Assessing the validity of EQ-5D-5L in people with head & neck cancer: Does a generic quality of life measure perform as well as a disease-specific measure in a patient population?

BACKGROUND: Head and neck cancer (HNC) is an important cause of morbidity and mortality globally. Radical treatment methods may result in facial disfigurement and/or functional difficulties with subsequent adverse impacts on health-related quality of life (HRQoL). Guidelines suggest that HRQoL should be measured repeatedly throughout treatment to enable refined treatment protocols and tailored follow-up support but questionnaires are often long and burdensome. We compared condition-specific and generic metrics to assess HRQoL for people with this condition. METHODS: We used data from the prospective Head and Neck 5000 clinical cohort study - 5511 participants with a new diagnosis of HNC between 2011 and 2014. HRQoL data were collected at baseline from 2065 people who completed both the condition-specific EORTC-QLQ-C30 and the shorter, generic EQ-5D-5L questionnaires. RESULTS: There was strong evidence of association between comparable scales on each questionnaire at baseline: higher levels of functioning and lower levels of reported symptoms assessed with EQ-5D-5L were associated with lower EORTC-QLQ-C30 symptom scores. A moderate relationship (0.61) was found between overall QoL in the EQ-5D-5L index and self-perceived health (EQ VAS). CONCLUSIONS: HRQoL data collected from the generic EQ-5D-5L and cancer-specific EORTC-QLQ-C30 questionnaires are comparable at baseline for people diagnosed with HNC. This would allow a reduced burden of data collection but the EQ-5D-5L may not be sensitive to some condition-specific symptoms. Clinicians and researchers must clarify their aims and outcomes of interest before choosing their HRQoL measures. Further work is required to examine the ability to detect change in these measures over time.

Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis.

Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase-3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma.