Tormod Skogstad Nilsen

• Bøhn, Skh; Oldervoll, Line Merethe; Reinertsen, Kristin Valborg; Selland, Mette; Fosså, Alexander & Kiserud, Cecilie E. [Vis alle 17 forfattere av denne artikkelen] (2024). The feasibility of a multidimensional intervention in lymphoma survivors with chronic fatigue. Supportive Care in Cancer. ISSN 0941-4355. 32(1). doi: 10.1007/s00520-023-08204-5.
• Johansen, Merethe Lia; Eriksrud, Ola; Thorkildsen, Joachim; Norum, Ole-Jacob Anderssen; Wisløff, Torbjørn & Taksdal, Ingeborg [Vis alle 7 forfattere av denne artikkelen] (2023). Muscle strength characteristics following megaprosthetic knee reconstruction for bone sarcoma. Surgial oncology. ISSN 0960-7404. 48. doi: 10.1016/j.suronc.2023.101944. Fulltekst i vitenarkiv Vis sammendrag

  Objective: To assess muscle strength characteristics in patients with resection and megaprosthetic reconstruction of the knee for bone sarcoma compared to age- and sex-matched controls. Methods: This was a cross-sectional, case-control study. Muscle strength characteristics for knee extension and -flexion were assessed isokinetically at three different joint velocities: 60, 120 and 180°/s, and by the rate of force development (RDFmax) in knee extension. The Toronto Extremity Salvage Score (TESS) was used in patients. Results: Eighteen patients (91.6 months postop.) and 18 controls were included. Relative to controls, patients generated maximal torques of 19%, 23% and 23% in knee extension at 60, 120 and 180°/s, respectively. For knee flexion, patients generated maximal torques of 58%, 53% and 60% at 60, 120, and 180°/s, relative to the controls. RDFmax of the operated leg was 2.75 ± 2.13 N/ms, 7.16 ± 4.78 N/ms for the non-operated leg, and 7.95 ± 4.29 N/ms for the controls. The mean TESS score was 84.0. Conclusion: Patients reached approximately 20% of the maximal knee extension torque. In isometric assessments, they used double the amount of time to generate one-third of the maximal force compared to the controls despite good TESS scores.

• Gorski, Piotr Patryk; Raastad, Truls; Ullrich, Max; Turner, Daniel; Hallén, Jostein & Sarvari, Sebastian [Vis alle 8 forfattere av denne artikkelen] (2022). Aerobic Exercise Training Resets the Human Skeletal Muscle Methylome Ten Years after Breast Cancer Treatment and Survival. The FASEB Journal. ISSN 0892-6638. 37(1). doi: 10.1096/fj.202201510RR. Vis sammendrag

  Background: Cancer survivors suffer impairments in skeletal muscle in terms of reduced mass and function. Interestingly, human skeletal muscle possesses an epigenetic memory of earlier stimuli, such as exercise. Long-term retention of epigenetic changes in skeletal muscle following cancer survival and/or exercise training have not yet been studied. We therefore investigated genome-wide DNA methylation (methylome) in skeletal muscle following a 5-month, 3/week aerobic-training intervention in breast cancer survivors 10-14 years after diagnosis and treatment. These results were compared to breast cancer survivors who remained untrained and to age-matched controls with no history of cancer, who undertook the same training intervention. Methods: Skeletal muscle biopsies were obtained from 23 females before(pre) and after(post) the 5-month training period. InfiniumEPIC 850K DNA methylation arrays and RT-PCR for gene expression performed. Results: The breast cancer survivors displayed a significant retention of increased DNA methylation (i.e.,hypermethylation) at a larger number of differentially methylated positions (DMPs) compared with healthy age-matched controls pre-training. Training in cancer survivors led to an exaggerated number of DMPs with a hypermethylated signature occurring at non-regulatory regions compared with training in healthy age-matched controls. However, the opposite occurred in important gene regulatory regions, where training in cancer survivors elicited a considerable reduction in methylation (i.e.,hypomethylation) in 99% of the DMPs located in CpG islands within promoter regions. Importantly, training was able to reverse the hypermethylation identified in cancer survivors back towards a hypomethylated signature that was observed pre-training in healthy age-matched controls at 300 (out of 881) of these island/promoter associated CpGs. Pathway enrichment analysis identified training in cancer survivors evoked this predominantly hypomethylated signature in pathways associated with: Cell cycle, DNA replication/repair, transcription, translation, mTOR signalling and the proteosome. Differentially methylated region (DMR) analysis also identified genes: BAG1, BTG2, CHP1, KIFC1, MKL2, MTR, PEX11B, POLD2, S100A6, SNORD104 and SPG7 as hypermethylated in breast cancer survivors, with training reversing these CpG island/promoter associated DMRs towards a hypomethylated signature. Training also elicited a largely different epigenetic response in healthy individuals than that observed in cancer survivors, with very few overlapping changes. Only one gene, SIRT2, was identified as having altered methylation in cancer survivors at baseline and after training in both the cancer survivors and healthy controls. Conclusions: Human skeletal muscle muscle may retain a hypermethylated signature as long as 10-14 years after breast cancer treatment/survival. Five months of aerobic training reset the skeletal muscle methylome towards signatures identified in healthy age-matched individuals in gene regulatory regions.

• Nilsen, Tormod Skogstad; Johansen, Sara Hassing; Thorsen, Lene; Fairman, Ciaran M.; Wisløff, Torbjørn & Raastad, Truls (2022). Does Androgen Deprivation for Prostate Cancer Affect Normal Adaptation to Resistance Exercise? International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 19(7). doi: 10.3390/ijerph19073820. Fulltekst i vitenarkiv Vis sammendrag

  Background: Loss of muscle mass and muscle function is a common side effect from androgen deprivation therapy (ADT) for prostate cancer (PCa). Here, we explored effects of heavy-load resistance training (RT) on lean body mass and muscle strength changes reported in randomized controlled trials (RCTs) among PCa patients on ADT and in healthy elderly men (HEM), by comparison of results in separate meta-analysis. Methods: RCTs were identified through databases and reference lists. Results: Seven RCTs in PCa patients (n = 449), and nine in HEM (n = 305) were included. The effects of RT in lean body mass change were similar among PCa patients (Standardized mean difference (SMD): 0.4, 95% CI: 0.2, 0.7) and HEM (SMD: 0.5, 95% CI: 0.2, 0.7). It is noteworthy that the within group changes showed different patterns in PCa patients (intervention: 0.2 kg; control: −0.6 kg) and HEM (intervention: 1.2 kg; control: 0.2 kg). The effects of RT on change in muscle strength (measured as 1 RM) were similar between PCa patients and HEM, both for lower body- (PCa: SMD: 1.9, 95% CI: 1.2, 2.5; HEM: SMD: 2.2, 95% CI: 1.0, 3.4), and for upper body exercises (PCa: SMD: 2.0, 95% CI: 1.3, 2.7; HEM: SMD: 1.9, 95% CI: 1.3, 2.6). Conclusions: The effects of RT on lean body mass and 1 RM were similar in PCa patients on ADT and HEM, but the mechanism for the intervention effect might differ between groups. It seems that RT counteracts loss of lean body mass during ADT in PCa patients, as opposed to increasing lean body mass in HEM.

• Scott, Jessica M.; Thomas, Samantha M.; Herndon, James E.; Douglas, Pamela S.; Yu, Anthony F. & Rusch, Valerie [Vis alle 15 forfattere av denne artikkelen] (2021). Effects and tolerability of exercise therapy modality on cardiorespiratory fitness in lung cancer: a randomized controlled trial. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 12(6), s. 1456–1465. doi: 10.1002/jcsm.12828. Fulltekst i vitenarkiv Vis sammendrag

  Background: Poor cardiorespiratory fitness (CRF) is a cardinal feature of post-treatment primary lung cancer. The most effective exercise therapy regimen to improve CRF has not been determined. Methods: In this parallel-group factorial randomized controlled trial, lung cancer survivors with poor CRF (below age–sex sedentary values) were randomly allocated to receive 48 consecutive supervised sessions thrice weekly of (i) aerobic training (AT)—cycle ergometry at 55% to >95% of peak oxygen consumption (VO2peak); (ii) resistance training (RT)—lower and upper extremity exercises at 50–85% of maximal strength; (iii) combination training (CT)—AT plus RT; or (iv) stretching attention control (AC) for 16 weeks. The primary endpoint was change in CRF (VO2peak, mL O2·kg−1·min−1). Secondary endpoints were body composition, muscle strength, patient-reported outcomes, tolerability (relative dose intensity of exercise), and safety. Analysis of covariance determined change in primary and secondary endpoints from baseline to post-intervention (Week 17) with adjustment for baseline values of the endpoint and other relevant clinical covariates. Results: Ninety patients (65 ± 9 years; 66% female) were randomized (AT, n = 24; RT, n = 23; CT, n = 20; and AC, n = 23) of the planned n = 160. No serious adverse events were observed. For the overall cohort, the lost-to-follow-up rate was 10%. Mean attendance was ≥75% in all groups. In intention-to-treat analysis, VO2peak increased 1.1 mL O2·kg−1·min−1 [95% confidence interval (CI): 0.0, 2.2, P = 0.04] and 1.4 mL O2·kg−1·min−1 (95% CI: 0.2, 2.5, P = 0.02) in AT and CT, respectively, compared with AC. There was no difference in VO2peak change between RT and AC (−0.1 mL O2·kg−1·min−1, 95% CI: −1.2, 1.0, P = 0.88). Favourable improvements in maximal strength and body composition were observed in RT and CT groups compared with AT and AC groups (Ps < 0.05). No between-group changes were observed for any patient-reported outcomes. Relative dose intensity of exercise was lower in RT and CT compared with AT (Ps < 0.05). Conclusions: In the context of a smaller than planned sample size, AT and CT significantly improved VO2peak in lung cancer survivors; however, the tolerability-to-benefit ratio was superior for AT and hence may be the preferred modality to target impaired CRF in post-treatment lung cancer survivors.

• Fairman, Ciaran M.; Nilsen, Tormod Skogstad; Newton, Robert U.; Taaffe, Dennis R.; Spry, Nigel & Joseph, David [Vis alle 13 forfattere av denne artikkelen] (2020). Reporting of Resistance Training Dose, Adherence, and Tolerance in Exercise Oncology. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 52(2), s. 315–322. doi: 10.1249/MSS.0000000000002127. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: While general guidelines (such as CONSORT or Consensus on Exercise Reporting Template) exist to enhance the reporting of exercise interventions in the field of exercise science, there is inadequate detail facilitating the standardized reporting of resistance training adherence in the oncology setting. The purpose of this study was to apply a novel method to report resistance training dose, adherence, and tolerance in patients with cancer. Methods: A total of 47 prostate cancer patients (70.1 ± 8.9 yr, body mass index, 28.6 ± 4.0) with bone metastatic disease completed an exercise program for 12 wk. We assessed traditional metrics of adherence (attendance and loss to follow-up), in addition to novel proposed metrics (exercise-relative dose intensity, dose modification, and exercise interruption). Total training volume in kilograms (repetitions × sets × training load (weight)) was calculated for each patient. Results: Attendance assessed from traditional metrics was 79.5% ± 17.0% and four patients (9%) were lost to follow-up. The prescribed and actual cumulative total dose of resistance training was 139,886 ± 69,150 kg and 112,835 ± 83,499 kg, respectively, with a mean exercise-relative dose intensity of 77.4% ± 16.6% (range: 19.4% –99.4%). Resistance training was missed (1–2 consecutive sessions) or interrupted (missed ≥3 consecutive sessions) in 41 (87%) and 24 (51%) participants, respectively. Training dose was modified (reduction in sets, repetitions, or weight) in 40 (85%) of patients. Importantly, using attendance as a traditional metric of adherence, these sessions would have all counted as adherence to the protocol. Conclusions: Traditional reporting metrics of resistance training in exercise oncology may overestimate exercise adherence. Our proposed metrics to capture resistance training dose, adherence, and tolerance may have important applications for future studies and clinical practice.

• Scott, Jessica M; Li, Nan; Liu, Qi; Yasui, Yutaka; Leisenring, Wendy & Nathan, Paul C [Vis alle 15 forfattere av denne artikkelen] (2018). Association of Exercise with Mortality in Adult Survivors of Childhood Cancer. JAMA Oncology. ISSN 2374-2437. 4(10), s. 1352–1358. doi: 10.1001/jamaoncol.2018.2254. Vis sammendrag

  Importance: Adult survivors of childhood cancer are at excess risk for mortality compared with the general population. Whether exercise attenuates this risk is not known. Objective: To examine the association between vigorous exercise and change in exercise with mortality in adult survivors of childhood cancer. Design, Setting, and Participants: Multicenter cohort analysis among 15 450 adult cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970 and 1999 enrolled in the Childhood Cancer Survivor Study, with follow-up through December 31, 2013. Exposures: Self-reported vigorous exercise in metabolic equivalent task (MET) hours per week. The association between vigorous exercise and change in vigorous exercise and cause-specific mortality was assessed using multivariable piecewise exponential regression analysis to estimate rate ratios. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary end points were cause-specific mortality (recurrence/progression of primary malignant neoplasm and health-related mortality). Outcomes were assessed via the National Death Index. Results: The 15 450 survivors had a median age at interview of 25.9 years (interquartile range [IQR], 9.5 years) and were 52.8% male. During a median follow-up of 9.6 years (IQR, 15.5 years), 1063 deaths (811 health-related, 120 recurrence/progression of primary cancer, 132 external/unknown causes) were documented. At 15 years, the cumulative incidence of all-cause mortality was 11.7% (95% CI, 10.6%-12.8%) for those who exercised 0 MET-h/wk, 8.6% (95% CI, 7.4%-9.7%) for 3 to 6 MET-h/wk, 7.4% (95% CI, 6.2%-8.6%) for 9 to 12 MET-h/wk, and 8.0% (95% CI, 6.5%-9.5%) for 15 to 21 MET-h/wk (P < .001). There was a significant inverse association across quartiles of exercise and all-cause mortality after adjusting for chronic health conditions and treatment exposures (P = .02 for trend). Among a subset of 5689 survivors, increased exercise (mean [SD], 7.9 [4.4] MET-h/wk) over an 8-year period was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise (rate ratio, 0.60; 95% CI, 0.44-0.82; P = .001). Conclusions and Relevance: Vigorous exercise in early adulthood and increased exercise over 8 years was associated with lower risk of mortality in adult survivors of childhood cancer.

• Nilsen, Tormod Skogstad; Scott, Jessica M; Michalski, Meghan; Capaci, Catherine; Thomas, Samantha M & Herndon, James E [Vis alle 9 forfattere av denne artikkelen] (2018). Novel Methods for Reporting of Exercise Dose and Adherence: An Exploratory Analysis. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 50(6), s. 1134–1141. doi: 10.1249/MSS.0000000000001545. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: The purpose of this study was to explore whether methods adapted from oncology pharmacological trials have utility in reporting adherence (tolerability) of exercise treatment in cancer. Methods: Using a retrospective analysis of a randomized trial, 25 prostate cancer patients received an aerobic training regimen of 72 supervised treadmill walking sessions delivered thrice weekly between 55% and 100% of exercise capacity for 24 consecutive weeks. Treatment adherence (tolerability) was assessed using conventional (lost to follow-up and attendance) and exploratory (e.g., permanent discontinuation, dose modification, and relative dose intensity) outcomes. Results: The mean total cumulative ‘‘planned’’ and ‘‘completed’’ dose was 200.7 T 47.6 and 153.8 T 68.8 METIh, respectively, equating to a mean relative dose intensity of 77% T 24%. Two patients (8%) were lost to follow-up, and mean attendance was 79%. A total of 6 (24%) of 25 patients permanently discontinued aerobic training before week 24. Aerobic training was interrupted (missing Q3 consecutive sessions) or dose reduced in a total of 11 (44%) and 24 (96%) patients, respectively; a total 185 (10%) of 1800 training sessions required dose reduction owing to both health-related (all nonserious) and non–health-related adverse events. Eighteen (72%) patients required at least one session to be terminated early; a total of 59 (3%) sessions required early termination. Conclusions: Novel methods for the conduct and reporting of exercise treatment adherence and tolerability may provide important information beyond conventional metrics in patients with cancer.

• Sedliak, Milan; Zeman, Michal; Buzgó, Gabriel; Cvečka, Ján; Hamar, Dušan & Laczo, Eugen [Vis alle 15 forfattere av denne artikkelen] (2018). Morphological, molecular and hormonal adaptations to early morning versus afternoon resistance training. Chronobiology International. ISSN 0742-0528. 35(4), s. 450–464. doi: 10.1080/07420528.2017.1411360. Vis sammendrag

  It has been clearly established that maximal force and power is lower in the morning compared to noon or afternoon hours. This morning neuromuscular deficit can be diminished by regularly training in the morning hours. However, there is limited and contradictory information upon hypertrophic adaptations to time-of-day-specific resistance training. Moreover, no cellular or molecular mechanisms related to muscle hypertrophy adaptation have been studied with this respect. Therefore, the present study examined effects of the time-of-day-specific resistance training on muscle hypertrophy, phosphorylation of selected proteins, hormonal concentrations and neuromuscular performance. Twenty five previously untrained males were randomly divided into a morning group (n = 11, age 23 ± 2 yrs), afternoon group (n = 7, 24 ± 4 yrs) and control group (n = 7, 24 ± 3 yrs). Both the morning and afternoon group underwent hypertrophy-type of resistance training with 22 training sessions over an 11-week period performed between 07:30–08:30 h and 16:00–17:00 h, respectively. Isometric MVC was tested before and immediately after an acute loading exclusively during their training times before and after the training period. Before acute loadings, resting blood samples were drawn and analysed for plasma testosterone and cortisol. At each testing occasion, muscle biopsies from m. vastus lateralis were obtained before and 60 min after the acute loading. Muscle specimens were analysed for muscle fibre cross-sectional areas (CSA) and for phosphorylated p70S6K, rpS6, p38MAPK, Erk1/2, and eEF2. In addition, the right quadriceps femoris was scanned with MRI before and after the training period. The control group underwent the same testing, except for MRI, between 11:00 h and 13:00 h but did not train. Voluntary muscle strength increased significantly in both the morning and afternoon training group by 16.9% and 15.2 %, respectively. Also muscle hypertrophy occurred by 8.8% and 11.9% (MRI, p < 0.001) and at muscle fibre CSA level by 21% and 18% (p < 0.01) in the morning and afternoon group, respectively. No significant changes were found in controls within these parameters. Both pre- and post-training acute loadings induced a significant (p < 0.001) reduction in muscle strength in all groups, not affected by time of day or training. The post-loading phosphorylation of p70S6Thr421/Ser424 increased independent of the time of day in the pre-training condition, whereas it was significantly increased in the morning group only after the training period (p < 0.05). Phosphorylation of rpS6 and p38MAPK increased acutely both before and after training in a time-of-day independent manner (p < 0.05 at all occasions). Phosphorylation of p70S6Thr389, eEF2 and Erk1/2 did not change at any time point. No statistically significant correlations were found between changes in muscle fibre CSA, MRI and cell signalling data. Resting testosterone was not statistically different among groups at any time point. Resting cortisol declined significantly from pre- to post-training in all three groups (p < 0.05). In conclusion, similar levels of muscle strength and hypertrophy could be achieved regardless of time of the day in previously untrained men. However, at the level of skeletal muscle signalling, the extent of adaptation in some parameters may be time of day dependent.

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• Nilsen, Tormod Skogstad; Sæter, Mali; Sarvari, Sebastian; Reinertsen, Kristin Valborg; Johansen, Sara Hassing & Edvardsen, Elisabeth Rustad [Vis alle 17 forfattere av denne artikkelen] (2023). Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial. JMIR Research Protocols. ISSN 1929-0748. 12. doi: 10.2196/45244. Fulltekst i vitenarkiv

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