Percutaneous ablation treatment in metastatic lung tumors: a single-center experience

Introduction

Although primary lung cancer is the most common cause of cancer-related deaths worldwide (18.4%), the lungs are the second most common organ for metastases (1,2). The efficacy of surgical resection in selected patients with metastatic lung disease has been demonstrated by many studies (3–5). However, in these patients, the need for repeated surgical intervention often arises due to high recurrence. Therefore, minimally invasive treatment methods, such as stereotactic body radiation therapy (SBRT) and percutaneous thermal ablation, have come to the fore as an alternative to surgical treatment in patients with limited pulmonary reserve, severe co-morbid diseases, and who cannot tolerate additional surgical intervention (6,7).

In recent years, many studies have proven that percutaneous thermal ablation is an effective second-line treatment method with low complication rates in stage 1 non-small cell lung carcinoma (NSCLC) and lung metastases (8). Radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CA) are percutaneous methods used for this purpose. Besides being practical and safe procedures, they have significant advantages such as preservation of lung function, no risk of radiation pneumonia, and being repeatable (9).

The aim of the present study was to evaluate the factors affecting the success of the treatment with technical success, complication rates, and long-term follow-up results in metastatic lung lesions in which we applied percutaneous thermal ablation.

Material and Methods

Patient and lesion characteristics

A total of 35 patients (22 men [62.9%], 13 women [37.1%]; age range = 41–75 years; mean age = 61.38 ± 9.518 years) were included in the study. Of the patients, 25 patients were referred to us for percutaneous ablation because they were not suitable for surgical treatment due to various reasons, mainly co-morbid diseases (71.4%); 6 (17.2%) patients had recurrence after surgical treatment and 4 (11.4%) did not agree to surgical treatment. CT-guided percutaneous ablation was performed for 70 metastatic lung lesions in 35 patients. Of the lesions, 45 (64.3%) were in the right lung and 25 (35.7%) were in the left lung. Solitary lesions were detected in 20 (57.1%) patients and multiple lesions were detected in 15 (42.9%) patients during the first procedure, and the mean number of lesions was 1.83 (range = 1–5 lesions). In 19 (54.3%) patients, only one lesion was treated. Percutaneous ablation was performed in 16 (45.7%) patients with multiple lesions (range = 2–10 lesions) in the same session or when new lesions appeared during follow-up. It was found that 11/70 (15.7%) lesions that underwent ablation were lesions that were not present during the first procedure but newly emerged during the follow-up, and 2 (2.8%) lesions were re-interventioned due to recurrence detected during the follow-up. The primary cancer diagnoses of the ablated metastatic lung lesions were rectal cancer in 14 (40%) patients, colon cancer in 12 (34.3%) patients, breast cancer in 4 (11.4%) patients, and other cancers in 5 (14.3%) patients. Extrapulmonary metastases were detected in 13 (37.1%) patients before the first procedure or during the follow-up.

The mean lesion size was 11.44 ± 6.138 mm (range = 3–31 mm). Of the lesions, 40 (57.1%) were ≤1 cm, 22 (31.4%) were 1.1–2 cm, 7 (10%) were 2.1–3 cm, and 1 (1.5%) was >3 cm. Patient and lesion characteristics are summarized in Table 1.

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Table 1.

Patient and lesion characteristics.

Characteristic	Value
Sex
Female	13 (37.1)
Male	22 (62.9)
Mean age (years)	61.34 (41–75)
Primary cancer
Rectum	14 (40.0)
Colon	12 (34.3)
Breast	4 (11.4)
Other	5 (14.3)
Extrapulmonary metastases	13 (37.1)
Mean lesion size (mm)	11.44 (3–31)
Lesion size (cm)
≤1	40 (57.1)
1.1–2	22 (31.4)
2.1–3	7 (10.0)
>3	1 (1.5)
Lung
Right	45 (64.3)
Left	25 (35.7)
Lesion number during diagnosis
Solitary	20 (57.1)
Multiple	15 (42.9)
Mean number of lesions (range)	1.83 (1–5)
Ablation technique
Radiofrequency ablation	53 (75.7)
Microwave ablation	17 (24.3)

Values are given as n (%) or mean (range).

Procedure

The procedures were performed under conventional CT guidance (Alexion, 16 slice; Toshiba Medical Systems Corporation, Tochigi, Japan) and under anesthesia (deep sedation or general anesthesia). Ablation procedures were performed by three interventional radiologists with >10 years of experience. Routine prophylactic single-dose IV antibiotic (Cefazolin 1 g) was administered to all patients before the procedure. At the beginning of the procedure, low-dose (120 kVp, 50 mAs) planning thorax CT images were obtained in all patients. The safest and shortest access to the pulmonary lesion was determined at the level of axial sections, and the needle entry site was marked on the patient's skin. Care was taken to avoid interlobar fissures, bulla formation, and large vascular structures on the access. Radiofrequency ablation was performed in 53/70 (75.7%) lesions and microwave ablation in 17/70 (24.3%) lesions in 35 patients. RFA operations were performed using CoATherm AK-F200 (Apro-Korea Inc., Republic of Korea) device with 18-G cooled-electrode, while Solero Microwave Tissue Ablation System (Angiodynamics, NY, USA) with a 15-G antenna was used for MWA operations. The probe/antenna size to be used was chosen to be at least 10 mm wider than the maximum diameter of the tumor. After sterile conditions were provided, percutaneous entry was made into the lesion with an appropriately sized RFA probe or MWA antenna for planned ablation size. In subpleural tumors, needle placement was ensured to be tangential to the pleura. In lesions close to critical organs and structures, protective techniques such as manual traction, iatrogenic pneumothorax, and hydrodissection were applied. After confirming with CT images that the probe or antenna used was in the lesion, ablation was performed at the selected time and settings in accordance with the thermal ablation technique used. After confirming that the values of 70°–90° were reached at the end of the ablation period, control CT images were obtained. The procedure was terminated in patients with a circumferential ground-glass density of at least 5 mm around the tumor. In case of insufficient ablation, additional ablation was performed at the recommended time and settings. Patients whose ablation was confirmed by control CT images were also evaluated for complications such as pneumothorax, pleural effusion, parenchymal hemorrhage, and hemothorax (Fig. 1). No additional intervention was performed in procedures that developed minimal (<2 cm) pneumothorax. These patients were followed up with 2-h and 4-h control chest X-rays. Manual aspiration with a 21-G needle was first applied in procedures that developed moderate to severe (>2 cm) pneumothorax. In patients who could not achieve adequate lung expansion or low oxygen saturation, an 8-Fr pigtail drainage catheter was placed and connected to the underwater drainage. If pneumothorax did not develop to a level requiring drainage during the first procedure in patients with multiple lesions, ablation was applied to other lesions in the same or opposite lung in the same session.

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Fig. 1.

Complications of (a) a pneumothorax and (b) parenchymal hemorrhage during the procedure. No additional intervention was required during follow-up.

Follow-up

Patients were followed up in the hospital for at least one day after the procedure. The patients were discharged from the hospital after evaluating pneumothorax, hemorrhage, subcutaneous emphysema, and ablation zone with 24-h control CT images. After discharge, the patients were evaluated every three months in the first year, every six months in the second year, and annually thereafter, in terms of size changes and the presence of new lesions, especially in the ablation area (Fig. 2). PET-CT was recommended at 3 and 12 months for patients with suspected recurrence.

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Fig. 2.

A 49-year-old female patient with rectal cancer and solitary lung metastasis (maximum diameter = 12 mm) treated using microvawe ablation. (a) Pre-procedure, (b) during ablation, and (c) postoperative follow-up CT images 24 h after the procedure; and (d–i) 3, 6, 9, 12, 18, and 24 months demonstrate the involution of the ablation zone and regression of the lesion.

Results

The width of the ablation area in the CT images obtained one day after the procedure was evaluated retrospectively in terms of the effectiveness of local ablative treatment and technical success. In only one patient, it was noted that the ablation zone expanded less than other areas due to its close proximity to the mediastinal main vascular structures (a distance of approximately 2 cm), and local recurrence developed in this patient during the follow-up. According to these results, the technical success rate in our study was calculated to be 98.6%.

Median overall survival (OS), progression-free survival (PFS), and local recurrence-free survival of the patients were 33.9 months (range = 25.6–42.1 months), 12 months (range = 4.9–19.2 months), and 24.2 months (range = 8.2–40.1 months), respectively. One- and two-year OS rates were 84% and 74%, respectively. When the median OS rates between the sexes were evaluated, this period was 25.9 months in male patients and 74.2 months in female patients, and the difference was statistically significant (P = 0.008). When we divided the patients into two groups according to their age as >65 years and <65 years, no statistically significant difference was found between the two groups in terms of OS and PFS (P = 0.932, P = 0.956, respectively). The lung side of the ablated lesion was also found to be a factor with a statistically significant effect on the median OS rate (right lung = 74.3 months, left lung = 19.2 months) (P = 0.037).

It was noted that the primary diagnosis of 2 (66.7%) patients with local recurrence was breast cancer and the other patient (33.3%) was rectal cancer. Local tumor progression rates at one and two years were 8% and 12%, respectively.

Median PFS times were calculated as 20.3 months and 11.4 months, respectively, according to the number of metastatic lung lesions being solitary and multiple, and the difference was statistically significant (P = 0.046). When this time was evaluated according to the number of lesions (≤3 and >3), the difference was also found to be statistically significant (P = 0.024) (14.3 months and 5.7 months, respectively).

In our study, when we classified the treated tumor sizes as <1 cm, 1–2 cm, and >2 cm, no statistically significant difference was found between the three groups in terms of OS and PFS (P = 0.289). In addition, when we classified the lesions as <1 cm and >1 cm, and <2 cm and >2 cm according to tumor sizes, no statistically significant difference was found between the groups in terms of OS and PFS (for 1 cm cutoff: P = 0.136, P = 0.257, respectively; for 2 cm cutoff: P = 0.365, P = 0.772, respectively) (Table 2).

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Table 2.

Variables related with OS and PFS rates.

			OS rate (%)				PFS rate (%)
		n	1 year	2 years	3 years	P	1 year	2 years	3 years	P
Age (years)	<65	19	88	72	39	0.932	58	31	16	0.956
	≥65	16	79	79	52		56	37	NA
Sex	Male	22	78	58	8	0.008	59	25	NA	0.376
	Female	13	92	92	77		54	36	18
Number	Solitary	20	88	78	56	0.340	66	45	45	0.046
	Multiple	15	78	69	34		44	15	0
Size (cm)	≤1	14	92	92	65	0.136	67	52	17	0.257
	>1	21	78	63	32		50	20	20
EPM	Yes	13	84	74	44	0.979	65	25	0	0.961
	No	22	83	74	41		51	40	40
Lung	Right	25	86	86	63	0.037	62	44	22	0.171
	Left	10	78	47	0		44	9	NA

EPM, extrapulmonary metastasis; NA, not applicable; OS, overall survival; PFS, progression-free survival.

No signs of recurrence were found in 17 (48.5%) patients as of their last follow-up after the procedure. Recurrence was detected in 18 patients during follow-up. Intrapulmonary newly developed lesions were detected in 9 of these 18 patients (9/35, 25.7%), while extrapulmonary new metastases were detected in 6 patients (6/35, 17.1%). While only local tumor progression was observed in 2 patients (2/35, 5.8%), local tumor progression and extrapulmonary new metastasis were detected in 1 patient (1/35, 2.9%). Local tumor progression was seen in 3/70 (4.3%) lesions in 35 patients who underwent percutaneous ablation, and two of these three lesions were ablated again.

In our study, in which no procedure-related mortality was observed, one or more minor complications were observed in 48.6% of the procedures. In a total of 23 (32.9%) interventions, pneumothorax developed during or after the procedure, and in 18 (78.3%) of them, the amount of pneumothorax was <2 cm in thickness, did not increase in the follow-up, and did not cause any symptoms. Since the size of the pneumothorax developed in 4 (17.4%) procedures was >2 cm, manual aspiration with a 21-G needle and a 50-ml injector was sufficient, while a percutaneous drainage catheter was placed in 1 (4.3%) patient. In addition, subcutaneous emphysema in 6 (8.6%) patients and parenchymal hemorrhage in the needle tract in 5 (7.1%) patients were observed in the early postoperative period or in the 24-h follow-up CT images. It was observed that subcutaneous emphysema and parenchymal tract hemorrhage were self-limited in the follow-up and did not require additional treatment.

Although the patients were routinely followed up for at least one day after percutaneous ablation procedures, the mean hospital stay of the patients included in the study was calculated as 1.43 days (range = 1–7 days).

During the median follow-up period of 33.8 ± 4.2 months, 12/35 (34.3%) patients with metastatic lung lesions died.

Discussion

Percutaneous ablative treatment methods applied in lung masses continue to be applied with increasing frequency today, after Dupuy et al. published the RFA procedures performed in three patients in 2000 under the title of Technical Innovation (10). Compared to surgical methods, it has become a good alternative treatment method for several reasons. These reasons can be stated as the preservation of the lung parenchyma in patients with bilateral/multiple metastatic masses and limited lung reserve, its use in patients with co-morbid diseases or those who refuse surgery, and the shorter hospital stay after the procedure and maybe lower cost. In our study, percutaneous ablation was performed because 71.4% of the patients were not suitable for surgical treatment due to their co-morbid diseases, 17.2% of the patients had recurrence after surgery, and 11.4% of them refused surgery.

In a large retrospective study in which the data of RFA procedures applied to 1037 metastatic lesions of 566 patients were shared in the literature, the median OS was 62 months, the five-year OS rate was 52%, and local tumor progression rates at one, two, three, and four years were reported as 5.9%, 8.5%, 10.2%, and 11%, respectively (8). In the same study, primary tumor type, disease-free duration, and presence of >3 metastases were found to be significant variables. In our study, the one- and two-year local tumor progression rates were 8% and 12%, respectively.

In the RAP-TURE study, which is the first prospective study on this subject, one- and two-year OS rates after RFA applied to patients with oligometastatic lung disease were reported to be 92% and 64%, respectively (11). In our study, one- and two-year OS rates were found to be 84% and 74%, respectively.

In the surgical literature, studies have clearly shown that especially >3 multiple metastases in the lung negatively affect survival after resection (12,13). However, the same literature certainty is not available for percutaneous ablation treatments, which allows multiple lesions to be treated in the same session as it is a less invasive method. There are positive and negative studies that the number of metastases in the lung affects survival after percutaneous ablation. Gillams et al. showed that single or multiple metastases had no effect on survival after radiofrequency ablation in 122 patients with colorectal inoperable lung metastases (13). Similarly, Hasegawa et al. reported that single or multiple metastases had no effect on the OS of the patients in their prospective randomized study in which they included radiofrequency ablation of 100 surgically resectable lung metastases of colorectal origin (14). Hiyoshi et al., on the other hand, included 188 colorectal lung metastases in 42 patients and showed that the number of metastases <3 or >3 had no effect on PFS after radiofrequency ablation (15). However, Baere et al., in their study including 1037 lung metastases in 566 patients, reported that the number of metastases, especially >3, negatively affects OS and PFS after radiofrequency ablation therapy (8). Similarly, Tselikas et al., in their study comparing radiofrequency ablation and surgical resection in lung metastases, emphasized that the increase in the number of metastases for both groups decreased PFS (16). Finally, Akhan et al., in their study, in which they included 112 lung lesions (101 metastatic and 11 NSCLCs) in 49 patients who were treated with radiofrequency ablation, showed that the presence of a single or multiple tumor affects recurrence-free survival (6). In our study, it was determined that both the presence of a single or multiple metastatic lung lesion and the number of metastases <3 or >3 had a statistically significant effect on the PFS of the patients.

In a prospective study involving 188 patients in whom colorectal cancer metastases were treated with RFA, PFS was 6.8 months and OS was 52.7 months. The presence of extrapulmonary metastases and a maximum tumor diameter >15 mm were reported as factors affecting OS (15). Compared to that study, the median PFS time in our study was calculated as 12 months, and although it was found to be higher, the median OS time was calculated as 33.9 months and was relatively lower. In our study, no statistically significant difference was found between tumor size and OS and PFS rates. We think that this may be due to the fact that only 8/70 (11.4%) tumors that underwent percutaneous ablation were >2 cm in our study. In addition, all metastatic lesions treated with ablation in this study were colorectal tumor metastases, whereas 9/35 patients treated in our study were non-colorectal tumor metastases. Since it is known that colorectal tumor metastases respond better to percutaneous ablation therapy (17), this may have led to a difference in the median OS of the patients between studies.

In one of the first prospective studies evaluating the efficacy of MWA therapy in the lung, one- and two-year OS rates were reported as 91.3% and 75%, respectively, in 80 patients with unresectable lung metastases. In the study, in which tumor size was the most important treatment success criterion, lesions >3 cm were associated with inadequate ablation (18). In our study, there was only one lesion >3 cm in which percutaneous ablation was applied.

According to the results of a large meta-analysis that compared RFA and MWA treatments in lung metastases and included 3432 patients, longer OS rates and higher one-, two-, three-, and five-year survival rates have been reported in patients treated with RFA, with similar local recurrence rates described for both techniques (19). In a retrospective study comparing MWA, RFA, and laser-induced thermotherapy methods applied to colorectal lung metastases of 109 patients, it was reported that the highest local tumor control rate was found in MWA with 88.3%, which was statistically significant (20). In our study, RFA was applied to the majority of the lesions (RFA: 75.7% vs. MWA: 24.3%), and no statistically significant difference was found between the OS and PFS rates of the two methods (P = 0.709, P = 0.187, respectively).

Local recurrence has been reported in the literature at rates in the range of 3%–38% (21–23). In our study, local recurrence was found at a rate of 4.3%, which is close to the lower limit of the rates defined in the literature. Although these rates are closely related to the follow-up method of the patients, we think that this may be due to the small size of the metastatic lesions we treated in our study (mean lesion size = 11.44 mm).

In our study, no procedure-related mortality was found in any of the patients who underwent percutaneous ablation. The most common complication was pneumothorax, with a rate of 32.9% (23/70). While most of these patients did not require additional treatment or intervention, manual aspiration was performed in four patients and percutaneous drainage was needed in only one patient. In the literature, pneumothorax rates are reported to be approximately 4%–61%, and percutaneous drainage is required in approximately 4%–28% of cases (24–27). In our study, the rate of pneumothorax requiring percutaneous drainage was calculated as 1.4% (1/70) when all procedures were taken into account, and it is significantly lower when compared to the literature. These low rates were thought to be due to the fact that the procedures were performed by experienced interventional radiologists with high ablation experience. In our study, hemorrhage in the needle tract was observed in 5 (7.1%) procedures, and it did not cause massive hemoptysis in any of these patients. In addition, post-procedure infection was not observed in any of our patients in the ablation area, and we think that the single-dose antibiotic prophylaxis we applied is sufficient for this reason. In the literature, in the presence of risk factors such as single lung, radiotherapy history, and primary tumor, it is recommended to continue amoxicillin-clavulanate or ofloxacin for 3–7 days, but these risk factors were not present in the patients in our study group.

The present study has some limitations. The retrospective nature of our study, like most studies in the literature, is one of the most important limitations. In addition, although there was no statistically significant difference between the RFA and MWA techniques applied in our study in terms of the survival of the patients, there was a numerical difference between them. Since there is no significant difference in OS and local recurrence rates between the two techniques in the literature, we think that it is appropriate to consider the superior features of the techniques during patient selection. Finally, we think that the small mean tumor size (11.44 mm) treated in our study also affected our success in the procedure as a limitation.

In conclusion, CT-guided percutaneous ablation therapy is a safe and effective method in metastatic lung lesions. Since the protocols on which surgical, SBRT and local ablative methods will be chosen in the treatment of these patients have not yet been clarified, patient selection should be made carefully, keeping the experience of the center and the operator in the foreground. During this selection, the number of lesions in particular is the most important factor in predicting treatment success.