Shimao Fukai

Performance Status and Smoking Status Are Independent Favorable Prognostic Factors for Survival in Non-small Cell Lung Cancer: A Comprehensive Analysis of 26,957 Patients with NSCLC

Background: Performance status (PS) is an important factor in determining survival outcome in non-small cell lung cancer (NSCLC) but is generally confounded by stage, age, gender, and smoking status. We investigated the prognostic significance of PS taking into account these important factors. Methods: Retrospective analysis of registry database of the National Hospital Study Group for Lung Cancer (NHSGLC) between1990 and 2005. Univariate analysis was performed using Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards model to identify independent prognostic factors. Results: A total of 26,957 patients with NSCLC were analyzed of which 12,613 patients (46.8%) had World Health Organization (WHO) PS = 0, 8,137 patients were never smokers (30.2%), and most of them were females (72.7%). The majority of PS = 0 patients presented with stage I disease (56.9%). Patients with PS = 0 constituted the group with the highest proportion of never smokers (36.7%). There was a significant difference in the median overall survival (OS) between patients with PS = 0 and PS = 1 (51.5 months versus 15.4 months, respectively; p < 0.0001) and among patients with various PS within individual American Joint Committee on Cancer stage (all p values <0.0001). Never smokers had significantly improved median OS than ever smokers (30.0 months versus 19.0 months, respectively; p < 0.0001). Multivariate analysis demonstrated good PS, never smoker (versus ever smoker; hazard ratio = 0.935, 95% confidence interval: 0.884–0.990; p = 0.0205), early stage, female gender, squamous cell carcinoma histology, and treatment were all as independent favorable prognostic factors. Conclusions: PS and smoking status are independent prognostic factors for OS in NSCLC.

Resection of the trachea infiltrated by thyroid carcinoma.

Twenty-four thyroid carcinoma patients with infiltration of the trachea were treated surgically. The histological diagnosis in these cases included papillary adenocarcinoma in 22 different patients, medullary carcinoma in one patient, and undifferentiated carcinoma in one patient. In 19 of the patients hemoptysis was noted, and dyspnea was present in ten patients. In 14 of the 24 patients the carcinoma was diagnosed by radiographs of the neck, while in seven patients it was demonstrated bronchoscopically. In three patients tracheal infiltration by thyroid carcinoma was diagnosed by biopsy of the tracheal wall at operation. When the tracheal wall was infiltrated by thyroid carcinoma, treatment consisted of circumferential resection of the involved segment of the trachea followed by an end-to-end anastomosis. Of the 24 patients, 17 survived and six died. In the 17 patients who survived, 13 were disease free. Of this number, six survived more than five years after the initial tracheal resection.

Gender, Histology, and Time of Diagnosis Are Important Factors for Prognosis: Analysis of 1499 Never-Smokers with Advanced Non-small Cell Lung Cancer in Japan

Background: There has been a growing interest in lung cancer in never-smokers. Methods: Utilizing a database from the National Hospital Study Group for Lung Cancer, information for never-smokers and ever-smokers with advanced non-small cell lung cancer was obtained from 1990 to 2005, including clinicopathologic characteristics, chemotherapy response, and survival data. Time of diagnosis was classified into two periods: 1990–1999 and 2000–2005. Multivariate analysis was performed using the Cox regression and logistic regression method, including gender, age, performance status, histology, stage, and period of diagnosis. Results: There were 1499 never-smokers and 3455 ever-smokers with advanced stage IIIB and IV diseases who received cytotoxic chemotherapy. Never-smokers generally included more females, were younger, with better performance status and more adenocarcinoma diagnosed (p < 0.0001 for all). Smoking status was a significant prognostic factor (never-smoker versus ever-smoker; hazard ratio [HR] = 0.880, 95% confidence interval [CI]: 0.797–0.970; p = 0.0105). In separate multivariate analysis for never-smokers and ever-smokers, female gender and better performance status (p < 0.0001 for both) were both favorable prognostic factors. However, adenocarcinoma histology (versus squamous cell carcinoma; HR = 0.790, 95% CI: 0.630–0.990; p = 0.0403) and the period after 2000 (versus before 2000; HR = 0.846, 95% CI: 0.731–0.980; p = 0.0254) were significant only in the never-smokers, and younger age (HR = 1.007, 95% CI: 1.003–1.011; p = 0.0010) was significant only in the ever-smokers. In an exploratory analysis, different profiles were observed in predictive factors for chemotherapy response between the two groups. Conclusions: Never-smokers with non-small cell lung cancer lived longer than ever-smokers. Gender, histology, and time of diagnosis are important factors for prognosis in these patients.

Effect of gefitinib re-challenge to initial gefitinib responder with non-small cell lung cancer followed by chemotherapy.

PURPOSE We investigated the efficacy of gefitinib re-challenge for the patients who responded to initial treatment with gefitinib and acquired resistance to gefitinib thereafter. EXPERIMENTAL DESIGN Medical records were retrospectively reviewed in the hospitals of National Hospital Organization from August 2002 to August 2008. Patients histologically or cytologically confirmed NSCLC were eligible if they once responded to initial treatment with gefitinib (CR, PR or SD) and then re-treated with gefitinib following subsequent chemotherapy. RESULT Twenty patients (16 PR, 4 SD) were enrolled in this study. After re-treatment with gefitinib, 5 cases showed PR and 8 cases SD. Overall response rate was 25% (5/20) and disease control rate was 65% (13/20) in the gefitinib re-treated patients. Median survival time from the start of the initial gefitinib and from the start of the re-administration of gefitinib were 34.0 and 10.0 months, respectively. CONCLUSION Re-administration of gefitinib was effective and therefore should be considered as one of the treatment option for the patients with NCLCL who once responded and acquired resistant to gefitinib following subsequent chemotherapy.

Phase I/II Study of Docetaxel and S-1 in Patients with Previously Treated Non-small Cell Lung Cancer

Introduction: The aim of this study was to determine and evaluate the recommended dose of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 and evaluate the efficacy and safety in patients with previously treated non-small cell lung cancer. Methods: In phase I, patients with previously treated non-small cell lung cancer were treated with docetaxel (starting dose 40 mg/m2) intravenously on day 1 and oral administration of S-1 at a fixed dose of 80 mg/m2 on days 1 to14 every 3 weeks. The recommended dose was the dose level preceding the maximum tolerated dose; once determined, patients were enrolled in phase II. Results: The recommended dose of docetaxel was 40 mg/m2 in combination with S-1 80 mg/m2/d. Of 30 patients enrolled in phase II part, 29 patients were eligible and analyzed. No complete response and 7 (24.1%) partial responses were observed, for an overall response rate of 24.1% (95% confidence interval, 10.3-43.5%). Median overall survival was 11.8 months. The 1-year survival rate was 42%. The grade 3 to 4 hematologic toxicities were neutropenia (34.5%), leukopenia (20.6%), and anemia (10.3%). The grade 3 to 4 nonhematological toxicities included fever 2 (6.9%), diarrhea 1 (3.4%), stomatitis 1 (3.4%), cerebral infarction 1 (3.4%), and pneumonitis 1 (3.4%). There was one treatment-related death due to relapse of drug induced pneumonitis. Conclusions: This combination chemotherapy is highly active and well tolerated in previously treated patients with non-small cell lung cancer. These results are encouraging and warrant additional investigation.

Long-term prognosis of patients with lung cancer detected on low-dose chest computed tomography screening

The effectiveness of lung cancer screening using low-dose chest computed tomography (CT) remains elusive. The present study examined the prognosis of patients with lung cancer detected on CT screening in Japanese men and women. Subjects were 210 patients with primary lung cancer identified on CT screening at two medical facilities in Hitachi, Japan, where a total of 61,914 CT screenings were performed among 25,385 screenees between 1998 and 2006. Prognostic status of these patients was sought by examining medical records at local hospitals, supplemented by vital status information from local government. The 5-year survival rate was estimated according to the characteristics of patients and lung nodule. A total of 203 (97%) patients underwent surgery. During a 5.7-year mean follow-up period, 19 patients died from lung cancer and 6 died from other causes. The estimated 5-year survival rate for all patients and for those on stage IA was 90% and 97%, respectively. Besides cancer stage, smoking and nodule appearance were independent predictors of a poor survival; multivariable-adjusted hazard ratio (95% confidence interval) was 4.7 (1.3, 16.5) for current and past smokers versus nonsmokers and 4.6 (1.6, 13.9) for solid nodule versus others. Even patients with solid shadow had a 5-year survival of 82% if the lesion was 20mm or less in size. Results suggest that lung cancers detected on CT screening are mostly curative. The impact of CT screening on mortality at community level needs to be clarified by monitoring lung cancer deaths.

Lung cancer in patients with chronic pyothorax.

Background and objective:  The aim of this study was to describe the features of lung cancers associated with chronic tuberculous pyothorax.

Impact of main bronchial lymph node involvement in pathological T1-2N1M0 non-small-cell lung cancer: multi-institutional survey by the Japan National Hospital Study Group for Lung Cancer

PurposeAccording to the TNM classification revised in 1997, stage II non-small-cell lung cancer (NSCLC) has an unfavorable prognosis. The purpose of this study was to analyze the prognostic factors for pathological T1-2N1M0 patients with NSCLC and elucidate the significance of main bronchial lymph nodes involvement.MethodsThis retrospective study analyzed patients in a prospective database of cases from an 11-year period (operations from 1992 to 2002, follow-up data until March 2008) obtained from the Japan National Hospital Study Group for Lung Cancer. Among them, a total of 319 patients with pathological T1-2N1M0 disease were identified, and all dissected lymph nodes were classified using the Naruke map.ResultsThe cumulative overall 5-year survival rate for patients with intralobar or interlobar lymph node involvement (n = 266) was 56.8%, and that for those with main bronchial lymph node involvement (n = 53) was 40.4% (P = 0.002). Among patients with multiple-station N1 nodal involvement including the main bronchial lymph nodes, patients with a lower lobe tumor (n = 12) had a significantly worse prognosis than those with an upper lobe tumor (n = 9) (13.3% vs. 55.6%, P = 0.033). Multivariate analysis demonstrated that age, histology, tumor size, and main bronchial lymph node involvement were independent prognostic factors for patients with pathological T1-2N1M0 disease.ConclusionInvolvement of the main bronchial lymph nodes is a significant factor to predict a worse prognosis in pathological T1-2N1M0 patients with NSCLC.

MALIGNANT CHANGE IN A SOLITARY HAMARTOMA OF THE LUNG

A case report of a malignant hamartoma of the lung observed in a 36‐year‐old housewife was presented. The hamartoma was non‐chondromatous (fibromyomatous), located beneath the pleura of the left upper lobe. The malignant lesion corresponded to anaplastic carcinoma of the lung. A review of the literatures on the malignant hamartoma of the lung revealed rare incidences of the tumor, but hamartoma and hamartomatous lesions of the lung should be regarded as one of the histopathological backgrounds where pulmonary carcinoma may arise. ACTA PATH. JAP. 27: 541–546, 1977.