Resection of primary central nervous system lymphoma: impact of patient selection on overall survival.

OBJECTIVE: Primary central nervous system lymphoma (PCNSL) is a rare CNS tumor with a poor prognosis. It is usually diagnosed by needle biopsy and treated mainly with high-dose chemotherapy. Resection is currently not considered a standard treatment option. A possible prolonged survival after resection of PCNSL lesions in selected patients has been suggested, but selection criteria for surgery, especially for solitary lesions, have never been established. METHODS: The authors retrospectively searched their patient database for records of adult patients (≥ 18 years) who were diagnosed and treated for a solitary PCNSL between 2005 and 2019. Patients were divided into groups according to whether they underwent resection or needle biopsy. Statistical analyses were performed in an attempt to identify variables affecting outcome and possible survival advantage and to characterize subgroups of patients who would benefit from resection of their tumor compared with undergoing biopsy only. RESULTS: A total of 113 patients with a solitary lesion of PCNSL were identified; 36 patients underwent resection, and 77 had a diagnostic stereotactic biopsy only. The statically significant preoperative risk factors included age ≥ 70 years (adjusted HR 9.61, 95% CI 2.42-38.11; p = 0.001), deep-seated lesions (adjusted HR 3.33, 95% CI 1.13-9.84; p = 0.030), and occipital location (adjusted HR 4.26, 95% CI 1.08-16.78; p = 0.039). Having a postoperative Karnofsky Performance Scale (KPS) score < 80 (adjusted HR 3.21, 95% CI 1.05-9.77; p = 0.040) and surgical site infection (adjusted HR 4.27, 95% CI 1.18-15.47; p = 0.027) were significant postoperative risk factors after the adjustment and selection by means of other possible risk factors. In a subgroup analysis, patients younger than 70 years who underwent resection had a nonsignificant trend toward longer survival than those who underwent needle biopsy (median survival 35.0 months vs 15.2 months, p = 0.149). However, patients with a superficial tumor who underwent resection had significantly longer survival times than those who underwent needle biopsy (median survival 34.3 months vs 8.9 months, p = 0.014). Patients younger than 70 years who had a superficial tumor and underwent resection had significantly prolonged survival, with a median survival of 35.0 months compared with 8.9 months in patients from the same group who underwent needle biopsy (p = 0.007). CONCLUSIONS: Specific subgroups of patients with a solitary PCNSL lesion might gain a survival benefit from resection compared with undergoing only a diagnostic biopsy.

Improvement in cognitive function after surgery for low-grade glioma.

OBJECTIVECognition is a key component in health-related quality of life (HRQoL) and is currently incorporated as a major parameter of outcome assessment in patients treated for brain tumors. The effect of surgery on cognition and HRQoL remains debatable. The authors investigated the impact of resection of low-grade gliomas (LGGs) on cognition and the correlation with various histopathological markers.METHODSA retrospective analysis of patients with LGG who underwent craniotomy for tumor resection at a single institution between 2010 and 2014 was conducted. Of 192 who underwent resective surgery for LGG during this period, 49 had complete pre- and postoperative neurocognitive evaluations and were included in the analysis. These patients completed a full battery of neurocognitive tests (memory, language, attention and working memory, visuomotor organization, and executive functions) pre- and postoperatively. Tumor and surgical characteristics were analyzed, including volumetric measurements and histopathological markers (IDH, p53, GFAP).RESULTSPostoperatively, significant improvement was found in memory and executive functions. A subgroup analysis of patients with dominant-side tumors, most of whom underwent intraoperative awake mapping, revealed significant improvement in the same domains. Patients whose tumors were on the nondominant side displayed significant improvement only in memory functions. Positive staining for p53 testing was associated with improved language function and greater extent of resection in dominant-side tumors. GFAP positivity was associated with improved memory in patients whose tumors were on the nondominant side. No correlation was found between cognitive outcome and preoperative tumor volume, residual volume, extent of resection, or IDH1 status.CONCLUSIONSResection of LGG significantly improves memory and executive function and thus is likely to improve functional outcome in addition to providing oncological benefit. GFAP and pP53 positivity could possibly be associated with improved cognitive outcome. These data support early, aggressive, surgical treatment of LGG.

Surgical Resection of Cerebral Metastases Leads to Faster Resolution of Peritumoral Edema than Stereotactic Radiosurgery: A Volumetric Analysis.

BACKGROUND: Surgical resection and stereotactic radiosurgery (SRS) are well-established treatment options for selected patients with oligo-brain metastases (BMs). The dynamics of edema resolution with each treatment method have not been well characterized. METHODS: Of 389 patients treated for BMs between 2012 and 2014, this study retrospectively identified 107 patients (150 metastases) who underwent either surgery or SRS as a single treatment method for BMs. The two groups of patients were matched for clinical parameters. Volumetric assessments of the tumor and associated edema were performed before treatment and then 2-3 months after treatment. RESULTS: In this study, 76 surgical cases were compared with 74 cases treated with SRS. The volume of the tumor and surrounding edema was significantly greater in the surgery group than in the SRS group. However, resolution of edema was significantly more rapid in the surgical group (p < 0.0001), accompanied by faster weaning from steroids. After a matching process based on the propensity of a patient to receive SRS, a subgroup cohort was analyzed (mean maximal diameter: 21 mm in the surgical group vs 20.8 mm in the SRS group; p = 0.9). At diagnosis, edema volume, but not tumor volume, was significantly greater in the surgical group. The resolution of edema 2-3 months after treatment was better in the surgical group than in the SRS group (89.6% vs 71.1% of baseline, respectively; p = 0.09), although this difference did not reach the level of significance. CONCLUSIONS: Resolution of tumor-associated edema in BMs suitable for either surgery or SRS was significantly faster after surgical resection than after SRS. Accordingly, when both treatment options are suitable, surgery appears to induce faster resolution of the edema.

Dynamics of FLAIR Volume Changes in Glioblastoma and Prediction of Survival.

BACKGROUND: The extent of tumor resection (EOTR) calculated by enhanced T1 changes in glioblastomas has been previously reported to predict survival. However, fluid-attenuated inversion recovery (FLAIR) volume may better represent tumor burden. In this study, we report the first assessment of the dynamics of FLAIR volume changes over time as a predictive variable for post-resection overall survival (OS). METHODS: Contemporary data from 103 consecutive patients with complete imaging and clinical data who underwent resection of newly diagnosed glioblastoma followed by the Stupp protocol between 2010 and 2013 were analyzed. Clinical, radiographic, and outcome parameters were retrieved for each patient, including magnetic resonance imaging (MRI)-based volumetric tumor analysis before, immediately after, and 3 months post-surgery. RESULTS: OS rate was 17.6 months. A significant incremental OS advantage was noted, with as little as 85 % T1-weighted gadolinium-enhanced (T1Gd)-EOTR measured on contrast-enhanced MRI. Pre- and immediate postoperative FLAIR-based EOTR was not predictive of OS; however, abnormal FLAIR volume measured 3 months post-surgery correlated significantly with outcome when FLAIR residual tumor volume (RTV) was <19.3 cm3 and <46 % of baseline volume (p < 0.0001 for both). Age and isocitrate dehydrogenase (IDH)-1 mutation were predictive of OS (p < 0.0001, Cox proportional hazards). CONCLUSIONS: OS correlated with the immediate postoperative T1Gd-EOTR measured by enhanced T1 MRI, but not by FLAIR volume. Diminished abnormal FLAIR volume at 3 months post-surgery was associated with OS benefit when FLAIR-RTV was <19.3 cm3 or <46 % of baseline. These threshold values provide a new radiological variable that can be used for prediction of OS in patients with glioblastoma immediately after completion of standard chemoradiation.

Craniectomy Versus Craniotomy for Posterior Fossa Metastases: Complication Profile.

OBJECTIVE: Surgical resection of posterior fossa metastases (PFM) includes either suboccipital craniotomy or suboccipital craniectomy. The optimal surgical technique is yet to be defined. We examined the association between the chosen surgical approach and the occurrence of postoperative complications. METHODS: We retrospectively evaluated medical records and imaging characteristics of patients who underwent resection of newly diagnosed PFM between 2003 and 2014 in our medical center to identify covariates that significantly affected postoperative complications. RESULTS: Of 917 patients with brain metastases, 88 patients underwent surgery for PFM and were included in the study. Craniectomy was performed in 54 cases (61%). Urgent postoperative posterior fossa decompression or cerebrospinal fluid diversion was performed in 4 patients (4.5%). Postoperative complications included postoperative central nervous system infection (n = 10 [12%]), cerebrospinal fluid leak (n = 3 [4%]), wound dehiscence (n = 6 [7%]), and long-term pseudomeningocele (n = 12 [14%]). The perioperative mortality rate was 2.3% (n = 2). Multivariate analysis that included patient baseline characteristics, imaging study parameters, and surgical approaches demonstrated that suboccipital craniectomy was associated with more postoperative complications (P = 0.03, odds ratio = 4.48, 95% confidence interval = 1.14-17.6). There was no correlation between patient baseline characteristics or surgical technique with the need for urgent postoperative posterior fossa decompression or cerebrospinal fluid diversion. CONCLUSIONS: Suboccipital craniotomy may be associated with a lower incidence of postoperative morbidity compared with suboccipital craniectomy and should be considered as the preferred approach for the resection of PFM.

Impact of Resecting Radiation Necrosis and Pseudoprogression on Survival of Patients with Glioblastoma.

INTRODUCTION: Radiation necrosis (RN) and pseudoprogression are known as postradiation treatment effects and may simulate tumor progression. The disease course of glioblastoma patients who had developed RN and the impact of resecting RN on survival have not been evaluated. This study examines the clinical course of patients considered candidates for repeat surgery for a recurring brain mass proven to be RN and compared these with patients who had true tumor recurrence at surgery. METHODS: Of 159 patients with glioblastoma who were reoperated on because of a presumed recurrent tumor requiring repeat surgery, 18 had RN as the major component of the resected mass. The characteristics and outcome of these 18 patients were retrospectively analyzed and compared with patients in whom active and bulky tumor was found during surgery. RESULTS: Radiation necrosis occurred significantly earlier than true tumor recurrence. Patients with RN harbored larger lesions and were significantly more symptomatic before the second surgery. Most patients with RN who underwent GTR of the lesion in the second operation experienced faster resolution of the surrounding edema compared with patients who underwent STR or biopsy only. There was no significant difference in survival between the 2 groups. CONCLUSIONS: These data provide an opportunity to examine the clinical course of a selected group of patients with histologically verified RN. Although RN is associated with more severe neurologic symptoms that improve after surgery, its occurrence or surgical removal carries no survival advantage compared with patients who undergo a repeat operation for true tumor recurrence.

Tumor location and IDH1 mutation may predict intraoperative seizures during awake craniotomy.

OBJECT: Intraoperative seizures during awake craniotomy may interfere with patients' ability to cooperate throughout the procedure, and it may affect their outcome. The authors have assessed the occurrence of intraoperative seizures during awake craniotomy in regard to tumor location and the isocitrate dehydrogenase 1 (IDH1) status of the tumor. METHODS: Data were collected in 137 consecutive patients who underwent awake craniotomy for removal of a brain tumor. The authors performed a retrospective analysis of the incidence of seizures based on the tumor location and its IDH1 mutation status, and then compared the groups for clinical variables and surgical outcome parameters. RESULTS: Tumor location was strongly associated with the occurrence of intraoperative seizures. Eleven patients (73%) with tumor located in the supplementary motor area (SMA) experienced intraoperative seizures, compared with 17 (13.9%) with tumors in the other three non-SMA brain regions (p < 0.0001). Interestingly, there was no significant association between history of seizures and tumor location (p = 0.44). Most of the patients (63.6%) with tumor in the SMA region harbored an IDH1 mutation compared with those who had tumors in non-SMA regions. Thirty-one of 52 patients (60%) with a preoperative history of seizures had an IDH1 mutation (p = 0.02), and 15 of 22 patients (68.2%) who experienced intraoperative seizures had an IDH1 mutation (p = 0.03). In a multivariate analysis, tumor location was found as a significant predictor of intraoperative seizures (p = 0.002), and a trend toward IDH1 mutation as such a predictor was found as well (p = 0.06). Intraoperative seizures were not associated with worse outcome. CONCLUSIONS: Patients with tumors located in the SMA are more prone to develop intraoperative seizures during awake craniotomy compared with patients who have a tumor in non-SMA frontal areas and other brain regions. The IDH1 mutation was more common in SMA region tumors compared with other brain regions, and may be an additional risk factor for the occurrence of intraoperative seizures.

Gliomas of the posterior fossa in adults.

Infratentorial gliomas are relatively rare tumors compared to their supratentorial counterparts. As such they have not been extensively characterized as a group and are usually excluded from clinical studies. Using our database we aimed to characterize adult gliomas involving the posterior fossa with respect to their clinical behavior and prognostic factors. We reviewed our neurosurgical and neuro-oncological data bases for adult patients diagnosed with gliomas involving the posterior fossa between 1996 and 2010. Of 1,283 glioma patients, 57 patients with gliomas involving the posterior fossa were identified (4.4 %). Tumors were further classified by location as primary brainstem (n = 21) and primary cerebellar (n = 18) tumors. On univariate analysis survival was correlated to tumor grade and KPS. In addition we have identified a unique group of patients (n = 18) with previously diagnosed supratentorial gliomas who subsequently developed noncontiguous secondary infratentorial extension of their tumors with subsequent rapid clinical deterioration. Gliomas of the posterior fossa comprise a heterogeneous group of tumors. Histological grade of the tumor was found to be the main prognostic factor. Survival of primary cerebellar gliomas is comparable to supra-tentorial gliomas, while brainstem gliomas in adults fare better than in the pediatric population. Secondary extension of supratentorial gliomas to the posterior fossa signifies a grave prognosis.

Outcome of elderly patients undergoing awake-craniotomy for tumor resection.

BACKGROUND: Awake-craniotomy allows maximal tumor resection, which has been associated with extended survival. The feasibility and safety of awake-craniotomy and the effect of extent of resection on survival in the elderly population has not been established. The aim of this study was to compare surgical outcome of elderly patients undergoing awake-craniotomy to that of younger patients. METHODS: Outcomes of consecutive patients younger and older than 65 years who underwent awake-craniotomy at a single institution between 2003 and 2010 were retrospectively reviewed. The groups were compared for clinical variables and surgical outcome parameters, as well as overall survival. RESULTS: A total of 334 young (45.4 ± 13.2 years, mean ± SD) and 90 elderly (71.7 ± 5.1 years) patients were studied. Distribution of gender, mannitol treatment, hemodynamic stability, and extent of tumor resection were similar. Significantly more younger patients had a better preoperative Karnofsky Performance Scale score (>70) than elderly patients (P = 0.0012). Older patients harbored significantly more high-grade gliomas (HGG) and brain metastases, and fewer low-grade gliomas (P < 0.0001). No significantly higher rate of mortality, or complications were observed in the elderly group. Age was associated with increased length of stay (4.9 ± 6.3 vs. 6.6 ± 7.5 days, P = 0.01). Maximal extent of tumor resection in patients with HGG was associated with prolonged survival in the elderly patients. CONCLUSIONS: Awake-craniotomy is a well-tolerated and safe procedure, even in elderly patients. Gross total tumor resection in elderly patients with HGG was associated with prolonged survival. The data suggest that favorable prognostic factors for patients with malignant brain tumors are also valid in elderly patients.

The impact of enrollment in clinical trials on survival of patients with glioblastoma.

The impact of enrollment in a clinical study on the survival of patients with glioblastoma has not been established. We retrospectively analyzed 564 patients with newly diagnosed glioblastoma treated between 1995 and 2008. They were divided into those enrolled in a clinical trial and randomized to a treatment or control arm, and those not enrolled and who received best standard of care (BSC). The three groups were matched for age and Karnofsky performance scale (KPS) score at presentation, and included only patients who underwent at least one tumor resection. Survival analysis was performed and multivariate Cox proportional hazards model and recursive partitioning analysis (RPA) identified predictors of survival. Following the matching process, 261 patients remained to form the final cohort. Of the 124 patients enrolled in a study, 81 (31.0%) were randomized to the treatment and 43 (16.5%) to the control arms. The overall median survival for the BSC (n=137), control, and treatment groups was 11.57 months (95% confidence interval [CI], 10.41-12.73), 16.27 months (95% CI, 14.10-18.43) and 16.10 months (95% CI, 14.34-17.86), respectively (p=0.002). Participation in a clinical trial, regardless of the arm, was a significant predictor of survival, as were age and KPS at diagnosis. The RPA also demonstrated a favorable impact of participation in a clinical trial. Additional tumor resections and various treatment modalities were administered with significantly higher frequency among patients enrolled in clinical studies. Thus, enrollment in a clinical study carried a significant survival advantage for patients with glioblastoma, raising practical and ethical issues regarding the quality of care of patients who receive "standard" therapy.