Tag: Oncology

Posted on

Vertebral body fracture rates after stereotactic body radiation therapy compared with external-beam radiation therapy for metastatic spine tumors

J Neurosurg Spine 33:870–876, 2020

Stereotactic body radiation therapy (SBRT) is utilized to deliver highly conformal, dose-escalated radiation to a target while sparing surrounding normal structures. Spinal SBRT can allow for durable local control and palliation of disease while minimizing the risk of damage to the spinal cord; however, spinal SBRT has been associated with an increased risk of vertebral body fractures. This study sought to compare the fracture rates between SBRT and conventionally fractionated external-beam radiation therapy (EBRT) in patients with metastatic spine tumors.

METHODS Records from patients treated at the University of California, San Francisco, with radiation therapy for metastatic spine tumors were retrospectively reviewed. Vertebral body fracture and local control rates were compared between SBRT and EBRT. Ninety-six and 213 patients were identified in the SBRT and EBRT groups, respectively. Multivariate analysis identified the need to control for primary tumor histology (p = 0.003 for prostate cancer, p = 0.0496 for renal cell carcinoma). The patient-matched EBRT comparison group was created by matching SBRT cases using propensity scores for potential confounders, including the Spinal Instability Neoplastic Score (SINS), the number and location of spine levels treated, sex, age at treatment, duration of follow-up (in months) after treatment, and primary tumor histology. Covariate balance following group matching was confirmed using the Student t-test for unequal variance. Statistical analysis, including propensity score matching and multivariate analysis, was performed using R software and related packages.

RESULTS A total of 90 patients met inclusion criteria, with 45 SBRT and 45 EBRT matched cases. Balance of the covariates, SINS, age, follow-up time, and primary tumor histology after the matching process was confirmed between groups (p = 0.062, p = 0.174, and 0.991, respectively, along with matched tumor histology). The SBRT group had a higher 5-year rate of vertebral body fracture at 22.22% (n = 10) compared with 6.67% (n = 3) in the EBRT group (p = 0.044). Survival analysis was used to adjust for uneven follow-up time and showed a significant difference in fracture rates between the two groups (p = 0.044). SBRT also was associated with a higher rate of local control (86.67% vs 77.78%).

CONCLUSIONS Patients with metastatic cancer undergoing SBRT had higher rates of vertebral body fractures compared with patients undergoing EBRT, and this difference held up after survival analysis. SBRT also had higher rates of initial local control than EBRT but this difference did not hold up after survival analysis, most likely because of a high percentage of radiosensitive tumors in the EBRT cohort.

Posted on

Impact of facility type and volume in low-grade glioma outcomes

J Neurosurg 133:1313–1323, 2020

The object of this study was to investigate the impact of facility type (academic center [AC] vs non-AC) and facility volume (high-volume facility [HVF] vs low-volume facility [LVF]) on low-grade glioma (LGG) outcomes.

METHODS This retrospective cohort study included 5539 LGG patients (2004–2014) from the National Cancer Database. Patients were categorized by facility type and volume (non-AC vs AC, HVF vs LVF). An HVF was defined as the top 1% of facilities according to the number of annual cases. Outcomes included overall survival, treatment receipt, and postoperative outcomes. Kaplan-Meier and Cox proportional-hazards models were applied. The Heller explained relative risk was computed to assess the relative importance of each survival predictor.

RESULTS Significant survival advantages were observed at HVFs (HR 0.67, 95% CI 0.55–0.82, p < 0.001) and ACs (HR 0.84, 95% CI 0.73–0.97, p = 0.015), both prior to and after adjusting for all covariates. Tumor resection was 41% and 26% more likely to be performed at HVFs vs LVFs and ACs vs non-ACs, respectively. Chemotherapy was 40% and 88% more frequently to be utilized at HVFs vs LVFs and ACs vs non-ACs, respectively. Prolonged length of stay (LOS) was decreased by 42% and 24% at HVFs and ACs, respectively. After tumor histology, tumor pattern, and codeletion of 1p19q, facility type and surgical procedure were the most important contributors to survival variance. The main findings remained consistent using propensity score matching and multiple imputation.

CONCLUSIONS This study provides evidence of survival benefits among LGG patients treated at HVFs and ACs. An increased likelihood of undergoing resections, receiving adjuvant therapies, having shorter LOSs, and the multidisciplinary environment typically found at ACs and HVFs are important contributors to the authors’ finding.

Posted on

Contemporary assessment of extent of resection in molecularly defined categories of diffuse low-grade glioma: a volumetric analysis

J Neurosurg 133:1291–1301, 2020

While the effect of increased extent of resection (EOR) on survival in diffuse infiltrating low-grade glioma (LGG) patients is well established, there is still uncertainty about the influence of the new WHO molecular subtypes. The authors designed a retrospective analysis to assess the interplay between EOR and molecular classes.

METHODS The authors retrospectively reviewed the records of 326 patients treated surgically for hemispheric WHO grade II LGG at Brigham and Women’s Hospital and Massachusetts General Hospital (2000–2017). EOR was calculated volumetrically and Cox proportional hazards models were built to assess for predictive factors of overall survival (OS), progression-free survival (PFS), and malignant progression–free survival (MPFS).

RESULTS There were 43 deaths (13.2%; median follow-up 5.4 years) among 326 LGG patients. Median preoperative tumor volume was 31.2 cm3 (IQR 12.9–66.0), and median postoperative residual tumor volume was 5.8 cm3 (IQR 1.1–20.5). On multivariable Cox regression, increasing postoperative volume was associated with worse OS (HR 1.02 per cm3; 95% CI 1.00–1.03; p = 0.016), PFS (HR 1.01 per cm3; 95% CI 1.00–1.02; p = 0.001), and MPFS (HR 1.01 per cm3; 95% CI 1.00–1.02; p = 0.035). This result was more pronounced in the worse prognosis subtypes of IDH-mutant and IDH-wildtype astrocytoma, for which differences in survival manifested in cases with residual tumor volume of only 1 cm3. In oligodendroglioma patients, postoperative residuals impacted survival when exceeding 8 cm3. Other significant predictors of OS were age at diagnosis, IDH-mutant and IDH-wildtype astrocytoma classes, adjuvant radiotherapy, and increasing preoperative volume.

CONCLUSIONS The results corroborate the role of EOR in survival and malignant transformation across all molecular subtypes of diffuse LGG. IDH-mutant and IDH-wildtype astrocytomas are affected even by minimal postoperative residuals and patients could potentially benefit from a more aggressive surgical approach.

Posted on

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas

J Neurosurg 133:1345–1354, 2020

Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.

METHODS Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher’s exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features.

RESULTS Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among “mutation unknown” samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor’s underlying driver mutation.

CONCLUSIONS Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

Posted on

Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas

J Neurosurg 133:1324–1331, 2020

Maximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression- free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes.

METHODS A total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression–free survival and overall survival were analyzed using an adjusted Cox proportional hazards model.

RESULTS One hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03).

CONCLUSIONS Fluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.

 

Posted on

Detailed analysis of 5-aminolevulinic acid induced fluorescence in different brain metastases at two specialized neurosurgical centers: experience in 157 cases

J Neurosurg 133:1032–1043, 2020

Incomplete neurosurgical resection of brain metastases (BM) due to insufficient intraoperative visualization of tumor tissue is a major clinical challenge and might result in local recurrence. Recently, visible 5-aminolevulinic acid (5-ALA) induced fluorescence was first reported in patients with BM. The aim of this study was thus to investigate, for the first time systematically, the value of 5-ALA fluorescence for intraoperative visualization of BM in a large patient cohort.

METHODS Adult patients (≥ 18 years) with resection of suspected BM after preoperative 5-ALA administration were prospectively recruited at two specialized neurosurgical centers. During surgery, the fluorescence status (visible or no fluorescence); fluorescence quality (strong, vague, or none); and fluorescence homogeneity (homogeneous or heterogeneous) of each BM was investigated. Additionally, these specific fluorescence characteristics of BM were correlated with the primary tumor type and the histopathological subtype. Tumor diagnosis was established according to the current WHO 2016 criteria.

RESULTS Altogether, 157 BM were surgically treated in 154 patients. Visible fluorescence was observed in 104 BM (66%), whereas fluorescence was absent in the remaining 53 cases (34%). In detail, 53 tumors (34%) showed strong fluorescence, 51 tumors (32%) showed vague fluorescence, and 53 tumors (34%) had no fluorescence. The majority of BM (84% of cases) demonstrated a heterogeneous fluorescence pattern. According to primary tumor, visible fluorescence was less frequent in BM of melanomas compared to all other tumors (p = 0.037). According to histopathological subtype, visible fluorescence was more common in BM of ductal breast cancer than all other subtypes (p = 0.008). It is of note that visible fluorescence was observed in the surrounding brain tissue after the resection of BM in 74 (67%) of 111 investigated cases as well.

CONCLUSIONS In this largest series to date, visible 5-ALA fluorescence was detected in two-thirds of BM. However, the characteristic heterogeneous fluorescence pattern and frequent lack of strong fluorescence limits the use of 5-ALA in BM and thus this technique needs further improvements.

Posted on

Sphenoorbital meningioma: a unique skull base tumor. Surgical technique and results

J Neurosurg 133:1044–1051, 2020

Sphenoorbital meningioma (SOM) is a unique skull base tumor, characterized by infiltrative involvement and hyperostosis primarily of the lesser wing of sphenoid bone, with frequent involvement of the orbital compartment. SOM often manifests with proptosis and visual impairment. Surgical technique and outcome are highly variable among studies reported in the literature. The authors present a single-surgeon experience with SOM.

METHODS A retrospective review of a prospectively maintained institutional database was performed. A blinded imaging review by 2 study team members was completed to confirm SOM, after which chart review was carried out to capture demographics and outcomes. All statistical testing was completed using JMP Pro version 14.1.0, with significance defined as p < 0.05.

RESULTS Forty-seven patients who underwent surgery between 2000 and 2017 were included. The median age at surgery was 47 years (range 36–70 years), 81% of patients were female, and the median follow-up was 43 months (range 0–175 months). All operations were performed via a frontotemporal craniotomy, orbitooptic osteotomy, and anterior clinoidectomy, with extensive resection of all involved bone and soft tissue. Preoperatively, proptosis was noted in 44 patients, 98% of whom improved. Twenty-eight patients (60%) had visual deficits before surgery, 21 (75%) of whom improved during follow-up. Visual field defect other than a central scotoma was the only prognostic factor for improvement in vision on multivariate analysis (p = 0.0062). Nine patients (19%) had recurrence or progression during follow-up.

CONCLUSIONS SOM is a unique skull base tumor that needs careful planning to optimize outcome. Aggressive removal of involved bone and periorbita is crucial, and proptosis and visual field defect other than a central scotoma can improve after surgery.

Posted on

Resection of tumors within the primary motor cortex using high-frequency stimulation

J Neurosurg 133:642–654, 2020

Brain mapping techniques allow one to effectively approach tumors involving the primary motor cortex (M1). Tumor resectability and maintenance of patient integrity depend on the ability to successfully identify motor tracts during resection by choosing the most appropriate neurophysiological paradigm for motor mapping. Mapping with a highfrequency (HF) stimulation technique has emerged as the most efficient tool to identify motor tracts because of its versatility in different clinical settings. At present, few data are available on the use of HF for removal of tumors predominantly involving M1.

METHODS The authors retrospectively analyzed a series of 102 patients with brain tumors within M1, by reviewing the use of HF as a guide. The neurophysiological protocols adopted during resections were described and correlated with patients’ clinical and tumor imaging features. Feasibility of mapping, extent of resection, and motor function assessment were used to evaluate the oncological and functional outcome to be correlated with the selected neurophysiological parameters used for guiding resection. The study aimed to define the most efficient protocol to guide resection for each clinical condition.

RESULTS The data confirmed HF as an efficient tool for guiding resection of M1 tumors, affording 85.3% complete resection and only 2% permanent morbidity. HF was highly versatile, adapting the stimulation paradigm and the probe to the clinical context. Three approaches were used. The first was a “standard approach” (HF “train of 5,” using a monopolar probe) applied in 51 patients with no motor deficit and seizure control, harboring a well-defined tumor, showing contrast enhancement in most cases, and reaching the M1 surface. Complete resection was achieved in 72.5%, and 2% had permanent morbidity. The second approach was an “increased train approach,” that is, an increase in the number of pulses (7–9) and of pulse duration, using a monopolar probe. This second approach was applied in 8 patients with a long clinical history, previous treatment (surgery, radiation therapy, chemotherapy), motor deficit at admission, poor seizure control, and mostly high-grade gliomas or metastases. Complete resection was achieved in 87.5% using this approach, along with 0% permanent morbidity. The final approach was a “reduced train approach,” which was the combined use of train of 2 or train of 1 pulses associated with the standard approach, using a monopolar or bipolar probe. This approach was used in 43 patients with a long clinical history and poorly controlled seizures, harboring tumors with irregular borders without contrast enhancement (low or lower grade), possibly not reaching the cortical surface. Complete resection was attained in 88.4%, and permanent morbidity was found in 2.3%.

CONCLUSIONS Resection of M1 tumors is feasible and safe. By adapting the stimulation paradigm and probe appropriately to the clinical context, the best resection and functional results can be achieved.

Posted on

To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment

J Neurosurg 133:273–280, 2020

The level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low. In so-called “high-risk” patients most centers currently apply an early aggressive adjuvant treatment after surgery. The aim of this assessment was to compare progression-free survival (PFS) and overall survival (OS) in patients receiving radiation therapy (RT) alone, chemotherapy (CT) alone, or a combined/consecutive RT+CT, with patients receiving no primary adjuvant treatment after surgery.

METHODS Based on a retrospective multicenter cohort of 288 patients (≥ 18 years old) with diffuse WHO grade II gliomas, a subgroup analysis of patients with a confirmed isocitrate dehydrogenase (IDH) mutation was performed. The influence of primary adjuvant treatment after surgery on PFS and OS was assessed using Kaplan-Meier estimates and multivariate Cox regression models, including age (≥ 40 years), complete tumor resection (CTR), recurrent surgery, and astrocytoma versus oligodendroglioma.

RESULTS One hundred forty-four patients matched the inclusion criteria. Forty patients (27.8%) received adjuvant treatment. The median follow-up duration was 6 years (95% confidence interval 4.8–6.3 years). The median overall PFS was 3.9 years and OS 16.1 years. PFS and OS were significantly longer without adjuvant treatment (p = 0.003). A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years, p = 0.025). In the multivariate model (controlled for age, CTR, oligodendroglial diagnosis, and recurrent surgery), patients who received no adjuvant therapy showed a significantly positive influence on PFS (p = 0.030) and OS (p = 0.009) compared to any other adjuvant treatment regimen. This effect was most pronounced if RT+CT was applied (p = 0.004, hazard ratio [HR] 2.7 for PFS, and p = 0.001, HR 20.2 for OS). CTR was independently associated with longer PFS (p = 0.019). Age ≥ 40 years, histopathological diagnosis, and recurrence did not achieve statistical significance.

CONCLUSIONS In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.

 

Posted on

Neurosurgical ablative procedures for intractable cancer pain

J Neurosurg 133:144–151, 2020

Cancer patients suffering from severe refractory pain may benefit from targeted ablative neurosurgical procedures aimed to disconnect pain pathways in the spinal cord or the brain. These patients often present with a plethora of medical problems requiring careful consideration before surgical interventions. The authors present their experience at an interdisciplinary clinic aimed to facilitate appropriate patient selection for neurosurgical procedures, and the outcome of these interventions.

METHODS This study was a retrospective review of all patients who underwent neurosurgical interventions for cancer pain in the authors’ hospital between March 2015 and April 2018. All patients had advanced metastatic cancer with limited life expectancy and suffered from intractable oncological pain.

RESULTS Sixty patients underwent surgery during the study period. Forty-three patients with localized pain underwent disconnection of the spinal pain pathways: 34 percutaneous-cervical and 5 open-thoracic cordotomies, 2 stereotactic mesencephalotomies, and 2 midline myelotomies. Thirty-nine of 42 patients (93%) who completed these procedures had excellent immediate postoperative pain relief. At 1 month the improvement was maintained in 30/36 patients (83%) available for follow-up. There was 1 case of hemiparesis. Twenty patients with diffuse pain underwent stereotactic cingulotomy. Nineteen of these patients reported substantial pain relief immediately after the operation. At 1 month good pain relief was maintained in 13/17 patients (76%) available for follow-up, and good pain relief was also found at 3 months in 7/11 patients (64%). There was no major morbidity or mortality.

CONCLUSIONS With careful patient selection and tailoring of the appropriate procedure to the patient’s pain syndrome, the authors’ experience indicates that neurosurgical procedures are safe and effective in alleviating suffering in patients with intractable cancer pain.

Posted on

Clinical features and operative technique of transinfundibular craniopharyngioma

J Neurosurg 133:119–128, 2020

Transinfundibular craniopharyngioma (TC) is one of the 4 subtypes of suprasellar craniopharyngioma. In this study, the authors analyzed the clinical features of and operative technique for TC.

METHODS A total of 95 consecutive cases of suprasellar craniopharyngioma that had been resected via the endoscopic expanded endonasal approach were retrospectively reviewed. Patients were divided into 2 groups: 34 in the TC group and 61 in the nontransinfundibular craniopharyngioma (NC) group. Clinical and radiographic features, intraoperative findings, histopathological and genetic findings, and surgical outcomes were analyzed and compared between groups.

RESULTS Compared with NC, TC was mostly seen in adult patients (97.1%); it was rare in children (2.9%). Clinical presentations tended toward headache, hydrocephalus, and diabetes insipidus. The relatively smaller volume, midline location (consistent with the stalk position), unidentifiable stalk, no shift of the third ventricle, and greater likelihood to involve the third ventricle and cause hydrocephalus were the characteristic features of TC in the preoperative MRI study. According to the degree of vertical extension of the tumor, the 34 TCs could be classified into 3 subtypes: type 1, entity was limited to stalk (n = 2, 5.9%); type 2, tumor extended up to the third ventricle (type 2a) or down to the subdiaphragmatic cavity (type 2b) (n = 23, 67.6%); and type 3, tumor extended in both directions (n = 9, 26.5%). For TC resection, the chiasm–pituitary corridor, lamina terminalis corridor, and pituitary corridor could be used separately or jointly. Most of the TCs originated from the infundibulum–tuber cinereum, grew within and along the long axis of the infundibulum, and the pituitary stalk was not usually preserved in TCs (20.6%), whereas the rate of preservation was higher (80.3%) in NCs. Bilateral hypothalamic injury was found in nearly all TCs if radical resection was performed, whereas the relationship between NCs and hypothalamus was either compression (32.8%) or unilateral invasion (67.2%). Meanwhile, the postoperative endocrine and neuropsychological function outcomes in patients with TC were worse than in patients with NC. The genetic analysis with whole-exome sequencing studies showed no differential mutations of CTNNB1 (b-catenin) and BRAF (V600E) between TC and NC subtypes, but there was a difference between adamantinomatous craniopharyngioma and papillary craniopharyngioma.

CONCLUSIONS TC is a special subtype of suprasellar craniopharyngioma, which is remarkably different from NC. Identification of this type of tumor preoperatively is essential for the planning of appropriate surgical approach and degree of excision.

Posted on

Surgical treatment of meningiomas located in the rolandic area

J Neurosurg 133:107–118, 2020

Surgical treatment of convexity meningiomas is usually considered a low-risk procedure. Nevertheless, the risk of postoperative motor deficits is higher (7.1%–24.7% of all cases) for lesions located in the rolandic region, especially when an arachnoidal cleavage plane with the motor pathway is not identifiable. The authors analyzed the possible role of navigated transcranial magnetic stimulation (nTMS) for planning resection of rolandic meningiomas and predicting the presence or lack of an intraoperative arachnoidal cleavage plane as well as the postoperative motor outcome.

METHODS Clinical data were retrospectively collected from surgical cases involving patients affected by convexity, parasagittal, or falx meningiomas involving the rolandic region, who received preoperative nTMS mapping of the motor cortex (M1) and nTMS-based diffusion tensor imaging (DTI) fiber tracking of the corticospinal tract before surgery at 2 different neurosurgical centers. Surgeons’ self-reported evaluation of the impact of nTMS-based mapping on surgical strategy was analyzed. Moreover, the nTMS mapping accuracy was evaluated in comparison with intraoperative neurophysiological mapping (IONM). Lastly, we assessed the role of nTMS as well as other pre- and intraoperative parameters for predicting the patients’ motor outcome and the presence or absence of an intraoperative arachnoidal cleavage plane.

RESULTS Forty-seven patients were included in this study. The nTMS-based planning was considered useful in 89.3% of cases, and a change of the surgical strategy was observed in 42.5% of cases. The agreement of nTMS-based planning and IONM-based strategy in 35 patients was 94.2%. A new permanent motor deficit occurred in 8.5% of cases (4 of 47). A higher resting motor threshold (RMT) and the lack of an intraoperative arachnoidal cleavage plane were the only independent predictors of a poor motor outcome (p = 0.04 and p = 0.02, respectively). Moreover, a higher RMT and perilesional edema also predicted the lack of an arachnoidal cleavage plane (p = 0.01 and p = 0.03, respectively). Preoperative motor status, T2 cleft sign, contrast-enhancement pattern, and tumor volume had no predictive value.

CONCLUSIONS nTMS-based motor mapping is a useful tool for presurgical assessment of rolandic meningiomas, especially when a clear cleavage plane with M1 is not present. Moreover, the RMT can indicate the presence or absence of an intraoperative cleavage plane and predict the motor outcome, thereby helping to identify high-risk patients before surgery.

 

Posted on

Is supratotal resection achievable in low-grade gliomas? Feasibility, putative factors, safety, and functional outcome

J Neurosurg 132:1692–1705, 2020

Surgery for low-grade gliomas (LGGs) aims to achieve maximal tumor removal and maintenance of patients’ functional integrity. Because extent of resection is one of the factors affecting the natural history of LGGs, surgery could be extended further than total resection toward a supratotal resection, beyond tumor borders detectable on FLAIR imaging. Supratotal resection is highly debated, mainly due to a lack of evidence of its feasibility and safety. The authors explored the intraoperative feasibility of supratotal resection and its short- and long-term impact on functional integrity in a large cohort of patients. The role of some putative factors in the achievement of supratotal resection was also studied.

METHODS Four hundred forty-nine patients with a presumptive radiological diagnosis of LGG consecutively admitted to the neurosurgical oncology service at the University of Milan over a 5-year period were enrolled. In all patients, a policy was adopted to perform surgery according to functional boundaries, aimed at achieving a supratotal resection whenever possible, without any patient or tumor a priori selection. Feasibility, general safety, and tumor or patient putative factors possibly affecting the achievement of a supratotal resection were analyzed. Postsurgical patient functional performance was evaluated in five cognitive domains (memory, language, praxis, executive functions, and fluid intelligence) using a detailed neuropsychological evaluation and quality of life (QOL) examination.

RESULTS Total resection was feasible in 40.8% of patients, and supratotal resection in 32.3%. The achievement of a supratotal versus total resection was independent of age, sex, education, tumor volume, deep extension, location, handedness, appearance of tumor border, vicinity to eloquent sites, surgical mapping time, or surgical tools applied. Supratotal resection was associated with a long clinical history and histological grade II, suggesting that reshaping of brain networks occurred. Although a consistent amount of apparently MRI-normal brain was removed with this approach, the procedure was safe and did not carry additional risk to the patient, as demonstrated by detailed neuropsychological evaluation and QOL examination. This approach also improved seizure control.

CONCLUSIONS Supratotal resection is feasible and safe in routine clinical practice. These results show that a long clinical history may be the main factor associated with its achievement.

Posted on

Petroclival meningiomas: long-term outcomes of multimodal treatments and management strategies based on 30 years of experience at a single institution

J Neurosurg 132:1675–1682, 2020

A thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution.

METHODS Ninety-two patients with petroclival meningiomas were treated surgically at the authors’ institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1–368 months) and 105 months (range 1–348 months), respectively.

RESULTS A posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively.

CONCLUSIONS The authors’ preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.

 

Posted on

Characterizing tumor invasiveness of glioblastoma using multiparametric magnetic resonance imaging

J Neurosurg 132:1465–1472, 2020

The objective of this study was to characterize the abnormalities revealed by diffusion tensor imaging (DTI) using MR spectroscopy (MRS) and perfusion imaging, and to evaluate the prognostic value of a proposed quantitative measure of tumor invasiveness by combining contrast-enhancing (CE) and DTI abnormalities in patients with glioblastoma.

METHODS Eighty-four patients with glioblastoma were recruited preoperatively. DTI was decomposed into isotropic (p) and anisotropic (q) components. The relative cerebral blood volume (rCBV) was calculated from the dynamic susceptibility contrast imaging. Values of N-acetylaspartate, myoinositol, choline (Cho), lactate (Lac), and glutamate + glutamine (Glx) were measured from multivoxel MRS and normalized as ratios to creatine (Cr). Tumor regions of interest (ROIs) were manually segmented from the CE T1-weighted (CE-ROI) and DTI-q (q-ROI) maps. Perfusion and metabolic characteristics of these ROIs were measured and compared. The relative invasiveness coefficient (RIC) was calculated as a ratio of the characteristic radii of CE-ROI and q-ROI. The prognostic significance of RIC was tested using Kaplan-Meier and multivariate Cox regression analyses.

RESULTS The Cho/Cr, Lac/Cr, and Glx/Cr in q-ROI were significantly higher than CE-ROI (p = 0.004, p = 0.005, and p = 0.007, respectively). CE-ROI had significantly higher rCBV values than q-ROI (p < 0.001). A higher RIC was associated with worse survival in a multivariate overall survival (OS) model (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.06–1.85, p = 0.016) and progression-free survival (PFS) model (HR 1.55, 95% CI 1.16–2.07, p = 0.003). An RIC cutoff value of 0.89 significantly predicted shorter OS (median 384 vs 605 days, p = 0.002) and PFS (median 244 vs 406 days, p = 0.001).

CONCLUSIONS DTI-q abnormalities displayed higher tumor load and hypoxic signatures compared with CE abnormalities, whereas CE regions potentially represented the tumor proliferation edge. Integrating the extents of invasion visualized by DTI-q and CE images into clinical practice may lead to improved treatment efficacy.

Posted on

Awake craniotomy with transcortical motor evoked potential monitoring for resection of gliomas in the precentral gyrus

J Neurosurg 132:987–997, 2020

Resection of gliomas in the precentral gyrus carries a risk of severe motor dysfunction. To prevent permanent, severe postoperative motor dysfunction, reliable intraoperative predictors of postoperative function are required. Since 2005, the authors have removed gliomas in the precentral gyrus with combined functional mapping and estimation of intraoperative voluntary movement (IVM) during awake craniotomy and transcortical motor evoked potentials (MEPs). The purpose of the current study was to evaluate whether intraoperative findings of combined monitoring of IVM during awake craniotomy and transcortical MEP monitoring were useful for predicting postoperative motor function of patients with gliomas in the precentral gyrus.

METHODS The current study included 30 patients who underwent resection of precentral gyrus gliomas during awake craniotomy from April 2000 to January 2018. All tumors were removed with monitoring of IVM during awake craniotomy and transcortical MEPs. Postoperative motor function was classified as stable or declined, with the extent of decline categorized as mild, moderate, or severe. We defined moderate and severe deficits were those that hindered daily life.

RESULTS In 28 of 30 cases, available waveforms were obtained with transcortical MEPs. The mean extent of resection (EOR) was 93%. Relative to preoperative status, motor function 6 months after surgery was considered stable in 20 patients and was considered to show mild decline in 7, moderate decline in 2, and severe decline in 1. Motor function 6 months after surgery was significantly correlated with IVM (p = 0.0096), changes in transcortical MEPs (decline ≤ or > 50%) (p = 0.0163), EOR, and ischemic lesions on postoperative MRI. Six patients with no change in IVM showed stable motor function 6 months after surgery. Only 2 patients with a decline in IVM and a decline in MEPs ≤ 50% had a decline in motor function 6 months after surgery (18%; 2/11 patients), whereas 11 patients with a decline in IVM and a decline in MEPs > 50% had such a decline in motor function (73%; 8/11 patients) including 2 patients with moderate and 1 with severe deficits. Three patients with moderate or severe motor deficits showed the lowest MEP values (< 100 μV).

CONCLUSIONS Combined judgment from monitoring of IVM during awake craniotomy and transcortical MEPs is useful for predicting postoperative motor function during removal of gliomas in the precentral gyrus. Maximum resection was achieved with an acceptable morbidity rate. Thus, these tumors should not be considered unresectable.

Posted on

The endoscopic transpterional port approach: anatomy, technique, and initial clinical experience

J Neurosurg 132:884–894, 2020

The evolution of microsurgical and endoscopic techniques has allowed the development of less invasive transcranial approaches. The authors describe a purely endoscopic transpterional port craniotomy to access lesions involving the cavernous sinus and the anterolateral skull base.

METHODS Through single- or dual-port incisions and with direct endoscopic visualization, the authors performed an endoscopic transpterional port approach (ETPA) using a 4-mm straight endoscope in 8 sides of 4 formalin-fixed cadaveric heads injected with colored latex. A main working port incision is made just below the superior temporal line and behind the hairline. An optional 0.5- to 1-cm second skin port incision is made on the lateral supraorbital region, allowing multiangle endoscopic visualization and maneuverability. A 1.5- to 2-cm craniotomy centered over the pterion is done through the main port, which allows an extradural exposure of the cavernous sinus region and extra/intradural exposure of the frontal and temporal cranial fossae. The authors present a pilot surgical series of 17 ETPA procedures and analyze the surgical indications and clinical outcomes retrospectively.

RESULTS The initial stage of this work on cadavers provided familiarity with the technique, standardized its steps, and showed its anatomical limits. The clinical ETPA was applied to gain access into the cavernous sinus, as well as for aneurysm clipping and meningioma resection. Overall, perioperative complications occurred in 1 patient (6%), there was no mortality, and at last follow-up all patients had a modified Rankin Scale score of 0 or 1.

CONCLUSIONS The ETPA provides a less invasive, focused, and direct route to the cavernous sinus, and to the frontal and temporal cranial fossae, and it is feasible in clinical practice for selected indications with good results.

Posted on

Intraoperative 3D ultrasound–guided resection of diffuse low-grade gliomas

J Neurosurg 132:518–529, 2020

Extent of resection (EOR) and residual tumor volume are linked to prognosis in low-grade glioma (LGG) and there are various methods for facilitating safe maximal resection in such patients. In this prospective study the authors assess radiological and clinical results in consecutive patients with LGG treated with 3D ultrasound (US)–guided resection under general anesthesia.

METHODS Consecutive LGGs undergoing primary surgery guided with 3D US between 2008 and 2015 were included. All LGGs were classified according to the WHO 2016 classification system. Pre- and postoperative volumetric assessments were performed, and volumetric results were linked to overall and malignant-free survival. Pre- and postoperative health-related quality of life (HRQoL) was evaluated.

RESULTS Forty-seven consecutive patients were included. Twenty LGGs (43%) were isocitrate dehydrogenase (IDH)– mutated, 7 (14%) were IDH wild-type, 19 (40%) had both IDH mutation and 1p/19q codeletion, and 1 had IDH mutation and inconclusive 1p/19q status. Median resection grade was 93.4%, with gross-total resection achieved in 14 patients (30%). An additional 24 patients (51%) had small tumor remnants < 10 ml. A more conspicuous tumor border (p = 0.02) and lower University of California San Francisco prognostic score (p = 0.01) were associated with less remnant tumor tissue, and overall survival was significantly better with remnants < 10 ml (p = 0.03). HRQoL was maintained or improved in 86% of patients at 1 month. In both cases with severe permanent deficits, relevant ischemia was present on diffusionweighted postoperative MRI.

CONCLUSIONS Three-dimensional US–guided LGG resections under general anesthesia are safe and HRQoL is preserved in most patients. Effectiveness in terms of EOR appears to be consistent with published studies using other advanced neurosurgical tools. Avoiding intraoperative vascular injury is a key factor for achieving good functional outcome.

Posted on

Long-term outcomes of high-dose single-fraction radiosurgery for chordomas of the spine and sacrum

J Neurosurg Spine 32:79–88, 2020

The current treatment of chordomas is associated with significant morbidity, high rates of local recurrence, and the potential for metastases. Stereotactic radiosurgery (SRS) as a primary treatment could reduce the need for en bloc resection to achieve wide or marginal margins. Spinal SRS outcomes support the exploration of SRS’s role in the durable control of these conventionally radioresistant tumors. The goal of the study was to evaluate outcomes of patients with primary chordomas treated with spinal SRS alone or in combination with surgery.

METHODS Clinical records were reviewed for outcomes of patients with primary chordomas of the mobile spine and sacrum who underwent single-fraction SRS between 2006 and 2017. Radiographic local recurrence-free survival (LRFS), overall survival (OS), symptom response, and toxicity were assessed in relation to the extent of surgery.

RESULTS In total, 35 patients with de novo chordomas of the mobile spine (n = 17) and sacrum (n = 18) received SRS and had a median post-SRS follow-up duration of 38.8 months (range 2.0–122.9 months). The median planning target volume dose was a 24-Gy single fraction (range 18–24 Gy). Overall, 12 patients (34%) underwent definitive SRS and 23 patients (66%) underwent surgery and either neoadjuvant or postoperative adjuvant SRS. Definitive SRS was selectively used to treat both sacral (n = 7) and mobile spine (n = 5) chordomas. Surgical strategies for the mobile spine were either intralesional, gross-total resection (n = 5) or separation surgery (n = 7) and for the sacrum en bloc sacrectomy (n = 11). The 3- and 5-year LRFS rates were 86.2% and 80.5%, respectively. Among 32 patients (91%) receiving 24-Gy radiation doses, the 3- and 5-year LRFS rates were 96.3% and 89.9%, respectively. The 3- and 5-year OS rates were 90.0% and 84.3%, respectively. The symptom response rate to treatment was 88% for pain and radiculopathy. The extent or type of surgery was not associated with LRFS, OS, or symptom response rates (p > 0.05), but en bloc resection was associated with higher surgical toxicity, as measured using the Common Terminology Criteria for Adverse Events (version 5.0) classification tool, than epidural decompression and curettage/intralesional resection (p = 0.03). The long-term rate of toxicity ≥ grade 2 was 31%, including 20% grade 3 tissue necrosis, recurrent laryngeal nerve palsy, myelopathy, fracture, and secondary malignancy.

CONCLUSIONS High-dose spinal SRS offers the chance for durable radiological control and effective symptom relief with acceptable toxicity in patients with primary chordomas as either a definitive or adjuvant therapy.

 

 

Posted on

A novel robot-guided minimally invasive technique for brain tumor biopsies

J Neurosurg 132:150–158, 2020

As decisions regarding tumor diagnosis and subsequent treatment are increasingly based on molecular pathology, the frequency of brain biopsies is increasing. Robotic devices overcome limitations of frame-based and frameless techniques in terms of accuracy and usability. The aim of the present study was to present a novel, minimally invasive, robot-guided biopsy technique and compare the results with those of standard burr hole biopsy.

METHODS A tubular minimally invasive instrument set was custom-designed for the iSYS-1 robot-guided biopsies. Feasibility, accuracy, duration, and outcome were compared in a consecutive series of 66 cases of robot-guided stereotactic biopsies between the minimally invasive (32 patients) and standard (34 patients) procedures.

RESULTS Application of the minimally invasive instrument set was feasible in all patients. Compared with the standard burr hole technique, accuracy was significantly higher both at entry (median 1.5 mm [range 0.2–3.2 mm] vs 1.7 mm [range 0.8–5.1 mm], p = 0.008) and at target (median 1.5 mm [range 0.4–3.4 mm] vs 2.0 mm [range 0.8–3.9 mm], p = 0.019). The incision-to-suture time was significantly shorter (median 30 minutes [range 15–50 minutes] vs 37.5 minutes [range 25–105 minutes], p < 0.001). The skin incision was significantly shorter (median 16.3 mm [range 12.7–23.4 mm] vs 28.4 mm [range 20–42.2 mm], p = 0.002). A diagnostic tissue sample was obtained in all cases.

CONCLUSIONS Application of the novel instrument set was feasible in all patients. According to the authors’ data, the minimally invasive robot-guidance procedure can significantly improve accuracy, reduce operating time, and improve the cosmetic result of stereotactic biopsies.

Proudly powered by WordPress