Lina Jansen

Fear of recurrence and disease progression in long-term (≥5 years) cancer survivors - A systematic review of quantitative studies

Increasing proportions of patients diagnosed with cancer will become long‐term survivors (≥5 years post‐diagnosis). However, survivors may continue to experience negative effects of cancer and/or treatment, including fear of recurrence (FoR). This review aims to provide an overview of current knowledge on FoR, including determinants and consequences in long‐term cancer survivors, and to outline methodological and conceptual challenges that should be addressed in future research.

Reduced Risk of Colorectal Cancer Up to 10 Years After Screening, Surveillance, or Diagnostic Colonoscopy

BACKGROUND & AIMS Data from randomized controlled trials on the effects of screening colonoscopies on colorectal cancer (CRC) incidence and mortality are not available. Observational studies have suggested that colonoscopies strongly reduce the risk of CRC, but there is little specific evidence on the effects of screening colonoscopies. METHODS We performed a population-based case-control study of 3148 patients with a first diagnosis of CRC (cases) and 3274 subjects without CRC (controls) from the Rhine-Neckar region of Germany from 2003 to 2010. Detailed information on previous colonoscopy and potential confounding factors was collected by standardized personal interviews. Self-reported information on colonoscopies and their indications was validated by medical records. We used multiple logistic regression to assess the association between colonoscopy conducted for specific indications within the past 10 years and risk of CRC. RESULTS A history of colonoscopy was associated with a reduced subsequent risk of CRC, independently of the indication for the examination. However, somewhat stronger associations were found for examinations with screening indications (adjusted odds ratio [OR] 0.09, 95% confidence interval [CI] 0.07-0.13) than for examinations with diagnostic indications, such as positive fecal occult blood test result (OR, 0.33; 95% CI, 0.19-0.57), surveillance after a preceding colonoscopy (OR, 0.33; 95% CI, 0.24-0.45), rectal bleeding (OR, 0.28; 95% CI, 0.20-0.40), abdominal symptoms (OR, 0.15; 95% CI, 0.10-0.21), or other (OR, 0.21; 95% CI, 0.14-0.30). Colonoscopy was also associated with a reduced risk of cancer in the right colon, regardless of the indication, although to a smaller extent than for other areas of the colon (OR for screening colonoscopy, 0.22; 95% CI, 0.14-0.33). CONCLUSIONS In a population-based case-control study, the risk of CRC was strongly reduced up to 10 years after colonoscopy for any indication. Risk was particularly low after screening colonoscopy, even for cancer in the right colon.

Health-Related Quality of Life During the 10 Years After Diagnosis of Colorectal Cancer: A Population-Based Study

PURPOSE To compare long-term quality of life (QoL) of colorectal cancer survivors with QoL in the general population and investigate changes in QoL of survivors during the 10 years after diagnosis. PATIENTS AND METHODS Health-related QoL was assessed 1, 3, 5, and 10 years after diagnosis in a population-based cohort starting with 439 patients with colorectal cancer from Saarland, Germany, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. QoL after 5 and 10 years and time course of QoL during the 10 years after diagnosis were compared with controls from the general population of Germany, after controlling for sex and age. RESULTS Overall, 234 and 196 patients were still alive after 5 and 10 years, respectively. Of these survivors, 178 (76%) responded in the 5-year follow-up, 133 (68%) in the 10-year follow-up, and 117 (60%) participated in all follow-ups. Over the entire follow-up, younger survivors (age at diagnosis, < 60 years) reported restrictions in role, social, emotional, and cognitive functioning and specific problems like constipation, diarrhea, fatigue, and insomnia. Older survivors (age at diagnosis, ≥ 70 years) reported comparable or even better QoL than controls within the first 3 to 5 years after diagnosis and comparable to worse QoL 5 to 10 years after diagnosis. CONCLUSION Although younger survivors continuously reported detriments in various QoL dimensions during the 10-year period after diagnosis, detriments in older survivors became apparent in the long run only.

Quality of life in long-term breast cancer survivors – a 10-year longitudinal population-based study

Abstract 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.

Expression of oestrogen receptor β and prognosis of colorectal cancer

Background:Previous studies suggest that sex steroids influence colorectal cancer (CRC) carcinogenesis. The oestrogen receptor β (ERβ) is the predominantly expressed ER in the colon and loss of ERβ in CRC has been associated with advanced cancer stages.Methods:Information on vital status by the end of 2009 was obtained for 1262 CRC patients recruited between 2003 and 2007. The ERβ expression was immunohistochemically measured and associations of ERβ scores with overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) were evaluated using Cox proportional hazard models adjusted for prognostic factors, such as tumour stage and second primary tumours.Results:Of the 1101 tumour samples with successful measurement, 535 were ERβ negative (48.6%), 381 (34.6%) showed moderate and 185 (16.8%) showed high ERβ expression. Compared with high ERβ expression, lack of ERβ was associated with higher cancer stages as well as greater tumour extent. In multivariate analyses, ERβ negativity was associated with an increased hazard ratio for death (HR=1.61, 95% CI 1.09–2.40, P=0.02), death attributed to CRC (HR=1.54, 95% CI 0.99–2.39, P=0.06) as well as a poorer DFS (DFS HR=1.64, 95% CI 1.23–3.36, P=0.04). The associations were stronger in stage I-III patients (OS HR=2.20, 95% CI 1.28–4.06, P=0.007, DSS HR=2.38, 95% CI 1.20–5.39, P=0.02, respectively).Conclusions:Lack of ERβ expression is associated with advanced cancer stages and independently associated with poor survival.

Benefit finding and post-traumatic growth in long-term colorectal cancer survivors: Prevalence, determinants, and associations with quality of life

Background:As research on quality of life of colorectal cancer (CRC) survivors has mainly focused on downsides of cancer survivorship, the aim of this study is to investigate benefit finding (BF) and post-traumatic growth (PTG) in long-term CRC survivors.Methods:Benefit finding, PTG, and quality of life were assessed 5 years after diagnosis in a population-based cohort of 483 CRC patients using the benefit finding scale, the post-traumatic growth inventory, and the EORTC QLQ-C30. Prevalence of BF and PTG, determinants of moderate-to-high BF and PTG, and the association between BF, PTG, and quality of life were investigated.Results:Moderate to high levels of BF and PTG were experienced by 64% and 46% of the survivors, respectively. Survivors with the highest level of education and with higher depression scores reported less BF and PTG. The PTG increased with increasing stage and self-reported burden of diagnosis. Quality of life only correlated weakly with PTG (Pearsons r=0.1180, P=0.0112) and not with BF (r=0.0537, P=0.2456).Conclusion:Many long-term CRC survivors experience BF and PTG. As these constructs were not strongly correlated with quality of life, focusing solely on quality of life after cancer misses an important aspect of survivorship.

Sex Differences in Colorectal Cancer Survival: Population-Based Analysis of 164,996 Colorectal Cancer Patients in Germany

Risk of colorectal cancer (CRC) is considerably higher in men compared to women; however, there is inconclusive evidence of sex differences in CRC prognosis. We aimed to assess and explain sex differences in 5-year relative survival using standard and model-based period analysis among 164,996 patients diagnosed with CRC from 1997 to 2006 and reported to 11 German cancer registries covering a population of 33 million inhabitants. Age-adjusted 5-year relative survival was higher in women (64.5% vs. 61.9%, P<0.0001). A substantial survival advantage of women was confirmed in multivariate analysis after adjusting for CRC stage and subsite in subjects under 65 years of age (relative excess risk, RER 0.86, 95% CI 0.82–0.90), but not in older subjects (RER 1.01, 95% CI 0.98–1.04); this pattern was similar in the 1st and in the 2nd to 5th year after diagnosis. The survival advantage of women varied by CRC stage and age and was most pronounced for localized disease (RERs 0.59–0.88 in various age subgroups) and in patients under 45 years of age (RERs 0.59, 0.72 and 0.76 in patients with localized, regional or advanced disease, respectively). On the contrary, sex differences in survival did not vary by location of CRC. In conclusion, our large population-based study confirmed a survival advantage of female compared to male CRC patients, most notably in young and middle aged patients and patients with localized disease. The effect of sex hormones, either endogenous or through hormonal replacement therapy, might be the most plausible explanation for the observed patterns.

Recent improvement in survival of patients with multiple myeloma: variation by ethnicity

Abstract Survival for patients with multiple myeloma has increased during the first decade of the 21st century. However, it is unknown whether the improvements in survival have extended equally in all ethnic groups. Using data from the United States Surveillance, Epidemiology and End Results Program, we assessed trends in survival and disease-related mortality for patients with myeloma by ethnic group, including non-Hispanic whites (nHw), African-Americans (AA), Hispanics and people of Asian and Pacific Islander descent (API) from 1998–2001 to 2006–2009. Overall, age adjusted 5-year relative survival increased, from 35.6% in 1998–2001 to 44% in 2006–2009. The greatest improvements were observed for patients aged 15–49, for whom survival increased by + 16.8% units for nHw and + 14.4% units for AA, whereas improvement was less pronounced and not statistically significant in Hispanics and API. Excess mortality hazard ratios were 1.20 (95% confidence interval [CI]: 1.09–1.33) for AA and 1.25 (95% CI: 1.11–1.41) for Hispanics compared to nHw in 2006–2009. Although survival increased greatly for nHw with myeloma between 1998–2001 and 2006–2009, smaller increases were observed for people of other ethnic groups. Persistent excess mortality was seen for AA and Hispanic patients with myeloma. Ethnic inequalities persisted or even increased from earlier periods to 2006–2009. The results suggest that ethnic minorities may not have benefited from newer treatments to the same extent as nHw patients have.

Lack of absent in melanoma 2 (AIM2) expression in tumor cells is closely associated with poor survival in colorectal cancer patients

Functional studies on colorectal cancer cells indicated a protective role of the interferon‐inducible dsDNA sensor Absent in Melanoma 2 (AIM2) in cancer progression. Given that a high mutation rate and lack of AIM2 expression was previously detected in a subset of colorectal cancers, we here investigated the association of AIM2 expression in tumor cells and patient prognosis (5‐year follow‐up). A tissue microarray analysis of 476 matched tissue pairs (colorectal tumor and adjacent normal colon epithelium) was performed by two independent observers. Samples from 62 patients were excluded because of missing follow‐up information or due to neo‐adjuvant therapy before tissue sampling. Out of the remaining 414 tissue pairs, 279 (67.4%) displayed reduced AIM2 expression in cancer cells when compared to epithelial cells of their normal counterpart. Thirty‐eight patients (9.18%) had completely lost AIM2 expression in tumor cells. After adjustment for sex, age, cancer stage, tumor site, tumor grade and chemotherapy, complete lack of AIM2 expression was associated with an up to 3‐fold increase in overall mortality (HR = 2.40; 95% CI = 1.44–3.99) and disease specific mortality (HR = 3.14; 95% CI = 1.75–5.65) in comparison to AIM2‐positive tumor samples. Our results demonstrate that lack of AIM2 expression is closely associated with poor outcome in colorectal cancer. The data thus strongly substantiate a protective role of AIM2 against progression of colorectal tumors. Further studies are required to assess whether lack of AIM2 expression may be used as a biomarker for the identification of colorectal cancer patients with poor prognosis.

Socioeconomic deprivation and cancer survival in Germany: An ecological analysis in 200 districts in Germany

Although socioeconomic inequalities in cancer survival have been demonstrated both within and between countries, evidence on the variation of the inequalities over time past diagnosis is sparse. Furthermore, no comprehensive analysis of socioeconomic differences in cancer survival in Germany has been conducted. Therefore, we analyzed variations in cancer survival for patients diagnosed with one of the 25 most common cancer sites in 1997–2006 in ten population‐based cancer registries in Germany (covering 32 million inhabitants). Patients were assigned a socioeconomic status according to the district of residence at diagnosis. Period analysis was used to derive 3‐month, 5‐year and conditional 1‐year and 5‐year age‐standardized relative survival for 2002–2006 for each deprivation quintile in Germany. Relative survival of patients living in the most deprived district was compared to survival of patients living in all other districts by model‐based period analysis. For 21 of 25 cancer sites, 5‐year relative survival was lower in the most deprived districts than in all other districts combined. The median relative excess risk of death over the 25 cancer sites decreased from 1.24 in the first 3 months to 1.16 in the following 9 months to 1.08 in the following 4 years. Inequalities persisted after adjustment for stage. These major regional socioeconomic inequalities indicate a potential for improving cancer care and survival in Germany. Studies on individual‐level patient data with access to treatment information should be conducted to examine the reasons for these socioeconomic inequalities in cancer survival in more detail.