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  • American Society of Clinical Oncology (ASCO)  (411)
  • 1
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    Enhancing enrollment using cohort surveillance for phase II biomarkers driven studies in patients with gastric/GEJ and pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e15017-e15017
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e15017-e15017
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.e15017
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Phase 1 trial evaluating MRG-106, a synthetic inhibitor of microRNA-155, in patients with cutaneous t-cell lymphoma (CTCL).
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 7564-7564
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 7564-7564
    Abstract: 7564 Background: MRG-106 is an oligonucleotide inhibitor of miR-155, a microRNA with a strong mechanistic link to CTCL, selected based on its activity in mycosis fungoides (MF) cell lines. The objective of this first-in-human study is to evaluate the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of MRG-106 in MF patients. Methods: This Phase 1 trial employs a dose-escalation design to evaluate either intratumoral (IT, 75 mg/dose) or subcutaneous (SC, ≤ 900 mg/dose) administration of MRG-106. Patients were required to have biopsy-proven stage I-III MF and plaque- or tumor-stage lesions. Results: Fifteen patients (12M/3F, median age 59 years) have been dosed over 1-4 weeks. All patients tolerated the IT or SC administrations well with only minor local injection reactions in 8 patients. Thirteen of 15 patients completed dosing as scheduled. There were no clinically significant MRG-106 related adverse events with the exception of one grade 3 pruritus. The MTD has not yet been reached. In the IT cohort, a reduction of ≥50% in the baseline Composite Assessment of Index Lesion Severity (CAILS) score was observed in the MRG-106 treated lesions in all 4 evaluable patients who completed dosing; such responses were maintained to the End of Study visit (Day 28 or 35). Histological examination of pre- and post-treatment biopsies of the MRG-106-injected lesion from most patients revealed a trend in reduction in neoplastic cell density and depth; 1 patient had a complete loss of the neoplastic infiltrate. Gene expression analysis of the pre- and post-treatment biopsies showed reduction of the PI3K/AKT, JAK/STAT, and NFkB survival pathways and increased cell death consistent with the expected MRG-106 mechanism of action. In the SC cohorts, 3/8 patients had a maximal decrease in their modified Severity-Weighted Assessment Tool (mSWAT) of 〉 39% indicative of a significant response. One patient at the 900 mg SC dose level had a possible flare of their disease after 3 doses that resolved after 3 weeks. Conclusions: Based on favorable clinical safety, efficacy and PK data, additional patients are being accrued. Updated results will be presented as available. Clinical trial information: NCT02580552.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.7564
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Microwave ablation for hepatic malignancies: A multi-institutional analysis.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 4_suppl ( 2013-02-01), p. 218-218
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 218-218
    Abstract: 218 Background: Although many hepatobiliary centers have moved from radiofrequency ablation to microwave ablation (MWA), the factors that influence local control with MWA are not well described. We hypothesized that tumor size, number of tumors, and tumor histology significantly affected MWA success and recurrence-free survival (RFS). Methods: Consecutive patients with hepatic malignancy treated by MWA were included from 4 high-volume institutions (2003-2011), and grouped by histology: hepatocellular cancer (HCC), colorectal metastases (CM), neuroendocrine metastases (NM), and other cancers. Independent significance of variables was established with logistic regression and Cox proportional hazards models. Results: Four-hundred seventy three ablation procedures were performed (139 HCC, 198 CM, 61 NM, and 75 other) for a total of 875 tumors. Median follow-up was 18 months. Complete ablation was confirmed for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (Table). NM had greater odds of an incomplete ablation compared to other histologies (odds ratio: 3.07, 95% confidence interval [CI]: 1.08-8.67, p=0.035), however this was not significant in adjusted models. The local recurrence rate was 6.1% overall, and was highest for HCC tumors (10.3%, p=0.051). RFS did not vary significantly between histologies. In adjusted models, tumor size ≥3cm was the only variable predicting poorer RFS (hazard ratio: 1.60, 95% CI: 1.02-2.50, p=0.039). Independent predictors of poorer OS included age, number of tumors ablated, and tumor size ≥3cm. Conclusions: In this large dataset, patients with ≥3cm tumors showed a propensity for early recurrence, regardless of histology. Higher rates of local recurrence were noted in HCC patients, which may reflect underlying liver disease. Accounting for recurrence at any site, however, there were no significant differences in RFS between tumor histologies. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.4_suppl.218
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 24 ( 2023-08-20), p. 4035-4044
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 24 ( 2023-08-20), p. 4035-4044
    Abstract: Phase 3 NRG 0232 trial shows no benefit to adding EBRT to brachytherapy in localized prostate cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.22.01856
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 5
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    Preclinical modeling of the AKT inhibitor MK2206 and topotecan in small cell lung cancer (SCLC).
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e17537-e17537
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e17537-e17537
    Abstract: e17537 Background: Extensive-stage small cell lung cancer (SCLC) is an aggressive and lethal tumor. Despite its exquisite chemosensitivity, median survival is only 9-11 months. Topotecan is the only approved drug for relapsed SCLC and new treatments with demonstrated antitumor activity are urgently needed. Defects in PTEN and PI3KCA are common to SCLC (identified in 10-15% of tumor specimens), suggesting that inhibitors of the PI3K/AKT pathway should be evaluated. MK-2206 is a first- in-class oral allosteric AKT inhibitor that is both potent and highly selective against all AKT isoforms. Our aim is to determine if MK-2206 plus topotecan has superior anticancer activity compared to either agent alone in SCLC cell lines. Methods: Three SCLC cell lines (H526- PTEN/PI3K wild type; H69- PTEN wild type/PI3K mutated; H2196- PTEN mutated/PI3K wild type) were treated with MK2206, topotecan or the combination. Median Effect Analysis was conducted using proliferation assays to test the combination for synergy. Immunoblotting was performed to explore the targeted effect on the PI3K/AKT pathway while flow cytometry was used to determine cell cycle effects. Results: H526 cells were refractory to selective AKT inhibition, but sensitive to topotecan. In contrast, H69 cells were responsive to single-agent MK2206, but two orders of magnitude less sensitive to topotecan. The H2196 cell line was sensitive to both agents. All cell lines showed decreased phosphoAKT (S473) with MK2206. In the combination experiments, additive to moderately synergistic interactions were detected in all cell lines with the greatest synergism observed in the H69 cells. Increased PARP cleavage was observed in response to the combination treatment compared to single-agent topotecan suggesting that AKT inhibition improved the activity of topotecan. In H69, a prolonged G1/S-phase arrest was observed in the combination compared to single-agent treatment. Conclusions: MK2206 demonstrated antitumor activity in SCLC cell lines harboring PI3K or PTEN mutations and enhanced the activity of topotecan in wild type and mutant cell lines. Based on this data, a SWOG clinical trial of topotecan plus MK2206 versus topotecan in relapsed SCLC is in development.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e17537
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 6
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    ADRB2 expression in progressive metastatic castration-resistant prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 6_suppl ( 2020-02-20), p. 145-145
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 145-145
    Abstract: 145 Background: The net oncogenic effect of the G protein-coupled receptor β 2 adrenergic receptor ADRB2, which may induce neuroendocrine differentiation via cyclic AMP and protein kinase A and whose expression is epigenetically regulated by EZH2, is controversial. ADRB2 expression and associated clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) are unknown. Methods: This was a retrospective analysis of a cohort of men with mCRPC who were prospectively enrolled in the multi-center SU2C/PCF/AACR West Coast Prostate Cancer Dream Team study, in which biopsies of a metastatic site were obtained at disease progression. Specimens underwent laser capture microdissection and RNA-seq. ADRB2 expression was stratified by histology and transcriptional cluster based on prior unsupervised hierarchical transcriptome clustering, and correlated with EZH2 expression. ADRB2 expression (lowest quartile) was correlated with OS from time of biopsy by log rank test and a multivariable Cox proportional hazard model. Results: One-hundred and twenty-seven men with progressive mCRPC underwent metastatic biopsies and had sufficient tumor for RNA-seq. ADRB2 expression was lowest in the small cell-enriched transcriptional cluster (P 〈 0.001), and correlated inversely with EZH2 expression (r=-0.28, P 〈 0.01). Men with low ADRB2 expression had a shorter median OS than those with high (9.5 vs 18.9 mo, P=0.02). In multivariable analysis adjusting for small cell histology, performance status, LDH, and visceral metastases, high ADRB2 expression was associated with a trend towards longer OS (HR=0.65, 95% CI 0.41-1.02, P=0.06). Conclusions: Low ADRB2 expression is associated with worse OS in men with progressive mCRPC, and may be a means by which EZH2 confers resistance to antiandrogen therapy. Indirect ADRB2 stimulation with EZH2 inhibitors may improve outcomes. Validation in independent cohorts is necessary.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.6_suppl.145
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 7
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    Predictors of lymphopenia in esophageal cancer patients receiving photon or proton radiation therapy: A dosimetric analysis.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 4_suppl ( 2019-02-01), p. 147-147
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 147-147
    Abstract: 147 Background: Lymphopenia during radiation therapy (RT) has been associated with worse oncologic outcomes in a number of malignancies, including esophageal cancer (EC). No studies to date have investigated specific dosimetric parameters associated with this lymphopenia in EC. We performed an analysis of RT dose to multiple organs at risk (OARs) to investigate associations with grade 4 lymphopenia (G4L). Methods: Consecutive EC patients receiving curative intent chemoradiotherapy +/- surgery between July of 2015 and December of 2017 were included. Lymphocyte nadir was defined as the lowest lymphocyte count during RT. G4L was defined as absolute lymphocyte count 〈 200/mm 3 . Dose to OARs including aorta, body, bone marrow, heart, liver, lung, and spleen were calculated. Univariate logistic regression analyses were performed for each OAR at the 1, 5, 10, 15, 20, 30, 35, 40, and 50 Gy levels with volume receiving dose ‘x’(VxGy) analyzed as a continuous variable per 10% increase. Clinical tumor volume (CTV) and RT modality (photon vs. proton) as well clinical factors including sex, stage (I/II vs. III/IV), age (per 10 year increase), and BMI (per 5 unit increase) were also analyzed. Results: One hundred forty-four pts were identified for inclusion. Seventy-nine pts received photon RT and 65 proton RT. Chemotherapy was weekly carbotaxol (99%). G4L at nadir was 40% overall (56% photon, 22% proton). By organ, body V1-V30Gy (OR 1.45-8.18, p 〈 0.01), heart V1-V30Gy (OR 1.24-1.49, p 〈 0.01), liver V1-V35Gy (OR 1.23-2.75, p 〈 0.01), lung V1-V30Gy (OR 1.26-5.73 p 〈 0.01), and spleen V1-V40Gy (OR 1.26-1.49 p 〈 0.01) were highly associated with G4L whereas dose to aorta and bone marrow were not. Advanced stage (OR, 3.92 p 〈 0.01), photon vs. proton (OR 4.58 p 〈 0.01), and CTV (per 100 cc’s (OR=1.21, p 〈 0.01)) were also associated with G4L. Sex, age, and BMI were not associated with G4L. Conclusions: Low to intermediate dose volumes to OARs including body, spleen, liver, lungs, and heart were associated with G4L. These findings provide rational for the differences seen in rates of G4L for photon versus proton RT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.4_suppl.147
    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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  • 8
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    Genomic drivers of poor prognosis and enzalutamide resistance in metastatic castration-resistant prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 146-146
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 146-146
    Abstract: 146 Background: Metastatic castration-resistant prostate cancer (mCRPC) is the lethal form of the disease. Several recent efforts have identified genomic alterations in mCRPC, but the clinical implications of these alterations have not been fully elucidated. We conducted a prospective cohort study (n = 101) using whole genome sequencing (WGS) to analyze the association between key driver gene alterations and overall survival. We also performed whole-transcriptome RNA sequencing (RNA-seq) analyses to identify potential mechanisms of enzalutamide resistance in mCRPC. Methods: Metastasis biopsies were obtained in 101 mCRPC patients as part of the multi-institutional West Coast Prostate Cancer Dream Team project. Samples underwent WGS and RNA-seq. The resulting mutation, copy number, and structural variant calls were integrated to determine functional copy number status of candidate genes for downstream clinical analyses. We performed univariate and multivariable analyses to assess the prognostic significance of candidate genomic events with respect to overall survival. To nominate and investigate genomic pathways associated with enzalutamide resistance, we performed expression-based gene set enrichment analysis followed by cross-sectional enrichment and survival analyses related to the top nominated pathway. Results: RB1 loss was associated with poor overall survival (median 14.1 vs. 42.0 months, p 〈 0.001). When we compared enzalutamide resistant versus naïve samples using gene set enrichment analysis, we identified the Wnt/beta-catenin pathway as the top differentially expressed pathway in enzalutamide-resistant patients. Furthermore, CTNNB1 (beta-catenin) activating mutations were exclusive to enzalutamide-resistant patients (p = 0.013) and predictive of poor overall survival (median 13.6 vs. 41.7 months, p 〈 0.001). Conclusions: Impaired survival in mCRPC patients is associated with RB1 loss, identified by integrated genomic analysis of CRPC metastasis biopsies. Among men with mCRPC that was enzalutamide-resistant, the Wnt/beta-catenin pathway is nominated as an important predictive (and potentially therapeutic) pathway.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.146
    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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  • 9
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    Differential activity of afatinib (AFAT), cetuximab (CET), and erlotinib (E) in a patient-derived xenograft (PDX) model of acquired E resistance.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 8110-8110
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 8110-8110
    Abstract: 8110 Background: The UC Davis - Jackson Labs Consortium has established a PDX resource of over 50 NSCLC models (12 EGFR mutant) for experimental therapeutics and personalized medicine, using the NSG mouse. Here we report on a unique PDX model, LG703, derived from a patient at time of acquired E resistance. This tumor harbors EGFR L858R with no T790M mutation, high MET and very high EGFR protein expression. The patient is in remission following treatment with AFAT-CET. In this model, we investigated the respective contribution of CET and AFAT relative to E on tumor growth and signal transduction. Methods: Individual mice implanted with LG703 tumor fragments were randomized to E (50 mg/kg qd po), AFAT (20 mg/kg qd po), CET (10 mg/kg twice weekly iv), AFAT-CET, or vehicle control (n per arm = 12) for 3 weeks followed by a 75-day monitoring period. Changes in signal transduction mediators and RTKs were assessed after 6 and 24h treatment exposures using kinase arrays (R & D systems) and immunoblotting. Results: AFAT, CET and AFAT-CET resulted in complete tumor response (CR) during the 21-day treatment period; whereas E resulted in temporary growth delay. After cessation of treatment, E-treated mice progressed rapidly and AFAT-treated mice progressed within 2 weeks. Mice treated with CET or AFAT-CET remained in complete remission. At 6h, E and AFAT significantly ( 〉 70%) reduced EGFR phosphorylation as well as that of AKT1, AKT2, ERK1, p38a, RSK1 and p70S6K. At 24h, E-treated tumors had returned to baseline-like states for all factors, AFAT showed an intermediate response, and CET, alone or with AFAT, achieved the greatest inhibition of pEGFR with sustained inhibition of all downstream effectors. Conclusions: In the LG703 PDX model, CET and AFAT+CET resulted in CRs, mirroring the patient's response to similar therapy, associated with sustained inhibition of pEGFR and multiple downstream signaling factors. In contrast, E exhibited only temporary growth delay associated with transient inhibition of EGFR pathway factors. These experiments demonstrate the potential of this PDX resource to assess new therapeutic strategies in models representing individual patients. Supported by BJALCF.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.8110
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 10
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    The comprehensive methylation landscape of metastatic castration-resistant prostate cancer (mCRPC) identifies new phenotypic subtypes: Results from the West Coast Prostate Cancer Dream Team (WCDT).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 5507-5507
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5507-5507
    Abstract: 5507 Background: While recent studies have delineated the genomic landscape of mCRPC, its epigenomic landscape has not been as well characterized. The goal of this study was to define the comprehensive methylation landscape of mCRPC. Methods: mCRPC patients (pts) underwent a metastasis biopsy as part of a multi-institutional study (NCT02432001). Deep whole-genome bisulfite sequencing (mean depth 46x) was performed on fresh frozen tissue from 100 mCRPC patients; data was paired with deep whole-genome and transcriptome sequencing from the same samples. Unbiased hierarchical clustering of the mCRPC methylome was undertaken, and the survival of patients in each cluster was calculated using the Kaplan Meier method. Results: Unbiased hierarchical clustering revealed several distinct subtypes. 22% of mCRPC samples exhibited a novel epigenomic subtype associated with hyper-methylation. This hypermethylated (HM) cluster was significantly associated with somatic mutations in genes known to be involved in methylation, eg TET2 and DNMT3B, as well as in genes in which mutations have been associated with hyper-methylation in other cancer types ( IDH1 in glioblastoma and BRAF in colon cancer). mCRPC survival was 56.1 mos in pts with HM cancers compared to 35.6 mos in non-HM (p = .055). Methylome clustering also identified a unique cluster comprised of all patients with treatment-induced small cell/neuroendocrine cancer, a subtype previously associated with poor survival. Conclusions: This integrated study of whole-genome, whole methylome and whole-transcriptome sequencing provides the first comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer, and has identified at least two distinct subtypes. The clinical and therapeutic implications of methylation subtypes should be explored in future studies. Clinical trial information: NCT02432001 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.5507
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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