Martijn M. Stuiver

Effect of Low-Intensity Physical Activity and Moderate- to High-Intensity Physical Exercise During Adjuvant Chemotherapy on Physical Fitness, Fatigue, and Chemotherapy Completion Rates: Results of the PACES Randomized Clinical Trial

PURPOSE We evaluated the effectiveness of a low-intensity, home-based physical activity program (Onco-Move) and a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack) versus usual care (UC) in maintaining or enhancing physical fitness, minimizing fatigue, enhancing health-related quality of life, and optimizing chemotherapy completion rates in patients undergoing adjuvant chemotherapy for breast cancer. PATIENTS AND METHODS We randomly assigned patients who were scheduled to undergo adjuvant chemotherapy (N = 230) to Onco-Move, OnTrack, or UC. Performance-based and self-reported outcomes were assessed before random assignment, at the end of chemotherapy, and at the 6-month follow-up. We used generalized estimating equations to compare the groups over time. RESULTS Onco-Move and OnTrack resulted in less decline in cardiorespiratory fitness (P < .001), better physical functioning (P ≤ .001), less nausea and vomiting (P = .029 and .031, respectively) and less pain (P = .003 and .011, respectively) compared with UC. OnTrack also resulted in better outcomes for muscle strength (P = .002) and physical fatigue (P < .001). At the 6-month follow-up, most outcomes returned to baseline levels for all three groups. A smaller percentage of participants in OnTrack required chemotherapy dose adjustments than those in the UC or Onco-Move groups (P = .002). Both intervention groups returned earlier (P = .012), as well as for more hours per week (P = .014), to work than the control group. CONCLUSION A supervised, moderate- to high-intensity, combined resistance and aerobic exercise program is most effective for patients with breast cancer undergoing adjuvant chemotherapy. A home-based, low-intensity physical activity program represents a viable alternative for women who are unable or unwilling to follow the higher intensity program.

Efficacy of Cognitive Behavioral Therapy and Physical Exercise in Alleviating Treatment-Induced Menopausal Symptoms in Patients With Breast Cancer: Results of a Randomized, Controlled, Multicenter Trial

PURPOSE The purpose of our study was to evaluate the effect of cognitive behavioral therapy (CBT), physical exercise (PE), and of these two interventions combined (CBT/PE) on menopausal symptoms (primary outcome), body image, sexual functioning, psychological well-being, and health-related quality of life (secondary outcomes) in patients with breast cancer experiencing treatment-induced menopause. PATIENTS AND METHODS Patients with breast cancer reporting treatment-induced menopausal symptoms (N=422) were randomly assigned to CBT (n=109), PE (n=104), CBT/PE (n=106), or to a waiting list control group (n=103). Self-report questionnaires were completed at baseline, 12 weeks, and 6 months. Multilevel procedures were used to compare the intervention groups with the control group over time. RESULTS Compared with the control group, the intervention groups had a significant decrease in levels of endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms; P<.001; effect size, 0.31-0.52) and urinary symptoms (Bristol Female Lower Urinary Tract Symptoms Questionnaire; P=.002; effect size, 0.29-0.33), and they showed an improvement in physical functioning (36-Item Short Form Health Survey physical functioning subscale; P=.002; effect size, 0.37-0.46). The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats (problem rating scale of the Hot Flush Rating Scale; P<.001; effect size, 0.39-0.56) and an increase in sexual activity (Sexual Activity Questionnaire habit subscale; P=.027; effect size, 0.65). Most of these effects were observed at both the 12-week and 6-month follow-ups. CONCLUSION CBT and PE can have salutary effects on endocrine symptoms and, to a lesser degree, on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause. Future work is needed to improve the design and the planning of these interventions to improve program adherence.

Effects and moderators of exercise on quality of life and physical function in patients with cancer: An individual patient data meta-analysis of 34 RCTs

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.

Impact of shoulder complaints after neck dissection on shoulder disability and quality of life.

Objective To explore relationships between shoulder complaints after neck dissection, shoulder disability, and quality of life. To find clinical predictors for mid- to long-term shoulder disability. Study Design Prospective. Patients and Methods Shoulder pain, shoulder mobility, and shoulder droop, as well as scores on shoulder disability questionnaire and RAND-36 (quality of life), were measured at baseline, discharge (T1), and 4 months postoperatively (T2) on 139 patients admitted for neck dissection to major head and neck centers in the Netherlands. Results Shoulder mobility was significantly decreased at T1 and did not improve. Significant relationships between shoulder function, shoulder disability score, and RAND-36 domains were found. Two clusters of clinical symptoms could be identified as independent predictors for shoulder disability. Conclusions Objective deterioration in shoulder function after neck dissection is associated with perceived shoulder disability and related to physical functioning and bodily pain. Predictors for shoulder disability can be found.

Early Wound Complications After Inguinal Lymphadenectomy in Penile Cancer: A Historical Cohort Study and Risk-factor Analysis

BACKGROUND Complication rates after inguinal lymph node dissection (ILND) are high. Risk factors for early wound complications after ILND in patients with penile carcinoma have not yet been studied. OBJECTIVES To assess the frequency of early wound complications in a contemporary series and to identify clinical risk factors for early wound complications after ILND for penile carcinoma. DESIGN, SETTING, AND PARTICIPANTS We evaluated 237 ILNDs in 163 patients with penile cancer treated between 2003 and 2012 at the Netherlands Cancer Institute. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We assessed the occurrence of wound infection, skin-flap problems, and seroma formation and graded complications using the modified Clavien system. Univariable and multivariable penalised mixed effects logistic regression was used to identify clinical risk factors for occurrence of any complication (grade ≥ 1) and of moderate to severe complications (grade ≥ 2). RESULTS AND LIMITATIONS One complication or more occurred in 58% of the procedures, and 10% of those complications were severe. Wound infection occurred in 43%, seroma formation occurred in 24%, and skin-flap problems occurred in 16%. Palpable disease was the only factor associated with grade ≥ 1 complications in the univariable analysis (odds ratio [OR]: 0.43; p=0.02). In the multivariable model, after penalisation, no statistically significant risk factors remained. Univariable associations for grade ≥ 2 complications were present for body mass index (BMI; OR of 1.66 for a 5.8-point change in BMI; p=0.05) and sartorius muscle transposition (OR: 2.64; p=0.04). In the reduced multivariable model, the OR for sartorius muscle transposition was 2.12 (p=0.06) and for BMI was 1.76 (p=0.03). In addition, bilateral dissection approached significance in the multivariable model (OR: 2.17; p=0.06). This study is limited by its observational nature. CONCLUSIONS Wound complication rates after ILND are high in this cohort. BMI, sartorius muscle transposition, and bilateral dissection were the factors most strongly associated with the occurrence of grade ≥ 2 wound complications.

Why do patients choose (not) to participate in an exercise trial during adjuvant chemotherapy for breast cancer

Only between 25% and 50% of patients invited to participate in clinical trial‐based physical exercise programs during cancer treatment agree to do so. The purpose of this study was to identify factors associated significantly with the decision (not) to participate in a randomized controlled trial of physical exercise during adjuvant chemotherapy for breast cancer.

Alpe d'HuZes cancer rehabilitation (A-CaRe) research: four randomized controlled exercise trials and economic evaluations in cancer patients and survivors.

BackgroundPrevious studies showed that exercise in cancer patients is feasible and may reduce fatigue and improve physical fitness and quality of life. However, many previous studies had methodological weaknesses related to trial design, sample size, comparison group, outcome measures, short follow-up durations and programme content.PurposeThis paper aims to present the rationale and design of the clinical research subprogramme of the Alpe d’HuZes Cancer Rehabilitation (A-CaRe) programme.MethodA-CaRe Clinical Research includes four randomized controlled trials in patients: (a) after chemotherapy, (b) during chemotherapy, (c) after stem cell transplantation and (d) during childhood cancer. These trials compare high-intensity resistance and endurance exercise interventions with usual care or a waiting list control group. In two studies, a second intervention arm consisting of low-to-moderate intensity exercise is included. All four A-CaRe trials use similar methods.ResultsOutcome measures are carefully chosen based on the International Classification of Functioning Disability and Health model. Measurements will be performed prior to randomization (T0), after completion of the intervention (T1) and at follow-up (T2). The primary outcome measures are cardiorespiratory fitness, muscle strength and fatigue. Secondary outcome measures include health-related quality of life and psychosocial functioning. Furthermore, cost-effectiveness and cost-utility analyses are performed from a societal perspective.ConclusionWe hypothesize that exercise is more effective at improving physical fitness and thereby reducing fatigue and more cost-effective compared with usual care or a waiting list control group. If so, the programmes will be implemented in the Dutch clinical practice.

Tailoring exercise interventions to comorbidities and treatment-induced adverse effects in patients with early stage breast cancer undergoing chemotherapy: a framework to support clinical decisions

Abstract Purpose: Delivery of exercise interventions to patients with early-stage breast cancer undergoing chemotherapy requires complex clinical decisions. The purpose of this study was to develop a framework to support clinical decisions for tailoring exercise interventions to common comorbidities and cancer treatment-induced adverse effects. Method: Tailored exercise prescriptions were developed in four steps, following the i3-S strategy. All steps were based on current best available evidence, complemented with expert opinions. First, common comorbidities and treatment-induced adverse effects were identified. In the subsequent steps, contra-indications and restrictions for exercise were described, along with possible exercise adaptations. In the final step, the obtained information was synthesized into a framework. Results: Prevalent comorbidities were hypertension, heart disease, diabetes mellitus, (osteo)arthritis, chronic obstructive pulmonary disease, and obesity. Adverse effects included conditions induced by pretreatment (e.g., lymphedema as a result of surgery) or by chemotherapy (e.g., reduced blood cell counts). Adaptations to the recommended exercise program were related to exercise tolerance, safety, and hygiene. A framework was proposed to guide clinical decisions during the exercise intervention. Conclusion: Comorbidities and adverse effects of breast cancer treatment require exercise adaptations. The proposed framework provides guidance on tailored exercise prescriptions in patients with breast cancer undergoing chemotherapy. Implications for Rehabilitation Exercise is recommended for patients with breast cancer undergoing chemotherapy, but requires complex clinical decisions of the health professional. We identified the most important comorbidities and adverse effects of breast cancer treatment, and the resultant contra-indications and restrictions to exercise. We incorporated these findings into a clinical decision framework that provides suggestions for exercise adaptations in patients with breast cancer undergoing chemotherapy.

Salivary gland pleomorphic adenoma in the Netherlands : A nationwide observational study of primary tumor incidence, malignant transformation, recurrence, and risk factors for recurrence

INTRODUCTION Whereas salivary gland pleomorphic adenoma (SGPA) is the most common type of salivary gland tumor, little is known about its epidemiology because national cancer registries do not register this disease. OBJECTIVES To establish SGPA incidence trends, rates of secondary malignant transformation and recurrence and associated factors in the Netherlands. MATERIALS AND METHODS Data on incidence, epidemiology, secondary malignant transformation and recurrence were retrieved from the Dutch pathology registry (PALGA) for the years 1992, 1997, 2002, 2007, and 2012. Multivariate analysis was performed to discover the risk factors for recurrence. RESULTS 3506 cases of SGPA were recorded implying an overall European standardized rate of 4.2-4.9 per 100,000 person-years. Our figures showed a female preponderance (1:1.43) with an annual 1% rise in female incidence (95% confidence interval [CI]: 0.2-1.8) and a bimodal age distribution in women (p<0.0001). The overall 20-year recurrence rate was 6.7%, and median time to first recurrence was 7years. Positive and uncertain resection margins and younger age at diagnosis were risk factors for recurrence, with odds ratios (ORs) of 4.62 (95%CI 2.84-7.51), 4.08 (95%CI 2.24-7.43), and 0.42 (95%CI 0.29-0.63) respectively. Tumor locations in the minor salivary glands had lower odds of recurrence than tumors in the parotid (OR 0.24; 95% CI: 0.07-0.77; p<0.016). Malignant transformation occurred in 0.15% of SGPAs (3.2% of recurrences). CONCLUSION This first nationwide study clearly showed sex differences in SGPA epidemiology, possibly suggesting some underlying hormonal mechanism. Long-term recurrence risks were low, and secondary malignant transformation risks were very low.

Quality of primary care for resettled refugees in the Netherlands with chronic mental and physical health problems: a cross-sectional analysis of medical records and interview data

BackgroundA high prevalence of mental and physical ill health among refugees resettled in the Netherlands has been reported. With this study we aim to assess the quality of primary healthcare for resettled refugees in the Netherlands with chronic mental and non-communicable health problems, we examined: a) general practitioners’ (GP) recognition of common mental disorders (CMD) (depression and anxiety, and post-traumatic stress disorder (PTSD) symptoms); b) patients’ awareness of diabetes type II (DMII) and hypertension (HT); and c) GPs’ adherence to guidelines for CMD, DMII and HT.MethodsFrom 172 refugees resettled in the Netherlands, interview data (2010–2011) and medical records (n = 106), were examined. Inclusion was based on medical record diagnoses for DMII and HT, and on questionnaire-based CMD measures (Hopkins Symptom Checklist for depression and anxiety; Harvard Trauma Questionnaire for PTSD). GP recognition of CMD was calculated as the number of CMD cases registered in the medical record compared with those found in interviews. Patient awareness of HT and DMII was scored as the percentage of subjects diagnosed by the GP who reported their condition during the interview. GPs’ adherence to guidelines for CMD, DMII and HT was measured using established indicators.ResultsWe identified 37 resettled refugees with CMD of which 18 (49%) had been recognised by the GP. We identified 16 refugees with DMII and 14 with HT from the medical record; 24 (80%) were aware of their condition. Thirty-five out of these 53 (66%) resettled refugees with chronic mental and non-communicable disorders received guideline-adherent treatment.ConclusionThis study shows that awareness in resettled refugees of GP diagnosed DMII and HT is high, whereas GP recognition of CMD and overall guideline adherence are moderate.