Computerized tomography-Guided Microwave Ablation of Patients with Stage I Non-small Cell Lung Cancers: A Single-Institution Retrospective Study

INTRODUCTION

Lung cancer is the second most common cancer in both men and women with 228,150 new cases and 142,670 deaths in 2019.^[1] Stage I (T1-T2aN0M0) lung cancer includes tumors up to size <4 cm diameter without evidence of nodal or metastatic disease.^[2] According to National Comprehensive Cancer Network (NCCN) guidelines, surgical resection is the currently recommended first-line treatment for local control of Stage I non-small cell lung cancer (NSCLC).^[3] However, a significant cohort of patients cannot tolerate (due to associated comorbidities, age, and poor lung function) or refuse major surgery.^[4] Stereotactic ablative radiotherapy (SABR) or image-guided thermal ablation is less invasive options for local tumor control and has been increasingly offered in these patients. At present, the NCCN guidelines recommend SABR as the first-line therapy for Stage I NSCLC in patients who are not good surgical candidates.^[3] Radiofrequency ablation (RFA) is a heat-based, safe, and effective ablation technique that has been used in the lung and other organs for local tumor control.^[5-7] Due to some of its inherent limitations that include longer ablation times and susceptibility to “heat sink,” many operators now prefer microwave technology for heat-based ablations. In addition, microwave ablation (MWA) generates a larger heating radius within the poor conducting environment of the lung when compared to RFA.^[8] Although there are many studies reporting the efficacy of MWA in the liver and kidney, there is a paucity of data evaluating MWA in Stage I NSCLC.^[9-12] The relatively short follow-up periods, variable clinical efficacy, inclusivity, and methodology with the available data make meta-analysis challenging.^[13-17] Therefore, further study is needed to bolster the available data on outcomes of MWA in NSCLC with the goal of strengthening the pool of evidence for patients and clinicians.

The primary aim of this study was to evaluate the technical success, survival outcomes, and complications in patients with Stage I peripheral NSCLC treated with MWA at a single, rural academic tertiary care hospital, in the Mid-West United States. A secondary aim was to identify factors contributing to survival in this cohort.

MATERIAL AND METHODS

RESULTS

Technical, clinical success, local control, and complications

Pre-ablation tumors demonstrated avid FDG activity [Figure 1a]. Technical success was defined as the ability to successfully place the probe within the tumor and perform MWA as per the manufacturer’s recommendation to achieve the intended ablation zone [Figure 1b and c]. This was achieved in 100% of the cases. Clinical success, defined as the absence of FDG activity within the mass on initial follow-up PET imaging [Figure 1d], was achieved in 95.2% of the cases following percutaneous MWA (20/21 cases). The one patient who had residual PET activity was subsequently treated with chemotherapy. Local recurrence, defined as absence of FDG activity on initial follow-up but eventual return of activity within 5 mm of the ablation on subsequent scans, was observed in 10% (2/20) of cases. Of these patients, one opted for chemotherapy while the other opted for observation. Complications were minor as defined by Society of Interventional Radiology guidelines (requiring therapy, hospital admission <48 h) and occurred in 28.6% (6/21) of cases. Complications included pneumothorax requiring a chest tube (n = 5) and small pleural effusion (n = 1). There was no difference in the occurrence of a complication and OS following MWA (P = 0.439).

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Figure 1:

A 65 year-old female patient presenting with dyspnea diagnosed with biopsy proven Stage I adenocarcinoma of the left lung, who was deemed a non-surgical candidate. Axial fused pre ablation PET (a) showing a FDG active lesion in the lingula (white arrow). Axial procedural CT in a (b) showing the microwave probe in the lingular lesion (white block arrows). Post procedure axial CT (c) showing a ground glass opacity around the ablated zone (white line arrows) indicating a technical success. The axial fused PET 3 months after ablation (d) shows no activity in the lesion (white arrow), indicating clinical success.

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Overall and progression-free survival outcomes

Kaplan–Meier analysis was performed to evaluate overall (OS) and progression-free (PFS) survival following lung cancer MWA [Figure 2a and b]. Mean OS following diagnosis or MWA was 26.2 ± 15.4 months (range, 5–56 months) and 23.7 ± 15.1 months (range, 3-55 months). OS at 1, 2, and 5 years was 67.6%, 61.8%, and 45.7%, respectively. Mean PFS was 19.1 ± 16.2 months (range, 1–55 months). PFS at 1, 2, and 5 years was 44.5%, 32.9%, and 32.9%, respectively.

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Figure 2:

Kaplan-Meier curves for overall (a) and progression free (b) survival. PFS, progression free survival.

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DISCUSSION

NCCN guidelines recommend surgical resection for Stage I NSCLC.^[3] Patients who are not surgical candidates should be offered SABR or thermal ablation that can be performed with significantly less morbidity, yet a curative intent. The advantages of SABR are that it is non-invasive and does not require placement of a chest tube or overnight stay in hospital; however, dose fractionation with SABR means it does require multiple hospital visits. SABR is also associated with complications such as radiation-induced pneumonitis, chronic chest wall pain, and rib fractures.^[18-20] Furthermore, when the radiation dose is reduced to protect central mediastinal, hilar structures, or the chest wall, it appears to be less effective.^[21] A few studies suggest that SABR may be more toxic and less effective in elderly population.^[22] Thermal ablation is a minimally invasive option for local tumor control in patients with early-stage NSCLC who are not suitable for major surgery. RFA is the most established thermal ablation technique in terms of safety and efficacy. Although there are no randomized control prospective studies comparing SABR to RFA, recent systematic review and pooled analysis have shown better local control rates with SABR compared to RFA.^[23] This may be in part due to the poor performance of RFA in the poor conducting environment of the lung parenchyma.^[7] MWA is a newer technique that has been used as an alternative to RFA. The purported advantages of MWA over RFA include achieving higher temperatures, larger ablation zones, shorter ablation times, and reduced susceptibility to the heat-sink effect (inefficient ablation from the cooling effect of blood in adjacent vessels). These properties of MWA may be especially beneficial in the lung which has a high heat-sink effect and low thermal conductivity due to its large perfusion volume and ventilated air-filled spaces, respectively. However, studies evaluating MWA in Stage I peripheral NSCLC are sparse, and the available studies are limited in the reporting of long-term outcomes.^{[13,16,24-29]} There are no studies directly comparing MWA to SABR and the available data are limited to retrospective meta-analyses.^[30,31] The local control and OS in these studies are comparable to SABR.^[30,32] This suggests that MWA may provide an alternative treatment for patients with early-stage, inoperable NSCLC who cannot receive or would like to avoid SABR. In addition, MWA ablation can be repeated in the same location (in case of residual disease or local recurrence), which is generally not recommended following SABR due to dosimetric constraints.

In the present study, we achieved a very promising clinical success of 95.2% following MWA of early-stage NSCLC. OS in these patients at 1, 2, and 5 years post-ablation was 67.6%, 61.8%, and 45.7%, respectively. These results are consistent with the literature for MWA in early-stage NSCLC.^{[24,25,29,32-35]} Our study also observed PFS at 1, 2, and 5 years of 44.5%, 32.9%, and 32.9%, respectively, which is much lower than previously reported by Healey et al.^[16] However, most of these were from distant progression rather than local recurrence. Our local control following MWA was 90.5%. Symptomatic pneumothorax requiring a chest tube was the most common complication, and these were all recognized early and treated successfully. We did not observe any effect of complications on survival.

To identify potential prognostic factors following MWA, we performed univariate and multivariate analyses. Consistent with these prior studies, our results demonstrated a significant protective effect of female gender following MWA of NSCLC (HR: 0.10).^[36,37] Lung function before MWA was also identified as a potential prognostic factor in the present study. On average, we observed that long-term survivors had FEV1/FVC ratio and FEV1 values consistent with Global Initiative for Chronic Obstructive Lung Disease criteria Class II (GOLD) while non-survivors had a relative decrease in mean FEV1 (GOLD III), as reported in prior studies.^[38,39]

The negative effects of comorbidities on lung cancer mortality have been well established.^[40-42] Lung cancer patients are also more likely to have comorbidities such as COPD, diabetes, and hypertension.^[42,43] These associations are likely due to the strong connection between smoking and lung cancer.

In line with the previous studies, we also observed a strong trend toward negative effects on survival with several comorbidities. This included hyperlipidemia, diabetes, atrial fibrillation, obesity, and obstructive sleep apnea among others. Our results as well as others support the importance of managing and aggressively treating comorbidities in lung cancer regardless if surgery, SABR, or MWA is used to treat the primary tumor.

In addition, tumor histology may have important impact on the success of MWA. In this study, we observed a diagnosis of adenocarcinoma or neuroendocrine pathology had improved survival (87% increased odds of survival) following MWA compared to squamous cell carcinoma. This supports the findings of Gao et al. who observed survival following MWA with a diagnosis of adenocarcinoma was 14.7 months compared to 10.3 months non-adenocarcinoma.^[44] Interestingly, the histological subtype of adenocarcinoma has been identified as a prognostic factor for time to local recurrence following thermal ablation. Specifically, solid and micropapillary subtypes may demonstrate increased cumulative incidence of recurrence.^[44]

CONCLUSION

Our results are consistent with previous MWA studies with good clinical success and local control of Stage I peripheral NSCLC, thus serving as a positive endorsement for MWA as a safe and effective alternative to SABR. In addition, our long-term follow-up showed promising OS in patients with Stage I NSCLC following MWA. Larger sample sizes are needed to further define the effects of pre-ablation lung functions, comorbidities, and tumor biology on MWA outcomes and to discern the most optimal indications and guidelines for MWA in NSCLC.