The diagnosis of cancer and the journey through oncology treatment exemplify the intricate and multifaceted nature of the psychobiosocial condition-a complex interplay where biological, psychological, and social factors are deeply intertwined, each shaping the course of the disease and influencing the burden of its symptoms [5][6]. The reality of living with cancer transcends the confines of mere physical illness or psychological turmoil; it is fundamentally shaped by the dynamic interplay between these domains, which ultimately dictates symptom intensity and the path to recovery [7].

Cancer-related fatigue (CRF) vividly illustrates this psychobiosocial dynamic. It impacts an astonishing 25-99% of patients undergoing active treatment and lingers in the lives of about 30% of survivors long after treatment has ended [8]. This pervasive fatigue cannot be understood solely through the lens of cellular damage or the toxic effects of treatments. Instead, it is exacerbated by the profound stress that triggers dysregulation within the autonomic nervous system, emotional strain that feels all-consuming, the isolating shadows of social disconnect, and the haunting specter of existential uncertainty. Within this context, each biological, psychological, and social component feeds into a self-reinforcing cycle, where the presence of one factor intensifies the others, creating a nuanced tapestry of challenges that shape the cancer experience [9][10].

The relationship between psychological stress and oncological processes is not a simple one, as revealed by cellular-level research studies. Winter et al. (2022) found that stress-induced mitochondrial dysfunction creates direct linkages between cellular respiration and apoptotic pathways [11]. This discovery highlights the complex bidirectional interactions between psychological state and physiological processes at the molecular level. It is an interesting mechanism that explains how chronic stress not only exacerbates symptoms but can potentially undermine biological recovery processes. In a study of Miaskowski et al. (2020), they found that during the COVID-19 pandemic, oncology patients reported significantly elevated stress, coupled with increased symptom severity—a pattern consistent with psychobiosocial amplification dynamics [12]. Symptom Amplification as Core Mechanism Beyond fatigue, oncology patients experience a broad symptom spectrum: emotional dysregulation, cognitive impairment ("chemo-brain"), pain, autonomic dysregulation, and sensory hypersensitivity. These amplified symptoms often show minimal direct correlation with tumor burden or treatment intensity. Nevertheless, they demonstrate strong sensitivity to stress exposure, emotional state, and social context [13][14].

This pattern suggests that symptom amplification—the magnification of symptoms through dysregulation of emotional and autonomic systems—represents a core mechanism in the oncological experience. The Symptom Amplification Model (SAM), a crucial tool in our understanding and measurement of these symptom dynamics, provides a framework for conceptualizing them [2]. SAM distinguishes arousal-mediated amplification (heightened sympathetic activation, emotional hyperreactivity) from depletion-mediated amplification (energy depletion, diminished recovery capacity). Both mechanisms are prominent in oncology populations and interact with biological disease effects to determine total symptom burden.

Psycho-Oncology is dedicated to understanding and treating the psychological, social, and behavioral dimensions of cancer [2][5][13]. Psychosocial interventions have demonstrated their efficacy in the management of pain, fatigue, and emotional distress in a heterogeneous group of patients with oncology [11][12]. However, integration of evidence-based psychological interventions into standard cancer care remains inconsistent, and many patients lack access to specialized psycho-oncological support [14][15].

ReAttach therapy offers a transdiagnostic intervention specifically designed to address emotional dysregulation and autonomic nervous system imbalance across diverse psychobiosocial conditions [1]. The intervention focuses on restoring co-regulation capacities and reducing both arousal-mediated and depletion-mediated symptom amplification-mechanisms that transcend specific diagnoses and represent core processes across a broad spectrum of conditions in which biological, psychological, and social factors interact. The application of ReAttach in oncology is part of a larger research program that investigates its effectiveness across psychobiosocial conditions. This protocol, alongside parallel investigations of persistent post-concussion syndrome [1] and fibromyalgia, establishes a coherent framework for examining whether identical transdiagnostic mechanisms demonstrate therapeutic efficacy across distinct clinical presentations sharing common psychobiosocial etiology. Measurement Challenge and Digital Innovation: The challenge in evaluating interventions for psychobiosocial conditions lies in capturing the dynamic, fluctuating nature of symptoms that vary temporally in response to stress, emotion, activity, and social context. Traditional outcome measures-episodic questionnaires administered at fixed timepoints-miss this temporal granularity and may underestimate therapeutic effects that manifest as improved regulatory capacity rather than complete symptom absence [2]. The NeuroLog platform addresses this measurement challenge by integrating continuous, patient-driven symptom monitoring with emotional state tracking and trigger documentation [2]. This research approach transforms subjective patients' experiences into quantifiable longitudinal data, rendering psychobiosocial interactions visible. As a result, the data will show how emotions influence symptoms, how triggers precipitate flares, and how recovery patterns vary. SAM, as a measurement framework, is particularly suited for psychobiosocial conditions because it explicitly models these multidimensional temporal relationships, encouraging the audience about the potential of ReAttach therapy to improve regulatory capacity.

The NeuroLog platform functions as a standardized digital protocol and methodological infrastructure for research on psychobiosocial conditions, offering a replicable framework for future clinical trials. This standardization directly addresses a longstanding challenge in psycho-oncology research: the lack of consistent measurement approaches across studies, which limits comparability, meta-analytic synthesis, and cross-study interpretation (Carlson, 2023). Within this protocol, daily symptom tracking uses uniform 1–10 severity scales to generate quantitative, comparable data across participants and conditions. For oncology populations, this enables systematic documentation of multidimensional symptom profiles, including fatigue, pain, cognitive difficulties, nausea, and emotional distress, while preserving individual variability. NeuroLog also incorporates structured flare-event documentation, including defined severity thresholds (≥8/10), temporal characteristics, identified triggers, and functional impact, transforming episodic symptom exacerbations into analyzable clinical events suitable for pattern recognition and predictive modelling. Emotional-state measurement follows a consistent categorization of affective domains—such as anxiety, frustration, sadness, hope, and contentment—each rated for intensity. This facilitates examination of temporal relationships between emotional states and symptom fluctuations, and supports cross-condition comparisons, for example, between oncology, post-concussion, and fibromyalgia populations. Additionally, the platform’s adaptive assessment features dynamically adjust questioning based on symptom patterns, reducing patient burden while maintaining data quality, an essential feature for oncology patients with high symptom load.

The standardized protocol offers significant advantages for replication and scalability. An identical digital infrastructure allows seamless implementation across research sites, enabling multi-centre trials and larger, more diverse samples. Longitudinal consistency in categories and scales supports extended tracking of symptom trajectories, which is critical for studying survivorship and long-term recovery. Shared methodology across studies also enables direct cross-condition comparison, strengthening the investigation of therapeutic mechanisms and phenotypic patterns. Furthermore, complete documentation of the digital protocol enhances methodological transparency and reproducibility, addressing concerns regarding variability in psychosocial oncology research [15].

For doctoral-level research, the NeuroLog infrastructure provides a unified measurement system that supports systematic investigation of ReAttach therapy across multiple psychobiosocial conditions. By applying the same assessment framework in oncology, post-concussion syndrome, and fibromyalgia populations, this approach facilitates the identification of therapeutic mechanisms, validation of arousal-and depletion-based phenotypes, exploration of dose-response relationships, and development of a coherent publication strategy across studies. In this way, the NeuroLog protocol transforms individual case series into an integrated and cumulative research programme, strengthening the empirical foundation for developing evidence-based, transdiagnostic interventions for psychobiosocial conditions.

Based on the extensive clinical experience of the researchers in implementing ReAttach therapy in neurological rehabilitation settings, the researchers propose the following practical framework for the oncology study:

All participants will continue to receive standard oncological care throughout the study period. The ReAttach intervention is intended to provide psychosocial support in addition to, not as a substitute for, medical treatment. Recognizing the vulnerability of cancer patients and the ethical obligation to ensure ongoing care, this study does not feature a non-treatment control period. Instead, comparisons will be made between each participant's baseline data and their postintervention results. This approach acknowledges the ethical concerns associated with withholding potentially beneficial psychosocial support from cancer patients, which outweigh any scientific benefits of a control condition. Additionally, it aligns with the ethical guidelines of psycho-oncology research, emphasizing patient welfare and the integration of supportive interventions within comprehensive cancer care. This within-subject design offers strong evidence while upholding the ethical standards necessary for caring for vulnerable populations facing significant symptom burdens.

Adults between the ages of 18 and 70 who have received a cancer diagnosis and are battling a combination of at least three ongoing symptoms such as debilitating headaches, persistent dizziness, overwhelming fatigue, pervasive pain, emotional turmoil, or profound grief will be invited to take part in this transformative study. Recruitment efforts will be conducted in a variety of ways: through the compassionate outreach of general practitioners, referrals from occupational therapists, and direct engagement with potential participants. To ensure a systematic approach, a detailed recruitment log will be meticulously maintained, documenting each step of participant enrollment. Individuals must exhibit a strong desire for therapeutic intervention and be willing to provide written informed consent, affirming their commitment to participate in this vital research.

Individuals experiencing acute psychiatric crises or those grappling with conditions that hinder their ability to engage, such as profound cognitive impairments that make reliable self-reporting impossible, may find it challenging to utilize smartphone-based applications effectively.

ReAttach face-to-face sessions will be combined with OT-care as usual (goal-directed activity coaching, energy management, and graded participation tasks).

Neurolog is an innovative digital platform meticulously crafted to unravel the intricate web of emotional, biological, and societal factors that shape symptom severity in biopsychosocial conditions. Leveraging the groundbreaking Symptom Amplification Model, this platform shines a light on subtle trends and patterns in patient presentations, equipping practitioners with invaluable insights to refine and elevate their clinical interventions. Patients are empowered to document their physical and emotional symptoms on an intuitive scale from 1 to 10, while noting any pertinent societal or environmental triggers that may contribute to their condition. This holistic approach provides a vivid portrait of how their health challenges affect daily life and the overall quality of life. Clinicians benefit from a user-friendly dashboard that delivers real-time insights, fostering a dynamic, collaborative relationship between patients and practitioners. With a commitment to privacy, all data is meticulously anonymized at the source and stored in compliance with General Data Protection Regulation, ensuring patient confidentiality remains a top priority.

The researchers' focus on data analysis will be on the intricate changes in symptom dynamics, regulatory capacity, and amplification patterns throughout the intervention period, harnessing the wealth of continuous, real-world data generated by NeuroLog. At the heart of this exploration lies the Symptom Amplification Model (SAM), which will function as our primary analytical framework. This model enables us to conduct a multidimensional assessment of the interplay between arousal and depletion, revealing how these phenomena evolve. Our main objective is to examine changes in SAM-derived amplification indices from baseline to the post-intervention phase. Key components of our analysis will include arousal-mediated amplification, which highlights the effects of sympathetic overactivation and emotional hyperreactivity, and depletion-mediated amplification, which sheds light on diminished energy availability and hindered recovery processes. Additionally, we will assess the composite amplification load, a critical indicator of overall regulatory imbalance. These indices will be meticulously calculated from a rich tapestry of longitudinal symptom ratings, nuanced tracking of emotional states, and the contextual triggers that accompany these experiences. Our goal is to paint a comprehensive picture of the dynamic landscape of symptoms and their regulation during the intervention.

Future research endeavors should embrace the rigor of randomized controlled trials to validate the effectiveness of ReAttach therapy specifically within oncology patients. It is essential to conduct long-term follow-up studies to assess the sustainability of treatment effects. Furthermore, it is vital to deepen our understanding of the underlying mechanisms of change by employing the Symptom Amplification Model and to evaluate how innovative, continuous realworld monitoring tools, such as NeuroLog, can facilitate a more tailored approach to personalized care. Lastly, studies that focus on the feasibility and implementation of this intervention in clinical practice, as well as those that capture patients' rich experiences, will be crucial for optimizing and scaling this transformative therapy.