Predicting short-term treatment toxicity in head and neck cancer through a systematic review and meta-analysis

Introduction: Frailty is a recognized condition associated with poorer outcomes in patients with head and neck cancer (HNC). The objective of this study was to ascertain the prognostic significance of various frailty metrics on short-term treatment toxicity in patients with HNC undergoing curative-intent therapy.

Materials and methods: A systematic review was performed searching multiple databases. An inverse-variation, random-effects model was used to perform the meta-analysis to evaluate the prognostic significance of various frailty metrics on short-term treatment-related toxicity in this population.

Results: A total of 292,560 patients with HNC originating from 36 observational studies were analyzed. The most frequently reported frailty metrics were the modified frailty index (mFI), Geriatric 8 questionnaire (G8), Adjusted Clinical Groups (ACG), Groningen Frailty Indicator (GFI), and comprehensive geriatric assessment (CGA). The overall prevalence of frailty using any metric in all included studies was 7.5 %. The combined odds ratio (OR) for short-term treatment toxicity using the mFI was 2.60 (95 % CI of 1.81-3.72), G8 2.69 (95 % CI 1.37-5.28), ACG 3.43 (95 %CI 2.52-4.67), GFI 2.71 (95 % CI 1.11-6.62), and CGA 3.36 (95 % CI 1.18-9.53). The association of frailty with short-term treatment toxicity using various frailty metrics was more pronounced in patients with upfront surgery (OR 3.00, 95 %CI of 2.35-3.81) compared to definitive (chemo)radiotherapy 2.64 (95 % CI 1.04-6.68).

Discussion: Various frailty metrics exists in the HNC literature, with the most common being the mFI, G8, ACG, GFI, and CGA. Patients with HNC and frailty are more than twice as likely to suffer a short-term treatment-related toxicity when undergoing curative-intent HNC treatment than patients without frailty. This effect is more pronounced in patients undergoing upfront surgery.