Frailty Assessments for Risk Assessment in Gynecologic Oncology Patients

Recruiting

• Conditions: Oncology; Gynecologic Cancer; Frailty
• Interventions: Diagnostic Test: Clinical Frailty Scale; Diagnostic Test: Frailty Phenotype

• Registration Number: NCT05738252
• Lead Sponsor: Population Health Research Institute

Brief Summary

FARGO is a prospective cohort study that aims to determine the performance of preoperative frailty assessment based on the Frailty Phenotype (FP), compared to a perioperative cardiovascular risk assessment based on the combination of preoperative Revised Cardiac Risk Index (RCRI), age and occurrence of myocardial injury after noncardiac surgery (MINS), in predicting the composite of all-cause death or new disability at 6 months after surgery in patients aged 55 or older. Patients will have confirmed or suspected gynecologic cancer, undergoing cytoreductive or high-risk surgery with or without chemotherapy.

Detailed Description

Little is known about how to best predict postoperative outcomes, recovery from complications, and chemotherapy tolerance in an increasingly older and medically complex GO population. Measuring frailty may represent a comprehensive tool for risk prediction. The study 1) will help fill the current gap in knowledge; 2) will translate into clinical practice changes both locally, and when replicated in a larger multi-centre study, elsewhere in Canada and worldwide; and 3) will inform future studies on shared decision-making strategies and interventions.

By evaluating the role of frailty as a static or dynamic predictor of patient important outcomes, and by considering the complexity of these patients and also of their treatment trajectories, the study has the potential to fill those gaps and influence how care is delivered. By involving stakeholders in the evaluation of feasibility and acceptability of frailty assessment, this will inform a change in care that is sustainable, innovative, and patient-centred.

There have been substantial knowledge advancements about perioperative risk factors and the long-term impact of postoperative complications; however, oncology patients and patient-reported outcomes have been insufficiently studied. There is increased literature on frailty assessment in noncardiac surgery; however, studies that included GO patients are few and of low-quality. The study will overcome the limitations of the current knowledge and practice, and will potentially change healthcare delivery.

Study Timeline

• Study First Submitted: 2023-01-31
• Study First Submitted QC: 2023-02-10
• Study First Posted: 2023-02-22
• Study Start: 2023-06-15
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-12
• Last Update Posted: 2025-04-16
• Primary Completion: 2025-05
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 280

Inclusion Criteria

1. Age must be 55 years or older at registration

2. Must meet any one of the following criteria:

   1. Have stage II-IV ovarian or endometrial cancer, undergoing cytoreductive surgery via laparotomy, with or without neoadjuvant chemotherapy (NACT)
   2. Have any stage endometrial, uterine or cervical cancer planned for laparotomy where laparoscopy is deemed unfeasible/high-risk due to comorbidities
   3. Are undergoing laparotomy for pelvic mass, highly suspicious for malignancy; or
   4. Are undergoing laparotomy for gynecologic malignancy recurrence.

Exclusion Criteria

1. Unable to provide informed consent
2. Require urgent surgery within 24 hours of first consultation to the Gynecological Oncology team
3. Are undergoing neoadjuvant radiation therapy
4. Have a previously documented history of dementia
5. Have cognitive, language, vision, or hearing impairment that impacts ability to understand the directions for the completion of the study instruments
6. Are participating in a clinical trial investigating a new systemic therapy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group C	Clinical Frailty Scale	Post-chemotherapy, a small proportion of patients will not be deemed eligible for surgery by the treating physician (group C). Group C will be included in the evaluation of chemotherapy-related outcomes, and will also be asked to complete a follow-up visit 6 months from the end of their chemotherapy.
Group A	Clinical Frailty Scale	We expect that some of the eligible patients (Group A) will undergo surgery without NACT. Group A will undergo only one preoperative study visit (baseline) within 45 days prior to their surgery. Group A will complete the study assessments and follow-ups. Some patients of Group A will undergo adjuvant chemotherapy after surgery; this will not affect their study timeline.
Group A	Frailty Phenotype	We expect that some of the eligible patients (Group A) will undergo surgery without NACT. Group A will undergo only one preoperative study visit (baseline) within 45 days prior to their surgery. Group A will complete the study assessments and follow-ups. Some patients of Group A will undergo adjuvant chemotherapy after surgery; this will not affect their study timeline.
Group B	Clinical Frailty Scale	Patients undergoing NACT before their surgery (group B) will have a first baseline study assessment within 45 days prior to their first chemotherapy treatment; in this group, a second preoperative study visit will be repeated after chemotherapy is considered terminated at least 18 days post-chemotherapy cycle and within 45 days prior to surgery. Group B will complete the study assessments and follow-ups. Some patients of Group B will undergo adjuvant chemotherapy after surgery; this will not affect their study timeline.
Group B	Frailty Phenotype	Patients undergoing NACT before their surgery (group B) will have a first baseline study assessment within 45 days prior to their first chemotherapy treatment; in this group, a second preoperative study visit will be repeated after chemotherapy is considered terminated at least 18 days post-chemotherapy cycle and within 45 days prior to surgery. Group B will complete the study assessments and follow-ups. Some patients of Group B will undergo adjuvant chemotherapy after surgery; this will not affect their study timeline.
Group C	Frailty Phenotype	Post-chemotherapy, a small proportion of patients will not be deemed eligible for surgery by the treating physician (group C). Group C will be included in the evaluation of chemotherapy-related outcomes, and will also be asked to complete a follow-up visit 6 months from the end of their chemotherapy.

Primary Outcome Measures

Name	Time	Method
All-cause death or new disability at 6 months	6 months	Disability status is determined using the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0). New disability at any time point is based according to the following criteria that account for baseline disability scores: 1. For individuals with a disability score of \<25% at baseline, new disability is defined as a disability score ≥25% at follow-up; 2. For individuals with a disability score ≥25%, new disability is defined an increase in disability score of ≥8%.; Vascular death is defined as any death with a vascular cause and includes those deaths following a myocardial infarction, cardiac arrest, stroke, cardiac revascularization procedure (i.e., percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\] surgery), pulmonary embolus, hemorrhage, or deaths due to an unknown cause. Non-vascular death is defined as any death due to a clearly documented non-vascular cause (e.g. trauma, infection, malignancy).

Secondary Outcome Measures

Name	Time	Method
In-hospital delirium	During the index hospital admission for surgery up to the first 3 days after surgery or before discharge from hospital	Delirium during the first 3 days after surgery or before discharge from the hospital, based on Confusion Assessment Method (CAM). According to CAM, patients are diagnosed with delirium if they meet the first 2 criteria (acute onset with fluctuating course, AND attention deficit), and at least one of the second 2 criteria (disorganized thinking OR altered level of consciousness). Participants will be screened for postoperative delirium while in hospital, twice daily, during the first 3 days after surgery or until discharge (if before 3 days), by research personnel, using the 3D-CAM, or the CAM-ICU any time the participants are in the PACU or in ICU
Bleeding Independently Associated with Mortality after noncardiac Surgery	28 days after surgery	BIMS is a bleeding meeting any of the following 3 criteria: 1. Leading to a postoperative hemoglobin \<70 g/L; 2. Requiring transfusion of one or more units of red blood cells; 3. Judged to be the immediate cause of death
Length of stay	during index hospitalization for surgery	time spent in hospital immediately after surgery
Oncologic Outcomes: Cancer-specific death	at 6 and 12 months	Cancer-specific death is death directly attributable to the primary gynecological cancer or directly related to its treatment, in the absence of other causes of death.
New Disability	28 days, 6 months and 1 year after surgery	Disability status is determined using the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0). New disability at any time point is based according to the following criteria that account for baseline disability scores: 1. For individuals with a disability score of \<25% at baseline, new disability is defined as a disability score ≥25% at follow-up; 2. For individuals with a disability score ≥25%, new disability is defined an increase in disability score of ≥8%.; Definition of new disability at 28 days, 6 months, and 1 year after surgery will use as baseline disability score the WHODAS 2.0 score measured before surgery.
Major vascular complications	at 28 days, 6 months, and 1 year after surgery	defined as a composite of vascular death, and non-fatal myocardial infarction (or myocardial injury for the 28-day time point), stroke, symptomatic proximal venous thromboembolism, and cardiac arrest
Infection, and infection with sepsis	at 28 days, 6 months, and 1 year after surgery	Infection is defined as a pathologic process caused by the invasion of normally sterile tissue or fluid or body cavity by pathogenic or potentially pathogenic organisms.; The Third International Consensus Definitions Task Force defines sepsis as a "life-threatening organ dysfunction due to a dysregulated host response to infection." Based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria, sepsis will require a quick Sequential Organ Failure Assessment (qSOFA) Score ≥2 points due to infection. The qSOFA includes the following items and scoring system: 1. Altered mental status (1 point); 2. systolic blood pressure of 100 mm Hg or less (1 point), and; 3. respiratory rate of 22 breaths/min or more (1 point).
New clinically important atrial fibrillation	28 days after surgery, 6 months and 1 year after surgery	The definition of new clinically important atrial fibrillation requires the documentation of atrial fibrillation or atrial flutter of any duration on an ECG or rhythm strip, which results in angina congestive heart failure, symptomatic hypotension, or requires treatment with a rate controlling drug, antiarrhythmic drug, or electrical cardioversion.
Chemotherapy-related outcomes	Before Surgery, 6-months post-surgery	This will be measured at the end of any chemotherapy treatment when considered terminated: Change in health-related quality of life, defined as the difference in FACT-G7 score after chemotherapy compared to before chemotherapy.
All cause death	28 days and 1 year	Vascular death is defined as any death with a vascular cause and includes those deaths following a myocardial infarction, cardiac arrest, stroke, cardiac revascularization procedure (i.e., percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\] surgery), pulmonary embolus, hemorrhage, or deaths due to an unknown cause. Non-vascular death is defined as any death due to a clearly documented non-vascular cause (e.g., trauma, infection, malignancy).
Oncologic Outcomes: Progression Free Survival (PFS)	at 6 and 12 months	PFS, defined as the time from treatment initiation to tumor progression or recurrence or death from any cause, or to the date of censoring at the last time the subject was known to be alive. Cancer progression/recurrence will be defined as a measurable progression/recurrence documented on imaging.
Chemotherapy-related outcomes: total dose received	Before Surgery, 6-months post-surgery	This will be measured at the end of any chemotherapy treatment when considered terminated: Total dose received, defined as Relative Dose Intensity (RDI), as calculated as the percentage of the standard dose that was administered
Chemotherapy-related outcomes: time to completion of all chemotherapy cycles	Before Surgery, 6-months post-surgery	This will be measured at the end of any chemotherapy treatment when considered terminated: Time to completion of all chemotherapy cycles (number of days)
Acute congestive heart failure	28 days after surgery, 6 months and 1 year after surgery	The definition of congestive heart failure requires at least one of the following clinical signs (i.e. any of the following signs: elevated jugular venous pressure, respiratory rales/crackles, crepitations, or presence of S3) and at least one of the following: 1. Radiographic findings (i.e., vascular redistribution, interstitial pulmonary edema, or frank alveolar pulmonary edema) OR; 2. Heart failure treatment implemented with diuretics with documented clinical improvement.
Unplanned admission to ICU	during index hospitalization for surgery	admission to the ICU that was not planned
Chemotherapy-related outcomes: Change in health-related function or well-being	Before Surgery, 6-months post-surgery	This will be measured at the end of any chemotherapy treatment when considered terminated: Change in health-related function or well-being, defined as the difference in WHODAS 2.0 score after chemotherapy compared to before chemotherapy.
Chemotherapy-related outcomes: patient's decisional regret	Before Surgery, 6-months post-surgery	This will be measured at the end of any chemotherapy treatment when considered terminated: Patient's decisional regret, defined as "distress or remorse after a (health care) decision," assessed using the Decisional Regret scale, a validated a 5-item scale

Trial Locations

Locations (4)

Juravinksi Hospital; 🇨🇦 Hamilton, Ontario, Canada

Credit Valley Hospital; 🇨🇦 Mississauga, Ontario, Canada

Sunnybrook; 🇨🇦 Toronto, Ontario, Canada

University Health Network; 🇨🇦 Toronto, Ontario, Canada