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1.
Laurien J. Zeverijn Eleonora J. Looze Subotheni Thavaneswaran J. Maxime van Berge Henegouwen Robert J. Simes Louisa R. Hoes Katrin M. Sjoquist Hanneke van der Wijngaart Lucille Sebastian Birgit S. Geurts Chee K. Lee Gijsbrecht F. de Wit David Espinoza Paul Roepman Frank P. Lin Anne M. L. Jansen Wendy W. J. de Leng Vincent van der Noort Lindsay V. M. Leek Filip Y. F. L. de Vos Carla M. L. van Herpen Hans Gelderblom Henk M. W. Verheul David M. Thomas Emile E. Voest 《International journal of cancer. Journal international du cancer》2023,153(7):1413-1422
The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible. 相似文献
2.
Tryntsje Fokkema Robert Burggraaff Fred Hartgens Bas Kluitenberg Evert Verhagen Frank J.G. Backx Henk van der Worp Sita M.A. Bierma-Zeinstra Bart W. Koes Marienke van Middelkoop 《Journal of Science and Medicine in Sport》2019,22(3):259-263
Objectives
To investigate the prognosis and possible prognostic factors of running-related injuries (RRIs) in novice runners.Design
Prospective cohort study.Methods
Participants of Start to Run, a 6-weeks course for novice runners in The Netherlands, were asked to participate in this study. Before the start of the course a baseline questionnaire, on demographics, physical activity and perceived health, was sent to runners willing to participate. The 26- or 52-weeks follow-up questionnaires assessed information on RRIs and their duration. Only participants that sustained a RRI during follow-up were included in the analyses. An injury duration of 10 weeks or shorter was regarded as a relatively good prognosis, while an injury duration of more than 10 weeks was defined as a poor prognosis. To determine the associations between baseline characteristics and injury prognosis and between injury location and injury prognosis, multivariable logistic regression analyses were performed.Results
347 participants (48.8%) sustained an RRI during follow-up. The RRIs had an overall median duration of eight weeks (range: 1–52 weeks). Participants with a previous RRI were more likely to have a poor prognosis (OR 2.31; 95%CI 1.12–4.79), while a calf injury showed a trend towards an association with a relatively good prognosis (OR 0.49; 95%CI 0.22–1.11).Conclusions
The duration of RRIs in novice runners is relatively long, with only calf injuries being associated with a good prognosis. This emphasizes the need of injury prevention measures in novice runners and adequate support during and after an RRI, especially in runners with a previous injury. 相似文献3.
4.
Tryntsje Fokkema Fred Hartgens Bas Kluitenberg Evert Verhagen Frank J.G. Backx Henk van der Worp Sita M.A. Bierma-Zeinstra Bart W Koes Marienke van Middelkoop 《Journal of Science and Medicine in Sport》2019,22(1):106-111
Objectives
To determine the proportion of participants of a running program for novice runners that discontinued running and investigate the main reasons to discontinue and characteristics associated with discontinuation.Design
Prospective cohort study.Methods
The study included 774 participants of Start to Run, a 6-week running program for novice runners. Before the start of the program, participants filled-in a baseline questionnaire to collect information on demographics, physical activity and perceived health. The 26-weeks follow-up questionnaire was used to obtain information on the continuation of running (yes/no) and main reasons for discontinuation. To determine predictors for discontinuation of running, multivariable logistic regression was performed.Results
Within 26 weeks after the start of the 6-week running program, 29.5% of the novice runners (n = 225) had stopped running. The main reason for discontinuation was a running-related injury (n = 108, 48%). Being female (OR 1.74; 95% CI 1.13–2.68), being unsure about the continuation of running after the program (OR 2.06; 95% CI 1.31–3.24) and (almost) no alcohol use (OR 1.62; 95%CI 1.11–2.37) were associated with a higher chance of discontinuation of running. Previous running experience less than one year previously (OR 0.46; 95% CI 0.26–0.83) and a higher score on the RAND-36 subscale physical functioning (OR 0.98; 95% CI 0.96–0.99) were associated with a lower chance of discontinuation.Conclusions
In this group of novice runners, almost one-third stopped running within six months. A running-related injury was the main reason to stop running. Women with a low perceived physical functioning and without running experience were prone to discontinue running. 相似文献5.
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Medicine, Health Care and Philosophy - 相似文献
10.
Vincent van de Ven Chanju Lee Julia Lifanov Sarah Kochs Henk Jansma Peter De Weerd 《Hippocampus》2020,30(9):926-937
The hippocampus and dorsal striatum are both associated with temporal processing, but they are thought to play distinct roles. The hippocampus has been reported to contribute to storing temporal structure of events in memory, whereas the striatum contributes to temporal motor preparation and reward anticipation. Here, we asked whether the striatum cooperates with the hippocampus in processing the temporal context of memorized visual associations. In our task, participants were trained to implicitly form temporal expectations for one of two possible time intervals associated to specific cue‐target associations, and subsequently were scanned using ultra‐high‐field 7T functional magnetic resonance imaging. During scanning, learned temporal expectations could be violated when the pairs were presented at either the associated or not‐associated time intervals. When temporal expectations were met during testing trials, activity in left and right hippocampal subfields and right putamen decreased, compared to when temporal expectations were not met. Further, psycho‐physiological interactions showed that functional connectivity between left hippocampal subfields and caudate decreased when temporal expectations were not met. Our results indicate that the hippocampus and striatum cooperate to process implicit temporal expectation from mnemonic associations. Our findings provide further support for a hippocampal‐striatal network in temporal associative processing. 相似文献