Shoji Yomo, Kyota Oda, and Kazuhiro Oguchi
OBJECTIVE
Stereotactic radiosurgery (SRS) is the mainstay treatment for brain metastases (BMs) from lung cancer. In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic lung cancer and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for lung cancer BMs prolongs overall survival (OS), improves intracranial disease control, and raises safety concerns.
METHODS
Patients who underwent SRS for lung cancer BMs at Aizawa Hospital between January 2015 and December 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The two treatment groups, which had a similar likelihood of receiving concurrent ICIs, were generated by propensity score matching (PSM; match ratio 1:1) based on 11 potential prognostic covariates. Patient survival and intracranial disease control were compared between the groups with and without concurrent ICIs (ICI + SRS vs SRS) by time-dependent analyses, taking into account competing events.
RESULTS
Five hundred eighty-five patients with lung cancer BM (494 with non–small cell lung cancer and 91 with small cell lung cancer) were eligible. Of those patients, 93 (16%) received concurrent ICIs. Two groups, each with 89 patients (ICI + SRS group and SRS group), were generated by PSM. The 1-year survival rates of the ICI + SRS and SRS groups after the initial SRS were 65% and 50% and the median survival times were 16.9 and 12.0 months, respectively (HR 0.62, 95% CI 0.44–0.87, p = 0.006). The 2-year cumulative neurological mortality rates were 12% and 16%, respectively (HR 0.55, 95% CI 0.28–1.10, p = 0.091). The 1-year intracranial progression-free survival rates were 35% and 26% (HR 0.73, 95% CI 0.53–0.99, p = 0.047). The 2-year local failure rates were 12% and 18% (HR 0.72, 95% CI 0.32–1.61, p = 0.43) and the 2-year distant recurrence rates were 51% and 60% (HR 0.82, 95% CI 0.55–1.23, p = 0.34). Severe adverse radiation events (Common Terminology Criteria for Adverse Events [CTCAE] grade 4) occurred in 1 patient in each group, and CTCAE grade 3 toxicities were observed in 3 patients in the ICI + SRS group and in 5 in the SRS group (OR 1.53, 95% CI 0.35–7.7, p = 0.75).
CONCLUSIONS
The present study found that SRS with concurrent ICIs for patients with lung cancer BMs was associated with longer survival and durable intracranial disease control, with no apparent increase in treatment-related adverse events.
Danielle F. Miyagishima, Vinaik Sundaresan, Ana Gabriella Gutierrez, Tanyeri Barak, Jacky Yeung, Jennifer Moliterno, Declan McGuone, Elizabeth B. Claus, and Murat Günel
OBJECTIVE
The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite literature suggesting that meningiomas are sensitive to gonadal steroid hormones. Therefore, the authors sought to collect and compare data on this topic by performing a systematic review and meta-analysis of reported studies of HR status in meningiomas.
METHODS
A MEDLINE PubMed literature review conducted for articles published between January 1, 1951, and December 31, 2020, resulted in 634 unduplicated articles concerning meningiomas and HRs. There were 114 articles that met the criteria of detailed detection protocols for progesterone receptor (PR), estrogen receptor (ER), and/or androgen receptor (AR) using immunohistochemistry (IHC) or ligand-binding (LB) assays and simultaneous reporting of HR status with at least one variable among age, sex, histology, location, grade, or recurrence. Between-study heterogeneity and risk of bias were evaluated using graphical and statistical methods. The authors performed a multilevel meta-analysis using random-effects modeling on aggregated data (n = 4447) and individual participant data (n = 1363) with subgroup results summarized as pooled effects. A mixed-effects meta-regression using individual participant data was performed to analyze independently associated variables.
RESULTS
The 114 selected articles included data for 5810 patients with 6092 tumors analyzed to determine the expression of three HRs in human meningiomas: PRs, ARs, and ERs. The proportions of HR+ meningiomas were estimated to be 0.76 (95% CI 0.72–0.80) for PR+ and 0.50 (95% CI 0.33–0.66) for AR+ meningiomas. ER+ meningioma detection varied depending on the measurement method used and was 0.06 (95% CI 0.03–0.10) with IHC and 0.11 (95% CI 0.06–0.20) with LB assays. There were associations between age and PR and ER expression that varied between male and female patients. PR+ and AR+ were more common in female patients (OR 1.84, 95% CI 1.47–2.29 for PR and OR 4.16, 95% CI 1.62–10.68 for AR). Additionally, PR+ meningiomas were enriched in skull base locations (OR 1.89, 95% CI 1.03–3.48) and meningothelial histology (OR 1.86, 95% CI 1.23–2.81). A meta-regression showed that PR+ was independently associated with age (OR 1.11 95% CI 1.09–1.13; p < 0.0001) and WHO grade I tumors (OR 8.09, 95% CI 3.55–18.44; p < 0.0001). ER+ was negatively associated with meningothelial histology (OR 0.94, 95% CI 0.86–0.98; p = 0.044) and positively associated with convexity location (OR 1.12, 95% CI 1.05–1.18; p = 0.0003).
CONCLUSIONS
The association between HRs and meningioma features has been investigated but unexplained for decades. In this study the authors demonstrated that HR status has a strong association with known meningioma features, including WHO grade, age, female sex, histology, and anatomical location. Identifying these independent associations allows for a better understanding of meningioma heterogeneity and provides a foundation for revisiting targeted hormonal therapy in meningioma on the basis of proper patient stratification according to HR status.
Mary Jane Lim-Fat and Sunit Das
Adolescent and young adult (AYA) patients with glioma have historically had poorer outcomes than similar patients of younger or older age, a disparity thought to be attributable to the social and economic challenges faced by this group in the transition from childhood to adult life, delays in diagnosis, low participation of AYA patients in clinical trials, and the lack of standardized treatment approaches specific to this patient group. Recent work from many groups has informed a revision of the World Health Organization classification schema for gliomas to identify biologically divergent pediatric- and adult-type tumors, both types of which may occur in AYA patients, and revealed exciting opportunities for the use of targeted therapies for many of these patients. In this review, the authors focus on the glioma types of specific concern to practitioners caring for AYA patients and the factors that should be considered in the development of multidisciplinary teams to facilitate their care.
Botao Xiong, Bin Li, Rong Wen, Yuan Gao, Feilong Gong, Denghui Li, Yangyang Xu, Hao Deng, Linglong Xiao, Senlin Yin, Wei Zhang, Andres M. Lozano, and Wei Wang
OBJECTIVE
Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD.
METHODS
Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAc-ALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG.
RESULTS
The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude.
CONCLUSIONS
These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD.
Clinical trial registration no.: NCT02398318 (ClinicalTrials.gov)
Ildiko Hoffmann, Erin R. Lewis, Corrado Marini, John McNelis, Shankar Viswanathan, Jussi P. Posti, David A. Lieb, and Michael Lowery Wilson
OBJECTIVE
Venous thromboembolism (VTE) chemoprophylaxis in pediatric patients with traumatic brain injury (TBI) requires balancing the risk of progression of intracranial bleeding versus the risk of VTE. The identification of VTE risk factors requires analysis of a very large data set. This case-control study aimed to identify VTE risk factors in pediatric patients with TBI in order to develop a TBI-specific association model that can be used for VTE risk stratification in this population.
METHODS
The study included patients (aged 1–17 years) from the 2013–2019 US National Trauma Data Bank who were admitted for TBI in order to identify risk factors for VTE. Stepwise logistic regression was used to develop an association model.
RESULTS
Of 44,128 study participants, 257 (0.58%) developed VTE. Risk factors associated with VTE included age (OR 1.045, 95% CI 1.010–1.080), body mass index (OR 1.034, 95% CI 1.013–1.055), Injury Severity Score (OR 1.049, 95% CI 1.039–1.059), blood product administration (OR 1.436, 95% CI 1.008–2.046), presence of a central venous catheter (OR 3.333, 95% CI 2.431–4.571), and development of ventilator-associated pneumonia (OR 3.650, 95% CI 2.469–5.396). Based on this model, the predicted VTE risk in pediatric patients with TBI ranged from 0% to 16.8%.
CONCLUSIONS
A model that includes age, body mass index, Injury Severity Score, blood transfusion, use of a central venous catheter, and ventilator-associated pneumonia can help to risk stratify pediatric patients with TBI from the standpoint of implementation of VTE chemoprophylaxis.
Christine Marlow, Joshua A. Cuoco, Kristine Ravina, Cole A. Sloboda, and John J. Entwistle
BACKGROUND
Pure arterial malformations are characterized as unique cerebrovascular lesions with a dilated, coil-like appearance and tortuous arteries without early venous drainage. Historically, these lesions have been described as incidental findings with a benign natural history. However, pure arterial malformations can rarely demonstrate radiographic progression and develop associated focal aneurysms with an unclear risk of rupture. Whether radiographic progression of these lesions or the presence of an associated aneurysm warrants treatment remains controversial.
OBSERVATIONS
A 58-year-old male presented with sudden-onset left hemiparesis. Computed tomography revealed a large, acute, right frontotemporoparietal intraparenchymal hemorrhage with underlying irregular curvilinear calcifications. Diagnostic cerebral angiography revealed a dysplastic right middle cerebral artery dissecting aneurysm along the M2 segment associated with a pure arterial malformation, which was treated with endovascular flow diversion in a delayed fashion.
LESSONS
Pure arterial malformations with associated focal aneurysms may not exhibit a benign natural history as once thought. Intervention should be considered for ruptured pure arterial malformations to mitigate the risk of rerupture. Asymptomatic patients with a pure arterial malformation with an associated aneurysm should at least be followed closely with interval radiographic imaging to evaluate for malformation progression or changes in aneurysmal morphology.
Lisa B. E. Shields, Vasudeva G. Iyer, Yi Ping Zhang, and Christopher B. Shields
BACKGROUND
Differentiating foot drop due to upper motor neuron (UMN) lesions from that due to lower motor neuron lesions is crucial to avoid unnecessary surgery or surgery at the wrong location. Electrodiagnostic (EDX) studies are useful in evaluating patients with spastic foot drop (SFD).
OBSERVATIONS
Among 16 patients with SFD, the cause was cervical myelopathy in 5 patients (31%), cerebrovascular accident in 3 (18%), hereditary spastic paraplegia in 2 (12%), multiple sclerosis in 2 (12%), chronic cerebral small vessel disease in 2 (12%), intracranial meningioma in 1 (6%), and diffuse brain injury in 1 (6%). Twelve patients (75%) had weakness of a single leg, whereas 2 others (12%) had bilateral weakness. Eleven patients (69%) had difficulty walking. The deep tendon reflexes of the legs were hyperactive in 15 patients (94%), with an extensor plantar response in 9 patients (56%). Twelve patients (75%) had normal motor and sensory conduction, 11 of whom had no denervation changes of the legs.
LESSONS
This study is intended to raise awareness among surgeons about the clinical features of SFD. EDX studies are valuable in ruling out peripheral causes of foot drop, which encourages diagnostic investigation into a UMN source for the foot drop.
Shivani Baisiwala, Myungjun Ko, Humza Zubair, Kevin Li, Andrew C. Vivas, Richard Everson, Linda Liau, Ausaf Bari, and Kunal S. Patel
BACKGROUND
Gliosarcoma is a rare and highly malignant cancer of the central nervous system with the ability to metastasize. Secondary gliosarcoma, or the evolution of a spindle cell–predominant tumor after the diagnosis of a World Health Organization grade IV glioblastoma, has also been shown to metastasize. There is little information on metastatic secondary gliosarcoma.
OBSERVATIONS
The authors present a series of 7 patients with previously diagnosed glioblastoma presenting with recurrent tumor and associated metastases with repeat tissue diagnosis consistent with gliosarcoma. The authors describe the clinical, imaging, and pathological characteristics in addition to carrying out a systematic review on metastases in secondary gliosarcoma.
LESSONS
The present institutional series and the systematic review of the literature show that metastatic secondary gliosarcoma is a highly aggressive disease with a poor prognosis.
Juan Silvestre G. Pascual, Madeleine de Lotbiniere-Bassett, Katrina Hannah D. Ignacio, David Ben-Israel, Jessica M. Clark, and Yves P. Starreveld
BACKGROUND
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare headache disorder that has been associated with pituitary adenomas. Resection has been posited to be curative.
OBSERVATIONS
A 60-year-old female presented with a 10-year history of SUNCT, which had been medically refractory. Sellar magnetic resonance imaging (MRI) showed a 2 × 2 mm nodule in the right anterolateral aspect of the pituitary. Endoscopic endonasal transsphenoidal resection of the pituitary microadenoma with neuronavigation was performed. The patient felt immediate relief from the headaches. Postoperative MRI showed persistence of the pituitary microadenoma and the resection tract to be inferomedial to the lesion. The right middle and partial superior turbinectomy site was close to the sphenopalatine foramen (SPF). The patient was discharged on postoperative day 1 and remained headache-free without any medications at the 4-month follow-up.
LESSONS
Resection of pituitary lesions associated with SUNCT may not necessarily be the cause of SUNCT resolution. Manipulation of the middle and superior turbinate close to the SPF may lead to a pterygopalatine ganglion block. This may be the mechanism of cure for SUNCT in patients with related pituitary lesions who undergo endonasal resection.
