In this retrospective analysis, we evaluated the use of stereotactic body radiation therapy in the management of adrenal metastases from non-small cell lung cancer and report our single center experience.
Fifteen non-small cell lung cancer patients (9 male, 6 female) with 17 adrenal metastases referred to Gulhane Military Medical Academy Radiation Oncology Department were treated using active breathing control-guided stereotactic body radiation therapy between December 2009 and October 2013. Dose per fraction was 10 Gy to deliver a total dose of 30 Gy over 3 consecutive days for all metastatic adrenal lesions. The mean gross tumor volume was 28.4 cc (range 6.6-101.5) and mean planning target volume was 57.4 cc (range 16.5-143.8).
At a median follow-up of 16 months, local control was 86.7% and overall survival was 33.3%. Median disease-free survival was 10 months. Treatment response according to RECIST was categorized as complete response in 3 patients (20%), partial response in 5 patients (33.3%), stable disease in 5 patients (33.3%), and progressive disease in 2 patients (13.3%). Most common acute toxicity was grade 1 nausea (n = 7) and grade 1 fatigue (n = 12). There was no case of grade ≥3 acute or late toxicity.
Stereotactic body radiation therapy offers a safe and efficacious management strategy for adrenal metastases from non-small cell lung cancer by providing excellent local control with negligible treatment related toxicity.
Tumori 2015; 101(1): 98 - 103
Article Type: ORIGINAL RESEARCH ARTICLE
AuthorsHakan Gamsiz, Murat Beyzadeoglu, Omer Sager, Selcuk Demiral, Ferrat Dincoglan, Bora Uysal, Elif Onal, Bahar Dirican
- • Accepted on 30/05/2014
- • Available online on 05/02/2015
- • Published in print on 20/03/2015
This article is available as full text PDF.
The incidence of adrenal metastasis is reported to be in the range of 13% to 27% in autopsy series (1). Among the multiple cancer sites including lung, breast, melanoma, gastric and hepatocellular carcinomas, lung cancer has the greatest risk for metastatis to the adrenal glands (1). The high frequency of adrenal metastases at autopsy studies may be explained by the rich sinusoidal blood supply of the surrenal glands (2). Such metastases usually follow an insidious course as asymptomatic lesions and are mostly detected incidentally on cross-sectional follow-up imaging studies intended to investigate distant failure of the primary tumor. Although abrupt manifestation is rare, enlargement in the metastatic lesions may cause gastrointestinal symptoms including severe pain, abdominal discomfort, nausea and vomiting.
Systemic treatment has a long therapeutic history in the management of adrenal metastases and has been the mainstay upfront treatment for many years. However, recent years have witnessed unprecedented advances in cancer management, particularly in the discipline of radiation oncology. More precise treatments with modern techniques have prompted widespread adoption of more aggressive management for oligometastatic tumors in an attempt to improve treatment outcome. Attracted by favorable survival outcomes achieved with surgery of adrenal metastases (3-4-5-6-7-8-9-10), another viable local treatment modality, namely stereotactic body radiation therapy (SBRT), has been suggested as a noninvasive treatment tool in the management of these highly selected patients. The rationale of SBRT is to deliver a highly focused ablative dose of radiation to a well-defined extracranial target in 1 to 5 fractions. In the context of adrenal metastases, aggressive management with SBRT primarily aims to achieve excellent local control of the oligometastatic disease, which may potentially translate into improved survival as well. Given the paucity of data regarding its utility for this indication (11-12-13), we retrospectively evaluated the treatment outcomes of SBRT for adrenal metastases treated at our institution.
Materials and Methods
The retrospective study was conducted at Gulhane Military Medical Academy Radiation Oncology Department. Between December 2009 and October 2013, 15 non-small cell lung cancer (NSCLC) patients (9 male, 6 female) with 17 clinically diagnosed adrenal metastases were treated using active breathing control (ABC)-guided SBRT. Management of adrenal metastases with SBRT was decided after meticulous assessment. Treated patients had a Karnofsky Performance Status >70 with controlled primary NSCLC. Of the 15 total patients, 8 patients (53.3%) had adrenal metastasis only. The remaining 7 patients (46.7%) had oligometastatic disease with less than 5 metastases in no more than 2 involved organs. All patients had received at least 3 cycles of chemotherapy before SBRT, consisting primarily of platinum-based and taxane-based regimens. Chemotherapy was stopped at least 30 days before SBRT application in all patients. Adrenal metastases were diagnosed clinically on positron emission tomography scans, and histological confirmation was not mandatory. Informed consent was obtained from each patient prior to treatment with SBRT. Patient characteristics are shown in
|*Other metastases (with less than 5 metastases in no more than 2 involved organs).|
|Gender, no. (%)|
|No. of lesions||17|
|Histology, no. (%)|
|Squamous cell carcinoma||5 (33.3)|
|Non-small cell type||4 (26.7)|
|Overall treatment delivery time (min)|
|Location of adrenal metastases, no. (%)|
|Bilateral adrenal metastases, no. (%)||2 (13.3)|
|Status of oligometastatic disease, no. (%)|
|Controlled primary NSCLC, adrenal metastasis only||8 (53.3)|
|Controlled primary NSCLC, adrenal + other*||7 (46.7)|
|Prior chemotherapy, no. (%)||15 (100)|
Details of the ABC procedure have been described elsewhere (14-15-16-17). A training session was scheduled for all patients to make familiarize them with the ABC device (ABC, Elekta, UK). The 30-45 minute-long training session included the determination of individual breath-holding thresholds set at 75% of maximum inspiratory volume (moderate-deep inspiration breath-hold). Instructions were given to ensure using the mouthpiece properly between the teeth and lips to achieve a steady breathing pattern. Patients were trained to practice steady and reproducible breath-holds for optimal simulation and treatment with a typical breath-hold duration of 20 to 25 s.
After the training session, patients were immobilized for treatment simulation using the BODYFIX system, which consists of a vacuum cushion (Bluebag, ELEKTA), a vacuum pump, and a clear plastic sheet covering the patient’s torso with lower extremities. Patients were laid in a supine position on a Bluebag with both arms raised above the head using a T-shaped Wing Board (CIVCO, Kalona, IA, USA). Verbal instructions were given to enhance patient compliance. At the computed tomography (CT) simulator (GE Lightspeed RT, GE Healthcare, Chalfont St. Giles, UK) unit, planning CT images with 1.25 mm slice thickness were acquired at moderate-deep inspiration breath-hold.
Acquired images were transferred to the delineation workstation via the network. Advantage Sim MD simulation and localization software (Advantage SimMD, GE, UK) was used for delineation of target and critical structures on consecutive planning CT images. Optimal window-level was adjusted for each patient to assist in the contouring procedure. The clinical target volume was the same as the gross tumor volume, and the planning target volume was generated by expanding the clinical target volume isotropically by 3 to 5 mm in all directions. Stomach, duodenum, small and large bowels, kidneys, spinal cord, and liver were contoured as organs at risk. Data sets including the organs at risk and target volumes were then sent to the SBRT treatment planning system (ERGO++ planning system, Elekta). The dynamic conformal arc technique was used in treatment planning. Prescribed dose to the 90-100% isodose line encompassing the PTV was 10 Gy per fraction to deliver a total dose of 30 Gy over 3 consecutive days. Image-guided radiation therapy techniques including volumetric imaging with a cone beam CT (XVI, Elekta) were used on a daily basis to ensure precise delivery of the treatment at each fraction. All patients received high-precision SBRT using Elekta Synergy® Linear Accelerator with 6 MV photons.
A) SBRT treatment planning images of a patient with adrenal metastasis in ERGO planning system. B) Post-SBRT 6th month follow-up CT images of a patient (the same patient in
Response Evaluation Criteria in Solid Tumors (RECIST) was used for treatment response assessment. The categories were defined as:
The study population comprised 9 men (60%) and 6 women (40%), with a median age of 56 years (range 42-69). Histologically, the primary tumors were adenocarcinoma (n = 6), squamous cell carcinoma (n = 5), and non-small cell type (n = 4). Thirteen patients (86.7%) received SBRT for single metastatic lesion in the adrenal gland and 2 patients (13.3%) underwent SBRT for bilateral metastatic adrenal lesions. All lesions were treated using a total dose of 30 Gy over 3 consecutive days with 10 Gy per fraction. Median daily treatment length of an SBRT application was 14 minutes (range 12-29) depending on the treated number of targets. The mean gross tumor volume was 28.4 cc (range 6.6-101.5) and the mean planning target volume was 57.4 cc (range 16.5-143.8).
Treatment characteristics and outcomes
|Patient no.||GTV (cc)||PTV (cc)||Disease-free survival (mo)||Overall survival (mo)||Follow up (mo)|
|GTV = gross tumor volume; PTV = planning target volume.|
At a median follow-up of 16 months, local control was 86.7% and overall survival was 33.3% with negligible treatment-related toxicity. The median disease-free survival was 10 months. Treatment response according to RECIST was categorized as complete response in 3 patients (20%), partial response in 5 patients (33.3%), stable disease in 5 patients (33.3%), and progressive disease in 2 patients (13.3%).
The most common acute toxicity was grade 1 nausea (n = 7) and grade 1 fatigue (n = 12). No patient experienced adrenal or renal insufficiency during the follow-up period. One patient suffered from dyspeptic disorders 3 weeks after SBRT. Oral medication with a proton pump inhibitor achieved complete remission for the patient. No case of ≥ grade 3 acute or late toxicity was recorded.
Oligometastatic disease refers to limited metastatic spread of the primary cancer in an intermediate state between localized and widespread systemic disease (18). This distinct subgroup of metastatic disease carries a favorable prognosis and is well suited to metastasis-directed local therapies. In the context of adrenal metastases, aggressive local management with surgery has proved to be useful, as demonstrated in several studies (3-4-5-6-7-8-9-10). However, surgery is not devoid of complications and may not be preferable in a group of patients with comorbidities. Stereotactic irradiation in the form of stereotactic radiosurgery and SBRT, a relatively new local treatment modality, has gained popularity in recent years as a viable therapeutic option in the management of intracranial and extracranial targets, with promising results from many centers including ours (17, 19-20-21-22-23-24-25-26-27-28-29-30-31-32-33-34-35-36-37-38-39-40). While avoiding the risks of protracted hospital stays, hemorrhage, sepsis, and anesthesia as a non-invasive therapeutic approach, SBRT may achieve improved local control rates with preservation of adrenal functions. Moreover, the concept of enhanced antitumor immunity and abscopal effect suggests that radiotherapy directed at the oligometastatic focus may induce an adaptive immune response with potential implications for further improving treatment outcomes (41, 42).
Outcomes and survival after SBRT and laparoscopic adrenalectomy were compared in patients with isolated adrenal metastases in a retrospective, matched case-control study (33). No significant difference was found between the two modalities in terms of 6-month and 1-year median survival rates, and the authors concluded that SBRT might offer an alternative and less invasive therapeutic approach in the curative-intent treatment of isolated adrenal metastases (33). However, mean follow-up time was 18 months in the study, which should be considered in interpreting the results. Prospective studies with longer follow-up times are required to draw firm conclusions on long-term outcomes with these treatment modalities.
Emerging technological developments in the field of radiation oncology allow for more refined treatments with improved target contouring and precise treatment delivery under image guidance. The indications for SBRT are evolving in parallel to such advances, with compilation of data from several institutions throughout the world. Although the SBRT literature is growing at a rapid pace, experience regarding the SBRT of adrenal metastases is somewhat limited (31-32-33-34-35-36-37-38-39-40) (
Published series of SBRT for adrenal metastases
|Authors||No. of patients||No. of fractions||Dose (Gy)||Median follow-up(mo)||Outcomes: local control (LC) & survival||Toxicity|
|Chawla et al (31) (2009)||30||4-10||16-50||9.8||1-year LC: 55%||No patient developed acute or late grade 2-4 gastrointestinal, hepatic, renal, or dermatologic toxicity|
|2-year LC: 27%|
|1-year survival: 44%|
|2-year survival: 25%|
|Torok et al (32) (2011)||7||1 or 3||10-36||14||1-year survival: 63%||-|
|Median overall survival: 8 mo|
|Arnaud et al (33) (2011)||11||4-6||30-42||18||6-month survival: 77%||-|
|1-year survival: 62%|
|Katoh et al (34) (2011)||10||8||48||16||1-year LC: 78 %||No patient developed symptomatic adverse effects within the median follow-up period|
|1-year survival: 78 %|
|Scorsetti et al (35) (2012)||34||4-18||20-45||41||1-year LC: 66%||No patient developed grade ≥3 gastrointestinal, hepatic, renal, or dermatologic toxicity; grade 2 nausea in 2 patients|
|2-year LC: 32%|
|Median overall survival: 22 mo|
|Holy et al (36) (2011)||13||5||20-40||12||1-year LC: 77%||Acute: mild to moderate nausea in 6 patients Late: gastric & duodenal ulcer in 2 patients|
|1-year survival: 66.7 %|
|Median overall survival: 23 mo|
|Casamassima et al (37) (2012)||48||3||Median 36||16.2||1-year LC: 90%||Grade 2 adrenal insufficiency in 1 patient|
|2-year LC: 90%|
|1-year survival: 39.7%|
|2-year survival: 14.5%|
|Guiou et al (38) (2012)||9||5||20-37.5||7.3||1-year LC: 44%||No patient developed grade ≥3 acute or late toxicity|
|2-year LC: 44%|
|1-year survival: 52%|
|2-year survival: 13%|
|Oshiro et al (39) (2011)||11||1-27||30-60||10.1||1-year survival: 56%||No patient developed grade ≥3 acute or late toxicity; grade 2 duodenal ulcer in 1 pt|
|2-year survival: 33%|
|5-year survival: 22%|
|Ahmed et al (40) (2013)||13||5||33.75-60||12.3||1-year survival: 62.9%||No patient developed grade ≥3 acute or late toxicity|
|Median overall survival: 8 mo|
In conclusion, SBRT offers a safe and efficacious treatment modality in the management of adrenal metastases from NSCLC by providing high local control rates with negligible treatment-related toxicity.
- Gamsiz, Hakan [PubMed] [Google Scholar] , * Corresponding Author (email@example.com)
- Beyzadeoglu, Murat [PubMed] [Google Scholar]
- Sager, Omer [PubMed] [Google Scholar]
- Demiral, Selcuk [PubMed] [Google Scholar]
- Dincoglan, Ferrat [PubMed] [Google Scholar]
- Uysal, Bora [PubMed] [Google Scholar]
- Onal, Elif [PubMed] [Google Scholar]
- Dirican, Bahar [PubMed] [Google Scholar]
Department of Radiation Oncology, Gulhane Military Medical Academy, Ankara - Turkey