br Results br Demographic clinical and pathologic

Results
Demographic, clinical, and pathologic characteristics are pre-sented in Table 1. Twenty-one adrenalectomies for adrenal
Table 1 Demographic, Clinical, and Pathologic Characteris-tics of Patients
Characteristic N (%)
Gender
Primary lung cancer treatment
Radio-chemotherapy 2 (10)
Surgical lung resection
Pneumonectomy 2 (10)
Histologic type
Adenocarcinoma 14 (70)
Large-cell carcinoma 2 (10)
Squamous cell carcinoma 4 (20)
pT stage
pN stage
metastasis were performed in our department in the study period; 1 patient was excluded from analysis owing to the removal of a non-metastatic incidental adrenal lesion (pheochromocytoma). In the remaining 20 patients, we observed 10 patients with metachronous and 10 patients with synchronous metastatic disease. In 1 patient with synchronous oligometastatic disease, there was an adrenal PS-341 accompanied by a concurrent single cerebral metastasis; this last one was treated by surgery and adjuvant stereotactic radiotherapy on the residual cavity. In 18 patients, primary tumor was treated by surgery (14 lobectomies, 2 bi-lobectomies, 2 pneu-monectomies); 2 patients were treated by conventional thoracic chemo-radiotherapy. Adrenalectomy was performed by laparoscopy, laparotomy, and phrenotomy through thoracotomy in 10, 9, and 1 cases, respectively.
Focusing on molecular assessment of primary cancer and adrenal metastasis, we found gene mutations on the primary and secondary tumor in 13 and 17 patients of 16 and 18 samples available for DNA analysis, respectively (Table 2). All wild-type tumors (n ¼ 3) were squamous cell carcinomas. Among 14 patients in whom mo-lecular analysis was available for both primary tumor and metastasis, we found the same mutational pattern in primary cancer and metastasis in 12 cases, whereas additional (n ¼ 2) or missing (n ¼ 1) mutations in the metastasis were detected in 3 patients. No clinical  Antonio Mazzella et al
or treatment-related variable was correlated with discordant muta-tional pattern in this subset of patients.
Results of histologic and molecular phenotype are summarized in Table 2. Mutations occurred principally in the TP53 gene, in 11 lung primaries and 13 adrenal metastases, respectively; in most cases, they consisted of point mutation, without hotspot mutation. Driver genes, such as EGFR and KRAS, mutations were found in 2 and 3 primary tumors, respectively, and in 2 and 4 metastases, respectively. Interestingly, one patient exhibited an EGFR amplifi-cation only in the metastasis but not in the primary tumor, suggesting that amplification could be acquired during tumor pro-gression. Likewise, a not-activating BRAF mutation occurred de novo in 1 metastasis. Other driver mutations were observed on the MAPK and PTEN pathways (Table 2).
No significant difference in overall survival were observed with respect to metachronous or synchronous presentation of metastatic disease, to ipsilateral or contralateral character of adrenal metastasis with respect to primary lung cancer, to T or N parameter of primary tumor, to histologic type, or to divergent mutational status between primary and metastatic tumor (Table 3).
Discussion
Prognosis of lung cancer associated with adrenal metastasis is generally poor. When metastatic disease is limited to adrenal gland, surgical resection of adrenal metastasis may be proposed and would lengthen survival.18 Adrenalectomy (via laparoscopy or laparotomy) represents the gold standard in the “local” treatment of isolated adrenal gland metastases if the operation is technically possible and if patients are fit enough. Other therapeutic options include ste-reotactic body radiotherapy and radiofrequency ablation.9 The benefit of surgical resection of isolated adrenal metastasis has been poorly evaluated: 2 pooled analyses of 13 and 10 series of resected adrenal metastasis, including a total of 98 and 114 patients, respectively, are available in the literature.8,9 To our knowledge, molecular phenotyping of both primary and metastatic disease at adrenal level has not been reported so far. Thus, we aimed at per-forming NGS in lung and adrenal specimens, in the idea that this would provide additional information potentially useful in further management.