Hippocampal Sparing Research Articles

Prise en charge des cancers bronchiques à petites cellules de stade localisé i actualisation

Limited-stage small cell lung cancer (LS-SCLC) represents 15-20 % of all lung cancers, and because of its rapid tumor kinetics, less than a third of SCLC are discovered at limited stage. The different steps and modalities of its management are well defined and codified. They involve a comprehensive staging assessment using CT scans of the chest, abdomen, and pelvis, PET-CT scans, and ideally brain imaging using MRI to avoid missing a more extensive stage of the disease, which would significantly alter the treatment strategy. The treatment consists of a combination of chemotherapy with platinum/ etoposide and radiotherapy, possibly delivered in a hyperfractionated schedule with two daily sessions. SCLC is particularly both chemosensitive and radiosensitive, so that the initial evaluation shows frequently a complete response, and prophylactic cranial irradiation (PCI) is then recommended. Relapses are unfortunately frequent, less responsive to second line treatments, and therapeutic options are limited. No targeted agents or immunotherapy have robustly demonstrated efficacy in the treatment of LSSCLC. Even if hyperfractionated accelerated radiotherapy (HFART) at the dose of 45Gy in 30 fractions has given the best results, most clinicians use once-daily chemoradiation regimen (60-70Gy). Studies have evaluated dose escalation either with HFRAT or with conventional fractionation (66 to 70Gy). Several trials are currently investigating the addition of immunotherapy to chemoradiation, hippocampus sparing PCI or the omission of PCI. In rare cases of very early-stage SCLC, surgery or stereotactic radiotherapy may be envisaged.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Dosimetric Evaluation of Hippocampus Sparing Intensity Modulated Radiation Therapy in Patients With Stage T1-T2 and Stage T3-T4 Nasopharyngeal Carcinoma

PurposeTo compare the hippocampus (HPC) dose reduced by HPC-sparing IMRT plans between nasopharyngeal carcinoma (NPC) patients of stages T1-T2 and T3-T4, and to investigate the correlation between the dose of the hippocampus and the volume of PTVnx70 (the planning target volume of the primary tumor in the nasopharynx received 70 Gy). Methods and MaterialsFifty-eight NPC patients were retrospectively evaluated. HPC non-sparing IMRT or sparing IMRT for each patient was designed according to the protocol for NPC. Dose-volume histogram (DVH) was used to evaluate the IMRT plans for each patient. The difference values of HPC parameters (e.g., Dmin[NS] - Dmin[S]) between HPC sparing and non-sparing plans in stage T1-T2 Group and stage T3-T4 Group were compared. The correlations between the dose of the hippocampus and the volume of PTVnx70 were analyzed. ResultsThere was no significance between HPC-sparing and non-sparing IMRT plans. Compared with the HPC non-sparing plans, the HPC sparing plans significantly decreased both dosimetric and volumetric parameters for the HPC (P < 0.05), except for Dmin, D98%, and V5. The medians of Dmedian[NS] - Dmedian[S], Dmean[NS] - Dmean[S], D40%[NS] - D40%[S], V30[NS] - V30[S], V40[NS] - V40[S] and V50[NS] - V50[S] in the T1-T2 Group were significantly lower than in the T3-T4 Group (P < 0.05), respectively. Both dosimetric and volumetric parameters for the HPC were positively correlated with the volume of PTVnx70 in HPC-sparing and non-sparing plans (P < 0.05). The volume of PTVnx70 was positively correlated with Dmedian[NS] - Dmedian[S], Dmean[NS] - Dmean[S], D40%[NS] - D40%[S], V40[NS] - V40[S] and V50[NS] - V50[S] (P < 0.05). ConclusionsHPC-sparing IMRT plans may play a more significant role in decreasing Dmedian, Dmean, D40%, and V30 ∼ V50 of HPC in NPC patients with stages T3-T4 than those in stages T1-T2. PTVnx70 volume of NPC patients are positively correlated with all dosimetric and volumetric parameters of HPC and the reduction of specific dosage parameters by HPC-sparing IMRT plans.

A Randomised Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1–10 Brain Metastases

AimsTo assess in patients with 1–10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK. Materials and methodsA multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity. ResultsThe trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints. ConclusionA phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.

Sparing the Hippocampus in Prophylactic Cranial Irradiation Using Three Different Linear Accelerators: A Comparative Study.

Hippocampus protection, as an organ at risk in brain radiotherapy, might protect patients' quality of life. Prophylactic cranial irradiation (PCI) has been used traditionally in small cell lung cancer (SCLC) patients as it increases survival. This study aimed to discover the contributing parameters for a successful PCI with simultaneous protection of the hippocampus by using three different treatment machines. For this purpose, treatment plans were generated for 45 SCLC patients using three half-arcs in three linear accelerators (LINACs; Elekta Infinity, Synergy, and Axesse; Elekta Ltd, Stockholm, Sweden) with different radiation field sizes and multileaf collimator (MLC) leaf thickness characteristics. The prescribed dose was 25 Gy in 10 fractions. Thresholds for the hippocampus were calculated based on the Radiation Therapy Oncology Group 0933 dose constraints. The planning and treatment system templates were common to all three LINACs. Plan evaluation was based on the dosimetric target coverage by the 95% isodose, the maximum dose of the plan, the conformity index (CI), the degree of plan modulation (MOD), and the patient-specific quality assurance (QA) pass rate. The mean target coverage was highest for Infinity (97.3%), followed by Axesse (96.6%) and Synergy (95.5%). The mean maximum dose was higher for Synergy (27.5 Gy), followed by Infinity (27.0 Gy) and Axesse (26.9 Gy). Axesse plans had the highest CI (0.93), followed by Infinity (0.91) and Synergy (0.88). Plan MOD was lower for Synergy (2.88) compared with Infinity (3.07) and Axesse (3.69). Finally, patient-specific QA was successful in all Infinity plans, in all but one Synergy plan, and in 17/45 Axesse plans, as was expected from the field size in that treatment unit. Based on overall performance, the most favorable combination of target coverage, hippocampus sparing, and plan deliverability was obtained with the LINAC, which has the largest field opening and thinnest MLC leaves.

Safety and Feasibility of Hippocampal Sparing Cranial Radiation in Pediatric and Adolescent Acute Lymphoblastic Leukemia Patients: A Prospective Study.

Introduction Acute lymphoblastic leukemia (ALL) constitutes a significant portion of pediatric malignancies, with central nervous system (CNS) relapse posing a considerable threat to patient outcomes. While cranial radiation therapy (CRT)has been utilized to mitigate CNS relapse, it is associated with neurocognitive (NC) side effects. This study explores the feasibility and safety of using volumetric arc therapy (VMAT) with hippocampal sparing (HS) during cranial radiation therapy for ALL patients, aiming to reduce these side effects. Methodology This prospective observational study included pediatric and young adult patients with ALL who werein remission. HS was achieved using VMAT, and NC assessments were performed at baseline, six months, one year, and, to a limited extent, four years posttreatment. Results VMAT enabled precise hippocampal-sparing CRT with minimal dose to the hippocampus. Dosimetric analysis revealed that patients receiving 18 Gy had mean doses to planning target volume (PTV) and bilateral hippocampus of 18.9 and 9 Gy, respectively. Those receiving 12 Gy had corresponding doses of 13.3 and 7 Gy, respectively. Conformity and homogeneity indices were 0.9 and 0.1, and no brain relapses were observed among the patients in this study. NC assessments demonstrated no decline in intelligence quotient (IQ) scores over time, while only a subset of patients could be assessed at the four-year mark; telephone interviews suggested no significant cognitive decline. Conclusions This study highlights the potential of VMAT with HS as a promising approach to CRT for ALL patients in reducing the risk of NC side effects. The absence of brain relapses and preservation of NC function are encouraging findings, though larger studies are necessary to establish conclusive evidence.

Modulated Arc Therapy for hippocampal-avoidance whole brain radiation therapy: planning comparison with intensity modulated Radiation Therapy.

This study aimed to evaluate the modulated arc therapy (mARC) technique as a planning and treatment option for hippocampal sparing whole brain radiotherapy (HS-WBRT) following the Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) were selected retrospectively for 15 patients. Two types of plans were created for each patient, namely an intensity-modulated radiation therapy (IMRT) and a mARC plan. IMRT and mARC plans were compared in terms of plan quality indices, absorbed dose to organs at risk (OARs), number of monitor units (MUs), and treatment time. All plans in both techniques were considered clinically acceptable for treatment. However, IMRT plans presented a higher conformity (p = 0.01) as well as a higher homogeneity as compared to mARC plans, but this difference was not statistically significant (p > 0.05). In terms of the preservation of the hippocampus, it was observed that the IMRT plans achieved significantly lower doses for both 100% of its volume and for its maximum dose (p < 0.001). The evaluation of the remaining OARs showed that the IMRT technique resulted in lower doses, and significant differences were observed for the following organs: left cochlea (p < 0.001), left eye (p < 0.001), right eye (p = 0.03), both lenses of the eye (p < 0.001), and right optic nerve (p = 0.02). Despite these differences, the absolute differences in all dosimetric parameters were low enough to bear any clinical relevance. A drastic (close to 65%) and significant (p < 0.001) decrease was observed in the number of MUs for the mARC plans. This resulted in a substantial decrease in treatment time (60.45%, p < 0.001). It is concluded that the mARC technique is a feasible planning and treatment solution for HS-WBRT that meets the RTOG 0933 criteria. The main advantage of using mARC over IMRT for HS-WBRT is the considerable reduction in MUs and treatment time.

Incidence of hippocampal and perihippocampal brain metastases and impact on hippocampal-avoiding radiotherapy: A systematic review and meta-analysis

Background and PurposeIn patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy. Materials and MethodsMEDLINE, Embase, and Scopus were searched with the terms “Hippocampus”, “Brain Neoplasms”, and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included. ResultsForty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 − 27 %) and 9.2 % (3 − 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 − 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17). ConclusionThe overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life.

Neuroprotection in radiotherapy of brain metastases: A pattern-of-care analysis in Germany, Austria and Switzerland by the German Society for radiation Oncology − working group Neuro-Radio-Oncology (DEGRO AG-NRO)

Background and purposeMany patients with solid tumors develop brain metastases (BM). With more patients surviving long-term, preservation of neurocognitive function gains importance. In recent years, several methods to delay cognitive deterioration have been tested in clinical trials. However, knowledge on the extent to which these neuroprotective strategies have been implemented in clinical practice is missing. Materials and methodsWe performed an online survey regarding treatment patterns of BM in German-speaking countries, focused on the use of neuroprotective approaches. The survey was distributed among radiation oncologists (ROs) registered within the database of the German Society for Radiation Oncology (DEGRO). ResultsPhysicians of 78 centers participated in the survey. Whole brain radiotherapy (WBRT) is still preferred by 70 % of ROs over stereotactic radiotherapy (SRT) in patients with 6–10 BM. For 4–5 BM WBRT is preferred by 23 % of ROs. The fraction of ROs using hippocampal sparing (HS) in WBRT has increased to 89 %, although the technique is used on a regular basis only by a minority (26 %). The drug memantine is not widely prescribed (14% of ROs). A trend was observed for university hospitals to implement neuroprotective approaches more frequently. ConclusionThere is considerable heterogeneity regarding the treatment of BM in German-speaking countries and a general standard of care is lacking. Neuroprotective strategies are not yet standard approaches in daily clinical routine, although usage is increasing. Further clinical trials, as well as improvement of technical opportunities and reimbursement, might further shift the treatment landscape towards neuroprotective radiation treatments in the future.

Multi-pathological contributions toward atrophy patterns in the Alzheimer's disease continuum.

Heterogeneity in downstream atrophy in Alzheimer's disease (AD) is predominantly investigated in relation to pathological hallmarks (Aβ, tau) and co-pathologies (cerebrovascular burden) independently. However, the proportional contribution of each pathology in determining atrophy pattern remains unclear. We assessed heterogeneity in atrophy using two recently conceptualized dimensions: typicality (typical AD atrophy at the center and deviant atypical atrophy on either extreme including limbic predominant to hippocampal sparing patterns) and severity (overall neurodegeneration spanning minimal atrophy to diffuse typical AD atrophy) in relation to Aβ, tau, and cerebrovascular burden. We included 149 Aβ + individuals on the AD continuum (cognitively normal, prodromal AD, AD dementia) and 163 Aβ- cognitively normal individuals from the ADNI. We modeled heterogeneity in MRI-based atrophy with continuous-scales of typicality (ratio of hippocampus to cortical volume) and severity (total gray matter volume). Partial correlation models investigated the association of typicality/severity with (a) Aβ (global Aβ PET centiloid), tau (global tau PET SUVR), cerebrovascular (total white matter hypointensity volume) burden (b) four cognitive domains (memory, executive function, language, visuospatial composites). Using multiple regression, we assessed the association of each pathological burden and typicality/severity with cognition. (a) In the AD continuum, typicality (r = -0.31, p < 0.001) and severity (r = -0.37, p < 0.001) were associated with tau burden after controlling for Aβ, cerebrovascular burden and age. Findings imply greater tau pathology in limbic predominant atrophy and diffuse atrophy. (b) Typicality was associated with memory (r = 0.49, p < 0.001) and language scores (r = 0.19, p = 0.02). Severity was associated with memory (r = 0.26, p < 0.001), executive function (r = 0.24, p = 0.003) and language scores (r = 0.29, p < 0.001). Findings imply better cognitive performance in hippocampal sparing and minimal atrophy patterns. Beyond typicality/severity, tau burden but not Aβ and cerebrovascular burden explained cognition. In the AD continuum, atrophy-based severity was more strongly associated with tau burden than typicality after accounting for Aβ and cerebrovascular burden. Cognitive performance in memory, executive function and language domains was explained by typicality and/or severity and additionally tau pathology. Typicality and severity may differentially reflect burden arising from tau pathology but not Aβ or cerebrovascular pathologies which need to be accounted for when investigating AD heterogeneity.

CLO24-078: Hippocampal Optimization and Dosimetric Analysis on Feasibility of Hippocampal Sparing in Primary Gliomas-A Retrospective Dosimetric Study in a Tertiary Care Center.

CLO24-078: Hippocampal Optimization and Dosimetric Analysis on Feasibility of Hippocampal Sparing in Primary Gliomas-A Retrospective Dosimetric Study in a Tertiary Care Center.

Dosimetric evaluation of a hybrid treatment planning for whole-brain radiation with hippocampal sparing

Dosimetric evaluation of a hybrid treatment planning for whole-brain radiation with hippocampal sparing

Hippocampal sparing in whole-brain radiotherapy for brain metastases: controversy, technology and the future.

Whole-brain radiotherapy (WBRT) plays an irreplaceable role in the treatment of brain metastases (BMs), but cognitive decline after WBRT seriously affects patients' quality of life. The development of cognitive dysfunction is closely related to hippocampal injury, but standardized criteria for predicting hippocampal injury and dose limits for hippocampal protection have not yet been developed. This review systematically reviews the clinical efficacy of hippocampal avoidance - WBRT (HA-WBRT), the controversy over dose limits, common methods and characteristics of hippocampal imaging and segmentation, differences in hippocampal protection by common radiotherapy (RT) techniques, and the application of artificial intelligence (AI) and radiomic techniques for hippocampal protection. In the future, the application of new techniques and methods can improve the consistency of hippocampal dose limit determination and the prediction of the occurrence of cognitive dysfunction in WBRT patients, avoiding the occurrence of cognitive dysfunction in patients and thus benefiting more patients with BMs.

Unilateral hippocampal sparing during whole brain radiotherapy for multiple brain metastases: narrative and critical review.

The landscape of brain metastases radiotherapy is evolving, with a shift away from whole-brain radiotherapy (WBRT) toward targeted stereotactic approaches aimed at preserving neurocognitive functions and maintaining overall quality of life. For patients with multiple metastases, especially in cases where targeted radiotherapy is no longer feasible due to widespread dissemination, the concept of hippocampal sparing radiotherapy (HA_WBRT) gains prominence. In this narrative review we explore the role of the hippocampi in memory formation and the implications of their postradiotherapy lateral damage. We also consider the potential advantages of selectively sparing one hippocampus during whole-brain radiotherapy (WBRT). Additionally, by systematic evaluation of relevant papers published on PubMed database over last 20 years, we provide a comprehensive overview of the various changes that can occur in the left or right hippocampus as a consequence of radiotherapy. While it is important to note that various neurocognitive functions are interconnected throughout the brain, we can discern certain specialized roles of the hippocampi. The left hippocampus appears to play a predominant role in verbal memory, whereas the right hippocampus is associated more with visuospatial memory. Additionally, the anterior part of the hippocampus is more involved in episodic memory and emotional processing, while the posterior part is primarily responsible for spatial memory and pattern separation. Notably, a substantial body of evidence demonstrates a significant correlation between post-radiotherapy changes in the left hippocampus and subsequent cognitive decline in patients. In the context of individualized palliative radiotherapy, sparing the unilateral (specifically, the left, which is dominant in most individuals) hippocampus could expand the repertoire of strategies available for adapted WBRT in cases involving multiple brain metastases where stereotactic radiotherapy is not a viable option. Prospective ongoing studies assessing various memory-sparing radiotherapy techniques will define new standard of radiotherapy care of patients with multiple brain metastases.

Dosimetric and radiobiological comparison of IMRT, VMAT, and helical tomotherapy planning techniques in hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases.

To compare treatment planning and dosimetric outcomes for hippocampal sparing whole brain radiotherapy (WBRT) with the simultaneous integrated boost (SIB) in brain metastasis (BM) patients using tumour control probability (TCP) and normal tissue complication probability (NTCP) formalism between IMRT, VMAT, and HT techniques. In this retrospective study, the treatment data of 20 BM patients who typically received whole brain radiation with SIB treatment were used. Prescription doses of 30Gy and 36Gy was delivered in 10 fractions for WBRT and SIB, respectively. Niemierko and LKB models were applied for calculating TCP and NTCP. All the plans were evaluated for the RTOG 0933 protocol criteria and found acceptable. Additionally, the homogeneity of the PTV boost is 0.07 ± 0.01, 0.1 ± 0.04, and 0.08 ± 0.02 for IMRT, VMAT, and HT, respectively (P < 0.05). The percentage of TCP for the PTV boost was 99.99 ± 0.003, 99.98 ± 0.004, and 99.99 ± 0.002 of IMRT, VMAT, and HT, respectively, (P < 0.005). The NTCP value of the lenses was higher with the VMAT plan as compared to IMRT and HT Plans. The hippocampal NTCP values are equal in all three planning proficiencies. The techniques like IMRT, VMAT, and HT can reduce the dose received by hippocampus to the dosimetric threshold during the delivery of WBRT with hippocampal sparing and can simultaneously boost multiple metastases. Overall, the high-quality dose distribution, TCP, and NTCP comparison between all three planning techniques show that the HT technique has better results when compared to the VMAT and IMRT techniques.

Hippocampal region avoidance in whole brain radiotherapy in brain metastases: For all or for some? A real-world feasibility report.

Hippocampal sparing whole-brain radiotherapy (HS-WBRT) showed significantly lower long-term side effects compared to standard WBRT. Aim of this study is to describe a HS-WBRT real-world monoinstitutional experience within a retrospective cohort. Patients who completed HS-WBRT course, with Karnofsky Performance Status ⩾ 60 and radiological diagnosis of brain metastases (BMs) were enrolled. Treatment was performed using helical Tomotherapy scheduled in 30 Gy in 10 or 12 fractions or 25 Gy in 10 fractions. Oncological outcomes were clinically and radiologically assessed every three months. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.3. One hundred and nineteen patients from 2016 to 2020 met inclusion criteria; after a median follow-up of 18 months, 29 patients were alive; 6- and 12-months overall survival rates were 66% and 41%, respectively. HS-WBRT response was assessed for 72 patients. Median time to any progression and intracranial failure (IF) was 4.5 and 13.7 months, respectively. The 6- and 12-month IF rates were 85% and 57%. Among 40 patients (34%) who experienced IF, 17 (42%) were oligometastatic, 23 (58%) polymetastatic and 15/40 developed IF within the hippocampi avoidance zone. No grade (G) ⩾ 2 acute toxicities were reported and one G2 (dizziness) late toxicity was described. HS-WBRT is well tolerated, and despite the hippocampal sparing region, the oncological control is satisfying. Further investigation is warranted to find patients who could most benefit from a HS-WBRT approach.

Dosimetric comparison of hippocampal-sparing technologies in patients with low-grade glioma.

Radiotherapy (RT) plays an integral role in the management of low-grade gliomas (LGG). Late toxicity from RT can cause progressive neurocognitive dysfunction. Radiation-induced damage to the hippocampus (HCP) plays a considerable role in memory decline. Advancements in photon planning software have resulted in the development of multi-criteria optimization (MCO) and HyperArc technologies which may improve HCP sparing while maintaining planning target volume (PTV) target coverage. Three planning methods for hippocampal sparing (HS) were compared, volumetric modulated arc therapy (VMAT) without HS (VMAT_noHS), VMAT with HS (VMAT_HS), MCO with HS (MCO_HS), and HyperArc with HS (HyperArc_HS). Twenty-five patients were identified. The contralateral HCP was spared in 16 patients and bilateral HCP in 9 patients with superiorly located tumors. All 3 HS planning techniques showed significant reductions in dose to the spared HCP in contralateral cases but only VMAT_HS and MCO_HS achieved this in bilateral cases (P < .008). Only MCO_HS was superior to VMAT_HS in lowering the dose to both contralateral HCP and bilateral HCP in all measured metrics (P < .008). PTV and OAR (organ at risk) dose constraints were achieved for all plans. This retrospective dosimetric study demonstrated the feasibility of HS for low-grade glioma. All 3 HS planning techniques achieved significant dose reductions to the spared contralateral hippocampus, but only MCO_HS and VMAT_HS achieved this in bilateral cases. MCO was superior to other planning techniques for sparing both bilateral and contralateral hippocampi.

Dosimetric Comparison of Hippocampal Sparing Whole Brain Radiotherapy by Volumetric Modulated Arc Therapy, Linac-based Intensity-modulated Radiation Therapy and 3-D Conformal Radiation Therapy: A Cross-sectional Study

Introduction: Brain metastases are treated with Whole-Brain Radiotherapy (WBRT) using the 3-D Conformal Radiation Therapy (3DCRT) technique. Attempts have been made to perform dosimetric analysis of WBRT with hippocampal sparing using 3DCRT, Volumetric Modulated Arc Therapy (VMAT), and Linac-based Intensity Modulated Radiation Therapy (linac-based IMRT), anticipating technical challenges during contouring and treatment planning. Aim: To perform a dosimetric analysis and comparison ofhippocampal sparing cranial irradiation by 3DCRT, VMAT, and IMRT treatment plans in brain metastases patients. Materials and Methods: The analytical cross-sectional dosimetric study was conducted from November 2022 to September 2023 at Government Medical College, Kottayam, Kerala, India. Ten patients treated for brain metastases with WBRT using 3DCRT were considered for dosimetric analysis. The Planning Target Volume (PTV) dosimetry and hippocampal dosimetry were studied for all ten patients. The important dosimetric parameters included volume receiving 100% dose, Target Coverage (TC), Homogeneity Index (HI) in PTV dosimetry, the mean hippocampal dose, and maximal hippocampal dose in hippocampal dosimetry. The hippocampus and hippocampal avoidance volume were contoured. Treatment plans for 3DCRT, VMAT, and Linac-based IMRT were generated for each patient’s prescription dose of 30 Gy in 10 fractions. The non-parametric Kruskal-Wallis test was used for data analysis. Results: The mean whole brain Planned Target Volume (PTV) was 1190 cm3 . The mean hippocampal avoidance volume was 30 cm3 , which occupied 2.5% of the whole brain PTV. The average median dose received by the hippocampus was 30.05 Gy, 17.1 Gy, and 17.5 Gy for 3DCRT, Linac-based IMRT, and VMAT, respectively. The mean dose for the hippocampus was 31.03 Gy, 17.7 Gy, and 17.5 Gy for 3DCRT, Linac-based IMRT, and VMAT, respectively (p&lt;0.001). VMAT offered better hippocampal sparing compared to IMRT and 3DCRT. On average, VMAT offered a 2% improvement, and 3DCRT offered a 5% improvement in TC compared to IMRT. The HI of 3DCRT was 0.09, IMRT 0.199, and VMAT 0.150. Conclusion: VMAT and LINAC-based IMRT permit hippocampal-sparing WBRT with adequate target volume coverage and acceptable homogeneity when compared to 3DCRT plans. Thus, the dosimetric study suggests that modern radiotherapy techniques should be advocated for hippocampal-sparing WBRT.

The effect of hippocampal sparing during prophylactic cranial irradiation on the preservation of neurocognitive functions in patients with small cell lung cancer: a preliminary study

The effect of hippocampal sparing during prophylactic cranial irradiation on the preservation of neurocognitive functions in patients with small cell lung cancer: a preliminary study

Whole-brain radiotherapy with hippocampus sparing and simultaneous integrated boost to metastases: A plan quality comparison study between Ethos, HyperArc, VMAT and Tomotherapy

This study provides a concise and structured overview of a dosimetric comparison study conducted to assess the feasibility and effectiveness of 4 advanced radiotherapy techniques in treating brain metastases with hippocampus sparing and simultaneous integrated boost (HS-WBRT+SIB). Eleven patients with brain metastases previously treated with radiotherapy were included in the study. Planning CT scans with 2 mm slice thickness and MR imaging were used for contouring and dose prescription. The bilateral hippocampus and other organs at risk (OARs) were automatically contoured, and hippocampal avoidance regions (HAR) were defined as a 7 mm 3D expansion around the hippocampus. Gross tumor volume for each metastasis (GTVmet) and planning target volume for metastases (PTVmet) were delineated. The whole-brain CTV (CTVWB) and planning target volume for whole brain (PTVWB) were defined accordingly. Treatment planning and optimization were conducted using state-of-the-art radiotherapy techniques: Ethos, HyperArc, VMAT, and Tomotherapy. Tomotherapy achieved the highest D98% for PTVmet, indicating the best metastasis coverage. HyperArc plans showed the highest D98% for PTVWB, suggesting superior whole-brain coverage. Tomotherapy demonstrated significantly lower D98%, D2%, and Dmean values for the hippocampus, indicating its superiority in sparing the hippocampus. VMAT resulted in the lowest D2% values for the eyes, optic nerves, brainstem, and hypophysis, showing the best sparing of these critical structures. Tomotherapy consistently achieved lower Dmean values for parotids, oral cavity, and lips compared to the other techniques. The dosimetric comparison revealed distinct strengths and weaknesses for each radiotherapy technique. Tomotherapy excelled in sparing the hippocampus, while VMAT showed promise in sparing OARs. HyperArc plans demonstrated the best overall whole-brain coverage. These findings should guide clinicians in selecting the most suitable technique based on patient characteristics and institutional resources.

Genetic Drivers of Atypical Alzheimer’s Disease Neuropathologic Change

AbstractBackgroundQuantitative differences in neurofibrillary tangle density are not well captured by more global measures such as Braak staging. Indeed, amongst cases with high Alzheimer’s disease neuropathologic change (ADNC), quantitative differences in the distribution of neurofibrillary tangle density is associated with atypical, non‐amnestic clinical presentations. We sought here to study the effect of TREM2 and APOE risk genotypes on neuropathologically and clinically defined atypical Alzheimer’s disease.MethodsTREM2 variant versus wild‐type autopsy cases with an intermediate to high level of ADNC were identified from the Center for Neurodegenerative Disease Research Brain Bank at the University of Pennsylvania. Archived clinical records were used to classify cases into typical versus atypical AD. Neuropathologic classification of cases into typical versus atypical AD was based on quantification of neurofibrillary tangle density using PHF1 stained sections from neocortical and hippocampal regions. Morphology from Iba1 stained sections was used to quantify microglial reactivity.Results31 AD cases with TREM2 risk genotypes were compared to wild‐type TREM2 AD cases (n = 119). TREM2 variants were associated with a significantly higher proportion of atypical AD clinical phenotypes including behavioral/dysexecutive variants, primary progressive aphasias, posterior cortical atrophy, and others (19.33% versus 48.39%, Fisher’s exact test p = 0.002). These clinical phenotypes were associated with a significantly higher proportion of TREM2 variant cases with neuropathologically defined atypical AD, namely hippocampal sparing AD (8.7% versus 28.57%, Fisher’s exact test p = 0.046). Moreover, the proportion of microglia with a dystrophic morphology correlated with neurofibrillary tangle density and not amyloid burden. Finally, to get a sense of the magnitude of this TREM2 association relative to other genetic risk factors, we observed a non‐significant trend towards the absence of the APOE E4 risk genotype being associated with hippocampal sparing AD.ConclusionsThis clinicopathologic correlation study suggests that TREM2 risk variants are associated with clinically and neuropathologically defined atypical AD. Given that both TREM2 and APOE affect microglial reactivity to amyloid, the observed tendency towards TREM2 variant cases exhibiting hippocampal sparing AD suggests that altered microglial reactivity to amyloid may change downstream tauopathy patterns leading to atypical AD clinical phenotypes.