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524 Background: Gallbladder and other biliary tract tumors account for 0.6 % of all cancers. There is scarce data of Ampullary cancers, but it is known as an extremely rare neoplasia accounting just for 0.2% of gastrointestinal cancers and 7% of periampullary tumors. Most frequent histology is adenocarcinoma being intestinal and pancreatobiliary subtypes conditioning prognosis and treatment. Current approaches include, but not limited to: neo/adyuvant, radiation and palliative therapy. Methods: We conducted a retrospective study in a referral specialized center in Mexico city. We included patients with histologically confirmed ampullary cancer treated between 2008 and 2022, stages I-IV. We evaluated the frequency of surgery, radiation therapy and chemotherapy. Also, we registered, first line, subsequent and maintenance therapy and as for radiation and chemoradiation. Chi square and student T test were used for between group comparisons. Overall survival was performed using the Kaplan Meier method. Results: We included 220 patients with a median age of 60.3 years (range 28-84), female 51.8%. The clinical stage distribution was I 10%, II 16.4%, III 41.3%, IV 32.3%. Performance status 0 (26.5%), 1 (44.5%), 2 (15.6%), 3 (10.4%), 4 (2.8%). Histologic Subtype Adenocarcinoma not otherwise specified 45.7%, Intestinal Adenocarcinoma 27.1%, Pancreatobiliary Adenocarcinoma 16.7%, Mix Intestinal-Pancreatobiliary 6.2%, Signet Ring Cell Adenocarcinoma 2.4%, Neuroendocrine 1.9%. Curative intend surgery in 169 patients was possible in 90%. Initial treatment received was Adjuvant 40.9%, Palliative 27.7%, Neoadjuvant 2.3% and Never Received any kind of treatment in 29.1%. Adjuvant Treatment was given to 94 patients. Among them Gemcitabine and Capecitabine was the election of treatment in 34% and 23.4 respectively. First line Treatment. Patients receiving first line treatment (110 patients) were candidates to Gemcitabine, XELOX, and Gemcitabine-Cisplatin in 30%, 13.6% and 12.7% according to physicians and 56% other line of treatment. Patients who progressed to first line received a second line in 19%. Most frequent second line of treatment was Capecitabine 61.9% and Gemcitabine 23.8%. Of the whole population Median Overall Survival was 30.68 months, Disease Free survival: 30.71 months and 8.0 months for progression free survival in first line. Conclusions: To our knowledge first real world based large volume study reporting treatment patterns and oncologic outcomes of a rare entity.

e18592 Background: There is an increasing trend of integrating molecular profiling to devise treatment plans for solid malignancies. Tumor testing for specific clonal abnormalities is being supplanted by broad multigene panel testing from blood specimen, aptly labelled liquid biopsy. Due to varying utility across malignancies in differing contexts and issues of access and affordability, their adoption is not uniform. We attempt to characterize the pattern of utilization across tumor types and financial coverage schemes in an academic cancer institute in southeastern United States. Methods: All blood based next generation testing samples ordered by providers affiliated to Georgia Cancer center between January 1, 2017, and December 31, 2021, via Guardant platform for all solid tumors was included in this analysis. Guardant360 and Guardant360CDx assays tested for upto 83 cancer related genes in circulating cell-free DNA in patients of solid tumors. Primary cancer diagnosis, insurance information and turnaround time was obtained from Guardant. Results: 296 tests were sent from January 1, 2017, through December 31, 2021. The total number of tests performed in year 2017, 2018, 2019, 2020 and 2021 were 1, 3, 28, 99 and 165 respectively. Billing information was available for all cases, clinical information was available for 262 cases. Average turnaround time was 8.5 days overall. 221 Guardant360 was sent with average turnaround time of 10 days. 41 Guardant360CDx was sent with average turnaround time of 7 days. The frequency of malignancies in the order of dimensioning frequency were lung 50.7%, prostate 12.1%, breast 6.9%, kidney 3.8% and colorectal 3.4%. The remaining 22.1% comprised of pancreatic, melanoma, glioblastoma, and bladder malignancies. The test was covered by private insurance/employee health plan in 53.4% (158/296), Medicare in 31.1% (92/296) and Medicaid in 10.5% (31/296) (table). 4.7% (14/296) qualified for free of charge testing (financial indigent) and 0.3% (1/296) were self-pay (table). Conclusions: There is an increase in the utilization of liquid biopsy to perform comprehensive genomic analysis. The distribution of tumor types is not entirely explained by the incidence and availability of targeted therapies for each type. Private insurers accounted for most of the tests being done. The disparities in utilization of this platform across different tumor types and payment models deserve further exploration. T[Table: see text]

8513 Background: In advanced non-small cell lung cancer (NSCLC), high Programmed-Death-1 Ligand (PD-L1) (>50%) expression demonstrate superior response and survival with immune checkpoint inhibitors compared to chemotherapy. We hypothesize that it is safe and feasible to substitute durvalumab instead of chemotherapy concurrently with radiotherapy (RT) in patients with Locally Advanced-NSCLC (LA-NSCLC) and high PD-L1. Methods: NRG-LU004 (NCT03801902) is a Phase I study for patients with stage II-III unresectable or inoperable, LA-NSCLC with PD-L1> 50% (Dako 22C3 or Ventana SP263) expression. There were safety and expansion phases with a primary endpoint of safety. Patients started with 1500 mg durvalumab Q4 weeks and thoracic RT within 2 weeks from 1st infusion. Durvalumab continued once a month up to 1 year. In the safety cohort, 6 patients in cohort 1 were treated with accelerated fractionated RT (ACRT) to 60 Gy in 15 fractions, followed by a required safety hold for 90 days. During cohort 1 safety hold, cohort 2 patients were treated with conventional RT 60 Gy in 30 fractions (CONV) followed by a 60-day safety hold. A cohort advanced to the expansion phase to enroll 6 more patients if safety criteria (0-1 patients with a dose limiting toxicity [DLT]) were met. If both cohorts were deemed safe, patients would be randomized 1:1 to ACRT or CONV with safety defined as < 4 of 12 evaluable patients per arm experiencing a DLT. Feasibility was defined as at least 80% of patients in each arm receiving at least 80% of the planned dose of durvalumab during the first 8 weeks. Results: 24 evaluable patients enrolled between January 2019 and June 2021. No DLTs were reported in cohort 1, and 1 (unrelated bronchopulmonary hemorrhage leading to discontinuation of durvalumab) in cohort 2. Both safety cohorts advanced to the expansion phase. All but one patient (CONV) received RT per protocol/with an acceptable variation. At the time of analysis, 24% had received all 13 cycles of durvalumab. For the ACRT cohort, there were 4 grade 3, 1 grade 4 (lymphopenia), and 1 grade 5 AE (lung infection, assessed as unrelated to therapy). For CONV, there were 8 grade 3, 0 grade 4, and 1 grade 5 AE (respiratory failure, unrelated to therapy). For feasibility, 10 of 12 (85%) patients in the ACRT cohort received the second dose of durvalumab (2 not received due to shingles and unrelated death), while 9 of 12 (75%) of the CONV cohort received the second dose (reasons for not receiving: viral hepatitis, bronchopulmonary hemorrhage, and respiratory failure, all assessed as unrelated to therapy). Conclusions: Chemotherapy-free thoracic RT approaches (ACRT or CONV RT) are safe, when given with concurrent durvalumab in patients with PD-L1 high LA-NSCLC. A trial to compare immunoradiotherapy and consolidation durvalumab to standard chemoradiation and consolidation durvalumab is planned. Clinical trial information: NCT03801902.

e15023 Background: The pool of somatic alterations with prognostic and predictive significance in management of solid tumors is rapidly expanding. Multigene panel testing using next generation sequencing (NGS) technology from peripheral blood specimen is convenient and readily available in most oncology practices. Widespread adoption is lagging, in part due to anticipation of low probability of finding an actionable information. We share our experience of real-world utilization of this technology. Methods: Blood based next generation testing ordered by providers in Georgia (outside Atlanta) between January 1, 2015, and December 31, 2021, via Guardant platform for all solid tumors was included in this analysis. Guardant360 and Guardant360CDx assays sequenced circulating cell-free DNA to detect somatic alterations in up to 83 cancer associated genes. Data was obtained from Guardant360 on site of cancer, comprehensive genomic profile, and therapeutic options at the time of report. Results: 25 providers in Georgia from 11 institutions sent 335 blood samples from solid cancer patients. There were 192 males and 143 females. Most common cancers were lung and bronchus (45%), prostate (13%), breast (11%), pancreaticobiliary (8%), colorectal (4%), melanoma (3%) and kidney (3%). Any somatic mutations were detected in 85% (285/335) patients. A total 1524 alterations comprising of 977 unique alterations involving 83 genes were detected, with an average of 5.3 unique genomic alterations per patient. The genes that were altered at least 2% of times were TP53 (20%), ATM (5.5%), PI3KCA (4.3%), KRAS (3.8%), APC (3.5%), AR (2.8%), PDGFRA (2.8%), ARIDIA (2.5%) and BRAF (2.2%). Of all alterations, 11% (170/1524) were synonymous and 31% (474/1524) were variant of unknown significance. 85 samples had tumor mutational burden (TMB) results available, with 55% (47/85) having TMB > 10 mut/Mb. The average TMB was 14.9 mutations/Mb. Out of 252 specimens evaluated for microsatellite instability (MSI), 1 had high MSI. An FDA approved drug targeting the alteration/pathway was available for the same cancer in 4% (77/1524) and for other cancers in 19% (291/1524) of alterations. An approved drug matched to the alteration was available for the same cancer in 16% (54/335) patients and for other cancers in 45% (153/335) patients. 12.5% (42/335) patients were predicted not to benefit from certain drugs. 74% (249/335) had a clinical trial available for the mutations present. Conclusions: Eighty five percent solid tumor patients had a positive result in blood based NGS. Seventy four percent patients had at least one therapeutically applicable (suggestion for a drug to target the alteration approved for the same/different cancers or lack of benefit due to the alteration) information. Thus, blood based NGS yields clinically relevant and actionable information to guide management in solid tumors.

e15110 Background: Carcinogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is a common oncogenic mutation found in lung cancer. It is a gain-of-function mutation that is the most commonly mutated oncogene in NSCLC; occurs in about 30% of all lung adenocarcinomas. A lot of progress has been made in targeted therapies against other oncogenic drivers, such as EGFR, HER2, MET, BRAF mutations. However, KRAS mutant lung cancer is still very difficult to manage and options are limited. Most recently, K-ras G12C has a newly approved novel targeted therapy. Different KRAS mutations may also represent different outcomes. Multiple studies have been looking into mutant KRAS and investigating it in the clinical relevance in lung cancer. Here we characterize a cohort of KRAS subtypes in all tumor types of lung cancer from south-eastern Georgia. Methods: This is a retrospective study that evaluated patients with K-ras mutant lung cancer from Augusta, Georgia geographical area. Samples were obtained from May 15th, 2015 to January 4th, 2022 and patients with KRAS mutant lung cancers were identified via Guardant platform. Results: In our cohort of patients, a total of 622 patients were evaluated in which 531 patients had a lung cancer diagnoses. Of those 531 patients, 383 had lung adenocarcinoma, 109 lung squamous cell, 34 NSCLC, 3 small cell, 1 lung carcinoid, and 1 large cell lung carcinoma. Of the 531 lung cancer patients, 14 (2.6%) patients expressed KRAS mutation with 12 (3.1%) patients expressing KRAS with lung adenocarcinoma. NRAS was expressed separately in 2 patients and HRAS was expressed separately in 1 patient. Our cohort of patients with K-ras mutant NSCLC had TP53 co-mutation in 78 (14%), MSI-High mutation in 60 (11%) patients, and EGFR mutation in 23 (4.3%) patients. The most common KRAS subtype in lung adenocarcinoma was G12V (42%), G12C (42%), and Y64D (8.3%). Two patients were unable to identify the type of the K-ras mutation. In addition, 92% of the carriers for KRAS mutation in lung adenocarcinoma were males. Its been noted that G12C mutation is the most common; however, in south-east Georgia, G12V is as common as G12C. Conclusions: KRAS mutation subtypes have distinct genomic landscape which requires further assessment to guide future therapeutic development. In the geographical area of Augusta, Georgia, KRAS subtype G12V is as common as G12C.

e20001 Background: Multiple Myeloma (MM) is a neoplasm of the post-germinal center, terminally differentiated B-cells. MM accounts for 1% of all types of cancer and 10% for all hematologic malignancies. Chronic hepatitis C virus (HCV) is an infection that affects over 71 million patients worldwide. Cytotoxic agents and immunosuppressive therapy as steroids are the main line of therapy in lymphoid malignancies, but these drugs may exacerbate chronic viral hepatitis and cause uncontrolled replication of hepatitis viruses. The impact of HCV infection on MM patients remains unclear. Objective: To assess the impact of HCV infection on the prognosis and management of MM patients. Methods: A 10-year retrospective study of MM patients was conducted at Cairo University Clinical Oncology Department from January 2009 to April 2019. Results: During this time, 150 patients were diagnosed with MM, 109 (72.7%) were HCV negative, 24 (16%) were HCV positive, and 17 (11.3%) with unknown HCV status. The median age was 51 and 54 years for HCV negative and positive groups respectively, with a statistically insignificant difference (p-value > 0.2). In the multivariate analysis, HCV infection was not an independent factor related to overall survival (OS), however age, creatinine and hemoglobin levels correlated significantly with OS (p < 0.009, 0.008, 0.031 respectively). The median OS for the HCV negative group was 31.11 months (95% CI: 22.62 - 39.61) compared to 37.66 months (95% CI: 7.19 - 68.13) for the HCV positive group. The median progression-free survival (PFS) for all patients was 18.9 months, for HCV positive patients was 15.36 months (95% CI: 13.18 – 17.54), and for HCV negative patients was 20.49 months (95% CI: 14.13 – 26.85). Age below 60 years and creatinine level less than 2 mg/dL were statistically significant for favorable disease-free survival (DFS) (p < 0.030, 0.034 respectively). Conclusions: Age, creatinine and hemoglobin levels are significant prognostic factors in MM but HCV status doesn’t affect the overall survival or progression-free survival. HCV infection should not contraindicate MM therapy.

e21504 Background: Patients with NSCLC with liver metastasis tend to have significantly reduced overall survival (OS) compared to NSCLC with metastasis to other sites. We aimed looking at the patients with lung cancer at our institution over a five year period and assess the outcome of NSCLC with liver metastasis based on different treatment modalities. Methods: This is a retrospective study of patients with NSCLC and liver metastasis over the past five years. Patient data was securely collected and stratified based on demographics, histology, driver mutation analysis, date of diagnosis, place of metastasis, date of treatment, types of treatment received, and date of death, as applicable. Results: Eight of 132 patients had liver metastasis. Out of which one had SCLC and was treated with carboplatin-etoposide-atezolizumab with OS of 17 months. Remaining seven were NSCLC where five patients had adenocarcinoma and 2 had squamous histology. Pembrolizumab was part of treatment for all 4 patients with adenocarcinoma. 5th patient was treated with chemotherapy and had OS of 2 months. Female to male ratio 3:2 for adenocarcinoma and 0:2 for squamous histology with equal ethnic distribution. Two patients had squamous histology, both males and had average OS of 4.5 months. Conclusions: Patients with liver metastasis regardless of the histology, have short overall survival. However it was observed that such patients when treated with immunotherapy as part of their treatment modality do much better compared to those who did not. Specifically immunotherapy benefits are more pronounced in patients with adenocarcinoma histology compared to squamous. However further studies are indicated to evaluate personalized approach to therapy in NSCLC with liver metastasis. Our study was limited based on our limited number of patients.

3027 Background: Autophagy is a catabolic process triggered in cells during periods of stress to enable their survival. Established tumors utilize autophagy to survive periods of metabolic or hypoxic stress. Inhibition of early stage autophagy can rescue cancer cells, while inhibition of late stage autophagy will lead to cell death due to accumulation of damaged organelles. The antimalarial drugs CQ and HCQ inhibit late phase autophagy. The goal of our study is to assess the safety, tolerability and activity of combining CQ/HCQ with CG in advanced solid tumor patients who either progressed on other therapies or in whom CG is a therapeutic option. Methods: This single institution phase 1 dose-escalation study was designed to evaluate the maximum tolerated dose (MTD) of CQ, later substituted with HCQ, in combination with CG in patients with previously treated advanced solid tumors. Secondary objectives were to determine ORR, PFS and OS. A starting dose of 50 mg of CQ/HCQ was used in conjunction with CG, and increased in increments of 50 mg in each dose cohort. Grade 3 or greater toxicity that is treatment-related, and was not self-limited, or controlled in less than 7 days was considered dose limiting toxicity (DLT). Results: Twenty-three patients were enrolled with a median follow up of 6 months. HCQ 100 mg was found to be the MTD in combination with CG with ≥Grade 3 thrombocytopenia and/or neutropenia as dose-limiting. Median OS was 11 months, and the 1- and 3- year overall survival rates were 30% and 7%, respectively. Median progression free survival was 5 months and the 6-, 12-, and 18-months progression-free survivals were 48%, 21% and 14%, respectively (Table). Conclusions: The MTD identified for CQ/HCQ was lower than previously reported with concomitant use of chemotherapeutic regimes, likely due to the myelosuppressive nature of CG. Clinical trial information: NCT02071537. [Table: see text]

e14272 Background: K-RAS is a non-targetable mutation with no established predictive value. However, PD-L1 is the only approved predictive marker for immunotherapy in NSCLC. K-RAS mutation like PD-L1 has been associated with smoking. TP53 and K-RAS mutations have been identified in aggressive neoplasms. We hypothesized that K-RAS mutant NSCLC has higher PD-L1 expression suggestive of improved response to immunotherapy. Methods: The Caris database from 2016 - 2018 was queried and patients with NSCLC were identified. ≥1% staining for PD-L1 (22c3 antibody) was considered positive. PD-L1 expression as well as K-RAS and TP53 mutation status were analyzed and correlation between different variables were identified using ANOVA. Results: We identified 8,471 patients with NSCLC, where 66% had TP53 mutation and 26.9% had K-RAS mutation; both mutations were identified in 12% of the patients. In the subset of combined K-RAS and TP53 mutations there were 71.48% having positive PD-L1 expression with female predominance 1.4:1. Of the eight main K-RAS mutation subsets, G12C subset was the most common. Compared to other K-RAS subtypes, G12C was associated with the higher occurrence of PD-L1 positivity (62.68%,p < 0.04; Table). Conclusions: In comparison to other subsets of K-RAS mutation, G12C had the highest occurrence of PD-L1 expression, suggestive of improved response to immunotherapy. However, the subset of patients with combined K-RAS and TP53 mutations had a higher occurrence for the PD-L1 positive status of 71.48%. [Table: see text]

9100 Background: Loss of DNA repair fidelity is a common feature of human cancers and can drive genomic instability and tumor evolution. DNA repair deficiency has also emerged as a predictive biomarker of response to PARP inhibition and more recently to immune checkpoint inhibition. Information on relationship between DNA repair defects and TMB in NSCLC is limited. Methods: We analyzed molecular profiles of 5667 NSCLC tumors harboring mutations in DDR genes ( ATM, ATR, BARD1, BLM, BRCA1/2, BRIP1, CHEK1/2, ERCC2/3, FANCA/C/D2/E/F/G/L, MLH1, MSH2/6, MRE11, NBN, PALB2, POLE, PTEN, RAD50/51, WRN). Profiles included next-generation sequencing of 592 genes, TMB, and PD-L1 (22c3) by immunohistochemistry. Association of DDR gene mutations with immune biomarkers (TMB and PD-L1) was assessed. Results: Of the 5667 samples, 54% (n = 3060) had high TMB (defined as ≥10 mutations/Mb) with median TMB of 14 (range, 10-168). Among the remaining 46% (n = 2607) with low TMB, median TMB was 7 (range, 1-9). PD-L1 expression was high (≥50%) in 33% (n = 1878), intermediate (1-49%) in 26% (n = 1446), and negative ( < 1%) in 41% (n = 2343). Among all DDR mutated pts, 19% (n = 1058) had both high PD-L1 and high TMB, 35% (n = 2002) had high TMB alone, 15% (n = 820) had high PD-L1 alone. Most commonly mutated genes were RAD50 (52%), WRN (29%), CHEK2 (20%), ATM (19%), MRE11 (19%), and ATR (18%). Genes with a high likelihood of being associated with high TMB were ATM, ATR, BARD1, BRCA1, BRCA2, ERCC2, ERCC3, FANCA, MSH2, PALB2, and POLE. Strongest association was seen with BRCA1 (OR 1.81, 95% CI 1.47-2.22), PALB2 (OR 1.76, 95% CI 1.40-2.21), and POLE (OR 1.71, 95% CI 1.45-2.01). DDR genes mutations were not mutually exclusive - 77.5% (n = 4397) had 2 or more mutated genes. Tumors with ≥3 mutated genes were more likely to be associated with high TMB. No such correlation was observed with PD-L1 expression. Conclusions: The majority of NSCLC pts harboring DDR gene mutations have high TMB. Presence of ≥3 gene mutations and BRCA1, PALB2, and POLE mutations strongly correlate with high TMB. These patients may represent a unique subset that is more likely to benefıt from immune checkpoint blockade and PARP inhibition.

2626 Background: Early data suggests that co-occurring genetic events define biological heterogeneity in K-RAS mutant NSCLC, with K-RAS/ TP-53 (KP) co-mutated subset having potential therapeutic vulnerabilities to immune checkpoint blockade (ICB). To explore the immunological basis for these findings, we evaluated the immune biomarker profile (TMB/PD-L1) in KP mutant m-NSCLC using a large next-generation sequencing (NGS) dataset. Methods: Caris life sciences NGS dataset consisting of 1317 m-NSCLC tissue samples from 2016-18 was queried. PD-L1pos was defined as ≥ 1% staining using 22c3 Dako assay. TMB was measured by counting all somatic non-synonymous missense mutations using targeted NGS (592 genes). TMB-high (H) was defined as ≥ 10 mutations/Megabase (mut/Mb). P-values were calculated using Chi-square and Mann-Whitney test. Results: K-RAS mutations were identified in 28.7% (378/1317). Within this K-RAS mutant group, KP subset constituted 49.4% (187/378), remaining were K-RAS mutated/ TP-53 wild type (K-Pwt). 72.2 % (135/187) of KP had PD-L1pos with 51.9% (97/187) having PD-L1 ≥ 50%. KP had higher median TMB vs. K-Pwt (14.5 vs. 9.0 mut/Mb, pneg group, KP had higher % of TMB-H vs. K-Pwt (86.5 vs. 41.5%, pneg subgroup. Metastatic site-specific variations in TMB were also observed for the KP subset. These findings could have therapeutic implications in guiding patient selection for ICB and merit prospective investigation.[Table: see text]

e21548Background: Metastatic uveal melanoma (MUM) is associated with poor prognosis with a median overall survival (OS) of 4-15 months. Patients with MUM have low response rates to traditional trea...

514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP NET´s) are infrequent tumors, with a variety of symptoms depending of the kind of peptide they secrete as well as the affected organs. Long acting somatostatin analogues have shown an adequate rate of symptom control in functional tumors, they also have demonstrated antiproliferative effect, which is translated in a significant improvement of progression free and overall survival Methods: In this retrospective analysis of patients with metastatic GEP NET treated with long acting somatostatin analogues as first line, treated between 2005 and 2015, we evaluated clinical and pathological features, symptoms, disease control and survival adjusted with OMS classification Results: Our cohort included 95 patients with a mean age of 53 years. Primary affected sites were midgut (29.4%), followed by pNET (17.%), stomach (14.7%), and primary unknown in 14%. 20% of cases were functional tumors with diarrhea as the most common symptom in 70% and flushing in 50%. Considering the whole cohort the most prevalent symptom was abdominal pain in the 50% of cases. The OMS classification showed low grade tumors in 65% and 35% intermediate grade. Most common metastatic organ sites were; liver only 35%, liver and other 30%, peritoneum 10% and lymph nodes in 6%, non-specified sites in 19%. Somatostatine analogues used in first line were octreotide in 80% and lanreotide in 20%. Survival results demonstrated a progression free survival for the whole cohort of 84months. No differences between lanreotide and octreotide were observed. Conclusions: This study represents the first Mexican cohort of patients with GEP NET’s treated with somatostatin analogues with a long follow up.

9058 Background: Chemotherapy can benefit pts with advanced NSCLC with poor Eastern Cooperative Oncology Group (ECOG) PS, despite an increased toxicity risk vs those with good PS. Safety and efficacy of nab-P/carboplatin ( nab-P/C) induction followed by nab-P monotherapy in pts with advanced NSCLC and ECOG PS 2 are reported. Methods: Chemotherapy-naive pts with histologically/cytologically confirmed stage IIIB/IV NSCLC and ECOG PS 2 received 4 cycles of nab-P 100 mg/m2 d 1, 8 + C AUC 5 d 1 q3w. Pts without disease progression were eligible for monotherapy with nab-P 100 mg/m2d 1, 8 q3w until progression/unacceptable toxicity. Primary endpoint: percentage of pts discontinuing within the first 4 cycles due to treatment-emergent adverse events (TEAEs). Other endpoints: PFS, DCR, OS, ORR, and QoL. Results: Forty pts were treated during the first 4 cycles. Median age was 67.5 y, 60.0% were male, 92.5% were white, and 65.0% had nonsquamous histology. In the primary analysis, 9/40 pts (22.5%) discontinued due to TEAEs during induction. In total, 16/40 pts (40.0%) received nab-P as monotherapy. At the time of data cutoff, 4/40 pts remained on therapy beyond 11 cycles. In all treated pts, the median percentage of per-protocol dose of nab-P was 79.8% and the median nab-P dose intensity was 53.2 mg/m2/week (expected, 66.67 mg/m2/week). See table for other key safety and efficacy data. QoL by LCSS (global) was improved during the study, and similarly EQ-5D-5L dimensions were stable/improved at least once in the majority of pts. Conclusions: This nab-P–based regimen was well tolerated in PS 2 pts with advanced NSCLC. Efficacy outcomes are comparable with previous chemotherapy data with promising QoL. The results support the efficacy and tolerability of this regimen in these pts. NCT02289456. Clinical trial information: NCT02289456. [Table: see text]

e22237 Background: Recent preclinical data through a systematic drug-repurposing computational approach querying a large number of gene expression datasets identified TCAs as having a survival bene...

e19150 Background: Low Molecular Heparin (LMWH) is approved for treatment of and secondary prophylaxis against thromboembolic events in patients with cancer. However, its role in improving Overall ...

e20105 Background: UM is the rarest subset of all melanomas and has a distinct molecular pathogenesis. Once metastasis develop, the prognosis becomes very poor, however, overall survival (OS) is no...

e18513 Lymphopenia as the predictor of survival in chemo radiation (CRT) treated stage III non-small cell lung cancer (NSCLC) Background: Despite potential curative CRT treatment for locally advanc...

224 Background: Stromal tumors of the digestive tract are uncommon malignant diseases, and are subclassified as leiomyosarcomas and gastrointestinal stromal tumors (GIST) depending on the molecular expression of CD117 (KIT). GISTs represent 1% of malignant tumors affecting this anatomical site. Located diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since Tyrosine – kinase inhibitors were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods: We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results: We obtained information of 71 patients with metastatic, nonresectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%), with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%) most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 23.6m and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400mg per day. Treatment was well tolerated in most cases. Conclusions: Metastatic GIST evaluated in our center shows a different affection in gender and age, our population shows a different response to TKI’s, than reported in other series with superior overall survival, Poor prognosis is associated with lung affection. Biological studies will be started for the molecular evaluation of these tumors.

e18502 Background: LCNEC of the lung exhibits morphological and immunohistochemical characteristics of both neuroendocrine and large cell carcinoma. Optimal treatment for LCNEC remains unclear. Pat...

e13518 Background: The mammalian target of rapamycin (mTOR) is a critical signaling pathway in many tumors including cancers of the breast and colon, glioblastoma multiforme, and hepatocellular carcinoma (HCC). Preclinical studies demonstrated the combination of BEZ235, a competitive dual phosphatidylinositide 3-kinase (PI3K)/mTOR inhibitor, and the mTOR inhibitor, everolimus led to greater regression of a carcinogen-induced HCC than treatment with higher doses of either drug alone. Based on this, we initiated a study of BEZ235 combined with everolimus in patients with advanced solid tumors. Methods: A single institution phase Ib dose-escalation study. Patients with advanced solid malignancies, no available standard of care treatment option, and ECOG performance status 0-2 were eligible. Prior treatment with PI3K inhibitors was not allowed. Sequential cohorts of 3-6 patients were treated. The starting dose was everolimus 2.5 mg and BEZ235 200 mg daily in an oral sachet formulation. Cohort 2 received everolimus 2.5 mg and BEZ235 400 mg daily. Pharmacokinetic and pharmacodynamic studies were performed during the first cycle. The phosphorylation of specific downstream effectors of the mTOR pathway was assessed in peripheral blood mononuclear cells (PBMC). Results: Eleven patients, median age 58 (36-73 years) were treated. Tumors included non-small cell lung cancer, colon cancer, and glioblastoma, hepatocellular carcinoma, pancreatic cancer, esophageal cancer, adenoid cystic carcinoma of the larynx, and appendiceal carcinoma. Four patients were treated on cohort 1. None experienced dose-limiting toxicity. Seven patients were treated on the second dose cohort. One patient withdrew necessitating replacement and another developed grade 3 stomatitis from herpes virus requiring cohort expansion. The most common adverse events were thrombocytopenia, lymphopenia, transaminitis, diarrhea, nausea and fatigue. No tumor responses were noted. PBMC showed a decrease in 4E-BP1S65 phosphorylation on day 28 in 2 of 3 patients in cohort 1. Conclusions: The combination of BEZ235 and everolimus was well tolerated at these doses. The trial remains open to accrual. Clinical trial information: NCT01508104.

TPS3116 Background: Downregulation of a number of signaling pathways, including the mammalian target of rapamycin (mTOR) pathway, has been demonstrated to be efficacious in a large range of solid tumors such as breast, colon, endometrial, glial and hepatocellular carcinoma (HCC). However, we find that rapamycins lead to suppression of a negative feedback loop from S6 Kinase 1 (S6K1) to Protein Kinase B (PKB), leading to hyperactivation of PKB. In pre-clinical studies using a mouse model of carcinogen-induced HCC, we have demonstrated that combining BEZ235 (a potent and highly selective reversible ATP site competitive inhibitor of PI3K and mTOR) with everolimus (an allosteric inhibitor of mTOR) synergizes to inhibit tumor growth. BEZ235, an orally administered agent, has demonstrated preliminary antitumor activity in a first-in-human phase I study. The current study will evaluate this combination in patients with a variety of solid malignancies that includes glioblastoma multiforme (GBM). Methods: This study is divided into a phase 1b portion designed to determine safety of increasing doses of the combination, with extensive pharmacokinetics, pharmacodynamics and pharmacogenomics analysis; and a phase 2 portion that includes both solid tumors and GBM based on predominance of the mTOR and PI3K deregulation in these tumors, to determine preliminary anti-tumor activity and the recommended dose for phase 2 studies. We will also integrate biomarker assessment for gene expression products of the mTOR downstream pathway such as eukaryotic initiation factor 4E binding protein (4EBP1) and S6 kinase (S6K). The phase 1b portion has started accruing.

e15567 Background: Primary debulking surgery is considered the standard of treatment in advanced ovarian cancer (AOC) while neoadjuvant chemotherapy is used in non resectable stages. Methods: We retrospectively analyzed 68 AOC cases from January 2000 to December 2011. 35 received neoadjuvant chemotherapy (NAC) while 33 were resected primarily and received adjuvant chemotherapy (AC). To compare both groups we used T standard test and 2 sided chi -squared. Non parametric variables were analyzed with U Mann – Whitney. Overall survival(OS) was analyzed using Kaplan Meier method with log rank test. We considered statistically significant p-26 months for neoadjuvant and 27+/- 35 months for primary surgery (p=0.56). In a subgroup analysis of patients who received 6 neoadjuvant cycles vs perioperatory chemotherapy (3 pre and 3 postoperatory) we observed a significant survival difference, with a median of 62 months (95% CI 12-38) vs 12 months (95% CI 54 – 178) respectively (p=0.010). Conclusions: Non inferior survival or differences in surgical outcomes were observed with neoadjuvant therapy. Significant survival increase was observed in patients who received complete chemotherapy schedule before surgery, this evidence allowed to design a prospective trial in our Institution.

e18014 Background: EML4-ALK gene translocation is a novel carcinogenic change described in NSCLC in 2007. Prior studies report this translocation in 1-11% of screened patients (pts) and an association with never/light smoking, male sex, absence of EGFR or KRAS mutations, and adenocarcinoma histology. Compared to other NSCLC pts, ALK positive pts have similar responses to platinum chemotherapy, resistance to erlotinib, and no difference in OS. 82 ALK positive NSCLC pts were treated on a phase I trial of crizotinib (ALK inhibitor) with an ORR of 57% with 46 PRs and 1 CR. Phase II/III trials of crizotinib in selected pts are ongoing. We report the experience with EML4-ALK translocation NSCLC pts at the Ohio State University Comprehensive Cancer Center. Methods: ALK translocation screening was performed using FISH on pts with adenocarcinoma or light/never smokers, who were EGFR/KRAS mutation negative. FISH analysis was performed with LSI ALK dual color break-apart probe; a positive result was 10% or more tumo...

e12504 Background: This study aims at investigating the correlation between O6-methylguanine DNA-methyl transferase (MGMT) promoter methylation with Ki-67 labeling index to the response, time to pr...

TPS291 Background: Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancers diagnosed. In metastatic NSCLC, a platinum-based doublet remains the standard of care, with the addition of bevacizumab, an antiangiogenic agent, when feasible. Antiangiogenic agents result in improved response rates and survival, but bleeding is a significant potential toxicity. In particular, patients with squamous histology and a history of hemopytsis are excluded from treatment with this agent due to bleeding risk. Nab-paclitaxel, an albumin-bound formulation of paclitaxel, an agent commonly used in NSCLC treatment, was safe and effective in phase I/II studies, producing 16-30% response rates (RR). In a phase II study, combination treatment with nab-paclitaxel and carboplatin demonstrated improved efficacy (47% RR). The objective of this trial is to determine the response rate of nab-paclitaxel with carboplatin in patients who are ineligible for bevacizumab therapy. Methods: Eligible patients include a...

e22129 Background: ERCC1 is a useful marker of resistance to cisplatin and its analogues. Longer survival was noted in patients with ERCC1 negative expression when treated with platinum. VEGF and its receptor-KDR previously indicated poor prognosis with high tumor cell expression. Methods: From 1998–2008, a retrospective study included 32 patients with advanced NSCLC, where clinical variants as well as the levels of expression of VEGF and VEGFR using rabbit monoclonal Ab (VEGF: A-20, 1:100, SCBT; VEGFR: 55B11, 1:250, cell signaling) and immunohistochemistry for ERCC1 (Mouse monoclonal ab-8F1, Thermo Scientific, 1:200) were measured and co-related to the overall survival of those patients using Cox proportional hazards model. Results: Of the 32 patients, six received non-platinum and twenty six received platinum based regimens either first line or later. Eight patients were females (25%), three were African Americans (9%) and the median age was 62.5 (42–84). Females had a significantly higher overall survival; median survival of 30 months compared to 10.6 months for males (p=0.00089). There was no significant correlation between age and survival (p=0.2). Well differentiated NSCLC of any subtype showed better survival (p=0.04). VEGF low expression correlated with better overall survival (p=0.021). Among the 26 patients who received platinum based regimens, 11 (42%) were ERCC1 negative, 10 had strongly positive ERCC1 expression (39%) and 5 patients had weakly positive ERCC1 expression (19%). ERCC1 negativity was strongly associated with longer survival (p=0.0019) in patients treated with platinum based regimens, where patients treated with the first line platinum had better survival (p=0.034). VEGFR low expression was associated with longer survival in the same group of patients (p=0.013). Caucasians had better overall survival in comparison to African Americans (p=0.007). Higher White blood cell counts and platelet counts were associated with lower survival (p=0.0019 and 0.065 respectively). Conclusion: ERCC1 negativitiy with the first line platinum therapy, VEGF low expression, females, Caucasians as well as the absence of elevation of White blood cells and platelet counts correlate with improved overall survival in advanced NSCLC. No significant financial relationships to disclose.

e15117 Background: Retrieval of 12 lymph nodes (LN) is a current benchmark in colorectal cancer (CRC) resections according to the National Quality Forum (NQF). Series of multiple institutions contain variability in surgical and pathologic techniques for lymph node retrieval. To ensure consistency in retrieving lymph nodes for satisfactory staging, we present a 12 year experience by a single surgeon and single pathology lab at one VAMC on 157 patients (mean age 67) undergoing CRC resection. Furthermore, the use of chemotherapy for Stage II patients 12LN; 2)Number of LN identified and impact on AJCC tumor stage (TS) and overall survival; 3)Number of LN and WHO tumor grade (TG) with OS; 4)The impact of number of positive LN on OS. Results: Our mean LN found (14.75) is higher than the 12 recommended by the NQF and is not significantly associated with OS regardless of AJCC TS(p=0.06). The mean LN per TS was I=13.4(N=41)/II=16.3(N=56)/ III=14.3(N=38)/IV 14.2(N=22). Number of LN identified was not statistically significant in predicting TS(p=0.42) or OS(p=0.24). WHO TG is significantly associated to decreased OS, but only in AJCC TS II/III/IV and not stage I (Ip>0.05/IIp=0.008/ IIIp=0.01/IVp=0.025). Higher number of positive LN was associated with lower OS (per each +LN, survival decreases by 0.15 months p=0.001) Conclusions: Contrary to multicenter studies, total number of LN identified does not impact AJCC TS or OS. Higher WHO TG and higher number of positive LN is associated with worse OS. This suggests that the tumor biology is more indicative of OS rather than host response (reactive lymphoid tissue) to the tumor. Stage II patients No significant financial relationships to disclose.

8279 Background: As many as 60% of cancer patients are 65 or older. However, geriatric patients may receive care from physicians lacking formal training in geriatrics. Geriatric oncology is a growi...