{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:17:27Z","timestamp":1760059047121,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"French State Region","award":["CPER I2MT (2014\u20132021)","R-IRM (2021\u20132027)"],"award-info":[{"award-number":["CPER I2MT (2014\u20132021)","R-IRM (2021\u20132027)"]}]},{"name":"European Union","award":["CPER I2MT (2014\u20132021)","R-IRM (2021\u20132027)"],"award-info":[{"award-number":["CPER I2MT (2014\u20132021)","R-IRM (2021\u20132027)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Cryotherapy involves the insertion of cryoprobes into tumors to induce cell destruction through exposure to extremely low temperatures over several minutes. This localized treatment modality may enhance the efficacy of established therapies, such as radiotherapy, particularly for glioblastomas. Our study aimed to provide proof-of-concept for the efficacy of combining cryotherapy and radiotherapy in the treatment of subcutaneous murine brain tumors (GL-261) in immunocompetent C57BL\/6 mice. Methods: Tumor growth, survival and response were evaluated using MRI and histological analysis. Results: Partial cryotherapy alone showed no therapeutic efficacy. However, combining cryotherapy with radiotherapy significantly potentiated treatment outcomes. A statistically significant survival benefit was observed in the combined therapy group compared to control, cryotherapy and radiotherapy groups. Notably, 40% of mice receiving the combined treatment exhibited complete responses, with no detectable tumor cells on MRI or histological analysis. Furthermore, MRI-based monitoring revealed that the Apparent Diffusion Coefficient (ADC) map could predict complete response 14 days post-treatment, unlike caliper-based measurements. Conclusions: These findings suggest that cryotherapy may enhance radiotherapy efficacy, resulting in complete tumor regression in 4 out of 10 cases. ADC distribution may serve as a predictive marker for therapeutic response. However, given the limitations of the model, further studies in orthotopic models are needed to validate these findings and assess their clinical relevance.<\/jats:p>","DOI":"10.3390\/cancers17101692","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T03:51:03Z","timestamp":1747626663000},"page":"1692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Effects of Cryotherapy and Radiotherapy in Glioblastoma Treatment: Evidence from a Murine Model"],"prefix":"10.3390","volume":"17","author":[{"given":"H\u00e9l\u00e8ne","family":"Cebula","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Hautepierre University Hospital, 1, Avenue Moli\u00e8re, 67200 Strasbourg, France"},{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"},{"name":"Medicine Strasbourg University, 4 Rue Kirschleger, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-9572","authenticated-orcid":false,"given":"Chrystelle","family":"Po","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0305-711X","authenticated-orcid":false,"given":"Carole","family":"Mura","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"},{"name":"Radiobiology Laboratory, Institut de Canc\u00e9rologie Strasbourg Europe (ICANS), UNICANCER, 17 Rue Albert Calmette, 67033 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit","family":"Lhermitte","sequence":"additional","affiliation":[{"name":"Pathology Department, University Hospital of Strasbourg, 67098 Strasbourg, France"},{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, OnKO3T Team, Faculty of Pharmacy, 67401 Illkirch, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto Luigi","family":"Cazzato","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, University Hospital of Strasbourg, 1, Place de l\u2019H\u00f4pital, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Rame","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Le F\u00e8vre","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Institut de Canc\u00e9rologie Strasbourg Europe (ICANS), UNICANCER, 17 Rue Albert Calmette, 67033 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julien","family":"Todeschi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hautepierre University Hospital, 1, Avenue Moli\u00e8re, 67200 Strasbourg, France"},{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles-Henry","family":"Mallereau","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hautepierre University Hospital, 1, Avenue Moli\u00e8re, 67200 Strasbourg, France"},{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0952-7760","authenticated-orcid":false,"given":"Afshin","family":"Gangi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"},{"name":"Medicine Strasbourg University, 4 Rue Kirschleger, 67000 Strasbourg, France"},{"name":"Department of Interventional Radiology, University Hospital of Strasbourg, 1, Place de l\u2019H\u00f4pital, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4952-5572","authenticated-orcid":false,"given":"Georges","family":"No\u00ebl","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"},{"name":"Medicine Strasbourg University, 4 Rue Kirschleger, 67000 Strasbourg, France"},{"name":"Radiobiology Laboratory, Institut de Canc\u00e9rologie Strasbourg Europe (ICANS), UNICANCER, 17 Rue Albert Calmette, 67033 Strasbourg, France"},{"name":"Department of Radiation Oncology, Institut de Canc\u00e9rologie Strasbourg Europe (ICANS), UNICANCER, 17 Rue Albert Calmette, 67033 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"de Mathelin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Proust","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hautepierre University Hospital, 1, Avenue Moli\u00e8re, 67200 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-5806","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Burckel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France"},{"name":"Radiobiology Laboratory, Institut de Canc\u00e9rologie Strasbourg Europe (ICANS), UNICANCER, 17 Rue Albert Calmette, 67033 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. 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