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Volume effects of radiotherapy on the risk of second primary cancers: A systematic review of clinical and epidemiological studies

  • Neige Journy
    Correspondence
    Corresponding author at: INSERM U1018, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, 39 rue Camille Desmoulins, 94800 Villejuif, France.
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Imène Mansouri
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Rodrigue S. Allodji
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Charlotte Demoor-Goldschmidt
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France

    Department of Pediatric Onco-hematology, CHU Angers, Angers, France
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  • Debiche Ghazi
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Nadia Haddy
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Carole Rubino
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Cristina Veres
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Wael Salem Zrafi
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Sofia Rivera
    Affiliations
    Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France

    INSERM 1030 Molecular Radiotherapy, Villejuif, France

    Paris-Saclay University, Paris-Sud Medical School, Le Kremlin-Bicêtre, France
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  • Ibrahima Diallo
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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  • Florent De Vathaire
    Affiliations
    INSERM U1018, Paris-Sud XI University, Paris-Saclay University, Centre for Research in Epidemiology and Population Health (CESP), “Cancer & Radiations” Group, Gustave Roussy Cancer Campus, Villejuif, France
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Published:October 10, 2018DOI:https://doi.org/10.1016/j.radonc.2018.09.017

      Highlights

      • SPC risks increased with extended fields for Hodgkin lymphoma or childhood cancers.
      • No included studies estimated normal tissue dose–volume distribution.
      • Current clinical evidence on possible volume effects on SPC risks is very limited.
      • Biological mechanisms underlying volume effects on SPC risks are plausible.

      Abstract

      As modern radiotherapy, including intensity-modulated techniques, is associated with high dose gradients to normal tissues and large low-to-moderate dose volumes, the assessment of second primary cancer (SPC) risks requires quantification of dose–volume effects. We conducted a systematic review of clinical and epidemiological studies investigating the effect of the irradiated volume or dose–volume distribution to the remaining volume at risk (RVR) on SPC incidence. We identified eighteen studies comparing SPC risks according to the irradiated volume (i.e., in most studies, the size or number of fields used), and four studies reporting risk estimates according to the dose distribution to the RVR (after whole-body dose reconstruction). An increased risk of SPCs (mainly breast and lung cancers) with extended radiotherapy was observed among patients treated for Hodgkin lymphoma or childhood cancers. However, normal tissue dose distribution was not estimated, limiting the interpretation of those results in terms of volume effects on organs at risk. Studies considering whole-body exposures quantified dose–response relationships for point dose estimates, without accounting for dose–volume distributions. Therefore, they disregarded possible tissue effects (e.g. bystander and abscopal effects, stem cell repopulation) which may play a role in the induction of SPCs. Currently, there is no clinical or epidemiological information about a possible role of high dose gradients in surrounding organs, or increasing volumes of distant tissues exposed to low doses, in the risk of SPCs. Opportunities for future research nevertheless now exist, since methods and tools for estimating individual whole-body dose–volume distributions in large patient populations have been developed.

      Keywords

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