title: Rationale of hyperthermia for radio(chemo)therapy and immune responses in patients with bladder cancer: Biological concepts, clinical data, interdisciplinary treatment decisions and biological tumour imaging.
abstract: Bladder cancer, the most common tumour of the urinary tract, ranks fifth among all tumour entities. While local treatment or intravesical instillation of bacillus Calmette-Guerin (BCG) provides a treatment option for non-muscle invasive bladder cancer of low grade, surgery or radio(chemo)therapy (RT) are frequently applied in high grade tumours. It remains a matter of debate whether surgery or RT is superior with respect to clinical outcome and quality of life. Surgical resection of bladder cancer can be limited by acute side effects, whereas, RT, which offers a non-invasive treatment option with organ- and functional conservation, can cause long-term side effects. Bladder toxicity by RT mainly depends on the total irradiation dose, fraction size and tumour volume. Therefore, novel approaches are needed to improve clinical outcome. Local tumour hyperthermia is currently used either as an ablation therapy or in combination with RT to enhance anti-tumour effects. In combination with RT an increase of the temperature in the bladder stimulates the local blood flow and as a result can improve the oxygenation state of the tumour, which in turn enhances radiation-induced DNA damage and drug toxicity. Hyperthermia at high temperatures can also directly kill cells, particularly in tumour areas which are poorly perfused, hypoxic or have a low tissue pH. This review summarises current knowledge relating to the role of hyperthermia in RT to treat bladder cancer, the induction and manifestation of immunological responses induced by hyperthermia, and the utilisation of the stress proteins as tumour-specific targets for tumour detection and monitoring of therapeutic outcome.
authors.affiliation: a Department of Radiation Oncology , Technische Universität München, Klinikum rechts der Isar , Munich ;|b Department of Innovative Radiation Oncology, Department of Radiation Sciences , Helmholtz Zentrum München , Neuherberg , Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
authors.affiliation: a Department of Radiation Oncology , Technische Universität München, Klinikum rechts der Isar , Munich ;
authors.forename: Gregor
authors.initials: G
authors.lastname: Habl
authors.affiliation: a Department of Radiation Oncology , Technische Universität München, Klinikum rechts der Isar , Munich ;|b Department of Innovative Radiation Oncology, Department of Radiation Sciences , Helmholtz Zentrum München , Neuherberg , Germany.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D059248:Chemoradiotherapy; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced; D007113:Immunity, Innate; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins
keywords: Adaptive immunity; cytotoxicity; heat shock proteins; hyperthermia; innate immunity; molecular imaging