Wen-Juei Jeng

Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification on death and recurrence in completely resected stage I lung adenocarcinoma.

Objective: This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage I lung adenocarcinoma. Methods: Histological classification of 283 patients undergoing surgical resection for stage I lung adenocarcinoma was determined according to the IASLC/ATS/ERS classification after comprehensive histological subtyping with recording of the percentage of each histological component (lepidic, acinar, papillary, micropapillary, and solid) in 5% increments. Their impact on overall survival, recurrence, and postrecurrence survival was investigated. Results: The 5-year overall survival and recurrence-free rates were 81.6% and 76.9%, respectively. During follow-up, 57 (20.1%) patients developed recurrence. The 2-year postrecurrence survival rate was 72.3%. The solid predominant group is associated with significant more male sex, higher smoking exposure, larger tumor size, and more poorly differentiated histological grade. Lepidic predominant group had significantly better overall survival (P = 0.002). Micropapillary and solid predominant groups had significantly lower probability of freedom from recurrence (P = 0.004). Older age (P = 0.039), visceral pleural invasion to the surface (PL2) (P = 0.009), and high grade (micropapillary/solid predominant) of the new classification (P = 0.028) were predictors of recurrence in multivariate analysis. The solid predominant group tends to have significantly worse postrecurrence survival (P = 0.074). Conclusions: The new adenocarcinoma classification has significant impact on death and recurrence in stage I lung adenocarcinoma. Patients with PL2 and micropapillary/solid predominant pattern have significant higher risk for recurrence. This information is important for patient stratification for aggressive adjuvant chemoradiation therapy.

Predictive Value of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma in Tumor Recurrence and Patient Survival

PURPOSE This study investigated the pattern of recurrence of lung adenocarcinoma and the predictive value of histologic classification in resected lung adenocarcinoma using the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification system. PATIENTS AND METHODS Histologic classification of 573 patients undergoing resection for lung adenocarcinoma was determined according to the IASLC/ATS/ERS classification system, and the percentage of each histologic component (lepidic, acinar, papillary, micropapillary, and solid) was recorded. The pattern of recurrence of those components and their predictive value were investigated. RESULTS The predominant histologic pattern was significantly associated with sex (P < .01), invasive tumor size (P < .01), T status (P < .01), N status (P < .01), TNM stage (P < .01), and visceral pleural invasion (P < .01). The percentage of recurrence was significantly higher in micropapillary- and solid-predominant adenocarcinomas (P < .01). Micropapillary- and solid-predominant adenocarcinomas had a significantly higher possibility of developing initial extrathoracic-only recurrence than other types (P < .01). The predominant pattern group (micropapillary or solid v lepidic, acinar, or papillary) was a significant prognostic factor in overall survival (OS; P < .01), probability of freedom from recurrence (P < .01), and disease-specific survival (P < .01) in multivariable analysis. For patients receiving adjuvant chemotherapy, solid-predominant adenocarcinoma was a significant predictor for poor OS (P = .04). CONCLUSION In lung adenocarcinoma, the IASLC/ATS/ERS classification system has significant prognostic and predictive value regarding death and recurrence. Solid-predominant adenocarcinoma was also a significant predictor in patients undergoing adjuvant chemotherapy. Prognostic and predictive information is important for stratifying patients for aggressive adjuvant chemoradiotherapy.

Predictors of Death, Local Recurrence, and Distant Metastasis in Completely Resected Pathological Stage-I Non–Small-Cell Lung Cancer

Objective: This study investigated the factors predicting recurrence and death in patients with resected stage-I non–small-cell lung cancers according to the 7th edition of tumor, node, metastasis (TNM) classification for lung cancer. Methods: All patients undergoing surgical resection for pathological stage-I non–small-cell lung cancers at Taipei Veterans General Hospital between 1980 and 2000 were retrospectively reviewed. Those undergoing sublobar resection were excluded. The factors predicting overall survival (OS), overall recurrence, local recurrence, and distant metastasis were investigated. Results: A total of 756 patients were eligible. The 5-year OS rate and probability of freedom from recurrence were 57.3% and 70.2%, respectively. The 2-year local-recurrence–free and distant-metastasis–free rates were 90.7% and 82.1%, respectively. In multivariable analysis, the new T descriptor (T1a, T1b, and T2a) was the common factor that significantly affected OS (p = 0.003), overall recurrence (p = 0.004), and distant metastasis (p < 0.001). Smoking index more than 20, and number of mediastinal lymph nodes dissected/sampled of 15 or fewer were common factors that significantly predicted worse OS (p < 0.001, p < 0.001, respectively), lower probability of freedom from overall recurrence (p = 0.025, p = 0.009, respectively), and higher risk of local recurrence (p < 0.001, p = 0.030, respectively). Non–squamous-cell histology predicted higher risk of distant metastasis (p = 0.006). Conclusions: Risks of death and recurrence increase as the T descriptor upgrades in the new TNM system. The combination of risk factors can be used to identify high-risk subgroups of local recurrence and distant metastasis.

Prognostic factors of postrecurrence survival in completely resected stage I non-small cell lung cancer with distant metastasis

Objective Distant metastasis after surgical resection is the most frequent cause of death in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the patterns of distant metastasis and the prognostic factors of postrecurrence survival in patients with resected stage I NSCLC with distant metastases. Methods The clinicopathological characteristics of 166 patients with distant metastases after complete resection of stage I NSCLC at Taipei Veterans General Hospital between 1980 and 2000 were retrospectively reviewed. The patients were divided into two groups according to patterns of distant metastasis (single or multiple organ metastases). Predictors of postrecurrence survival were analysed. Results The patterns of distant metastasis included single organ metastasis in 106 (63.9%) and multiple organ metastases in 60 (36.1%) patients. The 1- and 2-year postrecurrence survival rates for those with single organ metastasis were 30.2% and 15.1%, respectively. The most common site of single organ metastasis was bone (32.1%), followed by the brain (29.2%). Multivariate analysis revealed that disease-free interval >16 months (HR 0.534; 95% CI 0.288 to 0.990; p=0.046) and treatment for distant metastasis (including re-operation, chemotherapy and/or radiotherapy) (HR 0.245; 95% CI 0.089 to 0.673; p=0.006) were significant predictors of better postrecurrence survival in resected stage I NSCLC with single organ metastasis. Conclusions A longer disease-free interval is a favourable prognostic predictor for postrecurrence survival in resected stage I NSCLC with single organ metastasis. Treatment for distant metastasis significantly prolongs postrecurrence survival.

Prognostic Significance of the Extent of Visceral Pleural Invasion in Completely Resected Node-Negative Non-small Cell Lung Cancer

OBJECTIVE Visceral pleural invasion (VPI) has been defined as invasion of the tumor beyond the elastic layer (PL1), including invasion to the visceral pleural surface (PL2). The aim of this study was to evaluate the prognostic factors and patterns of recurrence in resected node-negative non-small cell lung cancer (NSCLC) with VPI. METHODS We retrospectively reviewed the clinicopathologic characteristics of 355 patients with resected node-negative NSCLC with VPI at Taipei Veterans General Hospital between 1990 and 2006. The prognostic value and patterns of recurrence were analyzed and compared between PL1 and PL2 groups. RESULTS The median follow-up time was 54.2 months. The 5-year overall survival rate and probability of freedom from recurrence were 61.9% and 66.2%, respectively. The extent of VPI was PL1 in 300 patients (84.5%) and PL2 in 55 (15.5%). During follow-up, 107 patients (30.1%) developed recurrence. The patterns of recurrence included local recurrence only in 20 patients (18.7%), distant metastasis only in 59 (55.1%), and both local recurrence and distant metastasis in 28 (26.2%). Thirteen of the 107 patients (12.1%) with recurrence developed malignant pleural effusion. The percentage of malignant pleural effusion in the PL2 group was significantly higher than that in the PL1 group (P = .006). Patients with PL2 had significantly worse overall survival (P = .046) and lower probability of freedom from recurrence (P = .028) in multivariate analysis. CONCLUSIONS PL2 was a significant prognostic factor for recurrence and worse overall survival in node-negative NSCLC with VPI. This information is important for further design of clinical trials for aggressive adjuvant therapy.

Time Trends of Overall Survival and Survival after Recurrence in Completely Resected Stage I Non-small Cell Lung Cancer

Introduction: The seventh edition of the tumor, node, metastasis classification for lung cancer has been published in 2009. The aim of this study is to evaluate time trends of surgical outcomes and clinicopathologic factors in patients with pathological stage I non-small cell lung cancer according to the seventh edition of the tumor, node, metastasis classification. Methods: We retrospectively reviewed the clinicopathologic characteristics of 1249 patients with pathological stage I non-small cell lung cancer from Taipei Veterans General Hospital between January 1980 and December 2006, during the three periods of 1980–1990, 1991–2000, and 2001–2006. The overall survival, disease-specific survival, and postrecurrence survival were analyzed. Results: The 5-year overall survival rates during the three periods improved significantly: 53.7, 59.9, and 69.3%, respectively (p < 0.001). The 2-year postrecurrence survival rates during the three periods improved significantly: 10.6, 25.4, and 43.2%, respectively (p < 0.001). The percentage of female patients increased during each period: 15.4, 24.9, and 32.0%, respectively (p < 0.001). The percentage of adenocarcinoma also increased during each period: 51.2, 62.2, and 74.9%, respectively (p < 0.001). Tumor size during each period was 3.2, 3.2, and 2.8 cm, tending to be smaller when diagnosed in the last period (p < 0.001). The overall survival in patients with squamous cell carcinoma and those undergoing pneumonectomy or bilobectomy did not improve over time. Conclusions: Stage migration, improved postrecurrence survival, increased frequencies of female gender and adenocarcinoma, and decreased tumor size lead to improved overall survival over the past three decades.

Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma

BACKGROUND The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. METHODS A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. RESULTS Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. CONCLUSIONS Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern.

Prognostic Factors of Survival after Recurrence in Patients with Resected Lung Adenocarcinoma

Objective: Recurrence after surgical resection is the most common cause of treatment failure in patients with non–small-cell lung cancer. The aim of the study is to investigate the prognostic factors of postrecurrence survival (PRS) in patients of resected lung adenocarcinoma. Methods: The clinicopathological characteristics of 179 patients with recurrence after complete resection of lung adenocarcinoma at Taipei Veterans General Hospital between 2004 and 2010 were retrospectively reviewed. The prognostic and predictive effects of these clinicopathological variables in PRS were analyzed. Results: The pattern of recurrence included local only in 25 (15.4%), distant only in 56 (34.6%), and both local and distant in 81 (50.0%) of patients. The 2-year and 5-year PRS were 65.2% and 29.8%, respectively. The most common organ sites of metastasis were the contralateral lung (39.1%), followed by the brain (33.5%) and the bone (31.3%). Multivariate analysis revealed that micropapillary/solid predominant pattern group (versus acinar/papillary; hazard ratio = 2.615; 95% confidence interval: 1.395–4.901; p = 0.003) and no treatment for recurrence (p < 0.001) were significant prognostic factors of worse PRS. For patients receiving treatment for recurrence, micropapillary/solid predominant pattern group (versus acinar/papillary; hazard ratio = 2.570; 95% confidence interval: 1.357–4.865; p = 0.004) was a significant predictive factor of worse PRS. Treatment for recurrence with surgery (p = 0.067) tended to be a significant predictive factor of better PRS. Conclusions: In lung adenocarcinoma, micropapillary/solid predominant pattern group (versus acinar/papillary) was a significant poor prognostic factor for PRS.

Factors predicting organ-specific distant metastasis in patients with completely resected lung adenocarcinoma

The aim of the study is to demonstrate the relationship between clinicopathological variables and organ sites of metastasis in resected lung adenocarcinoma. The clinicopathological characteristics of 748 patients of resected lung adenocarcinoma at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. The prognostic value of clinicopathological variables for specific organ site metastasis-free survival was demonstrated. Among the 182 patients with distant metastasis, 93 (51.1%) patients developed contralateral lung metastasis, 81 (44.5%) had brain metastasis, 71 (39.0%) had bone metastasis, and 18 (8.9%) had liver metastasis during follow-up. Acinar predominant (Hazard ratio [HR], 0.468; 95% confidence interval [CI]: 0.250 to 0.877; P = 0.018) was significantly associated with less contralateral lung metastasis in multivariate analysis. Micropapillary predominant (HR, 2.686; 95% CI, 1.270 to 5.683; P = 0.010) was significantly associated with brain metastasis. Acinar predominant (HR, 0.461; 95% CI, 0.216 to 0.986; P = 0.046) was a significant prognostic factor for better contralateral lung metastasis-free survival in multivariate analysis. Micropapillary predominant (HR, 2.186; 95% CI, 1.148 to 4.163; P = 0.017) and solid predominant (HR, 4.093; 95% CI, 1.340 to 12.504; P = 0.013) were significant prognostic factors for worse brain metastasis-free survival and liver metastasis free-survival, respectively. There are significant differences in metastatic behavior between predominant pathological subtypes of lung adenocarcinoma. This information is important for patient follow-up strategy and identification of organ-specific distant metastasis. Prospective multi-institutional studies are mandatory for further validation.

Factors predicting occult lymph node metastasis in completely resected lung adenocarcinoma of 3 cm or smaller

OBJECTIVES The aim of the study is to demonstrate the relationship between clinicopathological variables and occult lymph node metastasis in resected lung adenocarcinoma. METHODS The clinicopathological characteristics of 471 patients with clinical N2-negative status undergoing resection for lung adenocarcinoma of 3 cm or smaller at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. The association between clinicopathological variables and lymph node metastasis was analysed by univariate and multivariate logistic regression. RESULTS Among the 471 patients, there were 386 (82.0%) patients with pathological N0 status, 35 (7.4%) with pathological N1 status and 50 (10.6%) with pathological N2 status. Greater tumour size (P = 0.002), presence of a micropapillary pattern (P < 0.001), presence of a solid pattern (P < 0.001) and predominant pattern group (micropapillary/solid predominant) (P = 0.001) were significantly associated with higher percentage of occult N2 lymph node metastasis. In multivariate analysis, greater tumour size (P = 0.008), presence of micropapillary pattern (P < 0.001) and presence of solid pattern (P = 0.001) were significant predictors of occult N2 lymph node metastasis in tumours of 3 cm or smaller. When histological pattern was entered as the predominant pattern in multivariate analysis, micropapillary/solid predominant pattern (P = 0.005) was also a significant predictor of occult N2 lymph node metastasis. CONCLUSIONS The presence of micropapillary or solid pattern, as well as micropapillary/solid predominant pattern, is significantly associated with occult N2 lymph node metastasis in lung adenocarcinoma. Radical mediastinal lymph node dissection may help to identify occult lymph node metastasis in these patients.