Outcome of 15 Versus 5 Fractions in Adjuvant Breast Radiotherapy in Women Over 65 Years

Not Applicable

Active, not recruiting

• Conditions: Breastcancer
• Interventions: Radiation: WBI 15 fractions; Radiation: WBI 5 fractions; Radiation: LNI 15 fractions; Radiation: LNI 5 fractions; Radiation: TWI 15 fractions; Radiation: SIB 15 fractions if needed; Radiation: TWI 5 fractions; Radiation: SIB 5 fractions if needed

• Registration Number: NCT03121248
• Lead Sponsor: University Hospital, Ghent

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.

Study Timeline

• Study First Submitted: 2017-01-13
• Study Start: 2017-02-15
• Study First Submitted QC: 2017-04-14
• Study First Posted: 2017-04-20
• Primary Completion: 2021-11-15
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-21
• Last Update Posted: 2023-12-22
• Study Completion: 2026-11-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 144

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TWI +/- LNI - observational - 15	TWI 15 fractions	TWI 15 fractions SIB 15 fractions if needed LNI 15 fractions
WBI + LNI - randomized - 5	SIB 5 fractions if needed	WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions
WBI - randomized - 5	SIB 5 fractions if needed	WBI 5 fractions SIB 5 fractions if needed
WBI + LNI - randomized - 15	WBI 15 fractions	WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions
WBI - randomized - 15	SIB 15 fractions if needed	WBI 15 fractions SIB 15 fractions if needed
WBI - observational - 15	WBI 15 fractions	WBI 15 fractions SIB 15 fractions if needed
WBI - observational - 5	WBI 5 fractions	WBI 5 fractions SIB 5 fractions if needed
WBI - randomized - 15	WBI 15 fractions	WBI 15 fractions SIB 15 fractions if needed
WBI + LNI - randomized - 5	WBI 5 fractions	WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions
WBI with LNI - observational - 5	WBI 5 fractions	WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions
TWI +/- LNI - observational - 15	LNI 15 fractions	TWI 15 fractions SIB 15 fractions if needed LNI 15 fractions
WBI + LNI - randomized - 15	SIB 15 fractions if needed	WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions
thoracic wall irradiation (TWI) +/- LNI - observational - 5	LNI 5 fractions	TWI 5 fractions SIB 5 fractions if needed LNI 5 fractions
WBI - randomized - 5	WBI 5 fractions	WBI 5 fractions SIB 5 fractions if needed
WBI - observational - 5	SIB 5 fractions if needed	WBI 5 fractions SIB 5 fractions if needed
WBI + LNI - randomized - 15	LNI 15 fractions	WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions
WBI with LNI - observational - 15	LNI 15 fractions	WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions
WBI with LNI - observational - 15	SIB 15 fractions if needed	WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions
thoracic wall irradiation (TWI) +/- LNI - observational - 5	TWI 5 fractions	TWI 5 fractions SIB 5 fractions if needed LNI 5 fractions
WBI - observational - 15	SIB 15 fractions if needed	WBI 15 fractions SIB 15 fractions if needed
WBI + LNI - randomized - 5	LNI 5 fractions	WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions
WBI with LNI - observational - 5	LNI 5 fractions	WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions
WBI with LNI - observational - 5	SIB 5 fractions if needed	WBI 5 fractions SIB 5 fractions if needed LNI 5 fractions
WBI with LNI - observational - 15	WBI 15 fractions	WBI 15 fractions SIB 15 fractions if needed LNI 15 fractions

Primary Outcome Measures

Name	Time	Method
Breast retraction (LENTSOMA)	2-5 years	Breast Cancer Conservative treatment.core (BCCT.core) objective measurement

Secondary Outcome Measures

Name	Time	Method
Overall survival	2 and 5 years	Number of patients alive, 2 and 5 years after adjuvant radiotherapy
Acute toxicity: number of patients with clinical relevant dermatitis (CTCAE v. 4.0)	1-8 weeks	Assessment of grade of dermatitis
Acute toxicity: number of patients with moist desquamation	1-8 weeks	CTCAE v. 4.0 (grade 3)
Chronic toxicity: measurement of patient satisfaction with breast esthetic outcome	Before radiotherapy and after 2 and 5 years	BREAST-Q questionnaire: Patient reported outcome, evaluating satisfaction with esthetic outcome.
Chronic toxicity - prevalence of radiation induced brachial plexopathy (RIBP) (standardized screening questionnaire), confirmed by electromyogram (EMG)	2 and 5 years	If a screening reveals unilateral pain, loss of function or muscular atrophy in the ipsilateral arm, an EMG will be performed to confirm/exclude RIBP
Breast cancer specific survival	2 and 5 years	Number of patients alive and without breast cancer recurrence at 2 and 5 years after adjuvant radiotherapy
Acute toxicity: number of patients with pain (CTCAE v. 4.0)	1-8 weeks	Grade 1: mild; Grade 2: moderate, limiting activity of daily living (ADL); grade 3: severe, limiting ADL
Chronic toxicity: prevalence of lymphedema	2 and 5 years	LENT Soma: score 0-4
Distant tumor control	2 and 5 years	Distant metastases free survival
Acute toxicity: number of patients with fatigue (MFI-20)	1-8 weeks	Questionnaire (20 questions)
Chronic toxicity: prevalence of telangiectasia	2 and 5 years	LENT Soma: Score 0-3
Chronic toxicity: prevalence of fatigue (MFI-20)	2 and 5 years	Questionnaire (20 questions)
Loco-regional tumor control	2 and 5 years	Ipsilateral or regional breast recurrence
Acute toxicity: number of patients with pruritus (CTCAE v. 4.0)	1-8 weeks	Grade 1: mild, localized topical intervention; Grade 2: intense, oral intervention, skin changes
Chronic toxicity: prevalence of fibrosis	2 and 5 years	LENT Soma: fibrosis (score 0-3)
Chronic toxicity: prevalence of pain	2 and 5 years	LENT Soma: score 0-4

Trial Locations

Locations (1)

Ghent University Hospital, Dept. Radiotherapy-Oncology; 🇧🇪 Ghent, Belgium