Xiaofei Li

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

BACKGROUNDnCisplatin-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.nnnMETHODSnWe 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.nnnFINDINGSnBetween 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.nnnINTERPRETATIONnAdjuvant 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.nnnFUNDINGnGuangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of Peoples Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.

Erlotinib versus vinorelbine plus cisplatin as adjuvant therapy in Chinese patients with stage IIIA EGFR mutation-positive non-small-cell lung cancer (EVAN): a randomised, open-label, phase 2 trial

BACKGROUNDnAdjuvant chemotherapy after radical resection of stage IIIA non-small-cell lung cancer (NSCLC) has quite poor outcomes. We aimed to investigate whether adjuvant erlotinib therapy improves 2-year disease-free survival compared with chemotherapy in epidermal growth factor receptor (EGFR) mutation-positive stage IIIA NSCLC.nnnMETHODSnIn this randomised, open-label, phase 2 trial, eligible patients aged 18-75 years who had undergone complete (R0) resection of histologically or pathologically confirmed stage IIIA EGFR mutation-positive NSCLC and had not received any previous anticancer therapies were enrolled. Patients were randomly assigned (1:1) to receive either adjuvant erlotinib (150 mg once daily administered orally) or vinorelbine and cisplatin chemotherapy (four cycles of vinorelbine [25 mg/m2 intravenously on days 1 and 8 of each 21-day cycle] plus cisplatin [75 mg/m2 intravenously on day 1 of each 21-day cycle]). Randomisation was done by Simons minimisation with a random element and was stratified by EGFR activating mutation type (exon 19 vs 21), histology (adenocarcinoma vs non-adenocarcinoma), and smoking status (smoker vs non-smoker). The primary endpoint in the unblinded intention-to-treat analysis was 2-year disease-free survival. This ongoing study is registered with ClinicalTrials.gov, number NCT01683175.nnnFINDINGSnBetween Sept 8, 2012, and May 21, 2015, 102 patients from 16 centres across China were enrolled and randomly assigned to receive erlotinib (n=51) or chemotherapy (n=51). Median follow-up was 33·0 months (IQR 17·8-43·1). 2-year disease-free survival was 81·4% (95% CI 69·6-93·1) in the erlotinib group and 44·6% (26·9-62·4) in the chemotherapy group (relative risk 1·823 [95% CI 1·194-2·784; p=0·0054). The difference in 2-year disease-free survival between the groups was 36·7% (95% CI 15·5-58·0; p=0·0007). Adverse events of any grade occurred in 29 (58%) of 50 patients in the erlotinib group and 28 (65%) of 43 patients in the chemotherapy group. Grade 3 or worse adverse events occurred in six (12%) of 50 patients in the erlotinib group versus 11 (26%) of 43 in the chemotherapy group; the most common of these in the erlotinib group was rash (in two [4%] of 50 patients) and in the chemotherapy group were decreased neutrophil count (in seven [16%] of 43 patients) and myelosuppression (in four [9%]). No treatment-related deaths were reported.nnnINTERPRETATIONnAdjuvant erlotinib improved 2-year disease-free survival in patients with EGFR mutation-positive stage IIIA NSCLC compared with chemotherapy, with a better tolerability profile. This study suggests that tyrosine kinase inhibitors could have a potentially important role as adjuvant therapy in EGFR mutation-positive stage IIIA NSCLC. However, this trial was a phase 2 study. Mature overall survival data are also needed. Ongoing studies will hopefully confirm the role of adjuvant EGFR tyrosine kinase inhibitor therapy in patients with NSCLC.nnnFUNDINGnNational Key Research and Development Program of China and Shanghai Roche Pharmaceuticals Ltd.

The Society for Translational Medicine: clinical practice guidelines for the postoperative management of chest tube for patients undergoing lobectomy

The Society for Translational Medicine and The Chinese Society for Thoracic and Cardiovascular Surgery conducted a systematic review of the literature in an attempt to improve our understanding in the postoperative management of chest tubes of patients undergoing pulmonary lobectomy. Recommendations were produced and classified based on an internationally accepted GRADE system. The following recommendations were extracted in the present review: (I) chest tubes can be removed safely with daily pleural fluid of up to 450 mL (non-chylous and non-sanguinous), which may reduce chest tube duration and hospital length of stay (2B); (II) in rare instances, e.g., persistent abundant fluid production, the use of PrRP/B <0.5 when evaluating fluid output to determine chest tube removal might be beneficial (2B); (III) it is recommended that one chest tube is adequate following pulmonary lobectomy, except for hemorrhage and space problems (2A); (IV) chest tube clearance by milking and stripping is not recommended after lung resection (2B); (V) chest tube suction is not necessary for patients undergoing lobectomy after first postoperative day (2A); (VI) regulated chest tube suction [-11 (-1.08 kPa) to -20 (1.96 kPa) cmH2O depending upon the type of lobectomy] is not superior to regulated seal [-2 (0.196 kPa) cmH2O] when electronic drainage systems are used after lobectomy by thoracotomy (2B); (VII) chest tube removal recommended at the end of expiration and may be slightly superior to removal at the end of inspiration (2A); (VIII) electronic drainage systems are recommended in the management of chest tube in patients undergoing lobectomy (2B).

Society for Translational Medicine expert consensus on training and certification standards for surgeons and assistants in minimally invasive surgery for lung cancer

Training and certification standards for surgeons and assistants in minimally invasive surgery for lung cancer.

Society for Translational Medicine Expert Consensus on the preoperative assessment of circulatory and cardiac functions and criteria for the assessment of risk factors in patients with lung cancer

Project name: methods for the preoperative assessment of cardiovascular functions and criteria for the assessment of risk factors in patients with lung cancer.

The Society for Translational Medicine: indications and methods of percutaneous transthoracic needle biopsy for diagnosis of lung cancer

In 1883, Leyden successfully performed percutaneous transthoracic needle biopsy (PTNB) of the lung in three patients with pneumonia according the records (1); three years later, Menetrier was the first recorded to employ this technique for the diagnosis of lung cancer (2).

Society for Translational Medicine Expert Consensus on the prevention and treatment of postoperative pulmonary infection in esophageal cancer patients

Esophageal cancer is ranked as the malignant tumor with the 6th highest morbidity and mortality rate worldwide. Chinese people are prone to develop esophageal cancer, and the number of new cases that occur every year account for more than half of the esophageal cancer patients worldwide (1,2). Although reports have confirmed the effectiveness of chemoradiotherapy for esophageal cancer, esophageal resection remains the primary means of treatment. Anastomotic leaks and pulmonary complications are the most common postoperative complications of esophageal cancer and carcinoma of the gastric cardia. Pulmonary complications have become more noticeable (3) as the incidence of postoperative anastomotic fistula (8–15%) has decreased due to the improvement of surgical techniques, the use of disposable staplers, and the continuous improvement of postoperative nutritional support Cervical and upper thoracic esophageal cancer are associated with a higher risk for postoperative pulmonary infection.

The Society for Translational Medicine: the assessment and prevention of venous thromboembolism after lung cancer surgery

Cancer is an independent major risk factor for venous thromboembolism (VTE), which is the second leading cause of death in medically and surgically treated patients with cancer (1-5). The association between VTE and lung cancer has been reported more than 20 years ago (6,7).

The Society for Translational Medicine: clinical practice guidelines for mechanical ventilation management for patients undergoing lobectomy

Patients undergoing lobectomy are at significantly increased risk of lung injury. One-lung ventilation is the most commonly used technique to maintain ventilation and oxygenation during the operation. It is a challenge to choose an appropriate mechanical ventilation strategy to minimize the lung injury and other adverse clinical outcomes. In order to understand the available evidence, a systematic review was conducted including the following topics: (I) protective ventilation (PV); (II) mode of mechanical ventilation [e.g., volume controlled (VCV) versus pressure controlled (PCV)]; (III) use of therapeutic hypercapnia; (IV) use of alveolar recruitment (open-lung) strategy; (V) pre-and post-operative application of positive end expiratory pressure (PEEP); (VI) Inspired Oxygen concentration; (VII) Non-intubated thoracoscopic lobectomy; and (VIII) adjuvant pharmacologic options. The recommendations of class II are non-intubated thoracoscopic lobectomy may be an alternative to conventional one-lung ventilation in selected patients. The recommendations of class IIa are: (I) Therapeutic hypercapnia to maintain a partial pressure of carbon dioxide at 50-70 mmHg is reasonable for patients undergoing pulmonary lobectomy with one-lung ventilation; (II) PV with a tidal volume of 6 mL/kg and PEEP of 5 cmH2O are reasonable methods, based on current evidence; (III) alveolar recruitment [open lung ventilation (OLV)] may be beneficial in patients undergoing lobectomy with one-lung ventilation; (IV) PCV is recommended over VCV for patients undergoing lung resection; (V) pre- and post-operative CPAP can improve short-term oxygenation in patients undergoing lobectomy with one-lung ventilation; (VI) controlled mechanical ventilation with I:E ratio of 1:1 is reasonable in patients undergoing one-lung ventilation; (VII) use of lowest inspired oxygen concentration to maintain satisfactory arterial oxygen saturation is reasonable based on physiologic principles; (VIII) Adjuvant drugs such as nebulized budesonide, intravenous sivelestat and ulinastatin are reasonable and can be used to attenuate inflammatory response.