ANZCTR - Registration

Registration number

ACTRN12623000183684

Ethics application status

Approved

Date submitted

18/11/2022

Date registered

21/02/2023

Date last updated

21/02/2023

Date data sharing statement initially provided

21/02/2023

Type of registration

Retrospectively registered

Titles & IDs

Public title

Strong for Oesophago-gastric Cancer Surgery - prehabilitation program for people with stomach cancer.

Scientific title

Strong for Oesophago-gastric Cancer Surgery (SOCS):
Efficacy of a personalised multidisciplinary enhanced prehabilitation program for patients undergoing oesophagectomy and gastrectomy

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1282-1437

Trial acronym

SOCS

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Oesophageal cancer

Gastric cancer

Condition category

Condition code

Cancer

Oesophageal (gullet)

Cancer

Stomach

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

A series of assessments related to physical function, diet and mental health will be performed to facilitate a three-month enhanced prehabilitation pre-surgical program that aims to improve physical, nutritional and psychological outcomes in patients with oesophago-gastric cancer.

Exercise intervention
A three-month optimised aerobic and resistance exercise training intervention, including high-intensity interval training, will be prescribed. All exercise sessions will be approximately 45 to 60 minutes and occur twice per week and supervised by an accredited exercise physiologist or physiotherapist. The intensity of these exercises will be moderate. Aerobic exercises may include walking on a treadmill or cycling, and resistance exercises may include weight training. The level of intensity will be tailored to the individual and will be assessed using Borg RPE methods by the treating clinician. Attendance will be recorded for each session, and follow-up phone calls to check in for those who do not attend.

Each participant will be asked to complete additional, unsupervised exercise training, for example, brisk walking or cycling, for at least 60 minutes per week to meet the current exercise guidelines for individuals with cancer set by the American College of Sports Medicine. Participants' unsupervised exercise training will be monitored weekly by reviewing their exercise training diary.

Nutritional intervention
Nutrition counselling/support will include an initial assessment, followed by a weekly or fortnightly appointment that will take approximately 30 minutes, to ensure patients meet their nutritional requirements. The nutritionist will discuss the patient weekly food intake and exercise patterns and provide feedback and suggestions around food and drink intake decisions and meal plans and ideas. The frequency of appointments will be determined by the treating dietician. To meet measured energy and predicted protein requirements via nutrition counselling encompassing high energy high, protein diet, food fortification strategies and utilisation of oral nutrition support in patients unable to meet their requirements through diet alone. Consideration of enteral nutrition support if oral intake is less than 60% of requirements despite education & supplementation of the diet. Attendance will be recorded for all nutritional appointments and follow-up calls for those who do not attend.

Immune-Modulating supplementation (e.g., IMPACT ®) shall be prescribed as 3 x 200ml tetra packs daily for five days pre & post-operatively, in accordance with evidence-based practice for the nutritional management of patients undergoing upper GI cancer surgery. The supplement contains ingredients including vitamin C and D, zinc, selenium, iron, and protein (including the amino acid glutamine).

Adherence and monitoring will occur through frequent interactions with the patients involved in the study including formal appointments, follow up phone calls and informal communication as required. A food diary will also be supported in collaboration with the exercise diary and reviewed with patients at face to face appointments.

Psychological intervention
The proposed prehabilitation intervention will address the barriers and enablers to complying with the three-month exercise intervention in participants who have been either identified by the Hospital Anxiety and Depression Scale (HADS) cut-off or by the supervising exercise physiologists monitoring the participants. It is important to note that participants who exceed eight or more on the HADS will be automatically referred to the psychological support intervention independent of their compliance/uptake of the exercise intervention. An initial assessment of 60 minutes will be performed for patients eligible for psychological support to determine the frequency of psychology appointments. The frequency of these appointments may be typically weekly, ranging from daily to monthly. Consultations with a psychologist can be face-to-face or in-person; however, this depends on patient preferences. All strategies, such as cognitive behavioural therapy and compliance enhancing techniques will be defined and at the discretion of the treating psychologist, and adherence will be determined by session attendance.

Medical optimisation
A small proportion of high-risk patients account for the majority of postoperative morbidity. The high-risk clinic aims to identify these patients preoperatively and institute strategies to reduce perioperative morbidity and mortality. This is a standard pre-operative anesthetic assessment clinic for those in preparation for surgery and takes approximately 20 minutes. In most cases only one appointment is required and is conducted face to face wherever possible. Specific aims include assessment of perioperative risk; optimisation of medical comorbidities, analgesia and functional status; and facilitation of informed decision-making and perioperative planning. This involves identifying goals and values unique to the patient, particularly in the event of planned or unplanned high-dependency unit/intensive care admission. All assessments will be completed in person during the operative assessment clinic and completed by an anesthetist. The treating anesthetist will determine the frequency of assessments based on their initial medical evaluation. Most participants will only require one evaluation however some participants may be asked to return again in 3 - 4 weeks time for a repeat assessment

Intervention code [1]

Rehabilitation

Intervention code [2]

Treatment: Other

Comparator / control treatment

Outcomes will be compared to historical control subjects with a diagnosis of oesophago-gastric cancer between the dates of Jan 2016 – Dec 2021.
These outcomes will be sourced from Austin Health medical records.

Control group

Historical

Outcomes

Primary outcome [1]

Rate of overall post-operative respiratory complication defined by the Esophagectomy Complication Consensus Group (ECCG) by medical record review.
For example, atelectisis and pneumonia.
Post operative respiratory complications will be collected by review of medical record by researchers and recorded in the study database.

Timepoint [1]

(1) Longer-term (three and five years post-operation)

Secondary outcome [1]

Individual surgical complication rate defined by the ECCG guidelines
Surgical complications will be collected by review of medical record by researchers and recorded in the study database.

Timepoint [1]

(1) 30 days post operation

Secondary outcome [2]

Rate of starting postoperative chemotherapy
Data regarding the rate of starting postoperative chemotherapy will be collected by review of medical record by researchers and recorded in the study database.

Timepoint [2]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation
(4) Longer-term (three and five years post-operation)

Secondary outcome [3]

Standard blood sampled biochemistry to monitor nutritional status, inflammation and response to nutritional intervention will include Albumin, Pre-albumin (transthyretin) and C-reactive protein as a composite measure.

Timepoint [3]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation

Secondary outcome [4]

Cardiopulmonary exercise testing on a stationary bike will be used to assess integrative cardiovascular function to determine peak oxygen uptake (VO2peak ml/kg/min).

Timepoint [4]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)

Secondary outcome [5]

Functional lower limb strength will be assessed by the 30-second sit-to-stand test. The 30-second sit-to-stand test is performed in an armless chair with an appropriate height of 43-46 cm. Participants will be instructed to fold their arms across their chests and perform the stand-up and sit-down movements quickly and safely within 30 seconds. The number of repetitions was recorded after each attempt.

Timepoint [5]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)

Secondary outcome [6]

Cardiorespiratory fitness will be assessed by the six-minute walk test. Participants will be instructed to walk back and forth around a series of cones in an indoor 30-metre corridor for six minutes. A stopwatch will be used to record the test duration. After the test has ceased, the total distance, resting heart rate, blood pressure, rating of perceived exertion and recovery time will be monitored.

Timepoint [6]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)

Secondary outcome [7]

Preoperative blood tests, including brain natriuretic peptide (BNP) will assess myocardial injury.

Timepoint [7]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)

Secondary outcome [8]

Muscle mass will be estimated using a validated computed tomography (CT) (equipment, manufacturer, location) analytic morphometric program (CoreSlicer). All patients will have a CT scan of the abdomen as part of their standard-of-care workup for cancer and during their follow-up to assess their response to therapy. The morphometric program will process a single imaging slice through the L3 vertebral level with manual adjustment to ensure accuracy. The analysis will be undertaken independently by two study personnel, with an average of the two measurements taken as the final reading. Total muscle area will be the primary measure of this analysis. However, subcutaneous and visceral fat area measures will also be recorded. All measures will be assessed as a composite measure.

Timepoint [8]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)

Secondary outcome [9]

A calorimeter measures energy expenditure (kJ), calculated from the amount of exhaled carbon dioxide (VCO2) and consumed oxygen (VO2). The calorimeter used in this study is the Fit mate GS ®, a non-invasive device that utilizes ventilated hood, which the patient breathes into the room air. The calorimeter is portable and can be utilised at the bedside or outpatient clinic. The mean resting energy expenditure is taken from a 5-minute steady state, which is then extrapolated to represent the 24-hour total resting energy expenditure and provides a precise energy requirement.

Timepoint [9]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) Seven days post-operation

Secondary outcome [10]

Weight (kg), height (m), and waist circumference (cm) will be measured in all patients using digital scales for weight, a tape measure for waist measurement and stadiometer for height, and BMI (kg/m2) calculated from measured values. Triceps skinfold (TSF) will be measured (in mm) using skinfold callipers to measure the fat pad over the left triceps muscle. This is a validated method to assess malnutrition. Mid-upper arm circumference (MUAC) will also be measured (in cm) on the left arm at the mid-point between the tip of the shoulder and tip of the elbow (olecranon process and the acromion). The mid-arm muscle area (MAMA) can then be calculated (MAMC = MUAC – p x TSF). The MAMA is a sensitive index of body protein reserve. Calf circumference will be measured (in cm) with the participant seated at the calf’s maximal circumference point on the perpendicular plane to the long axis. Calf circumference is a marker for diagnosing low skeletal muscle and sarcopenia. All measures will be assessed as a composite measure.

Timepoint [10]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation
(4) Longer-term (three and five years post-operation)

Secondary outcome [11]

The dietitian will assess the patient’s food intake via a diet history interview to determine usual food consumption patterns of the individual and detailed information on certain foods.

Timepoint [11]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation
(4) Longer-term (three and five years post-operation)

Secondary outcome [12]

Nutritional assessment will be determined by the scored Patient-Generated Subjective Global Assessment (PG-SGA), a validated nutrition assessment tool that allows rapid identification and prioritisation of malnutrition in hospitalised patients with cancer. The PG-SGA is determined from the patient’s nutritional history (weight change, dietary intake and gastrointestinal symptoms), clinical examination (physical signs of malnutrition including depletion of subcutaneous fat stores and muscle mass) and degree of functional impairment. Patients are then classified as well nourished (SGA A), mild-moderately malnourished (SGA B) or severely malnourished (SGA C), with a numerical score range from 0 (no problems) to 36 (worst problems). The patient-generated subject global assessment will be administered and performed by a member of the dietetics team.

Timepoint [12]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation

Secondary outcome [13]

Habitual physical activity will be assessed using a modified Godin Leisure-Time Exercise questionnaire to evaluate the past month’s duration and frequency of physical activity. A higher score is indicative of higher levels of physical activity participation.

Timepoint [13]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)

Secondary outcome [14]

The Duke Activity Status Index (DASI) is a structured 12-item survey assessing the ability to complete various physical tasks.

Timepoint [14]

(1) After neoadjuvant therapy (three months post-enrolment)

Secondary outcome [15]

Exercise self-efficacy will be assessed on the Exercise Self Efficacy 20-item questionnaire of which exercise beliefs, barriers to exercise and negative impact on cancer will be captured..

Timepoint [15]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)

Secondary outcome [16]

Illness perceptions will assess cognitive representations of illness using the revised Illness perception questionnaire (IPQ-R) across four subscales. These include personal control, illness coherence, consequences, and emotional representatives of illness.

Timepoint [16]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)

Secondary outcome [17]

Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer QLQ-30

Timepoint [17]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation
(4) Longer-term (three and five years post-operation)

Secondary outcome [18]

Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer QLQ-OES18 questionnaire.

Timepoint [18]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation
(4) Longer-term (three and five years post-operation)

Secondary outcome [19]

Hospital Anxiety and Depression Survey

Timepoint [19]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) Midpoint- three weeks after initiating neoadjuvant chemotherapy (three weeks post-enrolment)

Secondary outcome [20]

Patient Health Questionnaire-2 (PHQ-2) will provide a measure of patient psychological wellbeing

Timepoint [20]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation
(4) Longer-term (three and five years post-operation)

Secondary outcome [21]

Grip strength will be measured using a hand dynamometer (Saehan Medical, South Korea). The average of three attempts bilaterally (independent of hand dominance) will be documented.

Timepoint [21]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation

Secondary outcome [22]

The overall surgical complication rate data will be collected by medical review in accordance with ECCG guidelines and consultation with clinical treating team.

Timepoint [22]

(1) 30 days post operation

Secondary outcome [23]

Rate of the highest complication grade as defined by Clavien Dindo classification and will be obtained from the patient medical record reviewed by researchers.

Timepoint [23]

(1) 30 days post operation

Secondary outcome [24]

Postoperative length-of-stay (days) which will be obtained by reviewing patient medical records.

Timepoint [24]

(1) 30 days post operation

Secondary outcome [25]

30-day hospital readmission rate will be collected by accessing hospital records and reviewing clinical data.

Timepoint [25]

(1) 30 days post operation

Secondary outcome [26]

30-day intensive care unit readmission rate will be recorded by accessessing and assessing the patient medical records.

Timepoint [26]

(1) 30 days post operation

Secondary outcome [27]

30-day mortality rate will be collected by assessing patient medical record and relevant clinician correspondence.

Timepoint [27]

(1) 30 days post operation

Secondary outcome [28]

Rate of achieving textbook outcomes as defined by the Dutch Upper Gastrointestinal Cancer Audit and international consensus guidelines which will be record by auditing operation reports, medical record reviews and clinician documentation

Timepoint [28]

(1) 30 days post operation

Secondary outcome [29]

Days Alive and at Home within 30 days of surgery (DAH30): Total number of days spent at own residence or home within 30 days post-surgery. This data will be obtained by reviewing patient medical records, follow up appointments and where appropriate telephone calls to participants.

Timepoint [29]

(1) 30 days post operation

Secondary outcome [30]

Rate of completing postoperative chemotherapy will be collected by reviewing the patient medical records.

Timepoint [30]

(1) Baseline - before neoadjuvant chemotherapy (at the time of enrolment)
(2) After neoadjuvant therapy (three months post-enrolment)
(3) 30 days post operation
(4) Longer-term (three and five years post-operation)

Secondary outcome [31]

3- and 5-year disease-free survival duration defined from the time of surgery to the date of disease recurrence (by routine clinical, biochemical or radiological surveillance)

Timepoint [31]

(1) Longer-term (three and five years post-operation)

Secondary outcome [32]

3- and 5-year overall survival duration defined from the time of surgery to date of death

Timepoint [32]

(1) Longer-term (three and five years post-operation)

Eligibility

Key inclusion criteria

Any patient with gastric, gastroesophageal junction and oesophageal cancer

Scheduled to receive or undergoing neoadjuvant chemotherapy, radiotherapy or both

Elective oesophagectomy or gastrectomy following neoadjuvant treatment

Age equal to or above 18 years of age

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

Direct to surgery without neoadjuvant treatment

Stage 4 disease as determined by the Upper GI Cancer Multidisciplinary Team Meeting

Palliative intent treatment as determined by Upper GI Cancer Multidisciplinary Team Meeting

Undergoing local excision of cancer only, by endoscopy or surgery, without a radical lymphadenectomy

A neurological, musculoskeletal or cardiopulmonary condition deemed unsafe by the study doctor to participate in the enhanced prehabilitation program.

Study design

Statistical methods / analysis

Univariate, multivariate, Kaplan Meier and cox regression analysis will be used in this study. This study is powered to detect a clinically meaningful difference in overall respiratory complication rate. Based on data from our historical cohort, the overall rate of respiratory complications following oesophagectomy and gastrectomy at Austin Health is 40%. We consider a 20% absolute risk difference between study groups as clinically meaningful. Given the approximate ratio of 1:2 for historical cohort versus enhanced prehabilitation group, the total sample size required is 180 patients (historical cohort: 120, prehabilitation cohort: 60) to detect a 20% difference in respiratory complication rate between historical cohort (40%) and prehabilitation cohort (20%) with 80% statistical power (alpha <0.05). Given that on average, the Austin Hospital treats 30 oesophago-gastric cancer patients per year with curative-intent, this suggest that the prospective arm of this study will need to recruit for at least 2 years to achieve adequate statistical power to meet our primary endpoint.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

3/10/2022

Date of last participant enrolment

Anticipated

31/12/2024

Actual

Date of last data collection

Anticipated

31/01/2028

Actual

Sample size

Target

180

Accrual to date

1

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment postcode(s) [1]

3084 - Heidelberg

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Northern Eastern Melbourne Integrated Cancer Service (NEMICS)

Country [1]

Australia

Funding source category [2]

Hospital

Name [2]

Austin Health

Country [2]

Australia

Primary sponsor type

Hospital

Name

Austin Health

Country

Australia

Secondary sponsor category [1]

None

Name [1]

NA

Country [1]

Other collaborator category [1]

Other Collaborative groups

Name [1]

General & GastroIntestinal Surgery (GEGIS) Research Group

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

145 Studley Rd, Heidelberg VIC 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/09/2022

Approval date [1]

29/09/2022

Ethics approval number [1]

HREC/88598/Austin-2022

Summary

Brief summary

The majority of patients undergoing oesophageal/stomach cancer surgery have reduced fitness. This means they are at greater risk for, and struggle to overcome post-surgical complications, which leads to further morbidity and mortality. This study aims to assess whether a prehabilitation exercise and nutrition program administered to participants prior to surgery has any impact on their physical, nutritional and psychological wellbeing after surgery.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with gastric, gastroesophageal junction or oesophageal cancer, you are scheduled to receive or are currently undergoing chemotherapy, radiotherapy or both and you are going to undergo elective surgery to treat your cancer after completing these therapies.

Study details
All participants who choose to enrol in this study will be given a personalised diet and exercise program to follow for 3 months prior to their elective surgery. During the initial visit, participants will undergo a series of physical assessments to determine their current fitness levels and will be asked to provide a diet history to assess their nutrition status. It is anticipated that this initial assessment will take 60 minutes. After the initial assessment, participants will be given a personalised exercise plan to follow, this will include 2x 45-60 minute one-on-one sessions with a physiotherapist each week for 3 months. Participants will also be asked to undertake additional moderate exercise, e.g. walking, for at least one hour per week for the 3 months. Participants will also be given nutritional advice including suggested meal plans to address target areas (e.g. reducing carbohydrates or increasing protein or vitamin intakes) to follow over the 3 months prior to their surgery. For the 5 days prior to and 5 days after their surgery, participants will also be provided with an immune-modulating supplement (drink) to consume.
Participants who are assessed as at risk for anxiety and depression, and those participants who are struggling to comply with their exercise plan will also be offered one-on-one psychological counselling.
Data collected from participants who are undergoing these interventions will be compared to historical patients who received standard of care prior to their surgery.

It is hoped this research will demonstrate whether a targeted prehabilitation program has a positive effect on the physical, nutritional and mental wellbeing of patients who are undergoing treatment for gastric and oesophageal cancers. If this study does show a positive effect, the prehabilitation program may be expanded to a greater number of cancer patients.

Trial website

Public notes

Contacts

Principal investigator

Name

Dr David Liu

Address

Austin Health
145 Studley Rd, Heidelberg VIC 3084

Country

Australia

Phone

+61 402 857 529

Email

[email protected]

Contact person for public queries

Name

David Liu

Address

Austin Health
145 Studley Rd, Heidelberg VIC 3084

Country

Australia

Phone

+61 402 857 529

Email

[email protected]

Contact person for scientific queries

Name

David Liu

Address

Austin Health
145 Studley Rd, Heidelberg VIC 3084

Country

Australia

Phone

+61 402 857 529

Email

[email protected]

Trial Review

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