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PURPOSE Local consolidative therapy (LCT) for patients with synchronous oligometastatic non–small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients. METHODS We identified all patients presenting between 2000 and 2017 with stage IV non–small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis. RESULTS Of 194 included patients, 121 received comprehensive LCT to all sites of disease with either surgery or radiation. TP53 mutations were identified in 40 of 78 (55%), KRAS in 32 of 95 (34%), EGFR in 24 of 109 (22%), and STK11 in nine of 77 (12%). At median follow-up of 96 months, median OS and PFS were 26 (95% CI, 23 to 31) months and 11 (95% CI, 9 to 13) months, respectively. On multivariable analysis, patients with EGFR mutations had lower mortality risk (hazard ratio [HR], 0.53; 95% CI, 0.29 to 0.98; P = .044) compared with wild-type patients, and patients with STK11 mutations had higher risk of progression or mortality (HR, 2.32; 95% CI, 1.12 to 4.79; P = .023) compared with wild-type patients. TP53 and KRAS mutations were not associated with OS or PFS. Among 71 patients with known EGFR mutational status who received comprehensive LCT, EGFR mutations were associated with lower mortality compared with wild-type (HR, 0.45; 95% CI, 0.22 to 0.94; P = .032). CONCLUSION When compared with wild-type patients, those with EGFR and STK11 mutations had longer OS and shorter PFS, respectively. EGFR mutations were associated with longer OS among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy.

9061 Background: Many clinicopathological and molecular features are associate with clinical benefit from immune checkpoint inhibitors (ICIs) for patients with non-small-cell lung cancer (NSCLC), yet none was exclusive underscoring the heterogeneity of lung cancers. As images may provide a holistic view of cancer, we attempted deep learning to chest CT scans to derive a predictor of response to ICIs and test its benefit relative to known clinicopathological factors. Methods: 928 stage IV, EGFR/ALK-negative NSCLC patients treated with ICIs alone or in combination (MD Anderson GEMINI Database) were divided into training (CTtr = 572), validation (CTva = 78), and testing (CTte = 278) cohorts, balancing the distribution of clinicopathological and radiological factors. Progression-free (PFS) and overall survival (OS) were defined as outcomes. We analyzed whole lung, including tumor and normal parenchyma of chest CT images ≤ 3 months prior to ICI treatment. An ensemble learning model (CT-deep-learning) to clustering patients into high vs low risk groups of PFS or OS was developed by fusing risk scores from four independent deep learning networks (supervised, unsupervised, and hybrid). This CT-deep-learning model was further evaluated in different clinicopathological subgroups. Finally, a composite model (CT-Clinic-path) was built by combining image model with clinicopathological factors. Antolini's concordance index (C-index) was used to assess model performance. Results: Median PFS and OS were shorter in the high-risk vs low-risk group as defined by CT-deep-learning: PFS (CTtr: 4.2 vs 9.6 mons; HR 1.96; 95% CI 1.62-2.38; P < 0.0001; CTva: 3.7 vs 10.2 mons; HR 2.32; 95% CI 1.32-4.07; P = 0.0025; CTte: 3.6 vs 9.1 mons; HR 1.89; 95% CI 1.39-2.56; P < 0.0001) and OS (CTtr: 16.0 vs 31.4 mons; HR 2.19; 95% CI 1.72-2.79; P < 0.0001; CTva: 12.7 vs 28.6 mons; HR 2.01; 95% CI 1.04-3.88; P = 0.035; CTte: 14.8 vs 32.0 mons; HR 1.84; 95% CI 1.31-2.60; P = 0.0004). CT-deep-learning outperformed clinicopathologic features known to associate with ICI benefit, such as histology, smoking status, PD-L1 expression, and remained to be an independent (P < 0.001) prognostic factor on multivariate analysis. Furthermore, integrating CT-deep-learning to clinicopathological variables improved prediction performance with a net reclassification up to 7% (Clinic-path model, C-indices 0.60 – 0.62 vs CT-clinic-path model, 0.64 - 0.65 for PFS; Clinic-path model 0.64 – 0.67 vs CT-clinic-path model 0.69 – 0.71 for OS). Conclusions: We have developed and validated a deep learning signature associated with PFS and OS in ICI-treated NSCLC patients, which appears to be independent of and superior to known clinicopathological biomarkers. If validated, this signature may strengthen the predictive value of clinicopathological factors and facilitate selecting appropriate patients for ICI-based therapies.

9055 Background: The benefit of combination immune checkpoint inhibitor (ICI) with chemotherapy over ICI monotherapy in non-small cell lung cancer (NSCLC) remains underexplored. Methods: This retrospective cohort included patients with metastatic NSCLC from a single-institution database treated with ICI monotherapy or with chemotherapy between 1/2014-2/2020. Clinical progression-free survival (PFS) and overall survival (OS) were the primary outcomes. Propensity score adjustment for clinical and sociodemographic characteristics was used for analysis of first-line treatment outcomes. Results: A total of 1,139 patients (54% male; median age, 64.9) were included. Adenocarcinoma histology, smoking history, higher PD-L1 expression, and lower metastatic stage associated with improved PFS. However, PD-L1 expression and smoking associated with PFS only in adenocarcinoma (LUAD); squamous (LUSC) patients had shorter PFS independent of PD-L1 and smoking history (PD-L1 > 50% vs 1-49%: LUAD P < 0.001; LUSC P = 0.69; Former vs never smoker: LUAD P = 0.008; LUSC P = 0.89). In first-line patients (n = 680), treatment with ICI plus chemotherapy (ICI-chemo) associated with higher progression-free rates at 3 and 6 months compared with ICI-monotherapy (ICI-chemo vs ICI-mono: 3-month PFS, 85.2% vs 68.8%, P = 0.001; 6-month PFS, 66.4% vs 52.6%, P = 0.008). However, there was no difference overall in PFS or OS in either the full or propensity-matched cohort. Treatment with ICI and chemotherapy concurrently vs sequentially was associated with similar PFS (log-rank P = 0.12). Conclusions: In this real-world cohort, the addition of chemotherapy to ICIs may protect against early progression but does not influence long-term outcomes. Treatment with sequential vs concurrent ICI and chemotherapy produced similar outcomes. These findings suggest that combination therapy may maximally benefit patients at risk of early progression.

e20592 Background: Patient-derived xenograft (PDX) models can provide renewable cancer tissue resources, are being increasingly utilized for the molecular characterizations of cancers and preclinical studies on drug activities, and have the potential to advance biomarker identification. Previous research has demonstrated that PDX tumors preserve the histologic and morphologic characteristics and gene expression and mutation patterns of primary tumors, and correlate to patient survival. Tumor histological subtypes and differentiation grades are known to contribute to the success of PDX intake, but little is known about how molecular features associate with the success of PDX engraftment or whether PDX preserves subclonal architecture of primary tumors. Methods: To fill this void, we analyzed 252 primary tumor samples from the SPORE/ICON project at MD Anderson Cancer Center that were used for generating PDXs and had comprehensive genomic, transcriptomic, and immune profiling data available to evaluate the parameters impacting the intake success of lung cancer PDXs. In order to establish the impact of molecular features on PDX intake success we also assessed the fidelity of PDX in representing the molecular features of this cohort of primary tumors. Results: Only 36% of the primary tumors in this study successfully generated a PDX, with Squamous Cell Carcinoma PDX demonstrating an intake rate of 67% and Adenocarcinoma PDX demonstrating an intake rate of 21%. Genomic architecture derived from whole exome sequencing showed not only 43% (38-48%) of mutations shared, but also similar clonal architecture between primary tumors and PDX. Higher copy number aberration burden, high tumor purity and low immune infiltration in primary tumors were found to be associated with successful intake of PDX. Transcriptomics revealed 6,103 genes differentially expressed between primary tumors with successful PDX intake versus those which were unsuccessful. Pathway analysis of these genes indicated that inhibition of cell proliferation, signaling, and migration as well as DNA replication, recombination and repair were associated with PDX intake failure regardless of histology. Conclusions: These findings indicate that PDX intake success is regulated by molecular features and multiomic evaluation of lung cancer primary tumors can be used as a marker for determining which samples to use for PDX model generation.

Purpose Small observational studies have shown a survival advantage to undergoing cancer-directed surgery for malignant pleural mesothelioma (MPM); however, it is unclear if these results are generalizable. Our purpose was to evaluate survival after treatment of MPM with cancer-directed surgery and to explore the effect surgery interaction with chemotherapy or radiation therapy on survival by using the National Cancer Database. Patients and Methods Patients with microscopically proven MPM were identified within the National Cancer Database (2004 to 2014). Propensity score matching was performed 1:2 and among this cohort, a Cox proportional hazards regression model was used to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. Results Of 20,561 patients with MPM, 6,645 were identified in the matched cohort, among whom 2,166 underwent no therapy, 2,015 underwent chemotherapy alone, 850 underwent cancer-directed surgery alone, 988 underwent surgery with chemotherapy, and 274 underwent trimodality therapy. The remaining 352 patients underwent another combination of surgery, radiation, or chemotherapy. Thirty-day and 90-day mortality rates were 6.3% and 15.5%. Cancer-directed surgery, chemotherapy, and radiation therapy were independently associated with improved survival (hazard ratio, 0.77, 0.74, and 0.88, respectively). Stratified analysis revealed that surgery-based multimodality therapy demonstrated an improved survival compared with surgery alone, with no significant difference between surgery-based multimodality therapies; however, the largest estimated effect was when cancer-directed surgery, chemotherapy, and radiation therapy were combined (hazard ratio, 0.52). For patients with the epithelial subtype who underwent trimodality therapy, median survival was extended from 14.5 months to 23.4 months. Conclusion MPM is an aggressive and rapidly fatal disease. Surgery-based multimodality therapy was associated with improved survival and may offer therapeutic benefit among carefully selected patients.

8542 Background: The NEOSTAR study compared nivolumab (N) vs. nivolumab plus ipilimumab (NI) with major pathological response (MPR; ≤10% viable tumor) as primary outcome. We report updated rates of treatment failure (TF), including in patients whose tumors harbored genomic aberrations, and outcomes of additional treatments. Methods: Patients (pts) with stage I-IIIA resectable NSCLC (AJCC 7th) were randomized to either neoadjuvant N or NI followed by surgery (n = 44). TF was defined as radiographic and/or biopsy-proven recurrence from primary lung cancer and/or death (treatment or cancer-related). Additional systemic therapy at recurrence included immuno-oncology (IO)-based therapy (IO or chemo-IO), targeted therapy (TT), or chemotherapy. Disease control rate (DCR) was defined as the proportion of pts with radiographic objective responses and stable disease at first restaging. Cox proportional hazards model was used to associate baseline characteristics and time to TF. Results: A total of 44 randomized pts were evaluated, the median follow-up was 35 months (mts) as of February 4, 2021. Among the 12 TF pts (12/44, 27%), 42% (5/12) did not undergo surgery on trial, 9 (9/44, 20%) experienced recurrence and 6 (6/44, 14%) died (1 non-cancer-related, 5 cancer-related). TF was less likely in smokers vs. never smokers (hazard ratio = 0.20, 95% confidence interval = 0.06-0.65, p = 0.007). Among pts with pathological specimen resected on trial, MPR was achieved in 40% (12/30) of non-TF pts. Only 1 (1/7, 14%) TF pt achieved MPR, but died of a non-cancer related cause. TF-free survival rate at 2 years was 92% in MPR and 78% in non-MPR pts. Eight (8/9, 89%) pts had tumors with canonical oncodriver aberrations (5 EGFR mutations, 1 with STK11+ KRAS Q61H mutations, 1 ALK translocation and 1 RET fusions). Of the 9 recurrences, 44% (4/9) were treated with IO therapy, and all 7 pts with targetable aberrations were treated with TT (3 after retreatment with IO therapies). Of the 4 pts retreated with IO therapy, duration between end of neoadjuvant and retreatment were 20, 17, 23, and 19 mts. Duration from retreatment until progression (PD) were 1, 1, and 2 mts, respectively. Last pt was treated without PD for 2 mts but switched to TT due to discovery of genomic aberration. IO retreatment achieved 25% DCR (1/4). In comparison, the DCR for TT treated pts was 71% (5/7, p = 0.242). Median time to treatment was 21 mts, and median time to PD was not reached. Among 32 non-TF pts, 12 had genomic analysis and 7 aberrations were found in 6 pts (2 STK11, 2 ERBB2, 1 STK11 + 1 KRAS G12C, and 1 KRAS G12C mutation). Conclusions: A 27% TF rate was observed after neoadjuvant IO. TF was less likely to occur in smokers and MPR pts, and 42% of TF pts did not undergo curative-intent surgery on trial. Genomic aberrations were common in pts with recurrence (89%), and treatment with TT achieved 71% DCR vs. 25% DCR with IO-based retreatment. Clinical trial information: NCT: 03158129.

e14047 Background: Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with poor prognosis in non-small cell lung cancer (NSCLC); the biological underpinnings of this observation have not been fully elucidated. We examined the relationships between peripheral neutrophil counts (PMN), NLR, circulating cytokines and angiogenic factors (CAF), and tumor microenvironment (TME) features in NSCLC. Methods: 150 patients with resectable NSCLC were enrolled in an immunoprofiling project. A panel of 43 CAFs was used to analyze preoperative plasma samples. Chemotherapy-naïve patients with CAF and a complete blood count ≤30 days preoperatively were included (n = 66; Table). For a subset, transcriptional signatures (MCP-counter, n = 50) and flow cytometry (n = 19) were used to identify TME phenotypes. Results: Increased PMNs were associated with increased pro-inflammatory CAF such as IL-1b (r = 0.392) and IL-6 (r = 0.339), as well as Th17/Tc17 associated CAF IL-17A (r = 0.320) and TNF-a (r = 0.368). Elevated NLR was inversely correlated with the lymphocyte activation marker soluble CD27 (r = -0.320, p = 0.009). This negative association was mirrored in the TME, as tumor neutrophil signatures were inversely correlated with a local IFN-g gene signature (r = -0.626, p < 0.001). Interestingly, a Th17/Tc17 peripheral signature (elevated IL-17A) was associated with an enrichment of CD8+TIM3+ cells (r = 0.623, p = 0.042) in the tumor. While this requires confirmation in a larger cohort, this correlation provides a potential rationale for targeting TIM3 in this population. Upon analysis of clinical characteristics, peripheral PMNs and NLR were higher among patients with squamous histology (PMN p = 0.009; NLR p = 0.034) and positively correlated with tumor size (PMN r = 0.344, p = 0.004; NLR r = 0.363, p = 0.003). Conclusions: A relative neutrophilia in NSCLC patients is associated with an inflammatory milieu suggestive of a Th17/Tc17 presence and decreased lymphocyte activation that is reflected within the TME. Further investigation is needed to define the role of NLR as a predictive biomarker and to identify whether neutrophils or Th17/Tc17 T cells could serve as a therapeutic target to improve immunotherapy response in NSCLC.[Table: see text]

8504 Background: Neoadjuvant immune checkpoint inhibitors (ICIs) induce major pathologic response (MPR) rates of 20 to 45% in resected NSCLCs. We report the results of NEOSTAR - a phase 2 trial of neoadjuvant N or NI for NSCLCs. Methods: Pts with stage I-IIIA (single N2) resectable NSCLC (AJCC 7th), PS 0-1, were randomized to N (3 mg/kg IV, D1, 15, 29) or N plus I (1 mg/kg IV, D1) followed by surgery (n = 44). Primary endpoint: MPR (≤10% viable tumor), hypothesized to be higher than MPR to induction chemotherapy historical controls. Tumor immune infiltrates and pre- & post-ICI tumor PD-L1 % were assessed by flow cytometry & IHC. Wilcoxon ranked sum test & Fisher’s exact test were used for comparisons. Results: 44 pts were randomized, 23 N, 21 NI: mean age 66, 64% males, 18% never smokers, 59% adenocarcinomas, stages: IA 8 (18%), IB 15 (34%), IIA 7 (16%) IIB 5 (11%); IIIA 9 (20%). Only 3 pts received < 3 doses due to TRAEs (7%). 34 pts had surgery post ICIs (7 not resected [7/41], 17%, [2 N, 5 NI], 3 pending). There were 10 MPRs in 41 pts overall (24%, 4 N, 6 NI), of which 6 were path CRs (15%, 2 N [9%], 4 NI [21%]). Among 34 resected pts, MPR rate was 29% (N 20%, NI 43%). Median % of viable tumor was lower post NI vs N (20% vs 65%, p = .097). ORR (RECIST v1.1) was 22% (8 PRs [5 N, 3 NI], 1 CR [NI]); 15% of pts had PD (3 N, 3 NI). The proportion of CR+PR in MPR+ was higher than in MPR- (6 [60%] vs 2 [7%], p < .001). Surgical complications included 2 bronchopleural fistulas (BPFs) in N & 8 air leaks (5 N, 3 NI). G3-G5 TRAEs included a death due to BPF post steroid-treated pneumonitis (G5, N); G3 pneumonia, hypoxia, hypermagnesemia (1 each, all N), G3 diarrhea (1 NI). CD3+ & CD103+ tissue resident memory CD8+ TILs were higher in NI- vs N-treated tumors (CD3+ 81.2% vs 54.4%, p = .028; CD8+ 56.2% vs 38.3%, p = .069). Median pre-treatment tumor PD-L1 was higher in responders (MPR+, CR+PR) vs non-responders (80% vs 1%, p = .024), and the % of viable tumor was lower in tumors with PD-L1 > 1% vs PD-L1 ≤1% (median 20% vs 80%, p = .046). Conclusions: Overall a 24% MPR rate to neoadjuvant ICIs was observed. NI induced a higher % of non-viable tumor and of tissue resident memory TILs vs N. Antitumor activity was associated with higher pre-treatment PD-L1 levels. Clinical trial information: NCT03158129.

8555Background: Major pathologic response (mPR) in resected NSCLC following neoadjuvant chemotherapy correlates with long-term survival. This phase 1 study assessed the safety and efficacy of N add...

8576Background: Carcinogenesis may result from accumulation of genomic and epigenomic aberrations. It has been postulated that atypical adenomatous hyperplasia (AAH), the only recognized pre-neopla...

161 Background: Multiple clinical studies have shown that adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TIL) is remarkably effective in melanoma patients. Non-small cell lung cancer (NSCLC) shares similarities with melanoma in terms of mutational burden and sensitivity to immune checkpoint inhibitors. We therefore sought to test whether TIL ACT may represent a viable option for the treatment of NSCLC patients. We utilized tissue collected from patients enrolled on the prospective ImmunogenomiC prOfiling of Non-small cell lung cancer (ICON) study. Methods: TIL and tissue-infiltrating lymphocytes were expanded ex vivo from 97 freshly resected early-stage localized NSCLC tumors and 39 matched uninvolved lung tissues. Growth and functional characteristics of TIL were assessed via flow cytometry, TIL-tumor reactivity assays, and analysis of TCRβ sequencing data. Results: NSCLC showed an increased proportion of CD3+ lymphocytes within the tumor-infiltrating leukocyte component as compared to matched normal lung tissue. The TIL compartment included a suppressed CD8+ T cell subset expressing significantly higher levels of PD-1 and lacking cytolytic potential compared to T cells expanded from normal tissue. TIL contained a higher proportion of proliferating (Ki67+) CD8+CD103+ tissue-resident memory (TRM) cells expressing activation markers such as CTLA4, LAG3, PD1 and ICOS, and increased CD4+ Tregs. Despite a highly immunosuppressive environment, TIL expansion was achieved with a success rate of 68% (n = 97) but appeared hindered in patients undergoing neoadjuvant chemotherapy treatment prior to surgery (56.2%, n = 16 vs 72.5% success rate in therapy-naïve patients). In addition, expansion efficiency (number expanded and time of culture) of TIL and matched lung residing lymphocytes were significantly associated (r = 0.379, p = 0.017, n = 39). Importantly, expanded CD8+ TIL products were oligoclonal and showed reactivity toward autologous tumors. Conclusions: Although NSCLC TIL are functionally inhibited in vivo they can be successfully expanded ex vivo and demonstrate recognition of autologous tumor cells. These data suggest that TIL can potentially be used for adoptive T cell-based immunotherapy in NSCLC.

e20034 Background: Previous attempts to define tumor immune environment in non-small cell lung cancer (NSCLC) did not present comprehensive analyses. We established immunogenomic profiling project of NSCLC (ICON) to integrate immune, proteomic, genomic, transcriptomic, demographic, clinical, pathologic, and outcome data from surgically resected lung cancers. Methods: Tumor, normal lung tissue, and blood are collected at the time of surgery and blood after surgery up to 1 year. Samples are processed for tumor infiltrating lymphocyte (TILs) isolation and expansion; generation of patient derived xenografts (PDX), immunohistochemical (IHC) evaluation of immune cells and markers, genomic and proteomic analyses. Results: 73 (75%) out of 98 enrolled patients, median age 66 years, contributed samples to ICON; 33 (46%) males, 62 (85%) former smokers, 11 (15%) never smokers. 50 (68%) had adenocarcinoma, 17 (23%) squamous cell carcinoma, 3 (4%) small cell, and 3 (4%) pleomorphic carcinoma. 30 (41%) had stage I, 28 (38%) stage II, and 14 (19%) stage III disease, and one stage 4; 9 (12%) patients received neoadjuvant chemotherapy. Median tumor size was 4.0 cm and 67 (92%) underwent R0 resection. TIL expansion was successful in 47/67 (70%) cases. Phenotypic and functional analysis of freshly isolated and cultured TIL is ongoing. Preliminary results show suppression of intratumoral CD8+ cells as demonstrated by low perforin (p = 0.0002) and high CD8+ PD1 (p = 0.0007) levels as compared to normal tissue; however tumor CD8+CD28 co-stimulatory molecule expression was high p = 0.0003. PDX success rate has been 27%. IHC analyses show higher CD8+PD1, CD3, CD8+BTLA expression in SCC than in adenocarcinoma (p = 0.05). Exome sequencing and RNA sequencing from 19 patients show median mutation burden 466/tumor. Subclonal analysis, neoantigen prediction and expression status of predicted neoantigens are ongoing. Conclusions: ICON is an ambitious multi-team project designed to integrate wide range of tumor related data. Preliminary analysis demonstrates the project to be feasible with high rate of data acquisition. Tumors profiled from ICON will serve as a reference for the upcoming neoadjuvant single and dual checkpoint immunotherapy trial.

8537 Background: Neoadjuvant chemoradiation prior to surgery offers excellent locoregional control, while neoadjuvant chemotherapy I meant to offer improved systemic therapy in stage IIIA N2 non-small cell lung cancer (NSCLC). Data are lacking to select the optimal regimen. We compared oncologic outcomes for stage IIIA N2 NSCLC utilizing granular data from three experienced lung cancer treatment centers. Methods: This collaborative retrospective study unites 3 major thoracic centers with differing approaches to IIIA N2 NSCLC. Patients undergoing surgical resection post-neoadjuvant chemotherapy (CxT) or concurrent chemoradiation (CxRT) were included. Primary outcomes were overall and disease- free survival (OS and DFS). Results: Demographic data and outcome data are in Table 1. There were no differences in 5-year OS (CxT 40% vs CxRT 42%, p=0.265) nor in DFS (CxT 30% vs 31%, p=0.275). Recurrence rates (CxT47%vsCxRT48%,p=0.799) and patterns were identical (Local: CxT 10% vs CxRT 8%; and Distant: CxT 30%vsCxRT29%,p=0.764). There was no difference in peri-operative mortality. To address potential bias from differing staging strategies, we excluded patients without invasive mediastinal staging and there were still no differences in OS (CxT 40% vs CxRT 42%, p=0.364) and DFS (CxT 30% vs CxRT 31%, p=0.332) Multivariable analysis identified pnemonectomy (HR1.66,p

1532 Background: We hypothesized that telomere length in peripheral blood would have significant predictive value for risk of recurrence after curative resection in non-small cell lung cancer (NSCLC). Methods: This prospective study included 473 patients with histologically confirmed early stage NSCLC who underwent curative resection at MD Anderson Cancer Center between 1995 and 2008. Relative telomere length (RTL) of peripheral leukocytes was measured by real-time PCR. The risk of recurrence was estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) using a multivariable Cox proportional hazard regression model. Results: Median duration of follow-up was 61 months and 151 patients (32%) had developed recurrence at time of analysis. Patients who developed recurrence had significantly longer mean RTL compared to those without recurrence (1.13 vs 1.07, P=0.046). A subgroup analysis indicates that women had longer RTL compared to males (1.12 vs 1.06, P=0.025), and the patients with adenocarcinoma demonstrated longer RTL compared to those with other histologic types (1.11 vs 1.05, P=0.042). To determine if longer RTL in women and adenocarcinoma subgroup would predict risk of recurrence, multivariate Cox analysis adjusting for age, gender, stage, pack year and treatment regimens was performed. Longer telomeres were significantly associated with higher risk of developing recurrence in female (HR=2.25; 95% CI, 1.02-4.96, P=0.044) and adenocarcinoma subgroups (HR=2.19; 95% CI, 1.05-4.55, P=0.036). The increased risk of recurrence due to long RTL was more apparent in females with adenocarcinoma (HR=2.67; 95% CI, 1.19-6.03, P=0.018). Conclusions: This is the first prospective study to suggest that long RTL is associated with recurrence in early stage NSCLC after curative resection. Women and adenocarcinoma appear to be special subgroups in which telomere biology may play an important role. (Supported by NCI CA 111646, CA 55769, and CA 70907.)

490 Background: The exact benefit of preoperative chemotherapy prior to pulmonary metastasectomy for patients with metastatic colorectal carcinoma (CRC) is unknown. Here, we identify outcomes of preop chemo in pts w previously resected primary CRC who then had resectable pulmonary CRC metastases. Methods: We queried a prospectively collected database to identify pts who underwent pulmonary CRC metastasectomy and the specific chemo regimen given prior to but w/i 3 months of surgery. Two multivariate logistic analyses were performed to identify preop regimen as predictors of overall survival (OS) and progression free survival (PFS). Results: From Feb 2000 onwards, 229 pts underwent lung met resection (median age 61, range 24-82). Of those pts, 114 received preop chemo for a median duration of 4months (range 0.1-25.3mos). 41pts receiving 0-3 mos of preop chemo, 37 3-6mos, and 36 >6mos. 38pts received an oxaliplatin-based regimen (23 FOLFOX+bevacizumab [bev], 5 XELOX, 5 FOLFOX alone, 3 FOLFOX+cetuximab, 1 FOLFOX + novel TR-2/DR5 antibody, 1 oxali+irinotecan). 53 pts received an irinotecan-regimen. 29 received a capecitabine therapy. Pts on an oxali-based therapy had an improved OS vs alternate chemo regimen (mean OS 77.6 mos vs 54.2 mos, median OS not reached in oxali-group, p .001). However pts on an irinotecan-based regimen had a lower OS vs alternate chemo (median OS of 49.1mos vs 57.9mos, p .024). 5FU, capecitabine, or bev-based therapies did not significantly impact OS. The type of preop chemo regimen did not significantly affect PFS after lung met resection. Oxali-based regimen moved towards a favorable OS when compared to OS without any preop chemo but not of statistical significance (HR 0.69; 95% CI 0.287 to 1.663, p 0.409) while receiving a non-oxali-based preop regimen was associated with a shorter OS when compared to no preop chemo (HR 2.64; 95% CI 1.634 to 4.275, p

4086 Background: TMT strategy has the highest level-1 evidence for treating localized GEC. High rates of cCR (defined as post-chemoradiation negative endoscopic biopsy and physiologic uptake on PET) are common and have questioned the benefit from surgery in patients with cCR after chemoradiation. We hypothesized that cCR would be associated with a high rate of pathCR than < cCR. Methods: The data were analyzed retrospectively in 563 patients who had esophagectomy for GEC in between 2002 and 2010 at UTMDACC. Among them, 284 had TMT and post-chemoradiation endoscopic biopsies and PET (before surgery). Multiple statistical methods were used. Results: Of these 284 TMT patients, 218 (77%) patients achieved a cCR. However, only 67 (31%) of 218 had a pathCR. The sensitivity of cCR for pathCR was 97.1 % (67/69) but the specificity was low, 29.8 % (64/215). Intriguingly, 66 patients who had < cCR, only 2 patients (3%) had a pathCR. The difference in the rate of pathCR between the cCR and < cCR groups was significant (P < 0.001). Conclusions: Our data show that cCR is frequent after chemoradiation but the pathCR rate is not high and it is associated with specificity that is too low for clinical implementation. Therefore, all TMT-eligible patients, irrespective of the achievement of cCR or < cCR must be encouraged to undergo surgery. Therapies that overcome chemoradiation resistance and could increase the pathCR rate are needed for esophageal preservation in select GEC patients. Supported by UTMDACC and generous donors. [Table: see text]

66 Background: Although 3D-CRT is the current standard for treatment of esophageal cancers, IMRT improves dose conformality and reduces radiation exposure to normal tissue. There is no assessment of long term clinical outcomes comparing these two modalities. Methods: Between 1998-2008, 676 patients (3D-CRT=413, IMRT=263) with stage Ib-IVa (AJCC 2002 edition) esophageal cancers were treated with chemoradiation with or without surgery. To correct for potential bias inherent in observational studies, we employed inverse probability of treatment weighted (IPW) methods based on propensity scores. IPW survival plots and IPW log rank tests were used to adjust for potential bias in treatment selection. Treatment probabilities (propensity scores) were estimated using logistic regression. Results: IMRT patients were less likely to receive induction chemotherapy (35.7% vs 46.7%, p Conclusions: There was a substantially higher risk of non-cancer related deaths in 3D-CRT versus IMRT. While the true cause of death cannot be determined for many 3D-CRT patients, our results suggest that improvements in radiation technology may improve treatment-related mortality in management of esophageal cancer.

110 Background: Although 3D conformal radiation therapy (3D-CRT) is currently the de facto standard for the treatment of esophageal cancers, technologies such as Intensity Modulated Radiation Therapy (IMRT) or Proton Beam Therapy (PBT) are increasingly being used, but the evidence for the clinical benefits of these technologies are lacking. We hypothesized that radiation technology influences perioperative complications in esophageal cancer patients treated with neoadjuvant chemoradiation. Methods: We evaluated 423 patients (3D-CRT (n=208, 1998-2008), IMRT (n=165, 2004-2011), and PBT (n=50, 2006-2011)) treated with surgical resection after chemoradiation from 1998-2011 at M. D. Anderson Cancer Center. Postoperative complications (Pulmonary, GI, cardiac, wound healing) were recorded up to 30 days postoperatively. Kruskal-Wallis tests and Chi-square or Fisher’s exact tests assessed associations between continuous and categorical variables and the radiation technology, respectively. Logistic regression model tested the association between treatment technologies and complications adjusting for other significant patient characteristics. Results: While radiation modality was not significantly associated with postoperative GI (leak, ileus, fistula), cardiac (MI, AF, CHF), and wound complications, there was a significant reduction in postoperative pulmonary complications (ARDS, pleural effusion, respiratory insufficiency, pneumonia) for IMRT compared to 3D-CRT (OR 0.46, 95%CI 0.25, 0.83) and PBT compared to 3D-CRT (OR 0.26, 95%CI 0.09, 0.70), but not when IMRT was compared to PBT (OR 1.74, 95%CI 0.66, 4.61) after adjusting for preRT DLCO level. The median length of hospital stay was also significantly different between treatment modalities (12, 10, and 8 days for 3D-CRT, IMRT, and PBT, respectively, p Conclusions: Radiation technologies such as IMRT and PBT reduced postoperative pulmonary complication rates compared to 3D-CRT in esophageal cancer patients. This result needs to be confirmed in larger prospective studies.

4090 Background: High body mass index (H-BMI; ≥25 kg/m2) is common in US adults. We previously reported that H-BMI and low clinical stage were associated in a small cohort of esophageal carcinoma p...

7031 Background: Telomeres play a key role in maintaining chromosome stability. Shorter telomere length has been demonstrated to be a risk factor for lung cancer. A significant number of patients w...

7010 Background: Genetic polymorphic variants (SNPs) of DNA- and histone-modifying genes, in particular O6- methylguanine DNA-methyltransferase (MGMT), have been implicated in increased risk for de...

10060 Background: Sarcoma metastasizing to the heart is a difficult and complicated clinical problem, yet local control is feasible and effective for select patients with cardiac metastasis. Diligence is required to detect these lesions while still amenable to treatment, and echocardiogram remains the best tool for detecting cardiac disease. Methods: We reviewed all echocardiograms (1330) performed on 307 pediatric sarcoma patients treated at UT M. D. Anderson Cancer Center between 1997 and 2008. Measures of cardiac function and pathology (including size of ventricles and atria, function of ventricles and valves, presence of metastasis, and presence of pericardial effusion) were assigned numerical values. Fisher's exact test and the Wilcoxon rank-sum test compared clinical characteristics of patients with and without cardiac metastases. Results: The prevalence of cardiac metastases was 1.6% (5/307) with 95% confidence interval 0.5% to 3.8%. The presence of cardiac metastasis positively correlated with pericardial effusion (p = 0.001) and tricuspid valve insufficiency (p = 0.014). The probability of a patient with pericardial effusion having a cardiac metastasis was 28.6% (95% CI: 3.7%-71%). Of the 5 patients with documented sarcoma metastasis to the heart, 3 had widespread refractory disease, were given no cardiac-specific therapy, and rapidly died from disease. One patient who had widespread disease controlled with chemotherapy and radiation had open resection of 2 cardiac metastases which resulted in site-specific disease control for 6 months before succumbing to progressive extra-cardiac disease. Another patient had isolated cardiac metastasis, treated with open resection of 2 metastases followed by adjuvant chemotherapy, and has been without recurrent cardiac metastases for 5 years and 9 months. Conclusions: Durable local control for sarcoma metastasizing to the heart is possible and effective for select patients. Pericardial effusion merits evaluation for potential associated cardiac metastasis. Echocardiogram monitoring of sarcoma patients remains important, and should include screening for possible cardiac metastasis. No significant financial relationships to disclose.

7606 Objectives: To study the feasibility of detecting chromosomal deletions at the 3p and 10q regions in bronchoscopic brush biopsies and touch preparations by FISH and to study their distribution in different areas of the airway in patients with NSCLC. Methods: Bronchoscopic brush biopsies from the mainstem bronchus on the normal side contralateral to the tumor (NBB) and normal mainstem bronchus on the tumor side (TBB) were obtained from 120 patients who underwent surgical resection. Touch preparations from the tumor (TTP) and normal lung parenchyma from the involved lung (NTP) and from bronchi adjacent to the tumor (TAB) were also obtained. Two FISH assays using probes complementary to 3p22.1 and 10q22.3 were used for evaluation of chromosomal deletions at each site. The ratios of the percentage of deletions detected at different anatomical sites were compared using the Wilcoxon signed rank test. Correlations between deletions at TTP and other sites were estimated with a Spearman coefficient. Results: Contralateral normal bronchial tissue (NBB) showed a relatively low deletion rate of 3p and 10q compared to TTP (p No significant financial relationships to disclose.