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Nir Peled

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    MS 13 - How to Deal with CNS Metastases (ID 535)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: Advanced NSCLC
    • Presentations: 5
    • Now Available
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      MS 13.01 - Strategic Approach to CNS Metastasis (Now Available) (ID 7701)

      11:00 - 11:15  |  Presenting Author(s): Maurice Pérol

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Brain metastases (BMs) concern more than 10-15% of patients with stage IV NSCLC at baseline and more than 40% during the disease course. The wider use of MRI and improvement of extra-cranial systemic disease control contribute to increase the BMs incidence. The issue of BMs is critical in the management of NSCLC patients in the perspective of the neurological consequences of brain lesions. BMs occurrence is synonymous of a poor outcome in NSCLC but reflects in fact many different situations. Establishing a therapeutic strategy needs first to assess their prognosis; the most appropriate scale is the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers including as prognostic factors EGFR mutations and ALK rearrangement in addition to age, number of BMs, extra-cranial disease and Karnofsky status, with a median survival varying from 3.0 months for the worse subgroup (GPA 0.5-1) to 46.8 months for patients with oncogene addiction and good prognostic factors (GPA 3.5-4). The second step is to evaluate the indications, efficacy and side effects of available therapeutic "weapons". Corticosteroids are active against cerebral edema and improve symptoms. Whole brain radiotherapy (WBRT) has been for decades the treatment "reflex" of BMs but the emergence of stereotactic radiosurgery (SRS) or radiotherapy (SRT) and the issue of neurocognitive complications led to deferral or omission of WBRT in an increasing number of patients. WBRT remains indicated in patients with symptomatic, large (≥3 cm) and numerous BM. However, palliative WBRT did not provide any benefit in terms of survival, quality of life and QUALYs compared to supportive care alone in the Quartz trial; the subgroup analysis suggests a benefit only in patients with better prognostic factors. Neuroprotective strategies as sparing hippocampi during WBRT are currently evaluated. SRS defined by invasive contention with sub-millimeter accuracy or noninvasive SRT with millimeter accuracy are indicated in case of 1 to 3 BMs (but now up to 10 lesions) with a diameter <3 cm, alone or as a boost on the top of WBRT. SRS/SRT alone avoids neurocognitive toxicity of WBRT and provides a similar OS to that of surgical resection when using SRS/SRT for patients with operable lesions. Radionecrosis is observed in 10-17% of patients treated with SRS/SRT, making difficult the distinction with a tumor relapse. In spite of reduction in local and distant brain failures or in death from neurological causes, adjuvant WBRT after SRS/SRT does not improve overall survival and has a detrimental effect on neurocognitive functions and quality of life. Surgical resection of BMs achieves survival and functional benefit in addition to WBRT. Surgery is indicated in case of a symptomatic lesion, larger than 2 cm, with a mass effect, allowing fast improvement of symptoms. The invasive edge of BMs explains the high local recurrence rate after resection and the need for adjuvant radiotherapy. WBRT is progressively less used in favor of SRS/SRT despite a better intracranial control rate because of a higher rate of cognitive deterioration. Systemic treatment remains critical for extracranial systemic control of the disease. Brain-blood barrier limits the brain penetration of systemic agents, especially with efflux transporters as P-gp, for which many TKIs and cytotoxic agents are substrates. BMs usually cause brain-blood barrier disruption with heterogeneous drug penetration. Cytotoxic chemotherapy provides similar response rates in BMs to those of extracranial disease. Anti-PD-1 antibodies seem to be active in the brain but available data are scarce. First and second-generation EGFR TKIs have a low brain penetration but sufficient to obtain response rates similar to those achieved for systemic disease; duration of response might be inferior. Osimertinib has a better CNS penetration. For ALK+ disease, crizotinib is a P-gp substrate with a low blood/CSF concentration ratio and brain is the most frequent site of progression. Next-generation ALK TKIs have a better CNS diffusion; alectinib largely decreases the cumulative incidence of BMs compared to crizotinib. Concurrent administration of TKIs with brain radiotherapy is controversial and is not recommended outside of a clinical trial. Defining an optimal multidisciplinary strategy needs to take into account many parameters, including number, location and size of brain metastases, leptomeningeal lesions, neurological symptoms, risk factors for neurocognitive alteration, extracranial metastases and their control, primary lung tumor control, and identification of a targetable oncogenic addiction. In absence of a targetable genomic alteration, BMs at baseline can benefit from systemic treatment alone in selected patients with no neurological symptoms, small intracranial tumor burden, low risk of impending neurologic issues, on the condition that they are closely monitored; brain radiotherapy can be safely deferred to intracranial progression. Symptomatic BMs require local treatment, by favoring SRS/SRT rather than WBRT; adjuvant WBRT is not recommended but further close monitoring is mandatory to detect new intra-cranial lesions. Surgery is preferred for large lesions, posterior fossa location or diagnosis; adjuvant SRS/SRT is mandatory to avoid local recurrences. WBRT remains indicated for multiple symptomatic lesions not eligible for SRS/SRT except in poor PS patients. In case of EGFR mutations, asymptomatic patients with BMs are treated with first or second-generation EGFR TKIs but must be closely watched with repeated brain imaging. A recent retrospective study suggests that front-line SRS/SRT might improve overall survival as CNS remains a sanctuary site in oncogene-addicted disease. Symptomatic patients are locally treated, favoring SRS/SRT requiring only a short interruption of systemic treatment. For patients with ALK+ disease, the advent of alectinib as standard front-line treatment should change the management approach to BMs: the low incidence of BMs should allow spacing brain monitoring while the high intra-cranial response rate should permit to delay local treatment. For ALK+ patients developing BMs on ALK TKI, local treatment with SRS/SRT or surgery if necessary is the first option; switching to another TKI with a better brain penetration is another option for patients candidates to WBRT. The longer life expectancy of ALK+ patients leads to defer as far as possible the use of WBRT. However, improvement of intracranial control should be considered in patients at preferential risk of dying from intracranial progression, independently on mutational status.

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      MS 13.02 - SBRT vs. WBRT (Now Available) (ID 7702)

      11:15 - 11:30  |  Presenting Author(s): Paul Van Houtte  |  Author(s): D. Devriendt

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The management of brain metastases remains a challenging issue due to the detrimental impact on the patient quality of life and the wide range of clinical situations. The question is not a local treatment or WBRT but when and how to use the different modalities for each patient. Survival, an endpoint often used, is probably not the best way to evaluate the local efficacy: most patients will died from progressive extracranial disease. The brain tumor control (local or freedom from new brain metastases) is a better way to assess the impact of WBRT or SBRT. Another major problem is the great heterogeneity of the primary tumors and clinical situations. First, we should remember that most patients are not candidate for a local treatment (SBRT or surgery (S)) due to the number of lesions, locations, performance status, meningeal infiltration…and WBRT remains the standard treatment if a brain irradiation is needed. For patients with an “oligo metastatic disease”, many studies have clearly showed the superiority of a form of local treatment (S or SBRT) compared to WBRT at least in term of progression or control at the primary brain site (table1)(1-5). Another issue is to control the disease within the brain: new brain metastases are very common. WBRT has been tested either after S or SBRT to prevent the development of those new lesions: indeed adding WBRT let to a better brain tumor control but this did not translate in any major survival benefit. One major drawback of WBRT is its possible toxicity: the impact on the quality of life, the neurocognitive toxicity, the fatigue and the hair loss. In the EORTC trial, WBRT had a transitory negative impact on the physical or cognitive functioning and more fatigue in the early period of observation compared to the group of patients in the observation arm (6.). A current approach is to follow the patient after SBRT and in case of relapse to propose a salvage treatment which may be a new course of SBRT or even WBRT. Another question was to improve the local control after S adding SBRT. Postoperative SBRT has been proposed and several retrospective studies have shown the feasibility results. Two recently published randomized trials have compared postoperative SBRT to either WBRT or observation. The two main conclusions were less cognitive deterioration with SBRT compared to WBRT( 15% vs 48%) and less local relapse at the primary site compared to no treatment (at 1 year 43% vs 72%) but no difference in overall survival (4,5). An intriguing observation was the better local control at one year after postoperative WBRT compared to SBRT (4). Is there a group of patients benefiting from WBRT? In a new analysis of the Aoyama trial, patients with NSCLC were divided according to a graded prognostic assessment: a statistically significant benefit was observed only in the favorable group with a 6 months gain in median survival (7). A similar observation was reported in the RTOG trial testing the role of adding SBRT to WBRT with a median survival of 14 vs 21 months (8). Is it possible to reduce WBRT toxicity? The hippocampus region play an important role in the preservation of the neurocognitive functions: techniques have been developed to spare the hippocampus region keeping the dose below 7 Gy with a better quality of life and a very low risk of new brain metastases occurring in this spared regions (9). This approach should be tested in large scale phase III trial. Last but not least, the timing of the treatment should be individualized based on the patient needs, and in asymptomatic patients, SBRT may be safely postponed if a systemic treatment is to be administered.

      Authors Treatment Evaluation Time Local Control Brain Tumor Control
      Aoyama Kocher Andrews Brown Mahajan SBRT SBRT+WBRT Surgery Surg+WBRT SBRT SBRT+WBRT WBRT WBRT+SBRT Surg+WBRT Surg +SBRT Surg SURG.SBRT 1 Y 2 Y 1Y 1Y 1 Y 72% 88% 41% 73% 69% 81% 60% 74% 78% 55% 45% 72% 23% 53% 58% 77% 52% 67% 51% 62% 69% 32% 33% 43%
      · Estimated from figures References 1.Aoyama H., Tago M., Shirato H. for the Japanese Radiation Oncology study Group 99-1 (JROSG 99-1) investigators Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases. Secondary analysis of the JROSG-99 randomized clinical trial JAM Oncol. 2015; 1: 457-464 2.Kocher M., Soffietti R., Abacioglu U., et al Adjuvant whole-brain radiotherapy versus observation after surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J.Clin.Oncol. 2011; 29:131-141 3.Andrews D.W., Scott C.B., Sperduto D.W. et al Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial Lancet 2004; 363:1665-72 4.Brown PD, Ballman KV, Cerhan JH,et al Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.Lancet Oncol. 2017 Jul 4. pii: S1470-2045(17)30441-2. doi: 10.1016/S1470-2045(17)30441-2. [Epub ahead of print] 5.Mahajan A, Ahmed S, McAleer MF, et al Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017 Jul 4. pii: S1470-2045(17)30414-X. doi: 10.1016/S1470-2045(17)30414-X. [Epub ahead of print) 6.Soffietti R., Kocher M., Abacioglu U., et al A European Organiszation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation after surgical resection of one to three cerebral metastases: quality of life results J.Clin.Oncol. 2011; 31:65-72 7.Aoyama H., Tago M., Shirato H. et al Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial JAMA 2006; 295: 2483-91 8.Sperduto P.W., Shanley R., Luo X., et al Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation verus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA). Int.J.Radiat.Biol.Phys. 2014; 90: 526-531 9.Gondi V., Hermann B.P., Mehta M.P., Tome W.A. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int. J. Radiat. Oncol. Biol. Phys. 2012 ; 83 : 487–93

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      MS 13.03 - Target Therapy for ALK/ROS1 + NSCLC with CNS Metastasis (Now Available) (ID 7704)

      11:30 - 11:45  |  Presenting Author(s): Alice Shaw

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS 13.04 - The Role of Chemotherapy in the Management of CNS Metastasis (Now Available) (ID 7705)

      11:45 - 12:00  |  Presenting Author(s): Chong-Kin Liam

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The optimal management of patients with CNS metastases from lung cancer should be a multidisciplinary approach which encompasses supportive therapy, local CNS-directed therapies including surgery, stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT), and most importantly systemic therapy. In the case of patients with small cell lung cancer (SCLC), both the primary tumour and systemic metastases are generally chemosensitive, at least initially. Most studies suggested that brain metastases are as sensitive to systemic chemotherapy as extracranial disease. The concept of the brain as a pharmacologic sanctuary site for established metastases is in contrast with clinical observations of frequent responses in brain metastases to systemic chemotherapy. Response rates (RRs) of brain metastases from SCLC to systemic chemotherapy in treatment naive patients have been reported to range from 27% to 85%. RRs in previously treated patients with brain metastases range from 22% to 50% and are comparable to the RRs with second-line chemotherapy observed in extracranial disease. A meta-analysis of five studies with a single chemotherapy for pretreated patients showed RRs ranging from 33% to 43%.[1] Adding WBRT to chemotherapy increases the RR of the brain metastases, but does not appear to improve survival as shown in a phase III trial by the European Organization for Research and Treatment of Cancer.[2] For patients with advanced non-small cell lung cancer (NSCLC) without molecular drivers, chemotherapy is the mainstay of treatment. Although NSCLC is less responsive to systemic chemotherapy than SCLC, results of combining platinum compounds and third generation agents are substantially better than with earlier regimens. Platinum-based doublets are the cornerstone treatment in the first-line setting for metastatic NSCLC.[3] There is a presumed lack of effectiveness of systemic chemotherapy in CNS metastases from NSCLC because of the belief that chemotherapeutic drugs cannot cross the blood-brain barrier (BBB).[4] However, there is increasing evidence that the integrity of the BBB is impaired and disrupted in the presence of macroscopic CNS metastases. Despite a low penetration of the CNS, chemotherapy drugs have demonstrated encouraging activity against CNS metastases from NSCLC. A number of phase II studies reported RRs to cisplatin-based combination chemotherapy regimens ranging from 35% to 50%. Several clinical trials with upfront platinum-based chemotherapy have shown intracranial RRs ranging from 23% to 50% which correlated with and almost comparable to systemic RRs.[5 ]These data suggest that the intrinsic sensitivity of the tumour to the cytotoxic drug is more important in predicting response to the chemotherapeutic drug than the theoretical expected ability of the drug to penetrate the BBB. There are few randomised phase III trials of advanced or metastatic NSCLC evaluating different kinds of treatment in patients with brain metastases because generally, such patients have been excluded from clinical trials because of poor prognosis. Despite a penetration of CNS of less than 5%, pemetrexed demonstrated a consistent activity against brain metastases from NSCLC. One of the first evidence of pemetrexed activity against brain metastases came from a retrospective Italian study by Bearz and colleagues on 39 NSCLC patients with CNS metastases treated with pemetrexed as second or third line.[6] Although the patients were unselected for histology, the study reported an intracranial RR of 30.8%, with clinical benefit obtained in 69% of patients. All patients who had an overall response (i.e., partial response and stable disease) to pemetrexed had a benefit over cerebral metastases as well with partial response in 11 patients (28.2%) and stable disease in 21 (53.8%), with a clinical benefit rate of 82% for CNS metastases and an overall survival (OS) of 10 months. The addition of platinum compounds to pemetrexed slightly improved the outcome as shown in subsequent studies. In a phase II trial on 43 chemotherapy naïve NSCLC with brain metastases (93% with non-squamous histology) treated with pemetrexed and cisplatin for six cycles, the intracranial RR was 41.9%.[7] A comparable intracranial RR of 40% was observed when pemetrexed was combined with carboplatin in an observational study on 30 patients with adenocarcinoma and brain metastases.[8] These clinical trials showed that platinum-based regimens are active against brain metastases from NSCLC and high RRs can be achieved with pemetrexed-containing regimens in patients with non-squamous NSCLC. A post-hoc analysis of a large prospective observational European study on 1,564 patients with newly diagnosed advanced NSCLC receiving first-line platinum-based regimens showed that in the subgroup of 263 patients with brain metastases the median OS was 7.2 months which ranged from 5.6 months for patients treated with cisplatin/gemcitabine up to 9.3 months for those treated with platinum/pemetrexed.[9] In conclusion, systemic chemotherapy is an important part of the multidisciplinary managment of CNS metastases. Patients with small asymptomatic brain metastases from SCLC and NSCLC should be treated with the most active platinum-based combination chemotherapy upfront. Radiation therapy and other CNS-directed treatment may be deferred until the effects of the systemic chemotherapy on the CNS metastases can be determined. References 1. Grossi F, Scolaro T, Tixi L, et al. The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer. Crit Rev Oncol Hematol 2001; 37:61-7. 2. Postmus PE, Haaxma-Reiche H, Smit EF, et al. Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 2000; 18:3400. 3. Du L, Morgensztern D. Chemotherapy for Advanced- Stage Non-Small Cell Lung Cancer. Cancer J 2015;21:366-70. 4. Schuette W. Treatment of brain metastases from lung cancer: chemotherapy. Lung Cancer 2004; 45:S253-7. 5. Zimmermann S, Dziadziuszko R, Peters S. Indications and limitations of chemotherapy and targeted agents in non-small cell lung cancer brain metastases. Cancer Treat Rev 2014; 40:716-22. 6. Bearz A, Garassino I, Tiseo M, et al. Activity of Pemetrexed on brain metastases from Non-Small Cell Lung Cancer. Lung Cancer 2010; 68:264-8. 7. Barlesi F, Gervais R, Lena H, et al. Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01). Ann Oncol 2011; 22:2466-70 8. Bailon O, Chouahnia K, Augier A, et al. Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma. Neuro Oncol 2012; 14:491-5. 9. Moro-Sibilot D, Smit E, de Castro Carpeño J, et al. Non-small Non-small cell lung cancer patients with brain metastases treated with first-line platinum-doublet chemotherapy: Analysis from the European FRAME study. Lung Cancer 2015; 90:427-32.

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      MS 13.05 - Targeted Therapy for EGFR Positive Mutant NSCLC with CNS Metastasis (Now Available) (ID 7703)

      12:00 - 12:15  |  Presenting Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Central nervous system (CNS) metastases including brain metastasis (BM) and leptomeningeal metastasis (LM) are associated with poor prognosis in non-small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutations were initially reported in 2004 and currently defined the most prevalent actionable genomically classified subgroup of NSCLC, which account for 40% of Asian patients and 10-15% of White or African American patients. Patients with EGFR mutant NSCLC may have a higher incidence of CNS metastases due to prolonged survival with targeted agents and the increased quality of CNS imaging. More than 50% of NSCLC patients with EGFR mutation develop CNS metastases during their lifetime (1). The median overall survival (OS) for patients with BM is around 16 months (2) and 4.5-11 months for those with LM (3). Whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or surgery is widely used for BM, whereas no standard therapy is available for LM. Moreover, the benefit of radiotherapy is limited due to toxicities and long term sequelae. Brain is a privileged site, sheltered from the systemic circulation by the blood-brain-barrier (BBB), which is highly specialized structure with tight junctions created by the interaction between astrocytes, pericytes and endothelium. In addition, numerous efflux transporters (e.g. P-glycoprotein) have been identified, leading to prevent many traditional drugs from the circulation into the brain parenchyma. Although the permeation of EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib or erlotinib across the BBB has been reported, the cerebrospinal fluid (CSF) concentrations of TKIs at standard doses comprise only small fraction of the plasma concentration indicating the limited ability to permeate into the CSF (4). Several small series of phase II studies reported that EGFR TKIs, gefitinib, erlotinib or afatinib show CNS response rate of 55 to 89%, median PFS of 5.8 to 14.5 months and median OS of 15.9 to 22.9 months in patients with brain metastases. Recently, new generation EGFR TKI, AZD 3759 which is designed to effectively penetrate BBB demonstrated profound anti-tumor activity in preclinical models. Phase I study showed the free plasma concentration of AZD 3759 was approximately at the same range as that in CSF and yielded K~p,uu~,~CSF~ values of 1.18 and 1.00 for 200mg and 300mg, respectively. Tumor responses were observed in 83% and 72% of the patients with CNS and extracranial disease respectively in EGFR TKI naïve NSCLC (5). Osimertinib, a third generation EGFR TKI designed to target both activating EGFR mutation and T790M but sparing wild type EGFR, distributed into mouse brain to a greater extent than gefitinib (brain/plasma ratio 3.4 for osimertinib vs 0.21 for gefitinib). Osimertinib showed significant brain exposure and tumor shrinkage in preclinical brain metastases model. In 50 of 411 evaluable for CNS response in pooled AURA phase II study, osimertinib showed 53% of response rate and the median CNS PFS has not been reached (6). Confirmatory phase III study comparing osimertinib with platinum-doublets in T790M positive patients demonstrated significant improvement of PFS regardless of CNS metastases suggesting this agent has benefit in patients with CNS metastases. Recently released press showed that first-line osimertinib comparing with gefitinib/erlotinib (FLAURA) met the primary endpoint of PFS. It would be interesting to evaluate whether upfront use of osimertinib in EGFR mutant NSCLC can delay CNS metastases. Given the relatively high response rate in brain metastasis with EGFR TKI, the upfront use of EGFR TKI can delay other local therapies such as WBRT, SRS or surgery, leading to reduced side effects related to local therapy. However, the retrospective multi-institutional analysis demonstrated that the use of upfront EGFR TKI and deferral of radiotherapy is associated with inferior OS in patients with EGFR mutant NSCLC who developed brain metastases (7). Based on the potential synergistic effects of the combination of EGFR TKIs and radiotherapy due to opening of BBB by radiotherapy, several prospective trials were conducted. A phase II study of erlotinib combined with WBRT in 40 patients with NSCLC achieved 86% of response rate, 11.8 months of overall survival, whereas 19.1 months in patients with EGFR mutation (8). The Radiation Therapy Oncology Group conducted a phase II trial of WBRT and SRS alone or with either temozolomide or erlotinib for NSCLC patients with one to three brain metastases (EGFR mutation status was not tested). This study was closed early due to slow accrual and three arms did not show any differences in terms of efficacy. However, grade 3 to 5 toxicities were 41-49% in two concurrent drug combination arms. Thus, prospective randomized trial of SRS followed by EGFR TKI vs EGFR TKI followed by SRS at CNS progression is needed. Leptomeningeal disease (LM) is a fatal manifestation and its incidence is increasing in EGFR mutant NSCLC up to 10%. The prognosis remains very poor despite systemic treatment, intrathecal chemotherapy, radiotherapy and even molecular targeted therapy. Although EGFR TKIs have shown promising efficacy in the treatment of LM, especially with high dose or pulsatile dosing, the duration of efficacy is still limited with lack of survival improvement (9). Compared to gefitinib, erlotinib showed higher CSF concentrations (28.7 vs 3.7 ng/ml) and retrospective analysis showed promising activity with erlotinib in LM. It is not clear whether combination of intrathecal chemotherapy or WBRT can be applied to EGFR mutant NSCLC patients. Given the significantly higher penetration across the BBB (K~p,uu,brain ~=0.86) of AZD 3759, AZD3759 showed 28% of response rate (5/18) in TKI pretreated LM patients and 75% (3/4) in TKI naïve patients suggesting promising efficacy. The mean osimertinib concentration in CSF was 7.5nM in the T790M unselected cohort and AZD 9291 at 160mg once daily demonstrated encouraging activity with 43% of LM disease response and manageable tolerability (10). Both agents are currently being investigated in a larger cohort of patients with brain metastasis and leptomeningeal disease. Another challenge of conducting clinical trial in patients with LM is lack of standardized response evaluation method. Combinational measurements including neurological sign, CNS imaging and CSF cytology have been proposed, but further validation is warranted. In conclusion, CNS metastases in EGFR mutant NSCLC are increasing. Although EGFR TKI has been reported to improve clinical outcome, isolated or pre-dominant progression of CNS metastases remains a major issue in patients on EGFR inhibitors due to relative low penetration to BBB. New generation EGFR TKIs with better BBB penetration might have an impact on therapeutic strategies. Further studies are required to evaluate the optimal sequence of EGFR TKI therapy and radiotherapy. References Rangachari D, , et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer 2015; 88: 108-11. Fan Y, Xu X, Xie C. EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data. Onco Targets Ther 2014; 7: 2075-84. Umemura S, Tsubouchi K, Yoshioka H, et al. Clinical outcome in patients with leptomeningeal metastasis from non-small-cell lung cancer: Okayama Lung Cancer Study Group. Lung Cancer 2012; 77: 134-9. Togashi Y, Masago K, Masuda S, et al. Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer. Cancer Chemother Pharmacol 70: 399-405, 2012. Ahn MJ, Kim DW, Kim TM, et al. Phase I study of AZD3759, a CNS penetrable EGFR inhibitor, for the treatment of non-small-cell lung cancer (NSCLC) with brain metastasis (BM) and leptomeningeal metastasis (LM)., ASCO Meeting Abstracts. 34 (2016) 9003. Goss G, Tsai CM, Shepherd F, et al. CNS Response to osimertinib in patients with T790M-positive advanced NSCLC: Pooled data from two phase II trials. J Thorac Oncol Vol. 12 No. 1S (MA16.11)x William J. Magnuson, Nataniel H. Lester-Coll, et al. Management of brain metastases in tyrosine kinase inhibitor–naïve epidermal growth factor receptor–mutant non–small-cell lung cancer: A retrospective multi-institutional analysis. J Clin Oncol 35:1070-1077.James Chih-Hsin Yang Welsh JW, Komaki R, Amini A, et al. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. J Clin Oncol 31: 895-902, 2013. Yu HA, Sima CS, Reales D, et al. A phase I study of twice weekly pulse dose and daily low dose erlotinib as initial treatment for patients (pts) with EGFR-mutant lung cancers. J Clin Oncol33(Suppl 15s): 426s, 2015. Yang J.C.-H, Kim DW, Kim, SW, et al. Osimertinib activity in patients (pts) with leptomeningeal (LM) disease from non-small cell lung cancer (NSCLC): Updated results from BLOOM, a phase I study., ASCO Meeting Abstracts. 34 (2016) 9002.Search for articles by this authorAffiliations Cancer Research Center, National Taiwan University, Taipei/Taiwan

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    MA 02 - Emerging Targets (ID 656)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
    • Now Available
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      MA 02.06 - BRAF Mutant NSCLC: Correlation with PD-L1 Expression,TMB, MSI and Response to ICPi and Anti-BRAF Therapy (Now Available) (ID 10473)

      11:35 - 11:40  |  Author(s): Nir Peled

      • Abstract
      • Presentation
      • Slides

      Background:
      The efficacy of immune check-point inhibitors (ICPi) in BRAF mutant non-small cell lung cancer (NSCLC) is largely unknown. The correlation with different parameters predicting efficacy of ICPi (e.g., PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability status (MSI) in these tumors needs further evaluation.

      Method:
      A retrospective analysis of 30 patients with BRAF mutant advanced NSCLC treated between Aug 2013 and May 2017 was performed. The patients were divided into 2 groups: BRAF V600 E (Group A, N=16), non-V600E BRAF (Group B, N=14). PD-L1 was assessed by immunohistochemistry using 22C3 Dako antibody clone on Dako or Ventana's platform in 16 patients. TMB and MSI were assessed in 9 and 11 patients, respectively. Median progression-free survival (mPFS) with ICPi and targeted agents as well as median overall survival (mOS) were assessed in each group by Kaplan-Meier method.

      Result:
      Baseline characteristics of the cohort: median age 66y (range 39-98); males 53%; current/past smokers/never smokers/NA 13%/44%/40%/3%; adenocarcinoma/other histology 80%/20%; ECOG PS 0/1/2/3/4/NA 27%/33%/10%/13%/0%/17%. The distribution of TMB, PD-L1 expression and MSI status between the 2 groups is presented in Table 1. Ten patients received ICPi (nivolumab-8, pembrolizumab-2), and thirteen patients received anti-BRAF therapy (dabrafenib+trametinib-6, dabrafenib-4, vemurafenib-3). mOS and mPFS with ICPi and anti-BRAF therapy are summarized in Table 1. Four patients with BRAF V600 E PD-L1 ≥ 50% tumors were included in the series; one patients responded to dabrafenib+trametinib combination (response ongoing, 7.1months+); in two patients ICPi were initiated, response assessment pending. One patient with a non-V600E BRAF mutant NSCLC responded to dabrafenib for 6.7 months.Figure 1



      Conclusion:
      BRAF mutant NSCLC tumors are associated with high level of PD-L1 expression, low/intermediate TMB and MSI stable status. ICPi may induce prolonged responses both in BRAF V600E and non-V600E BRAF mutant NSCLC. Some non-V600E BRAF mutant NSCLC may benefit from anti-BRAF targeted therapy.

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    MA 18 - Global Tobacco Control and Epidemiology II (ID 676)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
    • Presentations: 1
    • Now Available
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      MA 18.11 - High Incidence of Lung Cancer in Early Stage TCC Patients (Now Available) (ID 9292)

      16:55 - 17:00  |  Author(s): Nir Peled

      • Abstract
      • Presentation
      • Slides

      Background:
      In recent years, clinical studies on screening for lung cancer have demonstrated an initial lung cancer detection rate of 0.8-2.2%, with a total of 2.4-4.7% in 34-78 months of follow up. The National Lung Screening Trial (NLST), which compared screening by LDCT to annual chest X-ray, showed a 20% decrease in mortality in the screened population. Transitional cell carcinoma of the bladder (TCC) has a high survival rate, and has similar risk factors to lung cancer. Thus, TCC patients may stand to benefit from lung cancer screening.

      Method:
      The SEER (Statistics, Epidemiology and End Results) database was used to determine the incidence, Person-years at risk and the average time to diagnosis of lung cancer in patients with localized TCC of the bladder (American Joint Committee on cancer, 6[th] ed., stages 0-1) in years 2000-2013. Cumulative Incidence rates were calculated and stratified by age, sex and county level smoking data.

      Result:
      Based on 88,564 patients with localized TCC (F:M ratio 1:3.3), the 5 year incidence of lung cancer was 3.16%, and 10 year incidence was 5.85%. among patients over 40 from counties with a high percentage of smokers, the 5 year incidence of lung cancer was 3.46%, and 10 year incidence was 6.64%. The median time until diagnosis of lung cancer was 3.89 years for men and 3.16 years for women for ages 60-79, the age group with the highest incidence. Figure 1



      Conclusion:
      Incidence of lung cancer is high in localized TCC patients and comparable to results seen in the high risk groups currently being screened. Early stage TCC patients may therefore stand to gain from lung cancer screening, and should be considered as potential screening candidates.

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    OA 17 - Immunotherapy II (ID 683)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
    • Now Available
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      OA 17.06 - Updated Analysis of KEYNOTE-024: Pembrolizumab vs Platinum-Based Chemotherapy for Advanced NSCLC With PD-L1 TPS ≥50% (Now Available) (ID 9582)

      15:25 - 15:35  |  Author(s): Nir Peled

      • Abstract
      • Presentation
      • Slides

      Background:
      KEYNOTE-024 (ClinicalTrials.gov, NCT02142738) is a multicenter, international, phase 3, randomized, open-label, controlled trial of treatment with the anti‒PD-1 antibody pembrolizumab vs platinum-based chemotherapy as first-line therapy for patients with advanced NSCLC of any histology with PD-L1 tumor proportion score (TPS) ≥50% and without EGFR mutations or ALK translocations. Results from the primary analysis of KEYNOTE-024 demonstrated that after a median follow-up of 11.2 months, pembrolizumab significantly improved PFS (HR=0.50; P<0.001) and OS (HR=0.60; P=0.005) and was associated with a lower rate of treatment-related AEs compared with chemotherapy.

      Method:
      Patients were randomly assigned to receive either 35 cycles of pembrolizumab 200 mg every 3 weeks or 4–6 cycles of investigator's choice of carboplatin/cisplatin + gemcitabine, carboplatin + paclitaxel, or carboplatin/cisplatin + pemetrexed with optional pemetrexed maintenance (for those with non-squamous histology). Randomization was stratified by ECOG performance status (0 vs 1), histology (squamous vs nonsquamous), and geographic region (East Asia vs non–East Asia). Treatment continued until disease progression per RECIST version 1.1, intolerable toxicity, or withdrawal of consent. Patients in the chemotherapy arm who experienced disease progression could cross over to receive pembrolizumab monotherapy. Response was assessed every 9 weeks by blinded independent central review per RECIST version 1.1. The primary endpoint was PFS; secondary endpoints were OS, ORR, and safety.

      Result:
      305 patients were enrolled (pembrolizumab, n=154; chemotherapy, n=151). At the time of data cutoff (July 10, 2017) after a median follow-up of 25.2 months, 73 patients (47.4%) in the pembrolizumab arm and 96 patients (63.6%) in the chemotherapy arm had died. The hazard ratio for OS was 0.63 (95% CI, 0.47–0.86; nominal P=0.002). Median (95% CI) OS was 30.0 (18.3–not reached) months in the pembrolizumab arm and 14.2 (9.8–19.0) months in the chemotherapy arm. The Kaplan-Meier estimate of OS at 12 months was 70.3% (95% CI, 62.3%–76.9%) for the pembrolizumab group and 54.8% (95% CI, 46.4%–62.4%) for the chemotherapy group. 82 patients allocated to the chemotherapy arm crossed over to receive pembrolizumab upon meeting eligibility criteria. Treatment-related adverse events were less frequent in the pembrolizumab arm than in the chemotherapy arm (76.6% versus 90.0%, respectively) as were treatment-related grade 3-5 adverse events (31.2% versus 53.3%).

      Conclusion:
      With more than half of patients having OS events and prolonged follow‒up, first-line pembrolizumab monotherapy remains superior to platinum-based chemotherapy despite the crossover from the control arm to an anti-PD1 inhibitor as subsequent therapy.

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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      P1.01-039 - Survival Impact of Next-Generation Sequencing in Lung Cancer (Now Available) (ID 10212)

      09:30 - 09:30  |  Author(s): Nir Peled

      • Abstract
      • Slides

      Background:
      Next-generation sequencing (NGS) enables a comprehensive genomic analysis of lung cancer patients. It has uncovered many novel genetic abnormalities and identified actionable genomic alterations in lung tumors that previously tested "negative" by conventional non-NGS tests. In this study, we evaluated the clinical impact of NGS, performed at different stages of the oncologic management, on overall survival of advanced lung cancer patients.

      Method:
      In this retrospective study, 178 consecutive non-small cell lung cancer (NSCLC) patients who performed hybrid capturing NGS were enrolled at the Thoracic Cancer Unit at Rabin Medical Center, Israel, between 2011-2017. Hybrid capture-based NGS was performed by Foundation Medicine and Gaurdant 360[TM] if tissue was not available.

      Result:
      178 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63±12.1 years. 83% had adenocarcinoma. NGS was performed upfront in 45.5% (81/178) and after 1[st] line failure in 54.5% (97/178). Treatment decision was taken toward targeted therapy subsequent to NGS analysis in 34% (61/178) of patients (29 and 32 respectively) with an objective response rate of 54%. Overall survival (OS) was evaluated for 51% (31/61) with a median of 12.2±14.1 months. For patients who performed upfront NGS, OS ranged between 1.8 to 32.5 months, with a median OS of 13.8 months. For patients who performed NGS on progression, OS ranged between 1.7 to 77.1, with a median OS of 12.7 months.

      Conclusion:
      Comprehensive tissue and liquid-based NGS have revealed targeted treatment options for one third of the patients. Overall Survival of patients treated with tailored therapy was positively impacted by earlier performed NGS.

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
    • Now Available
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      P2.07-048 - Immunotherapy vs. Targeted Therapy - Who Wins? A Case Series (Now Available) (ID 10234)

      09:30 - 09:30  |  Author(s): Nir Peled

      • Abstract
      • Slides

      Background:
      Data are mounting regarding rare mutations such as MET (exon 14 skipping mutation and MET amplification), ROS1 translocation and rare EGFR mutations and response to targeted therapy, simultaneously data are increasing concerning treatment of Non-Small Cell Lung Carcinoma (NSCLC) patients with immune check point inhibitors. As yet, the role of immunotherapy in patients with rare genomic alterations has not been determined. We describe a case series of patients who can benefit from both therapies and summarizes their response for each treatment.

      Method:
      We present a retrospective case series of four patients with NSCLC and genomic alterations, diagnosed and treated from November 2015 to June 2017 in a single tertiary center with targeted therapy and immunotherapy. Hybrid capture-based next generation sequencing was performed.

      Result:
      Two males and two females (mean age 58) were included. Three of them were diagnosed with Adenocarcinoma and the remaining one was diagnosed with squamous cell carcinoma. Each patient was diagnosed with a specific gene alteration (C-met exon 14 skipping mutation, EGFR Q861L, MET amplification and ROS1 translocation). Patients underwent targeted therapy as well as immunotherapy. Two patients had PD-L1 staining >50%. One patient demonstrated an early and durable complete response with immune check point inhibitors, one patient had progressed on immunotherapy quickly but respond well to targeted therapy, two patients responded as expected to targeted therapy and got immune check point inhibitors as a second line and still being treated with good response.

      Conclusion:
      The role of immunotherapy for patients with uncommon EGFR mutations, ROS1 and C-MET who express PD-L1 is still unclear. Further studies in this unique population are needed.

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    P3.01 - Advanced NSCLC (ID 621)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 2
    • Now Available
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      P3.01-056 - Intracranial Activity of Osimertinib in Naïve EGFRm T790M(-)And Treated EGFRm T790M(+) NSCLC Patients with Asymptomatic Brain Metastases  (Now Available) (ID 9819)

      09:30 - 09:30  |  Presenting Author(s): Nir Peled

      • Abstract
      • Slides

      Background:
      Osimertinib is an effective, irreversible EGFR-TKI selective for EGFR-TKI-sensitizing (EGFRm) and T790M[+] resistance mutations. Intracranial activity of osimertinib has been reported in T790M[+] patients; however its activity in EGFR-TKI naïve setting has not been investigated yet. Here, we present preliminary data of a phase II study assessing the intracranial activity of osimertinib in EGFRm NSCLC patients with asymptomatic brain metastases as 1[st] line therapy for naïve patients and as 2[nd] line therapy for EGFRm patients who progressed on EGFR TKI and harbor T790M[+]. Dose escalation from 80 mg QD to 160 mg QD was allowed in cases of brain progression.

      Method:
      A phase II, open label, two arm study is presented. Treatment-naïve (arm A) advanced NSCLC with sensitizing EGFRm and previously treated (arm B) with 1[st] or 2[nd]-generation EGFR TKIs (gefitinib, erlotinib or afatinib) in whom T790M[+] was diagnosed were enrolled to this study. Intracranial response was assessed by brain MRI scans every 6 weeks and systemic evaluation by PET-CT scan every 3 months unttil progression. The study plans to enroll 20 patients in each arm aiming to reach a statistical power of 0.8.

      Result:
      As of May 31 2017, 22 patients were enrolled; 15 patients in arm A and 7 patients in arm B, age 67.8±10.4 years, 14 females and 8 males. Preliminary outcome analysis is presented for 16 patients with a median follow up of 6.1 months (range 1.4-11.4 months). On May 31[st] 2017 data cut-off was performed. The Intracranial response rate (ICRR) was 81% (13/16 pts); 82% (9/11 pts) in arm A and 80% (4/5 pts) in arm B. Time to response was 6 weeks (1[st] MRI) in all responding patients. Intracranial disease control rate (IDCR) was 81% (13/16 pts) for the current follow up time of 6.1 months; median PFS not reached. Dose escalation was performed in 2 cases and data is not mature yet. Toxicity profile is similar to previous reported data.

      Conclusion:
      Osimertinib shows a promising intracranial response rate in naïve EGFRm NSCLC patients (82% ICRR) and in 2[nd] line T790M (+) setting with 80% ICRR. This study is still recruiting.

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      P3.01-060 - The Clinical Utility of ctDNA Gene Analysis in Lung Cancer (Now Available) (ID 9948)

      09:30 - 09:30  |  Author(s): Nir Peled

      • Abstract
      • Slides

      Background:
      Next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) enables a non-invasive option for comprehensive genomic analysis of lung cancer patients. In this study, we evaluated the impact of ctDNA sequencing on outcomes and treatment strategy.

      Method:
      In this retrospective study, data was collected from files of advanced non-small cell lung cancer (NSCLC) patients at the Thoracic Cancer Unit, Rabin Medical Center, Israel, between 2014-2017. Plasma samples were analyzed by a commercial test (Guardant360[TM]), using massively parallel paired-end synthesis to sequence a targeted 68-73 gene panel.

      Result:
      116 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63 years, 74% had adenocarcinoma. 41% performed ctDNA analysis before 1st line therapy (Group A) and 59% on progression (Group B), among them 41% after progression on EGFR TKIs (Group B1) and 59% on other treatments (Group B2). ctDNA analysis yielded actionable mutations (EGFR, ALK, RET, BRAF, MET, ERBB2 (HER2)) in 40.5%: 31% in group A, 47% in group B, 71% in group B1 and 30% in group B2. Treatment decision was taken toward targeted therapy subsequent to NGS in 26%.

      Genetic alterations frequencies among groups A, B, B1 and B2
      Group A 19 individual mutations Group B 52 individual mutations Group B1 34 individual mutations Group B2 18 individual mutations
      EGFR Sensitizing 52.5% (10/19) EGFR Sensitizing 42% (22/52) EGFR Sensitizing 59% (20/34) MET 55.6% (10/18)
      MET 16% (3/19) MET 27% (14/52) EGFR T790M 23% (8/34) ERBB2 16.7% (3/18)
      ERBB2 10.5% (2/19) EGFR T790M 15% (8/52) MET 12% (4/34) RET 16.7% (3/18)
      BRAF V600E 10.5% (2/19) ERBB2 8% (4/52) ERBB2 3% (1/34) EGFR Sensitizing 11.1% (2/18)
      RET 10.5% (2/19) RET 6% (3/52) ALK 3% (1/34)
      ALK 2% (1/52)
      Response assessment (RECIST) to targeted therapy showed complete response in 4%, partial response in 44%, stable disease in 37% and progressive disease in 15%. Response rate was 44% for group A, 50% for group B, 60% for group B1, 37.5% for group B2. Total objective response rate was 48% and disease control rate was 85%. Overall survival was evaluated for 40%, median was 14.4 months for patients who received targeted therapy vs 13.6 months for patients who received standard treatment.

      Conclusion:
      Comprehensive ctDNA testing revealed treatment options for 40.5% of patients analyzed. The highest impact was seen in progressors on EGFR therapy. These positive results emphasize the utility of liquid biopsy analysis to guide clinicians to select the most efficacious therapy for each patient.

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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
    • Now Available
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      P3.02-096 - The Interaction Between Mast Cells and Lung Cancer Cells Through Extracellular Vesicles (Now Available) (ID 10200)

      09:30 - 09:30  |  Author(s): Nir Peled

      • Abstract
      • Slides

      Background:
      Exosomes are nano-sized extracellular vesicles that mediate cell-to-cell communication by transferring molecules. Mast cells are secretory cells that complete their differentiation and maturation in the micro-environment of tissues containing blood vessels, and were observed in the periphery of certain tumors. It has been hypothesized that tumor cells affect their environment by passing genetic codes such as miRNA through exosomes. In this study, we investigated the presence of exosomal content in the micro-environment of lung cancer cells as a communication mechanism that drives tumor development.

      Method:
      Human mast cells (HMC1) were exposed to Human lung cancer cells (H1299) in in vitro setting. Exosomes were isolated from mast cells alone, lung cancer cells alone and from a co-culture of mast cells and lung cancer cells. As a control, exosomes were produced from mast cells that were activated by membranes of lung cancer cells. Exosomes quantity and quality were analyzed including its miRNA composition. Samples were run on an HTG EdgeSeq Processor using the HTG EdgeSeq miRNA WT assay. Each assay contains 2102 probes for miRNA, including 13 housekeeper genes, 5 negative process controls, and 1 positive process control. The HTG EdgeSeq Parser was used to align the FASTQ files to the probe list to collate the data. CPM (counts per million) was normalized and differential expression was analyzed using DESeq2.

      Result:
      We exposed mast cells to membranes of lung cancer cells, in order to examine induction of mast cells. Out of 2066 miRNA analyzed only 3 were significantly upregulated: miR-31-5p, miR-100-5p and miR-125b-5p. Interestingly, the profile of the pathways activated by these 3 upregulated miRNAs shows the focal adhesion and adherens junctions as one of the top results. A comparison was made between miRNA expression of exosomes from mast cells vs. exosomes from lung cancer cells. Out of 2066 miRNA analyzed, a total of 112 miRNA were differentely expressed. 79 miRNAs were downregulated, for example hsa-miR-6802-5p downregulated in HMC1 in comparison with H1299, and moreover hsa-miR-4700-5p. 33 miRNAs were significantly upregulated, for example miR-146b-5p/miR-146a-5p. Top upregulated miRNAs were tested using KEGG pathway and predicted to lead to the activation of the pathways like viral carcinogenesis, pathways in cancer and cell cycle.

      Conclusion:
      Mast cells and cancer cells do have common and discriminating exosomal content. Interestingly, mast cells have been induced by the presence of lung cancer cells’ membranes, through a change in the canonical pathways of focal adhesion, by the upregulation of only 3 miRNAs.

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    P3.03 - Chemotherapy/Targeted Therapy (ID 719)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
    • Now Available
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      P3.03-022 - Lung Cancer in Young Patients: Higher Rate of Driver Mutations and Brain Involvement but Better Survival (Now Available) (ID 9887)

      09:30 - 09:30  |  Presenting Author(s): Nir Peled

      • Abstract
      • Slides

      Background:
      Young patients with Non-small cell lung cancer (NSCLC) represent a distinct subset of patients. There are few reports describing younger patient’s characteristics and survival. Therefore, we conducted a retrospective study, in which we gathered clinical features of NSCLC patients under the age of 50 and matched patients who were older than 60 years at diagnosis.

      Method:
      Retrospective data of NSCLC patients was collected in a single tertiary hospital between January 2010 and December 2015. Patients were divided into 2 age groups according to the age at diagnosis: younger than 50 years (N=62) and older than 60 years (N=124). Their clinico-pathological characteristics, disease course and survival rate were analyzed.

      Result:
      The median age was 44 and 68 years of the younger and older cohort respectively. There were more never smokers (36% vs. 24%, p=0.08) and more brain metastasis (40% vs. 25%, p =0.04) in the younger group. Interestingly enough, upper lobes were more involved in the older vs. the younger cohort (p<0.001). A similar percentage of patients underwent NGS testing in both groups, but driver mutations were more common in the younger cohort: Epidermal Growth Factor Receptor (EGFR) mutations (32% vs. 25%, NS), Anaplastic Lymphoma Kinase (ALK) rearrangement (22% vs. 3%, p =0.002). Accordingly, the clinical impact of molecular testing on treatment decision was greater in the young vs. the older group (61% vs. 31%, p=0.002). Median survival was longer in the younger cohort, although not significantly different (34 vs. 21 months, p =0.1).

      Conclusion:
      Young patients with NSCLC have more driver mutations, more brain metastases and a trend of better survival. Therefore, this group of patients should undergo intensive mutation investigation and brain MRI on initial assessment.

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    P3.13 - Radiology/Staging/Screening (ID 729)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
    • Now Available
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      P3.13-030 - Metabolic Parameters of FDG PET at Early Evaluation of NSCLC Differ with Histological Subtypes (Now Available) (ID 10173)

      09:30 - 09:30  |  Author(s): Nir Peled

      • Abstract
      • Slides

      Background:
      Fluorodeoxyglucose Positron emission tomography (FDG PET) is a main tool in diagnosis and staging in patients with non small cell lung cancer (NSCLC). Metabolic parameters as standardized uptake value (SUV) and total lesion glycolysis (TLG) were reported to have independent prognostic and predictive value in different stages of disease and were shown to correlate with tumor activity and tumor burden. However, little is known regarding the correlation of these parameters with histologic subtypes of NSCLC. In this study we aimed to explore associations of FDG PET metabolic parameters in patients diagnosed with NSCLC and histologic subtypes of NSCLC.

      Method:
      We retrospectively evaluated 87 consecutive patients who underwent FDG PET scans in the workup of pulmonary nodules highly suspicious for malignancy. At total of 62 of them were found to have NSCLC; 44 with adenocarcinoma (ADC) and 18 with squamous cell carcinoma (SQCC). Measurements of hounsfield units (HU), region of interest (ROI), SUVmax, SUVmean, volume of interest (VOI) and TLG were obtained. Follow up for final staging at diagnosis and overall survival (OS) were obtained from electronic medical records. Statistical analysis was made with T-test and Mann-whitney u test.

      Result:
      In patients with SQCC, the mean ±standard deviation (SD) SUVmax and TLG (±SD) were found to be significantly higher than in patients with ADC (Table 1). Differences in OS showed a trend favoring SqCC but no significance was found (complete results from 16 more patients are pending). Figure 1



      Conclusion:
      FDG PET Metabolic characteristics such as SUVmax and TLG significantly differ between histological subtypes in NSCLC. This report joins others on the utility of functional imaging studies in NSCLC in assessing not just disease burden but also prognosis and function. Further analyses of the PET parameters prognostic impact according to histology subtype is ongoing and would be presented at the meeting.

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    WS 01 - IASLC Supporting the Implementation of Quality Assured Global CT Screening Workshop (By Invitation Only) (ID 632)

    • Event: WCLC 2017
    • Type: Workshop
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      WS 01.16 - Session 3: Added Value to Lung Cancer CT Screening Programs (ID 10654)

      11:30 - 11:30  |  Presenting Author(s): Nir Peled

      • Abstract
      • Slides

      Abstract not provided

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    WS 02 - IASLC Symposium on the Advances in Lung Cancer CT Screening (Ticketed Session SOLD OUT) (ID 631)

    • Event: WCLC 2017
    • Type: Symposium
    • Track: Radiology/Staging/Screening
    • Presentations: 2
    • Now Available
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      WS 02.11 - Session 3: Early Detection Biomarkers (ID 10588)

      14:00 - 14:00  |  Presenting Author(s): Nir Peled

      • Abstract

      Abstract not provided

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      WS 02.13 - New Approaches to Interventional Pulmonology for Lung Cancer Screening (Now Available) (ID 10626)

      14:30 - 15:00  |  Presenting Author(s): Nir Peled

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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