PURPOSE: Synchronous multiple small adenocarcinomas are detected more frequently than in the past; however, the genetic profile, treatment, and prognosis of patients remain unclear. For treatment decisions and prognostic applications, we evaluated epidermal growth factor receptor (EGFR), p53, and KRAS somatic mutations in synchronous multiple small lung adenocarcinomas. METHODS: The presence of EGFR, p53, and KRAS somatic mutations was determined in 64 synchronous multiple lung adenocarcinomas ≤2 cm in maximal dimension. Mutational analysis was performed on DNA extracted from paraffin-embedded tumors. RESULTS: Five-year disease-free survival (DFS) was 86.1 %, and overall survival was 95.8 %. EGFR, p53, and KRAS mutations were detected in 41 (64.1 %), 8 (12.5 %), and 4 (6.3 %) patients, respectively. The high frequency of genetic mutations resulted in a high discrimination rate of tumor clonality (68.8 %; 44/64) in the study group. Fourteen (31.8 %) patients were assessed as having the same clonality, whereas 30 (68.2 %) patients had different clonality, which further supported the concept of field cancerization. Multivariate analysis showed lymph node metastasis (p = 0.003) and smoking (p = 0.011) were significantly correlated with tumor relapse. Surgical method, clonality, and tumor location were not correlated with tumor relapse. CONCLUSIONS: Whether these tumors are different or the same clonal, sublobar resection of each lesion can achieve long-term DFS and is the treatment of choice for synchronous multiple small lung adenocarcinomas. Patients with lymph node metastasis are at risk of relapse and adjuvant chemotherapy is indicated.
PURPOSE:Synchronous multiple small adenocarcinomas are detected more frequently than in the past; however, the genetic profile, treatment, and prognosis of patients remain unclear. For treatment decisions and prognostic applications, we evaluated epidermal growth factor receptor (EGFR), p53, and KRAS somatic mutations in synchronous multiple small lung adenocarcinomas. METHODS: The presence of EGFR, p53, and KRAS somatic mutations was determined in 64 synchronous multiple lung adenocarcinomas ≤2 cm in maximal dimension. Mutational analysis was performed on DNA extracted from paraffin-embedded tumors. RESULTS: Five-year disease-free survival (DFS) was 86.1 %, and overall survival was 95.8 %. EGFR, p53, and KRAS mutations were detected in 41 (64.1 %), 8 (12.5 %), and 4 (6.3 %) patients, respectively. The high frequency of genetic mutations resulted in a high discrimination rate of tumor clonality (68.8 %; 44/64) in the study group. Fourteen (31.8 %) patients were assessed as having the same clonality, whereas 30 (68.2 %) patients had different clonality, which further supported the concept of field cancerization. Multivariate analysis showed lymph node metastasis (p = 0.003) and smoking (p = 0.011) were significantly correlated with tumor relapse. Surgical method, clonality, and tumor location were not correlated with tumor relapse. CONCLUSIONS: Whether these tumors are different or the same clonal, sublobar resection of each lesion can achieve long-term DFS and is the treatment of choice for synchronous multiple small lung adenocarcinomas. Patients with lymph node metastasis are at risk of relapse and adjuvant chemotherapy is indicated.
Authors: Julien P L Vincenten; Hendrik F van Essen; Birgit I Lissenberg-Witte; Nicole W J Bulkmans; Oscar Krijgsman; Daoud Sie; Paul P Eijk; Egbert F Smit; Bauke Ylstra; Erik Thunnissen Journal: PLoS One Date: 2019-10-16 Impact factor: 3.240