Zoekresultaten

Prophylactic exercises among head and neck cancer patients during and after swallowing sparing intensity modulated radiation: Adherence and exercise performance levels of a 12-week guided home-based program

The background and purpose of this paper is to investigate adherence, exercise performance levels and associated factors in head and neck cancer (HNC) patients participating in a guided home-based prophylactic exercise program during and after treatment [swallowing sparing intensity modulated radiation therapy (SW-IMRT)]. Fifty patients were included in the study. Adherence was defined as the percentage of patients who kept up exercising; exercise performance level was categorized as low: ≤1, moderate: 1–2, and high: ≥2 time(s) per day, on average. Associations between 6- and 12-week exercise performance levels and age, gender, tumour site and stage, treatment, intervention format (online or booklet), number of coaching sessions, and baseline HNC symptoms (EORTC-QLQ-H&N35) were investigated. Adherence rate at 6 weeks was 70% and decreased to 38% at 12 weeks. In addition, exercise performance levels decreased over time (during 6 weeks: 34% moderate and 26% high; during 12 weeks: 28% moderate and 18% high). The addition of chemotherapy to SW-IMRT [(C)SW-IMRT] significantly deteriorated exercise performance level. Adherence to a guided home-based prophylactic exercise program was high during (C)SW-IMRT, but dropped afterwards. Exercise performance level was negatively affected by chemotherapy in combination with SW-IMRT.

New approach methodologies (NAMs) for human-relevant biokinetics predictions

For almost fifteen years, the availability and regulatory acceptance of new approach methodologies (NAMs) to assess the absorption, distribution, metabolism and excretion (ADME/biokinetics) in chemical risk evaluations are a bottleneck. To enhance the field, a team of 24 experts from science, industry, and regulatory bodies, including new generation toxicologists, met at the Lorentz Centre in Leiden, The Netherlands. A range of possibilities for the use of NAMs for biokinetics in risk evaluations were formulated (for example to define species differences and human variation or to perform quantitative in vitro-in vivo extrapolations). To increase the regulatory use and acceptance of NAMs for biokinetics for these ADME considerations within risk evaluations, the development of test guidelines (protocols) and of overarching guidance documents is considered a critical step. To this end, a need for an expert group on biokinetics within the Organisation of Economic Cooperation and Development (OECD) to supervise this process was formulated. The workshop discussions revealed that method development is still required, particularly to adequately capture transporter mediated processes as well as to obtain cell models that reflect the physiology and kinetic characteristics of relevant organs. Developments in the fields of stem cells, organoids and organ-on-a-chip models provide promising tools to meet these research needs in the future.

Lymphedema and Trismus after Head and Neck Cancer, and the Impact on Body Image and Quality of Life

Background: To assess the prevalence of chronic lymphedema and trismus in patients > 6 months after head and neck cancer (HNC) treatment, and to explore how the severity of these conditions correlates with body image and quality of life. Methods: The cross-sectional sample included 59 patients, treated for HNC between six months to three years ago. Physical measurements were performed to assess the presence of external lymphedema and trismus (<36 mm). Furthermore, participants completed two questionnaires regarding body image (BIS) and quality of life (UW-QoL V4). Results: Lymphedema prevalence was 94.1% (95% CI 0.86–0.98), with a median severity score of 9 (range 0–24). Trismus prevalence in this sample was 1.2%. The median BIS score was 2, indicating a positive body image. The UW-QoL score showed a good QOL with a median of 100. Only the domain of saliva and overall related health had a lower median of 70 and 60, respectively. There was no correlation between lymphedema and body image (r = 0.08, p = 0.544). Patients with higher lymphedema scores reported poorer speech with a moderate correlation (r = −0.39, p = 0.003). Conclusion: Lymphedema is a highly prevalent, but moderately severe late side-effect of HNC with a limited impact on quality of life domains except for speech, in our cohort.

Association between computed tomography assessment of skeletal muscle index and muscle attenuation and chemotherapy intolerance in patients with head and neck cancer: preliminary results

Dysphagia, trismus and speech impairment following radiation-based treatment for advanced stage oropharyngeal carcinoma: a one-year prospective evaluation

OBJECTIVE: The objective was to assess swallowing, mouth opening and speech function during the first year after radiation-based treatment (RT(+)) after introduction of a dedicated preventive rehabilitation program for stage III-IV oropharyngeal carcinoma (OPC).METHODS: Swallowing, mouth opening and speech function were collected before and at six- and twelve-month follow-up after RT(+) for OPC as part of ongoing prospective assessments by speech-language pathologists .RESULTS: Objective and patient-perceived function deteriorated until 6 months and improved until 12 months after treatment, but did not return to baseline levels with 25%, 20% and 58% of the patients with objective dysphagia, trismus and speech problems, respectively. Feeding tube dependency and pneumonia prevalence was low.CONCLUSION: Despite successful implementation, a substantial proportion of patients still experience functional limitations after RT(+) for OPC, suggesting room for improvement of the current rehabilitation program. Pretreatment sarcopenia seems associated with worse functional outcomes and might be a relevant new target for rehabilitation strategies.

Drug-induced caspase 8 upregulation sensitises cisplatin-resistant ovarian carcinoma cells to rhTRAIL-induced apoptosis

Background: Drug resistance is a major problem in ovarian cancer. Triggering apoptosis using death ligands such as tumour necrosis factor-related apoptosis inducing ligand (TRAIL) might overcome chemoresistance. Methods: We investigated whether acquired cisplatin resistance affects sensitivity to recombinant human (rh) TRAIL alone or in combination with cisplatin in an ovarian cancer cell line model consisting of A2780 and its cisplatin-resistant subline CP70. Results: Combining cisplatin and rhTRAIL strongly enhanced apoptosis in both cell lines. CP70 expressed less caspase 8 protein, whereas mRNA levels were similar compared with A2780. Pre-exposure of particularly CP70 to cisplatin resulted in strongly elevated caspase 8 protein and mRNA levels. Caspase 8 mRNA turnover and protein stability in the presence or absence of cisplatin did not differ between both cell lines. Cisplatin-induced caspase 8 protein levels were essential for the rhTRAIL-sensitising effect as demonstrated using caspase 8 small-interfering RNA (siRNA) and caspase-8 overexpressing constructs. Cellular FLICE-inhibitory protein (c-FLIP) and p53 siRNA experiments showed that neither an altered caspase 8/c-FLIP ratio nor a p53-dependent increase in DR5 membrane expression following cisplatin were involved in rhTRAIL sensitisation. Conclusion: Cisplatin enhances rhTRAIL-induced apoptosis in cisplatin-resistant ovarian cancer cells, and induction of caspase 8 protein expression is the key factor of rhTRAIL sensitisation. © 2011 Cancer Research UK All rights reserved.