Diagnosis of axillary lymph node status in primary breast cancer without a surgical procedure

ISRCTN ISRCTN14341750
DOI https://doi.org/10.1186/ISRCTN14341750
Secondary identifying numbers NILS 1.0
Submission date
21/10/2018
Registration date
23/11/2018
Last edited
22/01/2024
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Today, breast cancer is diagnosed at an early stage due to public screening mammography and increased awareness of the disease in the community. As a consequence of early diagnosis, tumor size at time of diagnosis has decreased and the risk of spread to the lymph nodes now affects less than 30% of all breast cancer patients. Despite this, all breast cancer patients undergo a surgical procedure, sentinel lymph node biopsy, to define if axillary lymph nodes are infiltrated by cancer cells. In more than 70% of these patients, there have no cancer infiltration in their axillary lymph nodes and therefore, the procedure has no benefit. Sentinel lymph node biopsy can lead to side-effects such as pain and swelling.
The aim of the study is to evaluate the capacity of patient related and tumor characteristics to determine whether the cancer has spread to the lymph nodes, so that low-risk groups can avoid sentinel node biopsy.

Who can participate?
Patients diagnosed with invasive breast cancer at any age scheduled for primary surgery and without clinically pathological lymph nodes

What does the study involve?
There is no direct involvement for participants. Instead, their medical records and data will be analysed by the study team and they will receive breast cancer treatment as usual.

What are the possible benefits and risks of participating?
As there is no direct involvement of participants and they will receive routine treatment, there are no known benefits or risks to participants taking part in this study.

Where is the study run from?
Skåne University Hospital (Lund and Malmö) (Sweden)

When is the study starting and how long is it expected to run for?
January 2008 to December 2022

Who is funding the study?
1. Lund Univerisity (Sweden)
2. The Swedish Breast Cancer Fund (Sweden)
3. South Swedish Health Care Region (Sweden)
4. Erling Persson Foundation (Sweden)
5. Vetenskapsrådet [Swedish Research Council] (Sweden)

Who is the main contact?
Professor Lisa Rydén
lisa.ryden@med.lu.se

Contact information

Prof Lisa Rydén
Scientific

Lund University, Medicon Village, Scheleevägen 2
Lund
SE-22381
Sweden

ORCiD logoORCID ID 0000-0001-7515-3130
Phone +46-706720923
Email lisa.ryden@med.lu.se

Study information

Study designObservational prospective cohort study with retrospective estimation of nodal status
Primary study designObservational
Secondary study designCohort study
Study setting(s)Hospital
Study typeDiagnostic
Participant information sheet Not available in web format, please use contact details to request a participant information sheet
Scientific titleNILS: Non-Invasive Lymph node Staging
Study acronymNILS
Study objectivesPreoperatively available information on clinicopathological characteristics can aid in predicting nodal status in primary breast cancer
Ethics approval(s)1. Approved 15/08/2012, Lund University, ref: 2012/340
2. Approved 07/07/2019, Swedish Ethical Review Authority, ref: 2019-02139
3. Approved 15/02/2021, Swedish Ethical Review Authority, ref: 2021-00174
Health condition(s) or problem(s) studiedClinically node-negative primary breast cancer
InterventionCurrent intervention as of 31/08/2021:
Patients in this study are undergoing standard diagnostic work-up within the clinical pathway for breast cancer including a clinical examination, mammogram, ultrasound and core biopsy of the tumor before surgery. At time of surgery, they undergo standard procedure according to the multidisciplinary conference and the tumor and axillary nodes are pathologically examined. No extra diagnostic or interventional procedure is undertaken. Logistic regression and artificial neural network models are applied to predict nodal status from clinicopathological data. No
follow-up data is extracted as this is an observational diagnostic trial. Separate cohorts will be used for validation of the nomogram and ANN models.
_____

Previous intervention:
Patients in this study are undergoing standard diagnostic work-up within the clinical pathway for breast cancer including a clinical examination, mammogram, ultrasound and core biopsy of the tumor before surgery. At time of surgery, they undergo standard procedure according to the multidisciplinary conference and the tumor and axillary nodes are pathologically examined. No extra diagnostic or interventional procedure is undertaken. Logistic regression and artificial neural network models are applied to predict nodal status from clincopathological data. No follow-up data is extracted as this is an observational diagnostic trial.
Intervention typeOther
Primary outcome measureCurrent primary outcome measure as of 31/08/2021:
Axillary nodal status stratified by stage N0, N1 and N2, determined from pre-operatively available clinicopathological data after surgery compared with the predictive N-status by the algorithms
_____

Previous primary outcome measure:
Axillary nodal status stratified by stage N0, N1 and N2, determined from pre-operatively available clinicopathological data after surgery
Secondary outcome measuresFalse negative rate with negative predictive value of NPV max to 10% for prediction of N0, determined from sentinel node biopsy data after surgery
Overall study start date01/01/2008
Completion date21/12/2022

Eligibility

Participant type(s)Patient
Age groupAdult
SexFemale
Target number of participants800 primary cohort, 600 and 22000 in validation cohort
Key inclusion criteriaCurrent inclusion criteria as of 31/08/2021:
1. Invasive breast cancer
2. Clinically and ultrasound node-negative disease
3. Scheduled for primary surgery
4. Female
_____

Previous inclusion criteria:
1. Invasive breast cancer
2. Clinically node-negative disease
3. Scheduled for primary surgery
4. Female
Key exclusion criteria1. Male
2. Previous ipsilateral breast or axillary surgery
3. Previous neoadjuvant therapy
4. Palpable axillary lymphadenopathy
5. No axillary staging
Date of first enrolment01/01/2009
Date of final enrolment21/12/2022

Locations

Countries of recruitment

  • Sweden

Study participating centre

Skåne University Hospital
Lund and Malmö
22185
Sweden

Sponsor information

Lund University
University/education

Medicon Village 406, Scheleevägen 2
Lund
223 85
Sweden

Website www.med.lu.se
ROR logo "ROR" https://ror.org/012a77v79

Funders

Funder type

University/education

Lunds Universitet
Government organisation / Universities (academic only)
Alternative name(s)
Lund University, Universitas Lundensis, Universitas Gothorum Carolina, Royal Caroline Academy, Regia Academia Carolina, Lund University | Lund, Sweden | LU, Lunds universitet, LU
Location
Sweden
South Swedish Health Care Region

No information available

Bröstcancerfonden

No information available

Familjen Erling Perssons Stiftelse

No information available

Vetenskapsrådet
Government organisation / National government
Alternative name(s)
Swedish Research Council, VR
Location
Sweden

Results and Publications

Intention to publish date31/03/2023
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planA nomogram based on logistic regression data has been published and external validation is ongoing. Data analysis from ANN is finished and a manuscript is pending
IPD sharing planThe datasets analysed during the current study will be available upon request from Lisa Rydén (lisa.ryden@med.lu.se) for baseline characteristics after approval from regulatory authorities responsible of data sharing for Region Skåne. The dataset is kept pseudoanonymised and will be available for any researcher with a documented scientific experience in prediction models of nodal status in order to validate other prediction models generated from their own data. GDPR requires an informed consent to state that data sharing with third party is to be performed and this can be arranged by an opt-out procedure.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article Nomogram initial results 01/10/2017 Yes No
Basic results 02/11/2018 24/04/2019 No No
Results article Artificial neural network modeling initial results 21/06/2019 24/06/2019 Yes No
Other publications Nomogram validation 01/05/2021 31/08/2021 Yes No
Results article Retrospective validation study 16/01/2024 22/01/2024 Yes No

Additional files

ISRCTN14341750_BasicResults_02Nov2018.pdf
uploaded 24/04/2019

Editorial Notes

22/01/2024: Publication reference added.
21/12/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2022 to 21/12/2022.
2. The overall end date was changed from 31/12/2022 to 21/12/2022.
31/08/2021: The following changes have been made:
1. The ethics approval has been updated.
2. The overall trial end date has been changed from 31/12/2018 to 31/12/2022 and the plain English summary updated accordingly.
3. The intervention has been changed.
4. The primary outcome measure has been changed.
5. The participant inclusion criteria have been changed.
6. The participant age group has been changed from 'All' to 'Adult'.
7. The target number of participants has been changed from "800" to "800 primary cohort, 600 and 22000 in validation cohort" and the previously added final enrolment number removed.
8. The recruitment end date has been changed from 31/12/2012 to 31/12/2022.
9. Vetenskapsrådet (Swedish Research Council) has been added as a funder and the plain English summary updated accordingly.
10. Publication reference added.
11. The intention to publish date has been changed from 31/03/2019 to 31/03/2023.
24/06/2019: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the results publication.
24/04/2019: The basic results of this trial have been uploaded as an additional file.