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Iatrogenic influence on prognosis of radiation-induced contrast enhancements in patients with glioma WHO 1–3 following photon and proton radiotherapy

  • Tanja Eichkorn
    Correspondence
    Corresponding author at: Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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  • Jonathan W. Lischalk
    Affiliations
    Department of Radiation Oncology, Perlmutter Cancer Center at New York University Langone Health at Long Island, New York, NY, USA
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  • Elisabetta Sandrini
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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  • Eva Meixner
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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  • Sebastian Regnery
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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  • Thomas Held
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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  • Julia Bauer
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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  • Emanuel Bahn
    Affiliations
    Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Semi Harrabi
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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  • Juliane Hörner-Rieber
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    German Cancer Consortium (DKTK), Partner Site Heidelberg, Germany
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  • Klaus Herfarth
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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  • Jürgen Debus
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    German Cancer Consortium (DKTK), Partner Site Heidelberg, Germany
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  • Laila König
    Affiliations
    Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany

    Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany

    National Center for Tumor diseases (NCT), Heidelberg, Germany

    Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
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      Highlights

      • Misinterpretation of radiation-induced contrast enhancement (RICE) is frequent with a rate of 39% that were misinterpreted as tumor progression at initial RICE occurrence.
      • A tumor-specific therapy including chemotherapy or re-irradiation led to a RICE size progression in 86% and 92% of cases, respectively and RICE symptom progression in 57% and 65% of cases, respectively.
      • A RICE-specific therapy such as corticosteroids or Bevacizumab for larger or symptomatic RICE led to a RICE size regression in 81% of cases with symptom stability or regression in 62% of cases.
      • For RICE, correct diagnosis and treatment decisions are challenging and critical and should be made interdisciplinarily.

      Abstract

      Background and purpose

      Radiation-induced contrast enhancements (RICE) are a common side effect following radiotherapy for glioma, but both diagnosis and handling are challenging. Due to the potential risks associated with RICE and its challenges in differentiating RICE from tumor progression, it is critical to better understand how RICE prognosis depends on iatrogenic influence.

      Materials and methods

      We identified 99 patients diagnosed with RICE who were previously treated with either photon or proton therapy for World Health Organization (WHO) grade 1–3 primary gliomas. Post-treatment brain MRI-based volumetric analysis and clinical data collection was performed at multiple time points.

      Results

      The most common histologic subtypes were astrocytoma (50%) and oligodendroglioma (46%). In 67%, it was graded WHO grade 2 and in 86% an IDH mutation was present. RICE first occurred after 16 months (range: 1–160) in median. At initial RICE occurrence, 39% were misinterpreted as tumor progression. A tumor-specific therapy including chemotherapy or re-irradiation led to a RICE size progression in 86% and 92% of cases, respectively and RICE symptom progression in 57% and 65% of cases, respectively. A RICE-specific therapy such as corticosteroids or Bevacizumab for larger or symptomatic RICE led to a RICE size regression in 81% of cases with symptom stability or regression in 62% of cases.

      Conclusions

      While with chemotherapy and re-irradiation a RICE progression was frequently observed, anti-edematous or anti-VEGF treatment frequently went along with a RICE regression. For RICE, correct diagnosis and treatment decisions are challenging and critical and should be made interdisciplinarily.

      Keywords

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