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Prasad S. Adusumilli



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    MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Early Stage NSCLC
    • Presentations: 1
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      MA 13.14 - Surgical Outcomes and Survival Analysis Following Second Pulmonary Resection for Non-Small Cell Lung Cancer (ID 9374)

      15:45 - 17:30  |  Author(s): Prasad S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Background:
      The early detection and improved survival of resected non-small cell lung cancer (NSCLC) may increase the number of patients who eventually undergo subsequent pulmonary resection. We investigated the surgical outcomes and survival of patients following second and third pulmonary resections for NSCLC.

      Method:
      Patients who underwent second or third pulmonary resections without induction therapy for synchronous or metachronous NSCLC (511 patients, 535 procedures, 2000-2014) were included in the analysis.

      Result:
      Among 535 operations, 361 (67%) were sublobar resection and 103 (19%) were performed by minimally invasive approach, with the proportion of minimally-invasive procedures increasing in recent years (Fig. 1). The majority of re-resections were performed within 4 years of the previous resection (Fig. 2). Risk regression analysis demonstrated that predicted postoperative (ppo) FEV1 (p<0.001) and same side operation (p=0.002) were independent risk factors for severe complications (CTCAE grade ≧ 3; N=45). Multivariable Cox regression analysis revealed that age at subsequent surgery, male sex, ppoDLCO, interval from prior surgery, and tumor stage were independently associated with overall survival.

      Conclusion:
      In this large cohort of pulmonary re-resections for NSCLC, predicted postoperative pulmonary function tests were indictive of major complications and overall survival. Figure 1 Figure 2





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    MA 15 - Lung Cancer Biology II (ID 670)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      MA 15.09 - Circumferential Distribution and Distance from Main Tumor of Tumor Spread Through Air Spaces (STAS) Are Prognostic (ID 10143)

      15:45 - 17:30  |  Author(s): Prasad S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Background:
      The prognostic impact of the presence of tumor spread through air spaces (STAS) has been reported in lung adenocarcinoma (ADC). The aim of this study is to investigate the prognostic impact of the distribution, distance from the primary tumor, and quantification of STAS.

      Method:
      A cohort of 394 patients with pathologic stage I lung ADC (2012-2014) were investigated. The distribution of STAS around the tumor was classified into focal or circumferential. The distance of STAS was evaluated by counting the number of air spaces between the farthest STAS and the tumor edge. STAS was quantified by counting the number of STAS areas in the three most STAS- dense 20x high power fields (HPFs). The recurrence free probability (RFP) was analyzed by the Kaplan-Meier method with a log-rank test.

      Result:
      STAS was present in 211 (54%) cases. The presence of STAS was associated with a higher risk of recurrence (5-y RFP in STAS-positive vs. STAS-negative; 78% vs 90%, p<0.001, Fig 1A). Circumferential STAS was associated with a higher risk of recurrence than focal STAS (5-y RFP in circumferential vs. focal; 67% vs 87%, p=0.027, Fig 1B). A longer distance of STAS was associated with a higher risk of recurrence (5-y RFP >7 alveoli vs.≤7 alveoli, 69% vs. 91%, p=0.003, Fig 1C). Quantification of STAS was not prognostic (5-y RFP in >3/HPFs vs. ≤3/HPFs, 75% vs. 88 %, p=0.15). Figure 1 X



      Conclusion:
      Beyond just the presence of STAS, the distribution and distance of STAS can further stratify the risk of recurrence in stage I lung ADC.

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    MTE 07 - Molecular Biology: Minimum Requirement for Clinicians (Sign Up Required) (ID 556)

    • Event: WCLC 2017
    • Type: Meet the Expert
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 10/16/2017, 07:00 - 08:00, Room 501
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      MTE 07.01 - Molecular Biology that Clinicians Should Know: From a Clinical Viewpoint (ID 7783)

      07:00 - 08:00  |  Presenting Author(s): Prasad S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Abstract:
      This presentation will summarize the basics of cancer molecular biology and its application in lung cancer. The optimal treatment for patients with EGFR mutations in 2017, the need for tissue rebiopsy and plasma detection, and semiquantification methods will be discussed. The role of next-generation tyrosine kinase inhibitors that are approved in different countries will be summarized. The evolution of new targeted therapies and their current status of investigation will be presented. Additionally, the current status of combination targeted therapies with immunotherapy will be reviewed. The role of quantitative proteomics, plasma circulating tumor DNA, and high-throughput sequencing in current clinical practice will be summarized. By the end of the session, the audience will be familiar with the current status of driver genes, approved targeted therapies, and emerging concepts of combination therapies.

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    OA 02 - Mesothelioma: Challenges For New Treatment (ID 653)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Mesothelioma
    • Presentations: 1
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      OA 02.08 - Discussant - OA 02.05, OA 02.06, OA 02.07 (ID 10828)

      11:00 - 12:30  |  Presenting Author(s): Prasad S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    OA 18 - Lung Cancer Pathology and Genetics (ID 687)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      OA 18.06 - Three-Dimensional Assessment of Spread Through Air Spaces in Lung Adenocarcinoma: Insights and Implications (ID 8826)

      14:30 - 16:15  |  Author(s): Prasad S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Background:
      Tumor spread through air space (STAS) is a newly recognized form of invasion in lung adenocarcinoma and squamous cell carcinoma and growing evidence shows it is associated with recurrence and survival. The observation that tumor STAS clusters/nests or single cells within air spaces on two-dimensional H&E slides raised the question of how these cells could survive within air spaces without a vascular supply and this has led some to speculate STAS is an artifact. Herein, we perform the high resolution-high quality 3D reconstruction and visualization of normal lung and tumor in a lung adenocarcinoma to investigate the invasive pattern of STAS.

      Method:
      A formalin-fixed paraffin embedded block of invasive adenocarcinoma with micropapillary pattern and extensive STAS was studied. Following our histology 3D reconstruction standard procedure, 3D reconstruction was performed for analysis from 200 serial sections of H&E stained 20x (0.5um/pixel resolution) whole slide images. The relationship to alveolar walls between micropapillary structures within the tumor and STAS clusters in lung parenchyma distant from the tumor was evaluated.

      Result:
      3D reconstruction and analysis demonstrated the following novel features – a) in the main tumor area, micropapillary structures within airspaces were connected to alveolar walls, b) unlike in 2D evaluation where STAS appeared as ‘free-floating’ micropapillary clusters, in 3D evaluation many STAS clusters within air spaces are attached to alveolar walls, and c) STAS clusters that appear ring-like in 2D by 3D evaluation they are actually balls of tumor cells surrounding a central space.

      Conclusion:
      Our 3D reconstructed image analysis for the first-time demonstrates that most STAS cells are not ‘free-floating’, rather attached to the alveolar walls. In addition within the main tumor micropapillary clusters are attached to alveolar walls. These findings raise an intriguing hypothesis that STAS cells are clusters of tumor cells spread within alveolar spaces in a non-contiguous fashion to reattach to the alveolar walls at a distance possibly by co-option of alveolar wall capillaries to support their growth. This form of spread is analogous to the phenomenon of vascular spread where tumor cells spread freely within blood vessels to distant sites where they attach to endothelium and extravasate through the vessel walls to form metastases. It is possible the ball-like configuration of STAS clusters may facilitate movement through alveolar spaces distant from the main tumor. The frequent alveolar wall attachment of STAS observed on serial 3D imaging disputes the concept this is an artifact.

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    P1.13 - Radiology/Staging/Screening (ID 699)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.13-003 - Recurrence Dynamics in Resected Pathological Stage I Lung Adenocarcinoma Depend on the IASLC/ATS/ERS Histological Subtype (ID 9423)

      09:30 - 16:00  |  Author(s): Prasad S. Adusumilli

      • Abstract
      • Slides

      Background:
      Current practice guidelines recommend uniform follow-up protocol for all stage I lung adenocarcinoma (ADC) patients who underwent surgical resection. We hypothesized that the annual recurrence hazard of resected pathological stage I lung ADC patients vary according to the IASLC/ATS/ERS histological subtype.

      Method:
      Pathological stage I lung ADC patients who had undergone complete resection (R0) without induction therapy (N=1572, 1995-2012) were analyzed.

      Result:
      Among 1572 patients, 271 (18.5%) recurrences were identified (median follow-up 64.0 months) with highest peak of recurrence within first two years following resection. Patients who had undergone sublobar resection showed higher recurrence rate than those who had undergone lobectomy (Fig. 1A). The recurrence hazard increased as a function of the percentage of micropapillary (MIP) pattern (Fig. 1B), while the solid pattern contributed to the early recurrence (Fig. 1C). According to the presence of MIP and/or solid (SOL) pattern, the recurrence hazard is well stratified. Tumors without micropapillary and solid subtype show no peak with 2% of annual recurrence hazard within 10 years following resection, while tumors with both MIP and SOL patterns have the highest peak within 2 years compared to other MIP and SOL combinations.

      Conclusion:
      Patients with resected pathological stage I lung ADC show structured recurrence dynamics well stratified with the high risk histological subtypes, providing clinically useful prognostic information for patients and physicians. Figure 1



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    P2.05 - Early Stage NSCLC (ID 706)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
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      P2.05-021 - Occult Nodal Metastasis Following Lobectomy for Clinical Stage I Lung Adenocarcinoma: Implications for Sublobar Resection (ID 9436)

      09:30 - 16:00  |  Author(s): Prasad S. Adusumilli

      • Abstract
      • Slides

      Background:
      We investigated the incidence and location of occult nodal metastasis (ONM) in patients who had undergone lobectomy and lymph node dissection for clinical stage I lung adenocarcinoma (ADC). We performed a risk regression analysis to identify any associated radiologic and pathologic factors.

      Method:
      Clinical stage I lung ADC patients (stage II and III were excluded by CT and FDG-PET/CT scans) who underwent lobectomy and systematic lymph node dissection (N=715, 2005-2011) were included in the analysis. ONM were defined as pathologically diagnosed metastatic lymph nodes that are not suspected to be involved by cancer on both CT and PET scans.

      Result:
      Among 715 patients, 75 (10.5%) ONM were identified: 64 (85%) hilar or peribronchial and 32 (43%) mediastinal. Multivariable risk regression analysis identified tumor diameter, SUVmax, and lymphovascular invasion as risk factors (P<0.01). The incidence of subcarinal lymph node (LN) metastasis was very low among patients whose primary tumors were in the right upper lobe or left upper division (N=1/439, 0.2%). Lower mediastinal LN metastasis was rarely identified only when the primary tumor was located in the right lower or left lower lobe (N=2/210, 1.0%).

      Conclusion:
      One in ten patients with clinical stage I lung adenocarcinoma showed occult nodal metastases, with the highest incidence in hilar lymph nodes; this observation may be relevant for clinicians when considering sublobar resection for these patients. Figure 1



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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
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      P3.13-019 - Preoperative Needle Biopsy Does Not Increase the Risk of Pleural Recurrence in ≤3cm Lung Adenocarcinoma (ID 9526)

      09:30 - 16:00  |  Author(s): Prasad S. Adusumilli

      • Abstract

      Background:
      Percutaneous transthoracic needle biopsy (NB) has been widely used for the preoperative diagnosis of lung nodules. It has been proposed that the risk of pleural recurrence is high following lung resection in patients who underwent preoperative NB for sub-pleural nodules (Kashiwabara, et al. Cancer Invest 2016; Wang, et al. Sci Rep 2017). The aim of this study is to investigate the prognostic impact of preoperative NB for pleural recurrence in patients with early-stage lung adenocarcinoma (ADC).

      Method:
      Patients who underwent lung resection for pathologic stage I (≤3cm) lung ADC were included in the analysis (1995-2014, n=992; NB group 626 patients and no-NB group 366 patients). We compared the clinicopathologic characteristics and recurrence free probability (RFP, separately analyzed for any, locoregional, pleural, and distant recurrence) between NB and no-NB groups. The risk of pleural recurrence was evaluated in tumors both with and without visceral pleural invasion (VPI).

      Result:
      The NB cohort was associated with older age and larger tumor size compared to the no-NB cohort (p<0.05). There was no statistical difference in the incidence of VPI (VPI in NB, 12% vs. VPI in non-NB, 15%, p=0.2). In RFP analysis by Kaplan-Meier method with log-rank test, there was no statistical difference between NB and no-NB groups (NB vs. non-NB: 5-year RFP for any recurrence, 86% vs. 86%, p=0.8; locoregional recurrence, 93% vs. 94%, p=0.7; pleural recurrence, 98% vs. 96%, p=0.14; and distant recurrence 94% vs. 93%, p=1). In tumors both with and without VPI (n=128 and n=864, respectively), the risk of pleural recurrence was not higher after NB (Figure; 5-year RFP for pleural recurrence [NB vs. no-NB]: VPI positive, 93% vs. 83%, p=0.3; VPI negative, 98% vs. 97%, p=0.4). Figure 1



      Conclusion:
      Preoperative needle biopsy was not associated with an increased risk of pleural recurrence following lung resection.