Clinical trial NCT03121248: Outcome of 15 Versus 5 Fractions in Adjuvant Breast Radiotherapy in Women Over 65 Years
Official title: A Partially Randomized Patient Preference Trial, Comparing Adjuvant Hypofractionated Radiotherapy in 15 Versus 5 Fractions After Breast Conserving Surgery or Mastectomy for Early or Locally Advanced Breast Cancer in Women Above 65 Years
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breastcancer
Keywords: Accelerated radiotherapy
Older women
Hypo-fractonation
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2017-04-20
Enrollment: 144
Sex: FEMALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the effect of highly accelerated external beam radiotherapy (EBRT) in 5 fractions over 10 days compared to 15 fractions over 3 weeks for early as well as locally-advanced stage breast cancer.

Primary endpoint will be chronic toxicity (breast deformation and retraction). Secondary endpoints are acute toxicity, loco-regional and distant tumor control, patient reported QoL and cosmetic satisfaction. Patients with lymph node irradiation will be closely monitored for radiation induced plexopathy.

Detailed description: Over the age of 65, uptake of adjuvant radiotherapy after surgery for breast cancer declines, even in women with poor prognostic stage or adverse tumor characteristics.

Lowering the number of fractions may reduce reluctancy for radiotherapy in this age group.

In a preceding prospective phase I-II trial, evaluating EBRT over 10 days, results on technical feasibility and acute toxicity were positively evaluated.

However, data on the chronic effects of breast irradiation using high doses per fraction are still sparse.

This trial is developed to compare standard hypo-fractionation in 15 fractions (if needed with simultaneously integrated boost - SIB) with highly accelerated radiotherapy in 5 fractions.

Patients referred for adjuvant radiotherapy after breast conserving surgery will preferably be randomized, depending on the indication, to a study-arm with whole breast irradiation (WBI) +/- SIB or to a study-arm with WBI+/- SIB and lymph node irradiation (LNI).

If patients after breast conserving surgery (BCS) have a strong preference for 5 or 15 fractions, they will be invited to enter the parallel observational arm (patient preference).

Patients referred for adjuvant radiotherapy after mastectomy +/- LNI accepting to participate, can choose a 5 or 15-fraction schedule. No randomization is foreseen in this last observational group.

Eligibility criteria: Inclusion Criteria:

* breast conserving surgery or mastectomy for breast carcinoma
* multidisciplinary decision of adjuvant irradiation
* absence of distant metastases
* informed consent obtained, signed and dated before specific protocol procedures

Exclusion Criteria:

* History of previous radiation treatment to the same region
* Bilateral breast irradiation
* Life expectancy of less than 2 years
* Planned reconstructive breast surgery
* Condition making toxicity evaluation difficult, e.g. skin disorders, pre-existing brachial plexus injury, ...
* Inability to respect constraints on skin, heart, lungs, esophagus, ribs, brachial plexus or any other organ at risk
* Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
* Patient unlikely to comply with the protocol; i.e. uncooperative attitude, inability to return for follow-up visits or unlikely to complete the study

Primary outcomes:
measure: Breast retraction (LENTSOMA)
timeFrame: 2-5 years
Secondary outcomes:
measure: Acute toxicity: number of patients with clinical relevant dermatitis (CTCAE v. 4.0)
timeFrame: 1-8 weeks
measure: Acute toxicity: number of patients with moist desquamation
timeFrame: 1-8 weeks
measure: Acute toxicity: number of patients with pain (CTCAE v. 4.0)
timeFrame: 1-8 weeks
measure: Acute toxicity: number of patients with pruritus (CTCAE v. 4.0)
timeFrame: 1-8 weeks
measure: Acute toxicity: number of patients with fatigue (MFI-20)
timeFrame: 1-8 weeks
measure: Chronic toxicity: measurement of patient satisfaction with breast esthetic outcome
timeFrame: Before radiotherapy and after 2 and 5 years
measure: Chronic toxicity: prevalence of fibrosis
timeFrame: 2 and 5 years
measure: Chronic toxicity: prevalence of pain
timeFrame: 2 and 5 years
measure: Chronic toxicity: prevalence of telangiectasia
timeFrame: 2 and 5 years
measure: Chronic toxicity: prevalence of lymphedema
timeFrame: 2 and 5 years
measure: Chronic toxicity: prevalence of fatigue (MFI-20)
timeFrame: 2 and 5 years
measure: Chronic toxicity - prevalence of radiation induced brachial plexopathy (RIBP) (standardized screening questionnaire), confirmed by electromyogram (EMG)
timeFrame: 2 and 5 years
measure: Loco-regional tumor control
timeFrame: 2 and 5 years
measure: Distant tumor control
timeFrame: 2 and 5 years
measure: Breast cancer specific survival
timeFrame: 2 and 5 years
measure: Overall survival
timeFrame: 2 and 5 years
Other outcomes:
measure: Patient preference
timeFrame: Moment of intake, before allocation to study arm.
measure: QoL within perspective of cancer patients
timeFrame: 4 weeks, 1, 2 and 5 years
measure: QoL within perspective of breast cancer patients
timeFrame: 4 weeks, 1, 2 and 5 years
measure: QoL within perspective of healthy patients
timeFrame: 4 weeks, 1, 2 and 5 years
measure: Number of patients evolving to higher frailty score after radiotherapy
timeFrame: 4 weeks, 1, 2 and 5 years
measure: Cost Effectiveness Analysis
timeFrame: 5 years
measure: Technical feasibility of prone positioning
timeFrame: At the moment of simulation
measure: Technical feasibility of deep inspirational breath-hold in prone position
timeFrame: At the moment of simulation
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital, Dept. Radiotherapy-Oncology
Study officials:
affiliation: Ghent University Hospital, Dept. Radiotherapy-Oncology
name: Liv Veldeman, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
References: