A glimpse of the future?-bronchoscopic ablation of peripheral early stage lung cancer.
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ABSTRACT:
SUBMITTER: Steinfort DP
PROVIDER: S-EPMC8577971 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
A glimpse of the future?-bronchoscopic ablation of peripheral early stage lung cancer.
Steinfort Daniel P DP Rangamuwa Kanishka K
Translational lung cancer research 20211001 10
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Project description:Lung cancer is the leading cause of cancer-related death worldwide and lobectomy remains the standard of care for patients with early-stage non-small cell lung cancer (NSCLC). The combination of an aging population and the implementation of low-dose CT for lung cancer screening is leading to an increase in diagnosis of early stage NSCLC in medically "inoperable" patients. The recommended treatment for this latter group of patients is stereotactic body radiation therapy (SBRT). However, many patients cannot undergo SBRT because they have received prior radiation or because the tumor is located next to vital structures. Percutaneous ablative therapies have become an alternative to SBRT but, unfortunately, they all violate the pleura and are associated with high rate of pneumothorax. With a more favorable safety profile and the ability to provide also diagnosis and nodal staging, bronchoscopic ablation is hence emerging as a potential future therapeutic alternative for these patients. Herein we review the current state of the art including animal and human data that exists thus far. We also discuss technical and research challenges as well as future directions that this exciting new technology may take.
| S-EPMC6626814 | biostudies-literature
Project description:BackgroundTrans-bronchoscope treatment for early stage small peripheral lung cancer, such as photodynamic therapy (PDT), has been investigated. However, despite the efficacy of PDT, light delivery issues limit its application. A method of administering mineral oil with a high refractive index (RI) was previously proposed to enhance light delivery in branched or bent anatomic structures. Lipiodol has a high RI and an exhaustive history of use as a contrast medium for bronchography. We aimed to determine whether the use of lipiodol, like mineral oil, could enhance the illumination effect and therapeutic range of PDT for peripheral lung tumors.MethodsWe injected lipiodol into a pig lung model, guided by a bronchoscope under fluorescent surveillance, to simulate future treatment in humans, and then illuminated with PDT laser fiber to the lipiodol-infused lung to test the technique feasibility in a pig orally administered 20 mg/kg of 5-aminolevulinicc acid (5-ALA) 2 hours before treatment. We also attempted to determine the maximal tolerable light dose in this pilot study for the future studies in human.ResultsWe successfully injected lipiodol into peripheral lungs by this technique. The pig could tolerate up to a total of 40 mL of lipiodol and 800 J of red light, without severe acute fetal injury in a non-cancerous lung.ConclusionsThe technique of injecting lipiodol using bronchoscopy under fluorescent guidance was feasible in a pig model. We can apply the guide sheath through bronchoscopy under fluoroscope inspection. Lipiodol can be used as a light diffuser for the peripheral lung tumor PDT model. No severe lethal acute lung injury was caused by this PDT model under careful manipulation. Additional studies evaluating the dose correlation of the photosensitizer and light are needed.
| S-EPMC7399407 | biostudies-literature
Project description:Lung cancer remains the leading cause of cancer death worldwide, with the majority of cases diagnosed in an advanced stage. Early-stage disease non-small cell lung cancer (NSCLC) has a better outcome, nevertheless the 5-year survival rates drop from 60% for stage IIA to 36% for stage IIIA disease. Early detection and optimized perioperative systemic treatment are frontrunner strategies to reduce this burden. The rapid advancements in molecular diagnostics as well as the growing availability of targeted therapies call for the most efficient detection of actionable biomarkers. Liquid biopsies have already proven their added value in the management of advanced NSCLC but can also optimize patient care in early-stage NSCLC. In addition to having known diagnostic benefits of speed, accessibility, and enhanced biomarker detection compared to tissue biopsy, liquid biopsy could be implemented for screening, diagnostic, and prognostic purposes. Furthermore, liquid biopsy can optimize therapeutic management by overcoming the issue of tumor heterogeneity, monitoring tumor burden, and detecting minimal residual disease (MRD), i.e., the presence of tumor-specific ctDNA, post-operatively. The latter is strongly prognostic and is likely to become a guidance in the postsurgical management. In this review, we present the current evidence on the clinical utility of liquid biopsy in early-stage lung cancer, discuss a selection of key trials, and suggest future applications.
| S-EPMC10216452 | biostudies-literature
Project description:Advances in molecular biology and bioinformatics have resulted in the identification of a number of potential biomarkers that could be relevant in the management of patients with non-small-cell lung cancer (NSCLC). Although there is an increasing amount of literature related to these biomarkers, major issues need to be resolved including validity and reproducibility of results. Additionally, in order to interpret the existing literature accurately, a clear distinction must be made between the prognostic and predictive value of biomarkers. The practical applicability of biomarker discovery for patients with lung cancer includes the identification of patients with early-stage NSCLC who are most likely to benefit from adjuvant therapy. Information gleaned from biomarkers has the potential to help in evaluating the role of targeted therapies including immunotherapy in the neoadjuvant and adjuvant setting. The role of gene signatures and the use of newer platforms such as RNA, methylation, and protein signatures is being explored in patients with early-stage NSCLC. This review focuses on the applications of biomarker discovery in patients with early-stage NSCLC.
| S-EPMC4254270 | biostudies-other
Project description:BackgroundRadiofrequency ablation (RFA) is an established modality for percutaneous ablation of non-small cell lung cancer (NSCLC) in medically inoperable patients but is underutilized clinically due to side effects. We have developed a novel, completely endobronchial RFA catheter with an externally cooled electrode.ObjectivesThe objective of this study was to establish the safety and feasibility of bronchoscopic RFA using a novel, externally cooled catheter for ablation of peripheral NSCLC.MethodsPatients with stage I biopsy-confirmed NSCLC underwent bronchoscopic RFA of tumour 7 days prior to lobectomy. The RFA catheter was delivered bronchoscopically to peripheral NSCLC lesions, guided by radial endobronchial ultrasound, with positioning confirmed using intra-procedural cone beam CT. Pre-operative CT chest and histologic examination of resected specimens were used to establish distribution/uniformity of ablation and efficacy of tumour ablation.ResultsRFA in the first patient was complicated by dispersal of heated saline due to cough, resulting in ICU admission. The patient recovered fully and underwent uncomplicated lobectomy. Subsequently, the protocol was altered to mandate neuromuscular blockade with a pre-determined dose escalation, with algorithm-restricted energy (kJ) and irrigated saline volume (mL) constraints. A further 10 patients consented and seven underwent successful bronchoscopic RFA of peripheral NSCLC. No significant adverse events were noted. Ablation zone included tumour in all cases (proportion of tumour ablated ranged 8-72%), with uniform necrosis of tissue within ablation zones observed at higher energy levels. Ablation zone diameter correlated with RFA energy delivered (R2 = 0.553), with maximum long axis diameter of ablation zone 3.1 cm (22.9 kJ).ConclusionBronchoscopic RFA using an externally cooled catheter is feasible, appears safe, and achieves uniform ablation within the treatment zone. Uncontrolled escape of heated saline poses a major safety risk but can be prevented procedurally through neuromuscular blockade and by limiting irrigation.
| S-EPMC9986835 | biostudies-literature
Project description:BackgroundPatients with early-stage lung cancer are sometimes medically inoperable, and for patients with multiple primary lung cancers, surgical resection alone sometimes proves to be impractical. Local treatments like microwave ablation (MWA) are investigational alternatives for these patients. Most reported MWA procedures for lung cancers are performed percutaneously under CT guidance. MWA navigated by electromagnetic bronchoscopy (ENB) has been limitedly studied. In this study, we aimed to evaluate the safety and feasibility of MWA under ENB guidance in patients with inoperable early-stage lung cancers or multiple primary lung cancers which cannot be completely resected.MethodsFrom June 2019 to December 2020, preliminary attempts of ENB-guided MWA were made in five medically inoperable patients with a single early-stage lung cancer and ten patients with multiple primary lung cancers which were difficult to resect at the same time. For patients with concomitant pulmonary nodules which needed surgical resection, thoracoscopic resections were performed following ENB-guided MWA. The safety, feasibility, and technique effectiveness of treatments were evaluated.ResultsENB-guided MWA for 15 ground glass nodules (GGNs) in 15 patients was completed in accordance with the planned protocol. Biopsy of 13 GGNs showed malignancy. Five patients received simple ENB-guided MWA without simultaneous surgical resection and ten patients received simultaneous surgical resection for 13 concomitant pulmonary nodules. CT scan by the first postoperative week showed technique effectiveness of ablation for 11 nodules indicated for MWA. Four patients had mild complications after the procedure and recovered shortly after treatment.ConclusionsFor medically inoperable patients with a single GGN manifesting early-stage lung cancer and patients with multiple primary early-stage lung cancers which cannot be resected at the same time, ENB-guided MWA might be a safe and feasible alternative local treatment, whether combined with surgical resection or not. However, large, prospective, randomized, multicenter studies are needed to confirm its role in the treatment of early-stage lung cancer.
| S-EPMC8512468 | biostudies-literature
Project description:Limited early evidence indicates thermal ablation of non-small cell lung cancer (NSCLC) may induce alterations to the immune response that could enhance the efficacy of immunotherapy with immune checkpoint inhibitor therapy. This study reports pilot data demonstrating increased programmed death-ligand 1 (PD-L1) expression on tumour cells in response to bronchoscopic thermal vapour ablation. Five patients underwent bronchoscopic thermal vapour ablation under a treat-and-resect protocol, as part of a clinical safety and feasibility study, with lobectomy performed five days after thermal vapour ablation. PD-L1 (clone SP263) immunohistochemistry (IHC) tumour proportion score (TPS) was assessed on both baseline diagnostic biopsy specimens, and post-ablation resection specimens in five patients with stage I NSCLC. Two areas of the resection sample defined as viable tumour and injured tumour were examined. All tumours demonstrated 0% PD-L1 TPS at baseline. Three of five (60%) patients demonstrated an increase in PD-L1 TPS in areas of injured tumour to 20%, 30% and 50%. One patient demonstrated an increase in PD-L1 expression in an area of viable tumour to 5%. Changes in PD-L1 expression did not correlate with measures of systemic inflammation. Our findings comprise the first evidence that thermal ablation of NSCLC may induce PD-L1 expression. Further investigation is required to determine the extent of an adaptive immune response, and confirm the potential for augmentation of clinical response to immune check point inhibitor therapy in NSCLC.
| S-EPMC8264342 | biostudies-literature
Project description:ObjectivesTo compare patterns of care and overall survival (OS) between stereotactic body radiotherapy (SBRT) and percutaneous local tumor ablation (LTA) for non-surgically managed early-stage non-small-cell lung cancer (NSCLC).Materials and methodsThe National Cancer Database (NCDB) was queried from 2004 to 2014 for adults with non-metastatic, node-negative invasive adenocarcinoma or squamous cell carcinoma of the lung with primary tumor size ≤5.0 cm who did not undergo surgery or chemotherapy and received SBRT or LTA. Patterns of care were assessed with multivariate logistic regression. After propensity-score weighting with generalized boosted regression, OS was assessed with univariate and doubly-robust multivariate Cox regression.ResultsOf 15,792 patients, 14,651 (93%) received SBRT and 1141 (7%) received LTA. Increasing age (OR 1.01, p = .035), treatment at an academic institution (OR 2.94, p < .001), increasing tumor size (OR 1.05, p < .001), and more recent year of diagnosis (OR 1.43, p < .001) were predictive of treatment with SBRT, whereas comorbidities (OR 0.74, p = .003) and treatment at a high-volume facility (OR 0.05, p < .001) were predictive for LTA. At a median follow-up of 26.2 months, SBRT was associated with improved OS relative to LTA within a propensity-score weighted doubly-robust multivariate analysis (HR 0.71, p < .001). On weighted subgroup analyses, improved OS was observed with SBRT for tumor sizes >2.0 cm (HR 0.72, p < .001) and for those treated at high-volume facilities (HR 0.71, p < .001). No OS difference was found with SBRT or LTA in tumor sizes ≤2.0 cm (HR 0.90, p = .227).ConclusionWithin the NCDB, SBRT was more commonly utilized and was associated with improved OS when compared to percutaneous LTA for patients with non-surgically managed early-stage NSCLC. Patients with small tumor volumes likely represent an appropriate population for future prospective randomized comparisons between SBRT and LTA.
| S-EPMC7082035 | biostudies-literature
Project description: Not available
| S-EPMC6717328 | biostudies-literature