Radiotherapy Dose Escalation in High-Grade Gliomas
Authors: Michael A. LaCombe, June L. Chan, Howard M. Sandler, Benedick A. Fraass
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.99.802 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12149315 Radiotherapy Dose Escalation in High-Grade Gliomas Michael A. LaCombexMichael A. LaCombeSearch for articles by this author June L. ChanxJune L. ChanSearch for articles by this author , Howard M. SandlerxHoward M. SandlerSearch for articles by this author , Benedick A. FraassxBenedick A. FraassSearch for articles by this author Show More Evanston Northwestern Health Care, Evanston, ILUniversity of Michigan Medical Center, Ann Arbor, MI https://doi.org/10.1200/JCO.2002.99.802 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01082002In Reply to Drs Knisely and LaCombe:We thank Dr Knisely and Dr LaCombe for their comments in regard to our recent article in the Journal of Clinical Oncology.1 They highlight several important aspects of our work.As far as we know, there is no clearly accepted definition of tumor recurrence or progression for high-grade gliomas. Our definition was a modification of well-known protocol criteria for tumor progression and was primarily based on radiographic enlargement of the cross-sectional diameters, in square centimeters, of enhancing masses seen on serial magnetic resonance imaging. As part of the multidisciplinary neuro-oncology team at the University of Michigan, patients who participated in this study had their serial imaging scans reviewed at a weekly brain tumor board, where an experienced group of investigators helped define tumor recurrence versus radiation necrosis. Although noninvasive techniques cannot rule out radiation necrosis, the long-term clinical picture, seen beyond the initial scan identifying recurrence, usually delineates the ultimate nature of these lesions. The classification used for tumor recurrence in this study was, thus, an attempt to use our working definition and allow others to have a means for comparison.LaCombe calculated that “[planning target volume; PTV]3 received only 1.33 Gy per fraction (60 Gy total to PTV3).” It should be pointed out that the dose to the PTV3 was actually 60 biogray (see Table 1 in our article1). The term “biogray” refers to the equivalent dose received, accounting for differences in dose per fraction, for a given alpha:beta ratio. For example, 60 biogray is equivalent to 60 Gy given at 2 Gy per fraction. That being said, patients on this study received the biologic equivalent of 60 Gy in 2-Gy fractions to PTV3. Our data indicate that the prescribed biogray levels to the outer annuli have not resulted in more marginal misses. The word “biogray” may not be considered standard terminology; however, if we are to more accurately compare radiation treatment plans in the three-dimensional/intensity-modulated radiotherapy era, a system for comparing differing fractionation schemes will be needed. Terms like “biogray,” as defined in our article, may help unify our definitions and perhaps become the new standard terminology.As stated in our Discussion,1 any further dose escalation would involve keeping the outer PTVs (gross tumor volume + 2.5 cm and gross tumor volume + 1.5 cm) at the same biogray levels while only increasing the total central dose. The methods of achieving this have been covered extensively in the article by Lee et al.2 Although the concern that higher daily doses of radiation to normal brain tissue (ie, outer PTVs) could result in increased toxicity is certainly valid, the techniques used are meant to change only the final dose to the central volume.Malignant high-grade glioma remains a diagnosis with a poor prognosis despite aggressive attempts at controlling it with combinations of surgery, chemotherapy, and radiation. Our statement that “further dose escalation may prove to be beneficial in this setting” was not meant to suggest that this is the only reasonable approach. It is likely that radiation dose escalation will need to be combined with chemotherapeutic agents and/or molecularly targeted therapies to achieve success.1. Chan JL, Lee SW, Fraass BA, et al: Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol 20:: 1635,2002-1642, Link, Google Scholar2. Lee SW, Fraass BA, Marsh LH, et al: Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: A quantitative dosimetric study. Int J Radiat Biol Phys 43:: 79,1999-88, Crossref, Medline, Google Scholar