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Susan Cheung



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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-35 - Hypoxia Mapping Using Oxygen-Enhanced MRI in Lung Cancer (ID 14283)

      16:45 - 18:00  |  Author(s): Susan Cheung

      • Abstract
      • Slides

      Background

      Oxygen deprivation (hypoxia) is associated with worse non-small cell lung cancer (NSCLC) outcomes and predicts poor response to NSCLC treatments, including radiotherapy. There is an unmet need to develop non-invasive hypoxia biomarkers. We report the first preclinical and clinical evidence that oxygen-enhanced MRI (OE-MRI) can map and quantify therapy-induced change in NSCLC hypoxia.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In the preclinical study, radiation-induced changes in OE-MRI were first examined in a Calu-6 xenograft model of NSCLC. Tumours received a single 10Gy fraction of radiotherapy (n=9), chemoradiotherapy (5 x 2Gy fractions plus cisplatin; n=6) or control (n=9). Mice were imaged longitudinally using a multi-parametric MRI protocol (diffusion-weighted imaging (DWI), OE and dynamic contrast-enhanced (DCE)-MRI) at days 0, 3, 6 and 10 in all groups and then at day 13 (control), day 18 and 25 (radiotherapy) and day 18 (chemoradiotherapy). Pathology was obtained at cull in imaged mice and in a separate Calu6 cohort treated with a single 10Gy radiotherapy fraction (n=6) or control (n=9) at day 10. In the clinical study, twenty three stage I-IV NSCLC patients underwent an identical multi-parametric MRI for protocol development (n=6), twice prior to radiotherapy (n=10) and after 14±4 radiotherapy fractions (n=12). In all tumours we quantified the validated MRI hypoxia biomarker perfused oxygen-refractory (Oxy-R), which identifies absence of OE-MRI signal change in perfused tumour.

      4c3880bb027f159e801041b1021e88e8 Result

      By day 10, perfused Oxy-R (hypoxic) volume decreased relative to control in xenografts treated with either radiotherapy (p=0.029) or fractionated chemoradiotherapy (p=0.047). Hypoxia modification persisted in chemoradiotherapy treated tumors to day 16 and in radiotherapy treated tumors to day 22 (both p<0.001). Pimonidazole immunohistochemistry at day 10 showed lower hypoxic fraction in tumors treated with radiotherapy (p=0.026), relative to time matched controls. In addition, imaged xenografts also showed lower hypoxic fractions in radiotherapy (p=0.042) and chemoradiotherapy (p=0.041) treated tumors, relative to size matched control at cull. In the clinical study, OE-MRI was safe, feasible and well-tolerated. Perfused Oxy-R (hypoxic) volume demonstrated excellent repeatability with interclass correlation coefficient of 0.961 (95% CI 0.858-0.990). Visual inspection revealed that MRI hypoxia maps were spatially repeatable across a range of tumour and hypoxic volumes. In the absence of volumetric tumour change, perfused Oxy-R (hypoxic) volume decreased at mid-treatment (3.23 cm3 (95% CI 0-9.41 cm3)), compared to baseline (4.16 cm3 (95% CI 0-10.6 cm3)); p=0.0150.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings support using OE-MRI to detect and monitor hypoxia in clinical trials of hypoxia-modifying therapies or radiotherapy dose painting studies in patients with NSCLC.

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