Evaluation of a psychoneurological symptom cluster in patients with breast or digestive cancer: a longitudinal observational study

The presence of one psychoneurological symptom cluster (PNSC) composed of cancer-related fatigue (CRF), sleep difficulties, emotional distress, and pain is particularly well-documented among patients with cancer [1‐3]. Cognitive impairments are also frequently associated with this symptom cluster [4, 5]. CRF is a distressing, persistent, and subjective feeling of physical, emotional and/or cognitive tiredness or exhaustion, which is related to cancer or its treatment. It is not proportional to the person’s recent activity and interferes with their routine functioning [6]. This multidimensional symptom is considered as the most severe one endured by patients with cancer, having a high impact on their quality of life (QOL) [7‐9]. Yet, few attention has been received from the healthcare professionals [10]. Emotional distress (i.e., anxiety and depression), sleep difficulties (i.e., generally insomnia), pain, and cognitive difficulties (e.g., concentration or memory difficulties) are also very common among these patients and negatively influence their QOL [11]. In addition to their own negative consequences, these symptoms evolve together and reinforce each other, participating resulting in the high burden endured by patients with cancer [2, 12]. The mechanisms involved in the PNSC are uncertain [13, 14], but it is known that the more symptoms the patient presents, the lower their QOL [15]. Despite their severe impact and their persistence up to years after treatment completion, these symptoms remain underdiagnosed and undertreated [16]. The configuration of the PNSC (e.g., intensity of the relationships between different symptoms, core/central symptom of the cluster) seems to vary according to the cancer diagnosis [1, 2] and to evolve over time [17, 18]. Most studies in oncology focused on a single symptom, or on several symptoms considered independently from each other [3, 11, 19, 20]. However, the high prevalence of the PNSC underlines the relevance of studying multiple symptoms and their interactions.

Network analysis is an innovative method that underlines a deeper understanding of the connections between symptoms. By assessing and visualizing symptom clusters as dynamic systems of interacting symptoms, these analyses allow to study symptoms in their full complexity [1, 2, 12, 18] and to compare patterns of clustering between distinct populations [2, 21] or measurement times [1, 18]. Core symptoms within a network are the ones with the strongest associations with the other symptoms, which may play a critical role in activating them [22]. Thus, targeting them could allow to design more cost-effective interventions to impact the whole cluster [1‐3, 11, 17, 18, 20, 23]. As network analyses in symptom studies are scarce, there is no consensus regarding the core symptom of the PNSC yet, as it seems to vary according to the population studied, the phase of the cancer trajectory, and the methodology used. Depression [1, 20], CRF [2, 15, 18], distress [3, 17], or anxiety [23] have been recurrently shown to be the core symptoms in studies on patients with cancer.

Cancer symptom management has often consisted in a “single symptom approach”, with the prescription of one specific intervention for each symptom reported by the patient, leading to complicated self-management of symptoms [11]. In the context of symptom clusters, interventions with benefits on one than more symptoms are thus highly relevant. Approaches such as mind-body techniques [11, 24‐27], self-compassion learning [26‐30], and cognitive-behavioural therapy [11] are relevant components to be included in such interventions. Different studies [10, 31‐34] also suggested that the common-sense model of self-regulation of health and illness of Leventhal [31] (Fig. 1) could serve as a basis for developing interventions for cancer survivors, by targeting dysfunctional representations (top-down strategy) and enhancing adaptive coping (bottom-up strategy).

The studies discussed above however suffer from several limitations. First, literature on symptom clusters in oncology is heterogeneous, due to the different statistical procedures used, cancer diagnosis included, symptoms considered, and time since diagnosis. Most of them have been conducted during or shortly after treatment (i.e., generally up to one year), whereas symptoms can develop lately and persist for years after treatment [16]. Second, most of them were cross-sectional and lacked of a longitudinal evaluation of the symptom clusters [20]. Thus, there is a need for rigorous studies investigating the presence and evolution of the PNSC among distinct populations of cancer survivors [35]. There is also a critical need for cost-effective personalized interventions to alleviate these symptoms [18, 35]. Targeting a core symptom, determined for a specific population, to impact the whole PNSC seems to be of particular interest in oncology, and responds to the need for more personalized care.

This study will consist of a longitudinal observational study that will assess the evolution of the PNSC (i.e., CRF, emotional distress, pain, sleep difficulties) in two cohorts of patients who had cancer (women with breast cancer and patients with digestive cancer), over two years, through network analyses. Evolution of other common symptoms (e.g., cognitive difficulties, nausea/vomiting, appetite loss), QOL, coping strategies, and self-compassion will be assessed in parallel. To note, the results from this study, especially the core symptom determined in each cohort, will be used in a future study to develop a new mind-body group intervention based on the common-sense model of self-regulation of health developed by Leventhal [31]. A randomized-controlled pilot trial will then be conducted to assess its feasibility and first benefits to improve the PNSC.