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Objective assessment of intraoperative tumor fluorescence reveals biological heterogeneity within glioblastomas: a biometric study

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Abstract

Purpose

Heterogeneity within GBMs and variability of visualized fluorescence combine to confer practical limitations to the technique of optical imaging. A biometric analysis was planned to objectively ascertain and analyse this phenomenon

Methods

25 adult glioblastoma subjects undergoing resection were prospectively accrued. Biopsies were taken from various parts of the tumor and safe peritumoral zones. White light (WL) and visualized fluorescence was subjectively recorded. Corresponding histopathology [coalescent (C) or infiltrating (I) tumor] and protoporphyrin-IX (PPIX) levels were assayed.

Results

WL was very sensitive for detecting tumor. SF was more specific and had high positive predictive value for detecting tumor. WF on the other hand had a poor discriminatory efficacy. Mean PPIX levels were 3.0, 2.01 and 0.16 for SF, WF, and NF respectively. WF had a wide variable range of PPIX levels. Within the coalescent tumor areas, there was a variable distribution of fluorescence (both subjective as well as objective PPIX levels) with only 54% samples showing SF and high PPIX. In seven cases this discordance was noted within the same tumor (biological heterogeneity).

Conclusions

Fluorescence may miss important tumor areas even if objective assessment is used. Histologically similar tumor areas may exhibit contrasting fluorescence properties, a phenomenon which needs further investigation and elucidation of underlying mechanisms which could potentially be manipulated to optimize the utility of fluorescence guidance.

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Acknowledgements

We would like to acknowledge the help provided by our Biostatistician Ms Smruti Mokal from the Clinical Research Secretariat for the analysis and the project coordinator Mr. Deepak Prajapati for the logistic support in conducting the study.

Funding

This study was funded by a grant to the lead author Dr AM from Department of Biotechnology, Government of India (Sanction No.: 6242-P66/RGCB/PMD/DBT/ARVM/2015) as well as DAE CTC (Intramural Grant: IEC/0714/001).

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Authors and Affiliations

  1. Division of Neurosurgery, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National University, 1221, Homi Bhabha Block, Mumbai, India

    Aliasgar Moiyadi, Prakash Shetty & Vikas Singh

  2. Department of Surgical Pathology, Tata Memorial Centre, Homi Bhabha National University, Mumbai, India

    Epari Sridhar

  3. Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Homi Bhabha National University, Mumbai, India

    Vikram Gota & Murari Gurjar

  4. Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India

    Ghantasala Saicharan & Sanjeeva Srivastava

Authors
  1. Aliasgar Moiyadi
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  2. Prakash Shetty
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  4. Vikram Gota
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  6. Ghantasala Saicharan
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  7. Vikas Singh
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  8. Sanjeeva Srivastava
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Correspondence to Aliasgar Moiyadi.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

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. It was approved by the institute review board (IEC Approval: ACTREC IEC No. 139, dated 12th May 2014).

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It was obtained from all individual participants included in the study.

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Moiyadi, A., Shetty, P., Sridhar, E. et al. Objective assessment of intraoperative tumor fluorescence reveals biological heterogeneity within glioblastomas: a biometric study. J Neurooncol 146, 477–488 (2020). https://doi.org/10.1007/s11060-019-03338-1

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  • DOI: https://doi.org/10.1007/s11060-019-03338-1

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