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 » Introduction
 »  Materials and Me...
 » Results
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ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 6  |  Page : 56-60
 

Computed tomography-guided percutaneous microwave ablation of patients 75 years of age and older with early-stage nonsmall cell lung cancer


Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China

Date of Web Publication24-Dec-2015

Correspondence Address:
X Ye
Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.172514

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 » Abstract 

Background: We aimed to assess the clinical outcome of computed tomography (CT)-guided percutaneous microwave ablation (MWA) in patients 75 years of age and older with early stage peripheral nonsmall cell lung cancer (NSCLC). Materials and Methods: Twenty-eight patients, aged ≥75 years, with Stage I and lymph node-negative IIa peripheral NSCLC underwent CT-guided percutaneous MWA in our hospital between July 2007 and March 2015. The overall 1-, 2-, 3-, and 4-year survival rates were estimated using Kaplan–Meier analysis. Adverse events were recorded. Results: The median follow-up time was 22.5 months. The overall median survival time (MST) was 35 months (95% confidence interval [CI] 22.3–47.7 months), and the cancer-specific MST was 41.9 months (95% CI 38.8–49.9 months). The 1-, 2-, 3-, and 4-year overall survival rates were 91.7%, 76.5%, 47.9%, and 47.9%, while the cancer-specific survival rates were 94.7%, 73.9%, 64.7%, and 64.7%, respectively. Median time to local progression was 28.0 months (95% CI 17.7–38.3 months). Major complications were included pneumothorax (21.4%, requiring drainage), pleural effusions (3.6%, requiring drainage), and pulmonary infection (3.6%). Conclusions: CT-guided percutaneous MWA is safe and effective for the treatment of patients 75 years of age and older with medically inoperable early stage peripheral NSCLC.


Keywords: Elderly, microwave ablation, nonsmall cell lung cancer


How to cite this article:
Han X, Yang X, Ye X, Liu Q, Huang G, Wang J, Li W, Zheng A, Ni Y, Men M. Computed tomography-guided percutaneous microwave ablation of patients 75 years of age and older with early-stage nonsmall cell lung cancer. Indian J Cancer 2015;52, Suppl S2:56-60

How to cite this URL:
Han X, Yang X, Ye X, Liu Q, Huang G, Wang J, Li W, Zheng A, Ni Y, Men M. Computed tomography-guided percutaneous microwave ablation of patients 75 years of age and older with early-stage nonsmall cell lung cancer. Indian J Cancer [serial online] 2015 [cited 2019 Dec 9];52, Suppl S2:56-60. Available from: http://www.indianjcancer.com/text.asp?2015/52/6/56/172514



 » Introduction Top


Primary lung cancer remains the leading cause of the death from malignant tumors worldwide. Nonsmall cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases.[1] An increase in life expectancy in the general population has led to a rising incidence of lung cancer among elderly patients. Among newly diagnosed lung cancer cases, 50% of the patients are >65 years and 30–40% are >70 years.[2] Compared with their younger counterparts, elderly patients with NSCLC are often unsuitable for standard chemotherapy owing to severe chemotherapy-induced toxicity, comorbidities, and the resulting deterioration in the quality of life.[3],[4] Elderly patients are often underrepresented in clinical trials, and validated treatment options remain limited.[5] Therefore, lung cancer is among the most detrimental diseases affecting elderly population. Surgery is the preferred standard treatment of primary lung cancer.[6] However, patients with insufficient cardiopulmonary function, advanced age, other medical comorbidities, and metastatic pulmonary tumors are not suitable candidates for surgery, which is likely to yield low survival rates.[7] In recent years, image-guided percutaneous thermal ablations, such as radiofrequency ablation (RFA) and microwave ablation (MWA), has evolved as a minimally invasive treatment option for patients with early stage inoperable lung cancer.[8],[9],[10],[11]

As a novel technique for tumor ablation in the recent decade, MWA has been widely applied to treat multiple types of malignant tumors including liver, lung, metastatic bone, and renal tumors.[12],[13],[14],[15] The aim of this study was to evaluate the survival benefits and local control rates of MWA as an alternative treatment of elderly patients with inoperable peripheral Stage I and lymph node-negative IIa NSCLC.


 » Materials and Methods Top


Patients

Between July 2007 and March 2015, 28 elderly patients diagnosed with Stage I and lymph node-negative IIa NSCLC underwent MWA in our institution. 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 to conduct this study was obtained by the Institutional Review Board of Shandong Provincial Hospital Affiliated to Shandong University. All disease staging was carried out using UICC TNM-7.[16] All patients were evaluated by a multi-disciplinary group, including a radiation oncologist, thoracic surgeon, thoracic radiologist, and medical oncologist. The inclusion criteria were (1) stage cT1A-cT2BN0M0 pathological confirmed NSCLC, (2) age ≥75 years, (3) peripheral tumors, (4) unable to undergo thoracic surgery or refusal of alternative surgeries, (5) no medical history of other malignant tumors, and (6) normal cognition and without serious mental diseases such as schizophrenia or suicidal tendencies. The exclusion criteria were (1) Stage IIb-IV or lymph node-positive IIa, (2) age <75 years, (3) past medical history of other types of malignant tumor, (4) with severe psychological diseases, (5) central tumors, and (6) no pathological confirmation of NSCLC. Patient characteristics are listed in [Table 1]. The median follow-up postablation was 22.5 months (range: 4–53 months). All diagnoses were confirmed by biopsy, and tumor staging was validated by performing brain, lung, and abdominal contrast-enhanced computed tomography (CECT).
Table 1: Patient distribution and clinical characteristics

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Instrumentation

A GE Light Speed 16 or VCT 64 spiral CT system (GE Healthcare, Atlanta, GA, USA) was used for imaging guidance and monitoring. A MTC-3C MWA system (Vison-China Medical Devices R and D Center, Nanjing, China. Registration standard: YZB/country 1408–2003. No: SFDA [III] 20073251059), or KY-2450B MWA system (Kangyou Microwave Institute, Nanjing, China. Registration standard: YZB/country 0247–2011. No:SFDA [III]20073251059) was adopted. The main frequency was 2450 GHz, and the output power was 0–100 W (continually adjustable). The microwave antenna had an effective length of 100–180 mm and an outside diameter of 15–18 G, with a 15-mm active tip, and had a water circulation cooling system to reduce its surface temperature.

Therapeutic protocol

We administered local anesthetic agents along with preemptive analgesic agents.[17] All patients fasted for 12 h before the procedure. As preemptive analgesia, 10 mg morphine and 10 mg diazepam were administered 30 min before treatment, and 50 mg flurbiprofen axetil was administered 15 min before treatment. Two percentage lidocaine was injected at the puncture site for local anesthesia. MWA procedures were performed under CT-guidance. The detailed of MWA procedure was described in a previous publication.[8],[14] One antenna was applied for tumors ≤3.5 cm in diameter, and two for those >3.5 cm in diameter simultaneously.[8], 14, [18],[19],[20],[21] The antenna has a single slot. MWA with an output of 60–70 W/5–7 min and an ablative zone of nearly 3.5 cm × 3 cm was used, with a proposed ablative margin of 0.5 cm.

Evaluation

All patients underwent a noncontrast chest CT scan 24 h after the ablation procedure to detect early-onset, asymptomatic complications, and ground glass opacities surrounding the lesions. Local efficacy was assessed according to the standards drafted by Ye et al.[10] Complete ablation is indicated by lesion disappearance, complete cavernous formation, fibrotic progression or scar, solid nodule involution or no change without contrast enhanced signs on the CT scan, and/or atelectasis. Incomplete ablation is indicated by incomplete cavernous formation, with some solid or liquid components remaining and irregular peripheral or internal enhancement signs on CT scans, partial fibrosis with solid residues in the fibrotic lesion, which presents as irregular peripheral or internal enhancement signs on CT scans, and/or solid nodules with unchanged or increased size, which also present as irregular peripheral or internal enhancement signs on CT scans. A focal enhancement at the ablation site or enlargement of the ablated tumor after a series of shrinkage was considered local recurrence if technical success had been confirmed. Overall survival duration was defined as the interval between the date of the initial procedure and death or final follow-up. All patients of survival at 1, 2, 3, and 4 years were recorded.

Complication assessment

Complications were assessed according to the standards drafted by the International Working Group on Imagine-guided Tumor Ablation in 2005 and 2014.[22],[23] Major complications were defined as clinical symptoms during or after ablation that may be life-threatening, resulting in substantial damage, and dysfunction and requiring hospitalization or prolonged hospitalization. Minor complications were defined as self-limiting complications without sequelae and requiring only a short hospital stay for observation or treatment. Side effects referred to pain, postablation syndrome, and asymptomatic minor bleeding or fluid accumulation on CT.

Statistical analysis

The data were processed with SPSS for Windows version 19.0 (IBM, Chicago, IL, USA). Survival curves were constructed with the Kaplan–Meier method and compared with the log-rank test. P < 0.05 was considered statistically significant.


 » Results Top


Survival

The median follow-up postablation was 22.5 months (range: 4–53 months). All of the procedures were deemed technically successful. No patient was out of follow-up. Five patients died from noncancer-related causes, including 3 patients from nontumor-associated obstructive pneumonia and 2 patients from cardiocerebral events. None of the 5 patients had local recurrences or remote metastases. There were 5 patients died of tumor progression.

The overall median survival time (MST) was 35.0 months (95% confidence interval [CI], 22.3–47.7 months). The cancer-specific MST was 41.9 months (95% CI, 38.8 – 49.9 months). The 1-, 2-, 3-, and 4-year overall survival rates were 91.7%, 76.5%, 47.9%, and 47.9%, respectively [Figure 1]. The cancer-specific survival rates at 1-, 2-, 3-, and 4-year were 94.7%, 73.9%, 64.7%, and 64.7%, respectively [Figure 2].
Figure 1: The Kaplan–Meier plot of overall survival

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Figure 2: The Kaplan–Meier plot of cancer-specific survival

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Local efficacy

Local recurrence was confirmed in 9 patients (32.1%) by CECT. Median time to local progression was 28.0 months (95% CI, 17.7–38.3 months). The 1-, 2-, 3-, and 4-year local control rates were 80.5%, 73.8%, 22.1%, and 22.1% [Figure 3].
Figure 3: The Kaplan–Meier plot of overall local control rates

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Complications and management

No patient died during the procedure or in 30 days after MWA. Fourteen patients developed pneumothorax, eight of whom were managed with closed drainage, and the remaining six cases were self-limited. One patient with pneumothorax had co-existing subcutaneous emphysema. One patient had moderate hemoptysis during the procedure, which resolved quickly with ablation. Two patients with hydrothorax required interventional drainage. One patient developed pneumonia and were managed with sputum culture-specific antibiotics. A 79-year-old woman who had a history of stroke developed an acute callosal infarction 3 days after MWA and was cured within several days without sequelae.


 » Discussion Top


Lobectomy is the standard treatment of early-stage NSCLC. However, many patients with NSCLC are not medically fit for lobectomy because of insufficient pulmonary reserve, significant comorbidities, or other risk factors. Some of these patients may be candidates for sublobar resection (i.e., segmentectomy or wedge resection), but about 25% of the patients ≥65 years old may be deemed inappropriate to undergo any type of surgical excision.[24] The introduction of thermal ablation therapy has expanded the treatment opportunities for these patients. Kwan et al. reported no difference in overall survival following sub-lobar resection or thermal ablation for comparable elderly patients with Stage I NSCLC.[25] For over a decade, RFA has been used successfully to treat pulmonary tumors. The reported median survival in patients with Stage I NSCLC treated with RFA without chemotherapy or radiotherapy is 17.6–29 months.[11],[26]

Compared to RFA, MWA is a less studied but promising option because it offers larger ablation zones, reduced procedure times, and decreased heat-sink effects.[27],[28] Although several studies have retrospectively evaluated the safety and efficacy of CT-guided MWA in lung cancer patients, few have investigated the outcome in elderly patients with primary NSCLC after MWA. Elderly patients are more likely to be diagnosed with NSCLC in early stage.[29] However, the likelihood of elderly patients with early-stage disease not receiving any treatment significantly increases with age.[30] Unfortunately, MST of untreated Stage I/II NSCLC is only about 10 months according to previous investigations,[31] but in our study, both of the estimated overall and cancer-specific MST were apparently longer than 10 months.

From the follow-up result of this study, the overall MST was 35 months and the cancer-specific MST was 41.9 months. The 1-, 2-, 3-, and 4-year overall survival rates were 91.7%, 76.5%, 47.9%, and 47.9%, while the cancer-specific survival rates were 94.7%, 73.9%, 64.7%, and 64.7%, respectively. These results suggested that MWA was effective in improving the survival of patients 75 years of age and older with medically inoperable early stage peripheral NSCLC.

In this study, 9 patients (32.1%) had local recurrence, which was consistent with the local recurrence rates of 31.5% reported by Lanuti et al. and 31% reported by Hiraki et al.[32],[33] A retrospective investigation about pulmonary RFA in 153 patients revealed that the 1-, 2-, 3-, 4-, and 5-year local tumor progression-free rates were 45%, 25%, 25%, 25%, and 25% for tumors larger than 3 cm, respectively.[26] Based on our results, the 1-, 2-, and 3-year local control rates for tumors larger than 3.5 cm were higher, and the 4-year local control rate was similar. This finding may imply the advantage of MWA in treating larger tumors. Despite this, we still found that larger tumors were more likely to have local recurrence than the smaller ones. Three of the patients with local recurrence in our series underwent a second MWA procedure, which indicated the repeatability of MWA benefiting from the preservation of pulmonary volume and function. Another two patients with local recurrence underwent radiotherapy. For larger tumors, the combination of thermal ablation and radiotherapy may improve local control rates.[34]

Despite its clinical benefits, MWA can lead to some major complications, but in our study, most major complications were easily managed. Pneumothorax was the most common complication in our study. Zheng et al. reported that emphysema is an influencing factor of the need for chest tube placement for pneumothorax.[35] Similar findings were obtained in the current clinical trial. No massive hemoptysis was noted. Only moderate hemoptysis occurred during the punctures and was controlled by immediate ablation. Pleural effusion was the second most common complication in our study, but only 2 patients required drainage. Tajiri et al. concluded that higher pleural temperature was associated with the development of pleural effusions.[36] Nevertheless, through the case of perioperative cerebral infarction, we infer that despite being a minimally invasive procedure, MWA may heighten the risk of stroke for the elderly patients. Age >70, female sex, previous stroke or transient ischemic attack, history of hypertension, diabetes mellitus, renal insufficiency, dialysis, smoking, chronic obstructive pulmonary disease, peripheral vascular disease, cardiac disease (history of myocardial infarction within 6 months prior to surgery, atrial fibrillation, valvular cardiopathy), carotid stenosis, atherosclerosis of the ascending aorta, and the discontinuation of antithrombotic therapy before surgery are patient-related risk factors according to the literature.[37] Therefore, if possible, preoperative aspirin, beta blocker, statin, hypoglycemic agents, and angiotensin converting-enzyme inhibitor therapies should be continued in the perioperative period. Patients who are prescribed anticoagulation at high risk of thromboembolism should receive bridging anticoagulation during the perioperative period.


 » Conclusion Top


CT-guided percutaneous MWA is safe and effective for the treatment of patients 75 years of age and older with medically inoperable early stage peripheral NSCLC. However, our study has several limitations. First, our series was a retrospective study involving a medium-sized population. A larger sample size investigation should be conducted. Second, without the aid of positron emission tomography-CT or lymph node biopsy, CECT was employed to evaluate tumor staging before ablation and local recurrence after ablation, which might have caused staging inaccuracy. Third, the length of follow-up was not long enough to determine the 5-year survival rate. Finally, certain patients undergoing MWA were subsequently treated with systemic chemotherapy and/or external beam radiation therapy, which might have affected the clinical efficacy.

 
 » References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]

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