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

Breastcancer Clinical Trial

— HAI-5-III  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03121248
• Other study ID #: EC/2016/1386
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 15, 2017
• Est. completion date: November 15, 2026

Study information

• Verified date: December 2023
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 144
• Est. completion date: November 15, 2026
• Est. primary completion date: November 15, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Breastcancer

Intervention

Radiation:
• WBI 5 fractions
External beam radiotherapy in 5 fractions of 5,7Gy
• WBI 15 fractions
External beam radiotherapy in 15 fractions of 2,67Gy
• LNI 5 fractions
External beam radiotherapy in 5 fractions of 5,4Gy
• LNI 15 fractions
External beam radiotherapy in 15 fractions of 2,67Gy
• SIB 5 fractions if needed
Simultaneous boost of 5 x 6,2Gy (6,5Gy in case of involved resection margins) if needed
• SIB 15 fractions if needed
Simultaneous boost of 15x3,12Gy (3,33Gy in case of involved resection margins) if needed
• TWI 5 fractions
External beam radiotherapy in 5 fractions of 5,7Gy
• TWI 15 fractions
External beam radiotherapy in 15 fractions of 2,67Gy

Locations

Country	Name	City	State
Belgium	Ghent University Hospital, Dept. Radiotherapy-Oncology	Ghent

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient preference	Patients can accept clinical trial but refuse randomization. In this case they will be allocated to a patient preference study arm, existing also of a 5 or 15 fraction-schedule. The choice of the patient: acceptance or non-acceptance of study, acceptance or non-acceptance of randomization, in case of patient preference arm: acceptance or 5 or 15 fractions.	Moment of intake, before allocation to study arm.
Other	QoL within perspective of cancer patients	QLQ C30 - standardised questionnaire	4 weeks, 1, 2 and 5 years
Other	QoL within perspective of breast cancer patients	QLQ BR23 - standardised questionnaire	4 weeks, 1, 2 and 5 years
Other	QoL within perspective of healthy patients	EQ-D5: standardised questionnaire	4 weeks, 1, 2 and 5 years
Other	Number of patients evolving to higher frailty score after radiotherapy	Measurement of frailty using G8 geriatric screening tool	4 weeks, 1, 2 and 5 years
Other	Cost Effectiveness Analysis	Cost effectiveness analysis comparing 5 with 15 fractions	5 years
Other	Technical feasibility of prone positioning	Percentage of patients able to perform prone positioning on new breast board: yes or no.	At the moment of simulation
Other	Technical feasibility of deep inspirational breath-hold in prone position	Percentage of patients able to perform breath-hold procedure in prone position: yes or no.	At the moment of simulation
Primary	Breast retraction (LENTSOMA)	Breast Cancer Conservative treatment.core (BCCT.core) objective measurement	2-5 years
Secondary	Acute toxicity: number of patients with clinical relevant dermatitis (CTCAE v. 4.0)	Assessment of grade of dermatitis	1-8 weeks
Secondary	Acute toxicity: number of patients with moist desquamation	CTCAE v. 4.0 (grade 3)	1-8 weeks
Secondary	Acute toxicity: number of patients with pain (CTCAE v. 4.0)	Grade 1: mild; Grade 2: moderate, limiting activity of daily living (ADL); grade 3: severe, limiting ADL	1-8 weeks
Secondary	Acute toxicity: number of patients with pruritus (CTCAE v. 4.0)	Grade 1: mild, localized topical intervention; Grade 2: intense, oral intervention, skin changes	1-8 weeks
Secondary	Acute toxicity: number of patients with fatigue (MFI-20)	Questionnaire (20 questions)	1-8 weeks
Secondary	Chronic toxicity: measurement of patient satisfaction with breast esthetic outcome	BREAST-Q questionnaire: Patient reported outcome, evaluating satisfaction with esthetic outcome.	Before radiotherapy and after 2 and 5 years
Secondary	Chronic toxicity: prevalence of fibrosis	LENT Soma: fibrosis (score 0-3)	2 and 5 years
Secondary	Chronic toxicity: prevalence of pain	LENT Soma: score 0-4	2 and 5 years
Secondary	Chronic toxicity: prevalence of telangiectasia	LENT Soma: Score 0-3	2 and 5 years
Secondary	Chronic toxicity: prevalence of lymphedema	LENT Soma: score 0-4	2 and 5 years
Secondary	Chronic toxicity: prevalence of fatigue (MFI-20)	Questionnaire (20 questions)	2 and 5 years
Secondary	Chronic toxicity - prevalence of radiation induced brachial plexopathy (RIBP) (standardized screening questionnaire), confirmed by electromyogram (EMG)	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	2 and 5 years
Secondary	Loco-regional tumor control	Ipsilateral or regional breast recurrence	2 and 5 years
Secondary	Distant tumor control	Distant metastases free survival	2 and 5 years
Secondary	Breast cancer specific survival	Number of patients alive and without breast cancer recurrence at 2 and 5 years after adjuvant radiotherapy	2 and 5 years
Secondary	Overall survival	Number of patients alive, 2 and 5 years after adjuvant radiotherapy	2 and 5 years

External Links

•   HAI-5 feasilibility trial: results acute toxicity