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Norimitsu Kasahara
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-027 - Clinical Significance of Topoisomerase-II Expression in Patients with Non-Small Cell Lung Cancer Treated with Amrubicin (ID 8859)
09:00 - 16:00 | Author(s): Norimitsu Kasahara
- Abstract
Background:
Amrubicin (AMR) is one of treatment options in patients with previously treated advanced non-small cell lung cancer (NSCLC). Although topoisomerase-I (Topo-I) and topoisomerase-II (Topo-II) are identified as a targeting molecular of AMR, it remains unclear about the relationship between the efficacy of AMR and the expression level of these markers.
Method:
Between April 2004 and May 2014, 56 patients with advanced NSCLC who had received AMR were retrospectively analyzed. Clinical data including histological type, response to treatment, and survival were collected from medical records. The expression level of Topo II within tumor cell were evaluated by immunohistochemical staining.
Result:
The majority of enrolled patients were men (66.1%) and median age was 69 years (range, 43-78 years). The tumor samples consist of adenocarcinoma (69.6%), squamous cell carcinoma (21.4%), poorly differentiated carcinoma (3.6%), pleomorphic carcinoma (1.8%) and unclassified NSCLC (3.6%) Twenty percent of tumors had EGFR mutations. Percentages of tumors overexpressing Topo-I and Topo-II were 57% and 30%, respectively. Median progression-free survival (PFS) and overall survival (OS) for all patients was 2.4 and 10.9 months, respectively. Patients with low Topo-II expression had significantly longer OS than those with high Topo-II expression (12.9 months vs. 7.0 months, p<0.05) whereas there was no significant association between Topo-II expression status and PFS. The number of AMR treatment cycles, poor performance status, advanced stage and elevated Topo-II expression were significantly associated with unfavorable OS (P<0.05). Meanwhile, Topo-I expression status was not significantly associated with PFS or OS in the patients with NSCLC.
Conclusion:
The present study suggests that the expression levels of Topo-II (but not Topo-I) are associated with in patients with NSCLC receiving AMR.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-026 - Impact of PD-L1 Expression on 18F-FDG-PET in Pulmonary Squamous Cell Carcinoma (ID 7903)
09:30 - 16:00 | Presenting Author(s): Norimitsu Kasahara
- Abstract
Background:
2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with positron emission tomography (18F-FDG-PET) is clinically useful for the evaluation of cancer. The accumulation of 18F-FDG within tumor cells is implicated in the expression of glucose transporter 1 (GLUT1) and hypoxic inducible factor-1α (HIF-1α). Although anti-programmed death-1 (PD-1) antibody therapy is approved for non-small cell lung cancer (NSCLC), the predictive biomarkers remain unknown. It was recently reported that the expression of programmed death ligand 1 (PD-L1) was positively correlated with the expression of GLUT1 and HIF-1α. Based on these backgrounds, we investigated the relationship between the tumor immunity including PD-L1 expression and the degree of 18F-FDG uptake in surgically resected pulmonary squamous cell carcinoma (SQC).
Method:
One hundred and sixty-seven patients (153 men, 14 women) with SQC who underwent 18F-FDG PET were included in this study. Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1α, PD-L1, CD4, CD8, and Foxp3. Relationships of clinicopathological and molecular biological features to the degree of FDG uptake and survival were analyzed.
Result:
The SUVmax of 18F-FDG was significantly correlated with the expression of PD-L1 (p=0.0224) and GLUT1 (p=0.0075). The PD-L1 expression was significantly correlated either with GLUT1 (p=0.0059), HIF-1α (p<0.0001) or CD8 (p=0.0006). Other pairs exhibiting significant correlation are as follows: GLUT1 and HIF-1α (p=0.0072), HIF1α and CD8 (p=0.0072), CD8 and Foxp3 (p<0.0001). Univariate analysis demonstrated that advanced stage (p=0.0027), elevated SUVmax (p=0.0233), and elevated PD-L1 expression (p=0.0157) were associated with unfavorable overall survival (OS). Multivariate analysis also revealed that advanced stage (p=0.0445), elevated SUVmax (p=0.0382), and elevated PD-L1 expression (p=0.0173) were independent prognostic factors predicting unfavorable OS.
Conclusion:
18F-FDG uptake was significantly correlated with the expression of PD-L1 and GLUT1 in SQC. 18F-FDG PET may reflect the immune response in the tumor microenvironment involved in the regulation of PD-L1 expression.
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P2.15 - SCLC/Neuroendocrine Tumors (ID 716)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.15-016 - Clinical Significance of Topoisomerase-II Expression in Patients with Relapsed HGNEC of the Lung Treated with Amrubicin (ID 9331)
09:30 - 16:00 | Author(s): Norimitsu Kasahara
- Abstract
Background:
Amrubicin (AMR) monotherapy is one of treatment options in patients with relapsed high grade neuroendocrine carcinoma (HGNEC) of the lung. Although topoisomerase-II (Topo-II), a target of AMR, has been reported to be a predictive or prognostic marker for chemosensitivity and clinical outcomes in various types of malignancies, its role remains unknown in this population.
Method:
Eighty-four patients with relapsed HGNEC (consisting of small cell lung cancer [SCLC] and large cell neuroendocrine carcinoma [LCNEC]) who received AMR monotherapy between 2003 and 2015 were enrolled into this study. We retrospectively collected clinical data including histological type, anti-tumor effect, and survival data from medical records. The expression levels of Topo-II were examined by immunohistochemical staining in tumor specimens obtained from surgical resection or biopsy.
Result:
The majority of enrolled patients were men (89%) and had a histological type of SCLC (92%) with a median age of 70 years (range, 49-83 years). Twenty-three percent of patients had poor performance status of 2 to 4. Sixteen percent of patients exhibited Topo-II overexpression in the tumors. The overall response rates in patients with high and low expression of Topo-II were 38.5% and 25.7%, respectively (p = 0.34). In multivariate analysis, patients with high expression of Topo-II had significantly longer progression-free survival (Hazard Ratio [HR] 0.39, p < 0.01) and overall survival (HR 0.48, p = 0.04).
Conclusion:
Our findings suggest that Topo-II expression is associated with clinical outcomes in patients with relapsed HGNEC receiving AMR monotherapy.
