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Xiaorong Dong
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- 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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P1.01-56 - Concurrent Mutations in Chinese Lung Cancer Patients Carrying HER2 Genomic Aberrations (ID 13756)
16:45 - 18:00 | Author(s): Xiaorong Dong
- Abstract
Background
Although human epidermal growth factor receptor 2 (HER2, ERBB2) genomic aberration has been identified as therapeutic targets, clinical trials of HER2-directed therapies have disappointing results in lung cancer. We hypothesize that the concurrent alterations might be one of the reasons, thus the aim of this study was to describe frequent concurrent alterations in Chinese lung cancer patients harboring HER2 mutations.
a9ded1e5ce5d75814730bb4caaf49419 Method
A total of 147 cancer patients with HER2 mutations were enrolled in the study. Tumor biopsy, ctDNA and pleural effusion samples were collected for detection alterations using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (59-1021).
4c3880bb027f159e801041b1021e88e8 Result
Sixty-two of 147 patients with HER2 genomic aberrations were diagnosed as lung cancer. The HER2 gene was amplified in 11 (18%) patients, whereas HER2 mutations were detected in 48 patients, co-occurrence of HER2 amplification and mutations were in 3 patients. Thirty of the 62 patients (48.39%) had concurrent actionable mutations across 18 genes, which involved in RTK-PIK3CA-mTOR signaling pathways, cell-cycle pathway, DNA repair pathway, RAS-RAF-MAPK pathway and some others (details in table). Moreover, 7 patients had more than 2 concurrent mutations besides HER2 mutation/amplification.
Table 1. concurrent genetic alterations in HER2-altered lung cancer patients
Signaling pathway Concurrent
actionable
mutations
Number of
patients
RTK-PIK3CA-mTOR
EGFR 11 PIK3CA 4 STK11 2 FBXW7 1 TSC1 1 FLCN 1 C11orf30 1 Cell-cycle CDKN2A 5 CCND1 2 RB1 1 DNA repair BRCA2 1 ATM 1 RAS-RAF-MAPK BRAF 1 KRAS 1 Others MDM2 2 JAK2 2 SMARCA4 2 PTCH1 1
8eea62084ca7e541d918e823422bd82e Conclusion
Concurrent of actionable genetic alterations in HER2-altered Chinese lung cancer patients was common. The complex molecular profiles elucidate the importance of comprehensive analysis of genetic mutations when considering anti-HER2 targeted therapy.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-127 - Efficacy of Endostar Combined with Whole Brain Radiotherapy in Patients with NSCLC Brain Metastases (ID 14231)
16:45 - 18:00 | Presenting Author(s): Xiaorong Dong
- Abstract
Background
Brain metastasis (BM) is the leading cause of poor prognosis, recurrence, and death in non-small-cell lung cancer (NSCLC) patients. The effectiveness of whole-brain radiotherapy is unsatisfactory. Endostar was reported as an anti-angiogenic agent, which could promote vascular normalization in tumor. This study is to investigate the influence of endostar combined with cranial radiation to cerebral blood flow, immune status and survival of the patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
28 NSCLC patients with multiple brain metastasis（more than four）were randomly divided into two groups. The experimental group (n = 14) received WBRT (30Gy/10F) combined with Endostar (15mg/m2, 7days), and the control group (n=14) received WBRT (30Gy/10F) alone. Magnetic resonance perfusion imaging was carried out pre- and one month post-radiation to detect regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF) and mean transit time (MTT) of the contrast medium. The changes of blood T lymphocyte subpopulation, the cognitive function and overall healthy level were evaluated pre- and post- radiation every two months against the MMSE, MoCA and EORTC QLQ-C30 scales. Moreover, Tumor progression was established by certified oncologists based on whole brain MRI scan.
4c3880bb027f159e801041b1021e88e8 Result
In the endostar group, rCBV, rCBF and MTT had a 122%, 210% and 11% higher in the target lesion region one month post radiation, compared with baseline data, while in the control group, rCBV, rCBF and MTT had a 18%, 20% and 26% lower change. These results showed a significant improvement of the cerebral perfusion in the endostar group. The T lymphocyte subpopulation increased in the Endostar group, especially the CD8+ T lymphocyte with a significant difference compared with the control group(p=0.0233). At the same time, the intracranial PFS (iPFS) was 349 days vs. 287 days and the PFS was 229 days vs. undefined between the Endostar group vs. the control group, but neither with significant difference, may for the limit of sample size. After cranial radiation, the cognitive function, physical, role, social and emotional functions improved in the endostar group, while a small fluctuation in the control group.
8eea62084ca7e541d918e823422bd82e Conclusion
Our study showed that endostar could promote vessel normalization and improve cerebral perfusion, and ameliorate the immune status, cognitive function and quality of life of the patients, which may also improve the survival of the patients.
6f8b794f3246b0c1e1780bb4d4d5dc53
