Editor’s Note: To read another perspective on treatment of low-grade glioma, read “Point: Patients with Incidentally Found Gliomas Should Always Be Offered Treatment.”

For the purposes of this counter-perspective article, some strong assumptions will be made:

1. Magnetic resonance imaging (MRI) demonstrates a supratentorial tumor;
2. the radiographic appearance is typical of low-grade glioma;
3. the patient is asymptomatic; and
4. the diagnosis is secure.

With these assumptions, the case for conservative treatment of incidentally found supratentorial low-grade gliomas will be made.

Why Take a Conservative Approach?
There is no argument that early surgery and radiation therapy are appropriate for a subset of patients with low-grade glioma of the cerebral hemispheres. For other patients, the risk of malignant degeneration is often cited as a justification for early surgery in cases of low-grade glioma. However, it is a stretch to support early aggressive treatment for all patients. Porous evidence weakly and tenuously upholds the proposition that the natural history of low-grade gliomas is poor, and that low-grade gliomas uniformly degenerate into anaplastic gliomas or glioblastoma multiforme (2, 4). This argument does not hold water and should not be used as an indication for early aggressive “prophylactic” surgery; that is, recommending surgery at the present time with all its incumbent risks to try to prevent something that may or may not happen in the future is not justified.

Furthermore, the indolent nature of low-grade gliomas makes it challenging, in the absence of a controlled trial and an over-reliance on retrospective and observational studies, to evaluate the efficacy of any “prophylactic” intervention (3). There is concern that at some point in the future, the benefits of surgical treatment will be outweighed by the risks of such an intervention (1). For parietal lobe gliomas, Sanai et al. (1) found that with attempted resection with advanced neuro-navigation techniques, parietal language pathways are compromised at a surprisingly (and unacceptable) high rate even at an experienced brain tumor center, such as the University of California, San Francisco. This must be considered with the following facts: Gross-total-resection of intrinsic low-grade gliomas is rarely achieved, or at the least, very difficult, given their infiltrative nature and the subsequent risk of neurological morbidity (6); and studies correlating histological findings to radiographic abnormalities have confirmed the presence of tumor cells at a remote distance from the dominant lesion as seen on radiological imaging (10).

First, Do No Harm
Hence, in an asymptomatic neurologically intact patient, early aggressive surgery for low-grade glioma may be undertaken with the following conditions as reflected by a review of the literature (6): little to no chance of achieving cure (gross-total-resection); high risk of surgery and new neurological deficit; and without any survival advantage compared to patients that are treated conservatively. These terms would not be agreeable nor satisfactory to any neurosurgeon or patient. Under these circumstances, a pathway of conservative treatment must be followed. First, do no harm.

In conclusion, there has been clinical data to support a wait-and-see philosophy for incidentally found low-grade gliomas (4, 5, 7, 8). Recht et al. (4) found that deferring therapy did not worsen outcomes for patients with low-grade gliomas. If the rate of malignant transformation was examined from time of diagnosis, no differences were noted between the patients in the WAIT and NOWAIT groups. Moreover, there was no difference in survival or quality of life in the two cohorts. Similarly, Ali et al. (5) suggest that conservative management and close follow-up of incidental radiographic lesions consistent with low-grade glioma is a safe and effective strategy in the pediatric population. The risk of malignant transformation in pediatric low-grade gliomas is even lower than that of adults; pediatric gliomas do not share the same biological profile of the adult counterparts (8).

Recommended Surveillance
Once the diagnosis of a low-grade glioma is presumed based on neuroimaging studies, and a wait-and-see approach is recommended, adherence to follow-up is mandatory. A regular schedule of re-imaging with MRI at three months, six months and then annually is reasonable. Some authors also advocate perfusion studies, as the changes in relative cerebral blood volume may precede any changes in T1-weighted MR images by up to 12 months (8). Surgery and radiation therapy should not be offered until there is documented clinical deterioration or radiographic progression. These changes will manifest as the onset of neurological dysfunction, intractable seizures, enlargement of the tumor on serial imaging or new areas of enhancement within the mass lesion (9).

Andrew H. Jea, MD, FAANS, is associate professor of neurological surgery at Baylor College of Medicine in Houston and director of the Neurospine Program at Texas Children’s Hospital, also in Houston. The author reported no conflicts for disclosure.

References

1. Sanai N, Martino J. Berger MS. Morbidity profile following aggressive resection of parietal lobe gliomas. J Neurosurg 116: 1182-6, 2012.

2. Potts MB, Smith JS, Molinaro AM, Berger MS. Natural history and surgical management of incidentally discovered low-grade gliomas. J Neurosurg 116: 365-72, 2012.

3. Bacchus JN, Cairncross JG. Conservative treatment of supratentorial low-grade gliomas. In: Al-Mefty O, Origitano TC, Harkey HL, eds. Controversies in Neurosurgery. Thieme: New York, 1996. Pp. 58-59.

4. Recht LD, Lew R, Smith TW. Suspected low-grade glioma: is deferring treatment safe? Ann Neurol 31: 431-6, 1992.

5. Ali ZS, Lang SS, Sutton LN. Conservative management of presumed low-grade gliomas in the asymptomatic pediatric population. World Neurosurg 81: 368-73, 2014.

6. Hulou MM, Chiocca EA. Editorial: the management of low-grade glioma in adults. Neurosurg Focus 38: E8, 2015.

7. Shah AH, Madhavan K, Sastry A, Komotar RJ. Managing intracranial incidental findings suggestive of low-grade glioma: learning from experience. World Neurosurg 80: e75-7, 2013.

8. Di Rocco C, Frassanito P, Tamburrini G. The never-ending struggle between the two souls of the neurosurgeon: to wait or to intervene. World Neurosurg 81: 368-73, 2014.

9. Morantz RA. Treatment of supratentorial low-grade gliomas: surgical vs. conservative. In: Al-Mefty O, Origitano TC, Harkey HL, eds. Controversies in Neurosurgery. Thieme: New York, 1996. Pp. 60-62.

10. Kelly PJ, Daumos-Duport C, Scheithauer BW, Kall BA, Kispert DB. Stereotactic histologic correlations of computed tomography- and magnetic resonance imaging-defined abnormalities in patients with glial neoplasm s. Mayo Clin Proc 62: 450-9, 1987.