Neo-train: study protocol and feasibility results for a two-arm randomized controlled trial investigating the effect of supervised exercise during neoadjuvant chemotherapy on tumour response in patients with breast cancer.

BACKGROUND: Prehabilitation with exercise interventions during neoadjuvant chemotherapy (NACT) is effective in reducing physical and psychosocial chemotherapy-related adverse events in patients with cancer. In preclinical studies, data also support a growth inhibitory effect of aerobic exercise on the tumour microenvironment with possible improved chemotherapy delivery but evidence in human patients is limited. The aim of the study here described is to investigate if supervised exercise with high-intensity aerobic and resistance training during NACT can improve tumour reduction in patients with breast cancer. METHODS: This parallel two-armed randomized controlled trial is planned to include 120 women aged ≥ 18 years with newly diagnosed breast cancer starting standard NACT at a university hospital in Denmark (a total of 90 participants needed according to the power calculation and allowing 25% (n = 30) dropout). The participants will be randomized to usual care or supervised exercise consisting of high-intensity interval training on a stationary exercise bike and machine-based progressive resistance training offered three times a week for 24 weeks during NACT, and screening-based advice to seek counselling in case of moderate-severe psychological distress (Neo-Train program). The primary outcome is tumour size change (maximum diameter of the largest lesion in millimetre) measured by magnetic resonance imaging prior to surgery. Secondary outcomes include clinical/pathological, physical and patient-reported measures such as relative dose intensity of NACT, hospital admissions, body composition, physical fitness, muscle strength, health-related quality of life, general anxiety, depression, and biological measures such as intratumoural vascularity, tumour infiltrating lymphocytes, circulating tumour DNA and blood chemistry. Outcomes will be measured at baseline (one week before to 1-2 weeks after starting NACT), during NACT (approximately week 7, 13 and 19), pre-surgery (approximately week 21-29), at surgery (approximately week 21-30) and 3 months post-surgery (approximately 33-42 weeks from baseline). DISCUSSION: This study will provide novel and important data on the potential benefits of supervised aerobic and resistance exercise concomitant to NACT on tumour response and the tumour microenvironment in patients with breast cancer, with potential importance for survival and risk of recurrence. If effective, our study may help increase focus of exercise as an active part of the neoadjuvant treatment strategy. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04623554) on November 10, 2020.

Patient-Related Characteristics Associated with Treatment Modifications and Suboptimal Relative Dose Intensity of Neoadjuvant Chemotherapy in Patients with Breast Cancer-A Retrospective Study.

BACKGROUND: Reduced relative dose intensity (RDI) of neoadjuvant chemotherapy (NACT) in patients with breast cancer may compromise treatment outcome and survival. We examined patient-related characteristics associated with treatment modifications and suboptimal RDI and tumour response in patients with breast cancer. METHODS: In this observational study, electronic medical records were reviewed retrospectively for female patients with breast cancer scheduled for NACT at a university hospital in Denmark between 2017 and 2019. The RDI (ratio of delivered dose intensity in relation to standard dose intensity) was calculated. Multivariate logistic regression analyses examined associations of sociodemographics, general health and clinical cancer characteristics with dose reductions, dose delays, discontinuation of NACT and suboptimal RDI < 85%. RESULTS: Among 122 included patients, 43%, 42% and 28% experienced dose reductions, dose delays ≥3 days and discontinuation, respectively. A total of 25% received an RDI < 85%. Comorbidity, taking long-term medications and being overweight were statistically significantly associated with treatment modifications, while age ≥ 65 years and comorbidity were associated with RDI < 85%. Around one third of all patients had radiologic (36%) or pathologic (35%) complete tumour response, with no statistically significant differences by RDI < or ≥85% irrespective of breast cancer subtype. CONCLUSIONS: While most patients had RDI ≥85%, still one out of four patients received an RDI < 85%. Further investigations of possible supportive care initiatives to improve patients' treatment tolerability are needed, particularly among subgroups of older age or with comorbidity.

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.

Patients' experiences of the COVID-19 pandemic and the change to telephone consultations in cancer care.

PURPOSE: During the COVID-19 pandemic, teleconsultations have increasingly been used to reduce physical contact and thus risk of infection. This study investigated how patients with cancer experienced the COVID-19 pandemic and how they perceived the change from in-person consultations to telephone consultations in an oncology outpatient clinic. The aim was to provide insights that could optimize the future use of teleconsultations in cancer care. METHODS: This qualitative study included 15 patients with colorectal, breast, gynecological, lung, or prostate cancer treated at the outpatient clinic at the Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Denmark in June or July 2020. Data were collected through semi-structured individual interviews and analyzed by thematic analysis. RESULTS: Patients with cancer experienced social, psychological, and organizational consequences of the COVID-19 pandemic related to their cancer care. Not all patients were comfortable with telephone consultations. Six themes were identified: (1) double burden as a consequence of simultaneous cancer and the COVID-19 pandemic, (2) parameters for patient satisfaction with telephone consultations, (3) the importance of relatives attending consultations, (4) loss of information and nuances during telephone consultations, (5) the impact of physicians' language and communicative skills during telephone consultations, and (6) patients' suggestions for future telephone consultations. CONCLUSION: Beyond the COVID-19 pandemic, it is important that hospitals offering teleconsultations involve patients' preferences, consider for which patients and consultations the solution is suitable, which technology to use, how to prepare patients and relatives, and how to provide physicians with the necessary communicative skills.

A population-based survey of patients' experiences with teleconsultations in cancer care in Denmark during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, teleconsultations (TC) have been increasingly used in cancer care as an alternative to outpatient visits. We aimed to examine patient-related and cancer-specific characteristics associated with experiences with TC among patients with cancer during the COVID-19 pandemic. MATERIAL AND METHODS: This population-based survey included patients with breast, lung, gastrointestinal, urological, and gynaecological cancers with appointments in the outpatient clinics, Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Denmark in March and April 2020. Age- and sex-adjusted logistic regression analyses were used to study associations of sociodemographics, cancer and general health, anxiety, and health literacy with patients' experiences of TC in regards to being comfortable with TC, confident that the doctor could provide information or assess symptoms/side effects and the perceived outcome of TC. RESULTS: Of the 2119 patients with cancer receiving the electronic survey, 1160 (55%) participated. Two thirds of patients (68%) had consultations with a doctor changed to TC. Being male, aged 65-79 years, and having TC for test results were statistically significantly associated with more comfort, confidence, and perceived better outcome of TC. Having breast cancer, anxiety, low health literacy, or TC for a follow-up consultation were statistically significantly associated with less positive experiences with TC. Living alone, short education, disability pension, and comorbidity were statistically significantly associated with anxiety and low health literacy. CONCLUSIONS: Most patients reported positive experiences with TC, but in particular patients with anxiety and low health literacy, who were also the patients with fewest socioeconomic and health resources, felt less comfortable and confident with and were more likely to perceive the outcome negatively from this form of consultation. TC may be suitable for increasing integration into standard cancer care but it should be carefully planned to meet patients' different information needs in order not to increase social inequality in cancer.

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.

Mental, physical and social health benefits of immersive nature-experience for children and adolescents: A systematic review and quality assessment of the evidence.

In this systematic review, we summarised and evaluated the evidence for benefits of immersive nature-experience on children and adolescents' mental, physical and social health. An electronic search was performed for English language articles published between January 2004 and May 2017. Data were extracted from 84 publications that met the inclusion criteria. Study quality was assessed for a subset of the studies, i.e. controlled between- and within-subject studies, using a systematic assessment scheme, and the quality of the evidence was reviewed at an outcome level. Across heterogeneous types of immersive nature-experience, there was conditional support for benefits on self-esteem, self-efficacy, resilience and academic and cognitive performance. Correlational research evidenced higher levels of physical activity in natural environments than comparison conditions. Benefits for outcomes such as self-concept, problem solving, and mood were more inconclusive. In addition, social skill-oriented and behavioural indicators were improved, although the categories comprised different outcomes. Risk of bias, insufficient sampling methods and unsuited comparison groups were common study limitations.

Immersive Nature-Experiences as Health Promotion Interventions for Healthy, Vulnerable, and Sick Populations? A Systematic Review and Appraisal of Controlled Studies.

In this systematic review, we summarized and evaluated the evidence for effects of, and associations between, immersive nature-experience on mental, physical, and social health promotion outcomes. Immersive nature-experience was operationalized as non-competitive activities, both sedentary and active, occurring in natural environments removed from everyday environments. We defined health according to the World Health Organization's holistic and positive definition of health and included steady-state, intermediate, and health promotion outcomes. An electronic search was performed for Danish, English, German, Norwegian, and Swedish articles published between January 2004 and May 2017. Manual approaches, e.g., bibliographies from experts, supplemented the literature search. Data were extracted from 461 publications that met the inclusion criteria. To assess the status and quality of the evidence for health promotion effects of immersive nature-experience, we focused on the subset of studies based on controlled designs (n = 133). Outcome level quality of the evidence was assessed narratively. Interventions most often involved adventure-based activities, short-termed walking, and seated relaxation in natural environments. We found positive effects on a range of health promotion outcomes grouped under psychological wellbeing (n = 97; ≈55% positive; ≈13% mixed; ≈29% non-significant; 2% negative); psychosocial function (n = 67; ≈61% positive; ≈9% mixed; ≈30% non-significant); psychophysiological stress response (n = 50; ≈58% positive; ≈18% mixed; ≈24% non-significant), and cognitive performance (n = 36; ≈58% positive; ≈6% mixed; ≈33% non-significant; 3% negative); and social skills and relationships (n = 34; ≈70% positive; ≈7% mixed; ≈22% non-significant). Findings related to outcomes categorized under physical health, e.g., risk of cardiovascular disease, were less consistent (n = 51; ≈37% positive; ≈28% mixed; ≈35% non-significant). Across the types of interventions and outcomes, the quality of the evidence was deemed low and occasionally moderate. In the review, we identify, discuss, and present possible solutions to four core methodological challenges associated with investigating immersive nature-experience and health outcomes: (1) intervention and program complexity; (2) feasibility and desirability of randomization; (3) blinding of participants and researchers; and (4) transferability and generalizability. The results of the review have been published as a popular-scientific report and a scientific research overview, both in Danish language.