Clinical trial NCT06954623: Partial Breast Re-irradiation for Breast Cancer
Official title: Partial Breast Re-irradiation for Breast Cancer Recurrences After Repeat Breast-conserving Surgery With Proton Beam Therapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Breast Cancers
Keywords: re-irratdiation
proton beam
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
First posted: 2025-05-01
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Breast cancer is the most common malignancy in women. Breast-conserving surgery (BCS) with adjuvant whole-breast irradiation (WBI) is currently the standard of care in the oncological treatment of primary breast cancer and offers an equivalent alternative to mastectomy. The primary aim of adjuvant radiotherapy (RT) is to improve local control and thus improve overall survival and breast cancer-specific mortality. However, nodal-negative women have a 10-year risk for local recurrences after RT in up to 15.6%. The management of ipsilateral breast cancer recurrence depends on the extent of tumor disease and staging results at the time of recurrence and mastectomy is currently the standard of care for previously irradiated patients. The application of particle therapy using proton beam therapy (PBT) represents an innovative radiotherapeutic technique for breast cancer patients. This trial will be conducted as a prospective single-arm phase II study in 20 patients with histologically proven invasive breast cancer recurrences with negative margins after repeat BCS and with an indication for local re-irradiation. Required time interval will be 1 year after previous RT to the ipsilateral breast. Patients will receive partial breast re-RT with proton beam therapy in 15 once daily fractions up to a total dose of 40.05 GyRBE. The primary endpoint is defined as the cumulative overall occurrence of acute / subacute skin toxicity grade ≥3 within 6 months after the start of re-RT.

Detailed description: The therapeutic challenge in re-irradiation involves finding a balance between tumor control and the risk of severe toxicity from cumulative radiation doses in previously irradiated organs. Re-RT options include the use of brachytherapy (BT) \], intraoperative radiotherapy (IORT) or external beam RT with photons or electrons. Depending on the time interval since previous RT and applied technique, high-grade (≥3) toxicity rates for re-RT range from about 9% acute skin to 12 % - 17 % late fibrosis and 1% - 10 % G4 toxicity for BT, late grade 3 fibrosis of 21% for IORT and grade 3 toxicity (skin, esophagitis, wound dehiscence) of 7 - 24% - 35% for EBRT including late breast volume asymmetry in 12%, acute and late grade 4 ulceration (1-2%) and even grade 5 (treatment related deaths) in 1.2%.

The dosimetric profile of PBT with the Bragg Peak offers advantageous physical properties and has proven to be superior to photon-based techniques in respect of dose reduction to adjacent organs-at-risk (OAR) and effective target volume coverage with lower integral doses to the patient's whole body. In addition, this technique could potentially offer higher radiobiological effects and tumor responses \[28\], which is particularly advantageous in potentially more therapeutically resistant disease biology in breast cancer recurrences. Overall, prospective experience related to re-RT of the ipsilateral breast after recurrences is limited and most commonly involves the technique of invasive multicatheter brachytherapy.

Eligibility criteria: Inclusion Criteria:

* histologically confirmed recurrent (or new primary) ipsilateral invasive breast cancer or DCIS after prior RT of the ipsilateral breast
* indication for re-irradiation after repeat breast conserving surgery (e.g. lumpectomy, wide excision, ...)
* tumor size \< 3 cm
* clinically node-negative (cN0)
* negative resection margin (R0)
* time interval: start of re-RT to prior RT ≥ 12 months
* ECOG Performance status ≤ 2
* ability of subject to understand character and individual consequences of the clinical trial
* written informed consent
* ≥18 years of age

Exclusion Criteria:

* distant metastases

  * concomitant chemotherapy (concomitant endocrine hormonal therapy is allowed; sequential chemotherapy is allowed)
  * patients who have not recovered from acute toxicities of prior therapies
  * known carcinoma \< 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
  * pregnant or lactating women
  * participation in another competing clinical study or observation period of competing trials
  * history of active connective tissue disorder (i.e. systemic lupus erythematosus, scleroderma, dermatomyositis, xeroderma pigmentosum, ...)
  * medical implants, which are at the time of reirradiation not eligible for particle therapy at Heidelberg Ion Beam Therapy Center

Primary outcomes:
measure: skin toxicity
timeFrame: Within the first 6 months after the start of re-RT
Secondary outcomes:
measure: Local Tumor control
timeFrame: At 1, 2 and 5 years after re-RT
measure: Patients Quality of life
timeFrame: At 1, 2 and 5 years after re-RT
measure: Regional Tumor control
timeFrame: At 1, 2 and 5 years after re-RT
measure: Distant Tumor control
timeFrame: At 1, 2 and 5 years after re-RT
measure: progression-free survival
timeFrame: At 1, 2 and 5 years after re-RT
measure: overall survival
timeFrame: At 1, 2 and 5 years after re-RT
measure: Quality of life -C30
timeFrame: At 1, 2 and 5 years after re-RT
measure: Quality of life BR-42
timeFrame: At 1, 2 and 5 years after re-RT
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Department Radiation Oncology
Study officials:
affiliation: University Hospital Heidelberg
name: Juergen Debus, MD
role: PRINCIPAL_INVESTIGATOR
References: