This retrospective study was approved by four hospitals: Shandong Provincial Hospital Affiliated with Shandong University, Sun Yat-sen University Cancer Center, Teng Zhou Central People's Hospital Affiliated with Jining Medical College, and Jinan Military General Hospital of the Chinese People's Liberation Army. From May 2010 to June 2014, 94 patients were histologically verified with adrenal metastases from lung cancer. A total of 31 patients met the following inclusion criteria: 1) the patient had unilateral adrenal metastases from lung cancer that were metachronous; 2) the patient was medically inoperable due to renal or heart dysfunction, other comorbid medical conditions (such as severe diabetes), or advanced stage; 3) the patient refused surgery; and 4) the patient did not undergo local radiotherapy without being affected by chemotherapy or tyrosine kinase inhibitors. The exclusion criteria were: 1) uncontrolled infection around the lesion or systemic infection; 2) coagulation disorder, especially in patients with platelet count of < 50 × 10⁹/L who had received continuous anti-coagulation therapy; 3) unfit for MWA due to severely deficient hepatic, renal, or cardiopulmonary function; or 4) an Eastern Cooperative Oncology Group performance status of 0–2 (12). Patients were informed in detail of the risks and benefits associated with MWA treatment and provided written informed consent for the procedure. Ethical approval to conduct this study was obtained by the Institutional Review Boards of the participating hospitals.

A CT-guided biopsy was performed by an ablation operator for all lesions before MWA to determine tumor pathology. Pathological diagnosis was evaluated by the pathologist of the participating hospitals.

Local anesthetic and preemptive analgesia were used during MWA procedure (13). Patients abstained from solid food for 12 hours prior to the procedure. For preemptive analgesia, morphine (10 mg, subcutaneous), diazepam (10 mg, intramuscular), and flurbiprofen axetil (50 mg, intravenous) were injected before the procedure. An intravenous injection of flurbiprofen axetil (50 mg) was also administered after the procedure. Local anesthetic was applied at the selected puncture points using 2% lidocaine.

Treatment and follow-up of all patients were performed under multislice CT guidance (Lightspeed16; GE Healthcare, Waukesha, WI, USA). The adrenal gland of the patient in lateral, supine, or prone position was scanned using a slice thickness of approximately 3–5 mm. After adrenal gland CT scanning, the appropriate scanned layers were selected to confirm puncture angles and depths.

A commercially available KY-2450B MWA system (Nanjing Kang You Microwave Research Institute, Nanjing, China: SFDA certified No.: [2011] 3250282) or an ECO-2450B MWA system (ECO Microwave Electronic Institute, Nanjing, China. Registration standard: YZB/country 1475–2013. China: SFDA certified No.: [III] 20112251456) was used for MWA. In general, the ablation power selected was 60–70 W and the ablative duration ranged from 4 to 8 minutes as decribed previously (1415). For tumors larger than 3.5 cm, ablation was performed with 2 antennas (14151617). Immediately after the MWA procedure, CT scanning was performed again to evaluate the tumor size, tumor morphology, and the status of adjacent organs. In addition, any complications such as bleeding were recorded.

During the procedure, the patient's heart rate, blood pressure (BP), electrocardiogram, and peripheral blood oxygen saturation level were carefully monitored. BP monitoring was performed every 5 minutes initially and every 3 minutes after the start of the ablation using a BP cuff. Vital signs, clinical symptoms, and urine volumes were closely observed during post-MWA hospital stay.

To evaluate the efficacy of treatment, follow-up CT was performed for each patient at one month after ablation. According to Image-Guided Tumor Ablation: Standardization of Terminology and Reporting Criteria (2005 and 2014) (818), primary or secondary efficacy rate of MWA was assessed to determine local treatment efficacy. The lesion observed at one month after ablation was used as the baseline to determine local efficacy. Primary efficacy rate was defined by lesion disappearance, fibrotic progression or scar, solid nodule involution or no change, and a lack of contrast enhancement signs on CT scan following the initial ablation. Secondary efficacy rate included tumors that underwent successful repeat ablation following the identification of local tumor progression (8). Residual unablated tumor was defined when the initial follow-up CT demonstrated a focal area of definite enhancement (i.e., attenuation difference of 20 Hounsfield units or greater between pre- and post-contrast CT images) within the ablation zone. After the initial CT evaluation, CT was performed every three months. Local tumor progression was defined as the appearance of tumor foci at the edge of the ablation zone after at least one contrast-enhanced follow-up study documenting adequate ablation and an absence of viable tissue in the target tumor and surrounding ablation margin according to imaging criteria (8). Local efficacy of MWA was collectively assessed by a medical oncologist and two imaging doctors. The median follow-up duration post-ablation was 11.1 months (range, 4–32 months).

The assessment of complications and side effects was also based on Image-Guided Tumor Ablation: Standardization of Terminology and Reporting Criteria (818). Both major and minor complications were assessed. Major complications that occurred in the process of ablation or post-treatment were promptly treated. If untreated, these clinical symptoms might be life threatening and lead to dysfunction and prolonged hospital stay. Minor complications are self-limited. They lack substantial morbidity. They only require a short hospitalization period. Minor complications include pain, post-ablation syndrome, and asymptomatic bleeding or effusion that can only be seen on CT images.

Data were analyzed using IBM SPSS statistics software (version 22, Armonk, NY, USA). Chi-squared test was used to compare local recurrence rate and survival in two groups of patients (those with a tumor size larger than 3.5 cm and those with a tumor size smaller than 3.5 cm). Overall survival and local tumor progression-free survival were estimated using Kaplan-Meier method. All tests were two-sided. Statistical significance was considered when p value was less than 0.05.

The average age of the 31 patients was 64.9 years (range, 45–82 years), including 18 males and 13 females. Of the 31 adrenal metastases treated with MWA, 13 were located in the right adrenal gland and 18 were located in the left adrenal gland. The average (mean ± SD) tumor diameter was 3.46 ± 1.08 cm (range, 1.5–5.4 cm). Patient and tumor characteristics are summarized in Table 1.

The range of hospital stay was 2–3 days. Successful ablation was achieved for all patients (technical success rate of 100%). All 31 patients underwent CT scan immediately after MWA. The 31 lesions displayed lower densities and cavities of various sizes in the ablation area. Follow-up CT scan at 1 month after MWA revealed primary efficacy rate of 90.3% (28 of the 31 lesions). Three lesions (patient No. 2, 10, and 24) had residual unablated tumor. For tumors ≤ 3.5 cm, the primary efficacy rate was 100% (16/16) (Figs. 1, 2, 3).

During the follow-up period, local tumor progression was detected in 7 (22.6%) of 31 cases. Patient No. 17 experienced local progression at 3 months after MWA. Patients No. 7 and No. 27 experienced local progression at 4 month and 5 months after MWA, respectively. MWA was repeated for patient No. 7. The tumor did not progress during the remainder of the follow-up period. Two patients (No. 2 and No. 13) experienced progression after 6 months post-MWA. Patient No. 2 experienced residual unablated tumor after the initial MWA but achieved secondary efficacy after the second MWA. However, this patient's lesion still progressed. Patients No. 28 and No. 19 experienced local progression after 8 and 9 months post-MWA, respectively. The secondary efficacy rate was 66.7% (MWA was repeated in the 3 patients following local progression, 2 of the 3 patients did not progress during the remainder of the follow-up period). One of the 16 patients with tumor ≤ 3.5 cm and 6 of the 15 patients with tumor > 3.5 cm experienced tumor recurrence (recurrence rates of 6.3% and 40%, respectively). The group of patients whose tumor size was > 3.5 cm had a higher (p = 0.037) local recurrence rate than the group with tumors ≤ 3.5 cm.

The median follow-up duration post-MWA was 11.1 months (range, 4–32 months). One-year overall survival rate was 44.3%. Median overall survival time was 12 months (95% confidence interval: 8.6–15.4 months) (Fig. 4A). Median local tumor progression-free survival time was 9 months. Local tumor progression-free survival rate was 77.4% (Fig. 4B).

Pain was the most common side effect during the procedures. In these cases, the procedure was completed after the pain was treated. Moderate pain was experienced in 11 sessions and severe pain occurred in 3 sessions (Table 2). The incidence of moderate and severe pain was 38.9% (14/36). When severe pain occurred, the procedure was stopped and patients were treated with morphine injection and midazolam. After MWA, moderate pain was experienced in 4 sessions (11.1%, 4/36). No severe pain occurred after MWA. Eleven patients experienced post-ablation syndrome. Main symptoms were fever (under 38.5℃), fatigue, general malaise, nausea, and vomiting.

During the procedure, patient's BP was increased in 14 sessions (38.9%), including two sessions (5.6%) in which the patient experienced hypertensive crisis. For general increases in BP, nitroglycerin was used to maintain BP at 120–130/80–90 mm Hg. A general increase in BP did not affect the procedure. The procedure was stopped immediately if the patient's systolic pressure was increased beyond 200 mm Hg or diastolic pressure was increased beyond 110 mm Hg with symptoms of hypertensive crisis such as cephalalgia, palpitation, and dyspnea. These patients were treated with phentolamine and nitroglycerin. The procedure was continued when the BP was controlled and maintained at 120–130/80–90 mm Hg. For both patients who experienced hypertensive crisis, the procedure was continued after successfully treating the BP. In one (2.8%) session, local retroperitoneal hematoma was observed. However, CT scanning found that the hematoma was not enlarged at 24 h after the procedure. No other severe complications such as hemorrhoea, intestinal fistula, pancreatic fistula, or adrenal failure occurred in any patient. No patient died during the procedure or within 30 days after MWA.