Treatment-induced lesions in newly diagnosed glioblastoma patients undergoing chemoradiotherapy and heat-shock protein vaccine therapy

J Neurooncol. 2020 Jan;146(1):71-78. doi: 10.1007/s11060-019-03336-3. Epub 2019 Nov 14.


Objectives: Treatment-induced lesions represent a great challenge in neuro-oncology. The aims of this study were (i) to characterize treatment induced lesions in glioblastoma patients treated with chemoradiotherapy and heat-shock protein (HSP) vaccine and (ii) to evaluate the diagnostic accuracy of diffusion weighted imaging for differentiation between treatment-induced lesions and tumor progression.

Methods: Twenty-seven patients with newly diagnosed glioblastoma treated with HSP vaccine and chemoradiotherapy were included. Serial magnetic resonance imaging evaluation was performed to detect treatment-induced lesions and assess their growth. Quantitative analysis of the apparent diffusion coefficient (ADC) was performed to discriminate treatment-induced lesions from tumor progression. Mann-Whitney U-test and receiver operating characteristic (ROC) curves were used for analysis.

Results: Thirty-three percent of patients developed treatment-induced lesions. Five treatment-related lesions appeared between end of radiotherapy and the first vaccine administration; 4 lesions within the first 4 months from vaccine initiation and 1 at 3.5 years. Three patients with pathology proven treatment-induced lesions showed a biphasic growth pattern progressed shortly after. ADC ratio between the peripheral enhancing rim and central necrosis showed an accuracy of 0.84 (95% CI 0.63-1) for differentiation between progression and treatment-induced lesions.

Conclusion: Our findings do not support the iRANO recommendation of a 6-month time window in which progressive disease should not be declared after immunotherapy initiation. A biphasic growth pattern of pathologically proven treatment-induced lesions was associated with a dismal prognosis. The presence of lower ADC values in the central necrotic portion of the lesions compared to the enhancing rim shows high specificity for detection of treatment-induced lesions.

Keywords: Chemoradiotherapy; Glioblastoma; Heat-shock proteins; Immunotherapy; Magnetic resonance imaging.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy
  • Chemoradiotherapy / adverse effects*
  • Combined Modality Therapy
  • Diffusion Magnetic Resonance Imaging / methods*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glioblastoma / pathology*
  • Glioblastoma / therapy
  • Heat-Shock Proteins / immunology*
  • Humans
  • Immunotherapy, Active / adverse effects*
  • Male
  • Middle Aged
  • Necrosis
  • Neoplasms, Second Primary / etiology
  • Neoplasms, Second Primary / pathology*
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • Survival Rate


  • Heat-Shock Proteins