Whole Breast + Lymph Node Irradiation: Prone Compared to Supine Position in 15 or 5 Fractions

Breast Neoplasms Clinical Trial

— PRO-SURF  

Official title:

Whole Breast (WB) + Lymph Node Irradiation (LNI): Prone Compared to Supine Position in a Randomized Study With 15 or 5 Fractions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03280719
• Other study ID #: EC/2017/0256
• Secondary ID: CIV-BE-17-06-020
• Status: Completed
• Phase: N/A
• Start date: September 15, 2017
• Est. completion date: June 9, 2021

Study information

• Verified date: December 2022
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: June 9, 2021
• Est. primary completion date: July 7, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Lymph Node Metastases
• Lymphatic Metastasis
• Radiotherapy

Intervention

Device:
• Prone Radiotherapy
Prone positioning for regional nodal irradiation using the crawl breast couch.

Radiation:
• Acceleration
Accelerated irradiation in 5 fractions over 12 days with simultaneously integrated boost

Device:
• Supine Radiotherapy
Supine positioning for regional nodal irradiation using breastboard.

Radiation:
• Hypofractionation
Moderate hypofractionation in 15 fractions over 3 weeks with simultaneously integrated boost

Locations

Country	Name	City	State
Belgium	Radiotherapy department, UZ Ghent	Ghent	Oost-Vlaanderen

Sponsors (1)

Lead Sponsor	Collaborator
University Ghent

Country where clinical trial is conducted

Belgium, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Breast retraction	Rate of breast retraction or volume loss after radiotherapy	2 years after radiotherapy
Secondary	Acute toxicity - Dermatitis	Dermatitis measured by CTCAE v4.03	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Desquamation	Desquamation measured by CTCAE v4.03	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Breast oedema	Breast oedema measured by CTCAE v4.03	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Shoulder range of motion	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
Secondary	Acute toxicity - Arm circumference	Arm circumference measured in cm 15 cm above and below medial epicondyle	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Breast symptoms - pain	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
Secondary	Acute toxicity - Breast symptoms - sense of heaviness	Sense of breast heaviness defined as present or absent.	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Breast symptoms - itching	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
Secondary	Acute toxicity - Arm Symptoms - Pain	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
Secondary	Acute toxicity - Arm Symptoms - Sense of heaviness	Sense of arm heaviness defined as present or absent.	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Shoulder symptoms - Pain	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
Secondary	Acute toxicity - Shoulder symptoms - Impaired shoulder mobility	Impaired shoulder mobility on the irradiated side defined as present or absent	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Pain not in arm/shoulder/breast	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
Secondary	Acute toxicity - Dysphagia	Dysphagia measured according to CTCAE v4.03	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Dyspnea	Dyspnea measured according to CTCAE v4.03	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Cough	Cough measured according to CTCAE v4.03	Baseline and from radiation initiation until 8-16 days after radiation treatment
Secondary	Acute toxicity - Cardiac toxicity	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
Secondary	Non-breast retraction late treatment related toxicity	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
Secondary	Cosmesis	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
Secondary	Quality of life - General	EORTC questionnaire QLQ-C30	At baseline and at 1, 2 and 5 years after radiotherapy
Secondary	Quality of life - Breast specific questionnaire	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
Secondary	Locoregional and distant tumor control	Locoregional and distant tumor control	At 1, 2 and 5 years after radiotherapy
Secondary	Treatment duration	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
Secondary	Dose parameters of target tissues/organs at risk	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)
Secondary	Volume parameters of targets/organs at risk/hot spots - volume of the structures	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)
Secondary	Volume parameters of targets/organs at risk - relative volume receiving a certain dose	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)
Secondary	Setup accuracy	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)
Secondary	Treatment cost	Cost-Utility Analysis (CUA) using the EuroQoL 5D tool.	Baseline, 1st visit after radiotherapy and at year 1, 2 and 5