Cone Beam Computed Tomography Can Predict Survival of Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Chemoradiation Therapy

S162

International Journal of Radiation Oncology  Biology  Physics

Purpose/Objective(s): To observe the early changes of metabolic tumor heterogeneity and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC). Materials/Methods: From January 2007 to February 2010, 43 patients with NSCLC were included in the study. All patients were evaluated by 18F-fluorodeoxyglucose (18F-FDG) PET/CT before and after receiving radiation with concurrent cisplatin-based chemotherapy (CRT). Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) at 4 weeks after CRT began. Tumor heterogeneity was determined using 7 textural parameters (coefficient of variation [COV], skewness, kurtosis, contrast, energy, entropy, homogeneity) and the area under the cumulative intensity-volume histogram curve (AUCIVH). For comparison, conventional parameters (maximum and mean standardized uptake values [SUV], metabolic tumor volume, and total lesion glycolysis [TLG]) were also evaluated. Values on pretreatment PET/ CT, as well as changes early in the course of therapy, were compared with tumor response. Overall survival (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier method. Results: Compared with non-responders, RECIST responders showed significantly greater COV, contrast and AUC-IVH temporal changes during CRT (P Z .001, .006, .034, respectively). None of the SUV or other textural parameters predicted RECIST response. By Kaplan-Meier analysis, the patients with greater contrast and AUC-IVH changes had significantly higher 5-year OS (P Z .024, P Z .032) and DFS (P Z .014, P Z .017) than patients with little changes of metabolic heterogeneity. In multivariate analysis, contrast and AUC-IVH changes were statistically significant independent prognostic factors of OS (HR Z 2.72, P < .001; HR Z 2.56, P Z .008, respectively) and DFS (HR Z 2.09, P Z .023; HR Z 1.85, P Z .036, respectively). The remaining parameters during CRT did not show significant associations with OS and DFS. Receiver-operating characteristic curve analysis showed that temporal changes of tumor textural analysis serve as a prognostic factor with higher sensitivity (76%e92%) and specificity (83%e94%) than any baseline imaging parameter. Conclusion: Early in the course of CRT for locally advanced NSCLC, the metabolic tumor heterogeneity characterized by COV, contrast and AUCIVH may predict tumor response before changes in the SUV; furthermore, contrast and AUC-IVH can provide significant prognostic information; therefore, close monitoring of changes in metabolic tumor heterogeneity is an important step for personalized treatment of locally advanced NSCLC. Author Disclosure: X. Dong: None. X. Sun: None. L. Sun: None. J. Shaffer: None. X. Sun: None. X. Zhang: None. Z. Wang: None. H. Wan: None. J. Yu: None. L. Xing: None.

reduction >41.6% from day 1 to day 43 (HR Z 0.426, 95% CI: [0.19, 0.92], P Z .029). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 39% and survival improved by 1.5 months (b Z 0.15; 95% CI: [0.012 e 0.29], P Z .033). For patients whose TV decreased >41.6 or 41.6%, log-rank test demonstrated a separation in survival (P Z .025) with median survivals of 31.4 versus 13 months, respectively. Neither local recurrence (HR Z 0.76, 95% CI: [0.24, 2.41], P Z .64) nor distant recurrence (HR Z 0.65, 95% CI: [0.26, 1.64], P Z .36) correlated with TV decrease 41.6% from D1 to D43. Histological subtype was not associated with GTV decrease or survival (both P > .05). When adjusting for patient, tumor, and treatment characteristics, TV reduction >41.6% continued to be associated with better survival (HR Z 0.32, 95% CI: [0.14 e 0.77], P Z .01). Conclusion: Target volume reduction, as determined by CBCT during CRT as part of routine care, predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes. Author Disclosure: S.K. Jabbour: None. C.M. Descaris: None. M.P. Deek: None. L. Lin: None. S. Kim: None. W. Zou: None. C.B. Simone: None.

1014 Cone Beam Computed Tomography Can Predict Survival of Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Chemoradiation Therapy S.K. Jabbour,1 C.M. Descaris,2 M.P. Deek,1 L. Lin,3 S. Kim,1 W. Zou,1 and C.B. Simone, II3; 1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 2Robert Wood Johnson Medical School, New Brunswick, NJ, 3University of Pennsylvania, Philadelphia, PA Purpose/Objective(s): We sought to evaluate whether tumor response, assessed on cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT), could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Materials/Methods: We manually delineated primary tumor volumes (TVs) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Times to event data were calculated by univariate Cox regression. Percentage reductions in TV were calculated and then correlated to survival and pattern of first recurrence using linear regression. Results: We evaluated 61 patients with a median follow-up of 10.7 months. Median TV reduction was 41.6% (range 0e85.2%) from day 1 (D1) to 43 (D43) CBCTs. Overall survival was associated with TV

1015 Chemotherapy and Chest Radiation Therapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer: Rethinking Our Approach to Treating “Incurable” Disease S. Shin,1 A. Goldowsky,1 J. Suh,1 P.B. Schiff,2 E.B. Golden,3 and S.C. Formenti3; 1New York University School of Medicine and Langone Medical Center, New York, NY, 2NYU School of Medicine and NYU Langone Medical Center, New York, NY, 3New York University School of Medicine, New York, NY Purpose/Objective(s): Recent reports have shown an overall survival (OS) benefit to chemotherapy (CT) followed by (f/b) chest radiation therapy (RT) for patients with extensive-stage small cell lung cancer (ESSCLC) (Slotman et al, Lancet 2015). Evidence also suggests superior outcomes with concurrent chemoradiation therapy (CRT) over a sequential regimen. In patients with limited-stage SCLC (LS-SCLC), even timing of chest RT, given with (as opposed to after) the 1st two cycles of CT, confers an OS benefit; yet, no reports investigating the use of CT + chest RT as first-line treatment for ES-SCLC exist. We reported our institutional experience treating ES-SCLC patients with first-line CRT. Materials/Methods: Extensive-stage SCLC was defined as  bilateral hemithorax (Veterans Administration Lung Study Group). We identified 131 patients with ES-SCLC and 80 with LS-SCLC, treated from 2006e2014. Patients with brain metastases (n Z 17) or ECOG performance status > 2 (n Z 7) were excluded. A matched-pair analysis between treatment groups was performed. Groups for analysis included: CT + chest RT (LS-SCLC, n Z 16; ES-SCLC, n Z 7), CT (ES-SCLC, n Z 15), and CT f/b chest RT (ES-SCLC, n Z 11) (Table 1). Radiographic images were used to evaluate disease progression. Median survival (MS) was estimated using Kaplan-Meier curves and significance determined by log-rank analysis. Baseline lab values were acquired and analyzed by a two-tailed, ttest. A P value of < .05 was considered statistically significant (SS).

ePoster Abstracts 1015; Table 1 Diagnosis 1st-line treatment Median age (range) Sex ECOG performance status

LS-SCLC (n Z 16)

ES-SCLC (n Z 7)

ES-SCLC (n Z 15)

ES-SCLC (n Z 11)

CT+RT

CT+RT

CT

CT f/b RT

67 (57e79)

62 (55e78)

64 (49e81)

67 (48e83)

M: 44%, F: 56% 0: 0%, 1: 83%, 2: 17%

M: 29%, F: 71% 0: 0%, 1: 80%, 2: 20%

M: 60%, F: 40% 0: 0%, 1: 69%, 2: 31%

M: 45%, F: 55% 0: 10%, 1: 72%, 2: 18%