Clinical trial NCT06464341: 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
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: Axillary lymph node dissection
Isolated tumor cells
Neoadjuvant chemotherapy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Memorial Sloan Kettering Cancer Center
First posted: 2024-06-18
Enrollment: 583
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients will be included. There is no formal sample size calculation

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Axillary Lymph Node Dissection (ALND)
timeFrame: Day 0
measure: Number of Tailored Axillary Dissection (TAD)
timeFrame: Day 0
measure: Number of Sentinel Lymph Node Biopsy (SLNB)
timeFrame: one time assessment before surgery
measure: Number Axillary Radiotherapy
timeFrame: Up to 2 years
measure: Number of additional micrometastases
timeFrame: Day 0
measure: Number of additional macrometastases
timeFrame: Day 0
measure: Axillary recurrence
timeFrame: Up to 14 years
Secondary outcomes:
measure: Regional recurrence
timeFrame: Up to 14 years
measure: Locoregional recurrence
timeFrame: Up to 14 years
measure: Invasive recurrence
timeFrame: Up to 14 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Valleywise Health Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Samuel Oschin Cancer Institute
state: California
city: Miami
country: United States
facility: Miami University
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Clinic
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Brasília
country: Brazil
facility: Sirio-Libanes Hospital, Department of Oncology
city: Curitiba
country: Brazil
facility: Nossa Senhora das Gracias Hospital
city: Goiânia
country: Brazil
facility: Instituto de Mastologia e Oncologia
city: São Paulo
country: Brazil
facility: Santa Paula Hospital
city: São Paulo
country: Brazil
facility: Sirio-Libanes Hospital, Department of Oncology
city: Montréal
country: Canada
facility: Mc Gill University
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Essen
country: Germany
facility: KEM Evang. Kliniken Essen-Mitte
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Lübeck
country: Germany
facility: University Hospital Schleswig-Holstein Campus Lübeck
city: Neu Isenburg
country: Germany
facility: German Breast Group
city: Athens
country: Greece
facility: Athens Medical Center
city: Heraklion
country: Greece
facility: Heraklion University Hospital
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
city: Naples
country: Italy
facility: Instituto Nazionale Tumori (IRCCS)
city: Naples
country: Italy
facility: University of Naples Federico
city: Padua
country: Italy
facility: Veneto Institute of Oncology IRCCS
city: Pavia
country: Italy
facility: Istituti Clinici Scientifici Maugeri IRCCS,
city: Rozzano
country: Italy
facility: IRCCS Humanitas Research Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Zielona Góra
country: Poland
facility: University Hospital of Zielona Góra
city: Ljubljana
country: Slovenia
facility: Institute of Oncology Ljubljana
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital Gothenburg
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Zürich
country: Switzerland
facility: Breastcenter Zürich
city: Zürich
country: Switzerland
facility: University Hospital Zürich
city: Ankara
country: Turkey
facility: Gülhane Research and Training Hospital
city: Istanbul
country: Turkey
facility: Acıbadem Research Instıtute of Senology
city: Istanbul
country: Turkey
facility: Istanbul University Institute of Oncology
city: Istanbul
country: Turkey
facility: Istanbul University, Faculty of Medicine
city: Istanbul
country: Turkey
facility: Marmara University, School of Medicine
city: Zonguldak
country: Turkey
facility: Zonguldak Bulent Ecevit University
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Walter P. Weber, MD
role: PRINCIPAL_INVESTIGATOR
References: