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Commentary on the article: Sørensen BS et al., Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model

      FLASH radiotherapy, in which radiation doses are delivered with ultrahigh dose rate, receives increasing attention, with the numbers of publications exponentially increasing since 2019. So far, the majority of the studies have investigated the FLASH normal tissue sparing effect. However, a solid biological [
      • Friedl A.A.
      • Prise K.M.
      • Butterworth K.T.
      • Montay-Gruel P.
      • Favaudon V.
      Radiobiology of the FLASH effect.
      ] and physical [
      • Verhaegen F.
      • Wanders R.G.
      • Wolfs C.
      • Eekers D.
      Considerations for shoot-through FLASH proton therapy.
      ] explanation is currently lacking. Furthermore, FLASH radiotherapy seems to have isotoxic effects on tumors, although based only on tumor regrowth and mouse survival data. Sørensen et al, investigated the effects of FLASH radiotherapy in C3H mouse mammary carcinoma bearing CDF1 mice, with tumor efficacy and normal tissue sparing as read-outs [
      • Sorensen B.S.
      • Sitarz M.K.
      • Ankjaergaard C.
      • Johansen J.G.
      • Andersen C.E.
      • Kanouta E.
      • et al.
      Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model.
      ]. For the first time, the local tumor control assay as well as full dose–response curves were applied as endpoint enabling a proper comparison between FLASH and conventional dose rate effects. Results indicated similar effects on local tumor control, while preferential sparing of healthy tissue using FLASH radiotherapy [
      • Sorensen B.S.
      • Sitarz M.K.
      • Ankjaergaard C.
      • Johansen J.G.
      • Andersen C.E.
      • Kanouta E.
      • et al.
      Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model.
      ], essentially confirming previous studies [
      • Friedl A.A.
      • Prise K.M.
      • Butterworth K.T.
      • Montay-Gruel P.
      • Favaudon V.
      Radiobiology of the FLASH effect.
      ,
      • Wilson J.D.
      • Hammond E.M.
      • Higgins G.S.
      • Petersson K.
      Ultra-high dose rate (FLASH) radiotherapy: silver bullet or fool's gold?.
      ], but using clinically relevant endpoints [
      • Zips D.
      Tumour growth and response to radiation.
      ]. The study has also been awarded as best abstract within the radiobiology track at ESTRO2022.
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      Linked Article

      • Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model
        Radiotherapy and OncologyVol. 175
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          Radiotherapy (RT) is an important part of treatment in clinical cancer therapy. A key challenge in RT is to maximize the therapeutic ratio; the balance between cure and toxicity of treatment, by increasing the radiation effect in the tumor, while minimizing damage to surrounding healthy tissue. FLASH radiotherapy, in which the radiation dose is delivered with ultrahigh dose rate, above 40 Gy/s, has received a lot of attention, since it was demonstrated to induce less damage to normal tissue relative to conventional dose rates, while the effect in the tumor was unaltered [1-3].
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