Clinicopathological Features and Survival Outcomes of Resected Lung Adenosquamous Carcinoma: Results From a Nationwide Japanese Registry Data.

OBJECTIVES: The objective of this study was to clarify the clinicopathological features and prognostic factors of resected lung adenosquamous carcinoma (ASC) using a nationwide multi-institutional database. METHODS: We retrospectively reviewed the records of 15,542 patients who underwent complete R0 resection for ASC (n = 326), adenocarcinoma (AC, n = 11,820), or squamous cell carcinoma (SC, n = 3396) from a Japanese lung cancer registry in 2010. To reduce the selection bias, an inverse probability of treatment weighting (IPTW) method using a propensity score was implemented. RESULTS: The ASC group showed worse recurrence-free and overall survival (RFS and OS) than both the AC and SC groups (5-year OS: 57.5% in ASC, 83.9% in AC [< 0.001], and 62.3% in SC [P = .086]). In multivariate analyses, prognostic factors that affected OS for ASC included male, p-stage II-III, and postoperative complications within 30 days (grade ≥ 3 in the Clavien-Dindo classification). The sensitizing EGFR mutation was detected in 28 (21.5%) of 130 screened patients with ASC, but it did not affect either RFS, OS, or postrecurrence survival. Although more patients in the ASC group received adjuvant chemotherapy compared to the AC and SC groups, both multivariate and IPTW-adjusted analyses did not show positive impact of adjuvant chemotherapy on RFS and OS in ASC. CONCLUSIONS: In this nationwide registry study, lung ASC was more aggressive than both AC and SC. No apparent survival impact of conventional adjuvant chemotherapy prompted us to investigate novel adjuvant strategies to optimize survival outcomes.

Clinical outcomes of left upper segmentectomy vs. lobectomy for early non-small-cell lung cancer: a nationwide database study in Japan.

PURPOSE: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe. METHODS: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis. RESULTS: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38). CONCLUSION: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe.

Efficacy of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Metastatic Non-Small Cell Lung Cancer Patients with Poor Performance Status and Epidermal Growth Factor Receptor Mutations: Findings from the Japanese Lung Cancer Registry Database.

BACKGROUND: In advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations, those with impaired performance status (PS) treated with EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated comparable activities to good-PS patients. Due to the limited sample size and inclusion of older adult patients with good PS, these findings may not accurately depict the efficacy of EGFR-TKI in poor-PS patients. We investigated the benefit of EGFR-TKIs in this population and identified relevant prognostic factors. PATIENTS AND METHODS: This nationwide prospective registry study included 9872 patients with local or advanced NSCLC. Outcomes were compared between poor- and good-PS patients treated with EGFR-mutated lung cancer therapies. RESULTS: Of 9872 NSCLC patients, 1965 (19.9%) had EGFR mutations, with 1846 (93.9%) presenting common EGFR mutations. Poor PS (PS score ≥ 3) was noted in 171 patients (8.7%) and identified as an independent prognostic factor; those with poor PS had a significantly lower 1-year survival rate. The median overall survival (OS) for EGFR-TKI-treated good-PS patients was 31.5 (95% confidence interval, 29.6-33.4) months. Among poor-PS patients with EGFR mutations, 135 (78.9%) of whom were treated with EGFR-TKI had an OS of 15.5 (12.7-18.3) months, while those receiving only supportive care had an OS of 2.5 (1.4-3.6) months (P < .001). Hypoalbuminemia (< 3.5 g/dL), liver metastasis, and uncommon EGFR mutations were associated with poor prognosis. CONCLUSION: Poor PS at diagnosis was rare and associated with limited EGFR-TKI efficacy and a dismal prognosis. Liver metastasis and hypoalbuminemia may reduce EGFR-TKI efficacy in these patients.

Benefit of Adjuvant Chemotherapy for Patients Older Than 75 Years With Completely Resected p-Stage II-IIIA Non-Small-Cell Lung Cancer: A Retrospective Cohort Study Using Japanese Nationwide Real-World Data.

BACKGROUND: The efficacy of adjuvant chemotherapy (ACT) in elderly patients with completely resected p-stage II-IIIA non-small-cell lung cancer (NSCLC) remains unclear because all previous randomized controlled trials on ACT have been conducted among patients aged <75 years. Thus, this study aimed to evaluate the effectiveness of ACT in elderly patients with completely resected NSCLC. PATIENTS: We extracted the nationwide data of 812 patients aged ≥75 years who underwent lobectomy with mediastinal nodal dissection in 2010 and were diagnosed with p-stage II-IIIA NSCLC, from nationwide registry data accumulated in 2016. METHODS: We classified the 812 patients into 2 groups based on the ACT administration status and analyzed the differences in their postoperative overall survival (OS). RESULTS: Overall, 295 patients received ACT (36.3%; group A), whereas 517 patients did not (63.70%; group N). Group A showed significantly better OS as a whole (hazard ratio [HR]: 0.650 [95% confidence interval {CI}: 0.526-0.804]), in the p-stage II subset (HR: 0.688 [95% CI: 0.513-0.925]), and p-stage IIIA subset (HR: 0.547 [95% CI: 0.402-0.743]) than group N. Even after propensity score matching, group A showed significantly better OS as a whole (HR: 0.626 [95% CI: 0.495-0.792]), in the p-stage II subset (HR: 0.690 [95% CI: 0.493-0.964]), and p-stage IIIA subset (HR: 0.554 [95% CI: 0.398-0.772]) than group N. CONCLUSION: ACT is recommended even in elderly patients with completely resected p-stage II-IIIA NSCLC. Hence, physicians should not avoid ACT in patients with completely resected NSCLC based solely on age.

Is adjuvant chemotherapy for completely resected p-stage IA (>2 cm) and stage IB non-small-cell lung cancer beneficial for elderly patients? A large, retrospective cohort study based on real-world data from Japan.

OBJECTIVE: The efficacy of tegafur-uracil as adjuvant chemotherapy for patients with completely resected stage I non-small-cell lung cancer is proven; however, its efficacy for elderly patients remains unclear. Herein, we evaluated the effectiveness of adjuvant chemotherapy for elderly patients with completely resected stage I non-small-cell lung cancer based on real-world Japanese data using propensity score matching. METHODS: This retrospective study extracted data from a nationwide registry study, performed in 2016, on patients ≥75 years who underwent lobectomy with mediastinal nodal dissection for non-small-cell lung cancer in 2010 and were diagnosed with p-stage IA (>2 cm) or stage IB non-small-cell lung cancer. We classified the 1294 patients into two groups-Group A, postoperative adjuvant chemotherapy (n = 295, 22.8%) and Group N, no adjuvant chemotherapy (n = 999, 77.2%)-and analyzed differences in postoperative overall survival between groups. RESULTS: Group A showed no advantage in overall survival over Group N as a whole (hazard ratio: 0.824 [95% confidence interval: 0.631-1.076]), in p-stage IA (hazard ratio: 0.617 [95% confidence interval: 0.330-1.156]) and in p-stage IB (hazard ratio: 0.806 [95% confidence interval: 0.597-1.088]) subsets. Even after propensity score matching, Group A showed no significant advantage in overall survival over Group N as a whole (hazard ratio: 0.975 [95% confidence interval: 0.688-1.381]), in p-stage IA (hazard ratio: 1.390 [95% confidence interval: 0.539-3.586]) and in p-stage IB (hazard ratio: 0.922 [95% confidence interval: 0.633-1.343]). CONCLUSIONS: adjuvant chemotherapy for completely resected p-stage IA (>2 cm) and stage IB non-small-cell lung cancer showed no benefit for recommendation for elderly patients; considering the risk of adverse events, we do not recommend adjuvant chemotherapy for elderly patients.

Features of anaplastic lymphoma kinase rearrangement in early-stage lung cancer: Analysis of a nationwide Japanese database.

BACKGROUND AND OBJECTIVES: Anaplastic lymphoma kinase (ALK) rearrangement is a representative driver mutation in lung cancer. However, the biology of early-stage ALK-rearranged lung cancer remains unclear. We aimed to assess the clinicopathological features, prognostic implications, and influence of ALK rearrangement on the postoperative course in surgically resected lung cancer. METHODS: We retrospectively analyzed data from the Japanese Joint Committee of Lung Cancer Registry database. Of the 12 730 patients with lung adenocarcinoma, 794 (6.2%) were tested for ALK rearrangement and were included. RESULTS: ALK rearrangements were detected in 76 patients (10%). The 5-year overall survival (OS) rate was significantly higher in the ALK rearrangement-positive group than in the ALK rearrangement-negative group (p = 0.030). Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved OS (hazard ratio, 0.521; 95% confidence interval, 0.298-0.911; p = 0.022). Regarding the postrecurrence state, there was no difference in the initial recurrence sites between both groups. Administration of ALK-tyrosine kinase inhibitors (TKIs) improved postrecurrence survival in any treatment lines. CONCLUSION: In one of the largest national surveys, ALK rearrangement was associated with improved long-term outcomes in surgically resected patients. ALK-TKIs may be an important treatment strategy for ALK rearrangement-positive lung adenocarcinoma in the postrecurrence state.

Epidemiology, risk factors and impact of cachexia on patient outcome: Results from the Japanese Lung Cancer Registry Study.

BACKGROUND: Cancer cachexia is a syndrome that does not fully recover with nutritional support and causes appetite loss and body weight loss. It worsens a patient's quality of life and prognosis. In this study, the epidemiology of cachexia in lung cancer, its risk factors and its impact on chemotherapy response rate and prognosis were examined using the national database of the Japan Lung Cancer Society. Understanding these things related to cancer cachexia is important as a starting point in overcoming cancer cachexia in patients with lung cancer. METHODS: In 2012, 12 320 patients from 314 institutions in Japan were registered in a nationwide registry database (Japanese Lung Cancer Registry Study). Of these, data on body weight loss within 6 months were available for 8489 patients. We defined the patients with body weight loss ≥ 5% within 6 months, which is one of the three criteria listed in the 2011 international consensus definition of cancer cachexia, as cachectic in this study. RESULTS: Approximately 20.4% of the 8489 patients had cancer cachexia. Sex, age, smoking history, emphysema, performance status, superior vena cava syndrome, clinical stage, site of metastasis, histology, epidermal growth factor receptor (EGFR) mutation status, primary treatment method and serum albumin levels were significantly different between patients with and without cachexia. Logistic analyses showed that smoking history, emphysema, clinical stage, site of metastasis, histology, EGFR mutation, serum calcium and albumin levels were significantly associated with cancer cachexia. The response to initial therapy, including chemotherapy, chemoradiotherapy or radiotherapy, was significantly poorer in the patients with cachexia than in those without cachexia (response rate: 49.7% vs. 41.5%, P < 0.001). Overall survival was significantly shorter in the patients with cachexia than in those without cachexia in both univariate and multivariable analyses (1-year survival rate: 60.7% vs. 37.6%, Cox proportional hazards model, hazard ratio: 1.369, 95% confidence interval: 1.274-1.470, P < 0.001). CONCLUSIONS: Cancer cachexia was seen in approximately one fifth of the lung cancer patients and was related to some baseline patient characteristics. It was also associated with a poor response to initial treatment, resulting in poor prognosis. The results of our study may be useful for early identification and intervention in patients with cachexia, which may improve their response to treatment and their prognosis.

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data.

Introduction: Pembrolizumab is a programmed death-ligand 1 inhibitor that was initially indicated for monotherapy in patients with advanced lung cancer. The Japanese Lung Cancer Society conducted an observational study on pembrolizumab using confirmative data obtained through postmarketing all-case surveillance (PMACS), which was performed by a pharmaceutical company under the Japanese law in 2017. Methods: This multicenter observational study was conducted by the Japanese Lung Cancer Society using PMACS data with the newly created central registration system regarding patients with NSCLC who received pembrolizumab monotherapy between February 1, 2017 and June 30, 2017; a new database was created by adding the clinical information regarding prognosis for 3 years after therapy to the existing data collected by PMACS. Results: A total of 300 patients from 43 facilities were enrolled in this study. The median overall survival and progression-free survival after pembrolizumab initiation were 558 and 188 days, respectively. Moreover, the 1- and 3-year survival rates were 58.9% and 33.7%, respectively. Results of multivariate analysis revealed performance status (p < 0.0001), histology (p = 0.0118), previous chemotherapy (p = 0.0007), programmed death-ligand 1 expression status (p = 0.0195), and previous steroid use (p = 0.0460) as significant factors that affected overall survival. The toxicity profile was similar to that previously reported. Conclusions: In this first attempt to use PMACS data, we successfully collected clinical information and found the real-world efficacy and safety of pembrolizumab.

Hazard Function Analysis of Recurrence in Patients with Curatively Resected Lung Cancer: Results from the Japanese Lung Cancer Registry in 2010.

To optimize postoperative surveillance of lung cancer patients, we investigated the hazard function of tumor recurrence in patients with completely resected lung cancer. We analyzed the records of 12,897 patients in the 2010 Japanese Joint Committee of Lung Cancer Registry who underwent lobectomy to completely resect pathological stage I-III lung cancer. The risk of postoperative recurrence was determined using a cause-specific hazard function. The hazard function for recurrence exhibited a peak at approximately 9 months after surgery, followed by a tapered plateau-like tail extending to 60 months. The peak risk for intrathoracic recurrence was approximately two-fold higher compared with that of extrathoracic recurrence. Subgroup analysis showed that patients with stage IIIA adenocarcinoma had a continuously higher risk of recurrence compared with patients with earlier-stage disease. However, the risk of recurrence in patients with squamous cell carcinoma was not significantly different compared with that more than 24 months after surgery, regardless of pathological stage. In conclusion, the characteristics of postoperative tumor recurrence hazard in a large cohort of lung cancer patients may be useful for determining the time after surgery at which patients are at the highest risk of tumor recurrence. This information may improve stage-related management of postoperative surveillance.

The prognostic impact of lung adenocarcinoma predominance classification relating to pathological factors in lobectomy, the Japanese Joint Committee of Lung Cancer Registry Database in 2010.

OBJECTIVE: We studied the prognosis and clinicopathological background of lung adenocarcinoma predominance among patients who underwent lobectomy using data from the Japanese Joint Committee of Lung Cancer Registry. METHODS: Two thousand eight hundred sixty-three cases were extracted. Recurrence free survival (RFS) rates, overall survival (OS) rates and clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status were examined. RESULTS: Median follow-up period was 65.5 months. Adenocarcinoma predominance was sub-grouped according to OS and RFS rate. In pathological stage I, 5-year RFS and OS rates were respectively 92.2% and 95.8% in group A (adenocarcinoma-in-situ + minimally invasive adenocarcinoma), 89.3% and 92.1% in group B (lepidic), 79.2% and 89.7% in group C (papillary + acinar + variants) and 69.0% and 79.0% in group D (solid + micropapillary). In pathological stage II + IIIA, they were, 43.6% and 72.4% in B, 39.5% and 66.9% in C and 31.0% and 53.7% in D. Group D showed significant worst outcome both in stage I and II + IIIA. Up stage rate from clinical stage I to pathological stage II + IIIA was 0.0%, 3.7%, 15.9% and 33.3%. The frequency of lymph-vessel, vascular, pleura invasion and positive EGFR mutation were 0.0%, 0.0%, 0.0% and 57.1% in group A, 15.6%, 10.0%, 12.1% and 55.1% in B, 36.6%, 31.8%, 29.7% and 44.9% in C, 50.2%, 57.8%, 38.9% and 21.3% in D. In group D, lymph-vessel, vascular and pleura invasion were most, EGFR mutation was least frequent not only in pathological stage I but also stage II + IIIA. In multivariate analysis, age, pathological stage, vascular invasion, and group D were independent factors affected RFS and OS. CONCLUSION: Limited to lobectomy cases, solid + micropapillary was independent prognostic factor both in early and locally advanced stage. Its malignant degree was related to the frequency of pathological invasive factors and EGFR mutation status.

Limited resection for stage IA radiologically invasive lung cancer: a real-world nationwide database study.

OBJECTIVES: Radiologically invasive non-small-cell lung cancer, defined as consolidation size to maximum tumour diameter ratio of over 0.5, is associated with pathological invasiveness and worse prognosis. However, there are no real-world, nationwide database studies on limited resections that consider radiological invasiveness. This study aimed to investigate the prognostic validity of limited resection, such as segmentectomy and wedge resection, in cStage IA (TNM 8th edition) radiologically invasive lung cancer. METHODS: We conducted a retrospective analysis of patients who underwent complete resection according to the Japanese Joint Committee of Lung Cancer Registry Database. The relationship between surgical procedures and prognosis was examined using stratification by cT factor and radiological invasiveness. RESULTS: Among the 5,692 patients enrolled, lobectomy, segmentectomy and wedge resection were performed in 4,323 (80.0%), 657 (11.5%) and 712 (12.5%) patients, respectively. Multivariable analysis with or without propensity score matching indicated that older age, poor performance status and wedge resection were significantly associated with worse prognosis and that patients who underwent segmentectomy showed an equivalent prognosis to those who underwent lobectomy. Subset analyses revealed that segmentectomy showed an equivalent prognosis to lobectomy in patients with cT1b or less, but not in those with cT1c, especially for non-pure radiological invasive cT1c; 5-year overall survival rates were 91.4% vs 90.4% in cT1b with non-pure radiological invasiveness and 80.0% vs 83.8% in cT1b with pure radiological invasiveness, respectively. CONCLUSIONS: Segmentectomy can be an alternative to lobectomy in patients with radiologically invasive lung cancer with cT1b or less but not in those with cT1c.

Efficacy of platinum agents for stage III non-small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study.

BACKGROUND: Platinum-based chemoradiotherapy is the standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC). However, few studies have evaluated the efficacy of subsequent chemotherapy for relapsed NSCLC following platinum-based chemoradiotherapy. This study aimed to evaluate the efficacy of platinum-doublet chemotherapy as a second-line treatment for patients with unresectable stage III NSCLC. METHODS: We retrospectively evaluated patients with unresectable stage III NSCLC treated with cytotoxic chemotherapy following platinum-based chemoradiotherapy who were registered in a nationwide registry NSCLC database. Patients were divided into the platinum-doublet chemotherapy (platinum) group and single-agent chemotherapy (non-platinum) group based on the type of second-line chemotherapy. RESULTS: The platinum group (n = 119) showed significantly better overall survival (OS) than the non-platinum group (n = 201) (median OS: 21.5 vs. 10.5 months, hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.40-0.73, p < 0.001). OS from the beginning of chemoradiotherapy was also significantly better in the platinum group than in the non-platinum group (median OS: 34.9 vs. 21.8 months, HR: 0.58, 95% CI: 0.43-0.79, p = 0.001). In the multivariate analysis, platinum-doublet chemotherapy as second-line therapy, female sex, clinical stage IIIA, and duration of ≥ 8.6 months from the beginning of first-line therapy to the beginning of second-line therapy were associated with significantly better OS. CONCLUSION: Platinum-doublet chemotherapy as a second-line therapy may prolong survival in unresectable stage III NSCLC patients following platinum-based chemoradiotherapy. Thus, re-administration of platinum agents may be a promising treatment for unresectable stage III NSCLC treated with platinum-based chemoradiotherapy.

Preoperative renal dysfunction and long-term survival after surgery for non-small cell lung cancer.

OBJECTIVE: To investigate the association of preoperative renal dysfunction and long-term outcomes following lung cancer surgery. METHODS: Using the Japanese Lung Cancer Registry data, we retrospectively examined 16,377 patients who underwent surgery for non-small cell lung cancer during 2010. Patients' renal function status was categorized as follows: serum creatinine <1.5 mg/dL (control, n = 16,169), serum creatinine ≥1.5 mg/dL with no dialysis (nondialysis-dependent chronic kidney disease, n = 113), and dialysis-dependent end-stage renal disease (n = 95). The association of patients' characteristics with overall survival was evaluated using multivariate Cox proportional hazard model. RESULTS: The 5-year overall survival rates in patients with dialysis-dependent end-stage renal disease and with nondialysis-dependent chronic kidney disease were significantly worse than that in the control group (52.9% and 57.5% vs 78.0%; P < .001 for both comparisons), but were comparable to the reported 5-year overall survival rates in the natural history of end-stage renal disease (∼60%) and moderate to severe chronic kidney disease (∼50%). Cancer causes not related to lung cancer accounted for 62.2% of deaths in dialysis-dependent end-stage renal disease, which was more frequent than that in the control group (P = .002). Dialysis-dependent end-stage renal disease and nondialysis-dependent chronic kidney disease were independent risk factors for overall survival after lung cancer surgery (hazard ratio, 2.05 [P < .001] and hazard ratio, 2.04 [P = .001], respectively). CONCLUSIONS: Preoperative renal dysfunction may be adversely associated with overall survival after lung cancer surgery. Our findings could aid patients to set proper expectation of the risks and benefits about surgery for lung cancer.

Clinical Impacts of EGFR Mutation Status: Analysis of 5780 Surgically Resected Lung Cancer Cases.

BACKGROUND: To elucidate the clinical, pathologic, and prognostic impacts of epidermal growth factor receptor (EGFR) mutation and mutation subtypes in early-stage lung cancer, the study investigators conducted a retrospective analysis of the Japanese Joint Committee of Lung Cancer Registry database (a nationwide database for patients with surgically resected lung cancer; n = 18,973). METHODS: Of 13,951 patients classified as having nonsquamous non-small cell lung cancer in the database, 5780 patients (41.0%) had been tested for an EGFR mutation and were included in this study. RESULTS: An EGFR mutation was detected in 2410 patients (41.7%), and the presence of an EGFR mutation was significantly correlated with clinicopathologic factors such as the presence of ground-glass opacity (P < .001) and better prognosis. Analysis of initial recurrence sites identified significantly higher frequencies of brain and adrenal gland metastases in patients with and without an EGFR mutation, respectively. Of 2410 patients with EGFR mutations, 983 (40.8%) had an exon 19 deletion (Exon 19 Del), 1170 (48.5%) had an L858R mutation, and 257 (10.7%) had other EGFR mutations. A higher smoking rate was found in patients with other EGFR mutations (P = .02). In the comparison of Exon 19 Del and L858R, we found that Exon 19 Del correlated with younger age (P < .001), a higher rate of pure solid tumors (P < .001), advanced pathologic stage (trend P < .001), and poorer recurrence-free survival (P = .001). CONCLUSIONS: In addition to the clinicopathologic and prognostic impacts of EGFR mutation status, tumors with Exon 19 Del have a more aggressive phenotype and patients have a poorer prognosis than with L858R in early-stage lung cancers.

Clinical features and outcomes of patients with stage I multiple primary lung cancers.

The number of patients with multiple primary lung cancers (MPLC) is rising. We studied the clinical features and factors related to outcomes of MPLC patients using the database of surgically resected lung cancer (LC) cases compiled by the Japanese Joint Committee of Lung Cancer Registry. From the 18 978 registered cases, 9689 patients with clinical stage I non-small-cell lung cancer who achieved complete resection were extracted. Tumors were defined as synchronous MPLC when multiple LC was simultaneously resected or treatment was carried out within 2 years after the initial surgery; metachronous MPLC was defined as second LC treated more than 2 years after the initial surgery. Of these cases, 579 (6.0%) were synchronous MPLC and 477 (5.0%) metachronous MPLC, with 51 overlapping cases. Female sex, nonsmoker, low consolidation-tumor ratio (CTR), and adenocarcinoma were significantly more frequent in the synchronous MPLC group, whereas patients with metachronous MPLC had higher frequencies of male sex, smoker, chronic obstructive pulmonary disease (COPD), and nonadenocarcinoma. There was no significant difference in survival rate between patients with and without synchronous or metachronous MPLC. Age, gender, CTR for second LC, and histological combination of primary and second LC were prognostic indicators for both types of MPLC. Logistic regression analysis showed that female sex, history of malignant disease other than LC, and COPD were risk factors for MPLC incidence. The present findings could have major implications regarding MPLC diagnosis and identification of independent prognostic factors, and provide valuable information for postoperative management of patients with MPLC.

Construction of a survival tree for dependent censoring.

In this study, we examined the problem of constructing a model for time-to-event data considering dependent censoring. Our goal was to construct a set of subgroups of covariate space, wherein each element had the same failure model considering the dependency of failure and censoring times. As such, a model was constructed based on the parametric form from the identifiability problem of censoring. We used the copula to represent the dependency between failure and censoring times. Under the assumption of parametric models for failure and censoring times and a copula function, which have unknown parameters, we proposed a method for constructing the tree-structured model through the test statistics. We subsequently evaluated the performance of the splitting rule and tree obtained using the proposed method and compared it with the general method that assumes independent censoring through simulation studies. We also present the analysis results for AIDS clinical trial research to show the utility of the method.

Impact of the preoperative body mass index on the postoperative outcomes in patients with completely resected non-small cell lung cancer: A retrospective analysis of 16,503 cases in a Japanese Lung Cancer Registry Study.

OBJECTIVES: The aim of this study was to evaluate the impact of the preoperative body mass index (BMI) on the postoperative outcomes in patients with completely resected non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The data of patients with NSCLC in whom R0 resection was achieved were extracted from the database of NSCLC samples accumulated by the Japanese Joint Committee of Lung Cancer Registry in the year 2010, and the surgical outcomes including postoperative morbidity, mortality and the prognosis, were evaluated. RESULTS: Among 18,978 registered lung cancer cases, 16,509 patients (9996 men and 6513 women) were extracted. The median of age was 69 years old, and the histologic types included adenocarcinoma (n = 12,029), squamous cell carcinoma (n = 3286), large-cell carcinoma (n = 488) and others. The patients were divided into three groups according to their BMI: normal (BMI 18.5 to <25), underweight (BMI < 18.5) and overweight (BMI ≥ 25). Multivariate logistic regression analyses of factors associated with postoperative morbidity and mortality showed no significant differences among the three groups. In comparison to the normal group, the overall survival (OS) of the underweight group was significantly worse (p < 0.001) while that of the overweight group was marginally better (p = 0.075). A multivariate analysis of factors associated with OS showed that in addition to the age, sex and clinical stage, the preoperative BMI (underweight group vs. normal group: hazard ratio [HR] 1.417 [95% confidence interval {CI}: 1.278-1.572, p < 0.001], overweight group vs. normal group: HR 0.883 [95% CI: 0.806-0.967, p = 0.007]) was an independent prognostic factor. A multivariate analysis for the disease-free survival (DFS) also showed the preoperative BMI to be an independent significant prognostic factor. CONCLUSIONS: The preoperative BMI is an independent prognostic factor in patients with completely resected NSCLC. A low preoperative BMI was associated with significantly poor survival in Japan.

Key prognostic factors for EGFR-mutated non-adenocarcinoma lung cancer patients in the Japanese Joint Committee of Lung Cancer Registry Database.

INTRODUCTION: The efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-adenocarcinoma (ADC) non-small cell lung cancer patients is not well established. Herein, we investigated key prognostic factors influencing the efficacy of EGFR-TKIs in these patients. METHODS: A total of 12,320 lung cancer patients pathologically diagnosed in 2012 at teaching hospitals in Japan were retrospectively selected. The follow-up survey was closed in 2016. RESULTS: EGFR-mutated non-ADC patients were more prone to malignant pleural effusion (MPE) and distant metastasis than ADC patients (P = 0.071 and 0.022, respectively). EGFR-mutated ADC patients were likely to have a longer median overall survival (OS) than non-ADC patients [hazard ratio (HR) 1.3 (95 % CI, 0.97-1.8, P = 0.072)-29.5 months (95 % CI, 27.9-31.1 months) versus 19.5 months (95 % CI, 10.8-28.2 months) (P = 0.068)]. There was no significant difference in median OS between EGFR-positive ADC and non-ADC patients receiving treatment with first-generation EGFR-TKI. Among EGFR-positive non-ADC patients, the median OS was significantly longer for patients receiving EGFR-TKI treatment than for those who did not [HR 4.5 (95 % CI, 2.1-9.8, P < 0.001)-25.5 months (95 % CI, 8.1-42.9 months) versus 7.5 months (95 % CI, 3.4-11.6 months) (P < 0.001)]. While there was no significant difference in the median OS for ADC patients with either 19 del or L858R mutations, the median OS was significantly longer for EGFR-mutated non-ADC patients with 19 del than for those with L858R mutation (HR 3.2 [95 % CI, 1.5-6.9, P = 0.004]; it was not reached for 19 del and was 15.5 months for L858R [95 % CI, 6.6-24.4 months], P = 0.002). DISCUSSION: EGFR-mutated non-ADC patients were more prone to MPE and distant metastasis. Both ADC and EGFR del19-positive non-ADC patients can benefit from EGFR-TKI treatment, whereas EGFR L858R-positive non-ADC patients might require different therapeutic options.

Survival and prognostic factors in elderly patients receiving second-line chemotherapy for relapsed small-cell lung cancer: Results from the Japanese Joint Committee of Lung Cancer Registry.

OBJECTIVES: Most patients with small-cell lung cancer (SCLC) experience relapse because of the emergence of drug-resistant tumor cells. Therefore, second-line therapy is subsequently required to prolong their survival. However, it is unclear whether second-line chemotherapy can provide a survival benefit to elderly patients with relapsed SCLC. Therefore, this study aimed to evaluate survival and identify prognostic factors in an elderly population. MATERIALS AND METHODS: Based on a nationwide registry database of patients with SCLC (the Japanese Joint Committee of Lung Cancer Registry), we retrospectively reviewed medical records of patients aged ≥ 75 years with relapsed SCLC who subsequently received second-line chemotherapy. Survival time since the initiation of second-line chemotherapy was evaluated. RESULTS: Among 731 patients aged ≥ 75 years with SCLC who were accumulated by the nationwide registry database, this study included 228 patients, comprising 190 men and 38 women with a median age of 78 years. The number of patients with performance status (PS) of 0-1 and 2-4 was 196 and 32, respectively. The overall survival (OS) and 1-year survival rates were 7.5 months and 24 %, respectively. A multivariate analysis identified PS, clinical stage at the time of starting first-line therapy, and the interval from the start of first-line therapy to that of second-line therapy as independent prognostic factors. CONCLUSION: This study with the nationwide registry database showed that among the relapsed elderly SCLC patients who received second-line chemotherapy, a substantial OS may be expected in patients with good PS, at an early clinical stage at the time of starting first-line therapy, and with a longer interval from the start of first-line therapy to that of second-line chemotherapy.

A Japanese lung cancer registry study on demographics and treatment modalities in medically treated patients.

This study provides the benchmark statistics on medically treated patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in Japan. Demographic background, treatment, and prognosis were obtained from patients with lung cancer pathologically diagnosed in 2012, who received nonsurgical treatment. Descriptive statistics and their associations with survival were analyzed. In total, 12 320 patients were registered from 314 institutions in Japan. The median age was 70 years, and 73% of the patients were male. The number (%) of stages I, II, III, and IV diseases were 468 (3.8%), 421 (3.4%), 3260 (26.5%), and 8171 (66.3%), respectively. NSCLC and SCLC accounted for 9872 (80.1%) and 2353 (19.1%) patients, respectively. Thoracic radiotherapy-based therapy, chemotherapy, and palliative care alone were administered to 2572 (20.9%), 7790 (63.2%), and 1952 (15.8%) patients, respectively. Clinical TNM stage was one of the strongest prognostic factors with the 3-year survival rates of 62.9%, 47.3%, 40.0%, 27.8%, 37.5%, 26.5%, and 18.2% for stages IA, IB, IIA, IIB, IIIA, IIIB, and IV, respectively. Among 6158 patients with NSCLC treated with chemotherapy, the 3-year survival rate was 33.4% in patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) at some point in their clinical course, whereas it was 17.4% in patients who did not. The 3-year survival rate of SCLC was only 15.9%. In conclusion, approximately two-thirds of the patients were diagnosed as stage IV at the initial diagnosis. Use of EGFR-TKIs significantly improved the survival of patients with NSCLC.