Lung Adenocarcinoma has a Higher Risk of Lymph Node Metastasis than Squamous Cell Carcinoma: A Propensity Score-Matched Analysis.

BACKGROUND: Controversy still exists in which subtype of non-small-cell lung cancer [squamous cell carcinoma (SCC) or adenocarcinoma] is more likely to have lymph node (LN) metastasis. The aim of this study is to compare the pattern of LN metastasis in two cohorts of matched patients surgically treated for SCC or adenocarcinoma. METHODS: A retrospective analysis of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy without preoperative treatment for lung SCC or adenocarcinoma was conducted in this study. Data for analysis consisted of age, gender, tumor size, lobe-specific tumor location, tumor location (peripheral or central), and pathologic findings. We conducted the propensity score-matched (PSM) analysis to eliminate potential bias effects of possible confounding factors. RESULTS: From January 2015 to December 2016 in our department, we finally included a total of 387 patients (including 63 patients with SCC and 324 patients with adenocarcinoma) for analysis. For the unmatched cohort, there was no sufficient evidence of significantly different number of positive LNs (P = 0.90) and rate of LN metastasis (P = 0.23) between SCC patients and adenocarcinoma patients. However, potential confounding factors, for example gender, tumor size, tumor location, tumor differentiation, and total number of dissected LNs, were significantly different between patients with SCC and those with adenocarcinoma. In the analysis of matched cohort after PSM analysis, those above confounding factors were comparable between the two groups. However, patients with adenocarcinoma had significantly more mean positive LNs (2.2 and 0.7; P = 0.008) and a higher rate of LN metastasis (53% and 29%; P = 0.016) than those with SCC. CONCLUSIONS: Lung adenocarcinoma had a higher risk of LN metastasis than SCC, suggesting that different therapeutic modalities may be indicated for the two different subtypes of lung cancer.

Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study.

BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. FINDINGS: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. INTERPRETATION: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature. FUNDING: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.

[The Development of Huaxi Intelligent Endoscopic Skill Training and Assessment System].

OBJECTIVE: To develop a novel objective standardized endoscopic skill training and assessment system based on artificial intelligence technology. METHODS: By designing five basic skill parts of endoscopic operation including vision location, clamping, delivering, shearing and suturing, we achieved objective standardized indexes which gained automatically with image recognition and refined perception. RESULTS: With Huaxi intelligent endoscopic skill training system, the accurate rates of vision location, clamping, delivering, shearing and suturing were 90%, 95%, 99%, 90%, and 89%, respectively. The response and performance time were 8-10 s, <1 s, <1 s, 1-3 s, and <1 s, respectively. CONCLUSION: Huaxi intelligent endoscopic skill training and assessment system has preliminarily possessed the capability to assess the endoscopic skills of surgeons objectively.

[The Methods and Clinical Significance of Early Diagnosis of Lung Cancer].

Lung cancer is the leading contributor to morbidity and mortality from cancer worldwide, with its 5-year overall survival being only about 15.6%. Due to the lack of specific early screening methods for lung cancer, about 75% patients are diagnosed late. Therefore, it remains the big challenge for the early diagnosis of lung cancer. We need to pay more attention to the screening of lung cancer, and more precise assessment and management to the pulmonary nodules screened out. Further study on liquid biopsy, optimization of new fiberoptic bronchoscopy and the sampling methods to harvest small volume of lung tissue, could be helpful to improve the early diagnosis of lung cancer.

[Diagnosis and Surgical Treatment of Lung Ground-glass Opacities:a Review of 663 Cases].

OBJECTIVES: To retrospectively investigate the clinical characteristics, surgical treatments of the patients with lung ground-glass opacities (GGO). METHODS: All the patients, who underwent surgical resection of GGO in our department from Jan. 2013 to Dec. 2016 were retrospectively reviewed. The clinicpathological features were analyzed. RESULTS: A total of 663 patients were included in this study. The rate of malignancy was 92.6% (614/663). The diameter of GGO in benign group [(0.8±0.2) cm] was significant smaller than that in malignant group [ (1.5±0.8) cm](P<0.001). The rate of irregular margin in malignant group was far higher than that in benign group (93.8% vs. 20.4%, P<0.001), but other CT signs such as vacuole sign, plural retraction, speculation and lobulation did not show significant difference between the two groups. A total of 652 (98.3%) cases were resected by video-assisted thoracoscopic surgery (VATS), and only 11 (1.7%) cases were resected by thoracotomy. A total of 336 (50.7%) patients underwent lobectomy, 226 (34.1%) underwent segmentectomy and 101 (15.2%) undewent wedge resection. The rate of surgery-related complications was 9.0% (60/663), and one (0.2%) patient died. CONCLUSIONS: With careful selection of GGO by experienced surgeons, the rate of malignancy is very high. Surgical resection may be recommended for highly suspected malignant cases. Sublobar resection or lobcotomy by VATS can achieve good treatment effect.

[Effect of Recombinant Super-compound Interferon (rSIFN-co) on Proliferation and Apoptosis of Human Pulmonary Adenocarcinoma Cell A549].

OBJECTIVE: To investigate the effect of recombinant super-compound interferon (rSIFN-co) on the proliferation and apoptosis of pulmonary adenocarcinoma cell line A549. METHODS: Screening tests were conducted to determine the concentrations of rSIFN-co that have a significant impact on A549 and the optimal concentration and duration for the test of rSIFN-co combined with Cisplatin. A549 cells were treated with rSIFN-co, Infergen, rSIFN- co+ Cisplatin, Infergen + Cisplatin, and Cisplatin, respectively, and compared with those cultured in normal medium. The viable A549 cells from Day 1 to Day 7 were detected by MTT assay. Cell apoptosis was detected by flow cytometry (FCM). Apoptosis-associated proteins, Fas and Bcl-2 were detected by immunofluoroscence at 48 h. RESULTS: Effective concentrations of rSIFN-co ranged from 1 to 64 µg/mL, and a minimal of 2 µg/mL Cisplatin was needed. The optimal test condition was set at 5 µg/mL rSIFN-co combined with 2 µg/mL Cisplatin for a duration of 48 h. rSIFN-co demonstrated a stronger inhibiting effect on cell proliferation than Infergen. The inhibiting efficiency of rSIFN-co+Cisplatin was also stronger than that of Infergen+Cisplatin. Apoptosis of A549 cells induced by rSIFN-co was also more significant than that of Infergen (P = 0.000). Cells treated with rSIFN- co+ Cisplatin has a higher apoptosis rate than those treated with rSIFN-co (P = 0.004) or Cisplatin (P = 0.023). rSIFN-co increased the expression of Fas and decreased the expression of Bcl-2. Cells treated with rSIFN-co showed lower fluoroscence intensity of Bcl-2 than those treated with Infergen (P < 0.05). CONCLUSION: rSIFN-co inhibits the proliferation of A549 and its effect is stronger than that of Infergen. Cisplatin can further enhance the inhibiting effect of rSIFN-co. The inhibiting efficiency may be associated with the expression of apoptosis-related genes.

[Clinical epidemiology and histological characteristics of patients with lung cancer in West China Hospital of Sichuan University].

OBJECTIVE: To identify changes in patterns of primary bronchogenic carcinoma. METHODS: We reviewed clinical data of patients with primary bronchogenic carcinoma, who were identified as permanent residents of Sichuan province and were treated in West China Hospital of Sichuan University in 2000 and 2010. The distributions of gender, age, urban/rural residency, smoking history, occupational exposure and histological types of tumor were compared between the 2000 group and 2010 group. RESULTS: A total of 2 167 patients (616 in 2000 and 1551 in 2010) met the inclusion criteria. Compared with the 2000 group, the 2010 group had a lower proportion of male patients (male/female sex ratio dropped from 2.78:1 to 2.13:1, P = 0.013), more patients from medium and small sized cities (patients from large city decreased from 42.1% to 32.0%, P < 0.001, and patients from medium and small sized cities decreased from 39.9% to 31.7%, P < 0.001), more patients from rural areas (patients from townships increased from 5.5% to 8.1%, P = 0.041, and patients from villages increased from 12.5% to 28.2%, P < 0.001). No significant difference in age was found in the two cohorts of patients. The proportion of squamous cell carcinoma dropped from 44.8% in 2000 to 28.7% in 2010 (P < 0.001). The proportion of adenocarcinoma increased from 43.0% in 2000 to 53. 1% in 2010 (P < 0.001). The proportion of small cell lung cancer increased from 3.7% in 2000 to 11.9% in 2010 (P < 0.001). The proportion of squamous cell carcinoma in male patients was higher than that of female patients (60.7% vs. 36.6% in 2000; 75.8% vs. 42.9% in 2010). The proportion of adenocarcinoma was higher in female patients than that of male patients (60.7% vs. 36.6% in 2000; 75.8% vs. 42.9% in 2010). The proportion of squamous cell carcinoma was higher in elderly patients (> or = 60) than that of young patients (< 45) (50.5% vs. 33.8% in 2000; 30.2% vs. 15.6% in 2010). The proportion of adenocarcinoma in young patients was higher than of elderly patients (54.9% vs. 36.9% in 2000; 57.1% vs. 51.8% in 2010). Squamous cell carcinoma was predominate in smoking patients (55.6% in 2000; 40.9% in 2010). Adenocarcinoma was predominate in no-smoking patients (58.4% in 2010; 75.7% in 2010) and the patients exposed to risk occupations (46.2% in 2000; 60.2% in 2010). CONCLUSION: Over the past decade, the percentages of female patients, adenocarcinoma and small cell lung cancer increased significantly in the patients with lung cancer. Male gender, old age (> or = 60) and smoking are risk factors of squamous cell carcinoma. Female gender, young age (< 45) and occupational exposure are risk factors of adenocarcinoma.

[Video-assisted thoracoscopic surgery lobectomy: expanding indications based on the optimization of surgical techniques].

Video-assisted thoracoscopic surgery (VATS) lobectomy is a less invasive procedure when compared with the traditional thoracotomy. With the development of operative techniques, VATS lobectomy has become a definite procedure for stage I and some stage II a lung cancer. However, it is still controversial due to operative difficulty whether it is feasible to perform thoracoscopic surgery in anatomic pulmonary segmentectomy, bronchial sleeve lobectomy, bronchial and arterial sleeve lobectomy, large tumor (> 5 cm), pneumonectomy and resection of Pancoast tumor. Some difficulties in performing thoracoscopic lobectomy such as: pleural cavity adhesions or atresia, local invasion, interlobar fissure dysplasia, bleeding, as well as "troublesome hilum", were once thought to be indication for conversion to thoracotomy. We proposed a new concept of thoracoscopic lung resection: "single-direction thoracoscopic lobectomy", which has been proved to be simple, safe, and effective and has been widely accepted in our country. In practice, we are still proceeding with further exploration, technical optimization and expanding its application in more complicated lung surgery. For instance, we have developed strategies of "fast recovery" and "mini-invasive diagnosis and synchronous treatment of lung cancer" and a series of stylized techniques such as thoracoscopic adhesiolysis, bloodless technique, suction-compressing angiorrhaphy technique, presumptive control of the main pulmonary artery, hollow-out method in thoracoscopic lobectomy. With accumulative experience utilizing these innovative techniques, we believe that thoracoscopic lobectomy would become the mainstream for surgical management of pulmonary diseases.

[Improving the procedures of video-assisted thoracoscopic surgery bronchial sleeve lobectomy for lung cancers].

OBJECTIVE: To modify and improve the procedures of video-assisted thoracoscopic surgery (VATS) bronchial sleeve lobectomy for lung cancers. METHODS: From December 2010 to July 2012, 11 patients with nonsmall cell lung cancers underwent VATS bronchial sleeve lobectomy in our department, which included 7 cases of right upper lobectomy, 3 cases of left upper lobectomy and 1 case of left lower lobectomy. We modified the surgical procedures in relation to the distribution of VATS ports, the techniques of dissecting hilar structures and the method of bronchial reconstruction. The position of incisions for the left side differed from the right side. The lobe was resected with the technique of "hollow out" and the bronchus was reconstructed using a running prolene stitch. RESULTS: Blood loss of these 11 patients ranged from 50-400 (median 200) mL. The operations were completed within 200-320 (median 235) minutes and the duration needed for bronchial reconstruction ranged from 35 to 60 (median 50) minutes. A total of 8-28 (median 15) lymph nodes were dissected. There was no conversion to thoracotomy or blood transfusion. Chest drainage tubes were removed within 2-12 (median 3) days after surgery. The patency of bronchial anastomosis was confirmed by bronchoscopy. Postoperative complications occurred in three patients, which included one case of bronchial pleural fistula (BPF) and two cases of pneumonia. The patient suffered from BPF died 49 days after surgery from intrabronchial bleeding. The postoperative hospital stay of those patients ranged from 8 to 49 (median 8) days. The reconstructed bronchus continued to work well during the three month follow-up visits. CONCLUSION: VATS bronchial sleeve lobectomy is feasible and safe. The modifications of the surgical procedures may promote the use of this complex operation.

[Cardio-pulmonary exercise capacity in patients with lung cancers: a comparison study between video-assisted thoracoscopic lobectomy and thoracotomy lobectomy].

OBJECTIVE: To determine the effect of video-assisted thoracoscopic lobectomy on the pulmonary rehabilitation of patients with lung cancers. METHODS: Between September 2010 and December 2011, 138 patients. with lung cancers were treated with lobectomy: 68 using video-assisted thoracoscopic surgery (VATS) and 70 using thoracotomy. The preoperative and postoperative (7 d and 30 d) pulmonary functions and Cardio-pulmonary Exercise Capacities as well as postoperative (7 d and 30 d) DE Morton Index of the two groups of patients were assessed. The two groups of patients had similar in clinical characteristics. RESULTS: (1) Patients in the VATS group had greater FEV1 (1.64 +/- 0.21) L and PEF [(310.58 +/- 30.13) L/min] on the 7 d after operations than those with thoracotomy [FEV1 (1.34 +/- 0.11) L and PEF (270.18 +/- 25.67) L/min], P < 0.05. (2) Patients in the VATS group had lower fatigue index (0.27 +/- 0.08) and dyspnea index (0.28 +/- 0.17) on the 7 d after operations than those with thoracotomy (0.44 +/- 0.10 fatigue index and 0.39 +/- 0.09 dyspnea index), P < 0.05. (3) Patients in the VATS group had longer 6-min walking distance on the 7 d [(490.57 +/- 118.33) m] and 30 d [(524.32 +/- 140.87) m] after operations than those with thoracotomy [(395.07 +/- 100.19) m at 7 d and (471.10 +/- 118.57) m at 30 d], P < 0.05. (4) Patients in the VATS group had higher DE Morton index (74.58 +/- 16.23) on the 7 d after operations than those with thoracotomy (55.87 +/- 14.79), P < 0.05. CONCLUSION: VATS lobectomy for curative lung cancer resection appears to provide a superior functional health recovery compared with thoracotomy.

[Safety and technical feasibility of single-direction VATS lobectomy: a review of 1040 cases].

OBJECTIVE: To evaluate the safety and technical feasibility of single-direction video-assisted thoracoscopic lobectomy for patients with pulmonary diseases. METHODS: From May 2006 to Sep 2012, 1040 patients with pulmonary diseases were treated by single-direction video-assisted thoracoscopic lobectomy. These included 565 men (54.3%) and 475 women (45.7%), with a mean age of (56.3 +/- 13.2) years. The patients suffered from lung cancer (800), benign disease (205), pulmonary metastases (34), and lymphoma (1). Their perioperative data were collected and reviewed. RESULTS: Of the 1040 patients, 7 died (0.67%); 18 (1.73%) were converted to open surgery; 134 had postoperative complications (12.88%). The patients underwent an average of (169 +/- 64) min operations, lost an average of (93 +/- 113) mL (range, 5-935 mL) blood, had an average of (3.3 +/- 1.9) cm (range, 1.2-12 cm) diameters of mass removed and an average (15.8 +/- 7.7) (range, 5-52) lymph nodes dissected. The patients had an average of (3.8 +/- 2.6) days (range, 1-16 days) drainage during an average of (7.0 +/- 2.8) days (range, 4-19 days) postoperative hospital stay. CONCLUSION: Single-direction thoracoscopic lobectomy is a safe and feasible surgical procedure in the treatment of pulmonary diseases.

[Immune functions of patients following lobectomy for lung cancers: a comparative study between video-assisted thoracoscopic surgery and posterolateral thoracotomy].

OBJECTIVE: To compare acute inflammatory responses and immunosuppression to lobectomy in lung cancer patients with video-assisted thoracoscopic surgery (VATS) and posterolateral thoracotomy (PLT). METHODS: A total of 103 patients who underwent either a VATS (n = 51) or a PLT (n = 52) lobectomy for early non-small cell lung cancers (NSCLC, stage I ) were recruited for this study. Blood samples of the participants were taken preoperatively and at 24 h and 72 h post-operatively for analyses of C-reactive protein (CRP), interleukin (IL)-6, IL-2 receptors (IL-2R), and serum amyloid A (SAA). Blood samples taken pre-operatively and at 2 d and 7 d post operations were also analyzed for total lymphocytes, NK cells, CD4+ T, and CD8+ T. RESULTS: Patients in the VATS group lost significantly less blood than those in the PLT group (P = 0.001). Patients in the PLT group had significantly higher serum SAA than those in the VATS group (P = 0. 006). Significant reduction of CD8+ T was found in the patients with PLT after operations (P < 0.01). Patients in the PLT group had significantly lower at CD8+ T 7 d post operations than those in the VATS group (P = 0.015). CONCLUSION: VATS pulmonary lobectomy is associated with reduced acute inflammatory responses and immunosuppression compared with the PLT approach.

[An analysis of the clinicopathological features and misdiagnosis of 16 adults pulmonary sequestration].

OBJECTIVE: To explore the clinicopathological features of adult pulmonary sequestration and summarize the misdiagnosis experiences. METHODS: Data of 16 cases of adult pulmonary sequestration (18 years), who were confirmed by surgery and biopsy in our hospital were collected and reviewed. RESULTS: The median age of all the patients was 38.5 years. The female seemed to be more likely to suffer from adult pulmonary sequestration (n = 12) with cough to be the most frequent symptom (n = 9). CT scans revealed most of the lesions were located in the left lower lobes of the lungs (n = 9). Half of the lesions were characterized by pulmonary cyst-like changes and/or multiple cystic bronchiectasis (n = 8), followed by soft tissue mass in or out of the lung fields (n = 7). Enhanced CT scans showed abnormal arteries from the systemic circulation. Only two cases were diagnosed as pulmonary sequestration correctly in the primary diagnosis. The remaining were mostly misdiagnosed as pulmonary cyst-like changes with bronchiectasis (n = 6) or tumors (n = 6). According to the findings during surgery, 13 cases were intralobar pulmonary sequestrations; 3 cases were extralobars, whose tissues were all detected dysplasia and chronic inflammatory by histopathological examinations. CONCLUSIONS: The misdiagnosis rate of pulmonary sequestration is high because of its non-specific clinical symptoms. Since it is characterized by abnormal arteries and pulmonary dysplasia, enhanced CT scans should be used as a preferred screening method for suspected cases, especially for those middleaged patients with cystic or mass-like lesions in the left lower lobes of the lungs.

[Complete video-assisted thoracoscopic anatomic segmentectomy for pulmonary diseases: the early experiences].

OBJECTIVE: To evaluate the safety and feasibility of video-assisted thoracic surgery (VATS) anatomic segmentectomy for pulmonary diseases. METHODS: Between November 2009 and July 2011, 20 patients received consecutive VATS anatomic segmentectomy by single surgical group. There were 3 male and 17 female, aging from 32 to 81 years with a mean of 53 years. The patients included 12 cases of non-small cell lung cancer (NSCLC) (5 cases of bronchioloalveolar carcinoma, 6 cases of adenocarcinoma, and 1 case of squamous cell carcinoma), 7 cases of benign diseases (3 cases of bronchiectasis, 2 cases of inflammatory pseudotumor, 1 case of tuberculosis, and 1 case of sclerosing hemangioma) and 1 case of metastasis tumor. The locations of resected segments included 1 anterior segment, 3 posterior segments, 4 apical segments, and 2 superior segments in the right side; and 5 lingular segments, 3 trisegments, and 2 superior segments in the left side. Simultaneously, 3 patients with bronchiectasis underwent segmentectomy and lobectomy, 1 of 6 patients with adenocarcinoma underwent lingulectomy and thymectomy. The pathological TNM stages of 12 NSCLC patients were 9 cases of T1aN0M0, 1 case of T1bN0M0 and 2 cases of T2aN0M0. RESULTS: Of these 20 patients, the median operative time was 155 minutes (range, 120 to 235 minutes), the median blood loss was 50 ml (range, 10 to 600 ml), the median drainage duration was 3 d (range, 1 to 6 d), and the median hospital stay was 6 d (range, 3 to 9 d). One patient who had undergone lingulectomy had a 600 ml intraoperative bleeding from lingular artery, and the bleeding was controlled by suturing the rupture under VATS. Bloody sputum occurred in 2 patients, prolonged air leak occurred in one patient for 5 days, and one patient developed subcutaneous emphysema that spontaneously resolved. No mortality was observed for 30 days after the surgery. CONCLUSIONS: VATS anatomic segmentectomy is a feasible and safe technique with acceptable operative time, less blood loss, fewer complications, and shorter hospital stay.

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study.

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis.

BACKGROUND: There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients. METHODS: A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients. RESULTS: After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy. CONCLUSION: Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.

Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial.

PURPOSE: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% (P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (P = .316) and 5y DFS rates were 22. 6% and 23.2% (P = .928), respectively. CONCLUSION: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

Genomic signatures define three subtypes of EGFR-mutant stage II-III non-small-cell lung cancer with distinct adjuvant therapy outcomes.

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

The advancement of predictive diagnosis and molecular mechanism in multiple primary lung cancer.

Due to the advanced diagnostic technique and better understanding for multiple primary lung cancers (MPLC), the increasing incidence of MPLC has been reported. Very often, MPLC are misdiagnosed as metastasis because of lacking efficient molecular biomarkers for prediction and diagnosis. Studies on the molecular mechanism for tumorgenesis and progression of MPLC may therefore facilitate the discovery of biomarkers for disease diagnosis and prognosis, so that an individual and rational treatment can be achieved. We tried to further our understanding and improve the diagnostic skill for MPLC by reviewing the current status and the latest advancement of molecular markers related to MPLC.