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Background For virtually every patient with colorectal cancer (CRC), hematoxylin-eosin (HE)-stained tissue slides are available. These images contain quantitative information, which is not routinely used to objectively extract prognostic biomarkers. In the present study, we investigated whether deep convolutional neural networks (CNNs) can extract prognosticators directly from these widely available images. Methods and findings We hand-delineated single-tissue regions in 86 CRC tissue slides, yielding more than 100,000 HE image patches, and used these to train a CNN by transfer learning, reaching a nine-class accuracy of >94% in an independent data set of 7,180 images from 25 CRC patients. With this tool, we performed automated tissue decomposition of representative multitissue HE images from 862 HE slides in 500 stage I-IV CRC patients in the The Cancer Genome Atlas (TCGA) cohort, a large international multicenter collection of CRC tissue. Based on the output neuron activations in the CNN, we calculated a 'deep stroma score,' which was an independent prognostic factor for overall survival (OS) in a multivariable Cox proportional hazard model (hazard ratio [HR] with 95% confidence interval [CI]: 1.99 [1.27-3.12], p = 0.0028), while in the same cohort, manual quantification of stromal areas and a gene expression signature of cancer-associated fibroblasts (CAFs) were only prognostic in specific tumor stages. We validated these findings in an independent cohort of 409 stage I-IV CRC patients from the 'Darmkrebs: Chancen der Verhütung durch Screening' (DACHS) study who were recruited between 2003 and 2007 in multiple institutions in Germany. Again, the score was an independent prognostic factor for OS (HR 1.63 [1.14-2.33], p = 0.008), CRC-specific OS (HR 2.29 [1.5-3.48], p = 0.0004), and relapse-free survival (RFS; HR 1.92 [1.34-2.76], p = 0.0004). A prospective validation is required before this biomarker can be implemented in clinical workflows. Conclusions In our retrospective study, we show that a CNN can assess the human tumor microenvironment and predict prognosis directly from histopathological images., Author(s): Jakob Nikolas Kather 1,2,3,4,*, Johannes Krisam 5, Pornpimol Charoentong 1,3, Tom Luedde 4, Esther Herpel 6,7, Cleo-Aron Weis 8, Timo Gaiser 8, Alexander Marx 8, Nektarios A. Valous 1,3, [...]

(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. [ABSTRACT FROM AUTHOR]

Background Vitamin D plays a role in detoxifying free radicals, which might explain the previously reported lower mortality in colorectal cancer (CRC) patients with higher vitamin D concentrations. Objectives We aimed to assess whether the associations of 25-hydroxyvitamin D [25(OH)D] with prognosis in CRC patients differ by total thiol concentration (TTC), a biomarker of antioxidant capacity. Methods CRC patients who were diagnosed from 2003 to 2010 and recruited into a population-based study in southern Germany (n  = 2,592) were followed over a period of 6 y. 25(OH)D and TTC were evaluated from blood samples collected shortly after CRC diagnosis. Associations of 25(OH)D with all-cause and CRC mortality according to TTC were estimated using multivariable Cox proportional hazards regression. Results There was a weak positive correlation between 25(OH)D and TTC (r  = 0.26, P  < 0.001). 25(OH)D was inversely associated with mortality among patients in the lowest and middle TTC tertiles, but no associations were found among patients in the highest TTC tertile (P -interaction = 0.01). Among patients in the lowest/middle TTC tertiles, those in the middle and highest (compared with lowest) 25(OH)D tertiles had 31% and 44% lower all-cause mortality (P  < 0.001) and 25% and 45% lower CRC mortality (P  < 0.001), respectively. However, in the highest TTC tertile, 25(OH)D was not associated with all-cause (P  = 0.638) or CRC mortality (P = 0.395). Conclusions The survival advantages in CRC patients with adequate vitamin D strongly depend on antioxidant capacity and are most pronounced in cases of low antioxidant capacity. These findings suggest that TTC and other biomarkers of antioxidant status may be useful as the basis for enhanced selection criteria of patients for vitamin D supplementation, in addition to the conventional judgment based on blood 25(OH)D concentrations, and also for refining selection of patients for clinical trials aiming to estimate the effect of vitamin D supplementation. [ABSTRACT FROM AUTHOR]

Background: In rectal cancer, prediction of tumor response and pathological complete response (pCR) to neoadjuvant treatment could contribute to refine selection of patients who might benefit from a delayed- or no-surgery approach. The aim of this study was to explore the association of clinical and molecular characteristics of rectal cancer with response to neoadjuvant treatment and to compare patient survival according to level of response. Methods: Resected rectal cancer patients were selected from a population-based cohort study. Molecular tumor markers were determined from the surgical specimen. Tumor response and pCR were defined as downstaging in T or N stage and absence of tumor cells upon pathological examination, respectively. The associations of patient and tumor characteristics with tumor response and pCR were explored, and patient survival was determined by degree of response to neoadjuvant treatment. Results: Among 1536 patients with rectal cancer, 602 (39%) received neoadjuvant treatment. Fifty-five (9%) patients presented pCR, and 239 (49%) and 250 (53%) patients showed downstaging of the T and N stages, respectively. No statistically significant associations were observed between patient or tumor characteristics and tumor response or pCR. Patients who presented any type of response to neoadjuvant treatment had significantly better cancer-specific and overall survival compared with non-responders. Conclusion: In this study, patient characteristics were not associated with response to neoadjuvant treatment, and molecular characteristics determined after surgical resection of the tumor were not predictive of pCR or tumor downstaging. Future studies should include molecular biomarkers from biopsy samples before neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) and its treatment can lead to several physical and psychosocial impairments. Cancer rehabilitation aims to reduce morbidity and improve quality of life. The objective of this review was to summarize and evaluate evidence on changes in health-related outcomes among CRC patients undergoing inpatient rehabilitation therapy and on the effectiveness of such treatment. We conducted a systematic literature search including the electronic databases Pubmed and Web of Science to find observational and interventional studies, which investigated changes in health-related outcomes among CRC patients undergoing multidisciplinary inpatient rehabilitation programs or treatment effects. Study findings were synthesized narratively. Eleven studies were eligible and included in this review. Eight patient cohort studies addressed outcomes such as physical and functional status, fecal incontinence, anxiety and depression, and quality of life. Positive changes during rehabilitation therapy were observed for physical health (functional and physical status, fecal incontinence), and several dimensions of quality of life. Study findings concerning anxiety and depression were not conclusive. Studies that additionally conducted long-term follow-ups indicated that the improved health status after rehabilitative treatment waned over time. One RCT reported no effect of inpatient rehabilitation on distress and two randomized trials reported effects of exercise intensity on oxidative stress and immune response. Sample sizes were low (<100 included CRC patients) in eight studies and only the RCT included a comparison group (non-rehabilitants). The scientific evidence level was very limited. Due to the lack of a comparison group in most studies, we were only able to evaluate changes during/after inpatient rehabilitation therapy but not the effectiveness of treatment. However, study findings suggest that physical health and functional independence improve during inpatient rehabilitation, but improvements wane over time. Further large representative studies, in particular RCTs with long-term follow-up, are essential to evaluate the effectiveness of inpatient rehabilitation and identify determinants of treatment success. [ABSTRACT FROM AUTHOR]

Oxidative stress has been implicated in the initiation of several cancers, including colorectal cancer (CRC). Whether it also plays a role in CRC prognosis is unclear. We assessed the associations of two oxidative stress biomarkers (Diacron's reactive oxygen metabolites [d‐ROMs] and total thiol level [TTL]) with CRC prognosis. CRC patients who were diagnosed in 2003 to 2012 and recruited into a population‐based study in Germany (n = 3361) were followed for up to 6 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations of d‐ROMs and TTL (measured from blood samples collected shortly after CRC diagnosis) with overall survival (OS) and disease‐specific survival (DSS) were estimated using multivariable Cox regression. Particularly pronounced associations of higher d‐ROMs with lower survival were observed in stage IV patients, with patients in the highest (vs lowest) tertile having much lower OS (HR = 1.52, 95% CI = 1.14‐2.04) and DSS (HR = 1.61, 95% CI = 1.20‐2.17). For TTL, strong inverse associations of TTL with mortality were observed within all stages. In patients of all stages, those in the highest (vs lowest) quintile had substantially higher OS (HR = 0.48, 95% CI = 0.38‐0.62) and DSS (HR = 0.52, 95% CI = 0.39‐0.69). The addition of these biomarkers to models that included age, sex, tumor stage and subsite significantly improved the prediction of CRC prognosis. The observed strong associations of higher d‐ROMs and lower TTL levels with poorer prognosis even in stage IV patients suggest that oxidative stress contributes significantly to premature mortality in CRC patients and demonstrate a large potential of these biomarkers in enhancing the prediction of CRC prognosis beyond tumor stage. What's new? Oxidative stress has been implicated in the initiation of several cancers, including colorectal cancer (CRC). Whether oxidative stress also plays a role in CRC prognosis remains unclear, however. In this large CRC patient cohort study, higher reactive oxygen metabolites and lower total thiol levels were strongly associated with poorer prognosis. The addition of these biomarkers to models that included age, sex, tumor stage, and sub‐site significantly improved the prediction of CRC prognosis. The findings suggest that oxidative stress contributes significantly to premature mortality in CRC patients and demonstrate the potential of these biomarkers in enhancing the prediction of CRC prognosis. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PC) and its treatment may affect PC survivors differently with respect to age. However, little is known regarding age-specific health-related quality of life (HRQoL) in PC survivors 5 years or even ≥ 10 years post-diagnosis.Methods: The sample included 1975 disease-free PC survivors (5-16 years post-diagnosis) and 661 cancer-free population controls, recruited from two German population-based studies (CAESAR+, LinDe). HRQoL in both populations was assessed using the EORTC QLQ-C30 questionnaire. Additionally, PC survivors completed the PC-specific EORTC QLQ-PR25 questionnaire. Differences in HRQoL between survivors and controls, as well as differences according to age and time since diagnosis were analyzed with multiple regression after adjustment for age, education, stage, and time since diagnosis, where appropriate.Results: In general, PC survivors reported HRQoL and symptom-burden levels comparable to the general population, except for significantly poorer social functioning and higher burden for diarrhea and constipation. In age-specific analyses, PC survivors up to 69 years indicated poorer global health and social functioning than population controls. Stratification by time since diagnosis revealed little difference between the subgroups. On PC-specific symptoms, burden was highest for urinary bother and symptoms, and lowest for bowel symptoms. Younger age was associated with less urinary symptoms but higher urinary bother.Conclusion: Long-term disease-free PC survivors reported overall good HRQoL, but experienced persistent specific detriments. Our data suggest that these detriments do not improve substantially with increasing time since diagnosis. Targeted interventions are recommended to prevent PC-related and treatment-related symptoms becoming chronic and to enhance social functioning. [ABSTRACT FROM AUTHOR]

Introduction: Propensity score methods are increasingly used to address confounding related to treatment selection in observational studies. Studies estimating the effect of chemotherapy in colon cancer (CC) patients, however, often lacked information on pertinent comorbidities and functional status (FS). We assessed to what extent comorbidities and FS impact treatment decisions in colorectal cancer patients and explain the benefit of chemotherapy in stage III CC patients. Methods: Stage II-III colorectal cancer patients diagnosed in 2003–2014 and recruited into a population-based study were included (N=1102). Associations of comorbidity and FS with treatment patterns were examined with multivariable logistic regression. The contribution of lower comorbidity and higher FS to the benefit of chemotherapy was estimated with propensity score weighted Cox models in 430 stage III CC patients who were followed over a median time of 4.7 years. Results: In stage II (high-risk) and III CC patients, Charlson comorbidity scores 1, 2 and 3+ were associated with 57%, 66% and 70% lower odds of chemotherapy use, respectively. In combination with older age and poor FS, comorbidity was associated with 97% and 83% decreased odds of adjuvant chemotherapy use in CC and rectal cancer patients, respectively. In stage III CC patients, lower comorbidity and higher FS explained 38% and 24% of the overall and disease-specific survival benefits of chemotherapy, respectively. Selection bias was observed even in the comprehensive models, as chemotherapy was still associated with substantially higher non-disease-specific survival (hazard ratio (HR): 0.66; 95% confidence interval (CI): 0.46–0.92), especially in patients <75 years (HR: 0.33; 95% CI: 0.17–0.63). Conclusion: Lower comorbidity and higher FS of recipients of chemotherapy explain approximately 40% of the benefits of chemotherapy in stage III CC patients. Regardless of how comprehensive propensity score analyses might be in observational studies, treatment selection bias might persist and affect estimates of treatment effects. [ABSTRACT FROM AUTHOR]

Background: Previous research suggests an age differential in health-related quality of life (HRQOL) among long-term (5–10 years post-diagnosis, LTS) colorectal cancer (CRC) survivors. Few studies have specifically addressed the association of age differentials with HRQOL for very long-term CRC survivors (>10 years post-diagnosis, VLTS) and non-cancer population controls. We aimed to assess possible deficits in HRQOL of disease-free CRC-LTS and CRC-VLTS in comparison with non-cancer population controls, and whether the observed pattern varies by age and time since diagnosis. Methods: We used data from the CAncEr Survivorship - A multi-Regional (CAESAR+) study in collaboration with five population-based German cancer registries. HRQOL from controls was accessed from the Lebensqualität in DEeutschland (LinDE) study. All respondents completed the European Organization for Research and Treatment of Cancer Quality of Life Core-30 questionnaire. We calculated least square means of HRQOL scores. Analyses were adjusted for age, sex, and education, where appropriate. Results: The sample included 862 CRC-LTS, 400 CRC-VLTS and 1689 controls. CRC survivors reported overall good HRQOL but significantly poorer social functioning and more problems with dyspnea, constipation, diarrhea and finances than controls. When stratified by age, deficits in functioning and global health, and more problems with symptoms and finances were noted mainly among younger CRC survivors. Further stratification by time since diagnosis showed that similar deficits in HRQOL and symptoms were noted mainly among the younger CRC-LTS group when compared with controls. Generally, CRC-VLTS reported comparable HRQOL to controls. An exception was noted for diarrhea, whereby CRC survivors, regardless of age and time since diagnosis, reported significantly more problems with this symptom than controls. Conclusions: In comparison with non-cancer controls, disease-free CRC survivors reported overall good HRQOL but experience persistent specific detriments in HRQOL many years after diagnosis. In age stratified analyses, HRQOL deficits were noted mainly among younger CRC-LTS. [ABSTRACT FROM AUTHOR]

Immortal time bias (ITB) is still seen frequently in medical literature. However, not much is known about this bias in the field of cancer (pharmaco-)epidemiology. In context of a hypothetical beneficial beta-blocker use among cancer patients, we aimed to demonstrate the magnitude of ITB among 9876 prostate, colorectal, lung and pancreatic cancer patients diagnosed between 1998 and 2011, which were selected from a database linkage of the Netherlands Cancer Registry and the PHARMO Database Network. Hazard ratios (HR) and 95% confidence intervals from three ITB scenarios, defining exposure at a defined point after diagnosis (model 1), at any point after diagnosis (model 2) and as multiple exposures after diagnosis (model 3), were calculated to investigate the association between beta-blockers and cancer prognosis using Cox proportional hazards regression. Results were compared to unbiased estimates derived from the Mantel-Byar model. Ignoring ITB led to substantial smaller HRs for beta-blocker use proposing a significant protective association in all cancer types [e.g. HR 0.18 (0.07-0.43) for pancreatic cancer in model 1], whereas estimates derived from the Mantel-Byar model were mainly suggesting no association [e.g. HR 1.10 (0.84-1.44)]. The magnitude of bias was consistently larger among cancer types with worse prognosis [overall median HR differences between all scenarios in model 1 and Mantel-Byar model of 0.56 (prostate), 0.72 (colorectal), 0.77 (lung) and 0.85 (pancreas)]. In conclusion, ITB led to spurious beneficial associations of beta-blocker use among cancer patients. The magnitude of ITB depends on the duration of excluded immortal time and the prognosis of each cancer. [ABSTRACT FROM AUTHOR]

Background:With the increasing number and diversity of cancer survivors, studies of survivors’ physical, emotional, and social health are of growing importance. While there is a growing body of literature on the quality of life (QoL) of cancer patients during the early years past diagnosis, less is known regarding QoL in long-term survivors (LTS) (5 + years past diagnosis) and particularly in very long-term survivors (VLTS) (10 + years past diagnosis). The objective of our study is to: (1) compare QoL of long-term cancer survivors and population norms; and (2) assess whether any deficits in QoL of survivors observed 5–10 years past diagnosis persist beyond the 10th year past diagnosis. Methods:In total 6952 long-term cancer survivors (5–16 years past diagnosis of breast, colorectal, or prostate cancer) from Germany recruited in the context of the population-based CAESAR + study were compared with 1878 population-based controls without a history of cancer. QoL was assessed with the EORTC QLQ-C30. Differences in QoL between survivors and controls were assessed via multiple regression while controlling for age, gender, education, and case mix for survivors 5–9 years and 10 + years past diagnosis separately. Results:Overall QoL in long-term cancer survivors was comparable to population norms but specific deficits in social, role, emotional, cognitive, and physical functioning and symptoms such as insomnia, fatigue, dyspnea, constipation, diarrhea, and financial difficulties were more prevalent in LTSs. Detriments in QoL persisted during the observation period and affected particularly cancer survivors at younger ages (<50 years). Non-significant aggravations in QoL with longer time since diagnosis were observed in very young and very old cancer survivors. Conclusions:Detriments in health-related quality of life persist over more than a decade and affect predominantly younger patients. Improvements both in early and long-term follow-up care of cancer survivors seem warranted. [ABSTRACT FROM AUTHOR]

Introduction: The advent of tyrosine kinase inhibitors has produced 5-year survival of 90 + % for chronic myelocytic leukemia (CML) patients in clinical trials. However, population level survival has been lower, especially in older patients. Here, we examine survival of patients with CML in Germany and compare it to survival of patients in the United States (US). Methods: Data were extracted from the Surveillance, Epidemiology, and End Results database in the US and 11 cancer registries in Germany. Patients 15-69 years old diagnosed with CML were included in the analysis. Period analysis for 2002-2006 was used to provide the most up-to-date possible estimates of five-year relative survival. Results: Five-year relative survival was 68.7% overall in Germany and 72.7% in the US. Survival was higher in the US for all age groups except for ages 15-39 years, but the difference was only statistically significant for ages 50- 59 years (at 67.5% vs 77.7% in Germany and the US, respectively). Survival decreased with age, ranging from 83.1% and 81.9%, respectively, in Germany and the US for patients 15-39 years old to 54.2% and 54.5%, respectively, in patients 65-69 years old. Survival increased between 2002 and 2006 by 12.0% points in Germany and 17.1% points in the US. Conclusions: Five-year survival estimates were higher in the US than in Germany overall, but the difference was only significant for ages 50-59 years. Survival did not equal that seen in clinical trials for either country, but strong improvement in survival was seen between 2002 and 2006. [ABSTRACT FROM AUTHOR]

Background. Breast cancer survivors may experience adverse effects of cancer and/or treatment years after completion of therapy, which can considerably decrease quality of life (QoL). Little is known about the time course of QoL in breast cancer survivors beyond the fifth year post-diagnosis, when routine follow-up care has usually terminated. We therefore explored in detail whether and to what extent restrictions in breast cancer survivors persist and whether changes or aggravations in QoL occurred over time. Material and methods. QoL was assessed 1, 3, 5, and 10 years post-diagnosis in a population-based cohort of initially 387 female breast cancer patients from Saarland (Germany), using the EORTC QLQ-C30 and QLQ-BR23. Time course of QoL over 10 years post-diagnosis was assessed for survivors and survivors' QoL was compared cross-sectionally to the German general population after adjustment for age. Results. A total of 182 out of 238 patients alive (76.5%) responded in the 10-year, 160 patients (67.2%) participated in all follow-ups. Although breast cancer survivors and controls reported comparable general health and overall QoL, survivors reported significantly more restrictions on most functioning and symptom scales at each follow-up. Detriments in various QoL dimensions (e.g. physical and social functioning; pain, financial difficulties) aggravated from year 5 to 10. Generally, restrictions were largest for the youngest survivors. Conclusion. Relevant restrictions in QoL persist over years in breast cancer survivors and affect predominantly younger women. The aggravation of restrictions in QoL beyond the fifth year may indicate deficits in health care and psychosocial support of breast cancer patients after completion of routine follow-up care. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to describe the survival of patients diagnosed with oral cavity cancer in Germany. The analyses relied on data from eleven population-based cancer registries in Germany covering a population of 33 million inhabitants. Patients with a diagnosis of oral cavity cancer (ICD-10: C00-06) between 1997 and 2006 are included. Period analysis for 2002-2006 was applied to estimate five-year age-standardized relative survival, taking into account patients' sex as well as grade and tumor stage. Overall five-year relative survival for oral cavity cancer patients was 54.6%. According to tumor localization, five-year survival was 86.5% for lip cancer, 48.1% for tongue cancer and 51.7% for other regions of the oral cavity. Differences in survival were identified with respect to age, sex, tumor grade and stage. The present study is the first to provide a comprehensive overview on survival of oral cavity cancer patients in Germany. [ABSTRACT FROM AUTHOR]

Background. Esophagus and stomach cancers are associated with poor prognosis. But most published population-based cancer survival estimates for stomach and esophagus cancer refer to survival experience of patients diagnosed in the 1990s or earlier years. The aim of this study was to provide up-to-date survival estimates and trends for patients with stomach and esophagus cancer in Germany. Material and methods. Our analysis is based on data from 11 population-based cancer registries, covering 33 million inhabitants. Patients diagnosed with stomach and esophagus cancer in 1997-2006 were included. Period analysis was used to derive five-year relative survival estimates and trends by age, sex, cancer subsite, and stage for the time period of 2002-2006. German and US survival estimates were compared utilizing the SEER 13 database. Results. Overall age-standardized five-year relative survival was 31.8% and 18.3% for stomach and esophagus cancer, respectively, compared to 27.2% and 17.4% in the US. Survival was somewhat higher among female than among male patients for both cancer sites (33.6% vs. 30.6% and 21.5% vs. 17.5%, respectively) and much higher for non-cardia stomach cancer (40.4%) than for cardia cancer (23.4%). From 2002 to 2006, a moderate increase in five-year relative survival by 2.7 percent units was observed for non-cardia stomach cancer patients in Germany (p < 0.001). Conclusion. Five-year relative cancer survival has reached levels around 40% for patients with non-cardia stomach cancer in Germany in the early 21st century, whereas it remained at lower levels around 20% for patients with esophagus and cardia cancer. [ABSTRACT FROM AUTHOR]

Prior to the German reunification, cancer survival was much lower in East than in West Germany. We compare cancer survival between Eastern and Western Germany in the early twenty-first century, i.e. the second decade after the German reunification. Using data from 11 population-based cancer registries covering a population of 33 million people, 5-year age-standardized relative survival for the time period 2002-2006 was estimated for the 25 most common cancers using model-based period analysis. In 2002-2006, 5-year relative survival was very similar for most cancers, with differences below 3 % units for 20 of 25 cancer sites. Larger, statistically significant survival advantages were seen for oral cavity, oesophagus, and gallbladder cancer and skin melanoma in the West and for leukemia in the East. Our study shows that within two decades after the assimilation of political and health care systems, the former major survival gap of cancer patients in Eastern Germany has been essentially overcome. This result is encouraging as it suggests that, even though economic conditions have remained difficult in Eastern Germany, comparable health care provision may nevertheless enable comparable levels of cancer survival within a relatively short period of time. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the age-specific pattern of administration of chemotherapy and its association with long-term survival and quality of life (QoL) in stage II and III colorectal cancer patients. Methods. Chemotherapy allocation according to disease and patient characteristics was investigated in a population-based cohort of 562 stage II and III colorectal cancer patients. Five years after diagnosis, survival was determined and QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items and a tumor specific module. The association among chemotherapy, survival, and QoL was examined while controlling for potential confounders. Results. Chemotherapy was administered in 71% of patients aged <60 years and in only 20% of patients aged ≥80 years. A significant association between chemotherapy and longer survival time was found for stage III cancer only. Chemotherapy was associated with higher symptom levels for trouble with taste, anxiety, and hair loss. In age-specific analyses, younger survivors (<70 years at time of follow-up) with a history of chemotherapy reported significantly lower physical, role, and cognitive functioning and higher pain, appetite loss, hair loss, and trouble with taste symptom levels. In contrast, for older survivors (≥70 years), only two (hair loss and dry mouth) out of 38 QoL scores were significantly associated with chemotherapy. Discussion. Chemotherapy is associated with lower long-term QoL, especially in younger survivors. In cases of uncertain survival benefits of chemotherapy, consideration of its long-term effects on QoL should be incorporated into final decisions on treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known about the health-related quality of life in very long-term cancer survivors 10 and more years post-diagnosis. Therefore, we compared the health-related quality of life of survivors of breast, colorectal, and prostate cancer (14–24 years post-diagnosis) with that of same-aged non-cancer controls, according to age, sex, and disease status (disease-free vs. stage IV, recurrence, metastasis, or second cancer). We found that the overall global health status/quality of life of cancer survivors 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. 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. (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. [ABSTRACT FROM AUTHOR]

An individual's inherited genetic variation may contribute to the 'angiogenic switch', which is essential for blood supply and tumor growth of microscopic and macroscopic tumors. Polymorphisms in angiogenesis-related genes potentially predispose to colorectal cancer (CRC) or affect the survival of CRC patients. We investigated the association of 392 single nucleotide polymorphisms (SNPs) in 33 angiogenesis-related genes with CRC risk and survival of CRC patients in 1754 CRC cases and 1781 healthy controls within DACHS (Darmkrebs: Chancen der Verhütung durch Screening), a German population-based case-control study. Odds ratios and 95% confidence intervals (CI) were estimated from unconditional logistic regression to test for genetic associations with CRC risk. The Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% CIs for survival. Multiple testing was adjusted for by a false discovery rate. No variant was associated with CRC risk. Variants in EFNB2, MMP2 and JAG1 were significantly associated with overall survival. The association of the EFNB2 tagging SNP rs9520090 (p < 0.0001) was confirmed in two validation datasets (p-values: 0.01 and 0.05). The associations of the tagging SNPs rs6040062 in JAG1 (p-value 0.0003) and rs2241145 in MMP2 (p-value 0.0005) showed the same direction of association with overall survival in the first and second validation sets, respectively, although they did not reach significance (p-values: 0.09 and 0.25, respectively). EFNB2, MMP2 and JAG1 are known for their functional role in angiogenesis and the present study points to novel evidence for the impact of angiogenesis-related genetic variants on the CRC outcome. [ABSTRACT FROM AUTHOR]

Despite consistent evidence that comorbidities and functional status (FS) are strong prognostic factors for colorectal cancer (CRC) patients, these important characteristics are not considered in prognostic nomograms. We assessed to what extent incorporating these characteristics into prognostic models enhances prediction of CRC prognosis. CRC patients diagnosed in 2003–2014 who were recruited into a population-based study in Germany and followed over a median time of 4.7 years were randomized into training (n = 1608) and validation sets (n = 1071). In the training set, Cox models with predefined variables (age, sex, stage, tumor location, comorbidity scores, and FS) were used to construct nomograms for relevant survival outcomes. The performance of the nomograms, compared to models without comorbidity and FS, was evaluated in the validation set using concordance index (C-index). The C-indexes of the nomograms for overall and disease-free survival in the validation set were 0.768 and 0.737, which were substantially higher than those of models including tumor stage only (0.707 and 0.701) or models including stage, age, sex, and tumor location (0.749 and 0.718). The nomograms enabled significant risk stratification within all stages including stage IV. Our study suggests that incorporating comorbidities and FS into prognostic nomograms could substantially enhance prediction of CRC prognosis. [ABSTRACT FROM AUTHOR]

Introduction Population-level survival has improved for common haematologic malignancies in the early 21st century. However, relatively few population-level data are available for rare haematologic malignancies. Methods Data were extracted from 12 cancer registries in Germany and the Surveillance, Epidemiology and End Results database in the United States (US). Cases of haematologic malignancies with an incidence of less than 1 per 100,000 were selected for analysis. Period analysis was used to determine 5-year relative survival (RS) for the years 2003–2012, and modelled period analysis was used to determine changes in survival between 2003–2007 and 2008–2012. Results Seven individual haematologic malignancies which met criteria were identified. Overall 5-year age-adjusted RS was 62.4% in Germany and 57.0% in the US in 2003–2012, with a good deal of variability by individual haematologic malignancy, ranging from less than 30% for chronic monomyeloid leukaemia to greater than 85% for hairy cell leukaemia and mycosis fungoides. Five-year RS increased significantly between 2003–2007 and 2008–2012 for patients with mantle cell lymphoma, Burkitt's lymphoma and hairy cell leukaemia in Germany and for patients with mantle cell lymphoma and anaplastic large-cell kinase+ anaplastic lymphoma in the US. Conclusions Survival for rare haematologic malignancies varied considerably by cancer entity. Overall 5-year RS was slightly higher in Germany compared to the US. Survival estimates increased for a minority of haematologic malignancies between 2003–2007 and 2008–2012. Further research into the best treatment options for rare malignancies is needed to further improve survival. [ABSTRACT FROM AUTHOR]

Background: The proportion of cases notified by death certificate only (DCO) is a commonly used data quality indicator in studies comparing cancer survival across regions and over time. We aimed to assess dependence of DCO proportions on the age structure of cancer patients. Methods: Using data from a national cancer survival study in Germany, we determined age specific and overall (crude) DCO proportions for 24 common forms of cancer. We then derived overall (crude) DCO proportions expected in case of shifts of the age distribution of the cancer populations by 5 and 10 years, respectively, assuming age specific DCO proportions to remain constant. Results: Median DCO proportions across the 24 cancers were 2.4, 3.7, 5.5, 8.5 and 23.9% in age groups 15-44, 45-54, 55-64, 65-74, and 75+, respectively. A decrease of ages by 5 and 10 years resulted in decreases of cancer specific crude DCO proportions ranging from 0.4 to 4.8 and from 0.7 to 8.6 percent units, respectively. Conversely, an increase of ages by 5 and 10 years led to increases of cancer specific crude DCO proportions ranging from 0.8 to 4.8 and from 1.8 to 9.6 percent units, respectively. These changes were of similar magnitude (but in opposite direction) as changes in crude 5-year relative survival resulting from the same shifts in age distribution. Conclusions: The age structure of cancer patient populations has a substantial impact on DCO proportions. DCO proportions should therefore be age adjusted in comparative studies on cancer survival across regions and over time. [ABSTRACT FROM AUTHOR]