A phase II study of laser interstitial thermal therapy combined with doxorubicin in patients with recurrent glioblastoma.
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ABSTRACT: Background
The blood-brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability.Methods
Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6-8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared to historical controls treated with bevacizumab salvage therapy (n = 50) or LITT with standard BBB-permeable salvage therapy (n = 28). Cox proportional-hazards models examined the contribution of age, gender, MGMT promoter status, and IDH-mutation status on any PFS and OS. Adverse events were also cataloged.Results
The Late Arm and all patients (Early Arm + Late Arm) demonstrated significant improvement in OS compared to historical controls treated with bevacizumab (p < 0.001) and LITT with standard salvage therapy (p < 0.05). No significant difference in any PFS was observed between either arm and historical controls. Low-dose doxorubicin was well tolerated with comparable adverse event rates between the arms.Conclusions
Low-dose doxorubicin given after LITT is well tolerated and correlated with higher OS compared to historical controls treated with bevacizumab or LITT with standard salvage chemotherapy. A larger study is needed to further characterize survival and progression patterns.
SUBMITTER: Butt OH
PROVIDER: S-EPMC8694207 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEvaluate 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.MethodsOf 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.ResultsThirty-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 (r = 0.53) with future areas of GBM recurrence (P < .01). Areas of future recurrence demonstrated a 37% increase in the ADC value (P < .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 (P < .01).ConclusionsDWI 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.
| S-EPMC7212867 | biostudies-literature
Project description:Despite the improved understanding of the molecular and genetic heterogeneity of glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into the role of the immune microenvironment has generated enthusiasm for testing immunotherapy (specifically, immune checkpoint inhibitors). However, to date, trials of immunotherapy in glioblastoma have not demonstrated a survival advantage. Combination approaches aimed at optimally inducing response to immune checkpoint inhibitors with radiotherapy are currently being investigated. Herein, the authors describe their experience of the potential benefit and clinical outcomes of using combination pembrolizumab (an immune checkpoint inhibitor) and laser interstitial thermal therapy in a case series of patients with recurrent IDH-wild-type glioblastoma.
| S-EPMC8988254 | biostudies-literature
Project description:BackgroundLaser interstitial thermal therapy (LITT) is a minimal invasive neurosurgical technique for the treatment of brain tumors. Results of LITT have been reported in a case series of patients with deep seated and/or recurrent glioblastoma or cerebral metastases. With this review we aim to summarize the currently available evidence regarding safety and effectiveness of LITT in patients with newly diagnosed glioblastoma (nGBM).MethodsA literature search was performed using electronic databases (PubMed and Embase). Papers were assessed for the methodological quality using the Risk Of Bias In Non- randomised Studies - of Interventions (ROBINS-I) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the quality of the evidence.ResultsWe identified 835 papers of which only 11 articles were eligible for our review. All papers suffered from serious or critical risk of bias, and the quality of evidence was graded as very low according to the GRADE criteria. None of the studies was randomized and reporting of confounders and other parameters was poor. Median overall survival (OS) ranged from 4.1 to 32 months and progression free survival (PFS) from 2 to 31 months. The mean complication rate was 33.7%. No quality of life or cost-effectiveness data were reported.ConclusionsDue to the low quality of the studies, it is not possible to draw firm conclusions regarding the (cost) effectiveness of LITT in patients with newly diagnosed glioblastoma. The low quality of evidence shows the need for a well-designed prospective multicenter randomized controlled trial.
| S-EPMC7832350 | biostudies-literature
Project description:BACKGROUND:Glioblastoma of the corpus callosum is particularly difficult to treat, as the morbidity of surgical resection generally outweighs the potential survival benefit. Laser interstitial thermal therapy (LITT) is a safe and effective treatment option for difficult to access malignant gliomas of the thalamus and insula. OBJECTIVE:To assess the safety and efficacy of LITT for the treatment of glioblastoma of the corpus callosum. METHODS:We performed a multicenter retrospective analysis of prospectively collected data. The primary endpoint was the safety and efficacy of LITT as a treatment for glioblastoma of the corpus callosum. Secondary endpoints included tumor coverage at thermal damage thresholds, median survival, and change in Karnofsky Performance Scale score 1 mo after treatment. RESULTS:The study included patients with de novo or recurrent glioblastoma of the corpus callosum (n = 15). Mean patient age was 54.7 yr. Mean pretreatment Karnofsky Performance Scale score was 80.7 and there was no significant difference between subgroups. Mean tumor volume was 18.7 cm3. Hemiparesis occurred in 26.6% of patients. Complications were more frequent in patients with tumors >15 cm3 (RR 6.1, P = .009) and were associated with a 32% decrease in survival postLITT. Median progression-free survival, survival postLITT, and overall survival were 3.4, 7.2, and 18.2 mo, respectively. CONCLUSION:LITT is a safe and effective treatment for glioblastoma of the corpus callosum and provides survival benefit comparable to subtotal surgical resection with adjuvant chemoradiation. LITT-associated complications are related to tumor volume and can be nearly eliminated by limiting the procedure to tumors of 15 cm3 or less.
| S-EPMC6939409 | biostudies-literature
Project description:BackgroundLaser 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.MethodsDemographics, 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.ResultsNinety 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.ConclusionsLITT 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.
| S-EPMC10129388 | biostudies-literature
Project description:BackgroundLaser interstitial thermal therapy (LITT) is a promising approach for cytoreduction of deep-seated gliomas. However, parameters contributing to treatment success remain unclear.ObjectiveTo identify extent of ablation (EOA) and time to chemotherapy (TTC) as predictors of improved overall and progression-free survival (OS, PFS) and suggest laser parameters to achieve optimal EOA.MethodsDemographic, clinical, and survival data were collected retrospectively from 20 patients undergoing LITT for newly diagnosed glioblastoma (nGBM). EOA was calculated through magnetic resonance imaging-based volumetric analysis. Kaplan-Meier and multivariate Cox regression were used to examine the relationship between EOA with OS and PFS accounting for covariates (age, isocitrate dehydrogenase-1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase hypermethylation). The effect of laser thermodynamic parameters (power, energy, time) on EOA was identified through linear regression.ResultsMedian OS and PFS for the entire cohort were 36.2 and 3.5 mo respectively. Patient's with >70% EOA had significantly improved PFS compared to ≤70% EOA (5.2 vs 2.3 mo, P = .01) and trended toward improved OS (36.2 vs 11 mo, P = .07) on univariate and multivariate analysis. Total laser power was a significant predictor for increased EOA when accounting for preoperative lesion volume (P = .001). Chemotherapy within 16 d of surgery significantly predicted improved PFS compared to delaying chemotherapy (9.4 vs 3.1 mo, P = .009).ConclusionIncreased EOA was a predictor of improved PFS with evidence of a trend toward improved OS in LITT treatment of nGBM. A strategy favoring higher laser power during tumor ablation may achieve optimal EOA. Early transition to chemotherapy after LITT improves PFS.
| S-EPMC8364818 | biostudies-literature
Project description:BackgroundImproved 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.MethodsA 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.ResultsFifty-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).ConclusionsThese 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.
| S-EPMC9248774 | biostudies-literature
Project description:INTRODUCTION:The recent emergence of laser interstitial thermal therapy (LITT) as a frontline surgical tool in the management of brain tumors and epilepsy is a result of advances in MRI thermal imaging. A limitation to further improving LITT is the diversity of brain tissue thermoablative properties, which hinders our ability to predict LITT treatment-related effects. Utilizing the mesiotemporal lobe as a consistent anatomic model system, the goal of this study was to use intraoperative thermal damage estimate (TDE) maps to study short- and long-term effects of LITT and to identify preoperative variables that could be helpful in predicting tissue responses to thermal energy. METHODS:For 30 patients with mesiotemporal epilepsy treated with LITT at a single institution, intraoperative TDE maps and pre-, intra- and post-operative MRIs were co-registered in a common reference space using a deformable atlas. The spatial overlap of TDE maps with manually-traced immediate (post-ablation) and delayed (6-month) ablation zones was measured using the dice similarity coefficient (DSC). Then, motivated by simple heat-transfer models, ablation dynamics were quantified at amygdala and hippocampal head from TDE pixel time series fit by first order linear dynamics, permitting analysis of the thermal time constant (?). The relationships of these measures to 16 independent variables derived from patient demographics, mesiotemporal anatomy, preoperative imaging characteristics and the surgical procedure were examined. RESULTS:TDE maps closely overlapped immediate ablation borders but were significantly larger than the ablation cavities seen on delayed imaging, particularly at the amygdala and hippocampal head. The TDEs more accurately predicted delayed LITT effects in patients with smaller perihippocampal CSF spaces. Analyses of ablation dynamics from intraoperative TDE videos showed variable patterns of lesion progression after laser activation. Ablations tended to be slower for targets with increased preoperative T2 MRI signal and in close proximity to large, surrounding CSF spaces. In addition, greater laser energy was required to ablate mesial versus lateral mesiotemporal structures, an effect associated with laser trajectory and target contrast-enhanced T1 MRI signal. CONCLUSIONS:Patient-specific variations in mesiotemporal anatomy and pathology may influence the thermal coagulation of these tissues. We speculate that by incorporating demographic and imaging data into predictive models we may eventually enhance the accuracy and precision with which LITT is delivered, improving outcomes and accelerating adoption of this novel tool.
| S-EPMC6034782 | biostudies-literature
Project description:ObjectiveMagnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRg-LITT) is an alternative to open epilepsy surgery. We assess safety and effectiveness of MRg-LITT for extratemporal lobe epilepsy (ETLE) in patients who are considered less favorable for open resection.MethodsWe retrospectively reviewed sequential cases of patients with focal ETLE who underwent MRg-LITT between 2012 and 2019. Epileptogenic zones were determined from standard clinical and imaging data ± stereoelectroencephalography (SEEG). Standard stereotactic techniques, MRI thermometry, and a commercial laser thermal therapy system were used for ablations. Anatomic MRI was used to calculate ablation volumes. Clinical outcomes were determined longitudinally.ResultsThirty-five patients with mean epilepsy duration of 21.3 ± 12.2 years underwent MRg-LITT for focal ETLE at a mean age 36.4 ± 12.7 years. A mean 2.59 ± 1.45 trajectories per patient were used to obtain ablation volumes of 8.8 ± 7.5 cm3 . Mean follow-up was 27.3 ± 19.5 months. Of 32 patients with >12 months of follow-up, 17 (53%) achieved good outcomes (Engel class I + II) of whom 14 (44%) were Engel class I. Subgroup analysis revealed better outcomes for patients with lesional ETLE than for those who were nonlesional, multifocal, or who had failed prior interventions (P = .02). Of 13 patients showing favorable seizure-onset patterns (localized low voltage fast activity or rhythmic spiking on SEEG) prior to ablation, 9 (69%) achieved good outcomes, whereas only 3 of 11 (27%) who show other slower onset patterns achieved good outcomes. Minor adverse events included six patients with transient sensorimotor neurologic deficits and four patients with asymptomatic hemorrhages along the fiber tract. Major adverse events included one patient with a brain abscess that required stereotactic drainage and one patient with persistent hypothalamic obesity. Three deaths-two seizure-associated and one suicide-were unrelated to surgical procedures.SignificanceMRI-guided laser interstitial thermal therapy (or MRg-LITT) was well-tolerated and yielded good outcomes in a heterogeneous group of ETLE patients. Lesional epilepsy and favorable seizure-onset patterns on SEEG predicted higher likelihoods of success.
| S-EPMC8019400 | biostudies-literature
Project description:BackgroundLaser interstitial thermal therapy (LITT) has recently gained popularity as a minimally invasive surgical option for the treatment of mesiotemporal epilepsy (mTLE). Similar to traditional open procedures for epilepsy, the most frequent neurological complications of LITT are visual deficits; however, a critical analysis of these injuries is lacking.ObjectivesTo evaluate the visual deficits that occur after LITT for mTLE and their etiology.MethodWe surveyed five academic epilepsy centers that regularly perform LITT for cases of self-reported postoperative visual deficits. For these patients all pre-, intra- and postoperative MRIs were co-registered with an anatomic atlas derived from 7T MRI data. This was used to estimate thermal injury to early visual pathways and measure imaging variables relevant to the LITT procedure. Using logistic regression, we then compared 14 variables derived from demographics, mesiotemporal anatomy, and the surgical procedure for the patients with visual deficits to a normal cohort comprised of the first 30 patients to undergo this procedure at a single institution.ResultsOf 90 patients that underwent LITT for mTLE, 6 (6.7%) reported a postoperative visual deficit. These included 2 homonymous hemianopsias (HHs), 2 quadrantanopsias, and 2 cranial nerve (CN) IV palsies. These deficits localized to the posterior aspect of the ablation, corresponding to the hippocampal body and tail, and tended to have greater laser energy delivered in that region than the normal cohort. The patients with HH had insult localized to the lateral geniculate nucleus, which was -associated with young age and low choroidal fissure CSF volume. Quadrantanopsia, likely from injury to the optic radiation in Meyer's loop, was correlated with a lateral trajectory and excessive energy delivered at the tail end of the ablation. Patients with CN IV injury had extension of contrast to the tentorial edge associated with a mesial laser trajectory.ConclusionsLITT for epilepsy may be complicated by various classes of visual deficit, each with distinct etiology and clinical significance. It is our hope that by better understanding these injuries and their mechanisms we can eventually reduce their occurrence by identifying at-risk patients and trajectories and appropriately tailoring the ablation procedure.
| S-EPMC7998682 | biostudies-literature