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To evaluate the complications from laser-induced thermotherapy (LITT) of malignant liver tumors and demonstrate that LITT is safe as an outpatient procedure.
During 8 years, 899 patients with malignant liver tumors were treated with magnetic resonance (MR) imaging-guided LITT. A total of 2,132 LITT procedures were performed to treat 2,520 lesions....
Context in source publication
Context 1
... the introduction of outpatient LITT, 783 inpatient LITT sessions had been performed for 5½ years in patient groups 1-3. The complications related to their inpatient treatment were one death (0.1%), 62 cases of pleural effusion (7.9%), one case of liver abscess (0.1%), 21 cases of subcapsular hematoma (2.7%), eight cases of subcutaneous hematoma (1.0%), and one case of abdominal hemorrhage (0.1%) (Table 3). No bile duct injuries occurred. ...
Citations
... Furthermore, Minor complications can also occur, including postprocedural fever (33.3%), pleural effusion not requiring thoracocentesis (7.3%), and subcutaneous hematomas (3.2%). [17] Another approach to addressing deep-tissue PTT is dual thermal therapy (DTT). [18,19] DTT relies on the principle that the thermal effects generated by both ultrasound and light can be combined to enhance the therapeutic depth. ...
Photothermal therapy (PTT) has garnered considerable attention as an attractive treatment tool for cancer due to precisely selective treatment and minimal side effects. The primary challenge of PTT, which hinders its widespread application, is the limited therapeutic depth. This limitation arises from optical scattering in biological tissues, causing inadequate heat distribution within the deep tissue. To overcome this challenge, ultrasound‐assisted PTT (ULTRA‐PTT) is proposed that leverages the temporary formation of gas bubbles induced by ultrasound within the light propagation path. These bubbles act as optical clearing agents, effectively reducing optical scattering in biological tissues. To facilitate ULTRA‐PTT, a dedicated handpiece consisting of a ring‐shaped ultrasound transducer and a laser delivery module is developed. In‐vivo experiments show that ULTRA‐PTT statistically outperforms conventional PTT in melanoma treatment, mostly due to its ability to deliver sufficient laser energy to deep‐seated cancer cells. These findings underscore the potential of ULTRA‐PTT to expand the clinical applications of PTT beyond local tumors occurring in superficial tissue.
... It is important to acknowledge the possible risks associated with IPTA, including major complications like tumor seeding, hemorrhage, pneumothorax, and injuries to the bowel and nerves, as well as minor issues such as pain and post-ablation syndrome [40][41][42][43]. However, in our application of the fusion technique within IPTA, we observed none of these complications, even though we have conducted control MRI, and peri-operative vitals were monitored, highlighting the potential effectiveness and safety of our approach. ...
Simple Summary
Secondary spinal column tumors are relatively common and can be managed using image-guided percutaneous thermal ablation (IPTA). However, relying on one imaging method can lead to overlooking and underestimating many tumors, resulting in ineffective targeting and treatment. Our study investigates a novel approach for addressing these spinal column tumors, which often cause severe symptoms. We use a combination of CBCT and MRI to precisely guide a minimally invasive thermal ablation procedure. This method ensures that we effectively deliver heat to the tumor, enhancing its accessibility and treatment efficiency. Our promising results show successful tumor coagulation and significant symptom improvement in all four patients. This innovative approach can establish an improved technique for targeting spinal column tumors, ultimately enhancing the treatment outcomes and overall quality of life.
Abstract
Spinal metastatic tumors are common and often cause debilitating symptoms. Image-guided percutaneous thermal ablation (IPTA) has gained significant recognition in managing spinal column tumors due to its exceptional precision and effectiveness. Conventional guidance modalities, including computed tomography, fluoroscopy, and ultrasound, have been important in targeting spinal column tumors while minimizing harm to adjacent critical structures. This study presents a novel approach utilizing a fusion of cone beam computed tomography with magnetic resonance imaging to guide percutaneous thermal ablation for four patients with secondary spinal column tumors. The visual analog scale (VAS) evaluated the procedure effectiveness during an 18-month follow-up. Percutaneous vertebroplasty was performed in two cases, and a thermostat was used during all procedures. Imaging was performed using the Stealth Station navigation system Spine 8 (SSS8) and a 1.5T MRI machine. The fusion of CBCT with MRI allowed for precise tumor localization and guidance for thermal ablation. Initial results indicate successful tumor ablation and symptom reduction, emphasizing the potential of CBCT–MRI fusion in spinal column tumor management. This innovative approach is promising in optimizing therapy for secondary spinal column tumors. Further studies are necessary to validate its efficacy and applicability.
... Photothermal therapy (PTT), as a tumor ablation strategy, has received extensive attention in recent years. Compared with traditional treatments, PTT has shown the advantages of high efficiency, low recurrence rate, and short treatment process for solid tumors (lung cancer [1], hepatoma [2], breast cancer [3], prostatic carcinoma [4], and rectal cancer [5]) in clinical practice. Most importantly, PTT is noninvasive or minimally invasive to alleviate the patient's suffering. ...
The over-expressed GSH in tumor microenvironment significantly weakens the lethal reactive oxygen species (ROS) generated by photodynamic therapy (PDT) and catalysis of nanoenzyme. Hence, it is necessary to excavate a versatile and effective vehicle with oxidative stress-enhancement and GSH-depletion capacity to break the redox homeostasis in tumor microenvironment. GO has been reported to possess GSH-depletion and peroxidase (POD)-like capacity. Based on this, PEGylated mesoporous carbon (MC-PEG) was prepared as ICG vehicle to compare with PEGylated graphene oxide (GO-PEG). Excitingly, MC-PEG was found to exhibit three times higher oxidative capacity by POD-like process than GO-PEG, and owned more effective and continuous GSH-depletion capacity to further amplify the oxidative stress. Meanwhile, MC-PEG exhibited better protective effect on the loaded ICG against unwanted light excitation than GO-PEG. Together with the higher photothermal conversion effect, under the NIR light irradiation, MC-PEG could markedly improve the temperature of tumor cells and produce more hydroxyl radical, continuously consume GSH and provide more better protection for ICG compared with GO-PEG, thus further boosting the combination of photothermal and photodynamic effects. The anti-tumor experiment in cell and in-vivo level both validated that ICG/MC-PEG showed better synergistic effect with lower IC50 value and higher tumor suppression rate than ICG/GO-PEG.
... Vogl et al. in 2002 reported a magnetic resonance imaging (MRI)-guided laser-induced thermotherapy (LITT) for 899 patients with malignant liver tumors [115]. A single dose of opioids (e.g., piritramide and pethidine) was administered intravenously for pain management during and after the treatment procedure. ...
... Table 3. Safety parameters used before, during, and after treatment. Reproduced with permission from [115]. ...
The development of new effective cancer treatment methods has attracted much attention, mainly due to the limited efficacy and considerable side effects of currently used cancer treatment methods such as radiation therapy and chemotherapy. Photothermal therapy based on the use of plasmonically resonant metallic nanoparticles has emerged as a promising technique to eradicate cancer cells selectively. In this method, plasmonic nanoparticles are first preferentially uptaken by a tumor and then selectively heated by exposure to laser radiation with a specific plasmonic resonant wavelength, to destroy the tumor whilst minimizing damage to adjacent normal tissue. However , several parameters can limit the effectiveness of photothermal therapy, resulting in insufficient heating and potentially leading to cancer recurrence. One of these parameters is the patient's pain sensation during the treatment, if this is performed without use of anesthetic. Pain can restrict the level of applicable laser radiation, cause an interruption to the treatment course and, as such, affect its efficacy, as well as leading to a negative patient experience and consequential general population hesitancy to this type of therapy. Since having a comfortable and painless procedure is one of the important treatment goals in the clinic, along with its high effectiveness, and due to the relatively low number of studies devoted to this specific topic, we have compiled this review. Moreover, non-invasive and painless methods for temperature measurement during photothermal therapy (PTT), such as Raman spectroscopy and nanothermometry, will be discussed in the following. Here, we firstly outline the physical phenomena underlying the photothermal therapy, and then discuss studies devoted to photothermal cancer treatment concerning pain management and pathways for improved efficiency of photothermal therapy whilst minimizing pain experienced by the patient.
... General anesthesia is not needed. This technique is not feasible in patients with more than 5 lesions and lesions greater than 5 cm in diameter [107]. ...
For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.
... We have developed a clinically translatable photothermal therapy modality termed MTPA that exhibits robust tumor specificity for HCC as well as favorable local and systemic immunologic ramifications relative to the current standard of care RFA. Although conceptually related ablation modalities such as laserinduced interstitial therapy 29,30 and photodynamic therapy exist, these approaches have minimal to no tumor specificity. The fact that MTPA relies on clinically approved drugs and devices reinforces its clinical translatability and underlines the technology's potential for clinical impact. ...
Thermal ablation is a standard therapy for patients with hepatocellular carcinoma (HCC). Contemporary ablation devices are imperfect, as they lack tumor specificity. An ideal ablation modality would generate thermal energy only within tumoral tissue. Furthermore, as hyperthermia is known to influence tumor immunity, such a tumor-specific ablation modality may have the ability to favorably modulate the tumor immune landscape. Here we show a clinically relevant thermal ablation modality that generates tumor-specific hyperthermia, termed molecularly targeted photothermal ablation (MTPA), that is based upon the excellent localization of indocyanine green to HCC. In a syngeneic rat model, we demonstrate the tumor-specific hyperthermia generated by MTPA. We also show through spatial and transcriptomic profiling techniques that MTPA favorably modulates the intratumoral myeloid population towards tumor immunogenicity and diminishes the systemic release of oncogenic cytokines relative to conventional ablation modalities.
... In practice, LITT is a well-established method and is widely applied to treat various tumors such as gliomas, radiation necrosis, brain tumors, liver metastases, and head and neck cancers. A study conducted on 899 patients with malignant liver tumors treated with MRI-guided LITT over eight years showed that the LITT is safe as an outpatient procedure [102]. Another survey of 381 patients treated with MR-guided LITT resulted in the average survival times of 45.7, 42.7, and 32 months for patients with liver metastasis, patients with colorectal liver metastases, and for HCC tumors, respectively [103]. ...
Microbubbles (MBs) have been extensively investigated in the field of biomedicine for the past few decades. Ul-trasound and laser are the most frequently used sources of energy to produce MBs. Traditional acoustic methods induce MBs with poor localized areas of action. A high level of energy is required to generate MBs through the focused continuous laser, which can be harmful to healthy tissues. As an alternative, plasmonic light-responsive nanoparticles, such as gold nanoparticles (AuNPs), are preferably used with continuous laser to decrease the energy threshold and reduce the bubbles area of action. It is also well-known that the utilization of the pulsed lasers instead of the continuous lasers decreases the needed AuNPs doses as well as laser power threshold. When well-confined bubbles are generated in biological environments, they play their own unique mechanical and optical roles. The collapse of a bubble can mechanically affect its surrounding area. Such a capability can be used for cargo delivery to cancer cells and cell surgery, destruction, and transfection. Moreover, the excellent ability of light scattering makes the bubbles suitable for cancer imaging. This review firstly provides an overview of the fundamental aspects of AuNPs-mediated bubbles and then their emerging applications in the field of cancer nanotechnology will be reviewed. Although the pre-clinical studies on the AuNP-mediated bubbles have shown promising data, it seems that this technique would not be applicable to every kind of cancer. The clinical application of this technique may basically be limited to the good accessible lesions like the superficial, intracavity and intraluminal tumors. The other essential challenges against the clinical translation of AuNP-mediated bubbles are also discussed.
... For patients with inoperable and/or unresectable tumors, current treatment approaches for metastatic liver lesions include radiofrequency, laser, and microwave thermal ablative options; cryosurgery; vascular approaches such as transarterial chemoembolization, radioembolization, and external beam radiation therapy schedules ranging from conventional low-dose-per-fraction (high total dose) treatments extending over many weeks to high-dose SABR treatments delivered in 5 treatment sessions. [13][14][15][16][17][18][19][20] It has not yet been determined what the optimal treatment is for medically inoperable and/or anatomically unresectable metastatic lesions of the liver. ...
Purpose/Objectives
We report long term outcomes from our phase I dose-escalation study to determine the maximum tolerated dose of single-fraction liver stereotactic ablative radiotherapy (SAbR) pooled with our subsequent single institutional experience with patients treated post-protocol at the highest dose level (40 Gy) established from the Phase I study.
Materials/Methods
Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SAbR on a Phase I dose escalation trial. At least 700 cc of normal liver had to receive <9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 post-protocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control.
Results
Median imaging follow-up for the combined cohort (n=33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for post-protocol patients. Median lesion size was 2.0 cm (range 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only three Grade 2 toxicities were observed in the entire cohort, with no Grade ≥ 3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%; 100% in the protocol group and 92.9% in the subsequent patients, respectively. Two-year overall survival for all treated patients was 82.0%.
Conclusion
For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long term follow-up; results in subsequent patients treated with single-fraction SAbR doses of 40 Gy confirm our earlier results.
... Later, MRI was developed to guide placement of the laser applicator and MR thermometry was used to simultaneously monitor thermocoagulation. 51 Thus, MRI with specific sequences can not only guide placement of laser probes but also allow accurate real-time evaluation of the extent of thermal ablation. In one study, 113 HCC patients were treated with MRI-guided LITT, and the therapeutic potential of this technique was evaluated. ...
Hepatocellular carcinoma (HCC) is one of the most deadly and frequent cancers worldwide, although great advancement in the treatment of this malignancy have been made within the past few decades. It continues to be a major health issue due to an increasing incidence and a poor prognosis. The majority of patients have their HCC diagnosed at an intermediate or advanced stage in theUSA or China. Curative therapy such as surgical resection or liver transplantation is not considered anoption of treatment at these stages.
Transarterial chemoembolization (TACE), the most widely used locoregional therapeutic approach, used to be the mainstay of treatment for cases with unresectable cancer entities. However, for those patients with hypovascular tumors or impaired liver function reserve, TACE is a suboptimal treatment option. For example, embolization does not result in complete coverage of a hypovascular tumor, and may rather promotes postoperative tumor recurrence, or leave residual tumor, in these TACE-resistance patients. In addition, TACE carries a higher risk of hepatic decompensation in patients with poor liver function or reserve.
Non-vascular interventional locoregional therapies for HCC include radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), laser-induced thermotherapy (LITT), cryosurgical ablation (CSA), irreversible Electroporation (IRE), percutaneous ethanol injection (PEI), and brachytherapy. Recent advancements in these techniques have significantly improved the treatment efficacy of HCC and expanded the population of patients who qualify for treatment. This review embraces the current status of imaging-guided locoregional non-intravascular interventional treatments for HCCs, with a primary focus on the clinical evaluation and assessment of the efficacy of combined therapies using these interventional techniques.
... Another interesting phenomenon is that compared with veins, bile ducts maintained better with a more complete structure and received less damage on the biliary epithelial cells. According to previous studies about RFA, it is assumed that bile ducts are more sensitive to thermal damage and less vulnerable to electric stimulations (7,24,25). ...
Background: Treatment of liver malignancies located at the hepatic hilar area has long been recognized as a challenge for both surgeons and interventional radiologists. Traditional locoregional thermal ablative therapies like radiofrequency ablation (RFA) have natural deficiencies to achieve complete ablation. Nanosecond pulsed electric field (nsPEF) has emerged as a novel electric power based locoregional therapy. It has been reported to effectively ablate liver malignancies while its effect on tumors located in hepatic hilar areas still lacks well-controlled follow-up studies.
Methods: This pre-clinical study was conducted to evaluate the safety and feasibility of nsPEF ablation in the hepatic hilar area and to investigate its effect on liver vasculature systems. Two-needle electrodes of the nsPEF were placed around the hepatic hilar areas in the rabbit liver under ultrasonic guidance. During and after the procedure of nsPEF ablation, electrocardiographs (ECG) was used to monitor cardiovascular activities and ultrasonography was used to detect vascular changes. The blood samples and liver specimens were collected at pre-treatment and at 2 hours, 2 days, 7 days, 14 days and 28 days post-treatment.
Results: Histopathological studies showed the targeted portal area was ablated accurately without perivascular sparing. The major structures of the large hepatic veins and bile ducts near hilar areas were preserved well. Follow-up biochemical tests showed a transient and mild impairment of liver function. The results of myocardial enzymes and routine blood test proved nsPEF won’t cause collateral damage on cardiac systems or increase potential infection risk. Ultrasonography and electrocardiographs found no massive hemorrhea and abnormal cardiac activities.
Conclusion: Our results demonstrate that nsPEF is safe and feasible in the ablation of large animal models. During the treatment, nsPEF would not disturb vital organ functions or cause irreversible complications. Furthermore, it can ablate the hepatic hilar area without damaging large hepatic vasculatures, which could be a promising method for non-thermal tumor ablation.
