Clinical trial NCT03102307: Registry Trial to Evaluate the Clinical Utilization of Targeted Axillary Dissection (TAD)
Official title: A Prospective, Multicenter, Registry Trial to Evaluate Utilization Frequency and Feasibility of Targeted Axillary Dissection (TAD) After Needle Biopsy and Clip Placement in Early Breast Cancer With Clinically Affected Lymph Nodes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Early Stage Breast Cancer
Keywords: Targeted axillary dissection
Sentinel node biopsy
Neoadjuvant chemotherapy
Lead sponsor: Kliniken Essen-Mitte
Sponsor class: OTHER
Collaborators: name: GBG Forschungs GmbH
First posted: 2017-04-05
Enrollment: 548
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with newly diagnosed invasive breast cancer with clinically affected lymph nodes

Brief summary: A downstaging of axillary tumor-spread can be achieved in about 40% of the patients receiving neoadjuvant chemotherapy (NACT). The impact of NACT on loco-regional tumor control has not yet been sufficiently investigated. Moreover the pathologic nodal status after NACT is a strong prognostic marker. Therefore it is most desirable to identify the approximately 40% of patients with pathologic complete response of the axilla, that could be spared from a potentially non beneficial axillary lymph node dissection (ALND). Attempts to identify these patients via sentinel lymph node biopsy (SLNB) after NACT have failed to provide acceptable false negative rates (FNR). The new concept of targeted axillary dissection (TAD) following NACT has shown promising results. Still multiple information about the clinical adoption of this procedure into clinical practice are missing. The SenTa registry trial is designed to assess the clinical implementation of TAD into general practice.

Detailed description: For decades the pathologic nodal status in early breast cancer has been of paramount importance, when evaluating the need for further adjuvant therapies. Nowadays tumor characteristics as receptor status and gene expression essays are increasingly included in this decision process. An increasing number of breast cancer patients are treated with neoadjuvant chemotherapy (NACT). A downstaging of axillary tumor-spread can be achieved in about 40% of the patients receiving NACT. The contribution of NACT to loco-regional tumor control is not fully integrated into the surgical treatment plan. The introduction of sentinel lymph node biopsy (SLNB) and the results of the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial led to a reduction in radicalness of axillary surgery in the adjuvant setting. The impact of NACT on loco-regional tumor control in the neoadjuvant setting has not yet been sufficiently investigated. Moreover the pathologic nodal status after NACT is a strong prognostic marker. Therefore it is most desirable to identify the approximately 40% of patients with pathologic complete response of the axilla and distinguish these patients from those with tumor residuals which might need additional postneoadjuvant treatment. So far attempts to identify these patients via SLNB after NACT have failed to provide acceptable false negative rates (FNR) as reported in the SENTINA (Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) trial and ACOSOG Z1071 trial.

Attempts have bee made to further improve FNR of SLNB after NACT in patients with clinically affected lymph nodes at initial presentation. A new concept of surgical axillary staging after NACT is the targeted axillary dissection (TAD). First results have shown to reduce FNR far below the desired threshold of 10%. In this procedure clinically suspicious lymph nodes are evaluated by core needle biopsy (CNB) or fine needle aspiration (FNA) before NACT. A clip is placed into the most suspicious appearing lymph node (target lymph node TLN) directly after biopsy. In case of proven metastasis surgical staging of the axilla is postponed to after completion of NACT. The targeted resection of the clipped node after NACT (target lymph node biopsy TLNB) displays a FNR of 2 - 4.2% according to first results published by Caudle et al. in 2016. In about 3 out of 4 patients the TLN equals a SLN if SLNB is performed simultaneously. The combination of TLNB and SLNB (together so called TAD) seems to further lower FNR. Cases in which tracer uptake in lymph nodes is impaired i.e. by tumor residuals and presumably result in a false negative SLNB can be covered by TLNB.

Clip placement in affected axillary lymph nodes for the purpose of following targeted resection has been implemented into international guidelines. But to date multiple insights into clinical application of TAD are missing. It is not known how often initial CNB/FNA of axillary lymph nodes and following clip placement is successful or has to be abandoned because of technical/medical contraindications. Moreover it is not known how often visualization of the clip after normalization of lymph node structures following NACT and month after initial clip placement is possible. Furthermore information about optimal clip material are lacking. In summary success rates for the targeted resection of the clipped node have to be investigated. Therefore the intraoperative detection rate of the clipped target lymph node is our primary outcome measure.

Patients with clinically affected lymph nodes at initial presentation are planned to be enrolled in multiple german breast centers. In accorndance to german guidelines it is aimed to evaluate the pathologic nodal status via CNB with following clip placement in all of these patients after informed consent. If CNB or clip placement cannot be achieved, technical/medical contraindications are recorded. As the SenTa trial is a registry trial, no strict directives for the further surgical treatment are made. If clip placement is successful, further procedures are left at the investigators choice according to initial pathologic nodal status and potential clinical response to NACT.

If no tumor manifestations are detected in initial CNB, SLNB with simultaneous targeted resection of the clipped node (TLNB) is recommended. The rationale for TLNB in this situation is a FNR of about 20% of initial CNB. On an individual basis upfront ALND can be offered.

If tumor manifestations are detected in initial CNB, targeted resection of the clipped node (TLNB) is strongly recommended because of obvious reasons. If NACT is not planned, upfront ALND should be offered. If patients are planned for NACT further procedures are left at the investigators discretion according to clinical response to NACT. Clinical response after NACT is assessed by axillary ultrasound and an optional needle biopsy if applicable. In case of clinical complete response, TLNB with simultaneous SLNB can be offered on an individual basis.

Eligibility criteria: Inclusion Criteria

* informed consent
* invasive mamma carcinoma verified by needle biopsy of the primary tumor
* nodal positive (cN+) verified by axillary ultrasound
* cT stage 1-4c, multifocality allowed
* no sign of distant metastasis (cM0)

Exclusion Criteria:

* prior history of breast cancer
* prior ipsilateral extensive surgery of breast or axilla
* inflammatory or extramammary breast cancer
* pregnancy
* inability to understand the studies purpose
* no written patient informed consent

Primary outcomes:
measure: Surgical detection rate of the clip labeled target lymph node
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
Secondary outcomes:
measure: Rate of patients not suitable for targeted axillary dissection (TAD)
timeFrame: 14 days
measure: Rate of representative and successful lymph node CNB
timeFrame: 14 days
measure: Rate of preoperative sonographic clip detection
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: Rate of patients treated with TAD after NACT
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: Rate of patients treated with upfront ALND after NACT
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: False negative rate for target lymph node biopsy (TLNB) alone
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: False negative rate for Sentinel Lymph Node Biopsy (SLN) alone
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: Detection Rate for Targeted Axillary Detection (TAD) (SLN and TLN detected)
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: Detection Rate for Sentinel Lymph Node Biopsy (SLNB)
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: Rate of patients,where the clip is found in a sentinel lymph node (SLN)
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: Number of excised lymph nodes during targeted axillary dissection (TAD)
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: Number of excised lymph nodes during sentinel lymph node biopsy (SLNB)
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
measure: Number of excised target lymph nodes (TLN) which are not a sentinel lymph node
timeFrame: 6 month for patients undergoing NACT after initial needle biopsy/clip placement and subsequent surgical resection of the clipped node
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
state: NRW
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Gelsenkirchen
country: Germany
facility: Evangelische Kliniken Gelsenkirchen
Study officials:
affiliation: Kliniken Essen-Mitte
name: Sherko Kümmel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kliniken Essen-Mitte
name: Johannes Holtschmidt, MD
role: STUDY_CHAIR
affiliation: Klinikum Esslingen
name: Thortsen Kühn, MD
role: STUDY_CHAIR
References:
citation: Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, Bedrosian I, Hobbs BP, DeSnyder SM, Hwang RF, Adrada BE, Shaitelman SF, Chavez-MacGregor M, Smith BD, Candelaria RP, Babiera GV, Dogan BE, Santiago L, Hunt KK, Kuerer HM. Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. J Clin Oncol. 2016 Apr 1;34(10):1072-8. doi: 10.1200/JCO.2015.64.0094. Epub 2016 Jan 25.
citation: Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Kuerer HM, Bowling M, Flippo-Morton TS, Byrd DR, Ollila DW, Julian TB, McLaughlin SA, McCall L, Symmans WF, Le-Petross HT, Haffty BG, Buchholz TA, Nelson H, Hunt KK; Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013 Oct 9;310(14):1455-61. doi: 10.1001/jama.2013.278932.
citation: Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Liedtke C, von Minckwitz G, Nekljudova V, Schmatloch S, Schrenk P, Staebler A, Untch M. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013 Jun;14(7):609-18. doi: 10.1016/S1470-2045(13)70166-9. Epub 2013 May 15.
citation: Kuemmel S, Heil J, Rueland A, Seiberling C, Harrach H, Schindowski D, Lubitz J, Hellerhoff K, Ankel C, Grasshoff ST, Deuschle P, Hanf V, Belke K, Dall P, Dorn J, Kaltenecker G, Kuehn T, Beckmann U, Potenberg J, Blohmer JU, Kostara A, Breit E, Holtschmidt J, Traut E, Reinisch M. A Prospective, Multicenter Registry Study to Evaluate the Clinical Feasibility of Targeted Axillary Dissection (TAD) in Node-positive Breast Cancer Patients. Ann Surg. 2022 Nov 1;276(5):e553-e562. doi: 10.1097/SLA.0000000000004572. Epub 2020 Nov 4.