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Efficient transdisciplinary cooperation promotes the rapid discovery and clinical application of new technologies, especially in the competitive sector of oncology. In this review, written from a clinical-scientist point of view, we used glioblastoma—the most common and most aggressive primary brain tumor as a model disease with a largely unmet clinical need, despite decades of intensive research—to promote transdisciplinary medicine. Glioblastoma stem-like cells (GSCs), a special tumoral cell population analogue to healthy stem cells, are considered largely responsible for the progression of the disease and the mediation of therapy resistance. The presented work followed the concept of translational science, which generates the theoretical backbones of translational research projects, and aimed to close the preclinical gap between basic research and clinical application. Thus, this generated an integrated translational precision medicine pipeline model based on recent theoretical and experimental publications, which supports the accelerated discovery and development of new paths in the treatment of GSCs. The work may be of interest to the general field of precision medicine beyond the field of neuro-oncology such as in Cancer Neuroscience.

AbstractObjectiveTo evaluate whether a structured exercise programme improved functional and health related quality of life outcomes compared with usual care for women at high risk of upper limb disability after breast cancer surgery.DesignMulticentre, pragmatic, superiority, randomised controlled trial with economic evaluation.Setting17 UK National Health Service cancer centres.Participants392 women undergoing breast cancer surgery, at risk of postoperative upper limb morbidity, randomised (1:1) to usual care with structured exercise (n=196) or usual care alone (n=196).InterventionsUsual care (information leaflets) only or usual care plus a physiotherapy led exercise programme, incorporating stretching, strengthening, physical activity, and behavioural change techniques to support adherence to exercise, introduced at 7-10 days postoperatively, with two further appointments at one and three months.Main outcome measuresDisability of Arm, Hand and Shoulder (DASH) questionnaire at 12 months, analysed by intention to treat. Secondary outcomes included DASH subscales, pain, complications, health related quality of life, and resource use, from a health and personal social services perspective.ResultsBetween 26 January 2016 and 31 July 2017, 951 patients were screened and 392 (mean age 58.1 years) were randomly allocated, with 382 (97%) eligible for intention to treat analysis. 181 (95%) of 191 participants allocated to exercise attended at least one appointment. Upper limb function improved after exercise compared with usual care (mean DASH 16.3 (SD 17.6) for exercise (n=132); 23.7 (22.9) usual care (n=138); adjusted mean difference 7.81, 95% confidence interval 3.17 to 12.44; P=0.001). Secondary outcomes favoured exercise over usual care, with lower pain intensity at 12 months (adjusted mean difference on numerical rating scale −0.68, −1.23 to −0.12; P=0.02) and fewer arm disability symptoms at 12 months (adjusted mean difference on Functional Assessment of Cancer Therapy-Breast+4 (FACT-B+4) −2.02, −3.11 to −0.93; P=0.001). No increase in complications, lymphoedema, or adverse events was noted in participants allocated to exercise. Exercise accrued lower costs per patient (on average −£387 (€457; $533) (95% confidence interval −£2491 to £1718; 2015 pricing) and was cost effective compared with usual care.ConclusionsThe PROSPER exercise programme was clinically effective and cost effective and reduced upper limb disability one year after breast cancer treatment in patients at risk of treatment related postoperative complications.Trial registrationISRCTN Registry ISRCTN35358984.

Background Most advanced elderly cancer patients experience fatigue, anorexia, and declining physical function due to cancer cachexia, for which effective interventions have not been established. We performed a phase I study of a new nonpharmacological multimodal intervention called the nutritional and exercise treatment for advanced cancer (NEXTAC) program and reported the excellent feasibility of and compliance with this program in elderly patients with advanced cancer who were at risk for cancer cachexia. We report here the background, hypothesis, and design of the next-step multicenter, randomized phase II study to evaluate the efficacy of the program, the NEXTAC-TWO study. Methods Patients with chemo-naïve advanced non-small cell lung cancer or pancreatic cancer, age ≥ 70 years, performance status ≤2, with adequate organ function and without disability according to the modified Katz index will be eligible. In total, 130 participants will be recruited from 15 Japanese institutions and will be randomized into either the intervention group or a control group. Computer-generated random numbers are allocated to each participant. Stratification factors include performance status (0 to 1 vs. 2), site of primary cancer (lung vs. pancreas), stage (III vs. IV), and type of chemotherapy (cytotoxic vs. others). Interventions and assessment will be performed 4 times every 4 ± 2 weeks from the date of randomization. Interventions will consist of nutritional counseling, nutritional supplements (rich in branched-chain amino acids), and a home-based exercise program. The exercise program will include low-intensity daily muscle training and lifestyle education to promote physical activity. The primary endpoint is disability-free survival. It is defined as the period from the date of randomization to the date of developing disability or death due to any cause. This trial also plans to evaluate the improvements in nutritional status, physical condition, quality of life, activities of daily living, overall survival, and safety as secondary endpoints. Enrollment began in August 2017. The study results will demonstrate the efficacy of multimodal interventions for elderly cancer patients and their application for the maintenance of physical and nutritional conditions in patients with cancer cachexia. This work is supported by a grant-in-aid from the Japan Agency for Medical Research and Development. Discussion This is the first randomized trial to evaluate the efficacy and safety of a multimodal intervention specific for elderly patients with advanced cancer. Trial registration Registered at August 23, 2017. Registry number: UMIN000028801 .

Background Exercise is an effective strategy to improve quality of life and physical fitness in breast cancer survivors; however, few studies have focused on the early survivorship period, minorities, physically inactive and obese women, or tested a combined exercise program and measured bone health. Here, we report the effects of a 16-week aerobic and resistance exercise intervention on patient-reported outcomes, physical fitness, and bone health in ethnically diverse, physically inactive, overweight or obese breast cancer survivors. Methods One hundred breast cancer survivors within 6 months of completing adjuvant treatment were assessed at baseline, post-intervention, and 3-month follow-up (exercise group only) for physical fitness, bone mineral density, serum concentrations of bone biomarkers, and quality of life. The exercise intervention consisted of moderate-vigorous (65–85% heart rate maximum) aerobic and resistance exercise thrice weekly for 16 weeks. Differences in mean changes for outcomes were evaluated using mixed-model repeated measure analysis. Results At post-intervention, the exercise group was superior to usual care for quality of life (between group difference: 14.7, 95% CI: 18.2, 9.7; p  < 0.001), fatigue (p < 0.001), depression (p < 0.001), estimated VO 2max (p < 0.001), muscular strength (p < 0.001), osteocalcin ( p  = 0.01), and BSAP ( p  = 0.001). At 3-month follow-up, all patient-reported outcomes and physical fitness variables remained significantly improved compared to baseline in the exercise group ( p  < 0.01). Conclusions A 16-week combined aerobic and resistance exercise program designed to address metabolic syndrome in ethnically-diverse overweight or obese breast cancer survivors also significantly improved quality of life and physical fitness. Our findings further support the inclusion of supervised clinical exercise programs into breast cancer treatment and care. Trial registration This trial is registered on ClinicalTrials.gov: NCT01140282 as of June 9, 2010.

Background Patients with breast cancer undergoing chemotherapy and radiotherapy experience fatigue and other treatment side effects. Integrative therapies combining physical activity and dietary counseling are recommended; however to date no large randomized controlled trial has been conducted during adjuvant therapy. The Adapted Physical Activity and Diet (APAD) intervention was evaluated for its ability to decrease fatigue (primary outcome), anxiety, depression, body mass index (BMI), and fat mass, and enhance muscular and cognitive performances, and quality-of-life (QoL). Methods Women diagnosed with early breast cancer ( N  = 143, mean age = 52 ± 10 years) were randomized to APAD or usual care (UC). APAD included thrice-weekly moderate-intensity mixed aerobic and resistance exercise sessions and 9 dietetic consultations. Patient-reported outcomes (PROs) and anthropometric, muscular, and cognitive variables were measured at baseline, 18 weeks (end of chemotherapy), and 26 weeks (end of radiotherapy and intervention), and at 6- and 12-month post-intervention follow-ups. Multi-adjusted linear mixed-effects models were used to compare groups over time. Results Significant beneficial effects of the APAD intervention were observed on all PROs (i.e., fatigue, QoL, anxiety, depression) at 18 and 26 weeks. The significant effect on fatigue and QoL persisted up to 12-month follow-up. Significant decreases in BMI, fat mass, and increased muscle endurance and cognitive flexibility were observed at 26 weeks, but did not persist afterward. Leisure physical activity was enhanced in the APAD group vs UC group at 18 and 26 weeks. No significant effect of the intervention was found on major macronutrients intake. Conclusions A combined diet and exercise intervention during chemotherapy and radiotherapy in patients with early breast cancer led to positive changes in a range of psychological, physiological and behavioral outcomes at the end of intervention. A beneficial effect persisted on fatigue and QoL at long term, i.e., 1 year post-intervention. Diet-exercise supportive care should be integrated into the management of early breast cancer patients. Trial registration The APAD study was prospectively registered on ClinicalTrials.gov ( NCT01495650 ; date of registration: December 20, 2011).

Purpose Breast cancer surgery may be associated with pain and physical symptoms in the upper limbs. Functional impairment and pain-related avoidance of movement may further increase disability level. This study aimed to investigate the potential effects of early postoperative virtual reality (VR) therapy on pain, range of motion (ROM), muscle strength, functionality, and fear of movement. Methods Forty women with breast cancer who had undergone unilateral mastectomy with axillary lymph node dissection and who were receiving adjuvant therapy were included in the study and randomly assigned to two groups: the Kinect-based rehabilitation group (KBRG) and the standardized physical therapy group (SPTG). The KBRG ( n  = 20) received VR therapy using Xbox Kinect-based games and the SPTG ( n  = 20) received standard physiotherapy. Study subjects were assessed at baseline and after the 6-week treatment. Outcome measures were pain (visual analogue scale), grip strength (dynamometer), functionality (disabilities of the arm shoulder and hand questionnaire), muscle strength (handheld dynamometer), ROM (digital goniometer), and fear of movement (Tampa kinesiophobia scale (TKS)). Results Both groups detected s ignificant changes in pain, ROM, muscle strength, grip strength, functionality, and TKS scores after the treatment ( p  < 0.01). Fear of movement was significantly improved in the KBRG and the SPTG displayed more improvement in functionality ( p  < 0.05). There were no differences in ROM, muscle strength, grip strength, and pain between the groups after the treatment ( p  > 0.05). Conclusion Kinect-based VR therapy resulted in significant outcomes that were comparable to those obtained under standard physiotherapy in the early postoperative phase in patients who had undergone breast cancer surgery. Trial registration This study is registered at ClinicalTrials.gov ( ClinicalTrials.gov identifier: NCT03618433).

Purpose This study aimed to compare the effects of virtual reality (VR) training and resistance exercises training on lymphedema symptom severity as well as physical functioning and QoL in women with breast cancer–related lymphedema (BCRL). Methods In a single blinded randomized trial, women diagnosed with unilateral BCRL were randomly divided into two groups: the Xbox Kinect group received VR Kinect-based games ( n  = 30) and resistance exercise group received resistance training ( n  = 30). In addition, both groups received complex decongestive physiotherapy (manual lymphatic drainage, compression bandages, skin care, and exercises). The intervention was conducted five sessions per week for 8 weeks. The outcome measures included excessive limb volume, visual analogue scale (VAS), the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire, shoulder range of motion (ROM), shoulder muscles strength, hand grip strength, and Study Short-Form (SF-36). The outcomes were evaluated pre and post intervention (week 8). Results Statistical significant differences were recorded in VAS (pain intensity), DASH, shoulder ROM ( p  < 0.001), bodily pain ( p  = 0.002), general health ( p  < 0.001), and vitality ( p  = 0.006) in favor of the Xbox Kinect group. However, there were statistically significant differences in shoulder flexion strength ( p  = 0.002), external rotation strength ( p  = 0.004), and abduction strength and handgrip strength ( p  < 0.001) in favor of the resistance exercise group. Conclusions The VR training was superior to resistance exercises training in BCRL management. The empirical findings support the VR as a new effective and encouraging intervention modality which can assist in improving physical functioning and quality of life in women with BCRL. Trial registration This study is retrospectively registered at ClinicalTrials.gov (ID: NCT04724356).

Background This study evaluated the impact of an exercise program on quality of life in older breast cancer survivors undergoing aromatase inhibitor therapy. Methods Older breast cancer survivors were randomized into two groups: combined training: resistance + aerobic exercise program for nine months ( n  = 18) or control group ( n  = 18). Quality of life was assessed by the questionnaires SF36, EORTC QLQ-C30, and EORTC QLQ-BR23 at baseline, and at three, six, and nine months. The exercise group performed 40 min of resistance exercises on machines followed by 30 min of aerobic training on a treadmill 3x/wk. Repeated measures ANOVA was used to compare the groups over time. Results Significant time x group interactions and moderate to high effect sizes were found for physical functioning, physical health, bodily pain, general health perception, vitality, social functioning, fatigue, sleep disturbance, body image, and upset by hair loss, favoring the exercise group. Conclusion This study demonstrated the potential benefits and high clinical relevance of exercise programs to improve quality of life in older breast cancer survivors undergoing aromatase inhibitor therapy.

Background Breast cancer (BC) is the most common type of cancer in women worldwide. Post-treatment, patients suffer from side effects and have various rehabilitation needs, which means that individualization is fundamental for optimal rehabilitation. This systematic review (SR) of SRs aims to evaluate the current evidence on rehabilitation interventions in female patients following BC treatment. Methods Full-text SRs published in English from 2009 were searched in Embase, PubMed, Cinahl Complete, PsycINFO, AMED, SCOPUS, and Cochrane Library. Inclusion criteria: SRs of randomized or non-randomized controlled trials investigating the effects of rehabilitation interventions in women following BC treatment. All outcomes were considered. Methodological quality was evaluated using the AMSTAR 2 tool and interrater agreement was evaluated. Out of 1269 citations retrieved, 37 SRs were included. Results Five rehabilitation areas were identified: exercise and physical activity (PA), complementary and alternative medicine (CAM), yoga, lymphoedema treatment, and psychosocial interventions. The most solid evidence was found in exercise/PA and yoga. Exercise interventions improved outcomes such as shoulder mobility, lymphoedema, pain, fatigue and quality of life (QoL). Effects of yoga were shown on QoL, anxiety, depression, sleep disturbance, fatigue and gastrointestinal symptoms. The effect of CAM was shown on nausea, pain, fatigue, anger and anxiety but these results need to be interpreted with caution because of low methodological quality in included studies in the SRs. Among the lymphoedema treatments, positive effects were seen for resistance training on volume reduction and muscle strength and psychosocial interventions such as cognitive behavioural therapy had positive effects on QoL, anxiety, depression and mood disturbance. Conclusions This SR of SRs show solid positive effects of exercise/PA and yoga for women following BC treatment, and provides extended knowledge of the effects of CAM, yoga, lymphoedema treatment and psychosocial interventions. It is evident that more than one intervention could have positive effects on a specific symptom and that the effects depend not only on intervention type but also on how and when the intervention is provided. The results can be used as a foundation for individualized rehabilitation and aid health care professionals in meeting patients’ individual needs and preferences. Trial registration PROSPERO ( CRD42017060912 ).