Hippocampal Avoidance Region Research Articles

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.

Distribution and Failure Patterns of Primary Central Nervous System Lymphoma Related to Hippocampus

Hippocampus (HC) injury by conventional whole brain radiotherapy (C-WBRT) contributes to the neurocognitive decline in primary central nervous system lymphoma (PCNSL). Hippocampal avoidance (HA-WBRT) could minimize neurocognitive impairment by reducing the radiation dose to HC. However, its feasibility in PCNSL has not been examined regarding the incidence of HC involvement and failures. In this retrospective study, we assessed the risk of hippocampal area involvement at diagnosis and after treatments in PCNSL patients. We identified 278 immunocompetent PCNSL patients diagnosed between 2000 and 2020. After high dose methotrexate-based induction chemotherapy, patients were observed or given consolidation therapy including RT, cytarabine alone, or autologous stem cell transplantation (ASCT). HC was contoured on T1 MRI image and expanded with a 5mm margin, generating hippocampal avoidance region (HAR). The extent of initial and recurrent lesions was evaluated using pre-induction and post-consolidation T1 contrast-enhanced MRI images. HC failure was defined as recurrence or progression at HAR and those who progressed after induction were excluded. The median follow up was 38.7 months (3.1-239.4). Of 278 patients diagnosed with PCNSL, 39.9% of them had initial lesions at HAR (Figure 1a). After induction therapy, 212 evaluable patients received following treatments: RT (n = 145, 68.4%) consisting of C-WBRT (n = 114), HA-WBRT (n = 23), and focal RT (n = 8), observation (n = 38, 17.9%), cytarabine only (24, 11.3%), and ASCT (n = 5, 2.4%). Intracranial failures occurred in 47.6% (n = 101) of patients, with 33.7% (n = 34) of them in HAR (Figure 1b). The multivariate analysis identified multifocal disease (HR 3.86, 95% CI 1.15-9.73, p = 0.004) as the only factor associated with the risk of HC failure. Those with unifocal lesion outside HAR showed the lowest HC failure rate, 7.0%, while the highest HC failure rate, 25.4% was observed in the subgroup with multifocal disease within HAR at diagnosis (Figure 2a). In the lowest risk group (unifocal lesion outside HAR, n = 66), C-WBRT was not significantly associated with HC failure (HR 0.57, CI 0.09-3.33, P = .572, Figure 2b) or intracranial failure (HR 0.88, CI 0.40-1.91, P = .748). Our data suggest the HA-WBRT could be explored in patients whose lesion is unifocal and located outside HAR. For patients without initial HAR involvement, hippocampal including WBRT did not significantly change HC failure. Further prospective study will be warranted to assess the feasibility of HA-WBRT in the subgroup with low risk of HC failure.

Hippocampal Avoidance Whole BRAIN Radiotherapy (HA-WBRT) with Simultaneous Integrated BOOST (SIB) vs. HA-WBRT in Multiple Brain Metastases: A Dosimetric Comparison

There has been a paradigm shift in managing multiple brain metastases. Various options include SRS, WBRT, and WBRT with Hippocampal avoidance (HA-WBRT). There is no consensus for the treatment of multiple brain metastases (>3 brain metastases). A new technique that has proven feasible is dose escalation in the form of simultaneous integrated boost. The aim of this study was to compare the dosimetry parameters of HA-WBRT plus simultaneous integrated boost versus HA-WBRT alone in multiple brain metastases. In a prospective trial,16 patients with multiple brain metastasis (≥ 3) from various primaries with good performance scores (ECOG PS ≤ 2) are recruited. All patients underwent CT simulation (1.5 mm slice thickness) and RT plans for HA-WBRT with (SIB) and HA-WBRT alone were made. A 5 mm margin was given to the bilateral hippocampus for Hippocampal Avoidance. In the HA-WBRT plan for the PTV i.e., whole brain plus 3 mm margin minus hippocampal avoidance region (H.A.), a dose of 30 Gy in 10 fractions is prescribed over two weeks. In HA-WBRT with SIB, a dose of 30 Gy in 10 fractions over two weeks is prescribed for the PTV, which is the clinical target volume, minus the hippocampal avoidance region (H.A.) minus the PTV Mets (1 mm margin to the GTV). A simultaneous Integrated Boost of 42.5 Gy in 10 # over two weeks is prescribed for PTVmets. Planning was done using a VMAT technique with 6MV F.F.F. beam energy in a treatment planning software. The mean B/L hippocampus volume is 3.47 cc. The mean dose of PTV D98% in HA-WBRT plans is 27.45 Gy, whereas in HA-WBRT with S.I.B. is 27.36 Gy (p = 0.90). V30 mean dose in HA-WBRT plans is 93.35%, and the mean dose in HA-WBRT SIB is 91.87% (p = 0.12). PTV D2% mean dose in HA-WBRT Is 36.06 Gy, and in HA-WBRT -S.I.B., it is 40.58 (p< 0.001). The mean bilateral hippocampus Dmax in HA-WBRT is 14.85 Gy, and in HA-WBRT-SIB is 14.25 Gy (p = 0.35). The mean Bilateral hippocampus D100% is 9.14 Gy in HA-WBRT and 9.01 Gy in HA-WBRT-SIB (p = 0.54). The mean brainstem Dmax in HA-WBRT is 36.82 Gy compared to 38.55 Gy in HA-WBRT-SIB (p = 0.02). In patients planned for a simultaneous boost along with hippocampal sparing whole brain radiotherapy, the mean dose to the hippocampal region did not increase. The Dmax of Brainstem, optic chiasma is significantly higher in HA-WBRT-). Our study, the mean dose to PTVmets is more than 45 Gy and more than 50 Gy to GTV with a BED of more than 65 Gy (α/ß = 10) to the metastases, which is equivalent to some ablative dose regimens. Simultaneous integrated boost along with hippocampal sparing radiotherapy thus helps in sparing the hippocampus and delivering higher doses to the metastases and intermediate doses to the rest of the brain, addressing the microscopic disease.

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.

Distribution and failure patterns of primary central nervous system lymphoma related to the hippocampus: Implications for hippocampal sparing irradiation.

20 Background: Hippocampus (HC) injury by conventional whole brain radiotherapy (C-WBRT) contributes to the neurocognitive decline in primary central nervous system lymphoma (PCNSL). Hippocampal avoidance (HA–WBRT) could minimize neurocognitive impairment by reducing the radiation dose to HC. However, its feasibility in PCNSL has not been examined regarding the incidence of HC involvement and failures. In this retrospective study, we assessed the risk of hippocampal area involvement at diagnosis and after treatments in PCNSL patients. Methods: We identified 278 immunocompetent PCNSL patients diagnosed between 2000 and 2020. After high dose methotrexate-based induction chemotherapy followed by observation or consolidation including RT, cytarabine alone, or autologous stem cell transplantation (ASCT). HC was contoured on T1 MRI image and expanded with a 5mm margin, generating hippocampal avoidance region (HAR). The extent of initial and recurrent lesions was evaluated using pre-induction and post-consolidation T1 contrast-enhanced MRI images. HC failure was defined as recurrence or progression at HAR and those who progressed after induction were excluded. The median follow up was 38.7 months (3.1-239.4). Results: Of 278 patients diagnosed with PCNSL, 39.9% of them had initial lesions at HAR. After induction therapy, 212 evaluable patients received consolidation as follows: RT (n=145, 68.4%) consisting of C-WBRT (n=114), HA-WBRT (n=23), and focal RT (n=8), observation (n=38, 17.9%), cytarabine only (24, 11.3%), and ASCT (n=5, 2.4%). Intracranial failures occurred in 47.6% (n=101) of patients, with 33.7% (n=34) of them in HAR. The multivariate analysis identified multifocal disease (HR 3.86, 95% CI 1.15-9.73, p=0.004) as the only factor associated with the risk of HC failure. Those with unifocal lesion outside HAR showed the lowest HC failure rate, 7.0%, while the highest HC failure rate, 25.4% was observed in the subgroup with multifocal disease within HAR at diagnosis. In the lowest risk group (unifocal lesion outside HAR, n=66), C-WBRT was not significantly associated with HC failure (HR 0.57, CI 0.09-3.33, P=.572) or intracranial failure (HR 0.88, CI 0.40-1.91, P=.748). Conclusions: Our data suggest the HA-WBRT could be explored in patients whose lesion is unifocal and located outside HAR. WBRT, including the hippocampus, did not significantly change HC failure for patients without initial HAR involvement. Further prospective study will be warranted to assess the feasibility of HA-WBRT in the subgroup with low risk of HC failure.

A "Seed-and-Soil" Radiomics Model Predicts Brain Metastasis Development in Lung Cancer: Implications for Risk-Stratified Prophylactic Cranial Irradiation.

Introduction: Brain is a major site of metastasis for lung cancer, and effective therapy for developed brain metastasis (BM) is limited. Prophylactic cranial irradiation (PCI) has been shown to reduce BM rate and improve survival in small cell lung cancer, but this result was not replicated in unselected non-small cell lung cancer (NSCLC) and had the risk of inducing neurocognitive dysfunctions. We aimed to develop a radiomics BM prediction model for BM risk stratification in NSCLC patients. Methods: 256 NSCLC patients with no BM at baseline brain magnetic resonance imaging (MRI) were selected; 128 patients developed BM within three years after diagnosis and 128 remained BM-free. For radiomics analysis, both the BM and non-BM groups were randomly distributed into training and testing datasets at an 70%:30% ratio. Both brain MRI (representing the soil) and chest computed tomography (CT, representing the seed) radiomic features were extracted to develop the BM prediction models. We first developed the radiomic models using the training dataset (89 non-BM and 90 BM cases) and subsequently validated the models in the testing dataset (39 non-BM and 38 BM cases). A radiomics BM score (RadBM score) was generated, and BM-free survival were compared between RadBM score-high and RadBM score-low groups. Results: The radiomics model developed from baseline brain MRI features alone can predict BM development in NSCLC patients. A fusion model integrating brain MRI features with primary tumor CT features (seed-and-soil model) provided synergetic effect and was more efficient in predicting BM (areas under the receiver operating characteristic curve 0.84 (95% confidence interval: 0.80−0.89) and 0.80 (95% confidence interval: 0.71−0.88) in the training and testing datasets, respectively). BM-free survival was significantly shorter in the RadBM score-high group versus the RadBM score-low group (Log-rank, p < 0.001). Hazard ratios for BM were 1.056 (95% confidence interval: 1.044−1.068) per 0.01 increment in RadBM score. Cumulative BM rates at three years were 75.8% and 24.2% for the RadBM score-high and RadBM score-low groups, respectively. Only 1.2% (7/565) of the BM lesions were located within the hippocampal avoidance region. Conclusion: The results demonstrated that intrinsic features of a non-metastatic brain exert a significant impact on BM development, which is first-in-class in metastasis prediction studies. A radiomics BM prediction model utilizing both primary tumor and pre-metastatic brain features might provide a useful tool for individualized PCI administration in NSCLC patients more prone to develop BM.

P03.04.B Garcin syndrome and hippocampal-sparing WBRT: successful resolution of a rare case

Abstract Background first case of a rare Garcin syndrome resolution in a young metastatic breast cancer(BC) patient treated with a hippocampal-sparing approach. Material and Methods we report a case of a 49-year-old caucasian female. The medical record review was relevant for BC diagnoses in 1997, when she was 26yo; complicated by bone and liver metastasis appeared in 2008. In March 2020, she was referred to our department complaining about increasingly worsening left otalgia with initial hearing loss, left facial numbness, and homolateral decreased facial sensitivity, left increased lacrimation, and tingling tongue. Clinical presentation was suggestive for a Guillain-Alajouanine-Garcin Syndrome (Garcin Syndrome), caused by a lytic lesion in the left sphenoid wing. A contrast MRI (02/04/2020) of the brain demonstrated a lytic lesions in the left sphenoid wing, that was noted to infiltrate surrounding bone of the sphenoid sinus wall, including clivus, left pterygoid process and petrous bone; two parietal and occipital bone lesions were identified with a partial leptomeningeal involvement. According to the good PS, she underwent to a hippocampal-sparing WBRT VMAT plus a sequential boost on sphenoid lesion. PTV and OARs were delineated according to a fused planning MRI/CT image. Bilateral hippocampal contours were generated on the set according to RTOG 0933 contouring atlas. After that, a hippocampal avoidance(HA) region was created by expanding the hippocampal contours by 5 mm in all directions according to Brown et al.The PTV-HA was defined as the WB parenchyma, meninges and skull, excluding the HA-region, dose prescription 30Gy/10fx; the PTV-Boost was defined as the sphenoidal metastases, dose prescription of sequential boost was 12Gy/4fx. VMAT was used to deliver the conformal RT plan. Planning priorities that should be followed were:Hippocampus, OpticChiasm, OpticNerve_L or OpticNerve_R, Lens_L or Lens_R. Results The neurological symptoms improved after the end of RT with a complete resolution two months later. At the last MRI, a year and a half from the end of RT, there was no evidence of brain lesion, and no neurological symptoms were referred. These are our results of plan sum: for PTV-HA D2%=43.43 Gy, D98%=26.36 Gy, V30=94.96%; for Hippocampus D100%=8.78 Gy, Dmax=17.24 Gy; for Left OpticNerve Dmax=33.51%; for Right OpticNerve Dmax=29.25%; for OpticChiasm Dmax=35.93%. Conclusion To our knowledge, this is the first described case using the VMAT technique to spare the hippocampus plus a boost in a rare case of Garcin Syndrome. Prevention of neurocognitive sequelae by hippocampal avoidance has shown promise in several studies as in this case. Sequential boost demonstrated to be feasible and effective.Advanced RT techniques may be used to customize a treatment that allows preserving cognitive impairment achieving good clinical results in the long-term survival of metastatic patients.

Hippocampal Metastasis Rate Based on Non-Small Lung Cancer TNM Stage and Molecular Markers.

Hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) is justified because of low hippocampal brain metastases (BM) rate and its prevention of cognitive decline. However, we hypothesize that the risk of developing BM in the hippocampal-avoidance region (HAR) may differ depending on the lung-cancer stage and molecular status. We retrospectively reviewed 123 patients with non-small cell lung cancer (NSCLC) at the initial diagnosis of BM. The number of BMs within the HAR (5 mm expansion) was counted. The cohort was divided into patients with and without BMs in the HAR, and their clinical variables, TNM stage, and epidermal growth factor receptor (EGFR) status were compared. The most influential variable predicting BMs in the HAR was determined using multi-variable logistic regression, classification and regression tree (CART) analyses, and gradient boosting method (GBM). The feasibility of HAR expansion was tested using generalized estimating equation marginal model. Patients with BMs in the HAR were more frequently non-smokers, and more likely to have extra-cranial metastases and EGFR mutations (p<0.05). Multi-variable analysis revealed that extra-cranial metastases were independently associated with the presence of BM in the HAR (odds ratio=8.75, p=0.04). CART analysis and GBM revealed that the existence of extra-cranial metastasis was the most influential variable predicting BM occurrence in the HAR (variable importance: 23% and relative influence: 37.38). The estmated BM incidence of patients without extra-cranial metastases in th extended HAR (7.5-mm and 10-mm expansion) did not differ significantly from that in the conventional HAR. In conclusion, NSCLC patients with extra-cranial metastases were more likely to have BMs in the HAR than those without extra-cranial metastases.

Optimization of hippocampus sparing during whole brain radiation therapy with simultaneous integrated boost—tutorial and efficacy of complete directional hippocampal blocking

PurposeHippocampus-avoidance whole brain radiotherapy with simultaneous integrated boost (HA-WBRT+SIB) is a complex treatment option for patients with multiple brain metastases, aiming to prevent neurocognitive decline and simultaneously increase tumor control. Achieving efficient hippocampal dose reduction in this context can be challenging. The aim of the current study is to present and analyze the efficacy of complete directional hippocampal blocking in reducing the hippocampal dose during HA-WBRT+SIB.MethodsA total of 30 patients with multiple metastases having undergone HA-WBRT+SIB were identified. The prescribed dose was 30 Gy in 12 fractions to the whole brain, with 98% of the hippocampus receiving ≤ 9 Gy and 2% ≤ 17 Gy and with SIB to metastases/resection cavities of 36–51 Gy in 12 fractions. Alternative treatment plans were calculated using complete directional hippocampal blocking and compared to conventional plans regarding target coverage, homogeneity, conformity, dose to hippocampi and organs at risk.ResultsAll alternative plans reached prescription doses. Hippocampal blocking enabled more successful sparing of the hippocampus, with a mean dose of 8.79 ± 0.99 Gy compared to 10.07 ± 0.96 Gy in 12 fractions with the conventional method (p < 0.0001). The mean dose to the whole brain (excluding metastases and hippocampal avoidance region) was 30.52 ± 0.80 Gy with conventional planning and 30.28 ± 0.11 Gy with hippocampal blocking (p = 0.11). Target coverage, conformity and homogeneity indices for whole brain and metastases, as well as doses to organs at risk were similar between planning methods (p > 0.003).ConclusionComplete directional hippocampal blocking is an efficient method for achieving improved hippocampal sparing during HA-WBRT+SIB.

Whole brain radiotherapy with hippocampal sparing using Varian HyperArc.

The purpose of this work was to evaluate using Varian HyperArc as a planning and treatment solution for whole brain radiotherapy (WBRT) with hippocampal sparing following Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Ten patients previously treated for intracranial lesions were retrospectively planned for WBRT with hippocampal sparing using HyperArc and a 2-arc coplanar VMAT technique. The whole brain and hippocampus were delineated on fused MRI and CT datasets. The planning target volume (PTV), defined as the whole brain excluding the hippocampal avoidance region, was prescribed 30 Gy in 10 fractions. Plans were evaluated using dosimetric parameters which included the volume of 105% of the prescription dose (V105%) and the maximum dose to the PTV, and the minimum dose to the hippocampus. The planning time, delivery time, and delivery quality assurance (QA) results were also evaluated. Statistical significance was performed between the HyperArc and coplanar VMAT metrics using the Wilcoxon signed-rank test with a significance level of 0.05. All plans met RTOG 0933 dosimetric criteria. HyperArc plans demonstrated significant improvements in PTV dosimetric quality which included a reduced V105% of 6 ± 7% and decreased maximum dose of 1.3 ± 0.3 Gy, compared to coplanar VMAT. Significant OAR sparing was also found for HyperArc plans that included a decreased minimum dose to the hippocampus of 0.3 ± 0.3 Gy. Coplanar VMAT plans resulted in significantly shorter planning and delivery times, compared to HyperArc, by 2.4 minutes and 1.5 minutes, respectively. No significant difference was found between the delivery QA results. This study demonstrated using Varian HyperArc as a planning and treatment solution for WBRT with hippocampal sparing following RTOG 0933 dosimetric criteria. The primary advantages of WBRT with hippocampal sparing using HyperArc, compared to coplanar VMAT, are the gains in OAR sparing and reduced high dose volumes to the PTV.

Automated contouring and planning pipeline for hippocampal-avoidant whole-brain radiotherapy

BackgroundWhole-brain radiotherapy (WBRT) remains an important treatment for over 200,000 cancer patients in the United States annually. Hippocampal-avoidant WBRT (HA-WBRT) reduces neurocognitive toxicity compared to standard WBRT, but HA-WBRT contouring and planning are more complex and time-consuming than standard WBRT. We designed and evaluated a workflow using commercially available artificial intelligence tools for automated hippocampal segmentation and treatment planning to efficiently generate clinically acceptable HA-WBRT radiotherapy plans.MethodsWe retrospectively identified 100 consecutive adult patients treated for brain metastases outside the hippocampal region. Each patient’s T1 post-contrast brain MRI was processed using NeuroQuant, an FDA-approved software that provides segmentations of brain structures in less than 8 min.Automated hippocampal segmentations were reviewed for accuracy, then converted to files compatible with a commercial treatment planning system, where hippocampal avoidance regions and planning target volumes (PTV) were generated. Other organs-at-risk (OARs) were previously contoured per clinical routine. A RapidPlan knowledge-based planning routine was applied for a prescription of 30 Gy in 10 fractions using volumetric modulated arc therapy (VMAT) delivery. Plans were evaluated based on NRG CC001 dose-volume objectives (Brown et al. in J Clin Oncol, 2020).ResultsOf the 100 cases, 99 (99%) had acceptable automated hippocampi segmentations without manual intervention. Knowledge-based planning was applied to all cases; the median processing time was 9 min 59 s (range 6:53–13:31). All plans met per-protocol dose-volume objectives for PTV per the NRG CC001 protocol. For comparison, only 65.5% of plans on NRG CC001 met PTV goals per protocol, with 26.1% within acceptable variation. In this study, 43 plans (43%) met OAR constraints, and the remaining 57 (57%) were within acceptable variation, compared to 42.5% and 48.3% on NRG CC001, respectively. No plans in this study had unacceptable dose to OARs, compared to 0.8% of manually generated plans from NRG CC001. 8.4% of plans from NRG CC001 were not scored or unable to be evaluated.ConclusionsAn automated pipeline harnessing the efficiency of commercially available artificial intelligence tools can generate clinically acceptable VMAT HA-WBRT plans with minimal manual intervention. This process could improve clinical efficiency for a treatment established to improve patient outcomes over standard WBRT.

Hippocampal Dosimetry In Patients Receiving Radiosurgery For ≥ 25 Brain Metastases: Implications For HA-WBRT

Increasingly radiosurgery is used to manage patients with higher numbers of brain metastases in one or more sessions over time. For patients with ≥ 25 brain metastases who had radiosurgery (SRS) in single or multiple sessions, we report our dosimetric analysis of the hippocampi and the incidence of perihippocampal tumor location in this same cohort. From a review of our prospective registry, 47 patients treated with Gamma Knife SRS for ≥ 25 brain metastases between June 2013 and March 2019 were identified. Bilateral hippocampal contours were auto-generated on gadolinium-enhanced 3D MP-RAGE reference MRIs and manually edited per the RTOG hippocampus contouring atlas. Following RTOG 0933 guidelines, hippocampal avoidance regions (HA-region) were created by 5mm volumetric expansions. MRIs were co-registered with each SRS session in Gamma Plan, and the doses from each session were summed to calculate cumulative bilateral, left, and right hippocampal doses. Distribution of metastases relative to the HA-region was analyzed. The median number of cumulative tumors irradiated per patient was 38 (range 25-116) in a median of 3 (range 1-12) SRS sessions. The median cumulative tumor volume was 7.0 cc (range 0.8 to 27 cc), and the median marginal dose for the largest tumor per session was 16 Gy (10-21Gy). Of the total 1941 treated tumors, 55 (2.8%) were located in the HA-region, occurring in 31 of the 47 (66%) patients. Dosimetry is reported in Table 1. No patient experienced ≥ grade 3 neurologic toxicity. Large numbers of brain metastases can be treated by SRS with cumulative doses to the hippocampi which compare favorably to those reported with HA-WBRT and without adverse neurologic outcome. In addition, for patients with tumors located in the HA-regions and a high burden of intracranial disease, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half our patients, a finding which precludes HA-WBRT, illustrating the importance of alternative hippocampus-sparing techniques such as SRS.Abstract 3704; TableAll PatientsNTIHATIHATIHA and >50 metastasesBilateral Hippocampus Mean (Gy)Median (Range)4.35 (1.71-12.26)3.03 (1.88-6.18)6.02 (1.71-12.26)9.48 (4.47-12.26)Bilateral Hippocampus D100 (Gy)Median (Range)1.75 (0.26-4.2)1.22 (0.54-3.47)2.03 (0.26-4.2)2.78 (2.15-4.2)Bilateral Hippocampus D40 (Gy)Median (Range)4.35 (1.52-10.29)2.97 (2.05-6.66)5.63 (1.52-10.29)8.97 (4.49-10.29)Bilateral Hippocampus Max (Gy)Median (Range)19.98 (3.29-63.24)7.09 (3.29-10.24)25.22 (11.11-63.24)35.34 (13.27-63.24)Left Hippocampus Mean (Gy)Median (Range)4.92 (1.20-14.30)3.44 (1.53-7.26)5.89 (1.20-14.30)10.03 (4.92-14.30)Abbreviations: NTIHA No Tumors in Hippocampal-Avoidance Region; TIHA Tumor(s) in Hippocampal-Avoidance Region Open table in a new tab

Automated Contouring and Planning for Hippocampal-Avoidant Whole-Brain Radiotherapy

Whole-brain radiotherapy (WBRT) remains an important treatment for over 200,000 cancer patients annually. Radiation dose to hippocampi predicts neurocognitive dysfunction. Hippocampal-avoidant WBRT (HA-WBRT) reduces neurocognitive toxicity compared to standard WBRT, but HA-WBRT contouring and planning are more complex and time-consuming than standard WBRT. We hypothesize that automated hippocampal segmentation and treatment planning can generate clinically acceptable HA-WBRT plans. We identified 40 consecutive patients with available MRI treated at one institution for brain metastases outside the hippocampal region. Each patient’s T1 post-contrast brain MRI was processed using FDA-approved software that can provide segmentations of brain structures in 5-7 minutes. Automated hippocampal segmentations were reviewed for accuracy and edited manually if necessary. These were converted to files compatible with a commercial treatment planning system, where hippocampal avoidance regions and planning target volumes (PTV) were generated. Other organs-at-risk (OARs) were previously contoured per clinical routine. A semi-automated knowledge-based planning routine was applied for a prescription of 30 Gy in 10 fractions using volumetric modulated arc therapy (VMAT) delivery. Plans were evaluated based on NRG-CC001 dose-volume objectives. Hippocampus segmentations were acceptable for 39 (97.5%) cases, with 1 case requiring minor manual editing. Automated plans had acceptable NRG-CC001 dose-volume objectives for PTV and OARs in 40 (100%) plans. Forty (100%) plans met PTV goals per protocol. For comparison, only 66.0% of plans on NRG-CC001 met PTV goals per protocol, with 26.3% within acceptable variation. In this study, 15 (37.5%) plans met OAR constraints per protocol and 25 (62.5%) were within acceptable variation, compared to 42.9% and 48.6% on NRG-CC001, respectively. No plans in our study had unacceptable dose to OARs, compared to 0.8% of manually generated plans from NRG-CC001. The median time for semi-automated planning was 9 minutes (range 7-13.5). A robust, semi-automated pipeline can generate clinically acceptable VMAT HA-WBRT plans in 15-20 minutes (plus time required to contour optic structures), without manual refinement of hippocampi in 97.5% of cases. This pipeline could improve clinical efficiency for a treatment proven to improve patient outcomes over standard WBRT.Tabled 1Abstract 2672; Table; Dose volume histogram for semi-automated HA-WBRTAutomated HA-WBRT Median (range)NRG-CC001Per ProtocolAcceptable VariationPTV D2% (Gy)34.3 (33.3-37.2)< 37.537.5-40PTV D98% (Gy)26.5 (25.5-28.8)> 2522.5-25PTV V30Gy (%)95 (95-95)> 9590-95Hippocampi D100% (Gy)8.1 (7.4-9.1)< 99-10Hippocampi Dmax (Gy)13.2 (9.7-15.7)< 1616-17Optic Nerves Dmax (Gy)29.9 (15.4-32.3)< 3030-37.5Optic Chiasm Dmax (Gy)30.2 (29.2-32.0)< 3030-37.5 Open table in a new tab

Incidence of hippocampal metastases in non‐small‐cell lung cancer

Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) develop brain metastases in 25-50% of cases during the course of their disease. Data on the incidence of metastases occurring in the hippocampus/perihippocampal zones are limited. This is important when considering hippocampal-sparing brain radiation (HS-BR), a method that could potentially reduce the neurocognitive impact of such treatment. The aim of this study was to assess the incidence of hippocampal/perihippocampal metastases in a cohort of patients with advanced NSCLC treated at our institution. This retrospective cohort study included NSCLC patients discussed at our institutional lung cancer multidisciplinary meeting between 2000 and 2016. MRI and contrast-enhanced CT (ceCT) brain images were reviewed to assess the incidence of hippocampal/perihippocampal metastases including metastases within the hippocampal subgranular zone and a 5mm margin (hippocampal avoidance region) defined as per the RTOG 0933 study. Of 2146 patients reviewed, 357 (16.6%) had brain metastases. A total of 335 patients had available MRI/ceCT brain images for review. Thirty (9%) patients had brain metastases in the hippocampal avoidance region, 8 (2.4%) with hippocampal metastases and 22 (6.6%) with perihippocampal metastases. Univariate analyses did not show an association between developing metastases in the hippocampal avoidance region and age (P=0.75), gender (P=0.91) and tumour type (P=0.298). The incidence of metastases in the hippocampal avoidance region in our large cohort of patients was 9%. With low rates of metastases in this region, HS-BR can be considered a feasible option in the management of patients with advanced NSCLC.

Comparison of dose distribution between VMAT and IMRT in patients with brain metastases during hippocampus-sparing whole brain radiotherapy

Objective To compare the dose distribution between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) in patients with brain metastases receiving hippocampus-sparing whole brain radiotherapy. Methods Forty-six patients with brain metastases admitted to our hospital from 2013 to 2016 were recruited in this study. After fusing the CT and MRI images, the hippocampus was delineated on the fusion images. The three-grade hippocampal avoidance regions were created by using a volumetric expansion of 3, 5 and 10 mm surrounding the hippocampus. The planning target volume (PTV) was calculated by subtracting the 5-mm expansion surrounding the hippocampus from the whole brain. The prescription dose was 30 Gy/10 fractions. The 7-field IMRT and single arc VMAT were designed for each case. The dose distribution of PTV, hippocampus and other organs at risk (OARs) were evaluated in both plans. Results The PTV was statistically compared between VMAT and IMRT: V95: 95.90% and 94.97%(P=0.000); V90: 98.17% and 97.48%(P=0.000); CI: 0.825 and 0.813(P=0.013); HI: 0.277 and 0.289(P=0.025). The hippocampal dose was also compared between VMAT and IMRT: the Dmax of hippocampus was 1 698.9 cGy for VMAT and 1 784.9 cGy for IMRT (P=0.002). The Dmean of hippocampus was 1 183.8 cGy for VMAT and 1 112.7 cGy for IMRT (P=0.000). No statistical significance was observed between IMRT and VMAT in protecting the OARs except the chiasma opticum (3 262.6 cGy and 3 529.3 cGy, P=0.000). The MU and treatment time of VMAT and IMRT were 651 and 2 768(P=0.000), and 188 s and 504 s (P=0.000). Conclusions The dose distribution of PTV in VMAT is significantly better than that in IMRT.VMAT is advantageous in protecting the hippocampus than IMRT.VMAT can significantly shorten treatment time and MU and enhance the equipment utilization. Besides, VMAT can achieve the goal of protecting the hippocampus and meet the prescription dose requirement of PTV. Key words: Neoplasms metastasis, brain/whole brain radiotherapy; Hippocampus-sparing; Neoplasms metastasis, brain/radiotherapy

PUB045 The Capability and Characteristic of Helical Tomotherapy at Sparing Hippocampus in Prophylactic Cranial Irradiation

Prophylactic cranial irradiation (PCI) is efficient at avoiding lung cancer intra-cranial metastasis. However, PCI may cause neurocognitive impairment because of the hippocampal toxicities. It is reported that hippocampus V7.3Gy > 40% is associated with long-term impairment. Considering helical tomotherapy (HT) has higher modulation capabilities, we investigated the capability and characteristic of HT at sparing hippocampus in PCI. Six anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. Under T1-weighted MRI, the hippocampus was contoured, and hippocampal avoidance regions (HAR) were created using a 5-mm volumetric expansion around the hippocampus. The prescription dose 3.0Gy * 10 fractions was assigned on planning target volume (PTV) which was defined as whole-brain minus HAR and bilateral hippocampus. During the HT plan optimization process, evaluation factors of PTV and other dosimetry factors were recorded whenever the mean dose of hippocampus decreased by every 2Gy. The average of six HT plans without hippocampus sparing constraints are as follow: hippo_Dmean 27.33±2.22Gy, HAR_Dmean 28.62±1.84Gy, PTV_Dmean 30.77±0.74Gy, PTV_D2% 30.93±0.61Gy, PTV_D98% 29.86±0.34Gy, PTV_V30Gy 0.97±0.02% and conformal index (CI) 0.85±0.03, homogeneity index (HI) 0.04±0.01, plan delivery duration 13.70±1.92min. When V7.3Gy of bilateral hippocampus achieved 40%, the average dosimetry factors are as follow: hippo_Dmean 8.26±0.24Gy, HAR_Dmean 12.88±1.27Gy, PTV_Dmean 31.00±0.47Gy, PTV_D2% 31.97±0.63Gy, PTV_D98% 21.74±5.44Gy, PTV_V30Gy 0.93±0.02%, CI 0.77±0.08, HI 0.35±0.20, plan delivery duration 21.30±4.97min. During the process of hippocampus sparing, HAR_Dmean decreased linearly as well. However, dosimetry variation of PTV presented three steps: plateau region (> 20Gy), gradient region (∼20 to ∼10Gy) and falling region (<10Gy). There’s almost no significant impact on the PTV dosimetry factors when hippo_Dmean was not lower than 15Gy. With the hippocampus dose decreasing, CI decreased linearly and slightly, however, HI was impaired severely in the falling region. Plan delivery duration time was significantly prolonged process (from 13min to 23 min).View Large Image Figure ViewerDownload Hi-res image Download (PPT)

37. Hippocampal sparing whole brain radiotherapy with volumetric modulated arc therapy

Introduction Hippocampal Avoidance whole brain radiotherapy (HA-WBRT) is a strategy that aims to mitigate the neuro-cognitive side effects of whole brain radiotherapy treatment. The purpose of this study was to investigate the feasibility and efficiency of using volumetric modulated arc therapy (VMAT) to spare the hippocampi while delivering the prescribed dose to the rest of the brain. Methods A total of four patients were replanned for hippocampal sparing for a prescription dose of 30 Gy in 10 fractions. A cranial mask system with a 25° angle, inclined board was utilized for patient positioning. The hippocampi were contoured and hippocampal avoidance regions were created using a 5 mm volumetric expansion around the hippocampi. The whole brain planning target volume was defined as the whole brain tissue minus hippocampal avoidance region. The VMAT plans were generated in Eclipse treatment planning system version 11 for a Varian True Beam STx linear accelerator equipped with a high definition multileaf collimator. Different beam arrangements were studied.The treatment plans were evaluated on target coverage, homogeneity of the PTV, and minimum, maximum, mean dose, D40% to the hippocampi and maximum and mean dose to the lens. The goal was to generate treatment plans that met the RTOG 0933 [1] criteria for HAWBRT treatment. Results The choice of beam arrangements consisted in six arcs with two non-coplanar arcs and different collimator rotation. All the VMAT plans achieved target coverage of the brain while maintaining hippocampal doses conform to the RTOG 0933 protocol. Concerning the PTV, the mean D98%, D95% and D2% were 27.3 ± 0.3 Gy, 29.0 ± 0.1 Gy and 30.8 ± 0.1 Gy, respectively. The mean values of homogeneity index and conformity index were 0.11 ± 0.01 and 0.94 ± 0.01, respectively. The D100%, mean and maximum doses to hippocampi were 7.9 ± 0.4 Gy, 10.1 ± 0.8 Gy and 14.6 ± 1.0 Gy, on average, respectively. On average, the mean and maximum doses to lenses were 4.5 ± 0.4 Gy and 5.2 ± 0.2 Gy respectively. Conclusion An inclined head board at 25° combined to six VMAT arcs with two non-coplanar arcs provided highly conformal plans that spared hippocampi and met the RTOG 0933 criteria. In the future, we plan to evaluate dose escalation on multiple brain metastases and assess the minimum distance from the metastases to the hippocampi to satisfy hippocampal avoidance.

SU‐F‐T‐401: Three‐Dimensional Conformal Planning Using Low‐Segment Multi‐Criteria Optimization for Hippocampal Avoidance Whole Brain Radiotherapy

Purpose:Hippocampus avoidance whole brain radiotherapy (HA‐WBRT) has been shown to reduce the risk of neurocognitive dysfunction. This type of treatment has the potential of insurance company payment denial due to increased cost of intensity modulated radiotherapy (IMRT), while the accepted modality for WBRT is three‐dimensional conformal radiotherapy (3DCRT). The purpose of this study is to assess HA‐WBRT treatment plans using 3DCRT and multi‐criteria optimization (MCO) that meets the RTOG 0933 criteria.Methods:Ten patients with brain metastases at least 0.5cm away from the hippocampal avoidance region as defined in RTOG 0933 were selected in this study. HA‐WBRT treatment plans with MCO 3DCRT technique (MCO‐3D) was generated with beam arrangements and dose constraints following the RTOG 0933 guidelines. MCO‐3D plans were compared with plans using MCO IMRT techniques (MCO‐IMRT) with same beam arrangements and dose constraints. Evaluation parameters included D98% D2% and dose homogeneity index of PTV, and Dmax and D100% of the hippocampi. The OAR doses were also evaluated.Results:For MCO‐IMRT plans, PTV D2% and hippocampi Dmax and D100% met RTOG 0933 objectives in all ten patients (PTV D2%&lt;37.5Gy; Hippocampi Dmax&lt;16Gy and D100%&lt;9Gy). One patient met the RTOG 0933 PTV D98% objective (PTV D98%&gt;25Gy) and 9/10 patients met acceptable variation (PTV D98%&lt;25Gy). For MCO‐3D plans, PTV D2% met RTOG 0933 objective for all patients; 1/10 patient for PTV D98% and 6/10 patients for Hippocampi Dmax and 7/10 patients for hippocampi D100% met RTOG 0933 objective. All the other patients met the RTOG 0933 acceptable variation requirement. (PTV D98%&lt;25Gy; Hippocampi Dmax&lt;17Gy and D100%&lt;10Gy).Conclusion:All dosimetric parameters of MCO‐3D plans met the criteria of at least acceptable variation per RTOG 0933. This may be helpful in cases where there is denial of patient's medical insurance coverage due to the use of IMRT for HA‐WBRT.

Incidence and relapse risk of intracranial metastases within the perihippocampal region in 314 patients with breast cancer

PurposeThe safe prerequisite of hippocampal-sparing whole brain radiotherapy (HS-WBRT) for patients with breast cancer is unclear. This study investigated the risk and relapse of perihippocampal (PH) metastases in breast cancer. MethodsConsecutive breast cancer patients with brain metastasis (BM) were reviewed. Metastases and hippocampi were contoured in cranial magnetic resonance imaging (MRI). The closest distance from metastasis to hippocampus was calculated. Clinical and radiographic variables were correlated with PH (in or within 5mm around the hippocampus) metastasis. The risk of post-treatment PH recurrence was estimated. ResultsThree hundred and fourteen patients with 1678 metastases exhibited a median breast cancer-specific overall survival (OS) and OS after BM (BMOS) of 75.4 and 14.3months, respectively. Hippocampal metastases were identified in 1.2% of metastases and 4.1% of patients. PH lesions comprised 3.5% of lesions in 11.1% of patients. The number and aggregated volume of BM were associated with PH disease probability (univariate). Only the number of BM significantly correlated with PH disease in the multivariate analysis. The patients with PH lesions exhibited more non-oligometastatic disease, increased tumor volume, and poor BMOS. One hundred and eleven patients without original PH lesions developed intracranial progression post-treatment. The risks of PH metastasis recurrence were 4.6% for WBRT and 6.8% for sub-therapeutic irradiation in the PH region. The increase in the absolute risk of PH recurrence with hippocampal-sparing irradiation was approximately 2%. ConclusionsThese novel findings indicate that BM from breast cancer exhibits low risks of metastases and relapse within the hippocampal avoidance region. Non-oligometastatic disease is associated with PH metastasis. Thus, HS-WBRT is considered safe and suitable for breast cancer.

SU‐E‐T‐449: Hippocampal Sparing Radiotherapy Using Intensity Modulated Radiotherapy and Volumetric Modulated Arc Therapy

Purpose:The hippocampus sparing during the cranial irradiation has become interesting because it may mitigate radiation‐induced neurocognitive toxicity. Herein we report our preliminary study for sparing the hippocampus with and without tilling condition for patient with brain metastases.Methods:Ten patients previously treated with whole brain were reviewed. Five patients tilted the head to around 30 degrees and others were treated without tilting. Treatment plans of linear accelerator (Linac)‐based volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) were generated for prescription dose of 30 Gy in 15 fractions. Hippocampal avoidance regions were created with 5‐mm volumetric expansion around the hippocampus. Whole brain, hippocampus and hippocampal avoidance volume were 1372cm3, 6cm3 and 30cm3 and hippocampal avoidance volume was 2.2% of the whole brain planned target volume in average. Organs at risk (OARs) are hippocampus, eyes, lens, and cochleae. Coverage index (CVI), conformity index (CI), homogeneity index (HI) and mean dose to OARs were used to compare dose characteristic of tilted and non‐tilted cases.Results:In IMRT, when CI, CVI and HI of whole brain were 0.88, 0.09 and 0.98 in both tilted and non‐tilted cases, absorbed dose of hippocampal avoidance volume in tilted cases were 10% lower than non‐tilted cases. Doses in other OARs such as eyes, lens, and cochleae were also decreased about 20% when tilting the head. When CI, HI and CVI in VMAT were 0.9, 0.08 and 0.99, the dose‐decreased ratio of OARs in both with and without tilting cases were almost the same with IMRT. But absolute dose of hippocampal avoidance volume in VMAT was 30% lower than IMRT.Conclusion:This study confirms that dose to hippocampus decreases if patients tilt the head. When treating the whole brain with head tilted, patients can acquire the same successful treatment Result and also preserve their valuable memory.