Background: Sarcoma is one of the refractory malignant tumors and often develops pulmonary metastasis. The purpose of this study was to evaluate the impact of surgical resection for metastatic lung tumors from sarcomas of soft tissue and bone retrospectively. Method: Between 2006 and 2015, we had a total of 158 patients with metastatic lung tumors from soft-tissue and bone sarcomas who underwent pulmonary metastasectomy for the first time. In total, 265 surgical procedures were performed in Okayama University Hospital in this period. We analyzed the age, sex, site of primary lesion, histology, extent of primary tumors at the initial diagnosis, extent of pulmonary metastases at the first pulmonary metastasectomy, presence or absence of local recurrence and/or extrapulmonary metastases with or before pulmonary metastases, operative procedures, size of the largest lesions resected, maximum number of the resected tumors, postoperative complications, and the prognosis at the end of 2018. Result: Average number of resected tumors per intervention was 4.0 (range 1-19). These sarcoma patients consisted of 36 males and 122 females, and their average age was 53.7 years (range 14-88 years). Leiomyosarcoma was the most common histological subtype (n ¼ 92, 58.2%) and uterus was the most common location of the primary disease (n ¼ 71, 44.9%). Operative procedures were composed of 202 partial resections, 35 segmentectomies with or without partial resections, 26 lobectomies with or without partial resections, 1 pneumonectomy, and 1 basal segmental auto-transplantation after pneumonectomy. The postoperative complications were limited, showing that pulmonary metastasectomies for sarcomas are acceptable. Overall 3-year survival after the first pulmonary metastasectomy was 50.6%. In univariate analysis, the survival was significantly better for the group with disease-free interval of more than 2 years from the date of the initial treatment for primary disease until the date of diagnosis for the first pulmonary metastasis, the one who underwent pulmonary resections three times or more, and the one in which size of the largest resected lesion was 20 mm or less. Those factors significant in univariate analysis were all significant in multivariate analysis. Conclusion: Surgical resections for metastatic lung tumors from sarcomas of soft tissue and bone were performed without major complications, indicating the acceptable feasibility. If disease-free interval is more than 2 years and the size of the largest resected lesion is less than 20 mm, patients may maximally benefit from pulmonary resection. In order to increase the opportunities of pulmonary resections, we should preserve the lung parenchyma as much as possible when performing pulmonary metatstasectomy, resulting in the better survival.
Background: Lung adenosquamous carcinomas (ASC) are morphologically mixed tumors that contain the two cell components adenocarcinomas (AC) and squamous cell carcinomas (SCC). However, to date, the genomic profile, TMB status, evolutionary relationship, and immune microenvironment of the two components still remain unclear. Method: Adenocarcinomas component (ACC) and squamous cell carcinomas component (SCCC) in ASC (n¼30) were validated by immunohistochemistry and obtained separately by means of laser capture microdissection. Gene panel and T cell receptor (TCR) repertoire sequencing were performed in both components. Normal tissues adjacent to the cancer were used as controls. The two components were compared from the dimension of somatic mutations, TMB, evolution, and the TCR clones. 626 AC tumors and 83 SCC tumors were also included for comparison with ASC. Results: Comparison of frequency of recurrently altered genes in lung SCCC, ACC, AC, and SCC were performed. EGFR (Fisher Exact test, p¼0.0476, OR 2.6) and MAP3K1 (p¼0.0020, OR 10.2) were enriched but no KRAS were found in ACC compared to AC. Compared with SCC, EGFR (p<0.0001, OR 14.3) is enriched in SCCC, while TP53 (p¼0.0129, OR 0.3) with lower mutation frequency. Different mutational spectra suggest that ACC is different from AC, and SCCC is different from SCC. Despite the heterogeneity, there were shared mutations in lung SCCC and ACC. 79% of ACC and 75% of SCCC samples harbored EGFR mutations. 46% of ACC and 64% of SCCC samples harbored TP53 mutations. In the evolutionary tree analysis, EGFR (in 75% of patients) and TP53 (43%) are the most frequent trunk genes. Above 90% (27/28) of patients had trunk genes, indicating that SCCC and ACC in ASC come from the same origin. In ACC, SCCC, AC, and SCC, 14%, 29%, 23%, and 48% of samples were identified as TMB-H respectively. The TMB index of SCCC was higher than that of ACC (Wilcoxon matched pairs test, p¼0.0065). The ACC TMB was equivalent to AC (Mann-Whitney test, p¼0.9352). The SCCC TMB is marginally lower than SCC (Mann-Whitney test, p¼0.0553). Significant difference is showed in the diversity of TCRs between ACC and SCCC (Wilcoxon matched pairs test, p¼0.0383). Although the difference is not significant, 65% (14/20) of SCC samples have a higher clonality index than ACC. Conclusion: Our study promote a better knowledge about ACC and SCCC from ASC, supporting the hypothesis that ACC and SCCC in ASC come from the same origin. However, two components also exhibit diverse genomic profile, TMB status, and TCR repertoire.
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