estimated. Patients from both groups who received less than 30 Gy to normal Lung were excluded from analysis of pulmonary Toxicity. Results : Grade 1 acute Lung Toxicity was higher (p = .009) in the “excessive margin” group compared to the “per protocol” group, whereas late Lung Toxicity was not significantly different (p = .94). The risk of Grade 2 or greater acute Toxicity increased as area of excess irradiated Lung increased. Overall Lung Toxicity, defined as the greater of either acute or late Toxicity, was evaluated by multivariate analysis, in relation to assigned dose, effective treated field area, and type of shielding. Overall maximum Lung Toxicity (≥ Grade 2) was significantly greater in the “excessive margin” group, when Lung treated beyond protocol margins exceeded an area of 35 cm2, than in the “per protocol” group, but only when the effective treated field size was ≥ 180 cm2 (68% vs. 37%; p = .02). This effect was independent of assigned total dose or type of shielding. Conclusion : For nonsmall cell Lung cancer treated with hyperfractionated irradiation, the risk of overall pulmonary Toxicity was increased for patients treated with field sizes in excess of protocol specified margins of tumor coverage in comparison to patients treated with protocol specified margins. This effect was seen only when the area of Lung treated beyond protocol margins exceeded 35 cm2 and when the overall field size was below 180 cm2.
James A Hayman - One of the best experts on this subject based on the ideXlab platform.
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radiation induced Lung Toxicity in non small cell Lung cancer understanding the interactions of clinical factors and cytokines with the dose Toxicity relationship
PMC, 2017Co-Authors: Peter G Hawkins, James A Hayman, Gregory P Kalemkerian, Paul Stanton, Randall Ten K Haken, Philip S Boonstra, S Hobson, Jason W D Hearn, M M Matuszak, Nithya RamnathAbstract:Abstract Background and purpose Current methods to estimate risk of radiation-induced Lung Toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean Lung dose (MLD) on RILT. Materials and methods Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4 weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. Results In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were −28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to −27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. Conclusions Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced Toxicity.
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combining physical and biologic parameters to predict radiation induced Lung Toxicity in patients with non small cell Lung cancer treated with definitive radiation therapy
International Journal of Radiation Oncology Biology Physics, 2012Co-Authors: Matthew H Stenmark, James A Hayman, Theodore S Lawrence, Shuanghu Yuan, Randall Ten K Haken, Xuwei Cai, Kerby Shedden, Timothy Ritter, Fengming Spring KongAbstract:Purpose To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1β), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) to ascertain their value in predicting radiation-induced Lung Toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III Lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-s1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-s1, and mean Lung dose into a single model yielded an improved predictive ability ( P Conclusions Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.
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elevation of plasma tgf β1 during radiation therapy predicts radiation induced Lung Toxicity in patients with non small cell Lung cancer a combined analysis from beijing and michigan
International Journal of Radiation Oncology Biology Physics, 2009Co-Authors: Lujun Zhao, James A Hayman, Gregory P Kalemkerian, Theodore S Lawrence, Luhua Wang, Xiaozhen Wang, Xiangzhi Zhu, Weizhi Yang, Dean E Brenner, Feng Ming KongAbstract:Purpose To test whether radiation-induced elevations of transforming growth factor-β1 (TGF-β1) during radiation therapy (RT) correlate with radiation-induced Lung Toxicity (RILT) in patients with non-small-cell Lung cancer (NSCLC) and to evaluate the ability of mean Lung dose (MLD) to improve the predictive power. Methods and Materials Eligible patients included those with Stage I–III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4–5 weeks (40–50 Gy) during RT. TGF-β1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was ≥ Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. Results A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-β1 ratio > 1 vs. 7.9% in patients with a TGF-β1 ratio ≤ 1 ( p 20 Gy vs. 17.4% if MLD ≤ 20 Gy ( p = 0.024). The incidence was 4.3% in patients with a TGF-β1 ratio ≤ 1 and MLD ≤ 20 Gy, 47.4% in those with a TGF-β1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-β1 ratio >1 and MLD > 20 Gy ( p Conclusions Radiation-induced elevation of plasma TGF-β1 level during RT is predictive of RILT. The combination of TGF- β1 and MLD may help stratify the patients for their risk of RILT.
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the predictive role of plasma tgf β1 during radiation therapy for radiation induced Lung Toxicity deserves further study in patients with non small cell Lung cancer
Lung Cancer, 2008Co-Authors: Lujun Zhao, James A Hayman, Gregory P Kalemkerian, Douglas A Arenberg, Susan E Lyons, Kerby Sheldon, Ming Chen, Moli S Yin, Jeffrey L Curtis, Mary A DavisAbstract:Summary Background This study aimed to further investigate the role of circulating TGF-β1 during radiation therapy (RT) in predicting radiation-induced Lung Toxicity (RILT). Methods and materials Patients with stages I–III non-small cell Lung cancer treated with RT based therapy were included in this study. Platelet poor plasma was obtained pre-RT, at 2 and 4 weeks during-RT, and at the end of RT. TGF-β1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint for RILT was ≥grade 2 radiation pneumonitis or fibrosis. Results Twenty-six patients with a minimum follow-up of 12 months were included. Six patients (23.1%) experienced ≥grade 2 RILT. There was no significant difference in absolute TGF-β1 levels pre-RT, at 2 and 4 weeks during-RT, or at the end of RT between patients with and without RILT. The TGF-β1 ratios (over the pre-RT levels) for patients with and without RILT at 2, 4 weeks during-, and the end of RT were 2.8 ± 2.2 and 1.0 ± 0.6 ( P = 0.123), 2.3 ± 1.3 and 0.8 ± 0.5 ( P = 0.001), 1.5 ± 0.9 and 0.8 ± 0.5 ( P = 0.098), respectively. Using 2.0 as a cut-off, the TGF-β1 ratio at 4 weeks during-RT predicted RILT with a sensitivity and specificity of 66.7% and 95.0%, respectively. Conclusion Elevation of plasma TGF-β1 level 4 weeks during-RT is significantly predictive of RILT. The role of plasma TGF-β1 in predicting RILT deserves further study.
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final Toxicity results of a radiation dose escalation study in patients with non small cell Lung cancer nsclc predictors for radiation pneumonitis and fibrosis
International Journal of Radiation Oncology Biology Physics, 2006Co-Authors: Feng Ming Kong, James A Hayman, Kent A Griffith, Gregory P Kalemkerian, Douglas A Arenberg, Susan E Lyons, Andrew T Turrisi, Allen S Lichter, Benedick A FraassAbstract:Purpose: We aimed to report the final Toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non–small-cell Lung cancer (NSCLC) by quantifying the dose–volume Toxicity relationship of the Lung. Methods and Materials: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-Lung Toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. Results: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 Lung Toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly ( p Conclusions: With long-term follow-up for Toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative Lung dose–volume Toxicity–based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients.
Gregory P Kalemkerian - One of the best experts on this subject based on the ideXlab platform.
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radiation induced Lung Toxicity in non small cell Lung cancer understanding the interactions of clinical factors and cytokines with the dose Toxicity relationship
PMC, 2017Co-Authors: Peter G Hawkins, James A Hayman, Gregory P Kalemkerian, Paul Stanton, Randall Ten K Haken, Philip S Boonstra, S Hobson, Jason W D Hearn, M M Matuszak, Nithya RamnathAbstract:Abstract Background and purpose Current methods to estimate risk of radiation-induced Lung Toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean Lung dose (MLD) on RILT. Materials and methods Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4 weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. Results In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were −28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to −27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. Conclusions Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced Toxicity.
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elevation of plasma tgf β1 during radiation therapy predicts radiation induced Lung Toxicity in patients with non small cell Lung cancer a combined analysis from beijing and michigan
International Journal of Radiation Oncology Biology Physics, 2009Co-Authors: Lujun Zhao, James A Hayman, Gregory P Kalemkerian, Theodore S Lawrence, Luhua Wang, Xiaozhen Wang, Xiangzhi Zhu, Weizhi Yang, Dean E Brenner, Feng Ming KongAbstract:Purpose To test whether radiation-induced elevations of transforming growth factor-β1 (TGF-β1) during radiation therapy (RT) correlate with radiation-induced Lung Toxicity (RILT) in patients with non-small-cell Lung cancer (NSCLC) and to evaluate the ability of mean Lung dose (MLD) to improve the predictive power. Methods and Materials Eligible patients included those with Stage I–III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4–5 weeks (40–50 Gy) during RT. TGF-β1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was ≥ Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. Results A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-β1 ratio > 1 vs. 7.9% in patients with a TGF-β1 ratio ≤ 1 ( p 20 Gy vs. 17.4% if MLD ≤ 20 Gy ( p = 0.024). The incidence was 4.3% in patients with a TGF-β1 ratio ≤ 1 and MLD ≤ 20 Gy, 47.4% in those with a TGF-β1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-β1 ratio >1 and MLD > 20 Gy ( p Conclusions Radiation-induced elevation of plasma TGF-β1 level during RT is predictive of RILT. The combination of TGF- β1 and MLD may help stratify the patients for their risk of RILT.
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the predictive role of plasma tgf β1 during radiation therapy for radiation induced Lung Toxicity deserves further study in patients with non small cell Lung cancer
Lung Cancer, 2008Co-Authors: Lujun Zhao, James A Hayman, Gregory P Kalemkerian, Douglas A Arenberg, Susan E Lyons, Kerby Sheldon, Ming Chen, Moli S Yin, Jeffrey L Curtis, Mary A DavisAbstract:Summary Background This study aimed to further investigate the role of circulating TGF-β1 during radiation therapy (RT) in predicting radiation-induced Lung Toxicity (RILT). Methods and materials Patients with stages I–III non-small cell Lung cancer treated with RT based therapy were included in this study. Platelet poor plasma was obtained pre-RT, at 2 and 4 weeks during-RT, and at the end of RT. TGF-β1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint for RILT was ≥grade 2 radiation pneumonitis or fibrosis. Results Twenty-six patients with a minimum follow-up of 12 months were included. Six patients (23.1%) experienced ≥grade 2 RILT. There was no significant difference in absolute TGF-β1 levels pre-RT, at 2 and 4 weeks during-RT, or at the end of RT between patients with and without RILT. The TGF-β1 ratios (over the pre-RT levels) for patients with and without RILT at 2, 4 weeks during-, and the end of RT were 2.8 ± 2.2 and 1.0 ± 0.6 ( P = 0.123), 2.3 ± 1.3 and 0.8 ± 0.5 ( P = 0.001), 1.5 ± 0.9 and 0.8 ± 0.5 ( P = 0.098), respectively. Using 2.0 as a cut-off, the TGF-β1 ratio at 4 weeks during-RT predicted RILT with a sensitivity and specificity of 66.7% and 95.0%, respectively. Conclusion Elevation of plasma TGF-β1 level 4 weeks during-RT is significantly predictive of RILT. The role of plasma TGF-β1 in predicting RILT deserves further study.
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final Toxicity results of a radiation dose escalation study in patients with non small cell Lung cancer nsclc predictors for radiation pneumonitis and fibrosis
International Journal of Radiation Oncology Biology Physics, 2006Co-Authors: Feng Ming Kong, James A Hayman, Kent A Griffith, Gregory P Kalemkerian, Douglas A Arenberg, Susan E Lyons, Andrew T Turrisi, Allen S Lichter, Benedick A FraassAbstract:Purpose: We aimed to report the final Toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non–small-cell Lung cancer (NSCLC) by quantifying the dose–volume Toxicity relationship of the Lung. Methods and Materials: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-Lung Toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. Results: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 Lung Toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly ( p Conclusions: With long-term follow-up for Toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative Lung dose–volume Toxicity–based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients.
