Dosimetric predictors of toxicity in a randomized study of short-course vs conventional radiotherapy for glioblastoma

Published:October 20, 2022DOI:


      • Critical structure constraints used in our randomized controlled trial of short-course versus conventional radiotherapy for patients with glioblastoma were appropriate for limiting grade 2 or higher toxicities.
      • Higher left-hippocampal mean doses were the most predictive for neuro-cognitive decline post-radiotherapy.
      • Routine contouring and use of dose constraints for the hippocampus is recommended.
      • Our left hippocampus sparing treatment model may help minimize neuro-cognitive decline in patients with glioblastoma treated with radiotherapy.



      There is no consensus on appropriate organ at risk (OAR) constraints for short-course radiotherapy for patients with glioblastoma. Using dosimetry and prospectively-collected toxicity data from a trial of short-course radiotherapy for glioblastoma, this study aims to empirically examine the OAR constraints, with particular attention to left hippocampus dosimetry and impact on neuro-cognitive decline.

      Methods and Materials

      Data was taken from a randomized control trial of 133 adults (age 18–70 years; ECOG performance score 0–2) with newly diagnosed glioblastoma treated with 60 Gy in 30 (conventional arm) versus 20 (short-course arm) fractions of adjuvant chemoradiotherapy ( Identifier: NCT02206230). The delivered plan’s dosimetry to the OARs was correlated to prospective-collected toxicity and Mini-Mental State Examination (MMSE) data.


      Toxicity events were not significantly increased in the short-course arm versus the conventional arm. Across all OARs, delivered radiation doses within protocol-allowable maximum doses correlated with lack of grade ≥ 2 toxicities in both arms (p < 0.001), while patients with OAR doses at or above protocol limits correlated with increased grade ≥ 2 toxicities across all examined OARs in both arms (p-values 0.063–0.250). Mean left hippocampus dose was significantly associated with post-radiotherapy decline in MMSE scores (p = 0.005), while the right hippocampus mean dose did not reach statistical significance (p = 0.277). Compared to the original clinical plan, RapidPlan left hippocampus sparing model decreased left hippocampus mean dose by 43 % (p < 0.001), without compromising planning target volume coverage.


      In this trial, protocol OAR constraints were appropriate for limiting grade ≥ 2 toxicities in conventional and short-course adjuvant chemoradiotherapy for glioblastoma. Higher left hippocampal mean doses were predictive for neuro-cognitive decline post-radiotherapy. Routine contouring and use of dose constraints to limit hippocampal dose is recommended to minimize neuro-cognitive decline in patients with glioblastoma treated with chemoradiotherapy.



      CTCAE (Common Terminology Criteria for Adverse Events), ECOG (Eastern Cooperative Oncology Group), EQD2 (equivalent dose in 2 Gy per fraction), MCO (Multi-Criteria Optimization), MMSE (Mini-Mental State Examination), OAR (organ at risk), PTV (planning target volume), RT (radiotherapy), RTOG (Radiation Therapy Oncology Group), QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic)
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