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T. Takagaki
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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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P2.02-046 - Assessment of PDL1 and Immunoprofiling Using Multiplex Quantitative Immunofluorescence in Lung Cancer: Clinical Implications (ID 10245)
09:30 - 09:30 | Author(s): T. Takagaki
- Abstract
Background:
Understanding of the “profile” of PD-L1 expression and its interplay with immune cells will provide important insights into lung cancer pathogenesis, and immunotherapeutic strategies targeting this important immune checkpoint protein. The aim was to investigate the correlation between multiplex immunofluorescence (mIF) expression of PD-L1, density and nature of tumor infiltrating immune cells in non-small cell lung carcinomas (NSCLC), and correlate those profiles with clinical and pathological variables including patient outcome.
Method:
We studied 194 stage II/III patients that underwent pulmonary resection, including 98 adenocarcinoma (ADC), 59 squamous cell carcinoma (SqCC), 15 large cells carcinomas (LCC) and 22 neuroendocrine carcinomas (NEC), primary tumors. Formalin-fixed and paraffin embedded (FFPE) tissue microarrays were constructed with five 1.5 mm cores representative of histologic patterns found in each tumor. mIF was performed using the Opal 7-color fIHC Kit™, scanning in the Vectra™ multispectral microscope and analyzed using the inForm™ software (Perkin Elmer, Waltham, MA). The markers studied were grouped in two 6-antibody panels: Panel 1, AE1/AE3 pancytokeratins, PD-L1 (clone E1L3N), PD-1, CD3, CD8 and CD68; and Panel 2, AE1/AE3, Granzyme B, CD45RO and CD57, FOXP3, and CD20. General linear model was used to evaluate the interaction among primary vs metastatic tumors, histologic type and TAICs and Cox's proportional hazard model for overall survival (OS).
Result:
Fifty-eight % out of 164 tumors were positive for PDL-1+ expression (5% cut-off) in malignant cells (EA1/EA3+). Significant higher levels of PD-L1+ expression were detected in NEC compared with other histologies (ADC, SqCC and LCC) (P=0.006). In the same way, we observed higher densities of cytotoxic T lymphocytes (CD3+CD8+) in NEC when compared with the lowest expression in SqCC (P=0.02). Large cell carcinomas presented high levels of memory/regulatory T cells (CD3+FOXP3+CD45RO+) compared with other histologic types but the difference didn´t achieve statistical significance. No difference was found for CD3+PD-L1+, CD68+PD-L1+, natural killer T lymphocytes (CD3+CD57+) and B lymphocytes (CD20+) among the histologic types. Difference between primary and metastatic tumors was found only for naive/memory T lymphocytes (CD3+ CD45RO+) (P=0.04). High CD3+FOXP3+CD45RO+ and CD3+PDL1+ expression were independent favorable prognostic factor for DFS and OS adjusted by smoking, primary vs metastatic, and histologic type [HR 2.68, 95% (CI 1.37–5.24), P=0.004; HR 2.11 (CI 1.07-4.18, P=0.03].
Conclusion:
High abundance of CD3+PD-L1+ cells and memory/regulatory T cells CD3+FOXP3+CD54RO are favorable prognostic factors for resected NSCLC, highlighting the importance of comprehensive assessment of both tumor and immune cells. Supported by CNPq P246042/2012-5 e CNPq 301411/2016-6; FAPESP 2013/10113-7.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-066 - CNS Metastases of Pulmonary Adenocarcinoma Harboring EGFR-Activating Mutations: a Multidisciplinary Approach, Including EGFR-TKis (ID 10395)
09:30 - 09:30 | Author(s): T. Takagaki
- Abstract
Background:
The incidence of CNS metastases among patients (pts) with pulmonary adenocarcinoma harboring EGFR-activating mutations seems to be increasing, probably related to their prolonged overall survival. A multidisciplinary approach, including radiation therapy, surgery and EGFR-TKIs, is absolutely essential for the management of these pts. We aimed to study the effectiveness of this multidisciplinary approach of CNS metastases in pts not previously treated with EGFR-TKis.
Method:
It is a retrospective, uni-institutional study, and all pts were consecutively identified and treated between 2009 and 2017. Eligible pts had to be diagnosed with pulmonary adenocarcinoma harboring EGFR-activating mutations (Sanger sequencing performed in either archived, or new, formalin-fixed and paraffin-embedded samples). CNS involvement was diagnosed based on CT scans, MRI and/or cerebrospinal fluid findings. All studied pts were treated with EGFR-TKIs (erlotinib or gefitinib) and other multimodality therapies including radiation therapy (whole brain or stereotactic radiosurgery), metastasectomy and/or intrathecal methotrexate, based on the decision of the multidisciplinary team.
Result:
35 pts were studied, with a median age 63 y.o. (35-90), being 26 (74%) female, 19 (54%) never-smokers, and 26 (74%) ECOG-PS 0-2. All pts received an EGFR-TKI (erlotinib or gefitinib), and 26 also were treated with radiation therapy, 11 were submitted to surgery, 2 to stereotactic radiosurgery and 1 received IT-MTX; 4/35 were treated with an EGFR-TKI only. Median treatment time with an EGFR-TKI was 7.6 mo. Median progression-free survival (mPFS) was 8.2 mo and the median overall survival (mOS) was 11.9 mo. Among those 25 pts whose tumors were diagnosed with an exon 19 deletion, mPFS was 8.2 mo. and mOS 11.9 mo., and among those 9 pts with L858R mutation, mPFS was 10.8 mo. and mOS 13.8 mo.
Conclusion:
Those pts diagnosed with pulmonary adenocarcinoma harboring EGFR-activating mutations treated with a multidisciplinary approach (including an EGFR-TKI) may derive promising PFS and OS results. The approach must be individualized, considering patient characteristics, tumor biology aspects and also the available healthcare resources.
