Xin Li, Hongbing Zhang, Jinghao Liu, Jun Chen (Department of Pulmonary Oncology, General Hospital of Tianjin Medical University, Tianjin 300052, China)
Funds: Tianjin Medical Key Construction Discipline - Other Disciplines of Surgery (Lung Oncology Surgery) (TJYXZDXK-061B)
Corresponding author: Chen Jun
E-mail:[email protected]
Prof. Jun Chen
Ph.D., Professor, Chief Physician, Doctoral Supervisor
Director of Tianjin Institute of Lung Cancer
Director of Tianjin Thoracic Tumor Center
Director of the Department of Pulmonary Oncology Surgery, General Hospital of Tianjin Medical University
Chairman of the Lung Cancer Professional Committee of the Chinese Geriatric Health Care Association
Vice Chairman of the Lung Cancer Prevention and Control Branch of the China Medical Promotion Association
Vice Chairman of the Translational Medicine Committee of the Chinese Society of Microcirculation
Vice Chairman of the Translational Medicine Branch of the Medical Doctor Association of the European and American Returned Scholars Association-Chinese Overseas Students Association
Member of the Standing Committee of the Thoracic Surgery Branch of the China Medical Promotion Association
Member of the Thoracic Surgery Branch of the Chinese Medical Doctor Association
Associate Editor-in-Chief of Chinese Journal of Lung Cancer
《Thoracic Cancer》编委
Lung cancer is the most common and deadliest cancer in the world, which seriously threatens people's lives and health. Surgical resection is the earliest treatment for lung cancer, and it is currently the most important treatment for lung cancer. With the advancement of medical technology, surgical methods and adjuvant treatment strategies are constantly being innovated, which brings new hope to lung cancer patients. Therefore, it is of great significance to summarize the latest research progress in the field of surgical treatment of lung cancer. The purpose of this article is to review the main advances in the surgical treatment of non-small cell lung cancer (NSCLC) in 2023, including the innovation of surgical techniques, minimally invasive surgery, adjuvant molecular targeted therapy, and the application of immunotherapy in the perioperative period of NSCLC.
【Keywords】non-small cell lung cancer, surgical treatment, immunotherapy, minimally invasive surgery, targeted therapy
As the most common malignant tumor in the world, lung cancer poses a huge challenge to public health. According to the latest data from the World Health Organization, lung cancer is the leading cause of cancer-related mortality [1-2]. In recent years, some progress has been made in the early diagnosis and treatment of lung cancer, but the survival rate of lung cancer is still low because most lung cancer patients are at an advanced stage when they are diagnosed. Therefore, exploring and implementing more effective treatment strategies is essential to improve the survival rate and quality of life of lung cancer patients.
Lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC) according to its biological characteristics, of which NSCLC accounts for about 85% of all lung cancer cases. The treatment strategies for NSCLC mainly include surgery, radiation therapy (referred to as radiotherapy), chemotherapy, targeted therapy and immunotherapy, among which surgery plays a crucial role in the treatment of early NSCLC. In 2023, significant progress has been made in the field of surgical treatment of NSCLC, not only involving innovations in surgical techniques, such as video-assisted thoracic surgery (VATS) and robot-assisted thoracic minimally invasive surgery surgery, RATS), which also includes the optimization of treatment strategies, such as the use of immunotherapy before and after surgery, and the use of targeted therapy drugs in postoperative adjuvant therapy. These advances represent a new era of NSCLC treatment, which is moving towards more personalized and precise treatment. The purpose of this article is to review the key developments in the surgical treatment of NSCLC in 2023, discuss the changes in the treatment mode of NSCLC, and put forward the prospects for future lung cancer treatment strategies and research directions. Through in-depth analysis of the latest research results and clinical trial data, it is hoped to provide a theoretical basis for the formulation of future treatment strategies for NSCLC and the selection of treatment methods for patients.
1. Innovation in surgical technology
1.1 VATS和RATS肺叶切除术
In thoracic surgery, VATS is associated with fewer perioperative complications, less pain, and faster recovery than thoracotomy [3]. However, proficiency in minimally invasive surgery requires extensive training for surgical residents, which is relatively difficult and takes more time and effort. Surgeons may face challenges such as poor depth perception, diminished spatial coordination due to two-dimensional optics, inflexible instrumentation, and counterintuitive movement [4]. In addition, surgeons are often subjected to physical stress by operating in uncomfortable positions for long periods of time, which can increase the complexity of the procedure and affect the patient's treatment outcomes.
Recently, the results of the VIOLET study were published: 503 patients with NSCLC were randomized to either VACS (n=247) or open lobectomy (n=256), with the primary endpoint being the use of the European Organization for Research and Treatment of Cancer (EUROCR) quality of life questionnaire core 30, QLQ-C30) at 5 weeks, the results showed that compared with the open surgery group, the median physical function in the VATS group was significantly better, with quality of life scores of 73 and 67, respectively (MD=4.65, 95%CI 1.69~7.61, P=0.008). 9). Although there was more postoperative air leakage and bleeding in the VATS group, the postoperative hospital stay was shorter, there were fewer serious adverse events and less pain after discharge and readmission, and the time of progression-free survival (PFS) after 1 year of follow-up (HR=0.74, 95%CI 0.43~1.27) or overall survival (overall). survival, OS) (HR=0.67, 0.32~1.40) were similar[5].
In recent years, RATS has emerged as a new minimally invasive surgical approach, providing surgeons with three-dimensional optics, a wider range of instrumental motion, and more advanced ergonomics [4]. For thoracic surgery, RATS has been shown to provide some benefits, but the technique remains controversial in terms of high operating costs and longer operative times resulting from the installation of robotic devices [6]. In addition, there has been controversy about the superiority of RATS in terms of morbidity, mortality, postoperative recovery, cost-effectiveness, and long-term safety. Recently, a meta-analysis of 26 studies included a total of 45 733 NSCLC patients (14 271 in the RATS group and 31 462 in the VATS surgery group). Five-year OS rates and recurrence rates were similar, but the RATS group had a significant reduction in perioperative blood loss, a lower rate of conversion to open surgery, a shorter hospital stay, improved lymph node dissection, and a higher five-year disease-free survival (DFS) rate [7]. The RVlob study is a single-center, open-label, prospective, randomized controlled trial to compare the efficacy of lobectomy with RATS [8]. A total of 320 patients with NSCLC were enrolled and randomly assigned to undergo either RATS (n=157) or VATS lobectomy (n=163); perioperative outcomes were similar in both groups, but the number of lymph nodes dissected and the positive rate of N1 lymph nodes were higher in the RATS group. The RAVAL study is an ongoing international, multicenter, randomized controlled trial comparing the advantages and disadvantages of RATS versus VATS lobectomy [9]. Preliminary results from the study suggest that RATS lobectomy is a cost-effective treatment that improves health-related quality of life in surgical patients, in addition to showing a larger number of lymph node samples in the RATS group. Not only for early-stage NSCLC, but also for locally advanced NSCLC, multiple studies have shown that RATS is feasible and effective. For example, Baig et al. [10] analyzed the US National Cancer Database, including N1 and N2 lymph node metastases or NSCLC with tumors > 5 cm, all of whom received neoadjuvant chemotherapy, radiotherapy, and then VATS or RATS, and enrolled a total of 9 512 patients (2 123 patients in the RATS group and 8 389 patients in the VATS group), with R0 resection rate, 30-day mortality, 90-day mortality, and 30 patients dThe readmission rate was similar between the two groups, but the thoracotomy conversion rate of VATS was significantly higher than that of RATS. In another study, 104 patients with central NSCLC underwent RATS sleeve lobectomy at 5 years with DFS and OS rates of 67.9 and 73.0 percent, respectively, and RATS lobectomy may be a more advantageous minimally invasive procedure for patients with central NSCLC [11].
1.2 Sublobectomy
With the popularization of computed tomography (CT) screening and the advancement of diagnostic methods, more and more lung cancers dominated by small-sized nodules and ground-glass nodules (GGO) are detected at an early stage. Whether sublobectomy (including wedge resection and anatomical segmentectomy) can replace lobectomy as the standard surgical procedure for these small nodules and GGO has been the focus of debate in recent years. A 2023 article published in The New England Journal of Medicine comprehensively analyzed the findings of the North American Lung Cancer Study Group, CALGB 140503, and JCOG0802 (a phase III multicenter prospective randomized study) and recommended that the indication for sublobectomy be expanded to include early-stage NSCLC [12]. Among them JCOG0802 study was a multicenter, open-label, phase III noninferiority study conducted in Japan, which enrolled 1 106 patients with clinical phase I.A NSCLC and randomly assigned to undergo lobectomy (n=554) or segmentectomy (n=552), with a median follow-up of 7.3 years, the 5-year OS rate in the segmentectomy group was 94.3% (95%CI 92.1%~96.0%), and the 5-year OS rate in the lobectomy group was 91.1% (95% The 5-year recurrence-free survival rate was 88.4%~93.2%) (non-inferiority P<0.000 1, superiority P=0.008 2), the 5-year recurrence-free survival rate was 88.0% (95%CI 85.0%~90.4%) in the segmentectomy group and 87.9% (95%CI 84.8%~90.3%) in the lobectomy group, and the 5-year recurrence-free survival rate was similar between the two groups (P=0.988). 9). The local recurrence rate in the segmentectomy group was about twice that of the lobectomy group (10.5%vs. 5.4%). The analysis of the causes of the results of this study is as follows: Because more lung parenchyma is preserved, patients in the segment resection group have the opportunity to receive a wider range of treatment when they develop local recurrence or other malignant or non-malignant lesions, resulting in higher OS rates. In addition, patients in the postoperative lobectomy group were found to have an average of 3.5% reduction in forced expiratory volume in 1 second compared to patients in the segmentectomy group, a result that favored the segmentectomy group, however, this difference did not meet the 10% clinical threshold preset in the study. In this study, patients with similar postoperative complication rates were similar in both groups and concluded that segmentectomy should be the standard surgical modality for patients with peripheral NSCLC ≤ 2 cm in diameter and <50 percent solid component [13]. Altorki et al. [14] in The New England Journalof The results of a multicenter phase III noninferiority study were reported in Medicine: 697 patients with peripheral (T1aN0M0) NSCLC were randomly assigned to sublobectomy (wedge resection or segmentectomy, n=340) or lobectomy (n=357), and the DFS of sublobectomy was not inferior to lobectomy after a median follow-up of 7 years (HR=1.01, 90% The CI was 0.83~1.24, the 5-year OS rate after lobectomy was similar to that after lobectomy (HR=0.95, 95%CI 0.72~1.26), the 5-year DFS rate after sublobectomy was 63.6% (95%CI 57.9%~68.8%), the 5-year DFS rate after lobectomy was 64.1% (95%CI, 58.5%~69.0%), and the 5-year OS rate after lobectomy was 80.3% (95% CI was 75.5%~84.3%), and the OS rate at 5 years after lobectomy was 78.9% (95%CI was 74.1%~82.9%). Therefore, the study concluded that sublobectomy was not inferior to lobectomy in patients with TCLC with the clinical stage T1aN0M0.
With the increase in the proportion of sublobectomy, nodule localization technology has also developed more and more rapidly, from traditional coil positioning to 125I particle localization and then to three-dimensional reconstruction technology positioning. In 2023, electromagnetic navigation bronchoscopy is becoming more and more popular due to guided diagnosis and dye labeling technology, through which it can create a virtual 3D model of a patient's lungs with CT and also perform bronchoscopy on a patient. A virtual 3D airway based on a preoperative CT scan navigates the bronchoscope to the target lesion, and then injects dye medium into the vicinity of the lesion. This hybrid technique significantly reduces the diffusion of dye and the occurrence of pneumothorax, and has become a new direction for the development of preoperative nodular localization in the future [15].
2. Progress in perioperative immunotherapy
The clinical use of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced lung cancer. A variety of antibodies have been developed to block the inhibitory immune checkpoint programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4. After the impressive results of immunotherapy in the treatment of advanced lung cancer, the next logic is to try the clinical use of ICIs in patients with non-metastatic NSCLC to improve the cure rate of early-to-mid-stage NSCLC and prolong the duration of OS.
In 2023, preliminary results from multiple Phase III studies in the treatment of perioperative ICIs were announced, including the AEGEAN, Neotoarch, KEYNOTE-671, and NADIM II studies (randomized phase II trials). In these studies, neoadjuvant ICIs plus chemotherapy significantly improved pathologic complete response (pCR) rates and major pathologic response rates and event-free survival (EFS) rates compared with neoadjuvant chemotherapy plus placebo, as well as OS rates in some trials. Similar to the results of the CheckMate816 study, a higher proportion of patients achieved pCR after neoadjuvant ICIs plus chemotherapy, and these patients achieved higher EFS rates. Therefore, an important clinical question remains the need for postoperative adjuvant monotherapy of ICIs in patients who have not reached pCR. In subgroup analyses of some perioperative ICIs trials, patients who did not achieve pCR had significantly better survival curves in the combination of ICIs plus chemotherapy than placebo (at least compared to similar data from the CheckMate816 study). These data may suggest that some patients with NSCLC will benefit from adjuvant ICIs monotherapy after neoadjuvant ICIs plus chemotherapy and subsequent surgical resection. The results of this study further suggest that drugs that cannot eradicate all cancer cells with preoperative treatment can eradicate cancer cells with monotherapy after surgery. This biological paradox should be explored in greater depth in future research. The efficacy of adjuvant atezolizumab monotherapy after postoperative platinum-doublet chemotherapy in the IMpower010 study has been demonstrated, and has been recommended in national and regional guidelines. Updated results from the 2023 IMpower010 study were published: as of April 18, 2022, with a median follow-up of 45.3 months, 127 of 507 patients (25%) died in the atezolizumab arm and 124 of 498 patients (24.9%) in the best supportive care group, and the median OS time was not estimated in the target treatment population (HR=0.99, 95% The CI was 0.78~1.28), and the incidence of adverse events reported in the latest study of atezolizumab remained unchanged from the data published in the previous study, with 53 (10.7%) of 495 patients being grade 3~4 and 4 (0.8%) being grade 5. The latest findings suggest that there is a positive trend in favor of atezolizumab in the analysis of the PD-L1 subgroup, which is mainly driven by the 50% stage II.~III.A subgroup ≥of PD-L1 tumor cells, and no new safety signals were observed after 13 months of additional follow-up, which supports the efficacy and safety of adjuvant atezolizumab therapy after postoperative chemotherapy for NSCLC [16].
3. Progress in perioperative targeted therapy
The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of epidermal growth factor receptor (EGFR)-mutated NSCLC has significantly improved survival time in patients with locally advanced and metastatic disease, and has shown great potential in patients with early-stage NSCLC undergoing surgical resection. The ADAURA study is an international randomized phase III clinical trial evaluating the role of the third-generation TKI osimertinib in completely resected EGFR mutant stage I.B~III.A [American Joint Committee on Cancer (AJCC) 7th edition staging) ± standard adjuvant chemotherapy in NSCLC. The results published in the study in 2022 showed that among 682 patients, compared with placebo, the 2-year DFS rate was significantly increased after 3 years of osimertinib treatment (89%vs. 52%; HR=0.20, 99%CI 0.14~0.30, P<0.001), and 98% of patients in the osimertinib group and 85% of patients in the placebo group survived at 2 years of treatment, with no CNS-related adverse events (HR=0.18, 95% The CI was 0.10~0.33), and adjuvant osimertinib also significantly reduced the risk of disease recurrence or death by 83% in the subgroup of patients with stage II.~III.A NSCLC (HR=0.17, 95%CI 0.11~0.26, P <0.001)[17]. In July 2023, the study published the latest research data in The New England Journal of Medicine: the 5-year OS rate in the osimertinib group was 85% in the osimertinib group and 73% in the placebo group (HR=0.49, 95%CI 0.33~0.73, P<0.001) in the overall population (patients with stage I.B~III.A disease), and the 5-year OS rate in the osimertinib group was 88% in the overall population (patients with stage I.B~III.A disease) , 78% (HR=0.49, 95%CI 0.34~0.70, P<0.001) in the placebo group, and a new serious adverse event, namely pneumonia associated with the 2019 novel coronavirus disease (which the investigator believes is not related to the trial protocol, and the patient has fully recovered). The results of this study suggest that adjuvant osimertinib in patients with stage I.B~III.A NSCLC harboring EGFR mutations who are completely resected may confer a significant overall survival benefit [18].
The patient population for stage III NSCLC is heterogeneous, with different staging features and different treatment options. Although randomized controlled trials evaluating the efficacy of perioperative neoadjuvant and/or adjuvant EGFR-TKIs may change clinical practice, conflicting OS results raise concerns. Few real-world studies have examined survival outcomes in patients undergoing perioperative chemotherapy and EGFR-TKI treatment for resected EGFR-mutated stage III adenocarcinoma. Although many studies have evaluated the role of perioperative EGFR-TKIs, patients with stage I.B~III.A disease exhibit great variability in prognosis, which may limit the application of these results in resectable stage III. EGFR-mutant adenocarcinoma. In 2023, a real-world retrospective study analyzed stage III (AJCC 8th staging) EGFR-mutant adenocarcinoma resected at a tertiary referral center in Taiwan Province of mainland China between January 2011 and December 2021 [19]. A total of 84 patients were included in the study, of which 63 received perioperative chemotherapy and 21 received perioperative EGFR-TKI (including the first and third generation EGFR-TKI), and the median PFS duration was significantly longer than that of perioperative chemotherapy (38.6 months versus 14.2 months, P=0.019). Perioperative chemotherapy patients had a longer median OS time than EGFR-TKI patients (111.3 months vs. 50.2 months, P<0.05), and perioperative patients treated with EGFR-TKI were an independent predictor of poor OS (HR=3.76, 95%CI 1.22~11.54), that is, although perioperative chemotherapy resulted in lower PFS, OS was better. This is in contrast to what is commonly seen in clinical practice, and while > 90% of patients in the chemotherapy group were treated with an EGFR-TKI after disease progression, only 44.4% of patients in the EGFR-TKI group received chemotherapy as follow-up therapy, and this low crossover rate may have been a factor in the poor OS in the EGFR-TKI group. In addition, the study also showed that fewer patients with disease progression in the EGFR-TKI group (47.6% vs. 85.7%) in the chemotherapy group died, but 90% of these patients (9/10) died. However, a growing body of evidence suggests the potential efficacy of neoadjuvant EGFR-TKIs in patients with resectable NSCLC, which has led to the design of randomized controlled studies, specifically the Phase II EMERGING-CTONG1103 trial and the Phase III NeoADAURA trial. Although the purpose of the NeoADAURA trial is to evaluate the efficacy of neoadjuvant osimertinib with or without chemotherapy, adjuvant systemic therapy with osimertinib or chemotherapy is permitted depending on the investigator's choice of optimal treatment. IN THE EMERGING-CTONG 1103 TRIAL, PATIENTS WERE DIVIDED INTO NEOADJUVANT, ADJUVANT ERLOTINIB, AND CHEMOTHERAPY. Neither study made a clear distinction between neoadjuvant and adjuvant therapy, leading to a more general "perioperative" approach [20-21]. Survival analysis in the 2023 EMERGING-CTONG 1103 trial showed that despite the PFS benefit, it did not translate into a difference in OS [21]. In addition, a limitation of this study is that only 69.7% of patients in the chemotherapy group received subsequent EGFR-TKI therapy after disease progression, which may confound OS outcomes. In the previous NEJ009 study, patients with EGFR-mutant NSCLC could benefit from a combination of chemotherapy and EGFR-TKI OS compared with EGFR-TKI alone [22]. In the ADAURA trial, a stratified subgroup analysis of the benefits of adjuvant chemotherapy showed that patients who received adjuvant chemotherapy had a superior two-year DFS compared with those who did not receive this therapy (HR 0.16 to 0.23) [23]. Therefore, more studies of perioperative targeted drug therapy should be designed and conducted to account for these differences and issues.
4. Summary
In 2023, with the advancement of minimally invasive surgical technology in the field of NSCLC surgical treatment, the optimization of perioperative ICIs treatment strategies, and the exploration of perioperative molecular targeted drug treatment strategies, new achievements and breakthroughs have been made, and it is expected that more surprising results will appear in the field of NSCLC treatment in 2024.
Bibliography:
[1] BAI R, LI L, CHEN X, et al. Neoadjuvant and adjuvant immunotherapy: opening new horizons for patients with early-stage non-small cell lung cancer[J]. Front Oncol, 2020, 10:575472.
[2] SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1):7-30.
[3] IKEDA N. Updates on minimally invasive surgery in non-small cell lung cancer[J]. Curr Treat Options Oncol, 2019, 20(2):16.
[4] ABBAS A E. Surgical management of lung cancer: history, evolution, and modern advances[J]. Curr Oncol Rep, 2018, 20(12):98.
[5] LIM E, HARRIS R A, MCKEON H E, et al. Impact of video-assisted thoracoscopic lobectomy versus open lobectomy for lung cancer on recovery assessed using self-reported physical function: VIOLET RCT[J]. Health Technol Assess, 2022, 26(48):161-162.
[6] RAJARAM R, MOHANTY S, BENTREM D J, et al. Nationwide assessment of robotic lobectomy for non-small cell lung cancer[J]. Ann Thorac Surg, 2017, 103(4):1092-1100.
[7] ZHANG J, FENG Q, HUANG Y, Ouyang L, et al. Updated evaluation of robotic- and video-assisted thoracoscopic lobectomy or segmentectomy for lung cancer: a systematic review and meta-analysis[J]. Front Oncol, 2022, 12:853530.
[8] JIN R, ZHENG Y, YUAN Y, et al. Robotic-assisted versus video-assisted thoracoscopic lobectomy: short-term results of a randomized clinical trial (RVlob Trial)[J]. Ann Surg, 2022, 275(2):295-302.
[9] Patel Y S, Hanna W C, Fahim C, et al. RAVAL trial: protocol of an international, multi-centered, blinded, randomized controlled trial comparing robotic-assisted versus video-assisted lobectomy for early-stage lung cancer[J]. PLoS One, 2022, 17(2):e0261767.
[10] BAIG M Z, RAZI S S, AGYABENG-DADZIE K, et al. Robotic-assisted thoracoscopic surgery demonstrates a lower rate of conversion to thoracotomy than video-assisted thoracoscopic surgery for complex lobectomies[J]. Eur J Cardiothorac Surg, 2022, 62(3):ezac281.
[11] LIU A, ZHAO Y, QIU T, et al. The long-term oncologic outcomes of robot-assisted bronchial single sleeve lobectomy for 104 consecutive patients with centrally located non-small cell lung cancer[J]. Transl Lung Cancer Res, 2022, 11(5):869-879.
[12] Rusch V W. Initiating the era of "precision" lung cancer surgery[J]. N Engl J Med, 2023, 388(6):557-558.
[13] SAJI H, OKADA M, TSUBOI M, et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial[J]. Lancet, 2022, 399(10335):1607-1617.
[14] ALTORKI N, WANG X, KOZONO D, et al. Lobar or sublobar resection for peripheral stage ia non-small-cell lung cancer[J]. N Engl J Med, 2023, 388(6):489-498.
[15] DUNN B K, BLAJ M, STAHL J, et al. Evaluation of electromagnetic navigational bronchoscopy using tomosynthesis-assisted visualization, intraprocedural positional correction and continuous guidance for evaluation of peripheral pulmonary nodules[J]. J Bronchol Interv Pulmonol, 2023, 30(1):16-23.
[16] FELIP E, ALTORKI N, ZHOU C, et al. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage Ⅱ-ⅢA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase Ⅲ trial[J]. Ann Oncol, 2023, 34(10):907-919.
[17] ETTINGER D S, WOOD D E, AISNER D L, et al. Non-small cell lung cancer, version 3.2022, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2022, 20(5):497-530.
[18] TSUBOI M, HERBST R S, JOHN T, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC[J]. N Engl J Med, 2023, 389(2):137-147.
[19] DETTERBECK F C. The eighth edition TNM stage classification for lung cancer: What does it mean on main street? [J]. J Thorac Cardiovasc Surg, 2018, 155(1):356-359.
[20] TSUBOI M, WEDER W, ESCRIU C, et al. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA[J]. Future Oncol, 2021, 17(31):4045-4055.
[21] ZHONG W Z, YAN H H, CHEN K N, et al. Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage ⅢA-N2 EGFR-mutant non-small-cell lung cancer: final overall survival analysis of the EMERGING-CTONG 1103 randomised phase Ⅱ trial[J]. Signal Transduct Target Ther, 2023, 8(1):76.
[22] HOSOMI Y, MORITA S, SUGAWARA S, et al. Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 Study[J]. J Clin Oncol, 2020, 38(2):115-123.
[23] WU Y L, JOHN T, GROHE C, et al. Postoperative chemotherapy use and outcomes from ADAURA: osimertinib as adjuvant therapy for resected egfr-mutated NSCLC[J]. J Thorac Oncol, 2022, 17(3):423-433.