Neural stem cell sparing by linac based intensity modulated stereotactic radiotherapy in intracranial tumors

Abstract

BackgroundNeurocognitive decline observed after radiotherapy (RT) for brain tumors in long time survivors is attributed to radiation exposure of the hippocampus and the subventricular zone (SVZ). The potential of sparing capabilities for both structures by optimized intensity modulated stereotactic radiotherapy (IMSRT) is investigated.MethodsBrain tumors were irradiated by stereotactic 3D conformal RT or IMSRT using m3 collimator optimized for PTV and for sparing of the conventional OARs (lens, retina, optic nerve, chiasm, cochlea, brain stem and the medulla oblongata). Retrospectively both hippocampi and SVZ were added to the list of OAR and their dose volume histograms were compared to those from two newly generated IMSRT plans using 7 or 14 beamlets (IMSRT-7, IMSRT-14) dedicated for optimized additional sparing of these structures. Conventional OAR constraints were kept constant. Impact of plan complexity and planning target volume (PTV) topography on sparing of both hippocampi and SVZ, conformity index (CI), the homogeneity index (HI) and quality of coverage (QoC) were analyzed. Limits of agreement were used to compare sparing of stem cell niches with either IMSRT-7 or IMSRT-14. The influence of treatment technique related to the topography ratio between PTV and OARs, realized in group A-D, was assessed by a mixed model.ResultsIn 47 patients CI (p ≤ 0.003) and HI (p < 0.001) improved by IMSRT-7, IMSRT-14, QoC remained stable (p ≥ 0.50) indicating no compromise in radiotherapy. 90% of normal brain was exposed to a significantly higher dose using IMSRT. IMSRT-7 plans resulted in significantly lower biologically effective doses at all four neural stem cell structures, while contralateral neural stem cells are better spared compared to ipsilateral. A further increase of the number of beamlets (IMSRT-14) did not improve sparing significantly, so IMSRT-7 and IMSRT-14 can be used interchangeable. Patients with tumors contacting neither the subventricular zone nor the cortex benefit most from IMSRT (p < 0.001).ConclusionThe feasibility of neural stem cell niches sparing with sophisticated linac based inverse IMSRT with 7 beamlets in an unselected cohort of intracranial tumors in relation to topographic situation has been demonstrated. Clinical relevance testing neurotoxicity remains to be demonstrated.

Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to the primary brain tumor: the result of dosimetric study and neurocognitive function assessment

“…Therefore, comparisons of the hippocampal dosimetric profile and NCF toxicity are difficult. Several studies reported consistent results with those of our study regarding the dosimetric profile of the hippocampus when applying the hippocampal-sparing strategy using various IMRT techniques for the radiotherapy of the primary brain tumor [ 2 , 7 – 17 ]. Pinkham et al reported the dosimetric feasibility of hippocampal-sparing IMRT in grade II and grade III gliomas.…”

“…However, unlike WBRT, the hippocampal-sparing strategy for the radiotherapy treatment of primary brain tumor has not been thoroughly evaluated. Although the dosimetric feasibility has been reported in a number studies [ 2 , 7 – 17 ], to our knowledge, there has been no report on the association between NCF and hippocampal-sparing radiotherapy.…”

Early-Delayed, Radiation-Induced Cognitive Deficits in Adult Rats are Heterogeneous and Age-Dependent

“…(39, 42, 56)] have been cited as the foundation for clinical treatment involving hippocampal sparing, that is, conforming radiation dose plans to greatly reduce the dose to the neurogenic zone of the hippocampus with the expectation of preventing or ameliorating treatment-induced cognitive deficits [e.g., see refs. (57–59)]. Significantly, however, data linking radiation-induced deficits in neurogenesis to cognitive changes, particularly to hippocampal-dependent learning and memory, come largely from experiments in which developing or very young adult animals were irradiated with single dose, not fractionated, WBI and were tested cognitively just a few months after irradiation (whereas cognitive deficits develop clinically many months or even years after treatment).…”

Normal Brain Sparing With Increasing Number of Beams and Isocenters in Volumetric-Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

“…However, animal study 13 and early data 14,15 have all pointed to a low tolerance dose and essential need to spare critical neurostem cell compartments including hippocampi in normal brain irradiation to improve neurocognitive functions of the patients. Given the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUAN-TEC) practice guideline and known correlation between low-level isodose volumes and the treatment complications, [16][17][18] maximally sparing the normal brain via technical improvements is therefore highly warranted.…”