Long-term Survivorship Challenges of Advanced/Metastatic GIST Patients Responding to Tyrosine Kinase Inhibitor Treatment: an Observational Study

Gastrointestinal stromal tumour (GIST) is a rare malignancy for which long-term treatment with tyrosine kinase inhibitors (TKIs), particularly imatinib, has substantially improved survival. As a result, an increasing number of patients live with advanced or metastatic disease under chronic TKI therapy, highlighting the need to better understand long-term survivorship, including health-related quality of life (HRQoL), treatment burden, and clinical outcomes.

This study is an international, multicentre observational study consisting of two components:

1. a retrospective cross-sectional study and 2. a prospective observational cohort (registry).

Study design and population

The retrospective component includes patients with unresectable or metastatic GIST receiving long-term TKI treatment (≥5 years). This component aims to evaluate the relevance and applicability of patient-reported outcome (PRO) instruments and to identify GIST-specific survivorship issues.

The prospective cohort includes patients with advanced or metastatic GIST who have received TKI therapy for at least 2 years. Participants will be enrolled across multiple centres in Europe and China.

Data collection

Data collection includes both patient-reported outcomes and clinical data.

Patient-reported outcomes are collected using validated questionnaires and study-specific item lists assessing HRQoL, survivorship issues, coping, and financial impact.

Clinical data are extracted from medical records and include disease characteristics, treatment history, tumour response, survival outcomes, and adverse events.

Follow-up

In the prospective cohort, participants will complete questionnaires at baseline and at annual follow-up assessments for up to 10 years. Clinical data will be collected longitudinally in parallel with routine care.

For patients who discontinue TKI therapy, reasons for discontinuation and subsequent clinical outcomes, including possible re-initiation of treatment, will be documented.

Study objectives

The primary objective is to determine the prevalence, risk factors, and longitudinal course of HRQoL problems among patients with unresectable or metastatic GIST receiving TKI therapy.

Secondary objectives include identifying factors associated with prolonged treatment and survival, describing clinical practice patterns, assessing treatment satisfaction and discontinuation, and evaluating outcomes following TKI interruption and re-introduction.

Ethical considerations

This is a non-interventional study. Participants will receive standard of care only. Study procedures consist primarily of questionnaire completion and data collection from medical records, representing minimal risk. Participants may withdraw at any time. Although no direct clinical benefit is expected, the study aims to generate knowledge to improve survivorship care for patients with GIST.

• Health-Related Quality of Life measured by EORTC QLQ-C30 [Time frame: Baseline and scheduled follow-up assessments (every year for 10 years)]
• Survivorship issues measured by EORTC QLQ-SURV100 [Time frame: Baseline and scheduled follow-up assessments (every year for 10 years)]
• Health status measured by EQ-5D-5L [Time frame: Baseline and at all scheduled follow-up assessments (every year for 10 years)]
• Overall Survival (OS) [Time frame: From diagnosis to death or last follow-up (follow-up will be 10 years)]
• Progression-Free Survival (PFS) [Time frame: From start of TKI treatment to progression, death, or last follow-up (follow-up is 10 years)]
• Tumour response assessed by RECIST [Time frame: At each radiologic assessment, annually up to 10 years.]
• Reasons for discontinuation of tyrosine kinase inhibitor (TKI) treatment [Time frame: Annually up to 10 years.]
• Coping style measured by Threatening Medical Situations Inventory (TMSI) [Time frame: Baseline and annually up to 10 years.]
• Illness cognitions measured by Illness Cognition Questionnaire (ICQ) [Time frame: Baseline and annually up to 10 years.]
• Financial toxicity measured by Financial Index of Toxicity (FIT) [Time frame: Baseline, annually up to 10 years.]
• Work productivity loss measured by Productivity Cost Questionnaire [Time frame: Baseline, annually up to 10 years.]
• Healthcare utilization and informal care use measured by Medical Consumption Questionnaire [Time frame: Baseline, annually up to 10 years.]