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Background: The efficacy of adjuvant targeted therapy for operable lung cancer is still under debate. Comprehensive genetic profiling is needed for detecting co-mutations in resected epidermal growth factor receptor ( EGFR )-mutated lung adenocarcinoma (ADC), which may interfere the efficacy of adjuvant tyrosine kinase inhibitor (TKI) treatment., Materials and Methods: Mutation profiling of 416 cancer-relevant genes was conducted for 139 resected stage I-IIIa lung ADCs with EGFR mutations using targeted next-generation sequencing. Co-mutation profiles were systematically analyzed., Results: Rare EGFR alterations other than exon 19 deletion and L858R, such as L861Q (∼3%) and G719A (∼2%), were identified at low frequencies. Approximately 10% of patients had mutations in EGFR exon 20 that could confer resistance to first-generation TKIs. Ninety-one percent of patients harbored at least one co-mutation in addition to the major EGFR mutation. TP53 was the top mutated gene and was found more frequently mutated at later stage. Markedly, NF1 mutations were found only in stage II-III ADCs. Conversely, RB1 mutations were more frequent in stage I ADCs, whereas APC mutations were observed exclusively in this group. Thirty-four percent of patients with EGFR TKI-sensitizing mutations had genetic alterations involving EGFR downstream effectors or bypass pathways that could affect the response to EGFR TKIs, such as PIK3CA , BRCA1 , and NOTCH1 ., Conclusion: Operable lung ADCs with EGFR TKI-sensitizing mutations are associated with a high proportion of co-mutations. Mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy., Implications for Practice: The efficacy of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer harboring EGFR mutation after surgical resection is still under debate. Next-generation sequencing of 416 cancer-relevant genes in 139 resected lung cancers revealed the co-mutational landscape with background EGFR mutation. Notably, the study identified potential EGFR TKI-resistant mutations in 34.71% of patients with a drug-sensitizing EGFR mutation and who were naive in terms of targeted therapy. A comprehensive mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy for these patients., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Background: This study aimed to investigate whether tumor volume (TV) is better than diameter for predicting the prognosis of patients with early-stage non-small cell lung cancer (NSCLC) after complete resection., Methods: This study retrospectively reviewed the clinicopathologic characteristics of 274 patients with early-stage NSCLC who had received pretreatment computed tomography (CT) scans and complete resection. TV was semi-automatically measured from CT scans using an imaging software program. The optimal cutoff of TV was determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. The prognostic significance of TV and other variables was assessed by Cox proportional hazards regression analysis., Results: Using 3.046 cm 3 and 8.078 cm 3 as optimal cutoff values of TV, the patients were separated into three groups. A larger TV was significantly associated with poor DFS and OS in the multivariable analysis. Kaplan-Meier curves of DFS and OS showed significant differences on the basis of TV among patients with stage 1a disease, greatest tumor diameter (GTD) of 2 cm or smaller, and GTD of 2-3 cm, respectively. Using two TV cutoff points, three categories of TV were created. In 54 cases (19.7%), patients migrated from the GTD categories of 2 cm or smaller, 2-3 cm, and larger than 3 cm into the TV categories of 3.046 cm 3 or smaller, 3.046-8.078 cm 3 , and larger than 8.078 cm 3 ., Conclusion: TV is an independent prognostic factor of DFS and OS for early-stage NSCLC. The findings show that TV is better than GTD for predicting the prognosis of patients with early-stage NSCLC.

Objectives: The purpose of this study was to investigate the prognostic impact of tumor volume (TV) on patients with stage I non-small cell lung cancer (NSCLC) after complete resection., Materials and Methods: We retrospectively reviewed the clinicopathological characteristics of 274 patients with stage I NSCLC who had received preoperative chest computed tomography (CT) scans and complete resection. TV was semi-automatically measured from chest CT scans by using an imaging software program. The optimal cutoff values of TV were determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were compared using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify risk factors for DFS and OS., Results: By using 3.046cm 3 and 8.078cm 3 as two optimal cutoff values of TV, the patients were separated into three groups. The 5-year DFS and OS for patients with TV≤3.046cm 3 , 3.046-8.078cm 3 , and>8.078cm 3 were 88.0%, 73.6%, and 62.1%, respectively (P<0.001), and 91.4%, 84.5%, and 73.3%, respectively (p<0.001). Multivariate analysis showed that age and TV were independent factors associated with DFS. Sex, age, histology, visceral pleural invasion, and TV were independent factors associated with OS. Stage Ia patients might be separated into three groups on the basis of TV with significantly different DFS and OS. Patients with tumor diameter≤2cm and 2-3cm were also stratified into two groups with significantly different DFS and OS on the basis of TV, respectively., Conclusion: TV is an independent risk factor for DFS and OS for stage I NSCLC after complete resection. TV might provide additional prognostic information over tumor diameter in patients with stage I NSCLC., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Body mass index (BMI) has a U-shaped association with lung cancer risk. However, the effect of BMI on prognosis is controversial. This retrospective study aimed to investigate the effect of BMI on the survival of patients with stage I non-small cell lung cancer (NSCLC) after surgical resection., Methods: In total, 624 consecutive stage I NSCLC patients who underwent radical resection were classified into four groups according to their BMI: underweight (BMI < 18.5 kg/m 2 ), normal weight (BMI = 18.5-22.4 kg/m 2 ), overweight (BMI = 22.5-28.0 kg/m 2 ), and obese (BMI > 28.0 kg/m 2 ). The effect of BMI on progression-free survival (PFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazards model. Postoperative complications in each group were analyzed using the Chi square test or Fisher's exact test., Results: A univariate analysis showed that PFS and OS were longer in the overweight group than in other groups (both P < 0.05). A multivariate analysis showed that OS was longer in the overweight group than in other groups (compared with the other three groups in combination: hazard ratio [HR] = 1.87, 95% confidence interval [CI] 1.30-2.68, P = 0.003; compared with the underweight group: HR = 2.24, 95% CI 1.18-4.25, P = 0.013; compared with the normal weight group: HR = 1.58, 95% CI 1.07-2.33, P = 0.022; compared with the obese group: HR = 2.87, 95% CI 1.48-5.59, P = 0.002), but PFS was similar among the groups (HR = 1.28, 95% CI 0.97-1.68, P = 0.080). A subgroup analysis showed an association between being overweight and prolonged OS in patients at stage T1a (P = 0.024), T1b (P = 0.051), and T2a (P = 0.02), as well as in patients with a non-smoking history (P = 0.001). Overweight patients had lower rates of postoperative complications, such as respiratory failure (compared with the underweight and obese groups: P = 0.014), myocardial infarction (compared with the obese group: P = 0.033), and perioperative death (compared with the other three groups: P = 0.016)., Conclusions: Preoperative BMI is an independent prognostic factor for stage I NSCLC patients after resection, with overweight patients having a favorable prognosis.

Background: To update the long-term outcomes after subclavian artery (SA) resection and reconstruction during surgery for thoracic inlet (TI) cancer through the anterior transclavicular approach., Methods: Between 1985 and 2014, 85 patients (60 men and 25 women; mean age, 52 years) underwent en bloc resection of thoracic-inlet non-small cell lung cancer (NSCLC) (n=69), sarcoma (n=11), breast carcinoma (n=3) or thyroid carcinoma (n=2) involving the SA. L-shaped transclavicular cervicothoracotomy was performed, with posterolateral thoracotomy in 18 patients or a posterior midline approach in 15 patients. Resection extended to the chest wall (>2 ribs, n=60), lung (n=76), and spine (n=15). Revascularization was by end-to-end anastomosis (n=48), polytetrafluoroethylene (PTFE) graft interposition (n=28), subclavian-to-common carotid artery transposition (n=8), or grafting of the autologous superficial femoral artery in an anterolateral thigh free flap (n=1). Complete R0 resection was achieved in 75 patients and microscopic R1 resection in 10 patients. Postoperative radiation therapy was given to 51 patients., Results: There were no cases of postoperative death, neurological sequelae, graft infection or occlusion, or limb ischemia. Postoperative morbidity consisted of pneumonia (n=16), phrenic nerve palsy (n=2), recurrent nerve palsy (n=4), bleeding (n=4), acute pulmonary embolism (n=1), cerebrospinal fluid leakage (n=1), chylothorax (n=1), and wound infection (n=2). Five-year survival and disease-free survival rates were 32% and 22%, respectively. Long-term survival was not observed after R1 resection., Conclusions: Subclavian arteries invaded by TI malignancies can be safely resected and reconstructed through the anterior transclavicular approach, with good long-term survival provided complete R0 resection is achieved.

Objectives: We examined the prognostic effect of the grading system based on the new IASLC/ATS/ERS classification in an Asian cohort of patients with early-stage lung adenocarcinoma., Materials and Methods: Patients with a lung adenocarcinoma less than 3cm in diameter that had undergone complete anatomic resection, diagnosed with pT1a-2aN0M0 consecutively from 2004 to 2013, were enrolled. All specimens were reviewed according to the new IASLC/ATS/ERS classification. The growth patterns were divided into three major categories: grade 1 for lepidic growth, grade 2 for acinar and papillary patterns, and grade 3 for solid and micropapillary patterns. Each tumor was then graded according to the modified grading system, the final score being the sum of the two most predominant grades. The correlations of clinical and pathological factors with disease-free survival (DFS) and overall survival (OS) were evaluated., Results: In total, 201 adenocarcinomas were eligible for score grading. Only 37 (18.4%) patients had a pure pathological growth pattern. Higher stage, greater tumor diameter, positive lymphovascular invasion, and a higher score were associated with shorter DFS. In contrast, stage no longer had a significant impact on OS in a multivariable analysis. Acinar/papillary-predominant tumors with a score of 3 or 4 were associated with better survival than those with a score of 5 (5-year DFS rate: 64.68 vs. 44.18%, HR=2.19, 95% CI: 1.24-3.87; 5-year OS rate: 85.61 vs. 68.59%, HR=3.03, 95% CI: 1.25-7.32)., Conclusion: The architectural scores may help to stratify survival differences among certain predominant growth subtypes of adenocarcinoma., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We proposed to identify the efficacy of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) using whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS)/surgery in brain metastases from patients with non-small cell lung cancer (NSCLC) and clarify the association between treatment outcome and EGFR gene mutation status. A total of 282 patients with NSCLC brain metastases who underwent WBRT/SRS/surgery alone or in combination with TKI were enrolled in our study from 2003-2013. Amplification mutation refractory system technology was used to determine the EGFR mutation status in 109 tissue samples. EGFR mutation detection was performed in 109 patients with tumor tissues. The EGFR positive rate was 50 % (55/109), including 26 exon 19 deletions and 24 L858R mutations. The median follow-up time was 28 months. The median overall survival, median progression-free survival of intracranial disease, and median progression-free survival of extracranial disease was significantly longer for patients with TKI treatment (31.9 vs 17.0 months, P < 0.0001; 19.8 vs 12.0 months, P < 0.0001; and 19.6 vs 12.3 months, P < 0.0001; respectively). In subgroup analysis within the TKI group, patients harboring EGFR mutations had better extracranial disease control (20.4 vs 14.1 months, P = 0.032). Administration of TKI agents with conventional therapy compared with conventional therapy alone might be beneficial for overall survival, progression-free survival of intracranial disease and progression-free survival of extracranial disease in patients with brain metastases from NSCLC independent of EGFR mutations.

High expression of fibrinogen and platelets are often observed in non-small cell lung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months; P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

There is no consensus in the salvage treatment for non-small-cell lung cancer (NSCLC) with acquired resistance to primary epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Fifty-one consecutive EGFR-mutated NSCLC patients with TKI retreatment after acquired resistance were enrolled in this study. The quantitation of mutation abundance was performed by real-time fluorescent quantitative PCR. The correlation between mutation abundance and outcomes of readministrated TKI was analyzed by survival analysis. Patients with high (H) mutation abundance (24/51) had a significantly (log-rank, P < 0.05) longer (5.27-2.53 months) median progression-free survival (PFS), compared with the low (L) abundance group (27/51), whereas the median overall survival showed no difference (21.00-18.20 months, log-rank P = .403) between the two groups. Objective response and disease control rates in group H and group L regarding the second round TKI treatment were 8.3, 70.8 and 0, 48.1 %, respectively. Groupings with different mutation abundances were significantly associated with PFS under multivariate Cox proportional hazards regression model [hazard ratio (HR) for group H vs. L, 0.527; P = .036]. Mutation abundance affects the efficacy of EGFR-TKIs readministration in NSCLC with acquired resistance. The quantitative mutation abundance of EGFR may be a potential predictor for selecting optimal patients to readministrate EGFR-TKIs after acquired resistance to primary TKI.

Circulating tumor cells (CTCs) enter peripheral blood from primary tumors and seed metastases. The genome sequencing of CTCs could offer noninvasive prognosis or even diagnosis, but has been hampered by low single-cell genome coverage of scarce CTCs. Here, we report the use of the recently developed multiple annealing and looping-based amplification cycles for whole-genome amplification of single CTCs from lung cancer patients. We observed characteristic cancer-associated single-nucleotide variations and insertions/deletions in exomes of CTCs. These mutations provided information needed for individualized therapy, such as drug resistance and phenotypic transition, but were heterogeneous from cell to cell. In contrast, every CTC from an individual patient, regardless of the cancer subtypes, exhibited reproducible copy number variation (CNV) patterns, similar to those of the metastatic tumor of the same patient. Interestingly, different patients with the same lung cancer adenocarcinoma (ADC) shared similar CNV patterns in their CTCs. Even more interestingly, patients of small-cell lung cancer have CNV patterns distinctly different from those of ADC patients. Our finding suggests that CNVs at certain genomic loci are selected for the metastasis of cancer. The reproducibility of cancer-specific CNVs offers potential for CTC-based cancer diagnostics.

Objective: The aim of this study was to evaluate if factors associated with dissected lymph nodes affect the outcome of completely resected stage II (T1-2N1) non-small cell lung cancer (NSCLC)., Methods: Clinical data of 121 patients with complete resection of stage II NSCLC in Sun Yat-sen University Cancer center from January 1998 to December 2004 were reviewed retrospectively and the effect of factors of dissected lymph nodes on overall survival (OS) and disease-free survival (DFS) of NSCLC was analyzed., Results: The univariate analysis demonstrated that the total number of removed lymph nodes, the number of involved N1 lymph nodes, the ratio of involved N1 lymph nodes and the total number of removed N2 lymph nodes were significant prognostic factors for OS. In the multivariate analysis, the total number of removed lymph nodes and the number of involved N1 lymph nodes were independent prognostic factors for OS. In both of univariate and multivariate analyses, tumor size, the total number of removed lymph nodes and the number of involved N1 lymph nodes were independent prognostic factors for DFS., Conclusion: For patients with completely resectable stage II NSCLC, 10 or more lymph nodes should be removed at the surgical resection. Total number of removed lymph nodes >or= 10 is a favorable prognostic factor and involved N1 >or= 3 is an adverse one.

Background and Objective: Surgery is the main therapy for patients with stage II non small cell lung cancer (NSCLC), but patients still have an unsatisfactory prognosis even though complete resection is usually possible. Adjuvant chemotherapy provides low rates of clinical benefit as well. We retrospectively analyzed prognostic factors of patients with completely resected stage II NSCLC to find patients with unfavorable factors for proper management., Methods: Clinical data of 220 patients with complete resections of stage II NSCLC at the Sun Yat sen University Cancer Center between January 1998 and December 2004 were retrospectively analyzed. Cumulative survival was analyzed by the Kaplan Meier method and compared by log rank test. Prognosis was analyzed by the Cox proportional hazards model., Results: The overall 3 and 5 year survival rates were 58.8% and 47.9%, respectively. The 3 and 5 year disease free survival rates were 45.8% and 37.0%, respectively. Of the 220 patients, 86 (39.1%) had recurrence or metastasis. A univariate analysis demonstrated that age (> 55 years), blood type, the presence of symptoms, chest pain, tumor volume (> 20 cm3), total number of removed lymph nodes (> or = 10), number of involved N1 lymph nodes (> or =3 ), total number of removed N2 lymph nodes (> 6), and the ratio of involved N1 lymph nodes (> or = 35%) were significant prognostic factors for 5 year survival. In the multivariate analysis, age (> 55 years), chest pain, tumor volume (> 20 cm3), total number of removed lymph nodes (> or = 10), and number of involved N1 lymph nodes (> or = 3) were independent prognostic factors for 5 year survival., Conclusions: For patients with completely resectable stage II NSCLC, having > 55 years, presenting chest pain, tumor volumes > 20 cm3, and > or = 3 involved N1 lymph nodes were adverse prognostic factors, and > or = 10 removed lymph nodes was a favorable one. Patients with poor prognoses might be treated by individual adjuvant therapy for better survival.

Objective: To evaluate the value of mediastinoscopy in preoperative staging of non-small cell lung cancer (NSCLC) based on survival analysis., Methods: 152 cases of potentially operable NSCLC were enrolled in this study. All cases underwent CT scan and mediastinoscopy for assessment of the mediastinal lymph node status before initial treatment. The definitive treatment was decided on the basis of mediastinoscopy and the survival rate was analyzed with a median follow-up of 30.5 months. Survival analysis was conducted by comparing the lymph node status which was determined by final pathology (groups pN0, pN1, pN2, pN3), CT scan (group cN0-1, cN2-3) and mediastinoscopy (group mN0-1, mN2, mN3)., Results: The 5-year survival rates in group pN0, pN1, pN2 and pN3 were 61.7%, 75.0%, 32.4% and 16.1%, respectively. Both groups pN0 and pN1 had significantly higher survival rates than those in groups pN2 and pN3 (P < 0.05). There were not significant differences between survival rates in groups cN0-1 and cN2-3 (P = 0.670), while the survival rate in group mN0-1 was significantly higher than that in groups mN2 and mN3 (P < 0.05)., Conclusion: Mediastinoscopy is of great value in preoperative staging of NSCLC. Not only does it detect lymph node metastasis more precisely but also better predict the prognosis than CT scan.

Objective: To discuss the strategy of mediastinoscopy for the evaluation of mediastinal lymph node status (metastasis or not) of non-small cell lung cancer (NSCLC) prior to surgery., Methods: From October 2000 to June 2007, 152 consecutive NSCLC cases pathologically proven and clinically staged I-III were enrolled in the study. Of the 152 cases, there were 118 males and 34 females. Age ranged 24-79 years old and the median age was 58. All cases underwent CT and mediastinoscopy for the evaluation of mediastinal lymph node status prior to surgery. Compared with the results of final pathology, the positive rate of mediastinoscopy and the prevalence of mediastinal lymph node metastasis were calculated in the NSCLC patients with negative mediastinal or hilar lymph nodes on CT scan (the shortest axis of mediastinal or hilar lymph nodes <1 cm). Clinical characteristics used as predictive factor including sex, age, cancer location, type of pathology, T status, cancer type (central or peripheral), size of mediastinal lymph nodes (the shortest axis <1 cm or >1 cm) on CT scan and serum CEA level were analyzed by univariate and multivariate analysis with Binary logistic regression model to identify risk factors of mediastinal metastasis., Results: The positive rate of mediastinoscopy was 11.6% (8/69) and the prevalence of mediastinal metastasis was 20.1% (14/69) in NSCLC with negative mediastinal or hilar lymph nodes on CT scan respectively. In clinical stage I (cT1-2N0M0) NSCLC the positive rate of mediastinoscopy was 11.3% (7/62), N2 accounting for 6.5% (4/62) and N3 4.8% (3/62), respectively; and the prevalence of mediastinal lymph node metastasis was 19.4% (12/62), N2 ccounting for 14.6% (9/62) and N3 4.8% (3/62), respectively. In the whole group both univariate and multivariate analysis showed that adenocarcinoma or mediastinal lymph nodes > or =1 cm in the shortest axis on CT scan was an independent risk factor to predict mediastinal lymph node metastasis. In NSCLC with negative mediastinal or hilar lymph nodes on CT scan both univariate and multivariate analysis showed that adenocarcinoma was a predictor of mediastinal lymph node metastasis. Conclusion We recommend the policy of routine mediastinoscopy in NSCLC prior to surgery if the mediastinal staging was only based on CT scan. Mediastinal lymph nodes > or =1 cm in the shortest axis on CT scan mandates preoperative mediastinoscopy. Adenocarcinoma also indicates mandatory mediastinoscopy even with negative mediastinal or hilar lymph nodes on CT scan.

Purpose: Approximately 30% of patients with stage IB non-small-cell lung cancer (NSCLC) die within 5 years after surgery. Current staging methods are inadequate for predicting the prognosis of this particular subgroup. This study identifies prognostic markers for NSCLC., Patients and Methods: We used computer-generated random numbers to study 148 paraffin-embedded specimens for immunohistochemical analysis. We studied gene expression in paraffin-embedded specimens of lung cancer tissue from 73 randomly selected patients with stage IB NSCLC who had undergone radical surgical resection and evaluated the association between the level of expression and survival. We used support vector machines (SVM)-based methods to develop three immunomarker-SVM-based prognostic classifiers for stage IB NSCLC. For validation, we used randomly assigned specimens from 75 other patients., Results: We devised three immunomarker-SVM-based prognostic classifiers, including SVM1, SVM2, and SVM3, to refine prognosis of stage IB NSCLC successfully. The SVM1 model integrates age, cancer cell type, and five markers, including CD34MVD, EMA, p21ras, p21WAF1, and tissue inhibitors of metalloproteinases (TIMP) -2. The SVM2 model integrates age, cancer cell type, and 19 markers, including BCL2, caspase-9, CD34MVD, low-molecular-weight cytokeratin, high-molecular-weight cytokeratin, cyclo-oxygenase-2, EMA, HER2, matrix metalloproteinases (MMP) -2, MMP-9, p16, p21ras, p21WAF1, p27kip1, p53, TIMP-1, TIMP-2, vascular endothelial growth factor (VEGF), and beta-catenin. The SVM3 model consists of SVM1 and SVM2. The three models were independent predictors of overall survival. We validated the classifiers with data from an independent cohort of 75 patients with stage IB NSCLC., Conclusion: The three immunomarker-SVM-based prognostic characteristics are closely associated with overall survival among patients with stage IB NSCLC.

Objective: To compare the value of CT and mediastinoscopy in assessment of mediastinal lymph node status in potentially operable non-small cell lung cancer (NSCLC)., Methods: From Oct. 2000 to Jun. 2007, 152 consecutive patients with pathologically proven and stage I to approximately III NSCLC were enrolled into the study. Of the 152 cases, there were 118 males and 34 females, with a median age of 58 years (range, 24 to approximately 79 years). Compared with the final pathology, the sensitivity, specificity, positive and negative predictive values and accuracy of CT and mediastinoscopy for preoperative evaluation of mediastinal lymph node status were calculated, respectively. The accuracy and diagnostic efficacy of CT and mediastinoscopy was compared by Pearson chi(2) test and ROC curve, respectively., Results: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of detection of mediastinal metastasis was 73.8%, 70.1%, 64.9%, 78.2% and 71.7% by CT, respectively, versus 83.1%, 100.0%, 100.0%, 88.8% and 92.8% by mediastinoscopy, respectively. Both the accuracy and diagnostic efficacy of mediastinoscopy were superior to CT (Pearson chi(2) test, P < 0.001; Z test of the areas under the ROC curve, P < 0.001). The complication rate of mediastinoscopy was 4.6%, and the false negative rate was 7.2%., Conclusion: Mediastinoscopy is safe and effective in preoperative assessment of mediastinal lymph node status in potentially operable NSCLC, while CT alone is inadequate.

Objective: To investigate the impact of visceral pleural invasion (VPI) on prognosis and staging in patients with stage Ib non-small cell lung cancer (NSCLC)., Methods: Clinical data of 232 patients with stage Ib NSCLC surgically treated by curative resection between January 1994 and December 2003 was retrospectively reviewed. Histopathological diagnosis was reviewed by an experienced pathologist. According to the tumor size and status of VPI, patients were stratified into three group: group A: tumor > 3 cm and VPI(-); group B: tumor < or = 3 cm and VPI (+); group C: tumor > 3 cm and VPI(+). There were 45 patients in group A, 96 in group B and 91 in group C. Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for multivariate analysis., Results: 187 (80.6%) patients had visceral plural invasion, while 45 (19.4%) had no. The 5-and 10-year survival rates of patients with VPI were 59.3% and 42.6%, while it was 70.1% and 56.7% for the patients without (P = 0.035), respectively. The 5-year survival rates of patients in group A, B and C were 70.1%, 61.9% and 56.2%; and 10-years survival rates were 56.7%, 50.6% and 35.9%, respectively (P = 0.018). VPI with large size of tumor was revealed by Cox multivariate analysis as an independent prognostic factor (RR = 1.530, 95% CI: 1.132-2.067, P = 0.006)., Conclusion: A significant difference in survival exists among the stage Ib NSCLC patients who have different T status, the patient with > 3 cm tumor and visceral plural invasion may have the worst prognosis. Further studies are still needed to assess whether it is necessary or not to modify the T2 statue of tumor > 3 cm with visceral plural invasion.

Objective: To investigate the prognostic effect of mediastinal lymph node dissection in patients with stage I non-small cell lung cancer (NSCLC)., Methods: The clinical data of 330 patients with stage I NSCLC who were treated with curative resection from January 1994 to December 2003 were reviewed retrospectively. According to the extent of mediastinal lymph node dissection and the pathology report, the patients were assigned to lung resection combined with mediastinal lymph node dissection (LND) group or with lymph node sampling (LNS) group. The Kaplan-Meier method was used for survival analysis. COX proportional hazards model was used for multivariate analysis., Results: There were 233 (70.6%) male patients and 97 (29.4%) female patients. The median age was 60 years old. Ninety-eight patients were in stage IA and 233 in stage IB. One hundred and forty patents were in group LND and 190 in group LNS. The mean number of removed lymph nodes in group LND and group LNS were (13.3 +/- 4.7) and (5.2 +/- 3.0) (P < 0.01), respectively. The mean of mediastinal lymph node station sampled in group LND and group LNS were (3.7 +/- 0.9) and (1.3 +/- 1.1) (P < 0.01), respectively. The 5-year and 10-year survival rates of patients in group LND were 72.0% and 66.1%, while in group LNS were 65.9% and 43.0% (P < 0.05), respectively. Other prognostic factors included symptom, staging, visceral pleura invasion and tumor size. LND was disclosed as a favourable prognostic factor at COX multivariate analysis, together with absence of symptom at diagnosis., Conclusion: As compared with LNS, LND can improve survival in stage I NSCLC.

Background & Objective: Multi-disciplinary management for non-small cell lung cancer (NSCLC) has been applied for more than ten years. The progresses in the diagnosis and management of NSCLC might change the factors affecting prognosis. This study was to explore the prognostic factors of NSCLC after complete resection., Methods: Clinical data of 899 NSCLC patients, underwent complete resection from Jan. 1997 to Apr. 2001 at Cancer Center of Sun Yat-sen University, were reviewed. The patients were followed up till 31st Mar. 2006. Survival rates were calculated by Kaplan-Meier method. The prognosis was analyzed by Cox proportional hazards model., Results: The 5-year survival rate of the 899 patients was 43.5% and the median survival time was 48 months. The 5-year survival rates were 81.0% for the patients at stage IA, 60.3% for stage IB, 56.9% for stage IIA, 45.7% for stage IIB, 23.5% for stage IIIA, 20.8% for stage IIIB, and 13.0% for stage IV. Univariate analysis showed that T stage, N stage, M stage, histological type, differentiation, chemotherapy for adenocarcinoma (ADC) at stages II and IV, and mediastinal radiotherapy for ADC at stage N2 were prognostic factors. Multivariate analyses showed that histological type, T stage, N stage, M stage and mediastinal radiotherapy for ADC at stage N2 were independent prognostic factors., Conclusion: Besides T stage, N stage, and M stage, histological type and mediastinal radiotherapy for ADC at stage N2 are also independent prognostic factors of NSCLC after complete resection.

Background & Objective: Small cell lung cancer (SCLC) is usually widely disseminated at the time of diagnosis due to its rapid growth. Therefore chemotherapy is the predominant form of treatment for SCLC. However, chemotherapy normally ended in failure as a consequence of recurrence of primary tumor or mediastinal lymphatic nodes. The objective of this study was to investigate whether combined surgical treatment for SCLC can control primary tumor more effectively and increase the survival of the patients., Methods: Fifty-one cases of limited SCLC treated with surgery from May 1981 to May 2001 in Cancer Center, Sun Yat-sen University were reviewed retrospectively., Results: According to 1997 international staging system, there were 7 patients with stage IB(13.7%), 5 with stage IIA(9.8%), 15 with stage IIB (29.4%), 20 with stage IIIA (39.2%) and 4 with stage IIIB (7.8%). Twelve patients received pneumonectomy, 35 lobectomy, 3 segmentectomy, and 1 exploration. Thirteen patients were treated with surgery alone and 38 of them combined with 2-6 cycles of pre- or post- operative chemotherapy. The median survival time was 20.8 months. The overall 1-, 3-, and 5-year survival rates were 43.0%, 25.9%, and 20.1%, respectively. The 1-, 3-, and 5-year survival rates for patients with stage IB were 100.0%, 80.0%, and 30.0% respectively, with stage II were 79.7%, 39.8%, and 34.5%, respectively, with stage III were 52.4%, 21.8%, and 5.46%, respectively. The 1-,3-, and 5-year survival rates for patients treated by surgery combined with chemotherapy were 77.5%, 38.5%, and 23.8% and that of surgery alone were 41.7%, 16.7%, and 8.3%, respectively (P< 0.01)., Conclusion: Combined surgical treatment can increase the survival rate of SCLC more effectively and should be considered as an important modality in multi-disciplinary treatment of limited small cell lung cancer.