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Review Lung Cancer Adrenal Oligometastases Secondary to Non- small Cell Lung Cancer—What is the Optimal Treatment Approach? Bryce Thomsen 1 and Alysa Fairchild 2 1. Faculty of Medicine, University of Alberta, Edmonton, AB, Canada; 2. Department of Radiation Oncology, Cross Cancer Institute, Edmonton, AB, Canada B ackground: Five-year overall survival (OS) for patients with stage IV non-small cell lung cancer (NSCLC) is a dismal 1%. However, approximately 7% have limited or solitary metastases, including to the adrenal gland. Radical treatment of these oligometastases (OM) could increase local control and improve OS. Our objective was to critically analyze data describing aggressive treatment of adrenal OM secondary to NSCLC. Methods: A literature search examining English publications describing surgery or radiotherapy (RT) was performed, supplemented by searching reference lists. Case reports of three or fewer patients, and articles from which NSCLC- or adrenal-specific clinical outcomes could not be abstracted, were excluded. Results: Twenty-nine studies met eligibility criteria (521 patients), 26 retrospective. No publications directly compare modalities. Four surgery studies described contemporaneous patients treated with palliative chemotherapy (CH) alone. Reported median OS ranged from 9.5–64 months after adrenalectomy, 8–23 months after RT, and 6–8.5 months after CH. Local failure after surgery was 14%, with response rates after RT 57–75%. Both appear well-tolerated. Conclusions: In patients with an adrenal OM secondary to NSCLC, aggressive treatment should be considered. However, due to the paucity of high quality evidence, it is unclear at present whether this approach alters the natural history of the disease. Keywords Oligometastasis, adrenal, non-small cell lung cancer, stereotactic body radiotherapy, adrenalectomy, laparoscopic Disclosure: Bryce Thomsen and Alysa Fairchild have nothing to declare in relation to this article. No funding was received for the publication of this article. Compliance with Ethics: This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: August 31, 2017 Accepted: October 30,2017 Citation: Oncology & Hematology Review, 2017;13(2):117–29 Corresponding Author: Alysa Fairchild, Department of Radiation Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, Canada, T6G 1Z2. E: alysa.fairchild@albertahealthservices.ca Lung cancer is the most common non-cutaneous cancer globally, and the foremost cause of cancer mortality. 1 Non-small cell lung cancer (NSCLC) accounts for 80–85% of all lung cancer. 2 Forty to fifty percent of patients diagnosed with NSCLC have disease which is incurable at presentation, due to pleural or pericardial effusion, or metastatic (distant) spread; 2,3 the latter is classified as stage IV. The treatment for widely metastatic stage IV NSCLC is typically palliative-intent systemic therapy and/ or radiotherapy (RT), with goals of increasing survival, improving quality of life (QOL), and controlling symptoms. Five-year overall survival (OS) for stage IV NSCLC is 1%. 4 Just over 20 years ago, Hellman and Weichselbaum coined the term ‘oligometastases’ (OM), describing a transitional state of metastatic disease burden, intermediate between relatively localized, and widely distributed. 5 The exact definition of OM continues to be debated, frequently comprising five or fewer lesions outside of the primary tumor and regional lymph nodes (LNs), 6 often additionally limited to one or two anatomic subsites. Approximately 7% of patients with metastatic NSCLC, in fact, have a solitary metastasis. 7 Reported 5-year OS for oligometastatic NSCLC ranges from 14–48%, depending on site(s) of OM and intrathoracic stage. 6 Ablative treatment, if delivered to sites of OM before the disease acquires the genetic alterations which confer widespread metastatic potential, could theoretically: increase the interval over which the disease is controlled; decrease metastatic load and subsequent seeding of additional locations; delay progression, at least locally; postpone initiation or switch of systemic therapy, avoiding the resulting toxicity, cost and detrimental impact on QOL; and possibly increase OS. 5,8–10 This scenario may be especially relevant to epidermal growth factor receptor (EGFR) mutant, or anaplastic lymphoma kinase (ALK) rearrangement patients who experience oligoprogression during therapy with a targeted agent, in whom radical local therapy may allow continuation of the same drug. 11 The adrenal gland is one of the common sites of metastases from NSCLC, with 30–60% harboring such lesions at autopsy. 3 Four to ten percent of patients with otherwise operable NSCLC will have a unilateral adrenal mass; 12–17 up to half of these are malignant (0.4–3.5%). 18–22 In this highly selected TOU CH MED ICA L MEDIA 117