Breastcancer
Conditions
Keywords
Accelerated radiotherapy, Older women, Hypo-fractonation
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.
Interventions
RADIATIONWBI 5 fractions
External beam radiotherapy in 5 fractions of 5,7Gy
RADIATIONWBI 15 fractions
External beam radiotherapy in 15 fractions of 2,67Gy
RADIATIONLNI 5 fractions
External beam radiotherapy in 5 fractions of 5,4Gy
RADIATIONLNI 15 fractions
External beam radiotherapy in 15 fractions of 2,67Gy
RADIATIONSIB 5 fractions if needed
Simultaneous boost of 5 x 6,2Gy (6,5Gy in case of involved resection margins) if needed
RADIATIONSIB 15 fractions if needed
Simultaneous boost of 15x3,12Gy (3,33Gy in case of involved resection margins) if needed
RADIATIONTWI 5 fractions
External beam radiotherapy in 5 fractions of 5,7Gy
RADIATIONTWI 15 fractions
External beam radiotherapy in 15 fractions of 2,67Gy
Sponsors
University Hospital, Ghent
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Breast retraction (LENTSOMA) | 2-5 years | Breast Cancer Conservative treatment.core (BCCT.core) objective measurement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 lymphedema | 2 and 5 years | LENT Soma: score 0-4 |
| Chronic toxicity: prevalence of fatigue (MFI-20) | 2 and 5 years | Questionnaire (20 questions) |
| 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 |
| Loco-regional tumor control | 2 and 5 years | Ipsilateral or regional breast recurrence |
| Distant tumor control | 2 and 5 years | Distant metastases free survival |
| 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 |
| 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) |
| 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 |
| 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: 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 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| QoL within perspective of breast cancer patients | 4 weeks, 1, 2 and 5 years | QLQ BR23 - standardised questionnaire |
| QoL within perspective of healthy patients | 4 weeks, 1, 2 and 5 years | EQ-D5: standardised questionnaire |
| Number of patients evolving to higher frailty score after radiotherapy | 4 weeks, 1, 2 and 5 years | Measurement of frailty using G8 geriatric screening tool |
| Cost Effectiveness Analysis | 5 years | Cost effectiveness analysis comparing 5 with 15 fractions |
| Technical feasibility of prone positioning | At the moment of simulation | Percentage of patients able to perform prone positioning on new breast board: yes or no. |
| Technical feasibility of deep inspirational breath-hold in prone position | At the moment of simulation | Percentage of patients able to perform breath-hold procedure in prone position: yes or no. |
| Patient preference | Moment of intake, before allocation to study arm. | 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. |
| QoL within perspective of cancer patients | 4 weeks, 1, 2 and 5 years | QLQ C30 - standardised questionnaire |
Countries
Belgium
Outcome results
None listed