Postoperative Re-irradiaTion With and Without HYPERthermia: Toxicity, Quality of Life and Survival in Patients With Locoregional Recurrent Breast Cancer (RT-HYPE)

In the Netherlands, breast cancer patients with locoregional recurrence (LRR) and high-risk factors are treated with postoperative re-irradiation with or without hyperthermia. Retrospective studies showed that 3-year locoregional control after postoperative re-irradiation with hyperthermia was 68-83%, and severe toxicity in up to 40% of LRR patients. Unfortunately, no prospective (randomized) data are available on clinical outcomes. Consequently, variation exists in hyperthermia-treatment and re-irradiation schedules. Prospective real-world data on oncological outcomes, toxicity and quality of life is highly needed for shared decision-making between patients and professionals. These data will be used in the design of a future randomized trial comparing postoperative re-irradiation and hyperthermia-treatment in high-risk LRR patients.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Hyperthermia; Locoregional Recurrence; Re-irradiation
• Intervention / Treatment: Other: No interventions, patient-reported outcomes (PROMs) and toxicity will be collected in both groups.

Detailed Description

The optimal management of LRR breast cancer is multidisciplinary, and based on various prognostic risk factors and previous treatments. The surgical treatment of local recurrences is salvage mastectomy after previous breast-conserving therapy, or local excision after previous mastectomy. Regional treatment of tumor-positive lymph nodes consists of axillary radiotherapy and/or lymph node dissection. High-risk LRR patients have an indication for postoperative irradiation to improve locoregional control and disease-free survival. In previously irradiated high-risk LRR patients, postoperative re-irradiation is administered with or without hyperthermia in the Netherlands depending on the treating center and treating professional. Before the preoperative systemic treatment era, primary re-irradiation with hyperthermia was the evidence-based standard of care in high-risk unresectable LRR. Hyperthermia was used to increase the therapeutic efficacy of re-irradiation. The introduction of preoperative systemic therapy in 2010 resulted in more resectable high-risk LRRs. This resulted in postoperative re-irradiation instead of primary re-irradiation in LRR patients, including variation in the use of hyperthermia. There is no evidence-based standard of care regarding the combination of postoperative re-irradiation with or without hyperthermia in high-risk LRR patients. The major problem is that only retrospective data and no prospective (randomized) data is available on oncological outcomes (survival and recurrence) and toxicity following postoperative re-irradiation and hyperthermia. Consequently, there is a high need to assess oncological outcomes and toxicity of postoperative re-irradiation with or without hyperthermia in a randomized controlled trial (RCT). So far, an RCT has not been feasible due to the large variation in postoperative re-irradiation and hyperthermia, and preferences regarding hyperthermia-treatment by professionals. In the RT-HYPE study, the investigators evaluate oncological outcomes, toxicity and quality of life in high-risk LRR patients, including the harmonization of hyperthermia-treatment. The results of the RT-HYPE study are needed for the optimization of the shared decision making (SDM) process on post-operative re-irradiation with or without hyperthermia, between professionals and patients. In addition, these results allow to set-up a future RCT comparing postoperative re-irradiation with and without hyperthermia treatment.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Lisca Wurfbain, MD; Phone Number: +31 6-25414750; Email: l.f.wurfbain@amsterdamumc.nl
• Study Contact Backup: Name: Desiree Van Den Bongard, Dr; Phone Number: +31 6-25414750; Email: h.j.vandenbongard@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC
    • Contact: Lisca Wurfbain, MD; Email: l.f.wurfbain@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients aged 18 years and older with an indication for postoperative re-irradiation with or without hyperthermia, eligible patients with a LRR with high-risk characteristics treated with mastectomy/local excision and postoperative re-irradiation, or mastectomy/local excision and postoperative re-irradiation with hyperthermia. Patients also treated with (neo-)adjuvant systemic treatment and/or with oligometastases (<=5 metastases), are allowed to be part of the study population.

Description

Inclusion Criteria:

• WHO performance scale ≤2
• >=18 years
• Patients with a LRR breast cancer after postoperative irradiation of the primary breast cancer. LRR is defined as a local and/or regional recurrence, including patients with a second primary ipsilateral breast cancer.
• Patients treated with salvage mastectomy with high-risk* tumor characteristics or local excision with an indication for postoperative re-irradiation.
• Previously treated with whole or partial breast irradiation.
• (Neo)adjuvant systemic therapy (NST) is allowed.
• Use of (FES/FDG-)PET-CT in staging of nodal and disseminated disease.
• Oligometastases in lymph nodes in the mediastinum, neck, contralateral axillary/supraclavicular region (up to a maximal number of five) is allowed.
• Adequate communication and understanding skills of the Dutch language.

Exclusion Criteria:

• Diagnosed with primary breast sarcoma
• Have a low-risk LRR after previous breast-conserving surgery/therapy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Postoperative re-irradiation with hyperthermia; Postoperative re-irradiation with hyperthermia in patients with locoregional recurrent breast cancer	Other: No interventions, patient-reported outcomes (PROMs) and toxicity will be collected in both groups.; Patients will receive standard of care. Patients need to fill in questionnaires, these are additional interventions for the included subject. Questionnaires for patient-reported outcomes (PROMs) and toxicity will be filled in one week before treatment, one week before re-irradiation, one week and three months after re-irradiation, one, two and five years after surgery.
Postoperative re-irradiation without hyperthermia; Postoperative re-irradiation without hyperthermia in patients with locoregional recurrent breast cancer	Other: No interventions, patient-reported outcomes (PROMs) and toxicity will be collected in both groups.; Patients will receive standard of care. Patients need to fill in questionnaires, these are additional interventions for the included subject. Questionnaires for patient-reported outcomes (PROMs) and toxicity will be filled in one week before treatment, one week before re-irradiation, one week and three months after re-irradiation, one, two and five years after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported toxicity according to PRO-CTCAE in LRR patients	Patient-reported toxicity according to PRO-CTCAE after a median follow-up of five years after diagnosis of (subsequent) LRR disease.	Five years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life at 2 and 5 years after diagnosis of LRR disease	EORTC-C30	at 2 and 5 years after diagnosis of LRR disease
Quality of Life at 2 and 5 years after diagnosis of LRR disease	EORTC -BR45	at 2 and 5 years after diagnosis of LRR disease
LRR-free survival in LRR patients		at 2 and 5 years after diagnosis of LRR disease
distant metastasis-free survival in LRR patients		at 2 and 5 years after diagnosis of LRR disease
breast-cancer event-free survival in LRR patients		at 2 and 5 years after diagnosis of LRR disease
overall survival in LRR patients		at 2 and 5 years after diagnosis of LRR disease
Referral patterns in patients diagnosed with LRR	Referral patterns (per institute, professional, patient-related factors including performance status, and travel distance).	5 year

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Borstkanker Onderzoek Groep; Comprehensive Cancer Centre The Netherlands; Dutch Cancer Society
• Investigators: Principal Investigator: Desiree Van Den Bongard, Dr, Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: June 4, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Body Temperature Changes; Heat Stress Disorders; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Hyperthermia; Breast Neoplasms; Health Services Administration; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Health Care Economics and Organizations; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Surveys and Questionnaires; Health Planning; Health Care Surveys; Health Services Research; Patient Outcome Assessment; Patient Reported Outcome Measures
• Other Study ID Numbers: 2012094

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