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  • 1
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    Online Resource
    Pooled Analysis of Individual Patient Data on Concurrent Chemoradiotherapy for Stage III Non–Small-Cell Lung Cancer in Elderly Patients Compared With Younger Patients Who Participated in US National Cancer Institute Cooperative Group Studies
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 25 ( 2017-09-01), p. 2885-2892
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 25 ( 2017-09-01), p. 2885-2892
    Abstract: Concurrent chemoradiotherapy is standard treatment for patients with stage III non–small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute–supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non–small-cell lung cancer from 1990 to 2012. Overall survival (OS), progression-free survival, and AEs were compared between patients age ≥ 70 (elderly) and those younger than 70 years (younger). Unadjusted and adjusted hazard ratios (HRs) for survival time and CIs were estimated by single-predictor and multivariable frailty Cox models. Unadjusted and adjusted odds ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable generalized linear mixed-effect models. Results A total of 2,768 patients were classified as younger and 832 as elderly. In unadjusted and multivariable models, elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95% CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly and younger patients had similar progression-free survival (HR, 1.01; 95% CI, 0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients had a higher rate of grade ≥ 3 AEs in unadjusted and multivariable models (OR, 1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively). Grade 5 AEs were significantly higher in elderly compared with younger patients (9% v 4%; P 〈 .01). Fewer elderly compared with younger patients completed treatment (47% v 57%; P 〈 .01), and more discontinued treatment because of AEs (20% v 13%; P 〈 .01), died during treatment (7.8% v 2.9%; P 〈 .01), and refused further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had a higher rate of death during treatment than younger patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.71.4758
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 2
    Online Resource
    Online Resource
    A pooled analysis of concurrent chemoradiotherapy (CCRT) for patients with stage III non-small cell lung cancer (NSCLC) who participated in U.S. cooperative group trials: Comparing the outcomes of elderly to younger patients (pts).
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 8508-8508
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 8508-8508
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.8508
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 3
    Online Resource
    Online Resource
    Clinical Cancer Advances 2007: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report From the American Society of Clinical Oncology
    American Society of Clinical Oncology (ASCO) ; 2008
    In:  Journal of Clinical Oncology Vol. 26, No. 2 ( 2008-01-10), p. 313-325
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 2 ( 2008-01-10), p. 313-325
    Abstract: For the third year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO publishes this report to demonstrate the important progress being made on the front lines of clinical cancer research today. The report is intended to give all those with an interest in cancer care—the general public, cancer patients and organizations, policymakers, oncologists, and other medical professionals—an accessible summary of the year's most important cancer research advances. These pages report on the use of magnetic resonance imaging for breast cancer screening, the association between hormone replacement therapy and breast cancer incidence, the link between human papillomavirus and head and neck cancers, and the use of radiation therapy to prevent lung cancer from spreading. They also report on effective new targeted therapies for cancers that have been historically difficult to treat, such as liver cancer and kidney cancer, among many others. A total of 24 advances are featured in this year's report. These advances and many more over the past several years show that the nation's long-term investment in cancer research is paying off. But there are disturbing signs that progress could slow. We are now in the midst of the longest sustained period of flat government funding for cancer research in history. The budgets for the National Institutes of Health and the National Cancer Institute (NCI) have been unchanged for four years. When adjusted for inflation, cancer research funding has actually declined 12% since 2004. These budget constraints limit the NCI's ability to fund promising cancer research. In the past several years the number of grants that the NCI has been able to fund has significantly decreased; this year, in response to just the threat of a 10% budget cut, the nation's Clinical Trials Cooperative Groups reduced the number of patients participating in clinical trials by almost 2,000 and senior researchers report that many of the brightest young minds no longer see the promise of a career in science, choosing other careers instead. It's time to renew the nation's commitment to cancer research. Without additional support, the opportunity to build on the extraordinary progress to date will be lost or delayed. This report demonstrates the essential role that clinical cancer research plays in finding new and better ways to care for the more than 1.4 million people expected to be diagnosed with cancer this year. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report. I hope you find it useful. Sincerely, Nancy E. Davidson, MD President American Society of Clinical Oncology
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2007.15.4088
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Phase II study of the oral MEK inhibitor selumetinib (AZD6244) in advanced acute myeloid leukemia (AML).
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 6582-6582
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 6582-6582
    Abstract: 6582 Background: RAS-RAF-MEK-ERK pathway is activated in 〉 75% of AML patients (pts). Selumetinib (AZD6244) is an orally bioavailable small molecule inhibitor of the MEK kinase. We report here the results of a phase II multicenter trial using selumetinib in advanced AML pts. Methods: Pts ≥18 years (yrs) with relapsed/refractory AML or ≥60 yrs old with untreated AML who were not candidates for standard chemotherapy were eligible. Pts received selumetinib 100mg twice daily. Pts were screened for KRAS, NRAS and FLT3 mutations. Analysis for p-ERK (downstream of MEK) was performed by flow-cytometry. Results: 47 pts (27 men) were enrolled. Median age was 69 yrs (range, 26-83). 85% were ≥60 yrs. Disease stage included previously untreated AML (13 pts, all were ≥ 60 yrs; 11 had prior therapy for antecedent hematologic disease), primary refractory AML (14 pts), 1 st relapse (8 pts) and beyond first relapse (12 pts). Overall, 51% pts had secondary AML. Median number of prior therapies was 2 (range, 0-6). 51% had poor-risk cytogenetics. 10 pts had a FLT3 ITD, 3 pts had an NRAS mutation and one pt had a KRAS mutation. Selumetinib was well tolerated. Median number of cycles administered was 1 (range, 1-21). 49% received ≥2 cycles. Grade ≥3 adverse events possibly related to the drug included fatigue, dyspnea, and nausea occurring in 9%, 9% and 6% respectively. 1 pt has partial response, 3 pts had minor response ( 〉 50% decrease in blood and/or marrow blasts lasting 〉 4 weeks), 2 pts had unconfirmed minor response (uMR: 〉 50% decline in marrow blasts without a follow up confirmatory biopsy), 4 pts had stable disease (median: 16.5 weeks, range: 9-85). No pt with FLT3 ITD or NRAS mutation responded. The sole pt with KRAS mutation had uMR with hematologic improvement in platelets. Analysis of p-ERK showed baseline activation in 15/21 (71%) pts, but no difference in baseline levels in the responders vs non-responders (p=0.27). Conclusions: Administration of selumetinib in advanced AML is associated with modest antileukemic activity, which is independent of baseline p-ERK levels. Given its favorable toxicity profile, combination with drugs that target relevant signaling pathways in AML should be considered. (Sponsored by NCI grant NO1-CM-62201)
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.6582
    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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  • 5
    Online Resource
    Online Resource
    Detection of urothelial carcinoma using plasma cell-free methylated DNA.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 5046-5046
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5046-5046
    Abstract: 5046 Background: Methylation profiling of circulating cell-free DNA (cfDNA) is a promising approach for non-invasive tumor detection due to the presence of tissue-specific epigenetic signatures that are detectable in cfDNA. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMedDIP-seq) is a sensitive, low-input, cost-effective, bisulfite-free approach to profiling cfDNA methylomes, capable of detecting and classifying various tumor types. We tested the feasibility of cfMeDIP-seq to detect urothelial carcinoma (UC) in plasma samples. Methods: We performed cfMeDIP-seq on plasma samples from 43 patients (pts): 18 metastatic UC (UC) pts, 12 pre-cystectomy non-metastatic UC pts, and 13 cancer-free controls. Six (50%) of pre-cystectomy cases were non-muscle invasive UC. cfDNA was immunoprecipitated and enriched using an antibody targeting 5-methylcytosine and PCR-amplified to create a sequence-ready library. The top differentially methylated regions (DMRs) between UC and control samples were used to train a regularized binomial generalized linear model using 80% of the samples as a training set. The 20% of withheld test samples were then assigned a probability of being UC or control. This process was repeated 100 times. Results: The average amount (standard deviation) of cfDNA isolated from 1 ml of UC plasma samples was 29.2 (27.4) ng/µL and 8.02 (3.58) ng/µL in cancer-free controls. We identified 9,826 DMRs in plasma samples at an adjusted p-value of 〈 0.01, which partitioned UC and control samples. Iterative training and classification of held out samples using the top 300 DMRs resulted in a mean AUROC of 0.987. Conclusions: cfMeDIP-seq is an interesting new approach for non-invasive detection of UC. cfMeDIP-seq demonstrates high sensitivity to detect UC across all stages of UC, including non-muscle invasive disease.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.5046
    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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  • 6
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    Online Resource
    Dose-Dense Temozolomide for Newly Diagnosed Glioblastoma: A Randomized Phase III Clinical Trial
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 32 ( 2013-11-10), p. 4085-4091
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 32 ( 2013-11-10), p. 4085-4091
    Abstract: Radiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O 6 -methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM. Patients and Methods This phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status. Results A total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P 〈 .001), PFS (8.7 v 5.7 months; HR, 1.63; P 〈 .001), and response (P = .012). There was increased grade ≥ 3 toxicity in arm 2 (34% v 53%; P 〈 .001), mostly lymphopenia and fatigue. Conclusion This study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2013.49.6968
    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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