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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). Case presentation: 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. [ABSTRACT FROM AUTHOR]

Introduction: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Abstract 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). Case presentation 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.

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. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates an imaging method for distinguishing different lesions in brain cancer patients using MRI scans. Glioblastoma is a highly aggressive brain tumor, and it is crucial to differentiate between actual tumor recurrence, radiation-induced damage, and side effects from a common treatment called Bevacizumab. Traditional MRI techniques often struggle to make these distinctions, leading to challenges in treatment decisions. This study explores the use of a specific MRI measurement, called Apparent Diffusion Coefficient (ADC) values, to improve diagnostic accuracy. By identifying unique patterns in ADC values, this method could help better determine the nature of brain lesions, ultimately leading to more precise and effective treatment plans for glioblastoma patients. Objectives: 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. Conclusion: The study demonstrates the potential of ADC values as noninvasive imaging biomarkers for differentiating recurrent glioblastoma from radiation necrosis and bevacizumab-induced cytotoxicity. [ABSTRACT FROM AUTHOR]

In brain metastases, radiation necrosis (RN) is a complication that arises after single or multiple fractionated stereotactic radiosurgery (SRS/FSRS), which is challenging to distinguish from local recurrence (LR). Studies have shown increased RN incidence rates in non‐small cell lung cancer (NSCLC) patients with oncogenic driver mutations (ODMs) or receiving tyrosine kinase inhibitors (TKIs). This study investigated enlarging brain lesions following SRS/FSRS, for which additional surgeries were performed to distinguish between RN and LR. We investigated seven NSCLC patients with ODMs undergoing SRS/FSRS for BM and undergoing surgery for suspicion of LR on MRI imaging. Descriptive statistics were performed. Among the seven patients, six were EGFR+, while one was ALK+. The median irradiation dose was 30 Gy (range, 20–35 Gy). The median time to develop RN after SRS/FSRS was 11.1 months (range: 6.3–31.2 months). Moreover, gradually enlarging lesions were found in all patients after 6 months post‐SRS/FSR. Brain radiation necrosis was pathologically confirmed in all the patients. RN should be suspected in NSCLC patients when lesions keep enlarging after 6 months post‐SRS/FSRS, especially for patients with ODMs and receiving TKIs. Further, this case series indicates that further dose reduction might be necessary to avoid RN for such patients. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is a feasible adjuvant therapeutic option for managing intracranial pathologies. One of the late complications of RT that frequently develops within months following RT is radiation necrosis (RN). Corticosteroids are the first-line therapeutic option for RNs; however, in case of unfavorable outcomes or intolerability, several other options, including bevacizumab, laser interstitial thermal therapy, surgery, and hyperbaric oxygen therapy (HBOT). Our goal was to investigate the feasibility and efficacy of the application of HBOT in RNs following RT and help physicians make decisions based on the latest data in the literature. We provide a comprehensive review of the literature on the current issues of utilization of HBOT in RNs. We included 11 studies with a total of 46 patients who underwent HBOT. Most of the cases were diagnosed with brain tumors or arteriovenous malformations. Improvement was achieved in most of the cases. HBOT is a noninvasive therapeutic intervention that can play a role in adjuvant therapy concurrent with RT and chemotherapy and treating RNs. HBOT resolves the RN through 3 mechanisms, including angiogenesis, anti-inflammatory modulation, and cellular repair. Previous studies demonstrated that HBOT is a feasible and well-tolerated therapeutic option that has shown promising results in improving clinical and radiological outcomes in intracranial RNs. Complications of HBOT are usually mild and reversible. HBOT is a feasible and effective therapeutic option in steroid-refractory RNs and is associated with favorable outcomes and a low rate of side effects. [Display omitted] [ABSTRACT FROM AUTHOR]

We report the case of a 70‐year‐old woman with metastatic brain tumors who underwent surgical removal of the tumor and radiation necrosis. The patient had a history of colon cancer and had undergone surgical removal of a left occipital tumor. Histopathological evaluation revealed a metastatic brain tumor. The tumor recurred six months after surgical removal, followed by whole‐brain radiotherapy, and the patient underwent stereotactic radiosurgery. Six months later, the perifocal edema had increased, and the patient became symptomatic. The diagnosis was radiation necrosis and corticosteroids were initially effective. However, radiation necrosis became uncontrollable, and the patient underwent removal of necrotic tissue two years after stereotactic radiosurgery. Pathological findings predominantly showed necrotic tissue with some tumor cells. Since the vascular endothelial growth factor (VEGF) and hypoxia‐inducible factor‐1α (HIF‐1α) were expressed around the necrotic tissue, the main cause of the edema was determined as radiation necrosis. Differences in the expression levels and distribution of HIF‐1α and VEGF were observed between treatment‐naïve and recurrent tumor tissue and radiation necrosis. This difference suggests the possibility of different mechanisms for edema formation due to the tumor itself and radiation necrosis. Although distinguishing radiation necrosis from recurrent tumors using MRI remains challenging, the pathophysiological mechanism of perifocal edema might be crucial for differentiating radiation necrosis from recurrent tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms. Methods: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes. Results: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT). Conclusion: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Differentiating recurrent cerebral metastasis (CM) from brain radiation necrosis (BRN) is pivotal for guiding appropriate treatment and prognostication. Despite advances in imaging techniques, however, accurately distinguishing these conditions non-invasively is still challenging. This single-center retrospective study reviewed 32 cases (28 patients) with confirmed cerebral metastases who underwent surgical excision of lesions initially diagnosed by MRI and/or MR perfusion scans from 1 January 2015 to 30 September 2020. Diagnostic accuracy was assessed by comparing imaging findings with postoperative histopathology. Conventional MRI accurately identified recurrent CM in 75% of cases. MR perfusion scans showed significantly higher mean maximum relative cerebral blood volume (max. rCBV) in metastasis cases, indicating its potential as a discriminative biomarker. No single imaging modality could definitively distinguish CM from BRN. Survival analysis revealed gender as the only significant factor affecting overall survival, with no significant survival difference observed between patients with CM and BRN after controlling for confounding factors. This study underscores the limitations of both conventional MRI and MR perfusion scans in differentiating recurrent CM from BRN. Histopathological examination remains essential for accurate diagnosis. Further research is needed to improve the reliability of non-invasive imaging and to guide the management of patients with these post-radiation events. [ABSTRACT FROM AUTHOR]

Purpose: Distinguishing recurrent brain tumor from treatment effects, including late time-to-onset radiation necrosis (RN), presents an on-going challenge in post-treatment imaging of neuro-oncology patients. Experiments were performed in a novel mouse model that recapitulates the relevant clinical histologic features of recurrent glioblastoma growing in a RN environment, the mixed tumor/RN model. The goal of this work was to apply single-voxel deuterium (2H) magnetic resonance spectroscopy (MRS), in concert with administration of deuterated glucose, to determine if the metabolic signature of aerobic glycolysis (Warburg effect: glucose → lactate in the presence of O2), a distinguishing characteristic of proliferating tumor, provides a quantitative readout of the tumor fraction (percent) in a mixed tumor/RN lesion. Procedures: 2H MRS employed the SPin-ECho full-Intensity Acquired Localized (SPECIAL) MRS pulse sequence and outer volume suppression at 11.74 T. For each subject, a single 2H MRS voxel was placed over the mixed lesion as defined by contrast enhanced (CE) 1H T1-weighted MRI. Following intravenous administration of [6,6-2H2]glucose (Glc), 2H MRS monitored the glycolytic conversion to [3,3-2H2]lactate (Lac) and glutamate + glutamine (Glu + Gln = Glx). Results: Based on previous work, the tumor fraction of the mixed lesion was quantified as the ratio of tumor volume, defined by 1H magnetization transfer experiments, vs. the total mixed-lesion volume. Metabolite 2H MR spectral-amplitude values were converted to metabolite concentrations using the natural-abundance semi-heavy water (1HO2H) resonance as an internal concentration standard. The 2H MR-determined [Lac] / [Glx] ratio was strongly linearly correlated with tumor fraction in the mixed lesion (n = 9), Pearson's r = 0.87, and 77% of the variation in the [Lac] / [Glx] ratio was due to tumor percent r2 = 0.77. Conclusions: This preclinical study supports the proposal that 2H MR could occupy a well-defined secondary role when standard-of-care 1H imaging is non-diagnostic regarding tumor presence and/or response to therapy. [ABSTRACT FROM AUTHOR]

Background: MRI treatment response assessment maps (TRAMs) were introduced to distinguish recurrent malignant glioma from therapy related changes. TRAMs are calculated with two contrast-enhanced T1-weighted sequences and reflect the "late" wash-out (or contrast clearance) and wash-in of gadolinium. Vital tumor cells are assumed to produce a wash-out because of their high turnover rate and the associated hypervascularization, whereas contrast medium slowly accumulates in scar tissue. To examine the real value of this method, we compared TRAMs with the pathology findings obtained after a second biopsy or surgery when recurrence was suspected. Methods: We retrospectively evaluated TRAMs in adult patients with histologically demonstrated glioblastoma, contrast-enhancing tissue and a pre-operative MRI between January 1, 2017, and December 31, 2022. Only patients with a second biopsy or surgery were evaluated. Volumes of the residual tumor, contrast clearance and contrast accumulation before the second surgery were analyzed. Results: Among 339 patients with mGBM who underwent MRI, we identified 29 repeated surgeries/biopsies in 27 patients 59 ± 12 (mean ± standard deviation) years of age. Twenty-eight biopsies were from patients with recurrent glioblastoma histology, and only one was from a patient with radiation necrosis. We volumetrically evaluated the 29 pre-surgery TRAMs. In recurrent glioblastoma, the ratio of wash-out volume to tumor volume was 36 ± 17% (range 1–73%), and the ratio of the wash-out volume to the sum of wash-out and wash-in volumes was 48 ± 21% (range 22–92%). For the one biopsy with radiation necrosis, the ratios were 42% and 54%, respectively. Conclusions: Typical recurrent glioblastoma shows a > 20%ratio of the wash-out volume to the sum of wash-out and wash-in volumes. The one biopsy with radiation necrosis indicated that such necrosis can also produce high wash-out in individual cases. Nevertheless, the additional information provided by TRAMs increases the reliability of diagnosis. [ABSTRACT FROM AUTHOR]

Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression. [ABSTRACT FROM AUTHOR]

Purpose: Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN). Materials and Methods: A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed. Results: The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, p=0.005). Conclusion: The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed. [ABSTRACT FROM AUTHOR]

Purpose: In this study we gathered and analyzed the available evidence regarding 17 different imaging modalities and performed network meta-analysis to find the most effective modality for the differentiation between brain tumor recurrence and post-treatment radiation effects. Methods: We conducted a comprehensive systematic search on PubMed and Embase. The quality of eligible studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. For each meta-analysis, we recalculated the effect size, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio from the individual study data provided in the original meta-analysis using a random-effects model. Imaging technique comparisons were then assessed using NMA. Ranking was assessed using the multidimensional scaling approach and by visually assessing surface under the cumulative ranking curves. Results: We identified 32 eligible studies. High confidence in the results was found in only one of them, with a substantial heterogeneity and small study effect in 21% and 9% of included meta-analysis respectively. Comparisons between MRS Cho/NAA, Cho/Cr, DWI, and DSC were most studied. Our analysis showed MRS (Cho/NAA) and 18F-DOPA PET displayed the highest sensitivity and negative likelihood ratios. 18-FET PET was ranked highest among the 17 studied techniques with statistical significance. APT MRI was the only non-nuclear imaging modality to rank higher than DSC, with statistical insignificance, however. Conclusion: The evidence regarding which imaging modality is best for the differentiation between radiation necrosis and post-treatment radiation effects is still inconclusive. Using NMA, our analysis ranked FET PET to be the best for such a task based on the available evidence. APT MRI showed promising results as a non-nuclear alternative. [ABSTRACT FROM AUTHOR]

Background and purpose: The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with dose-escalated regimens, the addition of protective concurrent bevacizumab (BEV) serves as an innovative approach. The current study aims to assess the dosimetric feasibility of the proposed concept. Materials and methods: A total of ten patients diagnosed with glioblastoma were included in this dosimetric analysis. Delineation of target volumes for the reference plans adhered to the ESTRO-EANO 2023 guideline. The experimental plans included an additional volume for the integrated boost. Additionally, the 60 Gy-volume was reduced by using a margin of 1.0 cm instead of 1.5 cm. To assess the risk of symptomatic RN, the Normal Tissue Complication Probability (NTCP) was calculated and compared between the reference and experimental plans. Results: Median NTCP of the reference plan (NTCPref) and of the experimental plan (NTCPex) were 0.24 (range 0.11–0.29) and 0.42 (range 0.18–0.54), respectively. NTCPex was a median of 1.77 (range 1.60–1.99) times as high as the NTXPref. In a logarithmic comparison, the risk of RN is enhanced by a factor of median 2.00 (range 1.66–2.35). The defined constraints for the organs at risk were feasible. Conclusion: When considering the potential protective effect of BEV, which we hypothesized might reduce the risk of RN by approximately two-fold, achieving isotoxicity with the proposed dose-escalated experimental plan for the PRIDE trial seems feasible.

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.

Differentiating recurrent cerebral metastasis (CM) from brain radiation necrosis (BRN) is pivotal for guiding appropriate treatment and prognostication. Despite advances in imaging techniques, however, accurately distinguishing these conditions non-invasively is still challenging. This single-center retrospective study reviewed 32 cases (28 patients) with confirmed cerebral metastases who underwent surgical excision of lesions initially diagnosed by MRI and/or MR perfusion scans from 1 January 2015 to 30 September 2020. Diagnostic accuracy was assessed by comparing imaging findings with postoperative histopathology. Conventional MRI accurately identified recurrent CM in 75% of cases. MR perfusion scans showed significantly higher mean maximum relative cerebral blood volume (max. rCBV) in metastasis cases, indicating its potential as a discriminative biomarker. No single imaging modality could definitively distinguish CM from BRN. Survival analysis revealed gender as the only significant factor affecting overall survival, with no significant survival difference observed between patients with CM and BRN after controlling for confounding factors. This study underscores the limitations of both conventional MRI and MR perfusion scans in differentiating recurrent CM from BRN. Histopathological examination remains essential for accurate diagnosis. Further research is needed to improve the reliability of non-invasive imaging and to guide the management of patients with these post-radiation events.

Brain radiation necrosis (BRN) is a significant and complex side effect of stereotactic radiotherapy (SRT). Differentiating BRN from local tumor recurrence is critical, requiring advanced diagnostic techniques and a multidisciplinary approach. BRN typically manifests months to years post-treatment, presenting with radiological changes on MRI and may produce neurological symptoms. Key risk factors include the volume of irradiated brain tissue, the radiation dose, and prior radiotherapy history. This manuscript reviews the diagnostic process for BRN, emphasizing the importance of assessing baseline risk, clinical evaluation, and advanced imaging modalities. Multimodal imaging enhances diagnostic accuracy and aids in distinguishing BRN from tumor relapse. Therapeutic management varies based on symptoms. Asymptomatic BRN may be monitored with regular imaging, while symptomatic BRN often requires corticosteroids to reduce inflammation. Emerging therapies like bevacizumab have shown promise in clinical trials, with significant radiographic and symptomatic improvement. Surgical intervention may be necessary for histological confirmation and severe, treatment-resistant cases. Ongoing research aims to improve diagnostic accuracy and treatment efficacy, enhancing patient outcomes and quality of life. This review underscores the need for a multidisciplinary approach and continuous advancements to address the challenges posed by BRN in brain tumor patients., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: 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., Methods: 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)., Results: Univariable logistic regression resulted in significant variables of the quantitative MT parameter 1/(R A ·T 2A ), 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 AREX Amide,0.625µT ( P  = .013), AREX NOE,0.625µT ( P  = .008), 1/(R A ·T 2A ) ( P  = .004), and T 1 ( P  = .004). The perfusion rCBV parameter did not reach significance., Conclusions: 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., Competing Interests: A.S.: Elekta/Elekta AB: Research grant, Consultant, Honorarium for past educational seminars, Travel Expenses. Varian: Honorarium for past educational seminars. BrainLab: Research grant, Consultant, Honorarium for educational seminars, Travel Expenses. AstraZeneca: Honorarium for educational seminars. ISRS: President of the International Stereotactic Radiosurgery Society (ISRS). Seagen Inc: Honorarium for education seminars and research grants. Cerapedics: Honorarium for educational seminars, Travel Expenses. CarboFIX: Honorarium for educational seminars. Servier: Honorarium for educational seminars. C.-L.T.: Travel accommodations/expenses & honoraria for past educational seminars by Elekta; belongs to the Elekta MR-Linac Research Consortium; advisor/consultant with Sanofi and AbbVie. S.M.: Research support from Novartis AG, honoraria from Novartis AG and Ipsen. None related to this work., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

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., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Radiation therapy with stereotactic radiosurgery (SRS) or whole brain radiation therapy is a mainstay of treatment for patients with brain metastases. The use of SRS in the management of brain metastases is becoming increasingly common and provides excellent local control. Cerebral radiation necrosis (RN) is a late complication of radiation treatment that can be seen months to years following treatment and is often indistinguishable from tumor progression on conventional imaging. In this review article, we explore risk factors associated with the development of radiation necrosis, advanced imaging modalities used to aid in diagnosis, and potential treatment strategies to manage side effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Functional precision medicine (FPM) represents a personalized and efficacious modality for treating malignant neoplasms. However, acquiring sufficient live tissue to perform FPM analyses is complicated by both difficult identification on imaging and radiation necrosis, particularly in cases of recurrence. The authors describe a case of planning biopsy trajectories for an FPM assay in a patient with recurrent high-grade glioma., Observations: A 25-year-old male with a history of recurrent high-grade glioma was scheduled for laser ablation and biopsy with ChemoID assaying after regions of potential recurrence were identified on follow-up imaging. Preoperative magnetic resonance (MR) spectroscopy of the regions showed areas of high choline/creatine ratios within lesions of radiation necrosis, which helped in planning the biopsy trajectories to selectively target malignancies for FPM analysis. ChemoID results showed high tumor susceptibility to lomustine, which was implemented as adjuvant therapy., Lessons: FPM therapy in the setting of recurrence is complicated by radiation necrosis, which can present as malignancy on imaging and interfere with tissue acquisition during biopsy or resection. Thus, operative approaches should be carefully planned with the assistance of imaging modalities such as MR spectroscopy to better ensure effective tissue acquisition for accurate FPM analysis and to promote more definitive treatment of recurrence.

The field of medicine is constantly advancing to improve patient care. As physicians, we must improve our knowledge by listening, reading, and practicing evidence-based medicine. Laser treatment has evolved over the years in many surgical specialties. Laser interstitial thermal therapy (LITT), also known as stereotactic laser ablation (SLA), was developed in neurosurgical procedures to treat recurrent or metastatic brain tumors, radiation necrosis, and epilepsy lesions. LITT procedures are advantageous in providing better patient outcomes, decreased hospital length of stay, and reduced total hospital cost. These procedures are performed as a multi-disciplinary approach; this article discusses the different types of LITT systems, indications, contraindications, types of anesthesia, perioperative anesthetic management, safety precautions, complications, recovery during and after LITT procedures, and the future of LITT procedures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kurnutala et al.)

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)., Material and Methods. A: 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., Conclusion: Preoperative radiosurgery with subsequent resection provides higher local control and lower incidence of leptomeningeal progression in patients with single brain metastases.

Purpose: Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN)., Materials and Methods: A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed., Results: The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, p =0.005)., Conclusion: The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)