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RecruitingNCT05491395PROMARTUpdated Aug 8, 2022

Hypofractionated Radiotherapy in Breast Cancer Patients With Prosthetic Reconstruction

An interventional study of Hypofractionation in Breast Cancer, sponsored by Barretos Cancer Hospital. Recruiting at 1 site in Brazil. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-08-08.

Sponsored by Barretos Cancer Hospital · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study summary

RATIONALE:

Radiotherapy (RT) can be indicated to patients submitted to breast-conserving surgery, but, despite the benefits, adjuvant RT can cause contracture generated by tissue fibrosis in patients with immediate prosthetic reconstruction, which could cause prosthesis loss. The biological explanation of this outcome is not fully understood, but recent advances in the analysis of patient-derived blood can contribute to establishing a connection of molecular alterations related to this clinical outcome.

There is not a consensus about using hypofractionated RT schemes for patients with BCS and breast reconstruction since no studies had investigated the reasons why some patients lose the prosthesis.

PURPOSE: This study will evaluate G3 toxicity rate in breast cancer patients with immediate prosthetic reconstruction, submitted to hypofractionated radiotherapy, analyzing capsular contracture, leakage, infection, and bad positioning in order to demonstrate the noninferiority of Hypo-RT with the conventional RT. Additionally, the molecular profile of blood samples will be investigated in order to find biomarkers related to inflammations processes and response to treatment.

Read the detailed description

General aim: To evaluated if hypofractionated accelerated radiotherapy in patients with breast cancer undergoing immediate breast implant reconstruction surgery is non inferior to conventional radiotherapy.

Aim 1 (Primary objective): Assess the G3 toxicity rate - loss of the prosthesis (complication that requires surgical intervention: capsular contracture, leakage, infection, malpositioning).

Aim 2 (Specific secondary objectives):

  • Compare local recurrence rate between two groups;
  • Compare quality of life index between two groups using EORTC QLQ-C30 / EORTC QLQ-BR45 scales during treatment, after 6 and 12 months after treatment ending;
  • Compare self-image differences between groups;
  • Compare acute and late radiodermatitis rates by CTCAE 4.0;
  • Analyse dosimetric planning differences considering the volumes of all breast and breast without prosthesis;
  • Study inflammation molecular markers, which may indicate an increased risk of fibrosis;
  • Evaluate the change in the profile of extracellular vesicles in patients treated with RT hypofractionated and conventional;
  • Evaluate the change in EV collagen production after in vitro irradiation, using co-culture experiments with breast cells and fibroblasts.
02

Conditions studied

  • Breast Cancer

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Keywords

  • breast cancer, radiation therapy, hypofractionated, biomarkers
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Women with confirmed histological diagnosis of invasive ductal carcinoma and lobular breast carcinoma;
  • Radical mastectomy with immediate reconstruction with a prosthesis;
  • Patients indicated for adjuvant RT;
  • Any lymph node status;
  • With or without adjuvant chemotherapy;
  • ECOG performance status from 0-2;
  • > 18 years old;
  • Informed Consent Form applied before any study-specific procedure.

Exclusion criteria

Exclusion Criteria:

  • Another histological diagnosis than invasive ductal carcinoma or lobular carcinoma;
  • Previous history of neoplasm and/or radiotherapy and/ or quimiotherapy before this study;
  • Distant metastatic disease;
  • Palliative treatment;
  • Patients with scleroderma / systemic lupus erythematosus.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
120 participants (estimated)

Study arms

  • Experimental
    Post Mastectomy Hypofractionated Radiotherapy Arm

    Post Mastectomy Hypofractionated Radiotherapy Arm

    Radiation: Hypofractionation

  • No intervention
    Post Mastectomy Conventional Radiotherapy

    Post Mastectomy Conventional Radiotherapy

Interventions

  • RadiationHypofractionation

    Hypofractionation scheme will comprise 40 Gy in 15 fractions

05

What researchers measure

Primary outcomes

  1. Assess the G3 toxicity rate

    loss of the prosthesis (complication that requires surgical intervention: capsular contracture, leakage, infection, malpositioning)

    Time frame: 2 years

Secondary outcomes

  1. Local recurrence

    Compare local recurrence rate between two groups

    Time frame: 5 years

  2. Assessment of quality of life through the EORTC Questionnaires European Organization for Research and Treatment of Cancer, where a high or low score may suggest good quality of life depending on the domain of the questionnaire

    Compare quality of life index between two groups using EORTC scales during treatment, after 6 and 12 months after treatment ending

    Time frame: 2 years

  3. Comparison of self-image using the EORTC Questionnaires European Organization for Research and Treatment of Cancer, where a high or low score may suggest good quality of life depending on the domain of the questionnaire

    Compare self-image differences between groups

    Time frame: 5 years

  4. Compare acute and late radiodermatitis rates by Common Terminology Criteria for Adverse Events (CTCAE) 4.0

    Acute and late radiodermatitis rateswill be evaluated by CTCAE 4.0 scale, using the adverse event (AE) reporting. A grading (severity) scale is provided for each AE term.

    Time frame: 2 years

  5. Dosimetric analysis

    Analyze dosimetric planning differences considering the volumes of all breast and breast without prosthesis

    Time frame: 5 years

  6. Inflammation markers screening - detection of cytokines with the CBA panel

    Study inflammation molecular markers, which may indicate an increased risk of fibrosis. The cytokines present in the plasma will be evaluated using the Cytometric Beads Array technique with the CBA panel - Human Th1/Th2/Th17CBAKit which, through beads, is able to identify the expression of cytokines expressed by Th1, Th2 standard lymphocytes and Th17, including IL-2, IL-4, IL-6, IL-10, IL-17A, TNF e IFN-γ. After proper labeling, the immunophenotypic analyzes will be performed in a BD FAC Symphony flow cytometer.

    Time frame: 3 years

  7. Extracellular vesicles isolation and characterization

    Evaluate the change in the profile of extracellular vesicles in patients treated with RT hypofractionated and conventional

    Time frame: 4 years

  8. Evaluate extracellular vesicles molecular profile

    Evaluate the change in EV collagen production after in vitro irradiation, using co-culture experiments with breast cells and fibroblasts

    Time frame: 4 years

06

Study locations

1 of 1 sites recruiting
  • Radiation Oncology Department
    Barretos, São Paulo 14784-400, Brazil
    Recruiting
07

References and documents

Publications

  • Halsted WS. I. The Results of Operations for the Cure of Cancer of the Breast Performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg. 1894 Nov;20(5):497-555. doi: 10.1097/00000658-189407000-00075. No abstract available. PubMed 17860107 ↗
  • Veronesi U, Saccozzi R, Del Vecchio M, Banfi A, Clemente C, De Lena M, Gallus G, Greco M, Luini A, Marubini E, Muscolino G, Rilke F, Salvadori B, Zecchini A, Zucali R. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med. 1981 Jul 2;305(1):6-11. doi: 10.1056/NEJM198107023050102. PubMed 7015141 ↗
  • Song SY, Chang JS, Fan KL, Kim MJ, Chang HP, Lew DH, Roh TS, Roh H, Kim YB, Lee DW. Hypofractionated Radiotherapy With Volumetric Modulated Arc Therapy Decreases Postoperative Complications in Prosthetic Breast Reconstructions: A Clinicopathologic Study. Front Oncol. 2020 Nov 17;10:577136. doi: 10.3389/fonc.2020.577136. eCollection 2020. PubMed 33282731 ↗
  • Liu L, Yang Y, Guo Q, Ren B, Peng Q, Zou L, Zhu Y, Tian Y. Comparing hypofractionated to conventional fractionated radiotherapy in postmastectomy breast cancer: a meta-analysis and systematic review. Radiat Oncol. 2020 Jan 17;15(1):17. doi: 10.1186/s13014-020-1463-1. PubMed 31952507 ↗
  • SBRT, Brazilian Society of Radiotherapy; Freitas NMA, Rosa AA, Marta GN, Hanna SA, Hanriot RM, Borges ABB, Gondim GRM, Pellizzon ACA, Veras IM, Almeida Junior WJ, Fernandez CRSHW, Batalha Filho ES, Castilho MS, Kuhnen FQ, Najas RMXF, Affonso Junior RJ, Leite ACC, Ribeiro HLM, Freitas Junior R, Oliveira HF. Recommendations for hypofractionated whole-breast irradiation. Rev Assoc Med Bras (1992). 2018 Sep;64(9):770-777. doi: 10.1590/1806-9282.64.09.770. PubMed 30672995 ↗
  • Van Poznak C, Somerfield MR, Bast RC, Cristofanilli M, Goetz MP, Gonzalez-Angulo AM, Hicks DG, Hill EG, Liu MC, Lucas W, Mayer IA, Mennel RG, Symmans WF, Hayes DF, Harris LN. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2015 Aug 20;33(24):2695-704. doi: 10.1200/JCO.2015.61.1459. Epub 2015 Jul 20. PubMed 26195705 ↗
  • Nimeus-Malmstrom E, Krogh M, Malmstrom P, Strand C, Fredriksson I, Karlsson P, Nordenskjold B, Stal O, Ostberg G, Peterson C, Ferno M. Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy. Breast Cancer Res. 2008;10(2):R34. doi: 10.1186/bcr1997. Epub 2008 Apr 22. PubMed 18430221 ↗
  • Tramm T, Kyndi M, Myhre S, Nord S, Alsner J, Sorensen FB, Sorlie T, Overgaard J. Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer. Acta Oncol. 2014 Oct;53(10):1337-46. doi: 10.3109/0284186X.2014.925580. Epub 2014 Jun 24. PubMed 24957550 ↗
  • Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Thery C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E968-77. doi: 10.1073/pnas.1521230113. Epub 2016 Feb 8. PubMed 26858453 ↗
  • Yin Z, Yu M, Ma T, Zhang C, Huang S, Karimzadeh MR, Momtazi-Borojeni AA, Chen S. Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1. J Immunother Cancer. 2021 Jan;9(1):e001698. doi: 10.1136/jitc-2020-001698. Erratum In: J Immunother Cancer. 2021 Oct;9(10):e001698corr1. doi: 10.1136/jitc-2020-001698corr1. J Immunother Cancer. 2022 Feb;10(2):e001698corr2. doi: 10.1136/jitc-2020-001698corr2. PubMed 33472857 ↗
  • Back M, Guerrieri M, Wratten C, Steigler A. Impact of radiation therapy on acute toxicity in breast conservation therapy for early breast cancer. Clin Oncol (R Coll Radiol). 2004 Feb;16(1):12-6. doi: 10.1016/j.clon.2003.08.005. PubMed 14768750 ↗
08

Registry details

Key details

Study ID
NCT05491395
Lead sponsor
Barretos Cancer Hospital
Responsible party
Sponsor
First posted
Aug 8, 2022
Start date
Jun 27, 2022
Primary completion
May 1, 2026 (estimated)
Completion
May 1, 2029 (estimated)
Last update
Aug 8, 2022

Study contacts

Marcos D Mattos, MD, MS
Contact
marcosbtos3@gmail.com
+5517981140230
Alexandre A Jacinto, MD, PhD
Contact
jacintoaa@gmail.com
+5517974001314
Marcos D Mattos, MD, MS
principal investigator · Barretos Cancer Hospital
Gabriela B Salvador, BS
study chair · Barretos Cancer Hospital
Wanessa F Altei, PhD
study chair · Barretos Cancer Hospital
Lais L Almeida, MD
study chair · Barretos Cancer Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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