Clinical trial NCT03975855: Evaluation of NeoNavia® Biopsy System in Axillary Lymph Nodes
Official title: Percutaneous Ultrasound-Guided Biopsy Evaluated for Axillary Lymph Node Sampling Efficacy (PULSE)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: Breast Cancer
Axillary Lymph Nodes
Biopsy
Lead sponsor: NeoDynamics AB
Sponsor class: INDUSTRY
First posted: 2019-06-05
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients recruited from eight university hospitals in Germany

Brief summary: The aim of the study is to document performance characteristics of a biopsy device indicated for use in axillary lymph nodes, to provide basic insights into the complexity of axillary biopsy procedures and generate hypothesis for further larger comparative trials.

This is a Sponsor-initiated prospective, multicenter, registry trial. Patients that present with suspicious axillary lymph nodes at the time of breast cancer diagnosis undergo axillary sampling using the NeoNavia biopsy system. This is in accordance with clinical routine and current clinical guidelines. The system incorporates a new mechanism for controllable and precise needle insertion and a newly developed sampling needle for high yield sampling acquisition. It is approved for use in the breast and axillary lymph nodes.

Detailed description: Determining axillary nodal status at the time of diagnosis is paramount for optimal staging and treatment planning. SLNB is indicated for patients with a clinical and radiological negative axilla. 25%-43% of breast cancer patients are reported to present with radiologically suspicious axillary lymph nodes at the time of diagnosis. In these patients, a pre-operative ultrasound-guided needle sampling of suspicious axillary lymph tissue is indicated.

This can rationalize patient care by identifying those with axillary metastases using merely a minimally-invasive intervention. These patients can be counselled with regards to proceeding directly to definitive axillary surgery in the form of axillary lymph node dissection (ALND) rather than sentinel node biopsy (SLNB), thereby omitting a potentially unnecessary surgical procedure. Patients with a negative axillary status can proceed to SLNB for definitive nodal status determination. Furthermore, in the paradigm of neoadjuvant treatment, confirming a histopathologic involvement of lymph nodes by US-guided needle biopsies enables for decision on neoadjuvant chemotherapy without the need for a surgical procedure.

The main challenge in performing CNB (Core Needle Biopsy) within the axilla is to avoid damaging the major vessels and nerves. Technical, operator and procedural requirements that mitigate risks in CNB sampling of the axilla have been reported in the literature. It is suggested that the operator shall fully acknowledge the detailed anatomy including vessels and nerves in the axilla, have good hand-eye coordination as well as be experienced in US-guided interventions. Proper positioning of the patient is reported to be important. Color Doppler ultrasound shall be used to assess the location of large vessels relative to the intended biopsy track and to avoid sampling a vascular component of the node. Perfect guiding and visualization of the needle tip at all times is reported to be essential. It is suggested that a biopsy device with a controllable needle action is safer to use. Omitting the firing action gives the operator greater control over the final needle tip placement.

Due to the difficulty of the procedure there may be inclusion bias in the reported studies. In one series, patients presenting with nodes adjacent to a vessel or located very deep and difficult to access were not asked to participate in the study and hence not subjected to CNB. In another study FNA (Fine Needle Aspiration) was performed instead of CNB when the lymph nodes were in close proximity to vessels. A recent German survey showed that merely 79% of breast centers (41/52) perform biopsies in the axilla (data on file), and anecdotal evidence suggests that in certain departments only the most experienced physician performs CNB procedures in axillary lymph nodes, risking economic/operational inefficiencies.

For the purpose of documenting the prevalence and composition of cases deemed challenging in this study, an experienced expert panel has compiled a comprehensive list of risk parameters characterizing the anatomic complexity and procedural difficulty of axillary lymph node needle biopsies.

Recently a new biopsy device indicated for the use in breast and axillary lymph nodes (NeoNavia biopsy system, NeoDynamics, Sweden) has become available. It incorporates a pneumatic needle insertion mechanism that is intended to provide better control of needle progression and enable stepwise insertion without noticeable deformation or displacement of surrounding tissue as visualized under ultrasound. Furthermore a new method of tissue acquisition is employed that has pre-clinically shown a higher sampling yield compared to CNB. These characteristics indicate that the device could be well suited for tackling even the most challenging cases of axillary lymph node biopsies. Initial clinical results indicate that in axillary lesions deemed "technically difficult", i.e. where prior US-guided biopsies with CNB or FNA had yielded non-diagnostic histology results, the NeoNavia device performed successfully thereby significantly altering clinical management.

Eligibility criteria: Inclusion Criteria:

* cT1-4c (multifocality / multicentricity permitted)
* Female / male patient aged ≥ 18 years
* cN+ based on the following criteria (at least one criteria must be met):

  * lymph node is palpable
  * cortical asymmetry (focal or diffuse cortical thickening of \>3mm) under US
  * cortex:hilum ratio \>2:1 under US
  * loss of hilum/cortex structure under US
* Written informed consent (ICF)

Exclusion Criteria:

* Suspicious lymph nodes after neoadjuvant therapy
* No confirmed breast cancer and no abnormality in the breast
* Patient uses Marcumar
* Pregnant and lactating women
* Known hypersensitivity reaction against local anesthesia
* Prior chemo or radiation therapy in breast or axilla
* Missing written informed consent

Primary outcomes:
measure: Rate of successful biopsies (= success rates)
timeFrame: after histopathological analysis af tissue samples, up to 1 week after biopsy
Secondary outcomes:
measure: Rate of patients presenting with risk parameters for an anatomically complex procedure
timeFrame: time of biopsy, 1 day
measure: Rate of cases in which it was possible to target the selected lymph node or, if present, the lesion inside the node
timeFrame: time of biopsy, 1 day
measure: Rate of cases in which pulses facilitated control during needle insertion
timeFrame: time of biopsy, 1 day
measure: Sensitivity
timeFrame: post-surgery, up to 200 days
measure: Specificity
timeFrame: post-surgery, up to 200 days
Other outcomes:
Locations:
city: Esslingen
country: Germany
facility: Klinikum Esslingen
state: BW
city: Tübingen
country: Germany
facility: Universitätsfrauenklinik Tübingen
state: BW
city: Frankfurt
country: Germany
facility: Agaplesion Markus Krankenhaus
state: HE
city: Rostock
country: Germany
facility: Universitäts-Frauenklinik
state: MV
city: Erkelenz
country: Germany
facility: HJK Erkelenz
state: NRW
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
state: NRW
city: Köln
country: Germany
facility: Uniklinik Köln
state: NRW
Study officials:
affiliation: Leading Principal Investigator
name: Marc Thill, PD Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kim KH, Son EJ, Kim EK, Ko KH, Kang H, Oh KK. The safety and efficiency of the ultrasound-guided large needle core biopsy of axilla lymph nodes. Yonsei Med J. 2008 Apr 30;49(2):249-54. doi: 10.3349/ymj.2008.49.2.249.
citation: Ganott MA, Zuley ML, Abrams GS, Lu AH, Kelly AE, Sumkin JH, Chivukula M, Carter G, Austin RM, Bandos AI. Ultrasound Guided Core Biopsy versus Fine Needle Aspiration for Evaluation of Axillary Lymphadenopathy in Patients with Breast Cancer. ISRN Oncol. 2014 Feb 4;2014:703160. doi: 10.1155/2014/703160. eCollection 2014.
citation: Damera A, Evans AJ, Cornford EJ, Wilson AR, Burrell HC, James JJ, Pinder SE, Ellis IO, Lee AH, Macmillan RD. Diagnosis of axillary nodal metastases by ultrasound-guided core biopsy in primary operable breast cancer. Br J Cancer. 2003 Oct 6;89(7):1310-3. doi: 10.1038/sj.bjc.6601290.