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  • 1
    In: Journal of Urology, Ovid Technologies (Wolters Kluwer Health), Vol. 206, No. Supplement 3 ( 2021-09)
    Type of Medium: Online Resource
    ISSN: 0022-5347 , 1527-3792
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of the American College of Surgeons Vol. 231, No. 4 ( 2020-10), p. S339-S340
    In: Journal of the American College of Surgeons, Ovid Technologies (Wolters Kluwer Health), Vol. 231, No. 4 ( 2020-10), p. S339-S340
    Type of Medium: Online Resource
    ISSN: 1072-7515
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e18776-e18776
    Abstract: e18776 Background: SARS-CoV-2 virus has been shown to persist in respiratory tract in immunocompromised patients. However, such data are lacking for both asymptomatic and symptomatic SARS-CoV-2 infection in cancer patients. We share our single center experience on duration of SARS-CoV-2 viral presence in the upper respiratory tract of cancer patients with SARS-CoV-2 infection (asymptomatic and symptomatic) detected by viral PCR. Methods: This is retrospective review of cancer patients with documented SARS-CoV-2 infection and measurement of viral shedding at Levine Cancer Institute. Testing indications were COVID-19 symptomatic illness, pre-procedural and pre-chemo testing. Prolonged shedding was defined as presence of viral RNA beyond 30 days after first positive test. To document viral clearance, patients required 2 negative SARS-CoV-2 PCR test separated by at least 24 hours and maximum 3 weeks apart either by nasopharyngeal or nasal PCR swab. Differences in distributions were identified between patients shedding virus more than 30 days and less than 30 days using uni- and multivariable logistic regression models. Statistical significance was set at p 〈 0.10 to enter the multivariable model, and p 〈 0.05 to remain. Results: Demographic data: median age 62 (range 20-93); 58.5% females; 70% White, 21% Black, and 7.4% Hispanics. Comorbidities included hypertension 43.2%, diabetes 16.7% and chronic lung disease 3.7%. Underlying malignancies were breast cancer 25%, hematologic cancer 22%, lung cancer 16% and genitourinary 11%. Chemotherapy was received by 26.5% patients within 4 weeks prior to testing. 162 patients were identified median duration of 18 days (range 4-90 days). Of these, 76% patients were tested for non-symptomatic indication with median duration of shedding 17 days (range 6-80) and 23% were tested for clinical symptoms with median duration of shedding 29 days (range 4-90) (p = 〈 0.001); 50% of patients never developed symptoms, whereas 35% patients with non-symptomatic testing indication, subsequently developed symptoms. Viral clearance by day 30, day 45, day 60 and day 90 was 78%, 93%, 97% and 100% respectively. Univariate analysis did not show difference between patients with prolonged shedding vs those shedding less than 30 days for age, gender, race, ethnicity, underlying malignancy, co-morbidities including body mass index, diabetes, chronic lung conditions, hypertension, or receipt of cytotoxic chemo. Multivariable analysis showed that presence of symptoms at any point during SARS-CoV-2 infection (OR 5.9, 95% CI 2.4-14.5, p 〈 0.001) was associated with prolonged shedding. Conclusions: Symptomatic SARS-CoV-2 infection is associated with prolonged viral shedding in cancer patients. Cancer patients can have asymptomatic SARS-CoV-2 infection. More studies are warranted to understand viral kinetics and its clinical implications in cancer patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 11519-11519
    Abstract: 11519 Background: Doxorubicin has been the traditional standard therapy for treatment of advanced soft tissue sarcoma (STS). The addition of cytotoxic agents leads to increased toxicity with minimal improvement in efficacy. Pembrolizumab monotherapy has demonstrated activity and tolerability in previous study of advanced STS. This study combined pembrolizumab with doxorubicin to determine safety and efficacy in the frontline setting. Methods: This single-center, single-arm, phase 2 trial enrolled subjects with unresectable or metastatic STS and no prior anthracycline therapy. Subjects were treated with pembrolizumab 200 mg IV and doxorubicin 60 mg/m2 (75 mg/m2 dose escalation per investigator discretion) IV every 3 weeks. The primary endpoint of safety, based on Bayesian stopping rules, evaluated if the severe or life-threatening treatment emergent adverse event (TEAE) rate exceeded 0.55. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression free survival (PFS). Efficacy and safety were based on RECIST 1.1 and CTCAE v 4.0, respectively. Kaplan-Meier methods evaluated time to event outcomes. Results: From 4/2017 to 12/2019, 30 subjects (53% female, median age 61.5 years, 10 patients 〉 70 years (33%)) were enrolled in the study with 6 (20%) patients still on treatment and 27 evaluable for response. The most common histologic subtypes were leiomyosarcoma (33%) and liposarcoma (23%), and a majority of patients demonstrated high grade disease (60%). Current analysis shows a median follow-up of 9.9 months. One subject experienced a stopping rule event (grade 3 autoimmune disorder). ORR was 33% (95% CI 17-54%), with documented disease control in 78% (95% CI 57.7-91.4%) of patients. Eight (30%) patients achieved a partial response, one (4%) patient achieved a complete response and 12 (44%) patients had stable disease. Preliminary results demonstrate median PFS of 6.9 months (PFS-6 mo: 52%) and median OS of 15 months (OS-6 mo: 81%) compared to historical PFS-6mo of 4.6 months and OS of 12.8 months with doxorubicin alone. 1 Most common grade 3+ TEAEs included neutropenia (11 [37%]), febrile neutropenia (6 [20%] ), anemia (5 [17%]), and nausea (4 [13%] ). Molecular and biomarker analysis is currently in progress. Conclusions: The combination of pembrolizumab with doxorubicin has manageable toxicity and preliminary promising activity in the treatment of anthracycline-naive advanced soft tissue sarcomas. Ref: 1. Lancet Oncol. 2014 Apr; 15(4):415-23. Clinical trial information: NCT03056001 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Cancer Medicine, Wiley, Vol. 12, No. 6 ( 2023-03), p. 7029-7038
    Abstract: Patients with unresectable dedifferentiated liposarcoma (DDLPS) have poor overall outcomes. Few genomic alterations have been identified with limited therapeutic options. Experimental Design Patients treated at Levine Cancer Institute with DDLPS were identified. Next generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) testing were performed on tumor tissue collected at diagnosis or recurrence/progression. Confirmation of genomic alterations was performed by orthologous methods and correlated with clinical outcomes. Univariate Cox regression was used to identify genomic alterations associated with clinical outcomes. Results Thirty‐eight DDLPS patients with adequate tissue for genomic profiling and clinical data were identified. Patient characteristics included: median age at diagnosis (66 years), race (84.2% Caucasian), and median follow‐up time for the entire cohort was 12.1 years with a range from approximately 3.5 months to 14.1 years. Genes involved in cell cycle regulation, including MDM2 (74%) CDK4 (65%), and CDKN2A (23%), were amplified along with WNT/Notch pathway markers: HMGA2, LGR5, MCL1, and CALR (19%–29%). While common gene mutations were identified, PDE4DIP and FOXO3 were also mutated in 47% and 34% of patients, respectively, neither of which have been previously reported. FOXO3 was associated with improved overall survival (OS) (HR 0.37; p  = 0.043) along with MAML2 (HR 0.30; p  = 0.040). Mutations that portended worse prognosis included RECQL4 (disease‐specific survival HR 4.67; p  = 0.007), MN1 (OS HR = 3.38; p  = 0.013), NOTCH1 (OS HR 2.28, p  = 0.086), and CNTRL (OS HR 2.42; p  = 0.090). Conclusions This is one of the largest retrospective reports analyzing genomic aberrations in relation to clinical outcomes for patients with DDLPS. Our results suggest therapies targeting abnormalities should be explored and confirmation of prognostic markers is needed. Dedifferentiated liposarcoma is one of the most common subtypes of soft tissue sarcoma yet little is known of its molecular aberrations and possible impact on outcomes. The work presented here is an evaluation of genetic abnormalities among a population of patients with dedifferentiated liposarcoma and how they corresponded with survival and risk of metastases. There were notable gene mutations and amplifications commonly found, some of which had interesting prognostic implications.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2659751-2
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  • 6
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 23 ( 2021-12-01), p. 6424-6431
    Abstract: Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS. Patients and Methods: This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m2 cycle 1 with subsequent escalation to 75 mg/m2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines. Results: Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9–56.1%], with documented disease control in 80.0% (95% CI, 61.4–92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS. Conclusions: Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e18753-e18753
    Abstract: e18753 Background: Cancer patients are more susceptible to developing severe disease associated with SARS-CoV-2 infection. Herein, data from a high-volume cancer center is presented highlighting risk factors associated with hospitalization with COVID-19 disease. Methods: Cancer patients in the Levine Cancer Institute COVID19 database who were tested for SARS-CoV-2 due to clinical illness from March 1, 2020 to October 29, 2020 with 90 days follow-up are described here. Patients’ demographic and clinical information were retrospectively entered into a REDCap database from chart reviews. Differences in distributions were identified between hospitalized and non-hospitalized patients using the chi-squared test with uni- and multivariable logistic regression models. Statistical significance was set at p 〈 0.05. Results: 228 patients with SARS-CoV-2 infection were identified, of whom 103 (45%) were hospitalized. Median age was 63 years (range 28-95). Race distribution for infection showed White 65%, followed by Black 26.8% and Hispanic ethnicity 16.7% , with a similar distribution for hospital admission. Median length of stay was 10 days (range 1-91) with no readmissions within 90 days. The most common underlying malignancies were breast (29.8%), hematologic (21.1%) and genitourinary (12.3%). The most common preexisting conditions included hypertension (55.7%), diabetes (27.2%) and cardiac disease (3.9%). The most common presenting symptoms were cough (50.2%), fever (38.4%), fatigue (37.8%) and shortness of breath (36.4%). Maximum oxygen requirements for hospitalized patients were ambient air (34%), nasal canula (34%), high/medium flow nasal canula (10%), non-invasive ventilation (13%) and mechanical ventilation (10%). Case fatality rate was 10% with diagnosis of COVID-19, including 21.4% of those admitted to the hospital and 51.7% of those admitted to the ICU. Univariable logistic regression analysis showed that age, sex, prior chemotherapy, upper gastrointestinal cancers, hematologic cancers, number of medical conditions, cardiac disease, chronic lung diseases, hypertension, and diabetes increased risk of hospitalization. Table shows results of multivariate analysis. Conclusions: The COVID-19 pandemic has caused high case fatality rates in our cancer patients. We identified age, cardiac disease, hematologic malignancy and receipt of chemotherapy within 4 weeks of diagnosis as risk factors for hospitalization. These data may help in prioritizing early intervention in vulnerable subgroups to improve survival outcomes. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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