Percutaneous CT-guided Microwave Ablation As Maintenance After First-line Treatment For Patients With Advanced NSCLC

Purpose:Lung cancer is the most common cause of death from cancer worldwide. Non-small cell lung cancer (NSCLC) accounts for 89% of lung cancer cases. Patients with advanced NSCLC are not eligible for radical surgery, systemic therapy is recommended insteadly. However, conventional first-line treatment has generated a plateau in overall response rate of 25-35%, time to progression (TTP) of 3-5 months, and median survival of 8-10 months; 1-year and 2-year survival rates are 30%-40% and 10%-15%, respectively. Most patients progress during first-line treatment, and even those responsive or stable to first-line treatment will progress inevitably during the following close observation. Thus, advanced NSCLC is an incurable disease with a poor prognosis.Maintenance therapy is applied as a systemic therapy to delay progression, and it usually involves either a non-platinum cytotoxic drug or a targeted agent. However, the following issues have been raised concerning the maintenance strategy:1) its application was limited by residual toxicity of first-line treatment and performance status, which led to the intolerance of long-term maintenance; 2) its efficacy was affected by response to first-line treatment, histologic subtype and genotypes; 3) it has not been evidently proven to improve OS, although it has been shown to improve PFS; and 4) it has not been demonstrated as superior to second-line therapy initiated at disease progression.Energy-based tumor ablation consists of the direct application of thermal and non-thermal therapies to eradicate or substantially destroy focal tumors. Microwave ablation (MWA) induces tumor cells’coagulation though high-temperature thermal injury using electromagnetic devices with frequencies from 300 MHz to 300 GHz. Percutaneous image-guided MWA is a minimally invasive therapeutic modality that has been recently proven to be safe and effective in lung cancer. The application of MWA is used to decrease local recurrence; furthermore, its efficacy is not affected by histologic subtype or genotypes theoratically. It was hypothesized that MWA may further eliminate residual tumors and decrease local recurrence after first-line treatment, thus prolonging survival and improving quality of life in a further step. We aim to evaluate the safety and efficacy of percutaneous computed tomography (CT)-guided MWA as maintenance after fist-line treatment for patients with advanced NSCLC and attempted to identify correlated predictors in our study.Materials and Methods:Patients with histologically verified advanced NSCLC (stage IIIB or IV) between January 2010 and March 2014 were involved, including those with recurrence and/or metastasis to advanced stage after initial radical surgery. First-line treatment:1) Chemotherapy regimens were all platinum-doublet regimens, all chemotherapy regimens were repeated every 3 weeks for four or six cycles; 2) Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) were administrated to patients with definite sensitizing mutations; 3) Concurrent chemo-radiation followed by chemotherapy was merely applied to patients with stage IIIB disease. The efficacy of chemotherapy, targeted therapy and radiotherapy was assessed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.After completion of first-line treatment, patients with partial response (PR) or stable disease (SD) were introduced to MWA based on multidisciplinary team (MDT) consultation.All MWA procedures were guided by CT. Local anesthesia and preemptive analgesia were performed with an electrocardiogram monitor. The entire course of treatment was separated into five steps-planning, targeting, monitoring, intraprocedural modification, and assessing treatment response. There were three MWA modes according to tumor size to make multiple overlaps achieve a large or conformal ablation zone:1) a single antenna’s insertion was used for small tumors (≤3 cm); 2) multiple insertions of a single antenna were applied for intermediate tumors (between 3-5 cm); 3) multiple antennas inserted simultaneously were used for large tumors (>5 cm).The antenna was placed into the deepest margin of the tumor with a well-fixed position, and was modified and repositioned according to imaging changes until the tumor was covered completely (plus an ablative margin of at least 5 mm, and ideally 10 mm around the tumor) or the planned imaging end point has been reached. At the end of each procedure, tract ablation was performed to prevent tumor seeding or tract bleeding before the antenna was removed.As a successful ablation zone was usually larger than the target tumor in a short time and with benign enhancement, RECIST could not assess ablation correctly; therefore, MWA was assessed by Image-guided Tumor Ablation Standardization of Terminology and Reporting Criteria. The 1-month post-ablation contrast-enhanced three-phase CT was used as the new baseline imaging for further assessments, thereafter, CT was performed every 3 months. Complications were reported according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.Complications, progression-free survival (PFS), overall survival (OS) and correlated predictors were analyzed.Results:Nineteen patients (54.3%) were assessed as having partial response to first-line treatment, while 16 patients (45.7%) were assessed as having stable disease. A total of 35 patients underwent 39 MWA procedures for 39 tumors.100% procedures were considered to be technically successful. Twenty-six procedures were performed with single antenna, while 13 procedures were performed with double antennas. The median power and duration of MWA was 70 W (range,60-75 W) and 7 minutes (range,3-15 minutes). The median time interval between best overall responses and initial MWA procedure was 1 month (range,7 days to 22 months).Local efficacy:At 1-month follow-up after initial MWA,32 tumors (82.1%) were assessed to be complete ablated, and seven tumors (17.9%) were incompletely ablated. Three of the incompletely ablated tumors were treated with additional MWA, however, only two were successfully treated finally. Therefore, the total local efficacy was 87.2%(34/39 tumors). Tumor size (cut off= 5 cm) was found to be significantly correlated with local efficacy (P=0.002).Survival:The median follow-up was 17.7 months (range,6-45 months), while the median follow-up after the initial MWA was 10.8 months (range,3-36 months). At the last follow-up, among the 34 "local efficacy" tumors, five (14.7%) were considered as local progression, and the median MWA-related local control time was 10.6 months (range,2.4-35.3 months). No significant prognostic factors were found to be correlated with MWA-related local control time.Among the total 35 patients,25 of them (71.4%) experienced progression due to local tumor progression (n=5) and distant metastases (n=20); the median MWA-related PFS and PFS were 5.4 months (range,0.7-35.3 months) and 11.8 months (range,3.2-44.7 months), respectively. Local efficacy was significantly correlated with MWA-related PFS (P=0.003). Time interval between best overall response and initial MWA was significantly correlated with PFS (P=0.011).Fourteen patients (40.0%) died, nine patients (25.7%) are living currently without progression. The causes of death were intrapulmonary progression (n=5), distant metastasis (n=8), and respiratory causes, such as acute exacerbation of chronic obstructive cardiopulmonary disease (n=1). The median MWA-related OS and OS were 10.6 months (range,3.1-36.2 months) and 17.7 months (range,5-45 months), respectively. Local efficacy was a predictor of both MWA-related OS (P=0.000) and OS (P=0.001).Complications:No death occurred during the procedure or within 30 days. Major complications were infrequent with a total incidence of 12.8%, these included symptomatic pneumothorax, bronchial fistula and pneumonia requiring intervention. Minor complications were common with a total incidence of 38.5%, these included asymptomatic or mild pneumothorax, pleural effusion, and hemorrhage. Side effects were common with a total incidence of 59%, these included pain graded 1-2 and post-ablation syndrome. Both minor complications and side effects were well-tolerated.Conclusions:1) patients benefitted from MWA as maintenance both in local control and survival; 2) as maintenance MWA was superior to conventional maintenance therapy with improved survival and well-tolerated complications.3) Definite local control and earlier MWA intervention were significantly correlated with improved survival. Therefore, MWA was a safe and effective maintenance after first-line treatment in patients with advanced NSCLC.