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ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 5  |  Page : 1269-1274

Computed tomography-guided cryoablation for adrenal metastases secondary to lung cancer


1 Department of Radiology, Xijing Hospital of Fourth Military University, Xi'an, China
2 Department of Urinary Surgery, Xijing Hospital of Fourth Military University, Xi'an, China
3 Department of Radiology, Xuzhou Central Hospital, Xuzhou, China
4 Department of Infectious Disease, Xijing Hospital of Fourth Military University, Xi'an, China

Date of Submission15-Oct-2020
Date of Decision04-Mar-2021
Date of Acceptance13-Jul-2021
Date of Web Publication27-Nov-2021

Correspondence Address:
Wei Zhang
Department of Infectious Disease, Xijing Hospital of Fourth Military University, 127 Changle Road, 710032 Xi'an
China
Ya-Yong Huang
Department of Radiology, Xuzhou Central Hospital, 199 Jiefang Road, 221009 xuzhou
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_1520_20

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 > Abstract 


Objectives: The objective of the study was to assess the clinical efficacy of computed tomography (CT)-guided cryoablation as a means to treat adrenal metastasis (AM) secondary to lung cancer.
Materials and Methods: This study was a single-center retrospective study that analyzed 39 consecutive patients with AM secondary to lung cancer who underwent CT-guided cryoablation in our center. The rates of complete ablation, local recurrence, local recurrence-free survival (RFS), and overall survival (OS) were analyzed.
Results: The rates of primary and secondary complete ablation were 94.9% and 100%, respectively, and none of the patients suffered from a hypertensive crisis associated with the treatment. Over the follow-up period, 20.5% of the patients experienced local recurrence, and the median RFS duration was 26 months. The cumulative 1-, 3-, and 5-year local RFS rates in this study were 84.6%, 51.3%, and 5.9%, respectively. Extra-adrenal gland metastases were detected in five patients. Over the course of follow-up, 26 patients died. The mean OS duration was 34 months with cumulative 1-, 3-, and 5-year OS rates of 89.7%, 53.4%, and 8.3%, respectively. Advanced age (P = 0.001), primary adenocarcinoma (P = 0.006), other primary lung cancers (P = 0.038), and primary Stage III lung cancers (P = 0.007) were all found to be independent predictive factors of poor OS in these patients.
Conclusion: CT-guided cryoablation can be safely and effectively used to control AM secondary to lung cancer, and patients with AM secondary to lung squamous cell carcinoma may be best suited for this form of treatment.

Keywords: Adrenal, cryoablation, lung cancer, metastasis, survival


How to cite this article:
Zhang WL, Ruan DL, Sun LJ, Wang T, Zhang W, Huang YY. Computed tomography-guided cryoablation for adrenal metastases secondary to lung cancer. J Can Res Ther 2021;17:1269-74

How to cite this URL:
Zhang WL, Ruan DL, Sun LJ, Wang T, Zhang W, Huang YY. Computed tomography-guided cryoablation for adrenal metastases secondary to lung cancer. J Can Res Ther [serial online] 2021 [cited 2022 May 28];17:1269-74. Available from: https://www.cancerjournal.net/text.asp?2021/17/5/1269/331304




 > Introduction Top


Tumors often metastasize to the adrenal gland,[1],[2],[3] ~27% of patients exhibited adrenal metastasis (AM) upon autopsy.[4],[5] No clinical trials have established beneficial local AM treatments, although surgical resection was proposed.[6],[7],[8],[9] Adrenalectomy, however, may not be an option for patients with certain comorbidities, and it is associated with prolonged postoperative hospitalization.[1],[2],[3] Alternative approaches to treating AM are thus essential.

AM treated with computed tomography (CT)-guided radiofrequency ablation, microwave ablation, or cryoablation[1],[2],[3] achieved local 1-year recurrence-free survival (RFS) rates of 71%–82%.[1],[2] However, these prior studies have evaluated AM secondary to a range of primary tumor types including liver and lung cancers, potentially introducing selection bias into these results.[1],[2],[3] Therefore, studies should evaluate AM secondary to specific cancers.

Consequently, this study assessed CT-guided cryoablation treatment of AM secondary to lung cancer.


 > Materials and Methods Top


Our Institutional Review Board (No. XJYY20200709) approved the present retrospective single-center study and waived the requirement for written informed consent.

Study design

Consecutive patients with AM secondary to lung cancer who underwent CT-guided cryoablation in our hospital between July 2011 and August 2019 were included in this study.

Patients who were eligible for the following inclusion criteria were included (a) not eligible for surgery or declined to undergo surgical resection as a means of treating AM; (b) had undergone lung cancer surgical resection; (c) had a tumor ≤5 cm in size; and (d) did not exhibit any extra-adrenal tumors.

Patients were excluded from this study if they (a) exhibited adrenal vein invasion or (b) were suffering from infections, active bleeding, or significant coagulatory dysfunction.

Diagnosis

AM was diagnosed based on patient history, abdominal CT findings, and percutaneous biopsy results. Patients were also evaluated for extra-adrenal tumors through chest CT, brain magnetic resonance imaging, and bone emission CT scans.

Cryoablation

Patients were placed in the prone position, and all procedures were guided by CT (Philips, Amsterdam, The Netherlands).

Argon-helium cryoablation (Cryo-hit, Galil Medical, Israel) was conducted under local anesthesia. Each cryoprobe had a 1.5 cm × 3.5 cm freezing area. Abdominal CT scans were used to localize tumors in each patient and to assess the tumor size [Figure 1]a, cryoprobes were then distributed according to tumor shape and size [Figure 1]b. The edge of the freezing area had a temperature of 0°C, while a temperature < −40°C is necessary to kill cells. The overall freezing area was 0.5–1 cm beyond the tumor edge, with a ≤1.5 cm interval between pairs of cryoprobes.[3]
Figure 1: A 55-year-old male that developed left adrenal metastasis following lung cancer resection. (a) Contrast-enhanced computed tomography images of a left adrenal metastasis exhibiting significant enhancement (arrow). (b) Cryoablation procedures. (c) Contrast-enhanced computed tomography scan exhibiting a lack of visible tumor enhancement after treatment (arrow)

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Following cryoprobe placement, tumors were subjected to two freeze-thaw cycles (10 min freezing, 3 min thawing). Freezing was achieved through rapid argon gas expansion within the sealed cryoprobes, which reached a minimum tip temperature of −140°C within a few seconds. Thawing was achieved by replacing argon with helium gas. Abdominal CT scans were repeated following treatment to confirm the dimensions of the frozen tissue produced using this cryoablation approach.

Postoperative management

After cryoablation, patients were monitored for approximately 30 min and then were subsequently returned to the ward if no discomfort was observed. Patient vital signs were then monitored for 6 h.

Follow-up

Follow-up was routinely conducted from the time of treatment to death or last visit through June 2020. Once per month, patients underwent standard physical examination and laboratory testing including tests of blood cell counts and adrenal hormone levels. In addition, postoperative CT scanning was conducted at 1, 3, 6, and 12 months following treatment, and every 12 months thereafter.

Definitions

Complete ablation was defined as a lack of any detectable tumor enhancement upon contrast-enhanced CT evaluation 5-day posttreatment [Figure 1]c, while residual enhancement was indicative of partial ablation.[3],[10],[11] This treatment was repeated 1-week posttreatment in cases where tumor enhancement remained detectable. Tumor recurrence was defined as the presence of a new tumor enhancement within the ablated region.[3],[11],[12] Local RFS was defined as the time between treatment and AM recurrence, death, or most recent follow-up. Overall survival (OS) was the time from treatment to death or most recent follow-up. Hypertension crisis was considered when the blood pressure exceed 180/120 mmHg.[10]

Statistical analysis

SPSS 16.0 (SPSS Inc., IL, USA) was used for statistical analyses. Continuous data are given as means and were compared through the t-tests, while categorical and numerical data were compared through the Chi-square tests and Fisher's exact test. The Kaplan–Meier curves were used to assess patient survival, and predictive factors of survival were identified through Cox regression analysis. Covariates that yielded a P < 0.1 in the univariate analyses were retained for multivariate analysis. The significance threshold for this study was P < 0.05.


 > Results Top


Patients

In total, 39 consecutive patients with AM secondary to lung cancer who underwent cryoablation were analyzed in the present study. Each enrolled patient had a single adrenal tumor. Corresponding baseline data are compiled in [Table 1]. No patient had bilateral AM. The primary lung cancer tumor types in these patients included squamous cell carcinoma (n = 16), adenocarcinoma (n = 16), and other tumor types (n = 7). No patient had previous small-cell-lung-cancer. At the time of tumor resection, tumor stages in these patients were Stage I (n = 14), II (n = 15), and III (n = 10). Of these patients, 19 underwent chemotherapy prior to AM detection.
Table 1: Baseline data of the 39 patients

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Assessment of cryoablation efficacy

CT-guided cryoablation was successfully conducted in all 39 patients, with a mean operative duration of 60 min (range: 50–70 min). Primary complete ablation was achieved in 94.9% of patients (37/39), while the remaining residual tumor enhancement in the other two patients was successfully eliminated upon subsequent cryoablation, with a 100% rate of secondary complete ablation.

Complications

Mild blood pressure increases were observed in eight (20.5%) patients in this study cohort during cryoablation, and treatment was suspended. These patients were treated with alpha blockers, at which time their blood pressure values returned to normal levels, and cryoablation procedures were successfully completed. No patients in this study suffered from a hypertensive crisis, hematoma, hemorrhage, or damage to surrounding tissues following cryoablation.

Local recurrence

Over a mean 33-month follow-up period, 22 patients underwent postcryoablation chemotherapy. Local recurrence was observed in eight (20.5%) patients within 9–39 months (median: 18 months), and repeat cryoablation was performed in these patients. The median duration of local RFS in this study cohort was 26 months, with cumulative 1-, 3-, and 5-year local RFS rates of 84.6%, 51.3%, and 5.9%, respectively [Figure 2]. Univariate Cox-regression analyses did not identify any risk factors associated with local tumor recurrence.
Figure 2: Kaplan–Meier curves pertaining to patient local recurrence-free survival

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Overall survival

Over the course of the follow-up period, 26 patients died because of tumor progression. Five of these patients experienced extra-adrenal metastases (liver: 3; bone: 1; and brain: 1). The mean OS in these patients was 34 months, with cumulative 1-, 3-, and 5-year OS rates of 89.7%, 53.4%, and 8.3%, respectively [Figure 3].
Figure 3: Kaplan–Meier curves pertaining to patient overall survival

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Cox regression analysis revealed that advanced age (hazard ratio: 1.103, 95% confidence interval [CI]: 1.040–1.170, P = 0.001), primary adenocarcinoma (hazard ratio: 4.983, 95% CI: 1.584–15.675, P = 0.006), other forms of primary lung cancer (hazard ratio: 3.771, 95% CI: 1.074–13.240, P = 0.038), and primary Stage III lung cancers (hazard ratio: 5.742, 95% CI: 1.615–20.412, P = 0.007) were independent predictive factors of poor OS [Table 2]. Chemotherapy following cryoablation was unrelated to patient survival in a multivariate Cox regression analysis (P = 0.054).
Table 2: Univariate and multivariate cox analyses of overall survival

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The mean OS durations were 56, 22, and 22 months in patients with primary squamous cell carcinoma, primary adenocarcinoma, and other forms of primary lung cancer in this study cohort, respectively [squamous cell carcinoma vs. adenocarcinoma, P = 0.041; squamous cell carcinoma vs. others, P = 0.008; adenocarcinoma vs. others, P = 0.725, [Figure 4]]. The mean OS durations were 45, 34, and 17 months in patients with primary Stage I, II, and III tumors, respectively [I vs. II, P = 0.403; I vs. III, P = 0.007; II vs. III, P = 0.120, [Figure 5]].
Figure 4: Overall survival based on the different pathological types

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Figure 5: Overall survival based on the different previous tumor stages

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 > Discussion Top


Adrenal metastases are commonly treated by CT-guided radiofrequency ablation and microwave ablation.[1],[2],[13],[14] More recently, however, cryoablation approaches have been employed to treat these and other malignant tumors as such approaches cause less pain, allow for visualization of the treatment zone, and are conducive to improved healing properties.[11],[12] In a prior study of CT-guided AM ablation, survival of patients with AM secondary to lung cancer was significantly lower than that of patients with AM secondary to other cancer types.[1]

Our data revealed that CT-guided cryoablation can be safely and effectively be used to treat AM secondary to lung cancer. In the present study cohort, the rates of primary and secondary complete ablation were 94.9% and 100%, respectively, and were comparable to those in other studies involving CT-guided radiofrequency, microwave, or cryoablation in patients with AM.[1],[2],[3] As 94.9% of patients exhibited primary complete AM ablation, this suggests that cryoablation can effectively damage the tumor tissue. While two patients exhibited residual tumor activity following treatment, a subsequent round of cryoablation was sufficient to eliminate the remaining malignant tissue.

The local control rates were a primary end point for the present study. Local recurrence was observed in 8/39 patients in the present study cohort (20.5%), which is comparable to rates observed in a prior study of microwave/radiofrequency ablation treatment of AM secondary to lung cancer (22%).[13] These rates were similar to those reported in prior studies of radiofrequency ablation of AM secondary to renal and liver cancers.[15],[16] Our local control rate (79.5%) was also very similar to that achieved in patients who underwent adrenalectomy (77%–83%).[3],[4]

Cumulative 1- and 3-year local RFS rates in this study cohort were 84.6% and 51.3%, respectively, which indicated that CT-guided cryoablation can achieve satisfactory rates of local tumor control in patients suffering from AM secondary to lung cancer. As the cumulative 5-year local RFS rate was just 5.9%, however, this indicates that additional systemic treatments will likely be necessary for these patients.

The 1-, 3-, and 5 year OS rates in this study (89.7%, 53.4%, and 8.3%, respectively) were similar to those in prior analyses of AM treatment through radiofrequency/microwave ablation.[1],[2] Cox regression analysis led us to determine that advanced age, primary adenocarcinoma, other primary lung cancers, and Stage III primary lung tumors were all independent predictors of OS in this study cohort. Age was likely prognostic in part because older patients have a higher mortality risk due to causes other than tumor progression relative to younger patients.[1] Lung cancer subtype is an important determinant of metastasis and patient survival. As many studies found that lung adenocarcinoma is more prone to lymph node metastasis relative to lung squamous cell carcinoma,[17],[18] this may explain why patients with primary squamous cell carcinoma in our study exhibited longer OS (56 months) relative to other patient groups.

Chemotherapy is commonly applied to treat patients with lung cancer. However, in a multivariate Cox regression analysis, we did not detect any significant association between chemotherapy and patient survival (P = 0.054). This may be attributable to the limited sample size of this study or potential chemoresistance in some of the treated patients.

Following cryoablation, five of the patients in the present study developed extra-adrenal metastases. While cryoablation is an effective treatment intervention, imaging-based follow-up is essential in order to rapidly identify and treat extra-adrenal tumor progression in a timely fashion.[3]

Previous studies found that ablation of adrenal tumors were found to be associated with the incidence of hypertensive crisis,[2],[11] however, there were no cases of hypertensive crisis in the present study cohort. This suggests that cryoablation may decrease the incidence of hypertensive crisis incidence.[3] Microwave ablation causes significant temperature increases in target tissues, which is known to be associated with higher hypertensive crisis rates than other forms of ablation.[3] Cases of ablation-related hypertensive crisis are also most commonly observed in patients with pheochromocytoma[11] but not in patients exhibiting other adrenal tumor types.[12]

This study has several limitations. For one, this was a retrospective analysis and thus was susceptible to selection bias. Furthermore, this was a single-center study with a small sample size, as such caution should be taken when generalizing the results of this study to larger patient populations or over longer follow-up periods. Third, this study did not include a comparison group of patients undergoing surgical tumor resection or other forms of ablation. As such, additional multicenter randomized controlled trials are essential to validate and expand upon these findings.


 > conclusion Top


In summary, CT-guided cryoablation can be safely and effectively used to control AM secondary to lung cancer, and patients with AM secondary to lung squamous cell carcinoma may be best suited for this treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Hasegawa T, Yamakado K, Nakatsuka A, Uraki J, Yamanaka T, Fujimori M, et al. Unresectable adrenal metastases: Clinical outcomes of radiofrequency ablation. Radiology 2015;277:584-93.  Back to cited text no. 1
    
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Frenk NE, Daye D, Tuncali K, Arellano RS, Shyn PB, Silverman SG, et al. Local control and survival after image-guided percutaneous ablation of adrenal metastases. J Vasc Interv Radiol 2018;29:276-84.  Back to cited text no. 2
    
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Zhang W, Sun LJ, Xu J, Fu YF, Zhuang Z×. Computed tomography-guided cryoablation for adrenal metastases: Local control and survival. Medicine (Baltimore) 2018;97:e13885.  Back to cited text no. 3
    
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Gao Y, Zheng L, Liang P, Cheng Z, Han Z, Tan SL, et al. Evaluating the efficacy and safety of ultrasound-guided percutaneous microwave ablation for the treatment of adrenal metastasis. J Cancer Res Ther 2020;16:1088-92.  Back to cited text no. 5
    
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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;40:838-46.  Back to cited text no. 6
    
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Muth A, Persson F, Jansson S, Johanson V, Ahlman H, Wängberg B. Prognostic factors for survival after surgery for adrenal metastasis. Eur J Surg Oncol 2010;36:699-704.  Back to cited text no. 7
    
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Howell GM, Carty SE, Armstrong MJ, Stang MT, McCoy KL, Bartlett DL, et al. Outcome and prognostic factors after adrenalectomy for patients with distant adrenal metastasis. Ann Surg Oncol 2013;20:3491-6.  Back to cited text no. 8
    
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Vazquez BJ, Richards ML, Lohse CM, Thompson GB, Farley DR, Grant CS, et al. Adrenalectomy improves outcomes of selected patients with metastatic carcinoma. World J Surg 2012;36:1400-5.  Back to cited text no. 9
    
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Zhang W, Shi YB, Zhuang ZX, Wang JP, Sun LJ, Fu YF. Computed tomography-guided cryoablation for adrenal pheochromocytoma: Safety and clinical effectiveness. Surg Laparosc Endosc Percutan Tech 2019;29:409-12.  Back to cited text no. 10
    
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Fu YF, Cao C, Shi YB, Zhang W, Huang YY. Computed tomography-guided cryoablation for functional adrenal aldosteronoma. Minim Invasive Ther Allied Technol 2021;30:169-73.   Back to cited text no. 11
    
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Adebayo O, Rogers RL. Hypertensive emergencies in the emergency department. Emerg Med Clin North Am 2015;33:539-51.  Back to cited text no. 12
    
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Botsa EI, Thanou IL, Papatheodoropoulou AT, Thanos LI. Thermal ablation in the management of adrenal metastasis originating from non-small cell lung cancer: A 5-year single-center experience. Chin Med J (Engl) 2017;130:2027-32.  Back to cited text no. 13
    
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Welch BT, Callstrom MR, Carpenter PC, Wass CT, Welch TL, Boorjian SA, et al. A single-institution experience in image-guided thermal ablation of adrenal gland metastases. J Vasc Interv Radiol 2014;25:593-8.  Back to cited text no. 14
    
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Huang J, Xie X, Lin J, Wang W, Zhang X, Liu M, et al. Percutaneous radiofrequency ablation of adrenal metastases from hepatocellular carcinoma: A single-center experience. Cancer Imaging 2019;19:44.  Back to cited text no. 15
    
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Mouracade P, Dettloff H, Schneider M, Debras B, Jung JL. Radio-frequency ablation of solitary adrenal gland metastasis from renal cell carcinoma. Urology 2009;74:1341-3.  Back to cited text no. 16
    
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Bao F, Yuan P, Yuan X, Lv X, Wang Z, Hu J. Predictive risk factors for lymph node metastasis in patients with small size non-small cell lung cancer. J Thorac Dis 2014;6:1697-703.  Back to cited text no. 17
    
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Cho S, Song IH, Yang HC, Kim K, Jheon S. Predictive factors for node metastasis in patients with clinical stage I non-small cell lung cancer. Ann Thorac Surg. 2013;96:239-45.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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