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  • American Society of Clinical Oncology (ASCO)  (3)
  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e18010-e18010
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e18010-e18010
    Abstract: e18010 Background: Cervical cancer is a global health problem. Despite scale up of prevention programs, there will be an ongoing need to improve the effectiveness of radiotherapy/cisplatin (RTCT) for women with established, locally advanced disease. We have shown that RTCT with the CXCR4 inhibitor plerixafor improves tumor control, reduces metastases and reduces RT-related side effects compared to RTCT alone. X4-136 is an oral CXCR4 inhibitor that is better suited to long-term, once daily use. In this study we examined: 1. The efficacy of RTCT and X4-136 in cervical cancer; 2. Biomarkers of response to RTCT and X4-136; and 3. Effects of RTCT and X4-136 on intestinal toxicity, an important dose-limiting RT side effect in these patients. Methods: Orthotopic cervical cancer xenografts derived from our patients were treated with RT (30 Gy; 2 Gy/day) and cisplatin (4 mg/kg/week ip) with or without concurrent X4-136 (100 mg/kg/day orally) for 3 weeks. Mice were sacrificed immediately after treatment for biomarker assessment. In separate experiments, mice had CT imaging weekly after treatment to evaluate tumor response. Acute and late intestinal toxicity was assessed histologically 3.5 and 90 days after treatment respectively. Results: RTCT alone increased CXCL12/CXCR4 signaling, intratumoral accumulation of myeloid cells and PD-L1 expression. The addition of X4-136 during RTCT abrogated these effects and improved tumor response in 2 cervical cancer models. Furthermore, the addition of X4-136 increased the proportion of surviving intestinal crypt cells in keeping with a reduction in acute RT toxicity, and reduced late histologic changes of late RT toxicity. Conclusions: The addition of X4-136 blunts RTCT-induced upregulation of the CXCL12/CXCR4 pathway, reduces intratumoral myeloid cells, improves tumor control and reduces side effects in cervical cancer. Few if any pharmacologic strategies have been identified previously that expand the therapeutic window with RT in this way. The combination of RTCT and CXCR4 inhibition warrants testing in clinical trials to validate these findings. These benefits may apply to other tumors where RTCT plays a curative role.
    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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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e13538-e13538
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e13538-e13538
    Abstract: e13538 Background: The Exercise in Cancer Decision Support (EXCEEDS) algorithm is an evidence-based, risk stratified framework. This framework allows for enhanced decision making for exercise pre-participation medical clearance and triage to cancer rehabilitation or exercise services across the cancer continuum. We conducted a Delphi study to examine utility and acceptability of the EXCEEDS algorithm for oncology stakeholders. Methods: Delphi study participants were randomized to two case studies, then made pre-participation medical clearance (yes/no) and intervention triage recommendations (cancer rehabilitation, clinically-supervised exercise, cancer-specific community-based exercise, and unsupervised exercise) in two conditions: independent (IND) and using EXCEEDS. Immediately following, participants rated algorithm acceptability in four domains using 4-point Likert scales (1- strongly disagree, to 4- strongly agree). We dichotomously coded accuracy (correct/incorrect) for each medical clearance and triage recommendation, then calculated the proportion of correct answers for each case to determine accuracy. We compared triage decision time (seconds) between conditions (IND vs. EXCEEDS) using paired-samples t-tests. We calculated the proportion of participants who ‘agreed’ (i.e., score ≥3) with each acceptability domain. Results: Oncology stakeholders (N=33) were mostly female (69.7%), 35-44 years old (42.4%), located in the United States (60.6%), and had at least 10 years of experience (60.6%). When using EXCEEDS, accuracy for medical clearance decisions improved in 3 of 4 cases (75%), triage decision accuracy improved in 4 of 4 (100%) cases, and triage time (seconds) improved significantly in 3 of 4 cases (75%, p 〈 .05). Table shows average improvement in decision accuracy and triage time for each case study. Most participants agreed that the algorithm was acceptable in each domain: “meets my approval” (n=21, 63.6%), “is appealing” (n=29, 87.9%), “enjoyable to use” (n=19, 57.6%), and “welcomed in my discipline or practice” (n=24, 72.7%). Conclusions: Accuracy and efficiency of decision-making for medical clearance and triage to cancer rehabilitation or exercise services was enhanced when using the EXEECDS algorithm. Most participants agreed the algorithm was acceptable. Future research is needed to validate the tool and explore avenues for dissemination and clinical implementation. % difference between EXCEEDS and Individual condition (EXCEEDS – IND) for medical clearance decision, triage decision and mean (M) and standard deviation (SD) of triage decision time.[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
    Location Call Number Limitation Availability
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 4083-4083
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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