Mei Xionge, Kok H Petra, Rodermond Hans M, van Bochove Gregor G W, Snoek Barbara C, van Leeuwen Caspar M, Franken Nicolaas A P, Ten Hagen Timo L M, Crezee Johannes, Vermeulen Louis, Stalpers Lukas J A, Oei Arlene L
Department of Radiation Oncology, University of Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR), Amsterdam, The Netherlands; Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Department of Radiation Oncology, University of Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands; Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Int J Radiat Oncol Biol Phys. 2024 Mar 1;118(3):817-828. doi: 10.1016/j.ijrobp.2023.09.048. Epub 2023 Oct 10.
Hyperthermia is a potent sensitizer of radiation therapy that improves both tumor control and survival in women with locally advanced cervical cancer (LACC). The optimal sequence and interval between hyperthermia and radiation therapy are still under debate.
We investigated the interval and sequence in vitro in cervical cancer cell lines, patient-derived organoids, and 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.
All 3 approaches confirmed that shortening the interval between hyperthermia and radiation therapy enhanced hyperthermic radiosensitization by 2 to 8 times more DNA double-strand breaks and apoptosis and 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 minutes) to 54% (interval <80 minutes). In vitro and in vivo results showed that the sequence of hyperthermia and radiation therapy did not affect the outcome.
Shortening the interval between hyperthermia and radiation therapy significantly improves treatment outcomes. The sequence of hyperthermia and radiation therapy (before or after) does not seem to matter.
热疗是一种有效的放射治疗增敏剂，可改善局部晚期宫颈癌（LACC）女性的肿瘤控制和生存率。热疗与放射治疗之间的最佳顺序和间隔仍存在争议。
我们在宫颈癌细胞系、患者来源的类器官以及无胸腺裸鼠的SiHa宫颈癌后肢异种移植模型中对间隔和顺序进行了体外研究，并将结果与58例接受热放疗的LACC女性的回顾性结果进行了比较。
所有3种方法均证实，缩短热疗与放射治疗之间的间隔可使热放射增敏作用增强2至8倍，DNA双链断裂和凋亡增加，细胞存活率降低10至100倍，延缓小鼠肿瘤生长，并使LACC女性的5年生存率从22%（间隔≥80分钟）提高到54%（间隔<80分钟）。体外和体内结果表明，热疗和放射治疗的顺序不影响结果。
缩短热疗与放射治疗之间的间隔可显著改善治疗效果。热疗和放射治疗的顺序（之前或之后）似乎无关紧要。
