IMMU-02. PHASE I/II STUDY OF LASER INTERSTITIAL THERMOTHERAPY (LITT) COMBINED WITH CHECKPOINT INHIBITOR FOR RECURRENT GLIOBLASTOMA (RGBM): PRELIMINARY RESULTS

BACKGROUND Recurrent glioblastoma (rGBM) has poor response rate and survival. Laser Interstitial Thermotherapy (LITT), a minimally invasive approach, improves survival but is not curative alone. Previous studies of LITT suggested the possibility of an abscopal effect. Indeed, GBM are known to harbor elevated levels of immunosuppressive cells such as Treg, M2 macrophages and MDSC both in the tumor microenvironment as well as in the systemic circulation. Checkpoint inhibition (CPI) immunotherapy has proven highly effective for some solid tumors. CPI in newly diagnosed GBM demonstrated safety in phase I trials (NRG BN-002). Further, preclinical studies targeting PD-1 with concurrent RT appears to be synergistic and improve survival. We hypothesized that LITT would block tumor-induced immunosuppression and introduce tumor neoantigens. However, there was no data regarding safety of pembrolizumab combined with LITT. We thus conducted a phase I/II study of LITT + pembrolizumab starting at three times relative to LITT. METHODS This is a three armed Phase I/II study based on timing of pembrolizumab (200 mg q 21 days) relative to LITT at 35d or 14d post-op, or 7d pre-op, with an expansion cohort phase II arm conducted at the earliest tolerated time of CPI administration. Adults with proven supratentorial rGBM with KPS >=70 and <= 2mg/d of dexamethasone were eligible. RESULTS Arm 1-2 of the phase I trial demonstrated no SAEs grade II or greater, but limited evidence of response. Arm 3 (neoadjuvant) pembrolizumab appears to be equally safe and has been expanded to phase II, demonstrating at least two CR among the first 3 patients (66.6%) with >= 9 month follow-up and patients remain clinically stable at 10 and 15 months post-op. CONCLUSIONS Neoadjuvant pembrolizumab combined with LITT for rGBM appears to be safe in this phase I trial, and demonstrates early evidence of response. The phase II trial is ongoing.

Treatment of the pilonidal sinus in children using laser radiation

The work carried out a comparative analysis of the results of surgical treatment of the epithelial-coccygeal course of ECC in 133 children aged 3 to 17 years, using laser-induced interstitial thermotherapy (LIT) and open excision. Comparative analysis was carried out according to the following criteria: duration of surgery, average time of hospital stay, duration of pain syndrome on a 10-point scale (VAS), the presence of complications in the early and late postoperative period. In the main group, the average time of hospital stay was 4.9 ± 0.3; the duration of surgical treatment was 17.2 ± 2.8 minutes. The duration of the pain syndrome was 5.3 ± 2.1 hours, and its severity was 2.7 ± 0.8 points. Average terms of epithelialization of fistulas are 3.1 ± 2.8 days. Recurrence of ECC was observed in 7 patients (11.7%), which required re-intervention. In 3 (5.0%) patients, LIT was used, and in 4 (6.7%), excision using plastics according to the Bascom method. In the comparison group, the duration of surgical treatment was 32.6 ± 5.4 minutes. The duration of inpatient treatment is 16.7 ± 1.4 days. Pain syndrome averaged 71.8 ± 11.9 hours, severity 6.5 ± 2.3 points. The number of relapses was 9 (12.3%), of which 5 (6.8%) children underwent laser treatment, and 4 (5.5%) repeated surgical excision with Bascom with recovery. This technique is an effective and minimally invasive method for treating ECC, which makes it possible to recommend this method for use in pediatric surgical practice.

Plasmonic Nanocomposite Implants for Interstitial Thermotherapy: Experimental and Computational Analysis

The ferromagnetic implant (thermoseeds) technique offers desirable features for interstitial thermotherapy. However, its efficacy has been reported to be limited by issues that are related to the properties of the metal alloys that are used to fabricate them and the high number of thermoseeds needed to achieve therapeutic temperature levels. Here, we present the results of a combination of experimental and computational analysis of plasmonic nanocomposite implants (photoseeds)—a combination of Au nanoparticles (NPs) and poly-dimethylsiloxane (PDMS)—as a model material. We performed structural and optical characterization of the Au NPs and repared Au-PDMS nanocomposites, followed by an elucidation of the heat generation capabilities of the Au-PDMS photoseeds in aqueous solution and in-vitro cancer cell suspension. Based on the experimental results, we developed a three-dimensional (3D) finite element method (FEM) model to predict in-vivo thermal damage profiles in breast tissue. The optical absorbance of the Au-PDMS photoseeds were increasing with the concentration of Au NPs. The photothermal measurements and the in-vivo predictions showed that the photothermal properties of the photoseeds, characteristics of the laser sources, and the duration of heating can be tuned to achieve therapeutic temperature levels under in-vitro and in-vivo conditions. Collectively, the results demonstrate the feasibility of using photoseeds for interstitial thermotherapy.

Laser interstitial thermotherapy (LITT) for the treatment of tumors of the brain and spine: a brief review

Introduction Laser Interstitial Thermotherapy (LITT; also known as Stereotactic Laser Ablation or SLA), is a minimally invasive treatment modality that has recently gained prominence in the treatment of malignant primary and metastatic brain tumors and radiation necrosis and studies for treatment of spinal metastasis has recently been reported. Methods Here we provide a brief literature review of the various contemporary uses for LITT and their reported outcomes. Results Historically, the primary indication for LITT has been for the treatment of recurrent glioblastoma (GBM). However, indications have continued to expand and now include gliomas of different grades, brain metastasis (BM), radiation necrosis (RN), other types of brain tumors as well as spine metastasis. LITT is emerging as a safe, reliable, minimally invasive clinical approach, particularly for deep seated, focal malignant brain tumors and radiation necrosis. The role of LITT for treatment of other types of tumors of the brain and for spine tumors appears to be evolving at a small number of centers. While the technology appears to be safe and increasingly utilized, there have been few prospective clinical trials and most published studies combine different pathologies in the same report. Conclusion Well-designed prospective trials will be required to firmly establish the role of LITT in the treatment of lesions of the brain and spine.

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

OBJECTIVEThe 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.METHODSThis 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.RESULTSEighty 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).CONCLUSIONSThe 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.

A thermometry software tool for monitoring laser-induced interstitial thermotherapy

The purpose of this study was to develop a thermometry software tool for temperature monitoring during laser-induced interstitial thermotherapy (LITT). C++ programming language and several libraries including DICOM Toolkit, Grassroots DICOM library, Insight Segmentation and Registration Toolkit, Visualization Toolkit and Quasar Toolkit were used. The software’s graphical user interface creates windows displaying the temperature map and the coagulation extent in the tissue, determined by the magnetic resonance imaging (MRI) thermometry with the echo planar imaging sequence and a numerical simulation based on the radiation and heat transfer in biological tissues, respectively. The software was evaluated applying the MRI-guided LITT to ex vivo pig liver and simultaneously measuring the temperature through a fiber-optic thermometer as reference. Using the software, the temperature distribution determined by the MRI method was compared with the coagulation extent simulation. An agreement was shown between the MRI temperature map and the simulated coagulation extent. Furthermore, the MRI-based and simulated temperatures agreed with the measured one – a correlation coefficient of 0.9993 and 0.9996 was obtained, respectively. The precision of the MRI temperature amounted to 2.4°C. In conclusion, the software tool developed in the present study can be applied for monitoring and controlling the LITT procedure in ex vivo tissues.