Takeshi Nawa

A decrease in lung cancer mortality following the introduction of low-dose chest CT screening in Hitachi, Japan

Recent US clinical trial demonstrated that CT screening prevents lung cancer death among high risk individuals. However, it remains unclear whether wide implementation of low-dose CT screening for lung cancer can decrease mortality in the community. Among residents in Hitachi City (Japan), where nearly 40% of inhabitants aged 50-69 years were estimated to have participated in the screening at least once from 1998 through 2009, the trend of lung cancer mortality was described in relation to the timing of implementation of the CT screening. Cancer mortality data were obtained from regional cancer registry and standardized mortality ratio (SMR) of lung cancer was calculated for each 5-year period during 1995-2009. In both men and women aged 60 years or older, age-specific lung cancer mortality rates were generally lower during 2005-2009 as compared with those during 1995-2004. For combined men and women aged 50-79 years, SMR was nearly unity prior to or during introductory phase of CT screening and during early period of implementation; however, it was significantly decreased during 2005-2009, well after the implementation of CT screening, with SMR (95% confidence interval) being 0.76 (0.67-0.86). Results suggest that wide implementation of low-dose chest CT screening may decrease lung cancer mortality in the community 4-8 years after introduction of the screening.

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.

Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer

To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The study involved 307 patients treated with erlotinib at 14 sites (17 departments) in Ibaraki (Japan) between December 2007 and December 2010. The tumor response and disease control rates were 11.1 and 46.3% in all patients, respectively. The median time to treatment failure and survival time were 1.6 months (95% confidence interval, 41–57 days) and 5.3 months (134–181 days) in all patients, respectively. Survival was significantly prolonged in EGFR mutation-positive patients compared with negative patients. EGFR mutation-negative patients who presented with a skin rash had significantly prolonged survival compared with those without a skin rash. The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies. We deduce that erlotinib is effective against NSCLC and is tolerated in clinical practice.

Low-dose computed tomography screening in Japan.

Lung cancer is a leading cause of cancer death in both male and female individuals in Japan. The effect of screening using chest radiography is assumed to be limited. In Japan, screening using low-dose computed tomography (CT) was initiated in 1993, and its dissemination has progressed with studies evaluating its efficacy, although it is not officially recommended. In addition to the academic activities of the Japanese Society of CT Screening, certification of physicians and radiologic technologists by the Japan Accreditation Council for CT Screening has been progressing. Currently, several hundred thousand low-dose CT screenings are performed annually in Japan. In Hitachi City, Ibaraki Prefecture, low-dose CT screening among employees and in communities started in 2001, and it was estimated that 40% of 50- to 69-year-old citizens had undergone screening at least once by March 2009. The lung cancer mortality rate in citizens in this age group decreased by 24% in 2005 to 2009 compared with the national statistics. Low-dose CT screening targeting the general population may be effective, but it is necessary to consider the target and interval of screening separately from those for the high-risk group. Observational study may play a role in evaluating the efficacy of screening in Japan.

Erlotinib for elderly patients with non-small-cell lung cancer: Subset analysis from a population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The incidence and mortality of lung cancer have increased worldwide over the last decades, with an observed increased incidence particularly among elderly populations. It has not yet been determined whether erlotinib therapy exhibits the same efficacy and safety in elderly and younger patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective subgroup analysis of data from a population-based observational study was to assess the efficacy and safety of erlotinib in an elderly (≥75 years, n=74) and a younger group of patients (<75 years, n=233) who received treatment for NSCLC. The time to treatment failure was similar in the elderly [median, 62 days; 95% confidence interval (95% CI): 44–80 days] compared with the younger group (median, 46 days; 95% CI: 35–53 days) (P=0.2475). The overall survival did not differ between the elderly and younger groups (median, 170 days; 95% CI: 142–239 days vs. median, 146 days; 95% CI: 114–185 days, respectively) (P=0.7642). The adverse events did not differ in incidence between the groups and were manageable, regardless of age. Among the NSCLC patients receiving erlotinib treatment, the outcomes of the elderly (≥75 years) and younger (<75 years) groups of patients were similar in our population-based observational study.

Efficacy of computer-aided diagnosis in lung cancer screening with low-dose spiral computed tomography: receiver operating characteristic analysis of radiologists’ performance

PurposeThe aim of this study was to evaluate the efficacy of a computer-aided diagnosis (CAD) system we developed that can also respond to subsolid nodules, for lung cancer screening using low-dose spiral computed tomography (LDCT).Materials and methodsThe institutional review board approved this study. A total of 30 positive cases (including 15 lung cancer cases) that needed further examination and 30 negative cases were used for the observer performance study. Three thoracic radiologists, five general radiologists, and three residents participated in this study in which they first read the original CT image on its own and then reassessed the same image with the assistance of CAD. Radiologists’ performance was evaluated using receiver operating characteristic (ROC) analysis.ResultsThe Az values without and with CAD were 0.872 and 0.910 for the thoracic radiologists, 0.864 and 0.924 for general radiologists, and 0.875 and 0.837 for residents, respectively. The detection accuracy improved significantly for the thoracic and general radiologists with our CAD system; however, no statistically significant difference between without or with CAD was seen for residents.ConclusionThis CAD system is beneficial in the detection of pulmonary nodules on LDCT when used by experienced radiologists.

Low-dose CT screening for lung cancer reduced lung cancer mortality in Hitachi City

Abstract Purpose: To detect early, curable lung cancer, screening using low-dose CT (CT screening) was initiated in Japan and Western countries around the early 1990s. Material and methods: In 2013, the National Lung Screening Trial (NLST) reported that annual CT screening for high-risk participants leads to a 16% reduction in lung cancer death. In Hitachi City, CT screening for citizens 50 years of age or older was started in 1998, and 30% of the citizens had received a CT examination at least once by 2006. Results: We reported excellent survival (5-year survival of 90%) of 210 patients with lung cancer detected by CT screening. Based on a time trend analysis, a significant reduction (24%) in lung cancer mortality was observed 4 to 8 years after the introduction of CT screening among Hitachi residents. CT images can detect numerous smoking-related factors represented by pulmonary emphysematous change (CT emphysema). If we can evaluate the risk of respiratory disease according to these images, the benefits of screening are expected to increase further. Conclusion: To establish the effectiveness of CT screening for the general population, an optimum screening schedule is desired based on the risk of individuals. In addition, long-term follow-up is necessary to evaluate the effects of radiation exposure.

Real Clinical Practice of Using Afatinib Therapy in NSCLC Patients with an Acquired EGFR T790M Mutation

Background/Aim: To describe real clinical outcomes when using afatinib therapy to treat non-small cell lung cancer patients who have an acquired EGFR T790M mutation. Materials and Methods: A retrospective chart review was conducted from January 2013 to November 2017 sourced from 15 medical institutes that cover a population of three million people. Results: There were 74 patients who met the above-mentioned criteria. Treatment outcomes with afatinib, in patients with or without tyrosine kinase inhibitor (TKI) therapy prior to afatinib, were similar to previously reported clinical trials. Stratification of patients by the presence or absence of TKI pretreatment before afatinib, and the presence or absence of an acquired T790M mutation found no statistical difference in overall survival. Conclusion: This population-based study found that the disadvantages of pretreatment before afatinib, and absence of an acquired T790M EGFR mutation, could be overcome by an appropriate treatment strategy in clinical practice.