Feasibility and safety of percutaneous computed tomography guided radiofrequency ablation of lymph nodes in oligometastatic patients: a single center’s experience

Abstract

Objectives:

To retrospectively evaluate feasibility and safety of CT-guided percutaneous radiofrequency ablation (RFA) of metastatic lymph nodes (LN) in terms of achieving local tumor control.

Methods:

Institutional database research identified 16 patients with 24 metastatic LNs who underwent percutaneous CT-guided radiofrequency ablation. Mean patient age was 66.6 ± 15.70 years (range 40–87) and male/female ratio was 8/8. Contrast-enhanced CT or MRI was used for post-ablation follow-up. Patient and tumor characteristics and RFA technique were evaluated. Technical and clinical success on per tumor and per patient basis as well as complication rates were recorded.

Results:

Mean size of the treated nodes was 1.78 ± 0.83 cm. The mean number of tumors per patient was 1.5 ± 0.63. The mean procedure time was 56.29 ± 24.27 min including local anesthesia, electrode(s) placement, ablation and post-procedural CT evaluation. Median length of hospital stay was 1.13 ± 0.34 days. On a per lesion basis, the overall complete response post-ablation according to the mRECIST criteria applied was 75% (18/24) of evaluable tumors. Repeat treatment of an index tumor was performed on two patients (three lesions) with complete response achieved in 87.5% (21/24) of evaluable tumors following a second RFA. On a per patient basis, disease progression was noted in 10/16 patients at a mean of 13.9 ± 6.03 months post the ablation procedure.

Conclusion:

CT-guided percutaneous RFA for oligometastatic LNs is a safe and feasible therapy.

Advances in knowledge:

With this percutaneous therapeutic option, metastatic LNs can be eradicated with a very low complication rate.

Introduction

Cancer is a leading cause of mortality worldwide and metastasis is the main cause of death in cancer patients.^1,2 Most solid tumors colonize distant sites through lymphatic vessels. Lymph node (LN) metastasis is common in patients with end stage cancer, being an indicator of cancer progression and worse disease stage.³ Rationale for treating metastatic LNs includes locoregional disease control with impact on progression free (PFS) and overall (OS) survival rates as well as palliative intent on terms of pain reduction or protection of surrounding vital and sensitive structures. Available therapies for distant LN metastasis include systemic therapy, surgery, radiation therapy and percutaneous ablation. Intravenously administered anti-cancer drugs are difficult to reach and maintain a high concentration of drug at the affected LN.⁴ Advantages of percutaneous ablation over surgery and radiation therapies include but are not limited to the minimally invasive character of the technique, the ability to effectively destroy tumors irrespective of histology and the preservation of patient enrollment in clinical trials; additionally, there is no need for discontinuation of systemic therapy except for chemotherapeutic drugs affecting coagulation

CT-guided radiofrequency ablation (RFA) has been used as a treatment strategy for primary and metastatic cancer in solid organs and LNs; it is considered to be a safe and effective therapy with excellent technical success which can be repeated to treat recurrences.^5–9 Adverse events are uncommon and usually include pain and local hematoma formation.^5–9

The purpose of the present study is to retrospectively evaluate technical feasibility and safety of CT-guided percutaneous RFA of LNs in oligometastatic patients.

Methods and materials

Authors have no conflict of interest to declare. No industry support was received for this study. Although this was a retrospective database research IRB approval was obtained.

Patient selection and evaluation

Institutional database research identified 16 patients (8 male:8 female) with 24 LN metastases who were treated by CT-guided RFA. Mean patient age was 66.63 ± 15.71 years (range 40–87). Inclusion criteria included oligometastatic patients ≥ 18 years old with LN disease confirmed either by prior biopsy or through imaging (defined as new or growing nodes in cases of histological proven primary cancer); up to five nodes with a maximum size of 3 cm; Karnofsky Performance Scale (KPS) score ≥60, coagulation parameters within normal limits and a life expectancy of >3 months. All patients had undergone either surgical resection or percutaneous ablation of the primary cancer; none of the patients had a history of previous treatment for locoregional lymphadenopathy. Patients were selected for RFA by a multidisciplinary team of medical, radiation, surgical and interventional oncologists based upon lesion size and location as well as upon safety and efficacy of the technique as reported in published studies.^5–9 All included patients and lesions should have been evaluable for the 6 months follow-up. Exclusion criteria included uncontrollable primary or metastatic disease, non-compliance of patients, uncontrollable INR, systematic or local infection, expected survival less than 3 months, ECOG <3 and presence of a medical or psychiatric illness that would preclude informed consent or follow-up. Contrast-enhanced CT or MRI was used for post-ablation follow-up. Each patient underwent laboratory tests (including renal function and coagulation tests) at least 24 h prior to the percutaneous ablation session. The patients were fully informed about the procedure, the possible complications and the surgical and medical alternatives available; informed written consent was obtained in all cases. Patient and tumor characteristics, RFA technique, complications and pattern of recurrence were evaluated.

Percutaneous ablation procedure

RFA was always performed in an inpatient setting. CT guidance with sequential scanning (120 Kv peak, 240 mAs wavelength and 2 mm slice thickness) was used for planning, targeting and intraprocedural modification during the ablation session. A combination of local anesthesia (performed by the Interventional Radiologist) and conscious sedation with fentanyl (employed by the anesthesiologist) was used to treat intraprocedural pain. Under local sterility, RFA was performed with percutaneous approach in all cases. Post the initial CT scan, skin entry point was selected. A 17G Radiofrequency electrode (RF AMICA probe, Hospital Service S.P.A. Rome/Italy) was inserted in the lesion of interest and its approach was evaluated with sequential CT scans (Figure 1). Once in the correct location, ablation session was performed according to the provided guidelines from the manufacturer concerning energy amount (watt), duration (minutes) and resultant ablation volume (centimeters). Whenever deemed necessary (and mainly based upon how centrally the electrode was located inside the node), the radiofrequency electrode was repositioned and a second ablation session was performed. Goal was to ablate the whole lesion including a circumferential zone of surrounding fat minimum 0.5 cm in extent. CT assessed ablation zone and potential immediate complications at the end of the ablation treatment. Patient remained in the hospital overnight and then discharged.

Figure 1.

A 50-year-old male patient with hepatocellular carcinoma and metastatic lymph node: A: CT axial scan illustrates the lymph node along the right mammary vessels. B: Patient underwent CT-guided percutaneous RFA; the active tip of the electrode was placed inside the lymph node. C: MRI 6 months post-RFA shows no contrast enhancement of the lymph node. RFA, radiofrequency ablation.

Outcome measures

Imaging and clinical follow-up was performed at 1, 3, 6 and 12 months post-ablation. The imaging performed at 1 month served as the post-treatment baseline study. The mRECIST response criteria were used for evaluating the efficacy of the ablation.^10,11 The definition of complications was assigned according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system.¹²

Results

Patient demographics are illustrated in Table 1. Neoplasmatic substrate including renal cell carcinoma (RCC) (n = 4), hepatocellular carcinoma (HCC) (n = 4), sarcoma (n = 2), gastric carcinoma (n = 2), breast carcinoma (n = 2) and colorectal carcinoma (n = 2) cases. The metastatic LNs were found in para-aortic (n = 12), cardiophrenic (n = 4), intra-abdominal (n = 2), supraclavicular (n = 4) and axillary (n = 2) locations. Mean size of the treated nodes was 1.78 ± 0.83 cm. The mean number of tumors treated per patient was 1.5 ± 0.63. The mean procedure time was 56.29 ± 24.27 min (range 31–110 min), including local anesthesia, electrode(s) placement, ablation and post-procedural CT evaluation. In 4/16 patients (4/24 nodes), hydrodissection with Dextrose 5% mixed with contrast medium was applied during the ablation procedure (Figure 2). Median length of hospital stay was 1.13 ± 0.34 days (range 1–2). Mean follow-up was 16.81 ± 8.82 months. No complications were recorded in the patients during the study’s evaluation period. During the follow-up period, there were no deaths related to the procedure.

Table 1.

PatIent demographics and details of the procedures performed

PATIENT	GENDER	PATIENT AGE	PRIMARY TUMOR	LESION NUMBER	LESION SIZE	LESION LOCATION	PROCEDURE TIME	LENGTH OF HOSPITAL STAY	FOLLOW UP (MONTHS)	DISEASE PROGRESSION (MONTHS)	DEATH DUE TO DISEASE PROGRESSION
1	F	56	Breast Ca	2	3.8, 2.4	Supraclavicular, Axillary	78	1	3	NA
2	F	66	Sarcoma	1	1.8	Supraclavicular	40	1	30	16
3	M	51	HCC	1	1.0	Cardiophrenic	65	2	14	NA
4	F	83	Gastric Ca	3	2.5, 1.5, 2.3	Para-aortic (x3)	87	2	10	6
5	F	73	Colon Ca	2	2.8, 2.7	Para-aortic (x2)	110	1	22	9	X
6	M	74	HCC	1	1.5	Cardiophrenic	31	1	20	16
7	M	69	RCC	2	2.5, 1.0	Para-aortic (x2)	80	1	15	NA
8	M	87	RCC	1	2.8	Intra abdominal	37	1	24	24	X
9	F	56	Breast Ca	1	3.0	Supraclavicular	59	1	3	7
10	F	40	Sarcoma	2	3.0, 1.0	Supraclavicular, Axillary	47	1	30	22
11	M	51	HCC	1	2.0	Cardiophrenic	37	1	14	NA
12	F	81	Gastric Ca	2	2.0, 1.5	Para-aortic (x2)	32	1	3	NA
13	F	75	Colon Ca	1	1.3	Para-aortic	41	1	22	10	X
14	M	74	HCC	1	1.2	Cardiophrenic	44	1	20	15
15	M	69	RCC	2	1.5, 1.0	Para-aortic (x2)	57	1	15	NA
16	M	85	RCC	1	2	Intra abdominal	40	1	24	14	X

HCC, hepatocellular carcinoma; RCC, renal cell carcinoma.

Figure 2.

A 61-year-old male patient with a solitary metastatic lymph node in para-aortic location post nephrectomy for renal cell carcinoma (white circle). B: Patient underwent CT-guided percutaneous RFA. Hydrodissection was performed with dextrose 5% mixed to contrast medium. C: CT scan post-i.v. contrast medium injection shows no contrast enhancement of the lymph node. i.v., intravenous; RFA, radiofrequencyablation.

On a per lesion basis, the overall complete response post-ablation according to the mRECIST criteria applied was 75% (18/24) of evaluable tumors. Repeat treatment of an index tumor was performed on two patients (three lesions) with complete response achieved in 87.5% (21/24) of evaluable tumors following a second RFA. Based on the mRECIST criteria applied, partial response was 25% (6/24) of evaluable tumors dropping down to 12.5% following a second RFA. Follow-up imaging at 3, 6 and 12 months post-RFA was available for 24/24 lesions (16/16 patients). The local recurrence free survival rate was 87.5% (21/24) throughout this period with no signs of local recurrence in the 21 fully ablated LNs (Figure 3). Imaging evaluation during the follow-up period depicted 4/21 fully ablated LNs which completely disappeared and 17/21 nodes which remained as non-enhancing ovoid lesions shrinking in size.

Figure 3.

A PET scan of a 73-year-old female patient with colorectal cancer showing avidity in a metastatic lymph node in para-aortic location (black circle). B: Patient underwent CT-guided percutaneous RFA. C: MRI 3 months post-RFA shows no contrast enhancement (white circle) of the lymph node. PET, positron emissiontomography; RFA, radiofrequency ablation.

On a per patient basis, disease progression on terms of distant metastases (other than LNs) was noted in 10/16 patients at a mean of 13.9 ± 6.03 months post the ablation procedure. In 8 out of these 10 patients, systemic therapy was combined to locoregional techniques (TACE or ablation), whilst in the rest two patients systemic therapy was solely performed. In details, imaging evaluation depicted systemic metastatic disease progression in locations other than the treated LNs as new lesions in the spine (2 RCC patients at 14 and 24 months respectively post the radiofrequency ablation of the LN, both treated with systemic therapy), in the liver (2 colon cancer patient at 9 and 15 months post-ablation respectively treated with systemic therapy and TACE - 2 HCC patient at 16 and 22 months respectively post-nodal ablation treated with TACE) and in the lung (2 sarcoma patients at 16 and 7 months respectively post the radiofrequency ablation of the LN treated with systemic therapy and percutaneous ablation – 2 colon cancer patient at 9 and 15 months respectively post-ablation treated with systemic therapy and ablation). At the time of manuscript submission, 4/16 patients had died due to disease progression.

Discussion

Data in the literature support the concept that within patients with metastatic cancer, a fraction of them have a distinct oligometastatic state that can be treated with local therapies with favorable outcomes in terms of survival and progression-free interval.^13,14 The present study adds to the growing number of case series showing that percutaneous ablation of metastatic LNs is an efficacious and safe technique in terms of achieving local tumor control.^{5–9,15–17} RFA has been used to treat metastatic LNs from different primary tumors including ovarian, renal cell and prostatic carcinoma, leiomyosarcoma, nasopharyngeal and esophageal, thyroid and hepatocellular carcinoma with excellent technical success while major complications are uncommon.^{5–9,15–17} Pan et al in a retrospective matched cohort analysis evaluated 199 HCC patients post-RFA of LNs in regional and distant sites reporting 84.4% local control rate at 3 months.⁵ Mu et al evaluated RFA in oligometastatic HCC patients with extrahepatic LN disease reporting 95.8% technique effectiveness rate.⁶ Similar to other studies, in the present case series, the treatment of metastatic LNs disease with RFA was successful (87.5% local control rate at 3 months) and well tolerated with no immediate or late complications. A potential explanation for the lack of post-ablation pain or swelling could be the limited amount of deposited energy necessary for LNs ablation due to the surrounding nodal capsule which might add up to a theoretic “oven effect”. In a recent paper by Tsoumakidou et al, percutaneous cryoablation has also been applied as salvage therapy in oligometastatic patients with no reports of major complications.¹⁸ CT-guidance offers excellent spatial resolution and field of view allowing detailed puncture route planning to reduce injury risk and achieve correct placement of the RFA electrode to minimize thermal damage in adjacent to the target structures.⁵ In all cases, we properly adjusted the power and timing of RFA to minimize thermal damage to adjacent organs achieving an uncomplicated result. Hydrodissection with Dextrose 5% was applied in two cases of para-aortic LNs. There is no doubt that peri - and postprocedural pain is limited during cryoablation in comparison to heat-based techniques, thus enabling the procedure to be held under moderate or mild anesthesia.¹⁸ In the present case series, all patients were treated under a combination of local anesthesia and conscious sedation with fentanyl.¹⁹

The local control rates achieved in this and previous studies (84.4–95.8%) support the use of RFA for this indication.^{5,7,9,15,16,18,20} Recurrence after RFA treatment of metastatic LNs is not common, whilst a second RFA session can be proposed for incomplete or partial response to ablation therapy during follow-up.^{5,7,9,15–17,20} In our study, a second RFA session was performed on two patients (three lesions). Size of the treated LNs as well as radiofrequency energy selection might be factors contributing to recurrence; however, the small sample size of the present study doesn’t allow drawing firm conclusions regarding the cause of recurrence.

Published data suggest that in oligometastatic patients, eradication of all clinically detectable disease sites actually benefits the OS rates; the safety profile of percutaneous RFA in this and other studies is acceptable, especially if one considers the invasiveness of surgical alternatives.^5,6,9,21 Karnes et al applied surgical dissection of prostate cancer nodal recurrence with 6% of the patients requiring post-surgical interventions due to Clavien II-IIIb complications.²¹ Duration of systemic tumor control seems to be the only variable associated with local and systemic disease control, likely indicating that more biologically aggressive tumors progress more rapidly despite local and systemic therapies.

There are several limitations of our study that should be taken into account. The first limitation is that our study is retrospective and thus subject to selection bias. Additionally, the sample size is small with a wide variety of neoplasmatic substrate which might introduce results’ biases. Similarly, mixed locations of the treated LNs render difficult the evaluation of site-specific complications. This study does not provide comparison with different local ablation techniques, nevertheless our findings suggest that RFA ablation of metastatic LNs is a safe and effective technique irrelevant of the tumor histology.

In conclusion, our results support that CT-guided RFA of LNs in oligometastatic patients is safe and feasible and can be repeated to treat recurrence irrespective of tumor histology. Large-scale prospective trials will provide solid proof concerning the usefulness of percutaneous ablation for the treatment of metastatic LNs in oligometastatic patients.