Interstitial Therapy Research Articles

The role of neuromodulation in the management of drug-resistant epilepsy.

Drug-resistant epilepsy (DRE) poses significant challenges in terms of effective management and seizure control. Neuromodulation techniques have emerged as promising solutions for individuals who are unresponsive to pharmacological treatments, especially for those who are not good surgical candidates for surgical resection or laser interstitial therapy (LiTT). Currently, there are three neuromodulation techniques that are FDA-approved for the management of DRE. These include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Device selection, optimal time, and DBS and RNS target selection can also be challenging. In general, the number and localizability of the epileptic foci, alongside the comorbidities manifested by the patients, substantially influence the selection process. In the past, the general axiom was that DBS and VNS can be used for generalized and localized focal seizures, while RNS is typically reserved for patients with one or two highly localized epileptic foci, especially if they are in eloquent areas of the brain. Nowadays, with the advance in our understanding of thalamic involvement in DRE, RNS is also very effective for general non-focal epilepsy. In this review, we will discuss the underlying mechanisms of action, patient selection criteria, and the evidence supporting the use of each technique. Additionally, we explore emerging technologies and novel approaches in neuromodulation, such as closed-loop systems. Moreover, we examine the challenges and limitations associated with neuromodulation therapies, including adverse effects, complications, and the need for further long-term studies.This comprehensive review aims to provide valuable insights on present and future use of neuromodulation.

Functional outcomes in MRI-guided laser interstitial therapy for temporal lobe epilepsy: a systematic review and meta-analysis.

The use of MRI-guided laser interstitial thermal therapy (MRgLITT) has emerged as a promising treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). Although the minimally invasive approach holds promise as an effective treatment for achieving seizure freedom, a comprehensive review of its impact on functional outcomes is still warranted. To address this need, this review aims to summarize data pertaining to the functional and neurocognitive outcomes following MRgLITT for TLE. Four primary electronic databases were screened following PRISMA guidelines by two independent reviewers. All functional data related to cognitive, behavioral, and emotional outcomes were gathered and analyzed as well as the neuropsychological tests issued to assess pre- and postoperative outcomes. The functional outcomes assessed were grouped into the 5 most common categories: verbal cognition, visual cognition, cognitive emotion, visual deficits, and other higher-order cognitive functioning. A total of 4184 studies were screened and ultimately 408 patients from 14 studies were included for analysis. Changes in functional areas were assessed by comparing pre- and postoperative scores across a comprehensive set of 31 different functional and cognitive assessments, and were tabulated as the percentage of patients whose status improved, declined, or was maintained, where possible. In verbal (n = 112) and visual (n = 42) cognition, the rates of patients experiencing a decline were 20.4% and 13.5%, respectively, and the rates of improvement were 24.9% and 16.7%, respectively. Other functional outcomes assessed, including cognitive emotion (n = 150), visual deficits (n = 325), and higher-order cognitive processes like attention/processing (n = 19), motor cognition (n = 18), and general executive function (n = 4), exhibited varying rates of decline, ranging from 10.5% to 25%. MRgLITT is an effective and minimally invasive surgical alternative treatment for TLE, but there is an observable impact on patient functioning and cognitive status. This review demonstrates the need for standardized methods that can accurately capture and quantify the associated risk of MRgLITT to optimize its effect on patient quality of life moving forward.

Transnasal targeted delivery of therapeutics in central nervous system diseases: a narrative review.

Currently, neurointervention, surgery, medication, and central nervous system (CNS) stimulation are the main treatments used in CNS diseases. These approaches are used to overcome the blood brain barrier (BBB), but they have limitations that necessitate the development of targeted delivery methods. Thus, recent research has focused on spatiotemporally direct and indirect targeted delivery methods because they decrease the effect on nontarget cells, thus minimizing side effects and increasing the patient's quality of life. Methods that enable therapeutics to be directly passed through the BBB to facilitate delivery to target cells include the use of nanomedicine (nanoparticles and extracellular vesicles), and magnetic field-mediated delivery. Nanoparticles are divided into organic, inorganic types depending on their outer shell composition. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes. Magnetic field-mediated delivery methods include magnetic field-mediated passive/actively-assisted navigation, magnetotactic bacteria, magnetic resonance navigation, and magnetic nanobots-in developmental chronological order of when they were developed. Indirect methods increase the BBB permeability, allowing therapeutics to reach the CNS, and include chemical delivery and mechanical delivery (focused ultrasound and LASER therapy). Chemical methods (chemical permeation enhancers) include mannitol, a prevalent BBB permeabilizer, and other chemicals-bradykinin and 1-O-pentylglycerol-to resolve the limitations of mannitol. Focused ultrasound is in either high intensity or low intensity. LASER therapies includes three types: laser interstitial therapy, photodynamic therapy, and photobiomodulation therapy. The combination of direct and indirect methods is not as common as their individual use but represents an area for further research in the field. This review aims to analyze the advantages and disadvantages of these methods, describe the combined use of direct and indirect deliveries, and provide the future prospects of each targeted delivery method. We conclude that the most promising method is the nose-to-CNS delivery of hybrid nanomedicine, multiple combination of organic, inorganic nanoparticles and exosomes, via magnetic resonance navigation following preconditioning treatment with photobiomodulation therapy or focused ultrasound in low intensity as a strategy for differentiating this review from others on targeted CNS delivery; however, additional studies are needed to demonstrate the application of this approach in more complex in vivo pathways.

An Initial Experience of Completion Hemispherotomy via Magnetic Resonance-Guided Laser Interstitial Therapy

Introduction: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy. Methods: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively. Results: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8–12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342–1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2–3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246–475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0–5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384–918). No MRgLITT-related complications occurred. Delayed retreatment (>1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy. Conclusion: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted.

Clinical factors associated with late seizure remission after failed epilepsy surgery

BackgroundSome patients who initially fail epilepsy surgery later become seizure-free, but it is not clear how the clinical characteristics of the patients or post-operative modifications of anti-seizure medication (ASM) regimens contribute to late seizure remission. MethodsWe performed a retrospective chart review of patients undergoing epilepsy surgery at the University of Washington Regional Epilepsy Center between 2007 and 2017, including patients receiving neocortical resection, temporal lobectomy, and hippocampal laser interstitial therapy (LITT) ablation. We assessed seizure freedom, ASM changes, seizure frequency at the first and last follow-up, and type of lesion. Two-tailed Fisher’s exact test and Mann-Whitney U test were used for statistical analyses. ResultsTwo hundred and fifteen patients undergoing epilepsy surgery between 2007 and 2017 had both first and last follow-ups. Ninety-eight (46%) were not seizure-free at the first follow-up (mean 1.1 years post-operative). By the last follow-up (mean 4.7 years post-operative), 20% of those not initially seizure-free had become so. Those who were seizure-free at the last visit had lower median seizures per month in the first post-operative year (0.21 versus 0.95 per month in those not seizure-free, p < 0.001). There was also a significantly higher proportion of patients with cavernomas who were seizure-free at the last visit (25% vs. 1% of those not seizure-free at the last visit; p = 0.001), but no other differences in clinical characteristics. Of the 98 patients who had seizures at the first follow-up, 63% underwent post-operative modification of their ASM regimens. The rate of late seizure freedom was similar for patients with or without ASM changes: 21% were seizure-free at the last visit with ASM changes and 19% without ASM changes. There were no significant differences in which ASMs were changed between those who became seizure-free and those who did not, but patients who were subjected to further medical management were less likely to have had mesial temporal sclerosis (MTS) than those who were not. A number of patients not initially seizure-free who underwent ASM changes achieved seizure freedom as long as 10 years post-surgery. ConclusionA substantial proportion of patients who initially fail epilepsy surgery will have late seizure remission. Those with cavernous hemangiomas were more likely to achieve late remission from seizures as were those with lower rates of seizures in the first year after surgery. The chances of achieving remission were similar in those with or without modification of their ASM regimens, but those with pre-operative MTS were more likely to achieve late seizure freedom without medication changes. At the individual level, patients may still achieve seizure freedom with ASM changes as long as ten years after the initial surgery.

Magnetic Resonance Imaging–Guided Laser Interstitial Therapy for In-Field Recurrence After Stereotactic Radiosurgery: Is Complete Ablation Required for Local Control?

Magnetic resonance imaging-guided laser interstitial therapy (MrLITT) presents a new valuable treatment alternative when the in-field recurrence (IFR) of metastatic brain tumors is difficult to safely access with open surgery or maximum radiation therapy has already been completed. To examine the effects of MrLITT on longevity outcomes based on volume of ablation. A retrospective study was carried out of 35 patients treated with MrLITT for IFR after radiosurgery for metastatic brain tumors at a single institution from 2010 to 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed with Kaplan-Meier and Cox regression analyses according to ablation volume. Univariate and multivariate analyses further assessed risk factors based on ablation volume. Kaplan-Meier analyses showed no significant differences between total and subtotal ablation groups in OS (61.1 vs. 49.7 weeks) and PFS (45.1 and 42.7 weeks), respectively (P > 0.05). In the subtotal ablation group, independent risk factors included preoperative tumor volume (hazard ratio [HR], 1.24; P= 0.05) for OS and residual tumor volume (HR, 2.62; P= 0.01) for PFS. Multivariate Cox regressions suggested no significant differences in OS (HR, 1.03; P= 0.19) and PFS (HR, 1.02; P= 0.24) between total and subtotal ablation groups, whereas preoperative tumor volume remained a risk factor for decreased OS (HR, 1.23; P= 0.004). MrLITT is an effective treatment option for IFR after radiosurgery for metastatic brain tumors. The benefits of more aggressive gross total ablations of deep targets near eloquent cortices are limited compared with effective subtotal ablations, but the amount of residual tumor volume left must be appropriately balanced.

Effects of Metabolic Heat on The Temperature Distribution of Human Hands Affected by Sarcoma Tumors Given Interstitial Hyperthermia Therapy

Effects of Metabolic Heat on The Temperature Distribution of Human Hands Affected by Sarcoma Tumors Given Interstitial Hyperthermia Therapy

Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common form of primary brain cancer and has the highest morbidity rate and current treatments result in a bleak 5-year survival rate of 5.6%. Interstitial therapy is one option to increase survival. Drug delivery by interstitial therapy most commonly makes use of a polymer implant encapsulating a drug which releases as the polymer degrades. Interstitial therapy has been extensively studied as a treatment option for GBM as it provides several advantages over systemic administration of chemotherapeutics. Primarily, it can be applied behind the blood–brain barrier, increasing the number of possible chemotherapeutic candidates that can be used and reducing systemic levels of the therapy while concentrating it near the cancer source. With interstitial therapy, multiple drugs can be released locally into the brain at the site of resection as the polymer of the implant degrades, and the release profile of these drugs can be tailored to optimize combination therapy or maintain synergistic ratios. This can bypass the blood–brain barrier, alleviate systemic toxicity, and resolve drug resistance in the tumor. However, tailoring drug release requires appropriate consideration of the complex relationship between the drug, polymer, and formulation method. Drug physicochemical properties can result in intermolecular bonding with the polymeric matrix and affect drug distribution in the implant depending on the formulation method used. This review is focused on current works that have applied interstitial therapy towards GBM, discusses polymer and formulation methods, and provides design considerations for future implantable biodegradable materials.

Брахитерапия локализованного рака предстательной железы отечественными источниками I-125: собственный опыт Национального медицинского исследовательского центра радиологии

Introduction. One of the effective and minimally invasive methods prostate cancer treatment is interstitial radiation therapy, the essence of which is the implantation of radioactive microsources into the tumor tissue. Brachytherapy of prostate cancer is performed in more than 20 clinics in the Russian Federation using mainly foreign microsources, but their high cost does not allow increasing the number of operations and opening new brachytherapy departments in the Russian Federation. Based on the model of foreign microsources such as seed No. 6711 (Nicomed Amersham), a technology for the manufacture of microsources with iodine-125 (IPPE SEED) has been developed at the State Research Center of the Russian Federation - IPPE, as well as a pilot production facility with a capacity of up to 50 thousand items per year. Materials and methods. In order to assess the safety of microsources for medical personnel during brachytherapy, local dosimetric control was carried out. As part of a clinical study in 2015, 36 patients with stage T1 – T2 prostate cancer underwent low-power brachytherapy using domestic microsources. Results. The obtained values of absorbed doses do not differ within the limits of measurement errors from the values of doses determined during the operation with foreign microsources under similar conditions. It follows from the data obtained that even the maximum values of the measured local absorbed doses do not pose a radiation hazard when using IPPE SEED microsources for brachytherapy. Among the treated patients, adverse reactions were in the expected manifestations of grade 1 dysuria according to the RTOG / EORTC classification. No gastrointestinal toxicity has been reported. Patient monitoring was continued in order to obtain long-term results of treatment. PSA disease-free survival at 5-year follow-up was 94.4%. Discussion. Clinical trials of Russian medical devices have demonstrated their safety for patients and medical personnel, which was proved by conducting dosimetry control during the procedure itself, as well as during examination of patients after brachytherapy. The effectiveness of Russian microsources I-125 during low-power brachytherapy is demonstrated by a decrease in PSA level from baseline by 87% at a follow-up period of 6 months. The disease-free survival rate for 5 years was 94.4%. The absence of significant radiation reactions both in the early and in the late postoperative period is important. The low cost of microsources produced by JSC «SSC RF – IPPE» relative to foreign analogs makes it possible to increase the number of operations performed annually, and also gives prospects for opening new divisions performing interstitial radiation therapy operations. Conclusions. Russian microsources «IPPE SEED» have successfully passed clinical trials, during which their effectiveness and safety were proved. The study also demonstrated high rates of relapse-free survival and a low level of adverse reactions in treated patients.

Effectiveness of laser therapy for the treatment of lumbosacral radiculoischemias

Introduction.The study was devoted to assessing the effectiveness of laser therapy in the treatment of spondylogenic radiculoischemias. Low-intensity laser therapy and vaporization technology were used.Aim – to improve treatment and outcomes in patients with compression of the spinal roots in herniated intervertebral discs using various methods of laser therapy.Materials and methods. In two groups, the results of treatment of 225 patients with clinical manifestations of spondylogenic lumbosacral radiculoischemias were analyzed using laser therapy techniques. In 115 cases (group 1), laser treatment was performed using the method of puncture polychannel laser disk decompression. In 110 patients (group 2), low-intensity percutaneous laser therapy was used. The dynamics of the clinical and neurological manifestations of the disease was recorded: the time of pain syndrome reduction, the dynamics of motor and sensory disorders of the corresponding root, changes in parameters according to the Roland-Morris and Oswestry Disability questionnaire.Results. In both groups, an improvement in clinical and neurological manifestations was obtained: the intensity of pain syndrome according to VAS decreased in more than 70 % of the observed individuals. A significant improvement in the parameters of vital activity was revealed according to scales with a long-lasting effect (more than 12 months) with an improvement in the blood supply to the spinal roots.Conclusion. Laser radiation has significant clinical effectiveness; the important parameters are the wavelength and rate of the radiation. Structural-modifying action and improvement of microcirculation (of arterial and venous bed) are achieved. Evaluation of the effectiveness of polychannel laser puncture decompression is advisable using scales and questionnaires. Low-intensity percutaneous laser therapy and monochannel interstitial laser therapy provide a targeted antiedemic and neuroprotective effect with the possibility of dosing and control. The treatment is highly effective and improves the prognosis of the disease.

LGG-21. MR-GUIDED LASER INTERSTITIAL THERMAL THERAPY FOR UNRESECTABLE AND SYMPTOMATIC PEDIATRIC LOW GRADE GLIOMA

BACKGROUNDPediatric low-grade gliomas (LGG) not amenable to resection, while often indolent, represent a significant source of cancer-related morbidity and an unmet therapeutic need. Standardly, these patients are treated with sequential lines of chemotherapy, while delaying as long as possible radiation. Magnetic resonance-guided laser interstitial therapy (LITT) is a minimally invasive procedure that utilizes real-time MR thermography to ablate brain lesions.METHODSA 15-year-old girl was diagnosed with a suprasellar, hypothalamic LGG, BRAF V600E mutation positive. The tumor was unresectable, and due to progressive vision loss and headaches, the patient underwent treatment. Despite sequential trials of thioguanine/procarbazine/lomustine/vincristine, carboplatin/vincristine, dabrafenib, and combination dabrafenib/trametinib, the patient continued to experience debilitating headaches, malnutrition, school absenteeism, and overall poor quality-of-life. Using real-time, sequential MRI-thermometry and the Neuroblate cooled directional laser catheter, the bulk of the enhancing tumor was heated to a killing temperature.RESULTSAt 1-year post LITT, the patient’s symptoms were dramatically improved, including greatly improved headaches, malnutrition, school absenteeism, and overall quality of life. LITT was generally well tolerated, though the patient had slight progressive left homonymous hemianopia, thought secondary to LITT impact on the optic tracts. The tumor progressively shrank over the year post-LITT to a peak of 42% volume reduction.CONCLUSIONWe report a case of a pediatric patient with an unresectable low grade glioma who underwent LITT with excellent clinical and radiographic effects. LITT should be considered for children with unresectable and morbid LGGs that fail to respond to more conventional therapies.

Current trends in the management of subependymal giant cell astrocytomas in tuberous sclerosis.

The management of subependymal giant cells astrocytomas (SEGAs) has been traditionally represented by surgical treatment through an open craniotomic approach. Though open surgery still represents a major option in the management of this kind of tumors, the introduction of mTOR inhibitors in the clinical practice, technological advances in neuroendoscopy and the more recent use of laser interstitial therapy have significantly enlarged the range of available management opportunities. A thorough review of the literature has been performed. Accordingly, current views in open surgical treatment, medical therapy, endoscopic tumor removal and new trends (such as laser interstitial thermal therapy) are discussed. The risk of significant neurological morbidity (5-50%) complicating open surgery has been for a long time representing a main drawback in the management of SEGAs. More recent series report a significant reduction of morbidity and mortality. The mTOR inhibitors have demonstrated efficacy in both warranting a tumor reduction by up to 60% of the tumor size and helping the control of seizures. However, the reported rate of side effects is as high as 30% and tumor recurrence is a documented occurrence at the time of mTOR inhibitor discontinuation. Endoscopic tumor removal has been more extensively considered an option due to the acquisition of new tools. Limits are still represented by tumor size (< 3 cm) and broad attachment of the tumor to the basal ganglia. Laser interstitial thermal therapy (LITT)is the more recently considered option. Though promising, only short follow-up is available so far, while data on medium- and long-term results of this treatment are completely lacking to date. Surgical treatment remains a mainstay of the management of SEGAs. The indication for an open craniotomic approach should be balanced with an endoscopic tumor removal or LITT according to patient conditions, presence or not of an active hydrocephalus and extension of the attachment of the tumor to the basal ganglia. The mTOR inhibitors do have a definite role both as primary and as adjuvant treatment, but consistent limitations are represented up to now by a not negligible rate of complications and the uncertainties related to the possibility of tumor recurrence once the medical treatment is discontinued.

Robot-assisted ultrasound navigation platform for 3D HIFU treatment planning: Initial evaluation for conformal interstitial ablation

Interstitial Ultrasound-guided High Intensity Focused Ultrasound (USgHIFU) therapy has the potential to deliver ablative treatments which conform to the target tumor. In this study, a robot-assisted US-navigation platform has been developed for 3D US guidance and planning of conformal HIFU ablations. The platform was used to evaluate a conformal therapeutic strategy associated with an interstitial dual-mode USgHIFU catheter prototype (64 elements linear-array, measured central frequency f = 6.5 MHz), developed for the treatment of HepatoCellular Carcinoma (HCC). The platform included a 3D navigation environment communicating in real-time with an open research dual-mode US scanner/HIFU generator and a robotic arm, on which the USgHIFU catheter was mounted. 3D US-navigation was evaluated in vitro for guiding and planning conformal HIFU ablations using a tumor-mimic model in porcine liver. Tumor-mimic volumes were then used as targets for evaluating conformal HIFU treatment planning in simulation. Height tumor-mimics (ovoid- or disc-shaped, sizes: 3–29 cm3) were created and visualized in liver using interstitial 2D US imaging. Robot-assisted spatial manipulation of these images and real-time 3D navigation allowed reconstructions of 3D B-mode US images for accurate tumor-mimic volume estimation (relative error: 4 ± 5%). Sectorial and full-revolution HIFU scanning (angular sectors: 88–360°) could both result in conformal ablations of the tumor volumes, as soon as their radii remained ≤ 24 mm. The presented US navigation-guided HIFU procedure demonstrated advantages for developing conformal interstitial therapies in standard operative rooms. Moreover, the modularity of the developed platform makes it potentially useful for developing other HIFU approaches.

Synergistic drug combinations for a precision medicine approach to interstitial glioblastoma therapy

Glioblastoma (GBM) is a highly aggressive and heterogeneous form of brain cancer. Genotypic and phenotypic heterogeneity drives drug resistance and tumor recurrence. Combination chemotherapy could overcome drug resistance; however, GBM's location behind the blood-brain barrier severely limits chemotherapeutic options. Interstitial therapy, delivery of chemotherapy locally to the tumor site, via a biodegradable polymer implant can overcome the blood-brain barrier and increase the range of drugs available for therapy. Ideal drug candidates for interstitial therapy are those that are potent against GBM and work in combination with both standard-of-care therapy and new precision medicine targets. Herein we evaluated paclitaxel for interstitial therapy, investigating the effect of combination with both temozolomide, a clinical standard-of-care chemotherapy for GBM, and everolimus, a mammalian target of rapamycin (mTOR) inhibitor that modulates aberrant signaling present in >80% of GBM patients. Tested against a panel of GBM cell lines in vitro, paclitaxel was found to be effective at nanomolar concentrations, complement therapy with temozolomide, and synergize strongly with everolimus. The strong synergism seen with paclitaxel and everolimus was then explored in vivo. Paclitaxel and everolimus were separately formulated into fibrous scaffolds composed of acetalated dextran, a biodegradable polymer with tunable degradation rates, for implantation in the brain. Acetalated dextran degradation rates were tailored to attain matching release kinetics (~3% per day) of both paclitaxel and everolimus to maintain a fixed combination ratio of the two drugs. Combination interstitial therapy of both paclitaxel and everolimus significantly reduced GBM growth and improved progression free survival in two clinically relevant orthotopic models of GBM resection and recurrence. This work illustrates the advantages of synchronized interstitial therapy of paclitaxel and everolimus for post-surgical tumor control of GBM.

Stereotactic laser interstitial thermal therapy for brainstem cavernous malformations: two preliminary cases

Brainstem cavernous malformations (CMs) often have high hemorrhage rates and significant posthemorrhage morbidity. The authors present two cases in which magnetic resonance thermography-guided laser interstitial therapy was used for treatment of pontine CMs after recurrent hemorrhage. Both patients showed significant symptomatic improvement and were hemorrhage-free at 12- and 6-month follow-up, respectively. Each had radiographic evidence of lesion involution on serial follow-up imaging. These early results demonstrate this treatment modality may be technically safe; however, larger case numbers and longer follow-up are needed to demonstrate efficacy.

Tumor Responsive and Tunable Polymeric Platform for Optimized Delivery of Paclitaxel to Treat Glioblastoma.

Current interstitial therapies for glioblastoma can overcome the blood-brain barrier but fail to optimally release therapy at a rate that stalls cancer reoccurrence. To address this lapse, acetalated dextran (Ace-DEX) nanofibrous scaffolds were used for their unique degradation rates that translate to a broad range of drug release kinetics. A distinctive range of drug release rates was illustrated via electrospun Ace-DEX or poly(lactic acid) (PLA) scaffolds. Scaffolds composed of fast, medium, and slow degrading Ace-DEX resulted in 14.1%, 2.9%, and 1.3% paclitaxel released per day. To better understand the impact of paclitaxel release rate on interstitial therapy, two clinically relevant orthotopic glioblastoma mouse models were explored: (1) a surgical model of resection and recurrence (resection model) and (2) a distant metastasis model. The effect of unique drug release was illustrated in the resection model when a 78% long-term survival was observed with combined fast and slow release scaffolds, in comparison to a survival of 20% when the same dose is delivered at a medium release rate. In contrast, only the fast release rate scaffold displayed treatment efficacy in the distant metastasis model. Additionally, the acid-sensitive Ace-DEX scaffolds were shown to respond to the lower pH conditions associated with GBM tumors, releasing more paclitaxel in vivo when a tumor was present in contrast to nonacid sensitive PLA scaffolds. The unique range of tunable degradation and stimuli-responsive nature makes Ace-DEX a promising drug delivery platform to improve interstitial therapy for glioblastoma.

A comparison of tandem ring and tandem ovoid treatment as a curative brachytherapy component for cervical cancer.

PurposeThe standard treatment for locally advanced stage cervical cancer is definitive radiotherapy, the quality of which affects both survival and side effects. Brachytherapy is a major component of definitive radiotherapy; it is administered using different techniques and applicators. The purpose of this study was to dosimetrically compare tandem ovoid (T-ovoid) and tandem ring (T-ring) brachytherapy treatments.Material and methodsBoth applicator sets were applied to the same 20 patients, and treatment plans were made three-dimensionally (3D), with high-risk clinical target volume (HR-CTV) and organs at risk contoured. The HR-CTV was defined according to post-external magnetic resonance results. The patients with residual tumors not exceeding one-third of the parametrium were included in this study, while patients with larger masses were excluded and received interstitial therapy. The doses were calculated for both plans. Optimization for the HR-CTV was made with the aim that the equivalent dose according to 2 Gy (EQD2) of 90% of the HR-CTV (D90) would be higher than 85 Gy, without exceeding the maximum dose for organs at risk. Then, pairwise dosimetric comparisons were performed.ResultsPlans were compared dosimetrically according to the HR-CTV, point A and B doses, and organs at risk. Although the point A and B doses were higher with T-ovoid use, the 3D HR-CTV coverage was statistically better with T-ring application (EQD2 of HR-CTV D90: 97.46 Gy for T-ring and 88.44 Gy for T-ovoid; p < 0.0001). In addition, the rectum and bladder doses were statistically lower with T-ring usage (EQD2 of rectum, 2 cc; T-ring, 63.10 Gy; T-ovoid, 74.99 Gy; p < 0.0001; EQD2 of bladder, 2 cc; T-ring, 85.26 Gy; T-ovoid, 89.05 Gy; p < 0.0001).ConclusionsIn our study with a limited number of samples, T-ring applicator seems to offer better 3D brachytherapy dosimetry for both HR-CTV and nearby organs at risk.

Феномен «биохимического скачка простат-специфического антигена» (bounce) после внутритканевой лучевой терапии рака предстательной железы источником высокой мощности дозы в режиме монотерапии

Феномен «биохимического скачка простат-специфического антигена» (bounce) после внутритканевой лучевой терапии рака предстательной железы источником высокой мощности дозы в режиме монотерапии

HIGH-DOSE-RATE BRACHYTHERAPY FOR PROSTATE CANCER: DIRECT IN VIVO DOSIMETRY IS AN IMPORTANT FACTOR IN INCREASING THE EFFECTIVENESS OF TREATMENT AND REDUCING THE INCIDENCE OF COMPLICATIONS

The technology of direct dosimetry was examined during a session of automated high-power interstitial gamma therapy for prostate cancer with a source of iridium-192 using a MKD-04 scintillation multi-detector dosimeter developed at the JSC ROSATOM. Miniature detectors of up to 5 pieces allow simultaneous measurements in areas of medical interest - the urethra and the rectum at different distances from the intrastats. The technology of direct dosimetry with rigid fixation of detectors is aimed at increasing quality assurance and reducing the frequency of complications. The dosimeter MKD-04 can be used for all types of automated brachytherapy, as well as in bundles of gamma-therapeutic devices to monitor the dose prescribed and actually received by the patient.

How Intraoperative Tools and Techniques Have Changed the Approach to Brain Tumor Surgery.

Surgical treatment of brain tumors remains an integral part of a comprehensive treatment plan. Here, we review technological advances that have enhanced what surgeons are capable of doing within and outside the traditional operating room. Extent of surgical resection has improved with the use of MRI and fluorescent dyes intraoperatively. Neurological injury during brain tumor surgery has decreased with appropriate use of neurophysiological monitoring. New operative scopes have enhanced ability of surgeons to visualize tissues during dissection. Laser interstitial therapy and radiation treatment have made possible the treatment of previously considered non-operable brain tumors in addition to replacing or serving as adjunct to surgical treatment of brain tumors. Surgery remains an important pillar in treatment of most brain tumors. Ongoing technological advances have augmented extent of what is possible in this realm.