Integrated insular phenotype (IIP) versus Berger–Sanai and Yasargil classifications: comparative prognostic value in surgery of insular gliomas

Acta Neurochirurgica (2025) 167:324

This study compares the Integrated Insular Phenotype (IIP), a three-level ordinal topographic classification of insular gliomas, with Berger–Sanai and Yasargil systems to evaluate prognostic performance for extent of resection, seizure control, and persistent neurological deficit at 90 days. Using retrospective analysis of 167 surgically treated patients, logistic regression and model metrics (AUC, AIC, LR χ2) assessed associations between classification complexity and outcomes.

Results show increasing IIP complexity strongly predicted lower resectability, poorer seizure control, and higher persistent deficit risk; IIP produced more stable odds ratios, lower AIC, and higher LR χ2 than traditional systems. The authors propose IIP as a practical risk-stratification tool to balance oncological radicality and functional safety, recommending multicenter prospective validation and integration with molecular and intraoperative technologies.

Integrated Insular Phenotype (IIP): An ordinal classification system for insular gliomas that incorporates tumor topographic complexity and multizonal involvement, outperforming traditional Berger–Sanai and Yasargil systems in prognostic accuracy for surgical outcomes.

Prognostic Value: IIP demonstrates superior and more stable associations with key surgical outcomes—extent of resection, seizure control, and persistent neurological deficit at 90 days—compared to Berger–Sanai and Yasargil classifications, as shown by higher informativeness, lower AIC, and more reproducible odds ratios.

Surgical Complexity: Higher IIP complexity (IIP-M) is linked to reduced likelihood of total/subtotal resection, poorer seizure control, and increased risk of persistent neurological deficits, while simpler phenotypes (IIP-L) are associated with more favorable outcomes.

Traditional Classifications: Berger–Sanai and Yasargil systems provide limited prognostic value; Berger–Sanai yields high but unstable odds ratios with wide confidence intervals, while Yasargil offers consistent but less discriminative results.

Clinical Implications: IIP can guide individualized surgical strategies by balancing oncological radicality against functional safety, supporting the principle of maximal safe resection and informing risk stratification.

Seizure Outcomes: Multizonal and widespread IIP phenotypes (IIP-M) are associated with poorer postoperative seizure control, reflecting the challenge of eliminating diffuse epileptogenic networks.

Study Limitations: The findings are based on a single-center retrospective cohort; external validation and integration with molecular, histopathological, and neurocognitive factors are needed for broader applicability.

Future Directions: Prospective multicenter validation, integration with intraoperative technologies, and use of AI/ML for risk stratification and personalized planning are recommended to enhance the utility of IIP in clinical practice

Pretreatment patient‐reported cognitive function in patients with diffuse glioma

Acta Neurochirurgica (2022) 164:703–711

Cognitive function is frequently assessed with objective neuropsychological tests, but patient-reported cognitive function is less explored. We aimed to investigate the preoperative prevalence of patient-reported cognitive impairment in patients with diffuse glioma compared to a matched reference group and explore associated factors.

Methods We included 237 patients with diffuse glioma and 474 age- and gender-matched controls from the general population. Patient-reported cognitive function was measured using the cognitive function subscale in the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The transformed scale score (0–100) was dichotomized, with a score of ≤ 75 indicating clinically important patient-reported cognitive impairment. Factors associated with preoperative patient-reported cognitive impairment were explored in a multivariable regression analysis.

Results Cognitive impairment was reported by 49.8% of the diffuse glioma patients and by 23.4% in the age- and gendermatched reference group (p < 0.001). Patients with diffuse glioma had 3.2 times higher odds (95% CI 2.29, 4.58, p < 0.001) for patient-reported cognitive impairment compared to the matched reference group. In the multivariable analysis, large tumor volume, left tumor lateralization, and low Karnofsky Performance Status score were found to be independent predictors for preoperative patient-reported cognitive impairment.

Conclusions Our findings demonstrate that patient-reported cognitive impairment is a common symptom in patients with diffuse glioma pretreatment, especially in patients with large tumor volumes, left tumor lateralization, and low functional levels. Patient-reported cognitive function may provide important information about patients’ subjective cognitive health and disease status and may serve as a complement to or as a screening variable for subsequent objective testing.

Frameless Stereotactic Radiosurgery on the Gamma Knife Icon: Early Experience From 100 Patients

Neurosurgery 86:509–516, 2020

The Gamma Knife (GK) Icon (Elekta AB) uses a cone-beam computed tomography (CBCT) scanner and an infrared camera system to support the delivery of frameless stereotactic radiosurgery (SRS). There are limited data on patients treated with frameless GK radiosurgery (GKRS).

OBJECTIVE: To describe the early experience, process, technical details, and short-term outcomes with frameless GKRS at our institution.

METHODS: We reviewed our patient selection and described the workflow in detail, including image acquisition, treatment planning, mask-based immobilization, stereotactic CBCT localization, registration, treatment, and intrafraction monitoring. Because of the short interval of follow-up, we provide crude rates of local control.

RESULTS: Data from 100 patients are reported. Median age is 67 yr old. 56 patients were treated definitively, 21 postoperatively, and 23 had salvage GKRS for recurrence after surgery. Forty-two patients had brain metastases, 26 meningiomas, 16 vestibular schwannomas, 9 high-grade gliomas, and 7 other histologies. Median doses to metastases were 20 Gy in 1 fraction (range: 14-21), 24 Gy in 3 fractions (range: 19.5-27), and 25 Gy in 5 fractions (range: 25-30 Gy). Thirteen patients underwent repeat SRS to the same area. Median treatment time was 17.7 min (range: 5.8-61.7). We found an improvement in our workflow and a greater number of patients eligible for GKRS because of the ability to fractionate treatments.

CONCLUSION: We report a large cohort of consecutive patients treated with frameless GKRS. We look forward to studies with longer follow-up to provide valuable data on clinical outcomes and to further our understanding of the radiobiology of hypofractionation in the brain.

Papillary Tumor of the Pineal Region: Systematic Review and Analysis of Prognostic Factors

Neurosurgery, Volume 85, Issue 3, September 2019: E420–E429

Clinical outcomes and biological behavior of papillary tumors of the pineal region (PTPR) are still under investigation. The best therapeutic strategy has not been defined.

OBJECTIVE: To perform a comprehensive patient-level analysis of all PTPR cases and identify their clinical features, treatment options, and prognostic factors.

METHODS: A search of the medical databases for case series and reports on PTPRs from January 2003 to June 2017 was performed. Data addressing PTPR’s clinical presentation, imaging, treatment, and histological features were. Variables associated with the primary outcome of 36-mo survival were identified through Cox regression models.

RESULTS: The initial search yielded 1164 studies, of which 71 were included (60 case reports and 11 case series), containing 177 patients (mean age 33.0 ± 15.3 yr and 53.2% male). Intracranial hypertension and hydrocephalus prevailed as the clinical picture. Surgery was performed on 82.0% and gross total resection (GTR) was achieved on 71.4%. A total of 56.8% recurred after a median 29-mo (quartiles 10.5-45.5). The 36-mo survival rate was 83.5% (95% confidence interval [CI] 76.2-89.2%). Good functional outcomes (Glasgow Outcome Scale 4/5) were observed in 60.0%. The variables of interest were inconsistently reported and the multivariable analysis final sample was 133 patients. After adjustment for age, tumor size (each additional centimeter, hazard ratio [HR] 1.99, 95% CI 1.12-3.53, P = .019) and surgical treatment (HR 0.16, 95% CI 0.05-0.45, P = .001) were associated with 36-mo survival.

CONCLUSION: Tumor size and surgery are associated with improvement in 36-mo survival. We did not observe any significant benefits from GTR or adjuvant treatments.

Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases

Neurosurgery, Volume 85, Issue 2, August 2019, Pages 257–263

The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial.

OBJECTIVE: To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group.

METHODS: A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan–Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox propor- tional hazards.

RESULTS: Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respec- tively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume param- eters predicted for death, neurologic death or toxicity.

CONCLUSION: SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

Emerging Applications of Therapeutic Ultrasound in Neuro-oncology

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Neurosurgery 79:643–654, 2016

Transcranial focused ultrasound (FUS) can noninvasively transmit acoustic energy with a high degree of accuracy and safety to targets and regions within the brain. Technological advances, including phased-array transducers and real-time temperature monitoring with magnetic resonance thermometry, have created new opportunities for FUS research and clinical translation.

Neuro-oncology, in particular, has become a major area of interest because FUS offers a multifaceted approach to the treatment of brain tumors. FUS has the potential to generate cytotoxicity within tumor tissue, both directly via thermal ablation and indirectly through radiosensitization and sonodynamic therapy; to enhance the delivery of therapeutic agents to brain tumors by transiently opening the blood-brain barrier or improving distribution through the brain extracellular space; and to modulate the tumor microenvironment to generate an immune response.

In this review, we describe each of these applications for FUS, the proposed mechanisms of action, and the preclinical and clinical studies that have set the foundation for using FUS in neuro-oncology.

Development of Stereotactic Mass Spectrometry for Brain Tumor Surgery

Neurosurgery 68:280–290, 2011 DOI: 10.1227/NEU.0b013e3181ff9cbb

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue.

OBJECTIVE: To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents.

METHODS: Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity.

RESULTS: Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence.

CONCLUSION: The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.