Intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy for high-grade gliomas: Does IMRT increase the integral dose to normal brain?

Purpose: To determine whether intensity-modulated radiotherapy (IMRT) treatment increases the total integral dose of nontarget tissue relative to the conventional three-dimensional conformal radiotherapy (3D-CRT) technique for high-grade gliomas.

Methods and Materials: Twenty patients treated with 3D-CRT for glioblastoma multiforme were selected for a comparative dosimetric evaluation with IMRT. Original target volumes, organs at risk (OAR), and dose–volume constraints were used for replanning with IMRT. Predicted isodose distributions, cumulative dose–volume histograms of target volumes and OAR, normal tissue integral dose, target coverage, dose conformity, and normal tissue sparing with 3D-CRT and IMRT planning were compared. Statistical analyses were performed to determine differences.

Results: In all 20 patients, IMRT maintained equivalent target coverage, improved target conformity (conformity index [CI] 95% 1.52 vs. 1.38, p < 0.001), and enabled dose reductions of normal tissues, including brainstem (D_mean by 19.8% and D_max by 10.7%), optic chiasm (D_mean by 25.3% and D_max by 22.6%), right optic nerve (D_mean by 37.3% and D_max by 28.5%), and left optic nerve (D_mean by 40.6% and D_max by 36.7%), p ≤ 0.01. This was achieved without increasing the total nontarget integral dose by greater than 0.5%. Overall, total integral dose was reduced by 7–10% with IMRT, p < 0.001, without significantly increasing the 0.5–5 Gy low-dose volume.

Conclusions: These results indicate that IMRT treatment for high-grade gliomas allows for improved target conformity, better critical tissue sparing, and importantly does so without increasing integral dose and the volume of normal tissue exposed to low doses of radiation.

Introduction

With the advent of computed tomography, which allows for visualization of the internal patient anatomy and potential targets, conventional three-dimensional conformal radiotherapy (3D-CRT) has become widespread in its use in nearly all treatment sites because of its advantages in improving conformity of dose around the target and thus sparing adjacent normal tissues as compared with treatment with conventional radiotherapy fields. Intensity-modulated radiotherapy (IMRT), a more sophisticated approach to delivering conformal radiotherapy, is now becoming increasingly used for its ability to further improve dose conformity and sparing of critical normal tissues, which becomes especially important in sites such as the head and neck, prostate, and brain where tumors are often in very close proximity to or abutting critical normal structures. The basis for IMRT relies on an inverse-planning system, which optimizes delivery of nonuniform beam fluences from multiple directions to allow the intended dose to reach the target with maximal sparing of dose to normal tissues. The treatment system involves use of multileaf collimators that divide each beam into many small beamlets, which are each modulated such that the overall beam intensity patterns achieve the desired target coverage and critical tissue sparing.

Comparison of plans using conventional radiotherapy technique with those using IMRT have clearly demonstrated that IMRT allows for improvement in target dose conformity and reduction in the maximum doses to organs at risk, while achieving comparable target coverage in many treatment sites including the lung, esophagus, nasopharynx, paranasal sinuses, paraspinal region, breast, parotid gland, prostate, and intracranial sites (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16). While these studies involved dosimetric comparisons, some also described improved clinical outcomes such as reduction in auditory toxicity in pediatric medulloblastoma patients treated with IMRT as compared with conventional radiotherapy (17). The dosimetric advantages of increased conformity and greater normal tissue sparing with IMRT certainly will make dose escalation in clinical trials potentially more feasible as dose to adjacent critical structures can be more easily maintained below maximal tolerance doses. A practical advantage of IMRT lies in its use of inverse-planning algorithms which greatly reduce the planning times required to achieve an optimal treatment plan when compared with conventional 3D-CRT, which can potentially increase the overall efficiency in a busy clinic or high-volume treatment facility.

Though IMRT has been demonstrated to have these theoretical advantages, as yet, none have been validated in any long-term prospective clinical trials. Furthermore, there is a question of whether IMRT would lead to an increase in the total cumulative dose to normal untreated tissues, often referred to as integral dose (ID) (1, 18), relative to conventional radiotherapy techniques. Some studies have reported an increase in ID with IMRT (15, 16, 19), whereas others have reported no increase in ID with IMRT (2, 10). With increased ID, the volume of normal tissue exposed to low doses of radiation also has been suggested to be increased by IMRT when compared with conventional radiotherapy. This has raised the concern that, particularly in children and patients with less aggressive malignancies, IMRT may potentially increase the incidence of second malignant neoplasms (20). Though it is not yet clear what minimum dose is sufficient for second malignant neoplasm induction, mean doses as low as 1.5 Gy to normal tissue in patients treated for tinea capitus were associated with increased risk of gliomas, meningiomas, and schwannomas (21). Additionally, the risk for malignant thyroid cancers was increased fourfold in the tinea capitus patients whose thyroid dose was 9 cGy. Most studies to date have evaluated the impact of IMRT on low to medium doses of radiation, but few if any have addressed the effect of IMRT on the volumes receiving very low doses, e.g. <5 Gy, which may be more relevant to increasing the risk of second malignant neoplasms.

This study seeks to determine if IMRT increases the ID to normal tissue and the volume of normal tissue exposed to very low to medium doses of radiation in a group of patients who had been treated with 3D-CRT for high-grade gliomas. We compared the best dosimetric IMRT plan to the original 3D-CRT plan for target coverage, conformity of prescribed dose volumes, critical tissue sparing, as well as total ID and ID in the very low to mid dose regions.