Volumetric modulated arc therapy (VMAT) for hippocampal-avoidance whole brain radiation therapy: planning comparison with Dual-arc and Split-arc partial-field techniques

Although whole brain radiation therapy (WBRT) provides palliation and prophylaxis, reduces local recurrence probability and improves overall survival [1‐5], it is evident that WBRT is associated with neurocognitive deficits [6‐10] due to radiation induced damage of neural stem cell (NSC) compartment in the hippocampus [11‐14]. It is hypothesized that the NSCs in the hippocampus are exquisitely radiosensitive, radiation inflammation causes alteration of the microenvironment and subsequently forces premature differentiation of neuronal progenitor cells and adoption of glial fates [15]. Previous published clinical study of Gondi et al. [16] has demonstrated that dose to 100% volume (D_100%) of the hippocampus exceeds 9 Gy and maximum dose (D_max) of the hippocampus exceeds 16 Gy in WBRT treatment course of 30 Gy in 10 fractions were associated with impair memory function. In addition, accumulated preclinical and clinical data have also suggested that neurocognitive deficits manifests at much lower radiation doses than previously expected (less than 10 Gy) [17]. Minimizing the radiation dose to the least possible level is of high clinical relevance since increased radiation dose to D_100% and maximum dose of the hippocampus corresponded to greater decline in memory function [16, 18]. It leads to the hypothesis that hippocampal sparing in patients receiving WBRT might delay or reduce the onset, and/or severity of neurocognitive deficit.

Radiation Therapy Oncology Group (RTOG) 0933 is a single-arm phase II clinical trial that studies the effectiveness of hippocampal sparing in WBRT and has demonstrated promising results in terms of memory preservation using the dose criteria (Table 1) in the protocol [16]. In the meantime, dosimetric characteristics of dual-arc conventional volumetric modulated arc therapy (dac-VMAT) in WBRT with hippocampal sparing have been reported in previous studies following RTOG 0933 criteria [19‐21]. The large irradiation field of dac-VMAT for whole brain planned target volume (PTV) required a wide jaw opening which may result in suboptimal multi-leaf collimator (MLC) movements as described in previous publication [22]: (1) Hardware restrictions for MLC movements; (2) Restricted MLC velocity from one gantry angle to another; (3) MLC may reach their limit of travelling distance when they are attempting to move to the distal part of the PTV. In extreme case, the MLC may not be able to shield the desire organs-at-risk (OARs) in distal part of PTV.

In order to prevent suboptimal MLC movements during hippocampal sparing, Shen et al. [23] has employed the partial-field technique in volumetric modulated arc therapy (VMAT) for WBRT and has reported reduced hippocampal dose; however, exact doses to the other OARs have not been described. In fact, radiation-induced toxicity to the other OARs, including the eyes, during WBRT have been described in previous publications with negative impact on patients’ quality of life [24, 25]. Therefore, radiation dose to the other adjacent OARs should not be overlooked and should also be considered during treatment planning of WBRT with hippocampal sparing.

Until recently, several researchers have employed both split-arc and partial-field technique together to eliminate scatter radiation and MLC limitations in VMAT planning. This technique is beneficial in sparing adjacent OARs in breast cancer [26], cervical [27, 28], anal [28, 29], and vaginal cancer [28]. To the best of the author’s knowledge, the formal literature is devoid of any reference to the application of both split-arc and partial-field technique in VMAT (sapf-VMAT) for WBRT with hippocampal sparing. In the present study, the dosimetric effect of the sapf-VMAT is studied to verify its sparing ability to hippocampus as well as to other OARs on WBRT.

The objective of the present study is to compare the dose sparing capability of dac-VMAT and sapf-VMAT at hippocampus during WBRT.

The QA of all treatment plans showed good correlation and reached a passing rate of 95% between treatment planning system-calculated dose and QA system calculated dose (Distance to agreement < 3 mm and dose difference < 3%). Results of dosimetric analysis of whole brain PTV and OARs for the 20 patients in the present study were summarized as mean ± standard deviation (SD) (Table 2). The mean dose-volume histograms (DVH) of the whole brain PTV (Fig. 4) and OARs (Fig. 5) using dac-VMAT and sapf-VMAT were compared.

In this planning study, two different techniques (dac-VMAT and sapf-VMAT) were compared in the treatment of 20 patients with brain metastases. All treatment plans were able to achieve the acceptable range of RTOG 0933 (Table 1). Radiation dose to the hippocampus and other OARs were reduced while the whole brain PTV coverage was not compromised.

The present study has suggested a radiation therapy technique – sapf-VMAT, which has consistently demonstrated lower hippocampus dose compared to dac-VMAT plans, with an average reduction of around 14.84, 18.98 and 15.58% in D_100%, D_max and D_mean of hippocampus respectively. Meanwhile, hippocampus D_100% and D_max have been reduced to an average of 7.86 Gy and 13.23 Gy in sapf-VMAT, which are less than the cutoff value of radiation induced neurocognitive deficit onset as described by Gondi et al. [16].

In the present study, dac-VMAT technique comprises 2 coplanar full arcs with large field size covering the whole brain with reference to previous published studies [19‐21]. The large irradiation field of whole brain PTV requires a larger jaw opening. This technique may produce a substantial low dose volume in the hippocampus, as a consequence of multi-leaf collimator (MLC) leakage and scatter radiation. The limitation of MLC movement in large field size dac-VMAT may also induce the island blocking problem [32, 33] (Fig. 7). The island blocking problem exists when ≥2 areas of whole brain PTV share the same MLC leaf pair, resulting in an area of hippocampus that is not blocked by the MLC, and hence increased low dose spillage to the hippocampus. Since reduced field size in either X1 and X2 collimator jaw has been employed for sapf-VMAT plans, an independent jaw can be moved to block off part of the field to reduce scatter radiation. This feature is useful for adjacent normal healthy tissue sparing, that is, the hippocampus. In addition, the reduced field size can shorten travelling distance of MLC, and therefore MLC movement is less likely to be restricted by its velocity and physical limitation. Thus, MLC in sapf-VMAT are capable of shielding the hippocampus in all gantry angles, while remaining enough dose coverage to whole brain PTV.

In the coplanar VMAT planning, constraint of radiation dose to the eyes and hippocampus is sometimes considered to be a difficult goal. Since the eyes and the hippocampus are collated on the same plane, which creates difficulties during optimization using dac-VMAT. In sapf-VMAT plans, the proposed split-arc design can help the optimizer to avoid irradiation of whole brain PTV with the expense of hippocampus and both eyes by collimator rotation between the arcs. The reduced treatment field size can also reduce the swept angle that both eyes lie within the treatment field, resulting in dose reduction in hippocampus and both eyes using sapf-VMAT.

In addition to tissue sparing, another major advantage of using sapf-VMAT is that the overall swept angle remains equal to the dac-VMAT for WBRT (i.e. 719.6°), although the number of treatment arcs in sapf-VMAT is increased to 4. Hence, no major increment in treatment delivery time (13 s more than dac-VMAT on average) is induced using sapf-VMAT. This technique will not impact on patient comfort on the treatment couch and affect the reproducibility of treatment position.

The sapf-VMAT plans generated in this study has resulted in higher averaged MU usage than the dac-VMAT plans (averaged difference of 166 MU). It is believed that the higher MU usage resulting from sapf-VMAT plans is a consequence of the highly conformal dose distributions and superior OAR sparing. Admittedly, higher MU has its drawbacks such as the potential increase in total body dose because of scattering and leakage from MLC. Therefore, in future improvement of the sapf-VMAT, efforts should be spent on reducing the MU usage while maintaining the plan quality.

The present study has proposed a radiation therapy technique, namely sapf-VMAT, that has employed split-arc and reduced field size. This technique has demonstrated significant dose reduction to the hippocampus and eyes compared to dac-VMAT. Therefore, the clinical usability and functional outcome of this strategy should be further investigated in sapf-VMAT.