Local Control and Survival after Image-Guided Percutaneous Ablation of Adrenal Metastases

CLINICAL STUDY

Local Control and Survival after Image-Guided Percutaneous Ablation of Adrenal Metastases Nathan E. Frenk, MD, Dania Daye, MD, PhD, Kemal Tuncali, MD, Ronald S. Arellano, MD, Paul B. Shyn, MD, Stuart G. Silverman, MD, Florian J. Fintelmann, MD, and Raul N. Uppot, MD ABSTRACT Purpose: To evaluate local control and survival after image-guided ablation of adrenal gland metastases. Materials and Methods: Image-guided ablations of adrenal metastases measuring < 5 cm performed at 2 academic medical centers between July 2002 and June 2016 were analyzed. There were 51 procedures performed on 46 tumors (mean diameter 2.8 cm ± 1.1; range, 0.7–4.9 cm) in 38 patients (mean age 66 y; range, 41–80 y) with renal cell carcinoma (n ¼ 17 patients; 45%), non–small cell lung cancer (n ¼ 10 patients; 26%), and other primary malignancies (n ¼ 11 patients; 29%). Treatment modalities included cryoablation (n ¼ 30 procedures; 59%), radiofrequency ablation (n ¼ 12 procedures; 24%) and microwave ablation (n ¼ 9 procedures; 18%). Technical success, primary and secondary efficacy, local progression rate, local progression-free survival, and overall survival were assessed. Mean follow-up was 37 months (range, 2–128 months). Statistical analysis was performed with univariate Cox hazards regression and Kaplan-Meier analyses. Results: Technical success, primary efficacy, and secondary efficacy were 96%, 72%, and 76%. Local progression rate during all follow-up was 25%. Local tumor progression-free survival at 1, 3, and 5 years was 82%, 69%, and 55%. Overall survival at 1, 3, and 5 years was 82%, 44%, and 34%. In 16 patients with isolated adrenal metastasis, median disease-free survival was 8 months; 4 patients had no evidence of disease during follow-up. Lung cancer was associated with decreased survival (hazard ratio 4.41, P ¼ .002). Conclusions: Image-guided ablation can achieve local control for adrenal metastases < 5 cm.

ABBREVIATIONS NSCLC ¼ non–small cell lung cancer, RCC ¼ renal cell carcinoma

From the Divisions of Interventional Radiology (N.E.F., R.S.A., R.N.U.) and Thoracic Imaging and Intervention (F.J.F.), Department of Radiology (D.D.), Massachusetts General Hospital, Harvard Medical School, Boston, 55 Fruit St, MA 02114; and Division of Abdominal Imaging and Intervention (K.T., P.B.S., S.G.S.), Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. Received May 26, 2017; final revision received July 21, 2017; accepted July 23, 2017. Address correspondence to N.E.F.; E-mail: [email protected] P.B.S. received funding for this research from Siemens Medical Solutions, Inc. (Hoffman Estates, Illinois). None of the other authors have identified a conflict of interest. From the SIR 2017 Annual Scientific Meeting. N.E.F. and D.D. contributed equally as co–first authors, and F.J.F. and R.N.U. contributed equally as co–last authors. © SIR, 2017 J Vasc Interv Radiol 2017; ▪:1–9 http://dx.doi.org/10.1016/j.jvir.2017.07.026

The adrenal glands are a common site for metastases, with adrenal metastases occurring in 3%–27% of patients with malignancy according to autopsy series (1–3). Although no randomized controlled trial has demonstrated the benefit of local treatment for metastases to the adrenal gland, a survival benefit has been shown in retrospective surgical case series after adrenalectomy in selected patients (4,5). However, adrenalectomy is not always feasible owing to patient comorbidities and may be associated with prolonged hospital admissions, prompting the need for a less invasive treatment. In published series of image-guided percutaneous ablation of adrenal tumors, local recurrence-free survival rates of 88% at 1 year have been reported (6–15). However, these studies are limited in that both primary and secondary adrenal neoplasms are included, the number of patients is small, and follow-up is limited. In addition, reported data include tumors measuring  5 cm, in which percutaneous ablation is known to generally have inferior results (16). The

2 ▪ Image-Guided Ablation of Adrenal Metastases

RESEARCH HIGHLIGHTS  Ablation of adrenal metastases < 5 cm was technically successful, with primary efficacy of 96% and secondary efficacy of 72% and 76%.  Although most patients who had isolated adrenal metastases developed progression, 25% had no evidence of disease at the end of follow-up (14–84 months).  The median overall survival for all patients was 30 months. Survival was significantly worse in patients with non–small cell lung cancer.  The estimated local control and overall survival of 75% and 65% at 2 years compare favorably with published results from surgery and radiation therapy.

purpose of this study was to evaluate local control and survival after image-guided percutaneous ablation of adrenal gland metastases measuring < 5 cm.

MATERIALS AND METHODS Patient Population A retrospective review of medical records at 2 large academic medical centers was performed. Institutional review board approval was received, and requirement for written informed consent was waived. All patients who had adrenal metastases treated with image-guided percutaneous ablation between July 2002 and June 2016 were included. Exclusion criteria were (a) tumor size  5 cm; (b) procedures performed for local debulking and symptomatic palliation, without intent for complete local control; and (c) patients with no follow-up, defined as absence of imaging and clinical follow-up beyond 1 month after the ablation. Adrenal metastases in 60 patients were treated with ablation (Table 1). Of these patients, 16 (27%) were excluded because of tumor size  5 cm, 4 (7%) were excluded because ablation was performed for palliation, and 2 (3%) were lost to follow-up. The resulting study population comprised 38 patients (male-to-female ratio 24:14; mean age 66 y) with 46 adrenal tumors that were treated with 51 procedures. There were 13 (34%) patients treated in 1 institution and 25 (66%) patients in the other. The series included 34 patients from a previously published investigation (17) that did not report local control or survival rates. In 31 (82%) patients, only 1 adrenal metastasis was ablated; in 6 (16%) patients, 2 metastases were ablated; and in 1 (3%) patient, 3 different adrenal metastases were ablated. Mean tumor diameter was 2.8 cm. The most common primary malignancies were renal cell carcinoma (RCC) (17 patients; 45%) and non–small cell lung cancer (NSCLC) (10 patients; 26%). In 19 patients, an isolated adrenal metastasis was found with no evidence of metastatic disease elsewhere; of these patients, 16 (42%) had had their primary tumor resected, and 3 (8%) still had

Frenk et al ▪ JVIR

the primary tumor. In 19 (50%) patients, metastases to the adrenal gland as well as extra-adrenal metastases were present. At some point during oncologic treatment, 29 of the 38 (76%) patients received systemic therapy. Two tumors (4%) had been treated with radiation therapy before the ablation. The diagnosis of adrenal metastasis was established by biopsy in 31 tumors (67%). In the remaining 15 tumors, the diagnosis was based on fluorodeoxyglucose avidity on positron emission tomography (PET) in 9 instances, the appearance of new lesions in 4 instances, and growth by at least 50% in 6 months in 2 instances (18,19).

Ablation Procedures Patients were seen in the interventional radiology clinic for evaluation before the procedure. Outpatient percutaneous image-guided ablation was performed on a subsequent day, followed by hospital admission for overnight observation. Among the 38 patients, 28 (74%) underwent 1 procedure, 7 (18%) underwent 2 procedures, and 3 (8%) underwent 3 procedures. Of the 51 procedures, 43 (84%) were performed under general anesthesia, 7 (14%) were performed under monitored anesthesia care, and 1 (2%) was performed under moderate sedation. Alpha blockade before the procedure consisting of doxazosin mesylate and metoprolol succinate was administered before 15 of 51 procedures (29%) as previously described (17). The decision to administer alpha blockade was based on the presence of residual normal adrenal tissue on imaging obtained before the procedure. Procedures were performed by 10 interventional radiologists, all with at least 8 years of experience with adrenal ablation. Choice of image guidance and ablation modality was at the interventional radiologist’s discretion and limited by available choices at the time of the procedure. Images were obtained intermittently (not real time), and no intravenous contrast material was used. Computed tomography (CT) was used in 36 procedures (71%). 5Slices 5 or 4 mm thick were obtained on a 16-slice LightSpeed (GE Healthcare, Milwaukee, Wisconsin) or a 40-slice SOMATOM Sensation Open (Siemens Medical Solutions, Forchheim, Germany) CT scanner. Magnetic resonance (MR) imaging was used in 10 procedures (20%), all cryoablations, with images obtained on either a Signa SP (GE Healthcare; 7 procedures) or a Siemens MAGNETOM Verio (Siemens Healthcare, Erlangen, Germany; 3 procedures) MR scanner. Sequences included T2-weighted half-Fourier acquisition single-shot turbo spin echo or spoiled gradient recalled acquisition in the steady state with 5- or 4-mm-thick slices. PET/CT with a Discovery ST (GE Healthcare) was used in 5 procedures (10%) as described elsewhere (20,21). Of 51 procedures, 30 were cryoablations (59%), 12 were radiofrequency (RF) ablations (24%), and 9 were microwave ablations (18%). One patient’s metastasis was treated with both RF ablation and ethanol injection because it was thought that residual tumor would remain after 1 RF ablation application and that overlapping applications would put adjacent vital structures at risk. Cryoablation was performed

Volume ▪ ▪ Number ▪ ▪ Month ▪ 2017

3

Table 1. Characteristics of Study Population Characteristics

Table 1. Characteristics of Study Population (continued) Value

Patients (N ¼ 38) Age, y, mean ± SD; range

66 ± 9.2; 41–80

Sex Female

14 (37)

Male Histology

24 (63)

RCC

17 (45)

NSCLC

10 (26)

Melanoma

2 (5)

Endometrial carcinoma

2 (5)

Other (colorectal, SCLC, breast, TCC, HCC, gastrinoma, salivary gland), 1 each

7 (18)

Extent of disease at time of ablation Isolated adrenal metastasis Primary tumor and adrenal metastasis Metastases in adrenal gland and other sites Systemic therapy at any time

16 (42) 3 (8) 19 (50)

Yes

29 (76)

No

9 (24)

Systemic therapy after ablation* Yes

18 (47)

No

20 (53)

Adrenal tumor number 1 2

31 (82) 6 (16)

3

1 (3)

Tumors (N ¼ 46) Diameter, cm, mean ± SD; range

2.8 ± 1.1; 0.7–4.9

Diameter group  3 cm > 3 cm and < 5 cm

31 (67) 15 (33)

Laterality Right

23 (50)

Left

23 (50)

Prior adrenal radiation therapy Yes

2 (4)

No

44 (96)

Prior biopsy Yes No

30 (70) 13 (30)

Procedures (N ¼ 51) Ablation modality RF ablation† Microwave ablation

12 (24)

Cryoablation

30 (59)

Anesthesia GETA

9 (18)

43 (84)

MAC

7 (14)

Moderate sedation

1 (2) continued

Characteristics Preprocedural alpha blockade Yes No

Value 15 (29) 36 (71)

Note–Values are presented as number (%) unless otherwise indicated. HCC ¼ hepatocellular carcinoma; GETA ¼ general endotracheal anesthesia; MAC ¼ monitored anesthesia care; NSCLC ¼ non-small cell lung cancer; RCC ¼ renal cell carcinoma; SCLC ¼ small cell lung cancer; TCC ¼ transitional cell carcinoma. *Systemic therapy after ablation and before progression (for patients with progression) or before end of follow-up (for remaining patients). † RF ablation combined with ethanol injection in 1 patient.

with a Galil (Galil Medical, Inc, Arden Hills, Minnesota) or Endocare (Endocare, Inc, Irvine, California) system. RF ablation was performed with a Cool-tip single electrode (Medtronic, Minneapolis, Minnesota), UniBlate single electrode (AngioDynamics, Latham, New York), StarBurst multitined electrode (RITA Medical Systems, Inc, Mountain View, California), cluster electrode (Radionics, Inc, Burlington, Massachusetts), or multitined LeVeen electrode (Boston Scientific, Marlborough, Massachusetts). Microwave ablation was performed with the Certus 140 (NeuWave Medical, Inc, Madison, Wisconsin) or AMICA (HS Hospital Service SpA, Aprilia, Italy) system. Tumors were ablated according to manufacturer recommendations. RF ablation was impedance controlled (Medtronic, Radionics, and Boston Scientific systems) or temperature based (RITA Medical Systems devices), microwave ablation was power and time based, and cryoablation used a double-freeze protocol. The objective of the treatment was to ablate the tumor and a surrounding margin of at least 5 mm, while sparing adjacent critical structures. Hydrodissection was performed in 10 procedures (20%) to separate adjacent structures from the tumor and the ablation zone. A noncontrast scan was obtained immediately after the procedure to evaluate for adequate coverage of the lesion and to assess for complications. All but 1 ablation procedure were completed as planned. In 1 case, RF ablation had to be aborted because the patient developed transient, self-limited ventricular tachycardia. Subsequent cardiac evaluation was unremarkable, and this patient underwent successful RF ablation 4 months later (procedure and outcome included in this study).

Adverse Events and Follow-up Adverse events were classified according to the Society of Interventional Radiology (SIR) guidelines (22,23). Hypertensive crisis was defined as systolic blood pressure spike > 180 mm Hg and at least 50 mm Hg above systolic blood pressure determined at the beginning of the procedure (24). Patients were followed clinically after the ablation. Serial

4 ▪ Image-Guided Ablation of Adrenal Metastases

Frenk et al ▪ JVIR

Figure 1. Flow chart demonstrating adrenal metastases ablated and follow-up (per tumor). Technical success was defined as complete tumor ablation with no visible residual tumor after 1 or 2 ablation procedures. Primary technique efficacy corresponds to tumors without local tumor progression throughout the entire follow-up period. Secondary technique efficacy corresponds to tumors either without local tumor progression or, if local tumor progression occurred, with no further local progression after repeat ablation. Interrupted lines correspond to the presence of residual tumor on follow-up imaging.

CT, MR imaging, or PET/CT scans were obtained starting 1 day or 1 month after the ablation, according to each institution’s protocol. If residual tumor was detected at the initial follow-up, the tumor was considered for repeat ablation. Residual tumor was diagnosed when nodular enhancement was identified at the site of the previously ablated tumor. Subsequent imaging was obtained at 3, 6, and

12 months after ablation and yearly thereafter. Follow-up ended with the most recent clinic visit or most recent imaging study before September 2016 or with the patient’s death. The mean follow-up period was 37 months ± 31 (range, 2–128 months). Only 1 patient was lost to follow-up 128 months after ablation; all other patients had follow-up available until their death or September 2016.

Volume ▪ ▪ Number ▪ ▪ Month ▪ 2017

5

Table 2. Univariate Cox Regression for Local Progression in Successfully Ablated Tumors (n ¼ 44) Variable Age

Hazard Ratio

95% CI

P Value

0.88

0.82–0.95

.002

0.56–6.13

.305

0.45–7.17 0.25–6.72

.387 .741

Sex Male

1.00

Female

1.86

Histology RCC

1.00

NSCLC Others

1.86 1.31

Extent of disease Figure 2. Local progression-free survival in successfully ablated tumors (n ¼ 44).

Definition of Outcomes Outcomes were defined based on published guidelines (25). Technical success was defined as imaging confirmation of complete tumor ablation with no visible residual tumor either after the first ablation (n ¼ 41) or after a second ablation (n ¼ 3) completed within 4 months of the first ablation. Local tumor progression was defined as the development of new enhancing tumor during follow-up after documentation of technical success. In successfully ablated tumors, primary technique efficacy was defined as the percentage of tumors without evidence of local tumor progression throughout the entire follow-up period; in successfully ablated tumors, secondary technique efficacy was defined as the percentage of tumors either without local tumor progression on imaging follow-up or, if local tumor progression occurred, with no further local progression after repeat ablation. In patients who had isolated adrenal metastases at the beginning of the study and whose adrenal tumors were successfully ablated, systemic progression was defined as the development of new metastases in the adrenal glands or elsewhere.

Data Collection and Statistical Analysis Two authors (N.E.F., F.J.F.) reviewed all medical records and imaging. The characterization of local or systemic recurrence was retrospectively established based on review of all available follow-up information, including clinic notes and imaging examinations. Technical success and adverse events were evaluated on a per procedure basis. Disease-free survival was evaluated on a per patient basis and only for patients with an isolated adrenal metastasis, starting from the ablation that achieved technical success. Technique efficacy (primary and secondary) was evaluated on a per tumor basis. Local progression-free survival was evaluated on a per tumor basis starting from the ablation that achieved technical success. Overall survival was evaluated on a per patient basis, starting with the first ablation. Overall survival analysis was controlled for systemic therapy at any point (both before and after ablation).

Isolated adrenal metastasis

1.00

Primary tumor and adrenal metastasis

1.35e–15

0–1

1.000

0.69

0.21–2.30

.557

Metastases in adrenal gland and other sites Systemic therapy after ablation* No

1.00

Yes

1.19

0.36–3.94

.771

1.00 0.6

1.55–1.69

.907

0.25–3.62

.947

8.42e–16

0

1.000

8.55

0.75–96.93

.083

0.33–3.64

.874

Size  3 cm > 3 cm and < 5 cm Side Right

1.00

Left

0.95

Ablation modality RF ablation† Microwave ablation Cryoablation Ablation date

1.00

First half of study

1.00

Second half of study

1.10

CI ¼ confidence interval; NSCLC ¼ non–small cell lung cancer; RCC ¼ renal cell carcinoma. *Systemic therapy after ablation and before progression (for patients with progression) or before end of follow-up (for remaining patients). † RF ablation combined with ethanol injection in 1 patient.

This applied to 29 of the 38 patients (76%). Analysis of local tumor control and systemic progression after ablation was controlled only for systemic therapy if it was administered after ablation. This applied to 18 of the 38 patients (47%). Descriptive data were presented as mean ± SD and range for continuous variables and as percentages for categorical variables. For statistical analysis, the clinical variables included patient age, sex, primary tumor histology (RCC, NSCLC, or others), extent of disease (isolated adrenal metastasis, primary tumor and adrenal metastasis, or metastases to the adrenal gland and other sites), and systemic therapy. Tumor characteristics included size ( 3 cm or > 3 cm) and side (right or left). Procedural characteristics included ablation modality and ablation date. Ablation date was stratified as ablation having taken place either in the

6 ▪ Image-Guided Ablation of Adrenal Metastases

first half (before May 11, 2010) or in the second half (after May 11, 2010) of the study period to evaluate for differences over time that could be attributed to learning curve. Univariate Cox hazards regression analysis was used to examine the association between clinical variables, tumor characteristics, and local progression or overall survival. Kaplan-Meier analysis was used to assess progression and survival probability estimates for the patient population over the study period. Statistical tests were 2-tailed, and the statistical significance level was set at P  .05. Results are presented with 95% confidence intervals (CIs). The difference in survival across histology strata was compared using the log-rank test. All statistical analyses were performed using STATA 14 (StataCorp LLC, College Station, Texas).

RESULTS Technical Success, Technique Efficacy, and Local Progression No residual tumor was seen in 41 of 46 tumors on first follow-up imaging; 3 of the 5 cases with residual tumors were successfully treated with a second ablation within 4 months, and technical success was therefore 96% (44 of 46) (Fig 1). Of the 46 tumors, 33 were successfully ablated and did not develop local progression during follow-up, corresponding to a primary technique efficacy of 72% (Fig 1). Of the 44 tumors that were successfully ablated, local progression was observed in 11 tumors (25%) at a mean of 15.4 months ± 16.8 (median 8 months; range, 3–58 months). Local progression-free survival at 1, 2, 3, and 5 years was 82% (95% CI [66%, 91%]), 75% (95% CI [58%, 86%]), 69% (95% CI [48%, 83%]), and 55% (95% CI [25%, 78%]) (Fig 2). Reablation of 2 of the 11 recurrent tumors was successful, and local control was achieved at the end of follow-up, whereas residual tumor remained after reablation of a third tumor. Therefore, secondary technique efficacy was 35 of 46 tumors (76%) (Fig 1). Older age was the only evaluated factor independently associated with decreased local progression (hazard ratio 0.88; 95% CI, 0.82–0.95; P ¼ .002) (Table 2).

Frenk et al ▪ JVIR

Table 3. Univariate Cox Regression for Systemic Progression in Patients with Isolated Adrenal Metastases (n ¼ 16) Variable Age Sex

Hazard Ratio

95% CI

P Value

0.97

0.91–1.03

.451

0.30–3.12

.976

Male

1.00

Female

0.98

Histology RCC

1.00

NSCLC

1.25

0.30–5.20

.758

Others

0.98

0.24–4.01

.986

0.72–7.61

.155

0.42–5.12

.535

0.35–3.81

.812

Systemic therapy after ablation* No

1.00

Yes

2.34

Size  3 cm

1.00

> 3 cm and < 5 cm

1.48

Side Right

1.00

Left

1.51

Ablation modality RF ablation†

1.00

Microwave ablation

3.74

0.32–41.89

.290

Cryoablation

6.49

0.78–53.75

.083

1.00 1.94

0.51–7.40

.330

Ablation date First half of study Second half of study

CI ¼ confidence interval; NSCLC ¼ non–small cell lung cancer; RCC ¼ renal cell carcinoma. *Systemic therapy after ablation and before progression (for patients with progression) or before end of follow-up (for remaining patients). † RF ablation combined with ethanol injection in 1 patient.

Systemic Progression Of the 16 patients who had an adrenal metastasis as the only site of disease, 4 never experienced recurrence: 1 patient with RCC died as a result of cirrhosis and hepatocellular carcinoma 20 months after the adrenal ablation, and the remaining 3 were alive and cancer-free at 14 months (1 with NSCLC), 48 months (1 with RCC), and 84 months (1 with colorectal carcinoma) after ablation. The other 12 patients had systemic progression at a mean of 9.6 months ± 13.9 (median 5.5 months; range, 1–51 months). Median systemic progression-free survival for those patients was 8 months (95% CI, 3–51). None of the evaluated factors was associated with systemic progression on univariate analysis (Table 3).

Figure 3. Overall survival for all patients (n ¼ 38).

Patient Survival During follow-up, 27 patients died at a mean 29.4 months ± 24.3 (median 25 months; range, 2–103 months) after ablation. One patient, who underwent ablation of an adrenal metastasis from RCC, died as a result of cirrhosis and hepatocellular carcinoma; all the other patients died as a

Volume ▪ ▪ Number ▪ ▪ Month ▪ 2017

7

Table 4. Univariate Cox Regression for Overall Survival in Study Population (n ¼ 38) Variable Age

Hazard Ratio

95% CI

P Value

0.98

0.94–1.01

.326

0.45–2.25

.983

1.72–11.28 0.58–4.09

.002 .382

Table 5. Adverse Events (Per Procedure) SIR Classification

Events

Description

Minor

3 (6%)

Intermittent urinary retention from catheterization (n ¼ 1), self-limited hematoma (n ¼ 1), hematuria during ablation (n ¼ 1)

Major

6 (12%)

Hemobilia and acute cholecystitis (n ¼ 1), hypertensive crisis with demand ischemia and cardiac troponin elevation (n ¼ 4), pneumothorax requiring chest tube (n ¼ 1)

Sex Male

1.00

Female

1.00

Histology RCC

1.00

NSCLC Others

4.41 1.54

Extent of disease

Note–SIR classification for complications.

Isolated adrenal metastasis

1.00

Primary tumor and adrenal metastasis

1.41

0.28–6.91

.670

Metastases in adrenal gland and other sites

2.33

0.97–5.63

.058

0.50–2.32

.830

0.69–3.32

.296

0.68–3.18

.323

Systemic therapy at any time No

1.00

Yes

1.08

Size  3 cm

1.00

> 3 cm and < 5 cm

1.51

Side Right

1.00

Left

1.47

Ablation modality RF ablation*

1.00

Microwave ablation

1.00

0.20–4.88

.994

Cryoablation

0.99

0.42–2.32

.995

1.00 1.05

0.47–2.32

.906

Ablation date First half of study Second half of study

CI ¼ confidence interval; NSCLC ¼ non–small cell lung cancer; RCC ¼ renal cell carcinoma. *RF ablation combined with ethanol injection in 1 patient.

Figure 4. Overall survival for all patients, stratified by histology. P ¼ .003 on log-rank test.

result of progression of their primary cancer. Overall survival at 1, 2, 3, and 5 years was 82% (95% CI [65%, 91%]), 65% (95% CI [47%, 78%]), 44% (95% CI [27%, 59%]), and

34% (95% CI [18%, 50%]). Median survival was 30 months (95% CI, 18–44) (Fig 3). The only risk factor associated with decreased survival was NSCLC histology (hazard ratio 4.41; 95% CI, 1.72–11.28; P ¼ .002) (Table 4, Fig 4).

Adverse Events Hypertensive crises occurred in 29 procedures (57%) and were managed by anesthesiology with beta and alpha blockers, hydralazine hydrochloride, and sodium nitroprusside. The hypertensive crises were associated with cardiac troponin elevation in 4 instances and had no complications in the remaining cases. All adverse events are detailed in Table 5. The median length of stay was 1 day (mean 1.7 d; range, 1–10 d), excluding 1 patient with a prolonged 65-day hospitalization for reasons unrelated to the ablation.

DISCUSSION Results of this study demonstrate that ablation of adrenal metastases < 5 cm achieves local tumor control with technical success and primary technique efficacy rates of 96% and 72%. Although 25% of the tumors developed local progression, repeat ablation achieved secondary technique efficacy of 76%. Moreover, although most patients who had adrenal metastases as the only site of disease developed local or systemic progression, 25% had no evidence of disease at the end of follow-up. Median overall survival for all patients was 30 months; overall survival was significantly worse in patients with NSCLC (hazard ratio 4.41; P ¼ .002). These data compare favorably with results of surgical management of adrenal metastases based on a 2014 systematic review (26): estimated local control and overall survival at 2 years for surgery were 84% and 46% compared with 75% and 65% in this study. Median hospital length of stay (1 d) after ablation was also shorter compared with the median 3-day hospitalization reported after laparoscopic adrenalectomy (27). This is in keeping with the results of a small retrospective case-controlled study comparing laparoscopic adrenalectomy with RF ablation for small (< 3 cm)

8 ▪ Image-Guided Ablation of Adrenal Metastases

adrenal adenomas. Both approaches had similar clinical results; however, RF ablation was associated with shorter procedure time, shorter hospital stay, and less pain after the procedure (28). A prospective comparison of surgical resection and percutaneous ablation of adrenal metastases has not been performed. The ablation results of this study also compare favorably with radiation therapy of adrenal metastases. Reported results of radiation include local control and overall survival rates at 2 years of 63% and 19%, respectively (26). Published case series of percutaneous ablation of adrenal metastases include a range of treatment modalities, such as RF ablation (with or without transarterial embolization or chemoembolization), microwave ablation, and cryoablation (7,8,11–13). Follow-up in those series is variable, with means ranging from 11.3 months (7) to 37.7 months (12). This likely affects the reported rates of local progression at the end of follow-up, which range from 0% (7) to 33% (13). The results of the present study are overall very similar to the results of Hasegawa et al (8), who published the largest series of adrenal ablations to date (41 tumors), with RF ablation with or without transarterial embolization. Secondary technique efficacy in the present study was 76% compared with 77% in the study by Hasegawa et al (8); local progression-free survival at 1, 3, and 5 years of 82%, 69%, and 55% in this study is comparable to their reported local tumor progression rates of 30%, 44%, and 44%; and overall survival in this study at 1, 3, and 5 years of 82%, 44%, and 34% is also very similar (75%, 35%, and 30%). Welch et al (11), who published the next largest cohort (37 tumors treated with cryoablation and RF ablation), had similar local recurrence–free survival and overall survival at 1 year (88% and 74%) but slightly better longer term results (local progression–free survival at 2 and 3 years of 88% and 88% and overall survival of 66% and 52%). Whether the results of Welch et al (11) are related to differences in technique and patient population or simply are due to a slightly smaller number of treated tumors and shorter follow-up (22.7 months compared with 37 months in the present study) cannot be assessed. This study has several limitations, including its retrospective design. Although it is retrospective, there was no significant loss to follow-up. As in all other retrospective studies, selection bias is an inherent limitation. However, patients who are referred for percutaneous ablation are often too ill for surgery owing to multiple comorbidities. Therefore, the survival data may underestimate the benefit of percutaneous ablation. Only patients with metastases < 5 cm were included; however, larger lesions are often treated in clinical practice for both palliation and attempt at local control. Because tumor size is a fundamental limitation of all image-guided ablation techniques, only tumors that had a reasonable chance of being successfully ablated were evaluated. Multiple interventional radiologists performed the procedures at 2 institutions, with a variety of ablation and image guidance modalities, in a variety of

Frenk et al ▪ JVIR

clinical scenarios (isolated metastases, multifocal tumors). Although the lack of uniformity can be interpreted as a limitation, it may more accurately reflect clinical practice; however, it does limit comparison of the role of different ablative modalities. Histologic diagnosis was not obtained for 15 of the 46 adrenal tumors, but interval growth and typical appearance on imaging in the setting of known metastatic malignancy justifies treatment in clinical practice. Finally, this series included multiple histologies, limiting evaluation of the relevance of percutaneous ablation for each tumor subtype. In conclusion, percutaneous ablation can achieve local control in adrenal metastases < 5 cm. As local control and survival rates compare favorably with published results of surgery and radiation, a comparative, prospective randomized study is warranted.

REFERENCES 1. Glomset DA. The incidence of metastasis of malignant tumors to the adrenals. Am J Cancer 1938; 32:57–61. 2. Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer 1950; 3:74–85. 3. Lam K-Y, Lo C-Y. Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. Clin Endocrinol (Oxf) 2002; 56: 95–101. 4. Vazquez BJ, Richards ML, Lohse CM, et al. Adrenalectomy improves outcomes of selected patients with metastatic carcinoma. World J Surg 2012; 36:1400–1405. 5. Solaini L, Ministrini S, Tomasoni M, et al. Adrenalectomy for metastasis: long-term results and predictors of survival. Endocrine 2015; 50: 187–192. 6. Wang Y, Liang P, Yu X, Cheng Z, Yu J, Dong J. Ultrasound-guided percutaneous microwave ablation of adrenal metastasis: preliminary results. Int J Hyperthermia 2009; 25:455–461. 7. Li X, Fan W, Zhang L, et al. CT-guided percutaneous microwave ablation of adrenal malignant carcinoma: preliminary results. Cancer 2011; 117: 5182–5188. 8. Hasegawa T, Yamakado K, Nakatsuka A, et al. Unresectable adrenal metastases: clinical outcomes of radiofrequency ablation. Radiology 2015; 277:584–593. 9. Kuehl H, Stattaus J, Forsting M, Antoch G. Transhepatic CT-guided radiofrequency ablation of adrenal metastases from hepatocellular carcinoma. Cardiovasc Intervent Radiol 2009; 31:1210–1214. 10. Mouracade P, Dettloff H, Schneider M, Debras B, Jung JL. Radiofrequency ablation of solitary adrenal gland metastasis from renal cell carcinoma. Urology 2009; 74:1341–1343. 11. Welch BT, Callstrom MR, Carpenter PC, et al. A single-institution experience in image-guided thermal ablation of adrenal gland metastases. J Vasc Interv Radiol 2014; 25:593–598. 12. Yamakado K, Anai H, Takaki H, et al. Adrenal metastasis from hepatocellular carcinoma: radiofrequency ablation combined with adrenal arterial chemoembolization in six patients. AJR Am J Roentgenol 2009; 192: W300–W305. 13. Wolf FJ, Dupuy DE, Machan JT, Mayo-Smith WW. Adrenal neoplasms: effectiveness and safety of CT-guided ablation of 23 tumors in 22 patients. Eur J Radiol 2012; 81:1717–1723. 14. Carrafiello G, Lagan
a D, Recaldini C, et al. Imaging-guided percutaneous radiofrequency ablation of adrenal metastases: preliminary results at a single institution with a single device. Cardiovasc Intervent Radiol 2008; 31:762–767. 15. Ren C, Liang P, Yu X-L, Cheng Z-G, Han Z-Y, Yu J. Percutaneous microwave ablation of adrenal tumours under ultrasound guidance in 33 patients with 35 tumours: a single-centre experience. Int J Hyperthermia 2016; 32:517–523. 16. Gillams A, Goldberg N, Ahmed M, et al. Thermal ablation of colorectal liver metastases: a position paper by an international panel of ablation
res Meeting 2013. Eur experts, the Interventional Oncology Sans Frontie Radiol 2015; 25:3438–3454.

Volume ▪ ▪ Number ▪ ▪ Month ▪ 2017

17. Fintelmann FJ, Tuncali K, Puchner S, et al. Catecholamine surge during image-guided ablation of adrenal gland metastases: predictors, consequences, and recommendations for management. J Vasc Interv Radiol 2016; 27:395–402. 18. Fassnacht M, Kenn W, Allolio B. Adrenal tumors: how to establish malignancy ? J Endocrinol Invest 2004; 27:387–399. 19. Boland GWL, Dwamena BA, Jagtiani Sangwaiya M, et al. Characterization of adrenal masses by using FDG PET: a systematic review and meta-analysis of diagnostic test performance. Radiology 2011; 259: 117–126. 20. Shyn PB, Tremblay-Paquet S, Palmer K, et al. Breath-hold PET/CT-guided tumour ablation under general anaesthesia: accuracy of tumour image registration and projected ablation zone overlap. Clin Radiol 2017; 72: 223–229. 21. Shyn PB. Interventional positron emission tomography/computed tomography: state-of-the-art. Tech Vasc Interv Radiol 2013; 16:182–190. 22. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003; 14: S199–S202.

9

23. Omary RA, Bettmann MA, Cardella JF, et al. Quality improvement guidelines for the reporting and archiving of interventional radiology procedures. J Vasc Interv Radiol 2002; 13:879–881. 24. Yamakado K, Takaki H, Yamada T, et al. Incidence and cause of hypertension during adrenal radiofrequency ablation. Cardiovasc Intervent Radiol 2012; 35:1422–1427. 25. Ahmed M, Solbiati L, Brace CL, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria—a 10-year update. Radiology 2014; 273:241–260. 26. Gunjur A, Duong C, Ball D, Siva S. Surgical and ablative therapies for the management of adrenal “oligometastases”—a systematic review. Cancer Treat Rev 2014; 40:838–846. €m E, Almquist M, Jacobsson H, Bergenfelz A. 27. Thompson LH, Nordenstro Risk factors for complications after adrenalectomy: results from a comprehensive national database. Langenbecks Arch Surg 2017; 402: 315–322. 28. Yang MH, Tyan YS, Huang YH, Wang SC, Chen SL. Comparison of radiofrequency ablation versus laparoscopic adrenalectomy for benign aldosterone-producing adenoma. Radiol Med 2016; 121:811–819.