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Yuichiro Hayashi
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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): Yuichiro Hayashi
- Abstract
- Presentation
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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P1.05 - Interventional Diagnostics/Pulmonology (Not CME Accredited Session) (ID 937)
- 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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P1.05-17 - Clinicopathological Characteristics of Primary Lung Cancers Associated with Emphysematous Bullae (ID 13204)
16:45 - 18:00 | Author(s): Yuichiro Hayashi
- Abstract
Background
Lung cancers associated with emphysematous bullae (EB) comprise approximately 5% of all primary lung cancers, but the clinicopathological characteristics remain unclear. This study aims to investigate the clinicopathological characteristics and postoperative prognosis of lung cancers associated with EB.
a9ded1e5ce5d75814730bb4caaf49419 Method
From 2008 through 2012, consecutive 517 patients who underwent complete surgical resection for primary lung cancer at our institution, were retrospectively reviewed. Lung cancer associated with EB was defined as lung cancer adjoining emphysematous airspace >1cm, without lung parenchyma, on preoperative thin-slice computed tomography scans. Among the 517 patients, 35 (6.8%) had lung cancers associated with EB (EB group). Their clinicopathological features and prognosis were retrospectively compared with those in the patients having lung cancer not associated with EB (non-EB group).
4c3880bb027f159e801041b1021e88e8 Result
The median follow-up duration was 42 months (range, 2-85 months). The median age of EB group was 70 (39-79) years, while that for non-EB group was younger 59 (33-91) years (p = 0.07). The EB group included more men (94% vs. 6%, p < 0.01), smokers (97% vs 63%, p < 0.01), and the patients with low FEV1.0% (< 70%) ( 91% vs 27%, p < 0.01). In the EB group, frequency of cancer in the right upper lobe was significantly higher than in the non-EB group (60% vs 25%, p < 0.01). Histologically, non-adenocarcinomas, including squamous cell carcinoma, neuroendocrine tumor and large cell carcinoma, were common in the EB group compared with in the non-EB group (57% vs 24%, p < 0.01). Among the EB group, 16 patients (45%) were p-stage I, 16 (45%) were p-stage II, three (9%) were p-stage III, and none (0%) were p-stage IV (WHO 8th classification). The 5-year overall survival (OS) rate for EB and non-EB groups was 75% and 88%, respectively, without significant difference (p = 0.20). The 5-year recurrence-free survival (RFS) rate was also not different between EB and non-EB groups (75% vs. 79%, p = 0.85). The multivariate analysis did not demonstrate that the association with EB to be a significant prognostic factor (p = 0.39).
8eea62084ca7e541d918e823422bd82e Conclusion
Lung cancers associated with EB have clinicopathological features including the predominance of men, heavy-smoking history, and non-adenocarcinoma histology compared with lung cancer not associated with EB. However, in the current analysis, the survival was not different between patients with lung cancers with and without EB.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P1.14 - Thymoma/Other Thoracic Malignancies (Not CME Accredited Session) (ID 946)
- 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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P1.14-26 - Long Term Outcome and Clinicopathological Features of Thymic Carcinoma - A Retrospective Study of 25 Cases at a Single Institution (ID 12371)
16:45 - 18:00 | Author(s): Yuichiro Hayashi
- Abstract
Background
Thymic carcinoma is a rare and invasive mediastinal tumor and the optimal treatment is not well defined currently. According to the Clinical report from Japanese Association for Research on the Thymus in 2015, surgical resection is the mainstream of treatment, and the 5-year overall survival was 61%. The patient with complete resection with a 5-year survival of 89%, 68%, 60% for stages I, II & III and IV, respectively. In order to clarify the long-term outcome and prognostic indicators in our facilities, we reviewed our institutional experience with cases of surgical resection for thymic carcinoma.
a9ded1e5ce5d75814730bb4caaf49419 Method
A single-institution retrospective study of patients operated for thymic carcinoma. Between 1998 and 2017, 25 patients with thymic carcinoma underwent surgical resection, and their clinical and pathological data were retrospectively reviewed. Overall survival (OS) rates were compared using a log- rank test and Survival curves were plotted using the Kaplan–Meier method.
4c3880bb027f159e801041b1021e88e8 Result
Twenty-five patients underwent surgery for thymic carcinoma. The IASLC/ITMIG thymic epithelial tumors Stage according to the 8thedition of the TNM classification was I in 9 patients, II in 6, III in 5, IV in 5. A complete resection was achieved in ten patients (40%) that were no recurrence and death in the follow-up period. There was no fetal complication and no postoperative mortality. Adjuvant radiotherapy and/or chemotherapy was offered to 22 patients. The median follow-up period was 37 months. The 5-year overall survival rate for all the patients were 78.2%. Patients who underwent an incomplete resection had a significantly worse survival as compared to those with complete resection in univariate analyses (p < 0.01).
8eea62084ca7e541d918e823422bd82e Conclusion
Our result indicated that complete resection could impact the overall survival of patients with thymic carcinoma after surgical resection.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- 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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P1.16-37 - Clinicopathological Characteristics and Prognostic Factors of Operable Non-Small Cell Lung Cancer Patients with the Diabetes Mellitus (ID 12430)
16:45 - 18:00 | Author(s): Yuichiro Hayashi
- Abstract
Background
Lung cancer patients have a high frequency of comorbidity. The diabetes mellitus (DM) has been reported to be associated with postoperative complication and survival in several types of cancers. The aim of this study was to investigate the impact of DM on postoperative complication and survival in operable non-small cell lung cancer (NSCLC) patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed 1231 patients who underwent surgical resection for NSCLC between 1996 and 2012. The outcomes were compared between the patients with DM (DM group, n=139) and without it (Non-DM group, n=1092). Patients were assigned to DM group if following conditions were identified; 1) a history of DM or medication use, and 2) preoperatively elevated fasting glucose (>126 mg/dL) or hemoglobin A1c (National Glycohemoglobin Standardization Program) level (≥ 6.5 %) in spite of the unrevealed history of DM. However, diabetes of all patients in DM group was controlled by dietary or sliding-scale insulin therapy. Postoperative complications were defined as events of grade 2 or more according to the Clavien-Dindo classification. A multivariate Logistic regression model was used to identify clinical factors associated with postoperative complication. Survival was evaluated by overall, relapse-free, and disease-specific survivals using Kaplan-Meier method, and a multivariate Cox proportional hazard model was used to identify prognostic factors.
4c3880bb027f159e801041b1021e88e8 Result
DM group included more elderly patients, males, smokers, patients with ischemic heart disease, patients taking antiplatelet or anticoagulant drugs, squamous cell carcinomas than non-DM group. DM group showed higher incidence of postoperative complications than non-DM group (28% vs. 21%, p=0.047). Logistic regression analysis showed that DM was an independent predictor for postoperative complication (OR: 1.851, 95% CI: 1.189-2.884). But, no significant difference was observed in thirty-day mortality between the two groups (2% vs. 1%, p=0.061). DM group showed a worse overall survival than non-DM group (p=0.024), and multivariate Cox analysis showed that DM was identified as an independent poor prognostic factor for overall survival (HR: 1.492, 95% CI: 1.053-2.113). DM group included more death from other disease than non-DM group (50% vs. 35%, p=0.048), and there was no significant difference in relapse-free and disease-specific survival between the two groups.
8eea62084ca7e541d918e823422bd82e Conclusion
The present study demonstrated that operable NSCLC patients with DM have distinct clinicopathological features. Although the presence of preoperative DM was associated with postoperative morbidity and worse overall survival, it did not increase perioperative and lung cancer-related mortalities. Operable NSCLC patients with DM can be still indicated for curative surgery if their perioperative diabetes was controlled.
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