Central nervous system immune interactome is a function of cancer lineage, tumor microenvironment, and STAT3 expression.

BACKGROUNDImmune cell profiling of primary and metastatic CNS tumors has been focused on the tumor, not the tumor microenvironment (TME), or has been analyzed via biopsies.METHODSEn bloc resections of gliomas (n = 10) and lung metastases (n = 10) were analyzed via tissue segmentation and high-dimension Opal 7-color multiplex imaging. Single-cell RNA analyses were used to infer immune cell functionality.RESULTSWithin gliomas, T cells were localized in the infiltrating edge and perivascular space of tumors, while residing mostly in the stroma of metastatic tumors. CD163+ macrophages were evident throughout the TME of metastatic tumors, whereas in gliomas, CD68+, CD11c+CD68+, and CD11c+CD68+CD163+ cell subtypes were commonly observed. In lung metastases, T cells interacted with CD163+ macrophages as dyads and clusters at the brain-tumor interface and within the tumor itself and as clusters within the necrotic core. In contrast, gliomas typically lacked dyad and cluster interactions, except for T cell CD68+ cell dyads within the tumor. Analysis of transcriptomic data in glioblastomas revealed that innate immune cells expressed both proinflammatory and immunosuppressive gene signatures.CONCLUSIONOur results show that immunosuppressive macrophages are abundant within the TME and that the immune cell interactome between cancer lineages is distinct. Further, these data provide information for evaluating the role of different immune cell populations in brain tumor growth and therapeutic responses.FUNDINGThis study was supported by the NIH (NS120547), a Developmental research project award (P50CA221747), ReMission Alliance, institutional funding from Northwestern University and the Lurie Comprehensive Cancer Center, and gifts from the Mosky family and Perry McKay. Performed in the Flow Cytometry & Cellular Imaging Core Facility at MD Anderson Cancer Center, this study received support in part from the NIH (CA016672) and the National Cancer Institute (NCI) Research Specialist award 1 (R50 CA243707). Additional support was provided by CCSG Bioinformatics Shared Resource 5 (P30 CA046592), a gift from Agilent Technologies, a Research Scholar Grant from the American Cancer Society (RSG-16-005-01), a Precision Health Investigator Award from University of Michigan (U-M) Precision Health, the NCI (R37-CA214955), startup institutional research funds from U-M, and a Biomedical Informatics & Data Science Training Grant (T32GM141746).

Laser Interstitial Thermal Therapy for Glioblastoma: A Single-Center Experience.

BACKGROUND: Surgical resection has been shown to prolong survival in patients with glioblastoma multiforme (GBM), although this benefit has not been demonstrated for reoperation following tumor recurrence. Laser interstitial thermal therapy (LITT) is a minimally invasive ablation technique that has been shown to effectively reduce tumor burden in some patients with intracranial malignancy. The aim of this study was to describe the safety and efficacy of LITT for recurrent and newly diagnosed GBM at a large tertiary referral center. METHODS: Patients with GBM receiving LITT were retrospectively analyzed. Overall survival from the time of LITT was the primary end point measured. RESULTS: There were 69 patients identified for inclusion in this study. The median age of the cohort was 56 years (range, 15-77 years). Median tumor volume was 10.4 cm3 (range, 1.0-64.0 cm3). A Kaplan-Meier estimate of median overall survival for the series from the time of LITT was 12 months (95% confidence interval 8-16 months). Median progression-free survival for the cohort from LITT was 4 months (95% confidence interval 3-7 months). Adjuvant chemotherapy significantly prolonged progression-free survival and overall survival (P < 0.01 for both) in the cohort. Gross total ablation was not significantly associated with progression-free survival (P = 0.09). CONCLUSIONS: LITT can safely reduce intracranial tumor burden in patients with GBM who have exhausted other adjuvant therapies or are poor candidates for conventional resection techniques.

The use of laser interstitial thermal therapy in the treatment of brain metastases: a literature review.

PURPOSE: The aim of this paper is to discuss the current evidence for Laser Interstitial Thermal Therapy (LITT) in the treatment of brain metastases, our current recommendations for patient selection and the future perspectives for this therapy. We have also touched upon the possible complications and role of systemic therapy coupled with LITT for the treatment of brain metastases. MATERIAL AND METHODS: Two authors carried out the literature search using two databases independently, including PubMed, and Web of Science. The review included prospective and retrospective studies using LITT to treat brain metastases. RESULTS: Twenty-two original articles were analyzed in this review, particularly clinical outcomes and complications. We have also provided our institutional experience in the use of LITT to treat brain metastases and addressed future perspectives for the use of this technology. CONCLUSIONS: The current literature supports LITT as a safe and effective therapy for patients with brain metastases that have failed SRS. Larger studies are still required to better evaluate the use of systemic therapy in concomitance with LITT. New images modalities may enable optimized treatment and outcomes.

A comparison of spinal laser interstitial thermotherapy with open surgery for metastatic thoracic epidural spinal cord compression.

OBJECTIVE: The proximity of the spinal cord to compressive metastatic lesions limits radiosurgical dosing. Open surgery is used to create safe margins around the spinal cord prior to spinal stereotactic radiosurgery (SSRS) but carries the risk of potential surgical morbidity and interruption of systemic oncological treatment. Spinal laser interstitial thermotherapy (SLITT) in conjunction with SSRS provides local control with less morbidity and a shorter interval to resume systemic treatment. The authors present a comparison between SLITT and open surgery in patients with metastatic thoracic epidural spinal cord compression to determine the advantages and disadvantages of each method. METHODS: This is a matched-group design study comprising patients from a single institution with metastatic thoracic epidural spinal cord compression that was treated either with SLITT or open surgery. The two cohorts defined by the surgical treatment comprised patients with epidural spinal cord compression (ESCC) scores of 1c or higher and were deemed suitable for either treatment. Demographics, pre- and postoperative ESCC scores, histology, morbidity, hospital length of stay (LOS), complications, time to radiotherapy, time to resume systemic therapy, progression-free survival (PFS), and overall survival (OS) were compared between groups. RESULTS: Eighty patients were included in this analysis, 40 in each group. Patients were treated between January 2010 and December 2016. There was no significant difference in demographics or clinical characteristics between the cohorts. The SLITT cohort had a smaller postoperative decrease in the extent of ESCC but a lower estimated blood loss (117 vs 1331 ml, p < 0.001), shorter LOS (3.4 vs 9 days, p < 0.001), lower overall complication rate (5% vs 35%, p = 0.003), fewer days until radiotherapy or SSRS (7.8 vs 35.9, p < 0.001), and systemic treatment (24.7 vs 59 days, p = 0.015). PFS and OS were similar between groups (p = 0.510 and p = 0.868, respectively). CONCLUSIONS: The authors' results have shown that SLITT plus XRT is not inferior to open decompression surgery plus XRT in regard to local control, with a lower rate of complications and faster resumption of oncological treatment. A prospective randomized controlled study is needed to compare SLITT with open decompressive surgery for ESCC.

Minimally Invasive Separation Surgery for Metastases in the Vertebral Column: A Technical Report.

BACKGROUND: Epidural spinal cord compression (ESCC) is a common and severe cause of morbidity in cancer patients. Minimally invasive surgical techniques may be utilized to preserve neurological function and permit the use of radiation to maximize local control. Minimally invasive techniques are associated with lower morbidity. OBJECTIVE: To describe a novel, minimally invasive operative technique for the management of metastatic ESCC. METHODS: A minimally invasive approach was used to cannulate the pedicles of the thoracic vertebrae, which were then held in place by Kirschner wires (K-wires). Following open decompression of the spinal cord, cannulated screws were placed percutaneously with stereotactic guidance through the pedicles followed by cement induction. Stereotactic radiosurgery is performed in the postoperative period for residual metastatic disease in the vertebral body. RESULTS: The minimally invasive technique used in this case reduced tissue damage and optimized subsequent recovery without compromising the quality of decompression or the extent of metastatic tumor resection. Development of more minimally invasive techniques for the management of metastatic ESCC has the potential to facilitate healing and preserve quality of life in patients with systemic malignancy. CONCLUSION: ESCC from vertebral metastases poses a challenge to treat in the context of minimizing potential risks to preserve quality of life. Percutaneous pedicle screw fixation with cement augmentation provides a minimally invasive alternative for definitive treatment of these patients.

Predictors of Local Control of Brain Metastasis Treated With Laser Interstitial Thermal Therapy.

BACKGROUND: Laser Interstitial Thermal Therapy (LITT) has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS. OBJECTIVE: To evaluate the predictive factors associated with local recurrence after LITT. METHODS: Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence. RESULTS: A total of 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence, and 31 radiation necrosis). Freedom from local recurrence at 6 mo was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 mo. Incompletely ablated lesions had a shorter median time for local recurrence (P < .001). Larger lesions (>6 cc) had shorter time for local recurrence (P = .03). Dural-based lesions showed a shorter time to local recurrence (P = .01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (P = .01). Patients receiving systemic therapy after LITT had longer time to local recurrence (P = .01). In multivariate Cox-regression model, the HR for incomplete ablated lesions was 4.88 (P < .001), 3.12 (P = .03) for recurrent tumors, and 2.56 (P = .02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%. CONCLUSION: Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.

Laser Interstitial Thermal Therapy to the Posterior Fossa: Challenges and Nuances.

BACKGROUND: Posterior fossa tumors are rare in adults and pose a challenge to treat due to the bony contour of the posterior fossa, complex anatomical structures including deep venous sinuses, and the proximity of the fourth ventricle and brain stem. We describe our experience with laser interstitial thermal therapy (LITT) for the management of brain metastases and radiation necrosis of the posterior fossa. METHODS: We retrospectively analyzed 13 patients with metastases and radiation necrosis of the posterior fossa managed with LITT. RESULTS: Thirteen patients with histopathologically confirmed radiation necrosis (n = 5) and metastases (n = 8) of the posterior fossa underwent LITT. The median preoperative tumor was 4.66 cm3, and median postoperative ablation cavity volume was 6.29 cm3. The median volume of the ablation cavity was decreased to 2.90 cm3 at a 9-month follow-up. The median volume of peritumoral edema was 12.25 cm3, which fell to a median of 5.77 cm3 at 1-month follow-up. The median progression-free survival was 7 months (range, 3-14 months) and the mean overall survival was 40 months (range, 2-49 months) after LITT. There were no intraoperative complications. One patient experienced palsy of the seventh and eighth cranial nerves on follow-up, attributable to LITT. CONCLUSIONS: Lesions of the posterior fossa are challenging to treat given their proximity to the dura and venous sinuses. Our findings demonstrate that LITT ablation may be a safe and feasible option for metastases and radiation necrosis of the posterior fossa. Larger studies are needed to confirm the efficacy of this approach.

Image guidance based on MRI for spinal interstitial laser thermotherapy: technical aspects and accuracy.

OBJECTIVE Image guidance for spinal procedures is based on 3D-fluoroscopy or CT, which provide poor visualization of soft tissues, including the spinal cord. To overcome this limitation, the authors developed a method to register intraoperative MRI (iMRI) of the spine into a neuronavigation system, allowing excellent visualization of the spinal cord. This novel technique improved the accuracy in the deployment of laser interstitial thermal therapy probes for the treatment of metastatic spinal cord compression. METHODS Patients were positioned prone on the MRI table under general anesthesia. Fiducial markers were applied on the skin of the back, and a plastic cradle was used to support the MRI coil. T2-weighted MRI sequences of the region of interest were exported to a standard navigation system. A reference array was sutured to the skin, and surface matching of the fiducial markers was performed. A navigated Jamshidi needle was advanced until contact was made with the dorsal elements; its position was confirmed with intraoperative fluoroscopy prior to advancement into a target in the epidural space. A screenshot of its final position was saved, and then the Jamshidi needle was exchanged for an MRI-compatible access cannula. MRI of the exact axial plane of each access cannula was obtained and compared with the corresponding screenshot saved during positioning. The discrepancy in millimeters between the trajectories was measured to evaluate accuracy of the image guidance RESULTS Thirteen individuals underwent implantation of 47 laser probes. The median absolute value of the discrepancy between the location predicted by the navigation system and the actual position of the access cannulas was 0.7 mm (range 0-3.2 mm). No injury or adverse event occurred during the procedures. CONCLUSIONS This study demonstrates the feasibility of image guidance based on MRI to perform laser interstitial thermotherapy of spinal metastasis. The authors' method permits excellent visualization of the spinal cord, improving safety and workflow during laser ablations in the epidural space. The results can be extrapolated to other indications, including biopsies or drainage of fluid collections near the spinal cord.

Spinal Laser Interstitial Thermal Therapy: A Novel Alternative to Surgery for Metastatic Epidural Spinal Cord Compression.

BACKGROUND: Although surgery followed by radiation effectively treats metastatic epidural compression, the ideal surgical approach should enable fast recovery and rapid institution of radiation and systemic therapy directed at the primary tumor. OBJECTIVE: To assess spinal laser interstitial thermotherapy (SLITT) as an alternative to surgery monitored in real time by thermal magnetic resonance (MR) images. METHODS: Patients referred for spinal metastasis without motor deficits underwent MR-guided SLITT, followed by stereotactic radiosurgery. Clinical and radiological data were gathered prospectively, according to routine practice. RESULTS: MR imaging-guided SLITT was performed on 19 patients with metastatic epidural compression. No procedures were discontinued because of technical difficulties, and no permanent neurological injuries occurred. The median follow-up duration was 28 weeks (range 10-64 weeks). Systemic therapy was not interrupted to perform the procedures. The mean preoperative visual analog scale scores of 4.72 (SD ± 0.67) decreased to 2.56 (SD ± 0.71, P = .043) at 1 month and remained improved from baseline at 3.25 (SD ± 0.75, P = .021) 3 months after the procedure. The preoperative mean EQ-5D index for quality of life was 0.67 (SD ± 0.07) and remained without significant change at 1 month 0.79 (SD ± 0.06, P = .317) and improved at 3 months 0.83 (SD ± 0.06, P = .04) after SLITT. Follow-up MR imaging after 2 months revealed significant decompression of the neural component in 16 patients. However, 3 patients showed progression at follow-up, 1 was treated with surgical decompression and stabilization and 2 were treated with repeated SLITT. CONCLUSION: MR-guided SLITT can be both a feasible and safe alternative to separation surgery in carefully selected cases of spinal metastatic tumor epidural compression. ABBREVIATIONS: cEBRT, conventional external beam radiation therapyESCC, epidural spinal cord compressionSLITT, spinal laser interstitial thermotherapySSRS, stereotactic spinal radiosurgeryVAS, visual analog scale.

Percutaneous surgery for treatment of epidural spinal cord compression and spinal instability: technical note.

OBJECTIVE An emerging paradigm for treating patients with epidural spinal cord compression (ESCC) caused by metastatic tumors is surgical decompression and stabilization, followed by stereotactic radiosurgery. In the setting of rapid progressive disease, interruption or delay in return to systemic treatment can lead to a negative impact in overall survival. To overcome this limitation, the authors introduce the use of spinal laser interstitial thermotherapy (sLITT) in association with percutaneous spinal stabilization to facilitate a rapid return to oncological treatment. METHODS The authors retrospectively reviewed a consecutive series of patients with ESCC and spinal instability who were considered to be poor surgical candidates and instead were treated with sLITT and percutaneous spinal stabilization. Demographic data, Spine Instability Neoplastic Scale score, degree of epidural compression before and after the procedure, length of hospital stay, and time to return to oncological treatment were analyzed. RESULTS Eight patients were treated with thermal ablation and percutaneous spinal stabilization. The primary tumors included melanoma (n = 3), lung (n = 3), thyroid (n = 1), and renal cell carcinoma (n = 1). The median Karnofsky Performance Scale score before and after the procedure was 60, and the median hospital stay was 5 days (range 3-18 days). The median Spine Instability Neoplastic Scale score was 13 (range 12-16). The mean modified postoperative ESCC score (2.75 ± 0.37) was significantly lower than the preoperative score (4.5 ± 0.27) (Mann-Whitney test, p = 0.0044). The median time to return to oncological treatment was 5 days (range 3-10 days). CONCLUSIONS The authors present the first cohort of sLITT associated with a percutaneous spinal stabilization for the treatment of ESCC and spinal instability. This minimally invasive technique can allow a faster recovery without prejudice of adjuvant systemic treatment, with adequate local control and spinal stabilization.

Utilization of laser interstitial thermotherapy guided by real-time thermal MRI as an alternative to separation surgery in the management of spinal metastasis.

OBJECT: High-grade malignant spinal cord compression is commonly managed with a combination of surgery aimed at removing the epidural tumor, followed by spinal stereotactic radiosurgery (SSRS) aimed at local tumor control. The authors here introduce the use of spinal laser interstitial thermotherapy (SLITT) as an alternative to surgery prior to SSRS. METHODS: Patients with a high degree of epidural malignant compression due to radioresistant tumors were selected for study. Visual analog scale (VAS) scores for pain and quality of life were obtained before and within 30 and 60 days after treatment. A laser probe was percutaneously placed in the epidural space. Real-time thermal MRI was used to monitor tissue damage in the region of interest. All patients received postoperative SSRS. The maximum thickness of the epidural tumor was measured, and the degree of epidural spinal cord compression (ESCC) was scored in pre- and postprocedure MRI. RESULTS: In the 11 patients eligible for study, the mean VAS score for pain decreased from 6.18 in the preoperative period to 4.27 within 30 days and 2.8 within 60 days after the procedure. A similar VAS interrogating the percentage of quality of life demonstrated improvement from 60% preoperatively to 70% within both 30 and 60 days after treatment. Imaging follow-up 2 months after the procedure demonstrated a significant reduction in the mean thickness of the epidural tumor from 8.82 mm (95% CI 7.38-10.25) before treatment to 6.36 mm (95% CI 4.65-8.07) after SLITT and SSRS (p = 0.0001). The median preoperative ESCC Grade 2 was scored as 4, which was significantly higher than the score of 2 for Grade 1b (p = 0.04) on imaging follow-up 2 months after the procedure. CONCLUTIONS: The authors present the first report on an innovative minimally invasive alternative to surgery in the management of spinal metastasis. In their early experience, SLITT has provided local control with low morbidity and improvement in both pain and the quality of life of patients.