- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03280719
Whole Breast + Lymph Node Irradiation: Prone Compared to Supine Position in 15 or 5 Fractions (PRO-SURF)
Whole Breast (WB) + Lymph Node Irradiation (LNI): Prone Compared to Supine Position in a Randomized Study With 15 or 5 Fractions
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Locoregional radiotherapy after lumpectomy and axillary node dissection diminishes the locoregional recurrence risk at 10 years by 21,2 % in women with pathologically confirmed lymph node involvement.
Excess dose to organs at risk can lead to acute and late side effects, such as tissue damage, organ malfunction and secondary cancers. Radiotherapy in prone position has helped reduce these risks for whole breast radiotherapy only, but has not yet been adequately investigated for patients also requiring regional nodal irradiation. One of the reasons is that there is no optimal patient support device available to allow regional nodal irradiation in prone position. To this end, a novel positioning device was developed at our center, allowing regional nodal irradiation in prone position. It was called the crawl breast couch because the patient position resembles a phase from the crawl swimming technique. A previous planning study by Deseyne et al. using this device shows a benefit (i.e. reduced dose) for the ipsilateral lung, the thyroid, as well as a minor benefit for the right lung, and contralateral breast (which already receive very low relative doses) while maintaining similar target coverage when compared to supine positioning.
Apart from the paradigm shift from supine to prone radiotherapy, in recent years, it has become clear that breast cancer cells are more sensitive to fraction dose than originally presumed. Large randomized trials confirm this hypothesis: moderate hypofractionation schemes in 15 or 16 fractions are at least equivalent in tumor control and toxicity although the total dose is lower than the traditional 50 Gy in 25 fractions. Further acceleration to 5 fractions is expected to have an even larger radiobiological advantage regarding tumor control. Additional advantages are patient comfort and a better use of radiotherapy resources.
This randomized trial with 2 x 2 factorial design tests 2 interventions for patients with breast cancer requiring whole-breast and regional nodal irradiation: radiotherapy in prone position with a specifically designed patient support device called the crawl breast couch, and accelerated radiotherapy in 5 fractions. The standard arm in this trial is supine hypofractionated radiotherapy.
The goal of this trial is to evaluate the effect of the prone crawl treatment position and/or accelerated schedule on acute and late toxicities, as well as quality of life and time management for breast cancer patients receiving whole breast and regional nodal irradiation after breast conserving surgery.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Oost-Vlaanderen
-
Ghent, Oost-Vlaanderen, Belgium, 9000
- Radiotherapy department, UZ Ghent
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Breast conserving surgery
- AND Multidisciplinary decision of adjuvant whole breast + regional nodal irradiation
- AND Informed consent obtained, signed and dated before specific protocol procedures
Exclusion Criteria:
- Mastectomy
- OR Bilateral breast irradiation
- OR Distant metastasis/metastases
- OR previous irradiation to the thoracic, cervical or axillary region and overlap of fields with current treatment
- OR life expectancy of less than 2 years
- OR pre-existing conditions or comorbidities making toxicity evaluation difficult, e.g. skin disorders
- OR pregnant or breast feeding
- OR mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
- OR patient unlikely to complete the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Supine Hypofractionated Radiotherapy
Supine Radiotherapy and Hypofractionation: Whole breast + regional nodal irradiation in supine position with a median dose of 15 x 2.67 Gy prescribed to the whole breast and nodal regions. Median dose of the simultaneously integrated boost is 3.12 Gy per fraction. |
Supine positioning for regional nodal irradiation using breastboard.
Other Names:
Moderate hypofractionation in 15 fractions over 3 weeks with simultaneously integrated boost
Other Names:
|
Experimental: Prone Hypofractionated Radiotherapy
Prone Radiotherapy and Hypofractionation: Whole breast + regional nodal irradiation in prone position with a 15 x 2.67 Gy dose prescription to the whole breast and nodal regions. Median dose of the simultaneously integrated boost is 3.12 Gy per fraction. |
Moderate hypofractionation in 15 fractions over 3 weeks with simultaneously integrated boost
Other Names:
Prone positioning for regional nodal irradiation using the crawl breast couch.
Other Names:
|
Experimental: Supine Accelerated Radiotherapy
Supine Radiotherapy and Acceleration: Whole breast + regional nodal irradiation in supine position with a median dose of 5 x 5.7 Gy to the whole breast. Lymph node regions receive a median dose of 5 x 5.4 Gy. Median dose of the simultaneously integrated boost is 6.2 Gy per fraction. |
Supine positioning for regional nodal irradiation using breastboard.
Other Names:
Accelerated irradiation in 5 fractions over 12 days with simultaneously integrated boost
Other Names:
|
Experimental: Prone Accelerated Radiotherapy
Prone Radiotherapy and Acceleration: Whole breast + regional nodal irradiation in prone position with a median dose of 5 x 5.7 Gy to the whole breast. Lymph node regions receive a median dose of 5 x 5.4 Gy. Median dose of the simultaneously integrated boost is 6.2 Gy per fraction. |
Prone positioning for regional nodal irradiation using the crawl breast couch.
Other Names:
Accelerated irradiation in 5 fractions over 12 days with simultaneously integrated boost
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Breast retraction
Time Frame: 2 years after radiotherapy
|
Rate of breast retraction or volume loss after radiotherapy
|
2 years after radiotherapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Acute toxicity - Dermatitis
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Dermatitis measured by CTCAE v4.03
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Desquamation
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Desquamation measured by CTCAE v4.03
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Breast oedema
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Breast oedema measured by CTCAE v4.03
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Shoulder range of motion
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Shoulder range of motion measured by maximal excursion in abduction-adduction and anteversion-retroversion, in degrees from anatomical reference position
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Arm circumference
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Arm circumference measured in cm 15 cm above and below medial epicondyle
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Breast symptoms - pain
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Breast pain measured on a scale: 0 (no pain) - 1 (pain on contact) - 2 (pain on contact and also occasionally spontaneous) - 3 (pain on contact and regularly spontaneous) - 4 (pain medication needed and specify which)
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Breast symptoms - sense of heaviness
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Sense of breast heaviness defined as present or absent.
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Breast symptoms - itching
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Itching in the breast on a scale: 0 (no itching) - 1 (occasional itching) - 2 (regular itching)
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Arm Symptoms - Pain
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Arm pain measured on a scale: 0 (no pain) - 1 (pain on contact) - 2 (pain on contact and also occasionally spontaneous) - 3 (pain on contact and regularly spontaneous) - 4 (pain medication needed and specify which)
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Arm Symptoms - Sense of heaviness
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Sense of arm heaviness defined as present or absent.
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Shoulder symptoms - Pain
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Pain in the irradiated shoulder as defined on a scale: 0 (no pain) - 1 (occasional pain) - 2 (regular pain)
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Shoulder symptoms - Impaired shoulder mobility
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Impaired shoulder mobility on the irradiated side defined as present or absent
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Pain not in arm/shoulder/breast
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Pain present in any other region than arm, shoulder or breast, defined on a scale: 0 (no pain) - 1 (occasional pain) - 2 (regular pain).
Painful locations are indicated on a figure.
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Dysphagia
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Dysphagia measured according to CTCAE v4.03
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Dyspnea
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Dyspnea measured according to CTCAE v4.03
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Cough
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Cough measured according to CTCAE v4.03
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Acute toxicity - Cardiac toxicity
Time Frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Troponin T value at last treatment session ± 1 day compared with baseline measurement.
|
Baseline and from radiation initiation until 8-16 days after radiation treatment
|
Non-breast retraction late treatment related toxicity
Time Frame: Baseline and from 6 months post radiotherapy until 5 years after radiotherapy
|
breast oedema, telangiectasia, color changes, fibrosis, shoulder symptoms, breast symptoms, arm symptoms, brachial plexopathy, heart toxicity, dyspnea, thyroid function, pain, fatigue.
|
Baseline and from 6 months post radiotherapy until 5 years after radiotherapy
|
Cosmesis
Time Frame: Baseline, 1st visit after radiotherapy and at year 1, 2 and 5
|
Photographic image analysis using BCCT.core using frontal images with different arm positions.
Reported cosmetic outcome is evaluated with radiotherapy specific items of the Breast Q questionnaire
|
Baseline, 1st visit after radiotherapy and at year 1, 2 and 5
|
Quality of life - General
Time Frame: At baseline and at 1, 2 and 5 years after radiotherapy
|
EORTC questionnaire QLQ-C30
|
At baseline and at 1, 2 and 5 years after radiotherapy
|
Quality of life - Breast specific questionnaire
Time Frame: At baseline and at 1, 2 and 5 years after radiotherapy
|
Supplementing the general quality of life outcome (QLQ-C30) with breast specific questionnaire using the EORTC QLQ-BR23 tool
|
At baseline and at 1, 2 and 5 years after radiotherapy
|
Locoregional and distant tumor control
Time Frame: At 1, 2 and 5 years after radiotherapy
|
Locoregional and distant tumor control
|
At 1, 2 and 5 years after radiotherapy
|
Treatment duration
Time Frame: At 3 weeks
|
Time registration from the moment the patient climbs the treatment couch until end of radiation.
The first fraction is not measured as unforeseen problems in the workflow, questions or difficulties might delay treatment and falsify the results.
The moment the patient mounts the treatment couch as well as the moment she climbs down, will be registered using a remote sensor.
The beam on time is automatically registered by the treatment software.
|
At 3 weeks
|
Dose parameters of target tissues/organs at risk
Time Frame: After treatment planning (Week 1-2 after inclusion)
|
Data extracted from dose-volume histograms (DVHs) and associated DVH planning files. the data are extracted from the developped treatment plan before treatment is initiated. Discrete values will be evaluated for all patients, more precisely the following: D02 as a surrogate for Dmax, D05, D50, D95, D100, mean dose. All these values are reported in Gray (Gy) Parameters evaluated for OARs: - Mean dose, D02, D05, all in Gray |
After treatment planning (Week 1-2 after inclusion)
|
Volume parameters of targets/organs at risk/hot spots - volume of the structures
Time Frame: After treatment planning (Week 1-2 after inclusion)
|
Data extracted from dose-volume histograms (DVHs) and associated DVH planning files. the data are extracted from the developped treatment plan before treatment is initiated. Volume of the targets and organs at risk is measured in cubic centimeters (cm³). Hot spots are defined as regions receiving either 105 or 107 % of the prescribed dose or more. |
After treatment planning (Week 1-2 after inclusion)
|
Volume parameters of targets/organs at risk - relative volume receiving a certain dose
Time Frame: After treatment planning (Week 1-2 after inclusion)
|
Data extracted from dose-volume histograms (DVHs) and associated DVH planning files. the data are extracted from the developped treatment plan before treatment is initiated. For Organs at risk, a V5, V10, V20, V30 will be calculated. This is the relative volume of a the structure receiving a dose of 5, 10, 20 or 30 Gy. The value is measured as a percentage (%) of the total structure volume. |
After treatment planning (Week 1-2 after inclusion)
|
Setup accuracy
Time Frame: Before each scheduled radiation treatment session (every treatment day starting from radiotherapy start until ± 3 weeks later)
|
Cone beam computed tomography verification directly prior to each scheduled radiation treatment session to determine shift between planned positioning and actual positioning.
Shifts are performed and registered in laterolateral, craniocaudal and anteroposterior directions.
No rotations are performed.
|
Before each scheduled radiation treatment session (every treatment day starting from radiotherapy start until ± 3 weeks later)
|
Treatment cost
Time Frame: Baseline, 1st visit after radiotherapy and at year 1, 2 and 5
|
Cost-Utility Analysis (CUA) using the EuroQoL 5D tool.
|
Baseline, 1st visit after radiotherapy and at year 1, 2 and 5
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Katrien Vandecasteele, MD, PhD, UZ Ghent
Publications and helpful links
General Publications
- Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16. doi: 10.1016/S0140-6736(11)61629-2. Epub 2011 Oct 19.
- Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 Dec 17;366(9503):2087-106. doi: 10.1016/S0140-6736(05)67887-7.
- Mulliez T, Veldeman L, van Greveling A, Speleers B, Sadeghi S, Berwouts D, Decoster F, Vercauteren T, De Gersem W, Van den Broecke R, De Neve W. Hypofractionated whole breast irradiation for patients with large breasts: a randomized trial comparing prone and supine positions. Radiother Oncol. 2013 Aug;108(2):203-8. doi: 10.1016/j.radonc.2013.08.040. Epub 2013 Sep 14.
- Kirby AM, Evans PM, Donovan EM, Convery HM, Haviland JS, Yarnold JR. Prone versus supine positioning for whole and partial-breast radiotherapy: a comparison of non-target tissue dosimetry. Radiother Oncol. 2010 Aug;96(2):178-84. doi: 10.1016/j.radonc.2010.05.014. Epub 2010 Jun 17.
- Mulliez T, Van de Velde J, Veldeman L, De Gersem W, Vercauteren T, Speleers B, Degen H, Wouters J, Van Hoof T, van Greveling A, Monten C, Berwouts D, De Neve W. Deep inspiration breath hold in the prone position retracts the heart from the breast and internal mammary lymph node region. Radiother Oncol. 2015 Dec;117(3):473-6. doi: 10.1016/j.radonc.2015.09.030. Epub 2015 Oct 8.
- Mulliez T, Veldeman L, Speleers B, Mahjoubi K, Remouchamps V, Van Greveling A, Gilsoul M, Berwouts D, Lievens Y, Van den Broecke R, De Neve W. Heart dose reduction by prone deep inspiration breath hold in left-sided breast irradiation. Radiother Oncol. 2015 Jan;114(1):79-84. doi: 10.1016/j.radonc.2014.11.038. Epub 2014 Dec 9.
- Deseyne P, Speleers B, De Neve W, Boute B, Paelinck L, Van Hoof T, Van de Velde J, Van Greveling A, Monten C, Post G, Depypere H, Veldeman L. Whole breast and regional nodal irradiation in prone versus supine position in left sided breast cancer. Radiat Oncol. 2017 May 26;12(1):89. doi: 10.1186/s13014-017-0828-6.
- FAST Trialists group, Agrawal RK, Alhasso A, Barrett-Lee PJ, Bliss JM, Bliss P, Bloomfield D, Bowen J, Brunt AM, Donovan E, Emson M, Goodman A, Harnett A, Haviland JS, Kaggwa R, Morden JP, Robinson A, Simmons S, Stewart A, Sydenham MA, Syndikus I, Tremlett J, Tsang Y, Wheatley D, Venables K, Yarnold JR. First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol. 2011 Jul;100(1):93-100. doi: 10.1016/j.radonc.2011.06.026.
- Monten C, Lievens Y, Olteanu LAM, Paelinck L, Speleers B, Deseyne P, Van Den Broecke R, De Neve W, Veldeman L. Highly Accelerated Irradiation in 5 Fractions (HAI-5): Feasibility in Elderly Women With Early or Locally Advanced Breast Cancer. Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):922-930. doi: 10.1016/j.ijrobp.2017.01.229. Epub 2017 Feb 1.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EC/2017/0256
- CIV-BE-17-06-020245 (Other Identifier: EUDAMED)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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