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

• 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

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.

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.

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.

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

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 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 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.

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.

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.

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.

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.

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.

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)