Up-front single-session radiosurgery for large brain metastases-volumetric responses and outcomes.

BACKGROUND: Patients presenting with large brain metastases (LBM) pose a management challenge to the multidisciplinary neuro-oncologic team. Treatment options include surgery, whole-brain or large-field radiation therapy (WBRT), stereotactic radiosurgery (SRS), or a combination of these. OBJECTIVE: To determine if corticosteroid therapy followed by SRS allows for efficient minimally invasive care in patients with LBMs not compromised by mass effect. METHODS: We analyzed the change in tumor volume to determine the efficacy of single-session SRS in the treatment of LBM in comparison to other treatment modalities. Twenty-nine patients with systemic cancer and brain metastasis (≥ 2.7 cm in greatest diameter) who underwent single-session SRS were included. RESULTS: Among 29 patients, 69% of patients had either lung, melanoma, or breast cancer. The median initial tumor size (maximal diameter) was 32 mm (range 28-43), and the median initial tumor volume was 9.56 cm3 (range 1.56-25.31). The median margin dose was 16 Gy (range 12-18). The average percent decrease in tumor volume compared to pre-SRS volume was 55% on imaging at 1-2 months, 58% at 3-5 months, 64% at 6-8 months, and 57% at > 8 months. There were no adverse events immediately following SRS. Median corticosteroid use after SRS was 21 days. Median survival after radiosurgery was 15 months. CONCLUSION: Initial high-dose corticosteroid therapy followed by prompt single-stage SRS is a safe and efficacious method to manage patients with LBMs (defined as ≥ 2.7 cm).

Intracranial leptomeningeal CNS ganglioneuroblastoma. First report and review of the literature.

BACKGROUND: CNS ganglioneuroblastoma in an extremely rare embryonal tumour, specifically in the pediatric population. Bad prognosis is documented due to aggressiveness and absence of protocolized treatment at the moment. CLINICAL DESCRIPTION: We present the case of a 5-year-old boy who presented with sudden loss of consciousness. CT scan was performed showing a large posterior fossa lesion with several intraventricular focal lesions, suggesting metastases, the largest one located inside the III ventricle. The patient underwent a posterior fossa resection of the lesion and a subtotal resection of the III ventricle lesion, with adjuvant chemotherapy. The evolution was poor and the patient finally died 3 months after diagnosis. CONCLUSION: Ganglioneuroblastoma is extremely likely to recur quickly and extensively. There is little knowledge about treatment options but is documented that gross total resection followed by adjuvant radiotherapy and chemotherapy is the best management in these patients.

Evaluation of the ability of the Brainlab Elements Cranial Distortion Correction algorithm to correct clinically relevant MRI distortions for cranial SRT.

PURPOSE: Cranial stereotactic radiotherapy (SRT) requires highly accurate lesion delineation. However, MRI can have significant inherent geometric distortions. We investigated how well the Elements Cranial Distortion Correction algorithm of Brainlab (Munich, Germany) corrects the distortions in MR image-sets of a phantom and patients. METHODS: A non-distorted reference computed tomography image-set of a CIRS Model 603-GS (CIRS, Norfolk, VA, USA) phantom was acquired. Three-dimensional T1-weighted images were acquired with five MRI scanners and reconstructed with vendor-derived distortion correction. Some were reconstructed without correction to generate heavily distorted image-sets. All MR image-sets were corrected with the Brainlab algorithm relative to the computed tomography acquisition. CIRS Distortion Check software measured the distortion in each image-set. For all uncorrected and corrected image-sets, the control points that exceeded the 0.5-mm clinically relevant distortion threshold and the distortion maximum, mean, and standard deviation were recorded. Empirical cumulative distribution functions (eCDF) were plotted. Intraclass correlation coefficient (ICC) was calculated. The algorithm was evaluated with 10 brain metastases using Dice similarity coefficients (DSC). RESULTS: The algorithm significantly reduced mean and standard deviation distortion in all image-sets. It reduced the maximum distortion in the heavily distorted image-sets from 2.072 to 1.059 mm and the control points with > 0.5-mm distortion fell from 50.2% to 4.0%. Before and especially after correction, the eCDFs of the four repeats were visually similar. ICC was 0.812 (excellent-good agreement). The algorithm increased the DSCs for all patients and image-sets. CONCLUSION: The Brainlab algorithm significantly and reproducibly ameliorated MRI distortion, even with heavily distorted images. Thus, it increases the accuracy of cranial SRT lesion delineation. After further testing, this tool may be suitable for SRT of small lesions.

Epidermal growth factor receptor-Mutated Non-small-cell Lung Cancer with Intracranial Progressions and Stable Extracranial Diseases Benefit from Osimertinib Regardless of T790M Mutational Status.

OBJECTIVES: Osimertinib has exhibited promising central nervous system (CNS) efficacy in Epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients. In real-world clinical practice, patients would turn to plasma genotyping or take osimertinib blindly after CNS progression on previous tyrosine kinase inhibitors (TKIs). However, the efficacy of osimertinib in those patients according to their T790M mutational status has not been explored. MATERIALS AND METHODS: Twenty-five patients who received osimertinib due to intracranial progressions with stable extracranial diseases after early-generation EGFR-TKI treatment were collected from 1032 EGFR-mutated NSCLC. Plasma samples were analyzed for EGFR mutations using next-generation sequencing (NGS) or polymerase chain reaction (PCR). RESULTS: Among the 25 patients, 17 patients took plasma genotyping before osimertinib treatment with 8 patients EGFR T790M mutation-positive and the rest started osimertinib blindly. The median progression-free survival (PFS) was 8.0 months (95% confidence interval [CI]: 6.12-9.94) and median intracranial PFS (iPFS) was 14.4 months (95% CI: 7.27-21.59) for the total population. No statistical difference was found in PFS and iPFS among patients with different EGFR T790M mutational statuses. Intracranial disease control rate (DCR) was 100.0% for 14 patients with evaluable intracranial lesions despite different T790M mutational statuses. DCR for extracranial lesions and overall lesions were 100.0%, 66.7%, and 87.5% for patients with T790M, no T790M, and unknown T790M mutational status, respectively. CONCLUSION: For EGFR-mutated NSCLC patients with only intracranial progressions after previous TKI treatments, osimertinib is a promising treatment option regardless of T790M mutational status from plasma genotyping.

Melanoma brain metastases in Ireland: surgical and systemic considerations.

BACKGROUND: Cerebral metastases is a common complication in patients with melanoma. There is a paucity of information in the Republic of Ireland regarding the factors associated with melanoma brain metastases (MBM). METHODS: Patients diagnosed with melanoma brain metastases in Ireland were retrospectively identified in Beaumont Hospital between 1999 and 2018. Patient demographics; age at diagnosis of primary melanoma, age at detection of MBM, year of detection of MBM, anatomical location of primary melanoma, BRAF mutation analysis and the number of metastases were investigated. Follow-up data were also derived, including overall survival. RESULTS: There has being a 158% increase in the incidence of primary melanoma from 1999 compared to 2016. Over the same time period 128 patients with melanoma brain metastases were diagnosed. There was a significant male predominance (n = 77/128; 60%; p < 0.0001). BRAF mutation and leptomeningeal disease were independent prognostic factors in our cohort with a median survival 8 months and 0.5 months, respectively. CONCLUSIONS: Male predominance, leptomeningeal disease and BRAF mutation represent important considerations in this population group. The results of this study add to our knowledge concerning outcomes in melanoma brain metastases and may be useful in clinical planning and future treatments.

Predicting response to radiotherapy of intracranial metastases with hyperpolarized [Formula: see text]C MRI.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. METHODS: Patients with intracranial metastases (N = 11) were scanned using hyperpolarized [Formula: see text]C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). RESULTS: The positive predictive value of [Formula: see text]C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 [Formula: see text], and the AUC from an ROC analysis was 0.77 [Formula: see text]. The distribution of [Formula: see text]C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, [Formula: see text]). CONCLUSIONS: Hyperpolarized [Formula: see text]C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.

Stereotactic Radiosurgery to Prevent Local Recurrence of Brain Metastasis After Surgery: Neoadjuvant Versus Adjuvant.

Over the past 15-20 years, stereotactic radiosurgery (SRS) has become the dominant method for treating patients with brain metastases (BM). The role of surgery for management of large tumors also remains important. Combining these two treatment modalities may well achieve the best local control, safety, and symptomatic relief in cases of neoplasms for which resection is desirable. After 10 years of retrospective studies that suggested patients might do better if surgery were followed by early adjuvant SRS, a prospective, randomized, controlled trial was conducted to compare such treatment with postoperative observation after tumor removal, and it showed significantly better local control in the former cohort, especially in smaller lesions, but no difference in overall survival. On the other hand, in the past 5 years, some groups have argued that neoadjuvant SRS before resection of BM might be superior to adjuvant SRS, while no clinical trial has yet been concluded that compares these two treatment strategies. For now, adjuvant and neoadjuvant SRS show evidence of utility in achieving better local control after surgical removal of BM in comparison with surgery alone, but no specific guidelines exist favoring one method over the other, and both should be considered beneficial in clinical care.

Evidence-Based Recommendations for Seizure Prophylaxis in Patients with Brain Metastases Undergoing Stereotactic Radiosurgery.

Symptomatic epilepsy is frequently encountered in patients with brain metastases (BM), affecting up to 25% of them. However, it generally remains unknown whether the risk of seizures in such cases is affected by stereotactic radiosurgery (SRS), which involves highly conformal delivery of high-dose irradiation to the tumor with a minimal effect on adjacent brain tissue. Thus, the role of prophylactic administration of antiepileptic drugs (AED) after SRS remains controversial. A comprehensive review and analysis of the available literature reveals that according to prospective studies, the incidence of seizures after SRS for BM varies from 8% to 22%, and there is no evidence that SRS increases the incidence of symptomatic epilepsy. Therefore, routine prophylactic administration of AED prior to, during, or after SRS in the absence of a seizure history is not recommended. Nevertheless, short-course administration of an AED may be judiciously considered (on the basis of class III evidence) for selected high-risk individuals.

Redistributing Central Target Dose Hot Spots for Hypofractionated Radiosurgery of Large Brain Tumors: A Proof-of-Principle Study.

OBJECTIVE: The present proof-of-principle study investigated radiobiological effects of redistributing central target dose hot spots across different treatment fractions during hypofractionated stereotactic radiosurgery (HSRS) of large intracranial tumors. METHODS: Redistribution of central target dose hot spots during HSRS was simulated, and its effects were evaluated in eight cases of brain metastases. To assess dose variations in the target across N number of treatment fractions, a generalized biologically effective dose (gBED) was formulated. The gBED enhancement ratio was defined as the ratio of gBED in the tested treatment plan (with central target dose hot spot redistributions across fractions) to gBED in the conventional treatment plan (without central target dose hot spot redistributions). RESULTS: At a median α value of 0.3/Gy, the tested treatment plans resulted in average gBED increases of 15.6 ± 3.5% and 8.3 ± 1.8% for α/ß ratios of 2 and 10 Gy, respectively. In comparison with conventional treatment plans, the differences in the Paddick conformity index and gradient index did not exceed 2%. CONCLUSION: Redistributing central target dose hot spots across different treatment fractions during HSRS may be considered promising for enhancing gBED in the target. It may be beneficial for management of large intracranial neoplasms; thus, it warrants further clinical testing.

Possible Overcoming of Tumor Hypoxia with Adaptive Hypofractionated Radiosurgery of Large Brain Metastases: A Biological Modeling Study.

OBJECTIVE: The present biological modeling study evaluated possible application of adaptive hypofractionated stereotactic radiosurgery (HSRS), which involves escalation of the prescription dose according to the gradual decrease in the tumor volume between treatment sessions separated by 2- to 3-week intervals, in the management of large brain metastases. METHODS: To investigate the effects of dose escalation during three-stage adaptive HSRS, a generalized biologically effective dose (gBED) model was applied. Accounting for both a nonuniform dose distribution inside the target and tumor hypoxia was implemented, and normal brain radiation dose distributions were assessed. RESULTS: In comparison with conventional three-stage HSRS (with an identical prescription dose of 10 Gy at each treatment session), adaptive HSRS resulted in a 30-40% increase in gBED. This effect was especially prominent in late-responding targets (with α/ß ratios from 3 to 10 Gy) and in neoplasms containing a high percentage of hypoxic cells. Despite dose escalation in the target, irradiation of the adjacent normal brain tissue was kept within safe limits at a level similar to that applied in conventional three-stage HSRS. CONCLUSION: Adaptive HSRS theoretically results in significant enhancement of gBED in the target and may possibly overcome resistance to irradiation, which is caused by tumor hypoxia. These advantages may translate into higher treatment efficacy in cases of large brain metastases.

Cumulative Intracranial Tumor Volume as a Prognostic Factor in Patients with Brain Metastases Undergoing Stereotactic Radiosurgery.

Approximately 25-35% of all cancer patients suffer from brain metastases (BM), and many of them-in particular, those with a limited number of intracranial tumors-are treated with stereotactic radiosurgery (SRS). Accurate prediction of survival remains a key clinical challenge in this population. Several prognostic scales have been developed to facilitate this prognostication, including the Recursive Partitioning Analysis (RPA) classification, the modified Recursive Partitioning Analysis (mRPA) subclassifications, the Basic Score for Brain Metastases (BS-BM), the Score Index for Radiosurgery (SIR), the Graded Prognostic Assessment (GPA), and the diagnosis-specific Graded Prognostic Assessment (dsGPA). However, none of these scales include consideration of the cumulative intracranial tumor volume (CITV), which is defined as the sum of all intracranial tumor volumes. Since there is mounting evidence that the CITV carries significant prognostic value in SRS-treated patients with BM, this variable should be considered during survival prognostication, along with other pertinent clinical, pathological, and molecular characteristics.

Differentiating Radiation-Induced Necrosis from Tumor Progression After Stereotactic Radiosurgery for Brain Metastases, Using Evaluation of Blood Flow with Arterial Spin Labeling (ASL): The Importance of Setting a Baseline.

OBJECTIVE: This study evaluated the usefulness of arterial spin labeling (ASL) for assessment of tumor blood flow (TBF) and cerebral blood flow (CBF) before Gamma Knife surgery (GKS) for intracranial metastases, in order to analyze the variability of perfusion characteristics at baseline and to reveal how these data may impact differentiation of radiation-induced effects from tumor progression during follow-up. METHODS: Radiological data from 87 patients with intracranial metastases of solid cancers, who underwent TBF/CBF analysis by means of ASL at the Hawaii Advanced Imaging Institute between 2015 and 2018 both before and after GKS, were reviewed retrospectively. Only cases with a largest tumor diameter of ≥10 mm were included in the study cohort (N = 53). RESULTS: In comparison with CBF in the healthy contralateral cerebral cortex, TBF before GKS was greater in 32 cases (60%), lesser in 7 cases (13%), and equivalent in 14 cases (27%). There was significant variability in TBF both within and between histologically different groups of tumors. CONCLUSION: Since, at baseline, approximately 40% of intracranial metastases have TBF that is lesser or equivalent to CBF, increased blood flow in the contrast-enhancing lesion after GKS may have insufficient sensitivity for identification of tumor progression. Availability of baseline TBF data may significantly facilitate differential diagnosis in such cases.

Neuroimaging characteristics and long-term prognosis of myxoma-related intracranial diseases.

PURPOSE: Myxoma-related intracranial diseases were rarely documented in history. The main purpose of our study is to provide a more comprehensive and detailed understanding of the pathogenesis, imaging features, surgical procedures and pathology of such patients through long-term follow-up. METHODS: From March 2012 to July 2018, baseline information that included neuroimaging and neuropathology data from 12 cardiac myxoma patients with neurological symptoms were retrospectively analysed, and the treatment options were discussed. Nine patients underwent long-term postoperative follow-up. RESULTS: Twelve cardiac myxoma patients with neurological symptoms were identified, and among them, 10 patients were postoperative patients who had undergone excision of cardiac myxoma, 5 patients had received craniotomy, and the others had received conservative treatment. Positive neuroimaging findings were found in all patients, including cerebral infarction (12/12, 100%), multiple intracranial aneurysms (8/12, 67%), and extravascular metastasis (6/12, 50%). After a long-term average follow-up of 27 months, an increased number of metastatic lesions or an enlargement of the intracranial aneurysms was found in 4 patients. CONCLUSIONS: Neuroimaging findings of myxoma-related intracranial lesions were diversed and usually presented as multiple cerebral infarction, aneurysm formation, focal intracranial haemorrhage and space-occupying lesions. Progress is over a long period of time after primary tumour resection. It is necessary for patients to be regularly examined within 2 years after cardiac myxoma resection using MRI+CTA/MRA/DSA in order to be ruled out. Stable and effective chemotherapy drugs are urgently needed.

Unmasking of intracranial metastatic melanoma during ipilimumab/nivolumab therapy: case report and literature review.

BACKGROUND: While data from several studies over the last decade has demonstrated that introduction of immunologic checkpoint blockage therapy with anti-CTLA-4/PD-1 drugs leads to improved survival in metastatic melanoma patients, relatively little is known about brain-specific therapeutic response and adverse events in the context of immunotherapeutic treatment of intracranial disease. Here we report two independent cases of new intracranial metastases presenting after initiation of combined checkpoint blockade Ipilimumab and Nivolumab for recurrent metastatic melanoma in the context of positive systemic disease response. CASE PRESENTATION: Case #1: A 43-year-old Caucasian male with Stage III melanoma of the left knee had subsequent nodal, hepatic and osseous metastases and was started on ipilimumab/nivolumab. He developed an intractable headache one week later. MRI revealed new enhancing and hemorrhagic brain metastases. After 6 weeks of immunotherapy, there was interval hemorrhage of a dominant intracranial lesion but substantial improvement in systemic metastatic disease. Durable, near complete intracranial and systemic response was achieved after completion of both induction and maintenance immunotherapy. Case #2: A 58-year old Caucasian woman with stage II melanoma of the right index finger developed cutaneous, pulmonary and hepatic metastases within 4 months of adjuvant radiation. Although combined checkpoint blockade resulted in improvement in both cutaneous and systemic disease, brain MR performed for eye discomfort demonstrated new enhancing and hemorrhagic brain metastases. Serial MR imaging five months later revealed only a solitary focus of brain enhancement with continued improved systemic disease. CONCLUSIONS: These cases raise the question of whether the initial immune activation and modulation of the blood brain barrier by Ipilimumab/Nivolumab somehow "unmasks" previously clinically silent metastatic disease, rather than representing new or progressive metastatic disease. An overview of currently available literature discussing the role of immune checkpoint blockade in the treatment of intracranial metastatic melanoma will be provided, as well as discussion highlighting the need for future work elucidating the response of brain metastases to anti-CTLA/PD-1 drugs and documentation of brain-specific adverse events.

Stereotactic Radiosurgery and Stereotactic Fractionated Radiotherapy in the Management of Brain Metastases.

The management of brain metastases (BM) remains an important and complex issue in the treatment of cancer-related neurological complications. BM are particularly common in patients diagnosed with lung, melanoma, or breast cancer. Over the past decade, therapeutic approaches for the majority of BM patients have changed. Considering and addressing the fact that patients with BM are living longer, the need to provide effective local control while preserving quality of life and neurocognition is fundamental. Over the past decade, SRS and SRT have become a more commonly chosen treatment option for BM. Despite significant advances in the treatment of BM, numerous questions remain regarding patient selection and optimal treatment sequencing. Clinical trials are critical to advancing our understanding of BM, especially as more therapeutic alternatives become available. Therefore, it is imperative for interdisciplinary teams to improve their understanding of the latest advances in SRS-SRT. This review aims to comprehensively explore SRS and SRT as treatments for BM, covering clinical considerations in their application (e.g., patient selection and eligibility), managing limited and multiple intact BM, addressing brainstem metastases, exploring combination therapies with systemic treatments, and considering the health economic perspective.

An Evaluation of Risk Factors for Intracranial Metastases of Sarcomas: A Systematic Review and Meta-Analysis.

INTRODUCTION: Sarcomas, a group of neoplasms comprising both tissue and bone soft tissue tumors, has an increasing prevalence in recent years. Prognosis significantly hinges on early detection, and if not detected early, may consequently metastasize. This review will be the first systematic review and meta-analysis characterizing the presentation and progression of brain metastases from bone and soft tissue cancers. METHODS: The PubMed, Scopus, and Web of Science databases were queried to identify studies reporting the incidence of intracranial brain metastases from primary sarcoma to the present. Abstract and full-text screening of 1822 initial articles returned by preliminary search yielded 28 studies for inclusion and data extraction. Qualitative assessment of the studies was conducted in accordance with the Newcastle-Ottawa Scale criteria. Meta-analyses were applied to assess risk factors on outcomes. RESULTS: The average age within the cohort was 27.9 years with a male and female prevalence of 59.1% and 40.9%, respectively. The odds ratio for living status (dead/alive) was calculated for several risk factors - male/female [OR 1.14, 95% CI 0.62, 2.07], single/multiple metastases [OR 0.67, 95% CI 0.35, 1.28], lung metastases/not [OR 1.63, 95% CI 0.85, 3.13], surgery/no surgery [OR 0.49, 95% CI 0.20, 1.21]. The standardized mean differences for duration from diagnoses to metastases were likewise analyzed - male/female [SMD 0.13, 95% CI -0.15, 0.42], single/multiple metastases [SMD 0.11, 95% CI -0.20, 0.42], lung metastases/not [SMD -0.03, 95% CI -0.38, 0.32], surgery/no surgery [SMD 0.45, 95% CI -0.18, 1.09]. The standardized mean differences for duration from metastases to death were analyzed - lung metastases/not [SMD 0.43, 95% CI -0.08, 0.95]. CONCLUSIONS: Our study observed no statistically significant differences in mortality rate among several patient risk factors. Consequentially, there lacks a clear answer as to whether or not an association between mortality rates exists with these patient factors. As such, it is important to continue research in brain-metastasizing sarcomas despite their relative rarity.

Prospective comparison of volumetric post-contrast T1-Sampling Perfection with Application optimized Contrasts by using different flip angle Evolutions and Magnetization-Prepared Rapid Acquisition with Gradient Echo in patients with metastatic melanoma.

INTRODUCTION: Volumetric turbo spin echo (3D-TSE) T1-weighted imaging techniques such as T1-SPACE (Sampling Perfection with Application optimized Contrasts by using different flip angle Evolutions) improve detection of intracranial metastases (IM) compared to volumetric magnetisation-prepared gradient recalled echo techniques such as MPRAGE (Magnetization-Prepared Rapid Acquisition with Gradient Echo). However, incomplete vascular suppression can produce false positives when using 3D-TSE. Research into 3D-TSE has generally targeted patients with known or suspected IM, but the clinical implications of false positives are greater in patients with lower likelihood of IM. This study examined additional findings identified by T1-SPACE in patients with metastatic melanoma, targeting patients with a lower incidence of IM. METHODS: Patients with metastatic melanoma and an upcoming brain MRI booking were identified prospectively. Consent for adding post-contrast T1-SPACE to the MRI protocol (which included MPRAGE) was obtained. Imaging was initially assessed without T1-SPACE. Subsequently, T1-SPACE images were examined and additional findings identified were recorded, including their correlation with MPRAGE. RESULTS: One hundred examinations were performed, 24 having evidence of active IM. T1-SPACE allowed identification of additional lesions in five patients, including two with small solitary IM not identified when first assessing MPRAGE. In 18 examinations, T1-SPACE identified additional equivocal findings, confidently attributed to artefact (most commonly normal vessels) following correlation with MPRAGE. CONCLUSION: T1-SPACE improves detection of small lesions in patients without known IM, changing patient management. False positives are common but can be clarified with MPRAGE. Combining T1-SPACE and MPRAGE allows both sensitivity and specificity to be optimised.

Improving the diagnosis of radiation necrosis after stereotactic radiosurgery to intracranial metastases with conventional MRI features: a case series.

BACKGROUND: The distinction between true disease progression and radiation necrosis after stereotactic radiosurgery to intracranial metastases is a common, but challenging, clinical scenario. Improvements in systemic therapies are increasing the importance of this distinction. A variety of imaging techniques have been investigated, but the value of any individual technique is limited. CASE PRESENTATION: Assessment should extend beyond simply the appearances of the lesion at a given timepoint, but also consider local anatomy and lesion evolution. Firstly, enlargement of a metastasis is affected by local anatomical boundaries, such as the dural reflections or cerebrospinal fluid spaces. In contrast, the radiation dose administered with stereotactic radiosurgery does not respect these anatomical boundaries and is largely concentric around the treated lesion. Therefore, new, non-contiguous enhancement across such a boundary can be confidently attributed to radiation necrosis. Secondly, the dynamic nature of radiation necrosis may result in a change in lesion shape, with different portions of the lesion simultaneously enlarging and regressing. Regression of part of a lesion indicates radiation necrosis, even if the overall lesion enlarges. This case series describes these two features and provides illustrative clinical examples in which these features allowed a confident diagnosis of radiation necrosis. CONCLUSIONS: The distinction between true disease progression and radiation necrosis should extend beyond just the appearances of the lesion. More nuanced interpretation incorporating a relationship to anatomical boundaries and a change in shape can improve accurate diagnosis of radiation necrosis.

Whole-brain Radiation Therapy for Intracranial Metastases as Initial or Late Treatment.

BACKGROUND/AIM: We examined the difference between whole-brain radiation therapy (WBRT) for intracranial metastases (IM) from lung cancer as an initial and as a late treatment affecting overall survival (OS). PATIENTS AND METHODS: Thirty-three patients who presented with IM at initial examination who received WBRT as the initial treatment (initial WBRT group) and 47 patients without IM or with asymptomatic IM at initial examination who received WBRT after systemic therapy, between January 2014 and December 2020, were retrospectively analyzed. Patients' OS after WBRT were compared. RESULTS: Median OS was significantly longer in patients treated with systemic anticancer therapy after WBRT than in patients who were not (176 vs. 47 days, respectively; p<0.001), and systemic anticancer therapy after WBRT was a significant prognostic factor (p<0.001). CONCLUSION: Treatment with systemic anticancer therapy after WBRT may prolong the survival of patients who present with IM at initial examination.

Resecting the dominant lesion: Patient outcomes after surgery and radiosurgery vs stand-alone radiosurgery in the setting of multiple brain metastases.

BACKGROUND: Brain metastases are the most common central nervous system (CNS) tumors, occurring in 300,000 people per year in the US. While there are immediate local benefits to surgical resection for dominant lesions, including reduction of tumor burden and edema, the survival benefits of surgical resection, over radiosurgery, remains unclear. METHODS: The University of Pennsylvania Health System database was retrospectively reviewed for patients presenting with multiple brain metastases from 1/1/16-8/31/18 with one dominant lesion > 2 cm in diameter, who underwent initial treatment with either resection of the dominant lesion or Gamma Knife radiosurgery (GKS). Inclusion criteria were age > 18, > 1 brain metastasis, and presence of a dominant lesion (>2 cm). We analyzed factors associated with mortality. RESULTS: 129 patients were identified (surgery=84, GKS=45). The median number of intracranial metastases was 3 (IQR: 2-5). The median diameter of the largest lesion was 31 mm (IQR: 25-38) in the surgery group vs 21 mm (IQR: 20-24) in the GKS group (p < 0.001). Mortality did not differ between surgery and GKS patients (69.1% vs 77.8%, p = 0.292). In a multivariate survival analysis, there was no difference in mortality between the surgery and GKS cohorts (aHR: 1.35, 95% CI: 0.74-2.45 p = 0.32). Pre-operative KPS (aHR: 0.97, 95% CI: 0.95-0.99, p = 0.004), CNS radiotherapy (aHR: 0.33, 95% CI: 0.19-0.56 p < 0.001), chemotherapy (aHR: 0.27, 95% CI: 0.15-0.47, p < 0.001), and immunotherapy (aHR: 0.41, 95% CI: 0.25-0.68, p = 0.001) were associated with decreased mortality. CONCLUSION: In our institution, patients with multiple brain metastases and one symptomatic dominant lesion demonstrated similar survival after GKS when compared with up-front surgical resection of the dominant lesion.