In the review article entitled “The Role of Percutaneous Image-Guided Thermal Ablation for the Treatment of Pulmonary Malignancies” (1) recently published in the American Journal of Roentgenology (AJR) by Mouli and colleagues, the authors reviewed thermal ablation techniques [radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation] for the treatment of pulmonary malignancies [non-small cell lung cancer (NSCLC) and metastasis] with respect to treatment mechanism, local efficacy, imaging modalities used for guidance, treatment response evaluation, and clinical outcomes. The authors also reviewed the comparative studies of thermal ablations with surgery and stereotactic beam radiotherapy (SBRT).
Ablation is a good candidate for treating pulmonary malignancies because lungs have heat and electrical insulating characteristics, which enable larger volumes of tissue to be ablated using thermal energy than is possible for other body tissues (2). Because thermal energy delivery is limited by the heat-sink effect of adjacent blood vessels and airways, the presence of vessels or bronchi greater than 3 mm in diameter within the ablation zone are predictors of incomplete local treatment (3). Ablation zones must exceed tumor dimensions to obtain adequate margins, and in practice, sufficient RFA-induced ground-glass opacity (GGO) indicates complete ablation (4). MWA permit larger ablation zones than RFA because delivers energy simultaneous using multiple probes, and thus, provides larger tumor ablation volumes and faster ablation times. Cryoablation uses compressed argon gas to generate subzero temperatures, but unlike heat-based ablation, cryoablation does not create GGO; instead, it creates iceballs.
CT is the preferred imaging modality for guidance during thermal ablation. It provides excellent contrast between tumors and normal lung parenchyma, and multi-planar CT images enable accurate and rapid probe placement. CT is also the modality of choice for post-ablation follow-up evaluations (Figure 1). Immediately after ablation therapy, targeted lesions are replaced by dense opacity surrounded by GGO (5). GGO margins of <3 mm have been associated with local treatment failure. During the early post-ablation period (<2 months), central dense opacity and surrounding GGO serves as the new “baseline”, and any increase in lesion size during follow-up should be considered local progression. However, morphologic evolution occurs in ablation zones and its extent depends on the thermal ablation methods used, for example, RFA-treated lesions show a relatively slow rate of involution, with a 40% decrease in size at 15 months after treatment, whereas cryoablated lesions show more rapid involution on follow-up CT images (6). PET/CT may be helpful for differentiating morphologic evolution and local recurrence, but early PET/CT within 3 months of ablation can be confounded by inflammatory changes.
Thermal ablation has been shown to be both safe and effective for the treatment of primary and secondary pulmonary malignancies in nonsurgical candidates. For stage I NSCLC treated by RFA, 1- and 5-year overall survival (OS) rates have been reported to be 78% and 27%, respectively (7). However, more recent studies have reported better outcomes [2-year OS rate of 69.8% (8), 3-year OS rate of 74–79% (9,10), and 5-year OS rate of 58.1% (11)], which could be explained by multiple factors, including technical improvements, better patient selection, and the use of molecular-targeted therapies. Long-term outcome data for the treatment of NSCLC by MWA or cryoablation are limited; 1- and 3-year OS rates of 75% and 29.2% after MWA were reported for 48 patients with NSCLC of various stages (12), and 2- and 5-year OS rates of 88% and 67.8% were reported after cryoablation in patients with stage I NSCLC (13).
Thermal ablation has a role in the setting of advanced disease or as salvage therapy. In one study, after RFA for recurrent NSCLC (n=51) initially treated surgically, 1- and 5-year OS rates were 97.7% and 55.7% (14), and in patients with stage III or IV NSCLC, longer median OS was found for patients treated with RFA and chemotherapy than for those that received chemotherapy alone (median OS, 42 vs. 29 months, respectively; P<0.03) (15).
Thermal ablation plays a role in the management of metastatic disease in selected patients with limited disease burden. In general, this population includes patients with up to four lesions per lung and with lesions <3.5 cm (16). In the largest series conducted to date on pulmonary metastases (566 patients with 1,037 metastases) treated by RFA, median OS was 62 months and 1- and 5-year OS rates were 92.4% and 51.5%, respectively (17); multivariable analysis showed that primary disease other than colorectum and kidney, disease-free interval ≤1 year, a tumor size >2 cm, and number of metastases ≥3 were associated with poor OS (17).
There are limited comparative studies of thermal ablation with surgery and SBRT. It has been reported local recurrence was higher for RFA, and OSs were similar for RFA (n=8) and surgery (n=14) in stage I NSCLC (18). In another study, though RFA-treated stage I and II NSCLC patients were significantly older than those treated surgically, no significant difference in OS was observed (15). An analysis conducted on the National Cancer Institute’s Surveillance, Epidemiology, and End Results database (n=1,897) found OS and cancer specific survival were not significantly different between propensity score matched NSCLC patients treated surgically or by ablation (19). In a comparative study between RFA and SBRT in patients (n=48 and 47, respectively) with NSCLC of <5 cm, 3-year local control and OS rates were similar (20).
For pulmonary metastasis, RFA has been shown to be comparable to surgical resection with reported 5-year OS rates of 27–70% (21). Furthermore, because thermal ablation techniques can be administered repeatedly without substantially diminishing pulmonary function (8), these techniques have particular benefit in the setting of recurrent or residual disease.
Local progression is the main obstacle of thermal ablation, and local failure is associated with a large tumor size (>2 cm) and insufficient ablation margin (17,22). Additional biomarkers (e.g., Ki-67, KRAS, and EGFR), inflammatory cytokines, and immune markers, and imaging findings have been the focus of studies aimed at the early prediction of local recurrence and treatment response (23,24).
In summary, thermal ablation has been shown to be safe and effective for the treatment of primary and secondary lung malignancies in nonsurgical candidates, although there has been no large randomized study comparing ablation to surgery or SBRT. The benefits of these techniques include the preservation of more lung tissue than is possible by surgical resection and a reduction in morbidity as compared with surgery. These benefits are particularly important for lung cancer patients with high levels of comorbidities or limited pulmonary functional reserve due to chronic obstructive pulmonary disease. Lesion size is the main determinant of treatment success and survival. Future studies are required to refine patient selection, procedural techniques, and the assessment of local recurrence.
Conflicts of Interest: The authors have no conflicts of interest to declare.
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