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Keisuke Kirita



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    OA01 - Advanced Diagnostic Approaches for Intrathoracic Lymph Nodes and Peripheral Lung Tumors (ID 117)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 1
    • Now Available
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      OA01.05 - Cryobiopsy Compared with Forceps Biopsy in Pathological Diagnosis and Biomarker Research in Lung Cancer: A Prospective, Single-Arm Study (Now Available) (ID 1564)

      10:30 - 12:00  |  Author(s): Keisuke Kirita

      • Abstract
      • Presentation
      • Slides

      Background

      Cryobiopsy is a novel transbronchial biopsy tool that enables the collection of larger samples than forceps biopsy. We evaluated the usefulness of cryobiopsy compared with forceps biopsy in pathological diagnosis and biomarker research in lung cancer.

      Method

      In this prospective single-arm study, 121 patients with or suspected of having lung cancer underwent concurrent transbronchial biopsy using a cryoprobe (ERBECRYO2) and forceps from the same lesion. Sample size and morphological classification were determined for patients whose cryobiopsy and forceps biopsy samples both contained tumor cells (n = 81). Patients diagnosed with non-small-cell lung carcinoma (NSCLC) with adequate samples from the two procedures (n = 65) were analyzed for programmed death ligand 1 (PD-L1) expression score (22C3). Genomic DNA and RNA were extracted from cryobiopsy and forceps biopsy formalin-fixed paraffin-embedded samples (20 NSCLC patients, 20 sections, 10 µm thick each) for whole-exome sequencing and RNA sequencing.

      Result

      Cryobiopsy samples were significantly larger than forceps biopsy samples (median 11.1 mm2[range: 3.3–135.0] vs. 2.0 mm2[0.7–6.6], p < 0.01). The confirmation rate of morphological classification of cryobiopsy samples was significantly higher than that of forceps biopsy samples (86% vs. 79%, p < 0.01, adenocarcinoma/squamous-cell carcinoma/small-cell carcinoma/other = 35/19/12/4 and 30/15/11/4, respectively). The success rate for evaluating PD-L1 score using cryobiopsy and forceps biopsy samples was 94% and 95%, respectively. A greater proportion of cryobiopsy samples tended to have PD-L1 > 1% than forceps biopsy samples (51% vs. 42%, p = 0.06). Significantly larger amounts of DNA (median 1.60μg vs. 0.58μg, p = 0.02) and RNA (median 0.62μg vs. 0.17μg, p < 0.01) were extracted from cryobiopsy samples than forceps biopsy samples. The success rate for whole-exome sequencing (90% vs. 15%, p < 0.01) and RNA sequencing (75% vs. 10%, p < 0.01) was higher for cryobiopsy samples than forceps biopsy samples. The median tumor-mutation burden in cryobiopsy samples was 84 (range 3–2396).

      Conclusion

      Cryobiopsy provided larger sample sizes compared with forceps biopsy, and were more useful for morphological classification, PD-L1 evaluation and genetic analysis.

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-72 - Clinical Feature and Management of Acquired Resistance to PD-1 Inhibitor in Advanced NSCLC (ID 1343)

      10:15 - 18:15  |  Author(s): Keisuke Kirita

      • Abstract
      • Slides

      Background

      Programmed cell death-1(PD-1) inhibitors have emerged as a standard treatment for patients with advanced non-small cell lung cancer (NSCLC). However, the patterns of disease progression (PD) after an initial response (acquired resistance) to a PD-1 inhibitor and the efficacy of continuous PD-1 inhibitor therapy beyond PD remain unclear.

      Method

      We retrospectively reviewed medical charts of advanced NSCLC patients treated with nivolumab or pembrolizumab as any line treatment at National Cancer Center Hospital East between January 2016 and October 2017. Acquired resistance was defined as disease progression after 6 months or more of treatment with a PD-1 inhibitor. Isolated disease progression was defined as progression in 1 site or organ, whereas systemic progression involved >1 site or organ. The clinical feature, PD pattern of acquired resistance, subsequent treatment and survival after acquired resistance were investigated.

      Result

      Fifty-nine patients were treated with a PD-1 inhibitor for 6 months or more, of whom 27 patients (46%) had acquired resistance. Only 1 patient received a PD-1 inhibitor as fist-line treatment. Twelve patients were diagnosed as adenocarcinoma, 4 as squamous-cell carcinoma and 11 as NSCLC-NOS. The response at 6 months of treatment was partial response in 17 patients (63%) and stable disease in 10 patients (37%). The median time to acquired resistance was 12.2 (95%CI 9.3-17.8) months. Progression in the lesion identified at baseline was observed in 16 patients (59%), new lesions appeared in 4 patients (15%) and both of them occurred in 7 patients (26%). Overall, the most frequent progression site was lung (n=14, 52%), followed by thoracic lymph node (n=7, 26%), pleura (n=6, 22%) and brain (n=4, 15%). The median number of progressed lesions was 2 and 67% of patients had progression limited to one (30%) or two (37%) lesions. Ten patients (37%) had isolated disease progression in lung (n=3), brain (n=3), thoracic lymph node (n=2), neck lymph node (n=1) and adrenal (n=1). In 11 patients, PD-1 inhibitor therapy was continued beyond PD with (n=4) or without local radiotherapy (n=7). The median OS after acquired resistance in patients with or without continuous PD-1 inhibitor therapy beyond PD was 9.9 months and 10.7 months, respectively.

      Conclusion

      Our results suggest that the most common pattern of acquired resistance to a PD-1 inhibitor was progression of thoracic lesion identified at baseline. One-third of the patients had isolated disease progression. The efficacy of continuous PD-1 inhibitor therapy beyond PD might be limited.

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