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Interval colorectal cancers (I-CRCs) arise during the interval time period between scheduled colonoscopies. Predicting which patients are at risk of I-CRCs remains an elusive undertaking, but evidence would suggest that most I-CRCs arise from lesions missed on index endoscopy. The procedural factors that lead to missed lesions are numerous and lack consensus in the literature. In Canada, the province of Newfoundland and Labrador has the highest incidence of CRCs. In this study our aim was to examine I-CRCs (3–60 months after last colonoscopy) in NL through a population-level analysis covering 67% of the province from 2001–2018. We estimated the I-CRC rate to be up to 9.3%. Median age of I-CRC diagnosis was 67.1 years with an interval time of 2.9 years. About 57% of these tumors occurred proximal to the splenic flexure, with 53% presenting as local disease. No temporal differences were observed in interval time or tumor distribution. On univariate and multivariable logistical regression, risk of right-sided I-CRC did not correlate to the index colonoscopy indication, bowel preparation quality, size of largest polyp removed, colonoscopy completion rate, or stage at presentation. Improvements in synoptic reporting utilization and national registries are needed to identity risk factors and reduce I-CRC frequency.

(1) Background: This is the first population-based study in Greece, with the aim to measure the changing trends of lung cancer (LC) and the associated risk factors before and after the economic crisis. Among the main objectives were the identification of LC hot spots and high-risk areas; (2) Methods: The study was conducted in Crete, the biggest island in Greece. Data (5057 LC cases) were collected from the Cancer Registry of Crete (CRC). The age-standardized incidence and mortality rates (ASIR, ASMR/100,000/year) were estimated, while additional indexes were used, including the adjusted Charlson’s comorbidity index (CCI%), the deprivation index (HPI-2), and the exposure to outdoor air pollution (OAP). The analysis was performed for two time periods (Period A: 1992–2008; Period B: 2009–2013); (3) Results: ASIR presented a significant increase during the economic crisis, while an even higher increase was observed in ASMR (Period A: ASMR = 30.5/100,000/year; Period B: ASMR = 43.8/100,000/year; p < 0.001). After 2009, a significant increase in the observed LC hot spots was identified in several sub-regions in Crete (p = 0.04). The risk of LC mortality increased even more for smokers (RR = 5.7; 95%CI = 5.2–6.3) and those living in highly deprived geographical regions (RR = 5.4; 95%CI = 5.1–5.8) during the austerity period. The multiple effect of LC predictors resulted in adjusted RRs ranging from 0.7 to 5.7 within the island (p < 0.05); (4) Conclusions: The increased LC burden after the onset of the economic crisis, along with a changing pattern of LC predictors stressed the urgent need of geographically oriented interventions and cancer control programs focusing on the most deprived or vulnerable population groups.

International audience; Introduction: The risk of inflammatory bowel disease-associated colorectal cancer (IBD-CRC) is known to increase with primary sclerosing cholangitis (PSC) and a family history of CRC. However, the impact of comorbidities such as liver disease, obesity, diabetes, chronic lung, heart, and renal disease, and psychiatric illness on the risk of IBD-CRC remains unclear. We evaluated the effect of these comorbidities on the risk of IBD-CRC.Methods: A retrospective review from 2009 to 2014 was conducted using the National Inpatient Sample data for adults 18 years and older. Patients with IBD (360,892), of whom 2,831 had CRC were identified using the International Classification of Diseases, Ninth Revision codes (ICD-9). Data on comorbidities were also obtained. Adjusted odds ratios (aOR) and confidence intervals (CI) were computed via logistic regression to evaluate the effect of comorbidities on the risk of IBD-CRC; the p-value was set at

Objectives To estimate observed and relative survival of prostate cancer patients in sub-Saharan Africa (SSA) and to examine the influence of age, stage at diagnosis and the Human Development Index (HDI). Patients and methods In this comparative registry study, we selected a random sample of 1752 incident cases of malign prostatic neoplasm from 12 population-based cancer registries from 10 SSA countries, registered between 2005 and 2015. We analyzed the data using Kaplan-Meier and Ederer II methods to obtain outcome estimates and flexible Poisson regression modeling to calculate the excess hazards of death Results For the 1406 patients included in the survival analyses, 763 deaths occurred during 3614 person-years of observation. Of patients with known stage, 45.2% had stage IV disease, 31.2% stage III and only 23.6% stage I and II. The 1 and 5-year relative survival for the entire cohort was 78.0% (75.4–80.7) and 60.0% (55.7–64.6), while varying between the registries. Late presentation was associated with increased excess hazards and a 0.1 increase in the HDI was associated with a 20% lower excess hazard of death, while for age at diagnosis no association was found. Conclusions We found poor survival of SSA prostatic tumor patients, as well as high proportions of late stage presentation, which are associated with inferior outcome. This calls for investment in health-care systems and action regarding projects to raise awareness among the population to achieve earlier diagnosis and improve survival.

Plasma cell myeloma (also called multiple myeloma), solitary plasmacytoma, and extramedullary plasmacytoma are primarily diseases of the elderly. Evidence suggests an association between excess body weight and multiple myeloma. Few population‐based studies have examined incidence and mortality of each site in one study. We analyzed incidence and death rates by site (solitary plasmacytoma, extramedullary plasmacytoma, and multiple myeloma) by gender, age, race/ethnicity, and rural‐urban status among adult males and females (aged 20 years or older) in the United States during 2003‐2016. Trends were characterized as average annual percentage change (AAPC) in rates. During 2003‐2016, overall incidence rates among adults were 0.45 for solitary plasmacytoma, 0.09 for extramedullary plasmacytoma, and 8.47 for multiple myeloma per 100,000 persons. Incidence rates for multiple myeloma increased during 2003‐2016 among non‐Hispanic whites (AAPC = 1.78%) and non‐Hispanic blacks (2.98%) 20‐49 years of age; non‐Hispanic whites (1.17%) and non‐Hispanic blacks (1.24%) 50‐59 years of age; and whites non‐Hispanic (0.91%), and non‐Hispanic blacks (0.96%). During 2003‐2016 overall myeloma (extramedullary plasmacytoma and multiple myeloma) death rates among adults was 4.77 per 100,00 persons. Myeloma death rates decreased during 2003‐2016 among non‐Hispanic white (AAPC = −1.23%) and Hispanic (−1.34%) women; and non‐Hispanic white (−0.74%), non‐Hispanic American Indian/Alaska Native (−3.05%) men. The US population is projected to become older and will have a larger proportion of persons who have had an earlier and longer exposure to excess body weight. The potential impact of these population changes on myeloma incidence and mortality can be monitored with high‐quality cancer surveillance data., Plasma cell myeloma (also called multiple myeloma), solitary plasmacytoma, and extramedullary plasmacytoma are primarily diseases of the elderly. Few population‐based studies have examined incidence and mortality of each site in one study. We analyzed incidence and death rates by site (solitary plasmacytoma, extramedullary plasmacytoma, and multiple myeloma) by gender, age, race/ethnicity, and rural‐urban status among adult males and females (aged 20 years or older) in the United States during 2003‐2016.

Purpose TP53germline (g) mutations, associated with the Li-Fraumeni syndrome (LFS), have rarely been reported in the context of hereditary breast and ovarian cancer (HBOC). The prevalence and cancer risks in this target group are unknown and counseling remains challenging. Notably an extensive high-risk surveillance program is implemented, which evokes substantial psychological discomfort. Emphasizing the lack of consensus about clinical implications, we aim to further characterize TP53g mutations in HBOC families. Methods Next-generation sequencing was conducted on 1876 breast cancer (BC) patients who fulfilled the inclusion criteria for HBOC. Results (Likely) pathogenic variants in TP53 gene were present in 0.6% of the BC cohort with higher occurrence in early onset BC TP53g variant (c.542G > A; c.375G > A) did not comply with classic LFS/Chompret criteria. Albeit located in the DNA-binding domain of the p53-protein and therefore revealing no difference to LFS-related variants, they only displayed a medium transactivity reduction constituting a retainment of wildtype-like anti-proliferative functionality. Conclusion Among our cohort of HBOC families, we were able to describe a clinical subgroup, which is distinct from the classic LFS-families. Strikingly, two families did not adhere to the LFS criteria, and functional analysis revealed a reduced impact on TP53 activity, which may suit to the attenuated phenotype. This is an approach that could be useful in developing individualized screening efforts for TP53g mutation carrier in HBOC families. Due to the low incidence, national/international cooperation is necessary to further explore clinical implications. This might allow providing directions for clinical recommendations in the future.

BackgroundCirculating tumor DNA (ctDNA) is a promising technology for treatment selection, prognostication, and surveillance after definitive therapy. Its use in the perioperative setting for patients with metastatic disease has not been well studied. We characterize perioperative plasma ctDNA and its association with progression-free survival (PFS) in patients undergoing surgery for peritoneal metastases.Patients and methodsWe recruited 71 patients undergoing surgery for peritoneal metastases and evaluated their plasma with a targeted 73-gene ctDNA next-generation sequencing test before and after surgery. The association between perioperative ctDNA, as well as other patient factors, and PFS was evaluated by Cox regression.ResultsctDNA was detectable in 28 patients (39.4%) preoperatively and in 37 patients (52.1%) postoperatively. Patients with high ctDNA [maximum somatic variant allele fraction (MSVAF) > 0.25%] had worse PFS than those with low MSVAF (

Renal tumors account for ~5% of all childhood cancer diagnoses. Among them, Wilms tumor is by far the most common. In this thesis, we investigated which factors play a role in the development and treatment of childhood renal tumors. Although current Wilms tumor treatment regimens lead to ~90% overall survival rates, they are associated with short- and long-term side effects, and still, not all children with Wilms tumors can be cured. We demonstrated that age is indeed an independent prognostic factor for event-free survival in patients treated with pre-operative chemotherapy. In the future, treatment may be further refined by including age and molecular markers in risk stratification. Furthermore, we investigated the role of (epi)genetic predisposition in a Dutch, nationwide cohort of children with Wilms tumors. Whole exome sequencing (WES) was offered in all cases where no genetic predisposition had been identified by targeted diagnostic testing. Where possible, DNA from resected normal kidney tissue was tested for Beckwith-Wiedemann spectrum, a relatively common Wilms tumor predisposing condition. We determined the prevalence of predisposing factors to be at least 33%, which is higher than previously thought. One of the most remarkable findings was the important contribution of variants in the DIS3L2-gene. Finally, we developed international surveillance guidelines, addressing all currently recognized Wilms tumor predisposition genes and syndromes. Overall, this thesis contributes to understanding relevant clinical, prognostic and underlying (epi)genetic factors in children with renal tumors.

Renal tumors account for ~5% of all childhood cancer diagnoses. Among them, Wilms tumor is by far the most common. In this thesis, we investigated which factors play a role in the development and treatment of childhood renal tumors. Although current Wilms tumor treatment regimens lead to ~90% overall survival rates, they are associated with short- and long-term side effects, and still, not all children with Wilms tumors can be cured. We demonstrated that age is indeed an independent prognostic factor for event-free survival in patients treated with pre-operative chemotherapy. In the future, treatment may be further refined by including age and molecular markers in risk stratification. Furthermore, we investigated the role of (epi)genetic predisposition in a Dutch, nationwide cohort of children with Wilms tumors. Whole exome sequencing (WES) was offered in all cases where no genetic predisposition had been identified by targeted diagnostic testing. Where possible, DNA from resected normal kidney tissue was tested for Beckwith-Wiedemann spectrum, a relatively common Wilms tumor predisposing condition. We determined the prevalence of predisposing factors to be at least 33%, which is higher than previously thought. One of the most remarkable findings was the important contribution of variants in the DIS3L2-gene. Finally, we developed international surveillance guidelines, addressing all currently recognized Wilms tumor predisposition genes and syndromes. Overall, this thesis contributes to understanding relevant clinical, prognostic and underlying (epi)genetic factors in children with renal tumors.

BackgroundHodgkin lymphoma survivors are at risk for second malignant neoplasm (SMN). How race/ethnicity affects the risk remains unclear.MethodsThis retrospective cohort study included 22,415 patients diagnosed with primary Hodgkin lymphoma from January 1992 to December 2015 in 13 Surveillance, Epidemiology, and End Results-based registries and divided patients into four groups: non-Hispanic whites, non-Hispanic blacks, Hispanics, and Asian/others. Taking non-Hispanic whites as a reference, both the proportional subdistribution hazard (PSH) and the cause-specific hazard (CSH) methods were used to calculate the SMN hazard ratio for other racial/ethnic groups with and without considering the competing mortality risk.Results1,778 patients developed SMN with a median follow-up of 11.63 years. In the adjusted PSH model, Hispanic, Asian/others, and non-Hispanic black patients had 26% (PSH, 0.74; 95% CI, 0.63–0.87), 20% (PSH, 0.80; 95% CI, 0.64–1.01), and 12% (PSH, 0.88; 95% CI, 0.75–1.03) decreased overall SMN hazard, respectively. Moreover, the PSH method revealed the racial/ethnic difference in the SMN risk in the skin, the respiratory system, and the endocrine system. These hazards were slightly higher and different with the use of the CSH approach. In addition to the aforementioned overall SMN and subtypes, adjusted CSH analysis also revealed the racial/ethnic disparities in the risk of subsequent female breast cancer, digestive cancer, and non-Hodgkin lymphoma.ConclusionsThe subtype and SMN risk among Hodgkin lymphoma survivors varied by race/ethnicity. The use of CSH and PSH provides a dynamic view of racial/ethnic effects on SMN risk in Hodgkin lymphoma survivors.

Like other Indigenous Circumpolar populations, Alaska Native (AN) people experience different patterns of cancer than their non-Indigenous counterparts. Every 5 years, the Alaska Native Tumour Registry releases a comprehensive report on cancer among AN people; this study provides 50 years of cancer surveillance data. Five-year annual-average age-adjusted incidence rates were calculated for time-periods ranging 1969–2018. AN data were compared with data for US whites (SEER 9). Mortality rates were calculated for 1994–2018 using data from the National Center for Health Statistics. During 2014–2018, there were 2,401 cases of invasive cancer among AN people. Among these, the most commonly diagnosed cancers were colorectal (405 cases, 17% of all cancers), lung and bronchus (373 cases, 16% of all cancers), and female breast (340 cases, 14% of all cancers). Lung cancer was the leading cause of cancer death, followed by colorectal and female breast cancers. These leading cancers are screenable, and preventable through lifestyle modifications including tobacco cessation, healthy eating and engaging in physical activity. These data provide important information to support cancer prevention and control among AN people. Cancer surveillance has been a valuable tool throughout the Circumpolar North to support reducing the burden of cancer among Indigenous populations. Abbreviations: ANAI: Alaska Native/American Indian; AN: Alaska Native; USW: U.S. White(s); ANMC: Alaska Native Medical Center; ANTR: Alaska Native Tumour Registry; IR: Incidence Rate; CI: Confidence Interval; RR: Rate Ratio; ICD-O-3: International Classification of Diseases for Oncology – Third Edition; SEER: Surveillance, Epidemiology and End Results.

Patients with primary sclerosing cholangitis (PSC) are at risk of hepatobiliary and gastrointestinal cancers. Increased risk of cancer is a result of the chronic, progressive fibro-inflammatory state which ultimately results in the destruction of biliary ducts. PSC is often associated with inflammatory bowel disease (IBD). Patients with PSC are at significant risk of cholangiocarcinoma (CCA), gall bladder malignancy and those with IBD are at increased risk of colorectal cancer. It is important to implement cancer surveillance protocols in these patients. The aim of these protocols is the prevention or early detection of cancerous or pre-cancerous lesions. Given that PSC is rare, large prospective studies evaluating the risk of malignancy in these patients are not available. A great deal of uncertainty exists regarding how to best implement cancer surveillance in these patients. About 50% of deaths in PSC patients are due to malignancy and many patients eventually progress to end-stage liver disease and succumb to hepatic failure. In this review, we cover cancer surveillance strategies in PSC patients based on existing literature and expert opinions.

Metformin, a drug prescribed to treat type 2 diabetes, has been reported to possess antitumor activity via immunity activation. However, the influence of metformin on natural killer (NK) cells is not fully understood. Here, we investigated whether metformin exerts a potent anticancer effect by activating NK cells. The results showed that sustained exposure to metformin enhances the cytolytic activity of NK-92 cells. Moreover, this enhancement of cytotoxicity by metformin was also observed in NK cells from healthy peripheral blood and cancer patient ascites. Mechanistically, metformin induced activation of the JAK1/2/3/STAT5 and AKT/mTOR pathways in a p38 MAPK-dependent manner rather than an AMPK-dependent manner. In vivo experiments, metformin also improved cancer surveillance of NK cells in mouse models of lymphoma clearance and metastatic melanoma. Additionally, combination treatment with metformin and anti-PD-1 antibodies increased the therapy response rates of B16F10 melanoma. Moreover, metformin treatment increased NK cell and T cell infiltration in tumors. Therefore, these results provide a deeper understanding of metformin on the effector function of NK cells and will contribute to the development and applications of metformin in cancer treatment strategies.

Hereditary leiomyomatosis and renal cell cancer is a genodermatosis with an autosomal dominant inheritance pattern. It is a tumour predisposition syndrome characterized by cutaneous and uterine leiomyomas, and increased susceptibility to develop renal cell carcinoma. There are 200–300 families with hereditary leiomyomatosis and renal cell carcinoma reported worldwide, but the syndrome is believed to be underdiagnosed. Cutaneous leiomyomas are small smooth muscle tumours that tend to grow over time. Larger lesions, in particular, can cause pain or itching. Uterine leiomyomas have a high penetrance in women with hereditary leiomyomatosis and renal cell cancer. They frequently cause symptoms, and surgical intervention is often necessary. Hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinomas have a high potential to metastasize. Patients are diagnosed by genetic testing if a pathogenic mutation is demonstrated in the gene encoding fumarate hydratase. Immunohistochemistry may be a useful diagnostic approach in patients without a detectable pathogenic mutation. Diagnosed patients should be monitored for renal tumours in a lifelong surveillance programme.

Background: Biomarkers play an important role in oncology, including risk assessment, treatment prediction, and monitoring the progression of disease. In breast cancer, many genes are used as biomarkers. Since, several SNP variations of hallmark – related genes have been reported to be of value in risk prediction in various cancers and populations, some genetic polymorphism loci were combined and reported as biomarkers for use in the risk assessment of breast cancer in Thai people. Methods: Twelve cancer gene hallmarks (15 polymorphic loci) were selected and genotyped in 184 breast cancer patients and 176 healthy individuals in Phitsanulok, Thailand. Results: AA genotype of CD44 rs187116 (c.67+4883G>A), the C allele of CD133 rs2240688 (c.*667A>C), the *2 allele (4 bp deletion) of NF-κB1 rs28362491 and the homozygous null allele genotype of GSTM1 were significantly associated with an increased risk of breast cancer (pA), CD133 rs2240688 (c.*667A>C), NF-κB1 rs28362491 and GSTM1 homozygous null allele genotype might be associated with an increased risk of breast cancer, and this gene combination could possibly be used as biomarkers for risk prediction, which would be of benefit in planning health surveillance and cancer prevention.

Population‐based cancer registries have improved dramatically over the last 2 decades. These central cancer registries provide a critical framework that can elevate the science of cancer research. There have also been important technical and scientific advances that help to unlock the potential of population‐based cancer registries. These advances include improvements in probabilistic record linkage, refinements in natural language processing, the ability to perform genomic sequencing on formalin‐fixed, paraffin‐embedded (FFPE) tissue, and improvements in the ability to identify activity levels of many different signaling molecules in FFPE tissue. This article describes how central cancer registries can provide a population‐based sample frame that will lead to studies with strong external validity, how central cancer registries can link with public and private health insurance claims to obtain complete treatment information, how central cancer registries can use informatics techniques to provide population‐based rapid case ascertainment, how central cancer registries can serve as a population‐based virtual tissue repository, and how population‐based cancer registries are essential for guiding the implementation of evidence‐based interventions and measuring changes in the cancer burden after the implementation of these interventions., Population‐based cancer registries have improved dramatically over the last 2 decades. These central cancer registries provide a critical framework that can elevate the science of cancer research.

Background: The increasing cancer burden remains a public health challenge. Quality and accurate population data is important to improve cancer control, screening, and treatment programmes for the sub-Saharan Africa region. Aim: The aim of this study was to establish hospital-based cancer surveillance system, thereby reporting the burden that cancer diagnosis and treatment place on 3 hospitals – an approach of health systems strengthening. Methods: A hospital-based cancer surveillance was established in 3 public health facilities that provide oncology services in KwaZulu-Natal. An active method was used for finding cancer cases. The cancer surveillance database was evaluated according to the criteria recommended for cancer registries. Analyses of data included descriptive and crude incidence rates. Results: A total of 2307 newly diagnosed cancer cases were reported in 2018, with a majority from Inkosi Albert Luthuli Central hospital (65.3%), followed by Greys hospital (30.8%) and then Addington hospital (3.94%). Most of the cancer cases were from the 2 major urban areas of the province (eThekwini and uMgungundlovu district). The most commonly diagnosed cancers from all combined 3 facilities for both sexes were breast, cervix, colorectal, Kaposi Sarcoma, and lung. Approximately half of the cancer cases had no staging, and 12.8% of the cases were diagnosed at stage 4. The mostly prescribed treatments for the patients were radiotherapy and chemotherapy. Conclusions: Based on our hospital-based surveillance, cancer burden is high in the 3 facilities. Strengthening cancer screening and diagnostic policies and procedures that will allow expansion of accurate cancer surveillance system is essential in KwaZulu-Natal and South Africa as a whole.

Individuals with pathogenic variants in genes predisposing to bowel cancer are encouraged to share this information within their families. Close relatives at 50% risk can have access to bowel cancer surveillance. However, many relatives remain unaware of their vulnerability or have insufficient information. We investigated the feasibility and acceptability of using a secure website to support information sharing within families at high risk of bowel cancer. Patients (n = 286) answered an anonymous cross-sectional survey, with 14 participating in telephone interviews. They reported that the diagnosis had a profound effect on them and their family relationships, and consequently desired more support from health professionals. Website content was created in response to the preferences of survey and interview participants. Reactions to the website from 12 volunteers were captured through remote usability testing to guide further refinement of the website. Participants welcomed the opportunity to store and share personal information via the website and wanted more information and help informing their relatives about the diagnosis. Important website topics were: healthy lifestyle, genetic testing, and how to talk to children about the diagnosis. A website providing online access to confidential documents was both feasible and acceptable and could translate into increased uptake of cancer surveillance, resulting in lower morbidity and mortality in these families.

PurposeCancer survivors diagnosed at an early age remain at risk for cancer recurrence and other chronic diseases. This study assessed engagement in surveillance for recurrence, cancer screening, and other recommended preventive health services among breast and colorectal cancer survivors with early-onset disease (≤ 50years) who were diagnosed in California.MethodsBreast and colorectal cancer survivors diagnosed with early-onset cancer between 1999 and 2009 were identified through the California Cancer Registry, the state-based cancer registry, and surveyed. Multivariable regression analyses were used to assess correlates of receipt of cancer surveillance, cancer screening, and other preventive health services.ResultsOf the 497 survivors that were invited to participate in the study, 156 completed the survey for a response rate of 31%. The sample was 50years of age on average (range 32-69years) with a mean time since diagnosis of 9years. The majority of the sample (71%) was a racial/ethnic minority (24% Latino, 15% African American, 29% Asian). Overall, 80% received appropriate surveillance for recurrence, and 72% received recommended screening for early detection of other cancers (breast, cervical, colorectal). Increasing age was associated with lower likelihood of early detection screening (adjusted odds ratio (aOR) 0.28, 95% confidence interval (CI) 0.11-0.69), and higher income was associated with a greater likelihood (aOR 4.89, 95% CI 1.62-14.81). Screening rates were highest for blood pressure (96%), cholesterol (86%), and diabetes (81%), followed by dental visits (64%) and flu vaccination (35%). Greater use of recommended preventive health services was associated with increasing age, female sex, higher education level, and having health insurance.ConclusionsAlthough the majority of survivors received appropriate surveillance for recurrence, engagement in other preventive health services varied substantially.Implications for cancer survivorsEfforts are needed to address gaps in the use of recommended cancer screening and preventive health services among cancer survivors, particularly survivors with early-onset disease who may be at increased risk for additional cancers and common chronic conditions over their lifetime.

Background: We aimed to establish a new approach for surveillance of cancer prevalence and survival in China, based on the Medical-Insurance-System-based Cancer Surveillance System (MIS-CASS). Methods: We constructed a standard procedure for data collection, cleaning, processing, linkage, verification, analysis, and estimation of cancer prevalence and survival (including both actual observations and model estimates) by conjoint use of medical insurance claims data and all-cause death surveillance data. As a proof-of-principle study, we evaluated the performance of this surveillance approach by estimating the latest prevalence and survival for upper gastrointestinal cancers in Hua County, a high-risk region for oesophageal cancer in China. Findings: In Hua County, the age-standardised relative 5-year survival was 39·2% (male: 36·8%; female: 43·6%) for oesophageal cancer and 33·3% (male: 29·6%; female: 43·4%) for stomach cancer. For oesophageal cancer, better survival was observed in patients of 45–64 years compared with national average estimates, and women of

One in every twenty-five persons in America is a racial/ethnic minority who lives in a rural area. Our objective was to summarize how racism and, subsequently, the social determinants of health disproportionately affect rural racial/ethnic minority populations, provide a review of the cancer disparities experienced by rural racial/ethnic minority groups, and recommend policy, research, and intervention approaches to reduce these disparities. We found that rural Black and American Indian/Alaska Native populations experience greater poverty and lack of access to care, which expose them to greater risk of developing cancer and experiencing poorer cancer outcomes in treatment and ultimately survival. There is a critical need for additional research to understand the disparities experienced by all rural racial/ethnic minority populations. We propose that policies aim to increase access to care and healthcare resources for these communities. Further, that observational and interventional research should more effectively address the intersections of rurality and race/ethnicity through reduced structural and interpersonal biases in cancer care, increased data access, more research on newer cancer screening and treatment modalities, and continued intervention and implementation research to understand how evidence-based practices can most effectively reduce disparities among these populations.

Blood-based liquid biopsies are considered a new and promising diagnostic and monitoring tool for cancer. As liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue biopsies. A multi-disciplinary workshop (n = 98 registrations) was organized to discuss routine implementation of liquid biopsies in cancer management. Real-time polls were used to engage with experts&rsquo, about the current evidence of clinical utility and the barriers to implementation of liquid biopsies. Clinical, laboratory and health economics presentations were given to illustrate the opportunities and current levels of evidence, followed by three moderated break-out sessions to discuss applications. The workshop concluded that tumor-informed assays using next-generation sequencing (NGS) or PCR-based genotyping assays will most likely provide better clinical utility than tumor-agnostic assays, yet at a higher cost. For routine application, it will be essential to determine clinical utility, to define the minimum quality standards and performance of testing platforms and to ensure their use is integrated into current clinical workflows including how they complement tissue biopsies and imaging. Early health economic models may help identifying the most viable application of liquid biopsies. Alternative funding models for the translation of complex molecular diagnostics, such as liquid biopsies, may also be explored if clinical utility has been demonstrated and when their use is recommended in multi-disciplinary consensus guidelines.

Objective An estimated 250 million people worldwide are chronically infected with hepatitis B virus (HBV), the leading cause of hepatocellular carcinoma (HCC) globally. The novel Sars‐cov2 virus continues to spread at an alarming rate, and with guidance at the onset of the pandemic recommending the deferral of HCC surveillance, the implications on liver cancer care are now emerging and highlight the urgent need for reorganisation of services. Methods We analysed how five HCC risk prediction scores could aid stratification of patients with chronic HBV. We calculated scores using parameters measured from 3 years prior (where available, n = 17) and at the time of HCC diagnosis in all adult patients with chronic HBV diagnosed with HCC (n = 46), and controls (n = 100). We compared the number of patients requiring cancer surveillance according to each score and regional surveillance guidance. Results The aMAP score had the highest discriminatory performance in HCC risk prediction at 3 years (area under receiver‐operating characteristic curve (auROC) of 0.824), followed by the mREACH B score (auROC of 0.719), and mPAGE B score (auROC of 0.742). However, only the mREACH B score had a negative predictive value (NPV) >99%. Applying the mREACH B score to our HBV cohort identified 11 patients requiring HCC surveillance, compared with 62 under current guidelines. Conclusion The use of HCC risk prediction scores could streamline the surveillance of patients with chronic HBV at a time of extremely limited resources. Overall, the mREACH B score had both a strong discriminatory performance and a high NPV, thus safely identifying low risk patients not requiring surveillance.

This article describes a rare case of isolated focal fibroadipose overgrowth of the forehead in a 15-year-old patient. Various overgrowth syndromes were considered in the differential diagnosis, including Proteus syndrome, facial infiltrating lipomatosis, and macrodystrophia lipomatosa. The diagnosis is primarily based on clinical presentation and imaging modalities. However, for academic and supporting diagnostic purposes a biopsy is advised, yet may not be in the best interest of the patient. Management was conservative with future perspective for surgical management after cessation of growth.

Rhabdoid tumors are rare aggressive malignancies in infants and young children with a poor prognosis. The most common anatomic localizations are the central nervous system, the kidneys, and other soft tissues. Rhabdoid tumors share germline and somatic mutations in SMARCB1 or, more rarely, SMARCA4, members of the SWI/SNF chromatin-remodeling complex. Rhabdoid tumor predisposition syndrome (RTPS) is a condition characterized by a high risk of developing rhabdoid tumors, among other features. RTPS1 is characterized by pathogenic variants in the SMARCB1 gene, while RTPS2 has variants in SMARCA4. Interestingly, germline variants of SMARCB1 and SMARCA4 have been identified also in patients with Coffin-Siris syndrome. Children with RTPS typically present with tumors before 1 year of age and in a high percentage of cases develop synchronous or multifocal tumors with aggressive clinical features. The diagnosis of RTPS should be considered in patients with rhabdoid tumors, especially if they have multiple primary tumors and/or in individuals with a family history. Because germline mutations result in an increased risk of carriers developing rhabdoid tumors, genetic counseling, and surveillance for all family members with this condition is recommended.

Objective To evaluate the accuracy of identifying cancer patients by use of medical claims data in a health insurance system in China, and provide the basis for establishing the claims-based cancer surveillance system in China. Methods We chose Hua County, Henan Province as the study site, and randomly selected 300 and 1,200 qualified inpatient electronic medical records (EMRs) as well as the New Rural Cooperative Medical Scheme (NCMS) claims records for cancer patients in Hua County People's Hospital (HCPH) and Anyang Cancer Hospital (ACH) in 2017. Diagnostic information for NCMS claims was evaluated on an individual level, and sensitivity and positive predictive value (PPV) were calculated taking the EMRs as the gold standard. Results The sensitivity of NCMS was 95.2% (93.8%-96.3%) and 92.0% (88.3%-94.8%) in ACH and HCPH, respectively. The PPV of the NCMS was 97.8% (96.7%-98.5%) in ACH and 89.0% (84.9%-92.3%) in HCPH. Overall, the weighted and combined sensitivity and PPV of NCMS in Hua County was 93.1% and 92.1%, respectively. Significantly higher sensitivity and PPV in identifying patients with common cancers than non-common cancers were detected in HCPH and ACH separately (P Conclusions Identification of cancer patients by use of the NCMS is accurate on individual level, and it is therefore feasible to conduct claims-based cancer surveillance in areas not covered by cancer registries in China.

Objectives One of the characteristics of colorectal cancer complicating Crohn's disease (CD) in the Japanese population is that it frequently occurs in the lower anorectal site. This study aimed to examine CD patients biopsied in the lower anorectal sites to investigate the significance and problems associated with this method of cancer surveillance. Methods Among 116 patients with CD duration of ≥10 years, we examined patients diagnosed with cancer using histological examination of the lower anorectal site (287 times). We also evaluated the detection rates of cancer and atypical cells using this method. Results Of the 116 patients, neoplastic lesions were detected through biopsy in 22 (19.0%), of which 18 had carcinomas and 4 had atypical cells. The clinicopathological traits of the cancer patients were early-age onset and chronic disease duration of CD before cancer diagnosis. Histologic findings were characterized by a high frequency of poorly differentiated adenocarcinoma and mucinous carcinoma. The 18 patients with cancer were assigned to groups A and B depending on the presence or absence of cancer-related symptoms, and their characteristics were compared. Of these, 5 patients whose cancer was detected without symptoms (group A) had better prognosis than those detected with symptoms (group B) based on survival curves. We next examined 103 patients for surveillance after excluding 13 patients who were diagnosed with cancer-related symptoms from the 116 patients and found a 5.8% (6 patients) detection rate of cancer and atypical cells. Conclusions Our results suggest the effectiveness of transanal histological testing for the surveillance of anorectal cancer with CD.

Background Cancer is the second leading cause of death in the Caribbean, including the islands of Trinidad and Tobago (TT). The population of TT consists of over 1.3 million people with diverse ancestral and sociocultural backgrounds, both of which may influence cancer incidence and mortality. The objective of this study was to examine incidence and mortality patterns and trends in TT. Methods Cancer surveillance data on 29,512 incident cancer cases reported to the Dr. Elizabeth Quamina Cancer Registry (population-based cancer registry of TT) between 1995 and 2009 were analyzed. Age-standardized rates, overall and by sex, ancestry, and geography, were reported. Results The highest incidence and mortality rates were observed for cancers related to reproductive organs in women, namely, breast, cervical, and uterine cancers, and prostate, lung and colorectal cancers among men. Average incidence rates were highest in areas covered by the Tobago Regional Health Authority (TRHA) (188 per 100,000), while average mortality rates were highest in areas covered by the North West Regional Health Authority (108 per 100,000). Nationals of African ancestry exhibited the highest rates of cancer incidence (243 per 100,000) and mortality (156 per 100,000) compared to their counterparts who were of East Indian (incidence, 125 per 100,000; mortality, 66 per 100,000) or mixed ancestry (incidence, 119 per 100,000; mortality, 66 per 100,000). Conclusions Our findings highlight the need for national investment to improve the understanding of the epidemiology of cancer in Trinidad and Tobago, and to ultimately guide much needed cancer prevention and control initiatives in the near future. Electronic supplementary material The online version of this article (10.1186/s12885-018-4625-x) contains supplementary material, which is available to authorized users.

// Elena Elimova 1, 8 , Rebecca S. Slack 2 , Hsiang-Chun Chen 2 , Venkatram Planjery 1 , Hironori Shiozaki 1 , Yusuke Shimodaira 1 , Nick Charalampakis 1 , Quan Lin 1 , Kazuto Harada 1 , Roopma Wadhwa 1 , Jeannelyn S. Estrella 3 , Dilsa Mizrak Kaya 1 , Tara Sagebiel 4 , Jeffrey H. Lee 5 , Brian Weston 5 , Manoop Bhutani 5 , Mariela Blum Murphy 1 , Aurelio Matamoros 4 , Bruce Minsky 6 , Prajnan Das 6 , Paul F. Mansfield 7 , Brian D. Badgwell 7 and Jaffer A. Ajani 1 1 Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 2 Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 3 Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 4 Department of Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 5 Department of Gastroenterology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 6 Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 7 Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 8 Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada Correspondence to: Jaffer A. Ajani, email: jajani@mdanderson.org Keywords: localized gastric adenocarcinoma, cancer surveillance, cost-effectiveness analysis, imaging studies, esophagogastroduodenoscopy Received: December 02, 2016 Accepted: June 02, 2017 Published: July 13, 2017 ABSTRACT Purpose: After therapy of localized gastric adenocarcinoma (GAC) patients, the costs of surveillance, relapse patterns, and possibility of salvage are unknown. Materials and Methods: We identified 246 patients, who after having a negative peritoneal staging, received therapy (any therapy which included surgery) and were surveyed (every 3–6 months in the first 3 years, then yearly; ~10 CTs and ~7 endoscopies per patient). We used the 2016 Medicare dollars reimbursed as the “costs” for surveillance. Results: Common features were: Caucasians (57%), men (60%), poorly differentiated histology (76%), preoperative chemotherapy (74%), preoperative chemoradiation (59%), and had surgery (100%). At a median follow-up of 3.7 years (range, 0.1 to 18.3), the median overall survival (OS) was 9.2 years (95% CI, 6.0 to 11.2). Tumor grade ( p = 0.02), p/yp stage ( p < 0.001), % residual GAC ( p = 0.05), the R status ( p = 0.01), total gastrectomy ( p = 0.001), and relapse type ( p = 0.02) were associated with OS. Relapse occurred in 79 (32%) patients (only 8% were local-regional) and 90% occurred within 36 months of surgery. P/yp stage ( p < 0.001) and total gastrectomy ( p = 0.01) were independent prognosticators for OS in the multivariate analysis. Only 1 relapsed patient had successful salvage therapy. The estimated reimbursement for imaging studies and endoscopies was $1,761,221.91 (marked underestimation of actual costs). Conclusions: The median OS of localized GAC patients was excellent with infrequent local-regional relapses. Rigorous surveillance had a low yield and high “costs”. Our data suggest that less frequent surveillance intervals and limiting expensive investigations to symptomatic patients may be warranted.

Sequence alterations of the mitochondrial DNA (mtDNA) have been identified in many tu-mor types. Their nature is not entirely clear. Somatic mutation or shifts of heteroplasmic mtDNA vari-ants may play a role. These sequence alterations exhibit a sufficient frequency in all tumor types investi-gated thus far to justify their use as a tumor marker. This statement is supported by the high copy num-ber of mtDNA, which facilitates the detection of aberrant tumor-derived DNA in bodily fluids. This will be of special interest in tumors, which release a relatively high number of cells into bodily fluids, which are easily accessible, most strikingly in urinary bladder carcinoma. Due to the wide distribution of the observed base substitutions, deletions or insertions within the mitochondrial genome, high efforts for whole mtDNA sequencing (16.5 kb) from bodily fluids would be required, if the method would be in-tended for initial tumor screening. However, the usage of mtDNA for sensitive surveillance of known tumor diseases is a meaningful option, which may allow an improved non-invasive follow-up for the urinary bladder carcinoma, as compared to the currently existing cytological or molecular methods. Fol-lowing a short general introduction into mtDNA, this review demonstrates that the scenario of a sensi-tive cancer follow-up by mtDNA-analysis deserves more attention. It would be most important to inves-tigate precisely in the most relevant tumor types, if sequencing approaches in combination with simple PCR-assays for deletions/insertions in homopolymeric tracts has sufficient sensitivity to find most tu-mor-derived mtDNAs in bodily fluids.

This thesis, describes investigations of the genetic background of a wide variety of rare endocrine tumors, including those of the thyroid, parathyroid, adrenal and paraganglia. In the first part, our studies focus on the role of molecular testing in diagnostics and treatment decision making in patients with DICER1 syndrome or advanced radioactive iodine refractory thyroid cancer. In the second part, we investigated the of genetic background of pediatric non-medullary thyroid carcinoma. In the third part we focused on genetic counseling in the following endocrine tumor predisposition syndromes: CDC73-related disorder, SDHA-associated paraganglioma and MEN2a syndrome. Our studies contributed to the debate on accurate estimation of disease penetrance. In order to provide answers to the questions - “Why do I have cancer? Are other relatives at risk? And if so, can we prevent cancer?” - patient- and family centered endocrine cancer care encourages active collaboration between the departments of endocrinology, oncology, surgery, pathology, chemistry, radiology, nuclear medicine and clinical genetics.

With recent advancements in a non-invasive approach to cancer diagnosis and surveillance, the term "liquid biopsy" has gained traction but is currently limited by technological challenges in identifying and isolating circulating tumor cells (CTCs), proteins, cell-free DNA (cfDNA), or other nucleic acids. Tumor tissue biopsy, especially in genitourinary (GU) system is sometimes inadequate and requires invasive surgical options, especially for upper tract urothelial cancer. Urine can prove to be "liquid gold" since it may be a more abundant source of tumor-derived material without the background noise; however, urine DNA (uDNA) may be associated with low mutant allele fraction (MAF). Molecular detection of mutations in uDNA requires a sensitive and accurate method of analysis that allows a high depth of sequencing while minimizing artifacts. Several sequencing approaches to address this hurdle using enhanced library preparation techniques such as Tagged amplicon deep sequencing (TAm-Seq), Safe-SeqS, FAST-SeqS, and CAPP-Seq approaches have been developed. Urine biopsy utilizing next-generation sequencing (NGS) can prove useful at all stages of urologic malignancy care, where urine can be collected to aid in clinical decision making through the identification of commonly known mutations, and potentially reduce or avoid all forms of invasive procedures.

Female breast cancer is the most common cancer diagnosed among Alaska Native (AN) women. We examined characteristics of and trends for female breast cancer among AN women. We assessed descriptive statistics, incidence trends (1969–2014), and cause-specific survival for female breast cancers recorded in the Alaska Native Tumor Registry. Results indicated that the majority of breast cancers among AN were diagnosed among women aged over 50 years, at local stage, and with Hormone receptor (HR)+/Human Epidermal Growth Factor (HER) 2− subtype. Five-year average incidence (95% CI) in the most recent time-period (2009–2014) was 145.0/100,000 (130.4, 159.5)); this was not statistically different from the previous time-period. Survival from breast cancer was high and varied by stage and cancer subtype. Hazard of death was greater among those diagnosed with regional/distant/unknown disease, relative to local disease (HR (95%CI): 4.65 (1.66, 12.98)), and higher among those with HER2−/HR− cancers, relative to those with HER2-/HR+ cancers (HR (95%CI): 6.59 (2.23, 19.49)). This study provides a comprehensive description of breast cancer among AN women, providing new and updated information on clinical and demographic factors, cancer incidence trends, regional variations and breast cancer survival. Abbreviations: AIAN: American Indian/Alaska Native; AN: Alaska Native; ANMC: Alaska Native Medical Center; ANTR: Alaska Native Tumor Registry; CI: Confidence Interval; HR: Hazard Ratio; ICD-O-3: International Classification of Diseases for Oncology – Third Edition; NHW – Non-Hispanic Whites; SEER: Surveillance, Epidemiology and End Results.

In this thesis, we performed several genotype and phenotype studies in hereditary and familial melanoma patient cohorts. In the first part, our studies focus on patients with the p16-Leiden founder mutation in the CDKN2A gene. This founder mutation is the major cause of the familial melanoma-pancreatic cancer syndrome in the Dutch population. We studied the cancer phenotype and modifiers of cancer risk in these p16-Leiden mutation carriers. We also evaluated the p16-Leiden pancreatic cancer (PC) surveillance program by studying the role of precursor lesions in the development and early detection of PC, by reflecting on the surgical management of early-stage screen-detected PC and by studying potential biomarkers for the early detection of PC. In the second part of this thesis, our focus shifts to Dutch melanoma families in general, of which ~85% do not harbor a germline CDKN2A mutation. We studied which clinical features are associated with the presence of a CDKN2A mutation in a melanoma family and we created a scoring system to predict CDKN2A mutation probability. Lastly, we genetically characterized melanoma families without a CDKN2A mutation for variants in other (candidate) melanoma predisposition genes.

Highlights • Sweet Syndrome is an acute, non-infectious rash with fever and leukocytosis. • It is either idiopathic, drug-induced or malignancy-associated (MASS). • MASS manifests with leukopenia, anemia, and thrombocytopenia. • MASS workup should include prompt punch biopsy and cancer surveillance screening. • In cervical cancer, MASS is often an ominous indicator of recurrence or progression., Background Sweet Syndrome, or acute febrile neutrophilic dermatosis, is a non-infectious, painful rash accompanied by fever, leukocytosis and skin biopsy showing neutrophilic dermal inflammation. It is either idiopathic, drug-induced or malignancy associated (MASS). MASS is uncommon in cervical cancer, and usually signals diagnosis, progression or recurrence. Clinical Course Two months following chemoradiation for stage IIIC2(r) squamous cell carcinoma (SCC) of the cervix, a 55-year-old female developed painful papules and plaques on her left toes. One week later she developed fever and the rash spread to her body. Labs revealed leukopenia and an elevated erythrocyte sedimentation rate. Punch biopsy showed neutrophilic dermal inflammation with papillary dermal edema and was negative for infectious immunohistochemistry. The clinical presentation and histopathological features were consistent with, and met diagnostic criteria for Sweet Syndrome. One month following Sweet Syndrome diagnosis and four months following chemoradiation, positron emission tomography scan revealed recurrence in the pelvic lymph nodes. At this time, she had residual rash on her thighs that responded to oral methylprednisolone. She declined further chemotherapy for recurrent SCC and opted for palliative care. Conclusion We present a rare case of MASS in cervical cancer associated with recurrence two months after chemoradiation.

Concern exists about the sustainability of traditional, oncologist‐led models of breast cancer survivorship care. However, many oncologists are hesitant about deferring survivorship care to primary care providers (PCPs). Our objective was to examine oncologists' perceptions of the role PCPs play in breast cancer survivorship and the rationale underlying these perceptions. One‐on‐one interviews with medical, radiation, and surgical oncologists in Wisconsin were conducted (n = 35) and transcribed. Data analysis was performed using an inductive approach to content analysis. Oncologist‐perceived barriers included: PCP's level of experience with cancer care; Lack of PCP comfort in providing survivorship care; Existing demands on PCPs' time; Patient preference for oncology‐led survivorship care. Oncologists described familiarity and trust in individual PCPs as factors that could mitigate barriers and lead to increased PCP involvement in survivorship care. Although a number of perceived barriers to PCP participation in survivorship were identified by Wisconsin oncologists, our findings support the direction of ongoing initiatives to facilitate PCP involvement. Our findings also suggest that early PCP involvement in survivorship may increase PCP comfort and patients' trust in PCPs in this role. The identified barrier most challenging to address may be the limited capacity of the current primary care system to manage follow‐up for breast cancer survivors.

The emergence of the human papillomavirus (HPV) as the primary etiology of oropharyngeal cancer has changed head and neck cancer (HNC) epidemiology. This study described change in the age at diagnosis of oropharyngeal and non-oropharyngeal HNC in the United States in the last four decades. Using a retrospective cohort analysis, the Surveillance, Epidemiology, and End Results dataset from 1975 to 2016 was queried for eligible adult cases of HNC, grouped as oropharyngeal (n = 31,702) versus non-oropharyngeal (n = 87,108). Age at diagnosis was compared by gender (female, male) using independent t-test, and by race/ethnicity (Hispanic, non-Hispanic black, non-Hispanic white, non-Hispanic other) using analysis of variance. Joinpoint regression estimated yearly increases/decreases in age of diagnosis by sex and race/ethnicity through annual percent changes (APC), which were summarized with average annual percent changes (AAPC). Mean age at diagnosis for oropharyngeal cancer was 60.3 years. While there was initially a decrease in age at diagnosis, a 0.37% annual increase occurred from 2002 to 2016 (APC = 0.37, 95% confidence interval (CI) 0.28, 0.45). For non-oropharyngeal cancer, mean age at diagnosis was 63.2 years, with a continuous increase in age at diagnosis throughout the study period (1975&ndash, 2016 AAPC = 0.08, 95% CI 0.04, 0.12). Females had higher average age at diagnosis than males for both sites, while blacks (57.4 years for oropharyngeal cancer, 59.0 years for non-oropharyngeal) had the lowest age at diagnosis of all races/ethnicity. Age at diagnosis of oropharyngeal cancer has increased significantly since 2002, while non-oropharyngeal HNC has increased significantly in the last four decades.

Introduction: Timeliness of data availability is a key performance measure in cancer reporting. Previous studies evaluated timeliness of cancer reporting using a single metric, yet this metric obscures the details within each step of the reporting process. To enhance understanding of cancer reporting processes, we measured the timeliness of discrete cancer reporting steps and examined changes in timeliness across a decade.Methods: We analyzed 76,259 cases of breast, colorectal and lung cancer reported to the Indiana State Cancer Registry between 2001 and 2011. We measured timeliness for three fundamental reporting steps: report completion time, report submission time, and report processing time. Timeliness was measured as the difference, in days, between timestamps recorded in the cancer registry at each step. We further examined the reporting pattern among facilities within each step.Results: Identifying and gathering details about cases (report completion) accounts for the largest proportion of time during the cancer reporting process. Although submission time accounts for a lesser proportion of time, there is wide variation among facilities. One-seventh (7 out of 49) facilities accounted for 28.4% of the total cases reported, all of which took more than 100 days to submit the completed cases to the registry.Conclusions: Measuring timeliness of the individual steps in reporting processes can enable cancer registry programs to target individual facilities as well as tasks that could be improved to reduce overall case reporting times. Process improvement could strengthen cancer control programs and enable more rapid discovery in cancer research.

© James M Flanagan, Hanna Skrobanski, Xin Shi, Yasemin Hirst. Background: Longer patient intervals can lead to more late-stage cancer diagnoses and higher mortality rates. Individuals may delay presenting to primary care with red flag symptoms and instead turn to the internet to seek information, purchase over-the-counter medication, and change their diet or exercise habits. With advancements in machine learning, there is the potential to explore this complex relationship between a patient’s symptom appraisal and their first consultation at primary care through linkage of existing datasets (eg, health, commercial, and online). Objective: Here, we aimed to explore feasibility and acceptability of symptom appraisal using commercial- and health-data linkages for cancer symptom surveillance. Methods: A proof-of-concept study was developed to assess the general public’s acceptability of commercial- and health-data linkages for cancer symptom surveillance using a qualitative focus group study. We also investigated self-care behaviors of ovarian cancer patients using high-street retailer data, pre- and postdiagnosis. Results: Using a high-street retailer’s data, 1118 purchases—from April 2013 to July 2017—by 11 ovarian cancer patients and one healthy individual were analyzed. There was a unique presence of purchases for pain and indigestion medication prior to cancer diagnosis, which could signal disease in a larger sample. Qualitative findings suggest that the public are willing to consent to commercial- and health-data linkages as long as their data are safeguarded and users of this data are transparent about their purposes. Conclusions: Cancer symptom surveillance using commercial data is feasible and was found to be acceptable. To test efficacy of cancer surveillance using commercial data, larger studies are needed with links to individual electronic health records.

Ginsenosides are the principal active components of ginseng and are considered attractive candidates for combination cancer therapy because they can kill tumors and have favorable safety profiles. However, the overall benefit of ginsenosides remains unclear, particularly in cancer immunosurveillance, considering the controversial results showing repression or promotion of immune responses. Here we identify a potentiating role of ginsenoside F1 (G-F1) in cancer surveillance by natural killer (NK) cells. Among 15 different ginsenosides, G-F1 most potently enhanced NK cell cytotoxicity in response to diverse activating receptors and cancer cells. G-F1 also improved cancer surveillance in mouse models of lymphoma clearance and metastatic melanoma that rely on NK cell activity. G-F1-treated NK cells exhibited elevated cytotoxic potential such as upregulation of cytotoxic mediators and of activation signals upon stimulation. NK cell potentiation by G-F1 was antagonized by insulin-like growth factor (IGF)-1 blockade and recapitulated by IGF-1 treatment, suggesting the involvement of IGF-1. Thus, our results suggest that G-F1 enhances NK cell function and may have chemotherapeutic potential in NK cell-based immunotherapy. We anticipate our results to be a starting point for further comprehensive studies of ginsenosides in the immune cells mediating cancer surveillance and the development of putative therapeutics.

Background: Italy has one of the highest paediatric cancer incidence rate in Europe. We compared cancer incidence and survival in children (0-14 years) and adolescents (15-19 years) resident in Palermo Province with statistics derived from Italian and European surveillance systems. Methods: We included all incident cancer cases, malignant tumours and non-malignant neoplasm of central nervous system (benign and uncertain whether malignant or benign), detected in children and adolescents by the Palermo Province Cancer Registry between 2003 and 2012. A joinpoint regression model was applied. Annual Average Percentage Changes were calculated. The Besag–York–Mollie model was used to detect any cluster. The 5-year survival analysis was computed using Kaplan-Meier and actuarial methods. Results: We identified 555 paediatric cancer incident cases (90% ‘‘malignant tumours only’’). No difference in incidence rates was highlight between Palermo Province and Italy 26 registries and between RTPP and Southern Europe. No joinpoint or significant trend was identified and no cluster was detected. The 5-year overall survival didn’t differ between Palermo Province and Italian AIRTUM pool. A borderline higher statistically significant survival was observed in age-group 1-4 when comparing PPCR to EUROCARE-5. Conclusions: The epidemiological surveillance documented in the Palermo Province a paediatric cancer burden in line with southern Europe and a 5-year survival in line with EUROCARE-5, together with a borderline higher survival in age-group 1-4. The study supports the supplementary role of general population-based cancer registries to provide paediatric cancer surveillance of local communities. The adoption of the new guidelines and recommendations, on which staging systems should be adopted by population-based cancer registries for the major childhood cancers, will make it easy to perform comparative studies on incidence and other outcomes of interest, particularly survival. Key messages: Use of population-based cancer registries to assess and control the impact of cancer diseases. Supplementary role of population-based cancer registries to carry out infant cancer surveillance.

Background Longer patient intervals can lead to more late-stage cancer diagnoses and higher mortality rates. Individuals may delay presenting to primary care with red flag symptoms and instead turn to the internet to seek information, purchase over-the-counter medication, and change their diet or exercise habits. With advancements in machine learning, there is the potential to explore this complex relationship between a patient’s symptom appraisal and their first consultation at primary care through linkage of existing datasets (eg, health, commercial, and online). Objective Here, we aimed to explore feasibility and acceptability of symptom appraisal using commercial- and health-data linkages for cancer symptom surveillance. Methods A proof-of-concept study was developed to assess the general public’s acceptability of commercial- and health-data linkages for cancer symptom surveillance using a qualitative focus group study. We also investigated self-care behaviors of ovarian cancer patients using high-street retailer data, pre- and postdiagnosis. Results Using a high-street retailer’s data, 1118 purchases—from April 2013 to July 2017—by 11 ovarian cancer patients and one healthy individual were analyzed. There was a unique presence of purchases for pain and indigestion medication prior to cancer diagnosis, which could signal disease in a larger sample. Qualitative findings suggest that the public are willing to consent to commercial- and health-data linkages as long as their data are safeguarded and users of this data are transparent about their purposes. Conclusions Cancer symptom surveillance using commercial data is feasible and was found to be acceptable. To test efficacy of cancer surveillance using commercial data, larger studies are needed with links to individual electronic health records.

Eser, Sultan (Balikesir Author), Background In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. Methods CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights.Findings For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). Interpretation The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer., American Cancer Society Centers for Disease Control and Prevention Swiss Re Swiss Cancer Research foundation Swiss Cancer League Institut National du Cancer La Ligue Contre le Cancer Rossy Family Foundation US National Cancer Institute Susan G Komen Foundation

BACKGROUND Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management. OBJECTIVE Cascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives. METHODS CASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages. RESULTS Descriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes. CONCLUSIONS Robust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions. TRIAL REGISTRATION ClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt).

Endoscopy is a keystone in the management of patients with inflammatory bowel disease (IBD). It is the fundamental diagnostic tool for IBD, and can help discern between ulcerative colitis and Crohn's disease. Endoscopic assessment provides an objective end point in clinical trials, and identifies patients in clinical practice who may benefit from treatment escalation and may assist risk stratification in patients seeking to discontinue therapy. Recent advances in endoscopic assessment of patients with IBD include video capsule endoscopy, and chromoendoscopy. Technological advances enable improved visualization and focused biopsy sampling. Endoscopic resection and close surveillance of dysplastic lesions where feasible is recommended instead of prophylactic colectomy.

Although chronic hepatitis B (CHB) affects approximately 2 million United States residents, there is no systematic screening of at-risk individuals, and most remain unaware of their hepatitis B virus (HBV) infection. Unmonitored and untreated, CHB results in a 25-30% risk of death from liver cancer and/or cirrhosis, inflicting an increasing healthcare burden in high-prevalence regions. Despite high prevalence in immigrant Asians and Pacific Islanders, among whom CHB is a leading cause of death, community and healthcare provider awareness remains low. Because safe and effective vaccines and effective antiviral treatments exist, there is an urgent need for integrated programmes that identify, follow and treat people with existing CHB, while vaccinating the susceptible. We describe an extant San Francisco programme that integrates culturally targeted, population-based, HBV screening, vaccination or reassurance, management and research. After screening over 3000 at-risk individuals, we here review our operational and practical experience and describe a simple, rationally designed model that could be successfully used to greatly improve the current approach to hepatitis B while ultimately reducing the related healthcare costs, especially in the high-risk populations, which are currently underserved.

Prostate cancer, the leading non-skin malignant cancer among men, affects black men disproportionately. Black men are typically diagnosed at an earlier age and have a higher rate of aggressive tumors compared to other races. This study investigates the relationship of socioeconomic status on prostate cancer severity and mortality among black men. The purpose of the study is to determine whether prostate cancer risk, the aggressiveness of disease, and mortality differ by socioeconomic status. Two datasets were utilized. A total of 715 black men with a prostate cancer diagnosis were studied using individual-level data from the linked Surveillance, Epidemiology, and End Results National, Longitudinal and Mortality Study (SEER NLMS) database. Socioeconomic status was assessed and stage and grade of prostate cancer from the medical histories of study participants were used to determined severity. Descriptive statistics and chi-square (X2) tests were used to assess bivariate relationships. Logistic regressions were used to model the likelihood of receiving a high or low stage and grade. The NLMS general population was the second dataset accessed to obtain a larger sample of prostate cancer mortality cases which were analyzed using Cox proportional hazard regression. There were over 50,000 black men in the study sample. The results of the study showed minor differences in the severity of prostate cancer between black men of low and high socioeconomic status. Education was the only variable that showed some significance for both stage and grade. Within-race differences were found between the socioeconomic status variables and mortality among black men. The lower the socioeconomic status, the greater the risk of mortality compared to those of higher socioeconomic status. While socioeconomic differences among black men did not explain the onset or severity of prostate cancer, it did provide some explanation for the high mortality. Much research is needed to assess other external factors such as access to medical care and prostate health education, discrimination, stress exposures, and social norms that might be related to the severity of and mortality from prostate cancer among black men.

Background: Surveillance for colorectal neoplasia in inflammatory bowel disease (IBD) is widely practised despite a lack of convincing mortality reduction. The psychological impact of this approach is largely unexplored. Aim: To examine psychological well-being among IBD subjects undergoing colonoscopic surveillance for colorectal cancer (CRC). Methods: A cross-sectional study was performed by interrogating an IBD database for subjects currently enrolled in colonoscopic surveillance programmes. Identified surveillance subjects were age- and gender-matched with IBD control subjects not meeting surveillance criteria. Subjects were mailed a questionnaire including demographic details, the Short Form 36 (SF-36) survey to assess quality of life, the Spielberger State-Trait Personality Inventory, the Multidimensional Health Locus of Control, and a Risk Perception Questionnaire. Results: One hundred and thirty-nine of 286 (49%) subjects responded, 53% male, 46% Crohn disease. Fifty-six per cent respondents were in the surveillance group. Surveillance subjects were older (55.4 vs 51.1 years; P = .048) with longer disease duration, but otherwise had comparable demographics with controls. Overall, quality of life was not significantly different between cohorts (mean SF-36 63.82 vs 65.48; P = 0.70). Groups did not differ on any locus of control classification (P = 0.52), nor was there any difference between mean scores on ‘state’ subscales of the Spielberger State- Trait Personality Inventory: anxiety (P = 0.91), curiosity (P = 0.12), anger (P = 0.81) or depression (P = 0.70). Both groups grossly overestimated their perceived lifetime risk of CRC at 50%, with no difference between surveillance and control subjects (P = 1.0). Conclusions: Enrolment in colonoscopic colon cancer surveillance does not appear to impair psychological well-being in individuals with IBD despite longer disease duration. IBD patients overestimate their risk of CRC. Refereed/Peer-reviewed

The use of circulating tumor DNA (ctDNA) as a novel and non-invasive test for the diagnosis and surveillance of cancer is a rapidly growing area of interest, with sequencing of ctDNA acting as a potential surrogate for tissue biopsy. Circulating tumor DNA has been detected incidentally during noninvasive prenatal testing and additionally in more than 75% of known cancer patients participating in ctDNA studies evaluating its sensitivity. In the setting of mutation-based targeted tumor therapy, it shows a concordance rate >80% when compared with gold-standard tissue biopsies. Through ctDNA detection and sequencing, a simple blood test becomes a liquid biopsy for cancer, surveying a patient’s entire circulation with the goal of early detection, prognostic information, personalized therapy options, and tracking for recurrence or resistance, all with fewer or no tissue biopsies. Given the recent first-ever FDA approval of a liquid biopsy, it is important for clinicians to be aware of the rapid advancements likely to bring these tests into our practices soon. Here we review the biology, clinical implications, and recent advances in circulating tumor DNA analysis.