Pre-operative stereotactic radiosurgery for cerebral metastatic disease: A retrospective dose-volume study.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) after maximal safe resection is an accepted treatment strategy for patients with cerebral metastatic disease. Despite its high conformality profile, the incidence of radionecrosis (RN) remains high. SRS delivered pre-operatively could be associated with a reduced incidence of RN. We sought to evaluate whether neoadjuvant SRS could reduce radiotherapy doses in a cohort of patients treated with post-operative SRS. METHODS: A cohort of 47 brain metastases (BM) treated at 2 academic institutions was retrospectively analyzed. Subjects underwent surgical extirpation of BMs and subsequent SRS to surgical bed. Post-operative volumetric and dosimetric data was collected from records or recreations of delivered plans; pre-operative data were derived from hypothetical radiotherapy courses and compared using Wilcoxon signed-rank tests. RESULTS: Higher planned tumor volume post-operatively (median[IQR] 12.28 [6.54, 18.69]cc vs 10.20 [4.53, 21.70]cc respectively, p = 0.4150) was observed. The median prescribed radiotherapy dose (DRx) was 16 Gy pre-operatively and 24 Gy post-operatively (p < 0.0001). Further investigations revealed improved pre-operative conformity index (1.23[1.20, 1.29] vs 1.29[1.23, 1.39], p = 0.0098) and gradient index (2.72[2.59, 2.98] vs 2.94[2.69, 3.47], p = 0.0004). A significant difference was found in normal brain tissue exposed to 10 Gy (12.97[6.78, 25.54]cc vs 32.13[19.42, 48.40]cc, p < 0.0001), 12 Gy (9.31[4.56, 17.43]cc vs 23.80[14.74, 36.56]cc, p < 0.0001), and 14 Gy (5.62[3.23, 11.61]cc vs 17.47[9.00, 28.31]cc, p < 0.0001), favoring pre-operative SRS. CONCLUSIONS: Neoadjuvant SRS is associated reduced DRx, better conformality profile and decreased radiation to normal tissue. These findings could support the use of neoadjuvant SRS for the treatment of BMs.

PA- and NP-led Ommaya clinics to manage leptomeningeal carcinomatosis.

OBJECTIVES: Physician assistants (PAs) and NPs are essential to quality care delivery. The need to demonstrate value and optimize PA and NP roles in neurology subspecialty clinics is unmet. We outline the development of a PA- and NP-led neuro-oncology procedural clinic and provide metrics to support the institutional and clinician value added. METHODS: We designed a PA- and NP-led Geisinger Ommaya Clinic (GOC) to manage leptomeningeal carcinomatosis (LMC) with defined clinician roles and the GOC treatment protocol. A retrospective review of 135 patients (2012-2019) compared survival outcomes for patients treated on the protocol compared with those treated off the protocol. RESULTS: Centralized care in the GOCs minimized shared physician encounters and improved PA and NP autonomy and utility. LMC therapy as part of the GOC protocol improved care continuity and survival outcomes. CONCLUSIONS: PA- and NP-led procedural clinics optimize use of these clinicians and open physician availability for nonprocedural duties. This research highlights the institutional patient and financial benefit while demonstrating the operational and leadership growth potential for PAs and NPs.

Early imaging marker of progressing glioblastoma: a window of opportunity.

PURPOSE: Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure. METHODS: A retrospective review of 609 GBM patients between 2006 and 2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan-Meier curves stratified by SI. Specificity and sensitivity were determined using a 2 × 2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI. RESULTS: Seventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥ 4 was the most significant prognostic indicator of death. CONCLUSION: Implications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.

Case Report of Immuno-Oncotherapy (IO) Provoked Encephalitis Mimicking Brain Metastasis in a Patient with History of Traumatic Brain Injury.

BACKGROUND: Immuno-oncotherapy (IO) has revolutionized systemic cancer care but remains experimental in brain tumors. IO treatment risks multiorgan autoimmune inflammatory responses that limit its use. The central nervous system (CNS) is an immune-specialized compartment with restricted cellular access, thus fewer cases are reported for immune-mediated encephalitis. Interestingly, patients with history of blood-brain barrier compromise are potentially at higher risk for immune cell trafficking to the CNS. CASE DESCRIPTION: We report the first case, to our knowledge, of a 70-year-old man with clear cell renal cell carcinoma with pulmonary metastases treated with lung irradiation, nephrectomy, and chemotherapy prior to switching to single-agent nivolumab IO. The patient presented with new-onset generalized tonic-clonic seizure and left visual field-cut. Review of patient history revealed remote traumatic brain injury (TBI). Brain imaging noted a solid-enhancing right occipital mass that was presumed metastasis versus lymphoma. Cerebrospinal fluid cytology was negative for malignancy but concerning for lymphoproliferative process not determined to be malignant. The patient started steroids and anti-epileptic therapy. After negative systemic cancer re-staging, IO was discontinued and steroids were initiated with demonstrated patient clinical improvement. CONCLUSIONS: We concluded the diagnosis of immune-mediated encephalitis secondary to IO with collection of reactive T-cells within the area of encephalomalacia. The area of encephalomalacia from prior TBI served to compartmentalize the reactive lymphocytes, giving the appearance of a mass. Taken together, new onset seizure in patients on IO might signal encephalitis and CNS metastatic mimicry should be considered in patients with a prior history of TBI and encephalomalacia.

Anterior Communicating Artery Complex Aneurysms: Anatomic Characteristics as Predictors of Surgical Outcome in 300 Cases.

OBJECTIVE: Anterior communicating artery (ACoA) complex aneurysms are challenging to treat microsurgically. The authors report their experience with microsurgical treatment of ACoA aneurysms and examine the anatomic characteristics of these aneurysms as predictors of outcome. METHODS: The authors queried their institution's aneurysm database for records of consecutive patients treated for ACoA aneurysms via microsurgical clip ligation. Data included patient demographics and clinical/radiographic presentation characteristics as well as operative techniques. Glasgow Outcome Scale (GOS) scores at hospital discharge and 6-month as well as 1-year follow-up were analyzed. RESULTS: Of 319 ACoA aneurysms that underwent treatment, 259 were ruptured and 60 were unruptured. Average GOS at 1-year follow-up for all patients was 4.6. Average GOS for patients with ruptured aneurysms correlated with Hunt and Hess grade at presentation, presence of frontal hemorrhages, and need for multiple clips during surgery. Notably, 142 (44.5%) of aneurysms originated mainly from the ACoA artery; 12 (3.8%) primarily from the A1 branch; 3 (0.9%) from the A2 branch; and 162 (50.8%) from the A1/A2 junction. Aneurysm projection was superior in 118 (37%), inferior in 106 (33.2%), anterior in 88 (27.6%), and posterior in 7 (2.2%). Patients with aneurysms originating from the A1 segment had worse outcomes. Posteriorly projecting aneurysms were more likely to be unruptured and larger than other aneurysm configurations. CONCLUSIONS: The aneurysm's exact location in relation to the adjacent neurovascular structures is potentially predictive of outcomes in the microsurgical treatment of ACoA aneurysms.

Pregnancy-associated Cushing's disease? An exploratory retrospective study.

PURPOSE: In most clinical series of Cushing's disease (CD), over 80% of patients are women, many of whom are of reproductive age. The year following pregnancy may be a common time to develop CD. We sought to establish the incidence of CD onset associated with pregnancy. METHODS: A retrospective review was conducted for patients with biochemically-proven CD. Demographics, clinical history, biochemistry, imaging, pathology, and outcomes were reviewed. Pregnancy-associated CD was defined as symptom onset within 1 year of childbirth. RESULTS: Over 10 years, 77 patients including 64 women (84%), with CD underwent endonasal surgery. Of the 64 women, 64% were of reproductive age (15-45 years) at the time of diagnosis, and 11 (27%) met criteria for pregnancy-associated CD. Of these 11 women, median number of pregnancies prior to onset of CD was 2 (range 1-4) compared to zero (range 0-7) for 30 other women with CD onset during reproductive age (p = 0.0024). With an average follow-up of 47 ± 34 months, sustained surgical remission rates for woman with pregnancy-associated CD, other women of reproductive age, and women not of reproductive age were 91%, 80% and 83%, respectively. The average lag-time from symptom onset to diagnosis for women with pregnancy-associated CD was 4 ± 2 years. CONCLUSIONS: In this exploratory study, over one quarter of women of reproductive age with CD appeared to have symptomatic disease onset within 1 year of childbirth. This relatively high rate of pregnancy-associated CD suggests a possible causal relationship related to the stress of pregnancy and pituitary corticotroph hyperactivity in the peripartum period. This possible association suggests a heightened degree of clinical suspicion and biochemical testing for CD may be warranted after childbirth. Further study of this possible link between pregnancy and CD is warranted.

Clinical, Pathological, and Surgical Outcomes for Adult Pineoblastomas.

INTRODUCTION: Pineoblastomas are uncommon primitive neuroectodermal tumors that occur mostly in children; they are exceedingly rare in adults. Few published reports have compared the various aspects of these tumors between adults and children. METHODS: The authors report a series of 12 pineoblastomas in adults from 2 institutions over 24 years. The clinical, radiologic, and pathologic features and clinical outcomes were compared with previously reported cases in children and adults. RESULTS: Patient age ranged from 24 to 81 years, and all but 1 patient exhibited symptoms of obstructive hydrocephalus. Three patients underwent gross total resection, and subtotal resection was performed in 3 patients. Diagnostic biopsy specimens were obtained in an additional 6 patients. Pathologically, the tumors had the classical morphologic and immunohistochemical features of pineoblastomas. Postoperatively, 10 patients received radiotherapy, and 5 patients received chemotherapy. Compared with previously reported cases, several differences were noted in clinical outcomes. Of the 12 patients, only 5 (42%) died of their disease (average length of survival, 118 months); 5 patients (42%) are alive with no evidence of disease (average length of follow-up, 92 months). One patient died of unrelated causes, and one was lost to follow-up. Patients with subtotal resections or diagnostic biopsies did not suffer a worse prognosis. Of the 9 patients with biopsy or subtotal resection, 4 are alive, 4 died of their disease, and 1 died of an unrelated hemorrhagic cerebral infarction. CONCLUSIONS: Although this series is small, the data suggest that pineoblastomas in adults have a less aggressive clinical course than in children.

Endoscopic extended transsphenoidal resection of craniopharyngiomas: nuances of neurosurgical technique.

Endoscopic approaches to the midline ventral skull base have been extensively developed and refined for resection of cranial base tumors over the past several years. As these techniques have improved, both the degree of resection and complication rates have proven comparable to those for transcranial approaches, while visual outcomes may be better via endoscopic endonasal surgery and hospital stays and recovery times are often shorter. Yet for all of the progress made, the steep learning curve associated with these techniques has hampered more widespread implementation and adoption. The authors address this obstacle by coupling a thorough description of the technical nuances for endoscopic endonasal craniopharyngioma resection with detailed illustrations of the important steps in the operation. Traditionally, transsphendoidal approaches to craniopharyngiomas have been restricted to lesions mostly confined to the sella. However, recently, endoscopic endonasal resections are more frequently employed for extrasellar and purely third ventricle craniopharyngiomas, whose typical retrochiasmatic location makes them ideal candidates for endoscopic transnasal surgery. The endonasal endoscopic approach offers many advantages, including direct access to the long axis of the tumor, early tumor debulking with minimal manipulation of the optic apparatus, more precise visualization of tumor planes, particularly along the undersurface of the chiasm and the roof of the third ventricle, and a minimal-access corridor that obviates the need for brain retraction. Although much emphasis has been placed on technical tenets of exposure and "how to get there," this article focuses on nuances of tumor resection "when you are there." Three operative videos illustrate our discussion of technical tenets.