Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04549558 |
| Other study ID # |
AssiutU AAHelmy |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 15, 2022 |
| Est. completion date |
June 15, 2023 |
Study information
| Verified date |
March 2022 |
| Source |
Assiut University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Breast cancer (BrCa) is the most common malignant neoplasm in women worldwide with a
continuous rise on both its incidence and cancer-related deaths. Accurate evaluation of the
presence, extent and status (benign or malignant) of axillary lymph nodes (ALNs) in patients
with BrCa has an important prognostic value, and is essential for disease staging and
treatment planning. Many radiological diagnostic modalities have been utilized to assess the
nature of ALNs in the pre-operative stage. Each modality has its weaknesses and strengths.
Multimodal imaging combines two or more imaging modalities into one system to produce details
in clinical diagnostic imaging that are more precise than any conventional imaging alone.
Therefore, the present study is designed to assess the role of simultaneous multi-modal
sonographic tools [conventional grey-scale ultrasound; US, Color-Doppler ultrasound; CDU,
strain ultrasound elastography; UE) in evaluating the nature (benign or malignant) of
ipsilateral ALNs in patients with primary BrCa together with comparing the diagnostic indices
of each with that of all-together (combined modalities). A total of 30 patients with BrCa and
US-visible ALNs will be included. All will be subjected to simultaneous examination by US,
CDU, UE and US-guided FNA cytology examination of their ipsilateral ALNs. Data will be
collected and analyzed using SPSS version 23. Area under the receiver Operating
Characteristic (ROC) curve will be calculated and the diagnostic indices of each modality and
of all modalities will be measured.
Description:
BACKGROUND Breast cancer (BrCa) is the most common malignant neoplasm in women worldwide with
a continuous rise on both its incidence and cancer-related deaths (1-3). Accurate evaluation
of the presence, extent and status of axillary lymph nodes (ALNs) in patients with BrCa has
an important prognostic value, and is essential for disease staging and treatment planning
(4).
Historically, axillary lymph node dissection (ALND) and histopathology was used for staging
BrCa, but with inevitable short- and long-term complications such as lymphedema, nerve
injury, seroma and infection (5). Afterwards, sentinel lymph node (SLN) biopsy (SLNB) has
gradually replaced ALND despite its invasive nature, unavoidable false negative results and
post-operative complication, which are far less than those encountered with ALND (6).
According to the American Society of Oncology Guidelines, If the SLNB results are negative,
no further dissection is done because there is no survival benefit for performing ALND in
this setting. Patients with positive SLNB results traditionally undergo "completion" ALND
(6,7)
Grey-scale ultrasound (US) is a non-invasive method that plays an important role in the
preoperative evaluation of ALNs and obtaining samples in patients with BrCa (8-11).
Nevertheless, US is operator dependent and focuses mainly on the morphological features lymph
nodes (LNs). Addition of Color-Doppler Ultrasound (CDU helps in assessing the presence and
distribution of vasculature pattern as well as the resistive index (RI) of ALNs (11-13).
Despite their promising results, US and CDU, studies showed very wide ranges and variations
in sensitivity and specificity (8-13).
Real-time strain ultrasound elastography (UE) is an imaging technique that utilizes the
long-established clinical concept that malignant lesions are often stiffer than normal
tissues. The stiffness, a characteristic that can't be assessed by US nor CDU (14) and the UE
has therefore been utilized to assess pathological changes in many organs, such as liver,
breast, thyroid, muscle, Kidney, Prostate, and cervical LNs (Nicely reviewed in 14).
Additionally, elastograms obtained by UE are color-coded images indicating differences in
stiffness of portions of a target tissue. These color maps or images arise from analysis of
the changes in the radiofrequency impulses before and after the rhythmic manual compression
directed along the radiation axis. In addition, UE images are produced simultaneously with
the conventional gray-scale US to ensure that images of the same node are precisely obtained
(14). UE has also been used in assessing ALNs, but with variable and conflicting results
(15,16). Two recent meta-analyses concluded that UE can provide additive useful information
regarding ALN assessment prior to surgical procedure selection (17,18).
Other imaging modalities such as mammography, magnetic resonance imaging (MRI),
multi-detector computed tomography (CT), Positron-emission tomography (PET-CT) were also
tried, but their wide use is limited by their moderate sensitivity, low specificity, need for
special protocol for ALNs assessment, law availability, high cost and radiation hazard
(19-25).
Multimodal imaging combines two or more imaging modalities into one system to produce details
in clinical diagnostic imaging that are more precise than any conventional imaging alone.
AIMS The present study is designed to assess the role of simultaneous multi-modal sonographic
tools (US, CDU, UE) in evaluating the nature (benign or malignant) of ipsilateral ALNs in
patients with primary BrCa together with comparing the diagnostic indices of each with that
of all-together (combined modalities). In other words, whether adding UE to conventional
grey-scale US and CDU will increase their diagnostic accuracy or not.
METHODS A: Type of the study: A prospective cohort diagnostic hospital-based study B: Study
Setting: Department of Diagnostic Radiology, Assiut University Hospitals.
C: Sample Size Calculation: The study will include 30 consecutive patients with primary BrCa
and ipsilateral ALNs of obscure nature visible by axillary conventional/grey-scale ultrasound
(US) scan. In Each patient, one or more LN may be examined.
D: Study tools: All participants will be subjected to the following:
I. Screening clinical physical and Grey-scale ultrasound examination of the axilla With
patients in the supine position, an experienced radiologist in conventional US, CDU, UE will
perform the physical clinical examination using a Gray-scale digital US scanner (General
Electric (GE, USA), equipped with a 7.5-13 MHz liner transducer will be performed first to
assess for the presence of ALNs. Only the ipsilateral axillary region will be evaluated.
II. Conventional (grey-scale) ultrasound (US) Scoring of the ALNs A gray-scale conventional
US scoring system of 5 criteria will be implemented. These include 1) Short-axis (S) diameter
(S >7 mm = score 1; S ≤7 mm = score 0), 2) Long-to-short axis (L/S) diameter ratio (L/S; <2 =
score 1; ≥ 2 = score 0), 3) The hilum long axis-to-node long axis (H/L) diameter ratio (H/L
<0.5 = score 1; H/L ≥ 0.5 = score 0). 4) Border (irregular = score 1; regular =score 0), and
5) Cortical thickness (T >3 mm = score 1; T ≤ 3 mm = score 0). When the node did not have a
hilar region, the cortical thickness will be regarded as ≥ 3 mm when the short-axis diameter
is >3 mm (26) and Figure 2.
III. Color Doppler Ultrasound (CDU) examination of the ALNs After US, CDU will be performed
as previously described (11-13) with the following precautions: 1) use of low wall filter and
low velocity scale to be able to detect slow flow. 2) adjust color gain to maximum to help
better blood flow demonstration and avoid noise artefacts. 3) place the transducer gently to
avoid superficial vessels compression that may lead to an increase in vascular resistance.
Intra-nodal blood flow in color Doppler studies will be classified into 4 categories: 1)
central flow; 2) peripheral flow; or 3) Mixed peripheral and central, 4) absent flow. Central
vessels are those appearing in both hilar and peri-hilar branches only. Peripheral vessels
are those in the periphery that have no connection with the hilar vessel. Lymph nodes with
both peripheral and central (mixed) flow will be grouped as mixed. If blood vessels are
detected, 3 Doppler spectral waveforms will be obtained, and their mean will be calculated
and considered as the resistivity index (RI). The RI is chosen as it is not dependent on the
angle of insonation, and therefore, it can be accurately calculated even in small vessels. RI
is calculated as follows: RI = Peak systolic velocity - end diastolic velocity/peak systolic
velocity
IV. Strain ultrasound elastography (UE) of the ALNs UE images will be evaluated with a
scoring system based on the percentage and distribution of the hypoechoic cortex regions with
a visible hilum in ALN (Pattern I) or all the hypoechoic lymph nodes with an absent hilum
(Pattern II).
In Pattern I (LN with Hila), scoring will be as follows (26):
1. the green portion occupied almost all of the cortex;
2. the blue portion occupies <50% of the cortex;
3. the blue portion occupies >50% of the cortex, with scattered the green portions;
4. the blue portion occupies almost all of the cortex;
5. the blue portion occupies almost all of the cortex, with a green ring on the edge of the
node.
In pattern II (LN without Hila), scoring will be as follows (26):
1. Green portion occupying almost all of the cortex.
2. Blue portion occupying less than 50% of the cortex.
3. Blue portion occupying more than 50% of the cortex, with a scattered green portion
4. Blue portion occupying almost all of the cortex.
5. Blue portion occupying almost all of the cortex, with a green ring on the edge of the
node.
Calculation of the Strain Ratio (SR) by UE. The SR is a ratio between the strain value of the
two regions of interest (ROI) A and B, where ROI-A is the deepest blue portions of the
hypoechoic regions within the nodes, and ROI-B is the surrounding soft and adipose tissue at
the same depth.
(SR = strain value of ROI-B / strain value of ROI-A) Of note, SR is automatically calculated
by the software built into certain equipment and displayed on its monitor (26).
V. Combined evaluation of gray-scale US, CDU and UE. The score of combined evaluation for
each lymph node will be the sum of the gray-scale US (5 points), the CDU (1 point), and the
UE (5 points) scores. A cut-off value will be evaluated with the pathological diagnosis.
VI. Ultrasound-guided FNA from the ALNs After completion of the above 3 sonographic
modalities' examinations, and under local anesthesia using 5 ml of subcutaneous 1% Xylocaine,
US-guided fine needle aspiration (FNA) will be performed by the same radiologist for all
visible ALNs using 20-22 gauge needles attached to a 10 ml plastic syringe. Under UE
guidance, the needle will be inserted into the cortex with 3 passes as routinely performed
and previously described (27). When 2 or more abnormal LNs are identified, the node that
looks the most suspicious will be aspirated. Samples will then be spread and fixed on
glass-slides using 95% alcohol and air-dried for Pap & Diff-Quik (American Scientific
Products, McGraw Park, IL, USA) staining in the Pathology Department prior to being examined.
The final pathological diagnosis for the LNs will be made by a pathologist blinded to the
imaging findings. Results of the US modalities will be correlated with the results of the
FNAC.
E: Data Management and Statistical Analyses Data collection will be done in a preformed "Data
Collection Form" (Appendix 1) prior to being entered in Microsoft Exel 2016. Afterwards, data
will be exported to the Statistical Package for Social Sciences (SPSS) version 23.0 software
package (SPSS, Inc., Chicago, IL, USA) for the statistical analysis. Comparisons of numeric
(continuous) variables and categorical variables will be done using the Wilcoxon's rank sum
test or Student's t-test and Chi-Square or Fisher's Exact test respectively and as
appropriate. The sensitivity, specificity, positive predictive value (PPV), negative
predictive value (NPV) and accuracy will be calculated to compare the diagnostic performance
of each modality. The areas under the receiver operating characteristic (ROC) curves (AUC)
will be calculated and compared using the U-test. All cutoff values will be determined
depending on the best accuracy identified by ROC curves. A probability value of (P<0.05) will
be considered Statistically significant for all tests. The cytopathological diagnosis will be
considered as the reference gold standard.
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