UNASSIGNED: Stereotactic radiosurgery (SRS) for the treatment of brain metastases delivers a high dose of radiation with excellent local control but comes with the risk of radiation necrosis (RN), which can be difficult to distinguish from tumor progression (TP). Magnetization transfer (MT) and chemical exchange saturation transfer (CEST) are promising techniques for distinguishing RN from TP in brain metastases. Previous studies used a 2D continuous-wave (ie, block radiofrequency [RF] saturation) MT/CEST approach. The purpose of this study is to investigate a 3D pulsed saturation MT/CEST approach with perfusion MRI for distinguishing RN from TP in brain metastases.
UNASSIGNED: The study included 73 patients scanned with MT/CEST MRI previously treated with SRS or fractionated SRS who developed enhancing lesions with uncertain diagnoses of RN or TP. Perfusion MRI was acquired in 49 of 73 patients. Clinical outcomes were determined by at least 6 months of follow-up or via pathologic confirmation (in 20% of the lesions).
UNASSIGNED: Univariable logistic regression resulted in significant variables of the quantitative MT parameter 1/(RA·T2A), with 5.9 ± 2.7 for RN and 6.5 ± 2.9 for TP. The highest AUC of 75% was obtained using a multivariable logistic regression model for MT/CEST parameters, which included the CEST parameters of AREXAmide,0.625µT (P = .013), AREXNOE,0.625µT (P = .008), 1/(RA·T2A) (P = .004), and T1 (P = .004). The perfusion rCBV parameter did not reach significance.
UNASSIGNED: Pulsed saturation transfer was sufficient for achieving a multivariable AUC of 75% for differentiating between RN and TP in brain metastases, but had lower AUCs compared to previous studies that used a block RF approach.

BACKGROUND: Central pain, characterized by neuropathic pain, can manifest due to injury to the superior spinothalamic tract. The brainstem includes sensory and motor pathways as well as nuclei of the cranial nerves, and therefore cancer metastasis in the region requires early intervention. Although stereotactic radiosurgery (SRS) is commonly employed for the treatment of brain metastasis, it poses risks of late complications like radiation necrosis (RN). RN exacerbates the progression of brain lesions within the irradiated area, and in the brainstem, it can damage multiple nerves, including the superior spinothalamic tract. Central neuropathic pain is often intractable and empirically managed with a combination of conventional drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. However, their efficacy is often limited, leading to a decline in performance status (PS) and quality of life (QOL).
METHODS: We present the case of a 53-year-old man diagnosed with stage IV lung cancer, referred to our palliative care team for managing severe central pain resulting from SRS-related RN in the pons. Despite administration of opioids, including oxycodone and hydromorphone, and adjuvant analgesics, the patient continued to require frequent use of immediate-release opioids. The addition of methadone alone proved successful in achieving optimal pain control.
CONCLUSIONS: Provided that RN in the brainstem can lead to intractable neuropathic pain, it is advisable to avoid SRS for brainstem metastasis when possible. Add-on methadone should be considered as a viable pain management medication for patients experiencing unresolved central pain.

Primary brain metastases are common in oncology. Preoperative stereotactic radiosurgery followed by surgical resection is a perspective approach.
OBJECTIVE: To evaluate own experience of preoperative radiosurgery followed by surgical resection (RS+S) of metastasis regarding local control, leptomeningeal progression, surgical and radiation-induced complications; to compare treatment outcomes with surgical resection and subsequent radiotherapy (S+SRT).
UNASSIGNED: Retrospective study included 66 patients with solitary brain metastasis. Two groups of patients were distinguished: group 1 (n=34) - postoperative irradiation, group 2 (n=32) - preoperative irradiation. The median age was 49.5 years (range 36-75).
RESULTS: Local 3-, 6- and 12-month control among patients with postoperative irradiation was 88.2%, 79.4% and 42.9%, in the group of preoperative irradiation - 100%, 93.3% and 66.7%, respectively (p=0.021). Leptomeningeal progression developed in 11 patients (8 and 3 ones, respectively). The one-year survival rate was 73.5% and 84.4%, respectively (p=0.33). Long-term surgical and radiation-induced complications occurred in 12 (18.2%) patients.
CONCLUSIONS: Preoperative radiosurgery with subsequent resection provides higher local control and lower incidence of leptomeningeal progression in patients with single brain metastases.
Метастазы рака в головной мозг сегодня являются распространенной проблемой в онкологии. Предоперационная стереотаксическая радиохирургия с последующим удалением опухоли — новый перспективный метод лечения.
UNASSIGNED: Оценить собственный опыт предоперационной радиохирургии с последующим хирургическим удалением метастаза с точки зрения локального контроля, лептоменингеальной прогрессии, хирургических и лучевых осложнений. Сравнить результаты лечения с группой пациентов с хирургическим удалением с последующим лучевым лечением метастаза в головной мозг.
UNASSIGNED: В ретроспективное исследование вошли 66 пациентов с подтвержденным одиночным метастазом рака в головной мозг, первая группа — 34 пациента с послеоперационным, вторая — 32 с предоперационным облучением. Медиана возраста составила 49,5 (от 36 до 75) лет.
UNASSIGNED: Локальный контроль в группе пациентов с послеоперационным облучением составил 88,2, 79,4 и 42,9% на сроках 3, 6 и 12 мес, а в группе предоперационного облучения — 100, 93,3 и 66,7% соответственно (p=0,021). Лептоменингеальная прогрессия развилась у 11 пациентов, 8 пациентов — в группе послеоперационного облучения и 3 — предоперационной радиохирургии соответственно. Однолетняя выживаемость составила 73,5 и 84,4% соответственно (p=0,33). У 12 (18,2%) пациентов в процессе наблюдения были выявлены отдаленные хирургические и постлучевые осложнения.
UNASSIGNED: У пациентов с одиночными метастазами в головной мозг предоперационная радиохирургия с последующим удалением опухоли обеспечивает более высокий ЛК и меньшую частоту лептоменингеального прогрессирования в сравнении с другим методом комбинированного лечения.

In this case series, we aimed to report our clinical experience with hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI) navigation in the management of recurrent glial brain tumors. Consecutive recurrent neuroglial brain tumor patients who underwent PET/MRI at preoperative or intraoperative periods were included, whereas patients with non-glial intracranial tumors including metastasis, lymphoma and meningioma were excluded from the study. A total of eight patients (mean age 50.1 ± 11.0 years) with suspicion of recurrent glioma tumor were evaluated. Gross total tumor resection of the PET/MRI-positive area was achieved in seven patients, whereas one patient was diagnosed with radiation necrosis, and surgery was avoided. All patients survived at 1-year follow-up. Five (71.4%) of the recurrent patients remained free of recurrence for the entire follow-up period. Two patients with glioblastoma had tumor recurrence at the postoperative sixth and eighth months. According to our results, hybrid PET/MRI provides reliable and accurate information to distinguish recurrent glial tumor from radiation necrosis. With the help of this differential diagnosis, hybrid imaging may provide the gross total resection of recurrent tumors without harming eloquent brain areas.

OBJECTIVE: Glioblastomas (GBM) are the most common primary invasive neoplasms of the brain. Distinguishing between lesion recurrence and different types of treatment related changes in patients with GBM remains challenging using conventional MRI imaging techniques. Therefore, accurate and precise differentiation between true progression or pseudoresponse is crucial in deciding on the appropriate course of treatment. This retrospective study investigated the potential of apparent diffusion coefficient (ADC) map values derived from diffusion-weighted imaging (DWI) as a noninvasive method to increase diagnostic accuracy in treatment response.
METHODS: A cohort of 21 glioblastoma patients (mean age: 59.2 ± 11.8, 12 Male, 9 Female) that underwent treatment with bevacizumab were selected. The ADC values were calculated from the DWI images obtained from a standardized brain protocol across 1.5-T and 3-T MRI scanners. Ratios were calculated for rADC values. Lesions were classified as bevacizumab-induced cytotoxicity based on characteristic imaging features (well-defined regions of restricted diffusion with persistent diffusion restriction over the course of weeks without tissue volume loss and absence of contrast enhancement). The rADC value was compared to these values in radiation necrosis and recurrent lesions, which were concluded in our prior study. The nonparametric Wilcoxon signed rank test with p < 0.05 was used for significance.
RESULTS: The mean ± SD age of the selected patients was 59.2 ± 11.8. ADC values and corresponding mean rADC values for bevacizumab-induced cytotoxicity were 248.1 ± 67.2 and 0.39 ± 0.10, respectively. These results were compared to the ADC values and corresponding mean rADC values of tumor progression and radiation necrosis. Significant differences between rADC values were observed in all three groups (p < 0.001). Bevacizumab-induced cytotoxicity had statistically significant lower ADC values compared to both tumor recurrence and radiation necrosis.
CONCLUSIONS: The study demonstrates the potential of ADC values as noninvasive imaging biomarkers for differentiating recurrent glioblastoma from radiation necrosis and bevacizumab-induced cytotoxicity.

BACKGROUND: This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS).
METHODS: Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpoints were local failure (LF), radiation necrosis (RN), leptomeningeal disease (LMD), a composite of these variables, and distant intracranial failure (DIF). Gray\'s test compared cumulative incidence, treating death as a competing risk with a random survival forests (RSF) machine-learning model also used to evaluate the data.
RESULTS: 183 patients were treated to 234 LBMs: 31.6% for postop-FSRS, 28.2% for SSRS, 20.1% for FSRS, and 20.1% for preop-SRS. The overall 1-year composite endpoint rates were comparable (21 vs 20%) between nonoperative and operative strategies, but 1-year RN rate was 8 vs 4% (p = 0.012), 1-year overall survival (OS) was 48 vs. 69% (p = 0.001), and 1-year LMD rate was 5 vs 10% (p = 0.052). There were differences in the 1-year RN rates (7% FSRS, 3% postop-FSRS, 5% preop-SRS, 10% SSRS, p = 0.037). With RSF analysis, the out-of-bag error rate for the composite endpoint was 47%, with identified top-risk factors including widespread extracranial disease, > 5 total lesions, and breast cancer histology.
CONCLUSIONS: This is the first study to conduct a head-to-head retrospective comparison of four SRS methods, addressing the lack of randomized data in LBM literature amongst treatment paradigms. Despite patient characteristic trends, no significant differences were found in LF, composite endpoint, and DIF rates between non-operative and operative approaches.

Brain metastases (BMs) are the most common intracranial tumor type and a significant health concern, affecting approximately 10% to 30% of all oncological patients. Although significant progress is being made, many aspects of the metastatic process to the brain and the growth of the resulting lesions are still not well understood. There is a need for an improved understanding of the growth dynamics and the response to treatment of these tumors. Mathematical models have been proven valuable for drawing inferences and making predictions in different fields of cancer research, but few mathematical works have considered BMs. This comprehensive review aims to establish a unified platform and contribute to fostering emerging efforts dedicated to enhancing our mathematical understanding of this intricate and challenging disease. We focus on the progress made in the initial stages of mathematical modeling research regarding BMs and the significant insights gained from such studies. We also explore the vital role of mathematical modeling in predicting treatment outcomes and enhancing the quality of clinical decision-making for patients facing BMs.

OBJECTIVE: The differentiation between adverse radiation effects (ARE) and tumor recurrence or progression (TRP) is a major decision-making point in the follow-up of patients with brain tumors. The advent of immunotherapy, targeted therapy and radiosurgery has made this distinction difficult to achieve in several clinical situations. Contrast clearance analysis (CCA) is a useful technique that can inform clinical decisions but has so far only been histologically validated in the context of high-grade gliomas.
METHODS: This is a series of 7 patients, treated between 2018 and 2023, for various brain pathologies including brain metastasis, atypical meningioma, and high-grade glioma. MRI with contrast clearance analysis was used to inform clinical decisions and patients underwent surgical resection as indicated. The histopathology findings were compared with the CCA findings in all cases.
RESULTS: All seven patients had been treated with gamma knife radiosurgery and were followed up with periodic MR imaging. All patients underwent CCA when the necessity to distinguish tumor recurrence from radiation necrosis arose, and subsequently underwent surgery as indicated. Concordance of CCA findings with histological findings was found in all cases (100%).
CONCLUSIONS: Based on prior studies on GBM and the surgical findings in our series, delayed contrast extravasation MRI findings correlate well with histopathology across a wide spectrum of brain tumor pathologies. CCA can provide a quick diagnosis and have a direct impact on patients\' treatment and outcomes.

Laser Interstitial Thermotherapy is a minimally invasive treatment option in neurosurgery for intracranial tumors, including recurrent gliomas. The technique employs the thermal ablation of target tissue to achieve tumor control with real-time monitoring of the extent by magnetic resonance thermometry, allowing targeted thermal injury to the lesion. Laser Interstitial Thermotherapy has gained interest as a treatment option for recurrent gliomas due to its minimally invasive nature, shorter recovery times, ability to be used even in patients with numerous comorbidities, and potential to provide local tumor control. It can be used as a standalone treatment or combined with other therapies, such as chemotherapy or radiation therapy. We describe the most recent updates regarding several studies and case reports that have evaluated the efficacy and safety of Laser Interstitial Thermotherapy for recurrent gliomas. These studies have reported different outcomes, with some demonstrating promising results in terms of tumor control and patient survival, while others have shown mixed outcomes. The success of Laser Interstitial Thermotherapy depends on various factors, including tumor characteristics, patient selection, and the experience of the surgical team, but the future direction of treatment of recurrent gliomas will include a combined approach, comprising Laser Interstitial Thermotherapy, particularly in deep-seated brain regions. Well-designed prospective studies will be needed to establish with certainty the role of Laser Interstitial Thermotherapy in the treatment of recurrent glioma.

OBJECTIVE: Radiation necrosis (RN) can be difficult to radiographically discern from tumor progression after stereotactic radiosurgery (SRS). The objective of this study was to investigate the utility of radiomics and machine learning (ML) to differentiate RN from recurrence in patients with brain metastases treated with SRS.
METHODS: Patients with brain metastases treated with SRS who developed either RN or tumor reccurence were retrospectively identified. Image preprocessing and radiomic feature extraction were performed using ANTsPy and PyRadiomics, yielding 105 features from MRI T1-weighted post-contrast (T1c), T2, and fluid-attenuated inversion recovery (FLAIR) images. Univariate analysis assessed significance of individual features. Multivariable analysis employed various classifiers on features identified as most discriminative through feature selection. ML models were evaluated through cross-validation, selecting the best model based on area under the receiver operating characteristic (ROC) curve (AUC). Specificity, sensitivity, and F1 score were computed.
RESULTS: Sixty-six lesions from 55 patients were identified. On univariate analysis, 27 features from the T1c sequence were statistically significant, while no features were significant from the T2 or FLAIR sequences. For clinical variables, only immunotherapy use after SRS was significant. Multivariable analysis of features from the T1c sequence yielded an AUC of 76.2% (standard deviation [SD] ± 12.7%), with specificity and sensitivity of 75.5% (± 13.4%) and 62.3% (± 19.6%) in differentiating radionecrosis from recurrence.
CONCLUSIONS: Radiomics with ML may assist the diagnostic ability of distinguishing RN from tumor recurrence after SRS. Further work is needed to validate this in a larger multi-institutional cohort and prospectively evaluate it\'s utility in patient care.