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

Brief summary public domain (ClinicalTrials.gov)

Older adults with gastrointestinal cancers may be more likely to experience side effects from chemotherapy and difficulties with everyday activities. These problems are not always explained by age alone. Changes in nutrition, physical strength, general health, and independence may also affect how well a person tolerates cancer treatment. The purpose of the VITAL-GI study is to better understand how health-related vulnerability in older adults is associated with chemotherapy side effects and changes in daily functioning over time. This is an observational study involving adults aged 65 years or older with gastrointestinal cancer that has not spread to distant parts of the body. Participants receive chemotherapy as part of their usual medical care, either before or after surgery, according to their treatment plan. The study does not assign chemotherapy treatments or change routine care. Researchers use questionnaires and clinical information to assess general health, nutrition, physical abilities, independence, and the risk of chemotherapy side effects. Assessments are performed when chemotherapy begins and approximately 3 and 6 months later. The study examines whether initial health assessments can help identify people who are more likely to experience serious chemotherapy side effects. It also examines how health, daily activities, symptoms, and quality of life change during treatment. The findings may help researchers better understand the supportive care needs of older adults receiving chemotherapy for gastrointestinal cancer.

Detailed description public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Other: Standard-of-Care Systemic Chemotherapy. Participants receive standard-of-care adjuvant or neoadjuvant chemotherapy for nonmetastatic or locally advanced gastrointestinal cancer, as determined by the treating oncologist according to tumor characteristics, disease stage, treatment intent, and established clinical practice. Chemotherapy regimens may include CAPOX, FOLFOX, capecitabine monotherapy, modified FOLFIRINOX, gemcitabine monotherapy, FLOT, or gemcitabine plus capecitabine, as clinically appropriate. Treatment selection, dosing, modifications, and supportive care are not assigned or directed by the study. The observational assessments do not involve any experimental drugs or investigational therapeutic interventions.

Arm public domain (ClinicalTrials.gov)

Adjuvant and Neoadjuvant Chemotherapy Cohort (): Adults aged 65 years or older with nonmetastatic or locally advanced gastrointestinal cancers receiving standard-of-care adjuvant or neoadjuvant chemotherapy. Participants undergo comprehensive geriatric assessments at baseline and approximately 3 and 6 months after chemotherapy initiation. Evaluations include geriatric vulnerability (G8 and VES-13), chemotherapy toxicity risk (CARG and CRASH), nutritional status, sarcopenia risk, functional independence, patient-reported symptoms, and quality of life. Chemotherapy-related adverse events, treatment modifications, hospitalizations, and clinical outcomes are assessed during follow-up. All systemic treatments are prescribed according to routine clinical practice. No investigational treatment is assigned, and study participation does not alter chemotherapy selection or standard clinical management.

Primary outcome public domain (ClinicalTrials.gov)

Predictive Performance of Geriatric 8 and Vulnerable Elders Survey-13 for Chemotherapy-Related Toxicity of Grade ≥2 According to the Common Terminology Criteria for Adverse Events. The predictive performance of the baseline Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) screening instruments will be evaluated for the occurrence of chemotherapy-related toxicity within 180 days of treatment initiation. G8 scores range from 0 to 17, with lower scores indicating greater vulnerability and a screening threshold of ≤14. VES-13 scores range from 0 to 10, with higher scores indicating greater vulnerability and a threshold of ≥3. The clinical outcome is at least one chemotherapy-related adverse event of grade ≥2, classified according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Each participant will be classified according to whether the outcome occurred. Predictive discrimination will be quantified using the area under the receiver operating characteristic curve (AUC; range 0-1), with 95% confidence intervals. Time frame: Baseline assessment before chemotherapy initiation; toxicity assessed from chemotherapy initiation through day 180..

Secondary outcome public domain (ClinicalTrials.gov)

Association of Geriatric 8 and Vulnerable Elders Survey-13 Scores With Strength, Assistance with Walking, Rise from a Chair, Climb Stairs, and Falls Questionnaire Scores. Time frame: Baseline, approximately 3 months, and approximately 6 months after chemotherapy initiation..

Secondary outcome public domain (ClinicalTrials.gov)

Association of Geriatric 8 and Vulnerable Elders Survey-13 Scores With Nutritional Status Assessed by the Mini Nutritional Assessment-Short Form. Time frame: Baseline, approximately 3 months, and approximately 6 months after chemotherapy initiation..

Secondary outcome public domain (ClinicalTrials.gov)

Association of Geriatric 8 and Vulnerable Elders Survey-13 Scores With Katz Activities of Daily Living. Time frame: Baseline, approximately 3 months, and approximately 6 months after chemotherapy initiation..

Secondary outcome public domain (ClinicalTrials.gov)

Association of Geriatric 8 and Vulnerable Elders Survey-13 Scores With Lawton-Brody Instrumental Activities of Daily Living. Time frame: Baseline, approximately 3 months, and approximately 6 months after chemotherapy initiation..

Secondary outcome public domain (ClinicalTrials.gov)

Association of Geriatric 8 and Vulnerable Elders Survey-13 Scores With Eastern Cooperative Oncology Group Performance Status. Time frame: Baseline, approximately 3 months, and approximately 6 months after chemotherapy initiation..

Secondary outcome public domain (ClinicalTrials.gov)

Overall Survival at 12 Months. Time frame: From chemotherapy initiation to death or censoring, with survival probability evaluated at 12 months..

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Age ≥65 years at the time of enrollment. * Histologically confirmed nonmetastatic or locally advanced gastrointestinal malignancy, including colorectal, pancreatic, gastric, biliary tract, or other protocol-eligible gastrointestinal cancers. * Clinical stage II or III disease, or locally advanced nonmetastatic disease without a separately specified stage II or III classification. * Planned initiation of standard-of-care adjuvant or neoadjuvant systemic chemotherapy, including fluoropyrimidine-, oxaliplatin-, irinotecan-, or gemcitabine-based regimens, as clinically appropriate. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at baseline. * Ability to undergo baseline comprehensive geriatric assessment and participate in scheduled follow-up evaluations at approximately 3 and 6 months after chemotherapy initiation. * Ability to complete the required geriatric, nutritional, sarcopenia, functional, symptom, and quality-of-life assessments independently or with assistance permitted under the study protocol. * Provision of written informed consent before study participation. Exclusion Criteria: * Evidence of distant metastatic disease (stage IV) at baseline. * ECOG performance status ≥3 at study enrollment. * No planned systemic cytotoxic chemotherapy during the study observation period. * Severe cognitive impairment or another condition preventing valid baseline geriatric and functional assessment when no protocol-approved assessment assistance is available. * Inability to provide informed consent according to the approved study procedures. * Concurrent participation in an interventional clinical trial that interferes with chemotherapy selection, toxicity assessment, or longitudinal study evaluations.

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 132 participants (actual).