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

Not Applicable

Completed

• Conditions: Breast Neoplasms; Radiotherapy; Lymph Node Metastases
• Interventions: Device: Supine Radiotherapy; Device: Prone Radiotherapy; Radiation: Hypofractionation; Radiation: Acceleration

• Registration Number: NCT03280719
• Lead Sponsor: University Ghent

Brief 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.

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 Timeline

• Study First Submitted: 2017-08-02
• Study First Submitted QC: 2017-09-07
• Study First Posted: 2017-09-12
• Study Start: 2017-09-15
• Primary Completion: 2020-07-07
• Study Completion: 2021-06-09
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-09
• Last Update Posted: 2022-12-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 61

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Supine Hypofractionated Radiotherapy	Hypofractionation	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 Hypofractionated Radiotherapy	Supine 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 Accelerated Radiotherapy	Supine 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.
Prone Accelerated Radiotherapy	Acceleration	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 Hypofractionated Radiotherapy	Prone 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.
Prone Hypofractionated Radiotherapy	Hypofractionation	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.
Prone Accelerated Radiotherapy	Prone 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.
Supine Accelerated Radiotherapy	Acceleration	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.

Primary Outcome Measures

Name	Time	Method
Breast retraction	2 years after radiotherapy	Rate of breast retraction or volume loss after radiotherapy

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Radiotherapy department, UZ Ghent; 🇧🇪 Ghent, Oost-Vlaanderen, Belgium