The goal of this observational study is to see how type 2 diabetes affects quality of life in cancer patients receiving immunotherapy. We want to know if patients with diabetes have a greater decline in quality of life over six months compared to those without. The main question we aim to answer is:

- How does quality of life change over six months in patients with versus without diabetes?

Participants will complete quality-of-life surveys at the start, then at 3 and 6 months. This will help us see if diabetes adds extra challenges during cancer treatment

Immune checkpoint inhibitors (ICIs) have transformed the management of multiple solid malignancies by improving survival and enabling durable disease control. By targeting inhibitory immune checkpoints such as PD-1, PD-L1, and CTLA-4, these therapies enhance anti-tumour immune responses. However, immune activation may also result in immune-related adverse events (irAEs), which can affect multiple organ systems and range from mild to life-threatening. As survival improves, long-term and chronic toxicities are increasingly recognised, highlighting the importance of patient-centred outcomes such as health-related quality of life (HRQoL).

Diabetes mellitus (DM) is a common comorbidity among patients with cancer and is associated with increased symptom burden, functional impairment, and reduced HRQoL. Type 2 diabetes (T2D) has also been associated with adverse cancer outcomes and may influence both the effectiveness and toxicity profile of systemic anticancer therapy, including ICIs. In addition, ICIs can induce immune-related diabetes mellitus (ir-DM), a rare but clinically significant form of new-onset insulin-dependent diabetes requiring lifelong insulin treatment. Despite its clinical relevance, the interaction between pre-existing diabetes, ICI therapy, and longitudinal HRQoL remains insufficiently characterised.

Although HRQoL is generally reported to remain stable during ICI therapy in unselected cancer populations, it is unknown whether similar patterns are observed in patients with pre-existing DM or in those who develop ir-DM during treatment. Given the metabolic, functional, and psychosocial burden associated with diabetes, this patient group may be particularly vulnerable to deterioration in HRQoL during immunotherapy.

The primary aim of this study is to compare longitudinal changes in HRQoL between patients with T2D and non-diabetic patients from baseline to 3 and 6 months after initiation of ICI therapy. The primary hypothesis is that patients with T2D will experience a greater decline in HRQoL over the first six months of treatment compared with non-diabetic patients.

This is a prospective, multicentre cohort study of adult cancer patients initiating ICI therapy. Data will be collected prospectively using a secure electronic case report form across participating centres.

At baseline, demographic characteristics, cancer type and stage, treatment intent and planned ICI regimen, diabetes status (no diabetes, type 1 diabetes, or type 2 diabetes), diabetes treatment status, performance status, and baseline patient-reported outcomes will be recorded.

During follow-up, data will be collected on ICI exposure, treatment discontinuation and reasons for discontinuation, immune-related adverse events, hospitalisations, disease progression, survival status, and the occurrence of immune-related diabetes mellitus.

Patient-reported outcomes will be assessed using the EORTC QLQ-C30 and EQ-5D-5L questionnaires in all participants, and the PAID questionnaire in participants with diabetes. Assessments will be performed at baseline and at 3 and 6 months after treatment initiation.

Immune-related diabetes mellitus will be defined as new-onset insulin-dependent diabetes occurring after initiation of ICI therapy and consistent with marked beta-cell failure, classified according to established international clinical recommendations.

This study will provide prospective real-world data on HRQoL trajectories and survival among cancer patients with and without diabetes receiving ICI therapy, and will estimate the incidence and clinical characteristics of immune-related diabetes mellitus in a nationwide setting.

Inclusion Criteria:

• Age ≥18 years.
• Histologically confirmed solid malignant tumor.
• Planned treatment with ICI monotherapy or dual-ICI combination therapy (metastatic, adjuvant, or neo-adjuvant settings).
• Previous systemic anticancer therapy other than ICI is allowed.
• Ability and willingness to provide written informed consent and to complete HRQoL questionnaires.
• Sufficient Danish language proficiency to read, and complete study questionnaires.

Exclusion Criteria:

• Previous ICI treatment within 6 months.
• Concurrent systemic anticancer therapy other than ICI.
• Declines or does not provide informed consent.
• Cognitive or physical impairment preventing valid consent or completion of patient-reported outcomes.

Adult patients with solid malignancies initiating immune checkpoint inhibitor therapy in routine clinical practice, with and without pre-existing type 2 diabetes.