2. Academic Validation
  3. Radiosensitization by hyperthermia critically depends on the time interval

Radiosensitization by hyperthermia critically depends on the time interval

  • Int J Radiat Oncol Biol Phys. 2023 Oct 9:S0360-3016(23)07970-1. doi: 10.1016/j.ijrobp.2023.09.048.
Xionge Mei 1,  H Petra Kok 2,  Hans M Rodermond 3,  Gregor G W van Bochove 4,  Barbara C Snoek 5,  Caspar M van Leeuwen 6,  Nicolaas A P Franken 7,  Timo L M Ten Hagen 8,  Johannes Crezee 9,  Louis Vermeulen 10,  Lukas J A Stalpers 11,  Arlene L Oei 12
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands;; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: x.mei@amsterdamumc.nl.
  • 2 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: h.p.kok@amsterdamumc.nl.
  • 3 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands;; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: h.rodermond@amsterdamumc.nl.
  • 4 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands;; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: g.g.vanbochove@amsterdamumc.nl.
  • 5 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands;; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: b.snoek2@amsterdamumc.nl.
  • 6 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: c.m.vanleeuwen@amsterdamumc.nl.
  • 7 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands;; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: n.a.franken@amsterdamumc.nl.
  • 8 Precision Medicine in Oncology (PrMiO), Department of Pathology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. Electronic address: t.l.m.tenhagen@erasmusmc.nl.
  • 9 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: h.crezee@amsterdamumc.nl.
  • 10 Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands;; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands; Oncode Institute, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: l.vermeulen@amsterdamumc.nl.
  • 11 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands;; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: l.stalpers@amsterdamumc.nl.
  • 12 Department of Radiation Oncology, Amsterdam UMC, location University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, Netherlands; Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands;; Cancer Center Amsterdam, Cancer Biology and Immunology, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: a.l.oei@amsterdamumc.nl.
PMID: 37820768 DOI: 10.1016/j.ijrobp.2023.09.048
Abstract

Background and purpose: Hyperthermia is a potent sensitizer of radiotherapy that improves both tumor control and survival in women with locally advanced cervical Cancer (LACC). The optimal sequence and interval between hyperthermia and radiotherapy are still under debate.

Experimental design: We investigated the interval and sequence in vitro in cervical Cancer cell lines and patient-derived organoids, in vivo in SiHa cervical Cancer hind leg xenografts in athymic nude mice and compared the results with retrospective results from 58 women with LACC treated with thermoradiotherapy.

Results: All three approaches confirmed that shortening the interval between hyperthermia and radiotherapy enhanced hyperthermic radiosensitization by 2 to 8 times more DNA double-strand breaks and Apoptosis, 10 to 100 times lower cell survival, delayed tumor growth in mice, and increased the 5-year survival rate of women with LACC from 22% (interval ≥ 80 min) to 54% (interval <80 min). In vitro and in vivo results showed that the sequence of hyperthermia and radiotherapy did not affect the outcome.

Conclusions: Shortening the interval between hyperthermia and radiotherapy significantly improves treatment outcomes. The sequence of hyperthermia and radiotherapy (before or after) does not seem to matter.

Keywords

Cervical cancer; Hyperthermia; In vivo mouse model; Patient-derived organoids; Radiotherapy; Time interval.

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