GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (8)
Material
Publisher
  • American Association for Cancer Research (AACR)  (8)
Person/Organisation
Language
Years
Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Abstract PS11-39: Phase II pilot study of trastuzumab biosimilar (herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis]
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS11-39-PS11-39
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS11-39-PS11-39
    Abstract: Background: Prognosis of patients with HER-2 positive metastatic breast cancer (MBC) has been revolutionized with the development of dual antibodies targeting HER-2 and antibody-drug conjugate, but resistance to anti-HER-2 therapy is inevitable ultimately. PI3K-AKT-mTOR pathway aberration is known to be one of the resistance mechanisms. This randomized phase 2 pilot study evaluated safety and efficacy of Herzuma® (trastuzumab biosimilar) plus Gedatolisib (dual PI3K/mTORC inhibitor) in patients with HER-2 positive MBC who progressed after multiple lines of therapy. Methods: Patients with HER-2 positive MBC with known PIK3CA pathologic mutation or amplification whose disease progressed after more than two HER-2 directed therapy were enrolled in the study. They received Herzuma® (8mg/kg IV for 1st cycle loading dose, and then 6mg/kg IV every 3 weeks) plus Gedatolisib (180mg on D1, 8, 15 of every 21 days). We evaluated efficacy of the combination treatment as interim analysis. The data cutoff of this interim analysis was Aug 4, 2020. Results: As a pilot study, 15 patients were enrolled and followed for a median of 2.3 months. At data cutoff, 11 patients were eligible for response assessment. All patients were confirmed to have pathologic PIK3CA aberrations: H1047R, H1047L, E542Q, E542K, E453K, N345K, and PIK3CA amplification. Five patients reached partial response (PR) as their best response, three were stable disease (SD), and three had progressive disease (PD). All patients who have reached PR remain on investigational treatment at the data cutoff point, and the longest one is on treatment for 7.8 months. One of the SD patients ended treatment due to disease progression, and the other two have been undergoing treatment. Overall, response rate was 45.5% and disease control rate was 72.7%. No fatal adverse events related to trial medication were reported. Conclusion: In this phase 2 pilot study, Trastuzumab biosimilar plus Gedatolisib presented 45.5% of response rate with manageable toxicity in patients with HER-2 positive MBC with PIK3CA aberration. Clinical trial information: NCT03698383 Acknowledgement: this research was supported by a grant of the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong Won Lee, Keon Uk Park, Eun Mi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Mi So Kim, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, In Hae Park, Kyong Hwa Park. Phase II pilot study of trastuzumab biosimilar (herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis] [abstract] . In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-39.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-PS11-39
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract P5-03-14: Prevalence of germline BRCA mutations in unselected Korean patients with HER2-negative breast cancer: A Prospective cohort study
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 5_Supplement ( 2023-03-01), p. P5-03-14-P5-03-14
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. P5-03-14-P5-03-14
    Abstract: Backgrounds Since OlympiAD study, National Comprehensive Cancer Network guideline recommends assessment of germline BRCA1/2 mutation in all patients with recurrent or metastatic breast cancer to identify candidates for PARP inhibitor therapy, which is not always possible in clinical practice due to limited resources for testing. Data on the prevalence of gBRCA mutation is still lacking, especially in patients with non-high risk for hereditary breast and ovarian cancer syndrome. In this study, we investigated prevalence of gBRCA mutation in unselected Korean patients with HER2-negative advanced BC in a prospective cohort and analyzed oncologic outcome. Methods Eligible patients were diagnosed with HER2-negative advanced BC and had initiated palliative systemic treatment. Peripheral blood was prospectively drawn from each patient and gBRCA mutation status was assessed by next generation sequencing using NGeneBio BRCAaccuTest®. In 100 patients, somatic mutations including BRCA1/2 from tumor tissue were investigated using targeted panel sequencing. To estimate the prevalence of gBRCA mutation with margin of error to be no more than ±4% at the 95% confidence interval in a population size of 20,000, 583 patients were to be enrolled. Results A total of 583 patients were enrolled between Oct 2019 and Mar 2022, and the prevalence of gBRCA mutation was analyzed in 570 patients, excluding ineligible patients. Median age was 54 years old (range 26-87) and 567 patients were female. 475 patients had HR+/HER2- BC and 94 patients had triple negative breast cancer (TNBC). The overall prevalence of gBRCA1/2 pathogenic mutation was 7.3% (42/570) in unselected patients. The prevalence of gBRCA1 mutation was 1.6%(9/570) overall, 0.8%(4/475) in HR+/HER2- BC, and 5.3%(5/94) in TNBC. The prevalence of gBRCA2 mutation was 5.8%(33/570) overall, 6.3%(30/475) in HR+/HER2- BC, 3.2%(3/94) in TNBC. Prevalence in low risk TNBC ( & gt;60 years at first BC diagnosis, no known family history of relevant cancer and unilateral breast cancer) was 10.5% (2/19, all 2 patients had gBRCA2 mutation). Prevalence in low risk HR+/HER2- ( & gt;40 years at first BC diagnosis, no known family history of relevant cancer and unilateral breast cancer) was 5.9% (18/307, 17 patients had gBRCA2 mutation). The overall prevalence of gBRCA1/2 pathogenic mutation in Korean patients with low risk HER2-negative advanced BC was 6.1%. The result of somatic mutation, treatment patterns and clinical outcome according to gBRCA1/2 mutation will be further analyzed. Conclusions The prevalence of gBRCA mutation among Korean patients with HER2-negative advanced BC classified as low risk (6.1%) in this study supports routine testing of gBRCA mutation in this population. Citation Format: Hee Kyung Ahn, Jee Hung Kim, Mirae Kim, Seri Park, Su-Jin Koh, Joo Hyuk Sohn, Myoung Joo Kang, Kyung Hae Jung, Kyoung Eun Lee, Jieun Lee, Sung Ae Koh, Yee Soo Chae, Jae Ho Byun, In Hae Park, Hee-Jun Kim, Jee Hyun Kim, Han Jo Kim, Joo Young Jung, Jung Lim Lee, Yoon Young Cho, Kyong Hwa Park, Ji-Yeon Kim, Seock-Ah Im, Yeon Hee Park. Prevalence of germline BRCA mutations in unselected Korean patients with HER2-negative breast cancer: A Prospective cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-14.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS22-P5-03-14
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Aberrant Transcript Usage Is Associated with Homologous Recombination Deficiency and Predicts Therapeutic Response
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 1 ( 2022-01-01), p. 142-154
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 1 ( 2022-01-01), p. 142-154
    Abstract: BRCA1/2 mutations account for only a small fraction of homologous recombination (HR) deficiency (HRD) cases. Recently developed genomic HRD (gHRD) tests suffer confounding factors that cause low precision in predicting samples that will respond to PARP inhibitors and DNA damaging agents. Here we present molecular and clinical evidence of transcriptional HRD (tHRD) that is based on aberrant transcript usage (aTU) of minor isoforms. Specifically, increased TU of nonfunctional isoforms of DNA repair genes was prevalent in breast and ovarian cancer with gHRD. Functional assays validated the association of aTU with impaired HR activity. Machine learning–based tHRD detection by the transcript usage (TU) pattern of key genes was superior to directly screening for gHRD or BRCA1/2 mutations in accurately predicting responses of cell lines and patients with cancer to PARP inhibitors and genotoxic drugs. This approach demonstrated the capability of tHRD status to reflect functional HR status, including in a cohort of olaparib-treated ovarian cancer with acquired platinum resistance. Diagnostic tests based on tHRD are expected to broaden the clinical utility of PARP inhibitors. Significance: A novel but widespread transcriptional mechanism by which homologous recombination deficiency arises independently of BRCA1/2 mutations can be utilized as a companion diagnostic for PARP inhibitors.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-21-2023
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract LB170: HER2-targeted interferon-beta-1a mutein, a potent immunocytokine for the treatment of HER2-positive cancers
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. LB170-LB170
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. LB170-LB170
    Abstract: Background: Interferon beta (IFN-β), a promising potent cytokine, has been attracting attention for treatment of cancer. The pleiotropic antitumor effects of IFN-β have been studied, with specific reference to their direct role on cancer cells and indirect action through the immune effector cells. However, its systemic toxicities and poor biophysical properties prevent IFN-β from being widely used for cancer therapy. Since the potential of cytokine therapies are impaired due to dose-limiting systemic toxicities, novel treatment methods should be developed to safely deliver effective drug quantities at the tumor sites. Like antibody-drug conjugates (ADCs), immunocytokine can be attempted to induce cytokine's organ-targeting and alleviate its systemic side effects. Here, we designed recombinant IFN-β mutein immunocytokines that comprise a HER2-targeting antibody and IFN-β mutein, and evaluate the antitumor properties against HER2-positive cancers.Method: A panel of human gastric cancer cell lines was treated with trastuzumab-IFN-β mutein to evaluate direct antitumor effect. In addition, to test the immune cell-mediated antitumor effect, cancer cells were co-cultured with effector cells (e.g. PBMC) in the absence or drug. The antitumor efficacy of trastuzumab-IFN-β mutein in vivo was tested in HER2-positive cancer xenograft models using nude mice or humanized mice. Result: Trastuzumab-IFN-β mutein directly inhibited the growth of HER2-positive gastric cancer cell lines and was more effective than trastuzumab or IFN-β mutein alone. Trastuzumab-IFN-β mutein also displayed enhanced immune cell-mediated cytotoxicity. Collectively, trastuzumab-IFN-β mutein may have indirect immune cell-mediated antitumor effects and direct cell growth inhibitory effects. Moreover, trastuzumab-IFN-β mutein significantly suppress tumor growth in HER2-positive cancer xenograft models. Tumor-infiltration of lymphocytes was enhanced by trastuzumab-IFN-β mutein, implying that the tumor-targeting IFN-β may have an antitumor effect through increased immune response. Conclusion: We have characterized and evaluated the antitumor properties of trastuzumab-IFN-β mutein in HER2-expressing cancers. Since IFN-β activates antitumor immune responses, it is expected to be administered in combination with immunotherapeutic drugs. Therefore, the study suggests that trastuzumab-IFN-β mutein is a promising candidate for the treatment of HER2-positive carcinoma. Citation Format: Chan Gyu Lee, Tae Eun Kim, Sungyoul Hong, Jongwan Chu, Ju Eun Kang, Hae Min Jeong, Young Kee Shin. HER2-targeted interferon-beta-1a mutein, a potent immunocytokine for the treatment of HER2-positive cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB170.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-LB170
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract 2697: YPN005, an oral CDK7 inhibitor, exhibits a significant antitumor activity in Myc-driven cancers
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2697-2697
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2697-2697
    Abstract: Background: CDK7 plays an important role in regulating cell cycle progression and gene via activation of cell cycle kinases (CDK1, CDK2, CDK4 and CDK6) and RNA polymerase II (PolII). Recent studies indicate that the inhibition of CDK7 is an attractive strategy for the treatment of cancer by down-regulation of c-Myc expression. (Wang et al 2018) We have investigated the therapeutic efficacy of YPN005, a novel oral CDK7 inhibitor, in triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC). Methods: We evaluated antiproliferative activity of YPN005 on TNBC and HCC cells and the expression of RNA PolII and c-Myc was studied by Western Blot analyses to investigate the mechanism of action. To identify a biomarker, we examined the correlation between the level of c-Myc expression and anticancer activity of YPN005 in vitro using HCC cells. The therapeutic efficacy of YPN005 was evaluated in TNBC xenograft mouse model. Results: YPN005 significantly inhibited the proliferation of TNBC and HCC cells and IC50s was determined as 10-20 nM and 5-30 nM range, respectively. Inhibition of cell proliferation was accompanied by a decrease in the levels of RNA PolII phosphorylation and c-Myc expression. Western Blot analyses revealed that the sensitivity of HCC cells to YPN005 was correlated with the level of c-Myc expression. In vivo xenograft model of TNBC showed that oral daily administration of YPN005 for 21 days (once, and 10mg/kg) efficiently inhibited the growth of tumor. All mice survived during the dosing period without significant changes of the hematologic profiles. Conclusion: We propose that oral administration of YPN005, an orally available CDK7 inhibitor, could be a potent and attractive approach to treat the Myc overexpressing cancers. Citation Format: Kwang-Ok Lee, Jakyung Yoo, Mi Jung Lee, Kang Woo Lee, Ji Eun Min, Jinhwan Kim, Ki-Nam Min, Tae Chul Roh, Kang-Sik Seo, Hae In Rhee, Jun Hee Lee, Da-Hye Jeon, Dae Seong Lim. YPN005, an oral CDK7 inhibitor, exhibits a significant antitumor activity in Myc-driven cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2697.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-2697
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Abstract P1-14-02: Neoadjuvant letrozole and lapatinib is feasible in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER-2) positive breast cancer [Neo-All-In]: First efficacy and safety report
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 9_Supplement ( 2015-05-01), p. P1-14-02-P1-14-02
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 9_Supplement ( 2015-05-01), p. P1-14-02-P1-14-02
    Abstract: Purpose Neo-ALL-In (NCT 01275859) is a single center, prospective study aimed to evaluate the recruitment feasibility, efficacy and safety profiles as well as biologic features of neoadjuvant letrozole plus lapatinib in postmenopausal women with ER and HER2 positive breast cancer. Methods Postmenopausal women with stage IIA to IIIB ER and HER-2 positive breast cancer were eligible. Patients received combination therapy of letrozole 2.5 mg orally daily plus lapatinib 1,500 mg orally daily for 18-21 weeks before surgery. Clinical responses were assessed by clinical palpation, ultrasonography (US), mammography and/or MRI. Tissue and/or blood samples were collected for analysis of biomarkers at three time points (baseline, day 15, and before surgery). Baseline Fluorine-18 Fluorodeoxyglucose (18F-FDG) and Fluorine-18 Fluoroestradiol (18F-FES) PET-CT imagings were obtained. Results Among twenty-four patients enrolled, 22 patients underwent surgery while 1 patient is currently on neoadjuvant therapy and the other patient is waiting for surgery. Among 22 patients completed surgery, 16 patients (72.7%) completed planned neoadjuvant letrozole and lapatinib, whereas 3 patients (13.6%) prematurely terminated the treatment and proceeded to surgery due to minimal clinical response or progression. Except grade 3 liver toxicities revealed in 3 patients (13.6%), which resulted in sequential dose reduction and discontinuation, adverse events were mainly grades 1 to 2 (Skin, 83.3%; GI, 77.3%), and these were generally tolerable with excellent compliance. Overall clinical response rates including complete and partial response was 72.7% (n=16), and pathologic complete response in breast (pCR; ypT0-is) was 4.5% (n=1). Clinical and pathologic responses of 22 patients by assessment modalitiesTotal (N=22, %)Clinical palpationUSMammographyMRpathologic response in breast (ypT0-is)pathologic response in breast and lymph nodes (ypT0-is N0)Overall responseCR1 (4.5)0 (0.0)0 (0.0)1 (4.5)1 (4.5)0 (0.0)1 (4.5)PR17 (77.3)12 (54.5)9 (40.9)9 (40.9)11 (50.0)15 (68.215 (68.2)No change3 (13.6)9 (40.9)13 (59.1)5 (22.7)9 (40.9)7 (31.8)4 (18.2)PD1(4.5)1 (4.5)0 (0.0)1 (4.5)1 (4.5)0 (0.0)2 (9.1)Not available/evaluable0 (0.0)0 (0.0)0 (0.0)6 (27.3)0 (0.0)0 (0.0)0 (0.0)CR, complete response; PR, partial response; PD, progressive disease; US, ultrasonography In analyses of biomarkers thus far, 81.8% of patients showed stationary expression of HER-2, 54.5% of patients showed decrease in Ki-67 expression, and 27.3% of patients showed increase in ER expression from baseline to surgery by immunothistochemistry (IHC) staining. Decreased expression of ER after surgery by IHC staining was significantly correlated with poor clinical response (p=0.004). However, no significant differences in baseline SUVmax in FDG-PET were found between responders and non-responders (8.8 VS 10.7, p=0.53). Conclusion This chemo-free combination neoadjuvant therapy was feasible, with comparable efficacy outcomes and manageable toxicities profiles. Updated data on 18F-FES PET-CT and biomarkers will be provided. Citation Format: Ji Hyun Park, Myoung Joo Kang, Jin-Hee Ahn, Jeong Eun Kim, Kyung Hae Jung, Gyung-Yub Gong, Hee Jin Lee, Byung-Ho Son, Sei-Hyun Ahn, Hak-Hee Kim, Hee Jung Shin, Dae-Hyuk Moon, Sung-Bae Kim. Neoadjuvant letrozole and lapatinib is feasible in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER-2) positive breast cancer [Neo-All-In] : First efficacy and safety report [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-14-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS14-P1-14-02
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract 4600: Biomarker analysis in circulating cell-free DNA in patients treated with sorafenib for advanced hepatocellular carcinoma
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4600-4600
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4600-4600
    Abstract: Purpose: We evaluated the potential role of Vascular Endothelial Growth Factor-A (VEGFA) amplification and genome-wide copy number variations (CNVs) using circulating cell-free DNA (cfDNA) as predictors of treatment outcome in hepatocellular carcinoma (HCC) patients treated with first-line sorafenib. Methods: Among 184 patients from a prospective biomarker cohort, who had started sorafenib between April 2015 and May 2016, 151 eligible patients were included in the analysis. Plasma cfDNA was extracted from peripheral blood in patients before starting sorafenib or healthy donors. Plasma VEGFA-to-EIF2C1 ratios (the VEGFA ratios) were determined using droplet digital polymerase chain reaction. We applied low depth whole genome sequencing in cfDNA to find CNVs and developed I-score to express genomic instability, which was defined as the sum of absolute Z-scores of sequenced reads on each chromosome. Results: The cfDNA concentrations were significantly higher in HCC patients than in healthy controls (0.71 vs. 0.34 ng/μL; p & lt;0.0001). Patients who had progressive disease with sorafenib as best tumor response had significantly higher cfDNA levels (0.82 vs. 0.63 ng/μL; p=0.006) and I-scores (3,405 vs.1,024; p=0.0017) than those who achieved disease control. The disease control rate was 52.0% for the cfDNA-high group (above the median) vs. 75.0% for the cfDNA-low group (p=0.003), and 49.3% for the I-score-high group (above the median) vs. 77.6% for the I-score-low group (p=0.0003). The cfDNA-high group also had significantly worse TTP (median, 2.2 vs. 4.1 months; HR=1.71; p=0.002) and OS (median, 4.1 vs. 14.8 months; HR=3.50; p & lt;0.0001) than the cfDNA-low group. Similarly, the I-score-high group had poorer TTP (median, 2.2 vs. 4.1 months; HR=2.09; p & lt;0.0001) and OS (median, 4.6 vs. 14.8 months; HR=3.35; p & lt;0.0001). In the multivariate analyses, cfDNA remained an independent prognostic factor for OS (p & lt;0.0001), and I-score for both TTP (p=0.011) and OS (p=0.010). Although the VEGFA ratio was significantly higher in HCC patients than in healthy controls (2.50 vs. 2.17; p & lt;0.0001), it was not significantly associated with treatment outcomes. Conclusions: Pretreatment cfDNA concentration and genome-wide CNVs in cfDNA are potential biomarkers predicting treatment outcomes in advanced HCC patients receiving first-line sorafenib. Citation Format: Sook Ryun Park, Chung Ryul Oh, Sun-Young Kong, Min Kyeong Kim, Kyong-Ah Yoon, Eun-Hae Cho, Junnam Lee, Jihoon Kang, Baek-Yeol Ryoo. Biomarker analysis in circulating cell-free DNA in patients treated with sorafenib for advanced hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4600.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-4600
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Abstract 5680: Clinical significance of low frequency EGFR and KRAS mutations of cell free DNA using Ion AmpliSeq Cancer Hotspot Panel in lung cancer patients
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5680-5680
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5680-5680
    Abstract: Cell free DNA (cfDNA) present in the blood stream shows great potential as a useful cancer marker for molecular diagnosis and cancer progression monitoring. Especially, analyzing the cfDNA with Next Generation Sequencing (NGS) technology allows high through put examination of various genes concurrently at a low cost. However, there are still debates regarding clinically meaningful variant frequency to identify mutations in cfDNA, especially with ultra-deep sequencing. In this study, we examined the clinical utility of Ion AmpliSeq Cancer Hotspot Panel v2 (ICP; Ion Torrent) with Proton platforms. ICP, covering 2800 COSMIC mutations from 50 cancer genes was used to analyze cfDNA of 125 serum samples from lung cancer patients. The percentage of on target was 92% with mean depth of 22,868x. We identified aberrations of TP53 (72%), EGFR (43%), PTEN (26%), PIK3CA (26%), BRAF (16%), KRAS (14%), KIT (10%) and RET (10%) with the cut-off criteria of variant frequency & gt;0.1% and p & lt;0.01. To validate the results, we analyzed EGFR gene status by direct sequencing in available 100 FFPE tumor tissues (tDNA). Out of 17 patients with EGFR mutations in tDNA, 9 patients showed very low frequency ( & lt;0.05%) of same EGFR mutation in cfDNA. To validate the results of ICP, droplet digital PCR (ddPCR) was carried out with same cfDNA. From those 9 patients, EGFR mutations in cfDNA were detected in five patients (minimum frequency 0.01%) by ddPCR. From the patients with wild type EGFR in tDNA, EGFR exon 19 deletion or exon 21 point mutation were detected by ICP in 19 patients using cfDNA. Again, ddPCR was carried out with same cfDNA to confirm the result. EGFR mutations were confirmed in nine patients (47.4%) by cfDNA ddPCR and among the 6 patients treated with EGFR TKI, 4 patients showed response or stabilization of disease. Also, we identified 18 patients with KRAS mutations in ICP results of 125 cfDNA. The result of ddPCR was matched in 80% of patients. Interestingly, 2 patients had multiple KRAS mutations in cfDNA with ICP as well as ddPCR. In our study, we demonstrated that ICP with Proton system is a useful assay to identify somatic mutations using cfDNA in lung cancer patients. Also, we suggest that even EGFR mutation of very low frequency ( & lt;0.05%) might have clinical significance in NGS analysis using cfDNA. Serial blood sample obtained during treatment in these patients will be analyzed by ICP and ddPCR. [This research was supported by the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C0066)] Citation Format: Jae Sook Sung, Jong Won Lee, Boyeon Kim, Saet Byeol Lee, Chang Won Park, Hae Mi Kim, Nak-Jung Kwon, Won Jin Jang, Yoon Ji Choi, Jung Yoon Choi, Eun Joo Kang, Kyung Hwa Park, Sung Yong Lee, Yeul Hong Kim. Clinical significance of low frequency EGFR and KRAS mutations of cell free DNA using Ion AmpliSeq Cancer Hotspot Panel in lung cancer patients [abstract] . In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5680. doi:10.1158/1538-7445.AM2017-5680
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-5680
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...