Hippocampal-sparing Whole Brain Radiotherapy Research Articles

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.

Feasibility of board tilt angle on critical organs during hippocampus-sparing whole-brain radiotherapy

The objective of this study was to investigate the impact of altering the board angle on critical organ doses during whole-brain irradiation. Tomography images of the head region of the rando phantom were taken at angles of 0°, 10°, 20°, 30°, and 40°. Target volume (PTV) and organ at risk (OAR) contours were created on CT images using RTOG 0933 criteria. Tomography images of the head region of the rando phantom were taken at angles of 0°, 10°, 20°, 30°, and 40°. Target volume (PTV) and critical organ contours were created on CT images using RTOG 0933 criteria. During this comparative study, we aimed to achieve a standardized dose distribution in the PTV. We evaluated the doses received by D2 (minimum dose received by 2% of the target volume), D98 (minimum dose received by 98% of the target volume), D50 (dose received by 50% of the target volume), and organs at risk (OAR) in the PTV using CT scans taken at different angles. Additionally, we compared the homogeneity index (HI), conformity index (CI), and treatment time (MU) values. This method aimed to decrease the dose of the OAR region near the target volume, specifically the hippocampus. Our findings indicate that a board angle of 300 offers the greatest protection in terms of critical organ doses.

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 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.

Dosimetric comparison of coplanar and noncoplanar volumetric modulated arc therapy for hippocampal-sparing whole-brain radiation therapy

Whole brain radiation therapy with hippocampal-sparing (HS-WBRT) is a novel treatment of brain metastases, which can relieve symptoms reduce recurrence in the central nervous system, and spare the hippocampus without compromising target coverage. This study aims to find out the superior combination of the treatment planning system and linear accelerator between Eclipse (version 15.6) with TrueBeam and uRT-TPOIS (vision R001.4) with uRT-linac 506c in HS-WBRT. The coplanar and noncoplanar volumetric modulated arc therapy (VMAT) for HS-WBRT plans were evaluated and compared on both combinations, respectively. Twenty patients for HS-WBRT were retrospectively selected at Peking Union Medical College Hospital (PUMCH) from 2021 to 2022. The coplanar and noncoplanar HS-WBRT treatment plans were designed by Eclipse and uRT-TPOIS referring to RTOG 0933 dose criteria, and their dosimetry parameters were compared. In addition, the plan complexity, monitor units, and beam-on time were recorded for Eclipse plans delivered on TrueBeam and uRT-TPOIS plans delivered on uRT-linac 506c. The results demonstrated that the dosimetric criteria of 4 types of HS-WBRT plans could meet the requirements of RTOG 0933. In terms of target coverage, dosimetric indexes of Eclipse plans and uRT-TPOIS plans were comparable, and the former is slightly better. As for metrics of organs-at-risk protection, coplanar and noncoplanar plans conducted by uRT-TPOIS were greatly superior to those by Eclipse. For coplanar and noncoplanar plans designed by the same treatment planning system, most of the dosimetric indexes had no significant difference. The monitor units of uRT-TPOIS plans was higher than that of Eclipse plans, but the modulation complexity of them were close, and uRT-TPOIS with uRT-linac 506c significantly reduced beam-on-time consumption by 9% on average for coplanar plans and 26% for noncoplanar plans compared to Eclipse with TrueBeam. This study firstly compared the coplanar and noncoplanar HS-WBRT treatment plans between Eclipse with TrueBeam and uRT-TPOIS with uRT-linac 506c in terms of dosimetry indexes, modulation complexity, and time consumption. It is shown that the radiation treatment solution of uRT-TPOIS with uRT-linac 506c is comparable with Eclipse with TrueBeam in terms of planning design, and significantly reduced the delivery time, which can be applied in clinical practice and promoted as a treatment format.

Hippocampal Sparing Whole Brain Radiation Therapy: 2 Arc Coplanar and 4 Arc Noncoplanar Planning Comparison

Whole brain radiation therapy (WBRT) has been shown to provide palliation but with negative neurocognitive effects associated with radiation-induced damage to the hippocampus. Sparing of the hippocampus has been shown to reduce the risk of neurocognitive deficit. Hippocampal sparing WBRT plan optimization is commonly done using 2 arc coplanar technique. The purpose of this work is to show that 4 arc noncoplanar plans will improve hippocampal sparing without compromising PTV coverage. Retrospective WBRT with hippocampal sparing using 2 arc coplanar and 4 arc noncoplanar VMAT technique were done on 10 patients previously treated for intracranial lesions. CT and MRI fused images were used to delineate the whole brain and hippocampus. Strictly following RTOG 0933 atlas guidelines, the hippocampus was manually delineated by a single Radiation Oncologist. Plans with prescription dose of 30 Gy in 10 fractions were generated using the 2 techniques. The 4 arc noncoplanar plan included 2 partial field arcs with couch angle at 90 degrees and 2 coplanar arcs. The 2 noncoplanar partial arcs consisted of a clockwise arc and a counterclockwise arc with gantry angles between 5 and 179 degrees. Lens were kept to < 7 Gy and pituitary gland to < 30 Gy. Dosimetric parameters from both techniques were compared by paired t-test. Radiation dose to the hippocampus was significantly reduced using 4 arc noncoplanar plan when compared to 2 arc coplanar plan. While hippocampus D100% were similar (7.25 Gy vs 7.32 Gy, p = 0.557), the mean dose (9.46 Gy vs 9.87 Gy, p = 0.003) and D0.03cc (12.48 Gy vs 12.94 Gy, p < 0.001) were significantly reduced with 4 arc noncoplanar plans. Whole brain PTV coverage remained at V100% = 95% for both techniques. However, the 4 arc noncoplanar plans showed significantly improved D2% (32.56 Gy vs 32.97 Gy, P = 0.003), D98% (28.11 Gy vs 27.91 Gy, P = 0.01), and homogeneity index (0.141 vs 0.159, P < 0.001). The 4 arc noncoplanar plans improved hippocampal sparing without compromising PTV coverage or compromise to other nearby organs at risk.

Dosimetric comparison between RapidArc and HyperArc in hippocampal-sparing whole-brain radiotherapy with a simultaneous integrated boost

The HyperArc technique is known for generating high-quality radiosurgical treatment plans for intracranial lesions or hippocampal-sparing whole-brain radiotherapy (WBRT). However, there is no reported feasibility of using the HyperArc technique in hippocampal-sparing WBRT with a simultaneous integrated boost (SIB). This study aimed to compare dosimetric parameters of 2 commercially-available volumetric-modulated arc radiotherapy techniques, HyperArc and RapidArc, when using hippocampal-sparing WBRT with a SIB to treat brain metastases.Treatment plans using HyperArc and RapidArc techniques were generated retrospectively for 19 previously treated patients (1 to 3 brain metastases). The planning target volumes for the whole brain (excluding the hippocampal avoidance region; PTVWB) and metastases (PTVmet) were prescribed 25 and 45 Gy, respectively, in 10 fractions. Each plan included homogeneous and inhomogeneous delivery to the PTVmet. Dosimetric parameters for the target (conformity index [CI], homogeneity index [HI], target coverage [D95%]), and nontarget organs at risk were compared for the HyperArc and RapidArc plans.For homogeneous delivery, dosimetric parameters, including mean CI, HI, and target coverage in PTVWB and PTVmet, were superior for HyperArc than RapidArc plans (all p < 0.01). The PTVWB and PTVmet target coverage for HyperArc plans was significantly greater than for RapidArc plans (96.17% vs 93.38%, p < 0.01; 94.02% vs 92.21%, p < 0.01, respectively). HyperArc plans had significantly lower mean hippocampal Dmax and Dmin values than RapidArc plans (Dmax: 15.53 Gy vs, 16.71 Gy, p < 0.01; Dmin: 8.33 Gy vs 8.93 Gy, p < 0.01, respectively). Similarly, inhomogeneous delivery of hyperArc produced a superior target and lower hippocampal dosimetric parameters than RapidArc, except for the HI of PTVmet (all p < 0.01).HyperArc generated superior conformity and target coverage with lower hippocampal doses than RapidArc. HyperArc could be an attractive technique for hippocampal-sparing WBRT with an SIB.

Hippocampal-sparing whole-brain radiotherapy under coplanar or noncoplanar VMAT.

Whole-brain radiotherapy (WBRT) can alleviate symptoms in patients with brain metastases. However, WBRT may damage the hippocampus. Volumetric modulated arc therapy (VMAT) can achieve a suitable coverage of the target region and a more conforming dose distribution whereas decreasing the dose to organs-at-risk (OARs). Herein, we aimed to compare the differences between treatment plans utilizing coplanar VMAT and noncoplanar VMAT in hippocampal-sparing WBRT (HS-WBRT). Ten patients were included in this study. For each patient, the Eclipse A10 treatment planning system was used to generate 1 coplanar VMAT (C-VMAT) and 2 noncoplanar VMAT treatment plans with various beam angles (noncoplanar VMAT A [NC-A] and noncoplanar VMAT B [NC-B]) for HS-WBRT. The prescribed dose was 30 Gy in 12 fractions. Treatment plans were established based on the OAR dose constraints of the Radiation Therapy Oncology Group 0933 (RTOG 0933). Parameters such as the global maximum dose, dose conformity, dose homogeneity of plans, and OAR doses were evaluated. The maximum biologically equivalent doses in 2-Gy fractions (EQD2) of OARs in C-VMAT were 9.17 ± 0.61, 42.79 ± 2.00, and 42.84 ± 3.52 Gy in the hippocampus, brain stem, and optic chiasm, respectively, which were the lowest among the 3 treatment plans. There was no significant difference in dose conformity among the 3 treatment plans. However, NC-A had a slightly better conformity than C-VMAT and NC-B. NC-A had the best homogeneity, and NC-B had the worst homogeneity (p = 0.042). NC-A and NC-B had the lowest and highest global dose maximum, respectively. Therefore, NC-A, which had an intermediate performance in terms of OAR doses, had the best quality parameters. We used the quality score table based on the p-value to evaluate the significant difference between each treatment technique from the multiparameter results. In terms of treatment plan parameters, only NC-A received a score of 2; for OAR doses, C-VMAT, NC-A, and NC-B received a score of 6, 3, and 5, respectively. For the overall evaluation, C-VMAT, NC-A, and NC-B received a total score of 6, 5, and 5, respectively. Rather than noncoplanar VMAT, 3 full-arc C-VMATs should be utilized in HS-WBRT. C-VMAT can simultaneously maintain treatment plan quality and decrease patient alignment time and total treatment time.

P11.57.B Combined surgery and radiotherapy for brain metastases. Retrospective analysis of a consecutive cohort of 118 patients

Abstract Background Despite current advances in systemic therapy for brain metastases, neurosurgery remains the preferred method of choice in patients with limited brain metastases. Postoperative radiotherapy indicated to reduce the risk of local recurrence is recommended in all patients after surgery. The aim of this retrospective study is to describe clinical characteristics and survival outcomes in consecutive cohorts of patients treated by this combined local treatment. Material and Methods Clinical data were retrieved from electronic medical records for consecutive patients who underwent surgery for brain metastases between 2007 and 2019. All patients underwent postsurgery radiotherapy. Local progression free survival (localPFS) evaluated the local control at the operated site. DistalPFS at the other parts of the brain. Univariable and multivariable analysis of survival characteristics was performed. The Median follow-up was 49 months. Results A total of 118 patients were included (54% women, median age 60 years, median Karnofsky index 80% at the time of radiotherapy). Single metastasis was treated in 66%, while 11% presented with more than 3 metastases. The most common primary diagnosis was lung cancer (33%) and breast (20%). Radical surgery was achieved in 92/117 (79 % of patients). In total, only 48/118 (41%) of patients underwent targeted radiotherapy (mostly fractionated stereotactic radiotherapy of 25Gy in 5 fractions). Significantly more patients (p&amp;lt;0.001) underwent targeted radiotherapy during 2016-2019 (45/48) compared to 2007-2015 period (3/48). A total of 20% of those who underwent postsurgery whole brain radiotherapy (WBRT) had a special technic of hippocampal sparing WBRT of WBRT with simultaneous integrated boost to remaining brain metastases. Median overall survival (OS) for all patients was 9 months (6.2 - 12), median localPFS 22 months (14 - not reached), median distalPFS 11 months (6.8 - 27) and median extracranialPFS 11 months (5.9 - 15). A significant (p=0.00017) difference in OS was while grouping patients according to Graded prognostic assessment (brainmetgpa.com). Significantly better OS was in the cohort of patients with targeted stereotactic radiotherapy (17months) vs. WBRT (5.6 months; p=0.00069) with no difference in local PFS, distal PFS or extracranialPFS. Multivariable analysis revealed type or radiotherapy, control of primary tumor, number of brain metastases 1-2 and the possibility to discontinue corticosteroids to be independent variables for OS. Conclusion Targeted fractionated stereotactic radiotherapy to tumor bed after metastasectomy was associated with improved survival compared to postsurgery WBRT in our cohort. Stereotactic radiotherapy should be preferred in all workplaces with adequate radiotherapy technology. Supported by Ministry of Health of the Czech Republic AZV, NV18-03-00469 and NV18-03-00398.

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

Simple SummaryDecline in cognitive function is a major problem for patients undergoing whole-brain radiotherapy (WBRT). Scientific interest has increased due to the high dropout rate of patients in the first months after WBRT and the early onset of cognitive decline. Therefore, the study of antiglutamatergic pharmacological prophylaxis and hippocampal-sparing WBRT techniques has been deepened based on the knowledge of the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline. In order to provide a summary of the evidence in this field, and to foster future research in this setting, this literature review presents current evidence on the prevention of radiation-induced cognitive decline and particularly on the role of memantine.Preserving cognitive functions is a priority for most patients with brain metastases. Knowing the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline (CD) led to testing both the antiglutamatergic pharmacological prophylaxis and hippocampal-sparing whole-brain radiotherapy (WBRT) techniques. These studies showed a relative reduction in CD four to six months after WBRT. However, the failure to achieve statistical significance in one study that tested memantine alone (RTOG 0614) led to widespread skepticism about this drug in the WBRT setting. Moreover, interest grew in the reasons for the strong patient dropout rates in the first few months after WBRT and for early CD onset. In fact, the latter can only partially be explained by subclinical tumor progression. An emerging interpretation of the (not only) cognitive impairment during and immediately after WBRT is the dysfunction of the limbic and hypothalamic system with its immune and hormonal consequences. This new understanding of WBRT-induced toxicity may represent the basis for further innovative trials. 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, the modern and advanced WBRT techniques based on both hippocampal-sparing and hypothalamic-pituitary-sparing, currently evaluated only in planning studies; (iv) test new timings of antiglutamatergic drugs administration aimed at preventing not only late toxicity but also acute effects.

Hybrid split-arc partial-field volumetric modulated arc therapy: an improved beam arrangement for linear accelerator-based hippocampal-avoidance whole brain radiation therapy

BackgroundThis technical note aims to verify the hippocampus and adjacent organs at risk (OARs) sparing ability of an improved beam arrangement, namely hybrid split-arc partial-field volumetric modulated arc therapy (VMAT) (Hsapf-VMAT) during whole brain radiation therapy (WBRT).Materials and methodsComputed tomography simulation images of 22 patients with brain metastases were retrieved in this retrospective planning study. The hippocampus was manually delineated according to the criterion of RTOG 0933. Plans delivering 30 Gy in 10 fractions were generated for each patient using split-arc partial-field VMAT (sapf-VMAT) and Hsapf-VMAT. The sapf-VMAT plans consisted of 4 arc fields of 179.9° each with reduced field size. The Hsapf-VMAT consisted of 4 arc fields similar to sapf-VMAT in addition to 2 lateral opposing static fields. Statistical comparisons between treatment plans of both techniques were performed using the paired t-test at 5% level significance.ResultsThe results demonstrated that Hsapf-VMAT can achieve superior dose sparing in hippocampus which is comparable to sapf-VMAT (p > 0.05). In both eyes, Hsapf-VMAT had significantly lower Dmean and Dmax compared to sapf-VMAT (p < 0.005). Decrease in Dmax of both lenses using Hsapf-VMAT (p < 0.005) were statistically significant when compared to sapf-VMAT. Hsapf-VMAT demonstrated significant reduction of Dmean and Dmedian to the optic nerves (p < 0.05). Whole brain planning target volume (PTV) coverage was not compromised in both techniques.ConclusionThe present study adopts a hybrid technique, namely Hsapf-VMAT, for hippocampal sparing WBRT. Hsapf-VMAT can achieve promising dose reduction to the hippocampus, both eyes and lenses. Therefore, Hsapf-VMAT can be considered an improved version of sapf-VMAT.

Improving on whole-brain radiotherapy in patients with large brain metastases: A planning study to support the AROMA clinical trial

PurposeTo develop a novel dose-escalated volumetric modulated arc therapy (VMAT) strategy for patients with single or multiple large brain metastases which can deliver a higher dose to individual lesions for better local control (LC), and to compare dosimetry between whole brain radiotherapy (WBRT), hippocampal-sparing whole brain radiotherapy (HS-WBRT) and different VMAT-based focal radiotherapy approaches. Methods and materialsWe identified 20 patients with one to ten brain metastases and at least one lesion larger than 15 cm3 who had received WBRT as part of routine care. For each patient, we designed and evaluated five radiotherapy treatment plans, including WBRT, HS-WBRT and three VMAT dosing models. A dose of 20 Gy in 5 fractions was prescribed to the whole brain or target volumes depending on the plan, with higher doses to smaller lesions and dose-escalated inner planning target volumes (DE-iPTV) in VMAT plans, respectively. Treatment plans were evaluated using the efficiency index, mean dose and D0.1 cc to the target volumes and organs at risk. ResultsCompared with WBRT, VMAT plans achieved a significantly more efficient dose distribution in brain lesions, especially with our DE-iPTV model, while minimising the dose to the normal brain and other organs at risks (OARs) (p < 0.05). ConclusionsVMAT plans obtained higher doses to brain metastases and minimised doses to OARs. Dose-escalated VMAT for larger lesions allows higher radiotherapy doses to be delivered to larger lesions while maintaining safe doses to OARs.

Oncological Outcomes After Hippocampus-Sparing Whole-Brain Radiotherapy in Cancer Patients With Newly Diagnosed Brain Oligometastases: A Single-Arm Prospective Observational Cohort Study in Taiwan.

BackgroundPromisingly, the technique of hippocampus sparing during WBRT (HS-WBRT) might preserve NCFs. In this research, we examined oncological outcomes, with emphasis on neurologic/non-neurologic causes of death, CNS progression, and leptomeningeal disease (LMD) recurrence in cancer patients who underwent HS-WBRT.MethodsOne hundred and fourteen cancer patients with newly diagnosed brain oligometastases underwent HS-WBRT were consecutively enrolled. The cumulative incidence of cancer-specific deaths (neurologic or non-neurologic), LMD recurrence, and the composite endpoint of CNS progression (CNS-CE) as the first event were computed with a competing-risks approach to characterize the oncological outcomes after HS-WBRT.ResultsPatients with intact brain metastases had a significantly increased likelihood of dying from non-neurologic causes of death associated with early manifestation of progressive systemic disease (hazard ratio for non-neurologic death, 1.78; 95% CI, 1.08–2.95; p = 0.025; competing-risks Fine–Gray regression), which reciprocally rendered them unlikely to encounter LMD recurrence or any pattern of CNS progression (HR for CNS-CE as the first event, 0.13; 95% CI, 0.02–0.97; p = 0.047; competing-risks Fine–Gray regression). By contrast, patients with resection cavities post-craniotomy had reciprocally increased likelihood of CNS progression which might be associated with neurologic death eventually.ConclusionsPatterns of oncological endpoints including neurologic/non-neurologic death and cumulative incidence of CNS progression manifesting as LMD recurrence are clearly clarified and contrasted between patients with intact BMs and those with resection cavities, indicating they are clinically distinct subgroups.Trial RegistrationClinicalTrials.gov, Identifier: NCT02504788, NCT03223675.

Plan Quality Comparison Between Hippocampus-Sparing Whole-Brain Radiotherapy Treated With Halcyon and Tomotherapy Intensity-Modulated Radiotherapy.

Objective: Hippocampus-sparing whole-brain radiotherapy using Halcyon, an instrument dedicated to volumetric modulated arc therapy, has not been studied till date; hence, we aimed to examine whether it can meet the RTOG0933 criteria. Based on this, we compared Halcyon to Tomotherapy, which also uses an O-ring-type linear accelerator. Methods: This exploratory, experimental, and retrospective study used 5 sets of computed tomography images in the head area to investigate the planning target volume, hippocampal doses, and irradiation time. Calculations were performed from 1 to 4 arcs to determine the optimal number of arcs in the Halcyon plan, which were compared to those of Tomotherapy. Results: The Radiation Therapy Oncology Group 0933 criteria could not be satisfied in Halcyon with 1 arc. With 2 arcs, the condition Dmax<16 Gy was not satisfied for 1 case in the hippocampus. Since there were no significant differences between 3 and 4 arcs, including the irradiation time, 3 arcs were considered the best. We compared Halcyon at 3 arcs with tomotherapy and found that tomotherapy was inferior to Halcyon at D98%; however, it was superior to Halcyon in other dose parameters. In contrast, the irradiation time in Halcyon was overwhelmingly superior, with the irradiation time for Halcyon being 1/ninth the time for Tomotherapy. Conclusion: Halcyon was effective in handling hippocampus-sparing whole-brain radiotherapy. We believe that 3-arc radiation is best suited for this procedure. Although Halcyon was inferior to Tomotherapy in terms of dose distribution excluding D98%, it was overwhelmingly superior in terms of irradiation time.

Automatic segmentation of hippocampus in hippocampal sparing whole brain radiotherapy: A multitask edge-aware learning.

This study aimed to improve the accuracy of the hippocampus segmentation through multitask edge-aware learning. We developed a multitask framework for computerized hippocampus segmentation. We used three-dimensional (3D) U-net as our backbone model with two training objectives: (a) to minimize the difference between the targeted binary mask and the model prediction; and (b) to optimize an auxiliary edge-prediction task which is designed to guide the model detection of the weak boundary of the hippocampus in model optimization. To balance the multiple task objectives, we proposed an improved gradient normalization by adaptively adjusting the weight of losses from different tasks. A total of 247 T1-weighted MRIs including 131 without contrast and 116 with contrast were collected from 247 patients to train and validate the proposed method. Segmentation was quantitatively evaluated with the dice coefficient (Dice), Hausdorff distance (HD), and average Hausdorff distance (AVD). The 3D U-net was used for baseline comparison. We used a Wilcoxon signed-rank test to compare repeated measurements (Dice, HD, and AVD) by different segmentations. Through fivefold cross-validation, our multitask edge-aware learning achieved Dice of 0.8483±0.0036, HD of 7.5706±1.2330mm, and AVD of 0.1522±0.0165mm, respectively. Conversely, the baseline results were 0.8340±0.0072, 10.4631±2.3736mm, and 0.1884±0.0286mm, respectively. With a Wilcoxon signed-rank test, we found that the differences between our method and the baseline were statistically significant (P<0.05). Our results demonstrated the efficiency of multitask edge-aware learning in hippocampus segmentation for hippocampal sparing whole-brain radiotherapy. The proposed framework may also be useful for other low-contrast small organ segmentations on medical imaging modalities.

Hippocampus-sparing whole-brain radiotherapy: dosimetric comparison between non-coplanar and coplanar planning

Hippocampus-sparing whole-brain radiotherapy: dosimetric comparison between non-coplanar and coplanar planning

Use of a Head-Tilting Baseplate During Tomotherapy to Shorten the Irradiation Time and Protect the Hippocampus and Lens in Hippocampal Sparing-Whole Brain Radiotherapy

Purpose:The aim of this study is to comparatively examine the possibility of reducing the exposure dose to organs at risk, such as the hippocampus and lens, and improving the dose distribution of the planned target volume with and without the use of a head-tilting base plate in hippocampal-sparing whole-brain radiotherapy using tomotherapy.Methods:Five paired images of planned head computed tomography without and with tilt were analyzed. The hippocampus and planning target volume were contoured according to the RTOG 0933 contouring atlas protocol. The hippocampal zone to be avoided was delineated using a 5-mm margin. The prescribed radiation dose was 30 Gy in 10 fractions. The absorbed dose to planning target volume dose, absorbed dose to the organ at risk, and irradiation time were evaluated. The paired t-test was used to analyze the differences between hippocampal-sparing whole-brain radiotherapy with head tilts and without head tilts.Results:Hippocampal-sparing whole-brain radiotherapy with tilt was not superior in planning target volume doses using the homogeneity index than that without tilt; however, it showed better values, and for Dmean and D2%, the values were closer to 30 Gy. Regarding the hippocampus, dose reduction with tilt was significantly greater at Dmax, Dmean, and Dmin, whereas regarding the lens, it was significantly greater at Dmax and Dmin. The irradiation time was also predominantly shorter.Conclusion:In our study, a tilted hippocampal-sparing whole-brain radiotherapy reduced the irradiation time by >10%. Therefore, our study indicated that hippocampal-sparing whole-brain radiotherapy with tomotherapy should be performed with a tilt. The head-tilting technique might be useful during hippocampal-sparing whole-brain radiotherapy. This method could decrease the radiation exposure time, while sparing healthy organs, including the hippocampus and lens.

Influence of Modulation Factor on Treatment Plan Quality and Irradiation Time in Hippocampus-Sparing Whole-Brain Radiotherapy Using Tomotherapy.

Objectives: Hippocampus-sparing whole-brain radiotherapy (HS-WBRT) using tomotherapy is known to provide a better dose distribution than volumetric-modulated arc therapy but requires an extended irradiation time. The present study aimed to investigate whether irradiation time can be shortened by reducing the modulation factor (MF) without losing the target dose distribution. Methods: Using six tilted computed tomography images in the head area, the planning target volume (PTV) and hippocampal doses, and the irradiation time was investigated with a jaw width of 1 cm, a pitch of 0.200, and the MF changed from 3.0 to 2.6, 2.2, 1.8, and 1.4. Results: No significant changes in the PTV or hippocampus were found with MF in the range from 3.0 to 1.8, but marked deterioration was found with that of 1.4. The irradiation time showed a linear relationship with the MF within the range from 3.0 to 1.8, with 1334, 1158, 986, and 817 s at modulation factors of 3.0, 2.6, 2.2, and 1.8, respectively. However, when the MF was 1.4, the irradiation time was 808 s. Conclusions: When HS-WBRT is performed with a tilted body position and a jaw width of 1 cm, with a MF of 1.8, a favorable balance between dose parameters and irradiation time is achieved, whereas with a MF of 1.4, the quality of the radiotherapy plan deteriorates, and the irradiation time is approximately the same as that with a MF of 1.8.

Executive summary from American Radium Society's appropriate use criteria on neurocognition after stereotactic radiosurgery for multiple brain metastases.

The American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines. The panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness. The panel agreed that SRS alone is usually appropriate for those with good performance status and 2-10 asymptomatic BM, and usually not appropriate for >20 BM. For 11-15 and 16-20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2-4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options. For patients with 2-10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.

Use of a head-tilting baseplate during volumetric-modulated arc therapy (VMAT) to better protect organs at risk in hippocampal sparing whole brain radiotherapy (HS-WBRT).

Coplanar arcs are used with limited arc range to prevent direct beam entrance through the lens, which is challenging for satisfactory planning of hippocampal sparing in whole brain radiotherapy (HS-WBRT) with VMAT. We evaluated the dosimetric impact of applying a head-tilting technique during VMAT, which allows unrestricted use of the arc range. Twenty patients with multiple brain metastases who had received two computed tomography (CT)-simulation sessions between January 2016 and December 2018 were included. One session was delivered in a traditional supine position; the other was delivered with a tilting acrylic supine baseplate (MedTec, USA) to elevate the patients' head by 40°. For each patient, a VMAT without (sVMAT) and with head-tilting (htVMAT) plan was generated. Conformity index (CI), homogeneity index (HI), and organ at risk (OAR) dose were evaluated. The Wilcoxon-signed test was used to compare the effect between two plans. The mean CI was 0.860±0.007 and 0.864±0.008 (p<0.05), and mean HI was 0.179±0.020 and 0.167±0.021 (p<0.05) for sVMAT and htVMAT, respectively. The mean dose to the hippocampus (9.91±0.30 Gy) was significantly lower in htVMAT than in sVMAT (10.36±0.29 Gy, P<0.05). htVMAT was associated with significantly reduced mean dose to the parotid gland, and right and left lens (4.77±1.97 Gy vs. 5.92±1.68 Gy, p<0.05; 3.29±0.44 Gy vs. 7.22±1.26 Gy, p<0.05; 3.33±0.45 Gy vs. 6.73±1.01 Gy, p<0.05, respectively). This is the first study to demonstrate that the head-tilting technique might be useful for HS-WBRT planning with VMAT. This method could remove the limitations associated with the arc range, resulting in improved dose distribution and conformity, while sparing healthy organs, including the hippocampus, lens, and parotid gland.