Proceedings of the 50th Annual ASTRO Meeting S59

For patients with TGFb1 data (267 cases), MLD, V20, and TGFb1 ratio were all significantly associated with risk of RILT(p\0.05). A model combining MLD with TGFb1 ratio appeared to be better than using MLD or V20 alone (p = 0.003). For pa-tients with higher MLD of RT such as stage III diseases (120 cases), RILT had an insignificant correlation with MLD (p = 0.20) anda significant correlation with TGFb1 ratio (p = 0.03). A TGFb1 ratio .1 was very significantly associated with RILT (odds ratio =6.6 compared to a ratio #1, p\0.001). In multivariate analysis (adjusted for age, gender, RT dose, and MLD or V20), TGFb1 ratioremained significant (odds ratio = 6.4, p \ 0.001). Model fits for the multivariate models were improved with the addition ofTGFb1 to MLD or to V20 (p \ 0.05). The crude rate of grade $2 RILT was 11.0% and 44.7% for patients with TGFb1 ratio#1 and .1, respectively.

Conclusions: Increases in TGFb1 during thoracic RT add predictive ability to dose-based metrics for RILT in patients withNSCLC, especially in those with stage III diseases.

Supported in part by ASCO CDA, 1NIH R21 CA127057-01A1, and NIH R01CA69579.

Author Disclosure: F.M.P. Kong, ASCO CDA, RTOG TRP #121and 1R21 CA127057-01A1., B. Research Grant; K. Griffith,None; L. Marks, NIH R01CA69579, B. Research Grant; L. Wang, None; J. Belderbos, None; W. Ji, None; J. Hubbs, None;S. Zhou, None; R.T. Haken, None; J. Lebesque, None.

128 Modeling Volume Effects for Pneumonitis in Multi-institutional Non-small Cell Lung Cancer (NSCLC) Data

using gEUD Atlases of Complication Incidence

A. Jackson1, E. D. Yorke1, J. S. A. Belderbos2, G. R. Borst3, K. E. Rosenzweig1, J. V. Lebesque3

1Memorial Sloan-Kettering Cancer Center, New York, NY, 2Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital,Amsterdam, The Netherlands, 3The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam,The Netherlands

Purpose/Objective(s): Dosimetric atlases of complication incidence efficiently summarize radiation exposures and complicationstatistics in treatment series, promoting meta-analysis (Jackson et al. Semin Radiat Oncol 16:260-268, 2006). Here, we model thedependence of radiation pneumonitis requiring steroids or worse toxicity at 6 months (RP, grade $3 RTOG or grade $2 SWOG)on the generalized equivalent uniform dose (gEUD), using prospective data from Memorial Sloan-Kettering Cancer Center(MSKCC) and The Netherlands Cancer Institute (NKI), and test the use of gEUD atlases for meta analysis by comparing exactand atlas based results.

Materials/Methods: Phase I dose escalation protocols for treatment of NSCLC were completed at MSKCC and NKI, giving dosesfrom 57.6-90 Gy and 60.75-94.5 Gy in 1.8-2 Gy and 2.25 Gy fractions, respectively. RP was scored prospectively in both protocols.Dose-volume histograms were available for 78 and 86 patients who met follow-up requirements, including 10 and 14 cases of RP,respectively. Doses were converted to normalized total doses in 2 Gy fractions with the linear quadratic model, a/b = 3 Gy. ThegEUDs were calculated for 21 values of the volume effect parameter a from log10a = �1 to +1 in steps of Dlog10a = 0.1. Wedetermined: the best fit logistic model of the dependence of RP on gEUD at each a; the range of a where gEUD was significantlycorrelated with RP; the likelihood profile for the model fits and associated confidence limits on the best fit value of a. Calculationswere repeated using data from a gEUD atlas (grid spacing: 0.1 in lnEUD) to assess its utility for meta-analysis. Analyses of com-bined and separate data sets were compared.

Results: gEUD was significantly correlated with RP for a \ 1.35. The most significant models had a \0.63 (where p \ 0.003).Best fits had a \ 0.16 (where the likelihood profile was flat). Upper 68% and 95% confidence limit on a was 0.76 and 1.91, re-spectively; lower limits could not be determined. Calculations using the atlas reproduced these general features: Significant cor-relation was found for a\1.24; the most significant models had a\0.63, where p\0.003; the best fits had a\0.25; the upper68% and 95% confidence limit on a was 0.83 and 2.16, respectively, with no lower limits. The p values were�10 times smaller inthe joint vs the individual data sets.

Conclusions: Correlations of RP with gEUD improved when the data sets were combined. The analysis showed a very large vol-ume effect for RP; best models had a\0.16. Confidence limits and ranges of significant correlation for a obtained using gEUD atlasvalues agreed to �10% with those from exact gEUDs. Both methods agreed that the likelihood profile was flat at the lower end ofthe calculated range. These results confirm the utility of atlases for meta-analysis.

Author Disclosure: A. Jackson, None; E.D. Yorke, None; J.S.A. Belderbos, None; G.R. Borst, None; K.E. Rosenzweig, None;J.V. Lebesque, None.

129 Induction Chemotherapy versus Chemoradiotherapy for Stage III Non-small Cell Lung Cancer

K. A. Higgins, R. Clough, L. Marks, C. Kelsey

Duke University Medical Center, Durham, NC

Purpose/Objective(s): The optimal therapy for stage III (N2) NSCLC is controversial. Induction therapy, either chemotherapy(CT) or chemoradiotherapy (CT-RT), is typically given before surgery in operable patients. The optimal induction regimen hasyet to be established and both approaches are utilized. However, N2 NSCLC comprises a heterogeneous population (e.g., singlestation vs multistation; macroscopic vs microscopic). We examined these and other factors in an attempt to define a subgroup ofpatients who may benefit from a combined modality induction regimen.

Materials/Methods: This IRB-approved retrospective review analyzed all patients with pathologically confirmed N2 NSCLCwho initiated induction therapy at Duke University between 1995-2006. A univariate regression analysis was utilized to assessoverall survival (OS), disease-free survival (DFS), and local control (LC) based on clinical and pathologic factors. Fisher’s exacttest was performed to compare patient subgroups and to assess the likelihood of achieving a mediastinal pathologic completeresponse (pCR).

Results: 98 patients were identified. Median age was 61 (range, 35-81). Median follow-up was 21 months in all patients, 36 monthsin survivors. Clinical and pathological characteristics were similar between the CT (n = 29) and CT-RT (n = 69) subgroups. Surgerywas subsequently performed in 76% after CT and 84% after CT-RT (p = 0.4). Postoperative death occurred in 5% of both groups.