Hippocampal Avoidance Whole Brain Radiation Research Articles

RADI-26. DOSIMETRIC EVALUATION OF 6 MV VERSUS 10 MV PHOTONS FOR HIPPOCAMPAL AVOIDANCE WHOLE BRAIN RADIOTHERAPY

OBJECTIVE: Whole brain radiotherapy (WBRT) causes neurocognitive decline. Hippocampal avoidance WBRT (HA-WBRT) reduces hippocampal irradiation, potentially mitigating neurocognitive sequelae. We compared hippocampal and brain dosimetry with HA-WBRT with 6 megavoltage (MV) versus 10 MV photon energies. METHODS: Twenty consecutive patients treated with WBRT were retrospectively replanned with HA-WBRT techniques using 6 MV and 10 MV photons. Coplanar volumetric modulated arc therapy was employed, with a prescription dose of 3000 cGy in 10 fractions. Planning was done with Eclipse version 13.6 or 15.6. Nine patients were planned with 2.5 mm multileaf collimator leaves, with the remainder planned with 5 mm leaves. The hippocampi were contoured and a HA structure was generated using a uniform 5 mm expansion. A planning target volume (PTV) was defined as the brain parenchyma minus the HA structure. NRG-CC001 dose constraints were used. For each variable, descriptive statistics were calculated. Comparisons were made using two-tailed Wilcoxon signed rank tests or paired t-tests. RESULTS: The minimum hippocampal dose (D100%) was improved with 6 MV plans, 841 cGy compared to 914 cGy with 10 MV (p< 0.005). The maximum hippocampal dose (D0.03cc) was reduced with 6 MV planning, 1614 cGy versus 1676 cGy for 10 MV (p< 0.0001). With 6 MV photons, a greater number of plans met NRG-CC001 constraints without deviations. 6 MV photons improved PTV coverage by the 95% isodose line, 96.6% compared to 95.9% for 10 MV (p=0.021). 6 MV photon plans decreased the volume of PTV receiving ≥105% of the prescription, 84.2% versus 87.9% for 10 MV (p=0.006). The mean dose, hot spots, and cold spots did not differ by photon energy. PTV dose constraints were always met. CONCLUSION: 6 MV photon HA-WBRT plans are dosimetrically superior to 10 MV, reducing hippocampal radiation dose, without compromise in brain coverage and improved target dose homogeneity.

Single-Fraction Stereotactic Radiosurgery Versus Hippocampal-Avoidance Whole Brain Radiation Therapy for Patients With 10 to 30 Brain Metastases: A Dosimetric Analysis

To compare normal tissue dosimetry between hippocampal-avoidance whole brain radiation therapy (HA-WBRT) and stereotactic radiosurgery (SRS) in patients with 10 to 30 brain metastases, and to describe a novel SRS strategy we term Spatially Partitioned Adaptive RadiosurgEry (SPARE). A retrospective review identified SRS treatment plans with >10 brain metastases located >5 mm from the hippocampi. Our Gamma Knife Icon (GKI) SPARE (GKI-Spr) technique treats multiple metastases with single-fraction SRS partitioned over consecutive days while limiting the total treatment time to ≤60 minutes per day. Hippocampal and normal brain dosimetry were compared among GKI-Spr, single-fraction single-day GKI (GKI-Sfr), and 30 Gy in 10 fractions HA-WBRT. Dose metrics were converted to equivalent dose in 2 Gy fractions. Ten cases were analyzed. Compared with HA-WBRT, GKI-Spr significantly reduced the median equivalent dose in 2 Gy fractions hippocampal maximum point dose, mean dose, and dose to 40% of the hippocampi (D40%) by 86%, 93%, and 93%, respectively, and similarly for GKI-Sfr by 81%, 92%, and 91%, respectively. The normal brain median mean dose was reduced by 95% with GKI-Spr and 94% with GKI-Sfr. Compared with GKI-Sfr, GKI-Spr further reduced all normal brain and hippocampal dose metrics (P ≤ .014). GKI yields superior hippocampal and normal brain dosimetry compared with HA-WBRT, and GKI-Spr results in further dosimetric advantages.

The Current and Evolving Role of Radiation Therapy for Central Nervous System Metastases from Breast Cancer

For patients with breast cancer who develop brain metastases, radiation therapy (RT) provides local control. Here, we review the current role for central nervous system RT, particularly focusing on the evolving role for stereotactic radiosurgery (SRS). SRS treats only known CNS disease as opposed to whole-brain radiation therapy (WBRT), which treats the entire brain parenchyma. SRS has been found to cause less neurocognitive decline than WBRT. SRS is currently utilized in patients with four or fewer brain metastases, but several ongoing trials are examining the use of SRS for greater than four metastases. For patients requiring WBRT, hippocampal avoidance WBRT and memantine concurrent with and adjuvant to WBRT have been found to reduce the risk of neurocognitive decline. Both SRS and WBRT are used as a local therapy for brain metastases. SRS is increasingly preferred given fewer long-term neurocognitive side effects.

Radiographic Features of Metastatic Brain Tumors from ALK-rearranged Non-small Cell Lung Cancer: Implications for Optimal Treatment Modalities.

Purpose: To investigate the radiological features on magnetic resonance imaging (MRI) of brain metastases (BM) from ALK-rearranged non-small cell lung cancer (NSCLC).Patients and Methods: We retrospectively evaluated data from 40 eligible patients with ALK-rearranged NSCLC. Radiographic features of metastatic brain tumors, including the number, size, location, and peritumoral brain edema size (PBES), were delineated using MRI.Results: 13 patients had metachronous BM (MBM), having developed BM at least 6 months after diagnosis with NSCLC. The remaining patients were categorized as having synchronous BM (SBM). Compared with patients in the SBM group, patients in the MBM group were found to have more favorable values for radiological features including BM number, BM size, and PBES. Ten (76.9%) of the 13 patients with MBM had ≤3 lesions and were asymptomatic, and none had developed a diffuse BM pattern, supporting the adoption of stereotactic radiosurgery (SRS) in the majority of these patients and against the administration of prophylactic cranial irradiation (PCI). Conversely, among the 27 patients with SBM, 15 (55.6%) patients had >3 lesions and 12 (44.4%) patients were symptomatic, highlighting the necessity of rapidly administrating brain radiotherapy, either as SRS or whole brain radiotherapy (WBRT). Importantly, only two patients (5.0%) had metastases in the hippocampus and peri-hippocampus region, and both were in the SBM group, indicating the feasibility of hippocampal avoidance WBRT in ALK-rearranged NSCLC.Conclusions: Both WBRT and SRS are appropriate for the treatment of BM in patients with ALK-rearranged NSCLC. The incidence of BM in the hippocampus and peri-hippocampus region is low in our radiological data. Nearly 80% of patients with metachronous BM have oligo-metastatic lesions, indicating that SRS is the preferred therapy while PCI is not indicated.

EP-1224: Treatment outcome of hippocampal avoidance whole-brain radiotherapy for multiple brain metastases

EP-1224: Treatment outcome of hippocampal avoidance whole-brain radiotherapy for multiple brain metastases

Assessment of multi-criteria optimization (MCO) for volumetric modulated arc therapy (VMAT) in hippocampal avoidance whole brain radiation therapy (HA-WBRT).

This study compared the dosimetric performance of (a) volumetric modulated arc therapy (VMAT) with standard optimization (STD) and (b) multi‐criteria optimization (MCO) to (c) intensity modulated radiation therapy (IMRT) with MCO for hippocampal avoidance whole brain radiation therapy (HA‐WBRT) in RayStation treatment planning system (TPS). Ten HA‐WBRT patients previously treated with MCO‐IMRT or MCO‐VMAT on an Elekta Infinity accelerator with Agility multileaf collimators (5‐mm leaves) were re‐planned for the other two modalities. All patients received 30 Gy in 15 fractions to the planning target volume (PTV), namely, PTV30 expanded with a 2‐mm margin from the whole brain excluding hippocampus with margin. The patients all had metastatic lesions (up to 12) of variable sizes and proximity to the hippocampus, treated with an additional 7.5 Gy from a simultaneous integrated boost (SIB) to PTV37.5. The IMRT plans used eight to eleven non‐coplanar fields, whereas the VMAT plans used two coplanar full arcs and a vertex half arc. The averaged target coverage, dose to organs‐at‐risk (OARs) and monitor unit provided by the three modalities were compared, and a Wilcoxon signed‐rank test was performed. MCO‐VMAT provided statistically significant reduction of D100 of hippocampus compared to STD‐VMAT, and Dmax of cochleas compared to MCO‐IMRT. With statistical significance, MCO‐VMAT improved V30 of PTV30 by 14.2% and 4.8%, respectively, compared to MCO‐IMRT and STD‐VMAT. It also raised D95 of PTV37.5 by 0.4 Gy compared to both MCO‐IMRT and STD‐VMAT. Improved plan quality parameters such as a decrease in overall plan Dmax and total monitor units (MU) were also observed for MCO‐VMAT. MCO‐VMAT is found to be the optimal modality for HA‐WBRT in terms of PTV coverage, OAR sparing and delivery efficiency, compared to MCO‐IMRT or STD‐VMAT.

Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Whole Brain Hippocampal Sparing Treatment Plans Based on Radiobiological Modeling.

Introduction:In this article, we report the results of our investigation on comparison of radiobiological aspects of treatment plans with linear accelerator-based intensity-modulated radiation therapy and volumetric-modulated arc therapy for patients having hippocampal avoidance whole-brain radiation therapy.Materials and Methods:In this retrospective study using the dose-volume histogram, we calculated and compared biophysical indices of equivalent uniform dose, tumor control probability, and normal tissue complication probability (NTCP) for 15 whole-brain radiotherapy patients.Results and Discussions:Dose-response models for tumors and critical structures were separated into two groups: mechanistic and empirical. Mechanistic models formulate mathematically with describable relationships while empirical models fit data through empirical observations to appropriately determine parameters giving results agreeable to those given by mechanistic models.Conclusions:Techniques applied in this manuscript could be applied to any other organs or types of cancer to evaluate treatment plans based on radiobiological modeling.

Role of Hippocampal-Avoidance Whole Brain Radiation Therapy (HA-WBRT) in Patients with Primary CNS Lymphoma (PCNSL)

Role of Hippocampal-Avoidance Whole Brain Radiation Therapy (HA-WBRT) in Patients with Primary CNS Lymphoma (PCNSL)

Automatic planning on hippocampal avoidance whole-brain radiotherapy

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D2% and D98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D100% and Dmax of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice.

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.

Dosimetric study of different radiotherapy planning approaches for hippocampal avoidance whole-brain radiation therapy (HA-WBRT) based on fused CT and MRI imaging.

The purpose of this study was to compare the dosimetric characteristics for hippocampal avoidance (HA) between the treatment plans based on fused CT and MRI imaging during whole brain radiotherapy (WBRT) pertaining to: (1) 3-dimensional conformal radiotherapy (3D-CRT), (2) dynamic intensity modulated radiation therapy (dIMRT), and (3) RapidArc for patients with brain metastases. In our study, HA was defined as hippocampus beyond 5 mm, and planning target volume (PTV) was obtained subtracting HA volume from the volume of whole brain. There were 10 selected patients diagnosed with brain metastases receiving WBRT. These patients received plans for 3D-CRT (two fields), dIMRT (seven non-coplanar fields) and RapidArc (dual arc). The prescribed dose 30 Gy in 10 fractions was delivered to the whole-brain clinical target volume of patients. On the premise of meeting the clinical requirements, we compared target dose distribution, target coverage (TC), homogeneity index (HI), dose of organs at risk (OARs), monitor units (MU) and treatment time between the above three radiotherapy plans. V90 %, V95 % and TC of PTV for 3D-CRT plan were lowest of the three plans. V90 %, V95 % and HI of PTV in RapidArc plan were superior to the other two plans. TC of PTV in RapidArc plan was similar with dIMRT plan (P > 0.05). 3D-CRT was the optimal plan in the three plans for hippocampal protection. The median dose (Dmedian) and the maximum doses (Dmax) of hippocampus in 3D-CRT were 4.95, 10.87 Gy, which were lowest among the three planning approaches (P < 0.05). Dmedian and Dmax of hippocampus in dIMRT were 10.68, 14.11 Gy. Dmedian and Dmax of hippocampus in RapidArc were 10.30 gGy, 13.92 Gy. These parameters of the last two plans pertain to no significant difference (P > 0.05). When WBRT (30 Gy,10F) was equivalent to single dose 2 Gy,NTDmean of hippocampus in 3D-CRT, dIMRT and RapidArc were reduced to 3.60, 8.47, 8.20 Gy2, respectively. In addition, compared with dIMRT, MU of RapidArc was reduced and the treatment time was shortened by nearly 25 %. All three radiotherapy planning approaches in our study can meet the clinical requirements of HA. Although TC in 3D-CRT was lowest, hippocampus was protected best by this plan. So many radiation fields and the design of non-coplanar fields lead to the complication of dIMRT. TC and HI in RapidArc were superior to the other two plans with the precise of meeting the clinical requirements. The difference in protection for hippocampus between dIMRT and RapidArc was statistically significant. In addition, RapidArc can remarkably reduce MU and the treatment time.

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: Local tumour control and survival.

Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D98% to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73%. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3%. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60%. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. Dmean to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration.

An efficient Volumetric Arc Therapy treatment planning approach for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT)

An efficient and simple class solution is proposed for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) planning using the Volumetric Arc Therapy (VMAT) delivery technique following the NRG Oncology protocol NRG-CC001 treatment planning guidelines. The whole-brain planning target volume (PTV) was subdivided into subplanning volumes that lie in plane and out of plane with the hippocampal-avoidance volume. To further improve VMAT treatment plans, a partial-field dual-arc technique was developed. Both the arcs were allowed to overlap on the in-plane subtarget volume, and in addition, one arc covered the superior out-of-plane sub-PTV, while the other covered the inferior out-of-plane subtarget volume. For all plans (n = 20), the NRG-CC001 protocol dose-volume criteria were met. Mean values of volumes for the hippocampus and the hippocampal-avoidance volume were 4.1cm3 ± 1.0cm3 and 28.52cm3 ± 3.22cm3, respectively. For the PTV, the average values of D2% and D98% were 36.1Gy ± 0.8Gy and 26.2Gy ± 0.6Gy, respectively. The hippocampus D100% mean value was 8.5Gy ± 0.2Gy and the maximum dose was 15.7Gy ± 0.3Gy. The corresponding plan quality indices were 0.30 ± 0.01 (homogeneity index), 0.94 ± 0.01 (target conformality), and 0.75 ± 0.02 (confirmation number). The median total monitor unit (MU) per fraction was 806MU (interquartile range [IQR]: 792 to 818MU) and the average beam total delivery time was 121.2 seconds (IQR: 120.6 to 121.35 seconds). All plans passed the gamma evaluation using the 5-mm, 4% criteria, with γ > 1 of not more than 9.1% data points for all fields. An efficient and simple planning class solution for HA-WBRT using VMAT has been developed that allows all protocol constraints of NRG-CC001 to be met.

Future directions in treatment of brain metastases.

Background:Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT.Methods:A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text.Results:The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline.Conclusions:Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT.

SU-E-T-581: Planning Evaluation of Step-And-Shoot IMRT, RapidArc and Helical TomoTherapy for Hippocampal-Avoidance Whole Brain Radiotherapy (HA-WBRT).

Several planning strategies are available for hippocampal- avoidance whole-brain radiotherapy (HA-WBRT) following RTOG protocol 0933, but have yet to be compared on a common set of patient data. In this inter-institutional investigation, we evaluate three modalities likely to be employed by protocol participants; step-and-shoot IMRT, volumetric modulated arc therapy, and helical tomotherapy. A common set of patients is used for comparison, including credentialing and successfully accrued patients. Eight patient datasets were selected and de-identified prior to planning. Structures were contoured by physicians per protocol using fused MRI datasets. Three plans were generated for each dataset: Philips Pinnacle 9-field non-coplanar IMRT using protocol recommended beam parameters, Varian's RapidArc using two coplanar arcs, and Accuray's TomoTherapy using a 1cm jaw width. With the goal of meeting the compliance criteria outlined in RTOG 0933 (target coverage and dose limits to the hippocampus and optic structures), three planners independently planned each modality without prior knowledge of the patient's other plans to reduce bias. The three plans for each patient were compared according to the protocol's dosimetric compliance criteria. A homogeneity index was also computed to compare target dose uniformity. All plans achieved the protocol dose criteria, except for one RapidArc plan with slightly inferior dose to the optic chiasm. TomoTherapy offered superior dose homogeneity for all patients. For the two linac based methods, RapidArc was found to provide dose homogeneity at least as good as, and in most cases superior to, 9-field step-and-shoot IMRT. Helical TomoTherapy offers superior dose homogeneity for HA-WBRT following RTOG 0933. Compared to step-and-shoot IMRT, volumetric modulated arc techniques, such as RapidArc, can offer improved homogeneity for HA- WBRT and are generally more efficient/expeditious to deliver than the noncoplanar 9-field arrangement recommended by the protocol, which uses 7 separate couch angles.