AB064. Two case reports & review of literature: perioperative surgical management of symptomatic large non-functioning pituitary masses in early pregnancy.

BACKGROUND: Pituitary masses during pregnancy pose many challenges, requiring inputs from multidisciplinary teams. Where surgery is required, such as in cases of impending pituitary apoplexy, timing must be carefully selected. Several case reports have suggested good outcome with surgery in later trimesters or postpartum. However, insufficient data exists on surgical strategies for such patients with severe visual symptoms in early pregnancy. We report two patients with pituitary masses requiring surgical excision. METHODS: Review of patients' notes and imaging, with literature review. RESULTS: A 35-year-old gravida 2 para 1 female at 9 weeks gestational age (GA) presented with chronic bitemporal hemianopia, with acute left eye blurring of vision, identified during a pre-employment screening test. Imaging revealed a 38 mm × 29 mm × 33 mm sellar mass with compression onto the optic chiasm. She had no significant hormonal imbalances other than hyperprolactinemia and newly diagnosed Hashimoto's thyroiditis. She underwent transsphenoidal resection, with histology showing pituitary adenoma with blood clots. Similarly, our second patient was a 37-year-old gravida 4 para 2 female at 12 weeks GA with worsening bitemporal hemianopia with a 25 mm × 21 mm × 18 mm sellar mass displacing and compressing the optic chiasm. After resection she had marked objective improvement in her vision, but developed diabetes insipidus, and final histology revealed pituicytoma. Preoperative considerations for timing of surgery include pituitary apoplexy or acutely worsening visual field deficit. The pituitary physiologically increases in size during pregnancy, which can compress the optic chiasm and worsen visual deficit. In the case of apoplexy, delayed identification can have devastating consequences. However, major surgery in the first trimester may increase spontaneous miscarriage. The effects of imaging investigations from radiation, or gadolinium contrast administration, are also uncertain. While surgical positioning remains unaffected, other intraoperative considerations include strictly avoiding hypotension and using pregnancy-safe agents. Postoperative considerations include correcting hormonal deficiencies of hypopituitarism, including acute central hypocortisolism, diabetes insipidus and interruption of gonadotrophin production which could negatively affect pregnancy. Fetal heart rate must also be assessed. CONCLUSIONS: Determining timing of surgery to ensure well-being of both mother and fetus involves a difficult balance of risks. In our two cases, a thorough discussion with multidisciplinary input was required to achieve good outcomes.

AB013. Infantile brainstem high grade glioma: a case report.

BACKGROUND: Congenital infantile brainstem high-grade gliomas (HGGs) are extremely rare. Given the limited literature characterizing this disease, management of these tumors remains challenging. Brainstem HGGs are generally associated with extremely poor prognosis. Limited reports of spontaneous regression of radiologically diagnosed infantile brainstem tumors exist in published literature. We aim to report a unique case of spontaneous regression of a rare infantile HGG brainstem glioma and to review the current literature. CASE DESCRIPTION: In this case report, we document the first histologically proven congenital brainstem HGG with molecular characteristics that did not fall under any previously well-defined pediatric brain tumor classifications. The patient is a full-term female delivered uneventfully via normal vaginal delivery with unremarkable antenatal and fetal abnormality scans. Neuroimaging revealed a relatively focal dorsally located pontomedullary tumor. She subsequently underwent suboccipital craniotomy and biopsy of the lesion. Formal histopathology revealed features consistent with HGG. Methylation profiling classified the neoplasm closest to either "glioblastoma, IDH wildtype, subclass midline" or "pediatric type diffuse HGG". The patient's post-operative recovery was uneventful. The initial plan was to consider safe surgical debulking when the child reaches 6 months of age. However, subsequent neuroimaging revealed spontaneous tumor regression after biopsy, up to 2 years of age. A review of the literature was also performed to identify previously reported infantile brainstem HGGs and the management for such tumors. CONCLUSIONS: Our case highlights the value of performing histopathological confirmation to guide management and the possible existence of a subcategory of a congenital brainstem HGG with better prognosis.

AB022. Management of first recurrence or progression of craniopharyngioma after resection alone: a systematic review and individual-participant data meta-analysis.

BACKGROUND: The initial management of craniopharyngioma is generally either gross total resection (GTR) or subtotal resection (STR) with adjuvant radiotherapy (RT). However, the optimal management strategy for recurrent/progressive craniopharyngioma remains unclear. METHODS: PubMed and Embase were systematically reviewed for studies that compared the outcomes of surgery and/or RT for the first recurrence/progression of craniopharyngioma after resection alone. The exposure was the treatment that was administered for the first recurrence/progression, and the outcomes were tumor regrowth and overall survival (OS). Subgroup analyses were performed by age at the treatment for the first recurrence/progression (<18 or ≥18 years old), duration between the first treatment and the first recurrence/progression (<2 or ≥2 years), and the initial treatment that was administered (STR or GTR). RESULTS: Of the 2,932 studies screened, 11 studies reporting a total of 80 patients were included. Across almost all subgroups, patients who received RT for the first recurrence/progression had a significantly lower risk of tumor regrowth than those who did not, regardless of whether surgery was performed and the extent of resection. There was no significant association between the treatment administered for the first recurrence/progression and OS, except for patients with a recurrence/progression <2 years after the first treatment, where GTR was associated with a higher risk of mortality. CONCLUSIONS: For patients with the first recurrence/progression of craniopharyngioma after resection alone, RT should be considered for better local control. In cases where RT is not administered, GTR is preferred over STR provided it can be safely performed, for improved local control.

AB035. Validation of EORTC brain cancer module (EORTC QLQ-BN20) for assessment of health-related quality of life in glioma patients in Singapore.

BACKGROUND: Existing international data has shown that glioma patients suffer from poorer health-related quality of life (HRQoL). The European Organization for Research and Treatment of Cancer (EORTC) brain cancer-specific Quality of Life Questionnaire (QLQ-BN20) was developed to be together with EORTC Core Quality of Life Questionnaire (QLQ-C30) for cancer patients, highlighting issues particularly relevant to brain tumor patients. It has since been translated and validated across numerous cohorts. However, its psychometric properties have yet to be examined in Singapore. This study aimed to validate the use of QLQ-BN20 in a nationally representative sample of glioma patients in Singapore. METHODS: Eighty-seven patients who had undergone neurosurgery for glioma from six hospitals in Singapore completed three self-reported measures of HRQoL (the EuroQol EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-BN20). Descriptive statistics summarized their characteristics and scores on the questionnaires. Psychometric properties of QLQ-BN20 examined included convergent and discriminant validity, internal consistency (Cronbach's alpha), and construct validity (Spearman's correlation). Clinical validity of QLQ-BN20 was determined based on whether QLQ-BN20 scores could differentiate patients with good and poor functional status as measured by Karnofsky Performance Scale and Barthel's Index. RESULTS: The QLQ-BN20 was demonstrated to have good convergent validity (item-own scale correlation >0.70) and discriminant validity (item-own scale correlation higher than item-other scale correlation). There is high internal consistency, both overall (α=0.88) and within multi-item subscales (α=0.74-0.88). Conceptually similar subscales between different tools were more strongly correlated. For instance, the QLQ-C30 physical functioning subscale and the QLQ-BN20 motor dysfunction subscale (r=-0.65, P<0.001), and the QLQ-C30 cognitive functioning subscale and the QLQ-BN20 cognitive deficits subscale (r=-0.51, P<0.001). QLQ-BN20 was also able to distinguish between functional statuses of patients (P<0.05). CONCLUSIONS: This study supports the validity and reliability of the EORTC QLQ-BN20 among patients with glioma in Singapore. There is good convergent and discriminant validity, internal consistency, construct validity, and clinical validity. The QLQ-BN20 is a valuable supplement to the QLQ-C30. Hence, we recommend expanding its use for all glioma patients and possibly brain cancer patients in Singapore.

AB050. Novel treatment vs. standard of care in melanoma-associated leptomeningeal metastases: a systematic review & network meta-analysis.

BACKGROUND: Melanoma stands as a prevalent instigator of leptomeningeal disease (LMD) within the realm of cancer. Given the poor prognosis accompanying this condition, ongoing trials explore a spectrum of treatment modalities in pursuit of more effective interventions. To ascertain the most effective therapeutic strategies, we aim to compare novel treatments against the current standard of care for melanoma-associated LMD. METHODS: A comprehensive search was conducted across multiple databases, including PubMed/Medline, EMBASE, Scopus, ScienceDirect and Web of Science for relevant studies published from January 2014 to January 2024. We included primary research studies, including observational studies, randomised control trials, quasi-experimental design studies, clinical trials, and experimental studies focusing on LMD caused by metastatic melanoma. Data extraction was conducted according to PRISMA guidelines and quality assessment/risk of bias is performed individually using the GRADE method. A network meta-analysis is conducted to evaluate the effects of multiple interventions within the study. Overall survival outcomes were quantified using log hazard ratio. RESULTS: Out of 680 records screened for eligibility, seven carefully chosen studies, meeting our specific inclusion criteria, provide insights into the management of 397 patients grappling with LMD due to metastatic melanoma. These studies vary in design: one observational cohort study with 29 participants, a clinical trial with 25 patients, four retrospective cohort studies ranging from 39 to 190 participants and one experimental study with 24 patients. CONCLUSIONS: Despite the escalating breakthroughs of treatment options in melanoma-associated LMD, further studies may be imperative to conclusively determine whether the newer therapeutic options yield superior outcomes compared to the current standard of care treatments.

AB088. Spinal cord diffuse midline glioma in adults: a case report and literature review.

BACKGROUND: Spinal cord diffuse midline gliomas are rare, infiltrative entities with an extremely grim prognosis. Standard of care is limited and extrapolated from those for intracranial gliomas, focusing on maximal safe resection, chemotherapy and radiation therapy. These do not prolong survival significantly and while advances in molecular profiling and targeted therapy have been promising, further research still needs to be performed. Here, we present a case of a young lady with a cervical cord diffuse midline glioma, along with a literature review of the disease and treatment options. CASE DESCRIPTION: A 35-year-old female presented with progressive neck pain and left sided weakness. MRI revealed an intramedullary cervical spinal cord lesion. The lesion progressed rapidly to the medulla, resulting in lower cranial nerve palsies and left hemiplegia. Investigations for autoimmune and infective causes were negative. Cervical laminectomy and debulking was performed. Histological analysis showed high grade diffuse glioma, IDH-wildtype, loss of H3K27me3 staining and H3K27M positivity. The patient was treated with fractionated radiation and temozolamide, followed by lomustine and bevacizumab. A literature review was performed to better understand the molecular features, natural history and treatment options for spinal cord high grade gliomas. Our case highlights the importance of maintaining broad differentials for patients exhibiting features of cervical myelopathy. Malignant spinal cord tumours could be a differential. Molecular testing can aid in achieving an accurate diagnosis to better understand prognosis and determine treatment options. Early, function-preserving debulking with neuromonitoring is feasible. Adjuvant therapy with chemotherapy and radiation can prolong survival. CONCLUSIONS: Spinal cord diffuse midline gliomas H3 K27-altered demonstrate rapid progression and a poor prognosis. They should be considered as a differential in patients with cervical myelopathy. Molecular testing for H3 K27 alterations facilitates an accurate diagnosis. Surgical debulking and adjuvant therapy are viable treatment options.

The effect of frailty on mortality and functional outcomes in spontaneous intracerebral haemorrhage.

INTRODUCTION: Limited data in patients with spontaneous intracerebral haemorrhage (SICH) showed that frailty was associated with mortality; however, there was insufficient data on functional outcomes. This study aimed to investigate the effect of frailty on overall mortality and 90-day functional outcomes in SICH. MATERIALS AND METHODS: We conducted a retrospective study of 1223 patients diagnosed with SICH from January 2014 to December 2020. Frailty was defined as a clinical frailty scale (CFS) score of 4-9. Binary cut-offs were defined using receiver operating curve analysis. 90-day poor functional outcomes (PFO) were defined as modified Rankin Scale (mRS) ≥3, and utility-weighted mRS (UW-mRS) were based on previous validated studies respectively. Regression analyses were conducted to investigate the association between frailty and outcomes. Confounders adjusted for included demographics, cardiovascular risk factors and haematoma characteristics. RESULTS: 1091 patients met the inclusion criterion. 167 (15.3 %) had 30-day mortality and 730 (66.9 %) had 90-day PFO. Frailty was significantly associated with lower overall survival (HR: 1.54; 95 % CI: 1.11-2.14, p=0.010), 90-day PFO (OR: 1.90; 95 % CI: 1.32-2.74; p<0.001) and poorer UW-mRS (ß: -0.06; 95 % CI: (-0.08 to -0.04); p<0.001) even after adjusting for confounders. CONCLUSIONS: Frailty was significantly associated with greater mortality and PFO after incident SICH, even after adjusting for a priori confounders. Frail male individuals may be predisposed to poorer outcomes from higher prevalence of cortical atrophy. The use of CFS in younger individuals may aid management by predicting outcomes after incident SICH. Identifying frail individuals with incident SICH could aid in decision-making and the surgical management of SICH.

Evaluation of ex vivo drug combination optimization platform in recurrent high grade astrocytic glioma: An interventional, non-randomized, open-label trial protocol.

INTRODUCTION: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients. METHODS: This is an interventional, non-randomized, open-label study, which aims to enroll 10 patients who will receive QPOP-guided chemotherapy at the time of first HGG recurrence following progression on standard first-line therapy. At the initial presentation of HGG, tumor will be harvested for primary PDO generation during the first biopsy/surgery. At the point of tumor recurrence, patients will be enrolled onto the main study to receive systemic therapy as second-line treatment. Subjects who undergo surgery at the time of recurrence will have a second harvest of tissue for PDO generation. Established PDOs will be subject to QPOP analyses to determine their therapeutic sensitivities to specific panels of drugs. A QPOP-guided treatment selection algorithm will then be used to select the most appropriate drug combination. The primary endpoint of the study is six-month progression-free survival. The secondary endpoints include twelve-month overall survival, RANO criteria and toxicities. In our radiological biomarker sub-study, we plan to evaluate novel radiopharmaceutical-based neuroimaging in determining blood-brain barrier permeability and to assess in vivo drug effects on tumor vasculature over time. TRIAL REGISTRATION: This trial was registered on 8th September 2022 with ClinicalTrials.gov Identifier: NCT05532397.

Effect of psoas muscle index on early postoperative outcomes in surgically treated spinal tumours in an Asian population.

BACKGROUND: Sarcopenia has been purported to be a pre-operative risk factor that affects patient outcomes in oncological surgery, but no study as of yet has investigated the effect of sarcopenia in patients with spinal tumours. Psoas muscle measurements, including the psoas muscle index (PMI), are an objective way to determine sarcopenia. OBJECTIVES: We investigated if PMI could predict post-operative outcomes (length of hospital stay and post-operative complications) in surgically treated spinal tumour patients in a multi-ethnic Asian population. METHODS: We conducted a retrospective cohort study of patients with spinal tumours who underwent surgery at our tertiary institution from January 2016 to January 2020. PMI was measured on T2-weighted MRI sequences, at the middle of the L3 vertebral body and measurements were collected by 2 independent raters. The primary outcome was length of hospital stay (LOS), and the secondary outcome was post-operative complications. ROC curve was used to attain the cut-off value for PMI and the population was then stratified into 2 groups; sarcopenic if PMI was less than 1.22 and non-sarcopenic if the PMI value was more than or equal to 1.22. Multivariable linear regression was used for LOS, while multivariate logistic regression was used for complications. RESULTS: 57 patients were included with a mean length of stay of 17.8 days (SD 25.1) and the total number of patients with complications were 20 (35.1 %). Mean LOS was significantly higher in the sarcopenic group compared to the non-sarcopenic group. Univariate analysis confirmed the association of lower psoas muscle index corresponding with longer lengths of stay and this was corroborated in a multivariable linear regression model. There were no significant associations between PMI and postoperative complications. CONCLUSIONS: Lower PMI values were significantly associated with a longer LOS. PMI may be warranted for risk stratifying Asian spinal tumour patients undergoing surgery.

Is Gamma Knife surgery, omitting adjunct whole brain radiation treatment, feasible for patients with 20 or more brain metastases?

Background: The importance of the number of brain metastases (BM) when deciding between whole brain radiation treatment (WBRT) and radiosurgery is controversial. We hypothesized that the number of BM is of limited importance when deciding radiation strategy, and offered Gamma Knife surgery (GKS) also for selected patients with 20 or more BM. Methods: The outcome following single session GKS for 75 consecutive patients harboring 20 or more (20+) BM was analyzed. Data was collected both retro- and prospectively. Results: The median survival time was 9 months. Two grade 3 complications occurred, 1 resolved and 1 did not. Sex and clinical condition at the time of GKS (ECOG value) were the only parameters significantly related to survival time. Eighteen patients developed leptomeningeal dissemination with or without distant recurrences (DR), and another 32 patients developed DR a total of 73 times. DR was managed with GKS 24 times, with WBRT 3 times and with systemic treatment or best supportive care 46 times. The median time to developing DR was unrelated to the number of BM, but significantly longer for patients older than 65 years, as well as for patients with NSCLC. Conclusions: GKS is a reasonable treatment option for selected patients with 20 or more BM. It is better to decide the optimal management of post-GKS intracranial disease progression once it occurs rather than trying to prevent it by using adjunct WBRT.

METTL8 links mt-tRNA m3C modification to the HIF1α/RTK/Akt axis to sustain GBM stemness and tumorigenicity.

Epitranscriptomic RNA modifications are crucial for the maintenance of glioma stem cells (GSCs), the most malignant cells in glioblastoma (GBM). 3-methylcytosine (m3C) is a new epitranscriptomic mark on RNAs and METTL8 represents an m3C writer that is dysregulated in cancer. Although METTL8 has an established function in mitochondrial tRNA (mt-tRNA) m3C modification, alternative splicing of METTL8 can also generate isoforms that localize to the nucleolus where they may regulate R-loop formation. The molecular basis for METTL8 dysregulation in GBM, and which METTL8 isoform(s) may influence GBM cell fate and malignancy remain elusive. Here, we investigated the role of METTL8 in regulating GBM stemness and tumorigenicity. In GSC, METTL8 is exclusively localized to the mitochondrial matrix where it installs m3C on mt-tRNAThr/Ser(UCN) for mitochondrial translation and respiration. High expression of METTL8 in GBM is attributed to histone variant H2AZ-mediated chromatin accessibility of HIF1α and portends inferior glioma patient outcome. METTL8 depletion impairs the ability of GSC to self-renew and differentiate, thus retarding tumor growth in an intracranial GBM xenograft model. Interestingly, METTL8 depletion decreases protein levels of HIF1α, which serves as a transcription factor for several receptor tyrosine kinase (RTK) genes, in GSC. Accordingly, METTL8 loss inactivates the RTK/Akt axis leading to heightened sensitivity to Akt inhibitor treatment. These mechanistic findings, along with the intimate link between METTL8 levels and the HIF1α/RTK/Akt axis in glioma patients, guided us to propose a HIF1α/Akt inhibitor combination which potently compromises GSC proliferation/self-renewal in vitro. Thus, METTL8 represents a new GBM dependency that is therapeutically targetable.

Adjuvant radiotherapy versus observation after gross total resection of WHO grade II ependymoma: a systematic review and individual-participant data meta-analysis.

BACKGROUND: The role of adjuvant radiotherapy (RT) after gross total resection (GTR) of the World Health Organization (WHO) grade II ependymoma is controversial. Therefore, we aimed to compare the outcomes of adjuvant RT against observation after GTR of WHO grade II ependymoma. We also compared the outcomes of adjuvant RT against observation after subtotal resection (STR) of WHO grade II ependymoma and performed further subgroup analysis by age and tumor location. METHODS: PubMed and Embase were systematically reviewed for studies published up till 25 November 2022. Studies that reported individual-participant data on patients who underwent surgery followed by adjuvant RT/observation for WHO grade II ependymoma were included. The exposure was whether adjuvant RT was administered, and the outcomes were recurrence and overall survival (OS). Subgroup analyses were performed by the extent of resection (GTR or STR), tumor location (supratentorial or infratentorial), and age at the first surgery (<18 or ≥18 years old). RESULTS: Of the 4,647 studies screened, three studies reporting a total of 37 patients were included in the analysis. Of these 37 patients, 67.6% (25 patients) underwent GTR, and 51.4% (19 patients) underwent adjuvant RT. Adjuvant RT after GTR was not significantly associated with both recurrence (odds ratio =5.50; 95% confidence interval: 0.64-60.80; P=0.12) and OS (P=0.16). Adjuvant RT was also not significantly associated with both recurrence and OS when the cohort was analyzed as a whole and on subgroup analysis by age and tumor location. However, adjuvant RT was associated with significantly longer OS after STR (P=0.03) with the median OS being 6.33 years, as compared to 0.40 years for patients who underwent STR followed by observation. CONCLUSIONS: Based on our meta-analysis of 37 patients, administration of adjuvant RT after GTR was not significantly associated with improvement in OS or recurrence in patients with WHO grade II ependymoma. However, due to the small number of patients included in the analysis, further prospective controlled studies are warranted.

Endovascular coiling versus neurosurgical clipping in the management of aneurysmal subarachnoid haemorrhage in the elderly: a multicenter cohort study.

The comparability of endovascular coiling over neurosurgical clipping has not been firmly established in elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Data were obtained from all patients with aSAH aged ≥60 across three tertiary hospitals in Singapore from 2014 to 2019. Outcome measures included modified Rankin Scale (mRS) score at 3 and at 6 months, and in-hospital mortality. Of the 134 patients analyzed, 84 (62.7%) underwent coiling and 50 (37.3%) underwent clipping. The endovascular group showed a higher incidence of good mRS score 0-2 at 3 months (OR = 2.45 [95%CI:1.16-5.20];p = 0.018), and a lower incidence of in-hospital mortality (OR = 0.31 [95%CI:0.10-0.91];p = 0.026). There were no significant difference between the two treatment groups in terms of good mRS score at 6 months (OR = 1.98 [95%CI:0.97-4.04];p = 0.060). There were no significant differences in the incidence of complications, such as aneurysm rebleed, delayed hydrocephalus, delayed ischemic neurological deficit and venous thromboembolism between the two treatment groups. However, fewer patients in the coiling group developed large infarcts requiring decompressive craniectomy (OR = 0.32 [95%CI:0.12-0.90];p = 0.025). Age, admission WFNS score I-III, and coiling were independent predictors of good functional outcomes at 3 months. Only age and admission WFNS score I-III remained significant predictors of good functional outcomes at 6 months. Endovascular coiling, compared with neurosurgical clipping, is associated with significantly better short term outcomes in carefully selected elderly patients with aSAH. Maximal intervention is recommended for aSAH in the young elderly age group and those with favorable WFNS scores.

Effect of sarcopenia and frailty on outcomes among patients with brain metastases.

PURPOSE: Sarcopenia and frailty have been associated with increased mortality and duration of hospitalization in cancer. However, data investigating these effects in patients with brain metastases remain limited. This study aimed to investigate the effects of sarcopenia and frailty on clinical outcomes in patients with surgically treated brain metastases. METHODS: Patients who underwent surgical resection of brain metastases from 2011 to 2019 were included. Psoas cross-sectional area and temporalis thickness were measured by two independent radiologists (Cronbach's alpha > 0.98). Frailty was assessed using the Clinical Frailty Scale (CFS) pre-operatively and post-operatively. Overall mortality, recurrence, and duration of hospitalization were collected. Cox regression was performed for mortality and recurrence, and multiple linear regression for duration of hospitalization. RESULTS: 145 patients were included, with median age 60.0 years and 52.4% female. Psoas cross-sectional area was an independent risk factor for overall mortality (HR = 2.68, 95% CI 1.64-4.38, p < 0.001) and recurrence (HR = 2.31, 95% CI 1.14-4.65, p = 0.020), while post-operative CFS was an independent risk factor for overall mortality (HR = 1.88, 95% CI 1.14-3.09, p = 0.013). Post-operative CFS (ß = 15.69, 95% CI 7.67-23.72, p < 0.001) and increase in CFS (ß = 11.71, 95% CI 3.91-19.51, p = 0.004) were independently associated with increased duration of hospitalization. CONCLUSION: In patients with surgically treated brain metastases, psoas cross-sectional area was an independent risk factor for mortality and recurrence, while post-operative CFS was an independent risk factor for mortality. Post-operative frailty and increase in CFS significantly increased duration of hospitalization. Measurement of psoas cross-sectional area and CFS may aid in risk stratification of surgical candidates for brain metastases.

Is two-staged gamma knife surgery a reasonable management option for very large cerebellar metastases? A case series of three patients.

OBJECTIVE: Two-staged gamma knife surgery (GKS) is a method that may extend the upper tumor volume limit for using GKS in the management of brain metastases. However, the safety of treating very large posterior fossa lesions with this technique has not been well demonstrated. Therefore, we analyzed our experience in treating cerebellar metastases larger than 12 cm3 with two-staged GKS. METHODS: Four consecutive patients harboring 12 to 30 cm3 cerebellar metastases scheduled two-staged GKS were included in the study, and all but one patient completed the treatment. The treatment doses were 10-13 Gy. All patients were followed with regular MR imaging and clinical assessments, and the tumor volumes were measured on all treatment and follow-up images. RESULTS: Tumor progression was not demonstrated in any of the patients. Tumor volumes decreased by, on average, more than half between the two stages. The median survival was 22 months, and no patient died due to intracranial tumor progression. Peritumoral edema at the first GKS resolved in all patients, replaced by asymptomatic mild T2 changes in two of them not requiring any treatment. No radiation-induced complication has developed thus far. CONCLUSION: Staged GKS seems to be a feasible management option for very large cerebellar metastases.

Trends in hemorrhagic stroke incidence and mortality in a National Stroke Registry of a multi-ethnic Asian population.

INTRODUCTION: High-quality epidemiological data on hemorrhagic stroke (HS) and its subtypes, intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), remains limited in Asian ethnicities. We investigated the trends in HS incidence and 30-day mortality from 2005 to 2019 in a multi-ethnic Asian population from a national registry. PATIENTS AND METHODS: Data on all stroke cases from the Singapore Stroke Registry from 2005 to 2019 were collected. Cases were defined using centrally adjudicated review of diagnosis codes. Death outcomes were obtained by linkage with the national death registry. Incidence (per 100,000 people) and 30-day mortality (per 100 people) were measured as crude and age-standardized rates. Trends were analyzed using linear regression. RESULTS: We analyzed 19,017 cases of HS (83.9% ICH; 16.1% SAH). From 2005 to 2019, age-standardized incidence rates (ASIR) for HS remained stable from 34.4 to 34.5. However, age-standardized mortality rates (ASMR) decreased significantly from 29.5 to 21.4 (p < 0.001). For ICH, ASIR remained stable while ASMR decreased from 30.4 to 21.3 (p < 0.001); for SAH, ASIR increased from 2.7 to 6.0 (p = 0.006) while ASMR remained stable. In subgroup analyses, HS incidence increased significantly in persons <65 years (from 18.1 to 19.6) and Malays (from 39.5 to 49.7). DISCUSSION: From 2005 to 2019, ASIR of HS remained stable while ASMR decreased. Decreasing ASMR reflects improvements in the overall management of HS, consistent with global trends. CONCLUSION: Population health efforts to address modifiable risk factors for HS in specific demographic subgroups may be warranted to reduce incidence and mortality of HS.

Outcomes after surgical revascularization for adult Moyamoya disease: A Southeast Asian tertiary centre experience.

There are numerous studies on the natural history and outcomes of adult Moyamoya disease (MMD) in the literature, but limited data from Southeast Asian cohorts. Hence, we aimed to retrospectively review the clinical characteristics and outcomes after surgical revascularization for adult MMD in our Southeast Asian cohort. Patients were included if they were above 18 years old at the first surgical revascularization for MMD, and underwent surgery between 2012 and 2022 at the National University Hospital, Singapore. The outcomes were transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, and all-cause mortality during the postoperative follow-up period. In total, 26 patients who underwent 27 revascularization procedures were included. Most patients were of Chinese ethnicity, and the mean (SD) age at the time of surgery was 47.7 (12.6) years. The commonest clinical presentation was intracerebral hemorrhage, followed by TIA and ischemic stroke. Direct revascularization with superficial temporal artery-middle cerebral artery (STA-MCA) bypass was the most common procedure (24/27 surgeries, 88.9 %). The mean (SD) follow-up duration was 4.2 (2.5) years, during which the overall incidence of postoperative TIA/stroke was 25.9 % (7/27 surgeries), with most cases occurring within 7 days postoperatively. There were no mortalities during the postoperative follow-up period. Risk factors for 30-day postoperative TIA/stroke included a higher number of TIAs/strokes preoperatively (p = 0.044) and indirect revascularization (p = 0.028). Diabetes mellitus demonstrated a trend towards an increased risk of 30-day postoperative TIA/stroke, but this was not statistically significant (p = 0.056). These high-risk patients may benefit from more aggressive perioperative antithrombotic and hydration regimens.

Prognostication of Outcomes in Spontaneous Intracerebral Hemorrhage: A Propensity Score-Matched Analysis with Support Vector Machine.

OBJECTIVE: The role of surgery in spontaneous intracerebral hemorrhage (SICH) remains controversial. We aimed to use explainable machine learning (ML) combined with propensity-score matching to investigate the effects of surgery and identify subgroups of patients with SICH who may benefit from surgery in an interpretable fashion. METHODS: We conducted a retrospective study of a cohort of 282 patients aged ≥21 years with SICH. ML models were developed to separately predict for surgery and surgical evacuation. SHapley Additive exPlanations (SHAP) values were calculated to interpret the predictions made by ML models. Propensity-score matching was performed to estimate the effect of surgery and surgical evacuation on 90-day poor functional outcomes (PFO). RESULTS: Ninety-two patients (32.6%) underwent surgery, and 57 patients (20.2%) underwent surgical evacuation. A total of 177 patients (62.8%) had 90-day PFO. The support vector machine achieved a c-statistic of 0.915 when predicting 90-day PFO for patients who underwent surgery and a c-statistic of 0.981 for patients who underwent surgical evacuation. The SHAP scores for the top 5 features were Glasgow Coma Scale score (0.367), age (0.214), volume of hematoma (0.258), location of hematoma (0.195), and ventricular extension (0.164). Surgery, but not surgical evacuation of the hematoma, was significantly associated with improved mortality at 90-day follow-up (odds ratio, 0.26; 95% confidence interval, 0.10-0.67; P = 0.006). CONCLUSIONS: Explainable ML approaches could elucidate how ML models predict outcomes in SICH and identify subgroups of patients who respond to surgery. Future research in SICH should focus on an explainable ML-based approach that can identify subgroups of patients who may benefit functionally from surgical intervention.