Treatment Of Multiple Brain Metastases Research Articles

Exploring feasibility criteria for stereotactic radiosurgical treatment of multiple brain metastases using five linac machines.

This study aimed to find descriptors that correlates with normal brain dose to determine the feasibility of performing fractionated stereotactic radiosurgery (SRS) for multiple brain metastases (BMs) using five linac machines. Thirty-two patients with 1-30 BMs were enrolled. Treatment plans were created using TrueBeam, Novalis Tx, TrueBeam Edge, Halcyon, and Tomotherapy linacs. The sum of all planning target volumes (PTVs) was defined as PTVall, and the brain region excluding PTVall was defined as normal brain. The total surface area (TSA) of the PTV was calculated from the sum of the surface areas of the equivalent spheres for each PTV. Volumes receiving more than 5, 12, and 18Gy (V5Gy, V12Gy, and V18Gy, respectively) were used for evaluation of normal brain dose. Correlations between normal brain dose and each tumor characteristic (number, PTVall, and TSA) were investigated using the Spearman rank correlation coefficient. Correlations between each characteristic and normal brain dose were statistically significant (p<0.05) across all machines. The correlation coefficients between each characteristic and V18Gy for the five machines were as follows: tumor number, 0.39-0.60; PTVall, 0.79-0.93; TSA, 0.93-0.99. The fit equations between TSA and V18Gy exhibited high coefficients of determination, ranging from 0.92 to 0.99 across five machines. This study devised fractionated SRS plans using for 1-30 BMs across five linac machines to find descriptors for determining SRS feasibility based on normal brain dose. TSA proved to be a promising descriptor of SRS feasibility for treating multiple BMs.

1901: Does clinical practice reflect data on the treatment of multiple brain metastases?

1901: Does clinical practice reflect data on the treatment of multiple brain metastases?

Plan quality assessment of modern radiosurgery technologies in the treatment of multiple brain metastases

Stereotactic radiosurgery (SRS) of multiple brain metastases has evolved over the last 40 years allowing centres to treat an increasing number of brain metastases in a single treatment fraction. HyperArcTM planning optimisation technique is one such development that streamlines the treatment of multiple metastases with a single isocentre. Several studies have investigated the plan quality of HyperArc compared to CyberKnife or Gamma Knife, however there are limited number of studies that include all three modalities. It is the aim of this study to provide an assessment of plan quality between the three SRS platforms across ten patients with multiple brain metastases ranging from three to eight metastases per patient. Strict planning workflows were established to avoid bias towards any particular treatment platform. Plan quality was assessed through dose to organs at risk, Paddick conformity index (PCI), gradient index (GI), global efficiency index (Gη) and dose to normal brain tissue. Results from this study found mean PCI observed across Gamma Knife plans was significantly lower than HyperArc and CyberKnife. HyperArc plans observed significantly shorter beam-on times which were 10 to 20 times faster than CyberKnife and Gamma Knife plans. Gamma Knife and CyberKnife were found to produce plans with significantly superior GI, global efficiency index and the volume of healthy brain receiving greater than 12 Gy (V12Gy) when compared to HyperArc plans. Lesion volume was seen to influence the relative difference in dose metrics between systems. The study revealed that all three treatment modalities produced high quality plans for the SRS treatment of multiple brain metastases, each with respective benefits and limitations.

Assessment of Radiation Dosage to the Hippocampi during Treatment of Multiple Brain Metastases Using Gamma Knife Therapy.

Background and Objectives: Brain metastases (BMs) pose significant clinical challenges in systemic cancer patients. They often cause symptoms related to brain compression and are typically managed with multimodal therapies, such as surgery, chemotherapy, whole brain radiotherapy (WBRT), and stereotactic radiosurgery (SRS). With modern oncology treatments prolonging survival, concerns about the neurocognitive side effects of BM treatments are growing. WBRT, though widely used for multiple BMs, has recognized neurocognitive toxicity. SRS, particularly Gamma Knife (GK) therapy, offers a minimally invasive alternative with fewer side effects, suitable for patients with a quantifiable number of metastases and better prognoses. Materials and Methods: A retrospective analysis was conducted on 94 patients with multiple BMs treated exclusively with GK at an academic medical center. Patients with prior WBRT were excluded. This study focused on the mean radiation dose received by the hippocampal area, estimated according to the 'Hippocampal Contouring: A Contouring Atlas for RTOG 0933' guidelines. Results: The precision of GK equipment results in mean doses of radiation that are lower than those suggested by RTOG 0933 and observed in other studies. This precision may help mitigate cognitive dysfunction and other side effects of hippocampal irradiation. Conclusions: GK therapy facilitates the administration of smaller, safer radiation doses to the hippocampi, which is advantageous even for lesions in the temporal lobe. It is feasible to treat multiple metastases, including cases with more than 10, but it is typically reserved for patients with fewer metastases, with an average of 3 in this study. This underlines GK's potential for reducing adverse effects while managing BMs effectively.

Effect of prescription isodose line on tissue sparing in linear accelerator-based stereotactic radiosurgery treating multiple brain metastases using dynamic conformal arcs.

Linear accelerator-based stereotactic radiosurgery (SRS) has become a mainstay for simultaneous management of multiple intracranial targets. Recent improvements in treatment planning systems (TPS) have enabled treatment of multiple brain metastases using dynamic conformal arcs (DCA) and a single treatment isocenter. However, as the volume of healthy tissue receiving at least 12Gy (V12) is linked to the probability of developing radionecrosis, balancing target coverage while minimizing V12 is a critical factor affecting SRS plan quality. Current TPS allow users to adjust various parameters influencing plan optimization. The purpose of this work is to quantify the effect of negative margins on V12 for cranial SRS plans managing multiple brain metastases. Using the Brainlab Elements v3.0 TPS (Brainlab, Munich, Germany), we calculated V10, V12, V15, monitor units, and conformity index for seventeen SRS plans treating 2-10 metastases on our Elekta Versa HD (Elekta, Stockholm, Sweden) linear accelerator. We compared plans optimized using 70%-90% prescription isodose lines (IDL) in 5% increments. Irrespective of the number of treated metastases, optimization at a lower prescription IDL reduced V10, V12, and V15 and increased MU compared to the 90% IDL (p<0.01). However, comparing the 70% and 75% IDL optimizations, there was little difference in tissue sparing. The conformity index showed no consistent trends at different IDLs due to a significant spread in case data. For our plans treating up to 10 metastases, diminishing returns for tissue sparing at IDLs below 80% paired with increasing treatment MU and dosimetric hot spot made optimization at lower IDLs less favorable. In our clinic, after consulting with a physician, it was determined that optimization at the 80% IDL achieved the best balance of V12, treatment MU, and maximum dose. Clinics implementing LINAC-based SRS programs may consider using similar evaluations to develop their own clinical protocols.

Whole brain irradiation–induced endothelial dysfunction in the mouse brain

Whole brain irradiation (WBI), also known as whole brain radiation therapy (WBRT), is a well-established treatment for multiple brain metastases and as a preventive measure to reduce the risk of recurrence after surgical removal of a cerebral metastasis. However, WBI has been found to lead to a gradual decline in neurocognitive function in approximately 50% of patients who survive the treatment, significantly impacting their overall quality of life. Recent preclinical investigations have shed light on the underlying mechanisms of this adverse effect, revealing a complex cerebrovascular injury that involves the induction of cellular senescence in various components of the neurovascular unit, including endothelial cells. The emergence of cellular senescence following WBI has been implicated in the disruption of the blood-brain barrier and impairment of neurovascular coupling responses following irradiation. Building upon these findings, the present study aims to test the hypothesis that WBI-induced endothelial injury promotes endothelial dysfunction, which mimics the aging phenotype. To investigate this hypothesis, we employed a clinically relevant fractionated WBI protocol (5 Gy twice weekly for 4 weeks) on young mice. Both the WBI-treated and control mice were fitted with a cranial window, enabling the assessment of microvascular endothelial function. In order to evaluate the endothelium-dependent, NO-mediated cerebral blood flow (CBF) responses, we topically administered acetylcholine and ATP, and measured the resulting changes using laser Doppler flowmetry. We found that the increases in regional CBF induced by acetylcholine and ATP were significantly diminished in mice subjected to WBI. These findings provide additional preclinical evidence supporting the notion that WBI induces dysfunction in cerebrovascular endothelial cells, which in turn likely contributes to the detrimental long-term effects of the treatment. This endothelial dysfunction resembles an accelerated aging phenotype in the cerebrovascular system and is likely causally linked to the development of cognitive impairment. By integrating these findings with our previous results, we have deepened our understanding of the lasting consequences of WBI. Moreover, our study underscores the critical role of cerebromicrovascular health in safeguarding cognitive function over the long term. This enhanced understanding highlights the importance of prioritizing cerebromicrovascular health in the context of preserving cognitive abilities.

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.

PRO: Do We Still Need Whole-Brain Irradiation for Brain Metastases?

(1) Background: In recent decades, the use of whole-brain radiation therapy (WBRT) in the treatment of brain metastases has significantly decreased, with clinicians fearing adverse neurocognitive events and data showing limited efficacy regarding local tumor control and overall survival. The present study thus aimed to reassess the role that WBRT holds in the treatment of brain metastases. (2) Methods: This review summarizes the available evidence from 1990 until today supporting the use of WBRT, as well as new developments in WBRT and their clinical implications. (3) Results: While one to four brain metastases should be exclusively treated with radiosurgery, WBRT does remain an option for patients with multiple metastases. In particular, hippocampus-avoidance WBRT, WBRT with dose escalation to the metastases, and their combination have shown promising results and offer valid alternatives to local stereotactic radiotherapy. Ongoing and published prospective trials on the efficacy and toxicity of these new methods are presented. (4) Conclusions: Unlike conventional WBRT, which has limited indications, modern WBRT techniques continue to have a significant role to play in the treatment of multiple brain metastases. In which situations radiosurgery or WBRT should be the first option should be investigated in further studies. Until then, the therapeutic decision must be made individually depending on the oncological context.

Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4–10 brain metastases: A nonrandomized controlled trial

Background and PurposeThere is no randomized evidence comparing whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases. This prospective nonrandomized controlled single arm trial attempts to reduce the gap until prospective randomized controlled trial results are available. Material and MethodsWe included patients with 4–10 brain metastases and ECOG performance status ≤ 2 from all histologies except small-cell lung cancer, germ cell tumors, and lymphoma. The retrospective WBRT-cohort was selected 2:1 from consecutive patients treated within 2012–2017. Propensity-score matching was performed to adjust for confounding factors such as sex, age, primary tumor histology, dsGPA score, and systemic therapy. SRS was performed using a LINAC-based single-isocenter technique employing prescription doses from 15-20Gyx1 at the 80% isodose line. The historical control consisted of equivalent WBRT dose regimens of either 3Gyx10 or 2.5Gyx14. ResultsPatients were recruited from 2017–2020, end of follow-up was July 1st, 2021. 40 patients were recruited to the SRS-cohort and 70 patients were eligible as controls in the WBRT-cohort. Median OS, and iPFS were 10.4 months (95%-CI 9.3-NA) and 7.1 months (95%-CI 3.9–14.2) for the SRS-cohort, and 6.5 months (95%-CI 4.9–10.4), and 5.9 months (95%-CI 4.1–8.8) for the WBRT-cohort, respectively. Differences were non-significant for OS (HR: 0.65; 95%-CI 0.40–1.05; P =.074) and iPFS (P =.28). No grade III toxicities were observed in the SRS-cohort. ConclusionThis trial did not meet its primary endpoint as the OS-improvement of SRS compared to WBRT was non-significant and thus superiority could not be proven. Prospective randomized trials in the era of immunotherapy and targeted therapies are warranted.

Optimization of isocenter position for multiple brain metastases single-isocenter stereotactic radiosurgery to minimize dosimetric variations due to rotational uncertainty

PurposeThis paper studied a novel calculation framework that can determine the optimal value isocenter position of single isocenter SRS treatment plan for multiple brain metastases, in order to minimize the dosimetric variations caused by rotational uncertainty. Materials and methods21 patients with 2–4 GTVswho received SRS treatment for multiple brain metastases in our institution were selected for the retrospective study. The PTVwas obtained by expanding GTV 1 mm isotropic margin. We studied a stochastic optimization framework, which determined the optimal value isocenter location by maximizing the average target dose coverageCtarget,meanwith a rotation error of no more than 1°. We evaluated the performance of the optimal isocenter by comparing theCtarget,meanand average dice similarity coefficient (DSC)with the optimal value and the center of mass (CM) respectively as the treatment isocenter. The extra PTV margin to achieve 100% target dose coverage was calculated by our framework. ResultsCompared to the CM method, the optimal value isocenter method increased the averageCtarget,meanof all targets from 97.0% to 97.7%and the average DSC from 0.794to 0.799. Throughout all the cases, the average extra PTV margin to obtain full target dose coverage was 0.7 mmwhen using the optimal value isocenter as the treatment isocenter. ConclusionWe studied a novel computational framework using stochastic optimization to determine the optimal isocenter position of SRS treatment plan for multiple brain metastases. At the same time, our framework gave the extra PTV margin to obtain full target dose coverage.

METASNCore: A new tool for palliative whole brain radiotherapy (WBRT) assessment in the era of targeted therapies.

e24154 Background: Palliative WBRT has been the main treatment for multiple brain metastases (BM). Recent studies report no benefit in survival or quality of life of WBRT compared to palliative supportive care in patients (pts) with poor prognosis. Several scores have been developed to support decision-making for selection of patients; despite this, the scales implemented so far do not consider the substantial impact of new developments in recent years. The purpose of this study was to develop and statistically validate a prognostic score in palliative pts with BMs who underwent WBRT. Methods: 239 pts with BM who received palliative WBRT between 2013-2022 in our center were analyzed retrospectively. Relevant clinicopathological features and their association with overall survival (OS) were measured using univariate and multivariate Cox regression models. The score was designed according to the value of the β coefficient of each variable with statistical significance (p &lt; 0.05) in the multivariate model. Extra 0.5 points were added to all variables with a statistical significance of p &lt; 0.001. Once the score was established, a comparison was performed according to Kaplan-Meier and the survival curves were analyzed with the log-rank test. Results: 149 pts (62.3%) were male and median age was 60 years. 139 (58,2%) were lung cancer (22,8% small cells), 35 (14,6%) breast cancer (53% luminal). 124 pts had ECOG 0-1 (52,1%) and 114 (47,9%) ECOG 2-3, 169 (70,7%) had extracranial disease and the most common symptom was headache (24,3%). All patients received 30Gys in 10 sessions. 37 pts (15,5%) had a specific target mutation and 15 (6,3%) received targeted therapy after WBRT. Median OS was 3,74 months (95% CI 3,28-4,20). After the multivariate analysis: ECOG, gastrointestinal (GI) or urothelial cancer, previous RT, protein C reactive (PCR), target drug treatment and chemotherapy after WBRT were shown to have independent prognostic value for the OS. Our score found 16% to 33% higher risk of the event taking place before per each point in the score. (HR (CI 95%): 1.243 (1.164 - 1.329). p &lt; 0.001) (table 1). We found that 48 pts were in group 0-4 points with mOS 6,89ms (CI 95% 3,18-10,62), 80 in group 4-7 points with mOS 4,01ms (CI 95% 3,40-4,62) and 90 pts in group &gt; 7 points with mOS 2,72ms (CI 95% 1,93-3,52). Conclusions: Some items in our cohort like ECOG, primary tumor site, PCR or post-WBRT systemic treatment (specially target treatment) are associated with OS and they could be useful in a score to select palliative pts to receive WBRT. More prospective and multicenter studies are necessary to corroborate our findings.[Table: see text]

PO-1953 Aperture-based IMPT as an alternative to Gamma Knife in the treatment of multiple brain metastases

PO-1953 Aperture-based IMPT as an alternative to Gamma Knife in the treatment of multiple brain metastases

Surgically Treated Brain Metastases from Uterine Origin: A Case Series and Systematic Review

We aimed to describe our institutional case series of 9 surgically treated uterine brain metastases and perform a survival analysis through a systematic review and a pooled individual patient data study. This study was divided into 2 sections: 1) a retrospective, single center patient series assessing outcomes of neurosurgical treatment modalities in patients with malignancy arising in the uterus with brain metastases and 2) a systematic review of the literature between 1980 and 2021 regarding treatment outcomes of individual patients with intracranial metastasis of uterine origin. Pooled cohort survival analysis was done via univariate and Cox regression multivariable analysis and Kaplan-Meier curves. Final statistical analysis included a total of 124 pooled cohort patients: one hundred fifteen patients from literature review studies plus 9 patients from our institution. Median age at the time of diagnosis was 54 years. Median time from diagnosis of the primary cancer to brain metastasis was 19 months (0-166 months). Surgery and radiotherapy resulted in the highest median OS of 11 months (P < 0.001). Multivariable analyses indicated that the presence of more than one central nervous systemlesion had an increased risk on OS (P= 0.003). Microsurgery, stereotactic radiosurgery, and whole brain radiotherapy remain the evidence-based mainstay applicable to the treatment of multiple brain metastases. Brain metastases of cancer arising in the uterus appear to result most often in multiple lesions with dismal prognosis. The seemingly most efficacious treatment modality is surgery and radiotherapy. However, this treatment is often not an option when more than 1 or 2 brain lesions are present.

Cross-irradiation in multiple isocenter frameless treatment for limited number of multiple brain metastases with volumetric modulated arc therapy

PurposeTo evaluate cross-irradiation among targets in multiple isocenter (multiISO) plans with simultaneous optimization for multiple brain metastases in frameless stereotactic radiotherapy. MethodsThree spherical targets separated by 3 cm were drawn on a brain CT image set. Volumetric modulated arc therapy (VMAT) plans consisting of single or two-arc beams were created using the multiISO method, in which partial arcs and selective couch angles were included to avoid cross-irradiation among the targets. Plans were evaluated using conformity index, dose volumes, and beam weight from cross-irradiation. Single isocenter (singleISO) plans were also produced and compared. The entire simulation was repeated for targets separated by 5 cm. A single patient case with two targets was also simulated for application. ResultsFor target distance of 3 cm, both the multiISO and singleISO plans with two beams were equivalent and favored based on the conformity index and dose volumes. The cross-irradiation was considerable and was not reduced effectively by partial arc or selective couch angles. With a 5- cm target distance, multiISO two-arc plans made of full or partial arc and selective couch angles were equivalent and adequate for treatment. The cross-irradiation was small and made negligible by partial arc or selective couch angles. The two-arc singleISO plan was acceptable but slightly inferior with respect to conformity index and low-dose volumes. ConclusionsMultiISO radiation treatment for multiple brain metastases was prone to cross-irradiation among targets, which led to target undercoverage from potential rotational error, though it was less than with the singleISO method. For the multiISO VMAT plan to be robust to rotational error, the plan should be designed with beams minimizing cross irradiation by incorporating a partial arc or selective couch angle to avoid irradiating neighboring targets, which is more effective for targets with greater separation.

Can Proton Linear Accelerator Beams and Minibeams Achieve Superior Plan Quality over Cyclotron-Generated Proton Beams and Photons in the Treatment of Multiple Brain Metastases?

<h3>Purpose/Objective(s)</h3> To compare plan quality and delivery timing among photon Volumetric Arc Therapy (VMAT), Intensity-Modulated Proton Therapy using cyclotron-generated proton beams (CPB), linear accelerator proton beams (LPB), and linear accelerator proton minibeams (LPMB). <h3>Materials/Methods</h3> Thirty-five brain lesions from twenty patients were planned using CPBs and compared against LPBs and LPMBs and VMAT. All proton plans were optimized with multi-field optimization technique using the Monte Carlo algorithm. Benchmarked on the photon plans, dose coverage to each lesion for each proton plan was set to 99% of the GTV receiving the prescription (Rx) dose for all plans. Conformity index (CI), gradient index (GI), V_12Gy, V_4.5Gy and mean dose of the brain were compared. To achieve similar PTV dose coverage to photons, ±2 mm setup uncertainty and ±2% range uncertainty were included in robust evaluation using V_100%Rx > 95% of the GTV for proton plans. Additionally, the plan delivery timing was assessed based on the proton modalities' energy switching and spot scanning times. <h3>Results</h3> All metrics of CI, GI, V_12Gy, V_4.5Gy, and mean brain dose for VMAT photon and three different proton plans are listed in Table 1. When compared to CPB generated plans, CI and GI were significantly better for the LPB and LPMB plans with a mean CI of 1.7 ± 0.5, 1.57 ± 0.4, and 1.4 ± 0.6 and a mean GI of 4.64 ± 1.48, 3.7 ± 1.1 and 2.8 ± 0.7, respectively. In comparison, mean CI and GI from photon VMAT plans were 2 ± 1.2, 4.7 ± 1.4. All proton plans achieved better V_4.5Gy than photon VMAT plans. LPBs reduced the mean brain dose by 17% compared to the CPB plans, and LPMB plans reduced the mean brain dose by 44%. While all plans had V_100%Rx of the GTV > 99% in the nominal scenario, in the voxel-wise worst scenario, 97.1%, 92.8% and 84.2% of the lesions had V_100%Rx > 95% for CPB, LPB, and LPMB, respectively, and in the worst-case scenario, 97.1%, 94.3% and 78.6% of the plans showed V_100%Rx > 95% among all lesions. The LPB energy switching time (5 ms) enables a rapid beam delivery, 58% faster on average than for CPB plans. LPMB beam delivery time can be further reduced by spot reduction planning (SRP) with equal plan quality. <h3>Conclusion</h3> We successfully quantified plan quality and evaluated robustness for CPBs, LPBs and LPMBs for brain metastases. The LPB and LPMB stand as an excellent alternative to CPB therapy and can significantly increase the preservation of normal tissue while ensuring fast delivery time.

Gradual Self-Training via Confidence and Volume Based Domain Adaptation for Multi Dataset Deep Learning-Based Brain Metastases Detection Using Nonlocal Networks on MRI Images.

Research suggests that treatment of multiple brain metastases (BMs) with stereotactic radiosurgery shows improvement when metastases are detected early, providing a case for BM detection capabilities on small lesions. To demonstrate automatic detection of BM on three MRI datasets using a deep learning-based approach. To improve the performance of the network is iteratively co-trained with datasets from different domains. A systematic approach is proposed to prevent catastrophic forgetting during co-training. Retrospective. A total of 156 patients (105 ground truth and 51 pseudo labels) with 1502 BM (BrainMetShare); 121 patients with 722 BM (local); 400 patients with 447 primary gliomas (BrATS). Training/pseudo labels/validation data were distributed 84/51/21 (BrainMetShare). Training/validation data were split: 121/23 (local) and 375/25 (BrATS). A 5 T and 3T/T1 spin-echo postcontrast (T1-gradient echo) (BrainMetShare), 3T/T1 magnetization prepared rapid acquisition gradient echo postcontrast (T1-MPRAGE) (local), 0.5T, 1T, and 1.16 T/T1-weighted-fluid-attenuated inversion recovery (T1-FLAIR) (BrATS). The ground truth was manually segmented by two (BrainMetShare) and four (BrATS) radiologists and manually annotated by one (local) radiologist. Confidence and volume based domain adaptation (CAVEAT) method of co-training the three datasets on a 3D nonlocal convolutional neural network (CNN) architecture was implemented to detect BM. The performance was evaluated using sensitivity and false positive rates per patient (FP/patient) and free receiver operating characteristic (FROC) analysis at seven predefined (1/8, 1/4, 1/2, 1, 2, 4, and 8) FPs per scan. The sensitivity and FP/patient from a held-out set registered 0.811 at 2.952 FP/patient (BrainMetShare), 0.74 at 3.130 (local), and 0.723 at 2.240 (BrATS) using the CAVEAT approach with lesions as small as 1 mm being detected. Improved sensitivities at lower FP can be achieved by co-training datasets via the CAVEAT paradigm to address the problem of data sparsity. 3 TECHNICAL EFFICACY STAGE: 2.

Novel approaches to the management of patients with 5-15 brain metastases: a narrative review.

The management of metastatic disease has been greatly influenced by molecular-based tumor classification and associated therapeutic targets, leading to a significant improvement in survival in many cases. This improvement, in both progression free survival and overall survival, has led to an increased incidence of brain metastases (BM) in a population with systemically well controlled disease or patients with promising therapeutic options available. Within this review, we discuss the paradigm of treatment for 5 to 15 BM, and how the treatment has evolved away from short-term palliation towards providing long term intracranial control. A review of literature pertaining to treatment of multiple BM was performed. We searched in PubMed to identify literature on treatment of multiple brain metastases. Only English literature published until February 1st, 2022 was reviewed. The management of 5-15 BM include multi-modality treatment pathways that are tailored towards each individual's primary cancer and burden of disease. Surgical resection of a dominant metastasis is still reserved for large symptomatic lesions, and is combined with post-operative local disease control. Overall, there is a shift away from whole brain radiation therapy (WBRT) due to side effect profile towards stereotactic radiosurgery (SRS). However, advances in WBRT continue to be studied, as well as the use of immunotherapy, targetable mutations, and synergistic effects between SRS and targeted therapies. The use of SRS to treat 5 to 15 BM is an increasingly acceptable and well-regarded practice, along with a combinatorial approach taking into account systemic options during all treatment timepoints.

Spatial uncertainty of Elekta stereotactic cones in the treatment of multiple brain metastases using multiple cones

PurposeTo evaluate the spatial accuracy of radiation centers (RCs) of Elekta stereotactic cones while changing the cone sizes during intra-fraction treatment of multiple brain metastases (MBM). Materials and methodsIn this study, nine cones of varying sizes (5, 10, 12.5, 15, 17.5, 20, 25, 30, and 35 mm) were used. The ball bearing (BB) was used as the target. The positions of BBs and RCs obtained using electronic portal imaging device (EPID) were transformed to a coordinate system X/Y/Z that was fixed with respect to the treatment room. ResultsThe positions of BBs when using cones sized between 12.5 and 35 mm were relatively stable. The maximum deviations between BBs and RCs were as follows: 1.11 mm in negative X and 1.30 mm in positive X, 0.87 mm in negative Y and 0.69 mm in positive Y, and 0.06 mm in negative Z and 0.58 mm in positive Z. The maximum offset between BBs and RCs gradually increased as the cone size decreased in the X and Y directions. The maximum offsets were 2.30, 1.56, and 0.64 mm in the X, Y, and Z directions, respectively, for the 12.5-mm cone. The maximum distance between the RCs was 0.43 mm when using the G135T270 beam between the 17.5-mm and 12.5-mm cones. ConclusionThe treatment of MBM with Elekta stereotactic cones demonstrated good spatial uncertainty. However, we need to pay particular attention to treatment using two or more cones in clinical practice. More external expansion margins are required in such cases.

Comparison with Conventional Arc and Split-Partial Arc Techniques of Volumetric Modulated Arc Therapy (VMAT) in Terms of Planning Efficiency for Stereotactic Radiotherapy (SRT) Treatment of Multiple Brain Metastases

Purpose: In stereotactic radiotherapy of multiple brain metastases (BM), Conventional Arc (CA) of the volumetric modulated arc therapy (VMAT) technique with on a single isocentric is a frequently used technique with Linac (Linear Accelerator) treatment devices. Reducing the dose of healthy brain tissue as well as improved delivery efficiency in SRT treatment of BM is important to reduce possible treatment toxicity. Therefore, multileaf collimator (MLC) movements in wide arcs of CA technique may result in non-optimal dose distribution and increasing low-dose volume in the brain. To evaluate improve the protection in brain of SPA technique having reduced field sizes which minimizes physical limitations of MLC moves. Methods: 28 patients with 3≤, ≥6 of multiple BM included in this retrospective planning study. All plans were generated 27 Gy in 3 fractions using conventional arcs with automated wide of fields and split partial arcs with the manual arrangement of fields according to tumors localization in brain. Dosimetric parameters included tumor coverage, conformity index (CI), gradient index (GI), V4Gy, V10Gy and V12Gy volumes of brain from both techniques were compared by Wilcoxon signed-ranked tests. Results: Both techniques satisfied clinical requirements in coverages of PTV and CI. CA technique had a significantly higher GI than SPA of VMAT (GI; 4.19 vs. 3.58; p &lt; 0.001). SPA technique was found significantly lower V4Gy (18.50 vs. 21.30 cm3, p &lt; 0.001), V10Gy (30.71 vs. 40.76 cm3, p &lt; 0.05) and V12Gy (213.32 vs. 305.71 cm3, p&lt;0.05) volumes. Conclusions: Due to rapid MLC modulation and less tongue-and-groove effect in arcs with smaller field widths, SPA technique can reduce OAR and brain dose radiation exposure in brain stereotactic radiotherapy for different tumor localizations in the brain. This technique may be the first choice compared to the CA technique for SRT of BM having distant and scattered targets.

Comparison of dosimetric impact of intra-fractional setup discrepancy between multiple- and single-isocenter approaches in linac-based stereotactic radiotherapy of multiple brain metastases.

IntroductionTreatment of multiple brain metastases by linac‐based stereotactic radiotherapy (SRT) can employ either a multiple‐isocenter (MI) or single‐isocenter (SI) approach. The purposes of this study were to evaluate the dosimetric results of MI and SI approaches and compare the impacts of intra‐fractional setup discrepancies on the robustness of respective approaches using isocenter shifts, whether the same magnitude of translational and rotational effects could lead to a significant difference between the two approaches.MethodsTwenty‐two patients with multiple brain metastases treated by linac‐based SRT were recruited. Treatment plans were computed with both the MI and SI approaches. For the MI approach, the isocenter was located at the geometric center of each planning target volumes (PTVs), whereas the isocenter of the SI approach was located midway between the PTV centroids. To simulate the intra‐fractional errors, isocenter displacements including translational and rotational shifts were hypothetically applied. Apart from the dosimetric outcomes of the two approaches, the impact of the isocenter shifts on PTVs and organs at risk (OARs) were recorded in terms of the differences (δ) in dose parameters relative to the reference plan and was then compared between the MI and SI approaches.ResultsBoth MI and SI plans met the plan acceptance criteria. The mean Paddick conformity index (Paddick CI) and Dmax of most OARs between MI and SI plans did not show a significant difference, except that higher doses to the left optic nerve and optic chiasm were found in SI plans (p = 0.03). After the application of the isocenter shifts, δCI increased with an increase in the magnitude of the isocenter shift. When comparing between MI and SI plans, the δCIs were similar (p > 0.05) for all extents of translational shifts, but δCIs were significantly higher in SI plans after application of all rotations particularly ±1.5° and ±2.0° shifts. Despite the result that the majority of δDMax of OARs were higher in the SI plans, only the differences in the left optic nerve and chiasm showed generally consistent significance after both translational ≥±1 mm and rotational shifts of ≥±1∘.ConclusionBoth MI and SI approaches could produce clinically acceptable plans. However, isocenter shifts brought dosimetric impacts to both MI and SI approaches and the effects increased with the increase of the shift magnitude. Although similar impacts were shown in plans of both approaches after translational isocenter shift, SI plans were relatively more vulnerable than MI plans to rotational shifts.