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  • 1
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    Pilot Study of Circulating Tumor Cells in Early-Stage and Metastatic Uveal Melanoma
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 6 ( 2019-06-20), p. 856-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 6 ( 2019-06-20), p. 856-
    Abstract: Nearly 50% of uveal melanoma (UM) patients develop metastatic disease, and there remains no current standard assay for detection of minimal residual disease. We conducted a pilot study to check the feasibility of circulating tumor cell (CTC) detection in UM. We enrolled 40 patients with early or metastatic UM of which 20 patients had early-stage disease, 19 had metastatic disease, and one was not evaluable. At initial blood draw, 36% of patients had detectable CTCs (30% in early-stage vs. 42% in metastatic), which increased to 54% at data cutoff (40% in early-stage vs. 68% in metastatic). Five early-stage patients developed distant metastases, 60% (3/5) had detectable CTCs before radiographic detection of the metastasis. Landmark overall survival (from study enrollment) at 24 months was statistically lower in CTC-positive vs. negative early-stage UM (p 〈 0.05). Within this small dataset, the presence of CTCs in early-stage UM predicted an increased risk of metastatic disease and was associated with worse outcomes.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11060856
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Pathologic complete response and serial circulating tumor cell monitoring during neoadjuvant therapy in nonmetastatic triple-negative breast cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e12111-e12111
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e12111-e12111
    Abstract: e12111 Background: ARTEMIS (A Randomized, TNBC Enrolling trial to confirm Molecular profiling Improves Survival) is a randomized trial to determine if precision guided neoadjuvant chemotherapy (NAC) influences rates of pathologic complete response in the breast and axillary nodes (pCR). We hypothesized that blood circulating tumor cell (CTC) identification before and/or after NAC (just before surgery) would be associated with pCR in non-metastatic TNBC patients. Methods: Blood was assessed for CTCs at baseline (pre-NAC) and after NAC (post-NAC), as part of an IRB approved study, ARTEMIS (2014 – 0185/PA15-1050). CTCs (per 7.5 ml blood) were identified using the Cell Search System (Menarini Silicon Biosystems). Samples 〉 one cell having morphologic criteria for malignancy were deemed CTC+. Fisher exact test was used to evaluate associations between CTC detection and clinicopathologic characteristics, and Chi 2 test was used to analyze associations between CTC detection pre- and post- NAC, and pCR. Results: Fifty-nine patients had pre-NAC and 43 patients had post-NAC CTC assessments. One or more CTC was detected in 13/59 (22%) patients pre-NAC and in 16/43 (37%) of post NAC samples. CTC detection was not associated with patient stage, tumor androgen receptor expression, vimentin expression, Ki-67 staining, or tumor-infiltrating lymphocyte levels. Pre-NAC CTC detection was not (chi 2 P = 0.98), but post-NAC (chi 2 P = 0.0017) CTC identification was negatively associated with pCR. Conclusions: CTC detection post-NAC was negatively associated with pCR in non-metastatic TNBC patients. These findings warrant larger studies studying serial CTC detection throughout treatment to assess response to NAC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e12111
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Abstract A12: Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 19_Supplement ( 2020-10-01), p. A12-A12
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 19_Supplement ( 2020-10-01), p. A12-A12
    Abstract: Introduction: Uveal melanoma (UM) is a rare melanoma; only 5% of cases at initial presentation have distant metastasis. As approximately 50% of patients will develop metastatic disease, there is a need to detect minimal residual disease (MRD). Liquid biopsy using circulating tumor cells (CTCs) has been evaluated in multiple tumors; high CTC count predicts for increased risk of metastasis. We conducted a pilot study to check feasibility of CTCs in UM and evaluate if CTCs vary with risk status in early-stage UM. Methods: We enrolled 40 UM patients ≥18 years, after obtaining informed consent in an IRB-approved protocol from 12/1/2014 to 2/1/2018. Peripheral blood was obtained to detect CTCs using CellSearch Circulating Melanoma Cell Assay. Demographic information, mutational analysis, date of diagnosis of primary UM or metastasis, and dates of CTC collection were collected. Risk stratification was done by gene expression profiling (GEP) by DecisionDX-UM assay. Landmark overall survival (OS) was calculated using “Landest” R package comparing CTC detected vs. not detected in early-stage UM. Results: 39 patients were available for analysis. Median age of whole cohort was 52 years (20-83 years), 100% were non-Hispanic Caucasians, and 44% were male and 56% female. 20 patients had early-stage vs. 19 patients had metastatic disease at enrollment. 87% (13/15) of early-stage disease had class II disease. GNAQ & GNA11 mutations were present in 36% (12/39) and 13% (5/29), respectively. At initial blood draw, 36% of the patients had detectable CTCs [30% (6/20) in early stage vs. 42% (8/19) in metastatic], which increased to 54% at median study follow-up of 16.4 months [40% (8/20) in early stage vs. 68% (13/19) in metastatic] . Mean CTCs were higher in metastatic (9) vs. early stage (1.83) (p & gt;0.05). 5 patients in early-stage disease developed distant metastasis; 60% (3/5) had detectable CTCs before radiographic detection of metastasis. Out 5, 80% had class II disease and 20% had unknown GEP. Landmark overall survival (from study enrollment) at 24 months was statistically worse in CTC detected vs. not detected in early-stage UM (P & lt;0.05). Conclusion: CTCs are more frequently detected in metastatic compared to early-stage UM. In early-stage UM, presence of CTCs predicts for increased risk of metastatic disease and is associated with worse outcome. Citation Format: Jason Roszik, Dan Gombos, Joshua Upshaw, Vanessa Sarli, Salyna Meas, Anthony Lucci, Carolyn Hall, Sapna Patel, Kartik Anand. Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A12.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.MEL2019-A12
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
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    Abstract P4-01-02: Circulating tumor cells detected after neoadjuvant therapy for inflammatory breast cancer are associated with early relapse despite pCR
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4_Supplement ( 2020-02-15), p. P4-01-02-P4-01-02
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P4-01-02-P4-01-02
    Abstract: Background: IBC is a rare and aggressive subtype of breast cancer. A significant number of IBC patients who achieve pathologic complete response (no residual tumor in breast and axillary nodes, pCR), still relapse after neoadjuvant chemotherapy (NAC). We hypothesized that circulating tumor cells (CTCs) identified in blood after NAC would add additional relapse risk information beyond just PCR alone. Methods: Blood was assessed for CTCs after NAC in 128 stage III IBC patients as part of an IRB approved study, (LAB04-0698) using the Cell Search® System (Menarini Silicon Biosystems). The presence of ≥ 1 CTC meeting morphological criteria for malignancy was considered a positive result. Fisher exact test was used to evaluate associations between CTC detection and clinicopathologic characteristics, and log-rank test was used to analyze associations between CTC detection after NAC, pCR, and relapse free survival. Results: Median follow-up was 2.4 years and mean patient age was 53 years. One or more CTC was identified after NAC in 36/128 (28%) of patients. Thirty-six patients (28%) had pCR following NAC. CTC detection was not associated with body mass index, estrogen, progesterone, or human epithelial growth factor receptor-2 (HER2) status, or Ki-67 staining (P= NS). Participants were grouped according to their post NAC CTC and pCR statuses as follows: CTC- and pCR (n = 28), CTC- and no pCR (n = 48), ≥1 CTC and pCR (n = 5) and ≥1 CTC and no pCR (n =18). Difference in recurrence free survival were identified in these groups, with worse relapse-free survival at 2 years identified in those with ≥1 CTCs and no pCR (log-rank p-value = & lt;0.0001). Conclusions: CTC detection after NAC identified non-metastatic IBC patients who achieved pCR, but remained at risk for relapse. This study warrants larger studies combining both PCR and CTC information in IBC patients to improve risk stratification and to identify patients who could derive benefit from additional adjuvant therapies to reduce their risk for relapse. Citation Format: Carolyn Hall, Salyna Meas, Boomadevi Narendran, Vanessa Sarli, Joshua Upshaw, Naoto Ueno, Bora Lim, Vicente Valero, Anthony Lucci. Circulating tumor cells detected after neoadjuvant therapy for inflammatory breast cancer are associated with early relapse despite pCR [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS19-P4-01-02
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
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    Abstract 456: Circulating tumor cells and cfDNA changes during radiotherapy in patients with head and neck cancer
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 456-456
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 456-456
    Abstract: Introduction: Head and neck cancer treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers such as circulating tumor cell (CTC) and cell-free DNA (cfDNA) during treatment may improve earlier detection of responders versus non-responders during definitive radiotherapy. Our work prospectively describes the changes in CTC and cfDNA enumeration during definitive radiotherapy. Methods: Patients with mucosal head and neck squamous cell carcinoma and intact gross tumor were eligible for the prospective IRB-approved PREDICT-HN study. Blood samples were collected pre-treatment, after first treatment, weekly, and post-treatment (CellSave and EDTA tubes). CTC was enumerated using the FDA-approved CellSearch (Menarini Silicon Biosystems) system. Filtered plasma were collected from the EDTA tubes and stored at -80C. cfNA from pre-, mid- and post-treatment timepoints were isolated from the filtered plasma using the MagMAX Nucleic Acid Isolation Kit (Thermo Fisher Scientific) and cfDNA were quantified with Qubit high sensitivity dsDNA assay (Invitrogen). Results: 339 blood samples were collected from 45 patients; 137 had detectable CTC. Eight patients had detectable CTCs (1-3/7.5ml blood) in pre-treatment samples. After 1 fraction of radiotherapy, 16 patients had CTCs detected with 12 who had no CTC detected pre-treatment. 19 (42%) patients had detectable CTC in week 6 of treatment. All patients had detectable CTC at some point during radiotherapy except for one patient who had no CTC detected pre, during and post-treatment. There was no correlation between cancer stage, nodal status and gross tumor volume with detection of CTC. Overall circulating cfDNA levels increased during treatment, with their highest level in the final week of treatment similar to when the majority of CTC were detectable in patients, and lowest at the post-treatment time-point. Conclusions: Our interim results showed, for the 1sttime, to our knowledge, that CTCs can be detected during radiotherapy of head and neck cancer, suggesting mobilization into peripheral circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, may indicate apoptotic change during radiotherapy. Combined cfDNA-CTC as an early marker of treatment response should be investigated. Citation Format: Sweet Ping Ng, Carolyn S. Hall, Salyna Meas, Vanessa N. Sarli, Houda Bahig, Baher Elgohari, Amy Moreno, Heath D. Skinner, Adam S. Garden, David I. Rosenthal, William H. Morrison, Jack Phan, G Brandon Gunn, Steven J. Frank, Clifton D. Fuller, Anthony Lucci. Circulating tumor cells and cfDNA changes during radiotherapy in patients with head and neck cancer [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 456.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-456
    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
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  • 6
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    Abstract 5881: PERIO-01: Initial safety experience and immunologic effects of a Class C TLR9 agonist using pressure- enabled drug delivery in a phase 1 trial of hepatic arterial infusion of SD-101 +/- checkpoint inhibition in metastatic uveal melanoma
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5881-5881
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5881-5881
    Abstract: Immune checkpoint inhibitors (ICI) have demonstrated limited success in patients with metastatic uveal melanoma (MUM) with liver involvement due to an immunosuppressive tumor microenvironment (TME) driven in part by myeloid-derived suppressor cells (MDSCs). Toll-like receptor-9 agonists (TLR-9A) have improved ICI response rates in cutaneous melanoma, but delivery challenges have limited their application for MUM. Hepatic arterial infusion (HAI) of TLR-9A using a pressure-enabled drug deliveryTM (PEDDTM) device has the potential to enhance responsiveness to ICI by optimizing delivery to intrahepatic tumors and reprogramming the TME, including elimination of MDSCs.PERIO-01 is an open-label first-in-human Phase 1 trial of SD-101 given by HAI using a PEDDTM in MUM (NCT04935229). The study consists of dose-escalation cohorts of single agent SD-101 alone and with ICI. SD-101 is delivered over 2 cycles, with 3 weekly doses per cycle. Research blood, tumor and normal liver biopsies are collected serially for correlative studies. At data cutoff, a total of 20 patients were enrolled, with 13 in the single agent dose escalation cohort (2, 4, and 8 mg) and 7 patients with SD-101 (2 mg) + nivolumab. The median age was 65.5 years with an equal gender distribution. Only 2 patients were treatment-naïve and the median number of liver metastases was 5.1. The average number of SD-101 infusions was 5.2. One patient in the combination cohort experienced a serious adverse event related to treatment - asymptomatic Grade 3 increase in liver enzymes. PEDDTM resulted in high drug levels in the liver (up to 2,340 ng/ml at 8mg) with only transient exposure in the periphery ( & lt;4 hours) with one Grade 2 cytokine related syndrome adverse event. Dose-dependent increases in canonical TLR9-associated cytokines (IL-18, IFNγ, IP-10, and soluble CD25) was observed across the 2mg, 4mg, and 8mg single-agent dose levels. Concordant with predicted mechanism of action, PEDDTM HAI administered SD-101 resulted in decreases in liver monocytic MDSCs in 4 of 4 patients with available multiplex immunofluorescence data. NanoString analysis from three patients revealed increases in ISG15, IL-9, IFNα, and IL-2 transcripts and decreases in ARG1 and IDO transcripts, with increased scores for macrophages, activated CD8 T cells, Th1 cells, and Th1 activation. For patients who received 2mg SD-101 + ICI with available liquid biopsy data, 4 of 7 demonstrated decreases in circulating tumor cells and 3 of 5 showing ctDNA decreases after the first cycle. In this first-in-human experience, HAI of SD-101 via PEDDTM was well tolerated and associated with encouraging immunologic activity. Evidence of biologic activity with 2 mg of SD-101 with nivolumab is encouraging and patients are currently enrolling at higher SD-101 dose levels + ICI. Citation Format: Sapna P. Patel, Cara Haymaker, Rahul A. Sheth, Joshua D. Kuban, Joshua Weintraub, Eric Wehrenberg-Klee, Paula Novelli, Carin Gonsalves, Robert Adamo, Virgina Honaker, Laura Timciuc, Tarin Hennegan, Juan C. Amador Molina, Dzifa Duose, Edwin R. Parras Cuenta, Anthony Lucci, Salyna Meas, Vanessa Sarli, Victor G. Prieto, Jason LaPorte, Ann-Marie Hulstine, Ashley Moody, Bryan Cox, David Geller, Diwakar Davar, Kamaneh Montazeri, Marlana Orloff, Steven C. Katz, Richard Carvajal. PERIO-01: Initial safety experience and immunologic effects of a Class C TLR9 agonist using pressure- enabled drug delivery in a phase 1 trial of hepatic arterial infusion of SD-101 +/- checkpoint inhibition in metastatic uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5881.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-5881
    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
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  • 7
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    Predicting treatment Response based on Dual assessment of magnetic resonance Imaging kinetics and Circulating Tumor cells in patients with Head and Neck cancer (PREDICT-HN): matching ‘liquid biopsy’ and quantitative tumor modeling
    Springer Science and Business Media LLC ; 2018
    In:  BMC Cancer Vol. 18, No. 1 ( 2018-12)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2018-12)
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/s12885-018-4808-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2041352-X
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  • 8
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    17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 23 ( 2023-06-06)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 23 ( 2023-06-06)
    Abstract: The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor–positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7’s miRNAs into EVs. In multiple patient cohorts, we observed increased levels of let-7a-5p and let-7d-5p in EVs derived from the blood of premenopausal ER+ BC patients, and elevated EV levels in patients with high BMI, both conditions associated with higher levels of 17β-estradiol. In brief, we identified a unique estrogen-driven mechanism by which ER+ BC cells eliminate tumor suppressor miRNAs in EVs, with effects on modulating tumor-associated macrophages in the microenvironment.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2122053120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
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    Correlation of circulating or disseminated tumor cells with the Oncotype DX Recurrence Score
    Springer Science and Business Media LLC ; 2020
    In:  Breast Cancer Research and Treatment Vol. 184, No. 3 ( 2020-12), p. 683-687
    Details
    In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 184, No. 3 ( 2020-12), p. 683-687
    Type of Medium: Online Resource
    ISSN: 0167-6806 , 1573-7217
    URL: Article
    DOI: 10.1007/s10549-020-05882-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2004077-5
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  • 10
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    Role of Liquid Biopsy in Clinical Decision-Making for Breast Cancer
    Springer Science and Business Media LLC ; 2019
    In:  Current Breast Cancer Reports Vol. 11, No. 2 ( 2019-6), p. 52-66
    Details
    In: Current Breast Cancer Reports, Springer Science and Business Media LLC, Vol. 11, No. 2 ( 2019-6), p. 52-66
    Type of Medium: Online Resource
    ISSN: 1943-4588 , 1943-4596
    URL: Article
    DOI: 10.1007/s12609-019-0308-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2493862-2
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