Longitudinal Geriatric Vulnerability, Chemotherapy Toxicity, and Functional Outcomes in Older Adults With Gastrointestinal Cancer

Background and Rationale Older adults with gastrointestinal malignancies are a clinically heterogeneous population. Differences in physiological reserve, nutritional status, functional independence, comorbidity burden, and physical performance may influence tolerance of systemic anticancer treatment. Chronological age and conventional performance status alone may not adequately characterize these differences. Geriatric screening instruments, including the Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13), can identify patients with increased vulnerability. The Cancer and Aging Research Group (CARG) toxicity score and Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) provide complementary approaches to chemotherapy toxicity risk assessment. However, baseline risk evaluation does not fully describe changes in vulnerability, nutrition, symptoms, and physical functioning during chemotherapy. The VITAL-GI study examines baseline geriatric vulnerability, chemotherapy-related toxicity, and longitudinal functional outcomes in older adults with nonmetastatic or locally advanced gastrointestinal cancer. Study Design and Setting VITAL-GI is a prospective, single-center, observational cohort study conducted in the Department of Medical Oncology at Ankara Etlik City Hospital, Ankara, Türkiye. The study population comprises adults aged 65 years or older receiving standard-of-care chemotherapy for nonmetastatic or locally advanced gastrointestinal malignancies, including colorectal, gastric, pancreatic, and biliary tract cancers. The expanded study scope includes patients receiving either adjuvant or neoadjuvant chemotherapy. Treatment selection, drug administration, supportive care, and treatment modifications are determined by the treating oncology team according to routine clinical practice. The study does not assign investigational treatment. Geriatric and Clinical Assessments Baseline evaluations characterize demographic and oncological characteristics, comorbidities, concomitant medications, Eastern Cooperative Oncology Group (ECOG) performance status, treatment characteristics, and routinely available laboratory measures. Geriatric vulnerability is evaluated using G8 and VES-13. Baseline chemotherapy toxicity risk is further characterized using CARG and CRASH scores when the required scoring components are available. Nutritional and physical vulnerability are assessed using the Mini Nutritional Assessment-Short Form (MNA-SF) and SARC-F questionnaire. Functional independence is assessed using the Katz Activities of Daily Living (ADL) and Lawton-Brody Instrumental Activities of Daily Living (IADL) instruments. Additional patient-reported assessments evaluate insomnia, fatigue, depressive symptoms, pain, and quality of life using established questionnaires. Longitudinal Follow-up Participants undergo clinical and geriatric assessments at baseline, approximately 3 months, and approximately 6 months after chemotherapy initiation. Repeated measurements are used to characterize changes in vulnerability, nutritional status, sarcopenia risk, functional independence, psychological symptoms, fatigue, sleep disturbance, pain, and quality of life. Chemotherapy-related adverse events are classified according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Treatment modifications, unplanned hospitalizations, and mortality are documented as clinical outcomes. Study Objectives The original registered objective focused on evaluating the ability of baseline G8 and VES-13 scores to identify patients at risk of CTCAE grade ≥2 chemotherapy-related toxicity. The expanded analytical objectives include evaluating the association of G8, VES-13, CARG, and CRASH scores with severe chemotherapy-related toxicity, defined as CTCAE grade ≥3, during the first 180 days of chemotherapy. Additional objectives include characterizing longitudinal changes in geriatric vulnerability and functional status, examining the relationship between early changes in geriatric assessment scores and subsequent clinical outcomes, and evaluating functional deterioration during treatment. Functional deterioration is characterized using changes in Katz ADL score, with exploratory analyses considering a composite outcome of death or functional deterioration. Statistical Approach Descriptive statistics summarize baseline demographic, clinical, oncological, and geriatric assessment characteristics. The discriminative performance of baseline risk scores is evaluated using receiver operating characteristic analysis. Associations between geriatric assessment scores and chemotherapy-related toxicity are examined using regression models with adjustment for relevant baseline clinical characteristics. Longitudinal changes are assessed using repeated-measures statistical models accounting for within-participant correlation. Additional exploratory analyses may evaluate outcomes after an early-treatment landmark, alternative toxicity definitions, competing mortality events, possible nonlinear risk associations, the influence of missing follow-up data, and the estimated clinical usefulness of prediction models. Internal validation and sensitivity analyses are used to assess the stability of exploratory findings. Interpretation emphasizes association and risk stratification rather than causal inference. Clinical Relevance By integrating baseline geriatric assessment with repeated evaluations during chemotherapy, VITAL-GI aims to characterize changes in vulnerability and identify clinically relevant patterns of toxicity and functional decline. The study may help inform future research on risk-adapted monitoring and supportive care strategies for older adults undergoing chemotherapy for gastrointestinal cancer.