Sparing the hippocampus and the hypothalamic- pituitary region during whole brain radiotherapy: a volumetric modulated arc therapy planning study

Abstract

Background: Feasibility testing of a simultaneous sparing approach of hippocampus, hypothalamus and pituitary gland in patients undergoing whole-brain radiotherapy (WBRT) with and without a concomitant boost to metastatic sites. Introduction: Cognitive impairment and hormonal dysfunction are common side effects of cranial radiotherapy. A reduced dose application to the patho-physiologically involved functional brain areas, i.e. hippocampus, hypothalamus and pituitary gland, could reduce these common side effects. While hippocampal sparing is already a common practice to improve cognitive outcome, technical experience of additional combined sparing of the hypothalamus/pituitary gland (HT-P) is insufficient. Methods: Twenty patients were included in the planning study. In 11 patients, a total dose of 36 Gy of WBRT (2 Gy per fraction) plus a simultaneous integrated boost (SIB) of 9 Gy (0.5 Gy per fraction, total dose: 45 Gy) to the brain metastases was applied. In 9 patients, prophylactic cranial irradiation (PCI) was simulated with a total dose of 30 Gy (2 Gy per fraction). In both patient cohorts, a sparing approach of the hippocampus and the HT-P area was simulated during WBRT. For all treatment plans, volumetric modulated arc therapy (VMAT) was used. Quality assurance included assessment of homogeneity, conformality and target coverage. Results: The mean dose to the hippocampus and HT-P region was limited to less than 50% of the prescribed dose to the planning target volume (PTV) in all treatment plans. Dose homogeneity (HI) of the target volume was satisfying (median HI = 0.16 for WBRT+SIB and 0.1 for PCI) and target coverage (conformation number, CN) was not compromised (median CN = 0.82 for SIB and 0.86 for PCI).

The Learning Curve and Inter-Observer Variability in Contouring the Hippocampus under the Hippocampal Sparing Guidelines of Radiation Therapy Oncology Group 0933

“…Nonetheless, the shape of the hippocampi contoured on CT scans fused with MRI was closer to the anatomical shape of the structure, particularly near the lateral ventricle and brainstem (Figure 6). The sizes and volumes of the hippocampi obtained in our study were similar to those reported in the literature [10,27,28] (length 4.5 cm, average width of body approximately 1 cm, mean hippocampal volume (delineated as dentate gyrus) for both LH and RH was 2.01 +/− 0.5 cm 3 ). A similar inter-observer study that analyzed variation in hippocampus delineation for PCI demonstrated that the greatest degree of delineation inaccuracy occurred in the posterior and anterior-medial borders (SD range 1-2.5 mm) on computed local shape variation [10].…”

“…Clearly, the last contoured cases showed the smallest degree of variation in hippocampal volumes. Marginally larger volumes of LH in comparison to RH obtained in our study are similar to data obtained from studies based on automated segmentation of the hippocampus [26,27]. The hippocampal outlines in the first three cases were characterized by a larger volume than in the other seven cases, which may be associated with the participants' uncertainty.…”

Memantine in the Prevention of Radiation-Induced Brain Damage: A Narrative Review

“…Therefore, together with the knowledge of CD after WBRT, awareness of neuroendocrine sequelae from the impaired hypothalamic-pituitary axis is growing [ 195 ]. Actually, the strong impact of irradiation on the hypothalamic-pituitary axis of pediatric subjects undergoing WBRT is well known but the possibility of a similar effect during WBRT for BM in adult subjects is recent [ 196 ]. In particular, there is a growing suspicion that acute hypothalamic dysfunction impairs the immune system’s ability to respond to infection and tumor progression.…”

“…These studies should aim to: (i) evaluate in greater detail the cognitive effects and, more generally, the quality of life impairment during and immediately after WBRT; (ii) study the mechanisms producing these “early” effects; (iii) test in “clinical studies” advanced RT techniques based on both hippocampal-sparing and hypothalamic-pituitary-sparing, currently evaluated only in “planning studies” [ 196 , 199 , 200 , 201 ]; (iv) test new timings of antiglutamatergic drugs administration (e.g., start memantine a few weeks before WBRT), aimed at preventing not only late toxicity but also the acute effects; (v) compare stereotactic RT versus HA-WRT plus memantine based on data showing a reduced risk of CD in patients with 4–15 BMs treated with stereotactic RT compared to standard WBRT +/− memantine [ 202 ].…”

High prevalence of anterior pituitary deficiencies after cranial radiation therapy for skull base meningiomas

“…Interestingly, P. Mehta and al [ 28 ]. reported, in a retrospective study, the importance of sparing the hippocampus and the hypothalamus during a whole brain radiotherapy, using a volumetric modulated arc therapy.…”