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Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults

Abstract

Target population

These recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM).

Question (Q1)

In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?

Recommendation

Level III: Adult patients with pGBM might derive benefit in treatment with TMZ, especially those who progress after more than 5 months of TMZ-treatment free interval.

Level III: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohyperthermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy.

There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits.

Question (Q2)

In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?

Recommendation

Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status.

There is insufficient evidence to compare fotemustine to other nitrosoureas.

There is insufficient evidence to make a recommendation about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen.

Question (Q3)

In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?

Recommendation

Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM.

Level III: Other cytotoxic therapies like perillyl acohol or ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy.

Question (Q4)

In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?

Recommendation

Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM.

There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM.

Question (Q5)

In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?

Recommendation

Level III: Oncolytic virotherapy is not suggested in patients with pGBM.

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Fig. 1

Data availability

All authors have ensured all data and materials as well as software applications or custom code supports their published claims and comply with field standards.

Abbreviations

OS:

Overall survival

PFS:

Progression-free survival

PFS6:

6 Month progression-free survival

PR:

Partial Response

CR:

Complete response

SD:

Stable disease

GBM:

Glioblastoma multiforme

TMZ:

Temozolomide

NU:

Nitrosourea

ORR:

Objective response rate

TFI:

Treatment free interval

BBC:

Bevacizumab-based chemotherapy

Bev:

Bevacizumab

TCCC:

6-Thioguanine, lomustine, capecitabine, celecoxib

TBI:

TMZ, Bev, irinotecan

TTF:

Tumor Treating Fields

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Acknowledgements

The guidelines task force would like to acknowledge the Congress of Neurological Surgeons Guidelines Committee for their contributions throughout the development of the guideline, and the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Review Committee for their review, comments, and suggestions throughout peer review, as well as the contributions of Trish Rehring, MPH, CHES, Senior Manager of Clinical Practice Guidelines for the CNS, and Mary Bodach, MLIS, from the Congress of Neurological Surgeons Guidelines Office for organizational assistance and reference librarian services, respectively as well as Jeremy Kupsco, PhD, Informationist, Emory University, for their valuable input as Medical Research Librarians. Throughout the review process, the reviewers and authors were blinded from one another. At this time the guidelines task force would like to acknowledge the following individual peer reviewers for their contributions: John O’Toole, MD, Brian Howard, MD, Jamie Van Gompel, MD, Howard Silberstein, MD, Navid Redjal, MD and Shawn Hervey-Jumper, MD.

Disclaimer of liability

This clinical systematic review and evidence-based guideline was developed by a multidisciplinary physician volunteer task force and serves as an educational tool designed to provide an accurate review of the subject matter covered. These guidelines are disseminated with the understanding that the recommendations by the authors and consultants who have collaborated in their development are not meant to replace the individualized care and treatment advice from a patient's physician(s). If medical advice or assistance is required, the services of a competent physician should be sought. The proposals contained in these guidelines may not be suitable for use in all circumstances. The choice to implement any particular recommendation contained in these guidelines must be made by a managing physician in light of the situation in each particular patient and on the basis of existing resources.

Funding

These guidelines were funded exclusively by the Congress of Neurological Surgery and the Joint Section on Tumors of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, which received no funding from any outside commercial sources to support the development of this document.

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All authors listed on this publication agree with the content included and give explicit consent to the submission of this publication. The authors obtained consent from the responsible authorities at the institute/organization where the work has been carried out, before the work was submitted. All authors whose names appear on the submission: (1) made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work; (2) drafted the work or revised it critically for important intellectual content.

Corresponding author

Correspondence to Isabelle M. Germano.

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All Guideline Task Force members were required to disclose all potential COIs prior to beginning work on the guideline, using the COI disclosure form of the AANS/CNS Joint Guidelines Review Committee. The CNS Guidelines Committee and Guideline Task Force Chair reviewed the disclosures and either approved or disapproved the nomination and participation on the task force. The CNS Guidelines Committee and Guideline Task Force Chair may approve nominations of task force members with possible conflicts and restrict the writing, reviewing, and/or voting privileges of that person to topics that are unrelated to the possible COIs. The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this series of articles.

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Germano, I.M., Ziu, M., Wen, P. et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults. J Neurooncol 158, 225–253 (2022). https://doi.org/10.1007/s11060-021-03900-w

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Keywords

  • Chemotherapy
  • Fotemustine
  • GBM
  • Oncolytic virus
  • Progressive
  • Temozolomide
  • TOCA511
  • TTF