Patterns of failure and comparison of different target volume delineations in patients with glioblastoma treated with conformal radiotherapy plus concomitant and adjuvant temozolomide

Department of Radiation Oncology, Sant' Andrea Hospital, University La Sapienza, Rome, Italy.
Radiotherapy and Oncology (Impact Factor: 4.86). 12/2010; 97(3):377-81. DOI: 10.1016/j.radonc.2010.08.020
Source: PubMed

ABSTRACT To analyze the recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with conformal radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ), and to compare the patterns of failure according to different target volume delineations.
One hundred and five patients with GBM which recurred after three-dimensional (3D) conformal RT plus TMZ were evaluated. The clinical target volume (CTV) used for our treatment planning (S'Andrea plans) consisted of residual tumor and resection cavity plus 2-cm margins according to recent randomized trials of the European Organisation for Research and Treatment of Cancer (EORTC). MRI scans showing tumor recurrences were fused with the planning computed tomography (CT), and the patterns of failure were analyzed dosimetrically using dose-volume histograms. For each patient a theoretical plan based on the addition of postoperative edema plus 2-cm margins according to current guidelines of Radiation Therapy Oncology Group (RTOG) was created and patterns of failure were evaluated.
The median overall survival and progression-free survival were 14.2 months and 7.5 months, respectively. Recurrences were central in 79 patients, in-field in 6 patients, marginal in 6 patients, and distant in 14 patients. Analysis of O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status showed different recurrence patterns of GBMs in patients with MGMT methylated compared with patients with MGMT unmethylated status. Recurrences occurred central/in-field and outside in 64% and 31% of methylated patients, and in 91% and 5.4% of unmethylated patients, respectively (P=0.01). Patterns of failure were similar between the different treatment plans, however the median volume percent of brain irradiated to high doses was significantly smaller for our plans than for RTOG plans (P=0.0001).
Most of patients treated with RT plus concomitant and adjuvant RT have central recurrences, however distant new lesions may occur in more than 10% of patients. The use of target delineation using postoperative residual tumor and cavity plus 2-cm margins is associated with smaller volumes of normal brain irradiated to high doses as compared with plans including expanded edema, without a significant increase of the risk of marginal recurrences. Future clinical randomized studies need to compare the different planning methods in terms of efficacy and risk of late radiation-induced toxicity.

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    • "This tumor is highly infiltrative, and recurrence after localized treatments such as conformal radiotherapy or surgery is common. This relapse usually occurs within a few cm of the treated region [6] [7] [8]. The introduction of temozolomide, a small molecule chemotherapy agent that has some penetration across the BBB, has improved clinical outcomes [9], but this improvement has been modest. "
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    • "More recently, Farace et al. [20] showed that huge changes in oedema are observed between pre-and postoperative MRI, which may be a consequence of steroid treatment and changes in mass effect and does not support the deliberate inclusion of the T2 abnormality in the CTV. In the modern era of radiotherapy with temozolomide, Minniti et al. [21] analysed 105 patients with recurrent GBM treated to a CTV comprising enhancing tumour plus 2 cm. They also constructed theoretical plans, including peritumoural oedema with a 2 cm margin, and concluded that treating the smaller volumes (without intentional inclusion of oedema) reduced the brain volumes treated to a high dose without a significant increase in the "
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