Diabetes mellitus in long-term survivors with colorectal, breast, or prostate cancer: Prevalence and prognosis. A population-based study.

BACKGROUND: Patients with cancer are at increased risk of diabetes mellitus (DM). Previous studies on the prevalence and prognostic impact of DM in cancer survivors were limited by small sample sizes or short follow-up times. We aimed to compare the patient-reported prevalence of DM in long-term cancer survivors (LTCS), who survived 5 years or more after cancer diagnosis, with that in cancer-free controls, and to estimate the mortality risk among LTCS according to DM status. METHODS: Our population-based cohort comprised 6952 LTCS diagnosed with breast, colorectal, or prostate cancer between 1994 and 2004, recruited in 2008-2011 (baseline), and followed until 2019. A total of 1828 cancer-free individuals served as controls. Multivariable logistic regression was used to compare the prevalence of DM in LTCS and controls, and according to covariates at baseline. Mortality among LTCS according to DM was assessed by Cox proportional hazards regression. RESULTS: A total of 962 (13.8%) LTCS at baseline reported DM. Prevalence of DM in LTCS was not higher than in cancer-free controls, both at baseline (odds ratio, 0.80; 95% CI, 0.66-0.97) and at follow-up (odds ratio, 0.83; 95% CI, 0.67-1.04). Prevalence of DM in LTCS was associated with cancer site, older age, lower education, higher socioeconomic deprivation, higher body mass index, physical inactivity, other comorbidities, and poorer prognosis (adjusted hazard ratio [all-cause mortality] = 1.29; 95% CI, 1.15-1.44). CONCLUSION: DM in LTCS is prevalent, but not higher than in cancer-free population controls. Cancer survivors with concurrent DM are at a potentially higher risk of death. PLAIN LANGUAGE SUMMARY: Cancer and diabetes mellitus (DM) are two serious threats to global health. In our study, prevalence of DM in long-term cancer survivors who survived 5 years or more after cancer diagnosis was not higher than in cancer-free controls. This should not be interpreted as an indication of a lower risk of DM in cancer survivors. Rather, it highlights the potentially poor prognosis in diabetic cancer survivors. Therefore, keeping a continuous satisfactory DM and hyperglycemia management is essential during long-term cancer survivorship.

Characteristics, Treatment Patterns and Survival of International Federation of Gynecology and Obstetrics Stage IV Epithelial Ovarian Cancer-A Population-Based Study.

BACKGROUND: The aim of the present study was to describe an unselected population of patients with diagnosis of FIGO stage IV OC. METHODS: Data from 1183 patients were available for analysis. RESULTS: The majority of patients (962/1183, 81.3%) received cancer-directed treatment. The median follow-up time was 3.8 years, and the median overall survival duration was 1.9 years. Notably, patients >80 years had a low overall survival rate (HR of age >80 years vs. ≤50 years was 3.81, 95%-CI [2.76, 5.27], p < 0.0001). The survival rate was best in patients with HGSOC (p < 0.0001). The highest overall survival rate was observed in patients in the group with surgical intervention followed by systemic treatment, with an unadjusted HR of 0.72, 95%-CI [0.59, 0.86], p = 0.007 vs. systemic treatment only. After adjustment for age and histology, survival differences between treatment schemes were smaller (HR 0.81, 95%-CI [0.66, 1.00], p = 0.12). CONCLUSIONS: In this cohort of patients with FIGO stage IV OC, more than 80% of the patients received cancer-directed treatment. Age and high-grade serous histology were determinants for survival. The highest overall survival rate was observed in patients who underwent surgery followed by systemic treatment.

Widening area-based socioeconomic inequalities in cancer mortality in Germany between 2003 and 2019.

Cancer mortality has declined in recent decades, but-due to a lack of national individual-level data-it remains unclear whether this applies equally to all socioeconomic groups in Germany. Using an area-based approach, this study investigated socioeconomic inequalities in cancer mortality and their secular trends on a German nationwide scale for the first time. Official cause-of-death data from 2003 to 2019 were linked to the district-level German Index of Socioeconomic Deprivation. Age-standardised mortality rates for all cancers combined and the most common site-specific cancers were calculated according to the level of regional socioeconomic deprivation. To quantify the extent of area-based socioeconomic inequalities in cancer mortality, absolute (SII) and relative (RII) indices of inequality were estimated using multilevel Poisson models. On average, cancer mortality was 50% (women) and 80% (men) higher in Germany's most deprived than least deprived districts (absolute difference: 84 deaths per 100,000 in women and 185 deaths per 100,000 in men). As declines in cancer mortality were larger in less deprived districts, the socioeconomic gap in cancer mortality widened over time. This trend was observed for various common cancers. Exceptions were cancers of the lung in women and of the pancreas in both sexes, for which mortality rates increased over time, especially in highly deprived districts. Our study provides first evidence on increasing socioeconomic inequalities in cancer mortality on a nationwide scale for Germany. Area-based linkage allows to examine socioeconomic inequalities in cancer mortality across Germany and identify regions with high needs for cancer prevention and control.

Trends in cancer incidence by socioeconomic deprivation in Germany in 2007 to 2018: An ecological registry-based study.

Age-standardized cancer incidence has decreased over the last years for many cancer sites in developed countries. Whether these trends led to narrowing or widening socioeconomic inequalities in cancer incidence is unknown. Using cancer registry data covering 48 million inhabitants in Germany, the ecological association between age-standardized total and site specific (colorectal, lung, prostate and breast) cancer incidence in 2007 to 2018 and a deprivation index on district level (aggregated to quintiles) was investigated. Incidence in the most and least deprived districts were compared using Poisson models. Average annual percentage changes (AAPCs) and differences in AAPCs between deprivation quintiles were assessed using Joinpoint regression analyses. Age-standardized incidence decreased strongly between 2007 and 2018 for total cancer and all cancer sites (except female lung cancer), irrespective of the level of deprivation. However, differences in the magnitude of trends across deprivation quintiles resulted in increasing inequalities over time for total cancer, colorectal and lung cancer. For total cancer, the incidence rate ratio between the most and least deprived quintile increased from 1.07 (95% confidence interval: 1.01-1.12) to 1.23 (1.12-1.32) in men and from 1.07 (1.01-1.13) to 1.20 (1.14-1.26) in women. Largest inequalities were observed for lung cancer with 82% (men) and 88% (women) higher incidence in the most vs the least deprived regions in 2018. The observed increase in inequalities in cancer incidence is in alignment with trends in inequalities in risk factor prevalence and partly utilization of screening. Intervention programs targeted at socioeconomically deprived and urban regions are highly needed.

Persisting Deficits in Health-Related Quality of Life of Colorectal Cancer Survivors 14-24 Years Post-Diagnosis: A Population-Based Study.

(1) Background: The health-related quality of life (HRQOL) of colorectal cancer (CRC) survivors >10 years post-diagnosis is understudied. We aimed to compare the HRQOL of CRC survivors 14-24 years post-diagnosis to that of age- and sex-matched non-cancer controls, stratified by demographic and clinical factors. (2) Methods: We used data from 506 long-term CRC survivors and 1489 controls recruited from German population-based multi-regional studies. HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Core-30 (EORTC QLQ-C30) questionnaire. We estimated differences in the HRQOL of CRC survivors and controls with multiple regression, adjusted for age at survey, sex, and education, where appropriate. (3) Results: CRC survivors reported poorer social functioning but better health status/QOL than controls. CRC survivors, in general, had higher levels of symptom burden, and in particular diarrhea and constipation, regardless of demographic or clinical factors. In stratified analyses, HRQOL differed by age, sex, cancer type, and having a permanent stoma. (4) Conclusions: Although CRC survivors may have a comparable health status/QOL to controls 14-24 years after diagnosis, they still live with persistent bowel dysfunction that can negatively impact aspects of functioning. Healthcare providers should provide timely and adapted follow-up care to ameliorate potential long-term suffering.

Change Toward Healthier Lifestyles Is Associated With Better Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors.

BACKGROUND: Little is known about how changes in a constellation of lifestyle factors affect health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. Our study aimed to investigate the association between changes in healthy lifestyle and HRQoL over time in survivors of stage I-IV CRC. METHODS: We included 2,283 long-term (≥5 years postdiagnosis) survivors. A healthy lifestyle score (HLS) comprising smoking, alcohol consumption, diet, physical activity, and body fatness was derived at diagnosis and 5-year follow-up (5YFU) and categorized as low, moderate, or high. We assessed HRQoL with the EORTC Quality of Life Questionnaire-Core 30 at 5YFU and 10-year follow-up. We used multivariable linear regression and linear mixed models to explore associations between changes in HLS and HRQoL over follow-up. RESULTS: A low baseline HLS was associated with poorer functioning and global health/QoL and a higher symptom burden at 5YFU compared with a high baseline HLS. An improved HLS from baseline to 5YFU was associated with better functioning, higher global health/QoL, and fewer symptoms at 5YFU than a maintained-high HLS. In longitudinal analyses, improved HLS was associated with better functioning at follow-up. Survivors with a maintained-high or an improved HLS reported generally less fatigue, pain, and dyspnea at follow-ups compared with survivors with a maintained-low or decreased HLS. CONCLUSIONS: Change toward a healthier lifestyle since diagnosis was associated with better HRQoL in long-term CRC survivors. Our results support the importance of maintaining and/or promoting a healthier lifestyle among CRC survivors postdiagnosis.

Survival trends of patients with non-metastatic gastric adenocarcinoma in the US and European countries: the impact of decreasing resection rates.

BACKGROUND: We previously observed decreasing resection rates of non-metastatic gastric adenocarcinoma (GaC) in the US and some European countries. If and to what extent these trends affect the trends in overall survival (OS) of patients with non-metastatic GaC at the population level remain unclear. This large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic GaC. METHODS: Individual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands, Belgium, Sweden, Norway, and Slovenia, and the US Surveillance, Epidemiology, and End Results database. We analyzed data for each country separately. Associations between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables, with and without including resection and chemotherapy as potential explanatory variables. RESULTS: A total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed, with an accumulated follow-up of 172,357 person-years. Without adjustment for resection, OS was improved only slightly in the US [hazard ratio (HR)per year = 0.99; HR≥vs.<2010 = 0.96], and no improvement was observed in the investigated European countries, with OS even worsening in Sweden (HRper year = 1.03; HR≥vs.<2010 = 1.17). After adjusting for resection, the increasing OS trend became stronger in the US (HRper year = 0.98; HR≥vs.<2010 = 0.88), and the temporal trend became insignificant in Sweden. In Slovenia (HRper year = 0.99; HR≥vs.<2010 = 0.92) and Norway (HRper year = 0.97; HR≥vs.<2010 = 0.86), improved OS over time emerged after resection adjustment. Improved OS in patients undergoing resection was observed in the US, the Netherlands, and Norway. Adjustment for chemotherapy did not alter the observed associations. Stratified analyses by tumor location showed mostly similar results with the findings in all patients with non-metastatic GaCs regarding the associations between year of diagnosis and survival. CONCLUSIONS: OS of patients with non-metastatic GaC mostly did not improve in selected European countries and was even worsened in Sweden, while it was slightly increased in the US in the early 21st century. Progress in OS of patients with non-metastatic GaC seems to have been impeded to a large extent by decreasing rates of resection.

Incidence and survival estimates for patients with myelodysplastic syndrome in the early 21st century: no evidence of improvement over time.

We examine changes in population level incidence and survival of patients diagnosed with myelodysplastic syndrome (MDS) in the United States in 2001-2016. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Period analysis was used to calculate one-, two-, and five-year survival. The incidence peaked at 5.6 per 100,000 in 2010 then decreased to 3.9 by 2016, with a decrease in the diagnoses of refractory anemia (RA) and RA with ringed sideroblasts (RARS) and a relative increase in RA with excess blasts (RAEB). Overall, one-, two-, and five-year relative survival decreased over time, going from 74.3%, 60.9%, and 42.3%, respectively, in 2008-2010 to 70.9%, 55.9%, and 37.6%, respectively, in 2014-2016. When survival was examined by histology, patients with RA/RARS and RAEB had similar survival expectations in 2008-2010 versus 2014-2016 and a decrease was observed for 5q-MDS. Our results highlight the need for new treatment options in MDS.

Risk of Colorectal Cancer Associated With Lifetime Excess Weight.

Importance: Excess weight is associated with increased cancer risk, but the risk may have been underestimated, as previous studies did not consider cumulative lifetime exposure. Objective: To assess the association of cumulative lifetime excess weight with risk of colorectal cancer (CRC). Design, Setting, and Participants: In a population-based case-control study conducted since 2003 in Germany, height and self-reported weight documented in 10-year increments starting at age 20 years up to the current age were obtained from 5635 individuals with CRC and 4515 persons serving as controls. Body mass index (BMI), calculated as weight in kilograms divided by height in meters squared, was calculated for each year of age from age 20 years to the current age by linear interpolation. Excess BMI (eBMI) at each year of age was determined as BMI - 25 and summed across ages to obtain the weighted number of years lived with overweight or obesity (WYOs), determined as year × eBMI. The eBMI was set to 0 in case of a BMI below 25. Associations with CRC risk were estimated for BMI at various ages and for WYOs by multiple logistic regression. Data analyses were performed from June 4, 2021, to December 17, 2021. Main Outcomes and Measures: Relative risk of CRC according to lifetime exposure to excess weight compared with relative risks according to BMI at various ages. Results: The mean (SD) age of the patients with CRC (n = 5635) was 68.4 (10.9) years; 3366 were men (59.7%); mean (SD) age of the control participants (n = 4515) was 68.5 (10.6) years; 2759 were men (61.1%). An association was observed between WYOs and CRC risk, with adjusted odds ratios (ORs) increasing from 1.25 (95% CI, 1.09-1.44) to 2.54 (95% CI, 2.24-2.89) from the first to the fourth quartile of WYOs compared with participants who remained within the normal weight range. Each SD increment in WYOs was associated with an increase of CRC risk by 55% (adjusted OR, 1.55; 95% CI, 1.46-1.64). This OR was higher than the OR per SD increase of eBMI at any single point of time, which ranged from 1.04 (95% CI, 0.93-1.16) to 1.27 (95% CI 1.16-1.39). Conclusions and Relevance: The results of this case-control study suggest a greater role of cumulative lifetime excess weight for CRC risk than estimated by traditional analyses based on BMI measures taken at a single point.

Quality of life, distress, and posttraumatic growth 5 years after colorectal cancer diagnosis according to history of inpatient rehabilitation.

PURPOSE: In Germany, almost every other colorectal cancer (CRC) patient undergoes inpatient cancer rehabilitation (ICR), but research on long-term outcomes is sparse. We aimed to assess health-related quality of life (HRQOL), distress, and posttraumatic growth among former rehabilitants and non-rehabilitants as well as respective differences and to estimate disease-related quality of life deficits in both groups. METHODS: HRQOL (EORTC-QLQ-C30/CR29), distress (QSC-R10), and posttraumatic growth (PTGI) were assessed according to past ICR in patients 5-year post-CRC-diagnosis in the German DACHS study. Least square mean differences in HRQOL scores and elevated distress levels (QSC-R10 > 14 points) by ICR were estimated by confounder-adjusted linear and logistic regression, respectively. Differences in PTGI scales were tested for statistical significance. EORTC-QLQ-C30 reference scores from population controls were accessed from the LinDE study to estimate disease-related deficits in both treatment groups. RESULTS: 49% of the included 1906 CRC survivors had undergone ICR. Rehabilitants reported lower HRQOL scores than non-rehabilitants in several dimensions of the EORTC-QLQ-C30/CR29. Differences were pronounced among younger survivors (< 70 years). In younger survivors, past ICR also predicted elevated distress. However, rehabilitants showed higher posttraumatic growth. When compared to 934 population controls, non-rehabilitants and older rehabilitants reported HRQOL scores (EORTC-QLQ-C30) similar to controls except higher levels of bowel dysfunctions, whereas younger rehabilitants experienced deficits regarding most scales (13/15). CONCLUSION: Our findings suggest a high disease burden 5 years after diagnosis in particular among younger CRC survivors who had undergone ICR. Observed HRQOL deficits are possibly linked to the initial indication for ICR and rehabilitants may benefit from effective follow-up concepts after ICR.

Associations of Body Mass Index at Different Ages With Early-Onset Colorectal Cancer.

BACKGROUND & AIMS: Incidence of colorectal cancer (CRC) in younger adults is increasing in many countries. Given the established association of body mass index (BMI) with CRC risk and the increasing obesity prevalence among younger generations, we aimed to evaluate the association of BMI at different ages during early adulthood with early-onset CRC. METHODS: Among 6602 patients with CRC and 7950 matched controls who were recruited in 2003-2020 in the Darmkrebs: Chancen der Verhütung durch Screening study, a population-based case-control study from Germany, 747 patients and 621 controls were younger than 55 years and included in this analysis. Self-reported height and weight at ages 20 years and 30 years and at approximately 10 years before diagnosis or interview were recorded in personal interviews. Associations of BMI with early-onset CRC were estimated using multiple logistic regression. RESULTS: Compared with participants with BMI <25 kg/m2, those with BMI ≥30 kg/m2 (obesity) at ages 20 years and 30 years and approximately 10 years before diagnosis or interview had 2.56- (95% confidence interval, 1.20-5.44), 2.06- (confidence interval, 1.25-3.40), and 1.88- (95% confidence interval, 1.30-2.73) fold risk of early-onset CRC. The association of BMI with early-onset CRC risk was particularly pronounced among, and essentially restricted to, the majority of participants with no previous colonoscopy. CONCLUSIONS: Obesity at early adulthood is strongly associated with increased risk of early-onset CRC. German Clinical Trials Register ID: DRKS00011793.

Validation of Genetic Markers Associated with Survival in Colorectal Cancer Patients Treated with Oxaliplatin-Based Chemotherapy.

BACKGROUND: Associations between candidate genetic variants and treatment outcomes of oxaliplatin, a drug commonly used for colorectal cancer patients, have been reported but not robustly established. This study aimed to validate previously reported prognostic and predictive genetic markers for oxaliplatin treatment outcomes and evaluate additional putative functional variants. METHODS: Fifty-three SNPs were selected based on previous reports (40 SNPs) or putative function in candidate genes (13 SNPs). We used data from 1,502 patients with stage II-IV colorectal cancer who received primary adjuvant chemotherapy, 37% of whom received oxaliplatin treatment. Multivariable Cox proportional hazards models for overall survival and progression-free survival were applied separately in stage II-III and stage IV patients. For predictive SNPs, differential outcomes according to the type of chemotherapy (oxaliplatin-based vs. others) were evaluated using an interaction term. For prognostic SNPs, the association was assessed solely in patients with oxaliplatin-based treatment. RESULTS: Twelve SNPs were predictive and/or prognostic at P < 0.05 with differential survival based on the type of treatment, in patients with stage II-III (GSTM5-rs11807, ERCC2-rs13181, ERCC2-rs1799793, ERCC5-rs2016073, XPC-rs2228000, P2RX7-rs208294, HMGB1-rs1360485) and in patients with stage IV (GSTM5-rs11807, MNAT1-rs3783819, MNAT1-rs4151330, CXCR1-rs2234671, VEGFA-rs833061, P2RX7-rs2234671). In addition, five novel putative functional SNPs were identified to be predictive (ATP8B3-rs7250872, P2RX7-rs2230911, RPA1-rs5030755, MGMT-rs12917, P2RX7-rs2227963). CONCLUSIONS: Some SNPs yielded prognostic and/or predictive associations significant at P < 0.05, however, none of the associations remained significant after correction for multiple testing. IMPACT: We did not robustly confirm previously reported SNPs despite some suggestive findings but identified further potential predictive SNPs, which warrant further investigation in well-powered studies.

Comorbidities, Rather Than Older Age, Are Strongly Associated With Higher Utilization of Healthcare in Colorectal Cancer Survivors.

BACKGROUND: Colorectal cancer (CRC) survivors generally have a higher healthcare utilization (HCU) than the general population due to cancer burden. However, it is unclear which factors are associated with this increased uptake. Our study aimed to (1) compare CRC-related and non-CRC visits to general practitioners (GPs) and medical specialists (MSs) by comorbidities, and (2) assess whether HCU differs by demographic, clinical, and psychological factors. METHODS: We used data from a German population-based cohort of 1,718 survivors of stage I-III CRC diagnosed in 2003 through 2010 who provided information on HCU at 5-year follow-up. Multivariable linear regression was used to calculate least-square means of CRC-related and non-CRC HCU according to the Charlson comorbidity index and comorbidity cluster, adjusting for relevant demographic, clinical, and psychological characteristics. RESULTS: A higher comorbidity level was associated with more CRC-related MS visits and non-CRC GP visits. In addition to being strongly associated with non-CRC GP visits, comorbidity clusters were associated with CRC-related GP and MS visits, but their association varied by specific cardiometabolic comorbidities. HCU was less dependent on prognostic factors for CRC, such as age and tumor stage, but was strongly associated with disease recurrence, depression, and emotional functioning. CONCLUSIONS: Comorbidities, rather than age or tumor stage, were related to HCU, suggesting that CRC survivors use healthcare mainly for reasons other than cancer 5 years postdiagnosis. Improved communication between primary and tertiary healthcare providers could enhance the medical care of cancer survivors with complex health needs and thereby also reduce healthcare costs.

Smoking Behavior and Prognosis After Colorectal Cancer Diagnosis: A Pooled Analysis of 11 Studies.

Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies, but current evidence on smoking in association with survival after CRC diagnosis is limited. Methods: We pooled data from 12 345 patients with stage I-IV CRC from 11 epidemiologic studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of prediagnostic smoking behavior with overall, CRC-specific, and non-CRC-specific survival. Results: Among 12 345 patients with CRC, 4379 (35.5%) died (2515 from CRC) over a median follow-up time of 7.5 years. Smoking was strongly associated with worse survival in stage I-III patients, whereas no association was observed among stage IV patients. Among stage I-III patients, clear dose-response relationships with all survival outcomes were seen for current smokers. For example, current smokers with 40 or more pack-years had statistically significantly worse overall, CRC-specific, and non-CRC-specific survival compared with never smokers (hazard ratio [HR] =1.94, 95% confidence interval [CI] =1.68 to 2.25; HR = 1.41, 95% CI = 1.12 to 1.78; and HR = 2.67, 95% CI = 2.19 to 3.26, respectively). Similar associations with all survival outcomes were observed for former smokers who had quit for less than 10 years, but only a weak association with non-CRC-specific survival was seen among former smokers who had quit for more than 10 years. Conclusions: This large consortium of CRC patient studies provides compelling evidence that smoking is strongly associated with worse survival of stage I-III CRC patients in a clear dose-response manner. The detrimental effect of smoking was primarily related to noncolorectal cancer events, but current heavy smoking also showed an association with CRC-specific survival.

Socioeconomic deprivation and cancer survival in a metropolitan area: An analysis of cancer registry data from Hamburg, Germany.

BACKGROUND: Few studies have investigated socioeconomic inequalities within cities. Yet, such analyses are particularly important given the increasing international trend to urbanization. Here we investigated area-based socioeconomic inequalities in cancer survival in Hamburg, a port city in the North of Germany (population: 1.84 million people). METHODS: Patients with a diagnosis of colorectal, lung, female breast, and prostate cancer in 2004-2018 (follow-up until 31.12.2018) and registered in the Hamburg cancer registry were included. Area-based socioeconomic deprivation on urban district level was assigned to the patients and grouped in five quintiles. Relative survival in 2014-2018 was calculated using the period approach. Trend analyses between 2004 and 2018 were conducted. Relative excess risks adjusted for age and stage were computed with model-based period analyses. FINDINGS: For the 73,106 included patients, age-standardized 5-year relative survival in 2014-2018 decreased with increasing deprivation with significant differences between the most and least deprived group of 14·7 (prostate), 10·8 (colorectal), 8·0 (breast), and 2·5 (lung) percent units. Standardization by cancer stage decreased the difference for prostate cancer to 8·5 percent units and for breast cancer to 3·6 percent units but had only a minor effect for colorectal and lung cancer. Similar socioeconomic inequalities were already present in 2004-08. INTERPRETATION: Strong socioeconomic inequalities in cancer survival were observed in Hamburg, which could be partly explained by differences in the stage distribution. Further research including information on screening participation as well as information on cancer care are important to further understand and finally overcome these inequalities. FUNDING: German Cancer Aid.

[Oral and pharyngeal cancer: incidence, mortality, and survival in Germany]. / Mundhöhlen- und Pharynxkarzinome: Inzidenz, Mortalität und Überleben in Deutschland.

BACKGROUND: Lip, oral cavity, and pharynx cancers (ICD-10: C00-C14) describe a heterogeneous group of tumors with strong variations in incidence, mortality, and survival by entity. OBJECTIVES: This work provides a detailed overview of epidemiologic measures for these tumor entities, taking into account heterogeneity in age, sex, location, and stage. MATERIAL AND METHODS: Incidence and mortality data for Germany for the years 1999-2016 were extracted from the interactive database of the Center for Cancer Registry Data (ZfKD). Age and stage distributions and five-year relative survival were calculated on the pooled ZfKD data set (diagnosis years 1999-2017). RESULTS: In 2016, overall incidence and mortality for all entities were 17.6 and 7.0 per 100,000 men and 6.5 and 1.8 per 100,000 women, respectively. The five-year relative survival in 2015-2017 was 53 and 63%, respectively. There were marked differences in survival as well as age and stage distributions between entities. Trend analyses showed an increase in age at diagnosis, particularly in male patients, and no change in stage distributions. However, five-year relative survival increased from 45% (men) and 59% (women) in 1999-2002 to 52% and 63% in 2013-2017. CONCLUSION: The marked heterogeneity of the studied tumors highlights the need to differentiate the analysis by sex and entity for meaningful interpretation of epidemiologic metrics. With the expansion of clinical cancer registration in Germany, additional analyses including other important clinical factors will be possible in the future.

Largely varying patterns and trends of primary cancer-directed resection for gastric carcinoma with synchronous distant metastasis in Europe and the US: a population-based study calling for further standardization of care.

AIMS: The role of resection remains debated in cases of metastatic gastric carcinoma (mGC). Some mGCs are technically resectable. At the population level, the real-world application of resection for mGC remains largely unclear in most Western countries. This large, population-based international investigation aimed to reveal the resection patterns and trends for mGC and the treatment-associated factors in Europe and the US. METHODS: Data on cases with microscopically-confirmed primary invasive stomach carcinoma with distant metastasis were obtained from the nationwide cancer registries of the Netherlands, Belgium, Norway, Sweden, Estonia, and Slovenia and the US Surveillance, Epidemiology, and End Results-18 database. We calculated age-standardized rates of primary cancer-directed resection and assessed resection trends using linear regression. We investigated associations of treatment with patient and cancer factors using multivariable-adjusted log-binomial regression. RESULTS: Among 133,321 patients with gastric cancer, overall, 40,215 cases with mGC diagnosed between 2003-2017 were investigated. Age-standardized resection rates significantly declined over time in the US, Belgium, Sweden, and Norway (by 5-14%). Resection rates greatly differed from 5% to 16% in 2013-2014. Cases with older ages, cardia tumors, or tumors involving adjacent structures were significantly less often operated across most countries. Sex was not significantly associated with resection. Across countries the association patterns and strengths differed largely. With multivariable adjustment, resection rates decreased significantly in all countries except Slovenia and Estonia (prevalence ratio per year = 0.90-0.98), and the decreasing trends were consistently observed in various stratifications by age and location. CONCLUSION: In Europe and the US, resection patterns and trends largely varied across countries for mGCs, which were mostly less often resected in the early 21st century. Various resection-associated factors were shown, with greatly varying association patterns and strengths. Our report could aid to identify discrepancies in clinical practice and highlight the great need for further clarifying the role of resection in mGCs to enhance standardization of care.

DNA Methylation-Based Estimates of Circulating Leukocyte Composition for Predicting Colorectal Cancer Survival: A Prospective Cohort Study.

Leukocytes are involved in the progression of colorectal cancer (CRC). The proportion of six major leukocyte subtypes can be estimated using epigenome-wide DNA methylation (DNAm) data from stored blood samples. Whether the composition of circulating leukocytes can be used as a prognostic factor is unclear. DNAm-based leukocyte proportions were obtained from a prospective cohort of 2206 CRC patients. Multivariate Cox regression models and survival curves were applied to assess associations between leukocyte composition and survival outcomes. A higher proportion of lymphocytes, including CD4+ T cells, CD8+ T cells, B cells, and NK cells, was associated with better survival, while a higher proportion of neutrophils was associated with poorer survival. CD4+ T cells outperformed other leukocytes in estimating the patients' prognosis. Comparing the highest quantile to the lowest quantile of CD4+ T cells, hazard ratios (95% confidence intervals) of all-cause and CRC-specific mortality were 0.59 (0.48, 0.72) and 0.59 (0.45, 0.77), respectively. Furthermore, the association of CD4+ T cells and prognosis was stronger among patients with early or intermediate CRC or patients with colon cancer. In conclusion, the composition of circulating leukocytes estimated from DNAm, particularly the proportions of CD4+ T cells, could be used as promising independent predictors of CRC survival.

Health-Related Quality of Life in Very Long-Term Cancer Survivors 14-24 Years Post-Diagnosis Compared to Population Controls: A Population-Based Study.

(1) Background: Little is known about the health-related quality of life (HRQoL) in very long-term cancer survivors (VLTCS) 10 and more years post-diagnosis. The objective was to compare cancer survivors' HRQoL 14-24 years post-diagnosis with that of same-aged non-cancer controls, stratified by age, sex, and disease status (disease-free vs. stage IV, recurrence, metastasis, or second cancer). (2) Methods: We recruited 2704 very long-term survivors of breast, colorectal and prostate cancer, and 1765 controls in German multi-regional population-based studies. The HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Differences in the HRQoL were estimated with multiple regression, controlling for age, sex (where appropriate), and education. (3) Results: The overall global health status/quality of life of VLTCS more than a decade after diagnosis was slightly higher than that of population controls of the same age, but more symptoms and lower functioning were reported. Differences were small but statistically significant. Results differed by age, sex, and disease status. (4) Conclusions: The findings point out the need for a comprehensive survivorship care program in order to monitor and treat potential late and long-term effects after the diagnosis and treatment of cancer. Survivorship care should be risk-adapted to survivors' needs according to sociodemographic and clinical factors.