Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study).

BACKGROUND: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. METHODS: Chemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. RESULTS: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm3, 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm3, 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015). CONCLUSIONS: No exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.

Effects of structured involvement of the primary care team versus standard care after a cancer diagnosis on patient satisfaction and healthcare use: the GRIP randomised controlled trial.

BACKGROUND: The growing number of cancer survivors and treatment possibilities call for more personalised and integrated cancer care. Primary care seems well positioned to support this. We aimed to assess the effects of structured follow-up of a primary care team after a cancer diagnosis. METHODS: We performed a multicentre randomised controlled trial enrolling patients curatively treated for breast, lung, colorectal, gynaecologic cancer or melanoma. In addition to usual cancer care in the control group, patients randomized to intervention were offered a "Time Out consultation" (TOC) with the general practitioner (GP) after diagnosis, and subsequent follow-up during and after treatment by a home care oncology nurse (HON). Primary outcomes were patient satisfaction with care (questionnaire: EORTC-INPATSAT-32) and healthcare utilisation. Intention-to-treat linear mixed regression analyses were used for satisfaction with care and other continuous outcome variables. The difference in healthcare utilisation for categorical data was calculated with a Pearson Chi-Square or a Fisher exact test and count data (none versus any) with a log-binomial regression. RESULTS: We included 154 patients (control n = 77, intervention n = 77) who were mostly female (75%), mainly diagnosed with breast cancer (51%), and had a mean age of 61 (SD ± 11.9) years. 81% of the intervention patients had a TOC and 68% had HON contact. Satisfaction with care was high (8 out of 10) in both study groups. At 3 months after treatment, GP satisfaction was significantly lower in the intervention group on 3 of 6 subscales, i.e., quality (- 14.2 (95%CI -27.0;-1.3)), availability (- 15,9 (- 29.1;-2.6)) and information provision (- 15.2 (- 29.1;-1.4)). Patients in the intervention group visited the GP practice and the emergency department more often ((RR 1.3 (1.0;1.7) and 1.70 (1.0;2.8)), respectively). CONCLUSIONS: In conclusion, the GRIP intervention, which was designed to involve the primary care team during and after cancer treatment, increased the number of primary healthcare contacts. However, it did not improve patient satisfaction with care and it increased emergency department visits. As the high uptake of the intervention suggests a need of patients, future research should focus on optimizing the design and implementation of the intervention. TRIAL REGISTRATION: GRIP is retrospectively (21/06/2016) registered in the 'Netherlands Trial Register' (NTR5909).

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study).

BACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .

Effects of and Lessons Learned from an Internet-Based Physical Activity Support Program (with and without Physiotherapist Telephone Counselling) on Physical Activity Levels of Breast and Prostate Cancer Survivors: The PABLO Randomized Controlled Trial.

BACKGROUND: We developed an Internet-based physical activity (PA) support program (IPAS), which is embedded in a patient portal. We evaluated the effectiveness and costs of IPAS alone (online only) or IPAS combined with physiotherapist telephone counselling (blended care), compared to a control group. METHODS: Breast or prostate cancer survivors, 3-36 months after completing primary treatment, were randomized to 6-months access to online only, blended care, or a control group. At baseline and 6-month post-baseline, minutes of moderate-to-vigorous PA (MVPA) were measured by accelerometers. Secondary outcomes were self-reported PA, fatigue, mood, health-related quality of life, attitude toward PA, and costs. (Generalized) linear models were used to compare the outcomes between groups. RESULTS: We recruited 137 survivors (participation rate 11%). We did not observe any significant between-group differences in MVPA or secondary outcomes. Adherence was rather low and satisfaction scores were low to moderate, with better scores for blended care. Costs for both interventions were low. CONCLUSIONS: Recruitment to the study was challenging and the interventions were less efficacious than anticipated, which led to lessons learned for future trials. Suggestions for future research are as follows: improved accessibility of the support program, increased frequency of support, and use of activity trackers.

Supervised exercise after oesophageal cancer surgery: the PERFECT multicentre randomized clinical trial.

BACKGROUND: This study investigated whether a supervised exercise programme improves quality of life (QoL), fatigue and cardiorespiratory fitness in patients in the first year after oesophagectomy. METHODS: The multicentre PERFECT trial randomly assigned patients to an exercise intervention (EX) or usual care (UC) group. EX patients participated in a 12-week moderate- to high-intensity aerobic and resistance exercise programme supervised by a physiotherapist. Primary (global QoL, QoL summary score) and secondary (QoL subscales, fatigue and cardiorespiratory fitness) outcomes were assessed at baseline, 12 and 24 weeks and analysed as between-group differences using either linear mixed effects models or ANCOVA. RESULTS: A total of 120 patients (mean(s.d.) age 64(8) years) were included and randomized to EX (61 patients) or UC (59 patients). Patients in the EX group participated in 96 per cent (i.q.r. 92-100 per cent) of the exercise sessions and the relative exercise dose intensity was high (92 per cent). At 12 weeks, beneficial EX effects were found for QoL summary score (3.5, 95 per cent c.i. 0.2 to 6.8) and QoL role functioning (9.4, 95 per cent c.i. 1.3 to 17.5). Global QoL was not statistically significant different between groups (3.0, 95 per cent c.i. -2.2 to 8.2). Physical fatigue was lower in the EX group (-1.2, 95 per cent c.i. -2.6 to 0.1), albeit not significantly. There was statistically significant improvement in cardiorespiratory fitness following EX compared with UC (peak oxygen uptake (1.8 ml/min/kg, 95 per cent c.i. 0.6 to 3.0)). After 24 weeks, all EX effects were attenuated. CONCLUSIONS: A supervised exercise programme improved cardiorespiratory fitness and aspects of QoL. TRIAL REGISTRATION: Dutch Trial Register NTR 5045 (www.trialregister.nl/trial/4942).

Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

Physical activity levels of women with breast cancer during and after treatment, a comparison with the Dutch female population.

Background: Physical activity has been shown to reduce side-effects of breast cancer and its treatment. As physical activity levels of patients with breast cancer are largely unknown, we investigated these levels and compared them to women from the general population. Methods: In this prospective cohort study, physical activity levels of women with breast cancer participating in the UMBRELLA cohort were assessed at radiotherapy intake and thereafter every 6 months up to 3 years with the SQUASH questionnaire, which was also used in a random sample of the Dutch population. We compared physical activity levels (no activity, low, moderate or high levels of sports, leisure time or total activity) between patients and the Dutch female population using multinomial logistic regression. Standardized Prevalence Ratios (SPR) were calculated to compare adherence to Dutch physical activity guidelines. Results: Women with breast cancer (nbaseline = 1655, n6 months = 1414, n12 months = 1186, n18 months = 957, n24 months = 744, n30 months = 555, and n36 months = 377) were less likely to spend time in physical activity compared to the general population (n = 11,710) until 3 years post-diagnosis, especially after 6 months (ORhigh-vs.-no activity = 0.34, 95% CI: 0.28-0.41). From 12 months onwards, patients were more likely to perform sports compared to the general population, especially patients who underwent systemic therapy. Guideline adherence was significantly lower in patients at baseline and 6 months (SPRbaseline = 89, 95% CI: 82-97; SPR6 months = 88, 95% CI: 81-96), and comparable to the general population at 12-36 months, especially in older women. Conclusions: Physical activity levels in women with breast cancer during and after treatment were lower compared to the Dutch female population. Three years post-treatment, they were still less physically active, although they spend more time in sport activities. As about half of the patients did not perform any sports, physical activity needs to be stimulated during and after treatment.

(Cost-)effectiveness of an internet-based physical activity support program (with and without physiotherapy counselling) on physical activity levels of breast and prostate cancer survivors: design of the PABLO trial.

BACKGROUND: Higher levels of physical activity (PA) after treatment are associated with beneficial effects on physical and psychosocial functioning of cancer survivors. However, survivors often do not meet the recommended levels of PA. In order to promote PA, we developed a closed internet-based program. The aim of the study is to evaluate the (cost-)effectiveness of an internet-based PA-promotion program, alone or combined with physiotherapy counselling, compared to usual care, on PA-levels of breast or prostate cancer survivors. In this multicenter randomised controlled trial (RCT), breast or prostate cancer survivors who completed their primary treatment 3-12 months earlier, will be randomised to either 6-months access to a fully-automated internet-based intervention alone, an internet-based intervention plus remote support by a physiotherapist, or a control group. The intervention is based on the Transtheoretical Model and includes personalized feedback, information, video's and assignments. Additionally, in a second arm, physiotherapy counselling is provided through monthly scheduled and on-demand telephone calls. The control group will receive usual care and a leaflet with PA guidelines. METHODS: At baseline, 6 and 12 months, the primary outcome (PA) will be measured during 7 consecutive days by accelerometers. Secondary outcomes are self-reported PA, fatigue, mood, health-related quality of life, and costs. The group differences for primary and secondary outcomes will be analyzed using linear mixed models. DISCUSSION: If proven to be (cost)effective, this internet-based intervention, either alone or in combination with telephone support, will be a welcome addition to previous RCT's. TRIAL REGISTRATION: Netherlands trial register (NTR6911), Date of trial registration: December 21, 2017.

Managing unsolicited findings in genomics: A qualitative interview study with cancer patients.

OBJECTIVE: Next-generation sequencing (NGS) is increasingly being employed in the context of personalized cancer treatment. Anticipating unsolicited findings that may arise during a NGS procedure is a key consideration; however, little is known about cancer patients' intentions, needs, and preferences concerning the return of unsolicited findings. METHODS: A qualitative design using individual semi-structured interviews with 24 cancer patients was utilized to explore patients' decisions on whether to receive unsolicited findings from NGS. These interviews were subsequently analyzed using the constant comparative method to develop codes and themes. RESULTS: We identified 4 interrelated themes that emerged in the context of the return of unsolicited findings. First, we describe how cancer patients expressed a strong need to control their lives. Second, we show the importance of family dynamics. Third, the NGS procedure regarding unsolicited findings is perceived as cognitively complex, and fourth, the procedure is also considered emotionally complex. CONCLUSIONS: The results of our study contribute to a better understanding of what cancer patients consider important and what may motivate and influence them when making decisions on the disclosure of unsolicited findings following NGS. We show how Joel Feinberg's classification of autonomy may help clinicians to better understand cancer patients' desire for autonomous decision making while also acknowledging the emotional and cognitive difficulties regarding the disclosure of unsolicited findings. These insights could be helpful for clinicians to guide patients through this complex process.

Randomised controlled trial protocol (GRIP study): examining the effect of involvement of a general practitioner and home care oncology nurse after a cancer diagnosis on patient reported outcomes and healthcare utilization.

BACKGROUND: Due to the ageing population and improving diagnostics and treatments, the number of cancer patients and cancer survivors is increasing. Policymakers, patients and professionals advocate a transfer of (part of) cancer care from the hospital environment to the primary care setting, as this could stimulate personalized and integrated care, increase cost-effectiveness and would better meet the patients' needs and expectations. The effects of structured active follow-up from primary care after cancer diagnosis have not been studied yet. Therefore the GRIP study aims to assess the effects of structured follow-up after a cancer diagnosis, by a primary care team including a general practitioner (GP) and a home care oncology nurse (HON), on satisfaction and healthcare utilization of patients treated with curative intent. METHODS: We will conduct a multicentre, two-arm randomised controlled trial in The Netherlands. We plan to include 150 patients who will be treated with curative intent for either breast, lung, colorectal, gynaecologic cancer, or melanoma. Further inclusion criteria are: age 18 years and older, able to answer questionnaires in Dutch, GP agrees to participate and the possibility to include the patient before the start of treatment. All patients receive care as usual. The intervention arm will receive additional structured follow-up consisting of a GP consultation before onset of treatment to empower the patient for shared decision making with the specialist and a minimum of three contacts with the HON during and after treatment. Primary outcomes are: patient satisfaction with care at the level of specialist, GP and nurse and healthcare utilization. Secondary outcomes include: quality of life, employment status, patient empowerment, shared decision making, mental health and satisfaction with given information. Repeated questionnaires, filled in by the participants, will be assessed within the 1-year study period. DISCUSSION: This randomised controlled trial will evaluate the effects of structured follow-up after a cancer diagnosis by a primary care team including a GP and HON, for patients undergoing treatment with curative intent. Results from the present study may provide the evidence needed to optimally rearrange responsibilities in cancer care delivery and consequently improve cancer care and patient related outcomes. TRIAL REGISTRATION: Trial number: NTR5909 .

Severe depression more common in patients with ductal carcinoma in situ than early-stage invasive breast cancer patients.

PURPOSE: Ductal carcinoma in situ (DCIS) is associated with an excellent prognosis; historical studies have shown similar levels of psychological distress in patients with DCIS and with early-stage invasive breast cancer (early-IBC). It is suggested that these results might have led to better patient education about prognosis after DCIS. This study reports the current levels of anxiety, depression, and health-related quality of life (HRQoL) in DCIS and early-IBC patients. METHODS: DCIS (n = 89) and early-IBC patients, T1-2N0, (n = 361) were selected from the UMBRELLA breast cancer cohort. Patient-reported outcomes were prospectively collected before the start of adjuvant radiotherapy (baseline) and at 3, 6, 12, 18, and 24 months thereafter. Mixed models were used to compare differences in levels of anxiety, depression, and HRQoL between DCIS and early-IBC patients. RESULTS: DCIS and early-IBC patients reported similar levels of anxiety, which were highest at baseline. Depression scores were comparable between groups, also after stratification by use of adjuvant chemotherapy. The proportion of patients reporting high-risk depression scores (i.e., Hospital Anxiety and Depression Sale score >8) was significantly higher among patients with DCIS at 6, 12 and 18 months, and this proportion increased over the first 18 months. Health-related quality of life was comparable between both groups. CONCLUSION: Severe depression scores are more common in DCIS patients, despite their excellent prognosis. These results suggest that further improvement of patient education and effective patient doctor communication about the prognostic differences between patients with DCIS and invasive breast cancer is still highly needed.

Innovation in neurosurgery: less than IDEAL? A systematic review.

BACKGROUND: Surgical innovation is different from the introduction of novel pharmaceuticals. To help address this, in 2009 the IDEAL Collaboration (Idea, Development, Exploration, Assessment, Long-term follow-up) introduced the five-stage framework for surgical innovation. To evaluate the framework feasibility for novel neurosurgical procedure introduction, two innovative surgical procedures were examined: the endoscopic endonasal approach for skull base meningiomas (EEMS) and the WovenEndobridge (WEB device) for endovascular treatment of intracranial aneurysms. METHODS: The published literature on EEMS and WEB devices was systematically reviewed. Identified studies were classified according to the IDEAL framework stage. Next, studies were evaluated for possible categorization according to the IDEAL framework. RESULTS: Five hundred seventy-six papers describing EEMS were identified of which 26 papers were included. No prospective studies were identified, and no studies reported on ethical approval or patient informed consent for the innovative procedure. Therefore, no clinical studies could be categorized according to the IDEAL Framework. For WEB devices, 6229 articles were screened of which 21 were included. In contrast to EEMS, two studies were categorized as 2a and two as 2b. CONCLUSION: The results of this systematic review demonstrate that both EEMS and WEB devices were not introduced according to the (later developed in the case of EEMS) IDEAL framework. Elements of the framework such as informed consent, ethical approval, and rigorous outcomes reporting are important and could serve to improve the quality of neurosurgical research. Alternative study designs and the use of big data could be useful modifications of the IDEAL framework for innovation in neurosurgery.

Cost-effectiveness of capecitabine and bevacizumab maintenance treatment after first-line induction treatment in metastatic colorectal cancer.

AIM: Capecitabine and bevacizumab (CAP-B) maintenance therapy has shown to be more effective compared with observation in metastatic colorectal cancer patients achieving stable disease or better after six cycles of first-line capecitabine, oxaliplatin, bevacizumab treatment in terms of progression-free survival. We evaluated the cost-effectiveness of CAP-B maintenance treatment. METHODS: Decision analysis with Markov modelling to evaluate the cost-effectiveness of CAP-B maintenance compared with observation was performed based on CAIRO3 study results (n = 558). An additional analysis was performed in patients with complete or partial response. The primary outcomes were the incremental cost-effectiveness ratio (ICER) defined as the additional cost per life year (LY) and quality-adjusted life years (QALY) gained, calculated from EQ-5D questionnaires and literature and LYs gained. Univariable sensitivity analysis was performed to assess the influence of input parameters on the ICER, and a probabilistic sensitivity analysis represents uncertainty in model parameters. RESULTS: CAP-B maintenance compared with observation resulted in 0.21 QALYs (0.18LYs) gained at a mean cost increase of €36,845, yielding an ICER of €175,452 per QALY (€204,694 per LY). Varying the difference in health-related quality of life between CAP-B maintenance and observation influenced the ICER most. For patients achieving complete or partial response on capecitabine, oxaliplatin, bevacizumab induction treatment, an ICER of €149,300 per QALY was calculated. CONCLUSION: CAP-B maintenance results in improved health outcomes measured in QALYs and LYs compared with observation, but also in a relevant increase in costs. Despite the fact that there is no consensus on cost-effectiveness thresholds in cancer treatment, CAP-B maintenance may not be considered cost-effective.

Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research.

BACKGROUND: Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG). METHODS/DESIGN: The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long-term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria. RESULTS: Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort- or cmRCT-designed studies are currently recruiting patients. CONCLUSION: This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types.

Trained clinical nurse specialists proficiently obtain bone marrow aspirates and trephine biopsies in a nearly painless procedure--a prospective evaluation study.

Patients often experience bone marrow examinations (BMEs) as frightening and painful. Varying operators and uncertainty about who will perform the BME worsen their anxiety. In our study, clinical nurse specialists (CNSs) were trained to perform BMEs to ensure continuity and to test the feasibility, patient satisfaction, and biopsy quality. This exploratory evaluation assessed 574 BMEs at our tertiary center between January 2012 and February 2013, 398 BMEs performed by CNS and 176 by physicians. Our aims were to determine whether BMEs by CNS yield results similar to those of physicians, analyzing (1) patient satisfaction with the BME (a) consent and (b) performance, (2) induced pain, and (3) quality of aspirates and length of trephine biopsies. When performed by CNS, 100 % of the patients were satisfied with the consent procedure and 99 % with the BME performance (physicians 99 and 91 %, respectively). The median pain score was low when both CNS and physicians performed the BME, with no or only mild pain in 92 and 76 % of patients, respectively. Bone marrow (BM) aspirates by CNS and physicians were assessed as technically evaluable in ~70 %; moreover, the median length of trephine biopsies was similar when performed by CNS or physicians with 12 and 13 mm, respectively. In conclusion, BMEs conducted by motivated CNS and within a structured training program are feasible and yield equal outcomes compared to physicians. The use of adequate pain management during BMEs by trained and experienced operators results in an extremely rare use of sedatives, low pain scores, and high patient satisfaction.

Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study.

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow-up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p-trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC.

Long-term effect of a nurse-led psychosocial intervention on health-related quality of life in patients with head and neck cancer: a randomised controlled trial.

BACKGROUND: Head and neck cancer (HNC) patients are prone to have a poor health-related quality of life after cancer treatment. This study investigated the effect of the nurse counselling and after intervention (NUCAI) on the health-related quality of life and depressive symptoms of HNC patients between 12 and 24 months after cancer treatment. METHODS: Two hundred and five HNC patients were randomly allocated to NUCAI (N=103) or usual care (N=102). The 12-month nurse-led NUCAI is problem-focused and patient-driven and aims to help HNC patients manage with the physical, psychological and social consequences of their disease and its treatment. Health-related quality of life was evaluated with the EORTC QLQ-C30 and QLQ H&N35. Depressive symptoms were evaluated with the CES-D. RESULTS: At 12 months the intervention group showed a significant (P<0.05) improvement in emotional and physical functioning, pain, swallowing, social contact, mouth opening and depressive symptoms. At 18 months, global quality of life, role and emotional functioning, pain, swallowing, mouth opening and depressive symptoms were significantly better in the intervention group than in the control group, and at 24 months emotional functioning and fatigue were significantly better in the intervention group. CONCLUSION: The NUCAI effectively improved several domains of health-related quality of life and depressive symptoms in HNC patients and would seem a promising intervention for implementation in daily clinical practice.

Mediators of physical exercise for improvement in cancer survivors' quality of life.

OBJECTIVE: Mediating mechanisms of a 12-week group-based exercise intervention on cancer survivors' quality of life (QoL) were examined to inform future exercise intervention development. METHODS: Two hundred nine cancer survivors ≥ 3 months posttreatment (57% breast cancer) aged 49.5 (± 10.4) years were assigned to physical exercise (n = 147) or wait-list control (n = 62). QoL, fatigue, emotional distress, physical activity, general self-efficacy and mastery were assessed at baseline and post-intervention using questionnaires. Path analysis was conducted using Mplus to explore whether improved physical activity, general self-efficacy and mastery mediated the effects of exercise on fatigue and distress and consequently QoL. RESULTS: The intervention was associated with increased physical activity (ß = 0.46, 95% confidence interval (CI) = 0.14;0.59), general self-efficacy (ß = 2.41, 95%CI = 0.35;4.73), and mastery (ß = 1.75, 95%CI = 0.36;2.78). Further, the intervention had both a direct effect on fatigue (ß = -1.09, 95%CI = -2.12;0.01), and an indirect effect (ß = -0.54, 95%CI = -1.00;-0.21) via physical activity (ß = -0.29, 95%CI = -0.64;-0.07) and general self-efficacy (ß = -0.25, 95%CI = -0.61;-0.05). The intervention had a borderline significant direct effect on reduced distress (ß = -1.32, 95%CI = -2.68;0.11), and a significant indirect effect via increased general self-efficacy and mastery (ß = -1.06, 95%CI = -1.89;-0.38). Reductions in fatigue (ß = -1.33, 95%CI =-1.85;-0.83) and distress (ß = -0.86, 95%CI = -1.25;-0.52) were associated with improved QoL. Further, increased physical activity was directly associated with improved QoL (ß = 3.37, 95%CI = 1.01;5.54). CONCLUSION: The beneficial effect of group-based physical exercise on QoL was mediated by increased physical activity, general self-efficacy and mastery, and subsequent reductions in fatigue and distress. In addition to physical activity, future interventions should target self-efficacy and mastery. This may lead to reduced distress and fatigue, and consequently improved QoL of cancer survivors.