Effects of the Cessation of Mass Screening for Neuroblastoma at 6 Months of Age: A Population-Based Study in Osaka, Japan.

BACKGROUND: In 2004, the Japanese government halted the 6-month mass screening program for neuroblastoma. We investigated whether its cessation had led to an increase not only in mortality due to this disease but also in the incidence of advanced-stage disease among older children. METHODS: Study subjects were neuroblastoma patients retrieved from the population-based Osaka Cancer Registry. Trends of incidence and mortality from neuroblastoma were analyzed by calendar year and birth cohort. Prognostic factors, including stage and v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) oncogene status, were compared before and after the cessation of mass screening. RESULTS: Age-standardized incidence rates in 2005-2009 (the cessation period of mass screening; 11.1 per million) were similar to those in 1975-1979 (the pre-screening period; 8.6 per million). Age-standardized mortality rates tended to decrease from 1975-1979 (4.0 per million) to 2005-2009 (2.7 per million) in parallel with the improvement in survival. Analysis by birth cohort indicated that the mortality rates in 2004-2005 (after cessation) for children 0-4 years of age were lower than those in 1975-1979 (O:E ratio 0.25; 95% confidence interval, 0.03-0.90). For children 1-9 years of age, there was a not significant difference in the distribution of stage, MYCN oncogene status, and DNA ploidy between 1991-2003 (the mass screening period) and 2004-2008 (after cessation). CONCLUSIONS: The cessation of mass screening for neuroblastoma does not appear to have increased mortality due to this disease or incidence of advanced-stage disease among older children.

Investigation of Spatial Clustering of Biliary Tract Cancer Incidence in Osaka, Japan: Neighborhood Effect of a Printing Factory.

BACKGROUND: In 2013, an unusually high incidence of biliary tract cancer among current or former workers of the offset color proof printing department of a printing company in Osaka, Japan, was reported. The purpose of this study was to examine whether distance from the printing factory was associated with incidence of biliary tract cancer and whether incident biliary tract cancer cases clustered around the printing factory in Osaka using population-based cancer registry data. METHODS: We estimated the age-standardized incidence ratio of biliary tract cancer according to distance from this printing factory. We also searched for clusters of biliary tract cancer incidence using spatial scan statistics. RESULTS: We did not observe statistically significantly high or low standardized incidence ratios for residents in each area categorized by distance from the printing factory for the entire sample or for either sex. The scan statistics did not show any statistically significant clustering of biliary tract cancer incidence anywhere in Osaka prefecture in 2004-2007. CONCLUSIONS: There was no statistically significant clustering of biliary tract cancer incidence around the printing factory or in any other areas in Osaka, Japan, between 2004 and 2007. To date, even if some substances have diffused outside this source factory, they do not appear to have influenced the incidence of biliary tract cancer in neighboring residents.

Joint and independent effect of alcohol and tobacco use on the risk of subsequent cancer incidence among cancer survivors: A cohort study using cancer registries.

Drinking alcohol and smoking tobacco are major modifiable risk factors for cancer. However, little is known about whether these modifiable factors of cancer survivors are associated with subsequent primary cancer (SPC) incidence, regardless of the first cancer sites. 27,762 eligible cancer survivors diagnosed between 1985 and 2007 were investigated for SPC until the end of 2008, using hospital-based and population-based cancer registries. The association between drinking, smoking and combined drinking and smoking (interaction) at the time of the first cancer diagnosis and incidence of SPCs (i.e., all SPCs, alcohol-related, smoking-related and specific SPCs) was estimated by Poisson regression. Compared with never-drinker/never-smoker, the categories ever-drinker/ever-smoker, current-drinker/current-smoker and heavy-drinker/heavy-smoker had 43-108%, 51-126% and 167-299% higher risk for all, alcohol-related and tobacco-related SPCs, respectively. The interaction of drinking and smoking had significantly high incidence rate ratios (IRRs) for SPCs among ever-drinker/ever-smoker and current-drinker/current-smoker, although ever drinking did not show a significant risk. Ever-drinker/ever-smoker had also significantly higher IRRs for esophageal and lung SPCs than never-drinker/never-smoker. Among comprehensive cancer survivors, ever and current drinkers only had a SPC risk when combined with smoking, while ever and current smokers had a SPC risk regardless of drinking status. Heavy drinking and heavy smoking were considered to be independent additive SPC risk factors. To reduce SPC incidence, it may be necessary (i) to reduce or stop alcohol use, (ii) to stop tobacco smoking and (iii) dual users, especially heavy users, should be treated as a high-risk population for behavioral-change intervention.

Advance and stagnation in the treatment of patients with lymphoma and myeloma: Analysis using population-based cancer registry data in Japan from 1993 to 2006.

There have been significant advances in the treatment of patients with lymphoma and myeloma. Although the improvements in survival outcome have been clearly addressed by clinical trials, these studies includes patients who are otherwise healthy and would be eligible for trials that the actual improvement in survival in the general patient population over time is yet to be elucidated. Therefore, we reviewed the cancer-registry data of patients with lymphoma and myeloma in Japan from 1993 to 2006 and estimated relative survival (adjusted for competing causes of death in same-age members of the general population) according to three periods of diagnosis (1993-1997, 1998-2002 and 2003-2006). We also estimated conditional 5-year relative survival (5-year survival rate of patients who have survived 5 years). A total of 26,141 patients were reviewed and analyzed. Relative survival improved in Hodgkin lymphoma (HL, N = 853, +20% improvement), diffuse large B-cell lymphoma (DLBCL, N = 4,919, +14% improvement) and follicular lymphoma (FL, N = 1,333, +13% improvement). In contrast, we found no significant improvement in survival since 1993 in peripheral T-cell lymphoma (PTCL, N = 667, +4% improvement), adult T-cell leukemia/lymphoma (ATLL, N = 2,166, -5% improvement) or multiple myeloma (MM, N = 4,914, -2% improvement). Conditional 5-year survival of HL, DLBCL, FL, PTCL, ATLL and MM was 88, 87, 79, 63, 53 and 45%, respectively. Relative survival of patients with HL, DLBCL and FL significantly improved from 1993 to 2006 in Japan; in contrast, no improvement was seen in other diseases, suggesting unmet need of novel treatment strategies.

An updated report on the trends in cancer incidence and mortality in Japan, 1958-2013.

The analysis of cancer trends in Japan requires periodic updating. Herein, we present a comprehensive report on the trends in cancer incidence and mortality in Japan using recent population-based data. National cancer mortality data between 1958 and 2013 were obtained from published vital statistics. Cancer incidence data between 1985 and 2010 were obtained from high-quality population-based cancer registries of three prefectures (Yamagata, Fukui and Nagasaki). Joinpoint regression analysis was performed to examine the trends in age-standardized rates of cancer incidence and mortality. All-cancer mortality decreased from the mid-1990s, with an annual percent change of -1.3% (95% confidence interval [CI]: -1.4, -1.3). During the most recent 10 years, over 60% of the decrease in cancer mortality was accounted for by a decrease in stomach and liver cancers (63% for males and 66% for females). The long-term increase in female breast cancer mortality, beginning in the 1960s, plateaued in 2008. All-cancer incidence continuously increased, with annual percent changes of 0.6% (95% CI: 0.5, 0.8) between 1985 and 2005, and 1.8% (95% CI: 0.6, 2.9) between 2005 and 2010. During the most recent 10 years, almost half of the increase in cancer incidence was accounted for by an increase in prostate cancer (60%) in males and breast cancer (46%) in females. The cancer registry quality indices also began to increase from ∼2005. Decreases in stomach and liver cancers observed for incidence and mortality reflect the reduced attribution of infection-related factors (i.e. Helicobacter pylori and hepatitis virus). However, it should be noted that cervical cancer incidence and mortality rates began to increase from ∼1990.

Long-term survival and conditional survival of cancer patients in Japan using population-based cancer registry data.

Although we usually report 5-year cancer survival using population-based cancer registry data, nowadays many cancer patients survive longer and need to be followed-up for more than 5 years. Long-term cancer survival figures are scarce in Japan. Here we report 10-year cancer survival and conditional survival using an established statistical approach. We received data on 1,387,489 cancer cases from six prefectural population-based cancer registries in Japan, diagnosed between 1993 and 2009 and followed-up for at least 5 years. We estimated the 10-year relative survival of patients who were followed-up between 2002 and 2006 using period analysis. Using this 10-year survival, we also calculated the conditional 5-year survival for cancer survivors who lived for some years after diagnosis. We reported 10-year survival and conditional survival of 23 types of cancer for 15-99-year-old patients and four types of cancer for children (0-14 years old) and adolescent and young adults (15-29 years old) patients by sex. Variation in 10-year cancer survival by site was wide, from 5% for pancreatic cancer to 95% for female thyroid cancer. Approximately 70-80% of children and adolescent and young adult cancer patients survived for more than 10 years. Conditional 5-year survival for most cancer sites increased according to years, whereas those for liver cancer and multiple myeloma did not increase. We reported 10-year cancer survival and conditional survival using population-based cancer registries in Japan. It is important for patients and clinicians to report these relevant figures using population-based data.

Socioeconomic inequalities in cancer survival: a population-based study of adult patients diagnosed in Osaka, Japan, during the period 1993-2004.

BACKGROUND: Long-term recession of the Japanese economy during the 1990s led to growing social inequalities whilst health inequalities also appeared. The 2007 National Cancer Control Program of Japan targeted "equalisation of cancer medical services", but the system to monitor health inequalities was still inadequate. We aimed to measure socioeconomic inequalities in cancer survival in Japan. MATERIAL AND METHODS: We analysed 13 common invasive, primary, malignant tumours diagnosed from 1993 to 2004 and registered by the population-based Cancer Registry of Osaka Prefecture. An ecological socioeconomic deprivation index based on small area statistics, divided into quintile groups, was linked to patients according to their area of residence at the time of diagnosis. We estimated one-, five-year and conditional five-year net survival by sex, period of diagnosis (1993-1996/1997-2000/2001-2004) and deprivation group. Changes in survival over time, deprivation gap in survival, and change in deprivation gap were estimated at one and five years after diagnosis using variance-weighted least square regression. RESULTS: The deprivation gap in one-year net survival was narrower than in five-year net survival and conditional five-year survival. During the study period, there was no change in deprivation gap, except for reductions for pancreas (men) and stomach (women), and an increase for lung (men) in one-year survival. We observed a linear association between level of survival and deprivation gap at five years and conditional five years, but no association at one-year survival. CONCLUSION: A wide deprivation gap in survival was observed in most of the adult, solid, malignant tumours, within the universal healthcare system in Japan. Overall, cancer survival improved in Osaka without any widening of inequalities in cancer survival in 1993-2004, shortly after the long-term economic recession and deep modifications in the social and work environments in Japan. The longer term impact of the recession on inequalities in cancer survival needs to be monitored using population-based cancer registry data.

Short-term projection of cancer incidence in Japan using an age-period interaction model with spline smoothing.

OBJECTIVE: In Japan, population-based cancer incidence data are reported several years behind the latest year of cancer mortality data. To bridge this gap, we aimed to determine a short-term projection method for cancer incidence. METHODS: Data between 1985 and 2007 were obtained from the population-based cancer registries in four prefectures (Miyagi, Yamagata, Fukui and Nagasaki). Three projection models were examined: generalized linear model with age and period (A + P linear); generalized linear model with age, period and their interactions (A*P linear); and generalized additive model with age, period and their interactions smoothed by spline (A*P spline). We performed a 5-year projection for the years 2000 and 2005, based on the data of 1985-95 and 1985-2000, respectively. Seven cancer sites (stomach, liver, colorectal, lung, female breast, cervix uteri and prostate) and all cancers combined were analyzed. The accuracy of projection was evaluated by whether each observed number fell within the 95% confidence interval of the projected number. RESULTS: The A*P spline model accurately projected 8 of 13 cancer site-sex combinations, whereas the number of site-sex combinations of accurate projection was 2 and 6 for A + P linear and A*P linear models, respectively. For liver and colorectal cancers, the A*P spline model alone performed accurate projections; the relative differences between projected and observed numbers of cancer incidence ranged between -0.4 and +10.9% for the A*P spline, and between +7.4 and +37.6% for the other two models. All three models failed to project sudden increases in prostate cancer between 2000 and 2005. CONCLUSIONS: The A*P spline model is a candidate method for the projection of cancer incidence in Japan. However, we need a continuous validation for prostate cancer.

Does removal of out-of-pocket costs for cervical and breast cancer screening work? A quasi-experimental study to evaluate the impact on attendance, attendance inequality and average cost per uptake of a Japanese government intervention.

Reducing out-of-pocket costs is known to improve mammography attendance, but an evidence gap remains concerning Pap smear testing. The Japanese government implemented a politically determined intervention to remove out-of-pocket costs for Pap smear tests and mammography attendance, costing US$148 million, in 2009. It targeted women when they reached the first year of a 5-year age group (i.e., 20, 25, 30 years) with the aim of reducing attendance inequality. Our objective is to evaluate the intervention in terms of uptake and average cost per uptake for cancer screening attendance and to assess socioeconomic inequalities in cancer screening attendance pre- and postintervention. A quasi-experimental study utilizing national repeated cross sections, observed pre- and postintervention, which compared intervention and comparison groups by the Difference-in-Differences method, was conducted. Outcome measures were uptake of cancer screening attendance resulting from the intervention with average cost per uptake and broad inequality indicators for cancer screening attendance according to socioeconomic inequality. In total, 34,043 age-eligible, noninstitutionalized women were analyzed. Uptake among the overall population was 13.9% point in the age- and income-adjusted model for Pap smear and 9.8% point for mammography, with an average cost of US$139 per uptake. The intervention increased inequality indicators in Pap smear attendance (more than +100%) but decreased inequality in mammography attendance (ranging from -12.9 to -74.1%) within the intervention group. In conclusion, removing out-of-pocket costs improves female cancer screening uptake in Japan but may not be cost-saving. Although cost removal reduces inequalities in attendance for mammography, it appears to increase inequalities in Pap smear attendance.

Conditional survival for longer-term survivors from 2000-2004 using population-based cancer registry data in Osaka, Japan.

BACKGROUND: We usually report five-year survival from population-based cancer registries in Japan; however these survival estimates may be pessimistic for cancer survivors, because many patients with unfavourable prognosis die shortly after diagnosis. Conditional survival can provide relevant information for cancer survivors, their family and oncologists. METHODS: We used the period approach to estimate the latest 10-year survival of 38,439 patients with stomach, colorectal, lung, breast and prostate cancer diagnosed between 1990 and 2004 and followed-up from 2000-04 in Osaka, Japan. Conditional survival is an estimate, with the pre-condition of having already survived a certain length of time. Conditional five-year relative survival of one to five years after diagnosis was calculated by site, age and stage for survivors under the age of 70. RESULTS: Five-year relative survival for stomach cancer was 60%. Conditional five-year relative survival was 77% one year after diagnosis and 97% five years after diagnosis. This means that 97% of patients who survive five years after diagnosis can survive a further five years. Conditional five-year relative survival improved successively with each additional year that patients lived after diagnosis for stomach, colorectal and lung cancer. These figures for breast and prostate cancer were stable at high survival. Liver cancer did not show an increase in conditional five-year survival. CONCLUSION: Conditional five-year survival is a relevant figure for long-term cancer survivors in Japan. It is important for population-based cancer registries to provide figures which cancer patients and oncologists really need.

Incidence of soft tissue sarcoma focusing on gastrointestinal stromal sarcoma in Osaka, Japan, during 1978-2007.

To clarify the incidence of soft tissue sarcoma and gastrointestinal stromal sarcoma in Osaka, Japan, we analyzed Osaka Cancer Registry's data. We identified a total of 6998 cases, except for those of bones and joints, during 1978-2007. The age-adjusted incidence rate of those sarcomas was 2.7 per 100 000 (male 2.8, female 2.6) person-years. The trend in the incidence for the last 10-year period (1998-2007) increased significantly overall and for females, while it was not significant for males. Except for cases not otherwise specified, the most prevalent histological subtype was leiomyosarcoma in digestive organs and gastrointestinal stromal sarcoma, followed by leiomyosarcoma excluding that in digestive organs and liposarcoma. Gastrointestinal stromal sarcomas were registered for the first time in 1988 and have increased since 1999, while leiomyosarcomas in digestive organs have decreased. Gastrointestinal stromal sarcoma might have been diagnosed as leiomyosarcoma in digestive organs before using immunohistochemistry.

Descriptive epidemiology of bile duct carcinoma in Osaka.

OBJECTIVE: An outbreak of bile duct carcinoma has been reported among workers in a certain printing company in Osaka, Japan, where there was no descriptive epidemiological study. We conducted descriptive studies of bile duct carcinoma in Osaka. METHODS: Based on the data from the Osaka Cancer Registry, the incidence and survival rate of intrahepatic and extrahepatic bile duct carcinomas, gallbladder carcinomas and hepatocellular carcinomas were analyzed. The study period was between 1975 and 2007, and total 108 407 incidents were retrieved from the Osaka Cancer Registry. Age- and sex-specific incidence rates and age-standardized incidence rates were calculated. Standardized incidence ratios were evaluated for each municipality in Osaka prefecture. Relative 5-year survival rates were also calculated for the cases diagnosed between 1993 and 2005. RESULTS: Age-standardized incidence rates of bile duct carcinomas increased distinctly from the middle of the 1970s to the early 1980s in males and the 1990s in females. However, no distinct increase in the incidence rates was observed in 2000. Standardized incidence ratios of those did not exceed the unity significantly in males between 1992 and 2007. In females, standardized incidence ratios exceeded the unity significantly in a few regions without any relation to the location of the printing company where the outbreak was reported. The relative 5-year survival rate is generally poor; however, patients who were diagnosed with localized disease at the age of 25-49 years showed a better survival. CONCLUSION: Neither change in trend nor regional accumulation of bile duct carcinoma was confirmed in Osaka, corresponding to the outbreak reported in the printing company.

An updated report of the trends in cancer incidence and mortality in Japan.

OBJECTIVE: The analysis of cancer trends in Japan has only been sporadically reported. We present a comprehensive report on the trends in cancer incidence and mortality in Japan using the most recent population-based data. METHODS: National cancer mortality data between 1958 and 2011 were obtained from published vital statistics. Cancer incidence data between 1985 and 2007 were obtained from high-quality population-based cancer registries of four prefectures (Miyagi, Yamagata, Fukui and Nagasaki). Joinpoint regression analysis was performed to examine the trends in age-standardized rates of cancer incidence and mortality. RESULTS: All-cancer mortality decreased from the mid-1990s, with an annual percent change of -1.3% (95% confidence interval: -1.4, -1.3), while all-cancer incidence continually increased from 1985, with an annual percent change of 0.7% (95% confidence interval: 0.6, 0.8). Major cancer sites, particularly the liver, colorectum and lung (males), showed a pattern of increasing incidence and mortality rates until the mid-1990s, stabilizing or decreasing thereafter. Stomach cancer showed a long-term decreasing trend for both incidence and mortality, while female breast cancer showed a continuously increasing trend. The incidence of prostate cancer, particularly at the localized stage, increased rapidly between 2000 and 2003, while that of mortality decreased from 2004. No changes were detected in the incidence or mortality for colorectal, female breast or cervical cancers after the establishment of national screening programs for these cancers. CONCLUSIONS: The analysis of cancer trends in Japan revealed a recent decrease in mortality and a continuous increase in incidence, which are considered to reflect changes in the underlying risk factors such as tobacco smoking and infection, and are partially explained by early detection and improved treatment.

Trends of stomach cancer mortality in Eastern Asia in 1950-2004: comparative study of Japan, Hong Kong and Singapore using age, period and cohort analysis.

To characterize the temporal trends of stomach cancer mortality in Eastern Asia and to better interpret the causes of the trends, we performed age, period and cohort analysis (APC analysis) on the mortality rates in Japan, Hong Kong and Singapore during 1950-2004, as well as the rates in the US as a control population. For the APC analysis, Holford's approach was used to avoid the identification problem. Age-standardized mortality rates (ASMR) decreased consistently in all four areas during the observation period in both males and females. Japan had the highest ASMR in both sexes, followed by Singapore, Hong Kong and the US, but the differences in ASMR among the four areas diminished with time. The results of APC analysis suggested that the decreasing mortality rates in Eastern Asia were caused by the combination of decreasing cohort effect since the end of the 1800s and decreasing period effect from the 1950s. The US showed similar results, but its decreases in the period and cohort effect preceded those of Eastern Asia. Possible causes for the decrease in the cohort effect include improvement in the socioeconomic conditions during childhood and a decrease in the prevalence of H. pylori infection, while possible causes for the decrease in the period effect include a decrease in dietary salt intake and improvements in cancer detection and treatment. These findings may help us to predict future changes in the mortality rates of stomach cancer.

Incidence of metachronous second primary cancers in Osaka, Japan: update of analyses using population-based cancer registry data.

Cancer survivors are at excess risk of developing second primary cancers, but the precise level of risk in Japanese patients is not known. To investigate the risk of survivors developing second primary cancers, we conducted a retrospective cohort study using data from the Osaka Cancer Registry. The study subjects comprised all reported patients aged 0-79 years who were first diagnosed with cancer between 1985 and 2004 in Osaka and who survived for at least 3 months, followed-up through to December 2005. A metachronous second primary cancer was defined as any invasive second cancer that was diagnosed between 3 months and 10 years after the first cancer diagnosis. The main outcome measures were incidence rates per 100,000 person-years, cumulative risk and standardized incidence ratios (SIR) of second primary cancer. Metachronous second primary cancers developed in 13,385 of 355,966 survivors (3.8%) after a median follow-up of 2.5 years. Sex-specific incidence rates of metachronous second primary cancer per 100,000 person-years increased with age, and were higher among men than women (except for the 0-49 years age group), but these rates did not differ over the study period. The 10-year cumulative risk was estimated as 13.0% for those who first developed cancer at 60-69 years of age (16.2% for men, 8.6% for women). The SIR among those with first cancer diagnosed at 0-39 and 40-49 years of age were 2.13 and 1.52, respectively, in both sexes, whereas the SIR among cancers of the mouth/pharynx, esophagus and larynx were much higher than one as for site relationships. We showed that cancer survivors in Osaka, Japan, were at higher risk of second primary cancers compared with the general population. Our findings indicate that second primary cancers should be considered as a commonly encountered major medical problem. Further investigations are required to advance our understanding to enable the development of effective measures against multiple primary cancers.

Trend analysis of cancer incidence in Japan using data from selected population-based cancer registries.

Population-based cancer registries are operated by over 80% of prefectures in Japan. However, only a limited proportion of the registries can provide long-term incidence data. Here, we aimed to establish a method for monitoring cancer incidence trends in Japan using data from selected prefectures. Based on the availability of long-term (≥ 20 years) high-quality data, we collected incidence data from five prefectures (Miyagi, Yamagata, Fukui, Osaka, and Nagasaki), which included an annual average of 54,539 primary cancer cases diagnosed between 1985 and 2004. Cancer mortality data for 1995-2004 were obtained from the vital statistics. Representativeness and homogeneity of the trends were examined by funnel plot analysis of log-linear regression coefficients calculated for the most recent 10 years of data (1995-2004) of age-standardized rates (ASR). The ASR of incidence for five prefectures in total (5-pref total) showed a significant decrease, with an annual percent change (APC) of -1.0 (95% confidence interval [CI] -1.4: -0.6) for males and -0.4 (95% CI -0.8: -0.1) for females. Excluding data from Osaka (4-pref total) reversed the decreasing trend; the corresponding APC was +0.4 (95% CI -0.2: +1.0) for males and +0.7 (95% CI +0.5: +0.9) for females. The APCs for the ASR of mortality for the 4-pref total (males, -1.5; females, -1.3) were more representative of nationwide data (males, -1.4 [95% CI -1.7: -1.2]; females, -1.1 [95% CI -1.4: -0.9]) than those for the 5-pref total (males, -1.7; females, -1.4). We conclude that using data from Miyagi, Yamagata, Fukui, and Nagasaki prefectures, with continuous monitoring of the representativeness of the data, is a provisionally relevant way to evaluate cancer incidence trends in Japan.

Trends in 'cure' fraction from colorectal cancer by age and tumour stage between 1975 and 2000, using population-based data, Osaka, Japan.

Since the 1960s, Japan has experienced a striking increase in the incidence of colorectal cancer, now the second most common cancer in the country. Meanwhile, the management of colorectal cancer has changed dramatically with the implementation of, for example, screening, endoscopy and adjuvant chemotherapy. It is therefore of interest to monitor the long-term trends in population 'cure' in Japan. We analysed 33 885 colorectal cancer cases diagnosed between 1975 and 2000 in Osaka. We applied the multivariable mixture cure model to estimate cure fraction and median survival time (MST) for 'uncured' patients, by sex, age, stage, period at diagnosis and subsite. For colon cancer, the cure fraction increased by about 25%, while MST for the uncured was prolonged from 8 to 12 months. The cure fraction was 5% higher in men than in women, while MST was similar in both. The cure fraction also increased for localized and regional tumours. For rectal cancer, the cure fraction increased by about 25-30%, but remained lower than for colon cancer. From the late 1970s, the cure fraction for colorectal cancer increased dramatically due to better management of detection and care for colorectal cancer. This improvement was obtained at the cost of shorter MST for uncured patients.

Burden of congenital hemophilia A requiring treatment in Japan: The HIKOBOSHI study.

Background: Treatment of congenital hemophilia A (HA) in Japan has greatly improved with the widespread adoption of prophylactic factor (F)VIII concentrates. However, it is unknown if this has translated into a real-world reduction in disease and treatment burden. Objectives: To describe HA disease burden in Japan based on information from two medical information databases, JMDC and Real World Data Co., Ltd. (RWD). Methods: Eligible individuals were diagnosed with congenital HA and prescribed FVIII concentrates, bypassing agents, or emicizumab. Treatment patterns and disease burden data were derived from health insurance claims and electronic medical records. Results: Data on 459 people with HA were retrospectively collected from 2005 to 2020 in the JMDC database (median [min, max] of 37 [2, 186] months of available records), and 229 people with HA from 1985 to 2020 in the RWD database (median [min, max] of 154 [0, 409] months of available records). Mean (standard deviation) ages at the time of the first record were 25.0 (16.8) years (JMDC) and 19.2 (20.3) years (RWD). In the JMDC database, mean monthly FVIII dose increased from 2201 IU in 2005 to 8239 IU in 2013 to 11,377 IU in 2019; HA-related drug costs increased accordingly. Mean (95% confidence interval) annual outpatient and out-of-hours visits decreased slightly between 2013 and 2019 (outpatient visits: from 22.9 [16.8-29.0] to 14.3 [12.6-16.1] per person; out-of-hours visits: from 1.3 [0.2-2.5] to 0.6 [0-1.4]). There was no change in mean number of hospitalizations. Conclusions: Challenges remain in HA, including treatment burden, outpatient visits, and hospitalizations.

AKATSUKI study: a prospective, multicentre, phase IV study evaluating the safety of emicizumab under and immediately after immune tolerance induction therapy in persons with congenital haemophilia A with factor VIII inhibitors.

INTRODUCTION: For persons with haemophilia A with factor (F) VIII inhibitors (PwHAwI), immune tolerance induction (ITI) therapy is indicated for inhibitor eradication; however, since PwHAwI on ITI were excluded from the emicizumab clinical development programme, there are limited safety data for emicizumab treatment under/immediately after ITI in PwHAwI. Accordingly, there is a need to collect safety and efficacy data on this concomitant treatment strategy. The AKATSUKI study aims to evaluate the safety of emicizumab under/immediately after ITI in PwHAwI; here we report details of the study protocol. METHODS AND ANALYSIS: AKATSUKI is an open-label, non-randomised, interventional, multicentre study. Twenty participants with congenital HA with FVIII inhibitors will be enrolled from 17 sites across Japan. Emicizumab will be administered subcutaneously, with an initial loading dose of 3 mg/kg once per week (QW) for the first 4 weeks, followed by a maintenance dose of 1.5 mg/kg QW, 3 mg/kg once every 2 weeks or 6 mg/kg once every 4 weeks. For ITI therapy, 50 IU/kg FVIII will be administered three times per week. For extended half-life FVIII, a dosing frequency of twice per week will be permitted. The primary endpoint is a comprehensive safety evaluation of adverse events (mainly thromboembolic events) and abnormal laboratory values over time. Secondary endpoints are the number of bleeds requiring coagulation factor treatment, the number of participants achieving a partially successful ITI response, FVIII inhibitor titres under/immediately after ITI, quality of life and time to achieve a negative FVIII inhibitor result (<0.6 BU/mL) and partial success in PwHAwI starting ITI after study enrolment. CONCLUSIONS: AKATSUKI will evaluate the safety of emicizumab administered under/immediately after ITI, providing reference data to inform treatment strategies in PwHAwI. ETHICS AND DISSEMINATION: The results of this study will be published in a peer-reviewed international journal and presented at national and/or international medical scientific conferences; the major findings of this study will be published on the jRCT registry website (https://jrct.niph.go.jp). TRIAL REGISTRATION NUMBER: jRCTs041200037.

Trends in the incidence of primary intracranial tumors in Osaka, Japan.

We analyzed the trends in the age-standardized incidence rates of 10,460 cases of primary intracranial tumors diagnosed during 1975 and 2004, Osaka, Japan using the Joinpoint regression analysis. During the period 1975-2004, the age-standardized incidence rates of total intracranial tumors increased until 1987 at 3.1% per year and then decreased significantly at -1.8% per year. The time trends were different according to the age groups. In the age group 0-19, the rate did not exhibit substantial increase or decrease. In the age group 20-74, the rates increased significantly until 1988 and then leveled off until 1999 and finally decreased. Whereas in the age group 75 and over, the rates increased drastically until 1984 and then leveled off. During the recent 10 year period 1995-2004, the age-standardized incidence rates of meningioma decreased significantly, but those of glioblastoma did not.