Xiuyi Zhi

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

BACKGROUNDnThe frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging.nnnMETHODSnA 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I-III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC).nnnFINDINGSnKaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5-80·0) in low-risk, 58·3% (48·9-66·6) in intermediate-risk, and 49·2% (42·2-55·8) in high-risk patients (p(trend)=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0-80·6) in low-risk, 57·4% (48·3-65·5) in intermediate-risk, and 44·6% (40·2-48·9) in high-risk patients (p(trend)<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages.nnnINTERPRETATIONnOur practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection.nnnFUNDINGnUCSF Thoracic Oncology Laboratory and Pinpoint Genomics.

Final overall survival results from a randomised, Phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802)

BACKGROUNDnThe OPTIMAL study was the first study to compare efficacy and tolerability of the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) erlotinib, versus standard chemotherapy in first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Findings from final overall survival (OS) analysis and assessment of post-study treatment impact are presented.nnnPATIENTS AND METHODSnOf 165 randomised patients, 82 received erlotinib and 72 gemcitabine plus carboplatin. Final OS analyses were conducted when 70% of deaths had occurred in the intent-to-treat population. Subgroup OS was analysed by Cox proportional hazards model and included randomisation stratification factors and post-study treatments.nnnRESULTSnMedian OS was similar between the erlotinib (22.8 months) and chemotherapy (27.2 months) arms with no significant between-group differences in the overall population [hazard ratio (HR), 1.19; 95% confidence interval (CI) 0.83-1.71; P = 0.2663], the exon 19 deletion subpopulation (HR, 1.52; 95% CI 0.91-2.52; P = 0.1037) or the exon 21 L858 mutation subpopulation (HR, 0.92; 95% CI 0.55-1.54; P = 0.7392). More patients in the erlotinib arm versus the chemotherapy arm did not receive any post-study treatment (36.6% versus 22.2%). Patients who received sequential combination of EGFR-TKI and chemotherapy had significantly improved OS compared with those who received EGFR-TKI or chemotherapy only (29.7 versus 20.7 or 11.2 months, respectively; P < 0.0001). OS was significantly shorter in patients who did not receive post-study treatments compared with those who received subsequent treatments in both arms.nnnCONCLUSIONnThe significant OS benefit observed in patients treated with EGFR-TKI emphasises its contribution to improving survival of EGFR mutant NSCLC patients, suggesting that erlotinib should be considered standard first-line treatment of EGFR mutant patients and EGFR-TKI treatment following first-line therapy also brings significant benefits to those patients.nnnCLINICALTRIALSGOV IDENTIFIERnNCT00874419.

Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC)

BACKGROUNDnThe OPTIMAL study found that erlotinib improved progression-free survival (PFS) versus standard chemotherapy in Chinese patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). This report describes the quality of life (QoL) and updated PFS analyses from this study.nnnPATIENTS AND METHODSnChinese patients ≥ 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received erlotinib (150 mg/day; n = 82) or gemcitabine-carboplatin (n = 72). The primary efficacy end point was PFS; QoL was assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, Trial Outcome Index (TOI) and Lung Cancer Subscale (LCS).nnnRESULTSnPatients receiving erlotinib experienced clinically relevant improvements in QoL compared with the chemotherapy group in total FACT-L, TOI and LCS (P < 0.0001 for all scales). Erlotinib scored better than chemotherapy for all FACT-L subscales from baseline to cycles 2 and 4 (non-significant). In the updated analysis, PFS was significantly longer for erlotinib than chemotherapy (median PFS 13.7 versus 4.6 months; HR = 0.164, 95% CI = 0.105-0.256; P < 0.0001), which was similar to the previously reported primary analysis.nnnCONCLUSIONnErlotinib improves QoL compared with standard chemotherapy in the first-line treatment of patients with EGFR mutation-positive advanced NSCLC.

Impact of examined lymph node count on precise staging and long-term survival of resected non-small-cell lung cancer: A population study of the US SEER database and a Chinese multi-institutional registry

Purpose We investigated the correlation between the number of examined lymph nodes (ELNs) and correct staging and long-term survival in non–small-cell lung cancer (NSCLC) by using large databases and determined the minimal threshold for the ELN count. Methods Data from a Chinese multi-institutional registry and the US SEER database on stage I to IIIA resected NSCLC (2001 to 2008) were analyzed for the relationship between the ELN count and stage migration and overall survival (OS) by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural break points were determined by Chow test. The selected cut point was validated with the SEER 2009 cohort. Results Although the distribution of ELN count differed between the Chinese registry (n = 5,706) and the SEER database (n = 38,806; median, 15 versus seven, respectively), both cohorts exhibited significantly proportional increases from N0 to N1 and N2 disease (SEER OR, 1.038; China OR, 1.012; both P < .001) and serial improvements in OS (N0 disease: SEER HR, 0.986; China HR, 0.981; both P < .001; N1 and N2 disease: SEER HR, 0.989; China HR, 0.984; both P < .001) as the ELN count increased after controlling for confounders. Cut point analysis showed a threshold ELN count of 16 in patients with declared node-negative disease, which were examined in the derivation cohorts (SEER 2001 to 2008 HR, 0.830; China HR, 0.738) and validated in the SEER 2009 cohort (HR, 0.837). Conclusion A greater number of ELNs is associated with more-accurate node staging and better long-term survival of resected NSCLC. We recommend 16 ELNs as the cut point for evaluating the quality of LN examination or prognostic stratification postoperatively for patients with declared node-negative disease.

VATS lobectomy facilitates the delivery of adjuvant docetaxel-carboplatin chemotherapy in patients with non-small cell lung cancer

BACKGROUNDnTo evaluate the safety and tolerability of docetaxel/carboplatin regimen in the post-operative setting of patients with non-small cell lung cancer (NSCLC).nnnMETHODSnEnrolment of 133 patients with stage Ib - IIIa NSCLC was undertaken in an open-label, single arm study to assess the safety and tolerability of docetaxel (75 mg/kg) and carboplatin (AUC 5.5) administered for 3 cycles after resection for curative intent. The primary endpoint of the study was safety, as reflected by a febrile neutropenia rate of <10%. Other endpoints assessed protocol compliance and the impact of minimally invasive surgical technique.nnnRESULTSnPatient accrual was completed at 1 center in the US and 10 centers in China in <6 months. Febrile neutropenia complicated treatment in 12 patients (9.0%), below the predetermined safety threshold of 14 patients. Four VATS and 8 open thoracotomy patients experienced febrile neutropenia (P=0.26). Completion of the three-cycle adjuvant regimen was achieved in 86% (95% CI, 77-95%) of patients. Sixty-two of 66 VATS patients compared to 53 of 67 open thoracotomy patients received all three doses according to protocol (P<0.01). Thirteen serious adverse events (9.8%) and no deaths were attributed to the study regimen.nnnCONCLUSIONSnIn this rapidly accrued study, docetaxel and carboplatin were well-tolerated in the adjuvant treatment of NSCLC. Adjuvant treatment compliance was higher among patients undergoing a minimally invasive surgical approach. (ClinicalTrials.gov number NCT00883675).

Chinese guidelines on the diagnosis and treatment of primary lung cancer (2011 version)

Chinese Guidelines on the Diagnosis and Treatment of Primary Lung Cancer (2011 Version) Xiuyi ZHI*, Yilong WU*, Shenglin MA, Tianyou WANG, Changli WANG, Jie WANG, Yuankai SHI, You LU, Lunxu LIU, Deruo LIU, Donghong CHEN, Yue YANG, Xiang DU, Hong BU, Qinghua ZHOU, Gening JANG, Baohui HAN, Gang CHENG, Ying CHENG, Shunchang JIAO Xiuyi ZHI and Yilong WU contributed equally to this paper. Beijing Lung Cancer Center, Department of Thoracic Surgery, Beijing Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Guangdong Lung Cancer Institute, Department of Thoracic Surgery, Guangdong General Hospital, Guangzhou 510030, China; Department of Radiation Therapy, Zhejiang Cancer Hospital, Hangzhou 310022, China; Department of Thoracic Surgery, Beijing Friendship Hospital, Beijing 100050, China; Department of Lung Cancer Surgery, Tianjin Cancer Hospital, Tianjin 300060, China; Department of Thoracic Medical Oncology, Beijing Cancer Hospital, Peking University, Beijing 100142, China; Department of Medical Oncology, Cancer Hospital, Chinese Aacademy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China; Department of Thoracic Surgery, Beijing Cancer Hospital, Peking University, Beijing 100142, China; Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China; Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China; Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China; Department of Medical Oncology, Beijing Hospital, Beijing 100005, China; Department of Medical Oncology, Jilin Cancer Hospital, Changchun 130012, China; Department of Medical Oncology, General Hospital of Chinese PLA, Beijing 100853, China Corresponding author: Xiuyi ZHI, E-mail: xiuyizhi@yahoo.com.cn DOI: 10.3779/j.issn.1009-3419.2012.12.01

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).

Clinical pathway for surgical treatment of primary lung cancer (2012 Edition)

Diagnosis is based on the “Diagnosis and Treatment Practices for Primary Lung Cancer (2011)” and the “Diagnosis Practices for Primary Lung Cancer (2011)” released by the Ministry of Health of China

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.