Journal of the National Cancer Center最新文献

Background

Esophageal cancer poses a significant global burden, while its patterns and trends remain to be clarified. The aim of this study is to provide an update on the incidence and mortality rates of esophageal cancer and their trends in China based on data from the National Cancer Registry.

Methods

We extracted data from the National Central Cancer Registry (NCCR) of China from 2000 to 2016 and performed comprehensive quality control. We calculated age-standardized rates of China (ASR China) and world (ASR world) using the Chinese population in 2000 and the Segi's world standard population, and performed a joinpoint regression analysis to examine the trend in incidence and mortality of esophageal cancer. The annual percent change (APC) and weighted average APC (AAPC) over the entire study period were estimated to measure the changing trend. Subgroup analyses were conducted by sex, region and pathological type.

Results

A total of 487 eligible cancer registries were included in the data analysis and 22 registries with uninterrupted registration data were used for trend analysis. In 2016, there were an estimated of 184,500 incident cases of esophageal cancer and 142,300 deaths in China. The crude incidence, ASR China and ASR world were 25.25/100,000, 11.00/100,000 and 11.13/100,000, respectively. And the crude mortality, ASR China and ASR world were 19.38/100,000, 8.25/100,000 and 8.28/100,000, respectively. Esophageal squamous cell carcinoma (ESCC) was the most common histological type, accounting for 85.79% of all cases, followed by esophageal adenocarcinoma (EAC) (11.00%) and others (3.21%). There was a decreasing trend of ASR world in incidence and mortality during 2000–2016 with the AAPC of -4.6% (95% CI: -5.7%, -3.4%) and -4.6% (95% CI: -5.2%, -3.9%). The pattern and trend of esophageal cancer differ in sex, region and pathological type.

Conclusions

The burden of esophageal cancer in China remains high with sex, regional and subtype differences. The incidence and mortality of esophageal cancer have continued to decline over the past decade, which was due in part to the reductions in risk factor exposure and the implementation of screening.

Background

The stage at diagnosis is a major factor in making treatment strategies and cancer control policies. However, the stage distribution for liver cancer in China was not well studied. In this multi-center hospital-based study, we aimed to identify the distribution and factors associated with stage at diagnosis for liver cancer in China.

Methods

We included patients diagnosed with primary liver cancer in 13 hospitals of 10 provinces covering various geographic and socioeconomic populations during 2016–2017 in China. The stage distribution overall, and by sex and age at diagnosis were analyzed. We used logistic regression to identify the factors associated with stage III-IV disease. We further compared these estimates with data from the USA.

Results

We included 2,991 patients with known stage at diagnosis in China. The proportion of patients diagnosed with stage I, II, III, and IV was 17.5%, 25.6%, 29.3%, and 27.6%, respectively. The proportion of stage III-IV cases was higher in women [65.1% vs 54.9%, adjusted odds ratio (OR) = 1.5, 95% CI: 1.2, 1.8] and those ≥ 60 years (61.6% vs 52.8%, OR = 1.4, 95% CI: 1.2, 1.6). We found an increased risk of stage III-IV among drinkers and those without a family history of cancer. Compared to the USA, our study population had a substantially higher proportion of stage III-IV cases (56.9% vs 45.6%).

Conclusion

The disparities in liver cancer stage at diagnosis among different populations within China, and between China and the USA, imply the necessity for improving cancer awareness and early detection for liver cancer in China.

Objective

To synthesize the knowledge about the association of total physical activity (TPA), leisure-time physical activity (LTPA), occupational physical activity (OPA) and lung cancer risk and explore the dose–response relationship between LTPA level and lung cancer.

Methods

PubMed and Web of Science were searched up to 17 November 2021. The summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects or fixed-effects model. The dose–response analysis was conducted with restricted cubic splines.

Results

We identified 25 articles (42 cohort studies) that assessed the physical activity–lung cancer association, including 9,983,295 study participants and 85,988 incident cases of lung cancer. When comparing the highest to the lowest level of TPA and LTPA, lung cancer risk reduced 22% (RR, 0.78; 95% CI: 0.70, 0.86) and 12% (RR, 0.88; 95% CI: 0.83, 0.93), respectively. We found an approximately U-shaped association between LTPA and lung cancer (P _{non-linearity} < 0.001), with the lowest risk at 15 metabolic equivalent of task hours per week (h/wk) of LTPA. Compared to participants with sitting occupations, lung cancer risk significantly increased among those being unemployed (RR, 1.33; 95% CI: 1.17, 1.51) or with standing occupations (RR, 1.37; 95% CI: 1.15, 1.63), but not among those with light or high OPA.

Conclusions

Our meta-analysis supported a protective effect of TPA and LTPA, but not OPA, on lung cancer risk. The novel finding of a U-shaped association between LTPA and lung cancer risk warrants further investigation.

Background

The incidence of early-onset colorectal cancer (EOCRC) has increased globally since the early 1990s. Comprehensively examining the risk factors would be helpful for risk stratification and the development of personalized colorectal cancer screening strategies.

Methods

We performed a prospective study of the Chinese population aged 30–50 years to identify potential risk factors during a median follow-up of 9.1 years. We compared the distribution of demographic characteristics, lifestyle factors, dietary habits, and medical history among 222 EOCRC cases and 87,833 normal controls. Multivariate adjusted Cox hazard models were used for estimating EOCRC risks of each risk factor.

Results

Our final analyses indicated that participants with a higher body mass index (HR, 1.04; 95% CI:1.00,1.08), regular alcohol consumption (HR, 1.69; 95% CI: 1.12, 2.91), higher intake of fish (HR, 1.64; 95% CI: 1.01, 2.67), hypertension (HR, 1.99; 95% CI: 1.04, 3.81), diabetes (HR, 2.20; 95% CI: 1.08, 4.49), and first-degree relatives with cancer (HR, 1.70; 95% CI: 1.23, 2.36) were at higher risk of EOCRC.

Conclusion

We identified several modifiable as well as nonmodifiable risk factors, such as higher BMI, alcohol and fish consumption, hypertension, and diabetes, were associated with EOCRC.

Background

Tumour mutational burden (TMB) has emerged as a predictive marker for responsiveness to immune checkpoint inhibitors (ICI) in multiple tumour types. It can be calculated from somatic mutations detected from whole exome or targeted panel sequencing data. As mutations are unevenly distributed across the cancer genome, the clinical implications from TMB calculated using different genomic regions are not clear.

Methods

Pan-cancer data of 10,179 samples were collected from The Cancer Genome Atlas cohort and 6,831 cancer patients with either ICI or non-ICI treatment outcomes were derived from published papers. TMB was calculated as the count of non-synonymous mutations and normalised by the size of genomic regions. Dirichlet method, linear regression and Poisson calibration models are used to unify TMB from different gene panels.

Results

We found that panels based on cancer genes usually overestimate TMB compared to whole exome, potentially leading to misclassification of patients to receive ICI. The overestimation is caused by positive selection for mutations in cancer genes and cannot be completely addressed by the removal of mutational hotspots. We compared different approaches to address this discrepancy and developed a generalised statistical model capable of interconverting TMB derived from whole exome and different panel sequencing data, enabling TMB correction for patient stratification for ICI treatment. We show that in a cohort of lung cancer patients treated with ICI, when using a TMB cutoff of 10 mut/Mb, our corrected TMB outperforms the original panel-based TMB.

Conclusion

Cancer gene-based panels usually overestimate TMB, and these findings will be valuable for unifying TMB calculations across cancer gene panels in clinical practice.

Pathogenic BRCA1 and BRCA2 (BRCA) variation is the genetic predisposition for high cancer risk affecting mostly breast and ovarian. BRCA variation information is widely used in clinical diagnosis, treatment, and prevention of BRCA-related cancer. The positive selection imposed on human BRCA leads to highly ethnic-specific BRCA variation to adapt different living environment on earth. Most of the human BRCA variants identified so far were from the European descendant populations and used as the standard reference for global human populations, whereas BRCA variation in other ethnic populations remains poorly characterized. This review addresses the origin of ethnic-specific BRCA variation, the importance of ethnic-specific BRCA variation in clinical application, the limitation of current BRCA variation data, and potential solutions to fill the gap.

Objective

Mathematical modeling and simulation is a useful research method to inform decision-making. This article aims to describe the National Cancer Center (NCC) modeling framework and how well it reproduces observed empirical data for six major cancers.

Methods

We developed the NCC modeling framework for six major cancers in China (lung, liver, stomach, colorectal, esophageal, and breast), which simulates the life-histories represented by states among normal, precancerous lesion, stage-specific invasive cancer, and death for six cancers separately. Each NCC simulation model could be illustrated as an integrated framework of 3 modules: a demography module, natural history module, and screening module. Combined with costs and health utilities data, the models could have many detailed outputs for informing decisions, including the harm of screening (e.g., false positives, complications, and overdiagnosis), healthcare costs, and benefits (quality-adjusted life years gained, cancer incidence and mortality, and investment returns). We calibrated the models to Chinese population-based observations on cancer incidence, mortality, and stage distribution. All models are validated by comparing model simulated results to data observed from nationwide cancer registration and a large prospective cohort study.

Results

The simulated results from the calibrated models consistently match the epidemiological patterns in six major cancer incidence, mortality, and stage distributions in China. Model projected age-specific cancer incidence and mortality were close to the observed data in the national cancer registration. The NCC modeling framework reproduced the cumulative cancer cases and deaths observed in the prospective cohort study at 7.0 and 10.8 years of follow-up. Model estimated net survival rates also consistent with population-based statistics.

Conclusion

The NCC modeling framework's ability to reproduce the observed population-level cancer statistics and the cancer cases in a prospective cohort study suggests its results are reliable to inform decision-making related to six major cancers in China.

Objective

To investigate the optimal management of patients with epidermal growth factor receptor gene (EGFR) mutant locally advanced non-small cell lung cancer (LA-NSCLC).

Methods

Patients with unresectable stage III lung adenocarcinoma (LAC) harboring EGFR mutations from 2012 to 2018 were analyzed retrospectively, and were categorized into three groups according to the primary treatment: chemoradiotherpy (CRT) (group 1), combined radiation therapy (RT) and EGFR-tyrosine kinase inhibitors (TKI) with/without chemotherapy (group 2), and EGFR-TKI alone until tumor progression (group 3). Inverse probability of multiple treatment weighting (IPTW) of propensity score was used to compare overall survival (OS) and progression free survival (PFS) between treatments and account for confounding.

Results

A total of 104, 105, and 231 patients were categorized into groups 1, 2, and 3, respectively. After IPTW adjustment, the median PFS for each group was 12.4, 26.2, and 16.2 months (log-rank P < 0.001), and the median OS was 51.0, 67.4 and 49.3 months (log-rank P = 0.084), respectively. Compared with those in group 1, patients in group 2 had significantly improved PFS [adjusted hazard ratio HR (aHR), 0.40; 95% confidence interval (CI): 0.29, 0.54; P < 0.001] and OS (aHR, 0.61; 95% CI: 0.38, 0.98; P = 0.039). Patients in group 3 had prolonged PFS (aHR, 0.66; 95% CI: 0.50, 0.87; P = 0.003), but not OS (aHR, 0.90; 95% CI: 0.62, 1.32; P = 0.595). Doubly robust IPTW analysis and multivariable Cox regression analysis yielded similar findings.

Conclusions

EGFR-TKIs after chemoradiation or combined with radiation alone correlated with the longest PFS and OS (versus CRT or TKIs alone) in patients with EGFR-mutant unresectable LA-NSCLC. Well-designed prospective trials were warranted.