Microwave Ablation with or Without Chemotherapy in Management of Non-Small Cell Lung Cancer: A Systematic Review

Abstract Introduction Microwave ablation (MWA) has emerged as a minimally invasive treatment for patients with inoperable non-small cell lung cancer (NSCLC). However, whether it is more effective as a standalone treatment or in combination with chemotherapy warrants further investigation. This systematic review assesses the efficacy and safety of MWA as a standalone treatment and in combination with chemotherapy in managing NSCLC. Methods Studies were included if MWA was used either as a standalone treatment or combined with chemotherapy for managing NSCLC, regardless of whether chemotherapy was administered before or after MWA. Results The patient cohort included 928 patients. In 63.8% of the cases, MWA was used alone, and in 36.2% with chemotherapy. Complications from MWA alone were higher (59.29% vs. 32.74%). The tumor stage in 52.36% of the cases who underwent MWA alone was stage I; however, it was the IV stage in 82.44% of the cases who underwent MWA combined with chemotherapy. Patients with available data and treated with MWA alone experienced higher local progression (26% vs. 18.5%), distant recurrence (51.5% vs. 38.5%), and both local and distant recurrence (10.8% vs. 2.6%). Reported complete response was 88.6% among cases that underwent MWA alone. While it was 78.0% in those who underwent combined MWA and chemotherapy. The median overall survival was higher in the MWA alone group (24.9 to 69.6 months vs. 21.3 to 23.90 months). Conclusion MWA combined with chemotherapy may represent a more effective option, with a slightly similar treatment response, reducing the risk of recurrence and minimizing complications. Introduction Lung cancer is the leading cause of cancer-related mortality among both men and women worldwide [1,2]. It primarily consists of two main types: non-small cell lung cancer (NSCLC), which comprises 85% of cases, and small cell lung cancer (15%). The World Health Organization classifies NSCLC into three main subtypes: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma [1]. NSCLC has one of the lowest five-year survival rates, hovering around 20% [3]. Cigarette smoking is the primary risk factor for lung cancer, responsible for 85% to 90% of cases. The risk is closely linked to smoking extent and exposure to carcinogens like asbestos, ionizing radiation, environmental toxins, and certain metals. Other risk factors include pulmonary fibrosis and alcohol consumption [1]. Occupational exposures, particularly to carcinogens like crystalline silica, asbestos, and radioactive materials, significantly increase lung cancer risk. In addition, familial clustering suggests a hereditary component to the disease [4]. Although smoking remains the leading cause, 12% of lung cancer cases are non-smokers, with higher rates in women [1,5]. The most common symptom of the disease is cough, followed by hemoptysis and chest pain [6]. Lung cancer is often diagnosed at intermediate or advanced stages due to its low early diagnostic rate, high malignancy, and complex biological characteristics [7]. However, low-dose computed tomography screening has improved early detection rates [8]. Surgical resection is the preferred treatment for early-stage NSCLC when the disease is operable. However, despite advancements in sub-lobar resection techniques to preserve lung function, more than 25% of patients with early-stage NSCLC are unable to undergo surgery due to factors like poor cardiopulmonary function, anatomical challenges, failure of conventional therapies, or personal choice. For these patients, non-surgical options such as stereotactic ablative radiotherapy, targeted therapies, and thermal ablation are typically recommended [6,8-10]. Thermal ablation therapies use various approaches to destroy cancer cells through heat or cold. In recent years, microwave ablation (MWA) has emerged as a viable alternative, offering outcomes comparable to lobectomy [8,9]. To our knowledge, no systematic review has been conducted on the effect of MWA alone or in combination with chemotherapy in managing NSCLC. This systematic review aims to evaluate the efficacy and safety of both treatment regimens in managing NSCLC. Methods Study design This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data sources and search strategy A systematic search on PubMed and Google Scholar was conducted to identify relevant English-language studies using MWA with chemotherapy or MWA alone in treating NSCLC. The search utilized the keywords "microwave ablation," "chemotherapy," "non-small cell lung cancer," "adenocarcinoma," "squamous cell carcinoma," and "large cell carcinoma." Eligibility criteria Studies were included if MWA was used either as a standalone treatment or combined with chemotherapy for managing NSCLC, regardless of whether chemotherapy was administered before or after MWA. Excluded studies included abstracts, retracted papers, case reports, reviews, and publications in predatory journals [11]. Study selection and data extraction The following data were extracted from each eligible article: author, year of publication, study design, sample size, patient demography, tumor characteristics, management, characteristics of the MWA (frequency, antenna length, anesthesia type, power, ablation time), the chemotherapy drug, complications, and the outcomes. Statistical analysis The extracted data were collected in a Microsoft Excel sheet (2021) and then transferred into the Statistical Package for the Social Sciences software (version 27). Qualitative analysis was conducted, and the data were presented as frequency, percentage, mean with standard deviation, and median with range. Results Study selection A total of 76 studies were identified through the search. Before screening, 17 studies were excluded due to duplication (n=6), retraction (n=3), and being available only as abstracts (n=8), leaving 59 studies for title and abstract screening. At this stage, 13 irrelevant studies were excluded. Irrelevant studies were those utilizing treatment modalities other than MWA with or without chemotherapy or where patients received other treatments before or after the primary intervention. Consequently, 46 studies underwent full-text screening, which led to the exclusion of 29 studies due to irrelevancy (n=15), unretrievable data (n=8), review articles (n=4), and case reports (n=2). Then, another study was excluded for being published in a predatory journal. Ultimately, 16 studies involving 928 cases met the eligibility criteria and were included [7-9,12-24] (Figure 1). The majority of included studies were cohort studies (n=14), along with two randomized controlled trials (RCTs) (Tables 1 and 2). Table 1. Clinical characteristics of the included studies. Author, year [Reference] Study design No. of cases Mean age) Gender Mean tumor size (cm) Tumor staging Tumor type Location (Lobe) Management Guidance Frequency (MHz) Antenna length (Max, mm) Antenna diameter (Max, G) Active tip (mm) Anesthesia M F I II III IV ADC SCC Other U&M L CS LA LA + CS LA + IV Shan et al. 2021 [7] RCT 67 61.5 46 21 3.8 0 0 0 67 29 38 N/A N/A N/A MWA + Chemo. CT N/A N/A N/A N/A 0 67 0 0 Wu et al. 2024 [8] Cohort 55 59.75 40 15 2.89 55 0 0 0 28 23 4 N/A N/A MWA CT 2450 180 19 N/A 55 0 0 0 Han et al. 2019 [9] Cohort 63# 82.1 40 23 N/A N/A N/A N/A N/A 47 17 1 N/A N/A MWA CT 2450 180 18 15 0 63 0 0 Lv et al. 2023 [12] Cohort 118 N/A 69 49 N/A N/A N/A N/A N/A 94 N/A N/A 73 45 MWA CT 2450 180 18 N/A 0 118 0 0 Xu et al. 2023 [13] Cohort 33* 68.4 19 14 4.4 6 3 7 1 25 7 1 N/A N/A MWA CT 2450 180 18 15 0 0 0 33 Li et al. 2023 [14] Cohort 19 71.42 15 4 2.06 19 0 0 0 6 12 1 14 5 MWA CT 2450 180 18 5 0 19 0 0 Hu et al. 2021 [15] Cohort 68 83.1 44 24 2.3 68 0 0 0 41 24 N/A N/A N/A MWA CT 2450 180 17 N/A N/A N/A N/A N/A Das et al. 2019 [16] Cohort 56 59.1 34 22 2.9 0 0 32 24 43 10 3 37 19 MWA CT N/A N/A 20 N/A 0 56 0 0 Wei et al. 2019 [17]** Cohort 18 74 9 9 3.3 0 0 8 10 13 N/A N/A 10 8 MWA CT 2450 180 20 N/A 0 18 0 0 Wei et al. 2019 [17]** Cohort 36 76 21 15 4.3 0 0 16 20 28 N/A N/A 24 12 MWA + Chemo. CT 2450 180 20 N/A 0 36 0 0 Wang et al. 2018 [18] Cohort 46 N/A 22 24 N/A 46 0 0 0 18 21 7 N/A N/A MWA CT N/A 200 N/A N/A N/A N/A N/A N/A Yao et al. 2018 [19] Cohort 54 56.65 37 17 3.01 54 0 0 0 27 16 11 30 24 MWA CT N/A N/A N/A N/A 54 0 0 0 Yang et al. 2014 [20] Cohort 47 69.4 30 17 N/A 47 0 0 0 28 13 N/A N/A N/A MWA CT 2450 180 20 15 0 47 0 0 Liu et al. 2013 [21] Cohort 15 71.25 11 4 2.55 15 0 0 0 N/A N/A N/A 10 5 MWA CT 2450 140 N/A 16 0 0 15 0 Wei et al. 2020 [22] RCT 148 59 96 52 3.6 0 0 31 117 116 N/A N/A N/A N/A MWA + Chemo. CT 2450 180 20 N/A 0 148 0 0 Wei et al. 2015 [23] Cohort 46 58.5 27 19 3.7 0 0 8 38 36 N/A N/A 32 14 MWA + Chemo. CT 2450 180 20 N/A 0 46 0 0 Wei et al. 2014 [24] Cohort 39 57 22 17 3.84 0 0 4 35 27 N/A N/A 28 11 MWA + Chemo. CT 2450 180 20 N/A 0 39 0 0 Table 2. Management and outcome.