Assessment of Diagnostic Accuracy of IOTA-ADNEX Model in Detecting the Risk of Malignancy in Ovarian Carcinomas

Background: Ovarian cancer has become a major public health issue which stood in 10 th rank of mortality within India. 2.4 % is the annual new cases of ovarian cancer in overall India. In 2008 it was the seventh leading cause of cancer deaths in women worldwide. 70% of cases are diagnosed with poor prognosis at an advanced stage. Ovarian malignancy death rate is of 70% within 2 yrs and 90% within five years. It’s a tough task for a gynecologist to identify ovarian cancer correctly .Ovarian malignancy is initially detected as adnexal mass. Exploratory laparotomy or laparoscopy with histopathology is a specific diagnostic procedure for adnexal mass. This study aims to study and analyse the diagnostic accuracy of IOTA ADNEX model in detecting the risk of malignancy in ovarian carcinomas. Objectives: To make pre-operative diagnosis of adnexal masses and conserve the in menstruating women with less aggressive management. Methodology: This prospective study will be conducted in Obstetrics & Gynaecology department of AVBRH, Wardha from September 2020 to July 2022. This will be conducted on 50 females presenting with adnexal mass. Patients will undergo transvaginal ultrasonography with HERA W10 ultra sound system with an endovaginal EA2-11B probe. The ultra sound evaluation we will include IOTA –ADNEX Model. The mass with the most complex structure will be chosen for analysis for Original Research Article Srinidhi and Jajoo; JPRI, 33(64A): 373-380, 2021; Article no.JPRI.80781 374 ultrasound imaging to know the chances of being malignant. Expected Results: Positive correlation between the IOTA –ADNEX model and histopathological report. Conclusion: IOTA-ADNEX model to be incorporated for ovarian malignancy diagnostic protocol.


INTRODUCTION
With more than 8,00,000 new cases occurring annually, cancer has become a major public health issue which stood in 10 th rank of mortality within India [1]. 2.4 % is the annual new cases of ovarian cancer in overall India [2]. In 2008 it was the seventh leading cause of cancer deaths in women worldwide [3]. 70% of cases are diagnosed with poor prognosis [4] at an advanced stage. Ovarian malignancy death rate is of 70% within 2 yrs and 90% within five years [5].
Till date researchers invented numerous screening methods however they have been ineffective [6] due to insufficient results. Because of its bizarre & nonspecific symptoms [7] its a tough task for a gynecologist to identify ovarian cancer correctly .Ovarian malignancy is initially detected as adnexal mass [5].
Exploratory laparotomy or laparoscopy with histopathology is a specific diagnostic procedure for adnexal mass.
Referral of such patients to Multidisciplinary Cancer team in a tertiary hospital with experienced gynecologic oncology surgeons to perform specialized surgical procedures to increase life span of the ovarian cancer patients by knowing high risk of malignancy in said mass.
In local hospitals, most women present with adnexal mass and nonspecific symptoms. Its important to ascertain is it necessary to perform a surgery and if if so its variant, pro's & con's of surgery in preoperative duration [8][9][10]. Earlier information of ovarian tumour either it is malignant or benign will lead to appropriate management of patients [5]. Implementing a methodology for better preoperative pelvic mass evaluation will help more women obtain first-line treatment from efficiently trained and skilled staff. Unfortunately, there is no established population based screening program for the disease [11][12]. For such referrals, sensitive and specific efficient techniques for diagnosis of an ovarian tumour are needed [13]. Various mathematical models, software programs and scoring systems, which depend on Serum Cancer antigen 125 ,ultrasonographic findings, Doppler MRI and Computerized tomography were suggested to attain better discrimination for malignant ovarian tumours.
Serum CA-125 , an ovarian cancer tumor marker where 85% of epithelial ovarian cancer has an evidence of rise of its concentration more than 35 U/ml with 83% sensitivity and 39.3% specificity only [10,14].
Gynecologic ultrasonography (US) is a valuable tool to detect ovarian mass presence, distinguishing among benign and malignant tumors, establishing the ovarian tumors management plan [15]. There are two primary explanations why using Ultra sonographic imaging are used to differentiate ovarian tumors from benign to malignant. The first accurate identification of tumors that are benign and malignant allows doctors to get an idea regarding plan of action: either medical or surgical management, method of surgery, open or minimally invasive or other extended researches, tumor marker & radio imaging like CT, or MRI [15] Next, among gynecological tumors ovarian cancer is not that prevalent, but it is a deadly illness with high levels of recurrence [15]. The majority of the patients have an advanced stage survival rate of less than 30 percent for five years at the time of diagnosis. 92.4 % is average 5year survival of early-stage cancer [15] therefore preliminary diagnosis by US increases the survival rate of a patient. This will give the most easiest follow-up or the most beneficial care in low expense to the patient.
For the differentiation of LR1, LR2 [15] and simple rules [15] have been introduced by IOTA group since 2005 , which reported that the diagnostic performance of these predictive models is superior than that of preexisting systems [15]. In 2014, a new better performance model was developed in this group [15] namelyadnex (ADNEX) model in view of evaluation of adnex into different tumours .3 clinical features and six US are used in this model to suspect the probability of adnexal masses malignancy. With IOTA-ADNEX model, perceptive efficiency of ovarian tumors was greater to existing current models 27-28 through various external validation studies. However, in terms of characterizing ovary tumors, there have been few prospective studies weighing the differences of this model and gynecologic experts.
The ADNEX model was designed and validated with the information from the IOTA phase 1-3 datasets, comprising of prospectively gathered patients presenting with adnex mass who were referred for an ultrasonographic examination to one of the participating centers [16]. If a female presented with a minimum one adnexal mass which is a non-physiological cyst & been selected for surgical care by the managing clinician following local guide lines were eligible for inclusion criteria.
10% of cut-off value was the calculated specificity for differentiating ovarian tumors in accuracy of IOTA-ADNEX Model for its validation .For operable group it shows 0.816 (95% CI: 0.680-0.912) and 0.795 (95% CI: 0.647-0.902) with significant difference (p = 0.005 in all participants and p = 0.017 in operable group) [16] and S N 0.9 (95% CI: 0.555-0.998) in all participants and the operable group. Later the accuracy of the ADNEX Model will be confirmed by the histopathology reports of that particular mass.

Rationale
This study is used to detect risk & differentiate among benign and malignant with IOTA-ADNEX Model and formulate management better prognosis depending on the type of tumour.

Aim
To analyse diagnostic accuracy of IOTA -ADNEX model in detecting the risk of malignancy in ovarian carcinomas.

Objective
 Pre-operative diagnosis of adnexal masses before surgery.  To conserve the fertility by decreasing morbidity and mortality associated with adnexal pathology in menstruating women (in cases of borderline tumours and stage I cancer ) with less aggressive management

METHODOLOGY
Firstly, the whole procedure is explained in their own language and written informed consent will be taken from the each patient presenting with the adnexal mass to the hospital. Peripheral venous blood will be sent to lab to measure CA-125, an ovarian tumour marker, which is a routine investigation sent for a adnexal mass patient. Then patient will undergo transvaginal ultrasonography with HERA W10 ultra sound system with an endovaginal EA2-11B probe.
Here in ultra sound evaluation we will include IOTA -ADNEX Model which includes age, referral center , maximum diameter of adnexal lesion & largest solid part, no. of locules , acoustic shadows in the mass, presence of ascitic fluid & serum CA 125 levels. In case if a patient presents with several masses, the mass with the most complex structure will be chosen for analysis for ultrasound imaging to know the chances of being malignant .with all these parameters the ADNEX score is calculated. If there is more than one mass with identical morphology, the largest or the most widely accessible mass will be used.  The risk percentage will be given in terms of patient specific risk relative risk & baseline risk *Based on the Two step clinical approach,if the patients specific risk of malignancy is less than 10% (cut off) it is considered as benign and if above 10% it is considered as malignant . *Patient will be taken for surgery accordingly in case of both benign and malignant. *Intra op findings of the mass to be noted to differentiate the specimen by its features and the specimen will be send to histopathology . *After knowing the pathological diagnosis by histopathology report which is gold standard ,will be compared with the IOTA ADNEX MODEL tool's malignancy risk prediction , of the presenting mass calculated beforehand.

DISCUSSION
With IOTA ADNEX model validation studies have attempted to find the ideal numerical value of malignancy risk. RMI is used in national guidelines of RCOG to differentiate ovarian tumors. RMI had lesser accuracy compared to mathematical models or SR or LR2, especially with low S N in a recent review article. Moreover, differentiating adnexal masses from benign and malignant subjective assessment is better than RMI or ROMA [15].
The benefit of usage of IOTA-ADNEX model in differentiating ovarian tumors has been concluded in various studies compared to different methods, like subjective evaluation. High negative predictive value, without including malignancy with high accuracy was the typical outcome of the ADNEX model in diagnosis of ovarian tumor characteristics .In addition. ADNEX model has good distinguishing accuracy against other tumors for stage II-IV ovarian malignancies [15].
As a screening tool for epithelial ovary tumors Serum CA-125 has been used most commonly since 198. This tumor marker has comparatively low S S as its value is raised in other benign conditions too. Several gynecologists use imaging studies, including Ultra Sound, CT, or MRI to address this constraint [15,16]. Above all, Ultrasonography is a primary imaging modality, and for those who have inconclusive Ultra sound results CT or MRI is a solution .Detailed analysis proven that sonography itself offers excellent outcomes of preoperative ovarian tumors and benign or borderline/malignancies characteristic assessment compared to other radiological imaging .  [17]. Other related studies were reviewed [18][19][20][21][22][23].

CONCLUSION
In conclusion, IOTA-ADNEX model should be incorporated into the model for predicting the inhospital mortality for ovarian malignancy .Considering its diagnostic accuracy might be relatively modest, further studies should validate the ultrasonography usefulness of adnexal masses.

DISCLAIMER
The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

ETHICAL APPROVAL
As per international standard or university standard written ethical approval will be collected and preserved by the author(s).

CONSENT
Written informed consent will be taken from the each patient presenting with the adnexal mass to the hospital.