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- Hiensch, Anouk E, et al.
(författare)
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Design of a multinational randomized controlled trial to assess the effects of structured and individualized exercise in patients with metastatic breast cancer on fatigue and quality of life : the EFFECT study.
- 2022
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1, s. 610-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many patients with metastatic breast cancer experience cancer- and treatment-related side effects that impair activities of daily living and negatively affect the quality of life. There is a need for interventions that improve quality of life by alleviating fatigue and other side effects during palliative cancer treatment. Beneficial effects of exercise have been observed in the curative setting, but, to date, comparable evidence in patients with metastatic breast cancer is lacking. The aim of this study is to assess the effects of a structured and individualized 9-month exercise intervention in patients with metastatic breast cancer on quality of life, fatigue, and other cancer- and treatment-related side effects.METHODS: The EFFECT study is a multinational, randomized controlled trial including 350 patients with metastatic breast cancer. Participants are randomly allocated (1:1) to an exercise or control group. The exercise group participates in a 9-month multimodal exercise program, starting with a 6-month period where participants exercise twice a week under the supervision of an exercise professional. After completing this 6-month period, one supervised session is replaced by one unsupervised session for 3 months. In addition, participants are instructed to be physically active for ≥30 min/day on all remaining days of the week, while being supported by an activity tracker and exercise app. Participants allocated to the control group receive standard medical care, general written physical activity advice, and an activity tracker, but no structured exercise program. The primary outcomes are quality of life (EORTC QLQ-C30, summary score) and fatigue (EORTC QLQ-FA12), assessed at baseline, 3, 6 (primary endpoint), and 9 months post-baseline. Secondary outcomes include physical fitness, physical performance, physical activity, anxiety, depression, pain, sleep problems, anthropometric data, body composition, and blood markers. Exploratory outcomes include quality of working life, muscle thickness, urinary incontinence, disease progression, and survival. Additionally, the cost-effectiveness of the exercise program is assessed. Adherence and safety are monitored throughout the intervention period.DISCUSSION: This large randomized controlled trial will provide evidence regarding the (cost-) effectiveness of exercise during treatment of metastatic breast cancer. If proven (cost-)effective, exercise should be offered to patients with metastatic breast cancer as part of standard care.TRIAL REGISTRATION: ClinicalTrials.gov NCT04120298 . Registered on October 9, 2019.
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| 2. |
- Hiensch, Anouk E, et al.
(författare)
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Doxorubicin-induced skeletal muscle atrophy : Elucidating the underlying molecular pathways.
- 2020
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 229:2
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Loss of skeletal muscle mass is a common clinical finding in cancer patients. The purpose of this meta-analysis and systematic review was to quantify the effect of doxorubicin on skeletal muscle and report on the proposed molecular pathways possibly leading to doxorubicin-induced muscle atrophy in both human and animal models.METHODS: A systematic search of the literature was conducted in PubMed, EMBASE, Web of Science and CENTRAL databases. The internal validity of included studies was assessed using SYRCLE's risk of bias tool.RESULTS: Twenty eligible articles were identified. No human studies were identified as being eligible for inclusion. Doxorubicin significantly reduced skeletal muscle weight (ie EDL, TA, gastrocnemius and soleus) by 14% (95% CI: 9.9; 19.3) and muscle fibre cross-sectional area by 17% (95% CI: 9.0; 26.0) when compared to vehicle controls. Parallel to negative changes in muscle mass, muscle strength was even more decreased in response to doxorubicin administration. This review suggests that mitochondrial dysfunction plays a central role in doxorubicin-induced skeletal muscle atrophy. The increased production of ROS plays a key role within this process. Furthermore, doxorubicin activated all major proteolytic systems (ie calpains, the ubiquitin-proteasome pathway and autophagy) in the skeletal muscle. Although each of these proteolytic pathways contributes to doxorubicin-induced muscle atrophy, the activation of the ubiquitin-proteasome pathway is hypothesized to play a key role. Finally, a limited number of studies found that doxorubicin decreases protein synthesis by a disruption in the insulin signalling pathway.CONCLUSION: The results of the meta-analysis show that doxorubicin induces skeletal muscle atrophy in preclinical models. This effect may be explained by various interacting molecular pathways. Results from preclinical studies provide a robust setting to investigate a possible dose-response, separate the effects of doxorubicin from tumour-induced atrophy and to examine underlying molecular pathways. More research is needed to confirm the proposed signalling pathways in humans, paving the way for potential therapeutic approaches.
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| 3. |
- Karakatsanis, Andreas, et al.
(författare)
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Axillary Staging in the Setting of a Preoperative Diagnosis of Ductal Cancer In Situ (DCIS) : Results of an International Expert Panel and a Critical Guideline Performance Using Frequentist and Bayesian Analysis
- 2020
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Ingår i: Annals of Surgical Oncology. - : Springer. - 1068-9265 .- 1534-4681. ; 27:Suppl. 2, s. S337-S338
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objective: Sentinel lymph node biopsy (SLNB) is not routine in DCIS. Guidelines suggest SLNB when there is high risk for underlying invasion (large size, high grade, symptomatic lesion) or for detection failure (e.g., after mastectomy). However, guidelines and current practice patterns are inconsistent. Moreover, whilst SLNB is thought to be feasible and accurate after wide local excision (WLE), there is less consensus to support its use after oncoplastic breast-conserving surgery (OPBCS), which can reduce the need for mastectomy (Mx) and is gradually adopted as standard of care. The study aim was to assess if guidelines or individualized assessment result in optimal selection of patients for upfront SLNB.Methods: A panel of 28 international experts (20 surgeons, 8 oncologists, Europe 20, USA 5, Asia/Australia 3) was formed, all blind to the identity of the others. They reviewed anonymized patient cases from the SentiNot study (n=184, m. age 60 years, DCIS m. size 4 cm, Grade 2/3= 36%/64%, mass lesions 13,4%, underlying invasion 24.5%) and answer if they would consider upfront SLNB and why. Consensus and majority were set to >75 and >50%. At the same time, 6 independent raters (4 surgeons, 2 oncologists) reviewed guidelines and assessed the same patient cases per each guideline. Accuracy in relation to underlying invasion was assessed by Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) was reported. Agreement was investigated by kappa statistics and decision-making patterns by logistic multivariate regression and cluster analysis. To allow for flexibility and adaptation to current knowledge, both a frequentist and a Bayesian approach were undertaken. Priors were adjusted after a literature review regarding the factors that are commonly thought to be associated with higher risk for underlying invasion.Results: A total of 44,896 decisions were retrieved and analysed. The panel reached consensus/majority for upfront SLNB in 41.3/61.4%, whereas individual rates ranged from 11 to 100%. Agreement among panelists was low (kappa=0.37). In multivariate regression analysis for the entire panel, type of surgery was the most common determinant, (simple WLE=less, OPBCS=more and Mx=constant for SLNB), followed by symptomatic diagnosis and DCIS size. Most (26) members had a clear decision-making pattern regarding SLND, based mainly on DCIS size and type of surgery. Individual decision-making performed modestly in identifying patients with underlying invasion (AUC range 0,47-0,59), resulting mainly in overtreatment in 44-77% of patients. The panel performed similarly by majority (AUC 0,5) and by consensus (AUC 0,55) but “undertreated” 60-75% of patients with invasion, failing to identify them as "high-risk." After the recognition of different decision-making patterns, panelists were divided in subgroups with similar decision-making pattern. Analysis identified subgroups with difference in SLNB rate but not with better AUC. The disagreement among panelists in the same subgroups was significant, not only regarding which patients should undergo SLNB, but also on what factors that recommendation was based on. Eight guidelines with relevant recommendations were identified [USA (ASCO/NCCN), Europe (ESMO), Sweden, Denmark, UK, Netherlands and Italy, retrieval date May 2019]. Agreement among raters for each guideline separately varied (kappa: 0.23-0.9). Interpretation as to whether SLNB should be performed ranged widely (40-90%) and with varying concordance (32-88%). No guideline demonstrated accuracy (AUC range 0.45-0.55). Overtreatment risk was high (50-90%), whereas 10-50% of patients with invasion were not identified as “high- risk.” Agreement across guidelines was low (kappa=0.24), meaning that different patients had similar risk to be treated inaccurately, regardless of which guideline was examined.Conclusions: Individualized decision-making and guideline interpretation may be highly subjective and with low accuracy in terms of prediction of invasive disease, resulting in almost random risk for over- or undertreatment of the axilla in patients with DCIS. This suggests that current views and guidelines should be challenged. More accurate preoperative workup and novel techniques to allow for delayed SLNB may be of value in this setting.
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| 4. |
- Wiggenraad, Fleur, et al.
(författare)
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Long-Term Favorable Effects of Physical Exercise on Burdensome Symptoms in the OptiTrain Breast Cancer Randomized Controlled Trial.
- 2020
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Ingår i: Integrative Cancer Therapies. - : SAGE Publications. - 1534-7354 .- 1552-695X. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We evaluate longitudinal changes in symptom clusters and core burdensome symptoms in breast cancer patients who participated in the OptiTrain trial. Methods: 240 women were randomized to 16 weeks of supervised exercise (RT-HIIT or AT-HIIT) or usual care (UC) during adjuvant chemotherapy. Symptom clusters were composed using the Memorial Symptom Assessment Scale (MSAS), assessed at baseline, 16 weeks and 12 months later. Three symptom clusters were formed. Results: Three symptom clusters were identified: "emotional," "treatment-related toxicity," and "physical," with core burdensome symptoms present over time. At 16 weeks, the reported burdens of "feeling sad" (RT-HIIT vs UC: effect size [ES] = -0.69; AT-HIIT vs UC: ES = -0.56) and "feeling irritable" (ES = -0.41 RT-HIIT; ES = -0.31 AT-HIIT) were significantly lower in both intervention groups compared with UC. At 12 months, the AT-HIIT group continued to have significantly lower scores for the core burdensome symptoms "feeling sad" (ES = -0.44), "feeling irritable" (ES = -0.44), and "changes in the way food tastes" (ES = -0.53) compared with UC. No between-group differences were found for physical symptoms. Conclusion: We identified 3 symptom clusters in breast cancer patients during and after adjuvant chemotherapy, composed of "emotional," "treatment-related toxicity," and "physical" symptoms. After treatment completion up to 12 months post-baseline, patients in the physical exercise groups reported lower symptom burden scores for emotional symptoms, compared with UC. Our findings indicate a preserved and long-term beneficial effect of physical exercise on self-reported emotional well-being in chemotherapy-treated breast cancer patients.
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