Abstract 3046
Background
We conduct a trial using neoadjuvant chemotherapy (nCRT) and verify the value of ctDNA and CTC as biomarkers for tumor response in the nCRT treatment of locally advance gastric adenocarcinoma.
Methods
Twenty milliliters of plasma were collected at 3 points: before nCRT; after 2 cycles of nCRT; and after surgery. Firefly ctDNA NGS assays were used to track ctDNA mutations previously characterized in paired tumor tissue by massively parallel sequencing. Using patient-specific mutation derived from exome sequencing of tumor tissues samples, bespoke amplicon-based sequencing panel were synthesized and used for ctDNA profiling. CTCs in 7ml peripheral blood were separated by a negative enrichment method and identified by FISH using two frequently proliferation chromosome probes, CEP8 and CEP17. Meanwhile, the HER2 expression in CTCs was determined by FISH and immunofluorescence. CEP8+ and/or CEP17+, DAPI+, CD45- cell were justified as CTCs, HER2 FISH+ or HER2 IF+, DAPI+, CD45- cells were justified as HER2 positive CTCs.
Results
In comparison to basal line value of pre-chemotherapy blood, the ctDNA loading were decreased in post-chemotherapy specimens of 8 patients with TRG1 by histopathological grading or partial and complete response by CT scan. However, the amount of ctDNA in 25 patients diagnosed as TRG 2 or 3 showed minor changes during the neoadjuvant therapy. 22 have integral FISH data (CTCs range from 0-29, average: 4.9, 2.7 and 4.0, positive rate: 82%,73% and 73%), and 12 have integral HER2 data (CTCS range from 0-9, average: 2.9, 2.2 and 2.9, positive rate: 25%, 50% and 33%). The dynamic variations were coincidence to the clinical evaluation. For HER2, we found three positive model in CTCs, single FISH or IF positive or double positive. Double positive HER2-CTCs are found in some patients. By negative enrichment and FISH, CTCs can be detected at a low cutoff of 2 cells in 73%∼82% patients.
Conclusions
The ctDNA and CTC alteration during neoadjuvant therapy are consistent with histopathological grading and response assessmentand and can be surrogate markers to prediction efficacy of nCRT for GC.
Clinical trial identification
NCT03425058 11/02/2018.
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Beijing Municipal Administration of Hospital Clinical Medicine Development of Special Funding Support (ZYLX201701).
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
3330 - Tumour-infiltrating lymphocytes and BRCA-like status in stage III breast cancer patients treated with intensified carboplatin-based chemotherapy
Presenter: Leonora De Boo
Session: Poster Display session 2
Resources:
Abstract
3971 - Unravelling the biological characteristics of MammaPrint extreme risk subgroups
Presenter: Rajith Bhaskaran
Session: Poster Display session 2
Resources:
Abstract
5871 - Residual Cancer burden as a prognostic factor in a large series of Neoadjuvant chemotherapy. Subgroup analysis per molecular surrogated subtypes
Presenter: Catalina Falo
Session: Poster Display session 2
Resources:
Abstract
5014 - Clinical validation of CanAssist Breast in a Spanish cohort
Presenter: Manjiri Bakre
Session: Poster Display session 2
Resources:
Abstract
2787 - Meta-analysis on association of pathological complete response with long-term survival outcomes in triple-negative breast cancer
Presenter: Peter A. Fasching
Session: Poster Display session 2
Resources:
Abstract
4301 - Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial
Presenter: Gaia Griguolo
Session: Poster Display session 2
Resources:
Abstract
3205 - Frequency of germline mutations in women's cancer susceptibility genes in a large cohort of Chinese breast cancer patients
Presenter: Ning Liao
Session: Poster Display session 2
Resources:
Abstract
4091 - Triple blinded Prospective Study assessing the Impact of Genomics & Artificial Intelligence Watson For Oncology (WFO) on MDT’s Decision of Adjuvant Systemic Therapy for Hormone Receptor Positive Early Breast Carcinoma-
Presenter: Somashekhar Sampige Prasannakumar
Session: Poster Display session 2
Resources:
Abstract
4359 - Prognostic significance of Progesterone Receptor levels in luminal-like Her2- early Breast Cancer patients. A retrospective single Cancer Center analysis.
Presenter: Anna Diana
Session: Poster Display session 2
Resources:
Abstract
1369 - PAM50 HER2-enriched subtype and pathological complete response in HER2-positive early breast cancer: a meta-analysis
Presenter: Francesco Schettini
Session: Poster Display session 2
Resources:
Abstract