Favorable prognosis and high discrepancy of genetic features in surgical patients with multiple primary lung cancers

Chen, Kezhong; Chen, Wei; Cai, Jianping; Yang, Fan; Feng, Li; Wang, Xun; Zhang, Jingbo; Zhao, Mingyu; Zhang, Jay; Wang, Jun

doi:10.1016/j.jtcvs.2017.08.141

Cited by 52 publications

(36 citation statements)

References 25 publications

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“…There are also reports [11,16,17] in the literature that multiple GGO patients with surgical resection,the prognosis is satisfactory, even sub-lobectomy does not affect the prognosis. In view of the good prognosis of multiple GGOs [18][19][20], we suggest that sub-lobectomy should be performed as much as possible for patients with multiple GGOs in the same period of surgery, which can ensure the prognosis and make the patient better quality of life. However, according to the rapid pathological results of the operation, the best resection plan was adopted.…”

Section: Discussionmentioning

confidence: 99%

Single-center experience of simultaneous bilateral uni-portal video-assisted thoracoscopic surgery for multiple ground-glass opacities

Zhang

et al. 2020

J Cardiothorac Surg

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Background: There is an increasing incidence rate of ground-glass opacity (GGO), especially for multiple GGOs (≥2). Whether it is safe and feasible to have bilateral simultaneous surgical resection remains unknown. The purpose of this study is to summarize the experience of surgical resection of patients with multiple GGOs in our Hospital in recent years, and to discuss the above questions. Methods: Clinical datas of patients who underwent one-stage bilateral uni-portal VATS resections of multiple pulmonary ground glass opacities and had routine pathological examination were collected from May 2016 to May 2019 in our hospital. Results: A total of 34 patients underwent simultaneous bilateral surgical resection of multiple GGO lesions, 28 were women,6 were men, the average age of total patients was 57.9 ± 6.7 years. All patients underwent bilateral uniportal video-assisted thoracoscopic surgery (Uni-portal VATS), the average intraoperative blood loss was 100.9 ± 67.7 ml, the average operation time was 140 ± 74.8 min, the average thoracic drainage time was 2.8 ± 3.1 days, and the average postoperative hospital stay was 4.2 ± 4.3 days. Postoperative complications including: 2 cases of infection, 3 cases of atrial fibrillation, and 5 cases of persistent air leakage for more than 3 days. All of them improved after treatment, and there were no serious complications and deaths in perioperative period. A total of 76 GGO lesions were resected, with a total malignancy rate of 81.6%, including 40 were pure GGO, of which 28 were malignant (70%), and the average diameter of them were 9.6 ± 3.8 mm; 36 were mixed GGO, of which 34 were malignant (94.4%), the average diameter of them were 15.6 ± 6.6 mm.Mean postoperative follow-up was 28.4 (range, 3-39) months. There was neither recurrence nor deaths at final follow-up. Conclusion: The malignancy rate of multiple GGOs is high. Therefore, when the lung function is allowed,one-stage bilateral uni-portal VATS can be considered. According to experience of main surgeon and the frozen biopsy, either sub-lobar resection or lobectomy was acceptable. The risk of postoperative complications and the prognosis were optimal.

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Section: Discussionmentioning

confidence: 99%

Single-center experience of simultaneous bilateral uni-portal video-assisted thoracoscopic surgery for multiple ground-glass opacities

Zhang

et al. 2020

J Cardiothorac Surg

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“…In addition, they reported that patients with at least 1 driver mutation had a high inconsistency rate of 80%. Recently, Chen et al 31 reported a high inconsistency rate (89.7%) in genetic alterations between tumors within individual patients. Liu et al 32 studied the genomic profiles of 15 LUAC, which showed different genomic profiles, indicating that they were independent primary tumors.…”

Section: Discussionmentioning

confidence: 99%

Concomitant EGFR Mutation and EML4-ALK Rearrangement in Lung Adenocarcinoma Is More Frequent in Multifocal Lesions

Fan

Dai

Wang

et al. 2019

Clinical Lung Cancer

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We retrospectively investigated the intertumoral heterogeneity of pathologic and genetic characteristics of multifocal lung adenocarcinomas (LUAC) with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) co-alterations. The prevalence of EGFR/ALK co-alterations was higher in the multifocal LUAC than in the unifocal LUAC. To determine appropriate treatment strategies, extensive molecular profiling could give us more information to distinguish primary lesions from metastatic lesions. Background: The coexistence of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement in patients with multifocal lung adenocarcinomas (LUAC) constitutes a rare molecular subtype of lung cancer. We aimed to investigate the intertumoral heterogeneity of pathologic and genetic characteristics of multifocal LUAC with EGFR/ALK co-alterations. Patients and Methods: A total of 1059 LUAC patients who underwent resection were investigated to screen for EGFR or ALK alterations using amplification refractory mutation system polymerase chain reaction and immunohistochemistry/fluorescence in situ hybridization. Molecular testing was extensively performed in patients with synchronous multifocal LUAC. Clonal evolution analysis was implemented using next-generation sequencing. Results: A total of 97 multiple synchronous lesions were observed among 1059 LUAC patients. Patients with at least 1 sample harboring EGFR mutation or ALK rearrangement were 62.89% (61/97) and 14.43% (14/97), respectively. Patients with concomitant EGFR and ALK alterations were 4.71% (4/97). Comparatively, patients with unifocal LUAC harboring EGFR mutation, ALK rearrangement, and EGFR/ALK coalterations were 58.25% (570/962), 6.44% (62/962), and 0.83% (8/962), respectively. The prevalence of EGFR/ALK co-alterations in the multifocal LUAC was significantly higher than that in the unifocal LUAC (4.71% (4/97) vs. 0.83% (8/962)). Furthermore, we present 4 cases of EGFR/ALK co-altered multifocal LUAC with different morphological and molecular patterns. In addition to radiographic, pathological, and molecular testing results, clonal evolutional analysis could also be used to distinguish intertumoral heterogeneity. Conclusion: The results highlight the importance of distinguishing synchronous primary tumors from intrapulmonary metastases, and of assessing the relative abundance of EGFR mutation and ALK rearrangement in patients with multifocal adenocarcinomas with EGFR/ALK co-alterations.

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“…Moreover, despite such tendencies in some individuals for neoplastic development, this has not necessarily correlated with a poorer prognosis, 8 consistent with findings produced by Chen and colleagues. 1 Interestingly, however, if the occurrence of multifocal disease in patients with multiple GGOs were related to a field effect, one would hypothesize that there would be greater concordance among the driver mutations of tumors within the same patient for those in group A. Nonetheless, this did not appear to be the case.…”

mentioning

confidence: 96%

“…colleagues 1 clearly showed that patients with multiple GGOs had better prognoses than did those with multiple solid nodules. In a somewhat unrelated but equally important outcome of interest, Chen and colleagues 1 also found a significant extent of discordance between genetic abnormalities when comparing tumors in a given individual patient (90%), suggesting that the secondary lesions developed as independent primary tumors rather than as intrapulmonary metastases.…”

mentioning

confidence: 99%

“…Because of their findings, Chen and colleagues 1 suggest that favorable outcomes after resection support surgery as a reasonable approach to patients with MPLC, especially those with multiple GGOs. 1 With regard to GGOs, recent articles have attempted to elucidate the risk of MPLC in patients with history of lung cancer and evidence of GGOs, as well as correlations with clinically aggressive behavior among patients with malignant ground glass lesions. [5][6][7] Although such investigations are in their infancy, it has been fairly well accepted that certain patients appear to have a field effect, with multiple GGOs and a predisposition toward development of lung adenocarcinoma.…”

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confidence: 99%

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Multifocal lung cancer within ground glass lesions: Are favorable outcomes consequent to surgical resection or inherent to the disease?

Antonoff

2018

The Journal of Thoracic and Cardiovascular Surgery

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Multiple primary lung cancer (MPLC) is a phenomenon that appears to be increasing in frequency, perhaps as a result of improved resolution of cross-sectional imaging as well as an aging population of lung cancer survivors. 1,2 The diagnosis of MPLC remains complicated, however, because it must be distinguished from metastatic disease. Although criteria for identifying MPLC have been proposed and standardized, 3,4 we still lack reliable and robust means of clearly discriminating patients with MPLC from those with satellite lesions and other intrapulmonary foci of metastatic disease. 1,2 In their article in this issue of the Journal, Chen and colleagues 1 describe their experience with patients who underwent resection of 2 or more malignant pulmonary lesions, with widely accepted criteria used for MPLC (differing histologic type, or same histologic type with anatomic separation and N<2 M0). 1,3,4 The investigators divided the patients into subgroups, with group A including patients with only ground glass opacity (GGO)-dominant lesions, group B including patients who had primary solid nodules with additional secondary GGOs, and group C including patients whose primary and secondary lesions were all solid in nature. After extracting samples for RNA and DNA evaluation, the investigators assessed for somatic mutations in EGFR, TP53, PIK3CA, and BRAF genes, as well as EML4-ALK, ROS1, and RET fusions. Ultimately, Chen and colleagues 1 sought both to characterize differences in survival among the 3 groups and to examine extent of concordance among driver mutations between tumors within individual patients. In this well-written article, Chen and colleagues 1 describe several important findings. The 5-year recurrence-free survival was best for those with GGOs and worst for those with solid nodules (100%, 68%, and 51% in groups A, B, and C, respectively). Further, such results were paralleled on analysis of the overall 5-year survival (100%, 81%, and 60%, respectively). Chen and

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Favorable prognosis and high discrepancy of genetic features in surgical patients with multiple primary lung cancers

Abstract: A high discordance of driver mutations between tumors in individual patients and a favorable prognosis were identified in patients with multiple primary lung cancers diagnosed by clinical-pathologic criteria, which support different strategies from those with metastatic disease.

Cited by 52 publications

References 25 publications

Single-center experience of simultaneous bilateral uni-portal video-assisted thoracoscopic surgery for multiple ground-glass opacities

Single-center experience of simultaneous bilateral uni-portal video-assisted thoracoscopic surgery for multiple ground-glass opacities

Concomitant EGFR Mutation and EML4-ALK Rearrangement in Lung Adenocarcinoma Is More Frequent in Multifocal Lesions

Multifocal lung cancer within ground glass lesions: Are favorable outcomes consequent to surgical resection or inherent to the disease?

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