Hypofractionated Radiotherapy in Breast Cancer Patients With Prosthetic Reconstruction

Official title

Randomized Phase III Clinical Trial of Hypofractionated Radiotherapy in Breast Cancer Patients With Immediate Prosthetic Reconstruction: PROMART Trial

Overview

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.

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.

Interventions

• Radiation Hypofractionation
  Hypofractionation scheme will comprise 40 Gy in 15 fractions

Primary outcome measures

• Assess the G3 toxicity rate [Time frame: 2 years]

Secondary outcome measures (8)

• Local recurrence [Time frame: 5 years]
• 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 [Time frame: 2 years]
• 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 [Time frame: 5 years]
• Compare acute and late radiodermatitis rates by Common Terminology Criteria for Adverse Events (CTCAE) 4.0 [Time frame: 2 years]
• Dosimetric analysis [Time frame: 5 years]
• Inflammation markers screening - detection of cytokines with the CBA panel [Time frame: 3 years]
• Extracellular vesicles isolation and characterization [Time frame: 4 years]
• Evaluate extracellular vesicles molecular profile [Time frame: 4 years]

Eligibility criteria

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

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 1 center

• Radiation Oncology Department — Barretos

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. PMID 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. PMID 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. PMID 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. PMID 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). 20 PMID 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. PMID 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. PMID 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 J PMID 24957550

Identifiers

NCT: NCT05491395 · 1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗