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).

Effects of home-based specialized palliative care and dyadic psychological intervention on caregiver burden: results from a randomized controlled trial.

Background The Domus study, a randomized controlled trial (RCT), evaluated the effect of home-based specialized palliative care (SPC) reinforced with a psychological intervention for the patient-caregiver dyad on increasing advanced cancer patients' time spent at home, as opposed to hospitalized, and the number of home deaths. As palliative care extends to include support for patients' families and may thus assist caregivers and decrease demands on them, in this study we evaluated a secondary outcome, caregiver burden.Material and Methods Patients with incurable cancer and their caregivers were randomized (1:1) to care as usual or home-based SPC. Caregiver burden was assessed using the Zarit Burden Interview (ZBI) at baseline and 2, 4, 8 weeks and 6 months after randomization. Intervention effects were assessed in mixed effects models.Results A total of 258 caregivers were enrolled. Eleven per cent of informal caregivers experienced severe caregiver burden at baseline. Caregiver burden increased significantly over time in both groups (p = 0.0003), but no significant effect of the intervention was seen on overall caregiver burden (p = 0.5046) or burden subscales measuring role and personal strain.Conclusion In line with the majority of previous RCTs, the Domus intervention was not able to significantly reduce caregiver burden. Future interventions should consider targeting only caregivers reporting the greatest caregiver burden.

Postoperative epilepsy and survival in glioma patients: a nationwide population-based cohort study from 2009 to 2018.

PURPOSE: Postoperative epilepsy is common in glioma patients and has been suggested to indicate disease progression, yet knowledge of its role as a prognostic factor is limited. This study investigates the association between postoperative epilepsy and survival amongst patients with gliomas. METHODS: We included 3763 patients with histopathologically diagnosed grade II, III, and IV gliomas from 2009 to 2018 according to the Danish Neuro-Oncology Registry. Information on epilepsy diagnosis was redeemed from the Danish National Patient Registry, the National Prescription Registry and the Danish Neuro-Oncology Registry. We used Cox proportional hazards models with 95% confidence intervals (CIs) to examine hazard ratios (HRs) for the association between postoperative epilepsy and risk of death. We examined the role of the timing of epilepsy in three different samples: Firstly, in all glioma patients with postoperative epilepsy; secondly, in patients with postoperative de novo epilepsy; thirdly, exclusively in a homogeneous sub-group of grade IV patients with postoperative de novo epilepsy. RESULTS: Glioma patients with postoperative epilepsy had an increased risk of death, regardless of prior epilepsy status (HR = 4.03; CI 2.69-6.03). A similar increase in the risk of death was also seen in patients with postoperative de novo epilepsy (HR = 2.08; CI 1.26-3.44) and in the sub-group of grade IV patients with postoperative de novo epilepsy (HR = 1.83; CI 1.05-3.21). CONCLUSIONS: Postoperative epilepsy may negatively impact survival after glioma diagnosis, regardless of preoperative epilepsy status. Postoperative epilepsy may be an expression of a more invasive growth pattern of the gliomas following primary tumor treatment.

Risk of somatic hospitalization in parents after cancer in a child, a nationwide cohort study.

OBJECTIVE: The diagnosis of cancer in a child is a profoundly stressful experience. The impact on parents' somatic health, including lifestyle-related diseases, however, is unresolved. This paper assesses parents' risk of hospitalization with somatic disease after a child's cancer diagnosis. METHODS: We conducted a nationwide population- and register-based study with parents of all children under age 20 diagnosed with cancer in Denmark between 1998 and 2013 and parents of cancer-free children, matched (1:10) on child's age and family type. We estimated HR with 95% CI in Cox proportional hazard models for 13 major International Classification of Diseases-10 disease groups, selected stress- and lifestyle-related disease-groups, and investigated moderation by time since diagnosis, parental sex, and cancer type. RESULTS: Among n = 7797 parents of children with cancer compared with n = 74,388 parents of cancer-free children (51% mothers, mean age 42), we found no overall pattern of increased risk for 13 broad disease groups. We found increases in digestive system diseases (HR 1.06, 95% CI 1.01-1.12), genitourinary system diseases (HR 1.08, 95% CI 1.02-1.14), and neoplasms (HR 1.20, 95% CI 1.13-1.27), the latter attributable mostly to increased rates of tobacco-related cancers and mothers' diet-related cancers. CONCLUSIONS: This is the first attempt to document the impact of childhood cancer on parents' somatic health. With the exception of increased risk for neoplasms, likely due to shared genetic or lifestyle factors, our findings offer the reassuring message, that the burden of caring for a child with cancer does not in general increase parents' risk for somatic diseases.

Dyadic coping in specialized palliative care intervention for patients with advanced cancer and their caregivers: Effects and mediation in a randomized controlled trial.

OBJECTIVE: Specialized palliative care (SPC) interventions increasingly include patient-caregiver dyads, but their effects on dyadic coping are unknown. We investigated whether an SPC and dyadic psychological intervention increased aspects of dyadic coping in patients with advanced cancer and their caregivers, whether dyad characteristics moderated effects and whether aspects of dyadic coping mediated significant intervention effects on caregivers' anxiety and depression. METHODS: We randomized 258 patients with incurable cancer and their caregivers to care as usual or accelerated transition from oncological treatment to home-based SPC and dyadic psychological support. In secondary outcome analyses, using mixed-effects models, we estimated intervention effects and 95% confidence intervals (CIs) for communication of stress and common coping, and moderation by dyad type and demographics. In path analyses, we investigated whether stress communication and common coping mediated intervention effects on caregivers' symptoms of anxiety and depression. (Clinicaltrials.gov NCT01885637). RESULTS: The intervention significantly increased common coping in patients and caregivers in couples (estimated difference, 0.68; 95% CI, 0.11 to 1.24) and stress communication by partner caregivers (0.97; 0.24 to 1.24). We found some support for different intervention effects for spouses and other dyads, but no evidence of mediation. CONCLUSIONS: Specialized palliative care and dyadic psychological intervention may affect aspects of dyadic coping. Common coping and stress communication did not mediate the previously found significant intervention effects on caregiver anxiety and depression, indicating that other mechanisms may have been central in the intervention.

Adherence to a long-term progressive resistance training program, combining supervised and home-based exercise for breast cancer patients during adjuvant treatment.

Background: The purpose of the study was to examine adherence and identify patient- and treatment-related factors associated with adherence to a 20-week combined supervised and home-based progressive resistance training program in women treated for breast cancer. Methodology: The study population consisted of the intervention group in a randomized clinical trial examining the effect of resistance exercise on lymphoedema prevention (n = 82). The full program lasted 50 weeks, with an initial 20 weeks combined supervised and home-based exercise followed by 30 weeks self-administered exercise. Information about attendance rates (supervised exercise) and exercise dairies (home-based exercise) in the first 20 weeks was available for 74 and 62 participants, respectively. Adherence was measured as numbers of exercise sessions performed divided by expected number of exercise sessions with >2/3 categorized as high adherence. Age-adjusted odds ratios (OR) were used to assess the associations between patient- and treatment-related factors with adherence. Results: The number of participants with high adherence to supervised exercise decreased in the late period (from week 11 onward) compared to the early period (65% vs. 48%) whereas the proportion of participants with high adherence to home-based exercise remained close to 55%. The most prominent factor associated with high adherence to supervised exercise was neoadjuvant chemotherapy [OR 7.09; 95% confidence interval (CI), 1.12-44.62]. For home-based exercise, lower adherence was seen in obese participants (OR 0.16; 95% CI, 0.04-0.65) and in participants with average or below average lower body muscle strength at baseline (OR 0.12; 95% CI, 0.03-0.46). Conclusion: The results of this study offer valuable information on factors associated with adherence to a program of supervised and home-based exercise. Interventions may be adapted to ensure higher adherence rates through supportive efforts targeted to women who are obese, have low muscle strength and who receive no or adjuvant chemotherapy (as opposed to neoadjuvant chemotherapy) during exercise.

Effects of live music during chemotherapy in lymphoma patients: a randomized, controlled, multi-center trial.

PURPOSE: Chemotherapy is associated with both somatic and psychological side effects. Music might ease these problems. Several randomized controlled trials have investigated the effect of music, but the results are inconclusive. We aimed to examine whether live or pre-recorded music listening decreases anxiety during chemotherapy in newly diagnosed lymphoma patients. METHODS: A total of 143 patients with non-Hodgkin and Hodgkin lymphomas were randomly assigned into three groups receiving either 30 min of patient-preferred live music (n = 47), 30 min of patient-preferred pre-recorded music (n = 47), or standard care (n = 49) during up to five outpatient chemotherapy sessions. The primary endpoint was anxiety measured by the Spielberger's State Anxiety Inventory. Secondary endpoints included blood pressure, pulse rate, nausea and vomiting, serum catecholamine levels pre- and post-intervention to measure arousal levels, and health-related quality of life. The Musical Ability Test was used to link musical ability to the primary endpoint. RESULTS: When adjusting for age, sex, diagnosis, number of sessions, and baseline anxiety, the linear mixed model showed a borderline statistically significant reduction in the primary outcome anxiety in the live music group compared to standard care (7% (95% CI, - 14% to 0%, p = 0.05), while the effect of pre-recorded music was non-significant (5% (95% CI, - 12% to + 3%, p = 0.18). No intervention effects were seen in secondary outcomes. CONCLUSION: Our findings suggest that patient-preferred live music reduces anxiety among patients with malignant lymphomas undergoing chemotherapy. Musical ability among this group of cancer patients seems not to be a determining factor for effect of music intervention.

Effect of home-based specialised palliative care and dyadic psychological intervention on caregiver anxiety and depression: a randomised controlled trial.

BACKGROUND: Specialised palliative care trials often fail to address intervention effects on caregiver anxiety and depression, particularly in bereavement. We evaluate effects of specialised palliative care and dyadic psychological intervention on caregiver anxiety and depression in a randomised controlled trial (RCT). METHODS: Patients with incurable cancer and limited antineoplastic treatment options and their caregivers, recruited from a university hospital oncology department, were randomised (1:1) to care as usual or accelerated transition from oncological treatment to home-based specialised palliative care. We assessed caregivers' symptoms of anxiety and depression with the Symptom Checklist-92 up to six months after randomisation and 19 months into bereavement, and estimated intervention effects in mixed effects models. RESULTS: The 'Domus' trial enrolled 258 caregivers. The intervention significantly attenuated increases in caregivers' symptoms of anxiety overall (estimated difference, -0.12; 95% confidence interval, -0.22 to -0.01, p = 0.0266), and symptoms of depression at eight weeks (-0.17; -0.33 to -0.02; p = 0.0314), six months (-0.27; -0.49 to -0.05; p = 0.0165), and in bereavement at two weeks (-0.28; -0.52 to -0.03; p = 0.0295) and two months (-0.24; -0.48 to -0.01; p = 0.0448). CONCLUSIONS: This first RCT evaluating specialised palliative care with dyadic psychological support significantly attenuated caregiver anxiety and depression before and during bereavement. (Clinicaltrials.gov: NCT01885637).

Prediagnosis epilepsy and survival in patients with glioma: a nationwide population-based cohort study from 2009 to 2018.

OBJECTIVE: Considering that epilepsy is common, and knowledge is lacking on its role especially for the prognosis of high-grade gliomas, the objective of this study was to investigate the association between epilepsy prior to glioma diagnosis and survival among glioma patients. METHODS: In a nationwide population-based cohort study, we included 3763 adult glioma patients diagnosed between 2009 and 2018 according to the Danish Neuro-Oncology Registry. Information on epilepsy was redeemed through Danish Neuro-Oncology Registry, National Patient Registry, and National Prescription Registry. Cox proportional hazard models with 95% confidence intervals (CIs) were applied to examine hazard ratios (HRs) for the association between epilepsy (< 1 year prior to glioma including epilepsy at onset; 1-10 years prior to glioma; no prior epilepsy) and risk of death, and whether it differed according to tumor grade and size, performance status, and treatment modalities. RESULTS: A 32% decreased risk of death in patients with epilepsy within 1 year prior to glioma compared to no prior epilepsy was found (HR = 0.68; CI 0.63-0.75). A favorable prognosis was seen for epilepsy in all glioma grades: II (HR = 0.55; CI 0.39-0.77), III (HR = 0.59; CI 0.48-0.73), and IV (HR = 0.85; CI 0.77-0.94). CONCLUSIONS: Patients with epilepsy within 1 year prior to glioma diagnosis had significant survival benefits compared to patients with no prior epilepsy. This association was significant for both low-grade gliomas (grade II) and high-grade gliomas (grade III and IV). Survival benefits in glioma patients with epilepsy at onset are possibly primarily attributable to tumor-specific histopathology, molecular biomarkers, and early diagnosis.

NAVIGATE: improving survival in vulnerable patients with lung cancer through nurse navigation, symptom monitoring and exercise - study protocol for a multicentre randomised controlled trial.

INTRODUCTION AND AIM: Low socioeconomic position (SEP) has been shown to be strongly associated with impaired lung cancer survival. Barriers related to receiving recommended treatment among patients with lung cancer with low SEP may include adverse health behaviour and limited physical and psychosocial resources influencing the ability to react on high-risk symptoms and to navigate the healthcare system. To address the underlying factors that drive both decisions of treatment, adherence to treatment and follow-up in vulnerable patients with lung cancer, we developed the Navigate intervention. The aim of this randomised controlled trial is to investigate the effect of the intervention on survival (primary outcome), lung cancer treatment adherence, health-related quality of life and other psychosocial outcomes as well as health costs and process evaluation (secondary outcomes) in a study population of vulnerable patients with lung cancer. METHODS AND ANALYSIS: This two-armed multicentre randomised trial will recruit patients from five lung cancer clinics in Denmark identified as vulnerable according to a screening instrument with nine clinical and patient-reported vulnerability criteria developed for the study. We will enrol 518 vulnerable patients >18 years old diagnosed with non-small cell lung cancer at all stages with a performance status <2. Participants will be randomly allocated to either standard treatment and intervention or standard treatment alone. The Navigate intervention is based on principles from motivational interviewing and includes three components of nurse navigation, systematic monitoring of patient-reported outcomes (PROs) and physical exercise in a person-centred delivery model. Data will be collected at baseline and 3, 6, 12 months after randomisation using questionnaires, clinical data and physical function tests. ETHICS AND DISSEMINATION: Ethics Committee, Region Zealand (SJ-884/EMN-2020-37380) and the Data Protection Agency in Region Zealand (REG-080-2021) approved the trial. Participants will provide written informed consent. Results will be reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05053997.

Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden: a register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. METHODS: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer. FINDINGS: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3-16·5) for childhood cancer survivors, 14·0% (13·5-14·5) for siblings, and 12·7% (12·4-12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31-1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28-1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals. INTERPRETATION: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors. FUNDING: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation.

Protocol for 'Resilient Caregivers': a randomised trial of a resilience-based intervention for psychologically distressed partner caregivers of patients with cancer.

INTRODUCTION: Intimate partners of patients with cancer often experience significant distress, but there is a lack of psychological interventions that specifically target this population. 'Resilient Caregivers' is a novel resilience-based intervention for distressed partner cancer caregivers. The intervention was developed according to a resilience framework focusing on meta-reflective skills, coping strategies and value clarification. The aim of this study is to evaluate the effectiveness of this intervention in a randomised trial. METHODS AND ANALYSIS: Eighty participants will be invited through the Oncology Department at Herlev Hospital, Denmark and randomised to either the intervention or usual care. Participants are eligible if they are partners (married or unmarried) of patients diagnosed with cancer and experience distress (>4 on the distress thermometer). 'Resilient Caregivers' consists of seven manualised group sessions (2.5 hours each), focusing on resilience in relation to being a partner caregiver of a patient with cancer. The primary outcome is symptoms of anxiety, while secondary outcomes include distress, depression, quality of life, sleep quality and resilience. Data will be collected at baseline, 3, 6 and 12 months follow-up using validated scales, and analysed using mixed models for repeated measures. ETHICS AND DISSEMINATION: This study will follow the ethical principles in the Declaration of Helsinki and has been reviewed by the Ethics Committee of the Capital Region of Denmark (Journal no. 18055373). Written informed consent will be obtained from all participants. Results will be reported through scientific peer-reviewed journals and relevant conferences. TRIAL REGISTRATION NUMBER: NCT04610034.

Somatic Disease in Survivors of Childhood Malignant Bone Tumors in the Nordic Countries.

Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of osteosarcoma (n = 440) or Ewing sarcoma (n = 180), diagnosed before the age of 20 years in Denmark, Finland, Iceland, and Sweden during 1943-2008, were followed in the national hospital registers. Overall rates of hospital contacts for any somatic disease and for 12 main diagnostic groups and 120 specific disease categories were compared with those in a matched comparison cohort (n = 3049) randomly selected from the national population registers. The rate of hospital contact for any somatic disease was 80% higher in survivors of malignant bone tumors than in comparisons and remained elevated up to 30 years after diagnosis. The rate of hospital contacts was higher after Ewing sarcoma (rate ratio (RR) 2.24; 95% confidence interval (CI) 1.76-2.85) than after osteosarcoma (RR 1.67; 95% CI 1.41-1.98). Elevated rates were observed for 11 main diagnostic groups, including infections, second malignant neoplasms, and diseases of the skin, bones, and circulatory, digestive, endocrine, and urinary systems. Survivors of malignant bone tumors in childhood are at increased risk of somatic diseases many years after diagnosis. This comprehensive study contributes new insight into the risk of late effects in survivors of osteosarcoma and Ewing sarcoma, which is an essential basis for optimal patient counseling and follow-up care.

Is the health literacy of informal caregivers associated with the psychological outcomes of breast cancer survivors?

PURPOSE: To investigate whether health literacy (HL) among informal caregivers of breast cancer (BC) survivors is associated with patient psychological outcomes. METHODS: We used data (n = 340 pairs) from baseline questionnaires administered in the MyHealth trial investigating nurse-led BC follow-up. All BC survivors and their invited caregivers were included immediately after completion of primary treatment. We performed multivariate regression analyses to examine the association between caregiver HL (nine dimensions as measured by the Health Literacy Questionnaire) as exposure and patient depression, anxiety, and health-related quality of life (HQoL) as outcomes. We further examined whether any association differed according to type of caregiver, patient HL, and patient activation (skill in managing one's health). RESULTS: Three dimensions, "ability to engage with providers" (ß = - 0.2), "navigating the system" (ß = - 0.2), and "understand health information" (ß = - 0.2), were significantly associated with lower patient depression (p < 0.05), while four dimensions, "having sufficient information" (ß = 0.3), "navigating the system" (ß = 0.2), "find health information" (ß = 0.2), and "understand health information" (ß = 0.2), were significantly associated with better patient HQoL (p < 0.05). No significant associations were found for anxiety. Patient HL and activation did not significantly modify the associations, while certain associations for depression were stronger in patients with non-partner caregivers. CONCLUSIONS: The HL of informal caregivers may play an important role in optimizing psychological outcomes in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Involving informal caregivers, who can provide support related to health information and services, may be beneficial for the psychological well-being of cancer survivors.

Gynaecological cancer leads to long-term sick leave and permanently reduced working ability years after diagnosis.

PURPOSE: The aim of the study was to investigate overall patterns in labour market affiliation, risk for permanently reduced work ability and prevalence of long-term sickness absence among women diagnosed with gynaecological cancer. METHODS: We followed 8451 women diagnosed with ovarian, endometrial or cervical cancer, and 72,311 women with no history of cancer in nationwide registers for up to 19 years (mean 7.5 years). We computed hazards ratios for permanently reduced working ability and annual proportions of long-term sick leave. RESULTS: Patterns of labour market affiliation varied by cancer diagnosis and stage. The hazard of permanently reduced working ability was increased for survivors of all three cancers but most pronounced for women diagnosed with advanced ovarian cancer. The highest hazard ratios were found 2-5 years after diagnosis, and they persisted for years in all groups and throughout the follow-up period of 19 years in women diagnosed with advanced cervical cancer. In the subgroups of women who continued to be potentially active on the labour market, long-term sick leave was more prevalent among cancer survivors than women with no history of cancer up to 10 years after diagnosis. CONCLUSIONS: Women diagnosed with localised as well as advanced gynaecological cancer are at prolonged risk for permanently reduced working ability and long-term sick leave. IMPLICATIONS FOR CANCER SURVIVORS: Gynaecological cancer can have long-term as well as permanent consequences for working ability, and survivors who remain active on the labour market might have to take more sick leave even years after cancer diagnosis than other women at their age.

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.

Vitamin D Vitamers Affect Vitamin D Status Differently in Young Healthy Males.

Dietary intake of vitamin D includes vitamin D3 (vitD3), 25-hydroxyvitamin D3 (25OH-D3), and vitamin D2 (vitD2). However, the bioactivity of the different species has not been scientifically established. The hypothesis in this study was that vitD3, 25OH-D3, and vitD2 have an equal effect on 25-hydroxyvitamin D in serum (vitamin D status). To test our hypothesis, we performed a randomized, crossover study. Twelve young males consumed 10 µg/day vitD3 during a four-week run-in period, followed by 3 × 6 weeks of 10 µg/day vitD3, 10 µg/day 25OH-D3, and 10 µg/day vitD2. The content of vitD3, vitD2, 25OH-D3, and 25-hydroxyvitamin D2 (25OH-D2) in serum was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hypothesis that the three sources of vitamin D affect vitamin D status equally was rejected. Based on the assumption that 1 µg vitD3/day will show an increase in vitamin D status of 1.96 nmol/L, the results showed that 23 µg vitD2 and 6.8 µg 25OH-D3 was similar to 10 µg vitD3. These results demonstrate that further investigations are necessary to determine how to quantify the total vitamin D activity based on chemical quantification of the individual vitamin D metabolites to replace the total vitamin D activity assessed in biological rat models.