OPTimizing Irradiation Through Molecular Assesment of Lymph Node After Primary Systemic Treatment — OPTIMALIIa  

Breast Cancer Clinical Trial

Official title: OPTimizing Irradiation Through Molecular Assesment of Lymph Node After Primary Systemic Treatment

Status Terminated

Clinical Trial Summary

Breast cancer management integrating surgery, systemic therapy and radiation therapy tends to systemic treatment as the first therapeutic option, continuing afterwards by surgery and radiation therapy with the scope of decreasing the locoregional treatment. This strategy implies doubts about what should be the locoregional treatment, because many patients have remissions and a significant number of them a complete response. The responses are associated with better clinical outcome although there are doubts about they are a surrogate marker of survival.

Nodal irradiation after systemic treatment in patients with breast cancer it is under discussion, particularly in the case of patients with initial clinical involvement experiencing complete remission. For this reason, some groups decide irradiation of all nodal regions and others choose no irradiation of the lymph nodes at all. To clarify this discussion the present study is proposed.

The "One Step Nucleic Amplification" (OSNA) is a technique developed by Sysmex Corporation that allows a complete analysis of sentinel nodes and provides a quantification of the tumor marker Cytokeratin 19 (CK19) messenger ribonucleic acid (mRNA) in the sentinel node. The result is expressed by the Tumour Load as number of copies per microliter. This technique has shown its diagnostic ability both without primary systemic treatment and after primary systemic treatment, being more reproducible than conventional processes.

In spite of this, fits to mention that the studies of validation used to obtain the European Conformity (CE) mark only included patients without previous systemic treatment to the surgery.

Clinical Trial Description

Breast cancer management integrating surgery, systemic therapy and radiation therapy tends to systemic treatment as the first therapeutic option, continuing afterwards by surgery and radiation therapy with the scope of decreasing the locoregional treatment. This strategy implies doubts about what should be the locoregional treatment, because many patients have remissions and a significant number of them a complete response. The responses are associated with better clinical outcome although there are doubts about they are a surrogate marker of survival.

According to a previous publication, in which the predictors of locoregional recurrence National Surgical Adjuvant Breast and Bowel Project 18 (NSABP18) and National Surgical Adjuvant Breast and Bowel Project 27 (NSABP27) studies are evaluated, both studies designed for viewing the value of neoadjuvant chemotherapy, good results of locoregional control are described, although in many cases radiotherapy was omitted or lymph node were not irradiated.

Therefore the need to nodal irradiation begins to be questioned, especially when they are negative after primary systemic treatment, regardless of their previous state. However the clinical guidelines recommend radiotherapy planning according to the previous stage. The problem is the local treatment indication is established based on the indications of irradiation without primary systemic therapy, as showed in retrospective studies, without the existence of randomized studies designed to analyze the role of radiotherapy in these circumstances. In the last American Society of Clinical Oncology (ASCO) preliminary results of a meta-analysis including three large studies of primary systemic treatment were presented.

Results show that irradiation improves local control in N1 patients achieving a complete remission, radiotherapy being an independent prognostic factor, in terms of locoregional control; however, they conclude that the optimal selection of patients remains unclear. The controversy remains, because there is no evidence to treat nodes after primary systemic therapy, whether there is a complete remission as if it does not, nor is it known that subgroup of patients may benefit more from local treatments. Long-term studies are needed to analyze this issue, leaving the decision being especially complicated in cases of clinically positive nodes experiencing a complete remission. The problem remains that often is not known exactly has been irradiated since, in many studies, irradiation is indicated at the discretion of the researcher.

Given these doubts, European Society conducted a survey to find out what was the attitude about these patients, and the findings shows that 75% of the centers irradiate in the N1 case. The American Society obtained similar results and in Spain 64% of respondents irradiate the lymph nodes. These three publications conclude that studies are needed to determine the importance of irradiation after primary systemic treatment and while waiting for these results, a consensus muts be reached as stated in ASCO 2015 summary.

The "One Step Nucleic Amplification" (OSNA) is a technique developed by Sysmex Corporation that allows a complete analysis of sentinel nodes and provides a quantification of the tumor marker CK19 mRNA in the sentinel node. The result is expressed by the Tumour Load as number of copies per microliter. This technique has shown its diagnostic ability both without primary systemic treatment and after primary systemic treatment, being more reproducible than conventional processes.

In spite of this, fits to mention that the studies of validation used to obtain the CE mark only included patients without previous systemic treatment to the surgery.

In summary, nodal irradiation after systemic treatment in patients with breast cancer it is under discussion, particularly in the case of patients with initial clinical involvement experiencing complete remission. For this reason, some groups decide irradiation of all nodal regions and others choose no irradiation of the lymph nodes at all. To clarify this discussion the present study is proposed. ;

Related Conditions & MeSH terms

• Breast Cancer

• NCT number: NCT03972696
• Study type: Interventional
• Source: Grupo de Investigación Clínica en Oncología Radioterapia
• Status: Terminated
• Phase: N/A
• Start date: January 2017
• Completion date: April 30, 2021