Capecitabine monotherapy as first-line treatment in advanced HER2-normal breast cancer - a nationwide, retrospective study.

Background and purpose: Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this setting is sparse. The purpose of the study is to evaluate outcomes of patients with Human Epidermal Growth Factor Receptor (HER2)-normal advanced breast cancer treated with capecitabine monotherapy as first-line treatment. MATERIAL AND METHODS: The study utilized the Danish Breast Cancer Group (DBCG) database and was conducted retrospectively across all Danish oncology departments. Inclusion criteria were female patients, with HER2-normal advanced breast cancer treated with capecitabine monotherapy as the first-line treatment from 2010 to 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 494 patients were included. Median OS was 16.4 months (95% confidence interval [CI]: 14.5-18.0), and median PFS was 6.0 months (95% CI: 5.3-6.7). Patients with estrogen receptor (ER)-positive disease had significantly longer OS (median: 22.8 vs. 10.5 months, p < 0.001) and PFS (median: 7.4 vs. 4.9 months, p = 0.003), when compared to ER-negative patients. Stratifying by age, patients under 45 years displayed a median PFS of 4.1 months, while those aged 45-70 years and over 70 years had median PFS of 5.7 and 7.2 months, respectively (p = 0.01). INTERPRETATION:  In this nationwide study, the efficacy of capecitabine as a first-line treatment for HER2-normal advanced breast cancer is consistent with other, mainly retrospective, studies. However, when assessed against contemporary and newer treatments, its effectiveness appears inferior to alternative chemotherapies or targeted therapies.

Nivolumab With or Without Ipilimumab Combined with Stereotactic Body Radiotherapy in patients with Metastatic Biliary Tract Cancer: A Randomized Phase 2 Study.

PURPOSE: Evaluate the clinical benefits of nivolumab with/without ipilimumab combined with stereotactic body radiotherapy (SBRT) in patients with pretreated metastatic biliary tract cancer (mBTC). EXPERIMENTAL DESIGN: The study was a phase 2 randomized trial with Simon's optimal 2-stage design requiring 36 evaluable patients per group after second stage. Sixty-one patients were included from September 2018 to January 2022 and randomized (1:1) to receive SBRT (15 Gy × 1 on day one to a primary or metastatic lesion) and nivolumab (3 mg/kg intravenously on day one and every 2 weeks) with/without ipilimumab (1 mg/kg intravenously on day one and every 6 weeks). Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients with complete response, partial response or stable disease. Decision to continue accrual into the second stage depended on CBR from first stage. RESULTS: Forty-two patients received SBRT/nivolumab/ipilimumab with a CBR of 31.0% (95% CI, 17.6-47.1). Five patients (11.9%) achieved partial response with median duration of 4.4 months (range, 1.1-21.5). Nineteen patients received SBRT/nivolumab. This group was closed after the initial stage based on a CBR of 10.5% (95% CI, 1.3-33.1). Adverse events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Grade ≥3 treatment-related adverse events occurred in 13 (31%) and 3 (16%) patients in the SBRT/nivolumab/ipilimumab and SBRT/nivolumab groups, respectively. One patient died from immune-related hepatitis in the SBRT/nivolumab/ipilimumab group. CONCLUSION: Combining SBRT, nivolumab and ipilimumab is well tolerated, feasible, and shows response in a subgroup of patients with mBTC.

Impact of breast-, gastrointestinal-, and lung cancer on prognosis in patients with first-time pulmonary embolism: A Danish nationwide cohort study.

BACKGROUND: Pulmonary embolism (PE) is described as a prognostic factor in patients with cancer however, the prognostic impact of PE remains unknown. This study investigated, the 1-year prognosis following PE in patients with breast-, gastrointestinal-, or lung cancer stratified by cancer status. METHODS: All Danish patients with first-time PE from 2008 to 2018 were included. Cancer status was categorized as no cancer, history of cancer, non-active cancer and active cancer. Unadjusted and age-stratified 1-year risk of death was estimated using the Kaplan-Meier estimator. Cause of death was reported using the Aalen-Johansen method. RESULTS: Of 35,679 patients with PE, 18% had a breast-, gastrointestinal-, or lung cancer. Patients with cancer were older compared with no cancer (69.8 years [IQR: 56.2-79.8]). One-year risk of death (95% confidence interval) for active breast-, gastrointestinal-, and lung cancer was 49.5% (44.0%-54.9%), 75.0% (72.5%-77.4%) and 80.1% (78.0%-82.3%) respectively, compared with 18.9% (18.4%-19.3%) for no cancer. Age-stratified analysis revealed no association with increasing age in non-active lung cancer and all active cancers. Further, non-cardiovascular death accounted for an increasing proportion by cancer status (no cancer < history of cancer < non-active cancer < active cancer). CONCLUSIONS: One-year risk of death was dependent on both cancer type and status; no association with age was found for patients with active cancers. Non-cardiovascular death was leading in non-active and active cancers. Thus, the occurrence of first-time PE could be regarded as a marker of cancer severity for patients with breast-, gastrointestinal-, and lung cancer.

Endocrine, cardiac and neuropsychological aspects of adult congenital adrenal hyperplasia.

OBJECTIVE: To investigate the metabolic, cardiovascular, and neuropsychological phenotype, quality of life (QoL), and hormonal regulation in individuals with congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired synthesis of cortisol in the adrenal cortex and, if untreated compensatory hyperandrogenism. CAH is associated with an increased cardiovascular and metabolic morbidity, possibly due to overtreatment with glucocorticoids, leading to weight gain, insulin resistance, and metabolic syndrome. DESIGN, PARTICIPANTS, MEASUREMENTS: Thirty-seven individuals with CAH and 33 age- and sex-matched controls were evaluated at a single centre at Aarhus University Hospital with echocardiography, electrocardiogram, 24-h blood pressure, biochemistry, anthropometrics, and autism spectrum, anxiety, depression, personality, cognitive failures, and QoL were assessed using questionnaires. RESULTS: CAH individuals had lower height than controls (170.5 vs. 182.9 cm in males and 160.2 vs. 170.1 cm in females, p < 0.01). Compared with female controls, females with CAH had higher haemoglobin (8.8 vs. 8.2 mmol/L, p = 0.003) and BMI (29.7 vs. 25.5 kg/m2, p = 0.006), reduced insulin sensitivity (HOMA-IR): 2.7 vs. 1.9, p = 0.018), prolonged E-wave deceleration time (193 vs. 174 cm, p = 0.015), and E/é ratios (5.4 vs. 4.5, p = 0.017), and lower self-reported QoL. Males with CAH had more cognitive complaints (p = 0.034) and higher autistic scores (19.9 vs. 14.9; p = 0.068) compared with male controls. More individuals with CAH than controls reported writing problems. CONCLUSION: A sex-specific comorbidity profile is evident in CAH, with females presenting with decreased metabolic and overall self-reported health, whereas males with CAH presented with increased cognitive complaints and autistic traits.

Nurse-Led Individualized Follow-Up Versus Regular Physician-Led Visits After Early Breast Cancer (MyHealth): A Phase III Randomized, Controlled Trial.

PURPOSE: Follow-up after breast cancer with regular visits has failed to detect recurrences, be cost-effective, and address patient needs. METHODS: MyHealth is a phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT02949167). Patients, who recently completed primary treatment for stage I-II breast cancer, were randomly assigned in variable block sizes and stratified by age and human epidermal growth factor receptor 2 status to intervention or control follow-up. The nurse-led intervention comprised three to five individual self-management sessions, regular reporting of symptoms, and navigation to health care services. The control follow-up comprised regular outpatient visits with the physician. The primary outcome was breast cancer-specific quality of life (QoL) measured by the Trial Outcome Index-Physical/Functional/Breast summary score of the Functional Assessment of Cancer Therapy-Breast 2 years after random assignment. Secondary outcomes were fear of recurrence, anxiety, depression, and health care utilization. Analyses were intention-to-treat and P values were two-sided with 95% confidence level set at 0.005 because of multiple comparisons. RESULTS: Among 1,101 eligible patients, 875 were invited and 503 were randomly assigned to control (n = 252) or intervention (n = 251) follow-up. At 2 years, patients in the intervention group reported a significantly and clinically relevant higher QoL (mean, 75.69 [standard deviation [SD], 12.27]) than patients in the control group (71.26 [SD, 14.08]), with a mean difference of 5.05 (95% CI, 3.30 to 6.79; P < .001). The intervention group reported significantly less fear of recurrence, anxiety, and depression; they had fewer physician consultations but more nurse contacts and an unchanged diagnostic imaging pattern. The effect on all outcomes was stable through a 3-year follow-up. CONCLUSION: The MyHealth study suggested a new strategy for follow-up after early breast cancer as it provided significant improvements in QoL.

Carboplatin plus Paclitaxel in Combination with the Histone Deacetylate Inhibitor, Vorinostat, in Patients with Recurrent Platinum-Sensitive Ovarian Cancer.

Background: This phase II study evaluated the efficacy and safety of the histone deacetylase (HDAC) inhibitor, vorinostat, administered in combination with paclitaxel and carboplatin in patients with platinum sensitive recurrent ovarian cancer. Methods: Women with recurrent platinum-sensitive ovarian, peritoneal, or Fallopian tube carcinoma, a performance status of 0-2, and good overall organ function were eligible. Patients received 6 courses of paclitaxel (175 mg/m2) and carboplatin area under the curve (AUC) of 5.0 mg/mL/min administered via intravenous infusion on day 1 of a 3-week schedule. In addition, patients received vorinostat 400 mg orally once daily on days -4 through 10 of Cycle 1 and days 1 through 14 of each subsequent treatment cycle. The primary endpoints were progression-free survival (PFS) and adverse events. The secondary endpoints were the objective response rate and overall survival. Results: Fifty-five patients were included. CR was obtained in 14 patients (26.4%) and PR in 19 patients (35.8%), resulting in an ORR of 62.2%. Twenty patients (37.7%) had SD. The median duration of response (DoR) was 12.6 (range 6-128) months. The median PFS was 11.6 months (95% CI, 10.3-18.0; p < 0.001). Median OS was 40.6 months (95% Cl, 25.1-56.1). The most common treatment-related adverse events (all grades) were fatigue, anemia, thrombocytopenia, neutropenia, anorexia, nausea, pain, sensory neuropathy, myalgia, stomatitis and diarrhea. Conclusions: Vorinostat combined with carboplatin plus paclitaxel was tolerable and generated significant responses including a long median overall survival in recurrent platinum-sensitive ovarian cancer.

Prognostic Value of Pretreatment Plasma C-Reactive Protein in Patients with Early-Stage Breast Cancer.

BACKGROUND: Breast cancer incidence is now the highest among all cancers and accountable for 6.6% of all cancer-related deaths worldwide. Studies of the prognostic utility of plasma C-reactive protein (CRP) measurement in early-stage breast cancer have given discrepant results. METHODS: We identified 6,942 patients in the Danish Breast Cancer Cooperative Group database with early-stage breast cancer diagnosed between 2002 and 2016 who had a measure of pretreatment plasma CRP. Outcomes were recurrence-free interval and survival for a period up to 10 years. We analyzed associations with plasma CRP using Fine-Gray proportional subdistribution hazards model with recurrence-free interval. Data on plasma CRP were analyzed per doubling of concentration and in relation to CRP levels of <3 mg/L, 3 to 10 mg/L, and >10 mg/L and stratified according to standard clinical parameters in sensitivity analyses. RESULTS: A doubling of the plasma CRP concentration was associated with increased risk of recurrence (multivariate adjusted HR, 1.05; 95% CI, 1.01-1.08) and shorter survival (HR, 1.13; 95% CI, 1.09-1.16) in multivariate analyses. Survival was shorter in patients with plasma CRP levels of 3 to 10 and >10 mg/L versus <3 mg/L, with multivariate adjusted HRs of 1.30; 95% CI, 1.17-1.45 and 1.65; 95% CI, 1.39-1.95, respectively. CONCLUSIONS: Elevated plasma CRP measured before treatment in patients with early-stage breast cancer is an independent biomarker of increased risk of recurrence and early death. IMPACT: CRP measures before treatment might be used to individualize follow-up of patients with early-stage breast cancer.

Palliative medical cancer treatment of the elderly.

Due to demographic changes the incidence of older patients with cancer will increase. The complexity of systemic treatment of cancer is also evolving. Older patients with cancer are underrepresented in clinical trials and do often not represent the older population treated in real-world setting. Knowledge on how to treat older patients with cancer is sparse and mostly based on pooled analyses from larger trials including older fit patients. Only few randomised trials include older patients with frailty. Clinical trials dedicated to older or frail patients with cancer are still an unmet need, as argued in this review.

Pulmonary Valve Replacement in Tetralogy of Fallot: Procedural Volume and Durability of Bioprosthetic Pulmonary Valves.

BACKGROUND: Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce. OBJECTIVES: This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort. METHODS: Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability. RESULTS: In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models. CONCLUSIONS: The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability.

Quality of Life in the Danish Fontan Population is Unchanged Over the Past Decade-A Nationwide Longitudinal Study.

Knowledge about health-related quality of life (HRQoL) over time in Fontan patients is sparse. We aimed to describe HRQoL over a ten-year period in a population-based Fontan cohort. Further, we compared HRQoL in Fontan patients with the general population. In 2011, Danish Fontan patients were invited to participate in a nationwide study assessing HRQoL. Depending on age, 152 participants filled out either the Pediatric Quality of Life Inventory or the 36-Item Short Form Health Survey. After a decade, patients from the initial study were invited to participate in a follow-up study. All were given the same questionnaire as in the first study, plus the 12-Item Short Form Health Survey (SF-12) as part of the Danish National Health Survey. HRQoL over time was described, and SF-12 scores were compared with the general population. A total of 109 Fontan patients completed the questionnaires in both studies. The mean patient age was 14.9 ± 6.6 years and 25.6 ± 6.5 years respectively. Despite an increase in complications, HRQoL did not decrease during the study period. Physical HRQoL scores were lower than mental HRQoL scores at both time points. The SF-12 physical component score was significantly lower in Fontan patients than in the general population (median score 52 vs. 56, p < 0.001), while the SF-12 mental component score was comparable (median score 51 vs. 50, p = 0.019). HRQoL remained stable over a ten-year period in a contemporary Danish Fontan cohort. Still, the physical HRQoL remained significantly lower than that of the general population.

Adult congenital heart disease training in Europe: current status, disparities and potential solutions.

OBJECTIVES: This study aimed to determine the status of training of adult congenital heart disease (ACHD) cardiologists in Europe. METHODS: A questionnaire was sent to ACHD cardiologists from 34 European countries. RESULTS: Representatives from 31 of 34 countries (91%) responded. ACHD cardiology was recognised by the respective ministry of Health in two countries (7%) as a subspecialty. Two countries (7%) have formally recognised ACHD training programmes, 15 (48%) have informal (neither accredited nor certified) training and 14 (45%) have very limited or no programme. Twenty-five countries (81%) described training ACHD doctors 'on the job'. The median number of ACHD centres per country was 4 (range 0-28), median number of ACHD surgical centres was 3 (0-26) and the median number of ACHD training centres was 2 (range 0-28). An established exit examination in ACHD was conducted in only one country (3%) and formal certification provided by two countries (7%). ACHD cardiologist number versus gross domestic product Pearson correlation coefficient=0.789 (p<0.001). CONCLUSION: Formal or accredited training in ACHD is rare among European countries. Many countries have very limited or no training and resort to 'train people on the job'. Few countries provide either an exit examination or certification. Efforts to harmonise training and establish standards in exit examination and certification may improve training and consequently promote the alignment of high-quality patient care.

Plasma YKL-40 is associated with prognosis in patients with metastatic pancreatic cancer receiving immune checkpoint inhibitors in combination with radiotherapy.

Background: YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein produced by various cell types including stromal, immune, and cancer cells. It contributes to cancer progression through tumor-promoting inflammation and has been shown to inhibit the cytotoxicity of T and NK lymphocytes. In vivo studies have demonstrated synergistic anti-cancer effects of blocking YKL-40 in combination with immune checkpoint inhibitors (ICIs). Biomarkers for the prediction of the response to ICIs are highly needed. We investigated the association between plasma YKL-40 and clinical benefit and survival in patients with metastatic pancreatic cancer (mPC) receiving ICIs and stereotactic body radiotherapy (SBRT). Methods: Blood samples were collected from 84 patients with mPC who participated in the randomized phase II CheckPAC study, in which patients received nivolumab with or without ipilimumab combined with a single fraction of SBRT. Plasma YKL-40 was measured using a commercial ELISA kit. Results: Elevated baseline plasma YKL-40 was an independent predictor of shorter overall survival (OS) (HR 2.19, 95% CI 1.21-3.95). A ≥ 40% decrease in plasma YKL-40 during treatment was associated with longer progression-free survival (p = 0.009) and OS (p = 0.0028). There was no correlation between plasma YKL-40 and the tumor burden marker CA19-9 at baseline or during treatment. Conclusion: This study contributes new knowledge regarding YKL-40 as a predictor of clinical benefit from ICIs and radiotherapy. These exploratory results warrant further investigation of YKL-40 as a biomarker for patients treated with immunotherapies. Clinical trial registration: Clinicaltrials.gov, identifier NCT02866383.

Patient mortality following new-onset heart failure stratified by cancer type and status.

AIM: Expected 1-year survival is essential to risk stratification of patients with heart failure (HF); however, little is known about the 1-year prognosis of patients with HF and cancer. Thus, the objective was to investigate the 1-year prognosis following new-onset HF stratified by cancer status in patients with breast, gastrointestinal, or lung cancer. METHODS AND RESULTS: All Danish patients with new-onset HF from 2000 to 2018 were included. Cancer status was categorized as history of cancer (no cancer-related contact within 5 years of HF diagnosis), non-active cancer (curative intended procedure administered) and active cancer. Standardized 1-year all-cause mortality was reported using G-computation. Age-stratified 1-year all-cause mortality was estimated using the Kaplan-Meier estimator. In total, 193 359 patients with HF were included, 7.3% had either a breast, gastrointestinal, or lung cancer diagnosis. Patients with cancer were older and more comorbid than patients without cancer. Standardized 1-year all-cause mortality (95% confidence intervals) was 24.6% (23.0-26.2%), 27.1% (25.5-28.6%), and 29.9% (25.9-34.0%) for history of breast, gastrointestinal and lung cancer, respectively, which was comparable to patients with non-active cancers. For active breast, gastrointestinal and lung cancer, standardized 1-year all-cause mortality was 36.2% (33.8-38.6%), 49.0% (47.2-50.9%), and 61.6% (59.7-63.5%), respectively. One-year all-cause mortality increased incrementally with age, except for active lung cancer. CONCLUSION: Standardized 1-year all-cause mortality was comparable for patients with history of cancer and non-active cancer regardless of cancer type, but varied comprehensively for active cancers. Prognostic impact of age was limited for active lung cancer. Thus, granular stratification of cancer is necessary for optimized management of new-onset HF.

Importance of familial predisposition to heart failure to the risk of anthracycline-related cardiotoxicity: A nationwide study.

BACKGROUND: Anthracycline-based chemotherapy has improved the prognosis of various malignancies, but increases the long-term risk of heart failure (HF). Identification of patients at risk prior to treatment initiation is warranted. Therefore, the aim of this study was to evaluate if a familial predisposition to HF increases the risk of anthracycline related HF. METHODS: Using nationwide Danish registries, all patients treated with anthracycline from 2004 to 16 were identified. The primary outcome was long-term HF risk. First-degree relatives were identified in the Danish Family Registry and exposure was defined as a first-degree biological relative with prior HF. Risk of HF was evaluated in a cumulative incidence function and the association in a multivariable Cox regression model. RESULTS: A total of 11,651 patients (median age 49.1 years (IQR: 43.6-53.7), 12.2% male) were included after exclusion of 46 with preanthracycline HF. Median follow-up was 3.8 years (IQR 1.9-6.4). In the group with a first-degree relative with HF (n = 1,608) 35 patients (2.2%) were diagnosed with HF vs 133 (1.3%) in the group without a first-degree relative with HF (n = 10,043), corresponding to incidence rates per 1,000 patient-years of 5.2 (CI:3.8-7.3) vs 3.0 (CI:2.5-3.5). The cumulative incidence of HF after 10 years was higher in the first-degree relative group (3.2% vs 2.0%, P = .004); adjusted hazard ratio 1.53 (CI:1.05-2.23, P = .03). CONCLUSION: In this nationwide register-based study having a first-degree relative with HF was associated with increased risk of anthracycline related HF, suggesting that attention towards family predisposition may be warranted when estimating the risk of anthracycline related cardiotoxicity.

Characteristics and Outcomes in Patients With Acute Aortic Dissection: A Nationwide Registry Study.

BACKGROUND: We aimed to describe characteristics and outcomes in a nationwide population of patients with acute type A and type B aortic dissection. METHODS: All patients in Denmark with a first-time diagnosis of acute aortic dissection between 2006 and 2015 were identified by national registries. The main outcomes were in-hospital mortality and long-term survival in hospital survivors. RESULTS: The study population comprised 1157 (68%) patients with type A aortic dissection and 556 (32%) patients with type B aortic dissection, median age of 66 (57-74) years and 70 (61-79) years, respectively. Men accounted for 64%. Median follow-up was 8.9 (6.8-11.5) years. Of patients with type A aortic dissection, 74% were managed surgically, whereas 22% of the patients with type B aortic dissection were managed with surgery or endovascular technique. In-hospital mortality was 27% for type A aortic dissection overall (surgery, 18%; no surgery, 52%) and 16% for type B aortic dissection (surgery or endovascular treatment, 13%; conservative treatment, 17%; P < .001, type A vs type B). Of patients discharged alive, survival was persistently better for type A aortic dissection than for type B aortic dissection (P < .001). Unadjusted 1- and 3-year survival of patients with type A aortic dissection discharged alive was 96% and 91%, respectively, for surgically managed and 88% and 78% without surgery. For type B aortic dissection, the numbers were 89% and 83% for endovascular/surgically managed and 89% and 77% for conservatively managed. CONCLUSIONS: We found higher in-hospital mortality for type A and type B aortic dissection than is reported from referral center registries. Type A aortic dissection had the highest mortality rate during the acute phase, whereas for patients who were discharged alive, the mortality rate was higher for patients with type B aortic dissection.

Satisfaction with and perceived benefits of needs-assessment related to rehabilitation after chemotherapy among patients with breast cancer.

PURPOSE: To investigate satisfaction with and perceived benefits of a model of needs-assessment related to rehabilitation (NARR) in women with early breast cancer after (neo)adjuvant chemotherapy. MATERIALS AND METHODS: Mixed methods were applied using survey (N = 200) along with interviews (N = 20). The survey included measurement of distress and self-assessed need of and satisfaction with the NARR. Type of experienced side/late effects were registered along with numbers of and reasons for referrals to rehabilitation. Individual semi-structured interviews were conducted. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed with thematic analysis. RESULTS: Overall, 217 patients participated in a NARR and 200 (92%) accepted participation in the survey. Furthermore, 20/37 (54%) invited patients were interviewed. After the NARR, 39 patients (20%) were referred to rehabilitation. While satisfaction was high, findings regarding distress and need of the NARR were equivocal and indicated a need for talking about experiences throughout the cancer trajectory. CONCLUSIONS: While only 20% had rehabilitation needs, satisfaction with the NARR was high and patients benefitted from being confirmed in normality of their experiences. It is recommended to address patients' side/late effects after chemotherapy for early breast cancer to identify rehabilitation needs, reduce distress, and improve quality of life.

One fifth of patients with early breast cancer were referred to rehabilitation after needs-assessments conducted 2 months after chemotherapy termination.Higher distress and higher self-reported need were significantly associated with not working and experiencing a higher number of side effects/late effects.It is recommended to address patients' side effects/late effects, including psychological distress, after termination of chemotherapy for early breast cancer to identify rehabilitation needs, reduce distress, and ultimately improve quality of life.

Exercise capacity in the Danish Fontan population remains stable after ten years of follow-up - is physical activity the key to success?

BACKGROUND: Most Fontan patients have impaired exercise capacity, and a further decline in exercise capacity over time seems inevitable. However, few longitudinal studies exist, and there is a lack of data from newer eras. We aimed to describe the natural evolution of exercise capacity over a 10-year period in a contemporary, population-based cohort of Danish Fontan patients. METHODS: The study was a nationwide, prospective study. A cardiopulmonary exercise test (CPET) was used to assess the exercise capacity. All Danish Fontan patients who participated in a national study in 2011 (CPET1), were invited to a follow-up visit in 2021 (CPET2). All patients who completed CPET1 and CPET2 with a respiratory exchange ratio over 1.0 were included. The main outcome was percent predicted VO2peak (%pred VO2peak). At the time of CPET2, patients filled out a questionnaire including questions regarding physical activity. RESULTS: Seventy-seven patients completed both CPET1 and CPET2, and seventy patients completed the questionnaire. The time interval between the two CPETs was 10.4 ± 0.9 years. The median age was 15 years at CPET1 and 26 years at CPET2. The exercise capacity remained stable with a mean %pred VO2peak of 53.8 ± 11.3 at CPET1 and 55.6 ± 10.9 in CPET2 (p = 0.314). Higher levels of vigorous physical activity were associated with higher %pred VO2peak in CPET2 in a multivariate regression model. CONCLUSION: The %pred VO2peak remained stable over a ten-year period in this population-based Fontan cohort. Higher levels of self-reported vigorous physical activity were associated with higher %pred VO2peak in the most recent CPET.

The Validity of a New Procedure-Based Definition of Cancer Status in Patients with Breast-, Lung- and Colorectal Cancer in the Danish National Patient Registry.

Background/Aim: The Danish National Patient Registry (DNPR) provides unique epidemiological insight, but often lacks granular data. We propose a procedure-based definition of cancer status in patients with breast-, lung- and colorectal cancer, which can be applied to administrative health databases. New definitions of cancer status are needed as mortality and morbidity are closely linked to cancer status, yet most studies only use duration since cancer diagnosis as a severity marker. The aim of the study was to validate a new pragmatic definition. Methods: Medical journals of 600 patients, with breast-, lung- and colorectal cancer from the Department of Oncology at Herlev-Gentofte Hospital were retrospectively reviewed. We defined active cancer as a cancer diagnosis, not followed by a potentially curative procedure within 6 months of the diagnosis. The remaining patients were characterized as having non-active cancer. This dichotomization was then compared to a cancer status assessment based on treatment received and paraclinical test such as their first post-procedural control scan. Based on this comparison, we calculated the positive predictive value (PPV) of our definitions of active and non-active cancer. Results: The calculated PPVs for active breast-, lung- and colorectal cancer were 87% (CI 95%: 0.74-0.99), 91% (CI 95%: 0.87-0.96) and 82% (CI 95%: 0.73-0.91). The PPVs for non-active breast-, lung- and colorectal cancer were 95% (CI 95%: 0.92-0.99), 91% (CI 95%: 0.82-0.99) and 73% (CI 95%: 0.66-0.81), respectively. Conclusion: We found an overall high PPV for both active and non-active cancer across all three types of cancer.

Pre-existing TGF-ß-specific T-cell immunity in patients with pancreatic cancer predicts survival after checkpoint inhibitors combined with radiotherapy.

BACKGROUND: Circulating transforming growth factor-ß (TGF-ß)-specific T cells that recognize TGF-ß-expressing immune regulatory cells have been described in patients with cancer. TGF-ß-derived peptide vaccination modulates the tumor microenvironment and has shown clinical effects in animal models of pancreatic cancer (PC). TGF-ß-expressing regulatory cells are especially elevated in PC and may prevent the clinical response to immune checkpoint inhibitors (ICIs). Thus, in the present study we investigated the significance of TGF-ß-specific T-cell immunity in patients with PC treated with ICI combined with radiotherapy in a randomized phase 2 study (CheckPAC). METHODS: Immune responses to a TGF-ß-derived epitope entitled TGF-ß-15 as well as epitopes from Clostridium tetani (tetanus) and influenza were measured in peripheral blood mononuclear cells (PBMCs) with interferon-É£ enzyme-linked immunospot assays. PBMCs were isolated before and after treatment. Correlations between immune response data and clinical data were evaluated with parametric and non-parametric statistical methods. Survival was analyzed with univariate and multivariate Cox-regression. TGF-ß-15 specific T cells were isolated and expanded and examined for recognition of autologous regulatory immune cells by flow cytometry. RESULTS: PBMCs from 32 patients were analyzed for immune responses to the TGF-ß-derived epitope entitled TGF-ß-15. Patients with a strong TGF-ß-specific immune response at treatment initiation had longer progression-free and overall survival, compared with patients with a weak or no TGF-ß-specific immune response. This remained significant in multivariate analysis. Patients with weak and strong TGF-ß-specific responses displayed similar responses towards viral antigens. Furthermore, we show that TGF-ß-specific T cells from a clinical responder specifically reacted to and lysed autologous, regulatory immune cells. Finally, mimicking a TGF-ß-15 vaccination, we showed that repeated stimulations with the TGF-ß-15 epitope in vitro enhanced the immune response to TGF-ß-15. CONCLUSION: A strong TGF-ß-15 specific immune response was associated with clinical benefit and improved survival after ICI/radiotherapy for patients with PC. Importantly, the lack of TGF-ß-specific T cells in some patients was not caused by a general immune dysfunction. TGF-ß-specific T cells recognized regulatory immune cells and could be introduced in vitro in patients without spontaneous responses. Taken together, our data suggest that combining TGF-ß-based vaccination with ICI/radiotherapy will be beneficial for patients with PC.

Reasons for declining participation in an exercise-based trial among older women with breast cancer receiving systemic anti-cancer treatment - a qualitative interview study.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer in the world. Exercise is widely recommended for patients with breast cancer during and after treatment. However, there is a lack of studies investigating barriers related to participation in real-world exercise-based trials for older patients with breast cancer. OBJECTIVE: To explore reasons for declining participation in an exercise-based trial among older patients with breast cancer during (neo)adjuvant or palliative systemic treatment. METHODS: A qualitative study using semi-structured interviews. Patients who declined participation in an exercise-based trial (N = 50) were invited to participate. Semi-structured interviews were conducted with 15 participants. Interviews were audio-recorded, transcribed verbatim and analyzed using thematic analysis. RESULTS: Identified main themes: 1) Lack of energy and resources, including two subthemes: 1a) Overwhelmed both mentally and physically, and 1b) The program is too comprehensive; 2) Uncertainty about reactions to chemotherapy; 3) The hospital is not the optimal exercise setting, including two subthemes: 3a) Transportation and time consumption, and 3b) No desire to spend additional time at the hospital; and 4) Staying active in my own way, including two subthemes: 4a) Motivation to exercise, and 4b) Preferences for exercise activities. CONCLUSION: Many barriers were identified, including time of recruitment, information overload, symptoms and side effects, and the hospital as the exercise setting due to practical challenges and negative feelings. Participants were motivated to exercise from knowledge about the benefits of exercising. Furthermore, they preferred activities that they were already involved in or had experience with.