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Shingo Matsumoto



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    OA03 - Advances in Lung Cancer Pathology (ID 897)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 205 BD
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      OA03.02 - Nationwide Comparative Study Of PD-L1 IHC Assays on Lung Cancer: Initial Report Of LC-SCRUM-IBIS Project (ID 11321)

      10:40 - 10:50  |  Author(s): Shingo Matsumoto

      • Abstract
      • Presentation
      • Slides

      Background

      Precision medicine requires accurate biomarkers for appropriate therapeutic decision. PD-L1 IHC is a predictive biomarker for immune checkpoint inhibitor (ICI), however, the complexity of PD-L1 IHC system could make interpretations confusion in practice. In this study, we compared four PD-L1 IHC systems using real-world clinical samples to reveal their properties and capability of harmonization as a part of nationwide immuno-oncology biomarker study of lung cancer (LC-SCRUM-IBIS).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Out of 1635 lung cancer patients enrolled in LC-SCRUM-Japan, four PD-L1 IHC assays (22C3, 28-8, SP263 and SP142) and whole-exome sequencing (WES) were analyzed in addition to NGS mutation screening by the Oncomine™ Comprehensive Assay (OCA). Planned accrual is 1000. IHC was evaluated by three certified lung pathologists independently. Three-tier scoring system (cutoff value of 1, 50%) applied for tumor cell (TC) in all assays, and TC+IC scoring algorism in SP142, according to the manufactural instruction. We calculated Spearman’s correlation coefficient and kappa value among TC proportion and the original protocol’s criteria of each assays. Discordant rate among assays was examined.

      4c3880bb027f159e801041b1021e88e8 Result

      486 patients (438 nonsmall, 48 small cell carcinoma) completed IHC study analysis from February to December 2017.

      Compared to 22C3, TC-score of 28-8 (kappa value 0.896) were and SP263 (0.729) showed good, and SP142 resulted slight (0.159) correlations. SP142-tc+ic score showed fair correlation with 22C3/28-8/SP263 TC-scores (kappa= 0.213/ 0.241/ 0.291, respectively).

      Our results showed substantial reproducibility of TC score among observers across different IHC assays (range of kappa: 0.675 – 0.837). Inter-observer concordance of the SP142-IC score was also acceptable (kappa 0.591-0.779). Of note, within 22C3 positive group (>1%), 4.5/15.6/67.7/55.0 % of 28-8/SP263/SP142-tc/SP142-(tc+ic) resulted in negative, respectively, indicating a risk of lower category switching for SP263 and SP142 compared to 22C3 and 28-8. A subset (8.3%) of 22C3-negative group resulted in SP142-positive and all such discrepancy was due to IC-positivity.

      There was no significant association between each PD-L1 expression and TMB by WES and OCA. Out of 77 patients treated with ICI, most responders (11/17, 65%) had PD-L1 high expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results revealed an excellent/moderate/slight correlation between 22C3 and 28-8/SP263/SP142. SP142-positive-cases were fewer and more rigorous than the other three assays. A subset of lung cancer showed IC-only PD-L1-positivity. Inter-observer reproducibility was substantial for TC and moderate for IC. The scoring algorism affected concordance trend in a modest way. For harmonization, we should aware of each assays properties. PD-L1 IHC is not a perfect but a feasible biomarker for patients’ selection of ICI therapy.

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    P1.09 - Pathology (Not CME Accredited Session) (ID 941)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.09-33 - Validity of Non-Small Cell Lung Cancer Not Otherwise Specified to Use Immunohistochemistry on Treatment Outcome (ID 11190)

      16:45 - 18:00  |  Author(s): Shingo Matsumoto

      • Abstract

      Background

      In non-small cell lung cancer, histologic samples have become significantly important to administrate tumor type specific cytotoxic and molecular-targeted therapies. When a biopsy sample shows lacking definite morphology, diagnosis is made into three subtypes, favour adenocarcinoma, favour squamous cell carcinoma and NOS-null, according to the immunohistochemistry (IHC) results. However, in terms of the patient outcome, validity of IHC-based these classification have been unknown yet.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A series of 152 advanced NSCLC patients whose diagnosis was made by morphology and homogeneously treated was enrolled. We performed IHC staining (TTF-1, SP-A, p40, and CK5/6) of these samples and refined diagnoses into 3 subtypes. We analyzed the pathological subgroup depends on IHC staining with clinical characteristics including molecular analysis, response of chemotherapy and prognosis.

      4c3880bb027f159e801041b1021e88e8 Result

      IHC profiling displayed that 50% of cases was favour Ad, 31% was favour SqCC, and 19% was NOS-null. On the patient background, there was no difference in age, smoking history, and PS, but there were differences in gender, and the favour Ad group had more females than other groups. EGFR mutation was significantly more expressed in favour Ad group than in the other groups, and molecular targeted drugs in initial treatment were used in favour Ad group in a large proportion. Compared with favour Ad and SqCC group, NOS-null group showed significantly poorer outcome in terms of median overall survival (OS). Between favour Ad and favour SqCC group, median OS was better in favour Ad group (19.5 months vs 15.0 months, p = 0.018). Excluding patients using molecular targeted drugs, there was no difference in median OS between favour Ad and favour SqCC group (15.2 months vs 15.0 months p = 0.29). Pemetrexed containing platinum regimen showed similar response rate as other platinum regimen in the favour Ad cohort (43% vs 46%), whereas poorer response in the favour SqCC (0% vs 50%) and NOS-null (0% vs 24%) cohort. Although patients to be received pemetrexed containing platinum regimen compared to those to be received other platinum regimen demonstrated a trend toward good PFS in favour Ad group, there were no statistically differences.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study made clear chemo-responsiveness, the expression frequency of driver mutation and prognosis in NSCLC favour Ad, SqCC and NOS-null. These findings support that histological subtyping in biopsy specimen by IHC would be mandatory to archive appropriate therapy.

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