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  • American Society of Clinical Oncology (ASCO)  (3)
  • 2020-2024  (3)
  • Medicine  (3)
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  • American Society of Clinical Oncology (ASCO)  (3)
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  • 2020-2024  (3)
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  • Medicine  (3)
RVK
  • 1
    Online Resource
    Online Resource
    Elective Cancer Surgery in COVID-19–Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.01933
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Cellworks Omics Biology Model (CBM) to identify amplifications of chromosome 11p and 1p predict paclitaxel and carboplatin resistance.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e21208-e21208
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e21208-e21208
    Abstract: e21208 Background: Paclitaxel and carboplatin (PC) is used to treat a wide variety of malignancies including gynecologic, breast, lung, and occult primary cancers. In NSCLC, PC led to a substantial improvement in 1-yr survival from 10% (P alone) to approximately 50% seen with the combination. Nevertheless, a large proportion of patients do not respond. An optimal cytotoxic strategy for managing NSCLC and the discovery of chemotherapy biomarkers to guide treatment selection remain unmet needs in the clinic. Cellworks CBM platform identified a unique chromosomal signature which permits a stratification of which patients are most likely to respond to PC treatment. Methods: 22 patients treated with PC were published in TCGA dataset and selected for analysis. The mutation and copy number aberrations from individual cases served as input into the CBM (generated from PubMed and other online resources) to create a patient-specific protein network map. Disease-biomarkers unique to each patient were identified within protein network maps. Digital drug simulations were conducted by measuring effect of PC on a cell growth score comprised of a composite of cell proliferation, apoptosis, and other cancer hallmarks. Drug simulations were systematically conducted to identify and evaluate therapeutic efficacy. The drug combination was mapped to the patient genome along with a rational mechanism of action and validated based on the genomic profile and its biological consequences. Results: Of the 22 patients treated with PC, 13 had clinical responses and 9 were non-responders. The computer simulation correctly predicted response in 16/22 with 72.73% accuracy, 55.56% specificity and 84.62% sensitivity. CBM identified novel amplified segments of Chromosome 11p and 1p were responsible for non-responsiveness to PC. Key genes on these chromosomes were identified belonging to the autophagy, reactive oxygen species (ROS) scavenging, DNA repair, and microtubule polymerization pathways. Amplification of AMBRA1, ATG13 and TRAF6 (11p) led to autophagy upregulation resulting in low ROS level, a well-documented resistance loop for chemotherapy. SIRT3 and CAT (11p), ROS scavenging genes, were also upregulated due to increase in copy number. CTH (1p) is another key enzyme involved in GSH-mediated ROS scavenging and was also upregulated. Biosimulation indicated a low ROS level was the key reason of resistance to PC. Heightened DNA damage repair due FANCF and ZNF143 (11p amp) and USP1 (1p amp), was another cause of PC resistance. These discoveries suggest that a combination of an autophagy inhibitor / BCL2 mimetic might prove useful to reverse PC resistance associated with 11p and 1p amp. Conclusions: This study highlights how CBM simulation platform can help to identify novel patient segments for therapy response prediction and use drug re-purposing to overcome chemotherapy resistance.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e21208
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Clinical activity of systemic VSV-IFNβ-NIS oncolytic virotherapy in patients with relapsed refractory T-cell lymphoma.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 2500-2500
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 2500-2500
    Abstract: 2500 Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach for relapsed refractory hematologic malignancies. The Indiana strain of Vesicular Stomatitis Virus was engineered to encode interferon beta (IFNβ) and sodium iodine symporter (NIS) to produce VSV-IFNβ-NIS. Virally encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. NIS was inserted to noninvasively assess viral biodistribution using SPECT/PET imaging. We present the results of the phase 1 clinical trial NCT03017820 of systemic administration of VSV-IFNβ-NIS among patients (pts) with relapsed refractory Multiple Myeloma (MM), T cell Lymphoma (TCL) and Acute myeloid Leukemia (AML). Methods: VSV-IFNβ-NIS was administered at 5x10 9 TCID 50 (50% tissue culture infectious dose) dose level 1 to dose level 4, 1.7x10 11 TCID 50 . The primary objective was to determine the maximum tolerated dose of VSV-IFNβ-NIS as a single agent. Secondary objectives were determination of safety profile and preliminary efficacy of VSV-IFNβ-NIS. Correlative objectives included monitoring viremia and virus shedding. Adverse events (AEs) are reported based on CTCAE V4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014) criteria. Results: 15 pts received VSV-IFNβ-NIS: MM (7), TCL(7) and AML(1); 3 pts were treated at each dose level (DL) 1 through 3 (respectively 0.05, 0.17, and 0.5 x 10 11 TCID 50 ), & 6 pts were treated at dose level 4 (1.7x10 11 TCID 50 ). There were no dose limiting toxicities. The most frequent grades 3 & 4 AEs were hematologic: lymphopenia (46.6 & 26.6%), neutropenia (13.3% & 6.7%). CRS grades 1 (6.7%) and 2 (46.6%) were the non-hematologic AEs of note; mostly at DL 4. Only 1 pt required transient pressor support. Responses were seen in pts with T cell lymphoma. At DL2, there was a partial response (PR) lasting 3 months in a pt, post 12 prior lines of therapy. At DL4 there was a 6 month PR in a pt with PTCL and another pt with cutaneous relapse of PTCL who enjoys an ongoing CR, more than 1 year post VSV infusion; both pts received 5 prior lines of therapy. Viremia was detected in all pts at the end of infusion only up to 72 hrs post infusion; no infectious virus was recovered in buccal swabs or urine. Neutralizing anti-VSV antibodies were present by day 29. IFN levels were detectable within 30 mins of infusion, peaking between 4 & 48 hrs. TCL pts mounted higher hIFNβ levels within 48 hrs; the pt with CR mounted peak hIFNβ response of 18213.3pg/ml at 48 hrs post infusion, 15-fold higher than any other pt. Conclusions: VSV-IFNβ-NIS can be safely administered by IV infusion among heavily pretreated pts with hematologic malignancies. VSV-IFNβ-NIS as a single agent appears to be most effective at DL4 among patients with TCL, with an ongoing CR in a patient at DL4 more than 1 year post administration. Future trials of combination strategies with immune-modulatory drugs are currently being planned. Clinical trial information: NCT03017820.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.2500
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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