Abstract 4039: Simultaneous quantification of activated immune cells and PD-L1 expressing circulating tumor cells (CTCs) in peripheral blood of cancer patients receiving checkpoint inhibitor therapy

2019 ◽  
Author(s):  
Rachel Krupa ◽  
Robin Richardson ◽  
Priscilla Ontiveros ◽  
Joseph Schonhoft ◽  
Jiyun Byun ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Simultaneous Quantification ◽  
Checkpoint Inhibitor Therapy

Concordancy of immunocytochemistry profiling of circulating tumor cells with immunohistochemistry for analysis of therapeutically relevant biomarkers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3047-3047
Author(s):  
Dadasaheb B Akolkar ◽  
Darshana Patil ◽  
Sudha S Murthy ◽  
Kiran Bendale ◽  
Revati Patil ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Tumor Tissue ◽  
Checkpoint Inhibitor ◽  
Matched Pairs ◽  
Tissue Analysis ◽  
The Status ◽  
Checkpoint Inhibitor Therapy ◽  
Selection Of

3047 Background: Immunohistochemistry (IHC) profiling of tumor tissue is the present standard for evaluation of therapeutically relevant biomarkers such as ER, PR, HER2, AR, ARv7, PD-L1 and MMR for selection of targeted, endocrine and checkpoint inhibitor therapy selection. However, this critical analysis is dependent on availability of tumor tissue obtained by an invasive biopsy. Challenges to this analysis include insufficient tumor tissue and inability to perform a repeat biopsy to obtain fresh tumor tissue. We have previously described an approach for negative enrichment of Circulating Tumor Cells (CTCs) from peripheral blood and for Immunocytochemistry (ICC) profiling of these CTCs for detection of diagnostically relevant tissue of origin and subtype specific markers, concordant with tumor tissue analysis. Methods: In the present study, we determined concordance between tumor tissue (HPE) and CTCs (ICC) for ascertaining the status of therapeutically relevant markers ER, PR, HER2, AR, ARv7 PD-L1 and MMR. We evaluated 201 matched pairs of tumor tissue (FFPE blocks) and CTCs obtained from peripheral blood. Results: Among the 743 paired assays on matched tumor tissue and CTCs, concordance (positive or negative) was observed in 651 matched pairs (87.6%). The concordance was 82.9% for ER, 100% for PR, 90.2 % for Her2, 93.8% for AR, 90% for Arv7, 85.1% and 87.6% for PD-L1 clones 22c3 and 28-8, and 85.6% for MMR (MLH1, MSH2, MSH6, and PMS2). Conclusions: The study findings indicate that ICC analysis of CTCs may be able to substitute IHC analysis of tumor tissue for profiling of therapeutically relevant markers. This approach may have application in cases where tumor tissue may be limiting and / or where an invasive biopsy to obtain tumor tissue may be unviable.

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

Extrachromosomal DNA (ecDNA) carrying amplified oncogenes as a biomarker for insensitivity to pembrolizumab treatment in gastric cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3123-3123
Author(s):  
Jason H. Christiansen ◽  
Nam-phuong Nguyen ◽  
Roel Verhaak ◽  
Hoon Kim ◽  
Vineet Bafna ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Patient Selection ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
P Value ◽  
Extrachromosomal Dna ◽  
Checkpoint Inhibitor Therapy ◽  
Gastric Cancer Patients

3123 Background: In the KEYNOTE-059 study, the anti-PD-1 checkpoint inhibitor pembrolizumab was shown to have a modest overall response of 11.6%. Common predictors of response including, high microsatellite instability (MSI-H), PD-L1 expression, tumor mutational burden (TMB) and tumor inflammation signature (TIS), were not individually sufficient for patient selection. Recent pancancer studies have highlighted a unique population of cancer patients whose tumors appear to be driven by oncogene amplifications on extrachromosomal DNA (ecDNA). These ecDNA-driven tumors are aggressive and characterized by high levels of genomic instability. We sought to understand if tumors that possess ecDNA may represent a subset of the patient group that is non-responsive to anti-PD-1 therapy. Methods: We determined the ecDNA status of gastric cancer patients (N = 108) using whole genome sequencing (WGS) from the TCGA Pan-cancer dataset These patients had been previously subtyped for EBV status, genomic stability (GS), microsatellite instability (MSI), and chromosomal instability (CIN). Patients that were ecDNA+ were re-classified into a set regardless of gastric subtype. Additionally, TMB, TIS, and PD-L1 expression levels were collected. Results: 32% of gastric cancer patients were positive for ecDNA signatures and mutually exclusive from the 23% of MSI-H patients. We found that ecDNA positive tumors had statistically significantly lower TIS than all other groups (p-value < 0.05) except CIN tumors (p-value = 0.09). The ecDNA positive tumors also had lower PD-L1 expression than all but GS tumors. Only MSI-H showed statistically significantly higher TMB scores compared to every other group (p-value < 0.001), no difference in TMB scores were observed between every other pair of groups. Conclusions: Patients whose tumors are ecDNA positive represent a unique population that display signatures for non-response to checkpoint inhibitor therapy, including MSS, low TIS, and PD-L1 expression. Thus, the determination of tumor ecDNA status may have utility as an additional patient selection strategy for checkpoint inhibitor therapy. As ecDNA are not limited to gastric cancers, this study highlights the importance of the development of a clinical diagnostic test for ecDNA status and the need for further research on ecDNA biology, its impact on immunotherapy response, and potential ecDNA-directed therapeutics

Detection of circulating tumor cells in peripheral blood of heavily treated metastatic breast cancer patients

Breast Cancer ◽  
2011 ◽  
Vol 18 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Nahomi Tokudome ◽  
Yoshinori Ito ◽  
Shunji Takahashi ◽  
Kokoro Kobayashi ◽  
Shinichiro Taira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients
Sign in / Sign up

Export Citation Format

Share Document