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J. Su
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-043 - Peripheral Blood CD45RA+ CCR7+ Naive T Cells Were Correlated with Prognosis in Non-Small Cell Lung Cancer Patients (ID 5999)
14:30 - 14:30 | Author(s): J. Su
- Abstract
Background:
CD45RA+ CCR7+ naive T cells were reported to generate effectors possessed the high potent cytotoxic activity and low level of "exhaustion" T cells in vitro. However the relationship between frequency of naïve T cells in peripheral blood and prognosis in non-small cell lung cancer (NSCLC) is not clear. In order to elucidate this relationship, we first analyzed the frequency of CD45RA+ CCR7+ naïve T cell in peripheral blood of healthy population and patients with NSCLC.
Methods:
The frequency of CD45RA+ CCR7+ naïve T cells was calculated by flow cytometry from healthy volunteers and NSCLC patients. The correlation of naive T cell frequency and overall survival (OS) of NSCLC patients who were treated with tyrosine kinase inhibitors (TKIs) or chemotherapy was statistically analyzed.
Results:
105 healthy volunteers (age rank 23-85year-old) and 137 NSCLC patients (age rank 33-86year-old) were enrolled in our study from 2013 October 1st to 2015 December 1st. Our results showed that the frequency of peripheral blood naïve T cells in NSCLC patients’ (Mean=17.8±5.7%) was significantly lower than that in healthy subjects’ (Mean=31.2±5.2%) (p<0.05). The frequency of naïve T cell was negatively correlated with the frequency of PD-1+CD8+ T cells (R[2]=0.1111, p<0.001) in peripheral blood of NSCLC patients, whereas, which was positively associated with the immune activity of CD8+ T cells and with the frequency of lymphoid stem cells or lymphoid progenitor cells in peripheral bloods (R[2]=0.1521, p<0.001). In the patients who were treated with TKIs，mOS in the group of high frequency of naïve T cells (>17.8%) was not reached, while that of group with low frequency (17.8%) was 19.0m (HR=0.3057, 95% CI 0.1127- 0.8291, p=0.0199). In patients who were administered chemotherapy, the mOS in the naïve T cells low frequency group was 12.0m, but in the high frequency group the median OS was undefined (HR=0.3286, 95% CI 0.1100 0.9817, p=0.0463).
Conclusion:
Our study shows that the CD45RA+ CCR7+ naïve T cells in peripheral blood closely related with immune response, and the frequency of naïve T cells in peripheral blood is positively associated with prognosis of NSCLC, which can be worked as a valuable prognostic factor for NSCLC patients.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-116 - Molecular Mechanism of Transformation from Adenocarcinoma to Small-Cell Lung Cancer after EGFR-TKI (ID 4983)
14:30 - 14:30 | Author(s): J. Su
- Abstract
Background:
In patients with advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations, EGFR-tyrosine kinase inhibitors (TKIs) are recommended as first-line treatment due to favorable clinical efficacy. However, acquired resistance inevitably develops after median progression-free survival (PFS) of 9-14 months. Among the mechanisms of acquired resistance, small-cell lung cancer (SCLC) transformation was reported to account for nearly 5%. However, the molecular details underlying this histological change and resistance to EGFR-TKI therapy remain unclear.
Methods:
15 out of 233 (6.4%) patients were confirmed to develop SCLC transformation after failure to EGFR-TKI. We analyzed the clinical parameters of these patients by using chi-square test and Kaplan-Meier analysis. To explore gene alterations that might contribute to SCLC transformation, next generation sequencing (NGS) was performed on four pairs of matched pre- and post-transformation tumor tissue samples. We further performed NGS on 11 matched circulating tumor DNA (ctDNA) to explore the potential mechanism of resistance to EGFR-TKI.
Results:
The median age of SCLC transformed patients was 53 years. 93.3% (14/15) patients harbored EGFR exon19 deletion. The median PFS and overall survival (OS) of SCLC-transformed patients treated with EGFR-TKI compared to those without transformation were 11.7 versus 11.9 months (P=0.473) and 29.4 versus 24.3 months (P=0.664), respectively. All 4 patients developed loss of heterozygosity of TP53/RB1 after transformation. Besides, increased copy number of five proto-oncogenes were identified in post-transformation tissue samples. Three patients developed EGFR T790M mutation in the post-transformation ctDNA rather than their tissue samples.
Conclusion:
SCLC transformation was commonly seen in patients harboring EGFR exon 19 deletion. The clinical outcomes of TKI and OS in SCLC transformed patients were similar to non-transformed patients. The loss of heterozygosity of TP53 and RB1 along with increased copy number of proto-oncogenes may lead to the SCLC transformation. The mechanisms of acquired resistance to TKI during SCLC transformation might be the emergence of classic drug resistance mutations, which was undetectable due to the intra-tumor heterogeneity.
