Waiting periods for the initiation of cancer treatment and the factors associated with delays in the Hokushin region of Japan.

To analyze the incidence of cancer during 2008-2012 in Beijing, China, and compare the cancer spectrum with that during 1998-1999. Data from the Beijing Cancer Registry (BCR), which covered 12 million residents and 16 administrative regions in Beijing, were checked and evaluated on basis of the criteria of data quality from the National Central Cancer Registry (NCCR) of China. Incidences were calculated stratified by cancer type, sex, areas (urban/rural), and age. The Chinese census population in 1982 and the world Segi's population were used for calculating the age-standardized incidences. A total of 177,101 new cancer cases were diagnosed in Beijing between 2008 and 2012. The crude incidence rate (CR) of all cancers was 282.64/100,000 (290.71/100,000 in males and 274.45/100,000 in females). The age-standardized rates by Chinese standard population (ASR-China) and by world standard population (ASR-world) were 124.46/100,000 and 161.18/100,000, respectively. Female breast cancer was the most common cancer, followed by lung cancer, colorectal cancer, liver cancer, and stomach cancer, with the CR of 59.87/100,000, 59.21/100,000, 32.49/100,000, 19.81/100,000 and 17.96/100,000, respectively. In urban areas, female breast cancer (68.50/100,000) was still the most common cancer, followed by lung cancer (61.23/100,000), colorectal cancer (37.23/100,000), prostate cancer (20.49/100,000) and stomach cancer (20.07/100,000). In rural areas, lung cancer (55.94/100,000) was the most common cancer, followed by female breast cancer (45.87/100,000), colorectal cancer (24.77/100,000), liver cancer (20.68/100,000) and stomach cancer (14.52/100,000). Great changes of the cancer spectrum were found from the period of 1998-1999 to the period of 2011-2012 in Beijing. The cancer burden in Beijing was heavier than the national average level. Cancer prevention and control strategies, especially for lung, colorectal, prostate and female thyroid cancers, should be enhanced.

Stigma May Exacerbate Disproportionately Low Guideline-Concordant Treatment Rates for Patients With Advanced-Stage Lung Cancer in the United States

National Institutes of Health State-of-the-Science Conference Statement: Multivitamin/Mineral Supplements and Chronic Disease Prevention

Purpose: Physical activity (PA) plays an important role in health outcomes for people with cancer, and pre-diagnosis PA influences PA behaviors after cancer treatment. Less is known about the PA of lung cancer patients, and the strong history of smoking could influence pre-diagnosis levels of PA and place them at risk for health problems. This study aimed to compare pre-diagnosis PA and its correlates in patients with lung cancer and other types of cancer (female breast, colorectal, and prostate cancer) and examine the relationship between pre-diagnosis PA and all-cause mortality. Methods: This study used data from the UK Biobank, which is a national cohort study with accelerometry data. We included 2662 participants and used adjusted linear regressions and survival analyses. Results: Male and female lung cancer groups spent a mean of 78 and 91 min/day in pre-diagnosis moderate to vigorous PA (MVPA), respectively; this is lower than the 3 other types of cancer (p < 0.001). Younger age and faster walking pace had a strong association with PA in all the four types of cancer (p < 0.01). Smoking status had a strong association with PA in the lung cancer group, while obesity had a strong association with PA in female breast, colorectal, and prostate cancer (p < 0.01). Higher levels of pre-diagnosis MVPA (≥1.5 h/day) were associated with a significantly lower all-cause mortality risk. Conclusions: The present study suggests that lung cancer patients are the most inactive population before diagnosis. The identified difference in correlates of PA suggest that cancer-specific approaches are needed in PA research and practices. This study also highlights the importance of high PA for individuals with high cancer risk.

Lung cancer management challenges amidst COVID-19 pandemic: hope lives here.

The worldwide burden of cancer and other non-communicable diseases (NCDs) is increasing. In 2005, NCDs were estimated to have caused more than 60% (35 million) of all deaths worldwide. For cancer an estimated 7.6 million deaths occurred in 2008 (around 20% of all NCD deaths). Without prevention or control the total cancer deaths is projected to rise to 13.1 million by 2030 whilst incidence will rise from 12.7 million in 2008 to 21.3 in 2030 based on demographic changes alone. The greatest percent increases will be in countries falling within the low and medium Human Development Index (HDI) categories. This phenomenon is mainly a consequence of the epidemiologic transition, i.e., a shift from infectious diseases to NCDs. Wider adoption of specific aspects of westernized lifestyles would translate to still greater increases in certain cancer types. In many countries the burden of cancer and other NCDs will therefore add to communicable diseases and malnutrition to impose a “double burden” on the poorest. These trends represent major challenges to health, poverty, sustainable development and equality. One consequence, especially in the lower HDI countries, is the implausibility of treating our way out of the cancer epidemic. Large variations in the type and number of cancers are observed in different regions of the world. Within high- and very high-HDI countries, prostate and breast cancers are the most common in males and females respectively, with lung and colorectal cancers ranking next in both sexes. Within low-HDI countries lung and breast cancers remain among the most common, but cancers of the cervix, stomach, liver, and Kaposi sarcoma are also among the leading types – all of which are cancers with infection-related aetiology. Medium-HDI countries are intermediate with respect to their patterns of cancer burden, reflecting an on-going transition from infection-related cancers to those most associated with a westernized lifestyle. The three most common types of cancer in medium-HDI countries are lung, stomach and liver cancers in males, and breast, cervix and lung cancer in females. In face of these increases in burden and variations in types of cancer, both primary and secondary cancer prevention offer many opportunities through implementing existing knowledge about environmental and lifestyle risk factors and using the natural history of the disease to establish screening and early detection. Reducing tobacco consumption through primary prevention has the capacity to contribute globally to the largest number of cancer deaths avoided; implementation of the international treaty of the WHO Framework Convention on Tobacco Control is vital. Effective tobacco control efforts have resulted in substantial declines in tobacco-related cancer deaths in the USA and several European countries demonstrating the effectiveness of a range of control methods. In relation to diet there are a number of clear potentially modifiable risk factors. Obesity is associated with an increased risk of breast, colorectal, endometrium, kidney, oesophageal and pancreatic cancers. Physical inactivity is also associated with breast, colorectal and endometrium cancer. Much less is known about specific nutrients or dietary components, although alcohol is associated with increased risks of liver, aero-digestive tract, breast and colorectal cancers; the consumption of red and processed meats as well as a diet low in fibre has also been associated with colorectal cancer. Recent estimates reported about 2 million cancer cases per year (16% of the global cancer burden) attributable to chronic infections, principally human papillomavirus (HPV); hepatitis B virus (HBV) and hepatitis C virus (HCV); and Helicobacter pylori (H. pylori). The contribution is substantially larger in low-resource countries (that include low- and medium-HDI countries) (26%) than in high-resource countries (8%) making the prevention or eradication of these infections a powerful tool to overcome inequalities in cancer incidence between poor and rich populations. Priorities include vaccination against HBV and HPV and avoidance of HCV transmission. Environmental causes of cancer, encompassing environmental contaminants or pollutants (e.g. radon, indoor and outdoor air pollution), naturally occurring toxins (e.g. aflatoxins, arsenic), occupationally-related exposures (e.g. asbestos) and radiation (X-rays and gamma radiation, as well as sunlight and UV tanning devices) can make substantial contributions to specific cancers or cancer clusters on a smaller scale. These exposures can also be amenable to low-cost modification by regulation, thus reducing the burden of some very lethal cancers with straightforward operable measures. The majority of cancers have a long latent phase and are preceded by pre-neoplastic lesions. Early detection and treatment of cancer or precancerous lesions resulted in substantial declines in cancer mortality in high-resource countries and would greatly improve survival in low-resource countries where access to expensive cancer treatment is limited. Firm evidence of efficacy of screening programmes in the reduction of cancer mortality exists for three cancer sites: the cervix uteri, breast, and colon-rectum. In relation to the lower HDI countries in particular there is a need to evaluate alternatives to mammographic screening for early detection of breast cancer. These may initially include improvements in breast awareness among women and health workers; facilitation of access of women with clinically detectable lumps to high-quality diagnostic facilities and of women with breast cancer to effective systemic treatment. Whilst much can be achieved based on current knowledge there is an important caveat. Namely, that knowing the cause does not automatically translate to having a strategy for prevention. For example, it is likely that a large proportion of stomach cancer could be prevented by H. pylori control, but currently neither a mechanism to achieve this, nor the effectiveness if achieved, is known. In analogous fashion far more research is required into behavioural change in relation to lifestyle factors such as diet, obesity and physical activity. Even for existing prevention strategies additional work is needed on their implementation into health care settings, particularly in lower HDI countries. At the same time, for a number of major cancers (e.g., colon, prostate, kidney, pancreas, brain, lympho-haematological malignancies) research is needed to identify as yet unknown risk factors. Finally, there is a remarkable opportunity for the recent advances in understanding the molecular basis of carcinogenesis to provide new tools and insights into aetiology and prevention. Among these opportunities are: improved exposure assessment; elucidation of mechanistic pathways related to defined exposures; identification of molecular markers which indicate risk of disease progression; and stratification of cancer cases by molecular subtype in relation to specific exposures. This broader concept of translational cancer research and its potential to inform cancer prevention stands at an exciting but critical point in time. It is only by complementing efforts to improve treatment with those aimed at prevention that the impending epidemic of this disease can be addressed. Citation Format: Christopher Paul Wild. Preventable exposures associated with human cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY14-01. doi:10.1158/1538-7445.AM2013-SY14-01

e15174 Background: Microsatellite instability-high (MSI-H) is the gain or loss of nucleotides from repetitive DNA caused by genomic hypermutability and a powerfully predictive phenotype for diagnosis, immunotherapy and prognosis in various types of cancer. Herein, we analyze the frequency of MSI-H for the understanding of epidemiology of MSI-H across major types of human cancer. Methods: MSI value was calculated by bioinformatics algorithm based on NGS from 539 genes panel in tumor tissue. Patients were divided into three classes as MSI-H, MSI-L and MSS based on MSI value. MSI-H was defined as above 10% positive of the 195 tested microsatellites sites, and this method was totally consistent with conventional MSI-PCR testing in research and development sample verification. We compared the differences of MSI-H ratio in eight types of human cancer including liver cancer, bile duct cancer, gastric cancer, colorectal cancer, pancreatic cancer, melanoma, glioma and lung cancer from 874 cancer cases via χ2 test, adjusted standardized residual or Fisher's exact test. Results: The ratios of MSI-H in eight types of solid tumors were 0% in 32 patients with bile duct cancer or 27 patients with pancreatic cancer, 0.6% (1/174) in liver cancer, 1.9% (1/54) in gastric cancer, 6.7% (8/119) in colorectal cancer, 3.1% (1/32) in melanoma, 4% (1/25) in glioma, and 0.5% (2/411) in lung cancer, respectively. Significant correlations between the MSI-H and cancer types were found by χ2 test (χ2 = 26.571, Cramer’s V coefficient = 0.174, p = 3.980×10−4). Only patients with colorectal cancer had absolute values of adjusted standardized residual above 3, its observed counts of MSI-H significantly higher than expected counts. Fisher’s exact test was performed to analyze the differences of MSI-H ratio across hepatobiliary (liver and bile duct) cancer, digestive tract (gastric and colorectal) cancer and lung cancer, and we found the MSI-H ratio of patients with digestive duct cancer was significantly higher than patients with hepatobiliary cancer ( p = 0.007) or lung cancer ( p = 4.599×10−4). Conclusions: Our study provided new references to cancer-specific properties and clinical diagnosis of MSI especially in East Asian populations. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.

Purpose: Brain metastases occur in approximately 8-10% of patients with cancer, and the incidence has increased over the past decades. The most common primary tumors responsible for brain metastases are lung cancer, melanoma, renal cell carcinoma (RCC), breast cancer and colorectal cancer, and the prognosis is still very poor with an overall 2-year survival rate of 8%. The precise mechanisms by which genomic and transcriptional abnormalities drive the formation of brain metastases remains unclear. Here, we conducted comprehensive genomic and transcriptional analysis with paired primary tumor tissue (or extracranial metastasis tissue) and brain metastasis tissue using whole-exome sequencing (WES), mRNA-Seq and global methylation profiling. Methods: All patient samples were collected at the University of Texas MD Anderson Cancer Center. Frozen, paired brain metastasis tissue and primary tumor tissue (or extracranial metastasis tissue) and white blood cells were acquired from RCC (n=12), breast cancer (n=17), lung cancer (n=15) and cutaneous melanoma (n=14) patients. DNA and RNA were extracted from regions of frozen tissue with at least 70% viable tumor cells and peripheral blood leukocytes. Libraries for WES and mRNA-Seq were prepared and sequenced on the Illumina HiSeq4000 platform. For methylation profiling, DNA was subjected to bisulfite conversion and analyzed using Illumina Infinium MethylationEPIC Beadchip arrays. Results: Genome-wide hypermutation due to POLE or POLD1 mutations was observed in one breast cancer patient and two lung cancer patients. Two of these cases acquired the hypermutation during development to brain metastasis. Somatic mutations or methylation of VHL gene were identified in 81.8% of RCC patients, and two patients had somatic VHL mutations in brain metastases only. Interestingly, Gene Set Enrichment Analysis revealed significant enrichment for hypoxia pathway transcripts in the RCC brain metastases relative to primary tumors. The most common alterations in breast and lung cancer patients were TP53 mutations with frequencies of 50.0% and 73.3%, followed by ERBB2 alterations (43.8%) in breast cancer patients and mutually exclusive alterations of EGFR (33.3%) and KRAS (26.7%) in lung cancer patients. Mutually exclusive alterations of NRAS (42.9%) and BRAF (42.9%) were also observed in melanoma patients. Gene expression and epigenetic analysis revealed characteristics of brain metastases depending on primary cancer types. Conclusions: Comprehensive genomic analysis of brain metastases from four different cancer types revealed that brain metastasis tissue has unique genomic, transcriptional and epigenetic profiles according to histopathology groups. Therefore, the therapeutic strategies should be designed based at least in part on tumor histiogenesis. Citation Format: Kazutaka Fukumura, Xizeng Mao, Xingzhi Song, Grant M. Fischer, Jie Yang, Erik P. Sulman, Michael A. Davies, Jianhua Zhang, Jason T. Huse. Comprehensive genomic analysis of brain metastases from multiple cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3406.

Mutational Signatures in Helicobacter pylori–induced Gastric Cancer: Lessons From New Sequencing Technologies

50 Background: Racial and ethnic disparities in the quality of cancer pain treatment are widely documented. The purpose of this study was to examine adjusted differences by race/ethnicity in the odds of reporting pain and differences in pain severity. Methods: This study used data from Cancer Care Outcomes Research and Surveillance Consortium (CanCORS), a nationally representative cohort study of colorectal and lung cancer patients. Patients were identified following incident colorectal or lung cancer diagnosis via rapid case ascertainment. Surveys were administered between three and five months following diagnosis. Pain was assessed via patient self-report using the Brief Pain Inventory. Control variables included sex, age, education, wealth, fatalism, marital status, survey language, self-reported health status, depression, cancer stage, and care at a Veterans Administration (VA) facility. Each control variable was first individually assessed as a potential mediator in the relationship between race/ethnicity and pain severity. Final models were fully adjusted with all control variables. Results: Among 3,216 individuals with colorectal cancer (16.4% black), 40% reported pain; among 2,545 with lung cancer (12% black), 57% reported pain. The odds of reporting pain did not differ by race/ethnicity in lung or colorectal cancer patients in adjusted analyses. None of the included covariates significantly mediated this relationship. However, among those reporting pain, pain severity was higher for black relative to white patients in both lung (p=0.002) and colorectal cancer (p=0.000). Conclusions: The odds of reporting presence of pain did not differ by race/ethnicity. However, among those reporting pain, blacks reported higher pain severity than whites in both cancer types, even after adjusting for patient and health status characteristics. Differential pain severity by race/ethnicity, particularly for black patients, may be an important consideration in assessing the quality of cancer pain management.

Inequality in Palliative Radiation Therapy: A Population-based Analysis

Background: Diabetes is associated with an increased risk of several cancers and overall mortality and cancer mortality. Previous studies have suggested that metformin use may decrease cancer mortality, though findings have been inconsistent. We examined metformin and other diabetes medication use and survival from breast, colorectal, lung, and gastric cancers with respect to timing of diabetes medication initiation. Methods: Electronic medical record (EMR) data on diabetes medication use was extracted for 2,890 participants from the Shanghai Men's Health Study (SMHS) and Shanghai Women's Health Study (SWHS) with incident breast (n = 633), colorectal (n = 892), lung (n = 822), or gastric (n = 543) cancers diagnosed after 2004. Individuals with and without diabetes diagnosis were analyzed for the association between diabetes medication use (metformin, sulfonylureas, and insulin) and cancer survival using Cox proportional hazards models. Results: After adjustment for patient and clinical characteristics, ever use of any diabetes medication was associated with a decrease in all-cause mortality among all four cancer types (HR = 0.84, 95% CI: 0.74, 0.94). Compared to non-users of any diabetes drug, lower mortality was observed among all cancer patients who ever took metformin (HR = 0.78, 95% CI: 0.65, 0.93) or sulfonylureas (HR = 0.80, 95% CI: 0.69, 0.93). When stratified by initiation of diabetes medication use with respect to cancer diagnosis, the association was significant for both metformin and sulfonylureas use, but only among those who initiated use after cancer diagnosis. When cancers were analyzed individually, significant associations were observed for lung and colorectal cancer cases for metformin or sulfonylureas use among those who initiated use after cancer diagnosis. The inverse associations were predominantly observed among those whose diabetes diagnosis could be verified by EMR. Diabetes medication use was not significantly associated with survival from breast or gastric cancer. Conclusions: Use of metformin or sulfonylureas was associated with improved survival among lung and colorectal cancer patients. The association was primarily observed among those who initiated diabetes medication use after cancer diagnosis. While a possible survival time bias can't be excluded, additional investigation on the topic is needed given the potential translational impact if our finding were proved to be true. Citation Format: Michelle L. Baglia, Yong-Bing Xiang, Gong Yang, Tao Zheng, Honglan Li, Mingrong You, Yong Cui, Yu-Tang Gao, Wei Zheng, Xiao-Ou Shu. Diabetes medication use in association with survival among patients of breast, colorectal, lung, and gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3419.

A quality of life assessment is useful in identifying a specific health impact on patients who are suffering from various medical conditions. This study estimated the quality of life among patients with cancers of the lungs, breast, colorectum, oesophagus, liver, and stomach in urban China and evaluates the associated factors. This study employed a random cluster sampling strategy to recruit patients with lung, breast, colorectal, oesophageal, liver, or stomach cancer from eleven third-grade class-A (the highest level) hospitals in Beijing between October 2013 and May 2014. We performed a quality of life survey that included solicitation of sociodemographic and clinical information and the use of a EuroQoL five-dimension three-level questionnaire. We applied the Chinese time trade-off method to calculate the health utility values, which were transformed into binary variables (using the median as the cut-off). In addition, multivariable logistic regression analysis was used to examine the factors associated with the quality of life. A total of 637 patients (91 with lung cancer, 152 with breast cancer, 60 with colorectal cancer, 108 with oesophageal cancer, 154 with liver cancer, and 72 with stomach cancer) were included in this study; the medians of the health utility values were 0.780, 0.800, 0.800, 0.860, 0.800, and 0.870, respectively. The most common concerns for patients of all six cancer types were pain/discomfort and anxiety/depression. The reported health status of patients was associated with various demographic and clinical variables. This study highlighted that pain relief and psychological support are important aspects of patient management for those with these types of cancer. Individuals with factors associated with a poorer quality of life should be targets for additional support.

We investigated the associations between the incidence rates of five typical cancer types and five air pollutants in 317 Japanese municipalities in 2017. We obtained the concentrations of the five air pollutants, i.e., sulfur dioxide (SO2), nitric oxide (NO), nitric dioxide (NO2), photochemical oxidants (Ox), and fine particulate matter (PM2.5), from Japan’s National Institute for Environmental Studies and calculated the yearly mean of each. We identified patients of both sexes with the five most common cancers in Japan’s National Cancer Registry, which covers all cancer patients in the country. For males, we included prostate, stomach, colorectal, lung, and liver cancers. For females, we included breast, colorectal, lung, stomach, and uterine cancers. We calculated the Spearman’s correlation coefficients between 25 pairs of air-pollutant concentrations and the age-standardized incidence rate of the cancer types for each sex. We used Poisson regression models to examine the dose–response relationships. We identified 11 significantly positive correlation coefficients at the Bonferroni-corrected alpha level for the five pollutants for the five cancers in both sexes. We observed significantly positive dose–response relationships between NO2 and colorectal cancer and PM2.5 and lung cancer for both sexes. We also observed significant dose–response relationships between SO2 and PM2.5 and liver cancer for males and between NO and lung cancer and NO2 and breast cancer for females. We did not observe significant associations with prostate, stomach, or uterine cancer. Our findings support the concept that exposure to air pollutants increases cancer incidence rates.

Previous studies have shown that asthma is a risk factor for lung cancer, while the mechanisms involved remain unclear. We attempted to further explore the association between asthma and non-small cell lung cancer (NSCLC) via bioinformatics analysis. We obtained GSE143303 and GSE18842 from the GEO database. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) groups were downloaded from the TCGA database. Based on the results of differentially expressed genes (DEGs) between asthma and NSCLC, we determined common DEGs by constructing a Venn diagram. Enrichment analysis was used to explore the common pathways of asthma and NSCLC. A protein-protein interaction (PPI) network was constructed to screen hub genes. KM survival analysis was performed to screen prognostic genes in the LUAD and LUSC groups. A Cox model was constructed based on hub genes and validated internally and externally. Tumor Immune Estimation Resource (TIMER) was used to evaluate the association of prognostic gene models with the tumor microenvironment (TME) and immune cell infiltration. Nomogram model was constructed by combining prognostic genes and clinical features. 114 common DEGs were obtained based on asthma and NSCLC data, and enrichment analysis showed that significant enrichment pathways mainly focused on inflammatory pathways. Screening of 5 hub genes as a key prognostic gene model for asthma progression to LUAD, and internal and external validation led to consistent conclusions. In addition, the risk score of the 5 hub genes could be used as a tool to assess the TME and immune cell infiltration. The nomogram model constructed by combining the 5 hub genes with clinical features was accurate for LUAD. Five-hub genes enrich our understanding of the potential mechanisms by which asthma contributes to the increased risk of lung cancer.