Publications by authors named "Gene H Barnett"

224 Publications

Adjuvant radiation versus observation with salvage radiation after gross-total resection of WHO grade II meningiomas: a propensity score-adjusted analysis.

J Neurosurg 2021 Oct 8:1-8. Epub 2021 Oct 8.

1Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland.

Objective: After gross-total resection (GTR) of a newly diagnosed WHO grade II meningioma, the decision to treat with radiation upfront or at initial recurrence remains controversial. A comparison of progression-free survival (PFS) between observation and adjuvant radiation fails to account for the potential success of salvage radiation, and a direct comparison of PFS between adjuvant and salvage radiation is hampered by strong selection bias against salvage radiation cohorts in which only more aggressive, recurrent tumors are included. To account for the limitations of traditional PFS measures, the authors evaluated radiation failure-free survival (RFFS) between two treatment strategies after GTR: adjuvant radiation versus observation with salvage radiation, if necessary.

Methods: The authors performed a retrospective review of patients who underwent GTR of newly diagnosed WHO grade II meningiomas at their institution between 1996 and 2019. They assessed traditional PFS in patients who underwent adjuvant radiation, postoperative observation, and salvage radiation. For RFFS, treatment failure was defined as time from initial surgery to failure of first radiation. To assess the association between treatment strategy and RFFS while accounting for potential confounders, a multivariable Cox regression analysis adjusted for the propensity score (PS) and inverse probability of treatment weighted (IPTW) Cox regression analysis were performed.

Results: A total of 160 patients underwent GTR and were included in this study. Of the 121 patients who underwent observation, 32 (26.4%) developed recurrence and required salvage radiation. PFS at 3, 5, and 10 years after observation was 75.1%, 65.6%, and 45.5%, respectively. PFS at 3 and 5 years after salvage radiation was 81.7% and 61.3%, respectively. Of 160 patients, 39 received adjuvant radiation, and 3- and 5-year PFS/RFFS rates were 86.1% and 59.2%, respectively. In patients who underwent observation with salvage radiation, if necessary, the 3-, 5-, and 10-year RFFS rates were 97.7%, 90.3%, and 87.9%, respectively. Both PS and IPTW Cox regression models demonstrated that patients who underwent observation with salvage radiation treatment, if necessary, had significantly longer RFFS (PS model: hazard ratio [HR] 0.21, p < 0.01; IPTW model: HR 0.21, p < 0.01).

Conclusions: In this retrospective, nonrandomized study, adjuvant radiation after GTR of a WHO II meningioma did not add significant benefit over a strategy of observation and salvage radiation at initial recurrence, if necessary, but results must be considered in the context of the limitations of the study design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.4.JNS21559DOI Listing
October 2021

Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases.

Sci Rep 2021 Sep 13;11(1):18174. Epub 2021 Sep 13.

Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.

Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p < 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-97566-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438061PMC
September 2021

Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases.

Sci Rep 2021 04 5;11(1):7490. Epub 2021 Apr 5.

Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.

Steroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient's NLR. In a subgroup analysis, only in patients with NLR < 4 was there a significant difference in OS with upfront steroids (26.1 vs. 15.6 months, p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85328-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021556PMC
April 2021

Outcomes of salvage radiation for recurrent world health organization grade II meningiomas: a retrospective cohort study.

J Neurooncol 2021 Apr 15;152(2):373-382. Epub 2021 Feb 15.

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.

Purpose: The optimal modality of radiation-intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS)-in patients with recurrent WHO grade II meningiomas is not well-established. The purpose of this study was to compare progression-free survival (PFS) in patients undergoing salvage IMRT vs SRS. We compared PFS in those with and without history of prior radiation.

Methods: Forty-two patients with 71 tumor recurrences treated with IMRT or SRS were retrospectively reviewed. Thirty-two salvage treatments were performed on recurrent tumors never treated with prior radiation ('radiation-naïve' cohort), whereas 39 salvage treatments were performed on recurrent tumors previously treated with radiation ('re-treatment cohort').

Results: In the 'radiation-naïve' cohort, 3-year PFS for IMRT and SRS was 68.8% and 60.7%, respectively (p = 0.61). The median tumor volume for patients treated with IMRT was significantly larger than for patients treated with SRS (5.7 vs 2.2 cm; p = 0.04). The 3-year PFS for salvage IMRT or SRS in the 're-treatment' cohort was 45.4% vs 65.8% in the 'radiation-naïve' cohort (p = 0.008). When analyzing the outcome of multiple re-treatments, median PFS was 47 months for 1 or 2nd salvage radiation (IMRT or SRS) compared to 16 months for the 3rd or greater salvage radiation treatment (p = 0.003).

Conclusion: For salvage radiation of recurrent grade II tumors that are 'radiation-naïve', comparable 3-year PFS rates were found between IMRT and SRS, despite the IMRT group having significantly larger tumors. Salvage radiation overall was less successful in the 're-treatment' cohort compared with the 'radiation-naïve' cohort. Additionally, the effectiveness of radiation significantly declines with successive salvage radiation treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-021-03711-zDOI Listing
April 2021

Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome.

Clin Cancer Res 2021 Apr 4;27(7):2038-2049. Epub 2021 Feb 4.

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: Glioblastoma (GBM) immunotherapy clinical trials are generally initiated after standard-of-care treatment-including surgical resection, perioperative high-dose steroid therapy, chemotherapy, and radiation treatment-has either begun or failed. However, the impact of these interventions on the antitumoral immune response is not well studied. While discoveries regarding the impact of chemotherapy and radiation on immune response have been made and translated into clinical trial design, the impact of surgical resection and steroids on the antitumor immune response has yet to be determined.

Experimental Design: We developed a murine model integrating tumor resection and steroid treatment and used flow cytometry to analyze systemic and local immune changes. These mouse model findings were validated in a cohort of 95 patients with primary GBM.

Results: Using our murine resection model, we observed a systemic reduction in lymphocytes corresponding to increased tumor volume and decreased circulating lymphocytes that was masked by dexamethasone treatment. The reduction in circulating T cells was due to reduced CCR7 expression, resulting in T-cell sequestration in lymphoid organs and the bone marrow. We confirmed these findings in a cohort of patients with primary GBM and found that prior to steroid treatment, circulating lymphocytes inversely correlated with tumor volume. Finally, we demonstrated that peripheral lymphocyte content varies with progression-free survival and overall survival, independent of tumor volume, steroid use, or molecular profiles.

Conclusions: These data reveal that prior to intervention, increased tumor volume corresponds with reduced systemic immune function and that peripheral lymphocyte counts are prognostic when steroid treatment is taken into account.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-3262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026586PMC
April 2021

Clear cell histology portends a worse prognosis than other WHO grade II histologies.

J Neurooncol 2021 Jan 4;151(2):307-312. Epub 2021 Jan 4.

Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.

Purpose: Clear cell meningioma (CCM) is a rare WHO grade II meningioma variant, characterized by aggressive features and a high tumor recurrence rate. In this study, we compared overall and progression-free survivals between CCMs and other WHO grade II meningiomas.

Methods: A retrospective institutional database review was performed to identify all patients who underwent surgical resection of a WHO grade II meningioma between 1997 and 2019. Overall survival and progression-free survival were compared between patients with clear cell meningiomas and patients with other WHO grade II meningiomas. Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and survival.

Results: We included a total of 214 patients in this study (43 CCMs, 171 other WHO grade II meningiomas). Patients with CCMs had significantly shorter progression-free (p = 0.001) and overall (p = 0.026) survivals than patients with other grade II meningiomas. In multivariable analysis, clear cell histology was a significant and powerful independent predictor of tumor recurrence (HR 1.93; 95% CI 1.14-3.26) when controlling for tumor location, extent of resection, and adjuvant radiation. In multivariable analysis, clear cell histology correlated with increased mortality (HR 1.96, 95% CI 0.97-3.94), though this was not statistically significant.

Conclusion: This is the first study to compare overall and progression-free survivals between CCMs and other WHO grade II meningiomas. Clear cell histology predicts a higher risk of tumor recurrence and mortality than other grade II histologies. Future studies may help to understand the impact of these findings and the treatment implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-020-03668-5DOI Listing
January 2021

Extent of resection and survival outcomes in World Health Organization grade II meningiomas.

J Neurooncol 2021 Jan 17;151(2):173-179. Epub 2020 Nov 17.

Department of Neurological Surgery, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave., CA-51, Cleveland, OH, 44195, USA.

Purpose: WHO grade II meningiomas behave aggressively, with recurrence rates as high as 60%. Although complete resection in low-grade meningiomas is associated with a relatively low recurrence rate, the impact of complete resection for WHO grade II meningiomas is less clear. We studied the association of extent of resection with overall and progression-free survivals in patients with WHO grade II meningiomas.

Methods: A retrospective database review was performed to identify all patients who underwent surgical resection for intracranial WHO grade II meningiomas at our institution between 1995 and 2019. Kaplan-Meier analysis was used to compare overall and progression-free survivals between patients who underwent gross total resection (GTR) and those who underwent subtotal resection (STR). Multivariable Cox proportional-hazards analysis was used to identify independent predictors of tumor recurrence and mortality.

Results: Of 214 patients who underwent surgical resection for WHO grade II meningiomas (median follow-up 53.4 months), 158 had GTR and 56 had STR. In Kaplan-Meier analysis, patients who underwent GTR had significantly longer progression-free (p = 0.002) and overall (p = 0.006) survivals than those who underwent STR. In multivariable Cox proportional-hazards analysis, GTR independently predicted prolonged progression-free (HR 0.57, p = 0.038) and overall (HR 0.44, p = 0.017) survivals when controlling for age, tumor location, and adjuvant radiation.

Conclusions: Extent of resection independently predicts progression-free and overall survivals in patients with WHO grade II meningiomas. In an era of increasing support for adjuvant treatment modalities in the management of meningiomas, our data support maximal safe resection as the primary goal in treatment of these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-020-03632-3DOI Listing
January 2021

Peritumoral Brain Edema and Surgical Outcome in Secretory Meningiomas: A Matched-Cohort Analysis.

World Neurosurg 2021 01 3;145:e170-e176. Epub 2020 Oct 3.

Department of Neurosurgery and Rosa Ella Burkhardt Brain Tumor & Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. Electronic address:

Objective: Secretory meningioma (SM) is a rare subtype of benign meningioma reported to cause significant peritumoral brain edema (PTBE). Therefore, patients with SM may have more severe presenting symptoms and possibly increased postoperative complications. Our aim was to perform a statistically rigorous comparison of patients with SM with other nonsecretory World Health Organization grade I meningiomas and examine PTBE, postsurgical outcomes, and recurrence in a large series of cases.

Methods: A retrospective review of all patients at our institution with pathologically confirmed SM between 2000 and 2017 was performed. A control group of nonsecretory grade I meningiomas was matched 1:1 according to tumor location and size. Study groups were compared on clinical characteristics and outcomes using logistic, cumulative logit, and normal linear generalized estimating equations regression models.

Results: Fifty-five patients with SM met inclusion criteria and were matched with 55 control patients. After adjusting for size and location, the odds of a patient with SM having a more severe T2 edema grade were 8.9 (95% confidence interval, 3.8-21.1; P < 0.001) times higher, and the odds of any T2 edema were 6.2 (95% confidence interval, 2.2-17.6; P < 0.001) times higher. Significance remained even when adjusting for age. Postoperative complications, Simpson grade resection, neurologic outcome, and recurrence were not significantly different.

Conclusions: Patients with SM have significantly greater odds of having PTBE compared with patients with nonsecretory World Health Organization grade I meningiomas of a similar size and location. Despite this situation, surgical outcome and recurrence rates are similar.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.09.151DOI Listing
January 2021

The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies.

Cancer Discov 2020 11 23;10(11):1722-1741. Epub 2020 Jul 23.

Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, California.

Meningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into three biologically distinct groups (adipogenesis/cholesterol, mesodermal, and neural crest) distinguished by distinct hormonal lineage transcriptional regulators. Meningioma landscapes clustered with intrinsic brain tumors and hormonally responsive systemic cancers with meningioma subgroups, reflecting progesterone or androgen hormonal signaling. Enhancer classification identified a subset of tumors with poor prognosis, irrespective of histologic grading. Superenhancer signatures predicted drug dependencies with superior efficacy to treatment based upon the genomic profile. Inhibition of DUSP1, a novel and druggable meningioma target, impaired tumor growth . Collectively, epigenetic landscapes empower meningioma classification and identification of novel therapies. SIGNIFICANCE: Enhancer landscapes inform prognostic classification of aggressive meningiomas, identifying tumors at high risk of recurrence, and reveal previously unknown therapeutic targets. Druggable dependencies discovered through epigenetic profiling potentially guide treatment of intractable meningiomas..
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2159-8290.CD-20-0160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194360PMC
November 2020

Effect of Anatomic Segment Involvement on Stereotactic Radiosurgery for Facial Nerve Schwannomas: An International Multicenter Cohort Study.

Neurosurgery 2020 12;88(1):E91-E98

Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, Virginia.

Background: Facial nerve schwannomas are rare, challenging tumors to manage due to their nerve of origin. Functional outcomes after stereotactic radiosurgery (SRS) are incompletely defined.

Objective: To analyze the effect of facial nerve segment involvement on functional outcome for these tumors.

Methods: Patients who underwent single-session SRS for facial nerve schwannomas with at least 3 mo follow-up at 11 participating centers were included. Preoperative and treatment variables were recorded. Outcome measures included radiological tumor response and neurological function.

Results: A total of 63 patients (34 females) were included in the present study. In total, 75% had preoperative facial weakness. Mean tumor volume and margin dose were 2.0 ± 2.4 cm3 and 12.2 ± 0.54 Gy, respectively. Mean radiological follow-up was 45.5 ± 38.9 mo. Progression-free survival at 2, 5, and 10 yr was 98.1%, 87.2%, and 87.2%, respectively. The cumulative proportion of patients with regressing tumors at 2, 5, and 10 yr was 43.1%, 63.6%, and 63.6%, respectively. The number of involved facial nerve segments significantly predicted tumor progression (P = .04). Facial nerve function was stable or improved in 57 patients (90%). Patients with involvement of the labyrinthine segment of the facial nerve were significantly more likely to have an improvement in facial nerve function after SRS (P = .03). Hearing worsened in at least 6% of patients. Otherwise, adverse radiation effects included facial twitching (3 patients), facial numbness (2 patients), and dizziness (2 patients).

Conclusion: SRS for facial nerve schwannomas is effective and spares facial nerve function in most patients. Some patients may have functional improvement after treatment, particularly if the labyrinthine segment is involved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyaa313DOI Listing
December 2020

Laser Interstitial Thermal Therapy in the Treatment of Thalamic Brain Tumors: A Case Series.

Oper Neurosurg (Hagerstown) 2020 11;19(6):641-650

Neurological Institute, Department of Neurological Surgery, Cleveland Clinic, Cleveland, Ohio.

Background: Surgical options for patients with thalamic brain tumors are limited. Traditional surgical resection is associated with a high degree of morbidity and mortality. Laser interstitial thermal therapy (LITT) utilizes a stereotactically placed laser probe to induce thermal damage to tumor tissue. LITT provides a surgical cytoreduction option for this challenging patient population. We present our experience treating thalamic brain tumors with LITT.

Objective: To describe our experience and outcomes using LITT on patients with thalamic tumors.

Methods: We analyzed 13 consecutive patients treated with LITT for thalamic tumors from 2012 to 2017. Radiographic, clinical characteristics, and outcome data were collected via review of electronic medical records.

Results: Thirteen patients with thalamic tumors were treated with LITT. Most had high-grade gliomas, including glioblastoma (n = 9) and anaplastic astrocytoma (n = 2). The average tumor volume was 12.0 cc and shrank by 42.9% at 3 mo. The average hospital stay was 3.0 d. Median ablation coverage as calculated by thermal damage threshold (TDT) lines was 98% and 95% for yellow (>43°C for >2 min) or blue (>10 min), respectively. Median disease-specific progression-free survival calculated for 8 patients in our cohort was 6.1 mo (range: 1.1-15.1 mo). There were 6 patients with perioperative morbidity and 2 perioperative deaths because of intracerebral hematoma.

Conclusion: LITT is a feasible treatment for patients with thalamic tumors. LITT offers a cytoreduction option in this challenging population. Patient selection is key. Close attention should be paid to lesion size to minimize morbidity. More studies comparing treatment modalities of thalamic tumors need to be performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ons/opaa206DOI Listing
November 2020

Laser thermal therapy in the management of high-grade gliomas.

Int J Hyperthermia 2020 07;37(2):44-52

Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.

Laser interstitial thermal therapy (LITT) is a minimally invasive therapy that have been used for brain tumors, epilepsy, chronic pain, and other spine pathologies. This therapy is performed under imaging and stereotactic guidance to precisely direct the probe and ablate the area of interest using real-time magnetic resonance (MR) thermography. LITT has gained popularity as a treatment for glioma because of its minimally invasive nature, small skin incision, repeatability, shorter hospital stay, and the possibility of receiving adjuvant therapy shortly after surgery instead of several weeks as required after open surgical resection. Several reports have demonstrated the usefulness of LITT in the treatment of newly-diagnosed and recurrent gliomas. In this review, we will summarize the recent evidence of this therapy in the field of glioma surgery and the future perspectives of the use of LITT combined with other treatment strategies for this devastating disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02656736.2020.1767807DOI Listing
July 2020

Prediction of recurrent glioblastoma after laser interstitial thermal therapy: The role of diffusion imaging.

Neurooncol Adv 2019 May-Dec;1(1):vdz021. Epub 2019 Aug 20.

Department of Radiology, Cleveland Clinic, Cleveland, Ohio.

Background: Evaluate the utility of diffusion-weighted imaging (DWI) for the assessment of local recurrence of glioblastoma (GBM) on imaging performed 24 h following MRI-guided laser interstitial thermal therapy (LITT). We hypothesize that microscopic peritumoral infiltration correlates with early subtle variations on DWI images and apparent diffusion coefficient (ADC) maps.

Methods: Of 64 patients with GBM treated with LITT, 39 had MRI scans within 24 h after undergoing LITT. Patterns on DWI images and ADC maps 24 h following LITT were correlated with areas of future GBM recurrence identified through coregistration of subsequent MRI examinations. In the areas of suspected recurrence within the periphery of post-LITT lesions, signal intensity values on ADC maps were recorded and compared with the remaining peritumoral ring.

Results: Thirty-nine patients with GBM met the inclusion criteria. For predicting recurrent GBM, areas of decreased DWI signal and increased signal on ADC maps within the expected peritumoral ring of restricted diffusion identified 24 h following LITT showed 86.1% sensitivity, 75.2% specificity, and high correlation ( = 0.53) with future areas of GBM recurrence ( < .01). Areas of future recurrence demonstrated a 37% increase in the ADC value ( < .001), compared with findings in the surrounding treated peritumoral region. A significantly greater area under the receiver operating characteristics curve was determined for ADC values ( < .01).

Conclusions: DWI obtained 24 h following LITT can help predict the location of GBM recurrence months before the development of abnormal enhancement. This may alter future treatment planning, perhaps suggesting areas that may be targeted for additional therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/noajnl/vdz021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212867PMC
August 2019

Early obliteration of pediatric brain arteriovenous malformations after stereotactic radiosurgery: an international multicenter study.

J Neurosurg Pediatr 2020 Jun 26:1-8. Epub 2020 Jun 26.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs.

Methods: The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared.

Results: The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation.

Conclusions: Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.4.PEDS19738DOI Listing
June 2020

Image-guided surgery for meningioma.

Handb Clin Neurol 2020 ;170:201-207

Department of Neurological Surgery, Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, United States. Electronic address:

Image-guided surgery (IGS-neuronavigation) has revolutionized the field of neurosurgery over the past few decades. Although commonly used for the diagnosis and resection of intracranial gliomas and metastases, IGS is also useful for meningioma surgery, particularly for accessing deep tumors, creating an optimal craniotomy for superficial lesions, and for showing the location of critical neurovascular structures deep to the tumor in skull base surgery. An additional bonus in meningioma surgery is that so-called brain shift is minimal or nonexistent, allowing for ongoing accurate navigation during the surgical procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/B978-0-12-822198-3.00040-9DOI Listing
April 2021

Clear Cell Meningioma: A Clinicopathologic Study of a Rare Meningioma Subtype in 35 Patients.

World Neurosurg 2020 09 21;141:e334-e340. Epub 2020 May 21.

Department of Neurosurgery, Neurological Institute, Cleveland, Ohio, USA; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland, Ohio, USA; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address:

Objective: Clear cell meningioma (CCM) is a rare histologic variant, accounting for only 0.2%-0.8% of all meningiomas. Given their relative infrequency, few cases have been reported. We have presented one of the largest series of patients with intracranial CCM and reported the treatments and outcomes of these patients.

Methods: Patients with histologically proven CCM from 2003 to 2018 were identified for inclusion in the present study. Relevant clinical and radiographic data were obtained via retrospective review and analyzed. Kaplan-Meier and Cox proportional hazards analyses were used to compare overall and progression-free survival.

Results: A total of 35 patients had undergone surgical resection for CCM, including 18 women and 17 men, with a mean age of 59.3 years. Gross total resection was achieved in 22 patients (62.9%), and 11 patients (31.4%) had received adjuvant postoperative radiotherapy. Tumors recurred in 17 patients (48.6%), with a mean time to recurrence of 31.3 months. The mean postoperative follow-up was 66.3 months. On multivariable analysis, adjuvant radiotherapy and gross total tumor resection were both independently associated with prolonged progression-free survival (P < 0.033), although not with overall survival (P >0.274).

Conclusions: The data from the present series of 35 patients with CCM have shown distinct contrasts to previous series, with an older mean age and a nearly 1:1 male/female ratio. Although gross total resection and adjuvant postoperative radiotherapy were both independently associated with longer progression-free survival for patients with CCM, tumor recurrence has remained a challenge in the treatment of these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.05.120DOI Listing
September 2020

Lessons Learned in Using Laser Interstitial Thermal Therapy for Treatment of Brain Tumors: A Case Series of 238 Patients from a Single Institution.

World Neurosurg 2020 07 13;139:e345-e354. Epub 2020 Apr 13.

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA; Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Background: Laser interstitial thermal therapy (LITT) is a novel, minimally invasive alternative to craniotomy, and as with any new technology, comes with a learning curve.

Objective: We present our experience detailing the evolution of this technology in our practice in one of the largest patient cohorts to date regarding LITT in neuro-oncology.

Methods: We reviewed 238 consecutive patients with brain tumor treated with LITT at our institution. Data on patient, surgery and tumor characteristics, and follow-up were collected. Patients were categorized into 2 cohorts: early (<2014, 100 patients) and recent (>2015, 138 patients). Median follow-up for the entire cohort was 8.4 months.

Results: The indications for LITT included gliomas (70.2%), radiation necrosis (21.0%), and metastasis (8.8%). Patient demographics stayed consistent between the 2 cohorts, with the exception of age (early, 54.3; recent, 58.4; P = 0.04). Operative time (6.6 vs. 3.5; P < 0.001) and number of trajectories (53.1% vs. 77.9% with 1 trajectory; P < 0.001) also decreased in the recent cohort. There was a significant decrease in permanent motor deficits over time (15.5 vs. 4.4%; P = 0.005) and 30-day mortality (4.1% vs. 1.5%) also decreased (not statistically significant) in the recent cohort. In terms of clinical outcomes, poor preoperative Karnofsky Performance Status (≤70) were significantly correlated with increased permanent deficits (P = 0.001) and decreased overall survival (P < 0.001 for all time points).

Conclusions: We observed improvement in operative efficiency and permanent deficits over time and also patients with poor preoperative Karnofsky Performance Status achieved suboptimal outcomes with LITT. As many other treatment modalities, patient selection is important in this procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.03.213DOI Listing
July 2020

National Trends and Factors Predicting Outcomes Following Laser Interstitial Thermal Therapy for Brain Lesions: Nationwide Inpatient Sample Analysis.

World Neurosurg 2020 07 3;139:e88-e97. Epub 2020 Apr 3.

Department of Neurosurgery, University of Louisville, Louisville, Kentucky, USA. Electronic address:

Background: Laser interstitial thermal therapy (LITT) is a stereotactic-guided technique, which is increasingly being performed for brain lesions. The aim of our study was to report the national trends and factors predicting the clinical outcomes following LITT using the Nationwide Inpatient Sample.

Methods: We extracted data from 2011-2016 using ICD-9/10 codes. Patients with a primary procedure of LITT were included. Patient demographics, complications, length of hospital stay, discharge disposition, and index-hospitalization charges were analyzed.

Results: A cohort of 1768 patients was identified from the database. Mean length of hospital stay was 3.2 days, 82% of patients were discharged to home, and in-hospitalization cost was $124,225. Complications and mortality were noted in 12.9% and 2.5% of patients following LITT, respectively. Non-Caucasian patients (estimate ratio [ER] 4.26), those with other insurance (compared with commercial, ER: 5.35), 3 and 4+ comorbidity indexes, patients with higher quartile median household income (second, third, and fourth quartile compared with first quartile), and those who underwent nonelective procedures were likely to have higher complications and less likely to be discharged home. Patients with 4+ comorbidity indexes were likely to have longer length of hospital stay (ER 1.39) and higher complications (ER: 7.95) and were less likely to be discharged home (ER: 0.17) and have higher in-hospitalization cost (ER: 1.21).

Conclusions: LITT is increasingly being performed with low complication rates. Non-Caucasian race, higher comorbidity index, noncommercial insurance, and nonelective procedures were predictors of higher complications and being less likely to be discharged home. In-hospitalization charges were higher in patients with higher comorbidity index and those with noncommercial insurance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.03.124DOI Listing
July 2020

Magnetic resonance-guided stereotactic laser ablation therapy for the treatment of pediatric brain tumors: a multiinstitutional retrospective study.

J Neurosurg Pediatr 2020 Mar 27:1-9. Epub 2020 Mar 27.

Departments of7Neurosurgery and.

Objective: This study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors.

Methods: Data from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed.

Results: A total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3-72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created.

Conclusions: SLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.1.PEDS19496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885863PMC
March 2020

Stereotactic radiosurgery for pediatric brain arteriovenous malformations: long-term outcomes.

J Neurosurg Pediatr 2020 Feb 7:1-9. Epub 2020 Feb 7.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years).

Methods: The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated.

Results: The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%-68.0%), 77.1% (95% CI 72.1%-81.3%), and 88.1% (95% CI 82.5%-92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%-7.2%), 9.7% (95% CI 6.4%-13.7%), and 14.5% (95% CI 9.5%-20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%-10.7%) and 6.9% (95% CI 3.1%-12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%-9.7%) over 15 years.

Conclusions: AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2019.12.PEDS19595DOI Listing
February 2020

The effect of Gamma Knife radiosurgery on large posterior fossa metastases and the associated mass effect from peritumoral edema.

J Neurosurg 2020 Jan 24:1-9. Epub 2020 Jan 24.

1Department of Neurosurgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland.

Objective: Gamma Knife radiosurgery (GKRS) as monotherapy is an option for the treatment of large (≥ 2 cm) posterior fossa brain metastases (LPFMs). However, there is concern regarding possible posttreatment increase in peritumoral edema (PTE) and associated compression of the fourth ventricle. This study evaluated the effects and safety of GKRS on tumor and PTE control in LPFM.

Methods: The authors performed a single-center retrospective review of 49 patients with 51 LPFMs treated with GKRS. Patients with at least 1 clinical and radiological follow-up visit were included. Tumor, PTE, and fourth ventricle volumetric measurements were used to assess efficacy and safety. Overall survival was a secondary outcome.

Results: Fifty-one lesions in 49 consecutive patients were identified; 57.1% of patients were male. At the time of GKRS, the median age was 61.5 years, and the median Karnofsky Performance Status score was 90. The median number of LPFMs and overall brain metastases were 1 and 2, respectively. The median overall tumor, PTE, and fourth ventricle volumes at diagnosis were 4.96 cm3 (range 1.4-21.1 cm3), 14.98 cm3 (range 0.6-71.8 cm3), and 1.23 cm3 (range 0.3-3.2 cm3), respectively, and the median lesion diameter was 2.6 cm (range 2.0-5.07 cm). The median follow-up time was 7.3 months (range 1.6-57.2 months). At the first follow-up, 2 months posttreatment, the median tumor volume decreased by 58.66% (range -96.95% to +48.69%, p < 0.001), median PTE decreased by 78.10% (range -99.92% to +198.35%, p < 0.001), and the fourth ventricle increased by 24.97% (range -37.96% to +545.6%, p < 0.001). The local control rate at first follow-up was 98.1%. The median OS was 8.36 months. No patient required surgical intervention, external ventricular drainage, or shunting between treatment and first follow-up. However, 1 patient required a ventriculoperitoneal shunt at 23 months from treatment. Posttreatment, 65.30% received our general steroid taper, 6.12% received no steroids, and 28.58% required prolonged steroid treatment.

Conclusions: In this retrospective analysis, patients with LPFMs treated with GKRS had a statistically significant posttreatment reduction in tumor size and PTE and marked opening of the fourth ventricle (all p < 0.001). This study demonstrates that GKRS is well tolerated and can be considered in the management of select cases of LPFMs, especially in patients who are poor surgical candidates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2019.11.JNS191485DOI Listing
January 2020

Outcomes of stereotactic radiosurgery for pilocytic astrocytoma: an international multiinstitutional study.

J Neurosurg 2019 Nov 29:1-9. Epub 2019 Nov 29.

13Rose-Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland, Ohio.

Objective: The current standard initial therapy for pilocytic astrocytoma is maximal safe resection. Radiation therapy is considered for residual, recurrent, or unresectable pilocytic astrocytomas. However, the optimal radiation strategy has not yet been established. Here, the authors describe the outcomes of stereotactic radiosurgery (SRS) for pilocytic astrocytoma in a large multiinstitutional cohort.

Methods: An institutional review board-approved multiinstitutional database of patients treated with Gamma Knife radiosurgery (GKRS) between 1990 and 2016 was queried. Data were gathered from 9 participating International Radiosurgery Research Foundation (IRRF) centers. Patients with a histological diagnosis of pilocytic astrocytoma treated using a single session of GKRS and with at least 6 months of follow-up were included in the analysis.

Results: A total of 141 patients were analyzed in the study. The median patient age was 14 years (range 2-84 years) at the time of GKRS. The median follow-up was 67.3 months. Thirty-nine percent of patients underwent SRS as the initial therapy, whereas 61% underwent SRS as salvage treatment. The median tumor volume was 3.45 cm3. The tumor location was the brainstem in 30% of cases, with a nonbrainstem location in the remainder. Five- and 10-year overall survival rates at the last follow-up were 95.7% and 92.5%, respectively. Five- and 10-year progression-free survival (PFS) rates were 74.0% and 69.7%, respectively. On univariate analysis, an age < 18 years, tumor volumes < 4.5 cm3, and no prior radiotherapy or chemotherapy were identified as positive prognostic factors for improved PFS. On multivariate analysis, only prior radiotherapy was significant for worse PFS.

Conclusions: This represents the largest study of single-session GKRS for pilocytic astrocytoma to date. Favorable long-term PFS and overall survival were observed with GKRS. Further prospective studies should be performed to evaluate appropriate radiosurgery dosing, timing, and sequencing of treatment along with their impact on toxicity and the quality of life of patients with pilocytic astrocytoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2019.9.JNS191335DOI Listing
November 2019

Pathologic Correlation of Cellular Imaging Using Apparent Diffusion Coefficient Quantification in Patients with Brain Metastases After Gamma Knife Radiosurgery.

World Neurosurg 2020 Feb 13;134:e903-e912. Epub 2019 Nov 13.

Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA; Rose Ella Burkhart Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Objective: To evaluate the role of apparent diffusion coefficient (ADC) in differentiating radiation necrosis (RN) from recurrent tumor after Gamma Knife radiosurgery (GKRS) for brain metastases (BMs).

Methods: Forty-one patients with BM who underwent surgical intervention after GKRS at Cleveland Clinic (2006-2017) were included in this retrospective study. The ADC values of the growing lesions and the contralateral hemisphere were calculated using picture archiving and communication system. These values were correlated to the percentage of RN identified on pathologic evaluation of the surgical specimen.

Results: The median age of the patients was 59 years (range, 25-86 years), and lung cancer (63.4%) was the most common malignancy. Median initial (pre-GKRS) target volume of the lesions was 5.4 cc (range, 0.135-45.6 cc), and median GKRS dose was 18.0 Gy. Surgical resection or biopsy was performed at a median of 176 days after GKRS. Two variables were statistically significant predictors of predominate RN (75%-100%) in the surgical specimen: 1) ADC of the lesion on the preresection magnetic resonance imaging (MRI) and 2) initial pre-GKRS target volume. ADC >1.5 × 10 mm/s within the lesion on MRI predicted significant RN on pathologic evaluation of the lesion (P < 0.05). Similarly, when the target volume before GKRS was large (>10 cc), the risk of identifying significant necrosis in the pathologic specimen was elevated (P < 0.05).

Conclusions: Our data suggest that the combination of lesion ADC on MRI prior to surgical intervention and the initial target volume can predict RN with reasonable accuracy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2019.11.037DOI Listing
February 2020

Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis.

Neuro Oncol 2020 02;22(2):267-277

Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio.

Background: The impact of activating alterations in non-small cell lung cancer (NSCLC) (epidermal growth factor receptor [EGFR] mutation/anaplastic lymphoma kinase [ALK] translocation) in prognosticating patients with brain metastasis (BM) is not well defined. This study was sought to identify this impact in NSCLC patients with BM accounting for the known validated variables.

Methods: Among 1078 NSCLC-BM patients diagnosed/treated between January 1, 2000 and December 31, 2015, three hundred and forty-eight with known EGFR/ALK status were analyzed. Overall survival (OS) and intracranial progression-free survival (PFS) were measured from the time of BM.

Results: Ninety-one patients had either ALK (n = 23) alterations or EGFR (n = 68) mutation and 257 were wild type (WT; negative actionable mutations/alterations). Median age of EGFR/ALK+ NSCLC BM patients was 60 years (range 29.8-82.6 y) and ~50% (n = 44) had Karnofsky performance status (KPS) score >80. Median number of BM was 2 (1 to ≥99). The median OS for the ALK/EGFR+ NSCLC BM was 19.9 versus 10.1 months for the WT (P = 0.028). The number of BM in the EGFR/ALK+ group did not impact OS (BM = 1 with 21.1 months vs 2-3 with 19.1 months and >3 with 23.7 months, P = 0.74), whereas fewer BM in the WT cohort had significantly better OS (BM = 1 with 13.8 mo, 2-3 with 11.0 mo and >3 with 8.1 mo; P = 0.006) with the adjustment of age, KPS, symptoms from BM and synchronicity.

Conclusions: Number of BM does not impact outcomes in the EGFR/ALK+ NSCLC patients, implying that targeted therapy along with surgery and/or radiation may improve OS irrespective of the number of BM. Number of BM, extracranial metastasis (ECM), and KPS independently affected OS/PFS in WT NSCLC BM, which was consistent with the known literature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noz155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442419PMC
February 2020

Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF).

Neurosurgery 2020 09;87(4):664-671

Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases.

Objective: To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS).

Methods: A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis.

Results: Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005).

Conclusion: SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyz428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780439PMC
September 2020

Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma.

Int J Radiat Oncol Biol Phys 2019 12 25;105(5):1106-1112. Epub 2019 Aug 25.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio.

Purpose: Malignant transformation (MT) of adult grade 2 glioma (low-grade glioma [LGG]) is associated with adverse survival. We sought to describe the incidence, outcomes, and risk factors for MT of molecularly classified LGG.

Methods And Materials: We reviewed a single-institutional database of adults who received a diagnosis of LGG with data allowing for molecular classification from 1980 to 2018 to evaluate time to MT and its associated risk factors. MT was defined as pathologic confirmation of grade 3-4 glioma and/or imaging characteristics consistent with MT by multidisciplinary consensus.

Results: Among the included 486 adults with molecularly classified LGG, median age was 39 years (range, 18-78), median tumor size was 3.9 cm (range, 0.3-13.0), and 262 (54%) were male. Molecular classification was IDH1p/19q in 169 (35%), IDH1p/19q in 125 (26%), and IDH in 192 (40%) patients. Adjuvant management was observation in 246 (51%) patients, temozolomide alone in 82 (16%), radiation therapy alone in 63 (13%), and radiation therapy concurrent with temozolomide in 81 (17%). Temozolomide monotherapy was more likely to be given to IDH1p/19q patients (P < .001). Median follow-up was 5.3 years. MT occurred in 84 (17%) patients, with a 5-year freedom from MT of 86% (95% confidence interval [CI], 82%-90%). Median overall survival after MT was 2.4 years (95% CI, 1.5-3.3) and was associated with molecular classification (P = .03) and grade at MT (P < .001). Factors associated with MT were male sex (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6; P = .009), tumor size ≥5 cm (HR, 3.5; 95% CI, 2.0-6.2; P < .001), IDH1p/19q (HR, 2.7; 95% CI, 1.3-5.6; P = .009) or IDH classification (HR, 5.5; 95% CI, 2.5-11.8; P < .001), and adjuvant temozolomide monotherapy (HR, 3.8; 95% CI, 1.4-10.3; P = .008).

Conclusions: MT of LGG has a poor prognosis associated with unfavorable molecular groups. Analysis of our large cohort identified adjuvant temozolomide monotherapy as the only modifiable risk factor for MT and provides the first clinical evidence of temozolomide-associated MT among molecularly classified adult LGG. This novel finding supplements our understanding of temozolomide-induced hypermutation and informs precision management of LGG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2019.08.025DOI Listing
December 2019

The benefit and risk of stereotactic radiosurgery for prolactinomas: an international multicenter cohort study.

J Neurosurg 2019 Aug 2:1-10. Epub 2019 Aug 2.

1Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.

Objective: The most common functioning pituitary adenoma is prolactinoma. Patients with medically refractory or residual/recurrent tumors that are not amenable to resection can be treated with stereotactic radiosurgery (SRS). The aim of this multicenter study was to evaluate the role of SRS for treating prolactinomas.

Methods: This retrospective study included prolactinomas treated with SRS between 1997 and 2016 at ten institutions. Patients' clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications.

Results: The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087).

Conclusions: In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2019.4.JNS183443DOI Listing
August 2019

Fractionated Gamma Knife radiosurgery for skull base meningiomas: a single-institution experience.

Neurosurg Focus 2019 06;46(6):E8

1Department of Neurosurgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

OBJECTIVEGamma Knife radiosurgery (GKRS) has been successfully used for the treatment of intracranial meningiomas given its steep dose gradients and high-dose conformality. However, treatment of skull base meningiomas (SBMs) may pose significant risk to adjacent radiation-sensitive structures such as the cranial nerves. Fractionated GKRS (fGKRS) may decrease this risk, but until recently it has not been practical with traditional pin-based systems. This study reports the authors' experience in treating SBMs with fGKRS, using a relocatable, noninvasive immobilization system.METHODSThe authors performed a retrospective review of all patients who underwent fGKRS for SBMs between 2013 and 2018 delivered using the Extend relocatable frame system or the Icon system. Patient demographics, pre- and post-GKRS tumor characteristics, perilesional edema, prior treatment details, and clinical symptoms were evaluated. Volumetric analysis of pre-GKRS, post-GKRS, and subsequent follow-up visits was performed.RESULTSTwenty-five patients met inclusion criteria. Nineteen patients were treated with the Icon system, and 6 patients were treated with the Extend system. The mean pre-fGKRS tumor volume was 7.62 cm3 (range 4.57-13.07 cm3). The median margin dose was 25 Gy delivered in 4 (8%) or 5 (92%) fractions. The median follow-up time was 12.4 months (range 4.7-17.4 months). Two patients (9%) experienced new-onset cranial neuropathy at the first follow-up. The mean postoperative tumor volume reduction was 15.9% with 6 patients (27%) experiencing improvement of cranial neuropathy at the first follow-up. Median first follow-up scans were obtained at 3.4 months (range 2.8-4.3 months). Three patients (12%) developed asymptomatic, mild perilesional edema by the first follow-up, which remained stable subsequently.CONCLUSIONSfGKRS with relocatable, noninvasive immobilization systems is well tolerated in patients with SBMs and demonstrated satisfactory tumor control as well as limited radiation toxicity. Future prospective studies with long-term follow-up and comparison to single-session GKRS or fractionated stereotactic radiotherapy are necessary to validate these findings and determine the efficacy of this approach in the management of SBMs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2019.3.FOCUS1963DOI Listing
June 2019

Stereotactic Laser Ablation as Treatment of Brain Metastases Recurring after Stereotactic Radiosurgery: A Systematic Literature Review.

World Neurosurg 2019 Aug 30;128:134-142. Epub 2019 Apr 30.

Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address:

Background: The optimal treatment of brain metastases recurring after radiosurgery (BMRS) remains an area of active investigation. Stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy) has recently emerged as a potential treatment option.

Objective: To summarize the available literature on SLA as treatment of BMRS and synthesize findings on local control, overall survival, neurologic outcome, imaging findings, morbidity, and postprocedure clinical course.

Methods: We performed a comprehensive search of PubMed for articles investigating SLA as treatment of BMRS.

Results: Thirteen peer-reviewed publications met our search criteria. Local control was a function of the percentage of tumor that was thermally ablated. In completely ablated tumors, 3-month local control was 80%-100%. Median survival ranged from 5.8 to 19.8 months. About two-thirds of treated lesions showed postablation expansion of contrast-enhancing volume and fluid-attenuated inversion recovery volume. Expansion could start within an hour of treatment, and resolution typically occurred within 6 months. Notably, maximal expanded contrast-enhancing volume could reach >3-fold the preoperative lesion volume. The incidence of SLA-related permanent neurologic injuries was <10%. The most common complications were hemorrhage, thermal injury causing neurologic deficit, and malignant cerebral edema. Nearly all patients were treated with dexamethasone, but there was variability in the dose and duration of therapy. Median hospital stay was 1-2 days (range, 1-5 days), and most treated patients were discharged home (range, 59.5%-100%).

Conclusion: Our analysis provides support for continued development of SLA as a treatment of BMRS. Standardization of periprocedural management will be needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2019.04.200DOI Listing
August 2019
-->