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Yoshihiro Miyata



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    MA10 - Emerging Technologies for Lung Cancer Detection (ID 129)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
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      MA10.11 - Sensitivity and Optimal Clinicopathological Features of Genetic Targeted Liquid Biopsy in pN0M0 Lung Adenocarcinoma (Now Available) (ID 788)

      15:15 - 16:45  |  Author(s): Yoshihiro Miyata

      • Abstract
      • Presentation
      • Slides

      Background

      Liquid biopsy for diagnosis of early-stage lung cancer is still challenging. The optimal marker and methodology has not been established. In Asia, almost 40-50% of lung adenocarcinomas harbor the EGFR mutation and L858R is a representative of a somatic EGFR mutation. We evaluated the usefulness of the EGFR somatic mutation in liquid biopsy using droplet digital PCR (ddPCR), which is a sensitivity device to detect several types of genetic mutations.

      Method

      We examined weather L858R could be detected from preoperative ctDNA by ddPCR. Cases without EGFR mutation (wild type) were utilized as negative control. All involved cases underwent surgical resection after preoperative HRCT and PET-CT. Serum for ctDNA extraction was collected before the operation. L858R in the primary site was confirmed by resected surgical specimen. Clinicopathological features (e.g.: whole and invasive tumor size on HRCT, SUV max on PET-CT, histological subtype) were also explored for an optimal liquid biopsy candidate.

      Result

      Forty-five pN0M0 lung adenocarcinoma patients harboring L858R were enrolled. Twenty-one and 24 cases showed part-solid and pure solid appearance on HRCT, respectively. Median whole and invasive tumor size on HRCT was 21 and 19 mm, respectively. 91.1% (41/45) cases were clinical stage IA1-IB and 97.8% (44/45) cases were pathological stage IA1-IB. In wild type cases, positive droplet for L858R was almost completely undetectable. Whereas, L858R was significantly detected in 7 EGFR mutant cases (sensitivity is 15.56%, 7/45). Among 7 positive cases, 6 cases showed pure solid appearance in preoperative HRCT. Except for pure solid appearance, there was no significant features related to the positive result. If cases are limited to pure solid appearance, 25.0% (6/24) of cases could be diagnosed by liquid biopsy. Even small-sized tumors (1.1 cm in diameter) or tumors with slight accumulation on PET-CT (SUV max 0.5) could be detected if it showed pure solid appearance on HRCT.

      Conclusion

      L858R can be a definitive marker for liquid biopsy using ddPCR in pN0M0 lung adenocarcinoma. 15.56% (7/45) of cases were diagnosed in pN0M0 cases. Limited to pure solid tumor, 25.0% (6/24) could be detected. Liquid biopsy can be a useful diagnostic option, especially for tumors with pure solid appearance.

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    P1.13 - Staging (ID 181)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Staging
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.13-13 - High-Risk Clinical Stage I Non-Small Cell Lung Cancer Based on High-Resolution Computed Tomography Findings   (ID 743)

      09:45 - 18:00  |  Author(s): Yoshihiro Miyata

      • Abstract
      • Slides

      Background

      Perioperative systemic therapy for stage I non-small cell lung cancer (NSCLC) has not been established. The purpose of this study was to identify the high-risk patients for recurrence in clinical stage I NSCLC who were potentially candidates for systemic therapy in addition to standard lobectomy.

      Method

      After excluding patients who underwent sublobar resection, 397 patients with clinical stage I NSCLC who underwent lobectomy with systematic lymph node dissection between April 2007 and March 2016 were analyzed. Solid component size on high-resolution computed tomography (HRCT) was used as tumor size on the basis of the 8th edition of TNM classification. Relapse-free survival (RFS) was estimated using Kaplan-Meier method, and multivariable Cox proportional hazards model was used to identify independent prognostic factors for RFS.

      Result

      Five-year RFS of all patients was 73.6%. Multivariable Cox analysis revealed that age (hazard ratio [HR], 1.04 (95% confidence interval [CI], 1.01– 1.06; P = 0.005), solid component size (mm) (HR, 1.06 (95% CI, 1.04–1.09; P <0.001), and pure solid type (HR, 1.79 (95% CI, 1.10–2.91; P = 0.02) were independent prognostic factors for RFS. When patients were divided into high-risk group for recurrence (solid component size of >2 cm or pure solid type) and low-risk group (solid component size of <2 cm and part solid type), there was a significant difference in RFS between high-risk group (n = 298; 5-y RFS, 65.0%) and low-risk group (n = 129; 5-y RFS, 91.0%; P <0.001). Lymphatic invasion (29.5% vs. 9.3%, P <0.001), vascular invasion (36.6% vs. 7.8%, P <0.001), pleural invasion (28.4% vs. 9.3%, P <0.001), and lymph node metastasis (17.9% vs. 1.6%, P <0.001) were more frequent in high-risk group than in low-risk group.

      Conclusion

      In clinical stage I NSCLC, patients with solid component size of >2 cm or pure solid type on HRCT were high-risk group for recurrence. These patients may be potential candidates for systemic therapy such as neoadjuvant immunotherapy.

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 3
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-01 - Surgical Outcome of Early Stage Lung Cancer Related vs Unrelated to Honeycomb Lesions with Interstitial Pneumonia (Now Available) (ID 45)

      09:45 - 18:00  |  Author(s): Yoshihiro Miyata

      • Abstract
      • Slides

      Background

      Lung cancer complicated with idiopathic interstitial pneumonia (IIPs) is known to lead to worse prognosis. Recently, it has been reported that the pathological characteristics differ between the lung cancer arising the honeycomb lesion of interstitial pneumonia (H-IIP group) and arising in other lesions (NH-IIP group). In this study, we aimed to assess the clinicopathologic outcome of resected lung cancer in each group.

      Method

      From a single center database of 1065 consecutive patients with clinical stage IA non-small cell lung cancer who had undergone preoperative high-resolution computed tomography and F-18-fluorodeoxyglucose positron emission tomography/ computed tomography, 112 patients with a radiologically determined IIP (H-IIPs; n=33, NH-IIP; n=79) were included in this study. Examination of clinicopathological outcomes were performed comparing each group.

      Result

      Median solid tumor size of each group were similar (18.4mm vs 18.6mm p=0.928), but median ground gloss opacity rate is significantly higher in NH-IIP group (6.7% vs 21.4% p=0.042). In the histopathological types, H-IIP group had significantly high rate of squamous cell carcinoma (45.5% vs 27.9%) and NH-IIP group had adenocarcinoma (27.3% vs 57.0%). As in previous reports, the proportion of EGFR mutation in adenocarcinomas tended to be high in NH-IIPs and also the high proportion of lepidic predominant. The disease-free survival (DFS) and overall survival (OS) were worse in patients of H-IIP group compared to NH-IIP group (DFS p=0.028, OS p=0.035). In a multivariate analysis, the H-IIP group and lower diffusing capacity for carbon of preoperative pulmonary functional test were significant worse predictors of OS and RFS (P < 0.001, respectively).

      Conclusion

      Lung cancer arising the honeycomb lesion of IIP had a great unfavorable impact on the prognosis of NSCLC, because of the worse pathological features.

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      P1.17-09 - Surgical Outcomes of Complex Versus Simple Segmentectomy for Stage I Non-Small Cell Lung Cancer (ID 803)

      09:45 - 18:00  |  Author(s): Yoshihiro Miyata

      • Abstract

      Background

      As segmentectomy becomes widely used for lung cancer treatment, “complex segmentectomy,” which makes several, intricate intersegmental planes, remains controversial because of procedural complexity and risk of increased complications and incurability. Questions remain regarding mortality, morbidity, surgical margin, lymph nodes dissection, and postoperative pulmonary function. We evaluated operative and postoperative outcomes of complex compared to simple segmentectomy.

      Method

      We retrospectively reviewed clinical stage I lung cancer patients who could tolerate lobectomy and underwent complex or simple segmentectomy between April 2007 and March 2017. Clinicopathologic, operative, and postoperative results of the complex (n = 117) and simple (n = 92) segmentectomy groups were compared.

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      Result

      No significant differences were detected in age, sex, comorbidities, preoperative pulmonary function, tumor histology, and size. Although only median operative time (180 vs. 143.5 minutes; P < 0.0001) was significantly longer in the complex group, 30-day mortality (0% vs. 0%), overall complications (24.8% vs. 22.8%), and prolonged air leakage (11.9% vs. 10.9%) were nearly equivalent between the two groups, respectively. The complex group showed comparable results in median surgical margin distance (16.0 vs. 17.5 mm) and number of dissected lymph nodes (6.0 vs. 7.0 nodes). Margin relapse occurred in two patients in the simple group but none occurred in the complex group. Both groups also showed similar postoperative pulmonary functions.

      Conclusion

      Complex segmentectomy is a safe option in the treatment of lung cancers with adequate operative outcomes.

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      P1.17-13 - Next Generation Sequencing of the Circulating Small RNA from Serum Identifies Small RNA-Based Biomarker Panel for Stage I-II Lung Adenocarcinoma (ID 989)

      09:45 - 18:00  |  Author(s): Yoshihiro Miyata

      • Abstract

      Background

      Circulating small RNAs have been reported as biomarkers for cancer diagnosis, including lung cancer. The purpose of this study is to identify the small RNA for the early detection of lung adenocarcinoma. In this study, we used next generation sequencing (NGS) in order to screen and validate expressions of the small RNAs between persons with and without adenocarcinoma and built the RNA-based biomarker panel.

      Method

      We used next generation sequencing in all phases (screening set, validation set, and the panel evaluation set) and researched micro RNAs(miR) and transfer RNA fragments(tRF) as small RNAs. We analyzed the RNAs from serum of 21 patients with adenocarcinoma and 20 healthy control for screening and assessed small RNAs from 22 patients with adenocarcinoma and 20 healthy control for validation. Regarding significantly upregulated and downregulated small RNAs, we built RNA-based biomarker panel and evaluated the panel with a different dataset (33 patients with adenocarcinoma and 27 healthy control).

      Result

      Based on screening and validation set, four miR and one tRF were upregulated. Tow miR and nine tRF were downregulated. An area under the curve value of each small RNA was 0.65 to 0.85. Among them, nine small RNA were adopted to the biomarker panel by using multiple regression analysis. In the cohort of screening and validation set, the panel showed a sensitivity of 93.0% and specificity of 88.0%, with an area under the curve value of 0.983, which was much larger than that of a single RNA. The panel was evaluated with a different dataset and showed a sensitivity of 90% and specificity of 74.1% when the threshold was 1.8.

      Conclusion

      In conclusion, we built the small RNA-based biomarker panel which included nine small RNA and our results showed the diagnostic efficacy of the panel. Further investigation is required to understand the cause for the expression change of each small RNA.

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    P2.17 - Treatment of Early Stage/Localized Disease (ID 189)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.17-01 - Analysis of Clinical Features and Prognosis of Non-Small Cell Lung Cancer Exceeding 30 mm Depending on the Ground Glass Opacity (GGO) Ratio (ID 230)

      10:15 - 18:15  |  Author(s): Yoshihiro Miyata

      • Abstract
      • Slides

      Background

      The ground glass opacity (GGO) ratio is associated with the prognosis of small (<30 mm) non-small cell lung cancer (NSCLC). However, the clinical features, especially the GGO ratio, and prognosis of NSCLC exceeding 30 mm are not well known. Therefore, this study aimed to determine the characteristics of patients with NSCLC exceeding 30 mm and analyze the clinical significance of the GGO ratio on prognosis.

      Method

      Totally, 271 patients with NSCLC tumors exceeding 30 mm on preoperative computed tomography scans and who underwent complete resection at our institution between January 2007 and December 2017 were included. The patients were divided into three groups based on the GGO ratio: pure solid tumors, GGO ratio 0–40%, and GGO ratio ≥40%. The cut-off value of 40% was determined based on the recurrence rate for each GGO ratio group. Clinical feature and prognosis of each group were analyzed.

      Result

      Of the included patients, 147 (54%) had pure solid nodule, 67 (25%) had nodules with a GGO ratio 0–40%, and 57 (21%) had nodules with a GGO ratio ≥40%. Among the patients with a GGO ratio ≥40%, 10 underwent limited resection (segmentectomy in 9 patients and wedge resection in 1); no patients experienced recurrence. Among the 147 patients with pure solid nodules, 47 (32%) experienced recurrence. Among the 67 and 57 patients with GGO ratio 0–40% and GGO ratio ≥40%, 16 (24%) and 2 (4%), respectively, experienced recurrence. The 3-year recurrence-free survival (RFS) rate was significantly shorter in patients with pure solid nodules (60.5%) than in patients with GGO ratio 0–40% (74.0%; p=0.010) and GGO ratio ≥40% ( 93.6%; p<0.001). Moreover, RFS was significantly shorter in patients with GGO ratio 0–40% than in patients with GGO ratio ≥40% (p=0.009). Similar results were observed for overall survival (OS). The 3-year OS rate was significantly shorter in patients with pure solid nodules (79.1%) than in patients with GGO ratio 0–40% (88.2%; p=0.046) and GGO ratio ≥40% (95.6%; p<0.001). Moreover, OS was shorter in patients with GGO ratio 0–40% than in patients with GGO ratio ≥40% with marginal significance (p=0.052).

      Conclusion

      A pure solid nodule was a major component among NSCLC tumors exceeding 30 mm. Among such patients, as the GGO ratio decreased, the recurrence rate increased. A GGO ratio of 40% is the appropriate cut-off value, and patients with GGO ratio ≥40% have better prognosis compared to patients with GGO ratio <40% or pure solid nodules. The prognosis of patients with GGO ratio ≥40% who undergo limited resection may be similar to that of patients undergoing lobectomy, the standard operation procedure.

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