{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:04:39Z","timestamp":1793239479642,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>(1) Background: Mild hyperthermia (mHT, 39\u201342 \u00b0C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy. mHT triggers a series of therapeutically relevant biological mechanisms, e.g., it can act as a radiosensitizer by improving tumor oxygenation, the latter generally believed to be the commensurate result of increased blood flow, and it can positively modulate protective anticancer immune responses. However, the extent and kinetics of tumor blood flow (TBF) changes and tumor oxygenation are variable during and after the application of mHT. The interpretation of these spatiotemporal heterogeneities is currently not yet fully clarified. (2) Aim and methods: We have undertaken a systematic literature review and herein provide a comprehensive insight into the potential impact of mHT on the clinical benefits of therapeutic modalities such as radio- and immuno-therapy. (3) Results: mHT-induced increases in TBF are multifactorial and differ both spatially and with time. In the short term, changes are preferentially caused by vasodilation of co-opted vessels and of upstream normal tissue vessels as well as by improved hemorheology. Sustained TBF increases are thought to result from a drastic reduction of interstitial pressure, thus restoring adequate perfusion pressures and\/or HIF-1\u03b1- and VEGF-mediated activation of angiogenesis. The enhanced oxygenation is not only the result of mHT-increased TBF and, thus, oxygen availability but also of heat-induced higher O2 diffusivities, acidosis- and heat-related enhanced O2 unloading from red blood cells. (4) Conclusions: Enhancement of tumor oxygenation achieved by mHT cannot be fully explained by TBF changes alone. Instead, a series of additional, complexly linked physiological mechanisms are crucial for enhancing tumor oxygenation, almost doubling the initial O2 tensions in tumors.<\/jats:p>","DOI":"10.3390\/cancers15051394","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T01:31:06Z","timestamp":1677115866000},"page":"1394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["From Localized Mild Hyperthermia to Improved Tumor Oxygenation: Physiological Mechanisms Critically Involved in Oncologic Thermo-Radio-Immunotherapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-3188","authenticated-orcid":false,"given":"Peter","family":"Vaupel","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3612-4622","authenticated-orcid":false,"given":"Helmut","family":"Piazena","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9-University Medicine, Cooperative Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-8340","authenticated-orcid":false,"given":"Markus","family":"Notter","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Lindenhofspital Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0163-8677","authenticated-orcid":false,"given":"Andreas R.","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca-L.","family":"Grosu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1748-4852","authenticated-orcid":false,"given":"Felix","family":"Scholkmann","sequence":"additional","affiliation":[{"name":"Biomedical Optics Research Laboratory, Department of Neonatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"},{"name":"Institute of Complementary and Integrative Medicine, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-6431","authenticated-orcid":false,"given":"Alan Graham","family":"Pockley","sequence":"additional","affiliation":[{"name":"John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham NG11 8NS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2616-3137","authenticated-orcid":false,"given":"Gabriele","family":"Multhoff","sequence":"additional","affiliation":[{"name":"TranslaTUM\u2014Central Institute for Translational Cancer Research, Technische Universit\u00e4t M\u00fcnchen (TUM), 81675 Munich, Germany"},{"name":"Department of Radiation Oncology, Klinikum Rechts der Isar (TUM), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"ref_1","first-page":"145","article-title":"A moderate thermal dose is sufficient for effective free and TSL based thermochemotherapy","volume":"163\u2013164","author":"Franckena","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Crezee, J., Franken, N.A.P., and Oei, A.L. (2021). Hyperthermia-based anti-cancer treatments. Cancers, 13.","DOI":"10.3390\/cancers13061240"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1080\/02656736.2022.2113826","article-title":"Biological modeling in thermoradiotherapy: Present status and ongoing developments toward routine clinical use","volume":"39","author":"Kok","year":"2022","journal-title":"Int. J. Hyperth."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1080\/02656736.2022.2067596","article-title":"Strong correlation between specific heat capacity and water content in human tissues suggests preferred heat deposition in malignant tumors upon electromagnetic irradiation","volume":"39","author":"Vaupel","year":"2022","journal-title":"Int. J. Hyperth."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2000267","DOI":"10.1002\/adtp.202000267","article-title":"The effects of localized heat on the hallmarks of cancer","volume":"4","author":"Hannon","year":"2021","journal-title":"Adv. Therap."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/02656730310001619514","article-title":"Physiological mechanisms underlying heat-induced radiosensitization","volume":"20","author":"Vujaskovic","year":"2004","journal-title":"Int. J. Hyperth."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1080\/02656730500204487","article-title":"Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment","volume":"21","author":"Song","year":"2005","journal-title":"Int. J. Hyperth."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/02656730600689066","article-title":"Tissue physiology and the response to heat","volume":"22","author":"Horsman","year":"2006","journal-title":"Int. J. Hyperth."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3109\/02656731003596259","article-title":"Pathophysiological and vascular characteristics of tumours and their importance for hyperthermia: Heterogeneity is the key issue","volume":"26","author":"Vaupel","year":"2010","journal-title":"Int. J. Hyperth."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"518","DOI":"10.3109\/02656736.2012.699134","article-title":"Blood flow and associated pathophysiology of uterine cervix cancers: Characterisation and relevance for localised hyperthermia","volume":"28","author":"Vaupel","year":"2012","journal-title":"Int. J. Hyperth."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3109\/02656736.2015.1091093","article-title":"The future of biology in driving the field of hyperthermia","volume":"32","author":"Dewhirst","year":"2016","journal-title":"Int. J. Hyperth."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dewhirst, M.W., Oleson, J.R., Kirkpatrick, J., and Secomb, T.W. (2022). Accurate three-dimensional thermal dosimetry and assessment of physiologic response are essential for optimizing thermoradiotherapy. Cancers, 14.","DOI":"10.3390\/cancers14071701"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.addr.2020.01.003","article-title":"Molecular and biological rationale of hyperthermia as radio- and chemosensitizer","volume":"163\u2013164","author":"Oei","year":"2020","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.3389\/fonc.2020.01690","article-title":"Quo vadis oncological hyperthermia (2020)?","volume":"10","author":"Lee","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Notter, M., Thomsen, A.R., Nitsche, M., Hermann, R.M., Wolff, H.A., Habl, G., Munch, K., Grosu, A.L., and Vaupel, P. (2020). Combined wIRA-hyperthermia and hypofractionated re-irradiation in the treatment of locally recurrent breast cancer: Evaluation of therapeutic outcome based on a novel size classification. Cancers, 12.","DOI":"10.3390\/cancers12030606"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Notter, M., Stutz, E., Thomsen, A.R., and Vaupel, P. (2021). Radiation-associated angiosarcoma of the breast and chest wall treated with thermography-controlled, contactless wIRA-hyperthermia and hypofractionated re-irradiation. Cancers, 13.","DOI":"10.3390\/cancers13153911"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3109\/02656736.2015.1099746","article-title":"Hyperthermia and radiotherapy in the management of head and neck cancers: A systematic review and meta-analysis","volume":"32","author":"Datta","year":"2016","journal-title":"Int. J. Hyperth."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.ijrobp.2015.12.361","article-title":"Hyperthermia and radiation therapy in locoregional recurrent breast cancers: A systematic review and meta-analysis","volume":"94","author":"Datta","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3389\/fonc.2017.00132","article-title":"Integrating hyperthermia into modern radiation oncology: What evidence is necessary?","volume":"7","author":"Peeken","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-3-030-34461-0_18","article-title":"Hypoxia compromises anti-cancer immune responses","volume":"1232","author":"Multhoff","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3109\/02656730903413375","article-title":"Tumour infiltrating host cells and their significance for hyperthermia","volume":"26","author":"Muthana","year":"2010","journal-title":"Int. J. Hyperth."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1101206","DOI":"10.1080\/2162402X.2015.1101206","article-title":"The dual role of NK cells in antitumor reactions triggered by ionizing radiation in combination with hyperthermia","volume":"5","author":"Finkel","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00262-019-02460-3","article-title":"Immune biological rationales for the design of combined radio- and immunotherapies","volume":"69","author":"Hader","year":"2020","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/02656736.2015.1106011","article-title":"Combination of ionising radiation with hyperthermia increases the immunogenic potential of b16-f10 melanoma cells in vitro and in vivo","volume":"32","author":"Werthmoller","year":"2016","journal-title":"Int. J. Hyperth."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.radonc.2011.05.056","article-title":"Radiation combined with hyperthermia induces HSP 70-dependent maturation of dendritic cells and release of pro-inflammatory cytokines by dendritic cells and macrophages","volume":"101","author":"Schildkopf","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.addr.2020.07.007","article-title":"Hyperthermia can alter tumor physiology and improve chemo- and radio-therapy efficacy","volume":"163\u2013164","author":"Dunne","year":"2020","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1007\/s00723-021-01383-6","article-title":"Oxygenation status of malignant tumors vs. normal tissues: Critical evaluation and updated data source based on direct measurements with pO2 microsensors","volume":"52","author":"Vaupel","year":"2021","journal-title":"Appl. Magn. Reson."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1088\/0967-3334\/24\/2\/370","article-title":"Tumour tissue monitoring during photodynamic and hyperthermic treatment using bioimpedance spectroscopy","volume":"24","author":"Gersing","year":"2003","journal-title":"Physiol. Meas."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.semradonc.2004.04.008","article-title":"Tumor microenvironmental physiology and its implications for radiation oncology","volume":"14","author":"Vaupel","year":"2004","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3109\/02656736.2016.1167259","article-title":"Enhanced tumour perfusion following treatment with water-filtered IR-A radiation to the thorax in a patient with head and neck cancer","volume":"32","author":"Rich","year":"2016","journal-title":"Int. J. Hyperth."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Molls, M., Vaupel, P., Nieder, C., and Anscher, M.S. (2009). Pathophysiology of solid tumors: In The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies, Springer.","DOI":"10.1007\/978-3-540-74386-6"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Osinsky, S., Friess, H., and Vaupel, P. (2011). Tumor Hypoxia in the Clinical Setting, Adacemperiodyka.","DOI":"10.15407\/akademperiodyka.169.272"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gautherie, M. (1990). Biological Basis of Oncologic Thermotherapy, Springer.","DOI":"10.1007\/978-3-642-74939-1"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Baronzio, G.F., and Hager, E.D. (2006). Hyperthermia in Cancer Treatment: A Primer, Springer Science.","DOI":"10.1007\/978-0-387-33441-7"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/978-1-4419-1241-1_57","article-title":"No sustained improvement in tumor oxygenation after localized mild hyperthermia","volume":"662","author":"Kelleher","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3109\/02656730903479855","article-title":"The effect of mild temperature hyperthermia on tumour hypoxia and blood perfusion: Relevance for radiotherapy, vascular targeting and imaging","volume":"26","author":"Sun","year":"2010","journal-title":"Int. J. Hyperth."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3109\/02656739609027682","article-title":"Divergent changes of flow through individual blood vessels upon localized heating","volume":"12","author":"Rhee","year":"1996","journal-title":"Int. J. Hyperth."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-1-4615-0075-9_23","article-title":"Microcirculatory function, tissue oxygenation, microregional redox status and ATP distribution in tumors upon localized infrared-A -hyperthermia at 42 \u00b0C","volume":"530","author":"Thews","year":"2003","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_39","unstructured":"Teicher, B.A. (1993). Drug Resistance in Oncology, Marcel Dekker."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/bjc.1998.442","article-title":"Localized hypothermia: Impact on oxygenation, microregional perfusion, metabolic and bioenergetic status of subcutaneous rat tumours","volume":"78","author":"Kelleher","year":"1998","journal-title":"Br. J. Cancer."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/BF02326781","article-title":"Investigations on the influence of thrombocytes and temperature on the whole blood- and plasma-viscosity as comparative measurements between a capillary- and a plate-cone-viscosimeter (author\u2019s transl)","volume":"31","author":"Leonhardt","year":"1975","journal-title":"Experientia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1113\/EP085504","article-title":"Increases in core temperature counterbalance effects of haemoconcentration on blood viscosity during prolonged exercise in the heat","volume":"101","author":"Buono","year":"2016","journal-title":"Exp. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s10544-019-0426-5","article-title":"Microfluidics-based device for the measurement of blood viscosity and its modeling based on shear rate, temperature, and heparin concentration","volume":"21","author":"Khnouf","year":"2019","journal-title":"Biomed. Microdevices"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF00413173","article-title":"Circulatory and metabolic responses of malignant tumors during localized hyperthermia","volume":"98","author":"Vaupel","year":"1980","journal-title":"J. Cancer. Res. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R193","DOI":"10.1007\/s004240000061","article-title":"Effect of pH on red blood cell deformability","volume":"440","author":"Kuzman","year":"2000","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1158\/0008-5472.CAN-10-4482","article-title":"Mild elevation of body temperature reduces tumor interstitial fluid pressure and hypoxia and enhances efficacy of radiotherapy in murine tumor models","volume":"71","author":"Sen","year":"2011","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1158\/0008-5472.CAN-13-3696","article-title":"Releasing pressure in tumors: What do we know so far and where do we go from here? A review","volume":"74","author":"Ariffin","year":"2014","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3389\/fonc.2015.00165","article-title":"Overview of methods for overcoming hindrance to drug delivery to tumors, with special attention to tumor interstitial fluid","volume":"5","author":"Baronzio","year":"2015","journal-title":"Front. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.ijrobp.2011.02.049","article-title":"Acute versus chronic hypoxia: Why a simplified classification is simply not enough","volume":"80","author":"Bayer","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20477","DOI":"10.1073\/pnas.1006646107","article-title":"NADPH oxidase-mediated reactive oxygen species production activates hypoxia-inducible factor-1 (HIF-1) via the ERK pathway after hyperthermia treatment","volume":"107","author":"Moon","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13046-016-0399-7","article-title":"Hyperthermia induced HIF-1\u03b1 expression of lung cancer through akt and erk signaling pathways","volume":"35","author":"Wan","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Osinsky, S., Friess, H., and Vaupel, P. (2011). Tumor Hypoxia in the Clinical Setting, Academperiodyka.","DOI":"10.15407\/akademperiodyka.169.272"},{"key":"ref_53","first-page":"6449","article-title":"Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review","volume":"49","author":"Vaupel","year":"1989","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Vaupel, P., and Piazena, H. (2023). Hyperhydration of cancers: A characteristic biophysical trait strongly increasing O2, CO2, glucose and lactate diffusivities, and improving thermophysical properties of solid malignancies. Adv. Exp. Med. Biol., in press.","DOI":"10.1007\/978-3-031-42003-0_22"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/BF00582204","article-title":"Oxygen diffusivity in tumor tissue (DS-carcinosarcoma) under temperature conditions within the range of 20\u201340 \u00b0C","volume":"372","author":"Grote","year":"1977","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_56","first-page":"H1825","article-title":"Temperature dependence of oxygen diffusion and consumption in mammalian striated muscle","volume":"264","author":"Bentley","year":"1993","journal-title":"Am. J. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1113\/JP278810","article-title":"Revisiting the Warburg effect: Historical dogma versus current understanding","volume":"599","author":"Vaupel","year":"2021","journal-title":"J. Physiol."},{"key":"ref_58","first-page":"628","article-title":"Microcirculation modifications by localized microwave hyperthermia and hematoporphyrin phototherapy","volume":"20","author":"Bicher","year":"1981","journal-title":"Bibl. Anat."},{"key":"ref_59","first-page":"168","article-title":"Impact of localized microwave hyperthermia on the pH-distribution in malignant tumors (author\u2019s transl)","volume":"158","author":"Vaupel","year":"1982","journal-title":"Strahlentherapie"},{"key":"ref_60","first-page":"73","article-title":"Blood flow, tissue oxygenation, and pH-distribution in malignant tumors upon localized hyperthermia. Basic pathophysiological aspects and the role of various thermal doses","volume":"159","author":"Vaupel","year":"1983","journal-title":"Strahlentherapie"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-3-642-82955-0_3","article-title":"Physiological effects of hyperthermia","volume":"104","author":"Vaupel","year":"1987","journal-title":"Recent Results Cancer Res."},{"key":"ref_62","first-page":"217","article-title":"Effect of localizes microwave hyperthermia on physiological responses","volume":"61","author":"Bicher","year":"1980","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_63","unstructured":"Altman, P.L., and Dittmar, D.S. (1971). Biological Data Book, Federation of American Societies for Experimental Biology. [2nd ed.]."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1007\/s10439-010-9948-y","article-title":"Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels","volume":"38","author":"Dash","year":"2010","journal-title":"Ann. Biomed. Eng."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"808025","DOI":"10.3389\/fmed.2021.808025","article-title":"Effects of carbon dioxide and temperature on the oxygen-hemoglobin dissociation curve of human blood: Implications for avalanche victims","volume":"8","author":"Woyke","year":"2021","journal-title":"Front. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/jnci\/60.4.835","article-title":"Relationship between temperature and blood supply or consumption of oxygen and glucose by rat mammary carcinomas","volume":"60","author":"Gullino","year":"1978","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Vaupel, P. (2022). Water-Filtered Infrared A (wIRA) Irradiation, Springer Nature.","DOI":"10.1007\/978-3-030-92880-3"},{"key":"ref_68","first-page":"207","article-title":"Impact of localized hyperthermia on the cellular microenvironment in solid tumors","volume":"61","author":"Vaupel","year":"1982","journal-title":"Natl. Cancer Inst. Monogr."},{"key":"ref_69","unstructured":"Overgaard, J. (1984). Hyperthermic Oncology, Springer."},{"key":"ref_70","first-page":"S217","article-title":"Tumour pO2 can be increased markedly by mild hyperthermia","volume":"27","author":"Iwata","year":"1996","journal-title":"Br. J. Cancer Suppl."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S0360-3016(98)00516-1","article-title":"Changes in oxygenation status and blood flow in a rat tumor model by mild temperature hyperthermia","volume":"43","author":"Shakil","year":"1999","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1667\/0033-7587(2001)155[0515:IOTOBM]2.0.CO;2","article-title":"Improvement of tumor oxygenation by mild hyperthermia","volume":"155","author":"Song","year":"2001","journal-title":"Radiat. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1038\/sj.bjc.6601457","article-title":"Combined hyperthermia and chlorophyll-based photodynamic therapy: Tumour growth and metabolic microenvironment","volume":"89","author":"Kelleher","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3109\/02656730903453546","article-title":"Mild temperature hyperthermia and radiation therapy: Role of tumour vascular thermotolerance and relevant physiological factors","volume":"26","author":"Griffin","year":"2010","journal-title":"Int. J. Hyperth."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3109\/02656739709012378","article-title":"Can mild hyperthermia improve tumour oxygenation?","volume":"13","author":"Horsman","year":"1997","journal-title":"Int. J. Hyperth."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0360-3016(99)00362-4","article-title":"Temperature-dependent changes in physiologic parameters of spontaneous canine soft tissue sarcomas after combined radiotherapy and hyperthermia treatment","volume":"46","author":"Vujaskovic","year":"2000","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1080\/02656730600836386","article-title":"Changes in tumour oxygenation during fractionated hyperthermia and radiation therapy in spontaneous canine sarcomas","volume":"22","author":"Thrall","year":"2006","journal-title":"Int. J. Hyperth."},{"key":"ref_78","first-page":"5347","article-title":"Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas","volume":"56","author":"Brizel","year":"1996","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1080\/0265673031000121517","article-title":"Ultrasound guided pO2 measurement of breast cancer reoxygenation after neoadjuvant chemotherapy and hyperthermia treatment","volume":"19","author":"Vujaskovic","year":"2003","journal-title":"Int. J. Hyperth."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1158\/1078-0432.CCR-04-0133","article-title":"Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer","volume":"10","author":"Jones","year":"2004","journal-title":"Clin. Cancer. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1159\/000224991","article-title":"pO2 distribution in tumor tissue of DS-carcinosarcoma","volume":"30","author":"Vaupel","year":"1974","journal-title":"Oncology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1080\/02656736.2016.1235731","article-title":"Hypofractionated re-irradiation of large-sized recurrent breast cancer with thermography-controlled, contact-free water-filtered infra-red-A hyperthermia: A retrospective study of 73 patients","volume":"33","author":"Notter","year":"2017","journal-title":"Int. J. Hyperth."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/5\/1394\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:39:45Z","timestamp":1760121585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/5\/1394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,22]]},"references-count":82,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cancers15051394"],"URL":"https:\/\/doi.org\/10.3390\/cancers15051394","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,22]]}}}