Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases.

BACKGROUND: Single session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2cm) to determine the safety of preoperative SRS at escalating doses. METHODS: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity. RESULTS: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%. CONCLUSION: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

The impact of opioid administration for post gamma knife radiosurgery frame removal: a prospective quality-improvement study.

PURPOSE: In our center, five Gamma Knife proceduralists differed in opioid administration practices prior to Leksell frame removal, providing the opportunity to improve the care of patients with brain metastases by studying whether opioid medications improve pain scores and patient satisfaction during Gamma Knife treatment in a prospective, pseudorandomized fashion. METHODS: We prospectively administered a questionnaire to patients undergoing Gamma Knife Radiosurgery for metastases between November, 2017 and July, 2018. Using multivariable methods, we assessed whether opioid pain medication administration influenced the change in pain scores after frame removal, and whether they influenced patient satisfaction on how often their pain was controlled, and their overall satisfaction. RESULTS: We included 142 patients. Mean age was 65.2 ± 10.8 years and 52.7% were female. Morphine was the most commonly administered medication. Pain increases were greater around frame removal than placement. Opioids were not associated with any difference in the change in pain scores before and after frame removal, or patient satisfaction. Patients with higher pre-removal pain scores had smaller increases in pain scores after removal; they also had worse pain control and overall satisfaction with their treatment. CONCLUSION: Morphine administration prior to frame removal did not improve pain scores or pain control satisfaction. Absence of efficacy may be related to delayed onset of action, and stronger and faster-acting agents should be explored. Pre-removal pain scores were associated with decreased pain control and overall satisfaction, further identifying earlier and stronger pain treatment as a potential area for improvement.

18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.

Efficacy of laser interstitial thermal therapy for biopsy-proven radiation necrosis in radiographically recurrent brain metastases.

Background: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies. Methods: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival. Results: Ninety patients met the inclusion criteria. Four patients underwent 2 ablations on the same day. Median hospitalization time was 32.5 hours. The median time to corticosteroid cessation after LITT was 13.0 days (0.0, 1229.0) and cumulative incidence of lesional progression was 19% at 1 year. Median post-procedure overall survival was 2.55 years [1.66, infinity] and 77.1% at one year as estimated by KaplanMeier. Median KPS remained at 80 through 2-year follow-up. Seizure prevalence was 12% within 1-month post-LITT and 7.9% at 3 months; down from 34.4% within 60-day prior to procedure. Conclusions: LITT for RN was not only again found to be safe with low patient morbidity but was also a highly effective treatment for RN for both local control and symptom management (including seizures). In addition to averting expected neurological death, LITT facilitates ongoing systemic therapy (in particular immunotherapy) by enabling the rapid cessation of steroids, thereby facilitating maximal possible survival for these patients.

The Impact of Extent of Ablation on Survival of Patients With Newly Diagnosed Glioblastoma Treated With Laser Interstitial Thermal Therapy: A Large Single-Institutional Cohort.

BACKGROUND: Upfront laser interstitial thermal therapy (LITT) can be used as part of the treatment paradigm in difficult-to-access newly diagnosed glioblastoma multiforme (ndGBM) cases. The extent of ablation, though, is not routinely quantified; thus, its specific effect on patients' oncological outcomes is unclear. OBJECTIVE: To methodically measure the extent of ablation in the cohort of patients with ndGBM and its effect, and other treatment-related parameters, on patients' progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective study was conducted on 56 isocitrate dehydrogenase 1/2 wild-type patients with ndGBM treated with upfront LITT between 2011 and 2021. Patient data including demographics, oncological course, and LITT-associated parameters were analyzed. RESULTS: Patient median age was 62.3 years (31-84), and the median follow-up duration was 11.4 months. As expected, the subgroup of patients receiving full chemoradiation was found to have the most beneficial PFS and OS (n = 34). Further analysis showed that 10 of them underwent near-total ablation and had a significantly improved PFS (10.3 months) and OS (22.7 months). Notably, 84% excess ablation was detected which was not related to a higher rate of neurological deficits. Tumor volume was also found to influence PFS and OS, but it was not possible to further corroborate this finding because of low numbers. CONCLUSION: This study presents data analysis of the largest series of ndGBM treated with upfront LITT. Near-total ablation was shown to significantly benefit patients' PFS and OS. Importantly, it was shown to be safe, even in cases of excess ablation and therefore could be considered when using this modality to treat ndGBM.

Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins.

Glioblastoma (GBM) treatment includes maximal safe resection of the core and MRI contrast-enhancing (CE) tumor. Complete resection of the infiltrative non-contrast-enhancing (NCE) tumor rim is rarely achieved. We established a safe, semi-automated workflow for spatially-registered sampling of MRI-defined GBM regions in 19 patients with downstream analysis and biobanking, enabling studies of NCE, wherefrom recurrence/progression typically occurs. Immunophenotyping revealed underrepresentation of myeloid cell subsets and CD8+ T cells in the NCE. While NCE T cells phenotypically and functionally resembled those in matching CE tumor, subsets of activated (CD69hi) effector memory CD8+ T cells were overrepresented. Contrarily, CD25hi Tregs and other subsets were underrepresented. Overall, our study demonstrated that MRI-guided, spatially-registered, intraoperative immunosampling is feasible as part of routine GBM surgery. Further elucidation of the shared and spatially distinct microenvironmental biology of GBM will enable development of therapeutic approaches targeting the NCE infiltrative tumor to decrease GBM recurrence.

Immediate Titanium Mesh Cranioplasty After Debridement and Craniectomy for Postcraniotomy Surgical Site Infections and Risk Factors for Reoperation.

BACKGROUND: We previously published a novel strategy for management of postcraniotomy bone flap infection consisting of single stage debridement, bone flap removal, and immediate titanium mesh cranioplasty. METHODS: Postcraniotomy patients with surgical site infections treated with surgical debridement, bone flap removal, and immediate titanium mesh cranioplasty were retrospectively reviewed. The primary outcome measure was reoperation due to persistent infection or wound healing complications from the titanium mesh. RESULTS: We included 48 patients, of which 15 (31.3%) were female. The most common primary diagnoses were glioblastoma (31.3%), meningioma (18.8%), and vascular/trauma (16.7%). Most patients had a history of same-site craniotomy prior to the surgery complicated by surgical site infection and 47.9% had prior cranial radiation. Thirty-six (75.0%) patients achieved resolution of their infection and did not require a second operation. Twelve (25.0%) patients required reoperation: 6 (12.5%) patients were found to have frank intraoperative purulence on reoperation, whereas 6 (12.5%) had reoperation for poor wound healing without any evidence of persistent infection. Cochran Armitage trend test revealed that patients with increasing number of wound healing risk factors had significantly higher risk of reoperation (P = 0.001). Prior intensity modulated radiotherapy alone was a significant risk factor for reoperation (6.5 [1.40-30.31], P = 0.002). Median follow-up time was 20.5 weeks. CONCLUSIONS: Immediate titanium mesh cranioplasty at the time of debridement and bone flap removal is an acceptable option in the management of post-craniotomy bone flap infection. Patients with multiple wound healing risk factors are at higher risk for reoperation.

The Pain Control Efficacy of Zolpidem versus Melatonin after Intervertebral Disc Herniation Surgery under General Anaesthesia: A Randomised Clinical Trial.

Background: Postoperative pain management has been linked with multiple clinically relevant complications such as thromboembolism, myocardial ischaemia, and cardiac arrhythmias. Objectives: The present study moves towards an evidence-based approach to the therapeutic efficacy of zolpidem and melatonin in a better clinically meaningful pain relief following intervertebral disc herniation surgery under general anaesthesia. Materials and Methods: Undertaking a randomised, parallel-group, double-blind, clinical trial, 60 patients meeting eligibility (mean age ≈ 39, 50% female and 50% men) were offered intervertebral disc surgery at the Arak-based Valiasr Hospital and stratified into two interventional arms by block randomisation. Data including (i) pain (visual analog scale) and sedation (Ramsay sedation scale) scores during recovery and at all five initial 24-h time points (two, four, six, 12, 24); (ii) adverse events inclusive of mild nausea and dizziness, pethidine consumption; and (iii) ongoing haemodynamic parameters, including heart rate, blood pressure, and oxygen saturation were collected. Data were analysed at a significance level of P = 0.05 (SPSS 20.0, IBM Corp). Results: Our results showed no perceived statistically significant between-arm difference in three functional haemodynamic parameters, duration of surgery, and adverse events, as well as in sedation and pain scores (P < 0.05). Our results showed no between-arm difference in analgesia and sedation, haemodynamic changes, and postoperative adverse events. Conclusion: The findings taken together lent a strong support for the highly encouraging efficacy of both drugs in affording adequate analgesia at 24 postoperative hours without any adverse events needing to be thought of. Therefore, both zolpidem and melatonin were promising postoperative pain relievers, while no drug is demonstrably superior to the other.

Distinct Cell Adhesion Signature Defines Glioblastoma Myeloid-Derived Suppressor Cell Subsets.

In multiple types of cancer, an increased frequency in myeloid-derived suppressor cells (MDSC) is associated with worse outcomes and poor therapeutic response. In the glioblastoma (GBM) microenvironment, monocytic (m) MDSCs represent the predominant subset. However, the molecular basis of mMDSC enrichment in the tumor microenvironment compared with granulocytic (g) MDSCs has yet to be determined. Here we performed the first broad epigenetic profiling of MDSC subsets to define underlying cell-intrinsic differences in behavior and found that enhanced gene accessibility of cell adhesion programs in mMDSCs is linked to their tumor-accelerating ability in GBM models upon adoptive transfer. Mouse and human mMDSCs expressed higher levels of integrin ß1 and dipeptidyl peptidase-4 (DPP-4) compared with gMDSCs as part of an enhanced cell adhesion signature. Integrin ß1 blockade abrogated the tumor-promoting phenotype of mMDSCs and altered the immune profile in the tumor microenvironment, whereas treatment with a DPP-4 inhibitor extended survival in preclinical GBM models. Targeting DPP-4 in mMDSCs reduced pERK signaling and their migration towards tumor cells. These findings uncover a fundamental difference in the molecular basis of MDSC subsets and suggest that integrin ß1 and DPP-4 represent putative immunotherapy targets to attenuate myeloid cell-driven immune suppression in GBM. SIGNIFICANCE: Epigenetic profiling uncovers cell adhesion programming as a regulator of the tumor-promoting functions of monocytic myeloid-derived suppressor cells in glioblastoma, identifying therapeutic targets that modulate the immune response and suppress tumor growth.

Combination effects of mesenchymal stem cells transplantation and anodal transcranial direct current stimulation on a cuprizone-induced mouse model of multiple sclerosis.

Multiple sclerosis (MS) has no absolute treatment, and researchers are still exploring to introduce promising therapy for MS. Transcranial direct current stimulation (tDCS), is a safe, non-invasive procedure for brain stimulating which can enhance working memory, cognitive neurohabitation and motor recovery. Here, we evaluated the effects of tDCS treatment and Mesenchymal stem cells (MSCs) transplantation on remyelination ability of a Cuprizone (CPZ)-induced demyelination mouse model. tDCS significantly increased the motor coordination and balance abilities in CPZ + tDCS and CPZ + tDCS + MSCs mice in comparison to the CPZ mice. Luxol fast blue (LFB) staining showed that tDCS and MSCs transplantation could increase remyelination capacity in CPZ + tDCS and CPZ + MSCs mice compared to the CPZ mice. But, the effect of tDCS with MSCs transplantation on remyelination process was larger than each of treatment alone. Immunofluorescence technique indicated that the numbers of Olig2+ cells were increased by tDCS and MSCs transplantation in CPZ + tDCS and CPZ + MSCs mice compared to the CPZ mice. Interestingly, the combination effect of tDCS and MSCs was larger than each of treatment alone on Oligodendrocytes population. MSCs transplantation significantly decreased the TUNEL+ cells in CPZ + MSCs and CPZ + tDCS + MSCs mice in comparison to the CPZ mice. Also, the combination effects of tDCS and MSCs transplantation was much larger than each of treatment alone on increasing the mRNA expression of BDNF and Sox2, while decreasing P53 as compared to CPZ mice. It can be concluded that the combination usage of tDCS and MSCs transplantation enhance remyelination process in CPZ-treated mice by increasing transplanted stem cell homing, oligodendrocyte generation and decreasing apoptosis.

Efficacy of intraoperative epidural dexamethasone and bupivacaine in reduction of pain and disability following lumbar discectomy.

Background: In lumbar disc herniation, although surgery can provide relief from pain in the low back and lower extremities, many drugs can provide more relief; thus, the aim was the evaluation of epidural dexamethasone and bupivacaine efficacy in lumbar disc herniation surgery. Methods: A total of 42 cases were evaluated in a triple-blind randomized clinical trial study. Patients were divided into intervention and control groups based on permuted block randomization. The patient's condition was assessed based on the Visual Analogue Scale (VAS) at 3, 6, 12, and 24 h and 1, 3, and 6 months after surgery. In addition, the patient's disability was assessed by Oswestry disability index (ODI) at 1 and 6 months after surgery. Results: Of the 42 evaluated cases, age (44.0 ± 12.4, P = 0.4) and hospitalization duration (1.9 ± 0.3 days, P = 0.02) had statistically significant difference between two groups. The severity of low back pain before surgery was 2.9 ± 1.9 (P = 0.74), and 3 hours after surgery was 4.9 ± 1.9 in the control group and 2.8 ± 1.3 in the intervention group (P = 0.03), and there was a statistically significant difference between the two groups. In addition, based on the repeated measure test, there was no significant difference between the two groups. ODI value was before surgery 31.7 ± 8.3 (P = 0.77), 5.2 ± 2.4 (P = 0.9) at 1 month after surgery, and 4.5 ± 1.8 (P = 0.6) at 6 months after surgery, and there was no statistically significant difference between the two groups. Conclusion: Dexamethasone and bupivacaine can be effective in post-operation pain control, although this difference between the two groups was not statistically significant.

Combination laser interstitial thermal therapy plus stereotactic radiotherapy increases time to progression for biopsy-proven recurrent brain metastases.

Background: Improved survival for patients with brain metastases has been accompanied by a rise in tumor recurrence after stereotactic radiotherapy (SRT). Laser interstitial thermal therapy (LITT) has emerged as an effective treatment for SRT failures as an alternative to open resection or repeat SRT. We aimed to evaluate the efficacy of LITT followed by SRT (LITT+SRT) in recurrent brain metastases. Methods: A multicenter, retrospective study was performed of patients who underwent treatment for biopsy-proven brain metastasis recurrence after SRT at an academic medical center. Patients were stratified by "planned LITT+SRT" versus "LITT alone" versus "repeat SRT alone." Index lesion progression was determined by modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Results: Fifty-five patients met inclusion criteria, with a median follow-up of 7.3 months (range: 1.0-30.5), age of 60 years (range: 37-86), Karnofsky Performance Status (KPS) of 80 (range: 60-100), and pre-LITT/biopsy contrast-enhancing volume of 5.7 cc (range: 0.7-19.4). Thirty-eight percent of patients underwent LITT+SRT, 45% LITT alone, and 16% SRT alone. Median time to index lesion progression (29.8, 7.5, and 3.7 months [P = .022]) was significantly improved with LITT+SRT. When controlling for age in a multivariate analysis, patients treated with LITT+SRT remained significantly less likely to have index lesion progression (P = .004). Conclusions: These data suggest that LITT+SRT is superior to LITT or repeat SRT alone for treatment of biopsy-proven brain metastasis recurrence after SRT failure. Prospective trials are warranted to validate the efficacy of using combination LITT+SRT for treatment of recurrent brain metastases.

Ten-Year Institutional Experience to Predict Risk of Calvarial Bone Flap Loss Using Long-Term Outcome Data.

BACKGROUND: Calvarial bone flap (CBF) loss is a common complication following craniotomy and subsequent skull reconstruction can be challenging. Defining predictors of CBF failure not only improves patient outcomes but reduces the need for complex reconstruction often requiring plastic surgery consultation. As CBF failure can occur many years following craniotomy, this study aimed to determine risk factors of CBF loss using long-term follow-up. MATERIALS AND METHODS: This retrospective study included patients who underwent craniotomy with CBF reinsertion between 2003 and 2013 at a tertiary academic institution. Patients were included if demographics, comorbidities, and long-term outcomes were available. Multivariable logistic regression modeled the odds of CBF failure, defined as permanent removal for bone flap-related issues. The median follow-up was 6.9 years (interquartile range: 1.8-10.8 y). RESULTS: There were 222 patients who met inclusion criteria and underwent craniotomy with CBF reinsertion, primarily for tumor resection or intracranial pressure relief. CBF failure occurred in 76 (34.2%) patients. Up to 4 CBF reinsertions were performed in both failure and nonfailure groups. The risks of CBF loss increased with each additional CBF elevation by 17-fold ( P <0.001), male sex by 3-fold ( P =0.005), and tumor etiology by 3-fold ( P =0.033) ( C -index=0.942). CONCLUSIONS: Each CBF reinsertion dramatically increases the risk of CBF loss. This finding may optimize patient selection and surgical planning. Early multidisciplinary discussions between plastic surgeons and neurosurgeons may avoid multiple CBF elevations and prevent the adverse sequela of high-risk calvarial reconstruction efforts.

Sex-Specific Differences in Low-Grade Glioma Presentation and Outcome.

PURPOSE: In addition to established prognostic factors in low-grade glioma (LGG), studies suggest a sexual dimorphism with male sex portending worse prognosis. Our objective was to identify the effect of sex on presentation and outcomes in LGG. METHODS AND MATERIALS: We conducted a retrospective cohort study of adults (aged ≥18 years) diagnosed with LGG (World Health Organization 2016 grade 2 glioma). Patients with IDH wild-type tumors were excluded. Patients were matched between male and female sex by age, treatment, and surgery via propensity score matching. Patient, tumor, and treatment characteristics were analyzed by sex. Endpoints included overall survival (OS), next intervention-free survival (NIFS), progression-free survival, and malignant transformation-free survival. Kaplan-Meier analyses and Cox proportional hazards regression multivariable analysis with backward elimination were completed. RESULTS: Of the 532 patients identified, 258 (48%) were men. Men were more likely to present with seizure (69.38% vs 56.57%, P = .002), but no other statistically significant differences between sexes at presentation were identified. Five-year OS was higher in women at 87% (95% confidence interval [CI], 83%-91%) versus 78% (95% CI, 73%-84%) in men (P = .0045). NIFS was significantly higher in female patients at 68% (95% CI, 62%-74%) versus 57% (95% CI, 51%-64%) in men (P = .009). On multivariable analysis, female sex was independently associated with improved OS (hazard ratio [HR], 1.54; 95% CI, 1.16-2.05; P = .002), NIFS (HR, 1.42; 95% CI, 1.42; P = .004), and malignant transformation-free survival (HR, 1.62; 95% CI, 1.24-2.12; P = .0004). In patients with molecularly defined LGG (IDH and 1p19q status; n = 291), female sex remained independently associated with improved OS (HR, 1.79; 95% CI, 1.16-2.77; P = .008) and NIFS (HR, 1.45; 95% CI, 1.07-1.96; P = .016). CONCLUSIONS: In this study, female sex was independently associated with improved outcomes. These findings support intrinsic sex-specific differences in LGG behavior, justifying further studies to optimize management and therapeutics based on sex.

Efficacy of laser interstitial thermal therapy (LITT) for newly diagnosed and recurrent IDH wild-type glioblastoma.

Background: Treatment options for unresectable new and recurrent glioblastoma remain limited. Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data were analyzed to determine clinical outcomes for patients with new and recurrent IDH wild-type glioblastoma. Methods: Demographics, intraprocedural data, adverse events, KPS, health economics, and survival data were prospectively collected and then analyzed on IDH wild-type newly diagnosed and recurrent glioblastoma patients who were treated with laser ablation at 14 US centers between January 2016 and May 2019. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable differences in survival, and median survival numbers. Results: A total of 29 new and 60 recurrent IDH wild-type WHO grade 4 glioblastoma patients were treated. Positive MGMT promoter methylation status was present in 5/29 of new and 23/60 of recurrent patients. Median physician-estimated extent of ablation was 91%-99%. Median overall survival (OS) was 9.73 months (95% confidence interval: 5.16, 15.91) for newly diagnosed patients and median post-procedure survival was 8.97 months (6.94, 12.36) for recurrent patients. Median OS for newly diagnosed patients receiving post-LITT chemo/radiation was 16.14 months (6.11, not reached). Factors associated with improved survival were MGMT promoter methylation, adjuvant chemotherapy within 12 weeks, and tumor volume <3 cc. Conclusions: Laser ablation is a viable option for patients with new and recurrent glioblastoma. Median OS for IDH wild-type newly diagnosed glioblastoma is comparable to outcomes observed in other tumor resection studies when those patients undergo radiation and chemotherapy following LITT.

Cognitive function after concurrent temozolomide-based chemoradiation therapy in low-grade gliomas.

PURPOSE: We sought to evaluate the effects of concurrent temozolomide-based chemoradiation therapy on neurocognitive function in patients with low-grade glioma (LGG). MATERIALS/METHODS: We included adult patients with LGG who were treated postoperatively with radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Patients were evaluated with comprehensive psychometric tests at baseline (prior to RT + TMZ) and at various time intervals following RT + TMZ. Baseline cognitive performance was analyzed by sex, age, education history, history of seizures, IDH mutation status, and 1p/19q codeletion status. Changes in neurocognitive performance were evaluated over time. RESULTS: Thirty-seven LGG patients (mean age 43.6, 59.5% male) had baseline neurocognitive evaluation. Patients with an age > 40 years old at diagnosis and those with an education > 16 years demonstrated superior baseline verbal memory as assessed by HVLT. No other cognitive domains showed differences when stratified by the variables mentioned above. A total of 22 LGG patients had baseline and post RT + TMZ neurocognitive evaluation. Overall, patients showed no statistical difference between group mean test scores prior to and following RT + TMZ on all psychometric measures (with the exception of HVLT Discrimination). CONCLUSION: Cognitive function remained stable following RT + TMZ in LGG patients evaluated prospectively up to 2 years. The anticipated analysis of RTOG 0424 will provide valuable neurocognitive outcomes specifically for high risk LGG patients treated with RT + TMZ.

Management Strategies for Large Brain Metastases.

Brain metastases represent the most common intracranial neoplasm and pose a significant disease burden on the individual and the healthcare system. Although whole brain radiation therapy was historically a first line approach, subsequent research and technological advancements have resulted in a larger armamentarium of strategies for treatment of these patients. While chemotherapeutic options remain limited, surgical resection and stereotactic radiosurgery, as well as their combination therapies, have shifted the paradigms for managing intracranial metastatic disease. Ultimately, no single treatment is shown to be consistently effective across patient groups in terms of overall survival, local and distant control, neurocognitive function, and performance status. However, close consideration of patient and tumor characteristics may help delineate more favorable treatment strategies for individual patients. Here the authors present a review of the recent literature surrounding surgery, whole brain radiation therapy, stereotactic radiosurgery, and combination approaches.

Time to Steroid Independence After Laser Interstitial Thermal Therapy vs Medical Management for Treatment of Biopsy-Proven Radiation Necrosis Secondary to Stereotactic Radiosurgery for Brain Metastasis.

BACKGROUND: Radiation necrosis (RN) after stereotactic radiosurgery (SRS) for brain metastases (BM) can result in significant morbidity, compounded by the effects of extended steroid therapy. Laser interstitial thermal therapy (LITT) is a minimally invasive procedure that can offer definitive treatment for RN while potentially obviating the need for prolonged steroid use. OBJECTIVE: To compare LITT vs medical management (MM) in the treatment of RN. METHODS: A multicenter, retrospective study was performed of SRS-treated patients with BM who developed biopsy-proven RN and were treated with LITT or MM. Clinical outcome data were compared by treatment modality. RESULTS: Seventy-two patients met criteria with a median follow-up of 10.0 months (4.2-25.1), and 57 patients (79%) underwent LITT. Four MM (27%) and 3 LITT patients (5%) demonstrated radiographic progression (P = .031) at a median of 5.3 and 4.0 months (P = .40). There was no significant difference in overall survival (LITT median of 15.2 vs 11.6 months, P = .60) or freedom from local progression (13.6 vs 7.06 months, P = .40). Patients stopped steroid therapy earlier in the LITT cohort at a median of 37 days compared with 245 days (P < .001). When controlled for follow-up duration, patients treated with LITT were 3 times more likely to be weaned off steroids before the study end point (P = .003). CONCLUSION: These data suggest that LITT for treatment of biopsy-proven RN after SRS for BM significantly decreases time to steroid independence. Prospective trials should be designed to further validate the utility of LITT for RN and its impact on steroid-induced morbidity.