Is gastric cancer becoming a rare disease? A global assessment of predicted incidence trends to 2035.

OBJECTIVES: The incidence of gastric cancer continues to decrease globally, approaching levels that in some populations could define it as a rare disease. To explore this on a wider scale, we predict its future burden in 34 countries with long-standing population-based data. METHODS: Data on gastric cancer incidence by year of diagnosis, sex and age were extracted for 92 cancer registries in 34 countries included in Cancer Incidence in Five Continents Plus. Numbers of new cases and age-standardised incidence rates (ASR per 100 000) were predicted up to 2035 by fitting and extrapolating age-period-cohort models. RESULTS: Overall gastric cancer incidence rates are predicted to continue falling in the future in the majority of countries, including high-incidence countries such as Japan (ASR 36 in 2010 vs ASR 30 in 2035) but also low-incidence countries such as Australia (ASR 5.1 in 2010 vs ASR 4.6 in 2035). A total of 16 countries are predicted to fall below the rare disease threshold (defined as 6 per 100 000 person-years) by 2035, while the number of newly diagnosed cases remains high and is predicted to continue growing. In contrast, incidence increases were seen in younger age groups (below age 50 years) in both low-incidence and high-incidence populations. CONCLUSIONS: While gastric cancer is predicted to become a rare disease in a growing number of countries, incidence levels remain high in some regions, and increasing risks have been observed in younger generations. The predicted growing number of new cases highlights that gastric cancer remains a major challenge to public health on a global scale.

Helicobacter pylori eradication for the prevention of gastric neoplasia.

BACKGROUND: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear. OBJECTIVES: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer. SEARCH METHODS: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1), MEDLINE (1946 to February 2020), and EMBASE (1974 to February 2020). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2019. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology. DATA COLLECTION AND ANALYSIS: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy. MAIN RESULTS: Six trials met all our eligibility criteria and provided extractable data in the previous version. Following our updated search, one new RCT was identified, meaning that seven trials were included in this updated review. In addition, one previously included trial provided fully published data out to 10 years, and another previously included trial provided fully published data out to 22 years of follow-up. Four trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Six trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (RR 0.54, 95% confidence interval (CI) 0.40 to 0.72, 7 trials, 8323 participants, moderate certainty evidence). Only two trials reported the effect of eradication of H. pylori on the development of subsequent oesophageal cancer. Sixteen (0.8%) of 1947 participants assigned to eradication therapy subsequently developed oesophageal cancer compared with 13 (0.7%) of 1941 participants allocated to placebo (RR 1.22, 95% CI 0.59 to 2.54, moderate certainty evidence). H. pylori eradication reduced mortality from gastric cancer compared with placebo or no treatment (RR 0.61, 95% CI 0.40 to 0.92, 4 trials, 6301 participants, moderate certainty evidence). There was little or no evidence in all-cause mortality (RR 0.97, 95% CI 0.85 to 1.12, 5 trials, 7079 participants, moderate certainty evidence). Adverse events data were poorly reported. AUTHORS' CONCLUSIONS: We found moderate certainty evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.

Global cancer statistics.

The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.

Cancer prevention as part of precision medicine: 'plenty to be done'.

Cancer burden worldwide is projected to rise from 14 million new cases in 2012 to 24 million in 2035. Although the greatest increases will be in developing countries, where cancer services are already hard pressed, even the richest nations will struggle to meet demands of increasing patient numbers and spiralling treatment costs. No country can treat its way out of the cancer problem. Consequently, cancer control must combine improvements in treatment with greater emphasis on prevention and early detection. Cancer prevention is founded on describing the burden of cancer, identifying the causes and evaluating and implementing preventive interventions. Around 40-50% of cancers could be prevented if current knowledge about risk factors was translated into effective public health strategies. The benefits of prevention are attested to by major successes, for example, in tobacco control, vaccination against oncogenic viruses, reduced exposure to environmental and occupational carcinogens, and screening. Progress is still needed in areas such as weight control and physical activity. Fresh impetus for prevention and early detection will come through interdisciplinary approaches, encompassing knowledge and tools from advances in cancer biology. Examples include mutation profiles giving clues about aetiology and biomarkers for early detection, to stratify individuals for screening or for prognosis. However, cancer prevention requires a broad perspective stretching from the submicroscopic to the macropolitical, recognizing the importance of molecular profiling and multisectoral engagement across urban planning, transport, environment, agriculture, economics, etc., and applying interventions that may just as easily rely on a legislative measure as on a molecule.

Worldwide Inverse Association between Gastric Cancer and Esophageal Adenocarcinoma Suggesting a Common Environmental Factor Exerting Opposing Effects.

OBJECTIVES: The incidence of esophageal adenocarcinoma (EAC) is increasing while adenocarcinoma of the stomach is decreasing. We have investigated whether the incidences of these two cancers and their time trends might be inversely related pointing to a common environmental factor exerting opposite effects on these cancers. METHODS: For cross-sectional analyses data were abstracted from "Cancer Incidence in Five Continents" (CI5) Volume X and GLOBOCAN 2012. Relevant ICD-10 codes were used to locate esophageal and gastric cancers anatomically, and ICD-O codes for the histological diagnosis of EAC. For longitudinal analyses, age standardized rates (ASRs) of EAC and total gastric cancer (TGC) were extracted from CI5C-Plus. RESULTS: Estimated (2012) ASRs were available for 51 countries and these showed significant negative correlations between EAC and both TGC (males: correlation coefficient (CC)=-0.38, P=0.006, females: CC=-0.41, P=0.003) and non-cardia gastric cancer rates (males: CC=-0.41, P=0.003 and females: CC=-0.43, P=0.005). Annual incidence trends were analyzed for 38 populations through 1989-2007 and showed significant decreases for TGC in 89% and increases for EAC in 66% of these, with no population showing a fall in the latter. Significant negative correlation between the incidence trends of the two cancers was observed in 27 of the 38 populations over the 19-50 years of available paired data. Super-imposition of the longitudinal and cross-sectional data indicated that populations with a current high incidence of EAC and low incidence of gastric cancer had previously resembled countries with a high incidence of gastric cancer and low incidence of EAC. CONCLUSIONS: The negative association between gastric cancer and EAC in both current incidences and time trends is consistent with a common environmental factor predisposing to one and protecting from the other.

Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people.

BACKGROUND: Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4. OBJECTIVES: To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved. SEARCH METHODS: In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards. DATA COLLECTION AND ANALYSIS: We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible. MAIN RESULTS: A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy. AUTHORS' CONCLUSIONS: Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.

Global incidence of oesophageal cancer by histological subtype in 2012.

OBJECTIVE: The two major histological types of oesophageal cancer--adenocarcinoma (AC) and squamous cell carcinoma (SCC)--are known to differ greatly in terms of risk factors and epidemiology. To date, global incidence estimates for individual subtypes are still lacking. This study for the first time quantified the global burden of oesophageal cancer by histological subtype. DESIGN: Where available, data from Cancer Incidence in Five Continents Vol. X (CI5X) were used to compute, age-specific, sex-specific and country-specific proportions of AC and SCC. Nine regional averages were computed for countries without CI5X data. The proportions were then applied to all oesophageal cancer cases from GLOBOCAN 2012 and age-standardised incidence rates calculated for both histological types. RESULTS: Worldwide, an estimated 398,000 SCCs and 52,000 ACs of the oesophagus occurred in 2012, translating to incidence rates of 5.2 and 0.7 per 100,000, respectively. Although SCCs were most common in South-Eastern and Central Asia (79% of the total global SCC cases), the highest burden of AC was found in Northern and Western Europe, Northern America and Oceania (46% of the total global AC cases). Men had substantially higher incidence than women, especially in the case of AC (male to female ratio AC: 4.4; SCC: 2.7). CONCLUSIONS: These first global estimates of oesophageal cancer incidence by histology suggested a high concentration of AC in high-income countries with men being at much greater risk. This quantification of incidence will aid health policy makers to plan appropriate cancer control measures in the future.

Global burden of cancer attributable to high body-mass index in 2012: a population-based study.

BACKGROUND: High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012. METHODS: In this population-based study, we derived population attributable fractions (PAFs) using relative risks and BMI estimates in adults by age, sex, and country. Assuming a 10-year lag-period between high BMI and cancer occurrence, we calculated PAFs using BMI estimates from 2002 and used GLOBOCAN2012 data to estimate numbers of new cancer cases attributable to high BMI. We also calculated the proportion of cancers that were potentially avoidable had populations maintained their mean BMIs recorded in 1982. We did secondary analyses to test the model and to estimate the effects of hormone replacement therapy (HRT) use and smoking. FINDINGS: Worldwide, we estimate that 481,000 or 3.6% of all new cancer cases in adults (aged 30 years and older after the 10-year lag period) in 2012 were attributable to high BMI. PAFs were greater in women than in men (5.4% vs 1.9%). The burden of attributable cases was higher in countries with very high and high human development indices (HDIs; PAF 5.3% and 4.8%, respectively) than in those with moderate (1.6%) and low HDIs (1.0%). Corpus uteri, postmenopausal breast, and colon cancers accounted for 63.6% of cancers attributable to high BMI. A quarter (about 118,000) of the cancer cases related to high BMI in 2012 could be attributed to the increase in BMI since 1982. INTERPRETATION: These findings emphasise the need for a global effort to abate the increasing numbers of people with high BMI. Assuming that the association between high BMI and cancer is causal, the continuation of current patterns of population weight gain will lead to continuing increases in the future burden of cancer. FUNDING: World Cancer Research Fund International, European Commission (Marie Curie Intra-European Fellowship), Australian National Health and Medical Research Council, and US National Institutes of Health.

Global burden of gastric cancer attributable to Helicobacter pylori.

We previously estimated that 660,000 cases of cancer in the year 2008 were attributable to the bacterium Helicobacter pylori (H. pylori), corresponding to 5.2% of the 12.7 million total cancer cases that occurred worldwide. In recent years, evidence has accumulated that immunoblot (western blot) is more sensitive for detection of anti-H. pylori antibodies than ELISA, the detection method used in our previous analysis. The purpose of this short report is to update the attributable fraction (AF) estimate for H. pylori after briefly reviewing new evidence, and to reassess the global burden of cancer attributable to H. pylori. We therefore reviewed the literature for studies comparing the risk of developing non-cardia gastric cancer (NCGC) in cases and controls, using both ELISA and multiple antigen immunoblot for detection of H. pylori. The results from prospective studies were combined, and the new pooled estimates were applied to the calculation of the AF for H. pylori in NCGC, then to the burden of infection-related cancers worldwide. Using the immunoblot-based data, the worldwide AF for H. pylori in NCGC increased from 74.7% to 89.0%. This implies approximately 120,000 additional cases of NCGC attributable to H. pylori infection for a total of around 780,000 cases (6.2% instead of 5.2% of all cancers). These updated estimates reinforce the role of H. pylori as a major cause of cancer.

Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.

Estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. We review the sources and methods used in compiling the national cancer incidence and mortality estimates, and briefly describe the key results by cancer site and in 20 large "areas" of the world. Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast (1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths).

Helicobacter pylori eradication for the prevention of gastric neoplasia.

BACKGROUND: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear. OBJECTIVES: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer. SEARCH METHODS: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 11), MEDLINE (1946 to December 2013), and EMBASE (1974 to December 2013). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2013. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology. DATA COLLECTION AND ANALYSIS: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy. MAIN RESULTS: Six trials met all our eligibility criteria and provided extractable data. Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Five trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (6 trials, 6497 participants, risk ratio (RR) of developing subsequent gastric cancer 0.66; 95% confidence interval (CI) 0.46 to 0.95; moderate-quality evidence). Only one trial reported effect of eradication of H. pylori on development of subsequent oesophageal cancer (2 (0.2%) among 817 participants assigned to eradication therapy, compared with 1 (0.1%) of 813 participants allocated to placebo; RR 1.99; 95% CI 0.18 to 21.91). The effect of H. pylori eradication on preventing death from gastric cancer compared with placebo or no treatment was uncertain due to wide confidence intervals (3 trials, 4475 participants, RR 0.67; 95% CI 0.40 to 1.11; moderate-quality evidence). There was no evidence of an effect on all-cause mortality (4 trials, 5253 participants, RR 1.09; 95% CI 0.86 to 1.38; moderate-quality evidence). Adverse events data were poorly reported. AUTHORS' CONCLUSIONS: We found limited, moderate-quality evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.

The burden of stomach cancer in indigenous populations: a systematic review and global assessment.

OBJECTIVE: Stomach cancer is a leading cause of cancer death, especially in developing countries. Incidence has been associated with poverty and is also reported to disproportionately affect indigenous peoples, many of whom live in poor socioeconomic circumstances and experience lower standards of health. In this comprehensive assessment, we explore the burden of stomach cancer among indigenous peoples globally. DESIGN: The literature was searched systematically for studies on stomach cancer incidence, mortality and survival in indigenous populations, including Indigenous Australians, Maori in New Zealand, indigenous peoples from the circumpolar region, native Americans and Alaska natives in the USA, and the Mapuche peoples in Chile. Data from the New Zealand Health Information Service and the Surveillance Epidemiology and End Results (SEER) Program were used to estimate trends in incidence. RESULTS: Elevated rates of stomach cancer incidence and mortality were found in almost all indigenous peoples relative to corresponding non-indigenous populations in the same regions or countries. This was particularly evident among Inuit residing in the circumpolar region (standardised incidence ratios (SIR) males: 3.9, females: 3.6) and in Maori (SIR males: 2.2, females: 3.2). Increasing trends in incidence were found for some groups. CONCLUSIONS: We found a higher burden of stomach cancer in indigenous populations globally, and rising incidence in some indigenous groups, in stark contrast to the decreasing global trends. This is of major public health concern requiring close surveillance and further research of potential risk factors. Given evidence that improving nutrition and housing sanitation, and Helicobacter pylori eradication programmes could reduce stomach cancer rates, policies which address these initiatives could reduce inequalities in stomach cancer burden for indigenous peoples.

Time to begin adjuvant chemotherapy and survival in breast cancer patients: a retrospective observational study using latent class analysis.

The analysis of time to treatment data and the evaluation of subsequent effects on health outcomes can be complex due to the nature of the data and the relationships amongst the variables. This study proposes an alternative method of analyzing such data using latent class analysis (LCA). The association between time to begin adjuvant chemotherapy after breast cancer surgery and survival was investigated using both "traditional" regression analysis and LCA. Women with breast cancer undergoing surgery and subsequent adjuvant chemotherapy in two English regions between January 01, 1998 and December 31, 2004 were identified from a linked cancer registry-Hospital Episode Statistics dataset (n = 10,366). Patient, tumor, and treatment information were extracted. A Cox proportional hazards model was used to analyze 5-year survival using regression analysis and LCA. Using "traditional" regression analysis, women beginning chemotherapy >10 weeks after surgery had worse survival in region 1 (HR = 1.49, 95% CI 1.13-1.95 compared to <3 weeks) but not region 2. LCA split the women into three groups representing short, medium, and long waits. The median time to begin chemotherapy in the "long" wait group was 70 (region 1) and 57 (region 2) days. In this group, increased time to begin chemotherapy was associated with worse survival (region 1 HR = 1.15, 95% CI 1.11-1.18; region 2 HR = 1.08, 95% CI 1.03-1.13 per week increase). LCA identified a group of 13-15% of women for whom a longer time to begin chemotherapy had an adverse effect on survival. This methodology provides an excellent framework in which to examine complex associations between the delivery of patient care and patient outcomes.

25 year trends in cancer incidence and mortality among adults aged 35-69 years in the UK, 1993-2018: retrospective secondary analysis.

OBJECTIVE: To examine and interpret trends in UK cancer incidence and mortality for all cancers combined and for the most common cancer sites in adults aged 35-69 years. DESIGN: Retrospective secondary data analysis. DATA SOURCES: Cancer registration data, cancer mortality and national population data from the Office for National Statistics, Public Health Wales, Public Health Scotland, Northern Ireland Cancer Registry, NHS England, and the General Register Office for Northern Ireland. SETTING: 23 cancer sites were included in the analysis in the UK. PARTICIPANTS: Men and women aged 35-69 years diagnosed with or who died from cancer between 1993 to 2018. MAIN OUTCOME MEASURES: Change in cancer incidence and mortality age standardised rates over time. RESULTS: The number of cancer cases in this age range rose by 57% for men (from 55 014 cases registered in 1993 to 86 297 in 2018) and by 48% for women (60 187 to 88 970) with age standardised rates showing average annual increases of 0.8% in both sexes. The increase in incidence was predominantly driven by increases in prostate (male) and breast (female) cancers. Without these two sites, all cancer trends in age standardised incidence rates were relatively stable. Trends for a small number of less common cancers showed concerning increases in incidence rates, for example, in melanoma skin, liver, oral, and kidney cancers. The number of cancer deaths decreased over the 25 year period, by 20% in men (from 32 878 to 26 322) and 17% in women (28 516 to 23 719); age standardised mortality rates reduced for all cancers combined by 37% in men (-2.0% per year) and 33% in women (-1.6% per year). The largest decreases in mortality were noted for stomach, mesothelioma, and bladder cancers in men and stomach and cervical cancers and non-Hodgkin lymphoma in women. Most incidence and mortality changes were statistically significant even when the size of change was relatively small. CONCLUSIONS: Cancer mortality had a substantial reduction during the past 25 years in both men and women aged 35-69 years. This decline is likely a reflection of the successes in cancer prevention (eg, smoking prevention policies and cessation programmes), earlier detection (eg, screening programmes) and improved diagnostic tests, and more effective treatment. By contrast, increased prevalence of non-smoking risk factors are the likely cause of the observed increased incidence for a small number of specific cancers. This analysis also provides a benchmark for the following decade, which will include the impact of covid-19 on cancer incidence and outcomes.

An international comparison of male and female breast cancer incidence rates.

Global international trends in female breast cancer incidence have been described previously but no comparable analysis of male breast cancer incidence rates has been conducted. We obtained male and female case and population data using Cancer Incidence in Five Continents (CI5). We calculated age-adjusted, sex-specific incidence rates and female-to-male incidence rate ratios (FMIRRs) and compared trends of such for the period 1988-2002. This analysis included 8,681 male breast cancer cases and 1.14 million female breast cancer cases. The highest male incidence rate was observed in Israel at 1.24 per 100,000 man-years, and the highest female incidence rate was observed in the United States at 90.7 per 100,000 woman-years. The lowest incidence rates for males (0.16) and females (18.0) were observed in Thailand. In general, male breast cancer incidence trends were variable; a minority of countries displayed evidence for an increase. In contrast, female incidence rates have been increasing in a majority of countries. The Pearson correlation coefficient (r) for male and female breast cancer incidence rates by country during 1988-2002 was 0.69. Male breast cancer rates were generally less than 1 per 100,000 man-years, in contrast to the much higher rates of female breast cancer, providing for an overall FMIRR of 122. The differences in both incidence rates and time trends between males and females may reflect sex differences in underlying risk factors, pathogenesis, and/or overdiagnosis. Conversely, the high correlation between male and female breast cancer incidences may indicate that both sexes share some common risk factors for breast cancer.

Kaposi sarcoma trends in Uganda and Zimbabwe: a sustained decline in incidence?

Trends in Kaposi sarcoma (KS) incidence over four decades were described for Zimbabwe and Uganda. KS data were retrieved from the population-based cancer registries of Bulawayo (1963-1971) and Harare (1990-2005), Zimbabwe and Kyadondo, Uganda (1960-1971 and 1991-2007). Joinpoint regression models were used to analyze time trends of KS incidence. Trends were compared to HIV/AIDS trends and were also described as rates versus birth cohort by age. In both countries, an increased incidence of KS accompanied the emergence of the HIV/AIDS epidemic (p-value < 0.0001). In Zimbabwe, KS incidence (both sexes, all ages) changed in parallel to that of HIV/AIDS prevalence, whereas in Uganda, despite an observed decrease in HIV/AIDS prevalence since 1992, we observed a decrease in KS incidence in men younger than 50 years (Annual Percent Change, APC after 1991 = -4.5 [-5.6; -3.4], p-value < 0.05) but not in men aged >50 years (APC after 1991 = 1.0 [-2.8; 5.0]) nor in women (APC = 1.0 [-0.6; 2.6]). In both populations, a period effect at older ages was observed, with initial increases in incidence in men followed subsequently by a downturn in rates of the same magnitude. The uniformly declining rates in younger men (aged less than 30 years) suggested that a recent cohort effect was also in operation with a reduced risk in generations born after the mid-1950s in Uganda and in the mid-1960s in Zimbabwe. The combined introduction of antiretroviral therapy and effective prevention programmes against HIV/AIDS appeared to be the key contributors to the KS decline observed in both Uganda and Zimbabwe.

Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions.

BACKGROUND: Country comparisons that consider the effect of fatal and non-fatal disease outcomes are needed for health-care planning. We calculated disability-adjusted life-years (DALYs) to estimate the global burden of cancer in 2008. METHODS: We used population-based data, mostly from cancer registries, for incidence, mortality, life expectancy, disease duration, and age at onset and death, alongside proportions of patients who were treated and living with sequelae or regarded as cured, to calculate years of life lost (YLLs) and years lived with disability (YLDs). We used YLLs and YLDs to derive DALYs for 27 sites of cancers in 184 countries in 12 world regions. Estimates were grouped into four categories based on a country's human development index (HDI). We applied zero discounting and uniform age weighting, and age-standardised rates to enable cross-country and regional comparisons. FINDINGS: Worldwide, an estimated 169·3 million years of healthy life were lost because of cancer in 2008. Colorectal, lung, breast, and prostate cancers were the main contributors to total DALYs in most world regions and caused 18-50% of the total cancer burden. We estimated an additional burden of 25% from infection-related cancers (liver, stomach, and cervical) in sub-Saharan Africa, and 27% in eastern Asia. We noted substantial global differences in the cancer profile of DALYs by country and region; however, YLLs were the most important component of DALYs in all countries and for all cancers, and contributed to more than 90% of the total burden. Nonetheless, low-resource settings had consistently higher YLLs (as a proportion of total DALYs) than did high-resource settings. INTERPRETATION: Age-adjusted DALYs lost from cancer are substantial, irrespective of world region. The consistently larger proportions of YLLs in low HDI than in high HDI countries indicate substantial inequalities in prognosis after diagnosis, related to degree of human development. Therefore, radical improvement in cancer care is needed in low-resource countries. FUNDING: Dutch Scientific Society, Erasmus University Rotterdam, and International Agency for research on Cancer.

Helicobacter pylori eradication in the prevention of gastric cancer: are more trials needed?

The incidence of gastric cancer has decreased in much of the world, but gastric cancer remains the second leading cause of cancer death globally, and the burden is growing in many countries in East Asia and Latin America. Chronic infection with Helicobacter pylori is the dominant cause of gastric cancer, and two recent randomized trials showed that H. pylori eradication significantly decreased gastric cancer risk. Population screening and treating individuals for H. pylori also appears to be cost-effective. Nevertheless, current clinical guidelines differ as to whether asymptomatic adults should be screened and treated for H. pylori, and no countries have yet implemented eradication programs. Some of this inaction may reflect lingering doubts about the effectiveness of H. pylori eradication in preventing gastric cancer, but there is also uncertainty about possible risks of mass antibiotic treatment and its impact on gut flora. Appropriately designed studies will help address these issues and hasten the implementation of population-wide prevention programs.

Optimum duration of regimens for Helicobacter pylori eradication.

BACKGROUND: The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens. OBJECTIVES: The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events. SEARCH METHODS: The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search. SELECTION CRITERIA: Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded. DATA COLLECTION AND ANALYSIS: Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori. MAIN RESULTS: In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H2RA) bismuth quadruple therapy (n = 3), H2RA bismuth-based triple therapy (n = 2), H2RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H2RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data. AUTHORS' CONCLUSIONS: Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.

Integrating patient reported outcomes with clinical cancer registry data: a feasibility study of the electronic Patient-Reported Outcomes From Cancer Survivors (ePOCS) system.

BACKGROUND: Routine measurement of Patient Reported Outcomes (PROs) linked with clinical data across the patient pathway is increasingly important for informing future care planning. The innovative electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system was developed to integrate PROs, collected online at specified post-diagnostic time-points, with clinical and treatment data in cancer registries. OBJECTIVE: This study tested the technical and clinical feasibility of ePOCS by running the system with a sample of potentially curable breast, colorectal, and prostate cancer patients in their first 15 months post diagnosis. METHODS: Patients completed questionnaires comprising multiple Patient Reported Outcome Measures (PROMs) via ePOCS within 6 months (T1), and at 9 (T2) and 15 (T3) months, post diagnosis. Feasibility outcomes included system informatics performance, patient recruitment, retention, representativeness and questionnaire completion (response rate), patient feedback, and administration burden involved in running the system. RESULTS: ePOCS ran efficiently with few technical problems. Patient participation was 55.21% (636/1152) overall, although varied by approach mode, and was considerably higher among patients approached face-to-face (61.4%, 490/798) than by telephone (48.8%, 21/43) or letter (41.0%, 125/305). Older and less affluent patients were less likely to join (both P<.001). Most non-consenters (71.1%, 234/329) cited information technology reasons (ie, difficulty using a computer). Questionnaires were fully or partially completed by 85.1% (541/636) of invited participants at T1 (80 questions total), 70.0% (442/631) at T2 (102-108 questions), and 66.3% (414/624) at T3 (148-154 questions), and fully completed at all three time-points by 57.6% (344/597) of participants. Reminders (mainly via email) effectively prompted responses. The PROs were successfully linked with cancer registry data for 100% of patients (N=636). Participant feedback was encouraging and positive, with most patients reporting that they found ePOCS easy to use and that, if asked, they would continue using the system long-term (86.2%, 361/419). ePOCS was not administratively burdensome to run day-to-day, and patient-initiated inquiries averaged just 11 inquiries per month. CONCLUSIONS: The informatics underlying the ePOCS system demonstrated successful proof-of-concept--the system successfully linked PROs with registry data for 100% of the patients. The majority of patients were keen to engage. Participation rates are likely to improve as the Internet becomes more universally adopted. ePOCS can help overcome the challenges of routinely collecting PROs and linking with clinical data, which is integral for treatment and supportive care planning and for targeting service provision.