Search

ZusammenfassungBewegungstherapie in individualisierter Form bei onkologischen Patienten ist vor, während und auch nach Abschluss der medizinischen Therapie machbar und sicher und kann Nebenwirkungen, wie beispielsweise dem Fatigue-Syndrom oder der Polyneuropathie entgegenwirken. Dieser Beitrag gibt einen Überblick über die aktuellen bewegungstherapeutischen Ansätze bei onkologischen Patienten.

Whole-body vibration (WBV) is a feasible and potentially beneficial exercise strategy for managing neuromuscular impairments like decreased strength or flexibility, mobility limitations and bone health in pediatric cancer survivors. However, as starting rehabilitation as early as possible is recommended to preserve physical function, this study investigated the feasibility of WBV for patients receiving cancer treatment for first cancer diagnosis. Eleven patients (various types of cancer, ages 7–17) participated in the supervised WBV intervention concomitant to acute cancer treatment, which involved chemotherapy. Training was implemented as part of a general exercise program and offered 3 days per week during hospitalization (warm-up, four progressive training exercises comprising 60–120 s, 21–27 Hz, 2 mm peak-to-peak-displacement). Feasibility, which was defined as the absence of WBV-related serious adverse events leading to study dropout, was primarily evaluated. Training documentation was additionally analyzed. As a main result, no serious adverse events leading to study dropout were reported. However, two incidents of bleeding (adverse events) were observed in patients with bleeding tendencies and low platelets (thrombocytes

Nuclear IRF1 is induced following ATG7 and BECN1 knockdown.

dnIRF1 blocks ICI sensitivity in LCC1 cells.

Patient/tumor characteristics of human breast cancer tissue microarrays.

Relationship between IRF1 and ATG7 in human tissue microarrays.

Efficient knockdown of IRF1 using siRNA.

Interferon regulatory factor-1 (IRF1) is a tumor suppressor that regulates cell fate in several cell types. Here, we report an inverse correlation in expression of nuclear IRF1 and the autophagy regulator ATG7 in human breast cancer cells that directly affects their cell fate. In mice harboring mutant Atg7, nuclear IRF1 was increased in mammary tumors, spleen, and kidney. Mechanistic investigations identified ATG7 and the cell death modulator beclin-1 (BECN1) as negative regulators of IRF1. Silencing ATG7 or BECN1 caused estrogen receptor-α to exit the nucleus at the time when IRF1 nuclear localization occurred. Conversely, silencing IRF1 promoted autophagy by increasing BECN1 and blunting IGF1 receptor and mTOR survival signaling. Loss of IRF1 promoted resistance to antiestrogens, whereas combined silencing of ATG7 and IRF1 restored sensitivity to these agents. Using a mathematical model to prompt signaling hypotheses, we developed evidence that ATG7 silencing could resensitize IRF1-attenuated cells to apoptosis through mechanisms that involve other estrogen-regulated genes. Overall, our work shows how inhibiting the autophagy proteins ATG7 and BECN1 can regulate IRF1-dependent and -independent signaling pathways in ways that engender a new therapeutic strategy to attack breast cancer. Cancer Res; 75(6); 1046–55. ©2015 AACR.

Silencing ATG7 and BECN1 induces IRF1 expression independently of ROS.

Model ranges, their range, and description.

Knockdown of IRF1 alters BECN1 and IGF1R/mTOR expression.

Supplementary figure legends

Purpose Colorectal cancer and its treatment are associated with debilitating side effects. Exercise may improve the physical and psychological wellbeing of cancer patients; however, evidence in colorectal cancer patients undergoing adjuvant chemotherapy is limited. This pilot study aimed to explore the effects of supervised aerobic exercise on cardiorespiratory fitness and patient-reported health outcomes in colorectal cancer patients undergoing adjuvant chemotherapy. Methods Patients who had undergone curative resection for colorectal cancer (stages II–III) and were scheduled to receive adjuvant chemotherapy were enrolled into this non-randomized controlled trial. Patients in the intervention group (IG) took part in a 6-month supervised aerobic exercise program, while the control group (CG) received usual care. Cardiorespiratory fitness (measured by peak oxygen consumption) was assessed at baseline and 6 months. Fatigue, quality of life, and physical activity levels were additionally assessed at 3 months. Results In total, 59 patients (33 in IG vs. 26 in CG) were enrolled into this study. Eighteen patients (9 in IG vs. 9 in CG) dropped out of the study prior to the 6-month follow-up. Significant improvements in cardiorespiratory fitness (p = .002) and selected patient-reported health outcomes, such as reduced motivation (p = .015) and mental fatigue (p = .018), were observed in the IG when compared to the CG. Conclusion To our knowledge, this is the first study to investigate the effects of a supervised aerobic exercise program in colorectal cancer patients undergoing adjuvant chemotherapy. The significant and clinically meaningful improvements in CRF warrant further randomized controlled trials to confirm these findings. Trials registration German Clinical Trials Register Identifier: DRKS00005793, 11/03/2014, retrospectively registered.

Optimized and individualized treatment options in oncology significantly improve the prognosis of patients. Accordingly, the management of side effects and the avoidance of long-term consequences is becoming increasingly more important. Numerous studies have shown a positive impact of physical activity and targeted exercise therapy on certain patient-related outcomes. Ideally, patients are introduced to exercise therapy directly after the diagnosis is made in order to enable adequate supportive monitoring and to sustainably reduce therapy-associated side effects. Meanwhile, scientific findings have resulted in concrete recommendations for action to effectively improve the main patient-related outcomes, such as fatigue or depression. A moderate endurance training in combination with individualized strength training seems to be of particular importance. In principle, oncological training and exercise therapy can be recommended to every cancer patient regardless of the form of cancer and the timing of therapy but taking the contraindications into account. Therefore, the aim of communal as well as national efforts should be to implement a comprehensive offer of professional exercise therapy to facilitate access of cancer patients to these services as well as to ensure adequate care during and after treatment.Optimierte und individualisierte Therapiemöglichkeiten in der Onkologie verbessern die Prognosen der Patienten deutlich. Demzufolge gewinnen das Nebenwirkungsmanagement und die Vermeidung von Langzeitfolgen immer mehr an Bedeutung. In der Literatur finden sich zunehmend Beweise dafür, dass sich körperliche Aktivität und gezielte Bewegungstherapie positiv auf bestimmte „patient-related outcomes“ auswirken. Idealerweise werden die Patienten direkt nach der Diagnosestellung an die Bewegungstherapie herangeführt, um eine adäquate supportive Begleitung zu ermöglichen und therapieassoziierte Nebenwirkungen nachhaltig zu reduzieren. Mittlerweile ergeben sich aus wissenschaftlichen Erkenntnissen konkrete Handlungsempfehlungen, die die wesentlichen „patient-related outcomes“, wie z. B. Fatigue oder Depressionen, effektiv verbessern. Ein moderates Ausdauertraining in Kombination mit individualisiertem Krafttraining scheint von besonderer Bedeutung zu sein. Grundsätzlich kann eine onkologische Trainings- und Bewegungstherapie unter Berücksichtigung von Kontraindikationen jedem Patienten, unabhängig von Krebsentität und Zeitpunkt der Therapie, empfohlen werden. Demzufolge sollte das Ziel kommunaler und nationaler Bestrebungen darin bestehen, fachspezifische bewegungstherapeutische Angebote flächendeckend zu implementieren, um Patienten den Zugang zu diesen zu erleichtern sowie eine adäquate Versorgung während und nach der Therapie zu gewährleisten.

Background Pediatric cancer leads to reduced participation in exercise and only few patients comply with national physical activity recommendations. Physically inactive behavior hinders motor development and increases physical and psychological adverse effects of therapy and incidence of sequelae. Currently, there is neither nationwide coverage nor uniform level of knowledge regarding exercise promotion. The objective of the guideline is to facilitate qualified exercise interventions through standardized procedures in addition to regular physiotherapy and overall avoid physical inactivity in pediatric cancer patients. Methods This guideline addresses the multidisciplinary treatment team and informs physiotherapists and decision-makers in tertiary care hospitals and health insurance companies. The requirements of the Association of the Scientific Medical Societies in Germany were followed. Contents were based on best practice experience of experts, patient advocates, as well as on scientific evidence. Results The guideline includes 11 recommendations. Recommendations 1-4 declare the relevance of implementing exercise interventions and address general framework conditions. Recommendations 5-11 focus on the design of exercise programs, prevention and safety issues, relative contraindications for specific training loads, and options to overcome barriers to exercise. Conclusion This guideline summarizes existing and established structures and evidence in the context of movement and exercise in pediatric oncology. It takes into consideration the rights, varying needs, and characteristics of children and adolescents as well as national and international experience in this field. In the future, relevant research gaps need to be addressed by high-quality intervention studies to provide the scientific background for a stronger evidence-based guideline.

The positive effects of oncological exercise therapy are sufficiently proven according to scientific studies. International evidence-based guidelines confirm this importance and recommend physical exercise as part of the standard therapy for cancer. The effects of physical activity on cancer-specific deficits are versatile ranging from positive impact on fatigue syndrome, mortality, incontinence, lymphoedema, CIPN, anxiety, depression to reduction of pain. According to current knowledge, sensorimotor training is recommended for the treatment of polyneuropathy. The actual effectiveness of vibration training in reducing symptom burden is undetermined. There are more than 100 randomized, controlled studies with the highest evidence rating for the management of CrF available. In this regard, exercise therapy is more effective than drug therapy in alleviating the symptomatology of CrF. In addition to the movement-therapeutic approach, a coordinated diet is necessary to avoid nutrition shortages.The evidence on physical activity in oncology must be considered not only in theory, but also in practice and be accepted as a general recommendation for oncology patients. The personalized OTT treatment concept represents a practical implementation and offers a targeted treatment option with low side effects.

ZusammenfassungEine der häufigsten Langzeitfolgen bei Krebsüberlebenden ist das Erschöpfungssyndrom, auch als „Cancer-Related Fatigue“ (CRF) bezeichnet. Eine Fatigue kann auch Jahre nach der Erkrankung noch bestehen bleiben und führt bei den Betroffenen zu erheblichen Einschränkungen des täglichen Lebens und der Lebensqualität. Bei der Behandlung einer chronischen Fatigue spielt die onkologische Bewegungstherapie eine entscheidende Rolle und konnte in mehreren Metaanalysen die stärkste Evidenz für eine erfolgreiche Symptombehandlung zeigen. Forschungsbedarf besteht jedoch weiterhin bezüglich einer optimalen Trainingssteuerung und Trainingsart, weshalb die multizentrische FatiGO-Studie konzipiert wurde, die die unmittelbare Wirksamkeit auf die Fatigue untersucht.

Background: Breast cancer is associated with many therapy-induced side effects that impact patients’ lives from diagnosis to long-term survivorship. Physical activity has become an important and proven supportive measure in treating side effects like loss of muscle strength, fatigue, chemotherapy-induced peripheral neuropathy, lymphedema, and loss of quality of life. Resistance training (RT) is an established exercise intervention for breast cancer patients, but the correct type, timing, intensity, and duration of exercise remain unclear. It is necessary to investigate different resistance training interventions and their effects on breast cancer patients by covering all stages of treatment, beginning with prehabilitation, through the period of acute therapy, to long-term survivorship. Conclusion: Upon evaluation of randomized controlled trials (RCTs) from the past decade, RT was found to be feasible and safe. Furthermore, there is evidence on the impact of RT on muscle strength, CRF and QoL amongst other factors. Studies implementing mixes of aerobic and strength exercises are rather common, but RCTs of RT-only protocols remain scarce. Different strength training protocols at distinct stages of breast cancer treatment have been conducted, but with the complexity of treatments and the variety of training styles, a large field of study remains. Key Messages: Although the overall data on RT for breast cancer patients has increased, there are many different methodological approaches and testing measures as well as gaps in study documentation. There is still very little of the evidence that would facilitate the compilation of standardized and individualized guidelines.