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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 8  |  Page : 27-32

Single institution experience treating adrenal metastases with stereotactic body radiation therapy


1 Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan, USA
2 Department of Radiation Oncology, Stony Brook University, Stony Brook, New York, USA

Date of Web Publication22-Mar-2019

Correspondence Address:
Dr. Farzan Siddiqui
Department of Radiation Oncology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, Michigan, 48202
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_655_16

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 > Abstract 


Objective: The objective of the study is to present our experience of treating adrenal metastases using stereotactic body radiation therapy (SBRT).
Materials and Methods: We retrospectively reviewed patients with adrenal metastases treated using SBRT from 2001 to 2014. Response Evaluation Criteria in Solid Tumors v1.1 was used. Maximum tumor response was defined as the greatest percentage tumor reduction noted on two or more post-SBRT CT scans.
Results: We identified 44 patients (median age 61.3 years, range: 25.8–85), with 54 adrenal metastases; primary diagnoses include non-small cell lung cancer (28 patients and 38 lesions), small cell lung cancer (1 patient), hepatocellular carcinoma (6 patients), and other (9 patients). Treatment was delivered in single (16 lesions, median dose 18 Gy [14–18]) or multiple fractions (38 lesions, median dose 30 Gy [16–40]). Median planning target volume was 49.65cc (3.21–984.54). Median response at first post-SBRT follow-up (median 1.65 months (m) (0.33–5.37), n = 46 lesions) was 10.8% with 91.3% local control. Median maximum tumor response was 31.8% (n = 32 lesions) at median follow-up of 5.4 m (0.9–44.8) with 96.6% local control. The response was comparable regardless of tumor histology or treatment fractionation. No patients experienced Grade 3/4 acute toxicities. One patient with a history of naproxen use required suturing with omental patch placement for perforated pyloric ulcer 14 m post-SBRT (18 Gy in single fraction) to the right adrenal metastasis; this region received <5 Gy. Ten patients treated for pain with available follow-up obtained relief.
Conclusions: SBRT is a safe and efficacious treatment for adrenal metastases, demonstrating local tumor control. Further study of the impact on survival and quality of life is warranted.

Keywords: Adrenal metastases, palliative radiation therapy, stereotactic body radiation therapy


How to cite this article:
Shah MM, Isrow D, Fareed MM, Wen N, Ryu S, Ajlouni M, Siddiqui F. Single institution experience treating adrenal metastases with stereotactic body radiation therapy. J Can Res Ther 2019;15, Suppl S1:27-32

How to cite this URL:
Shah MM, Isrow D, Fareed MM, Wen N, Ryu S, Ajlouni M, Siddiqui F. Single institution experience treating adrenal metastases with stereotactic body radiation therapy. J Can Res Ther [serial online] 2019 [cited 2020 Nov 27];15:27-32. Available from: https://www.cancerjournal.net/text.asp?2019/15/8/27/243491




 > Introduction Top


The adrenal gland consists of an outer cortex and an inner medulla. Pheochromocytomas originate in the medulla while the adrenal cortex harbors metastases as the second-most common entity after adenomas.[1] Metastatic adrenal lesions are noted in approximately 13%–35% of autopsied cases.[2],[3],[4] This sizeable incidence is attributed to the rich adrenal sinusoidal blood supply.[5] Lung, breast, renal, gastrointestinal tumors, and melanomas are among common primary tumors metastasizing to the adrenal glands.[6] Clinically, adrenal metastases are occult in the majority of cases. Computed tomography (CT), ultrasonography, magnetic resonance imaging, and positron emission tomography can help differentiate incidental adrenal adenomas and metastases.[7] Isolated adrenal gland metastases are encountered commonly in clinical practice today given globally increased overall survival rates and incorporation of follow-up imaging, particularly thoracic and abdominal CT scans in patients with metastatic disease.[8]

Surgical resection including open and laparoscopic adrenalectomy, radiofrequency ablation, and transarterial chemoembolization is used to treat adrenal metastases. Radiation therapy has been used historically as a noninvasive alternative, and palliative tool for treating these lesions; however, emerging data have shown its promising role in contributing to survival in these patients.[9],[10],[11],[12],[13],[14] More recently, the use of stereotactic body radiation therapy (SBRT) has been reported in patients with adrenal metastasis. This technique permits highly conformal delivery of high doses of radiation, thus offering the benefit of achieving high local control rates, making it a treatment modality comparable to surgery.[15]

In this retrospective analysis, we present our institutional experience using SBRT for the treatment of adrenal metastases, evaluating treatment response and local control.


 > Materials and Methods Top


We conducted an Institutional Review Board approved, retrospective review of 44 patients with 54 adrenal metastases treated with SBRT between the years 2001 and 2014 at our institution.

Stereotactic body radiation therapy technique

Simulation CT (Phillips, Cleveland, OH, USA) with oral and IV contrast was obtained after immobilizing patients using a custom foam mold with vacuum support (KGF Enterprise, Columbus, MI, USA) or Vac-Loc full-body cushion with vacuum support (Civco Medical Solutions, Kalona, IA, USA) for treatment planning. Before 2010, patients were simulated using a free breathing technique. Since 2010, four-dimensional (4-D) simulation CT techniques have been used. The gross tumor volume was defined based on the contrast-enhanced simulation scan. An internal target volume was defined with the use of 4-D simulation techniques. A 0–6 mm expansion was added for the planning target volume (PTV), with no expansion into the duodenum. The duodenum, stomach, kidneys, bowel, and the liver were contoured as organs-at-risk. Dose constraints were followed as specified in the American Association of Physicists in Medicine TG-101 guidelines.[16] Treatments were delivered using 7–9 stereotactic intensity-modulated radiation therapy beams or volumetric-modulated arc therapy. A frameless stereotactic system and a stereoscopic image guidance system were used for patient positioning on the Novalis BrainLab (Brainlab AG, Feldkirchen, Germany) system. An infrared camera and stereotactic localizer were used for the initial patient setup. Two stereoscopic X-ray images were taken to adjust the position of the patient with 6° of freedom. Final position verification was obtained using orthogonal portal films before delivery of radiation treatment. For patients treated on the Varian Trilogy and TrueBeam (Varian Medical Systems, Palo Alto, CA, USA) linear accelerators, the patient setup was assisted by daily cone-beam CT imaging, and final position verification with KV imaging was obtained before each fraction. Studied patients did not have fiducial markers placed.

Patients were selected for single or multiple fraction SBRT, as per discretion of the treating physician. Criteria that may have been used to determine fractionation include size/volume of metastasis, proximity to critical structures (duodenum, kidney), patient ability to lie supine for multiple fractions and logistical reasons such as patient travel distance.

Follow-up and response evaluation

Follow-up CT scans of the abdomen were obtained after completion of SBRT for response evaluation. The first posttreatment scan was obtained 6–8 weeks after completion of therapy and subsequent scans were obtained at 2–3-month intervals. Treatment details were reviewed, and tumor response was evaluated as per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.[17] Pretreatment CT scans were compared to the first post-SBRT scan and any subsequent scans obtained on further follow-up. For those lesions with two or more follow-up CT scans, “maximum tumor response” was defined as the greatest percentage reduction in tumor noted on any post-SBRT CT scan.


 > Results Top


Patient and adrenal lesion characteristics

Patient and treatment characteristics are outlined in [Table 1] and [Table 2]. Forty-four patients were identified with 54 metastatic adrenal lesions treated with SBRT between 2001 and 2014; median age at treatment was 61.3 years (range: 25.8–85 years). Primary diagnoses included: lung cancer in 28 patients with NSCLC (38 lesions) and 1 patient with SCLC, hepatocellular carcinoma in 6 patients, 8 patients with other malignancies while 1 patient had an unknown primary. Sixteen patients had solitary adrenal metastases at the time of SBRT. Twelve patients were treated for pain. Sixteen lesions received a single fraction with median dose of 18 Gy (range: 14–18 Gy) and median PTV of 44.7 cc (range: 3.21–186.26 cc). Thirty-eight lesions were treated with multiple fractions; median dose was 30 Gy (range: 14–40 Gy) and median dose/fraction was 7 Gy (range: 4–9 Gy). Median number of fractions was 5 (range: 3–6) and the median PTV was 65.84 cc (range: 6.26–984.54 cc) for multiple fraction SBRT [Table 3].
Table 1: Patient and lesion characteristics

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Table 2: Treatment characteristics

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Table 3: Treatment characteristics by tumor type and fractionation

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Median follow-up for 46 lesions on the first post-SBRT CT scan was 1.65 months (range: 0.33–5.37 months). For 32 lesions with 2 or more follow-up CT scans available for evaluation, the median follow-up was 5.4 months (range: 0.9–44.8 months). Four patients (8 lesions) did not have any follow-up imaging studies.

Treatment outcome

At first post-SBRT CT scan, median percent tumor size reduction as per RECIST 1.1 for all 46 lesions was 10.8% [Table 4]. At first follow-up, local control (complete response, partial response, or stable disease) for all lesions (n = 46), NSCLC lesions (n = 34), those treated with single fraction SBRT (n = 10) and multiple fraction SBRT (n = 36) was 91.3%, 91.2%, 80%, and 94.4%, respectively. Complete or partial response was seen in 8 out of 46 lesions; stable disease was seen in 34 lesions and progressive disease was seen in 4 lesions.
Table 4: Results at first poststereotactic body radiotherapy computed tomography scan

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Median “maximum tumor responses” (as defined above) on subsequent CT scans post-SBRT for all lesions (n = 32), NSCLC lesions (n = 22), those treated with single fraction SBRT (n = 6) and multiple fraction SBRT (n = 26) were 31.8%, 38.0%, 39.6%, and 30.7%, respectively [Table 5].
Table 5: Maximum tumor response

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At the time of analysis, 30 patients were deceased with median survival after SBRT of 6.7 months (range: 0.4–51.9 months); 14 patients were alive with median survival after SBRT of 13.2 months (range: 3.2–67.6 months). In a patient who is living 67.6 months after undergoing SBRT, the primary malignancy is NSCLC. He was treated to the left adrenal lesion three times in 4 years. Twelve patients presented with painful metastasis treated with SBRT; 10 patients had available follow-up, all of which stated pain relief.

Toxicity

SBRT was well tolerated with no acute Grade 3 or 4 toxicities. One patient underwent excision and suturing with omental patch placement for a 1 cm perforated ulcer on the anterior wall of the pylorus 14 months after treatment to right adrenal metastasis with single fraction of 18 Gy to a PTV of 26.3 cc. Treatment planning included a 4D CT at the time of simulation with Exac Trac imaging used before treatment. Maximum point dose to the stomach and duodenum was <12.4 Gy with <10 cc of the stomach and <5 cc of the duodenum receiving 11.2 Gy; <10 cc of the duodenum received 9 Gy. The anterior portion of the pylorus received <3 Gy. This patient with metastatic breast cancer lived 50.6 months post-SBRT.


 > Discussion Top


Open or laparoscopic adrenalectomy is considered a definitive treatment for adrenal metastases. A laparoscopic approach is associated with less blood loss and a shorter hospital stay.[13],[18] However, the percentage of major complications with surgery is around 10%–20%.[9],[11] Some patients are not eligible for adrenalectomy due to age, medical comorbidities, and unwillingness to undergo surgery. Furthermore, surgery is not suitable in patients with recurrent disease and local failure. In this group of patients, there is a need for an alternative, safe treatment of adrenal metastasis which produces results comparable to surgery.

The role of radiotherapy in treating adrenal metastases is addressed in a number of studies. In a retrospective review of 16 patients treated with palliative RT for symptomatic adrenal metastases, University of Pennsylvania reported an overall response rate of 75% with radiation doses ranging from 29.5 to 45.0 Gy in 2.5 Gy/fraction or 30 Gy in 3 Gy/fraction.[19] Another study from China reported a radiographic partial response of 73% in 22 patients with adrenal metastases from hepatocellular carcinoma treated with limited-field external beam RT to a median radiation dose of 50 Gy.[20]

SBRT has been used widely in patients with lung, liver, and spinal tumors with favorable outcomes. By reducing the volume of normal tissue exposed to high doses, SBRT significantly minimizes acute and late toxicity as compared to conventional hypofractionated regimens, with the added advantage of adrenal function preservation when compared to surgical intervention.[21],[22],[23]

Casamassima et al. demonstrated that overall survival, local and distant control are not influenced by primary tumor, synchronous versus metachronous presentation, unilateral or bilateral presentation, oligometastatic disease, and PTV. Local control after SBRT was 90% at 2 years.[24] Gamsiz et al. and Ahmed et al. report comparable local control rates in their retrospective reviews of adrenal metastatic lesions treated with SBRT.[25],[26] In a series of 13 patients treated by Rudra et al., the overall 1-year treated-metastasis control, distant control, and overall survival rates were 73%, 30%, and 90%, respectively.[27]

Feasibility and safety of SBRT for treating adrenal metastasis were further shown in two studies. Katoh et al. published a pilot study on 10 patients (most received 48 Gy in 8 fractions); the 1-year local control rate was 100% and survival was 78%.[28] At the University of Rochester, 30 patients underwent SBRT for adrenal metastases.[6] The prescribed doses ranged from 16 Gy in 4 fractions to 50 Gy in 10 fractions. The 1- and 2-year local control rates were 55% and 27%, respectively. In both studies, no RTOG grade 2 or greater toxicity was noted. In patients with an isolated adrenal metastasis median OS of 23 months was excellent and comparable to data after surgical removal. They suggested that future use of image-guided radiotherapy would offer sparing of the upper gastrointestinal tract from high doses of radiation.[29],[30],[31]

To the best of our knowledge, this study is the largest experience reported in the literature with 54 treated lesions, the largest series for lesions treated with single fraction as well as the largest series for patients with lung cancers.

Our results show local tumor control in excess of 90% for all groups including adrenal metastases from lung cancer and in those receiving single as well as multiple fraction SBRT. No significant difference in local control was observed in patients receiving single versus multiple fraction SBRT. In terms of symptomatic management, all patients treated for pain alleviation, with available follow-up, achieved durable pain control. As reported in most other studies, our patients did not experience acute toxicities. One patient with metastatic breast cancer experienced 1 cm perforated ulcer on the anterior wall of the pylorus which was treated surgically. She received a single fraction of 18 Gy to the right adrenal metastasis with PTV of 26.3cc, which is comparable to treatment volumes reported in other studies.[25],[32],[33] Maximum point doses to the stomach and duodenum were within constraints outlined in TG 101 and the anterior pylorus received a low dose of <3 Gy.[16] On further review of her plan and prior treatments, it is unlikely that the pyloric ulcer was an adverse effect of SBRT to the right adrenal metastasis. She was taking naproxen at the time of her ulcer, had received numerous chemotherapeutic drugs since diagnosis of her metastatic disease 23 years before SBRT and had received multiple courses of steroid therapy while undergoing chemotherapy, as well as radiosurgery to brain and spine metastases. This patient lived more than 4 years after completion of SBRT.


 > Conclusions Top


SBRT to adrenal metastasis demonstrates excellent tumor control regardless of histology and fractionation regimen. Further study is needed to evaluate the impact of SBRT to adrenal metastasis on survival and quality of life.

Financial support and sponsorship

Nil.

Conflicts of interest

Department of Radiation Oncology, Henry Ford Health System holds master research agreements and receives research grants from Varian Medical Systems, Palo Alto, CA and Philips Healthcare, Best, Netherlands. No financial interests in these entities or any other conflicts exist for all authors. Ning Wen reports grants from NIH, grants and personal fees from Varian Medical Systems, personal fees from Sun Nuclear Corporation. Farzan Siddiqui reports personal fees from St John's Providence Hospital, personal fees from Wayne State University-IBPRO 2015 course, personal fees from Varian Medical systems.



 
 > References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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