Brachytherapy

Abstract

I read with great interest the article by Koot et al.1 comparing the results of two completely different concepts of interstitial brachytherapy in the treatment of patients with glioblastoma multiforme (GBM). The regimens differ with regard to the extent of initial surgery (biopsy vs. cytoreductive surgery), the isotope used (iodine-125 vs. iridium-192), the dose given via external beam radiotherapy (EBRT) (10–30 grays [Gy] vs. 60 Gy), the brachytherapy target volume (contrast-enhancing region without margin vs. that with a 5-mm margin), and the timing of the treatment (initial brachytherapy with simultaneous EBRT vs. initial EBRT followed by interstitial boost). Despite these contrasting concepts, a median survival of 17 months and 16 months, respectively, was observed in defined subgroups (those age > 30 years with a Karnofsky performance score ≥ 70 and a nonmidline tumor) from both cohorts compared with a median survival of 10 months in a control group. Unfortunately, the authors missed an opportunity to shed more light on a central, unresolved issue concerning radiation therapy for GBM: the criteria defining the volume to be treated with higher-than-conventional doses. First, the report by Koot et al. lacks information concerning how the brachytherapy planning target volume (PTV) was defined. Apparently, the PTV definition was based on contrast enhancement on computed tomography (CT), and in some cases magnetic resonance imaging (MRI) was used instead or as additional information. Taking into account that these two imaging modalities already differ substantially in outlining malignant gliomas,2 it is essential to know how CT and MRI contributed to the PTV definition (combined volume or an overlap of both methods?). In addition, there was no information at all presented with regard to the definition of EBRT volumes and the imaging and criteria used to define disease progression. The authors only state that in the 1 cohort, 51% of the patients recurred “outside the margins of the isodose distribution” (the prescription isodose?) and that in the other group, all recurrences occured “at the original site” (inside the brachytherapy PTV or inside the EBRT PTV?). Interstitial brachytherapy in the treatment of GBM competes with noninvasive modalities such as high-dose proton/photon radiotherapy3 and stereotactic EBRT boost after conventional radiotherapy, with the latter currently being studied in what to my knowledge are ongoing randomized trials.4, 5 Both concepts have demonstrated comparable, although mixed, results in Phase II studies, with estimated survival advantages of 5–11 months compared with conventional treatment.4, 6 In contrast to the report by Koot et al.,1 these studies presented a thorough analysis of patterns of recurrence, demonstrating a true shift from the common central recurrence after conventional radiotherapy7 to marginal recurrence after central high-dose treatment. For example, Fitzek et al. observed histologically confirmed recurrent tumor within the high-dose volume in only 1 case despite a high reoperation rate of 57% in a group of 23 GBM patients treated with 90 cobalt gray equivalent with proton/photon irradiation.3 In contrast, new MRI enhancement after treatment within that same volume was found in 78% of patients, underscoring the difficulty in differentiating between necrosis and tumor recurrence. In a series of 78 GBM patients treated with a stereotactic EBRT boost, Shrieve et al. found only 38% of recurrences developed within 2 cm of the boost prescription isodose.6 To interpret the results of the study by Koot et al.,1 it would be helpful to know exactly where the recurrences (defined by imaging or pathology at reoperation) occured with regard to PTV or treated volume. If there is any benefit to high-dose radiotherapy by any method in the treatment of GBM, it lies in the treatment's ability to sterilize the central region of the solid tumor. Although this potential benefit must be weighed carefully against the risk of radiation-induced necrosis, several investigators have called for an extension of the high-dose target volume beyond the area of contrast enhancement.3, 8 The definition of such extended volumes may include additional information regarding tumor outline using modalities such as single photon computed emission tomography9 or transcranial sonography.10 In any case, the treatment of GBM patients beyond conventional radiotherapy doses and a potential optimization of current concepts calls for a clear definition of the target volumes used and a particularly thorough documentation of the patterns of tumor recurrence. [The authors were invited to reply and declined the invitation.] Dirk Vordermark M.D.*, * Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany