Towards a cancer mission in Horizon Europe: recommendations.

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice.

Long-term (up to 16 months) health-related quality of life after adjuvant tailored dose-dense chemotherapy vs. standard three-weekly chemotherapy in women with high-risk early breast cancer.

PURPOSE: To prospectively compare HRQoL effects of two modern adjuvant chemotherapy breast cancer treatment regimens at six time-points up to 16 months after random assignment. METHODS: The open-label, randomized, Phase 3 "Panther trial" was conducted between February 2007 and September 2011. 760 women, aged 65 years and younger, after surgery for non-metastatic node-positive or high-risk node-negative breast cancer were randomized 1:1 to the experimental group (four cycles of tailored and dose-dense adjuvant epirubicin and cyclophosphamide/2 weeks followed by four cycles of tailored dose-dense docetaxel/2 weeks) or standard group (three cycles of fluorouracil and epirubicin-cyclophosphamide/3 weeks followed by three cycles of docetaxel/3 weeks). HRQoL was assessed at all Swedish centres using EORTC QLQ-C30 and EORTC QLQ-BR23 at six points during 16 months before randomization. RESULTS: Response rates to questionnaires were highest at baseline 728/780 (93%) and lowest 16 months after randomization, 557/750 (74%). HRQoL declined during treatment in both groups. At the end of treatment, the experimental group reported statistically significantly lower HRQoL (P < 0.001) than the standard group on global health status, physical functioning, role functioning, social functioning, fatigue, sexual functioning, and systemic therapy effects. No differences were found for emotional functioning, body image, and arm and breast symptoms. There were no statistically significant differences between the groups at the first follow-up and at subsequent assessments. HRQoL levels at the 16-month follow-up were similar to baseline values. CONCLUSIONS: Negative HRQoL impact of the dose-dense and tailored strategy appears to be prominent during treatment, but HRQoL recover once treatment ends. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier: ISRCTN39017665.

Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial.

Importance: Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy. Objective: To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule. Design, Setting, and Participants: A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011. Interventions: Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. Main Outcomes and Measures: The primary end point was breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects. Results: Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97% with node-positive disease), 2000 received study treatment (≥1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P = .06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0.63-0.99; P = .04; 5-year EFS, 86.7% vs 82.1%). The groups did not differ in OS (HR, 0.77; 95% CI, 0.57-1.05; P = .09; 5-year OS, 92.1% vs 90.2%) or DDFS (HR, 0.83; 95% CI, 0.64-1.08; P = .17; 5-year DDFS, 89.4% vs 86.7%). Grade 3 or 4 nonhematologic toxic effects occurred in 527 (52.6%) in the tailored dose-dense group and 366 (36.6%) in the control group. Conclusions and Relevance: Among women with high-risk early breast cancer, the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer recurrence-free survival. Nonhematologic toxic effects were more frequent in the tailored dose-dense group. Trial Registration: clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier: ISRCTN39017665.

Feasibility and Outcomes of an Internet-Based Mindfulness Training Program: A Pilot Randomized Controlled Trial.

BACKGROUND: Interventions based on meditation and mindfulness techniques have been shown to reduce stress and increase psychological well-being in a wide variety of populations. Self-administrated Internet-based mindfulness training programs have the potential to be a convenient, cost-effective, easily disseminated, and accessible alternative to group-based programs. OBJECTIVE: This randomized controlled pilot trial with 90 university students in Stockholm, Sweden, explored the feasibility, usability, acceptability, and outcomes of an 8-week Internet-based mindfulness training program. METHODS: Participants were randomly assigned to either an intervention (n=46) or an active control condition (n=44). Intervention participants were invited to an Internet-based 8-week mindfulness program, and control participants were invited to an Internet-based 4-week expressive writing program. The programs were automated apart from weekly reminders via email. Main outcomes in pre- and postassessments were psychological well-being and depression symptoms. To assess the participant's experiences, those completing the full programs were asked to fill out an assessment questionnaire and 8 of the participants were interviewed using a semistructured interview guide. Descriptive and inferential statistics, as well as content analysis, were performed. RESULTS: In the mindfulness program, 28 out of 46 students (60%) completed the first week and 18 out of 46 (39%) completed the full program. In the expressive writing program, 35 out of 44 students (80%) completed the first week and 31 out of 44 (70%) completed the full program. There was no statistically significantly stronger intervention effect for the mindfulness intervention compared to the active control intervention. Those completing the mindfulness group reported high satisfaction with the program. Most of those interviewed were satisfied with the layout and technique and with the support provided by the study coordinators. More frequent contact with study coordinators was suggested as a way to improve program adherence and completion. Most participants considered the program to be meaningful and helpful but also challenging. The flexibility in performing the exercises at a suitable time and place was appreciated. A major difficulty was, however, finding enough time to practice. CONCLUSIONS: The program was usable, acceptable, and showed potential for increasing psychological well-being for those completing it. However, additional modification of the program might be needed to increase retention and compliance. CLINICALTRIAL: ClinicalTrials.gov NCT02062762; https://clinicaltrials.gov/ct2/show/NCT0206276 (Archived by WebCite at http://www.webcitation.org/6j9I5SGJ4).

Tailored chemotherapy doses based on toxicity in breast cancer result in similar quality of life values, irrespective of given dose levels.

BACKGROUND: From March 1994 to March 1998, breast cancer patients (an estimated relapse risk with 70% or more within five years with standard therapy) were randomised to treatment with tailored fluorouracil, epirubicin, and cyclophosphamide (FEC) therapy or FEC followed by marrow-supported high dose therapy in the Scandinavian Breast Group 9401 study. The aim of the present paper was to investigate differences in toxicity and eight health-related quality of life (HRQoL) variables (physical functioning, role functioning, emotional functioning, social functioning, cognitive functioning, fatigue, nausea-vomiting, and global quality of life) between women in the six dose steps used in the tailored and granulocyte colony stimulating factor supported FEC-arm at the assessment point 16 weeks after random assignment to treatment. METHODS: The European Organization and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-C30 were mailed to the patients. RESULTS: A total of 157 (87%) in the tailored FEC-group responded to the questionnaire within the time frame 16 weeks after inclusion in the study. Overall, toxicity was low, reaching grade 1-2 also in the higher dose steps. There were no overall differences between the dose steps on any of the tested HRQoL variables. Patients at dose step 4 scored statistically significantly higher on physical functioning than patients at dose step 1 (p = 0.022) and compared to those at dose step 2 (p = 0.014). Patients at dose steps -2 and -1 (combined to one group) reported statistically significantly higher mean scores on cognitive functioning than patients at dose step 1 (p = 0.022). CONCLUSION: Patients who received higher doses, based on the tailored dosing strategy, did not seem to have worse HRQoL than those who had lower doses.

Self-report mindfulness as a mediator of psychological well-being in a stress reduction intervention for cancer patients--a randomized study.

BACKGROUND: There is increasing recognition of mindfulness and mindfulness training as a way to decrease stress and increase psychological functioning. PURPOSE: The aims of this study were to examine the effects of mindfulness stress reduction training on perceived stress and psychological well-being and to examine if changes in mindfulness mediate intervention effects on these outcomes. METHODS: Seventy women and one man with a previous cancer diagnosis (mean age 51.8 years, standard deviation = 9.86) were randomized into an intervention group or a wait-list control group. The intervention consisted of an 8-week mindfulness training course. RESULTS: Compared to participants in the control group, participants in the mindfulness training group had significantly decreased perceived stress and posttraumatic avoidance symptoms and increased positive states of mind. Those who participated in the intervention reported a significant increase in scores on the five-facet mindfulness questionnaire (FFMQ) when compared to controls. The increase in FFMQ score mediated the effects of the intervention on perceived stress, posttraumatic avoidance symptoms, and positive states of mind. CONCLUSIONS: This study indicates that the improvements in psychological well-being resulting from mindfulness stress reduction training can potentially be explained by increased levels of mindfulness as measured with the FFMQ. The importance of these findings for future research in the field of mindfulness is discussed.

Individual psychosocial support for breast cancer patients: a randomized study of nurse versus psychologist interventions and standard care.

In a prospective, randomized study, an individual psychosocial support intervention performed by specially trained oncology nurses, or psychologists, were compared with standard care. Consecutive primary breast cancer patients about to start adjuvant therapy (n = 179) were included. Data were supplied by the questionnaires European Organisation for Research and Treatment of Cancer Quality of Life Study Group Core Quality of life questionnaire with 30 questions (EORTC QLQ-C30) and Breast Cancer Module with 23 questions (BR23), the Hospital Anxiety and Depression Scale, Spielberger's State-Trait Anxiety Inventory, and the Impact of Event Scale before randomization and 1, 3, and 6 months later. Patient files provided data on utilization of psychosocial support offered in routine care. Global quality of life/health status, nausea and vomiting, and systemic therapy side effects were the subscales showing significant Group by Time interactions, favoring the interventions. Intervention groups improved statistically significantly more than the standard care group regarding insomnia, dyspnea, and financial difficulties. Nurse patients experienced less intrusion compared with the standard care group. All groups showed statistically and clinically significant improvements with time on several subscales. The intervention groups, however, improved to a greater extent. Fewer patients in the intervention groups used psychosocial hospital support compared with the standard care group. In conclusion, psychosocial support by specially trained nurses using techniques derived from cognitive behavioral therapy is beneficial for breast cancer patients and may be a realistic alternative in routine cancer care.

Attitudes, subjective norms and perception of behavioural control as predictors of sun-related behaviour in Swedish adults.

BACKGROUND: Exposure to ultraviolet (UV) radiation is the major preventable cause of skin cancer. The aim of this study was to investigate the explanatory value of attitudes, subjective norms and perceived behavioural control on behaviours related to UV exposure. METHOD: A random population-based sample (n = 1752, 18-37 years of age) in the Stockholm County, Sweden, answered a questionnaire with items on sun related behaviours and beliefs. The items concerned issues influenced by the Theory of Planned Behaviour, that is, attitudes, subjective norms and perceived behavioural control. Logistic regression analysis was used to examine the associations between behaviours and beliefs. RESULTS: Positive attitudes towards being tanned and being in the sun were both strongly associated with time spent in the sun, intentional tanning, sunbed use, going on vacation to a sunny resort, intention to decrease sunbathing and use of protection against the sun. Perceiving sunbathing as risky was associated with using different ways to protect and intending to reduce sun exposure. Having people around oneself who frequently sunbathe was related to intentional tanning and vacations to sunny resorts. Finally, perceived behavioural control was associated with use of sunscreen and use of other ways to protect from the sun among women. CONCLUSION: The study identified factors on which primary preventive interventions towards decreasing sun exposure should be focused.

Quality of life in women with breast cancer during the first year after random assignment to adjuvant treatment with marrow-supported high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin or tailored therapy with Fluorouracil, epirubicin, and cyclophosphamide: Scandinavian Breast Group Study 9401.

PURPOSE: To compare, in high-risk breast cancer patients, the effects on health-related quality of life (HRQoL) of two adjuvant treatments. Treatments were compared at eight points during the first year after random assignment to treatment with tailored fluorouracil, epirubicin, and cyclophosphamide (FEC) therapy for nine courses versus induction FEC therapy for three courses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb) supported by peripheral-blood stem cells. PATIENTS AND METHODS: From March 1994 to March 1998, 525 breast cancer patients (estimated relapse risk > 70% within 5 years with standard therapy) were included in the Scandinavian Breast Group 9401 study. HRQoL evaluation, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Breast Cancer Module-23, included 408 of 446 eligible patients in Finland, Norway, and Sweden. RESULTS: Eighty-four percent to 95% of the patients completed questionnaires at eight points of assessment. Nostatistically significant overall differences were found between the tailored FEC group and the CTCb group for any of the HRQoL variables. Statistically significant differences over time were found for all HRQoL variables. HRQoL in the CTCb group demonstrated a steeper decrease, but a faster recovery than in the tailored FEC group. Emotional functioning improved with increased time from randomization. Higher levels of problems in body image and arm symptoms were reported in the tailored FEC group compared with the CTCb group. Sexual functioning and satisfaction were impaired during the study period. CONCLUSION: Both treatments had a negative influence on HRQoL during the treatment period. Despite the aggressive therapies, the patient's HRQoL returned to levels found at inclusion on most variables.