Cancer Epidemiology

Clinicopathologic and epidemiological characteristics of prognostic factors in post-surgical survival of colorectal cancer patients in Jiangsu Province, China Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Said Abasse Kassim, Weiyan Tang, Muhammad Abbas, Shenzhen Wu, Qingdao Meng, Chengcheng Zhang, Xiaobo Li, Rui Chen Abstract Poor survival among colorectal cancer (CRC) patients has been widely associated with clinico-epidemiological features and treatment regimen. In Jiangsu (China), however, it is not known which one of the prognostic factors explains the survival disparities among patients with CRC. This prospective study using 1078 patients (stages I-IV) that underwent surgery at Jiangsu Hospital, explored the relevant factors affecting the prognoses of right-side colon cancer (RCC), left-side colon cancer (LCC) and rectal cancer (ReC) patients. Of these cases, 234 (21.7%), 241 (22.4%) and 603 (55.9%) were found to have RCC, LCC and ReC respectively. Compared to LCC, RCC exhibited a greater proportion of older patients, poorly differentiated carcinomas, higher T-stage and higher TNM-stage. The overall survival (OS) for RCC was 60 vs.78 or 77 months for LCC or ReC respectively (P = 0.030). There were no significant differences in OS between LCC and ReC across the subgroups (P = 0.633). In multivariate analysis, RCC patients had age (>60 vs. ≤60 years, HR = 1.529, P = 0.019), N-stage (N1 vs. N0, HR = 4.056, P = 0.012) and M-stage (M1 vs. M0, HR = 3.442, P < 0.0001) as independent prognostic factors, whereas smoking status was found to be a predictor of mortality (smoker vs. nonsmoker, HR = 2.343, P = 0.017) for LCC. In addition, age (>60 vs. ≤60 years, HR = 2.199, P < 0.0001), alcohol consumption (drinker vs. nondrinker, HR = 0.510, P = 0.034), tumor grade (Poor vs. well/moderate, HR = 2.759, P = 0.031) and T-stage (T3-4 vs. T1-2, HR = 1.742, P < 0.0001) were found to be predictors of mortality for ReC. There were significant pairwise interactions across subgroups. Furthermore, significant differences were observed for LCC vs. RCC (OS, HR = 0.783, P = 0.039), but no statistically significant differences for ReC vs. RCC (P = 0.149) and LCC vs. ReC (P = 0.355). Nevertheless, significant differences remained between ReC vs. RCC for male (HR = 0.591, P = 0.009), drinker (HR = 0.396, P = 0.005), rural resident (HR = 0.437,P = 0.022), tumor grade (well/moderate, HR = 0.475, P = 0.022), T-stage (T1-2, HR = 0.362, P = 0.001), N-stage (N0, HR = 0.604, P = 0.011), M-stage(M0, HR = 0.401, P = 0.006) and TNM-stage (I-II, HR = 0.567, P = 0.005). Statistically significant differences were observed for LCC vs. RCC for gender (female, HR = 0.495, P = 0.003) and T-stage (T1-2, HR = 0.417, P = 0.010) as well as for LCC vs. ReC in patients with smoking habits (HR = 1.951, P = 0.002) and M-stage (M0, HR = 2.291, P = 0.003). These findings suggest that the variations in CRC post-surgical survival in China may be primarily explained with the clinicopathologic features and epidemiological characteristic of the patients. Patients with RCC had significantly worse OS compared to both LCC and ReC in several subgroups.

Incidence, mortality and outcome of meningiomas: A population-based study from Germany Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Bernd Holleczek, Daniel Zampella, Steffi Urbschat, Felix Sahm, Andreas von Deimling, Joachim Oertel, Ralf Ketter Abstract Background Meningiomas are mostly benign tumors that originate from the coverings of the brain and spinal cord. Compared to malignant glial tumors, meningiomas are relatively understudied with regard to their risk factors and epidemiology. In particular, population-based data on cancer burden and patient outcomes are scant. Methods Population-based data from Saarland, a federal state in South-Western Germany, were used; the data included 992 patients diagnosed with a first meningioma between 2000 and 2015. Incidence and mortality rates—as well as estimates of observed and relative survival and cumulative incidence of tumor recurrence up to 10 years after diagnosis—were derived by sex, age, WHO grade, and whether or not the patient had undergone surgery. Results This population-based study not only included patients treated in the regional university hospital but also those treated elsewhere or patients without any surgical treatment. The mean age of the patients at diagnosis was 63 years, and 70%, 28% and 3% had WHO grade I, II and III meningiomas, respectively. Ten-year observed and relative survival of all patients combined was 72% and 91% respectively. Tumor-related mortality varied by sex and increased with age at diagnosis and the WHO grade of the tumor. The overall 10-year cumulative incidence of meningioma recurrence was 9%. Conclusion This analysis represents the first modern population-based analysis of meningioma incidence and mortality and outcomes of patients with such neoplasms in Germany. Derived from an unselected sample of patients, this study may fill a hitherto existing gap in the literature on meningiomas.

Birthweight and risk of thyroid cancer and its histological types: A large cohort study Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Julie Aarestrup, Cari M. Kitahara, Jennifer L. Baker Abstract Background The aetiology of thyroid cancer is poorly understood, but it is possible that this malignancy has origins early in life. It is, however, currently unknown if birthweight, as an indicator of prenatal growth, is related to thyroid cancer risk. Objective To investigate if birthweight is associated with the later risk of thyroid cancer and its histological types. Methods 246,141 children (120,505 girls, 125,636 boys) from the Copenhagen School Health Records Register, born 1936–1989, were prospectively followed in the Danish Cancer Registry. Cox regressions were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). Results During follow up, 241 individuals (172 women, 69 men) were diagnosed with thyroid cancer (162 papillary, 53 follicular). Birthweight was significantly and positively associated with risk of thyroid cancer overall (HR = 1.30 [95% CI: 1.03–1.64] per kilogram). There were no sex differences in the associations. Birthweight was positively and significantly associated with follicular thyroid cancer (HR = 1.74 [95% CI: 1.07–2.82] per kilogram), and although there was an indication of a positive association, it did not reach statistical significance for the more common papillary type (HR = 1.20 [95% CI: 0.90–1.59] per kilogram). Conclusion A heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.

Increasing incidence and survival of corpus uteri cancer in Estonia over the past two decades Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Kristiina Ojamaa, Piret Veerus, Aleksei Baburin, Hele Everaus, Kaire Innos Abstract Background Corpus uteri cancer has become the fourth most common female cancer in Europe. In Estonia, the prevalence of obesity is increasing, and corpus uteri cancer survival has been relatively low. The aim of the study was to evaluate incidence, mortality and survival trends of corpus uteri cancer in Estonia by age, stage and histological subtypes with an emphasis on surgical treatment. Methods Estonian Cancer Registry data on incident cases of corpus uteri cancer were used to examine incidence trends (1995–2016) and calculate relative survival ratios (RSR) (1996–2016). Cases were classified by morphology and FIGO stage. Causes of Death Registry data were used to analyse corrected mortality (1995–2017). Results A total of 4281 cases were diagnosed in 1996–2016. A significant increase was seen in age-standardized incidence from 2009, while mortality remained stable throughout the study period. Significant increases were observed for type I cancers and age groups ≥65 years. Overall age-standardized 5-year RSR improved from 70% in 1996–2002 to 78% in 2010–2016. Survival increased for type I cancers, all age groups and all stages (significantly for stage IV). The proportion of surgically treated cases increased significantly from 85% to 89%, with the largest increases seen in older age groups and later stages. Discussion The rising corpus uteri cancer incidence in Estonia is driven by the type I cancer trend. Survival gain for later stages and older age groups likely reflected more frequent surgical treatment. To reduce mortality, further efforts are necessary to ensure appropriate care for all patients.

Screening baseline characteristics of early lung cancer on low-dose computed tomography with computer-aided detection in a Chinese population Publication date: October 2019 Source: Cancer Epidemiology, Volume 62 Author(s): Yuanyuan Liu, Hongbin Luo, Haomiao Qing, Xiaodong Wang, Jing Ren, Guohui Xu, Shibei Hu, Changjiu He, Peng Zhou Abstract Objectives This study investigated appropriate baseline characteristics for screening a Chinese population at high risk of early lung cancer, assisted by low-dose computed tomography (LDCT) with computer-aided detection (CAD). Included is a discussion of the viability of using LDCT in the screening guideline and optimizing the guideline. Methods In 2014, 1016 individuals from Sichuan Province were enrolled who satisfied the criteria for high risk according to the 2013 National Comprehensive Cancer Network (NCCN) Guidelines for Non-Small Cell Lung Cancer. From 2014 to 2018, each subject was followed using LDCT with CAD, and pathologically confirmed lung cancers and baseline nodule characteristics (size and density) were recorded. Positive risk was considered a non-calcified solid or part-solid nodule on LDCT with diameter ≥5 mm and ground-glass nodule ≥8 mm, as newly recommended by the China National Lung Cancer Screening Guideline. Results From 2014–2018, 13 cases of lung cancer were detected; 5 of these were early stage (38.5%). According to the NCCN criteria, 54 women were included and one of these (1.8%) developed lung cancer. The prevalence of lung cancer was 0.7% at baseline. For the entire population (excluding subjects with a tumor mass at baseline, n = 4), the rate of positivity was 20.4% at baseline; applying the Chinese criteria, the false positive rate was 19.5% (197/1012). Conclusions Further studies are warranted to establish appropriate eligible criteria and management strategies for Chinese populations.

Establishing population-based surveillance of diagnostic timeliness using linked cancer registry and administrative data for patients with colorectal and lung cancer Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Clare Pearson, Jess Fraser, Michael Peake, Roland Valori, Veronique Poirier, Victoria H. Coupland, Sara Hiom, Sean McPhail, Jodie Moffat, Georgios Lyratzopoulos, Jon Shelton Abstract Background Diagnostic timeliness in cancer patients is important for clinical outcomes and patient satisfaction but, to-date, continuous monitoring of diagnostic intervals in nationwide incident cohorts has been impossible in England. Methods We developed a new methodology for measuring the secondary care diagnostic interval (SCDI - first relevant secondary care contact to diagnosis) using linked cancer registration and healthcare utilisation data. Using this method, we subsequently examined diagnostic timeliness in colorectal and lung cancer patients (2014–15) by socio-demographic characteristics, diagnostic route and stage at diagnosis. Results The approach assigned SCDIs to 94.4% of all incident colorectal cancer cases [median length (90th centile) of 25 (104) days] and 95.3% of lung cancer cases [36 (144) days]. Advanced stage patients had shorter intervals (median, colorectal: stage 1 vs 4 - 34 vs 19 days; lung stage 1&2 vs 3B&4 - 70 vs 27 days). Routinely referred patients had the longest (colorectal: 61, lung: 69 days) and emergency presenters the shortest intervals (colorectal: 3, lung: 14 days). Comorbidities and additional diagnostic tests were also associated with longer intervals. Conclusion This new method can enable repeatable nationwide measurement of cancer diagnostic timeliness in England and identifies actionable variation to inform early diagnosis interventions and target future research.

Development of predictive models to identify advanced-stage cancer patients in a US healthcare claims database Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Daina B. Esposito, Leo Russo, Dina Oksen, Ruihua Yin, Vibha C.A. Desai, Jennifer G. Lyons, Patrice Verpillat, Jose L. Peñalvo, Francois-Xavier Lamy, Stephan Lanes Abstract Background Although healthcare databases are a valuable source for real-world oncology data, cancer stage is often lacking. We developed predictive models using claims data to identify metastatic/advanced-stage patients with ovarian cancer, urothelial carcinoma, gastric adenocarcinoma, Merkel cell carcinoma (MCC), and non-small cell lung cancer (NSCLC). Methods Patients with ≥1 diagnosis of a cancer of interest were identified in the HealthCore Integrated Research Database (HIRD), a United States (US) healthcare database (2010–2016). Data were linked to three US state cancer registries and the HealthCore Integrated Research Environment Oncology database to identify cancer stage. Predictive models were constructed to estimate the probability of metastatic/advanced stage. Predictors available in the HIRD were identified and coefficients estimated by Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation to control overfitting. Classification error rates and receiver operating characteristic curves were used to select probability thresholds for classifying patients as cases of metastatic/advanced cancer. Results We used 2723 ovarian cancer, 6522 urothelial carcinoma, 1441 gastric adenocarcinoma, 109 MCC, and 12,373 NSCLC cases of early and metastatic/advanced cancer to develop predictive models. All models had high discrimination (C > 0.85). At thresholds selected for each model, PPVs were all >0.75: ovarian cancer = 0.95 (95% confidence interval [95% CI]: 0.94–0.96), urothelial carcinoma = 0.78 (95% CI: 0.70–0.86), gastric adenocarcinoma = 0.86 (95% CI: 0.83–0.88), MCC = 0.77 (95% CI 0.68–0.89), and NSCLC = 0.91 (95% CI 0.90 – 0.92). Conclusion Predictive modeling was used to identify five types of metastatic/advanced cancer in a healthcare claims database with greater accuracy than previous methods.

Net survival in recurrence-free colon cancer patients Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Antoine Drouillard, Anne-Marie Bouvier, Olayidé Boussari, Gaëlle Romain, Sylvain Manfredi, Come Lepage, Jean Faivre, Valérie Jooste Abstract Purpose Conditional net survival in recurrence-free patients (CNS-RF) provides relevant clinical information and has never been assessed yet in a non-selected colon cancer population. We aimed to estimate conditional 5-year net survival in recurrence-free patients with colon cancer in the population-based Digestive Cancer Registry of Burgundy (France). Methods CNS-RF was estimated in the 3736 patients resected for cure for primary colon cancer between 1976 and 2006, using a flexible parametric model of net survival for every additional year survived at diagnosis and from 1 to 5 years thereafter. Results The net probability of surviving 5 more years increased from 72% at diagnosis to 92% for recurrence-free patients who survived 5 years after diagnosis. CNS-RF was over 90% 3 years after diagnosis in patients aged 75 and below. CNS-RF was over 95% in patients diagnosed after 2000 who were recurrence-free 3, 4 or 5 years after diagnosis. CNS-RF was similar between patients with stage I and II disease from 2 years after diagnosis and patients with stage III disease from 5 years after diagnosis. The initial differences in net survival related to gross features, clinical presentation, number of harvested nodes in stage II, and number of involved nodes in stage III disappeared after 2 years. Conclusions CNS-RF is a relevant measure of prognosis in patients who have already achieved a period of remission. Providing an updated estimation of prognosis in the years following diagnosis may improve the survivors' quality of life and access to credit or insurance.

Defining a mutational signature for endometrial cancer screening and early detection Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Laura Costas, Luis Palomero, Yolanda Benavente, Magdalena Guardiola, Jon Frias-Gomez, Miquel Ángel Pavón, Maite Climent, José Manuel Martinez, Marc Barahona, Mónica Salinas, Marta Pineda, Ilaria Bianchi, Jaume Reventós, Gabriel Capellà, Mireia Diaz, August Vidal, Josep Maria Piulats, Jordi Ponce, Joan Brunet, Francesc Xavier Bosch Abstract Introduction The current availability of genomic information represents an opportunity to develop new strategies for early detection of cancer. New molecular tests for endometrial cancer may improve performance and failure rates of histological aspirate-based diagnosis, and provide promising perspectives for a potential screening scenario. However, the selection of relevant biomarkers to develop efficient strategies can be a challenge. Materials and methods We developed an algorithm to identify the largest number of patients with endometrial cancer using the minimum number of somatic mutations based on The Cancer Genome Atlas (TCGA) dataset. Results The algorithm provided the number of subjects with mutations (sensitivity) for a given number of biomarkers included in the signature. For instance, by evaluating the 50 most representative point mutations, up to 81.9% of endometrial cancers can be identified in the TCGA dataset. At gene level, a 92.9% sensitivity can be obtained by interrogating five genes. Discussion We developed a computational method to aid in the selection of relevant genomic biomarkers in endometrial cancer that can be adapted to other cancer types or diseases.

Neuroblastoma in relation to joint effects of vitamin A and maternal and offspring variants in vitamin A-related genes: A report of the Children's Oncology Group Publication date: August 2019 Source: Cancer Epidemiology, Volume 61 Author(s): Angela L. Mazul, Clarice R. Weinberg, Stephanie M. Engel, Anna Maria Siega-Riz, Fei Zou, Kathryn S. Carrier, Patricia V. Basta, Zalman Vaksman, John M. Maris, Sharon J. Diskin, Charlene Maxen, Arlene Naranjo, Andrew F. Olshan Abstract Background There is evidence vitamin A plays a role in neuroblastoma. Not only is 13-cis-retinoic acid used as maintenance therapy for high-risk cases, but prenatal vitamin intake use may decrease neuroblastoma risk. We hypothesized that single nucleotide polymorphisms (SNPs) in vitamin A-related genes are may be associated with neuroblastoma risk and potentially be modified by vitamin A intake. Methods The Neuroblastoma Epidemiology in North America (NENA) study recruited 563 case-parent sets through the Children's Oncology Group's Childhood Cancer Research Network. We ascertained dietary nutrient intake through questionnaires and genotyped 463 SNPs in vitamin A-related genes from saliva DNA. Offspring and maternal log-additive risk ratios (RR) and stratum-specific RR for gene-environment interaction were estimated with a log-linear model. We avoided false positives due to multiple testing by using the false discovery rate (FDR). Results When all neuroblastoma cases were considered together, no offspring variants met the significance criteria (FDR Q-value < 0.2). One maternal SNP (rs12442054) was associated with decreased risk of neuroblastoma (RR: 0.61; 95% Confidence Interval (CI): 0.47–0.79, Q = 0.076). When the cases were categorized according to prognostic risk category and age at onset, nine offspring SNPs were significantly associated with intermediate-risk neuroblastoma. Maternal rs6776706 was associated with (RR: 0.49; 95% CI: 0.33–0.72, Q = 0.161) high-risk neuroblastoma and maternal rs11103603 (RR: 0.60; 95% CI: 0.45–0.79, Q = 0.127) was associated with neuroblastoma aged <1 year. For gene-environment interaction, maternal rs729147 was associated with decreased risk of neuroblastoma among mothers with vitamin A consumption above the recommendation. Conclusions Although there is biologic plausibility for the role of vitamin A in neuroblastoma, we found weak evidence of a relationship between vitamin A related genes and neuroblastoma.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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6948891480

alsfakia@gmail.com