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

Long-term Survivorship Challenges of Advanced/Metastatic GIST Patients Responding to Tyrosine Kinase Inhibitor Treatment: an Observational Study (EORTC-1944)

Gastrointestinal stromal tumours (GISTs) are rare malignancies arising along the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) have substantially improved survival for patients with unresectable or metastatic GIST. As a result, an increasing number of patients live with advanced disease under chronic TKI therapy, highlighting the need to understand long-term survivorship, including health-related quality of life (HRQoL), treatment burden, and clinical outcomes.

This international, multicentre observational study includes two components: a retrospective cross-sectional study to evaluate the relevance and applicability of patient-reported outcome instruments, and a prospective cohort to document long-term clinical outcomes, HRQoL, treatment patterns, and survivorship challenges.

Participants will include adults with advanced or metastatic GIST who have received TKI therapy for at least 2 years. Data will be collected from medical records and through validated patient-reported outcome questionnaires at baseline and annually for up to 10 years. This study aims to provide insight into HRQoL problems, treatment discontinuation, coping strategies, and the impact of financial toxicity among long-term survivors of GIST.

Study Overview

• Status: Recruiting
• Conditions: Gastrointenstinal Stromal Tumor (GIST)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 330

Contacts and Locations

• Study Contact: Name: Tessa van Amerongen, MSc, Drs.; Phone Number: 1476 +31 020 512 9111; Email: t.v.amerongen@nki.nl
• Study Contact Backup: Name: Olga Husson, Dr., Associate professor; Phone Number: +31 020 512 9111; Email: o.husson@nki.nl

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1066 CX
      • Recruiting
      • Antoni van Leeuwenhoek
      • Contact: Tessa van Amerongen, MSc, Drs.; Phone Number: 1476 +31 020 512 9111; Email: t.v.amerongen@nki.nl
      • Contact: Olga Husson, Dr., Associate professor; Phone Number: +31 020 512 9111; Email: o.husson@nki.nl
      • Principal Investigator: Olga Husson, Dr., Associate professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Advanced/metastatic GIST patients responding to tyrosine kinase inhibitor treatment

Exclusion criteria:

• Any psychiatric condition or cognitive impairment that would hamper completion of self-reported questionnaires.
• Patients who are too ill, as determined by the referring health care professional.

Part B - Prospective observational cohort Potentially, we estimate to be able to include 330 patients. According to the sample size calculation we need a minimum of 228 patients.

Inclusion criteri

Description

Inclusion Criteria:

• Age 18 years or older (no upper age limit);
• Advanced or metastatic GIST, diagnosis of GIST must be histologically proven;
• Treated with TKIs (eg. sunitinib, regorafenib, avapritinib, ripretinib) for at least 2 years; TKI treatment ongoing; interruptions up to 3 months are allowed;
• Able to read and answer questionnaires;
• Able to provide informed consent.

Exclusion Criteria:

• Patients receiving TKI in an adjuvant treatment setting.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before inclusion the study.
• Patients who are too ill (death is imminent), as determined by the referring health care professional.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-Related Quality of Life assessed using the Item List.	Outcome measure: HRQoL Item List; Measurement instrument: EORTC-developed item list (Item list developed in phase 1 of this study). List consists of HRQoL issues specifically relevant to GIST patients receiving long-term TKI treatment.; Patients will be asked to rate the HRQoL issues on relevance (4 point Likert scale (1) not relevant - (4) very relevant), to prioritize the 10 most important issues, and to indicate relevant issues missing from this list.; Analysis: prevalence, severity, and longitudinal course of HRQoL issues	Baseline and at all scheduled follow-up assessments (every year for 10 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-Related Quality of Life measured by EORTC QLQ-C30	The EORTC QLQ-C30 is a ) is a validated, 30-item HRQoL questionnaire consisting of five functional scales (physical, role, cognitive, emotional and social), a global quality of life scale, three symptom scales (fatigue, pain, nausea and vomiting) and a number of single items assessing common symptoms (dyspnea, loss of appetite, sleep disturbance, constipation and diarrhea) and perceived financial impact of the disease. Items are scored on a four-point Likert scale (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much). After linear transformation, all scales and single item measures range in score from 0-100. A higher score on the functional scales and global QoL means better functioning and HRQoL, whereas a higher score on the symptom scales means more complaints. To determine cut-off for impaired HRQoL, the thresholds for clinical importance of Giesinger et al will be used.	Baseline and scheduled follow-up assessments (every year for 10 years)
Survivorship issues measured by EORTC QLQ-SURV100	The EORTC QLQ-SURV100 assesses survivorship-related issues in cancer patients. The QLQ-SURV100 is a 100 item HRQoL questionnaire consisting of 13 functional scales, 9 symptom scales, a Symptom Checklist of Chronic Side Effects of Treatment, and 12 single items. Items are scored on a four-point Likert scale (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much). After linear transformation, all scales and single item measures range in score from 0-100.	Baseline and scheduled follow-up assessments (every year for 10 years)
Health status measured by EQ-5D-5L	The EQ-5D-5L measures health status in two parts: a descriptive part and the EuroQol Visual Analogue Scale (EQ-VAS). The descriptive part assesses health in five generic dimensions (mobility, self-care, usual activity, pain and discomfort, and anxiety and/or depression), each of which has five levels of response (no problems till extreme problems/unable to). Each health state can potentially be assigned a summary index score based on societal preference weights for the health state. These weights, sometimes referred to as 'utilities', are often used to compute QALYs for use in health economic analyses. Health state index scores range from 0 (equivalent to dead) to 1 (equivalent of perfect health), with higher scores indicating higher health utility. The EQ-VAS records the patient's self-rated overall health on a vertical visual analogue scale. Consists of 1 item, range 0-100 from "Worst Possible" to "Best Possible" health, higher scores represent better health.	Baseline and at all scheduled follow-up assessments (every year for 10 years)
Overall Survival (OS)	Definition: Time from diagnosis of unresectable or metastatic disease to death from any cause. Censoring: Patients alive at analysis → censored at last known alive date	From diagnosis to death or last follow-up (follow-up will be 10 years)
Progression-Free Survival (PFS)	Definition: Time from start of TKI treatment to to documented disease progression or death from any cause, whichever occurs first. Censoring: alive and progression-free → censored at last tumor assessment.	From start of TKI treatment to progression, death, or last follow-up (follow-up is 10 years)
Tumour response assessed by RECIST	Tumour response will be evaluated based on radiologic assessments according to Response Evaluation Criteria in Solid Tumors (RECIST). Response categories include complete response, partial response, stable disease, and progressive disease. The outcome measure is the proportion of patients in each response category.	At each radiologic assessment, annually up to 10 years.
Reasons for discontinuation of tyrosine kinase inhibitor (TKI) treatment	Reasons for treatment discontinuation will be collected from medical records and categorized into predefined groups, including toxicity, disease progression, patient preference, and other reasons. Frequencies of each category will be reported.	Annually up to 10 years.
Coping style measured by Threatening Medical Situations Inventory (TMSI)	The Threatening Medical Situations Inventory (TMSI) assesses coping style in response to medical stress. It includes two subscales: monitoring (information-seeking) and blunting (information avoidance). Each subscale score ranges from 6 to 30, with higher scores indicating a stronger tendency toward that coping style.	Baseline and annually up to 10 years.
Illness cognitions measured by Illness Cognition Questionnaire (ICQ)	The Illness Cognition Questionnaire (ICQ) is an 18-item instrument assessing illness-related cognitions across three domains: helplessness, acceptance, and perceived benefits. Items are scored on a 4-point Likert scale (1 = not at all, 4 = completely). Mean item scores are calculated for each domain, ranging from 1 to 4, with higher scores indicating a stronger presence of the respective cognition.	Baseline and annually up to 10 years.
Financial toxicity measured by Financial Index of Toxicity (FIT)	The Financial Index of Toxicity (FIT) assesses financial toxicity across domains including financial stress, financial strain, and lost productivity. Scores are derived from questionnaire items, with higher scores indicating greater financial toxicity.	Baseline, annually up to 10 years.
Work productivity loss measured by Productivity Cost Questionnaire	Selected items from the Productivity Cost Questionnaire assess the impact of disease on work productivity. Outcomes include presence and extent of productivity loss among participants engaged in paid work, including number of hours missed in the past 4 weeks.	Baseline, annually up to 10 years.
Healthcare utilization and informal care use measured by Medical Consumption Questionnaire	Selected items from the Medical Consumption Questionnaire assess healthcare utilization, including use of home care services and informal care provided by family members or acquaintances. Healthcare utilization is assessed by the number of contacts with healthcare providers and use of home care services in the past 3 months.	Baseline, annually up to 10 years.
Tyrosine Kinase Inhibitor (TKI) Plasma Concentration	In Dutch centers where therapeutic drug monitoring (TDM) is part of standard care, plasma concentrations of the participant's TKI (imatinib, sunitinib, or regorafenib) will be measured. Blood samples will be analyzed using a validated LC-MS/MS method. The time of the last dose intake and the time of blood sampling will be recorded. This measure allows assessment of the systemic exposure to the TKI and supports evaluation of pharmacokinetic variability during long-term treatment. Units of Measure: Nanograms per milliliter (ng/mL)	Baseline and annually up to 10 years.

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Principal Investigator: Winette V van der Graaf, Prof. dr., Antoni van Leeuwenhoek; Principal Investigator: Olga Husson, Dr., Associate professor, Antoni van Leeuwenhoek

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2025
• Primary Completion (Estimated): May 21, 2027
• Study Completion (Estimated): May 21, 2037

Study Registration Dates

• First Submitted: March 25, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Health-related quality of life; Imatinib; Tyrosine Kinase Inhibitor; Metastatic disease; Gastrointestinal Stromal Tumor (GIST)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplastic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: IRBd22-158; 004-2020 (Other Grant/Funding Number: European Organisation for Research and Treatment of Cancer (EORTC))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No