Gastrointenstinal Stromal Tumor (GIST)
Conditions
Keywords
Gastrointestinal Stromal Tumor (GIST), Tyrosine Kinase Inhibitor, Imatinib, Health-related quality of life, Metastatic disease
Brief summary
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.
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.
Interventions
None listed
Sponsors
The Netherlands Cancer Institute
European Organisation for Research and Treatment of Cancer - EORTC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Health-Related Quality of Life assessed using the Item List. | Baseline and at all scheduled follow-up assessments (every year for 10 years) | * 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health-Related Quality of Life measured by EORTC QLQ-C30 | Baseline and scheduled follow-up assessments (every year for 10 years) | 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. |
| Survivorship issues measured by EORTC QLQ-SURV100 | Baseline and scheduled follow-up assessments (every year for 10 years) | 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. |
| Health status measured by EQ-5D-5L | Baseline and at all scheduled follow-up assessments (every year for 10 years) | 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. |
| Overall Survival (OS) | From diagnosis to death or last follow-up (follow-up will be 10 years) | 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 |
| Progression-Free Survival (PFS) | From start of TKI treatment to progression, death, or last follow-up (follow-up is 10 years) | 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. |
| Tumour response assessed by RECIST | At each radiologic assessment, annually up to 10 years. | 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. |
| Reasons for discontinuation of tyrosine kinase inhibitor (TKI) treatment | Annually up to 10 years. | 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. |
| Coping style measured by Threatening Medical Situations Inventory (TMSI) | Baseline and annually up to 10 years. | 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. |
| Illness cognitions measured by Illness Cognition Questionnaire (ICQ) | Baseline and annually up to 10 years. | 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. |
| Financial toxicity measured by Financial Index of Toxicity (FIT) | Baseline, annually up to 10 years. | 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. |
| Work productivity loss measured by Productivity Cost Questionnaire | Baseline, annually up to 10 years. | 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. |
| Healthcare utilization and informal care use measured by Medical Consumption Questionnaire | Baseline, annually up to 10 years. | 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. |
| Tyrosine Kinase Inhibitor (TKI) Plasma Concentration | Baseline and annually up to 10 years. | 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) |
Countries
Netherlands
Contacts
CONTACTTessa van Amerongen, MSc, Drs.
CONTACTOlga Husson, Dr., Associate professor
PRINCIPAL_INVESTIGATORWinette V van der Graaf, Prof. dr.
Antoni van Leeuwenhoek
PRINCIPAL_INVESTIGATOROlga Husson, Dr., Associate professor
Antoni van Leeuwenhoek
Outcome results
None listed