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Reoxygenation during radiotherapy in intermediate-risk prostate cancer

Abstract : Hypoxia is a major risk factor of prostate cancer radioresistance. We evaluated hypoxia non-invasively, using 18 F-Misonidazole PET/CT prior to radiotherapy and after a dose of 20 Gy in intermediate-risk pros-tate cancer patients. Decreased hypoxic volumes were observed in all patients, suggesting that radiother-apy induces early prostate tumor reoxygenation. Hypoxia is a major factor of resistance to radiotherapy because it selects radioresistant mutant cells and reduced levels of oxygen decrease the amount of reactive oxygen species induced by irradiation [1]. In prostate cancer, hypoxic markers based on direct inva-sive measurement of oxygen levels [2,3] or hypoxia-related protein or gene expression [4,5] were shown to predict tumor aggressiveness and recurrence following irradiation. Because sampling some prostate areas using biopsies may not reflect the whole extent of hypoxia within the prostate, functional imaging of hypoxic regions may better reflect the intraprostatic heterogeneity of hypoxic regions. In two recent series of prostate cancer patients, FMISO detected a hypoxic signal in 33% to 63 % of patients [6,7], confirming results of previous smaller series [8,9]. We showed that FMISO-positive volumes were partly located both in cancerous areas and in the normal gland [6]. FMISO may therefore represent a potent non-invasive tool to map hypoxia within the whole prostate. Evaluating hypoxia using only one single image may be insufficient since hypoxia is a dynamic process and is influenced by treatment. Preclinical prostate cancer models [10] and clinical data in other tumors [11] suggest that reoxygenation frequently occurs during fractionated radiotherapy. To increase the dose to hypoxic areas in the context of a dose-painting strategy, chronic and stable hypoxia may imply the use of a simultaneous-integrated boost strategy, while intermittent or decreasing hypoxia may imply boosting hypoxic regions prior to fractionated radiotherapy [9,12]. It is therefore important to evaluate hypoxia before and during the course of radiotherapy. We hypothesized that FMISO could be used to evaluate radiotherapy-induced reoxygenation during the course of radio-therapy in intermediate-risk prostate cancer patients. Patients and methods Patient selection and treatment The study was approved by the local Ethics Committee and registered in the NCI database (NCT01898065). Inclusion criteria were NCCN-defined intermediate-risk prostate cancer patients in whom high-dose radiotherapy to the prostate without hormone therapy was indicated. Our goal was to evaluate the influence of radiother-apy on prostate cancer hypoxia. Since prostate hypoxia is affected by hormone therapy (HT), we excluded high-risk prostate cancer patients who are routinely treated with RT + HT [13]. We also excluded low-risk tumors because the need for improved radio-therapy is not striking since most patients are now on active surveillance instead of radical treatment and the tumor is often not visible on prostate MRI. Intermediate-risk prostate cancer is the most frequent and also the more heterogeneous group with
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Submitted on : Monday, August 12, 2019 - 2:08:53 PM
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Stéphane Supiot, Caroline Rousseau, Mélanie Dore, Catherine Cheze-Le-Rest, Christine Kandel-Aznar, et al.. Reoxygenation during radiotherapy in intermediate-risk prostate cancer. Radiotherapy and Oncology, Elsevier, 2019, 133, pp.16-19. ⟨10.1016/j.radonc.2018.12.022⟩. ⟨inserm-02265798⟩

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