Anne Maria May

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

Abstract 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.

Effects and moderators of physical activity on quality of life and physical function in patients with cancer

This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics. Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions. Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18, 95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.

Effects and moderators of physical activity on quality of life and physical function in patients with cancer: a meta-analysis of individual patient data from 34 randomized controlled trials

This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics. Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions. Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18, 95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.

Abstract P1-10-09: Are patients with breast cancer undergoing adjuvant treatment able to follow an exercise program with a moderate to high intensity?

PURPOSE: We recently showed in a randomized trial, the Physical Activity during Cancer Treatment (PACT) study, that an 18-week exercise program reduced complaints of fatigue and improved physical fitness in newly diagnosed breast cancer patients undergoing adjuvant treatment. The beneficial effects were probably underestimated due to high levels of physical activity in the control group that received usual care only. Another possibility for dilution of the effect might be limited participation of the intervention group in the supervised exercise program or low compliance, i.e., an adjustment of the prescribed exercise protocol. We set out to study participation and compliance and to find determinants of reduced compliance. METHODS: 102 patients in the PACT study were randomized into the intervention group that received a supervised exercise program 2 times a week for 18 weeks (36 sessions in total). Each session had a duration of 60 minutes and included a pre-specified period of aerobic interval exercises of specific intensities as well as muscle strength exercises. Sessions were supervised by physiotherapists, intensity was based on individual fitness characteristics and results were kept in a log. We computed attendance (percentage of total sessions attended) and compliance (adherence to the prescribed duration and intensity of the aerobic part and to the muscle strength part of each attended session). We computed for each woman the percentage of sessions the women complied with the protocol, and report median percentages for compliance with the aerobic exercises, duration and intensity, and with the muscle strength exercises separately. Determinants of low compliance that were included in linear regression models were: age, behavioral, physical and psychosocial factors. RESULTS: For 92 patients exercise logs were available. Patients were, on average, 50.2±7.8 years of age, all patients received chemotherapy and 70% received radiotherapy. Participation was high: patients participated in 83% (interquartile range 69-91%) of the sessions offered. Overall, also compliance was high: in 88% (63-97%) and 84% (65-94%) of all attended sessions patients were able to complete the aerobic (duration) and muscle strength program, respectively, as prescribed in the protocol. Compliance to the high-intensity part of the aerobic program was lower: in 50% (22-82%) of the sessions the intensity of the aerobic exercises was adjusted. Especially patients who received radiotherapy in addition to chemotherapy and patients who were more physically fatigued at baseline had a lower compliance to the high-intensity part of the aerobic exercises (β=-5.3 (confidence interval -9.4;-1.2) and β=-0.6 (-1.0;-0.1), respectively). CONLUSIONS: Participation in and compliance to an 18-week aerobic and muscle strength exercise program was high. Thus, patients are well capable to exercise during adjuvant treatment for breast cancer. This study shows that preferably high intensity aerobic exercises were adjusted in a significant number of participants rather than the duration or the strength exercises. This has to be taken into account when developing training programs, especially in those patients who receive both, radiotherapy and chemotherapy. Citation Format: May AM, Boer JH, Velthuis M, Steins Bisschop CN, Los M, Erdkamp F, ten Bokkel Huinink D, Bloemendal HJ, Rodenhuis C, de Roos MAJ, Verhaar M, van der Wall E, Peeters PHM. Are patients with breast cancer undergoing adjuvant treatment able to follow an exercise program with a moderate to high intensity?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-09.