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Koji Tsuta
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MA24 - Genomic Evolution, KEAP 3 and More Non-Coding RNA (ID 928)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 10:30 - 12:00, Room 205 BD
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MA24.03 - Biologic Profiling of Pre-Metastatic Niche in Completely Resected Pathological Stage I Non-Small Cell Lung Cancer (ID 13081)
10:40 - 10:45 | Author(s): Koji Tsuta
- Abstract
- Presentation
Background
Despite refinement of treatment strategy for non-small cell lung cancer (NSCLC), pathological Stage I NSCLC still develops recurrent disease in approximately 20% of patients even after complete resection. Recently, tumor microenvironment which promotes distant metastasis, or 'pre-metastatic niche', has been indicated to play pertinent roles in postoperative recurrence of cancer. Our aim is to investigate biologic profiles of pre-metastatic niche in pathological Stage I NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Eighteen (12.7%) of 141 patients with pathological Stage IA or IB NSCLC who underwent R0 lobectomy between Jan. 2008 and Dec. 2013 developed distant metastasis postoperatively. From archived formalin-fixed paraffin-embedded specimens, these 18 cases of postoperative distant metastasis and matched cases were selected for total RNA extraction. To overcome inherent bias in selecting control patients, one-to-one matched pairs were created using propensity score matching of which model included age, sex, smoking history, and pathological stage. The samples with inadequate mRNA quality/ quantity were excluded. Gene expressions were detected by nCounter (NanoString Technologies, WA, USA) with PanCancer Immune Profilling Panel and PanCancer Progression Panel. Detected expressions were then analyzed and compared between the two groups by nCounter Advanced Analysis (version 2.0.115). Genes with unadjusted P-value < 0.01 were regarded as candidates for further investigation
4c3880bb027f159e801041b1021e88e8 Result
From preliminary comparative study on 6 paired cases, distant metastasis group showed upregulations of TPM2, CCL21, SOX2, CXCL12, EGFL7, PTGDS, BGN, PS8L1, ID4 and TGFB, whereas it showed downregulations of MTOR and CCL8 compared to recurrence-free group.
In LATE-BREAKING ABSTRACT, we will report following results:
1) Complete dataset of the comparative analysis including all pairs with adequate mRNA.
2) Immunohistochemstry and/or in situ hybridization of the candidate genes/proteins on pathological sections.
8eea62084ca7e541d918e823422bd82e Conclusion
Biologic profilings of brain metastasis from NSCLC may subsequently help to understand underlying mechanism of postoperative distant metastasis and ultimately lead to novel targeted therapy.
Futher details will be added in LATE-BREAKING ABSTRACT.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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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): Koji Tsuta
- 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.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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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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P1.09-34 - Prognostic Impact of Invasive Size, Actual Tumor Size, and Mucinous Tumor Size in Invasive Mucinous Adenocarcinoma of the Lung. (ID 12752)
16:45 - 18:00 | Author(s): Koji Tsuta
- Abstract
Background
Currently, tumor size of invasive mucinous adenocarcinoma such as invasive mucinous adenocarcinoma (IMA) is defined by the spread of mucinous component regardless of the existence of tumor cells. The aim of this study is to investigate the prognostic impact of the size of invasive lesion, actual tumor spread, mucinous component in IMA.
a9ded1e5ce5d75814730bb4caaf49419 Method
Consecutive 19 patients with pN0M0 IMAs which were completely resected between Jan. 2009 and Dec 2015 were retrospectively analyzed. Invasive size (IS), actual tumor size (aTS), and mucinous tumor size (mTS, current T factor) were measured on the identical pathological section, and radiological tumor size (rTS) was also recorded by thorax computed tomography. The prognostic value for postoperative recurrence was evaluated by area under the receiver-operating characteristic (ROC) curves and compared by DeLong’s test.
4c3880bb027f159e801041b1021e88e8 Result
Based on mTS, study population included 2 patients T1a, 3 with T1b, 7 with T1c, 4 with T2a, and 3 with T2b. Median age, follow-up, IS, aTS, mTS, and rTS were 75 years, 39 monts, 11mm, 25mm, 26mm and 30mm, respectively. During follow-up, 1 mortality and 3 recurrences were observed. The area under the ROC curves for IS, aTS, mTS,, and rTS were 0.833 (p=0.074)、0.979 (p=0.01)、1.0 (p=0.007)、0.958(p=0.014). The mTS showed no significant difference compared to IS, aTS or rTS.
8eea62084ca7e541d918e823422bd82e Conclusion
In IMA, aTS and mTS might have prognostic value for recurrence. Prospective study with larger population would be necessary to validate the results.
6f8b794f3246b0c1e1780bb4d4d5dc53
