Cumulative incidence of second primary cancers in a large nationwide cohort of Danish cancer survivors: a population-based retrospective cohort study.

BACKGROUND: A new primary cancer is a serious late effect of a pre-existing cancer diagnosis, and can be attributed to hereditary cancer syndromes, immune or hormonal factors, cancer treatment, or modifiable lifestyle or environmental factors. We investigated the absolute and relative incidence of second primary cancers in a large cohort of Danish cancer survivors. Furthermore, we examined the association between alcohol-related, smoking-related, virus-related, and hormone-related first and second primary cancers. METHODS: In this retrospective cohort study, we identified a cohort of Danish adults (aged ≥40 years) diagnosed with cancer from Jan 1, 1997, to Dec 31, 2014 and alive 1 year after diagnosis. Follow-up was from date of first cancer diagnosis and lasted up to 24 years, ending on Dec 31, 2020. Cohort identification and information on second primary cancers was obtained from the Danish Cancer Registry, and comorbidity and sociodemographic information was obtained from Danish population-based registries. Overall, and for 27 cancer types, cumulative incidence functions and Cox proportional hazard regression models were used to estimate the incidence of second primary cancer and death, and hazard ratios (HRs) and 95% CIs of second primary cancer adjusted for sex, age and year of diagnosis, cohabitation status, income, and comorbidity. FINDINGS: 457 334 Danish adults were included in our study (230 150 [50·3%] male individuals and 227 184 [49·7%] female individuals; median age at diagnosis 68·3 years, IQR 59·7-76·6; median follow-up 3·6 years, IQR 0·6-9·3). The cumulative incidence of second primary cancer increased over time from 6·3% (95% CI 6·2-6·4) 5 years after diagnosis to 10·5% (10·4-10·6) 10 years after diagnosis and to 13·5% (13·4-13·7) 15 years after diagnosis. The highest cumulative incidence of second primary cancer 10 years after diagnosis was observed in survivors of cancers in the larynx (21·8%, 20·5-23·1), oropharynx and oral cavity (19·5%, 18·7-20·3), and bladder and urinary tract (18·5%, 18·0-19·0). Survivors of cancers related to alcohol (HR 1·09, 95% CI 1·06-1·13), smoking (1·73, 1·68-1·78), diet high in red or processed meat (1·32, 1·24-1·39), or virus (1·23, 1·13-1·35) were at increased risk of developing a second cancer with the same aetiology, whereas having had a hormone-related first cancer was associated with lower risk of a second hormone-related cancer (0·77, 0·73-0·81). INTERPRETATION: Our results could help optimise prevention efforts targeting modifiable risk factors to reduce risk of developing a second primary cancer. FUNDING: Nordic Cancer Union and The Health Foundation (Helsefonden).

Socioeconomic differences in health-related quality of life among cancer survivors and comparison with a cancer-free population: a PROFILES study.

PURPOSE: This study investigates the association between socioeconomic position (SEP) and health-related quality of life (HRQoL) in a cross-sectional cohort among cancer survivors and compares with cancer-free people. METHODS: Survivors of colorectal, hematological, gynecological, prostate, thyroid cancer, and melanoma diagnosed 2000-2014 were identified in the PROFILES registry, and an age- and sex-matched cancer-free population were identified in the CentER panel. HRQoL, education, and comorbidity were self-reported. Street-level income and clinical factors were obtained from Statistics Netherlands and the Netherlands Cancer Registry. Multivariable logistic regression was used to examine associations of SEP (measured by education and income) and impaired HRQoL among cancer survivors and the cancer-free population, adjusting for age, sex, and time since diagnosis. RESULTS: We included 6693 cancer survivors and 565 cancer-free people. Cancer survivors with low versus medium SEP more frequently reported impaired HRQoL (odds ratio (OR) range for all HRQoL outcomes, 1.06-1.78 for short education and 0.94-1.56 for low income). Survivors with high compared to medium SEP reported impaired HRQoL less frequently (OR range for all HRQoL outcomes, 0.46-0.81 for short education and 0.60-0.84 for low income). The association between SEP and HRQoL was similar in the matched cancer-free population. CONCLUSION: Low SEP was associated with impaired HRQoL in both cancer survivors and cancer-free people. IMPLICATIONS FOR CANCER SURVIVORS: Targeted care is warranted for cancer survivors with impaired HRQoL, especially among those with low SEP.

Socioeconomic position and the pre-diagnostic interval among patients diagnosed with head and neck squamous cell carcinoma - a population-based study from DAHANCA.

BACKGROUND: The socioeconomic differences in survival are pronounced for patients diagnosed with head and neck cancer; disease stage at diagnosis is suggested to be a main driver of this association. This nationwide, population-based study investigates socioeconomic differences in the pre-diagnostic interval and disease stage at diagnosis. MATERIAL AND METHODS: Information on patient-reported symptoms, symptom onset and disease-specific factors was obtained from the nationwide population-based Danish Head and Neck Cancer Group (DAHANCA) database for patients diagnosed with head and neck squamous cell carcinoma between 2008 and 2019 in Denmark. Socioeconomic position (SEP) was measured by individual-level education, income and cohabitation status obtained from administrative registers. Socioeconomic differences in the interval from symptom onset to diagnosis were investigated in general linear models with 95% confidence intervals (CIs); overall and by subsite, symptom and comorbidity score. Consultation patterns prior to diagnosis were examined using methods for change-point detection. Associations with advanced-stage disease were estimated in logistic regression models. RESULTS: Patients with low, medium and high SEP had a similar interval from patient-reported symptom onset to diagnosis of 10 weeks. Although this interval varied according to primary symptom and anatomical subsite, no apparent socioeconomic differences were observed within these subgroups. Aligned with the patient-reported symptom onset, a distinct increase in consultation rates was observed at 9 weeks (95% CI [7.3; 10.7]) for patients with low SEP and 7 weeks (95% CI [4.8; 9.2]) for patients with high SEP, with overlapping CIs. Patients with low compared to high SEP had increased odds for advanced-stage glottic and oral cavity squamous cell carcinoma. For the remaining subsites the association varied according to SEP-indicator and TNM-edition. CONCLUSION: The interval from symptom onset to diagnosis and consultation patterns were similar across SEP groups. Still, socioeconomic differences in stage at diagnosis were observed for some - but not all - subsites.

Social inequality in cancer survivorship: Educational differences in health-related quality of life among 27,857 cancer survivors in Denmark.

BACKGROUND: With a growing population of cancer survivors in Denmark, the evaluation of health-related quality of life (HRQoL) has become increasingly important. We describe variations in HRQoL between educational groups in a national population of cancer survivors. METHODS: We conducted a cross-sectional questionnaire study among breast, prostate, lung, and colon cancer survivors diagnosed in 2010-2019 in Denmark. We used the EORTC QLQ-C30 to assess HRQoL including physical, role, emotional, cognitive, social functioning, and symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Information on educational level and clinical data were extracted from national registers and clinical databases. Levels of impaired functioning and severe symptoms were identified using newly established thresholds for clinical importance. Multivariate logistic regression was used to examine associations between education and HRQoL. All statistical tests were 2-sided. RESULTS: In total, 27,857 (42%) participated in the study. Up to 72% and 75% of cancer survivors with short education (≤9 years) reported impaired functioning and severe symptoms, respectively. Cancer survivors with short compared to long education (>12 years) were more likely to report impaired functioning and severe symptoms, with for example significantly higher odds ratios (ORs) for impaired physical function (breast OR = 2.41, 99% CI = 2.01-2.89; prostate OR = 1.81, 99% CI = 1.48-2.21; lung OR = 2.97, 99% CI = 1.95-4.57; and colon cancer OR = 1.69, 99% CI = 1.28-2.24). CONCLUSIONS: Cancer survivors with short education are at greater risk of impaired HRQoL than survivors with long education 2-12 years after diagnosis. This underscores the need for systematic screening and symptom management in cancer aftercare, in order to reach all cancer survivors, also cancer survivors with short education.

Cardiovascular events after elective colorectal cancer surgery in patients with stage I-III disease with no previous cardiovascular disease.

BACKGROUND: The risk of cardiovascular events in patients treated for colorectal cancer is debated due to diverging results in previous studies. Colorectal cancer and cardiovascular disease share several risk factors such as physical inactivity, obesity, and smoking. Information about confounding covariates and follow-up time are therefore essential to address the issue. This study aims to investigate the risk of new-onset cardiovascular events for patients with stage I-III colorectal cancer receiving elective surgery compared to a matched population. MATERIAL AND METHODS: Using a prospective cohort, we compared cardiovascular events among 876 patients treated with elective surgery for incident stage I-III colorectal cancer diagnosed between January 1st, 2001 and December 31st, 2016 to a cancer-free cohort matched by age, sex, and time since enrollment (N = 3504). Regression analyses were adjusted for lifestyle, cardiovascular risk factors, and comorbidity. Multivariable analyses were used to identify risk factors associated with cardiovascular events in the postoperative (<90 days of elective surgery) and long-term phase (>90 days after elective surgery). RESULTS: After a median follow-up of 3.9 years, the hazard ratio (HR) for incident heart failure was 1.53 (95% CI 1.02-2.28) among patients operated for colorectal cancer. The postoperative risk of myocardial infarction or angina pectoris was associated with the use of lipid-lowering drugs. Long-term risks of cardiovascular events were ASA-score of III+IV and lipid-lowering drugs with HRs ranging from 2.20 to 15.8. Further, the use of antihypertensive drugs was associated with an HR of 2.09 (95% CI 1.06-4.13) for angina pectoris or acute myocardial infarction. Heart failure was associated with being overweight, diabetes, and anastomosis leakage. CONCLUSION: We observed an increased hazard of heart failure in patients operated on for stage I-III colorectal cancer compared to cancer-free comparisons. We identified several potential risk factors for cardiovascular events within and beyond 90 days of elective surgery.

Educational differences in healthcare use among survivors after breast, prostate, lung, and colon cancer - a SEQUEL cohort study.

BACKGROUND: Many cancer survivors experience late effects after cancer. Comorbidity, health literacy, late effects, and help-seeking behavior may affect healthcare use and may differ among socioeconomic groups. We examined healthcare use among cancer survivors, compared with cancer-free individuals, and investigated educational differences in healthcare use among cancer survivors. METHODS: A Danish cohort of 127,472 breast, prostate, lung, and colon cancer survivors from the national cancer databases, and 637,258 age- and sex-matched cancer-free individuals was established. Date of entry was 12 months after diagnosis/index date (for cancer-free individuals). Follow-up ended at death, emigration, new primary cancer, December 31st, 2018, or up to 10 years. Information about education and healthcare use, defined as the number of consultations with general practitioner (GP), private practicing specialists (PPS), hospital, and acute healthcare contacts 1-9 years after diagnosis/index date, was extracted from national registers. We used Poisson regression models to compare healthcare use between cancer survivors and cancer-free individuals, and to investigate the association between education and healthcare use among cancer survivors. RESULTS: Cancer survivors had more GP, hospital, and acute healthcare contacts than cancer-free individuals, while the use of PPS were alike. One-to-four-year survivors with short compared to long education had more GP consultations (breast, rate ratios (RR) = 1.28, 95% CI = 1.25-1.30; prostate, RR = 1.14, 95% CI = 1.10-1.18; lung, RR = 1.18, 95% CI = 1.13-1.23; and colon cancer, RR = 1.17, 95% CI = 1.13-1.22) and acute contacts (breast, RR = 1.35, 95% CI = 1.26-1.45; prostate, RR = 1.26, 95% CI = 1.15-1.38; lung, RR = 1.24, 95% CI = 1.16-1.33; and colon cancer, RR = 1.35, 95% CI = 1.14-1.60), even after adjusting for comorbidity. One-to-four-year survivors with short compared to long education had less consultations with PPS, while no association was observed for hospital contacts. CONCLUSION: Cancer survivors used more healthcare than cancer-free individuals. Cancer survivors with short education had more GP and acute healthcare contacts than survivors with long education. To optimize healthcare use after cancer, we need to better understand survivors' healthcare-seeking behaviors and their specific needs, especially among survivors with short education.

Phase III study of the European Organisation for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire.

PURPOSE: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales. METHODS: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales. RESULTS: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items. CONCLUSIONS: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study. IMPLICATIONS FOR CANCER SURVIVORS: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors.

Association of Smoking, Comorbidity, Clinical Stage, and Treatment Intent With Socioeconomic Differences in Survival After Oropharyngeal Squamous Cell Carcinoma in Denmark.

Importance: The socioeconomic gap in survival after cancer is pronounced among patients with head and neck cancer. Understanding the mechanisms of this gap is crucial to target intervention strategies. Objective: To investigate socioeconomic differences in survival after oropharyngeal squamous cell carcinoma (OPSCC) according to human papillomavirus (HPV) status and the extent to which smoking, comorbidity, clinical stage, and treatment intent explain the survival gap. Design, Setting, and Participants: This nationwide, population-based cohort study was based on prospectively collected information on all patients with a diagnosis of OPSCC from the Danish Head and Neck Cancer Group database and administrative registries. The study included 4600 patients born in 1921 or later, aged 30 years or older, and residing in Denmark 1 year prior to OPSCC diagnosis. Patients with missing information (547 [12%]) were excluded. Patients were diagnosed between January 1, 2008, and December 31, 2019, and followed up until December 31, 2021. Data were analyzed from June 6 to October 4, 2022. Exposure: Socioeconomic position (educational level, disposable income, or cohabiting status). Main Outcomes and Measures: Socioeconomic differences in 5-year overall survival were estimated in Cox proportional hazards regression models by HPV status. The indirect effect and proportion mediated by smoking, comorbidity, clinical stage, and treatment intent were estimated based on a counterfactual approach. Results: The analyzed cohort comprised 4053 patients (1045 women [26%] and 3008 men [74%]). The median age was 61 years (IQR, 55-68 years), and 2563 patients (63%) had HPV-positive OPSCC while 1490 patients (37%) had HPV-negative OPSCC. The 5-year standardized overall survival was 10% to 15% lower among patients with a lower educational level, with low disposable income, or who were living alone (patients with HPV-positive OPSCC, 68%-71%; patients with HPV-negative OPSCC, 31%-34%) than patients with a higher educational level, high disposable income, or a cohabiting partner (patients with HPV-positive OPSCC, 81%-86%; patients with HPV-negative OPSCC, 43%-46%). Among patients with HPV-positive OPSCC, a considerable part of this survival gap was estimated to be associated with differences in smoking (27%-48%), comorbidity (10%-19%), clinical stage (8%-19%), and treatment intent (16%-28%). Among those with HPV-negative OPSCC, comorbidity (12%-22%) and treatment intent (16%-42%) were the primary potential mediators. Conclusions and Relevance: This cohort study suggests that, regardless of HPV status, patients with low socioeconomic position had 10% to 15% lower 5-year overall survival than patients with high socioeconomic position. A substantial part of this survival gap was associated with differences in smoking, comorbidity, clinical stage, or treatment intent at diagnosis.

Socioeconomic inequality in cancer in the Nordic countries. A systematic review.

BACKGROUND: Despite structural and cultural similarities across the Nordic countries, differences in cancer survival remain. With a focus on similarities and differences between the Nordic countries, we investigated the association between socioeconomic position (SEP) and stage at diagnosis, anticancer treatment and cancer survival to describe patterns, explore underlying mechanisms and identify knowledge gaps in the Nordic countries. METHODS: We conducted a systematic review of population based observational studies. A systematic search in PubMed, EMBASE and Medline up till May 2021 was performed, and titles, abstracts and full texts were screened for eligibility by two investigators independently. We extracted estimates of the association between SEP defined as education or income and cancer stage at diagnosis, received anticancer treatment or survival for adult patients with cancer in the Nordic countries. Further, we extracted information on study characteristics, confounding variables, cancer type and results in the available measurements with corresponding confidence intervals (CI) and/or p-values. Results were synthesized in forest plots. RESULTS: From the systematic literature search, we retrieved 3629 studies, which were screened for eligibility, and could include 98 studies for data extraction. Results showed a clear pattern across the Nordic countries of socioeconomic inequality in terms of advanced stage at diagnosis, less favorable treatment and lower cause-specific and overall survival among people with lower SEP, regardless of whether SEP was measured as education or income. CONCLUSION: Despite gaps in the literature, the consistency in results across cancer types, countries and cancer outcomes shows a clear pattern of systematic socioeconomic inequality in cancer stage, treatment and survival in the Nordic countries. Stage and anticancer treatment explain some, but not all of the observed inequality in overall and cause-specific survival. The need for further studies describing this association may therefore be limited, warranting next step research into interventions to reduce inequality in cancer outcomes. STUDY REGISTRATION: Prospero protocol no: CRD42020166296.

Association between Health-Related Quality of Life and Completion of First-Line Treatment among Lung Cancer Patients.

Experts recommend assessing lung cancer patients' health-related quality of life (HRQOL) in the diagnostic evaluation. We investigated the association between HRQOL and completion of first-line treatment among lung cancer patients in a prospective cohort study. Clinical information on lung cancer patients was obtained from medical records, and information on quality of life and lung cancer-related symptoms was obtained through questionnaires at time of diagnosis. We used directed acyclic graphs to identify potential confounders and mediators between HRQOL and completion of first-line treatment. The association between functioning levels and symptoms and completion of first-line oncological treatment was estimated as odds ratios, with 95% confidence intervals, in logistic regression models. In all, 137 patients (52% men, mean age: 69 years) participated, out of 216 invited. Patients who reported reduced functioning had significantly increased ORs for not completing first-line treatment: poor physical function (OR 4.44), role function (OR 6.09), emotional function (OR 5.86), and social function (OR 3.13). Patients with fatigue (OR 7.55), pain (OR 6.07), appetite loss (OR 4.66), and financial difficulties (OR 17.23) had significantly increased ORs for not completing the first-line treatment. Reduced functioning and presence of symptoms were associated with not completing first-line treatment. An assessment of HRQOL could potentially aid the diagnostic evaluation and treatment planning for lung cancer patients.

Health-Related Quality of Life, Dysphagia, Voice Problems, Depression, and Anxiety After Total Laryngectomy.

OBJECTIVES/HYPOTHESIS: The aims were to determine health-related quality of life (HRQoL), including voice problems, dysphagia, depression, and anxiety after total laryngectomy (TL), and investigate the associations between HRQoL and the late effects. STUDY DESIGN: Cross-sectional study. METHODS: 172 participants having received a TL 1.6 to 18.1 years ago for laryngeal/hypopharyngeal cancer filled in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core and Head and Neck module (EORTC QLQ-C30, EORTC QLQ-H&N35), Voice-Related Quality of Life questionnaire (V-RQOL), M.D. Anderson Dysphagia Inventory (MDADI), and Hospital Anxiety and Depression Scale (HADS) questionnaires. RESULTS: Participants scored worse than normative reference populations on all scales/items of the EORTC questionnaires, except one, and almost half of the scales/items showed a clinically relevant difference. Moderate/severe dysphagia was present in 46%, moderate/severe voice problems in 57%, depression in 16%, and anxiety in 20%. Decreasing age, increasing numbers of comorbidities, increasing voice problems, increasing dysphagia, and increasing depression symptoms, were associated with a lowered EORTC QLQ-C30 summary score. CONCLUSION: A substantial proportion of participants experienced clinically significant late effects and increasing levels of these were associated with a lowered HRQoL. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:980-988, 2022.

Risk of Pharmacological or Hospital Treatment for Depression in Patients with Colorectal Cancer-Associations with Pre-Cancer Lifestyle, Comorbidity and Clinical Factors.

We investigated the risk of depression in colorectal cancer (CRC) patients and associated risk factors. The 1324 patients with CRC and 6620 matched cancer-free participants from the Diet, Cancer and Health study were followed for up to 16 years for either a first hospitalization for depression or antidepressant prescription after diagnosis of CRC cancer or study entry date. Information on the outcome and covariates was retrieved from the Danish Colorectal Cancer Group database, the national health registries and questionnaires. Cumulative incidence of depression was estimated, and Cox regression models were used to evaluate the association between risk factors and depression incidence. During follow-up, 191 (14.4%) patients with CRC and 175 (2.6%) cancer-free comparison persons experienced depression. After adjustments, in the first year after cancer diagnosis, patients with CRC had a 12-fold higher hazard compared with the cancer-free population (HR, 12.01; 95% CI, 7.89-18.28). The risk decreased during follow-up but remained significantly elevated with an HR of 2.65 (95% CI, 1.61-4.36) after five years. Identified risk factors were presence of comorbidities, advanced disease stage and use of radiotherapy, while life style factors (pre-cancer or at diagnosis) and chemotherapy did not seem to contribute to the increased risk.

Association between human papillomavirus status and health-related quality of life in oropharyngeal and oral cavity cancer survivors.

OBJECTIVES: The human papillomavirus (HPV) is a risk factor for a subgroup of head and neck cancers (HNC). HPV-positive and HPV-negative HNC patients encompass heterogeneous groups regarding risk factors, sociodemographic and clinical characteristics, which may influence health-related quality of life (HRQL) differently. Since this has been sparsely studied, our study investigated the association between HPV status and HRQL in HNC survivors in Denmark. MATERIALS AND METHODS: This cross-sectional study included 179 recurrence-free oropharyngeal and oral cavity squamous cell carcinoma (OSCC) survivors. HRQL was assessed on the EORTC QLQ-C30 and QLQ-H&N35 questionnaires. Linear and logistic regression models were adjusted for sociodemographic, clinical and lifestyle factors. RESULTS: Most unadjusted results showed better HRQL among HPV-positive (n = 119) compared to HPV-negative (n = 60) OSCC survivors (average 18 months since diagnosis). After adjustments, the HPV-positive survivors reported higher role functioning (mean difference [MD] 9.2, 95% confidence interval [CI] 0.1 to -18.4), and fewer problems with speech (MD -9.0, 95% CI -18.0 to -0.1), sexuality (MD -21.9, 95% CI -38.0 to -5.9) and opening mouth (MD -13.7, 95% CI -26.6 to -0.8) compared to HPV-negative survivors. CONCLUSION: Our findings support that HPV-positive OSCC survivors experience better HRQL than HPV-negative survivors. However, results indicate that sociodemographic, clinical and lifestyle factors explain most of the association between HPV status and HRQL. Findings suggest increased focus on the HPV-negative OSCC survivors with deteriorated HRQL in rehabilitation programs and future research to investigate the long-term effects of treatment among HPV-positive OSCC survivors who may develop symptoms later in survivorship.

Forming and ending marital or cohabiting relationships in a Danish population-based cohort of individuals with neurofibromatosis 1.

Individuals with neurofibromatosis 1 (NF1) may have problems in managing the transition between childhood and adulthood, such as forming a relationship or finding a partner. We aimed to determine the association between NF1 and forming and ending marital or cohabiting relationships by comparing a large Danish population of adults with NF1 with population comparisons. In this population-based cohort study, we compared a population of Danish adults who were hospitalized for or with complications to prior diagnosed NF1 (n = 787) with population comparisons matched on gender and birth year (n = 7787) through nationwide registries with annually updated information on marriage and cohabitation. Discrete-time survival models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the formation and termination of relationships, with adjustment for birth year, gender, and somatic and psychiatric comorbidities at entry. Individuals with NF1 were significantly less likely to form a relationship (HR = 0.65; 95% CI: 0.58-0.73), with the lowest association for individuals ≥33 years (HR 0.40; 95% CI: 0.25-0.63) and the highest for those aged 18-20 years (HR 0.82; 95% CI: 0.70-0.96). No significant difference was found for ending relationships (HR 1.00; 95% CI: 0.86-1.16). In conclusion, individuals who were hospitalized for NF1 are less likely to engage in marital or cohabiting relationships than population comparisons and are older when they form their first relationship. Once a relationship has been established, however, couples with a NF1-individual are not at greater risk of ending the relationship.

Long-term Somatic Disease Risk in Adult Danish Cancer Survivors.

IMPORTANCE: Long-term health effects of cancer in adult survivors are a major concern; however, it is difficult to differentiate between the consequences of cancer and cancer treatment and those of normal aging or comorbidity. OBJECTIVES: To provide an overview and investigate the temporal pattern of hospitalizations for medically verified incident somatic disease in adult survivors compared with cancer-free comparison people, taking into consideration pretreatment comorbidity and the socioeconomic position of the participants. DESIGN, SETTING, AND PARTICIPANTS: In this nationwide, population-based cohort-cohort study, 458 646 survivors of the 12 most frequent first primary cancers listed in the Danish Cancer Registry between January 1, 1997, and December 31, 2014, and 2 121 567 matched cancer-free comparison people were identified from the Danish Central Population Registry. Hospitalizations for somatic diseases after cancer diagnosis or study entry were identified from the National Patient Register and stratified according to the 11 main diagnostic groups in the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. A cohort of cancer survivors was formed for each combination of cancer type and diagnostic group, with a corresponding group of cancer-free people, resulting in 132 unique cohorts. Data analysis was performed from September 1, 2017, to January 15, 2018. MAIN OUTCOMES AND MEASURES: Risk of hospitalization and the temporal pattern of incidence were analyzed in Cox proportional hazards regression models. Cumulative incidence proportions were calculated by the pseudo-observation method. RESULTS: A total of 2 580 213 people were investigated, of whom 458 646 were cancer survivors (mean [SD] age, 69 [11.6] years; 230 793 [50.3%] male and 227 853 [49.7%] female) and 2 121 567 were comparison people (mean [SD] age, 69 [11.5] years; 1 054 465 [49.7%] male and 1 067 102 [50.3%] female). More cancer survivors vs comparison people had comorbid conditions at the time of cancer diagnosis or study entry (Charlson Comorbidity Index ≥1: 19% vs 13%). Overall, the risk of hospitalizations for somatic diseases was significantly higher for cancer survivors in almost all diagnostic groups (eg, diseases in the nervous system among breast cancer survivors: hazard ratio, 1.20; 95% CI, 1.17-1.22; diseases in the respiratory system in lung cancer survivors: hazard ratio, 5.85; 95% CI, 5.63-6.07; and diseases in blood and blood-forming organs in prostate cancer survivors: hazard ratio, 2.60; 95% CI, 2.50-2.71). CONCLUSIONS AND RELEVANCE: The findings suggest that adult survivors of the 12 most common cancers are at significantly higher risk for a broad range of somatic diseases that require hospitalization compared with matched cancer-free comparison people. The results of this study suggest the importance of close, targeted monitoring for new somatic disease during follow-up care of cancer survivors.

Effect of progressive resistance training on health-related quality of life in the first year after breast cancer surgery - results from a randomized controlled trial.

Aims: To examine the effect of progressive resistance training (PRT) on health related quality of life and a predefined symptom cluster of pain-sleep-fatigue. Methods: This study was a planned secondary analysis of a randomized controlled trial examining the effect of PRT on prevention of arm lymphedema in a population of women between 18 and 75 years undergoing breast cancer surgery with axillary lymph node dissection. Participants were allocated by computer randomization to usual care control or a PRT intervention in a 1:1 ratio. The intervention, initiated in the third post-operative week, consisted of three times PRT per week, supervised in groups in the first 20 weeks, and self-administered in the following 30 weeks. Questionnaire assessments were made at baseline, 20 weeks and 12 months, with the European Organization for Research and Treatment in Cancer Core questionnaire (EORTC QLQ C30) and the Functional Assessment of Chronic Illness Therapy-(FACIT) fatigue questionnaire. The symptom cluster of pain-sleep-fatigue was measured with a constructed score adding EORTC C30 subscales of insomnia, pain, and fatigue. Data were treated as repeated measurements and analyzed with mixed models. Results: Among 158 recruited participants, we found a clinically relevant increased emotional functioning with nine points at both follow-ups (p = .02), and 16 and 11 points at 20 weeks and 12 months respectively (p = .04) in social functioning. Furthermore, in the subgroup of women with the symptom cluster pain-sleep-fatigue present at baseline, a significant effect was found for global health status (p = .01) and social functioning (p = .02). Conclusion: To our knowledge, this is the first study to report clinically relevant effects of PRT on social and emotional functioning in the first postoperative year after breast cancer surgery. Furthermore, a subgroup of women with the pain-sleep-fatigue symptom cluster had particular benefit from PRT on global health status and social functioning.

Understanding the quality of life (QOL) issues in survivors of cancer: towards the development of an EORTC QOL cancer survivorship questionnaire.

BACKROUND: The number of cancer survivors is growing steadily and increasingly, clinical trials are being designed to include long-term follow-up to assess not only survival, but also late effects and health-related quality of life (HRQOL). Therefore it is is essential to develop patient-reported outcome measures (PROMs) that capture the full range of issues relevant to disease-free cancer survivors. The objectives of this project are: 1) to develop a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire that captures the full range of physical, mental and social HRQOL issues relevant to disease-free cancer survivors; and 2) to determine at which minimal time since completion of treatment the questionnaire should be used. METHODS: We reviewed 134 publications on cancer survivorship and interviewed 117 disease-free cancer survivors with 11 different types of cancer across 14 countries in Europe to generate an exhaustive, provisional list of HRQOL issues relevant to cancer survivors. The resulting issue list, the EORTC core questionnaire (QLQ-C30), and site-specific questionnaire modules were completed by a second group of 458 survivors. RESULTS: We identified 116 generic survivorship issues. These issues covered body image, cognitive functioning, health behaviors, negative and positive outlook, health distress, mental health, fatigue, sleep problems, physical functioning, pain, several physical symptoms, social functioning, and sexual problems. Patients rated most of the acute symptoms of cancer and its treatment (e.g. nausea) as no longer relevant approximately one year after completion of treatment. CONCLUSIONS: Compared to existing cancer survivorship questionnaires, our findings underscore the relevance of assessing issues related to chronic physical side effects of treatment such as neuropathy and joint pain. We will further develop a core survivorship questionnaire and three site-specific modules for disease-free adult cancer survivors who are at least one year post-treatment.