Clinical trial NCT03280719: Whole Breast + Lymph Node Irradiation: Prone Compared to Supine Position in 15 or 5 Fractions
Official title: Whole Breast (WB) + Lymph Node Irradiation (LNI): Prone Compared to Supine Position in a Randomized Study with 15 or 5 Fractions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Neoplasms
Radiotherapy
Lymph Node Metastases
Keywords: Prone position
Supine position
Hypofractionation
Accelerated radiotherapy
Regional nodal irradiation
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2017-09-12
Enrollment: 61
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Breast retraction
timeFrame: 2 years after radiotherapy
Secondary outcomes:
measure: Acute toxicity - Dermatitis
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Desquamation
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Breast oedema
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Shoulder range of motion
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Arm circumference
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Breast symptoms - pain
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Breast symptoms - sense of heaviness
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Breast symptoms - itching
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Arm Symptoms - Pain
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Arm Symptoms - Sense of heaviness
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Shoulder symptoms - Pain
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Shoulder symptoms - Impaired shoulder mobility
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Pain not in arm/shoulder/breast
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Dysphagia
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Dyspnea
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Cough
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Acute toxicity - Cardiac toxicity
timeFrame: Baseline and from radiation initiation until 8-16 days after radiation treatment
measure: Non-breast retraction late treatment related toxicity
timeFrame: Baseline and from 6 months post radiotherapy until 5 years after radiotherapy
measure: Cosmesis
timeFrame: Baseline, 1st visit after radiotherapy and at year 1, 2 and 5
measure: Quality of life - General
timeFrame: At baseline and at 1, 2 and 5 years after radiotherapy
measure: Quality of life - Breast specific questionnaire
timeFrame: At baseline and at 1, 2 and 5 years after radiotherapy
measure: Locoregional and distant tumor control
timeFrame: At 1, 2 and 5 years after radiotherapy
measure: Treatment duration
timeFrame: At 3 weeks
measure: Dose parameters of target tissues/organs at risk
timeFrame: After treatment planning (Week 1-2 after inclusion)
measure: Volume parameters of targets/organs at risk/hot spots - volume of the structures
timeFrame: After treatment planning (Week 1-2 after inclusion)
measure: Volume parameters of targets/organs at risk - relative volume receiving a certain dose
timeFrame: After treatment planning (Week 1-2 after inclusion)
measure: Setup accuracy
timeFrame: Before each scheduled radiation treatment session (every treatment day starting from radiotherapy start until ± 3 weeks later)
measure: Treatment cost
timeFrame: Baseline, 1st visit after radiotherapy and at year 1, 2 and 5
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Radiotherapy department, UZ Ghent
state: Oost-Vlaanderen
Study officials:
affiliation: UZ Ghent
name: Katrien Vandecasteele, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.
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.
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.
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.
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.