Clinical trial NCT03838419: Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer
Official title: Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
First posted: 2019-02-12
Enrollment: 202
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Breast cancer is the most frequent malignancy in women. Standard therapy for early-stage breast cancer is breast conserving surgery (BCS) followed by adjuvant whole breast irradiation (WBI), which usually requires a treatment time of 3-6 weeks. Several randomized controlled trials (RCTs) demonstrated that postoperative WBI after BCS significantly decreased the risk of local (in-breast) recurrence and improved breast cancer mortality as well as survival. However, one of the most common side-effects of radiotherapy is fatigue, which is reported in up to 80% of cancer patients during treatment. Especially in early-stage breast cancer patients it might be the only serious side-effect following adjuvant irradiation, as fatigue often significantly reduces quality of life due to resulting functional impairment and psychological distress. Fatigue additionally has a distinct socioeconomic impact: 75% of patients and 40% of caregivers are forced to change their employment status due to cancer-related fatigue.

For reducing treatment-related toxicity, several RCTs consequently addressed the question whether adjuvant WBI could be omitted in early-stage, low risk breast cancer patients treated with endocrine therapy. However, all these trials detected up to seven-time increased local recurrence rates without WBI following BCS. Both, longer duration of radiotherapy and larger radiation field sizes are known to be associated with increase in treatment-related fatigue. Accelerated partial breast irradiation (APBI), delivered exclusively to the original tumor location and not to the surrounding breast tissue, might therefore be an alternative treatment option with fewer side-effects for early-stage, low risk breast cancer patients. Few previous trials have already reported comparable outcomes for highly selected low-risk breast cancer patients for APBI compared to conventional WBI. First results also point out that APBI compared to WBI might be associated with less severity and intensity of fatigue.

One method for APBI is single-dose intraoperative radiotherapy (IORT) delivered directly to the tumor after resection. Data is still limited for APBI, hence current international and German guidelines suggest the use of APBI for low-risk early stage breast cancer patients but recommend the application of APBI preferably within a clinical trial.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed invasive breast cancer
* Total tumor size \< 2.5 cm
* cN0
* estrogen receptor positive, HER2-receptor negative on immunohistochemistry
* age \>= 50 years
* ECOG (Eastern Cooperative Oncology Group) Performance status ≤ 2
* Ability of subject to understand character and individual consequences of the clinical trial
* Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

* G3
* Extensive microcalcifications
* Invasive lobular carcinoma
* Clinically involved lymph nodes
* No invasive axillary lymph node staging planned
* Patients with significant mental or physical comorbidities that preclude regular follow-up
* Neoadjuvant chemotherapy or neoadjuvant endocrine therapy
* previous radiotherapy of the breast
* 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

Primary outcomes:
measure: Fatigue 12 weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Fatigue 5 weeks, 6 months, 2 years, 5 years after treatment start
timeFrame: 5 weeks, 6 months, 2 years, 5 years after treatment start
measure: Local tumor control in the index quadrant of the breast
timeFrame: 2 years and 5 years after treatment start
measure: Local tumor control in the ipsilateral breast
timeFrame: 2 years and 5 years after treatment start
measure: Quality of life employing EORTC (European Organisation for Research and Treatment of Cancer) Quality of life questionnaires (QLQ)-C30
timeFrame: 5 weeks, 12 weeks, 6 months, 2 years, 5 years after treatment start
measure: Quality of life employing BREAST-Q questionnaire
timeFrame: 5 weeks, 12 weeks, 6 months, 2 years, 5 years after treatment start
measure: Quality of life employing BCTOS (Breast Cancer Treatment Outcome Scale) questionnaire
timeFrame: 5 weeks, 12 weeks, 6 months, 2 years, 5 years after treatment start
measure: distant tumor control
timeFrame: 2 years and 5 years after treatment start
measure: Overall survival
timeFrame: 2 years and 5 years after treatment start
measure: Disease-free survival
timeFrame: 2 years and 5 years after treatment start
measure: Secondary malignancies
timeFrame: 2 years and 5 years after treatment start
measure: Acute toxicity
timeFrame: 5 weeks after treatment start
measure: Chronic toxicity
timeFrame: 6 months, 2 years and 5 years after treatment start
measure: Cosmesis
timeFrame: 5 weeks, 12 weeks, 2 years, 5 years after treatment start
measure: Regional tumor control
timeFrame: 2 years and 5 years after treatment start
Other outcomes:
measure: Explorative Endpoint
timeFrame: after surgery
Locations:
city: Heidelberg
country: Germany
facility: University Hospital of Heidelberg, Radiation Oncology
Study officials:
References:
citation: Forster T, Jakel C, Akbaba S, Krug D, Krempien R, Uhl M, Hafner MF, Konig L, Koerber SA, Harrabi S, Bernhardt D, Behnisch R, Krisam J, Hennigs A, Sohn C, Heil J, Debus J, Horner-Rieber J. Fatigue following radiotherapy of low-risk early breast cancer - a randomized controlled trial of intraoperative electron radiotherapy versus standard hypofractionated whole-breast radiotherapy: the COSMOPOLITAN trial (NCT03838419). Radiat Oncol. 2020 Jun 1;15(1):134. doi: 10.1186/s13014-020-01581-9.