Clinical trial NCT06452485: Postoperative Re-irradiaTion With and Without HYPERthermia: Toxicity, Quality of Life and Survival in Patients With Locoregional Recurrent Breast Cancer
Official title: Postoperative Re-irradiaTion With and Without HYPERthermia: Toxicity, Quality of Life and Survival in Patients With Locoregional Recurrent Breast Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Locoregional Recurrence
Breast Cancer
Re-irradiation
Hyperthermia
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Borstkanker Onderzoek Groep
name: Comprehensive Cancer Centre The Netherlands
name: Dutch Cancer Society
First posted: 2024-06-11
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Patient-reported toxicity according to PRO-CTCAE in LRR patients
timeFrame: Five years
Secondary outcomes:
measure: Quality of Life at 2 and 5 years after diagnosis of LRR disease
timeFrame: at 2 and 5 years after diagnosis of LRR disease
measure: Quality of Life at 2 and 5 years after diagnosis of LRR disease
timeFrame: at 2 and 5 years after diagnosis of LRR disease
measure: LRR-free survival in LRR patients
timeFrame: at 2 and 5 years after diagnosis of LRR disease
measure: distant metastasis-free survival in LRR patients
timeFrame: at 2 and 5 years after diagnosis of LRR disease
measure: breast-cancer event-free survival in LRR patients
timeFrame: at 2 and 5 years after diagnosis of LRR disease
measure: overall survival in LRR patients
timeFrame: at 2 and 5 years after diagnosis of LRR disease
measure: Referral patterns in patients diagnosed with LRR
timeFrame: 5 year
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
affiliation: Amsterdam UMC
name: Desiree Van Den Bongard, Dr
role: PRINCIPAL_INVESTIGATOR
References: