Main Session
Sep 27
PQA 01 - Gastrointestinal Cancer and Central Nervous System

2045 - Impact of Doses to Hippocampal Subregions on Neurocognitive Outcomes in Patients with Primary Brain Tumors Treated with Intensity Modulated Proton Therapy

03:00pm - 04:00pm ET
Poster Hall - Exhibit Hall A
Screen: 8
POSTER

Presenter(s)

Prashasti Sharma, MD - Tata Memorial Hospital, Mumbai, Maharashtr

A. Dasgupta1,2, P. Sharma Sr3, A. Rao4, A. Garg4, S. Goswami5, A. Sahu6, P. Shinde7, M. Konthoujam7, R. Punde7, L. Meena8, A. Chatterjee9, and T. Gupta10; 1Advanced Centre for Treatment, Research and Education in Cancer, Tata memorial centre, Mumbai, India, 2Homi Bhabha National Institute, Mumbai, India, 3Advanced Centre for Treatment, Research and Education in Cancer, Tata memorial Centre, Mumbai, India, 4Advanced Centre for Treatment, Research and Education in Cancer, Mumbai, India, 5Tata Memorial Centre, Mumbai, India, 6Department of Radio-diagnosis, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, 7Medical Physics, Advanced Centre for Treatment, Research and Education in Cancer, Mumbai, India, 8Department of Medical Physics, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, 9Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India, 10Department of Radiation Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Mumbai, India

Purpose/Objective(s):

Proton beam therapy (PBT) has demonstrated superior dosimetric outcomes and a better likelihood of neurocognitive preservation compared to photon therapy. However, the association of neurocognitive outcomes with doses to different hippocampal subregions is not explored for patients treated with PBT, which can further improve neurocognitive outcomes.

Materials/Methods:

Adults (>18 years) treated with curative intent intensity modulated proton therapy (IMPT) with at least 1 follow-up neurocognitive assessment (6 months after radiation completion) were included in the retrospective analysis. Hippocampal region subvolumes were contoured on planning MRIs (FSPGR, 3D-T2, 3D T2-FLAIR). The subregions included the bilateral hippocampal head, body, tail, and parahippocampal gyrus (PHG). Pre-radiation and follow-up evaluation were done using the NIMHANS Neuropsychological Battery, which evaluates 11 functional domains (processing speed, tracking, mental flexibility, attention, verbal learning, immediate recall, delayed recall, visuo-construction, visual memory, phonemic fluency, category fluency). Based on Z-score assessments, each domain was categorized into normal, mild, moderate, and severe deficits. Decline from one category was considered the endpoint, and the dosimetric variables from hippocampal subregions were considered for comparison (decline versus no decline). A p-value of <0.05 was considered statistically significant.

Results: Thirty-three patients treated between August 2023 and December 2025 were included. Doses ranged from 45 CGE to 59.4 CGE, and the most common histology included diffuse glioma (63%). 3 of 11 domains had early decline (= 10% of patients)-verbal learning (VL) in 33%, immediate recall (IR) in 45%, and delayed recall (DR) in 30%. Significant association of DL was seen for dosimetric parameters to left-sided structures (hippocampal head, entire hippocampus, PHG) as presented in the table, in particular head and PHG showed significant separation across the entire spectrum of dose volume histogram parameters (D10 to D90). No significant dosimetric correlation was seen with VL and IR.

Table: Dosimetric parameters (Dmean) for delayed recall

Conclusion:

A strong association was demonstrated with left hippocampal head and PHG dose and decline in delayed recall. Dose parameters suggesting low dose radiosensitivity of these structures (Dmean < 5 Gy) likely resulting from damage to the hippocampal stem cell niche.
Substructure

Decline (N=10)

Mean Gy

 No decline (N=23)

Mean Gy

 p-value
Left
Hippocampus

 8.6

 3.4

 0.04
Hippocampal head

 11.6

 4.3

 0.03
Hippocampal body

 7.2

 4.4

 0.07
Hippocampal tail

 7.4

 3.2

 0.06
PHG

 10.5

 4.2

 0.04
Right
Hippocampal head

 10.8

 6.8

 0.18
Hippocampal body

 14.1

 7.5

 0.19
Hippocampal tail

 9.6

 6.1

 0.34
Hippocampal head

 8.1

 6.3

 0.38
PHG

 10.9

 7.6

 0.13