Non-squamous Cell Lung Cancer Research Articles

Impact of tissue biomarker testing by in-house platform on result times in metastatic non-small cell lung cancer.

49 Background: Biomarker testing for actionable mutations is standard of care for patients diagnosed with metastatic non-small cell, non-squamous cell lung cancer. However, testing via third-party laboratories can take weeks to result, leading to treatment decision delays identified at our own institution. Methods: We conducted a retrospective chart review of metastatic non-small cell, non-squamous cell lung cancer patients treated at Orlando Regional Medical Center before (6/1/2021-5/31/2022) as well as after (1/1/2023-5/31/2023) the initiation of in-house next generation sequencing (NGS) tissue testing using Genexus. Endpoints included average and median time to result of plasma and tissue NGS both before and after initiation of in-house molecular testing. An independent two sample t-test was conducted with p<0.05 considered significant. Results: A total of 49 and 18 patients were included pre and post initiation of in house NGS, respectively. For patients with tissue testing, the average time from collection to result was 31.3 versus 13.9 days (p<0.01), median 29 versus 7 days. For patients who underwent plasma testing (n=49, n=10), average time from collection to result was 13.3 versus 9.6 days (p=0.38), median 9 versus 9 days. Conclusions: Time to comprehensive tissue testing result significantly decreased after the commencement of in-house NGS. Rapid turnaround time allows clinicians to select appropriate first-line treatment without delay in care. Further efforts are needed to expedite molecular testing in all stages of non-small cell lung cancer and evaluate sequential versus concurrent plasma and tissue testing.

Comprehensive molecular testing prior to first treatment among patient with metastatic non-small cell lung cancer.

431 Background: Nearly 60% of patients with non-small cell lung cancer will have actionable mutations identified via molecular testing. Of these patients, those treated with targeted therapy had longer overall survival than those who did not. Therefore, it is imperative molecular testing is both sent and resulted at time of first treatment. Despite this, multiple barriers remain with reported community rates of <50% with comprehensive molecular testing. We sought to understand testing practices at our institution. Methods: In this retrospective chart review, patients with stage IV, non-small cell, non-squamous cell lung cancer treated at Orlando Regional Medical Center between 1/2021-5/31/2022 were identified. Primary endpoints included rate of comprehensive molecular testing (EGFR, ALK, ROS1, RET, MET, BRAF, KRAS, ErbB2 and NTRK, either tissue or plasma) available prior to first line treatment. Results: Of the 73 patients who were included, 69 patients (94.8%) had comprehensive molecular testing results available prior to first line treatment. 48 (65.8%) patients had tissue testing results prior to first treatment. 44 (60.2%) patients had plasma testing results prior to first treatment. 14 (19.2%) patients had tissue testing sent, without results at time of first treatment. Conclusions: The comprehensive molecular testing rate at a large tertiary hospital is 94.8%, substantially higher than the rates reported in the literature. Despite this, 19.2% of patients had tissue testing sent but not resulted at time of first treatment. Future studies are needed to improve turnaround time of tissue based molecular testing results and evaluate concurrent versus sequential tissue and plasma testing.

Bevacizumab-Induced Thrombotic Microangiopathy (TMA) in Metastatic Lung Adenocarcinoma Patients Receiving Nivolumab Combined with Bevacizumab, Carboplatin and Paclitaxel: Two Case Reports

Anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs), combined with bevacizumab and platinum-based chemotherapy, have shown promising efficacy in treating metastatic non-squamous cell lung cancer in phase 3 clinical trials. However, drug-induced nephrotoxicity is an uncommon but threatening adverse effect when using this combination therapy, and should be evaluated and managed carefully. Here, we present two patients experiencing late-onset asymptomatic heavy proteinuria during the clinical trial. Kidney biopsies performed finally identified bevacizumab-induced thrombotic microangiopathy (TMA), and the proteinuria was decreased after discontinuing bevacizumab permanently. Our report suggests that a kidney biopsy is needed for those receiving ICIs in combination with bevacizumab and chemotherapy and experiencing nephrotoxicity such as heavy proteinuria.

Prognostic value of plasma D-dimer levels in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: a retrospective study.

Plasma D-dimer is of great significance for the clinical exclusion of tumor-related thrombosis. Previous studies have shown its predictive role in non-small cell lung cancer (NSCLC) treated with chemotherapy. However, whether pretreatment D-dimer could predict the efficacy and prognosis in NSCLC patients treated with immune checkpoint inhibitors (ICIs) remains unclear. Advanced NSCLC patients treated with ICIs at the Chinese PLA General Hospital between January 2015 and March 2019 were enrolled. Patients were divided into a pretreatment normal D-dimer group (≤0.5 µg/mL) and high D-dimer group (>0.5 µg/mL). Optimization-based approach was applied to balance baseline covariates between the 2 groups, including age, sex, histological type, smoking history, stage, Eastern Cooperative Oncology Group Performance Status (ECOG PS), lines of treatment, ICI drugs, brain metastasis, treatment type, and D-dimer levels. Kaplan-Meier analysis and Cox proportional hazards model were used for analyzing survival data, including progression-free survival (PFS, the time from initial ICI treatment to PD or death), overall survival (OS, the time between initial ICI treatment and death), and hazard ratio (HR). Follow-up of all patients was performed by searching electronic medical records and counseling telephone. The follow-up cut-off date was July 6, 2020. This study included 277 advanced NSCLC patients. Among the enrolled patients, 23.1% were female, 64.6% had non-squamous cell lung cancer, and 79.4% were stage IV. Univariate and multivariate analysis showed that pretreatment high D-dimer levels were independently associated with shortened PFS and OS (P<0.01). Subgroup analysis confirmed that pretreatment high D-dimer levels were associated with poor prognosis in most subsets. After balancing baseline covariates between the high D-dimer group and normal D-dimer group, the results indicated that patients with pretreatment high D-dimer levels had significantly shorter PFS [median: 6.4 vs. 11.5 months; HR, 1.70; 95% confidence ratio (CI): 1.25-2.37; P<0.001] and OS (median: 12.7 vs. 30.4 months; HR, 2.29; 95% CI: 1.54-3.41; P<0.001) than those with pretreatment normal D-dimer levels. Pretreatment plasma D-dimer could serve as a convenient prognostic biomarker for advanced NSCLC patients receiving ICI treatment. Patients with pretreatment high D-dimer levels may have poor PFS and OS.

Comparative study of death-associated protein kinase promoter methylation between nonsquamous and squamous subtypes of nonsmall cell lung cancer

Background Lung cancer is a leading cause of cancer-related mortality in the world. Nonsmall cell lung cancer (NSCLC) can be classified as nonsquamous cell carcinoma (non-SCC) and squamous cell carcinoma (SCC). NSCLC pathogenesis includes altered methylation patterns in multiple genes. Promotor methylation of death-associated protein kinase (DAPK) has been documented in various tumors. Aim To compare DAPK promoter methylation and clinical characteristics in patients of nonsquamous cell lung cancer with those of SCC. Patients and methods A case–control study was conducted on fresh-frozen tumor samples from 81 patients with primary NSCLC, including 43 non-SCC cases and 38 SCC cases, investigated in the Chest Department, Mansoura University Hospital, in the period from June 2017 to January 2020. A total of 40 patients matched for age and sex with nonmalignant lung lesions served as controls. Patients with age more than 18 years, radiological suggestions of lung cancer, and histologically diagnosed NSCLC were included, whereas patients with malignancies other than NSCLC or unfit for bronchoscopy were excluded. A pathologist histologically examined each lung tumor to define the type and other clinical characteristics of the tumor. DNA was isolated from fresh-frozen tissues, and the detection of DNA methylation was performed using methylation-specific PCR. Results NSCLC case groups included 43 nonsquamous cells and 38 squamous cells, with a mean age of 62.89±5.5 and 64.19±5.87 years, respectively. The control group included 40 patients, with a mean age of 61.37±6.64 years. There were statistically significant differences regarding smoking status (P=0.002) and the clinical characteristics suggestive of lung cancer between both patients with NSCLC and controls, but the differences between SCC and non-SCC were not significant. The results were significantly different between the two groups concerning chest radiograph and computed tomographic finding, where the peripheral mass was significantly higher in non-SCC than SCC (P&lt;0.001). DAPK promoter methylation was significantly higher for NSCLC (both SCC and non-SCC) as compared with controls (P≤0.001), but there was no significant difference between SCC and non-SCC groups. Conclusion Detection of the aberrant DAPK hypermethylation in tumor DNA from patients with NSCLC may provide an effective means for early auxiliary diagnosis of the malignancy but cannot distinguish between the histopathological types.

338 Biceps Metastasis Presenting as A Presumed Abscess in Patient with An Undiagnosed Non-Small Cell Lung Cancer - An Unusual Presentation

Abstract Lung cancer is the most common cancer worldwide and has highest cancer mortality. Around 50% of cases present with metastasis, however skeletal muscle metastasis is rarely reported. In this case we describe a fifty-nine-year-old male patient who presented complaining of fever and a mass on the distal biceps and proximal forearm over a five-month period, with no reported improvement despite debridement and antibiotics spanning three presentations to the emergency department. Subsequent biopsy at various anatomical sites showed adenocarcinoma, later identified as metastatic from a primary non squamous-cell lung cancer (NSCLC). Metastases from lung cancer are more commonly limited to liver and adrenal glands. Presentation of such a mass in skeletal muscle would raise suspicion for the more-commonly seen soft-tissue sarcoma or hemangiomas. This case illustrates a rare example of lung cancer metastatic to skeletal muscle, more specifically, the biceps. Presentation of the mass was also unique in its morphology of an abscess with purulent discharge, raising the importance of cytology and suspicion for malignancy in an abscess unresponsive to antibiotics. Non-small cell lung cancer can present with skeletal metastasis. A work-up of a mass or abscess of the muscle should include the possibility of soft tissue metastasis.

A Severe Case of Hypothyroidism: Immunotherapy Induced

Background: Immune check point inhibitors are playing a crucial role in the treatment of many cancers. Their primary role is to reactivate anti tumor cytotoxic T cells. Programmed cell death 1(PD 1) is a transmembrane protein expressed on T cells, B cells and Natural killer cells. PD 1 ligand is expressed in many tumor cells along with hematopoietic cells and their interaction directly inhibits apoptosis of the tumor cell. Pembrolizumab binds PD1. FDA approved pembrolizumab initially for nonsquamous cell lung cancer and metastatic melanoma that express PD1 ligand which showed improved survival compared to standard therapy. Additionally it has been used in several others tumors with more than 50% PD L1 expression. Although well tolerated, these agents can cause immune related adverse events. Thyroid dysfunction is reported to range between 3.2-10.1% patients receiving pembrolizumab. Clinical Case: 86 year old Caucasian female with past medical history of hypertension and osteoarthritis was diagnosed with stage III metastatic colon cancer in the hepatic flexure and underwent hemicolectomy. Pathology showed 6.5cm mass and 2/30 lymph nodes positive. Due to fear of side effects from chemotherapy, patient refused further treatment. Her follow up labs showed elevation of carcinoembyronic antigen (CEA). Her oncologist suggested Pembrolizumab, immunotherapy. She was started on 5 cycles every 3 weeks. She had fatigue and fell twice after first cycle, but her CEA levels were improving, so it was decided to continue treatment. Soon after fifth cycle she became extremely weak, lethargic, and unable to do any ADLS and was exhausted all the time. Her labs showed TSH 137, free T4 0.4. At that point decision was made to stop pembrolizumab. She was started on levothyroxine 25mcg by her oncologist and referred to me few months later. She complained of tiredness, low energy. On exam Pulse 78, Blood pressure 152/77. Her labs showed TSH 106 and Free T4 0.45. Her levothyroxine dose was increased to 75mcg and followed her 6 weeks later. Her energy levels improved significantly and she is back to her normal self. Her thyroid function was normal. At this point patient has decided not to undergo any treatments for colon cancer. Conclusion: Immune related thyroid events are increasingly noticed with wide use of pembrolizumab. There is insufficient evidence to suggest the cause of these events. Reversible destructive thyroiditis and overt hypothyroidism are the common clinical presentations. It is important to recognize patients at high risk for these adverse events so these highly efficacious agents can be safely used in patients. Thyroid has been a frequent target for anti PD 1 treatments, further research can be of benefit to use against thyroid cancers.

Prognostic significance of CT-determined sarcopenia in patients with metastatic pulmonary adenocarcinoma

The aim. To determine the prognostic significance of computed tomography (CT)-determined sarcopenia in patients with metastatic pulmonary adenocarcinoma. Materials and methods. Thirty patients with metastatic pulmonary adenocarcinoma who received polychemotherapy in the medical center “ONCOLIFE” from 2019 to 2020 were examined. The cross-sectional area was measured using archival CT images. The criteria of sarcopenia was skeletal muscle index at the level of the third lumbar vertebra &lt;55 cm2/m2 for men and &lt;39 cm2/m2 for women. Results. Among 30 patients with stage IV non-squamous cell lung cancer, sarcopenia was present in 17 (56.6 %) cases. The median age at diagnosis was 62 years. Patients with sarcopenia had worse 1-year overall survival than those without sarcopenia (23.5 % vs. 65.9 %, respectively, P = 0.024 by the log-rank test). A statistically significant gender difference was not observed for survival. Conclusions. CT-determined sarcopenia is an important prognostic marker in patients with metastatic pulmonary adenocarcinoma. Further study is needed to improve treatment outcomes of sarcopenia in patients with malignant neoplasms.

Stereotactic body radiotherapy for adenoid cystic carcinoma metastatic to the lung: a case report

BackgroundAdenoid cystic carcinoma (ACC) is a rare malignant tumor involving mostly the head and neck region, and frequently the salivary glands. The development of lung metastasis after treatment of the primary tumor is a common occurrence in ACC. Although lung metastases show a slow rate of growth, approximately 10% of patients die from distant metastases. The radioresistance of ACC limits the efficacy of conventional radiotherapy for lung metastases, and the optimal dose remains to be determined. Stereotactic body radiotherapy (SBRT) using CyberKnife can deliver a high dose to the lung tumor, while sparing the surrounding normal lung tissues, leading to favorable local control in non-squamous cell lung cancer and metastatic lung tumors. We report a case of lung metastases from ACC treated successfully with SBRT using CyberKnife.Case presentationA 76-year-old Japanese man with ACC who was treated with carbon ion radiotherapy for a primary oropharynx tumor presented with three metastatic lesions in the lung. The tumor masses were located in the right upper, right lower, and left lower lobes of the lungs. Surgical resection was not indicated because of the presence of multiple tumors. The patient underwent SBRT at 60 Gy in 10 sequential fractions for each tumor. The biologically effective dose based on an alpha/beta ratio of 2 Gy was 240 Gy per tumor. The percentage of the total lung volume irradiated with >20 Gy was 4.9%, 3.2%, and 2.6% for each tumor. The patient developed acute radiation pneumonitis during the initial therapy, which resolved at 6 months after the CyberKnife treatment. At 21 months after the first CyberKnife treatment, three tumors showed no signs of recurrence. No late toxicity was observed.ConclusionsSBRT using CyberKnife is an effective and feasible approach to the management of multiple lung metastases of ACC.

P60.03 Identifying Patterns in Responses to PD-1 Immunotherapy for Patients With Squamous Cell Lung Cancer and Non-Squamous Cell Lung Cancer

P60.03 Identifying Patterns in Responses to PD-1 Immunotherapy for Patients With Squamous Cell Lung Cancer and Non-Squamous Cell Lung Cancer

Long-term exposure to pemetrexed induces chronic renal dysfunction in patients with advanced and recurrent non-squamous cell lung cancer: a retrospective study

BackgroundPemetrexed (PEM) is administered over a long term to patients with non-squamous cell lung cancer as a maintenance therapy after platinum combination induction chemotherapy. Although decreased renal function owing to long-term PEM exposure has been reported, changes in the renal function of individual patients have not been reported. This study aimed to evaluate serum creatinine (Scr) in individual patients over time and determine whether long-term PEM exposure contributed to increased Scr.MethodsA retrospective study was performed using 90 non-squamous cell lung cancer patients, who had received maintenance therapy with PEM ± bevacizumab (BEV) after carboplatin + PEM ± BEV therapy at the Sapporo Minami-Sanjo Hospital from February 2012 to February 2019. Using Scr at the start of induction chemotherapy as the baseline, we calculated the correlation coefficient (r) of the rate of Scr change in an individual patient and the number of treatment courses to divide patients into two groups for comparison: patients with + 0.4 < r ≦ + 1.0 and an observed positive correlation (the r+0.4< group), and patients with − 1.0 ≦ r ≦ + 0.4 and no observed positive correlation (the r+0.4≧ group).ResultsStatistically significant differences between the r+0.4< group and the r+0.4≧ group were observed for the following parameters: the median cumulative dose of PEM (interquartile range) [9100 (6365, 12,260) mg/body vs. 5600 (4140, 7440) mg/body, P < 0.01]; the number of patients taking nonsteroidal anti-inflammatory drugs at the start of treatment [15 patients (31%) vs. 3 patients (7%), P < 0.01]; and the median number of treatment courses starting from induction chemotherapy [11 (8, 14) courses vs. 8 (6, 11) courses, P < 0.01]. Next, the results of univariate and multivariate analyses demonstrated that the cumulative dose of PEM (≧ 7000 mg/body vs < 7000 mg/body, OR 2.40; 95% CI, 1.22–4.75, P = 0.01) was an independent explanatory variable of the r+0.4< group.ConclusionsLong-term PEM exposure may induce chronic renal dysfunction. Hence, maintaining kidney function during PEM treatment by reducing the use of combination drugs and the risk of other renal dysfunctions, such as dehydration, may help patients continue therapy and contribute to their long-term survival.

Outcomes of incidental pulmonary nodules in head-and-neck squamous cell cancer patients treated with curative intent

Introduction: Incidental pulmonary nodule(s) (IPNs) are a common finding during staging imaging for the head-and-neck squamous cell cancers (HNSCC) treated with curative intent. Currently, the incidence of metastasis or synchronous malignancies and outcomes for IPN in this population is unknown. Methods: All cases (n = 2489) reviewed at a tertiary Australian Institution's head and neck (H and N) multidisciplinary meeting, from January 2010 to December 2014, were included. Of these patients, 310 (12.5%) had an HNSCC with an IPN that had been detected during staging imaging. These patients were also to undergo treatment by curative intent. Clinicopathological characteristics, the incidence of malignancy, progression-free survival, and overall survival (OS) were collected retrospectively over 5 years. Results: The median age of patients with an IPN was 66 (range 25–95) years. Tissue diagnosis of IPN was attempted in 46 (14.8%) patients due to radiological suspicion of malignancy. Malignancy was confirmed in 33 (11.0%) patients. From these, 33 patients, 11 (30.3%) had histological diagnoses of nonsquamous cell lung cancers and hence are not due to metastatic spread from a primary HNSCC. Age, gender, previous malignancies, smoking status, p16 status, stage, or primary site did not predict for malignancy. The incidence of pulmonary metastasis in patients who did not undergo tissue biopsy due to low clinical and radiological suspicion of malignancy (n = 244) occurred in 10 patients (4.1%). At the time of analysis, 91 (29.4%) patients had died, and tumor recurrence had occurred in 82 (26.5%) patients. The mean OS was 48 months (95% confidence interval: 44–51). OS was significantly associated with greater age (hazards ratio [HR] 1.04, P < 0.001); immunosuppression (HR 2.15, P = 0.013); and biopsy being attempted (HR 1.78, P = 0.013). There was no biopsy related mortality. Discussion: Detection of an IPN in patients undergoing workup for H and N cancer is common. The risk of malignancy in these IPNs however, is low. We did not identify any clinicopathological parameters to predict malignancy in this setting. Advanced age, current smoking status, and history of immunosuppression predict for poor outcomes. Further work is being undertaken to analyze radiological features that may predict malignancy in an IPN found during the radiological staging of HNSCC.

EP1.01-20 A Single-Arm Phase II Trial of Weekly Nanoparticle Albumin-Bound Paclitaxel Monotherapy After Standard Therapy for Advanced NSCLC

Few studies have investigated the clinical efficacy of later-line treatments after standard therapy for advanced non-small cell lung cancer (NSCLC). Nanoparticle albumin-bound paclitaxel was one of the useful option for treatment of NSCLC. We conducted PII trial for evaluating the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) following standard therapy for advanced NSCLC. The eligible patients having adequate organ functions with performance status 0−2 were enrolled after completing standard therapy. Standard therapy defined as chemotherapy including docetaxel and pemetrexed in patients with non-squamous cell lung cancer or docetaxel in patients with squamous cell lung cancer. After the ICI nivolumab was approved by the Ministry of Health, Labor and Welfare of Japan in December 2015, standard therapy was defined as including ICIs treatment. They received weekly nab-paclitaxel 100 mg/m2 intravenously on days 1, 8, and 15 every 3 weeks. The primary end point was objective response rate (ORR). Median progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated as secondary end points. This trial was discontinued because of late accrual. Twenty-two patients were enrolled from April 2013 and February 2019. All patients received chemotherapy including docetaxel and Six patients received ICIs treatment. Median follow-up interval was 6.7 months. The total ORR was 22.7% [95% CI: 7.8−45.4] and disease control rate (DCR) was 81.8% [95% CI: 59.7−94.8]. Median PFS was 3.4 months [95% CI: 2.3−4.1] and median OS was 7.4 months [95% CI: 4.2−10.7]. Hematological AEs of Grade 3/4 included anemia (18%), leukopenia (18%), and neutropenia (32%), and the most frequent nonhematological AEs were fatigue (50%) and peripheral neuropathy (36.4%). Severe AEs related to treatment were observed in only one patient. Although all patients received chemotherapy including docetaxel before protocol treatment, our tral suggested nab-paclitaxel may be a safe and effective later-line chemotherapeutic option for previously treated advanced NSCLC after standard of chemotherapies based on other trials.

Improving adherence to lung cancer guidelines: a quality improvement project that uses chart review, audit and feedback approach

IntroductionThe implementation of evidence-based clinical practice guidelines is one of the most effective interventions for improving quality of care. A gap between guidelines and clinical practice often exists, which may...

Characterizing biomarker testing over time in lung cancer patients using oncology electronic medical records (EMR).

e20056 Background: This study characterizes biomarker testing over time in Non-Small Cell Lung Cancer (NSCLC) patients treated within a clinical setting. There have been tremendous advances in treatments for NSCLC that target specific biomarkers such as epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and the Programmed cell death-ligand 1 (PD-L1) pathway. As we consider using oncology EMR records for future studies, it is critical to understand the extent to which biomarker testing is conducted in routine care, the extent to which testing has increased, and the types of patients for which it is done. Methods: This is a retrospective observational analysis derived from the COTA Oncology EHR database from January 1, 2015 through December 31, 2017. The data sets generated for the study included all relevant, retrospective patient-level, de-identified data available for patients with lung cancer, including EGFR, ALK, and PD-L1 testing regardless of age, gender, and stage at diagnosis. We examined characteristics associated with each type of test received as well as by those who had received all 3 biomarker tests, 1-2 of the tests, or no biomarker testing. Analyses were conducted using SAS V. 9.1 and stratified by data source. Results: There were 1,891 patients in the COTA database. Among newly diagnosed NSCLC patients, EGFR testing has been consistently conducted in patients during the study period (76 – 86%), while ALK testing [44% in 2015Q1 to 74% in 2017Q4] and PD-L1 testing [12% in 2015Q1 to 77% in 2017Q4] have steadily increased each quarter. Overall, testing was more likely to be conducted in non-squamous cell lung cancer patients, Stage IV lung cancer, and those without a history of smoking. For EGFR, testing was more prevalent among women and young age groups ( &lt; 64 years vs. 65 and older). Conclusions: Biomarker testing has rapidly increased for ALK and PD-L1, which correlates with the uptake of new targeted therapies. Further research could be conducted to understand clinical outcomes associated with this increase in testing as well as the impact on healthcare resource utilization.

Abstract No. 553 Preoperative embolization of bone cancers: tumor types, location, estimated blood loss, and blood transfusion requirements

Osseous metastases of certain primary cancers are hypervascular, such as renal cell carcinoma (RCC), and lead to concern for life-threatening high intra-operative blood loss and high intra-operative blood transfusion requirements. Some primary bone cancers can also appear hypervascular and in certain locations hemorrhage can lead to significant complications, such as the spine. Preoperative embolization of hypervascular osseous tumors is thought to decrease intra-operative bleeding. To evaluate intra-operative blood loss and blood transfusions after preoperative embolization, we reviewed our experience with preoperative embolization of osseous cancers. We reviewed imaging and medical charts for preoperative embolization by interventional radiology at a large academic institution for the past 4 years. Patient demographics, tumor type, tumor location, embolic agent(s) used, date of procedure and surgery, estimated blood loss (EBL), blood products administered and complications were reviewed. Thirteen bony tumors had preoperative embolization followed by surgical resection. The majority of the cancers, 62%, were renal cell carcinoma, followed by non-squamous cell lung cancer, 15%. The majority of cases involved the lower extremity, 62%, followed by the upper extremity, 23%, followed by the spine, 15%. The mean EBL for spine cases was 2850 mL versus 619 mL for non-spine cases, which was significantly different (p < 0.05). The EBL for lower extremity cases was 726 mL and for upper extremity cases was 333 mL. The mean EBL for RCC cases was higher than non-RCC cases (1051 mL versus 763 mL) but not significantly different (p = 0.8). The average packed red blood cells transfused was also highest for spine cases, 3 units versus 1.1 for extremity cases but this was not significantly different. The mean number of blood transfusions was also not significantly different depending on tumor type. There were no reported complications. No complications were reported with any of the preoperative embolizations or subsequent surgeries. EBL was significantly higher for spine cases. The mean EBL for RCC cases was higher than non-RCC cases but not significantly different.

P1.01-87 A Phase 1b Study of TRC105 In Combination with Paclitaxel/Carboplatin and Bevacizumab in Patients with Stage 4 Non-Squamous Cell Lung Cancer

Endoglin plays a critical role in angiogenesis and is implicated in resistance to VEGF inhibition. TRC105, an endoglin antibody, has been shown to potentiate the anti-angiogenic effect of bevacizumab (B) in pre-clinical models of human angiogenesis. Given the critical role of anti-angiogenic therapy in the treatment of advanced NSCLC and the tendency of the tumor to develop escape pathways of angiogenesis following treatment with anti-VEGF agent, investigation of dual anti-angiogenic therapy in advanced NSCLC is indicated. A standard (3+3) dose-escalation design of TRC105 with15 mg/kg bevacizumab (B), 200 mg/m2 paclitaxel (P) and 6 AUC carboplatin (C) given IV on day 1 of each 21-day cycle was employed, followed by an expanded cohort to further assess the safety and tolerability of the recommended phase 2 dose (RPTD) of TRC105. Patients completed induction therapy with TRC105 + B, P and C for a maximum of 6 cycles with those demonstrating no evidence of disease progression transitioned to a maintenance phase of TRC105 + B. Secondary endpoints: ORR, PFS, OS, PK, immunogenicity and angiogenic biomarkers. Key inclusion criteria: chemotherapy-naïve stage 4 NSQ-NSCLC, ECOG < 1, measurable disease and no significant cardiovascular comorbidities. Fifteen pts have been enrolled; three were unevaluable for efficacy due to DLT of Grade 3 rash and unrelated SAE’s of Grade 3 weakness and Grade 3 hypoxia. Four of 12 evaluable pts achieved PR, one with 81% tumor reduction. Median PFS was 6.54 months. Common adverse events regardless of relationship included epistaxis, fatigue, telangiectasia, diarrhea, headache and nausea. Common TRC105 related AEs included epistaxis, telangiectasia, fatigue and headache. One patient experienced Grade 5 neutropenic sepsis considered unrelated to TRC105 or B. Analysis of the angiogenic biomarkers will be presented. Induction treatment for six 3-week cycles withTRC105 + B, P, and C, followed by maintenance therapy with TRC105 + B until disease progression was tolerable and did not potentiate the toxicity of B, P or C. The combination of TRC105 + B, P and C demonstrated signs of activity including PR in 4 of 12 evaluable pts.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration for The Diagnosis and Genotyping of Lung Cancer

背景与目的超声气管镜针吸活检（endobronchial ultrasound guided tranbronchial needle aspiration, EBUS-TBNA）是临床怀疑肺癌患者的常用活检方式，在肺癌的诊断和分期中有着举足轻重的作用。然而该活检方式在诊断之余是否亦能提供充分的组织完成基因检测尚待研究。本文评价EBUS-TBNA所取得标本进行肺癌诊断及相关基因检测的可行性。方法对纵隔淋巴结肿大且临床怀疑肺癌诊断的患者进行EBUS-TBNA活检，所取得的标本进行病理诊断并对其中的非鳞非小细胞肺癌标本进行驱动基因检测。分析其诊断阳性率以及完成基因检测的可行性。结果入选377例患者平均单个淋巴结穿刺2.07针，确诊肺癌213例，经EBUS-TBNA诊断率92%。其中表皮生长因子受体（epidermal growth factor receptor, EGFR）基因、间变淋巴瘤激酶（anaplasticlymphoma kinase, ALK）融合基因、以及同时完成两个基因检测的患者分别为84例（90%）、105例（96%）及79例（90%）。单因素分析显示组织基因检测成功率与穿刺淋巴结针数、淋巴结大小及淋巴结部位无关，但与肿瘤病理类型相关。腺癌病理类型的EGFR基因突变及ALK融合基因检测的成功率均高于未分类非小细胞肺癌。结论EBUS-TBNA可提供充足的组织对肺癌进行诊断和基因分型。肿瘤病理类型可能是影响基因检测阳性率的因素。

Phase 1b/2 study of nivolumab in combination with an anti–IL-8 monoclonal antibody, BMS-986253, in a biomarker-enriched population of patients with advanced cancer.

TPS3109Background: Interleukin 8 (IL-8) is a chemokine that has been suggested to play a predominant role in tumor immune escape by promoting an immunosuppressive tumor microenvironment (TME). High levels of serum IL-8 are associated with a poor prognosis in various tumors (Sanmamed, MF, et al. Clin Cancer Res. 2014;20:5697-5707), such as melanoma, non-squamous small cell lung cancer (NSCLC), and renal cell carcinoma, and decreases in serum IL-8 levels have been suggested to be associated with response to anti–PD-(L)1 therapy with nivolumab in a small cohort of pts with melanoma and NSCLC (Sanmamed, MF et al. Ann Oncol. 2017;28:1988-1995). Preclinical studies showed synergetic antitumor activity by combining anti-CXCR2 with anti–PD-1 vs either agent alone in mouse. BMS-986253 is a fully human-sequence IgG1κ anti–IL-8 monoclonal antibody that abrogates signaling through both IL-8 receptors (CXCR1 and CXCR2), resulting in a complete blocking of IL-8 mediated pathway, and as such, can be used to assess the m...

P1.03-022 A Phase 1B Study of TRC105 in Combination with Paclitaxel/Carboplatin and Bevacizumab in Patients with Stage 4 Non-Squamous Cell Lung Cancer

P1.03-022 A Phase 1B Study of TRC105 in Combination with Paclitaxel/Carboplatin and Bevacizumab in Patients with Stage 4 Non-Squamous Cell Lung Cancer