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Improved local control without elective nodal radiotherapy in patients with unresectable NSCLC treated

YANG Kunyu, LIU Li, ZHANG Tao, WU Gang, CAO Fengjun, WANG Jianhua

《医学前沿（英文）》 2007年第1卷第4期页码 381-385 doi: 10.1007/s11684-007-0074-7

摘要： To investigate the influence of prophylactic elective nodal irradiation on the therapeutic results of definitive radiotherapy for patients with stage IIIA or stage IIIB unresectable non-small-cell lung cancer, 55 patients with clinically inoperable advanced non-small-cell lung cancer were studied. After four cycles of induction chemotherapy, the patients were divided into two groups at random. In one group, the elective nodal irradiation was included in clinical tumor volume (CTV) of definitive radiotherapy (ENI group); and in the other group, elective nodal irradiation was not included in CTV (non-ENI group). For the patients in the ENI group, the mean prescription dose for gross tumor volumes was 58.4 Gy, while for the patients in the non-ENI group, it was 65.8 Gy (<0.05). The responsive rates were 45.8% and 74.0% (<0.05), and the rate of the elective nodal failure (ENF) was 4.2% and 11.1%, respectively. Kaplan-Meier analysis showed that the mean local-progression-free survival time was 11.0 and 15.0 months, and one-year local-failure rates were 51.9% and 24.5% (<0.05). The median overall survival time was 13.0 and 15.0 months, respectively ( = 0.084). The one-year survival rates were 55.7% and 72.5%, and two-year survival rates were 0% and 19.9%. There was no significant difference in the occurrences of radiation-associated complications between the two groups. Our results showed that omitting elective nodal irradiation did not result in a high incidence of elective nodal failure. On the contrary, it decreased local failure by increasing prescription doses to the primary diseases and lymphadenopaphy, and thereby it may further prolong the patients survival.

关键词： significant difference irradiation unresectable non-small-cell induction chemotherapy influence

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Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

《医学前沿（英文）》 2023年第17卷第3期页码 493-502 doi: 10.1007/s11684-022-0946-x

摘要： Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.

关键词： ALK fusion next-generation sequencing fluorescence in situ hybridization immunohistochemistry variant allele frequency intratumoral heterogeneity targeted therapy

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Identification of an E3 ligase-encoding gene

Yanfei Zhang, Xinchun Zhao, Yongchun Zhou, Min Wang, Guangbiao Zhou

《医学前沿（英文）》 2020年第14卷第3期页码 318-326 doi: 10.1007/s11684-019-0708-6

摘要： In order to unveil ubiquitin pathway genes (UPGs) that are essential for non-small cell lung cancer (NSCLC) cell proliferation, we recently conducted a siRNA screening experiment to knockdown the expression of 696 UPGs found in the human genome in A549 and H1975 NSCLC cells. We found that silencing of one of the candidates, that encodes an E3 ubiquitin ligase essential for the repair of DNA interstrand cross-links in response to DNA damage, led to dramatic inhibition of NSCLC cell proliferation with significant -scores. Knockdown of suppressed colony forming activity of NSCLC cells. We further evaluated the significance of in NSCLCs and found that this gene was more elevated in tumor samples than in paired normal lung tissues and was inversely associated with the clinical outcome of patients with NSCLC. Moreover, expression was significantly higher in smokers than in non-smokers. These results show for the first time that is required for NSCLC cell proliferation and may have an important role in lung carcinogenesis.

关键词： RFWD3 NSCLC prognosis tobacco smoke