Multimodal Intervention During Neoadjuvant Chemotherapy in Patients With Early-breast Cancer as a Strategy to Improve Treatment Response: DIANA Trial (Multimodal Prehabilitation: DIet, ANxiety Control Psychotherapy, Physical Activity)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Hospital Clinic of Barcelona
- Enrollment
- 214
- Locations
- 1
- Primary Endpoint
- Residual Cancer Burden Index (RCB)
Study Overview
Brief Summary
The aim of this clinical trial is to evaluate whether following a multimodal prehabilitation program including physical exercise, nutritional support and psychological intervention during neoadjuvant chemotherapy in breast cancer patients could improve the pathological response to chemotherapy.
214 women with non-metastatic breast cancer with indication of chemotherapy before surgery will be eligible to participate. Patients will be randomly assigned to either the intervention group or the control group.
- Patients assigned to the intervention group (107 women) will undergo a directed multimodal prehabilitation program during the chemotherapy (4-6 months), including structured physical exercise, psychological intervention and nutritional guidance.
- Patients assigned to the control group (107 women) will undergo standard clinical management for their disease without multimodal prehabilitation.
The response to chemotherapy between the two groups will be evaluated and compared. It is expected that multimodal prehabilitation will increase the response to chemotherapy and will improve the postoperative recovery of patients and their quality of life, as well as reducing the number of complications from surgery and chemotherapy treatment. Changes in the tumor microenvironment are also expected after prehabilitation.
Detailed Description
Breast cancer (BC) is the most common neoplasm worldwide and the leading cause of death among women. Neoadjuvant chemotherapy (NACT) is currently one of the main therapeutic pillars. The pathological response after NACT has demonstrated prognostic value in BC, being also a determinant factor for posterior treatments. In recent years, research has increasingly focused on the impact of lifestyle changes on BC, such as physical exercise, diet, and psychological interventions. These actions are part of what is known as prehabilitation, defined as the set of strategies applied prior to surgery to optimize the physical and emotional condition of patients before the surgical intervention.
The individual application of these strategies in BC patients has shown improved oncological outcomes, with positive effects on quality of life and tolerance to medical treatments. Furthermore, evidence suggests that these interventions may favorably modulate the tumor microenvironment by reducing intratumoral hypoxia, enhancing antitumor immune responses, and modulating systemic pro-inflammatory states.
Despite the demonstrated benefits of prehabilitation in multiple medical and surgical fields, there is limited evidence regarding its impact on systemic treatment outcomes in BC patients. There is also a lack of solid evidence evaluating the role of multimodal prehabilitation (combining different prehabilitation strategies) in BC, as well as its effect on treatment response and tolerance.
The current study proposes the application of a multimodal prehabilitation program during the NACT window, based on structured physical exercise, psychological therapy (mindfulness or anxiety-control techniques), and nutritional counseling in BC patients, as a strategy to enhance treatment response through changes in the tumor microenvironment. Additionally, it will be assessed whether the intervention improves treatment tolerance and postoperative recovery, among others.
The study consists of a randomized, single-blind, controlled clinical trial with two parallel groups that will include 214 women diagnosed with non-metastatic breast cancer, eligible for NACT, and awaiting surgery at our center.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Masking Description
The pathologist responsible for analyzing the pathological response to the treatment will be blinded.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed diagnosis of non-metastatic breast cancer: stages cT1-T4, cN0-N3, M0, and candidates for neoadjuvant chemotherapy (NAC).
- •Age ≥ 18 years.
- •Signed informed consent.
Exclusion Criteria
- •Contraindication or physical inability to perform moderate-to-high intensity physical exercise.
- •Pregnant or breastfeeding patients.
- •Presence of other active synchronous neoplasms.
- •Metastatic breast cancer (stage IV).
- •Patients already engaging in regular physical exercise: more than 150 minutes of moderate or intense aerobic exercise per week.
- •Male breast cancer patients.
- •Personal history of a previous malignancy treated with chemotherapy.
- •Severe or poorly controlled psychiatric illness (including uncontrolled active substance abuse).
Arms & Interventions
Control
107 women that will follow the standard of care. Patients in the control group will receive proper information and recommendations about lifestyle modifications according to the most recent oncological guidelines. The benefits of physical exercise, a healthy diet and psychological support will be exposed, but such interventions will not be provided in our centre.
Prehabilitation
107 women that will follow the multimodal prehabilitation program during NACT (physical exercise, psychological intervention, nutritional support).
Intervention: Multimodal prehabilitation (Behavioral)
Outcomes
Primary Outcomes
Residual Cancer Burden Index (RCB)
Time Frame: From enrollment (baseline, day 1) until the end of treatment at 4-6 months (preoperative).
The main variable of the trial is the RCB index score, obtained from the histological specimen of the oncological surgery performed after NAC. The four levels of response of the RCB index (RCB 0, I, II and III) will be divided into a favorable profile of response (fRCB), that will include cathegories RCB 0 and I, and an unfavorable response profile (uRCB), including RCB II and III. It is estimated that the average rate of a favorable RCB (fRCB) score, including RCB 0 and RCB I, will be approximately 40% in the control arm. Parallelly, the expected rates of unfavorable RCB (uRCB) scores, including RCB II and RCB III, are 60%. The objective is to improve the response rates by 20% in the intervention group, with 60% of fRCB scores and 40% of uRCB scores in this group.
Secondary Outcomes
- Weight(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after surgery.)
- Body Mass Index(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after surgery.)
- Physical activity level(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.)
- Strength(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.)
- Estimated maximal oxygen uptake (VO2 max)(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical) and 1 year after the surgery.)
- Patient-perceived quality of life(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.)
- Anxiety and Depression levels(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.)
- Nutritional status(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 year after the surgery.)
- Adherence to mediterranean diet(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), 1 month after surgery and 1 year after the surgery.)
- Body image perception(1 year after the surgery)
- Tumor microenvironment (Gene expression analyses)(From enrollment (baseline, day 1) until the end of treatment at 4-6 months (postoperative).)
- Body Mass Index(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.)
- Tumor staging(At diagnosis or day 1 (clinical TNM or cTNM) and after surgery (pathological TNM or pTNM))
- Adverse effects of neoadjuvant chemotherapy(After the treatment (4-6 months later, presurgical).)
- Tumor cellularity after NACT(After the surgery (after NACT, 4-6 months from day 1))
- Post-surgical hospitalization(From the surgery (5-7 months after day 1) until 30 days after the operation.)
- Weight(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.)
- Assessment of vascular density in peritumoral areas(At enrollment (baseline, day 1) and at the end of treatment at 4-6 months (postoperative).)
- Chemotherapy completion rate(At the end of the treatment (4-6 months after day 1, preoperative))
- Pain control after oncological surgery(Since the surgery is done (5-7 months from day 1) until hospital discharge.)
- Hospitalization during NACT(At the end of the treatment (4-6 months after day 1, preoperative))
- Anxiety and Depression levels(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.)
- Strength(Before the chemotherapy (baseline or day 1) and after the treatment (4-6 months later, presurgical).)
- Post-operative complications(From the surgery (5-7 months from day 1) until 30 days after.)
- Physical activity level(Before the chemotherapy (baseline or day 1) and after the treatment (4-6 months later, presurgical).)
- Estimated maximal oxygen uptake (VO2 max)(Before the chemotherapy (baseline or day 1) and after the treatment (4-6 months later, presurgical).)
- Patient-perceived quality of life(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.)
- Mindfulness status(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.)
- Change in oxygen consumption (VO2) from baseline to post-neoadjuvant therapy(Before the chemotherapy (baseline or day 1) and after the treatment (4-6 months later, presurgical).)
- Prehabilitation program adherence(After the prehabilitation program (4-6 months from day 1, presurgical).)
- Nutritional status(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.)
- Adherence to mediterranean diet(Before the chemotherapy (baseline or day 1), after the treatment (4-6 months later, presurgical), and 1 month after surgery.)
Investigators
Helena Castillo
Medical Doctor (MD), Specialized in Gynecology and Obstetrics
Hospital Clinic of Barcelona