Saksham Gupta

Radiographic prediction of meningioma grade by semantic and radiomic features

Objectives The clinical management of meningioma is guided by tumor grade and biological behavior. Currently, the assessment of tumor grade follows surgical resection and histopathologic review. Reliable techniques for pre-operative determination of tumor grade may enhance clinical decision-making. Methods A total of 175 meningioma patients (103 low-grade and 72 high-grade) with pre-operative contrast-enhanced T1-MRI were included. Fifteen radiomic (quantitative) and 10 semantic (qualitative) features were applied to quantify the imaging phenotype. Area under the curve (AUC) and odd ratios (OR) were computed with multiple-hypothesis correction. Random-forest classifiers were developed and validated on an independent dataset (n = 44). Results Twelve radiographic features (eight radiomic and four semantic) were significantly associated with meningioma grade. High-grade tumors exhibited necrosis/hemorrhage (ORsem = 6.6, AUCrad = 0.62–0.68), intratumoral heterogeneity (ORsem = 7.9, AUCrad = 0.65), non-spherical shape (AUCrad = 0.61), and larger volumes (AUCrad = 0.69) compared to low-grade tumors. Radiomic and sematic classifiers could significantly predict meningioma grade (AUCsem = 0.76 and AUCrad = 0.78). Furthermore, combining them increased the classification power (AUCradio = 0.86). Clinical variables alone did not effectively predict tumor grade (AUCclin = 0.65) or show complementary value with imaging data (AUCcomb = 0.84). Conclusions We found a strong association between imaging features of meningioma and histopathologic grade, with ready application to clinical management. Combining qualitative and quantitative radiographic features significantly improved classification power.

Impact of Helmet Use on Severity of Epidural Hematomas in Cambodia

BACKGROUND Traumatic brain injury is a major cause of morbidity and mortality worldwide, often necessitating neurosurgical intervention to evacuate intracranial bleeding. Since the early 2000s, Cambodia has been undergoing a rapid increase in motorcycle transit and in road traffic accidents, but the prevalence of helmet usage remains low. Epidural hematomas are severe traumatic brain injuries that can necessitate neurosurgical intervention. METHODS This is a retrospective cohort study of patients with epidural hematoma secondary to motorcycle accidents who presented to a major national tertiary care center in Phnom Penh, Cambodia, between November 2013 and March 2016. All patients were diagnosed with computed tomography of the head. RESULTS In this cohort, 21.6% of patients in motorcycle accidents presented with epidural hematoma and 89.1% of patients were men, 47.6% were intoxicated, and were 87.8% were not wearing helmets at the moment of impact. Not wearing a helmet was associated with a 6.90-fold increase in odds of presenting with a moderate-to-severe Glasgow coma scale score and a 3.76-fold increase in odds of requiring craniotomy or craniectomy for evacuation of hematoma. Male sex was also associated with increased odds of higher clinical severity at presentation and indication for craniotomy or craniectomy, and alcohol intoxication at the time of accident was not associated with either. CONCLUSIONS Helmet usage is protective in reducing the severity of presentation and need for neurosurgical intervention for patients with epidural hematoma secondary to motorcycle accidents.

Ethical considerations of neuro-oncology trial design in the era of precision medicine

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

Predicting Readmission and Reoperation for Benign Cranial Nerve Neoplasms: a Nationwide Analysis

OBJECTIVE Readmission and reoperation are risks in the resection of benign cranial nerve tumors (BCNTs). This report analyzes the impact of patient-level and surgical factors on these adverse outcomes. METHODS This retrospective cohort review comprised patients with a diagnosis of BCNT enrolled in the American College of Surgeons National Surgical Quality Improvement Program registry from 2011 to 2015. Multivariate logistic regression was used to determine the impact of select medical and operative factors on the primary outcomes of readmission and reoperation within 30 days, adjusted for relevant covariates. RESULTS We identified 996 patients who underwent resection of a BCNT. The most frequent major complications were readmission (11%), reoperation (8%), surgical site infections (2.6%), and venous thromboembolism (1.5%). The most frequent indications for readmission were management of infection (2.5%), cerebrospinal fluid leak (2.3%), and hydrocephalus (0.5%). Repair of cranial and meningeal defects (3.0%), correction of lagophthalmos (1.2%), and repair of middle ear defects (1.0%) were the most common indications for reoperation. Logistic regression revealed that extremes of age were associated with readmission, whereas preoperative steroid usage, long operative time, and postoperative length of stay >3 days were associated with reoperation (P < 0.05). Obesity trended toward an association with readmission and reoperation. CONCLUSIONS Extremes of age were associated with readmission; preoperative steroid use, long operative time, and postoperative length of stay >3 days were associated with reoperation. Surgeons should consider these factors when assessing risk of postoperative complications for BCNTs.

Oversight in Surgical Innovation: A Response to Ethical Challenges

BackgroundSurgical innovation has advanced outcomes in the field, but carries inherent risk for surgeons and patients alike. Oversight mechanisms exist to support surgeon-innovators through difficulties associated with the innovation process.MethodsA literature review of ethical risks and oversight mechanisms was conducted.ResultsOversight mechanisms range from the historical concept of surgical exceptionalism to departmental, hospital, and centralized committees. These fragmentary and non-standardized oversight mechanisms leave surgeon-innovators and patients open to significant risk of breaching the ethical principles at the core of surgical practice. A systematized approach that mitigates these risks while maintaining the independence and dignity of the surgical profession is necessary. We propose an oversight framework that incorporates multiple structures tailored toward the ethical risk introduced by different forms of innovation.DiscussionWe summarize ethical risks and current regulatory structures, and we then use these findings to outline an oversight framework that may be applied to surgical practice.

Impact of helmet use on traumatic brain injury from road traffic accidents in Cambodia

ABSTRACT Objective: Rapid urbanization and motorization without corresponding increases in helmet usage have made traumatic brain injury due to road traffic accidents a major public health crisis in Cambodia. This analysis was conducted to quantify the impact of helmets on severity of injury, neurosurgical indication, and functional outcomes at discharge for motorcycle operators who required hospitalization for a traumatic brain injury following a road traffic accident in Cambodia. Methods: The medical records of 491 motorcycle operators who presented to a major tertiary care center in Cambodia with traumatic brain injury were retrospectively analyzed using multivariate logistic regression. Results: The most common injuries at presentation were contusions (47.0%), epidural hematomas (30.1%), subdural hematomas (27.9%), subarachnoid hemorrhages (12.4%), skull fractures (21.4%), and facial fractures (18.5%). Moderate-to-severe loss of consciousness was present in 36.3% of patients. Not wearing a helmet was associated with an odds ratio of 2.20 (95% confidence interval [CI], 1.15–4.22) for presenting with moderate to severe loss of consciousness compared to helmeted patients. Craniotomy or craniectomy was indicated for evacuation of hematoma in 20.0% of cases, and nonhelmeted patients had 3.21-fold higher odds of requiring neurosurgical intervention (95% CI, 1.25–8.27). Furthermore, lack of helmet usage was associated with 2.72-fold higher odds of discharge with functional deficits (95% CI, 1.14–6.49). In total, 30.1% of patients were discharged with severe functional deficits. Conclusions: Helmets demonstrate a protective effect and may be an effective public health intervention to significantly reduce the burden of traumatic brain injury in Cambodia and other developing countries with increasing rates of motorization across the world.

Medical management of meningioma in the era of precision medicine

Surgery is curative for most meningiomas, but a minority of these tumors recur and progress after resection. Initial trials of medical therapies for meningioma utilized nonspecific cytotoxic chemotherapies. The presence of hormone receptors on meningioma ushered in trials of hormone-mimicking agents. While these trials expanded clinical understanding of meningioma, they ultimately had limited efficacy in managing aggressive lesions. Subsequent detection of misregulated proteins and genomic aberrancies motivated the study of therapies targeting specific biological disturbances observed in meningioma. These advances led to trials of targeted kinase inhibitors and immunotherapies, as well as combinations of these agents together with chemotherapies. Prospective trials currently recruiting participants are testing a diverse range of medical therapies for meningioma, and some studies now require the presence of a specific protein alteration or genetic mutation as an inclusion criterion. Increasing understanding of the unique and heterogeneous nature of meningiomas will continue to spur the development of novel medical therapies for the arsenal against aggressive tumors.

Clinical applications of dynamic CT angiography for intracranial lesions

BackgroundDynamic CT angiography (dCTA) augments traditional CTA with temporal resolution and has been demonstrated to influence operative planning in skull base surgery.MethodsThree hundred twenty-five dynamic CTA cases from a single institution were reviewed for indication of study, findings, and comparison to other modalities of imaging.ResultsThe most frequent application of dCTA was pre-operative surgical planning (59.4%); resection of skull base tumors represented the majority of these pre-operative studies (93.3%). It was also used to evaluate new neurological symptoms (20.9%). Of these, the most common symptoms prompting a dCTA study included headache (22.1%) and visual field deficit (11.8%). The most commonly visualized vascular lesions were partial (22.9%) and complete vascular occlusions (9.0%). Dynamic CTA has also been useful in post-operative imaging for vascular malformations (9.5%) and tumors (2.5%). Finally, dCTA was employed to evaluate ambiguous abnormal findings observed on other imaging modalities (7.7%). Cerebral dCTA ruled out inconclusive abnormal vascular findings visualized on other imaging modalities (64.0%) more frequently than it confirmed them (32.0%), and was inconclusive in a singular case (4.0%).ConclusionsCerebral dCTA is an evolving new technology with a diverse spectrum of potential applications. In addition to its role in guiding pre-operative planning for skull base surgical cases, dynamic CTA offers excellent spatial and temporal resolution for assessment of vascular lesions.

Metastatic Gastrointestinal Stromal Tumor to the Skull

BACKGROUND Gastrointestinal stromal tumors (GISTs) arising from the interstitial cells of Cajal along the gastrointestinal tract rarely metastasize to the central nervous system (CNS) but require aggressive multimodal therapies when they do. We present a case of recurrent GIST metastasis to the skull and review the literature on management, including the role of molecular profiling in determining adjuvant treatment. CASE A 64-year-old woman presented with an enlarging palpable mass over her right eye. Magnetic resonance imaging revealed an enhancing T1-hypointense, T2-hyperintense right frontal calvarial lesion with lytic features on computed tomography. Pathology confirmed metastatic GIST to the skull with dural involvement. Molecular profiling revealed a mutation in exon 11 of KIT in her primary tumor, while the skull metastasis harbored an additional mutation in exon 17 associated with acquired drug resistance. CONCLUSION We review the epidemiology of GIST metastases and discuss potential reasons for its rare presentation to the CNS. Additionally, we highlight the diagnostic and prognostic value of molecular profiling for metastatic GIST, as well as its influence in arbitrating targeted molecular inhibitor therapy. Evolving molecular signatures, associated with treatment resistance, may play a pivotal role in future integration with multimodality treatment strategies for CNS GIST.