This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Buatti, J. M. Articles by Carlisle, T. L. Search for Related Content PubMed PubMed Citation Articles by Buatti, J. M. Articles by Carlisle, T. L.

Low-Grade Gliomas: Answering One Question in a Myriad of New Questions

University of Iowa College of Medicine, Iowa City, IA

TREATMENT FOR low-grade gliomas remains one of the most challenging neuro-oncologic management decisions. These tumors were previously termed benign gliomas, yet patients given the diagnosis have median survivals in the range of 5 to 7 years. Local recurrence and conversion to malignant glioma is the expected outcome. Despite this significant impact on the patient’s life, the survival duration of 5 years or more is sufficient for late effects of radiation therapy, or disability from surgery and chemotherapy to be prohibitive risks without a definitive documentation of benefit. Another problem in managing these tumors is that, although the mean survival is 5 years, the range of outcomes is far greater and, hence, less predictable than with malignant counterparts. These characteristics make management a constant struggle between too much and too little therapy. The article by Shaw et al¹ adds to our improved definition of too much therapy.

The intergroup randomized study by Shaw et al¹ of more than 200 patients with low-grade gliomas found no benefit to a dose of 64.8 Gy when compared with a dose of 50.4 Gy delivered in identical fractionation. More toxicity in the high-dose arm is documented. A previous European Organization for Research and Treatment of Cancer (EORTC) study randomized 379 patients and found no benefit to 59.4 Gy when compared with 45.0 Gy.² Comparison of the two trials suggested slightly better 5-year survival in the current study compared with the original EORTC study for both high-dose and low-dose arms, although reasons for this are not apparent. A recent additional randomized study from the EORTC compared early postoperative radiation with delayed radiation at the time of progression with a dose of 54 Gy to each group.³ No advantage was found in overall survival, although the time to progression was extended in the early radiotherapy group. Survival seemed similar to the present study. Despite these randomized studies supporting lower doses, the new intergroup study uses a dose of 54 Gy. The previous randomized studies support a dose of not more than 50.4 Gy and could make a case for 45 Gy as well. In fact, all data supports that less is better, and hence, 45 to 50.4 Gy should be the supported doses.

Interestingly, the recent article by Karim et al,³ which randomizes between early versus delayed radiotherapy to a dose of 54 Gy, reports the discussion as comparing believers and nonbelievers. The conclusion might be stated that the believers prevailed, although the data remained clearly neutral. Further examination of the data from the EORTC study supported that the quality-of-life index on the original study comparing 45 Gy and 59.4 Gy was significantly better for those in the 45-Gy arm, and toxicity in the present study also supported that less is better. Based on the cumulative data, the hypothesis that less radiation dose is better is believed by the authors.

The progressively more important questions for the treatment of low-grade gliomas have become how much surgery and surgical risk should be undertaken to achieve a better outcome.⁴ Additionally, the question of chemotherapy has to be revisited in an environment where nearly two thirds of tumors have oligodendroglial components, and it is known that the majority of malignant oligodendroglial tumors are responsive. This is addressed in the new intergroup study and is an important question. The role of specific genetic mutations in predicting response may also be important, as may specific imaging profiles and new agents that are being used in management of malignant glial tumors.

All of these complexities suggest that frank multidisciplinary discussion with the patient is a prerequisite for good management. A decision for surgery, radiation, chemotherapy, or observation all have risks and benefits that the individual should understand to make an informed decision. The availability of complex multimodality image guidance and availability of intraoperative assessment have become critical. Advanced technology radiation techniques to protect uninvolved tissues and lower doses between 45 and 50.4 Gy are supported. Delay of radiation for tumors in noneloquent regions and small asymptomatic tumors in eloquent regions should be discussed based on our current information. The role of chemotherapy is rapidly being explored in light of newer experience. There are a myriad of new questions and quandaries in decision-making. However, the radiation question is answered: less is better.

REFERENCES

1. Shaw E, Arusell R, Scheithauer B, et al: Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: Initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol 20: 2267-2276, 2002[Abstract/Free Full Text]

2. Karim AB, Maat B, Hatlevoll R, et al: A randomized trial on dose-response in radiation therapy of low-grade glioma: EORTC Study 22844. Int J Radiat Oncol Biol Phys 36: 549-556, 1996[CrossRef][Medline]

3. Karim ABMF, Afra D, Cornu P, et al: Randomized trial on the efficacy of radiotherapy for cerebral low-grade gliom in the adult: EORTC Study 2285 with the MRC Study BR04: An interim analysis. Int J Radiat Oncol Biol Phys 52 (2): 316-324, 2002[CrossRef][Medline]

4. Berger MS, Rostomily RC: Low grade gliomas: functional mapping resection strategies, extent of resection and outcome. J Neuroncol 34 (1): 85-101, 1997[CrossRef][Medline]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Buatti, J. M. Articles by Carlisle, T. L. Search for Related Content PubMed PubMed Citation Articles by Buatti, J. M. Articles by Carlisle, T. L.