Radiotherapy in Preoperative Setting With CyberKnife for Breast Cancer

Not Applicable

• Conditions: Early Breast Cancer
• Interventions: Radiation: Neoadjuvant radiotherapy

• Registration Number: NCT03520894
• Lead Sponsor: Azienda Ospedaliero-Universitaria Careggi

Brief Summary

The aim of this study is to prospectively evaluate, in patients affected by early breast cancer, safety and feasibility of single fraction radiotherapy with Cyberknife R in preoperative setting, and to identify factors predictive for outcome based on biologic and clinical parameters.

Detailed Description

Monocentric, open-label, single-arm phase II study evaluating safety and efficacy of neoadjuvant radiotherapy in early breast cancer patients. Patients eligible are women aged 50 or more years old, affected by histologically proven invasive breast cancer, with positive hormonal receptors, grading 1 or 2, HER-2 negative, without lymphovascular invasion, and tumour size up to 2 cm (measured on mammography, ultrasound or magnetic resonance), negative clinical nodal status, eligible for BCS.

Study Timeline

• Study First Submitted: 2018-04-19
• Study First Submitted QC: 2018-04-28
• Study Start: 2018-05-01
• Study First Posted: 2018-05-11
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-18
• Last Update Posted: 2019-10-22
• Primary Completion: 2022-05-01
• Study Completion: 2024-05-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 25

Inclusion Criteria

1. Signed informed consent
2. Women ≥ 50 years old
3. Histological diagnosis of invasive breast cancer
4. ER positive (≥ 10% of tumoral cells present ER) and/or PR positive (≥ 10% of tumoral cells present PR)
5. Grading 1 or 2
6. Her2 negative (IHC 0-1+; in patients with IHC 2+, absence of amplification at FISH
7. No lymphovascular invasion evidence at biopsy
8. Early breast cancer (T1 N0 M0) clinically and radiologically defined (ultrasound study/ magnetic resonance)
9. Patients eligible for BCS.

Exclusion Criteria

Extension of breast disease within 5 mm from the skin surface 2. Tumor size > 2 cm 3. Patients affected by collagenopathies 4. Patients with BRCA1/2 mutations 5. Previous irradiation to homolateral breast 6. Previous irradiation to homolateral thoracic wall 7. DCIS and/or Paget's disease 8. Psychiatric disorders preventing informed consent signature.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant radiotherapy arm	Neoadjuvant radiotherapy	Early breast cancer patients eligible for breast conservative surgery will undergo neoadjuvant radiotherapy with Cyberknife robotic system

Primary Outcome Measures

Name	Time	Method
Rate of acute skin toxicity events, measured according to RTOG/EORTC scale	15 days	Acute skin toxicity (from the end of radiotherapy to surgery) according to Radiation Therapy Oncology Group (RTOG)/ European Organization for research and treatment of cancer (EORTC) scale. Measuring acute skin toxicity from a minimum of 0 (no change over baseline) to a maximum of 4 (Ulceration, Hemorrage, necrosis)

Secondary Outcome Measures

Name	Time	Method
Number of patients dying for breast cancer at 36 months	36 months	cause-specific free survival measured at 36 months
Number of patients with pathologic complete response (pCR) after surgery,according to Chevalier score	30 days	Rate of pCR according to Chevalier score
Number of patients free from locoregional progression at 36 months	36 months	locoregional progression free survival measured at 36 months
Correlation of differential genetic expression, immunologic and histopathologic features of tumor sample and biomarkers in blood and urine samples with toxicity and rate of response to radiotheraèy	60 days	Radiogenomic: confirm of differential genetic expression of genes already validated in previous literature (30-Radiation- induced gene signature; AOI 16-gene breast signature; IRDS gene signature) with Next Generation Sequencing (NGS, RNA-seq) or Real Time PCR on frozen biopsy tissue.; Immunologic: quantitative analysis of infiltrating leucocytes (MS and M1 macrophages, CD8+ and CD4+ lymphocytes) with immunohistochemistry on fresh biopsy tissue Histopathologic: qualitative analyses (pericytes) and quantitative pattern of vascularization in immunohistochemistry.; Biochemical: analysis of oxidative stress markers on peripheral blood and urines: a) 1 hour before SBRT; b) 1 hour after SBRT; c) 1 week after SBRT; d) during 24 hours before BCS; e) during 2-4 weeks after BCS.
Number of patients with complete resection after surgical excision	30 days	Rate of complete resection R0 with margin\<1cm (except for deep margin)
Number of patients free from metastatic progression at 36 months	36 months	Metastasis progression free survival measured at 36 months
Number of patients dying for any cause at 36 months	36 months	global survival measured at 36 months
Rate of chronic skin toxicity events, measured according to CTCAE	90 days	Incidence of chronic skin toxicity (over 90 days since the end of radiotherapy; fibrosis, telangiectasia, tardive oedema) according to Common terminology criteria for adverse events (CTCAE) v 4.03. From a minimum of 1 (Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; * to a maximum of 4 (Life-threatening consequences; urgent intervention indicated
Rate of chronic extra-cutaneous toxicity, measured according to CTCAE	90 days	Incidence of chronic extra-skin toxicity (over 90 days from the end of radiotherapy; lung fibrosis, pericarditis, myocardial ischemia, valvulopathy, thoracic wall pain, fracture) according to according to Common terminology criteria for adverse events (CTCAE) v 4.03. From a minimum of 1 (Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; * to a maximum of 4 (Life-threatening consequences; urgent intervention indicated

Trial Locations

Locations (1)

Azienda Ospedaliero Universitaria Careggi; 🇮🇹 Florence, Italy