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The role of initial chemotherapy for the treatment of adults with diffuse low grade glioma

A systematic review and evidence-based clinical practice guideline

  • Topic Review & Clinical Guidelines
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Target population

Adult patients (older than 18 years of age) with newly diagnosed World Health Organization (WHO) Grade II gliomas (Oligodendroglioma, astrocytoma, mixed oligoastrocytoma).

Question

Is there a role for chemotherapy as adjuvant therapy of choice in treatment of patients with newly diagnosed low-grade gliomas?

Recommendations

Level III

Chemotherapy is recommended as a treatment option to postpone the use of radiotherapy, to slow tumor growth and to improve progression free survival (PFS), overall survival (OS) and clinical symptoms in adult patients with newly diagnosed LGG.

Question

Who are the patients with newly diagnosed LGG that would benefit the most from chemotherapy?

Recommendation

Level III

Chemotherapy is recommended as an optional component alone or in combination with radiation as the initial adjuvant therapy for all patients who cannot undergo gross total resection (GTR) of a newly diagnosed LGG. Patient with residual tumor >1 cm on post-operative MRI, presenting diameter of >4 cm or older than 40 years of age should be considered for adjuvant therapy as well.

Question

Are there tumor markers that can predict which patients can benefit the most from initial treatment with chemotherapy?

Recommendation

Level III

The addition of chemotherapy to standard RT is recommended in LGG patients that carry IDH mutation. In addition, temozolomide (TMZ) is recommended as a treatment option to slow tumor growth in patients who harbor the 1p/19q co-deletion.

Question

How soon should the chemotherapy be started once the diagnosis of LGG is confirmed?

Recommendation

There is insufficient evidence to make a definitive recommendation on the timing of starting chemotherapy after surgical/pathological diagnosis of LGG has been made. However, using the 12 weeks mark as the latest timeframe to start adjuvant chemotherapy is suggested. It is recommended that patients be enrolled in properly designed clinical trials to assess the timing of chemotherapy initiation once diagnosis is confirmed for this target population.

Question

What chemotherapeutic agents should be used for treatment of newly diagnosed LGG?

Recommendation

There is insufficient evidence to make a recommendation of one particular regimen. Enrollment of subjects in properly designed trials comparing the efficacy of these or other agents is recommended so as to determine which of these regimens is superior.

Question

What is the optimal duration and dosing of chemotherapy as initial treatment for LGG?

Recommendation

Insufficient evidence exists regarding the duration of any specific cytotoxic drug regimen for treatment of newly diagnosed LGG. Enrollment of subjects in properly designed clinical investigations assessing the optimal duration of this therapy is recommended.

Question

Should chemotherapy be given alone or in conjunction with RT as initial therapy for LGG?

Recommendation

Insufficient evidence exists to make recommendations in this regard. Hence, enrollment of patients in properly designed clinical trials assessing the difference between chemotherapy alone, RT alone or a combination of them is recommended.

Question

Should chemotherapy be given in addition to other type of adjuvant therapy to patients with newly diagnosed LGG?

Recommendation

Level II: It is recommended that chemotherapy be added to the RT in patients with unfavorable LGG to improve their progression free survival.

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Abbreviations

LGG:

Low grade glioma

RT:

Radiation therapy

PFS:

Progression free survival

OS:

Overall survival

TMZ:

Temozolomide

PCV:

Procarbazine, lomustine or CCNU, vincristine

ACNU:

Nimustine

MTD:

Mean tumor diameter

AEDs:

Anti-epileptic drugs

GTR:

Gross total resection

STR:

Subtotal resection

PR:

Partial resection

RTOG:

Radiation therapy oncology group

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Acknowledgments

We acknowledge the significant contributions of Laura Mitchell, Senior Manager of Guidelines for the CNS, the AANS/CNS Joint Guidelines Committee (JGC) for their review, comments and suggestions, and Anne Woznica and Mary Bodach for their assistance with the literature searches. We also acknowledge the following individual JGC members for their contributions throughout the review process: Kevin Cockroft, MD, Sepideh Amin-Hanjani, MD, Kimon Bekelis, MD, Isabelle Germano, MD, Daniel Hoh, MD, Steven Hwang, MD, Cheerag Dipakkumar Upadhyaya, MD, Christopher Winfree, MD, and Brad Zacharia, MD.

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Authors and Affiliations

  1. Department of Neurosurgery, Seton Brain and Spine Institute, 1400 N IH-35, Suite 300, Austin, TX, 78701, USA

    Mateo Ziu

  2. Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA

    Steven N. Kalkanis

  3. Center for Cancer Research, Neuro-Oncology Branch at National Cancer Institute, Bethesda, MD, USA

    Mark Gilbert

  4. Department of Neurosurgery, Kansas University Medical Center, Kansas City, KS, USA

    Timothy C. Ryken

  5. Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA

    Jeffrey J. Olson

Authors
  1. Mateo Ziu
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  2. Steven N. Kalkanis
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  3. Mark Gilbert
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  4. Timothy C. Ryken
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  5. Jeffrey J. Olson
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Corresponding author

Correspondence to Mateo Ziu.

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Disclosures

Dr. Kalkanis is a consultant for Arbor and Varian. Dr. Olson is a consultant for the American Cancer Society; has received research funding from the National Cancer Institute, Genentech, and Millennium; and has received investigational drug provision from Merck.

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Ziu, M., Kalkanis, S.N., Gilbert, M. et al. The role of initial chemotherapy for the treatment of adults with diffuse low grade glioma. J Neurooncol 125, 585–607 (2015). https://doi.org/10.1007/s11060-015-1931-x

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  • DOI: https://doi.org/10.1007/s11060-015-1931-x

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