M. Jeter

Association Between LGALS3 Gene Polymorphisms and Survival in Non–Small Cell Lung Cancer Patients Treated With Definitive Radiation Therapy

associated with a worse FFP (8.2 months vs 14.4 months, HRZ2.26 [1.1, 4.72] PZ.028). Conclusion: The primary tumor is the most common site of progression in patients with metastatic EGFR-mt NSCLC on a TKI. In 15% of patients, progression was limited to the primary site in the lung. Interestingly, patients with liver metastases have a higher incidence of primary site progression, warranting further evaluation. Additionally, FFP is improved in patients who have undergone upfront treatment to the primary site, regardless of modality, although this finding may be affected by selection bias. These findings will help inform treatment paradigms investigating local therapy in metastatic EGFR-mt NSCLC, including patients presenting with stage IV disease who ordinarily might not have definitive treatment to the primary site. Author Disclosure: D.M. Guttmann: Employee; Childrens Hospital of the University of Pennsylvania. A. Doucette: None. P.E. Gabriel: Employee; Penn Medicine. J.J. Morrissette: None. J. Kucharczuk: None. W.P. Levin: None. C.B. Simone: Employee; Nemours Alfred I. duPont Hospital for Children. E. Alley: None. C. Ciunci: None. J. Bauml: None. C. Langer: Research Grant; Bristol-Myers Squibb Company, ImClone Systems Incorporated, Pfizer, Eli Lilly and Companry, Genentech, OSI Pharmaceuticals, GlaxoSmithKline, Clovis, Merck, Nektar, Advantagene, Inovio, Ariad. C. Aggarwal: None. R. Cohen: Advisory Board; Takeda, Kolltan, Cerulean. T.L. Evans: None. A.T. Berman: None.

Polymorphisms of BMP4 and HIF-1A Are Associated With Patient-Reported Symptoms in Non-Small-Cell Lung Cancer Patients Treated With Definitive Chemoradiation Therapy

matching analyses for overall survival were determined using Cox-proportional hazards regression models. Results: In total, 52,352 patients met inclusion criteria. When stratified into dose groups, the median overall survival for those who received 59.460 Gy, 61-69 Gy, and 70 Gy was 17.9, 19.4, and 20.9 months, respectively (P < 0.001). A granular analysis of dose utilizing Cox-regression modeling was performed with binning of dose as follows: 59-60 Gy, 11,258 patients [median survival (MS) 17.9 months, hazard ratio (HR) 1.00, reference], 61-63 Gy, 10,659 patients (MS Z 18.5 months, HR Z 0.96, 95% CIZ 0.94-0.99), 64-65 Gy, 5,612 patients (MS Z 19.0 months, HR Z 0.95, 95% CI Z 0.91-0.98), 66 Gy, 7,043 patients (MS Z 20.9 months, HR Z 0.88, 95% CI Z 0.85-0.91), 67-69 Gy, 8,739 patients (MS Z 19.8 months, HR Z 0.91, 95% CI Z 0.86-0.94), 70 Gy, 6,121 patients (MS Z 21.2 months, HR Z 0.85, 95% CI Z 0.82-0.88), 71-85 Gy, 2,923 patients (MS Z 19.9 months, HR Z 0.88, 95% CI Z 0.84-0.92). While 66, 70, and 71 Gy resulted in increased OS in comparison to 59.4-60 Gy, no significant difference in OS was observed when comparing 66 versus 70 or 66 versus 71 Gy (HR Z 1.03, 95% CI Z 0.99-1.07 and HR Z 1.00, 95% CI Z 0.95-1.05, respectively). On multivariate analysis, higher dose remained statistically significant after adjusting for age, sex, race, Charlson-Deyo comorbidity score, insurance type, income, facility type, clinical stage, histology, and chemotherapy type. Propensity score matching was performed and confirmed findings from univariate and multivariate analyses. Conclusion: Dose escalation above the current standard dose of 60 Gy was associated with improved OS in this cohort of stage III NSCLC patients treated with chemoradiotherapy. In addition there appears to be no statistically significant benefit to dose greater than 66 Gy in this setting. This data may serve as a framework for future studies analyzing dose escalation in NSCLC. Author Disclosure: J.V. Brower: None. A. Amini: None. C.R. Hullett: None. A.P. Wojcieszynski: None. M. Bassetti: None. M.E. Witek: None. S. Chen: None. M. Yu: None. A.M. Baschnagel: None.

Prognostic Factors for Overall Survival in Stage IIIA/IIIB Non-small Cell Lung Cancer After Definitive (Chemo)radiation Therapy

frequently develop acute esophageal toxicity (AET). Studies investigating the dose-effect relationship with qualitative AET scores have resulted in a wide range of dosimetric predictive parameters, while the underlying biological processes and local dose-effect relation have not been investigated. The purpose of this study was to correlate the planned dose distribution to post-CRT local esophageal FDG-PET uptake as a surrogate for local inflammation, and subsequently utilize the derived local dose-effect for AET prediction. Material/Methods: Patients treated with 24 x 2.75 Gy IMRT plus daily low dose Cisplatin and having a post-RT PET (PETpost) scan acquired within 3 months after cCRT were retrospectively selected. The outer wall of the esophagus was delineated on the planning CT and propagated to the PETpost-CT through deformable registration. The value of PETpost in relation to AET was evaluated by comparing the mean esophageal SUVof the highest 50% (SUV50%) between gr 50 Gy were associated with elevated FDG uptake, when the PETpost was acquired within 4 weeks after cCRT. After 4 weeks no dose effect was observed. The derived local dose effect model parameters, based on data acquired within 4 weeks (nZ47), were D50 Z 93 Gy and k Z 9.4. The SUV50% was significantly higher for gr 2 AET (2.2 vs. 2.7, pZ0.008). The average DPET was 54.1 Gy (1SDZ11.3) for gr<2, and 60.3 Gy (1SDZ4.3) for gr 2 AET (pZ0.001). DPET based prediction of AET gr 2 had the highest likelihood compared to Dmean (pZ0.06), V35 (pZ0.05) and V60 (pZ0.29). Conclusions: Esophageal uptake of FDG post-cCRT is associated with acute esophageal toxicity, and was only observed for RT dose above 50Gy. Predictability of grade 2 AET was improved by using the derived local relation between RT dose and PETpost SUV. With this biological response model, planning constraints onand predictability of AET can be done more accurately. Author Disclosure: J. Nijkamp: None. M. Rossi: None. J. Belderbos: None. W. Uyterlinde: None. M. Kwint: None. M. van den Heuvel: None. W. Vogel: None. J. Sonke: None.

Lung Perfusion Score Can Predict Future Pulmonary Complications After Radiation Therapy in Patients With Lung Cancer

17% to 24%) and 23% (95% C.I. 19% to 27%), respectively. In univariate analyses, smoking status (150 current smokers, 371 previous smokers, and 46 nonsmokers, p\0.001), nodal status (104 node negative, 363 node positive, p = 0.029), volume of normal lung (median 3486 cc, range 1252 to 7870 cc, p = 0.003), percent of total lung represented by the GTV (median 3.5%, range \0.1% to 37.5%, p = 0.010), use of 4D-CT (N = 122, p = 0.048) and IMRT (N = 84, p = 0.034), mean dose to (normal) lung (median 21.1 Gy, range 2.1 Gy to 40.1 Gy, p \ 0.001), relative volumes of normal lung rV5 to rV65, in increments of 5 Gy were associated with TRP with statistical significance by univariate analyses. In multivariate analyses (MV), higher rV30 (p \ 0.001), nonsmoker (p = 0.001), and former smoker (p = 0.030) were the only 3 independent factors with increased risk of TRP. Each of the factors significant by univariate, analysis but not by MV analysis, is significantly associated (Mann-Whitney test) with differences in rV30. Further analysis demonstrated that the majority of non-smokers were healthy women who had smaller lung volume with adenocarcinoma, who received induction chemotherapy, and had higher mean V30-45, compared with smokers. Conclusions: The only clinical factor other than dose-volume factors that significantly impacts TRP risk is smoking status. Many different dose-volume factors were significantly associated with differences in time to TRP. Additional analysis is needed to identify what dose range of lung radiation is most important biologically. Based on the fits of the MV models, we can identify patient subgroups with markedly different risk, but we have not yet identified a high-risk group with an expected incidence of .50%. Therefore, there are undoubtedly other risk factors yet to be identified.