45 Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors

Late effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Yet other than head and neck cancer (HNC) specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer(OPC). The National Comprehensive Cancer Network (NCCN) defines fatigue as “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning” [1]. It is one of the most prevalent and distressing late effects of cancer treatment [2,3]. Chronic fatigue is fatigue lasting for six months or more [4,5]. In a cross-sectional study of patients with HNC, a moderate-to-severe fatigue rate of 18% at least 1 year after radiotherapy was reported [6]. This is high in comparison to a prevalence rate in the general population of approximately 0.5-1% [7,8]. During head and neck radiotherapy normal brain tissues may receive a low radiation dose, and this could have a detrimental effect on neurocognitive function[9-11]. Several small retrospective HNC series report neurocognitive dysfunction within 2 years of treatment[12-14]. Observed cognitive decline appears to persist >5 years post-treatment[15-16] and memory problems, fatigue, anxiety and reduced QoL are reported in HNC survivors[17-22]. These studies are limited by small sample sizes, heterogeneity of HNC patients sampled or having a sole focus on nasopharyngeal cancer. In addition, neurocognition has often been assessed using screening tools which lack sensitivity and domain-specific information. In addition, previous studies have mostly had quantitative methodology[23], which although valuable, lacks contextual information on how late effects may impact on patients’ everyday lives. In view of the typical profile of patients with HPV OPC the need to preserve QoL is highly relevant. Therefore, we undertook the ROC-oN study (Radiotherapy for Oropharyngeal Cancer and impact on Neurocognition reference 22/WM/0207), a mixed method cross sectional study evaluating fatigue and neurocognitive function in patients following RT +/- chemotherapy for OPC and impact on QoL. This work is part of the multicentre study ROC-oN which was approved by the West Midlands Research Ethics Committee in October 2022 (22/WM/0207), evaluating fatigue and neurocognitive function in adult patients following radiotherapy +/- chemotherapy) for oropharyngeal cancer >/=24 months post-treatment and impact of these issues on quality of life. The full study involved patients with OPC being invited to complete a quantitative survey as well as an online, unsupervised cognitive test battery, after which a subset of participants were invited for qualitative interviews to investigate the lived experience of fatigue and neurocognitive deficits in survivors and impact on their daily lives. Semi-structured interviews were conducted and reflexive thematic analysis was performed. The NCCN definition of fatigue was adopted [1]. As both fatigue and neurocognition are multidimensional constructs, there is some overlap between the emotional and cognitive aspects of fatigue and neurocognitive function, and fatigue will impact on neurocognitive performance. For the purpose of this study, emotional/cognitive fatigue was considered a psychobiological state caused by demanding neurocognitive tasks, presenting as a feeling of tiredness, lack of energy, decreased motivation and alertness[24,25], while physical fatigue referred to the physical sensation of tiredness and impact of fatigue on physical activity[1,26]. A total of 257 ROC-oN study participants expressed an interest in being interviewed, of whom 33 were approached and 21 were interviewed. 11 men and 10 women participated, median age was 58 years and median time post-treatment was 5 years (inter quartile range 4-8 years). Interviews took on average 52 minutes (range 41-70minutes) and produced six themes with sub-themes Participants described fatigue that persisted beyond the acute period as well as changes in neurocognitive abilities across several neurocognitive domains with memory and attention commonly affected. This negatively influenced paid and unpaid work, as well as emotions and mood. Participants described navigating the new normal by adopting self-management strategies and accepting external support. They felt there was a lack of recognition of these late effects and expressed being poorly informed and unprepared for these. Follow up services were thought to be inadequate. Fatigue and neurocognitive impairment were frequently experienced by survivors of oropharyngeal cancer, at least two years after treatment. Emotional and cognitive fatigue were most affected, along with cognitive complaints across several domains, with a likely strong correlation between these late effects. Patients felt ill-prepared for these late sequelae, highlighting opportunities for the improvement of patient information and support services.

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