Thermal ablation of stage I non-small cell lung carcinoma.
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ABSTRACT:
SUBMITTER: Ridge CA
PROVIDER: S-EPMC4078110 | biostudies-other | 2014 Jun
REPOSITORIES: biostudies-other
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Project description:Introduction:Heterogeneity of non-small cell lung carcinoma (NSCLC) among patients is currently not well studied. Pathologic markers and staging systems have not been a precise predictor of the prognosis of an individual patient. Hence, we hypothesize to develop a transcript-based signature to categorize stage IIIA-NSCLC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), plus identify markers that could indicate the prognosis of the disease. Methods:Human Transcriptome Array 2.0 (HTA) and NanoString nCounter® platform were used for high-throughput gene-expression profiling. Initially, we profiled stage IIIA-NSCLC through HTA and validated through NanoString. Additionally, two metastatic markers SPP1 and CDH2 were validated in 47 NSCLC stage IIIA samples through real-time PCR. Results:We observed distinct gene clusters in LUAD and LUSC with down-regulation of six genes and up-regulation of 57 genes through HTA. Ninety-six transcripts were randomly selected after analyzing HTA data and validated on the NanoString platform. We found 40 differentially expressed transcripts that categorized NSCLC into LUAD and LUSC. SPP1 is significantly overexpressed (4.311±1.27 fold in LUAD and 13.41±3.82 fold in LUSC compared to control), and the CDH2 transcript was significantly overexpressed (11.53 ± 4.027-fold compared to control) only in LUSC. Discussion:These markers enable us to categorize stage IIIA NSCLC into LUAD and LUSC plus these markers may be helpful to understand the pathophysiology of NSCLC. However, more data required to make these findings useful in general clinical practice.
| S-EPMC7685366 | 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.
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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:IntroductionNon-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Currently, surgical resection is the gold standard of treatment. However, as patients are becoming medically more complex presenting with advanced disease, minimally invasive image-guided percutaneous ablations are gaining popularity. Therefore, comparison of surgical, ablative and second-line external beam therapies will help clinicians, as management of NSCLC changes. We will conduct a meta-analysis, reviewing literature investigating these therapies in adult patients diagnosed with stage 1 NSCLC, with neither hilar nor mediastinal nodal involvement, confirmed either through cytology or histology regardless of type.Methods and analysisWe will search electronic databases (MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, Cochrane) from their inception to January 2021 to identify randomised controlled trials (RCTs), cluster RCTs and cohort studies comparing survival and clinical outcomes between any two interventions (lobectomy, wedge resection, video-assisted thoracoscopic surgery/robot-assisted thoracoscopic surgery, radiofrequency ablation, microwave ablation, cryoablation and consolidated radiation therapies (external beam radiation therapy, stereotactic body radiation therapy, and 3D conformal radiation therapy). The primary outcomes will include cancer-specific survival, lung disease-free survival, locoregional recurrence, death, toxicity and non-target organ injury. We will also search published and unpublished studies in trial registries and will review references of included studies for possible inclusion. Risk of bias will be assessed using tools developed by the Cochrane collaboration. Two reviewers will independently assess the eligibility of studies and conduct the corresponding risk of bias assessments. For each outcome, given enough studies, we will conduct a network meta-analysis. Finally, we will use the Confidence in Network Meta-Analysis tool to assess quality of the evidence for each of the primary outcomes.Ethics and disseminationWe aim to share our findings through high-impact peer review. As interventional techniques become more popular, it will be important for providers in multidisciplinary teams caring for these patients to receive continuing medical education related to these interventions. Data will be made available to readers.Prospero registration numberCRD42021276629.
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Project description:A squamous cell lung cancer patient was treated with pneumonectomy. A recurrent lung cancer (adenocarcinoma) was found 45 months later and successfully biopsied and treated with microwave ablation. After 18 months of follow up, no evidence of tumor recurrence was observed.
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Project description:Systemic treatment in small cell lung carcinoma has been a challenge for oncologists for decades. The high propensity for recurrence is usually due to distant metastasis, which makes systemic treatment an essential component of treatment in small cell lung carcinoma. The regimen of cisplatin and etoposide (established in the mid-1980's) concurrently with thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) remains the standard of care in limited stage disease. Despite numerous trials, this regimen has not been improved upon. The standard combination regimen of cisplatin and etoposide has been compared to alternative platinum-containing regimens with drugs like epirubicin, irinotecan, paclitaxel, topotecan, pemetrexed, amrubicin and belotecan. Non-platinum containing regimens like ifosfamide and etoposide have also been tested. Attempts to intensify therapy have included the addition of a third drug like paclitaxel, ifosfamide, tirapazamine, tamoxifen, and thalidomide. Maintenance therapy following induction with chemotherapy, vandetanib and interferon-alpha have also been attempted. Molecularly directed targeted therapies and immunotherapeutic agents are areas of active research. In this review, we discuss the various systemic therapy options in limited stage small cell lung carcinoma, from the historical regimens to the modern-day therapy and promising areas of research. We also discuss the role of growth factors, the optimal number of chemotherapy cycles, the use of prognostic and predictive factors, the optimal timing of chemotherapy and the treatment of special populations of patients including older patients, and patients with comorbidities.
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Project description:Background: Approximately 20% resectable non-small cell lung cancer (NSCLC) patients are treated non-surgically due to various reasons. The aim of the present study was to compare the effectiveness of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in patients with stage IA NSCLC who were ineligible for surgery using the surveillance, epidemiology and end-results (SEER) Database. Methods: Using the SEER registry, we identified a total of 6,195 IA NSCLC patients who received SBRT or RFA between 2004 and 2015 because of ineligibility for surgical resection due to various reasons. Complete clinical information was available in all these patients. Overall survival (OS) and cancer-specific survival (CSS) were compared between RFA and SBRT groups by using propensity score matching (PSM), inverse probability of treatment weight (IPTW), and overlap weighting analysis. Additionally, an exploratory analysis was conducted to determine the effectiveness of RFA treatment based on the subsets of clinically relevant patients. Results: Of the 6,195 nonsurgical IA NSCLC patients, 191 patients (3.1%) received RFA and the other 6,004 patients (96.9%) received SBRT. The one-, three- and five-year OS in the unmatched RFA and SBRT groups were 83.3%, 48.5%and 29.1% vs. 83.8%, 48.3% and 27.4%, respectively, there was similar results in the PSM, IPTW, overlap weighing analysis. Nonsurgical IA NSCLC patients receiving RFA seemed to have better five-year survival than those receiving SBRT, though the difference was not statistically significant (OS, HR; 0.986; 95% CI, 0.827-1.175, P=0.8738; CSS, HR; 0.965; 95% CI, 0.765-1.219, P=0.7663). We found that the odds of receiving RFA decreased with larger tumor size (>2, <3 cm, OR; 0.303; 95% CI, 0.191-0.479; >3 cm, OR; 0.153; 95% CI, 0.093-0.251) compared with tumor size <1 cm. In subgroup analysis, patients receiving RFA seemed to have better OS than those receiving SBRT, though the difference was not statistically significant. This specific trend was even more obvious in patients with tumors <1cm in diameter (P=0.1577). Conclusion: In comparison with SBRT, RFA did not seem to adversely affect CSS and OS of IA NSCLC patients who were not suitable for surgical treatment. In addition, RFA seemed to offer better survival to IA NSCLC patients, especially those with tumors <1 cm.
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