scholarly journals A phase II study of laser interstitial thermal therapy combined with doxorubicin in patients with recurrent glioblastoma

Author(s):  
Omar H Butt ◽  
Alice Y Zhou ◽  
Jiayi Huang ◽  
William A Leidig ◽  
Alice E Silberstein ◽  
...  

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.

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii25-iii25
Author(s):  
Emily Lerner ◽  
Ethan Srinivasan ◽  
Eric Sankey ◽  
Matthew Grabowski ◽  
Andrew Griffin ◽  
...  

Abstract Introduction Laser interstitial thermal therapy (LITT) is a minimally-invasive treatment option often used for patients with deep-seated intracranial lesions. It has been implemented as a definitive treatment for radiation necrosis (RN), which occurs in 9–14% of patients after stereotactic radiosurgery (SRS) for brain metastases (BM). Medical management (MM) with steroids is a common first-line therapy, with variable response and numerous side effects, especially regarding immunotherapy. Methods Patients with biopsy-proven RN after SRS for BM who received LITT or MM at two academic centers were retrospectively reviewed. Treatment failure was defined as radiographic progression that necessitated a change in management. Measurements of total (TLV) and contrast-enhancing lesion volume (ceLV) were obtained from MRI by semi-automated analysis using the BrainLab iPlan Cranial 3.0 software. Results Seventy-two patients were followed for 10.0 (4.2–25.1) months and 57 (79%) received LITT. Steroid cessation occurred at a median of 37 days post-LITT compared to 245 days after MM (p<0.01). On Kaplan-Meier analyses, there was no significant difference between the two groups in overall survival (LITT median of 15.2 months vs 11.6 months, p = 0.60) or freedom from local progression (13.6 months vs. 7.06 months), though LITT trended to show a benefit in both metrics. When controlled for follow-up duration, patients treated with LITT were three times more likely to be weaned off steroids prior to the study endpoint compared to those who were medically managed (p=0.003). The LITT cohort demonstrated a general radiographic trend of initially increased CeLV followed by contraction, with significant decreases from pre-operative at 10–12 months (p<0.01). The MM group did not demonstrate any statistically significant radiographic trends. Conclusion These results suggest that LITT for RN significantly reduces the time to steroid cessation and characterize a stereotyped radiographic response to LITT. Future prospective studies will be important to their validation.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii206-ii206
Author(s):  
Hassan Fadel ◽  
Sameah Haider ◽  
Jacob Pawloski ◽  
Hesham Zakaria ◽  
Farhan Chaudhry ◽  
...  

Abstract INTRODUCTION Glioblastoma (GBM) is uniformly associated with a poor prognosis and inevitable recurrence. Management of recurrent GBM remains unclear, with repeat surgery often employed with varying degrees of success. We evaluated the efficacy of Laser Interstitial Thermal Therapy (LITT) for recurrent GBM when compared to a carefully matched cohort of patients treated with repeat surgical resection. METHODS A retrospective single-institution database was used to identify patients who underwent LITT or surgical resection of recurrent GBM between 2014-2019. LITT patients were matched with surgical resection patients according to baseline demographics, comorbidities, tumor location, and eloquence. Subgroup analysis matching similar patients for tumor volume was also completed. Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. RESULTS A LITT cohort of 20 patients was matched to 50 similar patients who underwent repeat surgical resection. Baseline characteristics were similar between both cohorts apart from tumor volume, which was larger in the surgical cohort (17.5 cc vs. 4.7 cc, p< 0.01). On long-term follow-up, there was no difference in OS (HR, 0.72; 95%CI, 0.36-1.45) or PFS (HR, 0.67; 95%CI, 0.29-1.53) between the LITT and surgical cohorts when controlling for tumor volume. Subgroup analysis of 23 LITT patients matched according to tumor volume with 23 surgical patients with similar clinical characteristics also found no difference in OS (HR, 0.66; 95%CI, 0.33-1.30) or PFS (HR, 0.58; 95%CI, 0.90-1.05) between the cohorts. LITT patients had shorter length of stays (1 vs. 4 days, p< 0.001) and a higher rate of home discharge (84% vs. 67%, p=0.172) compared to the surgical cohort. CONCLUSION After matching for demographic, clinical, and tumor characteristics, there was no difference in outcomes between patients undergoing LITT compared to surgical resection for recurrent GBM. LITT patients had similar survival outcomes yet shorter hospital stays and more favorable dispositions, potentially mitigating post-treatment complications.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii144-ii144
Author(s):  
Elizabeth Ginalis ◽  
Shabbar Danish

Abstract INTRODUCTION There is a paucity of studies assessing the use of magnetic resonance-guided laser interstitial thermal therapy (LITT) in the elderly population. METHODS Geriatric patients (≥65 years) treated with LITT for intracranial tumors at a single institution from January 2011 to November 2019 were retrospectively identified. We grouped patients into two cohorts: 65-74 years (group 1) and 75 years or older (group 2). Baseline characteristics, operative parameters, postoperative course, and morbidity were recorded. RESULTS There were 55 patients who underwent 64 distinct LITT procedures. The majority of tumors (62.5%) treated were recurrent brain metastasis/radiation necrosis. The median hospital length of stay was 1 day, with no significant difference between age groups. Hospital stay was significantly longer in patients who presented with a neurological symptom and in those who experienced a postoperative complication. The majority of patients (68.3%) were discharged to their preoperative accommodation. Rate of discharge to home was not significantly different between age groups. Those discharged to rehabilitation facilities were more likely to have presented with a neurological symptom. Nine patients (14.1%) were found to have acute neurological complications, with nearly all patients showing complete or partial recovery at follow-up. The 30-day postoperative mortality rate was 1.6% (n = 1). The complication and 30-day postoperative mortality rate were not significantly different between age groups. CONCLUSIONS LITT can be considered as a minimally invasive and safe neurosurgical procedure for treatment of intracranial tumors in geriatric patients. Careful preoperative preparation and postoperative care is essential as LITT is not without risk. Appropriate patient selection for cranial surgery is essential as neurosurgeons treat an increasing number of elderly patients, but advanced age alone should not exclude patients from LITT.


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i31-i32
Author(s):  
Christopher Hong ◽  
Di Deng ◽  
Nanthiya Sujijantarat ◽  
Alberto Vera ◽  
Veronica Chiang

Abstract Many publications report laser-interstitial thermal therapy (LITT) as a viable alternative treatment to craniotomy for radiation necrosis (RN) and re-growing tumor occurring after stereotactic radiosurgery (SRS) for brain metastases. No studies to-date have compared the two options. The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for regrowing lesions in patients previously treated with SRS for brain metastases. Data were collected from a single-institution chart review of patients treated with LITT or craniotomy for previously irradiated brain metastasis. Of 75 patients, 42 had recurrent tumor (56%) and 33 (44%) had RN. Of patients with tumor, 26 underwent craniotomy and 16 LITT. For RN, 15 had craniotomy and 18 LITT. There was no significant difference between LITT and craniotomy in ability to taper off steroids or neurological outcomes. Progression-free survival (PFS) and overall survival (OS) were similar for LITT versus craniotomy, respectively: %PFS-survival at 1-year = 72.2% versus 61.1%, %PFS-survival at 2-years = 60.0% versus 61.1%, p = 0.72; %OS-survival at 1-year = 69.0% versus 69.3%, %OS-survival at 2-years = 56.6% versus 49.5%, p = 0.90. This finding persisted on sub-analysis of smaller lesions under < 3cm in diameter. Craniotomy resulted in higher rates of pre-operative deficit improvement than LITT (p < 0.01). On sub-group analysis, the single factor most significantly associated with OS and PFS was pathology of the lesion. About 40% of tumor lesions needed post-operative salvage with radiation after both craniotomy and LITT. LITT was as efficacious as craniotomy in achieving local control of recurrent irradiated brain metastases and facilitating steroid taper, regardless of pathology. Craniotomy appears to be more advantageous for providing symptom relief in those with pre-operative symptoms.


2020 ◽  
Vol 20 (1) ◽  
pp. 18-23
Author(s):  
Kyle P O’Connor ◽  
Ali H Palejwala ◽  
Camille K Milton ◽  
Victor M Lu ◽  
Chad A Glenn ◽  
...  

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is being used for the treatment of recurrent glioblastoma multiforme (GBM). Lesions can be treated using 1 or multiple LITT fibers depending on the preference of surgeons. Usually, more fibers are needed for coverage of larger tumors. OBJECTIVE To investigate and analyze how tumor size affected the number of LITT fibers used. METHODS This is a retrospective review of patients undergoing treatment of recurrent GBM. Patients were treated with up to 4 LITT fibers for adequate tumor coverage. Patient demographics, tumor characteristics, length of stay, complications, and biopsy results were recorded. RESULTS A total of 43 cases were treated using LITT, and of these cases, 31 consisted of contiguous lesions. We used more fibers to treat larger tumor volumes. On average, for each 5 cc of tumor volume, a fiber was added for proper coverage (P = .554). Complications and length of stay were similar across the groups (P = .378, P = .941). CONCLUSION LITT can be used for the treatment of recurrent GBM. For each 5 cc of tumor volume, a LITT fiber can be added to the treatment plan.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi245-vi245
Author(s):  
Ali Palejwala ◽  
Kyle O’connor ◽  
Chad Glenn ◽  
Michael Sughrue

Abstract There have been publications that propose the use of laser interstitial thermal therapy (LITT) as a viable alternative to craniotomy for the treatment of glioblastoma (GBM). The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for patients with recurrent GBM. To adequately match the cohorts, we included only pre-treatment tumor volumes of under 15 cc. We retrospectively collected data on all patients presenting with recurrent GBM, with a recurrence volume under 15 cc. These patients were either treated with LITT or craniotomy by the senior author. Data included demographics, tumor location and volume, tumor markers, perioperative complications, re-initiation of adjuvant chemotherapy, and long-term follow up data. We performed 23 LITT treatments and 34 craniotomies for recurrent GBM in patients that met selection criteria. There was no significant difference in the patients’ age, tumor volume (6.38 for craniotomy versus 5.765 cc for LITT), location, and post-procedure KPS. Patients that underwent LITT had significantly reduced inpatient stays in comparison to craniotomy (1.7 versus 4.2 days). They also had less perioperative complications (13.0% versus 32.3% for craniotomy). It was found that 28 out of the 34 patients that underwent craniotomy were able to undergo adjuvant therapy; in comparison, 15 out of the 23 patients who underwent LITT had undergone adjuvant therapy. Of these patient’s that underwent adjuvant therapy, 87% of patients were able to receive bevacizumab or a clinical trial versus 42% after craniotomy. Progression-free survival (PFS) and overall survival (OS) after procedure were similar for LITT versus craniotomy, respectively: % PFS-survival at 6 months = 23.5% versus 21.7%. Overall survival did not significantly differ at 9 months versus 9.9 months respectively. LITT appears to be safe and may be as efficacious as craniotomy in achieving progression free survival for small to moderate volume recurrent GBM.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2074-TPS2074 ◽  
Author(s):  
Adilia Hormigo ◽  
John Mandeli ◽  
Constantinos Hadjipanayis ◽  
Sacha Gnjatic ◽  
Seunghee Kim-Schulze ◽  
...  

TPS2074 Background: Glioblastoma (GBM) the most frequent malignant brain tumor in the adult has a dismal prognosis and limited treatment options. Current advances have highlighted how tumors and specifically GBM evade the immune system by exploiting the mechanisms of tolerance and inducing local and systemic immunosuppression. Another hurdle in the treatment of GBM is the blood-brain barrier (BBB). Recent work suggests that MRI-guided laser interstitial thermal therapy (LITT) can increase the permeability of the BBB and may have an abscopal effect. Therefore, utilizing MRI-guided LITT, a potential immunogenic cell death-inducing procedure that disrupts the BBB and makes Avelumab a PD-L1 monoclonal antibody being more accessible to GBM tumors, seem a valid approach for immunomodulation and successful implementation of a combined regimen to treat brain cancer. Methods: This is a prospective non-randomized open label to characterize the tolerability and safety profile of Avelumab in combination with LITT in patients with recurrent glioblastoma who were treated with radiation therapy with concurrent Temozolomide chemotherapy at diagnosis, and whose tumor at recurrence measures less then 3 cm3. Avelumab is administered within a week after real-time MRI-guided LITT therapy and every 2 weeks thereafter. On part A patients are treated with intravenous Avelumab alone and on part B patients receive Avelumab in combination with MRI-guided LITT. Part A completed enrollment without DLT. Enrollment on part B began in October 2018. A Simon minimax two-stage design is being used for efficacy. Toxicity will be scored using the NCI-CTCAE 4.03 criteria. Blood samples and tumor tissue will be collected for correlative studies. Quantification of the changes in inflammatory and immunosuppressive profiles across time points for patients receiving treatment with Avelumab will be obtained. This information will instruct future immunotherapy approaches to treat GBM and the rational for those combinations. Clinical trial information: NCT03341806.


2016 ◽  
Vol 41 (4) ◽  
pp. E12 ◽  
Author(s):  
Jonathan G. Thomas ◽  
Ganesh Rao ◽  
Yvonne Kew ◽  
Sujit S. Prabhu

OBJECTIVE Glioblastoma (GBM) is the most common and deadly malignant primary brain tumor. Better surgical therapies are needed for newly diagnosed GBMs that are difficult to resect and for GBMs that recur despite standard therapies. The authors reviewed their institutional experience of using laser interstitial thermal therapy (LITT) for the treatment of newly diagnosed or recurrent GBMs. METHODS This study reports on the pre-LITT characteristics and post-LITT outcomes of 8 patients with newly diagnosed GBMs and 13 patients with recurrent GBM who underwent LITT. RESULTS Compared with the group with recurrent GBMs, the patients with newly diagnosed GBMs who underwent LITT tended to be older (60.8 vs 48.9 years), harbored larger tumors (22.4 vs 14.6 cm3), and a greater proportion had IDH wild-type GBMs. In the newly diagnosed GBM group, the median progression-free survival and the median survival after the procedure were 2 months and 8 months, respectively, and no patient demonstrated radiographic shrinkage of the tumor on follow-up imaging. In the 13 patients with recurrent GBM, 5 demonstrated a response to LITT, with radiographic shrinkage of the tumor following ablation. The median progression-free survival was 5 months, and the median survival was greater than 7 months. CONCLUSIONS In carefully selected patients with recurrent GBM, LITT may be an effective alternative to surgery as a salvage treatment. Its role in the treatment of newly diagnosed unresectable GBMs is not established yet and requires further study.


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