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This study will evaluate 1493 members of the St. Jude Lifetime Cohort Study (SJLIFE) who have completed a baseline functional assessment six or less years ago when 18-45 years of age.

Kirsten Ness, PT, PhD

Advances in cancer therapies have led to increasing numbers of adult survivors of pediatric malignancy. Unfortunately, treatment of childhood cancer continues to require agents designed to destroy malignant cell lines, and normal tissue is not always spared. While early treatment- related organ specific toxicities are not always apparent, many childhood cancer survivors report symptoms that interfere with daily life, including exercise induced shortness of breath, fatigue and reduced capacity to participate in physical activity. These symptoms may be a hallmark of premature aging, or frailty. Frailty is a phenotype most commonly described in older adults; it indicates persons who are highly vulnerable to adverse health outcomes. Frailty may help explain why nearly two thirds of childhood cancer survivors have at least one severe chronic health condition 30 years from diagnosis, why childhood cancer survivors are more likely than peers to be hospitalized for non-obstetrical reasons, and why they have mortality rates more than eight times higher than age-and-gender matched members of the general population.

Frailty is a valuable construct because it can be distinguished from disability and co-morbidity, and is designed to capture pre-clinical states of physiologic vulnerability that identify individuals most at risk for adverse health outcomes. These investigators have recently presented data indicating that impaired fitness is present in survivors of childhood acute lymphoblastic leukemia, brain tumor and Hodgkin lymphoma. This is relevant because frailty, characterized by a cluster of five measurements of physical fitness, is predictive of chronic disease onset, frequent hospitalization, and eventually mortality in both the elderly and in persons with chronic conditions. Using a frailty phenotype as an early predictor of later chronic disease onset will allow identification of childhood and adolescent cancer survivors at greatest risk for adverse health. An early indicator of those at risk for adverse health will allow researchers to test, and clinicians to provide, specific interventions designed to remediate functional loss, and prevent or delay onset of chronic health conditions. The investigators goals include characterizing physical frailty over a five year time span in a population of young adult survivors of childhood cancer, as well as assessing the association between frailty and the increase in the number and severity of chronic health conditions.

PRIMARY OBJECTIVES:

* Evaluate the change in the proportion of young adult cancer survivors who are frail from baseline to a point five years later.
* Evaluate the association between frailty and worsening of chronic health conditions.
* Describe the association between demographic and treatment factors and risk for prevalent frailty.
* Estimate the effects of physical activity, diet and smoking on risk for prevalent frailty.

Participants will complete a study questionnaire to assess social support, complete body composition studies, walking speed test, physical activity monitoring, and difficulties in daily activities due to health condition. In addition, any data collected as part of the SJLIFE protocol, including questionnaires, medical history and physical, height and weight measurements, physical functioning assessment results (i.e. hand grip strength), and neuropsychological evaluation results, may also be used as part of the evaluation for this study. The information collected for this study will be compared to information collected at a previous SJLIFE clinic visit within the previous 6 years.

A Longitudinal Assessment of Frailty in Young Adult Survivors of Childhood Cancer

We will use McNemar's test to assess if the prevalence of frailty has significantly increased over the 5-year time period.

The event of interest, worsening of chronic condition, will be defined as binary outcome which will take value of 1 if, compared to baseline evaluation, a survivor develops a new chronic condition (grade ≥3) or if the chronic condition worsens over the 5-year time period (i.e. goes from grades 1-2 to grade ≥3 or dies due to chronic condition); otherwise it will take a value of 0.

We will examine the association in a path model (all variables are measured) as lifestyle factors are likely to be mediators of the association between treatment and the frailty outcome at the five year time point. Sex, age at diagnosis, radiation exposure, specific chemotherapy agent doses, and age will be included in the initial theoretical model as exogenous variables and physical activity, diet, smoking status and frailty will be included as endogenous variables. Other variables, like medication use, baseline chronic disease, etc. will be evaluated for their contributions to the outcomes.

National Cancer Institute (NCI)

St. Jude Children's Research Hospital

Patients who will be receiving neo-adjuvant chemotherapy prior to surgery.

Patients who do not have planned chemotherapy.

A way to summarize the overall level of fitness or frailty of an older adult after they had been evaluated by an experienced clinician

Clinical Frailty Scale

Defined by the presence of three from the following five clinical features: weakness, slow walking speed, unintentional weight loss, exhaustion, and low physical activity

Frailty Phenotype

Julie My Van Nguyen, MD

Emily Di Sante, MA

Tiffany Zigras, MD

Danielle Vicus, MD

Liat Hogen, MD

Maura Marcucci, MD

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.

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.

Frailty Assessments for Risk Assessment in Gynecologic Oncology Patients

Frailty Assessments for Risk Assessment in Gynecologic Oncology Patients Undergoing Surgery and Chemotherapy

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).

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

New disability will be assessed utilizing the 12-item WHODAS 2.0 assessment, and will be defined as a disability score ≥25% at follow-up, or a score increase of ≥8% for those already disabled at baseline.

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 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).

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

death directly attributable to the primary gynecological cancer or directly related to its treatment, in the absence of other causes of death

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

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.

admission to the ICU that was not planned

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.

time spent in hospital immediately after surgery

defined as Relative Dose Intensity (RDI), as calculated as the percentage of the standard dose that was administered, using the formula below:

1. Carboplatin RDI (%) = total dose administered / total standard dose \*100
2. Paclitaxel RDI (%) = total dose administered / total standard dose \*100

defined as "distress or remorse after a (health care) decision," assessed using the Decisional Regret scale, a validated a 5-item scale

defined as the difference in WHODAS 2.0 score after chemotherapy compared to before chemotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Longitudinal Assessment of Frailty in Young Adult Survivors of Childhood Cancer	NCT02256137	Acute Lymphobla... Brain Tumor Hodgkin Lymphom...		18 Years - 45 Years	St. Jude Children's Research Hospital
Frailty Assessments for Risk Assessment in Gynecologic Oncology Patients	NCT05738252	Gynecologic Can... Frailty Oncology	Clinical Frailt... Frailty Phenoty...	55 Years - 110 Years	Population Health Research Institute
A Longitudinal Assessment of Frailty in Young Adult Survivors of Childhood Cancer	NCT02256137	Acute Lymphobla... Brain Tumor Hodgkin Lymphom...		18 Years - 45 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for frailty phenotype