Measure of Stage Migration Due to Significant Nodes Detected on Imaging in Patients with Uterocervical Cancer Using the FIGO 2018 Staging System

Abstract

Background

While the earlier International Federation of Gynecology and Obstetrics (FIGO) staging guidelines for carcinoma cervix were only based on clinical examination findings, the revised guidelines published in 2018 incorporated imaging and pathological assessments to the staging system.

Aims and Objectives

This article compares the imaging-based new FIGO staging system with the old clinical staging and assesses the degree of stage migration.

Methods

In this institutional review board-approved retrospective study, consecutive patients who were diagnosed with uterocervical cancer and underwent imaging (i.e., computed tomography [CT]/magnetic resonance imaging [MRI]/positron emission tomography-CT [PET-CT]/ultrasound [USG]) between 2013 and 2017 were reviewed. Imaging findings were documented, and stage was assigned as per the revised 2018 FIGO staging system for cervical cancer and compared with the previous FIGO staging system. The degree of stage migration was compared between the new and the old FIGO staging systems. The degree of stage migration due to significant lymph nodes detected on different imaging modalities was assessed.

Results

274 patients with a mean age of 51 years and a range of 20 to 80 years were reviewed. The distribution as per the FIGO 2009 were: 0.3% (n = 1) in stage IA1 and IA2, 6.2% (n = 17) in stage IB1, 1% (n = 3) in stage IB2, 4% (n = 11) in stage IIA, 44.5% (n = 122) in stage IIB, 0.7% (n = 2) in stage IIIA, 27% (n = 74) in stage IIIB, 5.8% (n = 16) in stage IVA, and 7.2% (n = 20) in stage IVB. Among all these patients, 66.4% (n = 182) patients underwent USG, 53.6% (n = 147) underwent CT, 42.7% (n = 117) had MRI, and 3.6% (n = 10) underwent PET-CT. Only 4% (n = 8) and 0.5% (n = 1) patients who underwent USG at staging were detected to have significant parailiac and para-aortic nodes, respectively. On the other hand, 7.66% (n = 21) had significant para-aortic and 44.16% (n = 121) had significant parailiac nodes on other cross-sectional imaging modalities. There was stage migration in 36.86% of patients, with 23.72% upstaged to stage IIIC1.

Conclusion

Fewer lymph nodes were detected on USG than other cross-sectional imaging modalities. Adopting the new FIGO resulted in stage migration in 36.86% of patients, predominantly due to lymph node metastases detected on imaging.

 

MissingLinkText

Keywords

uterocervical cancer - carcinoma cervix - stage migration - FIGO 2018 - lymph node metastasis

Introduction

Carcinoma of the uterine cervix is a major health problem in India, and each year, approximately 120,000 women have symptoms related to this disease.[1] In India, the total number of deaths due to cervical cancer accounts for 15.2% of total deaths around the world.[1] Until the recent update to the International Federation of Gynecology and Obstetrics (FIGO) staging system for the carcinoma cervix, the tumors were staged based on clinical examination. Due to limited access to advanced imaging in low resource setting, pelvic and para-aortic nodal involvement did not feature in the staging system though they are recognized prognostic factors for recurrence and survival.[1]

Since the last publication of the FIGO staging system for cervical cancer in 2009, there have been considerable advancements in imaging modalities. Even though the staging continues to be clinical, clinicians around the world have started using imaging modalities to guide their treatment and for prognostication.[2] The 2018 FIGO cervical cancer staging system keeps the backbone of clinical staging, while incorporating results from imaging and pathology, acknowledging its contribution to treatment planning and prognostication.[3] [4] One of the substantial changes from the previous staging system is that stage IB is now subdivided into three rather than two.[5] In the updated system, stage IB disease, there is increase in the substage with every 2 cm increment in size of the tumor: size < 2cm is staged as IB1, stage IB2 is tumor size of 2 to 4 cm, and stage IB3 is tumor size > 4 cm.[6] [7] In the updated 2018 staging system, para-aortic and parailiac lymph node metastases are assigned stage IIIC, regardless of the size of tumor and local invasion. In such patients, stage IIIC1 is designated to parailiac lymph nodal spread and stage IIIC2 is designated to para-aortic lymph node spread.[1] The use of imaging modalities, such as a positron emission tomography-computed tomography (PET-CT)/CT/magnetic resonance imaging (MRI)/ultrasound (USG), or pathology from a biopsy are necessary to assign either stage IIIC1 or IIIC2. According to the new FIGO 2018 staging system, when imaging is used to diagnose parailiac or para-aortic lymph node metastasis, patients are staged as IIIC1r or IIIC2r, where “r” refers to radiology. Likewise, when a lymph node biopsy pathological report is used, staging is done as IIIC1p or IIIC2p, where “p” refers to pathology.[8] [9] The previous meta-analysis by Selman et al[10] had shown the heterogeneous diagnostic capabilities of the different imaging modalities. However, in resource-poor settings, practitioners will need to make do with what is available. Thus, in this retrospective study, we studied the rates of detection of significant lymph nodes in the different imaging modalities that were used for the evaluation of patients with carcinoma cervix who were staged and treated according to the previous FIGO staging system and the contribution of imaging to stage migration according to the new FIGO staging system (2018).

 

MissingLinkText

Materials and Methods

Study Setting and Study Population

This was an institutional review board (IRB)-approved (IRB reference number 12891, dated 08.06.2020) retrospective cohort study conducted in a tertiary care teaching hospital in South India. The IRB waived informed consent. Consecutive patients who were diagnosed with cervical cancer and underwent imaging (i.e., CT/MRI/PET-CT/USG) in our center between 2013 and 2017 were included in the study. [Fig. 1] shows a patient flowchart with inclusion and exclusion criteria.

Fig. 1 Flowchart of methodology of data assessment.

 

MissingLinkText

Imaging Modalities and Image Interpretation

We assessed all the consecutive patients who underwent USG/CT/MRI/PET-CT at the time of diagnosis. These imaging modalities were used to look for lymph node involvement in patients who were diagnosed with cervical cancer. The lymph nodes were interpreted based on different imaging modalities used at the time of diagnosis. On USG, nodes which were ≥ 10 mm in size or necrotic nodes were considered significant, whereas on CT and MRI, para-aortic nodes of ≥ 10 mm and parailiac nodes ≥ 8 mm in size were considered metastatic.[11] Apart from size, nodes with necrosis, irregular shape, loss of fatty hilum, round nodes, and those with heterogeneous signal intensity on MRI were also considered metastatic.[12] An maximum standardized uptake value (SUVmax) of > 4 in a lymph node was considered significant on PET-CT.[13] The stages were documented as per the previous FIGO (2008) and the revised FIGO (2018) staging systems. The old clinical FIGO stage, histopathology findings, and treatment history of the patients were obtained from the electronic medical records.

 

MissingLinkText

 

MissingLinkText

Statistical Analysis

Descriptive statistics were reported as mean (standard deviation), range for continuous variables, and frequency with percentage for categorical variables. The proportions of patients with lymph node metastases per stage and per imaging modality and the stage migration were reported as percentage. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) software version 22.0 (IBM Corp., Armonk, New York, United States).

 

MissingLinkText

Results

Demographics

A total of 274 patients within the age range of 20 years to more than 70 years were included in the final analysis. The maximum number of patients was within the age group 40 to 50 years (39.1%). On histopathological analysis of the tumors, we found that most of the patients had poorly differentiated squamous cell carcinoma (SCC), accounting for 41.6% of the total number of patients, followed by moderately differentiated SCC (∼37.50%). The other histopathological types included: adenocarcinoma (3.69%), well-differentiated SCC (7.95%), adenosquamous carcinoma (1.8%), carcinoma in situ (5.5%), and poorly differentiated SCC (1.8%).

 

MissingLinkText

Imaging Modalities

[Fig. 2] demonstrates the usage of various imaging modalities over the years. Our study found that, in 36.9% (n = 100) of patients, USG was used as the primary modality for staging. CT was used as the primary imaging modality for staging in 27.7% of patients (n = 75). Note that 33.6% (n = 91) patients underwent MRI, and 1.82% (n = 5) underwent PET-CT for staging.

Fig. 2 Trends of use of imaging modality of choice at the time of diagnosis.

[Fig. 3] illustrates the various imaging modalities used in staging patients within our cohort. In our study, 36.5% (n = 100) patients who initially had USG as the primary imaging modality, underwent advanced imaging techniques such as CT, MRI, and PET-CT for further evaluation and staging. Also, 28.1% (n = 77) and 33.58% (n = 92) patients underwent CT and MRI as the primary imaging, respectively.

Fig. 3 Different imaging modalities among the study population.

 

MissingLinkText

Lymph Nodes

In our study, the combined mean value of the significant node was 14.41 mm with a size range from 8 to 43 mm. Note that 17.61% (n = 25) nodes were round in morphology, 21.83% (n = 31) were necrotic, 4.13% (n = 5) were irregular in shape, and 9.09% (n = 11) were heterogeneous on various cross-sectional imaging. All the patients who underwent PET-CT had significant SUVmax values. In our analysis, out of all the significant nodes according to size criteria, 44.16% of the patients had significant parailiac node involvement and 7.66% were found to have significant para-aortic lymph node involvement.

 

MissingLinkText

Stage Migration

[Tables 1] and [2] compare the old FIGO staging system and the new FIGO 2018 staging system. Our analysis showed stage migration was seen across all the stages in comparison of the old FIGO to the new FIGO 2018 system. A maximum number of stage migration was seen to stage IIICI (n = 65) due to better detection of occult lymph nodes. Four percent of patients (n = 11) were upstaged to stage IVA due to better assessment of metastatic disease. Four patients (1.46%) were upstaged to IIA1, IIA2, and IIB and 6 patients (2.19%) to IIIC2 according to the new FIGO system. Note that 1.82% of patients (n = 5) were upstaged to IB2, while 0.36% (n = 1) to IIIB and IVB.

Table 1 Distribution of patients—comparison between the old FIGO and new FIGO 2018 staging system

	Old FIGO staging (N%)	New FIGO 2018 staging (N%)
IA1	1 (0.4)	1
IA2	1 (0.4)	1
IB1	17 (6.2)	3 (1.09)
IB2	3 (1.1)	9 (3.3)
IB3		11 (4)
IIA	11 (4)
IIA1	4 (1.5)	9 (3.3)
IIA2	3 (1.1)	13 (4.75)
IIB	122 (44.5)	92 (33.6)
IIIA	2 (0.7)
IIIB	74 (27)	13 (4.7)
IIIC1		75 (27.3)
IIIC2		14 (5.1)
IVA	16 (5.8)	22 (8)
IVB	20 (7.3)	11 (4)
Total	274	274

Abbreviation: FIGO, International Federation of Gynecology and Obstetrics.

Table 2 Distribution of patients—comparison between the old FIGO and new FIGO 2018 staging system demonstrating stage migration

	New FIGO stage
Old FIGO stage	1A1	1A2	1B1	1B2	1B3	2A1	2A2	2B	3B	3C1r	3C2r	4A	4B
1A1	1	0	0	0	0	0	0	0	0	0	0	0	0
1A2	0	1	0	0	0	0	0	0	0	0	0	0	0
1B1	0	0	2	5	0	4	2	2	0	2	0	0	0
1B2	0	0	0	0	0	0	2	0	0	1	0	0	0
2A	0	0	0	1	1	2	0	1	0	5	0	0	1
2A1	0	0	0	0	0	3	0	0	0	1	0	0	0
2A2	0	0	0	0	0	0	0	2	0	1	0	0	0
2B	0	0	0	3	8	0	3	71	1	31	4	1	0
3A	0	0	0	0	0	0	0	0	0	2	0	0	0
3B	0	0	1	0	2	0	6	16	10	27	2	10	0
4A	0	0	0	0	0	0	0	0	2	2	1	10	1
4B	0	0	0	0	0	0	0	0	0	3	7	1	9

Abbreviation: FIGO, International Federation of Gynecology and Obstetrics.

 

MissingLinkText

Imaging Modality and Stage Migration

Our study found that a maximum number of patients had undergone USG as the first imaging modality, approximately 36.9% (n = 100). However, our analysis showed that the diagnostic rate for pelvic nodes was 10.7% (n = 11) and that for para-aortic nodes was 2.9% (n = 3). In comparison, CT and MRI were superior for assessing the pelvic and para-aortic nodes. Our analysis showed, of all the patients who underwent CT, 48.29% (n = 71) patients had significant parailiac nodes and 10.88% (n = 16) patients had significant para-aortic nodes. In contrast, on MRI, 38.46% (n = 45) patients had significant parailiac nodes and 3.42% (n = 4) patients had significant para-aortic nodes. PET-CT showed significant parailiac nodes in 50% (n = 5) of patients and para-aortic nodes in 10% (n = 1) of patients.

 

MissingLinkText

 

MissingLinkText

Discussion

Carcinoma cervix is the fourth most common cancer in women worldwide, with an estimated 604,127 new cases annually.[12] It is the second most common cancer in Indian women, followed by breast cancer, with an estimated 75,209 new cases annually.[14] It is well known that cross-sectional imaging such as CT/MRI and PET-CT delineates parametrial infiltration and the local extent of the tumor with greater sensitivity and specificity as compared with ultrasonography and clinical examination.[6] [15] [16] However, due to logistic reasons and resource constraints, USG was the most common imaging modality used for staging until recently.[17] The revised FIGO 2018 staging system highlighted the role of imaging and included it in the staging system with major modifications in stages II and III.[18] Our study describes the degree of stage migration between the new FIGO staging system introduced in 2019 and the old FIGO system. It highlights the different imaging modalities used for staging and the real-life detection rates of lymph node metastases using different modalities. Given that carcinoma cervix is more prevalent among women of lower socioeconomic groups, our study results are very relevant.

Our study found that there was stage migration in all the stages of carcinoma cervix. Although, over the years, there was an increase in the use of cross-sectional imaging modalities such as CT and MRI, USG was still the first imaging modality used for staging due to better accessibility and its cost-effectiveness. Although our study demonstrated limited diagnostic performance of USG in the assessment of para-aortic and parailiac nodes, enhanced training and refinement of technique may significantly improve its utility in low resource setting.[19]

We found that cross-sectional imaging had better diagnostic performance for significant pelvic and para-aortic nodes, which was the main reason for upstaging many patients with carcinoma cervix.[20] A meta-analysis by Selman et al[10] showed that PET-CT was more accurate than MRI or CT for the lymph nodal status diagnosis. They also found that MRI and CT were inferior to PET-CT, even though they were widely available. Their review suggested that the imaging methods currently used for detecting the lymph node status may be inaccurate. PET-CT may be less invasive and accurate for assessing lymph node status than sentinel node biopsy.[10] Our analysis found that MRI and CT had significant detection rates for lymph nodal metastases. PET-CT, even though not commonly used, when done, had higher detection rates of lymph node metastases. Despite limited diagnostic performance for lymph node metastases, limitations in detecting early-stage cervical cancers, and the study being conducted in a tertiary care hospital with all imaging modalities available, USG was the first and the primary imaging modality used for the detection and preliminary staging of cervical cancer in more than a third of cervical cancer patients (36.9%) in our center alongside the PAP smear test and clinical examination. This is a direct reflection of poor affordability of diagnostic care among women with carcinoma cervix. In low-resource health settings, USG may be the only available imaging modality. For these reasons, it is important to understand the lymph node detection rates using USG and harness its potential. Bowel gas and over- or underdistension of the bladder, choice of USG machine settings, equipment quality, and training gaps are key factors that may influence the diagnostic performance of USG for lymph node metastases. Methods are needed to improve diagnostic accuracy of USG. [Figs. 4] to [7] show examples of metastatic nodes on different imaging modalities.

Fig. 4 Ultrasound of the abdomen showing significant right parailiac node (A) and para-aortic nodes (B) in one of our patients from the study population.

Fig. 5 Computed tomography (CT) performed in one of our patients in the study population shows an enlarged right parailiac node (yellow arrow). This patient was clinically staged as IIB. According to the new International Federation of Gynecology and Obstetrics (FIGO) 2018, the patient was restaged as IIIC1r.

Fig. 6 Contrast-enhanced computed tomography (CECT) of a patient from our cohort with significant para-aortic node (star).

Fig. 7 Magnetic resonance imaging (MRI) pelvis shows a large mass in the cervix (orange circle) with parametrial infiltration and enlarged necrotic right parailiac lymph node metastases (orange arrow).

In our study, we found that 53.64% of patients underwent CT, and 42.7% of patients had MRI. It was found that 7.66% of patients had significant para-aortic nodes and 44.16% had significant parailiac nodes. Of the 274 patients in our study, 36.86% were upstaged when the FIGO 2018 staging system was used. Stage migration in these patients was attributable to the detection of lymph node metastasis in 30.29%. The degree of stage migration in our study cohort was comparable with the results of other studies ([Table 3]).[21] [22] [23] [24]

Table 3 Stage migration according to the FIGO stage 2018 (a comparison of various studies)

Stage migration according to FIGO stage 2018	Yan et al[21] (N = 662)	Zeng et al[22] (N = 251)	Grigsby et al[23] (N = 1,282)	Tomizawa et al[24] (N = 221)	Dhamija et al (N = 226)	Our analysis (N = 274)
Place of study	China	China	USA	Japan	India	India
IBI	149 (22.5%)	96 (38.2%)	1 (0.08%)
IB2	122 (18.4%)	109 (43.4%)	13 (1%)			5 (1.82%)
IB3	91 (13.7%)	28 (11%)	39 (3%)
IIA1	52 (7.8%)		1 (0.08%)			4 (1.46%)
IIA2	59 (9%)					4 (1.46%)
IIB			12 (0.9%)	83 (37.5%)		4 (1.46%)
IIIB			72 (5.6%)			1 (0.36%)
IIIC1	171(25.8%)	18 (7%)	380 (29.6%)	67 (30.3%)	19 (8.4%)	65 (23.72%)
IIIC2	16 (2.4%)		140 (11%)	30 (13.6%)	43 (19%)	6 (2.19%)
IVA					2 (0.8%)	11 (4%)
IVB			90 (7%)		8 (3.5%)	1 (0.36%)

Abbreviation: FIGO, International Federation of Gynecology and Obstetrics.

Our study maps the use of various imaging modalities in the staging of cervical cancer. It brings to light the degree of stage migration, especially caused by the detection of lymph node metastases on imaging. However, the result of our study is limited by its retrospective nature and referral bias. Fewer early-stage cervical cancer patients in our cohort reflect our practice as a tertiary care referral center where the majority of patients have an advanced stage at presentation. While we could study the detection rates of lymph node metastases in different imaging modalities, a direct head-to-head comparison of different modalities was not possible since patients only underwent one or two of these modalities. However, ours is real-world data on the use of different imaging modalities in cervical cancer patients. In our clinical setting, the selection of imaging modalities such as CT/MRI is not guided by standardized training protocols but is instead largely influenced by the patient's financial capacity. Often necessitating a more pragmatic and cost conscious approach to imaging decisions. We could not present survival outcomes and follow-up data since it was beyond the current study's scope, which is a limitation.

In conclusion, a significant number of patients with cervical cancer had a change of stage or stage migration when the old and the new FIGO staging systems were applied. Of them, 30.29% were due to lymph node metastases. In resource-constraint health care settings, the diagnostic yield of expertly performed USG warrants further evaluation to determine its potential role in guiding clinical decision-making.

 

MissingLinkText

 

MissingLinkText

Conflict of Interest

None declared.

• References

• 1 Lee SI, Atri M. 2018 FIGO staging system for uterine cervical cancer: enter cross-sectional imaging. Radiology 2019; 292 (01) 15-24
• 2 Bhatla N, Berek JS, Cuello Fredes M. et al. Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynaecol Obstet 2019; 145 (01) 129-135
• 3 Dhamija E, Gulati M, Manchanda S. et al. Imaging in carcinoma cervix and revised 2018 FIGO staging system: implications in radiology reporting. Indian J Radiol Imaging 2021; 31 (03) 623-634
• 4 Bhatla N, Singhal S, Dhamija E, Mathur S, Natarajan J, Maheshwari A. Implications of the revised cervical cancer FIGO staging system. Indian J Med Res 2021; 154 (02) 273-283
• 5 Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynaecol Obstet 2018; 143 (Suppl. 02) 22-36
• 6 Salib MY, Russell JHB, Stewart VR. et al. 2018 FIGO staging classification for cervical cancer: added benefits of imaging. Radiographics 2020; 40 (06) 1807-1822
• 7 Matsuo K, Machida H, Mandelbaum RS, Konishi I, Mikami M. Validation of the 2018 FIGO cervical cancer staging system. Gynecol Oncol 2019; 152 (01) 87-93
• 8 Tomizawa K, Kaminuma T, Murata K. et al. FIGO 2018 staging for cervical cancer: influence on stage distribution and outcomes in the 3D-image-guided brachytherapy era. Cancers (Basel) 2020; 12 (07) 1770
• 9 Singh N, Rous B, Ganesan R. BAGP Information document: 2018 FIGO staging System for Cervix Cancer, version 1.5, September 2021
• 10 Selman TJ, Mann C, Zamora J, Appleyard TL, Khan K. Diagnostic accuracy of tests for lymph node status in primary cervical cancer: a systematic review and meta-analysis. CMAJ 2008; 178 (07) 855-862
• 11 Jung W, Park KR, Lee KJ. et al. Value of imaging study in predicting pelvic lymph node metastases of uterine cervical cancer. Radiat Oncol J 2017; 35 (04) 340-348
• 12 Dhamija E, Baby A, Bhatla N. et al. Radiological evaluation of metastatic lymph nodes in carcinoma cervix with emphasis on their infiltrative pattern. Indian J Med Res 2021; 154 (02) 383-390
• 13 Brunette LL, Bonyadlou S, Ji L. et al. Predictive value of FDG PET/CT to detect lymph node metastases in cervical cancer. Clin Nucl Med 2018; 43 (11) 793-801
• 14 Mathur P, Sathishkumar K, Chaturvedi M. et al; ICMR-NCDIR-NCRP Investigator Group. Cancer Statistics, 2020: report from National Cancer Registry Programme, India. JCO Glob Oncol 2020; 6: 1063-1075
• 15 Fischerova D, Frühauf F, Burgetova A, Haldorsen IS, Gatti E, Cibula D. The role of imaging in cervical cancer staging: ESGO/ESTRO/ESP guidelines (Update 2023). Cancers (Basel) 2024; 16 (04) 775
• 16 Mansoori B, Khatri G, Rivera-Colón G, Albuquerque K, Lea J, Pinho DF. Multimodality imaging of uterine cervical malignancies. AJR Am J Roentgenol 2020; 215 (02) 292-304
• 17 Hsiao YH, Yang SF, Chen YH. et al. Updated applications of ultrasound in uterine cervical cancer. J Cancer 2021; 12 (08) 2181-2189
• 18 Sponholtz SE, Mogensen O, Hildebrandt MG. et al. From FIGO-2009 to FIGO-2018 in women with early-stage cervical cancer; does the revised staging reflect risk groups?. Gynecol Oncol 2021; 163 (02) 281-288
• 19 Fischerova D, Smet C, Scovazzi U, Sousa DN, Hundarova K, Haldorsen IS. Staging by imaging in gynecologic cancer and the role of ultrasound: an update of European Joint Consensus statements. Int J Gynecol Cancer 2024; 34 (03) 363-378
• 20 Olthof EP, Bergink-Voorthuis BJ, Wenzel HHB. et al. Diagnostic accuracy of MRI, CT, and [¹⁸F]FDG-PET-CT in detecting lymph node metastases in clinically early-stage cervical cancer - a nationwide Dutch cohort study. Insights Imaging 2024; 15 (01) 36
• 21 Yan DD, Tang Q, Chen JH, Tu YQ, Lv XJ. Prognostic value of the 2018 FIGO staging system for cervical cancer patients with surgical risk factors. Cancer Manag Res 2019; Jun 13; 11: 5473-5480
• 22 Zeng J, Qu P, Hu Y, Sun P, Qi J, Zhao G, Gao Y. Clinicopathological risk factors in the light of the revised 2018 International Federation of Gynecology and Obstetrics staging system for early cervical cancer with staging IB: A single center retrospective study. Medicine (Baltimore) 2020; Apr; 99 (16) e19714
• 23 Grigsby PW, Massad LS, Mutch DG. et al. FIGO 2018 staging criteria for cervical cancer: Impact on stage migration and survival. Gynecol Oncol 2020; Jun; 157 (03) 639-643
• 24 Tomizawa K, Kaminuma T, Murata K. et al. FIGO 2018 staging for cervical cancer: influence on stage distribution and outcomes in the 3D-image-guided brachytherapy era. Cancers (Basel) 2020; Jul 2; 12 (07) 1770

Publication History

Article published online:
25 June 2025