<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03280719</url>
  </required_header>
  <id_info>
    <org_study_id>EC/2017/0256</org_study_id>
    <secondary_id>CIV-BE-17-06-020245</secondary_id>
    <nct_id>NCT03280719</nct_id>
  </id_info>
  <brief_title>Whole Breast + Lymph Node Irradiation: Prone Compared to Supine Position in 15 or 5 Fractions</brief_title>
  <acronym>PRO-SURF</acronym>
  <official_title>Whole Breast (WB) + Lymph Node Irradiation (LNI): Prone Compared to Supine Position in a Randomized Study With 15 or 5 Fractions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Ghent</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Ghent</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this trial is to evaluate the effect of the prone crawl treatment position and/or&#xD;
      accelerated schedule on acute and late toxicities, as well as quality of life and time&#xD;
      management for breast cancer patients receiving whole breast and regional nodal irradiation&#xD;
      after breast conserving surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Locoregional radiotherapy after lumpectomy and axillary node dissection diminishes the&#xD;
      locoregional recurrence risk at 10 years by 21,2 % in women with pathologically confirmed&#xD;
      lymph node involvement.&#xD;
&#xD;
      Excess dose to organs at risk can lead to acute and late side effects, such as tissue damage,&#xD;
      organ malfunction and secondary cancers. Radiotherapy in prone position has helped reduce&#xD;
      these risks for whole breast radiotherapy only, but has not yet been adequately investigated&#xD;
      for patients also requiring regional nodal irradiation. One of the reasons is that there is&#xD;
      no optimal patient support device available to allow regional nodal irradiation in prone&#xD;
      position. To this end, a novel positioning device was developed at our center, allowing&#xD;
      regional nodal irradiation in prone position. It was called the crawl breast couch because&#xD;
      the patient position resembles a phase from the crawl swimming technique. A previous planning&#xD;
      study by Deseyne et al. using this device shows a benefit (i.e. reduced dose) for the&#xD;
      ipsilateral lung, the thyroid, as well as a minor benefit for the right lung, and&#xD;
      contralateral breast (which already receive very low relative doses) while maintaining&#xD;
      similar target coverage when compared to supine positioning.&#xD;
&#xD;
      Apart from the paradigm shift from supine to prone radiotherapy, in recent years, it has&#xD;
      become clear that breast cancer cells are more sensitive to fraction dose than originally&#xD;
      presumed. Large randomized trials confirm this hypothesis: moderate hypofractionation schemes&#xD;
      in 15 or 16 fractions are at least equivalent in tumor control and toxicity although the&#xD;
      total dose is lower than the traditional 50 Gy in 25 fractions. Further acceleration to 5&#xD;
      fractions is expected to have an even larger radiobiological advantage regarding tumor&#xD;
      control. Additional advantages are patient comfort and a better use of radiotherapy&#xD;
      resources.&#xD;
&#xD;
      This randomized trial with 2 x 2 factorial design tests 2 interventions for patients with&#xD;
      breast cancer requiring whole-breast and regional nodal irradiation: radiotherapy in prone&#xD;
      position with a specifically designed patient support device called the crawl breast couch,&#xD;
      and accelerated radiotherapy in 5 fractions. The standard arm in this trial is supine&#xD;
      hypofractionated radiotherapy.&#xD;
&#xD;
      The goal of this trial is to evaluate the effect of the prone crawl treatment position and/or&#xD;
      accelerated schedule on acute and late toxicities, as well as quality of life and time&#xD;
      management for breast cancer patients receiving whole breast and regional nodal irradiation&#xD;
      after breast conserving surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">June 9, 2021</completion_date>
  <primary_completion_date type="Actual">July 7, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Breast retraction</measure>
    <time_frame>2 years after radiotherapy</time_frame>
    <description>Rate of breast retraction or volume loss after radiotherapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Dermatitis</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Dermatitis measured by CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Desquamation</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Desquamation measured by CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Breast oedema</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Breast oedema measured by CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Shoulder range of motion</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Shoulder range of motion measured by maximal excursion in abduction-adduction and anteversion-retroversion, in degrees from anatomical reference position</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Arm circumference</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Arm circumference measured in cm 15 cm above and below medial epicondyle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Breast symptoms - pain</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Breast symptoms - sense of heaviness</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Sense of breast heaviness defined as present or absent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Breast symptoms - itching</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Itching in the breast on a scale: 0 (no itching) - 1 (occasional itching) - 2 (regular itching)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Arm Symptoms - Pain</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Arm Symptoms - Sense of heaviness</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Sense of arm heaviness defined as present or absent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Shoulder symptoms - Pain</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Pain in the irradiated shoulder as defined on a scale: 0 (no pain) - 1 (occasional pain) - 2 (regular pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Shoulder symptoms - Impaired shoulder mobility</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Impaired shoulder mobility on the irradiated side defined as present or absent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Pain not in arm/shoulder/breast</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Dysphagia</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Dysphagia measured according to CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Dyspnea</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Dyspnea measured according to CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Cough</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Cough measured according to CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity - Cardiac toxicity</measure>
    <time_frame>Baseline and from radiation initiation until 8-16 days after radiation treatment</time_frame>
    <description>Troponin T value at last treatment session ± 1 day compared with baseline measurement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-breast retraction late treatment related toxicity</measure>
    <time_frame>Baseline and from 6 months post radiotherapy until 5 years after radiotherapy</time_frame>
    <description>breast oedema, telangiectasia, color changes, fibrosis, shoulder symptoms, breast symptoms, arm symptoms, brachial plexopathy, heart toxicity, dyspnea, thyroid function, pain, fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cosmesis</measure>
    <time_frame>Baseline, 1st visit after radiotherapy and at year 1, 2 and 5</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life - General</measure>
    <time_frame>At baseline and at 1, 2 and 5 years after radiotherapy</time_frame>
    <description>EORTC questionnaire QLQ-C30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life - Breast specific questionnaire</measure>
    <time_frame>At baseline and at 1, 2 and 5 years after radiotherapy</time_frame>
    <description>Supplementing the general quality of life outcome (QLQ-C30) with breast specific questionnaire using the EORTC QLQ-BR23 tool</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Locoregional and distant tumor control</measure>
    <time_frame>At 1, 2 and 5 years after radiotherapy</time_frame>
    <description>Locoregional and distant tumor control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment duration</measure>
    <time_frame>At 3 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose parameters of target tissues/organs at risk</measure>
    <time_frame>After treatment planning (Week 1-2 after inclusion)</time_frame>
    <description>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:&#xD;
D02 as a surrogate for Dmax, D05, D50, D95, D100, mean dose. All these values are reported in Gray (Gy)&#xD;
Parameters evaluated for OARs:&#xD;
- Mean dose, D02, D05, all in Gray</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume parameters of targets/organs at risk/hot spots - volume of the structures</measure>
    <time_frame>After treatment planning (Week 1-2 after inclusion)</time_frame>
    <description>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.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume parameters of targets/organs at risk - relative volume receiving a certain dose</measure>
    <time_frame>After treatment planning (Week 1-2 after inclusion)</time_frame>
    <description>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.&#xD;
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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Setup accuracy</measure>
    <time_frame>Before each scheduled radiation treatment session (every treatment day starting from radiotherapy start until ± 3 weeks later)</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment cost</measure>
    <time_frame>Baseline, 1st visit after radiotherapy and at year 1, 2 and 5</time_frame>
    <description>Cost-Utility Analysis (CUA) using the EuroQoL 5D tool.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Breast Neoplasms</condition>
  <condition>Radiotherapy</condition>
  <condition>Lymph Node Metastases</condition>
  <arm_group>
    <arm_group_label>Supine Hypofractionated Radiotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Supine Radiotherapy and Hypofractionation:&#xD;
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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prone Hypofractionated Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prone Radiotherapy and Hypofractionation:&#xD;
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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Supine Accelerated Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Supine Radiotherapy and Acceleration:&#xD;
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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prone Accelerated Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prone Radiotherapy and Acceleration:&#xD;
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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Prone Radiotherapy</intervention_name>
    <description>Prone positioning for regional nodal irradiation using the crawl breast couch.</description>
    <arm_group_label>Prone Accelerated Radiotherapy</arm_group_label>
    <arm_group_label>Prone Hypofractionated Radiotherapy</arm_group_label>
    <other_name>Crawl position</other_name>
    <other_name>Prone regional nodal irradiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Acceleration</intervention_name>
    <description>Accelerated irradiation in 5 fractions over 12 days with simultaneously integrated boost</description>
    <arm_group_label>Prone Accelerated Radiotherapy</arm_group_label>
    <arm_group_label>Supine Accelerated Radiotherapy</arm_group_label>
    <other_name>HAI-5</other_name>
    <other_name>Hyper-accelerated irradiation</other_name>
    <other_name>5 fractions</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Supine Radiotherapy</intervention_name>
    <description>Supine positioning for regional nodal irradiation using breastboard.</description>
    <arm_group_label>Supine Accelerated Radiotherapy</arm_group_label>
    <arm_group_label>Supine Hypofractionated Radiotherapy</arm_group_label>
    <other_name>Supine regional nodal irradiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionation</intervention_name>
    <description>Moderate hypofractionation in 15 fractions over 3 weeks with simultaneously integrated boost</description>
    <arm_group_label>Prone Hypofractionated Radiotherapy</arm_group_label>
    <arm_group_label>Supine Hypofractionated Radiotherapy</arm_group_label>
    <other_name>Moderate hypofractionation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Breast conserving surgery&#xD;
&#xD;
          -  AND Multidisciplinary decision of adjuvant whole breast + regional nodal irradiation&#xD;
&#xD;
          -  AND Informed consent obtained, signed and dated before specific protocol procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mastectomy&#xD;
&#xD;
          -  OR Bilateral breast irradiation&#xD;
&#xD;
          -  OR Distant metastasis/metastases&#xD;
&#xD;
          -  OR previous irradiation to the thoracic, cervical or axillary region and overlap of&#xD;
             fields with current treatment&#xD;
&#xD;
          -  OR life expectancy of less than 2 years&#xD;
&#xD;
          -  OR pre-existing conditions or comorbidities making toxicity evaluation difficult, e.g.&#xD;
             skin disorders&#xD;
&#xD;
          -  OR pregnant or breast feeding&#xD;
&#xD;
          -  OR mental condition rendering the patient unable to understand the nature, scope and&#xD;
             possible consequences of the study&#xD;
&#xD;
          -  OR patient unlikely to complete the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Katrien Vandecasteele, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UZ Ghent</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Radiotherapy department, UZ Ghent</name>
      <address>
        <city>Ghent</city>
        <state>Oost-Vlaanderen</state>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <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>
    <PMID>22019144</PMID>
  </reference>
  <reference>
    <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>
    <PMID>16360786</PMID>
  </reference>
  <reference>
    <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>
    <PMID>24044803</PMID>
  </reference>
  <reference>
    <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>
    <PMID>20561695</PMID>
  </reference>
  <reference>
    <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>
    <PMID>26455452</PMID>
  </reference>
  <reference>
    <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>
    <PMID>25497557</PMID>
  </reference>
  <reference>
    <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>
    <PMID>28549483</PMID>
  </reference>
  <reference>
    <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>
    <PMID>21752481</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>28366576</PMID>
  </reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>December 9, 2022</last_update_submitted>
  <last_update_submitted_qc>December 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prone position</keyword>
  <keyword>Supine position</keyword>
  <keyword>Hypofractionation</keyword>
  <keyword>Accelerated radiotherapy</keyword>
  <keyword>Regional nodal irradiation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Lymphatic Metastasis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03280719
org study id: EC/2017/0256
secondary id: CIV-BE-17-06-020245
nct id: NCT03280719
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Breast retraction
time frame: 2 years after radiotherapy
description: Rate of breast retraction or volume loss after radiotherapy
measure: Acute toxicity - Dermatitis
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Dermatitis measured by CTCAE v4.03
measure: Acute toxicity - Desquamation
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Desquamation measured by CTCAE v4.03
measure: Acute toxicity - Breast oedema
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Breast oedema measured by CTCAE v4.03
measure: Acute toxicity - Shoulder range of motion
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Shoulder range of motion measured by maximal excursion in abduction-adduction and anteversion-retroversion, in degrees from anatomical reference position
measure: Acute toxicity - Arm circumference
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Arm circumference measured in cm 15 cm above and below medial epicondyle
measure: Acute toxicity - Breast symptoms - pain
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: 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)
measure: Acute toxicity - Breast symptoms - sense of heaviness
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Sense of breast heaviness defined as present or absent.
measure: Acute toxicity - Breast symptoms - itching
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Itching in the breast on a scale: 0 (no itching) - 1 (occasional itching) - 2 (regular itching)
measure: Acute toxicity - Arm Symptoms - Pain
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: 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)
measure: Acute toxicity - Arm Symptoms - Sense of heaviness
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Sense of arm heaviness defined as present or absent.
measure: Acute toxicity - Shoulder symptoms - Pain
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Pain in the irradiated shoulder as defined on a scale: 0 (no pain) - 1 (occasional pain) - 2 (regular pain)
measure: Acute toxicity - Shoulder symptoms - Impaired shoulder mobility
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Impaired shoulder mobility on the irradiated side defined as present or absent
measure: Acute toxicity - Pain not in arm/shoulder/breast
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: 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.
measure: Acute toxicity - Dysphagia
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Dysphagia measured according to CTCAE v4.03
measure: Acute toxicity - Dyspnea
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Dyspnea measured according to CTCAE v4.03
measure: Acute toxicity - Cough
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Cough measured according to CTCAE v4.03
measure: Acute toxicity - Cardiac toxicity
time frame: Baseline and from radiation initiation until 8-16 days after radiation treatment
description: Troponin T value at last treatment session ± 1 day compared with baseline measurement.
measure: Non-breast retraction late treatment related toxicity
time frame: Baseline and from 6 months post radiotherapy until 5 years after radiotherapy
description: breast oedema, telangiectasia, color changes, fibrosis, shoulder symptoms, breast symptoms, arm symptoms, brachial plexopathy, heart toxicity, dyspnea, thyroid function, pain, fatigue.
measure: Cosmesis
time frame: Baseline, 1st visit after radiotherapy and at year 1, 2 and 5
description: 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
measure: Quality of life - General
time frame: At baseline and at 1, 2 and 5 years after radiotherapy
description: EORTC questionnaire QLQ-C30
measure: Quality of life - Breast specific questionnaire
time frame: At baseline and at 1, 2 and 5 years after radiotherapy
description: Supplementing the general quality of life outcome (QLQ-C30) with breast specific questionnaire using the EORTC QLQ-BR23 tool
measure: Locoregional and distant tumor control
time frame: At 1, 2 and 5 years after radiotherapy
description: Locoregional and distant tumor control
measure: Treatment duration
time frame: At 3 weeks
description: 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.
measure: Dose parameters of target tissues/organs at risk
time frame: After treatment planning (Week 1-2 after inclusion)
description: 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
measure: Volume parameters of targets/organs at risk/hot spots - volume of the structures
time frame: After treatment planning (Week 1-2 after inclusion)
description: 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.
measure: Volume parameters of targets/organs at risk - relative volume receiving a certain dose
time frame: After treatment planning (Week 1-2 after inclusion)
description: 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.
measure: Setup accuracy
time frame: Before each scheduled radiation treatment session (every treatment day starting from radiotherapy start until ± 3 weeks later)
description: 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.
measure: Treatment cost
time frame: Baseline, 1st visit after radiotherapy and at year 1, 2 and 5
description: Cost-Utility Analysis (CUA) using the EuroQoL 5D tool.
arm group label: Supine Hypofractionated Radiotherapy
arm group type: Active Comparator
description: 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.
arm group label: Prone Hypofractionated Radiotherapy
arm group type: Experimental
description: 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.
arm group label: Supine Accelerated Radiotherapy
arm group type: Experimental
description: 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.
arm group label: Prone Accelerated Radiotherapy
arm group type: Experimental
description: 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.
intervention type: Device
intervention name: Prone Radiotherapy
description: Prone positioning for regional nodal irradiation using the crawl breast couch.
arm group label: Prone Accelerated Radiotherapy
arm group label: Prone Hypofractionated Radiotherapy
other name: Crawl position
other name: Prone regional nodal irradiation
intervention type: Radiation
intervention name: Acceleration
description: Accelerated irradiation in 5 fractions over 12 days with simultaneously integrated boost
arm group label: Prone Accelerated Radiotherapy
arm group label: Supine Accelerated Radiotherapy
other name: HAI-5
other name: Hyper-accelerated irradiation
other name: 5 fractions
intervention type: Device
intervention name: Supine Radiotherapy
description: Supine positioning for regional nodal irradiation using breastboard.
arm group label: Supine Accelerated Radiotherapy
arm group label: Supine Hypofractionated Radiotherapy
other name: Supine regional nodal irradiation
intervention type: Radiation
intervention name: Hypofractionation
description: Moderate hypofractionation in 15 fractions over 3 weeks with simultaneously integrated boost
arm group label: Prone Hypofractionated Radiotherapy
arm group label: Supine Hypofractionated Radiotherapy
other name: Moderate hypofractionation
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Katrien Vandecasteele, MD, PhD
role: Principal Investigator
affiliation: UZ Ghent
facility: 
country: Belgium
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.
PMID: 22019144
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.
PMID: 16360786
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.
PMID: 24044803
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.
PMID: 20561695
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.
PMID: 26455452
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.
PMID: 25497557
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.
PMID: 28549483
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.
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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.
PMID: 28366576
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Lymphatic Metastasis