Role of Proton Beam Therapy in Spinal Chordomas: A Narrative Review of The Literature.

Chordomas are rare malignant neoplasms arising from vestigial remnants of the embryonic notochord. Approximately 55-70% of chordomas develop within the vertebral column. Their affinity to develop within the bones of the axial skeleton and propensity to locally invade and recur makes them challenging candidates for complete surgical excision. Adjuvant therapies are hence necessary to improve outcomes; for which chemotherapy has been observed to be largely ineffective, owing to the tumour being resistant to it. Radiotherapy is the current adjuvant therapy of choice for chordoma management. Over the years, proton beam therapy (PBT) has been the subject of medical attention, given the dosimetric benefits it confers over traditional radiotherapy, allowing more concentrated radiation to be given to the target of interest and reducing damage to surrounding normal tissue. A review of the current literature reveals PBT offers significantly better outcomes when used as an adjuvant to maximal surgical resection rather than as a definitive therapy.

Evolution of RANO in Assessing Brain Tumour Outcomes.

Assessing treatment response is extremely important in management of brain tumours. Response assessment in neuro-oncology (RANO) was introduced in 2008 for the purpose of making recommendations for it by addressing and countering the limitations in previously reported response criteriae. Subsequently, multiple RANO working groups have been formed to cater to different tumour types and to update their previous recommendations to counter the limitations in their criteria. Herein we have a summarized list of RANO criteria for adult brain tumours.

Photodynamic Therapy in Adult Intra-axial Brain Tumours.

The management of high-grade gliomas is challenging considering their infiltrative nature, involvement of the eloquent cortex, and high recurrence rate. Photodynamic therapy (PDT) is an emerging modality that selectively destroys tumour cells while preserving normal brain tissue. Its safety, and the concurrent use with surgery, radiation, and chemotherapy, is some of its appealing tenets. Here, we present a review of the literature regarding the mechanism, safety, and efficacy of PDT.

RAPNO efforts in Brain Tumour Outcomes.

Assessing treatment efficacy for brain tumours has evolved since its inception with the introduction of MacDonald's criteria, which pioneered the utility of imaging to determine an objective and quantifiable response to treatment. This criterion failed to distinguish pseudo response or progression from progression and did not account for non-enhancing disease therefore; the response assessment in neuro-oncology (RANO) working group was established to account for these limitations. Since, its commencement it has worked to determine response assessment for multiple tumours. As paediatric tumours exhibit heterogeneous and variable-enhancing characteristics, the response assessment in paediatric neuro-oncology (RAPNO) working group was formed to create separate criteria. Six response criteria have been published to date, and the article summarizes them.

Prognostic Value of BRAF Mutation in Glioblastoma.

With advances in molecular genetics, exploring targetable mutations for treating glioblastoma (GBM) patients, has become a centre of interest in modern day neuropathology. BRAF mutation has been extensively reported in several brain tumours. Recent studies report identification of BRAF mutation in GBM patients, especially isocitrate dehydrogenase wildtype glioblastomas (IDH-WT GBM), and its potential role in patient outcomes. Here we discuss the existing literature on the prognostic value of BRAF mutation in GBM.

Role of Machine Learning in Liquid Biopsy of Brain Tumours.

Liquid biopsy has multiple benefits and is used extensively in other fields of oncology, but its role in neuro-oncology has been limited so far. Multiple tumour-derived materials like circulating tumour cells (CTCs), tumour-educated platelets (TEPs), cell-free DNA (cfDNA), circulating tumour DNA (ctDNA), and miRNA are studied in CSF, blood (plasma, serum) or urine. Large and complex amounts of data from liquid biopsy can be simplified by machine learning using various algorithms. By using this technique, we can diagnose brain tumours and differentiate low versus highgrade glioma and true progression from pseudo-progression. The potential of liquid biopsy in brain tumours has not been extensively studied, but it has a bright future in the coming years. Here, we present a literature review on the role of machine learning in liquid biopsy of brain tumours.

Dorsal intercostal artery flap; A reliable option for coverage of myelomeningocele defects: A case series.

Meningomyelocele is a common congenital condition and its reconstruction poses a challenge for surgeons. The dorsal intercostal artery (DICA) flap offers a one-stage tension-free closure with adequate results. This study, spanning from January 2019 to September 2022, analyses the outcome of nine DICA flaps for meningomyelocele reconstruction, where the average size of the DICA flap was 6.8 x 4.6 cm for an average defect of 6.33 x 4 cm. Notably, no post-operative blood transfusion was required, nor any complications occurred except for one patient's septic shock-related death. Two had post-operative cerebrospinal fluid (CSF) leak, repaired primarily with one requiring VP shunt. Based on our experience, the DICA flap, with its consistent anatomy, is a reliable option for the reconstruction of meningomyelocele defects.

The role of 18F-FDG PET/CT in Neurolymphomatosis: A Comprehensive Imaging Approach.

Neurolymphomatosis (NL) is an uncommon and rare neurologic disorder characterised by extranodal lymphoma, where the tumour cells invade the cranial nerves, nerve plexus, nerve root, spinal nerve roots, trunk nerves or peripheral nerves. MRI is the modality of choice, but is often challenging in detection of early recurrence, assessing residual disease and response evaluation. 18FFDG PET/CT has superior diagnostic performance compared with body CT in the evaluation of NL. 18F-FDG PET-CT is helpful in evaluation of disease extent and potential to guide biopsy. 18F-FDG PETCT is a highly sensitive technique for early localisation of NL than MRI or CT alone. Besides diagnostic and prognostic value in NL, it might be very helpful in response assessment.

Molecular imaging with 68Ga-PSMA PET/CT in high grade glioma: A biomarker for tumour neo-angiogenesis.

There are several promising radiotracers used for both staging and restaging of primary and recurrent brain tumours based on various mechanisms of tracer localization in tumour cells. 68Ga-PSMA PET has extremely low background uptake in normal brain tissue and consequently high tumour-to-brain ratio making it a promising imaging radiotracer for gliomas. 68Ga-PSMA demonstrates utility in evaluating high grade glioma during both initial workup or when suspecting recurrence. Herein the authors evaluate the role of this imaging modality and the potential future it holds in the management of high grade gliomas.

Consensus guidelines for the management of vestibular schwannoma for lowand middle-income countries.

Vestibular Schwannoma (VS), previously known as acoustic neuroma, constitutes the majority of tumours found in the cerebellopontine angle (CPA). Most guidelines for managing CPA tumours have been developed by high-income countries (HICs). However, these guidelines often fall short in addressing the unique challenges encountered in low- and middle-income countries (LMICs), such as Pakistan. In LMICs, issues related to a limited healthcare workforce, inadequate infrastructure, and constrained financial resources hinder the effective implementation of these HIC-derived guidelines. Additionally, it has been observed that VS tends to present at a larger size in LMICs compared to HICs. Given that VS is the predominant type of CPA tumour and other types are covered under separate guidelines, this article aims to provide practical, contextspecific recommendations for the screening, diagnosis, and management of Vestibular Schwannoma in LMIC settings. Our focus is to bridge the gap in care strategies and adapt them to the resource constraints and clinical realities of LMICs.

Consensus guidelines for the management of pineal region tumours for low- and middle-income countries.

Pineal region tumours are rare and mainly arise at a younger age. They can be categorized into various types: germ cell tumours (GCT), pineal parenchymal tumours (PPT), meningiomas, gliomas, pineoblastoma, pineal parenchymal tumours of intermediate differentiation, papillary tumours of the pineal region, and SMARCB1- mutant desmoplastic myxoid tumour. Within GCT, germinomas are the most prevalent, comprising the majority of tumours in this region, while nongerminomatous GCTs are also present. In rare instances, metastases from other sites may manifest. These tumours often lead to obstructive hydrocephalus and commonly exhibit symptoms related to mass effect, including headache, nausea, vomiting, and impaired gait stability. Different subtypes of pineal region tumours exhibit distinct radiological characteristics, thus imaging remains the primary diagnostic tool. Histologic diagnosis necessitates biopsy, unless in cases of germ cell tumours, particularly germinomas, which can be identified through elevated levels of tumour markers like alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in both cerebrospinal fluid (CSF) and serum. While benign tumours might be effectively treated with radical resection alone, malignant tumours demand additional chemotherapy and radiotherapy following surgical removal.

Quality of life in survivors of pediatric medulloblastoma: a systematic review and meta-analysis.

INTRODUCTION: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. The mainstay of treatment is maximum surgical resection and craniospinal radiation, which may be followed by chemotherapy. The debilitating effect of the tumor and the intensive treatment approaches in MB lead to long-term neuropsychological, physical, and chronic medical problems. We conducted a systematic review to assess the quality of life (QoL) in the long-term survivors of MB and the factors leading to compromised QoL. METHODS: We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for our review. A comprehensive literature search was performed using PubMed, Cochrane Library, Digital Commons Network, and Wiley Online Library databases to search for articles having quality of life, medulloblastoma, and pediatric survivors in title or abstract. We removed duplicates and screened through titles, and full texts. Twelve articles were included in our study. Articles using and reporting all domains of PaedsQL were included in the meta-analysis. The PaedsQL scores of survivors and their caregivers were compared. Subgroup analysis was conducted for craniospinal and proton radiotherapy groups. RESULTS: As compared to other posterior fossa tumors, MB survivors have the lowest QoL scores. There is a difference in the perception of QoL of survivors between caregivers and survivors themselves with survivors rating themselves higher in several domains. The overall PaedsQL scores were significantly different for both groups (p < 0.001). Subgroup analysis showed that the difference between those who were treated with craniospinal or proton radiation was not significant (p = 0.76). For the subscales, physical (p = 0.005), psychosocial (p = 0.0003), and school (p = 0.03) perceptions were significantly different for the survivors and their caregivers; however, psychosocial (p = 0.80) and emotional (p = 0.93) scales were not different for the survivors or caregivers. Patient characteristics related to a worse QoL included disease severity, metastatic disease, lesser family income, smaller current ventricle size, need for permanent hydrocephalus treatment, and lesser age at diagnosis. CONCLUSION: An analysis of various studies, using different measures of QoL, concludes that QoL is compromised in all pediatric survivors of MB; however, the perception of QoL of the survivors is better than objective or caretaker-rated QoL.

Quality of life in children operated for spina bifida; low- and middle-income country perspective.

INTRODUCTION: Spina bifida is a potentially disabling congenital condition and affects the quality of life (QOL). We aimed to assess clinical outcomes and QOL in children who underwent spina bifida repair at our hospital. METHODS: This was a retrospective cohort study on children who underwent spina bifida repair at our hospital over 10 years. Phone calls were made to parents of the children, and the Health Utility Index Mark 3 (HUI 3) score was used to assess QoL, and degree of disability. Demographics and clinical data were obtained from the medical chart review. Statistical analysis was done using SPSS (version 21). RESULTS: Eighty children with a median age of 1.1 months (IQR 0.03-2.0) at the time of presentation, were included in this study. The mean follow-up period was 6.04 ± 2.54 years and the median HUI-3 score was 0.64 (IQR: 0.40 - 0.96) on a scale of 0 (dead) to 1 (perfectly healthy). Based on the severity of disability, 12 (23.1%) children had mild disability, 4 (7.7%) had moderate disability, and 23 (44.2%) had severe disability. Factors including a leaking spina bifida and paraplegia at presentation; radiological findings of hydrocephalus and Chiari malformation, were associated with a significantly low QOL. Children who required CSF diversion (EVD/ VP shunt) during the repair or at a later stage also had significantly low QOL. CONCLUSION: In LMIC, children with myelomeningocele (MMC) born with lower limb weakness, hydrocephalus, Chiari malformation, and those presenting with leaking MMC, have a significantly low QoL at a mean follow-up of 6 years.

Exploring the 'January effect' at a university hospital in Pakistan: a retrospective cohort study investigating the impact of trainee turnover on patient care quality outcomes.

OBJECTIVE: There are reports of a potential rise in a teaching hospital's morbidity and mortality rates during the trainee turnover period, i.e., with the induction of new residents and house staffs, and the changeover of clinical teams. The published literature displays mixed reports on this topic with lack of reproducible observations. The current study was conducted to explore existence of any such phenomenon (January effect) in Pakistan. METHODS: This retrospective cohort study was conducted at Aga Khan University Hospital, Karachi, Pakistan. Five-year (2013-2018) record of all the patients in all age groups related to these outcomes was retrieved and recorded in specifically designed questionnaire. Different outcome measures were used as indicators of patient care and change in these outcomes at the time of new induction was related to possible January effect. RESULTS: During the five-year study period, more than 1100 new trainees were inducted into the post graduate medical education program (average of 237 per year) with more than 22,000 inpatient admissions (average of 45,469 per year). Some patterns were observed in frequencies of surgical site infections, medication errors, sentinel events, patient complaints, and adverse drug reactions. However, these were not consistently reproducible and could not be directly attributed to the trainee turnover. All other indicators did not show any pattern and were considered inconclusive. No effect of overlap was observed. CONCLUSIONS: Inconsistency in the patient care quality indicators do not favor existence of January effect in our study. Further research is recommended to establish our results.

Assessing the validity of admission test into the internship programme at a private university in Pakistan.

OBJECTIVE: To report the development and validity assessment of a comprehensive model of assessment method comprising written test and multiple mini interviews for selection in a medical internship programme. METHODS: The psychometric validation study was conducted at the Aga Khan University, Karachi, and comprised anonymised scores of written admission test, multiple mini interviews and exit written exams for all the interns who completed their internships in 2018 and 2019. Correlation between admission and exit tests, and predictions were assessed. Data was analysed using SPSS 20. RESULTS: There were 160 interns; 80(50%) each in 2018 and 2019. Mean scores were 68.8±4.40% for written tests and 76.7±4.66% for multiple mini interviews. The mean score for exit examination was 68.1±6.84%. The Cronbach's alpha of scores on the written admission test was 0.82 and 0.88 for the two years, respectively, while for the multiple mini interviews, the corresponding values were 0.81 and 0.94. The written admission and exit tests were moderately correlated (0.44) while the correlations of multiple mini interviews scores with written admissions and exit tests were -0.28 and 0.04, respectively. CONCLUSIONS: The selection process should comprise multiple measures of assessment to ensure the selection of the best candidates.

Effect of post-operative infections on glioblastoma outcomes.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumour with a poor prognosis. The risk of developing a post-operative infection after craniotomy is the highest in GBM patients. Historical beliefs suggest that post-operative infections render a survival advantage in GBM patients, however recent clinical neurosurgical reports involving large multicentric patient cohorts do not support this claim. Nonetheless, the relationship has not been extensively studied which poses the need for further large, scaled studies to determine the association between post-operative infections and survival benefit in GBM patients.

Spinal meningiomas: Management and outcomes.

Spinal meningiomas are relatively rare, benign, intradural, extramedullary tumours, that are typically slow-growing and well-defined. Surgery is always the first line for treating spinal meningiomas. Here, we have discussed the existing literature on spinal meningiomas and the role of surgery in determining the outcomes.

Intramedullary Subependymoma Of Lower Thoracic Cord.

Spinal subependymoma (SSE) is a rare intramedullary, benign tumour. Surgical excision isthe preferred approach. However, the interwoven pattern of neural tissue within the tumour dictates the extent of resection. Where gross total resection is linked with possible neurological deficits, subtotal resection or close observation may support better functional outcomes. The evidence for the management of SSE is based mostly on case reports. Herein, we review the existing literature regarding treatment options and clinical outcomes of spinal subependymoma.

Primary Cardiac Sarcomas: Risk of Brain Metastases and Management.

Primary cardiac neoplasms are very rarely encountered, and the most common type of malignant tumours occurring primarily in the heart are sarcomas. These carry a lethal prognosis on account of their late presentation and aggressive spread. They have a high propensity for cerebral metastases. Such cases are exceptionally uncommon, and till date only a few examples are available. Currently, there is no standard protocol for the management of primary cardiac sarcoma with brain metastases.

Intracranial metastasis of testicular germ cell tumours.

Brain metastasis from testicular germ cell tumour (TGCT) is rare and represents only 2% of metastatic brain tumours. Although TGCTs have a good survival rate, the prognosis of brain metastasis is poor. Due to the rarity of the diagnosis, there are limited studies on the topic and a standardized treatment protocol does not exist. Surgical management has long been considered a positive prognostic factor; however, recent studies have investigated the impact of chemotherapy and radiotherapy in these patients. Current literature suggests multiplicity of brain lesions and treatment with chemotherapy or radiotherapy alone can have a poor impact on the prognosis of the disease. However, studies with larger cohorts are required to understand and develop the optimal treatment protocol for patients with brain metastasis from TGCT.