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T. Matsunaga



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    MA10 - Facing the Real World: New Staging System and Response Evaluation in Immunotherapy (ID 393)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      MA10.05 - Proposals for the Novel Clinical T Categories Based on the Presence of Ground Glass Opacity Component in Lung Adenocarcinoma (ID 6041)

      14:20 - 15:50  |  Author(s): T. Matsunaga

      • Abstract
      • Presentation
      • Slides

      Background:
      In lung adenocarcinomas, the histologic lepidic growth pattern tends to correlate with the ground glass opacity (GGO) component, while solid components correspond with invasive adenocarcinoma. The Eighth edition of the TNM staging system suggests that the tumor size be determined according to the invasive size excluding the lepidic component. However, this new concept causes fatal confusion, i.e., tumors are classified into a same T category despite the part-solid or pure-solid appearances provided they showed a same solid component size.

      Methods:
      Between 2008 and 2012, we retrospectively evaluated 719 surgically resected cN0 lung adenocarcinomas that measures 30mm or less in total dimension to assess the prognostic impact on the presence of GGO among the Eighth TNM classification. According to the new T category, it was defined based on the solid component size as follow: Tis; 0 cm (pure-GGO), T1mi; ≤ 5 mm, T1a; 6-10 mm, T1b; 11-20 mm, T1c; 21-30mm. Furthermore, all tumors were classified into 2 groups, i.e., GGO or Solid arms based on the presence of GGO component.

      Results:
      Of the cases, 133 (18%) were categorized in Tis, 88 (12%) in T1mi, 121 (17%) in T1a, 244 (34%) in T1b and 133 (19%) in T1c, respectively. Multivariate analysis revealed that both a presence of GGO and solid component were independently significant prognostic factors (p=0.007, 0.002). The 5y-overall survival (OS) was 99.2% in Tis, 95.8% in T1mi, 96.5% in T1a, 81.8% in T1b and 66.4% in T1c (p=0.038) with a median follow-up period of 56 months. When we evaluated the impact of T category based on GGO presence, the 5y-OS was significantly different between GGO and Solid arm in each T categories (T1a; 99.0% vs. 95.7%, p=0.045, T1b; 89.8% vs. 73.3%, p=0.004, T1c; 90.0% vs. 62.6%, p=0.046). Furthermore, clinical T categories significantly separated the OS in Solid arm (p=0.015) (T1a vs. T1b; p=0.090, T1b vs. T1c; p=0.037). In contrast, the 5y-OS was approximately 90% or more in GGO arm despite their T categories. Moreover, regarding radiological and pathological correlations, the rates of AIS was only 65% in Tis, and 51% showed invasive adenocarcinoma even in T1mi.

      Conclusion:
      Clinical T category should be considered based on the presence of GGO on thin-section CT, and tumor size should be applied exclusively to radiological solid lung cancer. In contrast, oncological outcomes of the tumor with GGO component were excellent despite their T categories, which should be described as Tis for pure-GGO, and T1a for part-solid tumor.

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    P1.05 - Poster Session with Presenters Present (ID 457)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
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      P1.05-002 - The Prognostic Impact of EGFR Mutation Status and Mutation Subtypes in Patients with Surgically Resected Lung Adenocarcinomas (ID 3932)

      14:30 - 15:45  |  Author(s): T. Matsunaga

      • Abstract

      Background:
      EGFR mutation status is a well-established predictor of the efficacy of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer. Recently, the differences in EGFR mutation subtypes were also reported to be associated with the efficacy of EGFR TKIs. However, the prognostic impact of EGFR mutation status and mutation subtypes remains controversial.

      Methods:
      We retrospectively reviewed 945 consecutive patients with surgically resected adenocarcinomas who had their EGFR mutation status analyzed between January 2010 and December 2014. Overall survival (OS) and recurrence-free survival (RFS) were analyzed in three cohorts (all patients, pathological stage I patients, and patients with exon 21 L858R point mutation or exon 19 deletions) using Kaplan-Meier methods and Cox regression models.

      Results:
      The median follow-up time was 42 months. The results for EGFR mutation status, mutation subtype, and the comparison data of OS/RFS are summarized in the attached Table. Positive EGFR mutation status was significantly associated with longer OS/RFS in all patients and was also associated with longer OS in pathological stage I patients. However, no significant differences were observed in OS/RFS between patients with exon 21 L858R point mutation and those with exon 19 deletions. In a Cox regression model for OS, the EGFR mutation status was a significant prognostic factor that was independent of well-established prognostic factors such as age, pathological stage, vascular invasion, lymphatic permeation, and serum CEA level.

      3y-RFS 5y-RFS P 3y-OS 5y-OS P
      All Pts 0.009 < 0.001
      EGFR mut＋ (N = 423) 84.6% 76.7% 95.2% 89.0%
      EGFR mut- (N = 522) 78.8% 71.2% 84.9% 76.5%
      p stage I Pts 0.102 < 0.001
      EGFR mut＋ (N = 352) 93.4% 85.4% 98.2% 94.5%
      EGFR mut- (N = 392) 90.6% 82.8% 92.6% 85.9%
      Subtypes 0.385 0.507
      Ex 21 L858R (N = 224) 84.8% 79.6% 95.2% 90.0%
      Ex 19 del (N = 164) 84.7% 74.3% 97.5% 95.8%


      Conclusion:
      Positive EGFR mutation status is a favorable prognostic factor in patients with surgically resected lung adenocarcinomas. However, EGFR mutation subtypes (exon 21 L858R point mutation or exon 19 deletions) have no prognostic impact.

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    P1.08 - Poster Session with Presenters Present (ID 460)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Surgery
    • Presentations: 1
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      P1.08-067 - The Feasibility of Lung Second Surgery for 2nd Primary Lung Cancer (ID 4113)

      14:30 - 15:45  |  Author(s): T. Matsunaga

      • Abstract

      Background:
      2[nd] primary lung cancer often has been encountered because of improvement of treatment outcome for lung cancer. If close follow up was performed after first surgery, 2[nd] primary lung cancer often was detected in early stage. And local therapy was indicated for this 2[nd] primary lung cancer. However, there is no rule whether stereotactic radiation therapy or surgery should be chosen. The aim of this study was to evaluate the feasibility of second surgery.

      Methods:
      We reviewed retrospectively 123 consecutive patients with past history of lung resection who underwent second surgery for 2[nd] primary lung cancer between 2008 and 2015 at our institution. i) These 123 cases were divided into 2 groups, contralateral and ipsilateral surgery groups. The difference between two groups of surgical difficulties (operation time and blood loss) and feasibility (post-operative complication and length of hospital stay) were evaluated by using Mann-Whitney U-test and Fisher’s exact test. ii) 82 cases who underwent contralateral surgery was picked up and divided into 3 groups, both lobectomy, lobectomy and limited surgery and both limited surgery. The difference between 3 groups of surgical difficulties and feasibility were evaluated by using same methods. iii) Furthermore, 41 cases who underwent ipsilateral surgery divided into 4 groups by procedure: completion pneumonectomy, lobectomy, segmentectomy and wedge resection. The difference between 4 groups of surgical difficulties and feasibility were evaluated by using same methods.

      Results:
      i) Not only operation time (161min vs 123min, p<0.001) but blood loss (30g vs 15g, p=0.002) were more in ipsilateral cases than in contralateral cases significantly. However, there was no significant difference in feasibility. ii) In contralateral cases, there were no significant difference between 3 groups in surgical difficulties and feasibility. iii) In ipsilateral cases, completion pneumonectomy had more operation time and blood loss than other procedures significantly (p=0.005, p=0.002, respectively) However, there was no significant difference in occurrence of post-operative complication.

      Conclusion:
      Ipsilateral surgery, especially completion pneumonectomy for 2[nd] primary lung cancer was more difficult procedure. However, ipsilateral and contralateral surgery was equivalent feasibility. Contralateral 2[nd] primary lung cancer is indication for surgery. However, second surgery for ipsilateral 2[nd] primary lung cancer requires careful consideration.

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    P3.04 - Poster Session with Presenters Present (ID 474)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Surgery
    • Presentations: 2
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      P3.04-023 - Perioperative Management of Antiplatelet Therapy in Patients with Coronary Stent Who Need Thoracic Surgery (ID 4588)

      14:30 - 15:45  |  Author(s): T. Matsunaga

      • Abstract

      Background:
      Guidelines recommend delaying noncardiac surgery in patients after coronary stent procedures for 6 -12 months after drug-eluting stents (DES) and for 6 weeks after bare metal stents (BMS). It is often replaced by bridging heparin for the prevention of perioperative stent thrombosis in Japan, although there is no evidence for heparin replacement. The aim of this study was to investigate the perioperative complication between the patients with continuation of antiplatelet therapy (APT) and that with substitution of heparin after interruption of APT in thoracic surgery.

      Methods:
      A retrospective study was done on 75 patients after coronary stent procedures performed thoracic surgery with APT or bridging heparin in perioperative from June 2008 to October 2015. We evaluated the perioperative outcomes between the patients with APT (APT group) and that with bridging heparin interrupting APT (non APT group).

      Results:
      Males were 13 cases (76%) and median age was 73.5 years in APT group. Fifteen cases (88%) with APT had angina in past history. The type of stent was drug eluting stent (71%), bare metal stent (24%) and biological absorption stent (6%) in APT group. Surgical procedures with wide wedge resection (12%), segmentectomy (12%), lobectomy (71%), and others (6%) were performed in APT group. Median operative time was 119 minutes and median operative blood loss was 18ml in APT group. There was no difference with operative time and blood loss in APT group compared in non APT group (p=0.128 and p=0.923). Cardiovascular events was not observed in both groups. One case had Hemothorax and reoperation in APT group and one case had hemosputum in non APT group. There was no difference in complication in both groups. Perioperative death was not observed in both groups.

      Conclusion:
      There was no difference between the patients with and without the discontinuation of antiplatelet agent in perioperative cardiovascular and embolic events. On the other hand, it seems that the compensatory of bleeding to continue antiplatelet agent is too large, because a few cases were forced completion pneumonectomy and acute exacerbation of interstitial pneumonia due to bleeding. Among the patients with coronary stent undergoing thoracic surgery, it might be less the benefits of the surgery with continuation of antiplatelet agent.

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      P3.04-029 - A Prospective Randomized Trial of Perioperative Administration of Neutrophil Elastase Inhibitor in Patients with Interstitial Pneumonias (ID 4255)

      14:30 - 15:45  |  Author(s): T. Matsunaga

      • Abstract

      Background:
      Although the acute exacerbation of interstitial pneumonia is a lethal complication after pulmonary resection for lung cancer patients with idiopathic interstitial pneumonias (IIPs), there are no established methods to prevent its occurrence. This prospective randomized study was conducted to evaluate whether the perioperative administration of neutrophil elastase inhibitor prevents the acute exacerbation of interstitial pneumonia.

      Methods:
      Between October 2009 and April 2015, 130 IIP patients with suspected lung cancer tumors were randomly assigned to two groups before surgery: in Group A (n=65), sivelestat sodium hydrate was perioperatively administered for 5 days; in Group B (n=65), no medications were administered. The primary endpoint was the frequency of the acute exacerbation of IIPs. The secondary endpoints were perioperative changes in the patients’ LDH, CRP, KL-6, SP-D and SP-A values, and the safety of the preoperative administration of sivelestat sodium hydrate. Multivariate analyses were performed using a logistic regression model to identify the predictors of acute exacerbation.

      Results:
      IIPs was radiologically classified into the following patterns: usual interstitial pneumonia (UIP) (n=23), possible UIP (n=28) and inconsistent with UIP (n=23). Sublobar resection, lobectomy and pneumonectomy were performed in 16, 112, and 2 patients, respectively. There were no statistically significant differences in patient characteristics between the groups. Two patients in group A and one patient in group B developed an acute exacerbation of IIPs. A preoperative partial pressure oxygen (PaO2) level of < 70mmHg was the only predictive factor identified in the multivariate analysis (p = 0.019, HR 19.2). The administration of neutrophil elastase was not associated with the development of an acute exacerbation, or with short- or long-term mortality. The KL-6, SP-D, SP-A levels on postoperative days 1 and 5 were lower in group A than in group B, and the LDH and CRP levels on postoperative day 5 were lower in group B than in group A; however the differences were not statistically significant. No subjective adverse events that could potentially be attributed to the administration of neutrophil elastase inhibitor were observed.

      Conclusion:
      The perioperative administration of neutrophil elastase inhibitor appeared to be safe; however, it could not prevent the development of acute exacerbation after pulmonary resection in lung cancer patients with IIPs.