=Paper=
{{Paper
|id=Vol-3777/short6
|storemode=property
|title=Uncertainty Estimation Method for Determining Bone Density in Patients with Infiltrating Intraductal Carcinoma Undergoing Anti-Cancer Therapy
|pdfUrl=https://ceur-ws.org/Vol-3777/short6.pdf
|volume=Vol-3777
|authors=Viktor Reshetnik,Irina Muryzina,Marcus Frohme,Victoriia Alekseeva,Alla Dzyza,Alina Nechyporenko
|dblpUrl=https://dblp.org/rec/conf/profitai/ReshetnikMFADN24
}}
==Uncertainty Estimation Method for Determining Bone Density in Patients with Infiltrating Intraductal Carcinoma Undergoing Anti-Cancer Therapy==
https://ceur-ws.org/Vol-3777/short6.pdf
Uncertainty Estimation Method for Determining Bone
Density in Patients with Infiltrating Intraductal
Carcinoma Undergoing Anti-Cancer Therapy
Viktor Reshetnik1, Irina Muryzina 2, Marcus Frohme3, Victoriia Alekseeva2,3,4 Alla Dzyza2
and Alina Nechyporenko 1,3
1
Kharkiv National University of Radioelectronics, Nauky avenue 14, Kharkiv, 61166, Ukraine
2
Kharkiv National Medical University, Nauky avenue 4, Kharkiv, 61022, Ukraine
3
Technical University of Applied Sciences Wildau (TH Wildau), Hochschulring 1, Wildau, 15745, Germany
4
Kharkiv International Medical University, Molochna street 38, Kharkiv, 61001, Ukraine
Abstract
Identification of a bone density is crucial in all branches of medicine. Assessing bone density is a labor-
intensive process. Bone density is quite unstable and depends on many factors, both physiological (aging,
hormonal balance) and pathological (medication use, various underlying conditions).
The aim of our study is to determine bone density in patients with malignant breast tumors undergoing
anti-cancer therapy.
Material and Methods. The study included 50 women aged 60-70 years who were diagnosed with
infiltrating intraductal carcinoma. According to established protocols, MSCT is recommended for this
category of women at intervals of once every six months. The first MSCT scan was performed immediately
after the diagnosis was made, before the start of treatment, and the second scan was conducted six months
later.
Results. The maximum radiological density was 75.8954±37.9477 Hu in the group of women who had been
receiving treatment for six months, compared to 93.9388±46.9694 Hu in the group of patients who did not
take the drug. Meanwhile, the minimum density showed a slight increase from 29.7295±14.8647 Hu to
38.6919±19.3460 Hu, which can be attributed to the compensatory mechanisms of the body.
Conclusions. In the course of this study, bone density in patients with infiltrating intraductal carcinoma
undergoing anti-cancer therapy was determined using uncertainty estimation. It was found that after six
months, the first to respond to changes in density was the maximum bone density.
Keywords
Infiltrarive intraductal adenocarcinoma, multislice computer tomography , radiological bone density 1
1. Background
Identification of a bone density is crucial in all branches of medicine. Assessing bone density is a
labor-intensive process [1, 2]. Bone density is quite unstable and depends on many factors, both
physiological (aging, hormonal balance) [5] and pathological (medication use, various underlying
conditions) [6]. The difficulty in determining bone density is due to its structure. Currently, data on
bone density primarily concern long bones, determined using dual-energy X-ray absorptiometry
(DEXA) [7], which requires additional time and personnel, making it economically unfeasible despite
being the gold standard for osteoporosis diagnosis. Assessing trabecular bone density poses
significant challenges due to its spongy structure and numerous intertrabecular spaces. Multislice
computed tomography (MSCT) is one method used to determine bone density [8]. One of the simplest
methods for measuring bone density is the radiological method (often computed tomography, less
frequently magnetic resonance imaging). Radiological research methods can accurately and
effectively determine the bone density of any area of the human skull in both physiological and
ProfIT AI 2024: 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024), September 25–27,
2024, Cambridge, MA, USA
alinanechiporenko@gmail.com (A. Nechyporenko); viktor.reshetnik@nure.ua (V. Reshetnik); mfrohme@th-wildau.de
(M. Frohme); vik13052130@gmail.com (V. Alekseeva); irina_muryzina@ukr.net (I.Muryzina) ); av.dzyza@knmu.edu.ua(A.
Dzyza)
0000-0001-9063-2682 (A. Nechyporenko); 0000-0002-8021-4310 (V. Reshetnik); 0000-0001-9063-2682 (M. Frohme); 0000-
0001-5272-8704 (V. Alekseeva); 0000-0001-9209-0717 (I.Muryzina); 0000-0001-9944-4194 (A. Dzyza)
© 2024 Copyright for this paper by its authors.
Use permitted under Creative Commons License Attribution 4.0 International (CC BY 4.0).
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pathological conditions [9]. However, the majorities of studies focus on the physiological state or
investigate radiological density in the presence of tooth and jaw pathology, particularly the alveolar
process of the upper jaw.
To explore the biological mechanisms underlying changes in bone density, especially the
compensatory mechanisms that might lead to an increase in minimum density, you could focus on
several key areas such as bone remodeling process, Wolf law, homeostasis of microelements,
hormones, genetic faktors. An increase in minimum density may suggest that osteoblast activity is
heightened or more efficient, possibly as a compensatory mechanism in response to earlier bone loss
or mechanical stress.
One of the advanced methods for calculating density could be the use of uncertainty estimation.
Measurement uncertainty is a characteristic of inaccuracy of measurements, adopted at the
international level [10], which is associated with the measurement result and characterizes the range
of values that can reasonably be attributed to the measured value.
Using MSCT and uncertainty estimation, it is possible to determine bone density not only under
physiological conditions but also in the presence of pathological processes, one of which is breast
cancer. This disease is the most common type of cancer among women in 157 out of 185 countries
worldwide [11, 12].
The progress in our framework of knowledge is pushing breast cancer (BC) treatment forward,
while new details widen its inner diversity and at the same time they solidify our views at the
consistency between carcinoma’s features and approaches to its management. Considering
sensitivity of many BC subtypes to sex steroid hormones (SSH) the maintenance of disruption of the
pathways that keeps afloat communication between tumour cells and these agents is viewed as the
pivotal issue of recurrences prevention [13]. From the other hand, deprivation of a woman under 50
years old from estrogen’s beneficial influence does affect adversely her body in different aspects. Of
course, to rescue the life from such insidious foe as BC is worth that and it is not the question to
discuss itself, but to explore how deep and fast the fallouts of these interventions is very important
in order to clarify when new perils would emerge at the extent of the true jeopardy to the quality of
life. Age under 50 yo and luminal A breast cancer requires use of gonadotropin-releasing-hormone
agonists (aGnRH). When the bone tissue is exposed to the profound estrogen deficiency it is getting
devoid of what constitutes bone density due to the preponderance of constructive work over
destructive processes. Unfortunately, there is no chance to counteract by the use of hormonal
replacement therapy whereas bisphosphonates aren’t able to bridge all the gaps [14].
Given all of the above, the aim of our study is to determine bone density in patients with
malignant breast tumors undergoing anti-cancer therapy.
2. Material and Methods
The study included 50 women aged 60-70 years who were diagnosed with infiltrating intraductal
carcinoma. According to established protocols, MSCT is recommended for this category of women
at intervals of once every six months. The first MSCT scan was performed immediately after the
diagnosis was made, before the start of treatment, and the second scan was conducted six months
later. Our study put under scrutiny the pace of the bone density loss driven by aGnRH use in women
under 50 yo passing through their BC treatment (diphereline 22.5 mg 6 months alone and combined
with tamoxifen).
To determine the short-term effects of Diphereline, we conducted a study six months after the
initiation of treatment with Diphereline. Bone density was measured in the region of the first cervical
vertebra, specifically in the part of the vertebra closest to the spinal canal. The maximum and
minimum bone densities were calculated separately.
The study was approved by the bioethics committee of Kharkiv National Medical University
(protocol No. 1 dated 08.11.2018).
The research was conducted at the Clinical Institute of Emergency Surgery, Kharkiv, based on
the existing collaboration agreement between this medical institution and Kharkiv National Medical
University. CT scans were performed on a Toshiba Aquilion-64 spiral computed tomography
scanner. The Toshiba Aquilion 64 CT machine is considered the only true volumetric 64-slice CT
scanner with 64 detector channels, 3-D cone beam algorithms and volume reconstruction on the
market. Automated features in the Toshiba Aquilion 64 CT scanner's SUREWorkflow software
enable the operator to monitor a patient's heart rate prior to scanning.
Toshiba's 3-D Quantum denoising allows for reducing patient radiation exposure by up to 40%
without loss of image quality. Each Toshiba Aquilion 64 CT scanner also features volume
reconstruction, enabling you to scan a large volume in a minimum of time as Volume Viewing
automatically reconstructs scanned data into the isotropic volume used for diagnosis [15].
Preference was given to multislice computed tomography (MSCT) due to its simplicity and the
ability to determine density during this investigation. Density calculations were based on the
Hounsfield scale – a scale of gray shades widely used in MSCT. This scale is relative, with water
(density assumed as 0 HU) and air (-1000 HU) as benchmark values. Each organ and tissue has its
characteristic density value, and in the presence of pathological processes, radiological density may
decrease (more rarely, increase). The obtained images were examined using the RadiANT DiCOM
Viewer program [15].
All inputs of uncertainty form a standard uncertainty. To calculate the standard uncertainty,
we used the formula:
u с (HН ) = u 2А (HHi ) + u 2В (HHi ) (1,
where uA(HHi) is a standard type А uncertainty, а uB(HHi) is a standard type В uncertainty.
Standard type A uncertainty was calculated using the formula:
n
1
u(H Hi ) = å
n(n - 1) i =1
( H Hi - H H ) 2 (2)
where Hнi – i-th value of the sample measurements, Нн is the mathematical expectation, n is the
number of measurements in the sample.
Standard type B uncertainty was calculated using the formula:
dH
u( H H ) = H H (3)
3 ×100
where d H is a measurement error of software not exceeding 0.0001.
After calculating these values, an interval estimation of uncertainty was calculated, namely
extended uncertainty U according to the formula:
U=kuc (4)
where k is the coverage ratio.
3. Results and discussions
The results of measurements taking into account the expanded uncertainty U are given in the tables
1 and 2. Assessing the data in the table, we can conclude that the probabilistic spread of U value is
in the ±U range relative to the measured uc value, and the degree of certainty for U values in this
interval is determined by the probability (confidence level) p = 0.95. Calculation of uncertainty is a
quite rarely used method in medicine [16], and is more commonly used in laboratory diagnosis.
According to the literature analysis there are no research papers describing proposed approach.
Group 1 includes the subjects who underwent MSCT immediately after the diagnosis, before the
administration of Diphereline. Group 2 includes the same women who underwent CT (MSCT) six
months after the administration of Diphereline.
As can be seen from Table 1, under the influence of diphereline, the maximum bone density
decreases and is 75.8954±37.9477 Hu, at the first CT measurement, this indicator was 93.9388±46.9694
Hu
Table 1
The maximum radiological bone density in 2 groups
Indicator Group 1 Group 2
UA (Х) 46,969 37,948
UВ (Х) 0,00053772 0,00068470
Us (X) 46,9694 37,9477
U(X) 93,9388 75,8954
Table 2
The minimum radiological bone density in 2 groups
Indicator Group 1 Group 2
UA (Х) 14,8647 19,3460
UВ (Х) 0,00003424 0,00001889
Us (X) 14,8647 19,3460
U(X) 29,7295 38,6919
The results of determining the minimum bone density in this group of women were quite
unexpected. First, it's important to note that in both groups, the minimum density is relatively low,
which may be attributed to the age of the women and hormonal changes associated with menopause.
However, after six months of Diphereline treatment, the follow-up MSCT revealed a slight increase
in minimum density, which rose from 29.7295±14.8647 Hu to 38.6919±19.3460 Hu (see Fig. 1 and 2).
It can be hypothesized that the maximum bone density is the first to respond to Diphereline, which
may have more favorable prognostic implications regarding the development of complications. The
use of bisphosphonates appears to be justified six months after the start of treatment to maintain
maximum bone density at an adequate level.
As for the increase in minimum density, it is likely not directly related to the drug itself;
otherwise, we would observe a similar trend in maximum density as well. These changes in density
may be due to the compensatory mechanisms of the body.
It is well-known fact that even short streak (<6 months) leaves the evident signs of the bone
density decline that takes years to repair [13] let alone the 2-year duration. Of course there are
individual swings stipulated by personal background but all of them are more or less subject to some
mean pattern. SCT taken as the follow-up after the beginning of the treatment also allows tracing
individual bone density decline captured by scan.
By the use of proposed approach that includes assessment of bone density by МSCT as the
scheduled follow-up (every 6 month) we obtain the mean curve of the decline inherent mainly for
these patients. It turned out that despite quite significant drop of bone density within first 6 months
it is rather sluggish comparatively with the next year when the curve of decline slides steeply down.
Perhaps this slump is driven by the exhaustion of the resource stocks.
Proposed approach of bone density assessment by the same МSCT within conventional follow-
up schedule in the case of being implemented into standard management lets trace a patient’s bone
density decline in comparison with the calculated mean decline’s curve and, if it lowers deeper than
expected, may justify the expedience to reconsider the management in favour of earlier intervention
with this regard.
2000
1800
Maximal Density, Hu 1600
1400
1200
1000
800
600
400
200
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49
Measurements
Figure 1: Maximal bone density in 2 groups of patients
500
400
300
Minimal Density, Hu
200
100
0
-100 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49
-200
-300
-400
-500
Measurements
Figure 2: Minimal bone density in 2 groups of patients
Within the scope of investigating how diphereline affects bone density, our findings are
consistent with the broader research in the field of healthcare-related intelligent systems. Previous
studies on intelligent expert systems for evaluating medical staff knowledge about infections
associated with medical care [14, 15], along with research on smart systems, data-driven healthcare
services, and the use of smart technologies in medical services, contribute to the expanding
knowledge in bone density detection [16-19]. The integration of smart systems and data-driven
approaches in healthcare, as discussed by several authors [20-22], highlights the critical role of
technology in enhancing medical outcomes.
4. Conclusions
In the course of this study, bone density in patients with infiltrating intraductal carcinoma
undergoing anti-cancer therapy was determined using uncertainty estimation. It was found that after
six months, the first to respond to changes in density was the maximum bone density. The maximum
radiological density was 75.8954±37.9477 Hu in the group of women who had been receiving
treatment for six months, compared to 93.9388±46.9694 Hu in the group of patients who did not take
the drug. Meanwhile, the minimum density showed a slight increase from 29.7295±14.8647 Hu to
38.6919±19.3460 Hu, which can be attributed to the compensatory mechanisms of the body.
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