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  • 1
    Online Resource
    Online Resource
    Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 18 ( 2021-06-20), p. 1995-2004
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 18 ( 2021-06-20), p. 1995-2004
    Abstract: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent ( P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.03614
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Identification of patients at risk for delirium on a medical oncology hospital ward.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 31_suppl ( 2014-11-01), p. 130-130
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 31_suppl ( 2014-11-01), p. 130-130
    Abstract: 130 Background: Delirium is a distressing experience for patients with cancer. Incidence rates of delirium vary between 5 and 88 percent. We studied the incidence of delirium on our medical oncology ward, along with its predisposing and precipitating factors, in order to identify patients who may benefit from screening and early interventions. Methods: We evaluated patients admitted to our medical oncology ward between January 2011 and June 2012 for delirium. In this period a screening program with the Delirium Observation Screening Scale was initiated. Risk factors for delirium were extracted from the patient’s chart. We developed a prediction model to identify patients who are at risk to develop delirium and optimized this model with a cohort of patients with a delirium diagnosed between June 2012 and September 2013. Results: 1,733 admittances of 574 individual patients were recorded in the study period. Sixty episodes of delirium were identified in 52 patients. The patients had a mean age of 60 years, and most patients (70%) had advanced cancer. The most prevalent predisposing and precipitating factors were age 〉 70, drug intoxication, infection and metabolic imbalances (abnormalities in sodium, potassium, calcium, albumin or glucose levels), which were present in 21, 25, 22, and 18 percent, respectively. The prediction model revealed that patients who were electively admitted had a very low risk to develop delirium (1%), but patients admitted for an emergency with at least one metabolic abnormality, such as hyperkalemia, were at high risk for developing a delirium (delirium risk 33%). Conclusions: Based on our analyses for risk factors of delirium, we developed a new prediction model for the risk for delirium in patients with cancer admitted to an oncology ward that may be used for targeted screening and to study preventive therapy in order to improve their quality of life.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.31_suppl.130
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Mass Spectrometry-Based Proteomics: From Cancer Biology to Protein Biomarkers, Drug Targets, and Clinical Applications
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  American Society of Clinical Oncology Educational Book , No. 34 ( 2014-05), p. e504-e510
    Details
    In: American Society of Clinical Oncology Educational Book, American Society of Clinical Oncology (ASCO), , No. 34 ( 2014-05), p. e504-e510
    Abstract: KEY POINTS Current mass spectrometry platforms provide comprehensive and quantitative inventories of a large number of proteins (up to ∼10,000) in complex biologic and clinical samples. For protein identification, proteins are typically digested to peptides with sequence-specific proteases such as trypsin to improve detectability in the mass spectrometer and to provide multiple measurements per protein. Bioinformatic tools link mass spectrometric information on the molecular weight of tryptic peptides and their in situ generated fragments to general amino acid sequence databases, or more recently to cancer genome-based protein sequences to enable the identification of protein variants (proteogenomics). Protein biomarkers are advantageous molecules for diagnostic applications as they are directly connected to (patho-)physiology and may be coupled to routine, antibody-based assays. Phosphoproteomics can uncover the activity of endogenous signaling networks in (cancer) cells and (tumor) tissues and enables the identification of candidate driver kinases for therapeutic targeting in cancer. Targeted mass spectrometry approaches have been developed into valuable high-throughput tools for specific and sensitive multiplexed validation of protein biomarkers derived from global discovery experiments as a first step toward their potential clinical application.
    Type of Medium: Online Resource
    ISSN: 1548-8748 , 1548-8756
    URL: Article
    DOI: 10.14694/EdBook_AM.2014.34.e504
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2431126-1
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  • 4
    Online Resource
    Online Resource
    Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer: Results From the Randomized CROSS Trial
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 3 ( 2018-01-20), p. 268-275
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 3 ( 2018-01-20), p. 268-275
    Abstract: To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and –Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were chosen as predefined primary end points. Predefined secondary end points were global QOL (GQOL; QLQ-C30), fatigue (FA; QLQ-C30), and emotional problems (EM; QLQ-OES24). Results A total of 363 patients were analyzed. No statistically significant differences in postoperative HRQOL were found between treatment groups. In the nCRT group, PF, EA, GQOL, FA, and EM scores deteriorated 1 week after nCRT (Cohen’s d: −0.93, P 〈 .001; 0.47, P 〈 .001; −0.84, P 〈 .001; 1.45, P 〈 .001; and 0.32, P = .001, respectively). In both treatment groups, all end points declined 3 months postoperatively compared with baseline (Cohen’s d: −1.00, 0.33, −0.47, −0.34, and 0.33, respectively; all P 〈 .001), followed by a continuous gradual improvement. EA, GQOL, and EM were restored to baseline levels during follow-up, whereas PF and FA remained impaired 1 year postoperatively (Cohen’s d: 0.52 and −0.53, respectively; both P 〈 .001). Conclusion Although HRQOL declined during nCRT, no effect of nCRT was apparent on postoperative HRQOL compared with surgery alone. In addition to the improvement in survival, these findings support the view that nCRT according to the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study–regimen can be regarded as a standard of care.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.73.7718
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    A phase I trial of cabazitaxel ± rhenium-188-HEDP in patients with metastatic castration resistant prostate cancer who progressed on or after a docetaxel containing treatment.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. e16508-e16508
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e16508-e16508
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.e16508
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    Androgen receptor and estrogen receptor imaging in patients with metastatic breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 11553-11553
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 11553-11553
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.11553
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    Loss of Chromosome 18q11.2-q12.1 Is Predictive for Survival in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 20 ( 2018-07-10), p. 2052-2060
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 20 ( 2018-07-10), p. 2052-2060
    Abstract: Patients with metastatic colorectal cancer (mCRC) have limited benefit from the addition of bevacizumab to standard chemotherapy. However, a subset probably benefits substantially, highlighting an unmet clinical need for a biomarker of response to bevacizumab. Previously, we demonstrated that losses of chromosomes 5q34, 17q12, and 18q11.2-q12.1 had a significant correlation with progression-free survival (PFS) in patients with mCRC treated with bevacizumab in the CAIRO2 clinical trial but not in patients who did not receive bevacizumab in the CAIRO trial. This study was designed to validate these findings. Materials and Methods Primary mCRC samples were analyzed from two cohorts of patients who received bevacizumab as first-line treatment; 96 samples from the European multicenter study Angiopredict (APD) and 81 samples from the Italian multicenter study, MOMA. A third cohort of 90 samples from patients with mCRC who did not receive bevacizumab was analyzed. Copy number aberrations of tumor biopsy specimens were measured by shallow whole-genome sequencing and were correlated with PFS, overall survival (OS), and response. Results Loss of chromosome 18q11.2-q12.1 was associated with prolonged PFS most significantly in both the cohorts that received bevacizumab (APD: hazard ratio, 0.54; P = .01; PFS difference, 65 days; MOMA: hazard ratio, 0.55; P = .019; PFS difference, 49 days). A similar association was found for OS and overall response rate in these two cohorts, which became significant when combined with the CAIRO2 cohort. Median PFS in the cohort of patients with mCRC who did not receive bevacizumab and in the CAIRO cohort was similar to that of the APD, MOMA, and CAIRO2 patients without an 18q11.2-q12.1 loss. Conclusion We conclude that the loss of chromosome 18q11.2-q12.1 is consistently predictive for prolonged PFS in patients receiving bevacizumab. The predictive value of this loss is substantiated by a significant gain in OS and overall response rate.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.77.1782
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Efficacy and predictors of response of nivolumab in treatment-refractory MSI solid tumors: Results of a tumor-agnostic DRUP cohort.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 2590-2590
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2590-2590
    Abstract: 2590 Background: Microsatellite unstable (MSI) tumors represent 4% of all cancer diagnoses and are known to be sensitive to immune checkpoint inhibitors (ICI). Despite the progress made, a significant proportion of patients with MSI tumors does not respond, highlighting the urgent need to identify additional predictive biomarkers. In this study, we evaluated the efficacy of the PD-1 inhibitor nivolumab across pre-treated solid MSI tumors and performed extensive biomarker analysis to better characterize ICI-effectiveness in this setting. Methods: Adult patients with MSI tumors who exhausted all standard of care treatment options were eligible for inclusion and were enrolled in the Drug Rediscovery Protocol (DRUP), a clinical trial that treats cancer patients with approved targeted- and immunotherapies outside their registered indication, based on their tumor molecular profile (NCT0295234). Patients were treated with nivolumab (four cycles of 240 mg every 2 weeks, followed by 480 mg every 4 weeks) until disease progression or unmanageable toxicity. Primary endpoint was clinical benefit (CB, objective response (OR) or stable disease ≥ 16 weeks). Whole genome sequencing and RNA sequencing were performed on pre-treatment biopsies to reveal potential predictors of response or resistance to anti-PD1. Results: 130 evaluable patients were enrolled with in total 16 different tumor types. CB was observed in 62% (95% CI 46 – 54) ( N = 80) with an OR in 45% (95% CI 53 – 70) ( N = 58). After a median follow-up of 14.5 months (95% CI 13 – 19), median progression free survival was 18 months (95% CI 9 – not reached) and median overall survival was not reached. HLA class I status and mutational burden were not significantly associated with CB. However, in depth biomarker analyses identified that mutational burden was predictive of CB in HLA-wildtype patients (52%) but not in HLA class I mutants (48%). Strikingly, in contrast to the paradigm that neoantigen-specific adaptive immunity is primarily involved in clearing MSI tumors, transcriptomics indicated that, compared to non-CB, CB was characterized by significantly higher expression of key modulators in innate immunity, including non-classical HLA transcripts (P = 4.2x10 -3 ), NKGD2 ligands MICA/MICB (P = 6.4x10 -3 ), killer immunoglobulin-like receptors ( P = 0.047) and butyrophilins ( P = 0.024). Conclusions: Nivolumab proved highly effective in pre-treated, advanced solid MSI tumors. Genomic analysis revealed that neoantigen burden only determined ICI-effectiveness in patients with wildtype HLA class I. Furthermore, transcriptomics revealed a central role of innate immunity in ICI-effectiveness in MSI tumors, which aligns with the fact that these tumors frequently lose HLA class I antigen presentation. Together, these results inform novel biomarker strategies to further refine precision medicine in this patient population. Clinical trial information: NCT0295234 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.2590
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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