Frailty and Postoperative Outcomes After Gastric Cancer Surgery (TOREGA)

November 25, 2023 updated by: Manuel Ramón Pera Román, Parc de Salut Mar

The Impact of Frailty on the Postoperative Outcomes of Gastric Cancer Surgery

Background. Gastric cancer is an important health care problem even though treatment advances, and it is diagnosed mainly in elderly. Surgery is the main treatment for gastric cancer and is associated with a high rate of postoperative complications and mortality, even higher in older patients. Chronological age seems not to be the main factor influencing the worse outcome of older patients, comorbidities and frailty have also been taken into account recently.

Methods. Participation in the study will be offered to all centers that are currently part of the Spanish EURECCA (EUropean REgistry of Cancer CAre) Esophagogastric Cancer Registry. The impact of the frailty on different outcome variables will be evaluated. The main outcome variable will be 90-day mortality after the intervention. Health-Related Quality of Life (HRQoL) will also be evaluated.

Objective. The objective of the study is to value the impact of frailty on gastric cancer surgery outcomes therein the Spanish EURECCA Esophagogastric Cancer Registry.

Study Overview

Status

Completed

Conditions

Detailed Description

Introduction

Gastric cancer is the fifth most frequent cancer and the third cause of death due to cancer. The increase in life expectancy cause it to be diagnosed more and more in elderly people, with an average age at diagnosis of 68 years in the West.

Surgery is the main treatment for gastric cancer and is associated with a high rate of postoperative complications and mortality, which is even higher in elderly patients (data from the ACS-NSQIP between 2007 and 2013: 30-day severe morbidity from 16.3% in 80 years and 30-day mortality from 1.2% in 80 years).

Generally, advanced chronological age is considered a negative prognostic factor for complications and hospital stay in major surgery. Age per se, however, seems to be responsible only in part for the increased risk of postoperative complications.

Greater risks seem to be associated with other factors such as comorbidities, so, in the preoperative evaluation, variables such as the Charlson comorbidity index have been introduced. Another variable that has emerged recently for the estimation of perioperative risk is frailty, which is defined as "a medical syndrome with multiple causes and contributors that is characterized by a decrease in strength, endurance and physiological capacity, which increases the risk of the vulnerability of the individual and/or death". Surgery is a major stress factor that can disrupt physiological homeostasis; therefore, frailty has a clinical significance when considering surgery in elderly patients.

There are two main ways to measure frailty: one by clinical definitions of a fragile phenotype and another by frailty indexes that assess the accumulated deficits in multiple domains. Measures to assess frailty are numerous and this is a limitation when standardizing and comparing studies; among the most used there are the Fried criteria, the frailty index of the Canadian Study of Health and Aging (CSHA-FI) and the modified frailty index of Velanovich (mFI: modified Frailty Index).

Other indices widely used in the clinic are the Geriatric 8 (G8), which is recommended above all in elderly patients with cancer and the Groningen index (GFI: Groningen Frailty Indicator). The prevalence of frailty in elderly patients (65 years or older) is highly variable, probably due to the diversity in the definitions of frailty (4.0-59.1% in community residences, 10.4-56.0% in patients who are candidates for elective surgery) (18, 19, 20). The prevalence of frailty increases in females and with age (being 15.7% in patients aged 80-84 years and 26.1% in patients older than 85 years).

Frailty appears in several studies as a more important indicator than chronological age with respect to postoperative results. There are evidences that relate frailty, evaluated with different indices, with the increase of postoperative complications, hospital stay, need of discharge to convalescence centers, health costs, short and long term mortality, after major surgery.

Therefore, it is important to identify fragile patients to implement prevention programs through global geriatric assessments (CGA Comprehensive Geriatric Assessment). Just by having more clinical attention for more fragile patients after major surgery there can be better results of short and long-term postoperative mortality. Likewise, as demonstrated in randomized clinical studies, prehabilitation and global geriatric assessment programs improve the results in terms of postoperative complications and hospital stay.

The CGA is an established method to evaluate and optimize the physical state, the psychological, functional and social problems in elderly patients in order to improve the results of the treatments. It implies an interdisciplinary evaluation of multiple domains, followed by planning for analysis, treatment, rehabilitation and long-term follow-up.

This allows, in the first place, to intervene before an operation, to increase the physiological reserve of a patient, especially with exercise and nutrition. In addition, the therapeutic decision can be guided by adapting the surgical recommendations to the physiological capacity of the patient; second, the knowledge of the increased risk of complications and the possible need for transfer to institutions (especially in patients who live alone) prepares patients and their families for postoperative evolution.

The majority of studies published in the literature on the relationship between frailty and postoperative results are retrospective studies, which evaluate populations of patients undergoing major surgery and who, in general, analyze short-term results (30-day mortality). None of these takes into account the impact of surgery on the quality of life of this group of patients. Among all these studies there is very little information about the influence of frailty in gastric cancer surgery. There is only one retrospective study that focuses only on gastric cancer surgery, using the Groningen index and revealing an increase in in-hospital mortality and serious complications (Clavien-Dindo complications score ≥ 3) in fragile patients.

Objective

The aim of the present study is to assess the impact of frailty on the results of gastric cancer surgery (long-term postoperative morbidity and mortality, hospital stay, readmissions, need of transfer to institution of medium or long stay and quality of life).

Methods

This is a prospective and multicenter cohort study, within the Spanish EURECCA Esophagogastric Cancer Project, to investigate the impact of frailty on the postoperative results of surgery for gastric cancer in elderly patients.

Participation in the study will be offered to all centers that are currently part of the Spanish EURECCA Esophagogastric Cancer Registry. Those hospitals that show their desire to participate must sign the Letter of Commitment.

The impact of the frailty on different outcome variables will be evaluated. The main outcome variable will be 90-day mortality after the intervention. Other secondary outcome variables will also be evaluated: incidence of serious complications (Clavien-Dindo complications score ≥ 3), Complication Comprehensive Index (CCI) score, hospital stay, incidence of death in patients suffering from a complication (failure-to-rescue), hospital readmission within the first 30 days after the discharge, destination of the patient after discharge from hospital [home, social health centers, or geriatric residence], mortality at 12 months after the intervention, quality of life before the intervention and at 12 months.

For the assessment of frailty (frailty screening), two questionnaires will be used:

  • Questionnaire G8: This is a questionnaire with 8 questions, easy to use, with a total score that varies from 0 to 17 points. Previous studies suggest the score ≤ 14 as a cut-off point to identify the fragile patient, with a sensitivity of 92% and specificity of 52%.
  • Modified frailty index: This index was described by Velanovich et al., based on a previously validated simplification of the frailty index CSHAFI (Canadian Study of Health and Aging Frailty Index), which was specifically designed to analyze data included in the National Surgical Quality Improvement Program of the American College of Surgeons (ACSNSQIP). It consists of 11 questions with 1 point assigned to each of them on the functional, endocrine, respiratory, cardiovascular and neurological status of the patient. It allows to divide the patients into 4 groups: without frailty (FI = 0), slightly fragile (FI = 1), moderately fragile (FI = 2) and severely fragile (FI ≥ 3).

Postoperative complications will be classified according to the recommendations proposed by the European Chapter of the International Gastric Cancer Association (EGCA) (unpublished data), its severity through the classification of Clavien-Dindo and the CCI. In particular, the CCI will be calculated using the free application that can be found on the website: www.assessurgery.com/calculator_single/.

Health-Related Quality of Life (HRQoL) will be evaluated with the validated Quality of Life questionnaires of the European Organization for Research and Treatment of Cancer (EORTC-QLQ), QLQ-C30 (30 items Core Quality of Life Questionnaire, version 3.0) and with the specific module for gastric cancer QLQ-STO22 (22 items Stomach Quality of Life Questionnaire). The permission for its use by the EORTC is available.

  • The EORTC-QLQ-C30 is a questionnaire that reflects the multidimensionality of HRQoL in patients with cancer. It is composed of 30 questions distributed in five functional scales (physical, role, cognitive, emotional and social), three scales of symptoms (fatigue, pain and nausea and vomiting), a global health scale and a series of additional questions to evaluate symptoms commonly referred by patients diagnosed with cancer (dyspnea, loss of appetite, insomnia, constipation and diarrhea) and the perceived financial impact.
  • The EORTC-QLQ-STO22 questionnaire contains 22 structured items in five domains (dysphagia, food restrictions, pain, reflux and anxiety) and four specific items (dry mouth, alteration of taste perception, body image and hair loss) related to the symptoms of the disease.

The calculation of the sample size is based on the primary objective of comparing fragile versus non-fragile patients with respect to postoperative mortality at 90 days after the intervention. Based on mortality data previously published in a retrospective study by Mosquera et al., it is estimated that mortality for the group of non-frail patients is 0.6% and for the group with frailty 4.3%. From the data of the literature, a prevalence of 23% of frailty is calculated in the population of patients with gastric cancer and age ≥ 70 years undergoing gastrectomy.

For a power of 80% and a level of significance of 95% in a unilateral analysis, it is estimated that 276 non-fragile patients and 92 fragile patients would be needed to detect as statistically significant the difference between the proportion of patients who die between both groups.

The characteristics of fragile and non-fragile patient groups will be compared through frequency tables. The Chi-square test will be used to compare the differences between the categorical variables and the ANOVA test for the continuous variables. Different analyzes are proposed according to the study variables that are to be analyzed. For dichotomous type response variables (90- day mortality, 12-month mortality, incidence of serious complications, incidence of in-hospital death in patients with complications, and hospital readmission at 30 days after discharge), a multivariate logistic regression will be used to evaluate the risk (odds ratio) of these variables. For continuous response variables (ICC score) at 30 days after the intervention, and number of days of hospital stay), linear regression models will be used. For the variable categorical response of the patient after hospital discharge, an ordinal logistic regression model will be done. All regression models will be adjusted for age, sex, body mass index (BMI), type of gastrectomy, center volume, neoadjuvant treatment and degree of frailty. Regarding HRQoL analysis, the mean scores and 95% confidence intervals for the different domains of preoperative HRQoL and one year after surgery will be calculated. Changes of more than 10 points on a scale from 0 to 100 will be considered clinically relevant as previously suggested in other publications.

Study Type

Observational

Enrollment (Actual)

432

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Spain
      • Badalona, Spain
        • H. U. Germans Trias i Pujol

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

70 years and older (Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The possibility to participate to the study will be offered to all the hospitals members of the Spanish EURECCA Esophagogastric Cancer Registry. The hospitals that will participate must sign a commitment. Every patient that fit the eligibility criteria will be part of the study.

Description

Inclusion Criteria:

  • ≥ 70 years patients diagnosed with gastric cancer candidates for radical resection

Exclusion Criteria:

  • metastatic patients
  • patients candidates for palliative treatment
  • patients without a signed informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
90-day mortality
Time Frame: 90 days after surgery
Mortality at 90 days after surgery
90 days after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hospital stay
Time Frame: 30 days after surgery
Number of days of hospital stay
30 days after surgery
Severe complications
Time Frame: 30 days after surgery

Postoperative complications Clavien-Dindo score ≥ III

Clavien-Dindo score:

Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions

Grade II Requiring pharmacological treatment with drugs other than such allowed for grade I complications

Grade III Requiring surgical, endoscopic or radiological intervention

  • IIIa Intervention not under general anesthesia
  • IIIb Intervention under general anesthesia

Grade IV Life-threatening complication requiring Intensive Care Unit-management

  • IVa single organ dysfunction (including dialysis)
  • IVb multiorgandysfunction Grade V Death of a patient

Higher values represent a worse outcome.
30 days after surgery
Complication Comprehensive Index
Time Frame: 30 days after surgery

Complication Comprehensive Index from www.assessurgery.com/calculator_single/

The CCI® calculator is an online tool to support the assessment of patients' overall morbidity. The Comprehensive Complication Index (CCI®) is based on the complication grading by Clavien-Dindo Classification and implements every occurred complication after an intervention. The overall morbidity is reflected on a scale from 0 (no complication) to 100 (death). CCI® =√ (wC1 + wC2 ...+ wCx ) /2.

Higher values represent a worse outcome.
30 days after surgery
Failure to rescue
Time Frame: 30 days after surgery
Postoperative death after a treatable complication
30 days after surgery
Patient discharge facility
Time Frame: 30 days after surgery
Facility where the patient goes after the hospital stay
30 days after surgery
Readmission
Time Frame: 30 days after discharge
Readmission within 30 days after discharge
30 days after discharge
12-month mortality
Time Frame: 12 months after surgery
Mortality at 12 months after surgery
12 months after surgery
Health-related Quality of life before the intervention (EORTC-QLQ-C30)
Time Frame: 2 weeks before surgery

Quality of life before the intervention evaluated with the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30 questionnaire:

- The EORTC-QLQ-C30 (30 items Core Quality of Life Questionnaire) includes five functional scales, three symptom scales, a global health status/QoL scale, and six single items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level (a high/healthy level of functioning in functional scales, a high Quality of Life in Quality of Life scales, a high level of symptomatology/problems in symptom scales).
2 weeks before surgery
Health-related Quality of life before the intervention (EORTC-QLQ-STO22)
Time Frame: 2 weeks before surgery

Quality of life before the intervention evaluated with the EORTC (European Organization for Research and Treatment of Cancer) QLQ-STO22 questionnaire:

- The QLQ-STO22 (22 items Stomach Quality of Life Questionnaire) consists of five multi-item symptoms scales and four single symptoms items. All of the scales and single-item measures range in score from 0 to 100. Higher scores represent greater level of symptoms.
2 weeks before surgery
Health-related Quality of life at 12 months (EORTC-QLQ-C30)
Time Frame: 12 months after surgery

Quality of life before the intervention evaluated with the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30 questionnaire:

- The EORTC-QLQ-C30 (30 items Core Quality of Life Questionnaire) includes five functional scales, three symptom scales, a global health status/QoL scale, and six single items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level (a high/healthy level of functioning in functional scales, a high Quality of Life in Quality of Life scales, a high level of symptomatology/problems in symptom scales).
12 months after surgery
Health-related Quality of life at 12 months (EORTC-QLQ-STO22)
Time Frame: 12 months after surgery

Quality of life before the intervention evaluated with the EORTC (European Organization for Research and Treatment of Cancer) QLQ-STO22 questionnaire:

- The QLQ-STO22 (22 items Stomach Quality of Life Questionnaire) consists of five multi-item symptoms scales and four single symptoms items. All of the scales and single-item measures range in score from 0 to 100. Higher scores represent greater level of symptoms.
12 months after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Parc de Salut Mar

Investigators

  • Principal Investigator: Manuel Pera, Parc de Salut Mar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 5, 2019

Primary Completion (Actual)

April 30, 2023

Study Completion (Actual)

April 30, 2023

Study Registration Dates

First Submitted

May 9, 2018

First Submitted That Met QC Criteria

June 22, 2018

First Posted (Actual)

June 26, 2018

Study Record Updates

Last Update Posted (Actual)

November 28, 2023

Last Update Submitted That Met QC Criteria

November 25, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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