HRQoL in Advanced Soft Tissue Sarcoma Patients Treated With Chemotherapy.

The HOLISTIC Study: Health-related Quality Of Life in Patients With Advanced Soft Tissue Sarcomas Treated With Chemotherapy

The benefits of cancer treatments, such as chemotherapy, are traditionally measured by outcomes such as progression free survival and overall survival. The degree to which treatments affect symptoms of disease, patient functioning and HRQoL are rarely measured or incorporated in the main endpoints of large-scale clinical trials. Systemic treatments for the majority of patients with advanced STS are not curative but aim to improve patients' HRQoL through reduction of symptoms, slowing or halting disease progression, and may extend life for some patients. Despite this, there is little research into the impact of chemotherapy on HRQoL for advanced STS patients. In order for patients to make an informed decision about chemotherapy and the predicted effects on all aspects of their lives, clinicians should be able to provide data on HRQoL. This will also enhance the shared decision-making process between clinicians and their patients. Given that survival benefits of treatment beyond 2nd line chemotherapy are marginal, and HRQoL data are lacking for patients treated with third line systemic treatment, simultaneous collection of HRQoL data in patients treated with 1st and 3rd line chemotherapy will enable assessment of the course of HRQoL in patients at the beginning, and further along, their treatment trajectory. After discontinuation of 1st or 3rd line chemotherapy, all patients will be followed up at 2-3 month intervals to determine trajectory of quality of life over time, irrespective of whether or not they receive subsequent line(s) of chemotherapy.

Study Overview

• Status: Unknown
• Conditions: Quality of Life
• Intervention / Treatment: Other: Questionnaire

Detailed Description

Eligible patients with advanced soft tissue sarcoma will be introduced to this study by their hospital consultant during their routine outpatient appointment. Before deciding if he/she would like to take part, the patient will be provided with a patient information sheet which describes the study in detail. Participation in the study is entirely voluntary and their care will not be affected if he/she chooses not to take part.

The patient information sheet explains that this study involves completing regular questionnaires online, or by paper-and-pencil, about health-related quality of life, expectations of treatment, preferences for making treatment choices and thoughts at the end of chemotherapy.

If a patient agrees to take part, he/she will be asked to sign an informed consent form indicating their willingness to participate. Each patient will be given unique login details to complete the consent form online using the PROFILES website. If he/she prefers to receive paper versions of the questionnaires and complete a paper version of the informed consent form.

After informed consent has been given, each patient will be asked to complete the first questionnaire. This will take around 15-20 minutes to complete. Further questionnaires are completed every time the patient attends hospital for treatment with chemotherapy (each cycle). These questionnaires will take around 10-15 minutes to complete. Most patients have a maximum of six cycles of chemotherapy and therefore will complete six questionnaires during treatment. At the end of chemotherapy, patients will complete one further questionnaire. During follow-up patients will be asked to complete questionnaires online (or by paper) at home every 2-3 months. The maximum time a patient will participate in the study is 2 years.

Only after a participant has given consent, the research team will collect information for their medical files such as the date of their cancer diagnosis and any previous treatments received. This information will be linked to the questionnaire data at the end of the study, in order to analyse whether it is associated with health-related quality of life.

• Study Type: Observational
• Enrollment (Anticipated): 132

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • Royal Marsden Hospital
    • Contact: Julie Curtis; Phone Number: 02086613050; Email: julie.curtis@icr.ac.uk
    • Principal Investigator: Winette van der Graaf, PhD
    • Sub-Investigator: Robin Jones

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients aged ≥18 years with advanced soft tissue sarcoma.

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of advanced (not amenable to curative surgical resection) soft tissue sarcoma (histology confirmed by sarcoma histopathologist)
• Starting 1st line palliative chemotherapy or 3rd line palliative chemotherapy according to standard treatment guidelines.
• Able to communicate in English
• Mental capacity to provide informed consent and to participate in the study (as determined by the treating physician).
• Patients must be able to complete questionnaires themselves (a prerequisite for 'patient reported outcome' data).
• Patients must be under treatment or follow-up at one of the participating centres

Exclusion Criteria:

• Patients with GIST, Ewing sarcoma, rhabdomyosarcoma and desmoplastic small round cell tumour.
• Patients who have already started 1st line or 3rd chemotherapy.
• Patients who are too ill to receive any further systemic treatment (death is imminent), as determined by the referring health care professional

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Questionnaire adminstration; All patients who participate will complete questionnaires	Other: Questionnaire; Online/paper questionnaires

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in global health-related quality of life score after treatment with 1st line chemotherapy.	Patients will complete the EORTC-QLQ-C30 questionnaire at baseline and each cycle of chemotherapy. Question 30 asks patients to rate their global health-related quality of life on a scale from 1(very poor)- 7 (excellent). After linear transformation, patients will have a score from 0-100. A higher score on global health-related quality of life question means better HRQoL. Change in global HRQoL over treatment with first-line chemotherapy will be presented using descriptive statistics such as mean and standard deviation after each cycle. Change in global HRQoL will be tested using a paired sample t test from baseline to 4 cycles with a 2 sided 5 % significance level. For patients who do not complete 4 cycles, the last score/observation (post baseline) will be carried forward for the analysis. A sensitivity analysis will also be performed excluding those patients who do not reach 4 cycles. If data is not normally distributed, then the Wilcoxon test will be used.	After up to six cycles of chemotherapy (approximately six months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in physical, cognitive, social, role and emotional functioning scores after treatment with first-line chemotherapy.	Patients will complete the EORTC-QLQ-C30 questionnaire at baseline and each cycle of chemotherapy. After linear transformation, all functioning scores will produce a score from 0-100. A higher score on the functional scales means better functioning.	After up to six cycles of chemotherapy (approximately six months)
Health-related quality of life symptoms scores after treatment with first line chemotherapy	Patients will complete the EORTC-QLQ-C30 questionnaire at baseline and each cycle of chemotherapy. After linear transformation, all single items will produce a score from 0-100. A higher score on symptom scales means more complaints.	After up to six cycles of chemotherapy (approximately six months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in global health-related quality of life score after third-line chemotherapy	Patients will complete the EORTC-QLQ-C30 questionnaire at baseline and each cycle of chemotherapy. Question 30 asks patients to rate their global health-related quality of life on a scale from 1(very poor)- 7 (excellent). After linear transformation, patients will have a score from 0-100. A higher score on global health-related quality of life question means better HRQoL. Change in global HRQoL (continuous) after treatment with third-line chemotherapy will be presented descriptively over time using mean (SD) and graphics.	From start of 3rd line chemotherapy to cessation of 3rd line chemotherapy. (1-12 months)
Patient preference for collaborative decision-making	Control preference scale: This scale is widely used to measure patient preferences for treatment decision making with health care providers. Patients are asked to chose from five options the phrase that best describes the role that they have a) actually taken in dealing with cancer diagnosis/treatment decisions and b) the role that they would have preferred. The options are: 1) I prefer to make the final treatment decision. 2) I prefer to make the final treatment decision after seriously considering my doctor's opinion. 3) I prefer that my doctor and I share responsibility for deciding which treatment is best. 4) I prefer that my doctor makes the final treatment decision, but seriously considers my opinion. 5) I prefer to leave all treatment decisions to my doctor. Patients are grouped into those who would prefer an active role in decision making (response 1 or 2), a collaborative role (response 3), or a passive role (response 4 or 5).	2 years.
Decisional conflict	The decisional conflict scale measures personal perception of decision making and certainty or uncertainty over their choice. This includes determining the level of information and support to make the choice, whether the decision was in line with their values and how satisfied they are, or were, with their decision. Items are given a score value of 0 (no) or 1 (yes). The total score can only be calculated if all four items are answered. The sum of the four items will range from 0 (extremely high decisional conflict) to 4 (no decisional conflict). A score of 3 or less indicates decisional conflict. Results will be descriptive.	2 years
Patients' expectations of treatment with chemotherapy	Patients are asked how likely they think that chemotherapy will improve survival, cure their cancer and improve symptoms due to cancer. The answers are on a four point scale: very likely, somewhat likely, a little likely and not likely at all. This single question will enable us to assess expectations of chemotherapy among sarcoma patients and results will be descriptive.	2 years
Decisional Regret scores	Patients' retrospective views on their decision to receive chemotherapy will be assessed using the decisional regret scale. Patients are asked to think about the decision they have made and show how strongly they agree/disagree with 5 statements: It was the right decision, I regret the choice that I made, I would go for the same choice if I had to do it over again, the choice did me a lot of harm, the decision was a wise one. Items 2 and 4 should be reverse-coded so that, for each item, a higher number will indicate more regret. To help others interpret the score more readily with other scales ranging from 0 to 100, these scores can then be converted to a 0-100 scale by subtracting 1 from each item then multiply by 25. To obtain a final score, the items are summed and averaged. A score of 0 means no regret; a score of 100 means high regret.	2 years
Work ability index scores	The validity and reliability of the work ability has been assessed in correlation analyses and used in many international research studies. These questions assess the ability to work taking into account the demands of the work, health status and resources. There are seven questions from which we selected two general questions to inform future patients who are receiving chemotherapy on their ability to work during and after chemotherapy. These two questions are scored 0-10 and 1-6 will be descriptive scores.	2 years
Patient preference for quantity versus quality of life.	Quality-Quantity Questionnaire (QQQ): This tool is a validated construct consisting of eight questions which measure patient attitudes towards tradeoff of quantity versus quality of life (four questions for length of life (LOL) and four questions for quality of life (QOL)). For LOL and QOL a separate score is calculated. The total score for all four questions (LOL or QOL) is calculated and the minimum score (4) is then subtracted. This answer is then divided by the range (20-4) to create a rescaling of 0-100. Decision-making in patients with advanced soft tissue sarcomas is extremely complex. The patients' concerns are of utmost importance when weighing up the benefits and risks of toxic treatment such as chemotherapy.	2 years

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust
• Collaborators: Institute of Cancer Research, United Kingdom
• Investigators: Principal Investigator: Winette van der Graaf, PhD, Royal Marsden NHS Foundation Trust

Publications and helpful links

General Publications

• Younger E, Jones RL, Desar IME, Peckitt C, van der Graaf WTA, Husson O. Health-related quality Of Life In patients with advanced Soft TIssue sarcomas treated with Chemotherapy (The HOLISTIC study): protocol for an international observational cohort study. BMJ Open. 2020 Jun 1;10(6):e035171. doi: 10.1136/bmjopen-2019-035171. Erratum In: BMJ Open. 2020 Jun 25;10(6):e035171corr1.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2018
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: CCR4782

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No