|Year : 2017 | Volume
| Issue : 4 | Page : 683-688
Repeated percutaneous microwave ablation for local recurrence of inoperable Stage I nonsmall cell lung cancer
Xia Yang, Xin Ye, Guanghui Huang, Xiaoying Han, Jiao Wang, Wenhong Li, Zhigang Wei, Min Meng
Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250001, Shandong, China
|Date of Web Publication||13-Sep-2017|
Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250001, Shandong
Source of Support: None, Conflict of Interest: None
Background: The safety and effectiveness of repeated computed tomography-guided percutaneous microwave ablation (MWA) in the management of local recurrence (LR) in patients with medically inoperable Stage I nonsmall cell lung cancer (NSCLC) were retrospectively evaluated.
Materials and Methods: From February 2008 to August 2014, 104 patients with medically inoperable Stage I NSCLC received MWA. Patients with LR were given repeat MWA. The clinical outcomes and complications of repeat MWA for LR were evaluated.
Results: At a median follow-up of 47 months, LR occurred in 24/104 (23.1%) patients within 12 ± 8 months after MWA. LR rates were higher in tumors >3.5 cm than that of tumors ≤3.5 cm (35.7% vs. 18.4%). Local control of the repeat MWA was achieved in 21 of 24 (87.5%) patients. Overall survival (OS) and progress-free survival (PFS) for patients without LR were similar to that of with LR and receiving repeat MWA (OS: 48 m vs. 41.5 m; PFS: 42 m vs. 32 m). The OS rates were 100%, 74.6%, 60.6%, and 27% for patients without LR at 1, 2, 3, and 5 years, and they were 96.4%, 69.5%, 60.6%, and 26.1% for patients with repeat MWA for LR. Repeat MWA for LR was not associated with more significant complications.
Conclusion: The LR was higher in tumors >3.5 cm than that of in tumors ≤3.5 cm. For patients with LR, it was feasible and effective to use MWA repeatedly to achieve the similar OS and PFS as patients without LR. No additional complications were reported in the repeat MWA compared to the original MWA.
Keywords: Computed tomography guided, local recurrence, microwave ablation, nonsmall cell lung cancer, percutaneous
|How to cite this article:|
Yang X, Ye X, Huang G, Han X, Wang J, Li W, Wei Z, Meng M. Repeated percutaneous microwave ablation for local recurrence of inoperable Stage I nonsmall cell lung cancer. J Can Res Ther 2017;13:683-8
|How to cite this URL:|
Yang X, Ye X, Huang G, Han X, Wang J, Li W, Wei Z, Meng M. Repeated percutaneous microwave ablation for local recurrence of inoperable Stage I nonsmall cell lung cancer. J Can Res Ther [serial online] 2017 [cited 2018 Aug 16];13:683-8. Available from: http://www.cancerjournal.net/text.asp?2017/13/4/683/214475
| > Introduction|| |
With continuous development in cross-sectional imaging techniques, more and more lung cancer is diagnosed in the early stage. Surgery remains the optimal selection for early-stage lung cancer, and the 5-year survival rate after surgical resection was reported to be approximately 43%–77%. However, there are certain patients with poor medical conditions, such as cardiopulmonary dysfunctions, diabetes, the elderly (>75-year-old), and other concomitant diseases, that make them not suitable for surgery. Recently, percutaneous computed tomography (CT)-guided thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), has evolved as a minimally invasive treatment option for early-stage inoperable lung cancer.,,,,,,, Compared to other local treatments such as surgery or radiotherapy, both RFA and MWA were indicated to be safe and effective., MWA has several advantages over RFA, including larger volumes of necrosis in a shorter procedure time, less “heat sink” effect for better treatment of perivascular tissue, and maximizing the ablation zone size by positioning multiple MWA antennas into larger lesions simultaneously.,,, One of the most extraordinary characteristics of this thermal ablation is that it can be applied repeatedly. It means that for patients with local recurrence (LR) and multi-metastasis in the lung, thermal ablation could be repeatedly applied as an effective treatment. However, little information has been reported on the feasibility and effectiveness of repeat thermal ablation. This study has characterized repeat MWA for treating LR in patients with medically inoperable Stage I nonsmall cell lung cancer (NSCLC) treated initially with lung MWA. The safety, effectiveness, and complications of repeat MWA were retrospectively evaluated.
| > Materials and Methods|| |
From February 2008 to August 2014, 104 patients (67 males, 37 females; mean age 69 years, ranged 51–89 years) with Stage I (T1-2aN0M0) NSCLC have received percutaneous CT-guided MWA at our hospital. Patients and tumor characteristics were listed [Table 1]. Because the PET-CT was expensive in the institution, NSCLC clinical staging was confirmed by contrast CT within a mean of 10 days preablation (range 5–15 days) after excluding distant metastasis (such as brain and bone) by MRI and ECT bone scan. All tumors were histologically proved by CT-guided core biopsy involving the recurrence sites. Patients were grouped by the presence or absence of LR after the original MWA treatment. LR was referred to as the contrast enhancement of CT (CECT) scans and proved by re-biopsy histopathology in the site of ablation, where it was diagnosed as complete ablation after the initial MWA.
All patients were evaluated by an interdisciplinary group consisting of a radiation oncologist, thoracic surgeon, thoracic radiologist, and medical oncologist. Patients met the following criteria were included in this study: (1) Stage IA or IB (T1-2N0M0), patients with poor lung function (forced expiratory volume in 1 s [FEV1] <1 L, FEV1 predicted [FEV1%] <50%, and maximum ventilator volume <50%); (2) patients who were medically inoperable with renal (endogenous creatinine clearance <50 ml/min) or heart dysfunction (New York Heart Association III/IV) and other comorbid medical conditions (i.e., severe diabetes); (3) patients who refused surgery. Patients who received previous therapy on the treated lesion were excluded. Patients were informed in detail about the risks and benefits associated with MWA treatment and provided written informed consent for the ablation procedure. Ethics approval of this study has obtained from the Institutional Review Board of Shandong Provincial Hospital Affiliated to Shandong University.
Computed tomography-guided microwave ablation
All lung MWAs were performed percutaneously with either a (1) MTC-3C MWA system (Nanjing Qi Ya Research Institute of Microwave Electric, China. Registration standard: YZB/country 1408-2003. NO: SFDA (III) 20073251059) or (2) a KY-2450B MWA system (Kangyou Microwave Institute, Nanjing, China. Registration standard: YZB/country 0247-2011. NO: SFDA (III) 20113251059). Both of the MWA systems had the same parameters. The microwave emission frequency was 2450 ± 50 MHz with an output power of 0–100 W. Microwave antennae had effective length of 100–180 mm and 14G–20G outside diameter with a 15-mm active tip, and a water circulation cooling system was applied to reduce the surface temperature of the antennae. CT (GE-lightspeed 64 V spiral, USA) was applied to guide the MWA and assess the outcomes. Local anesthesia and preemptive analgesia were performed. Preoperative localization was confirmed by the observation of CT images and movement of patient positions (supine position, lateral position, prone position, etc.). Treatment plan was designed with CT images in which the location-coordinate scale of CT was adhered to the body surface of the tumor area longitudinally. The treatment plan included: (1) to determine the location, size, shape, and relation to the nearby organs of nodular lesion; (2) to position the punctured points on body surface; and (3) to determine the best entry route from the punctured point to the deepest margin of the lesion. In addition, the treatment plan included selecting the number of total microwave antenna (single antenna was involved for tumors ≤3.5 cm and double antennae were applied for tumors 3.6–5.0 cm according to the heating effect of the antenna). In this study, single antenna was applied in 74 cases of tumors and double antennae were applied in 30 cases of tumors. Repeat MWA used the same parameters including wattage and ablation time as the initial MWA at the IR site. Track ablations were performed in both the original MWA and the repeat MWA to avoid the implantation metastasis.
All patients received a noncontrast chest CT scan 24–48 h after the ablation to detect potential complications and ground-glass opacity. Patients were requested to have serial repeat CECT scans at 1, 2, and 3 months, every 3 months in the 1st year after surgery, and then every 6 months for thereafter. Local control was referred to as no focal or diffuse enhancement of the ablated lesion on the CECT of follow-up imaging. The progress-free survival (PFS) for patients with LR was the time from the repeat MWA to the time of local or distant metastasis.
Microwave ablation complication assessment
Complication assessment was guided by standards which were set by the International Working Group on Imagine-Guided Tumor Ablation in 2005.
Data analysis was performed with SPSS 13.0 (SPSS Inc., Chicago, IL, USA) statistical software. Survival curves to estimate overall survival (OS) and disease-free survival were constructed using the Kaplan–Meier method and compared using the log-rank test. Comparison of LR between groups was performed by Chi-square test. Comparison of tumor diameter between groups with and without LR was performed by student t-test. Statistical significance level was set at P < 0.05.
| > Results|| |
According to the review of consecutive data from February 2008 to August 2014, 104 patients (67 males, 37 females; mean age 69 years, ranged 51–89 years) with Stage I (T1-2aN0M0) NSCLC received percutaneous CT-guided MWA at our hospital. One-hundred and twenty-eight sessions were identified, including 104 sessions for the original tumor and 24 sessions of the repeat MWA for LR, with a median follow-up of 47 months (ranged 4–78 months). LR after the initial MWA occurred in 24 of 104 treatments (23.1%) within 12 ± 8 months (ranged 3–26 months) [Table 1]. In the 24 cases of CT-diagnosed LR, 21 cases were proved by re-biopsy histopathology and the other 3 recurrence sites were adenocarcinoma originally. The mean maximum diameter for all patients was 2.3 ± 1.3 cm. For patients with and without LR, the mean maximum diameters were 3.2 ± 1.8 cm and 1.9 ± 1.2 cm (P = 0.00016), respectively. LR was higher in tumors with a maximum diameter between 3.6 and 5.0 cm (10/28, 35.7%) than tumors ≤3.5 cm (14/76, 18.4%) (P = 0.009). Twenty-four patients with LR were given repeat MWA as soon as LR was diagnosed [Figure 1]. The local control rate was 76.9% (80/104) for the primary MWA and 87.5% (21/24) for the repeat MWA for patients with LR. For all of the 104 patients, the 3-year OS rate was 61.1% and the 5-year survival rate was 27.8%. The OS rates were 100%, 74.6%, 60.6%, and 27% for patients without LR at 1, 2, 3, and 5 years, and they were 96.4%, 69.5%, 60.6%, and 26.1% for patients with repeated MWA for LR. The OS for patients both without LR and with repeat MWA for LR was similar (48 m vs. 41.5 m, P = 0.84, hazard ratio [HR] = 1.101) [Figure 2]. The PFS for patients without LR and with repeat MWA for LR was 42 and 32 months, respectively (P = 0.58, HR = 1.382) [Figure 3].
|Figure 1: A 77-year-old-man had an adenocarcinoma in the left upper lobe and was referred for microwave ablation. (a) Computed tomography image before the original microwave ablation. (b) Computed tomography image during the original microwave ablation. (c) 6 months after the original microwave ablation. (d) Twenty-nine months after the original microwave ablation showed local progression (arrow). (e) Computed tomography scan obtained in the repeat microwave ablation. (f) Nineteen months after the repeat microwave ablation indicated the complete ablation|
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|Figure 2: Overall survival for patients without local recurrence was 100%, 74.6%, 60.6%, and 27% at 1, 2, 3, and 5 years, respectively; median survival was 48 months. For patients with repeated microwave ablation for local recurrence, the overall survival was 96.4%, 69.5%, 60.6%, and 26.1% at 1, 2, 3, and 5 years, respectively; median survival was 41.5 months|
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|Figure 3: The progress-free survival for patients without local recurrence and with repeat microwave ablation for local recurrence was 42 and 32 months, respectively (P = 0.58, hazard ratio = 1.382)|
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Side effects and complications of microwave ablation treatment
The procedure was safe and completed for all patients, not only for patients without LR but also for LR patients with repeat MWA. No patients died in the original MWA or repeat MWA during the procedure or within 30 days after MWA.
Pain was the main side effect during the original and repeat MWA procedure. In the original MWA, moderate-to-severe pain occurred in 48 sessions (46.2%), and in the repeat MWA, it occurred in 10 sessions (41.7%) (P = 0.69). The main reason for pain was the distance to the chest wall being <1.5 cm, which could be alleviated with instant subcutaneous injection of morphine. No additional severe pain was identified in the repeat MWA, compared to that of in the original MWA.
The main symptoms included fever (under 38.5°C), fatigue, general malaise, nausea, and vomiting and occurred in 32 cases (30.8%) in the original MWA and 8 cases (33.3%) in the repeat MWA. No significant difference was observed between the two groups (P > 0.05). The postablation syndrome regressed without special treatment for any patient.
Pneumothorax was the most common complication not only in the original MWA but also in the repeat MWA. A chest tube was applied when the pneumothorax could not be alleviated by aspiration in the process of ablation or when the pneumothorax increased and resulted in chest distress after the ablation. There were a total of 56/104 (53.8%) pneumothoraxes, and chest tube drainage was required in 18 patients (17.3%) in the original MWA. Thirty-two of fifty-six (57.1%) pneumothoraxes occurred in the procedure and others were detected 24 h after the procedure. In the repeat MWA, a pneumothorax occurred in 11/24 (45.8%), with 4 patients (16.7%) required chest tube drainage. Seven out of eleven (63.6%) pneumothoraxes occurred in the procedure and others were detected 24 h after the procedure. Other complications, including hemoptysis, pleural effusion, and pneumonia, occurred in the original and repeat MWA are no significantly different [Table 2]. Three patients in the original MWA suffered from bronchopleural fistula with pleural tube drainage, but none of these cases occurred in the repeat MWA. Three patients were diagnosed as invasive pulmonary aspergillosis after the original MWA, and there was no special infection case after the repeat MWA. The average stay in hospital was 5.1 days for the original MWA and 4.8 days for the repeat MWA. The main reasons for the prolonged hospital stay were the major complications including severe pneumothorax, continuous pleural effusion, and refractory infection secondary to the bronchopleural fistula.
| > Discussion|| |
Recently, with the development of thermal ablation techniques, MWA has been proven to be an effective treatment for early-stage NSCLC, especially for patients with concomitant diseases not suitable for surgery. Many clinical studies have indicated that for Stage I NSCLC, thermal ablation including RFA, MWA, and cryoablation has provided the same OS as surgery and stereotactic radiotherapy.,, Our previous study indicated that in 47 cases of Stage I NSCLC at a median follow-up period of 30 months, the median time to the first recurrence was 45.5 months. The local control rates at 1, 3, and 5 years after MWA were 96%, 64%, and 48%, respectively. The median cancer-specific and median OS were 47.4 and 33.8 months, respectively. These results indicated that local control was good in MWA for the treatment of Stage I NSCLC. In this study, our clinical outcomes indicated that for these 104 cases of Stage I NSCLC treated with MWA, the OS for patients with or without LR was 41.5 and 45 months, respectively. These clinical studies have presented MWA as an effective treatment for Stage I NSCLC.
Several studies have reported that local control and OS outcomes were better in tumors with a diameter <3.5 cm than that of in tumors >3.5 cm after MWA., In this study, the total LR was 23.1% for all tumors. For tumors exceeding 3.5 cm, the LR was clearly higher than in tumors <3.5 cm (40% vs. 16.2%) (P < 0.05). The limited ablation size of the MWA technique has been the main contributing reason. In this study, 30 ablations applied double antennae, and LR occurred in 12 cases. Many factors would influence the ablation effect: (1) the irregular tumor shapes made it difficult for optimizing the ablation antenna to fully cover the whole mass and completely kill tumor cells, resulting in tumor residues; (2) the tumor was too close to large blood vessels, resulting in tumor residues around the vessel due to the “heat sink” effect; or (3) the tumor was adjacent to important organs such as mediastinal structures. In this study, some tumors were found to be incompletely ablated because they were adjacent to the pericardium [Figure 4]. In addition, although complete ablation was achieved after the original MWA, there was still LR in some patients [Figure 4]. It may be resulted from the lung scar carcinoma which has been proposed in recent years. The injuries, inflammation, and infection after the original MWA and other chronic lung diseases might lead to the malignant transformation.
|Figure 4: A 73-year-old-man with an adenocarcinoma in the left inferior lobe close to the pericardium (arrow). (a) Computed tomography image before the original microwave ablation. (b) Computed tomography image of the original microwave ablation. (c) Three months after the original microwave ablation indicated the complete ablation (arrow). (d) Twenty months after the original microwave ablation shows local enhancement (arrow). (e) Computed tomography scan obtained during the repeat microwave ablation. (f) Eighteen months after the repeat microwave ablation showed complete ablation|
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One of the extraordinary characteristics of MWA and RFA is that it could be applied repeatedly. There are several studies illustrating the feasibility and effectiveness of repeated MWA. Michael Lanuti et al. reported the clinical outcome of repeat RFA in the treatment of locoregional recurrence in patients with high-risk Stage I NSCLC. Forty-five patients were treated with RFA, and 21 cases were diagnosed as having locoregional recurrence. Five cases were treated with repeat RFA, and local control was achieved in 2 cases. Repeat RFA was not associated with any significant complication or procedure-related 30-day mortality. Tomohisa also reported re-RFA for recurrent lung tumors previously treated with RF ablation. Although only 10 patients were observed, the study indicated that re-radiofrequency was feasible without any major complication. Our study indicated that repeat MWA was effective as an alternative choice for LR after the original MWA. Similar OS and PFS can be obtained for patients with repeat MWA for LR as the patients without LR.
Pneumothorax was still the most common complication in the repeat MWA. In the present study, pneumothorax occurred in 45.8% of patients with repeat MWA for LR, and 16.7% of patients required chest tube drainage. Other complications including hemoptysis, pleural effusion, pneumonia, and bronchopleural fistula, occurred in the original and repeat MWA with no significantly different frequency. These results indicated that repeat MWA was safe and feasible for the treatment of LR.
There were certain limitations in this retrospective study, including the small number of patients, especially in the LR group and the short follow-up time for all the patients. The alternative treatment for patients with LR including radiotherapy or brachytherapy could also be compared with the repeat MWA from the perspectives of clinical effects and complications.
| > Conclusion|| |
Good long-term results can be achieved in MWA treatment of medically inoperable Stage I NSCLC. Repeat MWA has been a safe and effective method for the treatment of LR without detrimental effect to survival. However, as a local treatment method, more definitive and randomized trials about MWA in the treatment of high-risk or medically inoperable Stage I NSCLC should be carried out in the future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]