Nodal Burden and Nodal Recurrence in Patients With Isolated Tumor Cells After Neoadjuvant Chemotherapy Treated With Axillary Dissection or Nodal Radiation: the OPBC-05/EUBREAST-14R/ICARO Study

Breast Cancer Clinical Trial

— ICARO  

Official title:

Nodal Burden and Nodal Recurrence in Patients With Isolated Tumor Cells After Neoadjuvant Chemotherapy Treated With Axillary Dissection or Nodal Radiation: the OPBC-05/EUBREAST-14R/ICARO Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06464341
• Other study ID #: 2023-00418: bb23Weber
• Status: Active, not recruiting
• Start date: May 4, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purposes of this multicenter retrospective cohort study are to determine the residual nodal burden in patients with isolated tumor cells detected in the SLN or the clipped node after NAC and to determine oncologic outcomes in this group of patients after ALND or nodal RT or observation.

Description:

In the context of upfront surgery, the extent of disease in the sentinel lymph nodes (SLNs) significantly predicts the chances of additional non-SLN metastases during axillary lymph node dissection (ALND). For patients with minimal SLN disease (isolated tumor cells [ITCs] and micrometastases), the probability of further non-SLN metastases is between 10-20%. In contrast, for patients with macrometastases, the risk increases to 27-33%. In patients undergoing neoadjuvant chemotherapy (NAC), those with positive SLNs exhibit a greater residual nodal burden compared to those treated with upfront surgery. For patients with remaining micro- or macrometastases post-NAC, additional positive lymph nodes are found in over 60% of ALND specimens, regardless of receptor subtype. Consequently, ALND remains the standard care for any residual nodal disease after NAC. Residual ITCs after NAC are present in about 1.5% of all patients undergoing NAC. There is limited data on the likelihood of discovering additional positive lymph nodes in this group, with fewer than 35 documented cases examining residual nodal burden. Therefore, the benefit of ALND for minimal residual disease is uncertain, and axillary management for patients with nodal ITCs is not standardized. Although omitting ALND reduces arm morbidity, identifying residual nodal disease can influence adjuvant therapy recommendations. Despite the lack of consensus on the oncologic safety of omitting ALND in this group, care patterns indicate a growing adoption of this approach. Given the rarity of this clinical scenario and the absence of forthcoming prospective studies, this study utilized real-world data from a large international cohort to determine the incidence of residual non-SLN involvement in patients with ITCs in the SLNs post-NAC, and to compare clinical outcomes in patients with and without ALND as definitive axillary treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 583
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Consecutive patients affected with T1-4 N0-3 breast cancer
• For cN+: Biopsy proven confirmation is required
• For cN0: any axillary staging technique including palpation is allowed
• Residual ITCs in the SLN or clipped node
• At least 1-year follow-up (12/2021 or later depending on the time of data collection)
• For cN0: SLNB with single or dual tracer mapping
• For cN+: SLNB with dual mapping or targeted axillary dissection (TAD: imaging-guided localization of sampled node in combination with SLN procedure with or without dual mapping)
• Underwent TAD/SLNB +/- ALND +/- axillary RT

Exclusion Criteria:

• Male patients
• Patients with nodal pCR
• Patients with residual nodal micro- or macrometastases
• Stage IV disease at presentation
• Inflammatory breast cancer (T4d) at presentation

Related Conditions & MeSH terms

• Breast Cancer
• Recurrence

Intervention

Other:
• Observational study no intervention
Observational study no intervention

Locations

Country	Name	City	State
Germany	KEM Evang. Kliniken Essen-Mitte	Essen
Germany	University Hospital Heidelberg	Heidelberg
Germany	German Breast Group	Neu Isenburg
Greece	Athens Medical Center	Athens
Greece	Heraklion University Hospital	Heraklion
Italy	Instituto Nazionale Tumori (IRCCS)	Naples
Italy	Veneto Institute of Oncology IRCCS	Padua
Italy	Istituti Clinici Scientifici Maugeri IRCCS,	Pavia
Italy	IRCCS Humanitas Research Hospita	Rozzano
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Netherlands	Antoni van Leeuwenhoek	Amsterdam
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Spain	Hospital del Mar	Barcelona
Switzerland	Kantonsspital Baden	Baden
Switzerland	University Hospital Basel	Basel	Basel-Stadt
Switzerland	Breastcenter Zürich	Zürich
Turkey	Gülhane Research and Training Hospital	Ankara
Turkey	Istanbul University	Istanbul
Turkey	Istanbul University, Faculty of Medicine	Istanbul
Turkey	Marmara University, School of Medicine	Istanbul
Turkey	Research Institute of Senology Acibadem	Istanbul
Turkey	Bulent Ecevit University	Zonguldak
United Kingdom	Cambridge University Hospital	Cambridge
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Memorial Sloan Kettering Cancer Center

Countries where clinical trial is conducted

United States,  Germany,  Greece,  Italy,  Korea, Republic of,  Netherlands,  Slovenia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Axillary Lymph Node Dissection (ALND)	Evaluation of the number of ALNDs performed	one time assessment at surgery
Primary	Number of Tailored Axillary Dissection (TAD)	Evaluation of the number of TAD performed	one time assessment at surgery
Primary	Number of Sentinel Lymph Node Biopsy (SLNB)	Evaluation of the number of SLNB performed	one time assessment before surgery
Primary	Number Axillary Radiotherapy	Evaluation of the number of axillary radiotherapy performed	Up to 2 years
Primary	Number of additional micrometastases	Evaluation of the number of additional micrometastases removed by ALND	one time assessment at surgery
Primary	Number of additional macrometastases	Evaluation of the number of additional macrometastases removed by ALND	one time assessment at surgery
Primary	Axillary recurrence	Evaluation of the number of axillary recurrence	Up to 14 years
Secondary	Regional recurrence	Evaluation of the number of regional recurrence	Up to 14 years
Secondary	Locoregional recurrence	Evaluation of the number of locoregional recurrence	Up to 14 years
Secondary	Invasive recurrence	Evaluation of the number of invasive recurrence	Up to 14 years