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

Abstract

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.

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Acknowledgements

This work was supported by the National Institutes of Health (P01 CA118816). We would like to thank Sarah Nelson for her support.

Funding

This study was funded by the National Institutes of Health (P01 CA118816).

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Correspondence to Paula Alcaide-Leon.

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Paula Alcaide Leon, Marisa Lafontaine, Janine M. Lupo, Hideho Okada, Jennifer L. Clark and Javier E. Villanueva-Meyer declares that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Alcaide-Leon, P., Luks, T.L., Lafontaine, M. et al. Treatment-induced lesions in newly diagnosed glioblastoma patients undergoing chemoradiotherapy and heat-shock protein vaccine therapy. J Neurooncol 146, 71–78 (2020). https://doi.org/10.1007/s11060-019-03336-3

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Keywords

  • Glioblastoma
  • Heat-shock proteins
  • Magnetic resonance imaging
  • Chemoradiotherapy
  • Immunotherapy