A RETROSPECTIVE COHORTSTUDY ON THE DIAGNOSTIC ACCURACY OF INTERNATIONAL

OVARIAN TUMOR ANALYSIS (IOTA) SIMPLE RULES AND IOTA ADNEX MODEL IN
IDENTIFYING BENIGN AND MALIGNANT ADNEXAL MASSES WITH HISTOPATHOLOGIC
CORRELATION

1
ABSTRACT:

Background: Ovarian masses are common problems in women and they often

present with vague symptoms. They can be physiologic or pathologic and can be

differentiated into functional cysts, benign or malignant ovarian tumors.

Given the late detection, poor prognosis, and high mortality of women with

ovarian malignancy, it is of utmost importance to correctly diagnose them

preoperatively by a combination of clinical examination, ultrasonography, and

tumor marker CA 125 and to distinguish them from benign ovarian lesions for

proper management and improved survival rate.

Objective/s: To determine the accuracy of IOTA Simple Rules and IOTA ADNEX

Model in the evaluation of adnexal masses by correlating the sonographic with

histopathological results.

Methods: All patients who have undergone transvaginal and transabdominal

ultrasound performed by OB-Gyne Sonologists who are all familiar with the IOTA

group definitions of ultrasound features of adnexal masses were included.

Ultrasound results of all patients who underwent ultrasound using IOTA were

retrieved. The sonographic findings using IOTA was compared with the

histopathological results, to determine the accuracy of IOTA in diagnosing

various adnexal tumors.

Results: A total of 57 subjects were included, age ranged from 14 to 72 years

with a mean of 41.72 years (sd=15.13). Ultrasound report showed that 18

(31.6%) had IOTA simple rules result only while 28 (49.1%) had IOTA adnex

model result only and 11 (19.3%) had results both for IOTA simple rules and

IOTA adnex model. Of the 29 patients with IOTA simple rules, 4 subjects or

13.8% showed malignant results both by IOTA simple rules and histopath while

17 (58.6%) had benign results in both test. Inconclusive results were noted in 4

(13.8%) subjects. No significant difference noted in the results of the IOTA simple

2
rules and histopath (p=0.13). The sensitivity and specificity were 100% (95% CI:

51.0% - 100%) and 81.0% (95% CI: 60.0% - 92.3%), respectively. The probability

that a patient had malignant histopath result given that she is malignant by IOTA

simple rules was 50.0% (95% CI: 21.5% - 78.5%). Moreover, the probability that

a patient had benign histopath result given that she is benign by IOTA simple

rules was 100.0% (95% CI: 81.6% - 100%). There is a good agreement noted

between the IOTA adnex and the histopath result as seen in the Kappa value of

0.60. Of the 39 patients with IOTA adnex model results, 11 subjects or 28.3%

showed malignant results both by IOTA adnex and histopath while 17 (43.6%)

had benign results in both test. Discordant findings were noted in 11 (28.2%)

subjects in whom 9 had a malignant finding noted in the IOTA adnex but turned

out benign in histopath while 2 patient had benign finding in IOTA adnex but

turned out malignant by histopath. No significant difference was noted in the

results of the IOTA adnex model and histopath (p=0.07). The sensitivity and

specificity were 84.6% (95% CI: 57.8% - 95.7%) and 65.4% (95% CI: 46.2% -

80.6%), respectively. The probability that a patient had malignant histopath result

given that she is malignant by IOTA adnex was 55.0% (95% CI: 34.2% - 74.2%).

Moreover, the probability that a patient had benign histopath result given that she

is benign by IOTA adnex was 89.5% (95% CI: 68.6% - 97.1%).

Conclusion: The results of the study shows that both IOTA simple rules and

IOTA adnex model were comparable with the histopath result in diagnosing

benign and malignant adnexal masses. Thus, these two methods can be used in

differentiating between malignant and benign adnexal masses.

Key Word: IOTA simple rules, IOTA adnex model, Adnexal mass, Ovarian

malignancy

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INTRODUCTION:

The ovaries are paired gonads in females, the role of which are steroidogenesis,

germ cell maturation, storage and release. Accumulation of fluid inside the

functional unit of the ovary leads to non-neoplastic enlargement of the ovary

known as functional cysts. Functional ovarian cysts are caused by temporary

hormonal disorders, can reach 6-8 cm in size, asymptomatic, unilocular, contain

clear fluid, and regress spontaneously in contrast to ovarian neoplastic cysts 1.

Benign ovarian tumors generally manifest in the late reproductive age but

dermoid cysts and mucinous cystadenomas are common in the reproductive age

group. No correlation is seen between parity and benign ovarian tumors. Most

are asymptomatic but some may manifest heaviness, abdominal enlargement, or

dull ache in the abdomen. Complications include torsion, intracystic hemorrhage,

infection, pseudo-mucinous peritonitis and malignancy 1.

Approximately two-thirds ovarian tumors occur in the reproductive age group.

Less than 5% are found in children. Benign serous tumors are more common in

the reproductive age group. Mucinous cystadenomas are most often diagnosed

in the 4th- 6th decade of life. At younger age groups (those below 21 years of

age), germ cell tumors consist approximately 60% of malignant tumors of the

ovary, accounting for two-thirds of ovarian cancer in the 1 st two decades of life.

Mucinous cancer is seen in 53-54 years of age. Most serous cancers are

diagnosed between 40-69 years of age2.

Ovarian cancer is one of the major health problems in women, having more than

225, 000 new cases and 140, 000 deaths yearly 3,4. It is the 5th most common

cause of cancer in the Philippines5. Specific risk factors include early menarche,

nulliparity, infertility, low number of pregnancies, history of endometrial cancer or

breast cancer, or menstrual irregularities, late age of menopause, high BMI, long

term use of hormone replacement therapy, and genetic mutations 5,6. Patients with

ovarian cancer are usually asymptomatic leading to its late detection and

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diagnosis5. Having only a 5-year survival rate of less than 30%, it is important to

differentiate benign from malignant adnexal masses to arrive at an accurate

preoperative diagnosis of ovarian cancer which is crucial in early detection and

management7.

In the past several years, many studies have focused on the characterization of

ovarian masses as benign or malignant. The role of ultrasound in making the

correct diagnosis of ovarian masses, cannot be undermined. Magnetic

resonance imaging (MRI) and Computed tomography (CT) are far more

expensive, with more radiation exposure. Ultrasound in such is more non-

invasive and cost-effective, ultrasound is being widely used not only for pregnant

women but in diagnosing uterine, cervical, and ovarian pathologies. However,

even if ultrasonography is an effective modality, histopathology remains the gold

standard in arriving at the final diagnosis. Accurate methods to preoperatively

diagnose adnexal tumors are vital for proper patient management 5. The

importance of preserving fertility in ovarian cancer patients makes the

preoperative diagnosis of ovarian masses more relevant.

Several morphological scoring systems have been developed and used in the

past including the Sassone scoring in 1991 and Lerner scoring in 1994 but the

International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) have

recommended the use of IOTA Scoring System in the classification of adnexal

masses. The use of IOTA Simple Rules was introduced as well as Logistic

Regression Model, LR1 and LR2, mathematical risk models which try to

differentiate benign and malignant masses. In 2014, the IOTA ADNEX model

which is the first predictive multiclass polytomous model was introduced 9.

In 2008, Timmerman et al proposed the simple ultrasound-based rules in

differentiating benign from malignant ovarian masses through a standardized

examination technique. The model included 5 ultrasonographic features

suggesting benignity and 5 features suggesting malignancy. The B-features or B-

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rules include the following: B1-unilocular cyst; B2-presence of solid components

where the largest component measures < 7 mm; B3-presence of acoustic

shadowing; B4-smooth multilocular tumor with largest diameter measuring < 100

mm; B5-no blood flow. The M rules include the following: M1-irregular solid

tumor; M2-presence of ascites; M3-presence of at least 4 papillary structures;

M4-presence of irregular multilocular solid tumor with largest diameter ≥100 mm;

M5-very strong blood flow. Presence of 1 or more B-features will classify the

mass as benign while presence of 1 or more M-features will classify the mass as

malignant. If B-features and M-features are both present, the mass will be

classified as inconclusive10.

The IOTA Asssessment of Different NEoplasias in the adneXa (ADNEX) Model is

a multiclass, polytomous model that was proposed in 2014 to differentiate benign

from borderline tumors, stage I invasive, stage II-IV invasive ovarian cancer,

metastatic cancer. This was the first risk model to predict not only whether a

mass is malignant or not, but determine the type of malignancy to a certain

range9. The model consists of 3 clinical predictors namely, age, level of serum

CA-125, and whether the hospital is an oncology center or not and 6

ultrasonographic predictors, namely, the maximum diameter of the largest mass

in mm, proportion of solid tissue (%), number of papillary projections present,

(0,1, 2, 3, >3), presence of more than 10 locules (yes/no), presence of acoustic

shadows (yes/no), presence of ascites (yes/no)9.

This study aims to determine the diagnostic accuracy of IOTA Simple Rules and

IOTA ADNEX Model in differentiating benign and malignant masses in our local

setting.

Research question: Among women who underwent transvaginal and

transabdominal ultrasound using IOTA in this institution, how accurate is the

International Ovarian Tumor Analysis (IOTA) Simple Rules and IOTA ADNEX

Model in diagnosing adnexal masses?

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P- Women who underwent transrectal or transvaginal with or without

transabdominal ultrasound using IOTAfrom January 1, 2019 to June 30, 2020 at

Valenzuela Medical Center and were also surgically intervened in the same

institution and whose specimens were submitted and read at the Pathology

Department of this institution.

I –International Ovarian Tumor Analysis

C- Histopathologic Result

O- Determine the accuracy of IOTA

General Objective:

The objective of this study is to determine the accuracy of IOTA Simple Rules

and IOTA ADNEX Model by correlating the sonographic results with

histopathological diagnosis.

Specific Objectives:

1. To determine the accuracy of 2D Ultrasound at Valenzuela Medical Center

(VMC) in the evaluation of adnexal masses by correlating it with

histopathological diagnosis.

2. To compute for the sensitivity, specificity, negative predictive value, and

positive predictive value of International Ovarian Tumor Analysis (IOTA)

Simple Rules and IOTA ADNEX Model in the evaluation of adnexal

masses with histopathological correlation.

Significance of the Study

The results of this study should benefit the following people:

1. Obstetrician-gynecologists who would want an accurate tool for

diagnosing adnexal masses.

2. Patients with adnexal masses who would want to know their prognosis

by relying on ultrasound findings using IOTA.

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Scope and Limitation of the Study

The study focused on women with adnexal masses who underwent either

transrectal or transvaginal scan with or without transabdominal ultrasound using

IOTA Simple Rules and IOTA ADNEX Model. Adnexal masses should have been

classified as benign, malignant or inconclusive using the IOTA Simple Rules

(See Table 1). These women underwent surgical intervention and subsequently

submitted their specimens for histopathological examination. The study was

conducted for 1 ½ years (from January 1, 2016 to December 31, 2020) and only

patients who were admitted and surgically intervened at Valenzuela Medical

Center were included.

Table 1. The IOTA Simple Rules for identifying benign or malignant adnexal mass

B-Rules (Rules for classifying a benign tumor)

B1 Unilocular
B2 Presence of at least one solid component with largest diameter <7

mm
B3 Presence of acoustic shadows
B4 Smooth multilocular tumor with largest diameter <100 mm
B5 No blood flow (color score of 1)
M- Rules (Rules for classifying a malignant tumor)
M1 Irregular solid tumor
M2 Presence of ascites
M3 At least 4 papillary structures
M4 Irregular multilocular solid tumor with largest diameter ≥100 mm
M5 Very strong blood flow (color score of 4)

METHODOLOGY:

Study Design:

This is a retrospective cohort study to evaluate the accuracy of International

Ovarian Tumor Analysis (IOTA) in women with ovarian masses at Valenzuela

Medical Center by comparing it with the gold standard which is histopathologic

diagnosis.

Subjects:

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All women who underwent transrectal or transvaginal with or without

transabdominal ultrasound using IOTA and were intervened at the Valenzuela

Medical Center with histopathological results were included in this study.

Inclusion Criteria:

 Female patients with unilateral or bilateral adnexal mass/masses

 Must have undergone transvaginal or transrectal ultrasound with or

without transabdominal scan in this institution

 Must have undergone surgical intervention at the Valenzuela Medical

Center within 120 days after the ultrasound.

 Should have submitted their specimens to histopathology for final

diagnosis

Exclusion Criteria:

 Female patients who underwent bilateral oophorectomy in the past

 Adnexal mass/masses co-existing with pregnancy

Procedure:

All patients have undergone transvaginal and transabdominal ultrasound using

GE s8 and GE s6 Ultrasound Machines in the said institution from January 1,

2018- December 31, 2019, performed by OB-Gyne Sonologists who are all

fellows of the Philippine Society of Ultrasound in Obstetrics and Gynecology with

a minimum of three years of practice in OB-Gyne Ultrasound and who are all

familiar with the IOTA group definitions of ultrasound features of adnexal

masses. These patients have been intervened within 120 days after performing

the scan, via exploratory laparotomy, salpingo-oophorectomy, total abdominal

hysterectomy with bilateral salpingo-oophorectomy, or complete ovarian staging

with specimens submitted and read at the Pathology Department for them to be

qualified subjects for the study. Ultrasound results of all patients who underwent

ultrasound using IOTA in the covered period were retrieved by the investigator

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from the Gynecology Census of the Valenzuela Medical Center Ultrasound

Section. After tabulating the results with their assigned alpha-numeric code, the

investigator reviewed the General Census Logbook of all patients who were

surgically intervened in our institution are listed with the corresponding

Histopathology Results at the Records Section. Those patients who underwent

transrectal or transvaginal with or without transabdominal ultrasound using IOTA

but were not admitted and intervened in our institution were excluded. After

excluding those patients who were not intervened, and listing all the patients

included, the investigator reviewed the histopathology results, to check who

among those subjects were able to submit the specimens for histopathology.

Those patients who were intervened in our institution but do not have

histopathological exam done in our institution were also excluded. The

sonographic findings using IOTA was compared with the histopathological

results, to determine the accuracy of IOTA in diagnosing various adnexal tumors.

The IOTA ADNEX Model uses three (3) clinical variables namely, age, serum

CA-125, and the type of center, whether oncology referral center or not, and six

(6) ultrasonographic variables namely, maximum diameter of the lesion,

maximum diameter of the largest solid part of the lesion (mm), more than 10 cyst

locules (yes or no), number of papillary projections (0,1,2,3, >3), presence or

absence of acoustic shadows, and presence or absence of ascites, respectively.

The ADNEX Model can be accessed and computed using the website

(http://www.iotagroup.org/adnexmodel). The risk will be calculated with a risk

estimate in percentage of five (5) different types of adnexal pathology, namely,

benign, borderline, stage I-invasive, stage II-IV invasive, and secondary

metastatic cancer. A risk estimate will also be given for the overall potential for

malignancy. A cut-off of ≥ 10% for the overall risk of malignancy will be used.

Sample Size:

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The sample size was calculated using a 95% level of confidence. With an

estimated sensitivity of 82% of IOTA in detecting malignancy in patients with

ovarian mass, at least 57 subjects are needed at 10% margin of error.

( z ) 2 pq
n
e2
Where:

n = is the number of subjects needed

p = estimated sensitivity of IOTA = 82%=0.82

q = 1 – p = 1 – 0.82 = 0.18

Zα = 95% confidence level = 1.96

e = error of 10%

Statistical Analysis:

Descriptive statistics were used to summarize the clinical characteristics of the

patients. Frequency and proportion were used for nominal variables and mean

and SD for interval/ratio variables. The point and 95% confidence intervals (CI’s)

of the sensitivity, specificity, positive predictive value, and negative predictive

values as well as likelihood ratios of IOTA Simple Rules and IOTA Adnex were

computed with histopathology result as the gold standard. Kappa values were

also computed to determine the degree of agreement of the IOTA simple rules

and IOTA Adnex with histopath result. Mc Nemar test was used to determine if

there is difference between the measurements. Null hypothesis will be rejected at

0.05α-level of significance. SPSS version 17 for Windows was used for data

analysis.

Ethical Considerations:

The investigator made a letter to the Department of Obstetrics and Gynecology

(Section of Ultrasound in Obstetrics-Gynecology) of Valenzuela Medical Center

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to be allowed access on records of patients who met the inclusion criteria for this

study. Records of patients were assigned alpha-numeric coding starting with

ASD-001 onwards instead of real names to protect the confidentiality of their

identities. No identifying marks were used to avoid breach of confidentiality.

Since this is a retrospective study, informed consent cannot be obtained from the

patients but the investigator ensured that confidentiality of data was observed at

all times, hence the investigator submitted a waiver for informed consent.

The author has no conflict of interest in doing this study.

RESULTS

A total of 57 subjects were included in this study. Their age ranged from 14 to 72

years with a mean of 41.72 years (sd=15.13). Around 50% were multipara.

Ultrasound reports showed that 18 (31.6%) had IOTA simple rules results only

while 28 (49.1%) had IOTA adnex model results only and 11 (19.3%) had results

both for IOTA simple rules and IOTA adnex model (Table 1).

Table 1. Demographic Characteristics of Subjects

Frequency Percentage

(n=57)
Age (in years)

≤18 4 7.1

19 – 34 19 33.3

≥35 34 59.6
Gravida

Nulligravida 13 22.8

Primigravida 3 5.3

Secundigravida 12 21.1

Multigravida 29 50.8
Parity

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 Nulliparous 13 22.8

Primiparous 4 7.0

Multiparous 40 70.2
Ultrasound Report

IOTA Simple Rules only 18 31.6

IOTA Adnex only 28 49.1

Both 11 19.3

Table 2 shows the results for IOTA simple rules and histopathology. Of the 29

patients, 4 subjects or 13.8% showed malignant results both by IOTA simple

rules and histopathology while 17 (58.6%) had benign results in both test.

Inconclusive results were noted in 4 (13.8%) subjects. Mc Nemar test showed

that considering the malignant and benign results only in IOTA simple rules,

there was no significant difference noted in the results of the IOTA simple rules

and histopath as shown by the p value of 0.13.

Table 1. Ultrasound (IOTA Simple Rules) versus Histolopathologic Diagnosis in the Identification

of Adnexal Masses

Histopathologic Results Total

Malignant Benign
IOTA Simple Rules

Malignant 4 4 8

Benign 0 17 17

Inconclusive 1 3 4
Total 5 24 29
p-value = 0.13 (NS) (Mc Nemar test) (between malignant and benign only)

Table 3 depicts the point estimates of the different measures of validity and their

95% confidence intervals. The sensitivity and specificity were 100% (95% CI:

51.0% - 100%) and 81.0% (95% CI: 60.0% - 92.3%), respectively. The probability

13
that a patient had malignant histopathologic result given that she is malignant by

IOTA simple rules was 50.0% (95% CI: 21.5% - 78.5%). Moreover, the

probability that a patient had benign histopathologic result given that she is

benign by IOTA simple rules was 100.0% (95% CI: 81.6% - 100%).

The positive likelihood ratio of 5.26 (95% CI: 2.17 – 12.68) indicates that the

probability of a malignant IOTA simple rules result among patients with malignant

histopathologic result was 5.26 times higher than the probability of a malignant

histopathologic result among patients with benign IOTA simple rules result. The

negative likelihood ratio is 0. There is A good agreement noted between the

IOTA adnex and the histopathologic result as seen in the Kappa value of 0.60.

Table 3. Sensitivity, Specificity, NPV, PPV, LR+ and LR- of Ultrasound

(IOTA) for Adnexal Masses

SISH FINDINGS Value 95% Confidence Interval (CI)

Sensitivity 100% 51.0% - 100%
Specificity 81.0% 60.0% - 92.3%
Positive Predictive Value 50.0% 21.5% - 78.5%
Negative Predictive Value 100% 81.6% - 100%
Positive Likelihood Ratio 5.26 2.17 – 12.68
Negative Likelihood Ratio 0 ---
Kappa Value 0.60 0.23 – 0.92

Table 3 shows the results for IOTA adnex and histopathology. Of the 39 patients,

11 subjects or 28.3% showed malignant results both by IOTA adnex and

histopathology while 17 (43.6%) had benign results in both test. Discordant

findings were noted in 11 (28.2%) subjects in whom 9 had a malignant finding

noted in the IOTA adnex but turned out benign in histopathology while 2 patient

had benign finding in IOTA adnex but turned out malignant by histopathology. Mc

Nemar test showed that considering the malignant and benign results only in

IOTA adnex model, there was no significant difference noted in the results of the

IOTA adnex model and histopathology as shown by the p value of 0.07.

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Table 3. Ultrasound (IOTA Adnex) versus Histolopathologic Diagnosis in the Identification of

Adnexal Masses

Histopath Total
Malignant Benign
IOTA Adnex

Malignant 11 9 20

Benign 2 17 19
Total 13 26 39
p-value = 0.07 (NS) (Mc Nemar test)

Table 4 depicts the point estimates of the different measures of validity and their

95% confidence intervals. The sensitivity and specificity were 84.6% (95% CI:

57.8% - 95.7%) and 65.4% (95% CI: 46.2% - 80.6%), respectively. The

probability that a patient had malignant histopathologic result given that she is

malignant by IOTA adnex was 55.0% (95% CI: 34.2% - 74.2%). Moreover, the

probability that a patient had benign histopathologic result given that she is

benign by IOTA adnex was 89.5% (95% CI: 68.6% - 97.1%).

The positive likelihood ratio of 2.45 (95% CI: 1.37 – 4.35) indicates that the

probability of a malignant IOTA adnex result among patients with malignant

histopathologic result was 2.45 times higher than the probability of a malignant

histopathologic result among patients with benign IOTA adnex result. The

negative likelihood ratio of 0.24 indicates that the probability of a benign IOTA

adnex result among participants with malignant histopathologic result was almost

one fourth of the probability of a benign IOTA adnex result among participants

with benign histopathologic result. There is a moderate agreement noted

between the IOTA adnex and the histopathologic result as seen in the Kappa

value of 0.44.

Table 4. Overall Sensitivity, Specificity, NPV, PPV , LR+ and LR- of Ultrasound (IOTA

Adnex) for Adnexal Masses

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 IOTA Adnex Value Confidence Interval (CI)-95%
Sensitivity 84.6% 57.8% – 95.7%
Specificity 65.4% 46.2% – 80.6%
Positive Predictive Value 55.0% 34.2% – 74.2%
Negative Predictive Value 89.5% 68.6% – 97.1%
Positive Likelihood Ratio 2.45 1.37 – 4.35
Negative Likelihood Ratio 0.24 0.06 – 0.87
Kappa Value 0.44 0.18 – 0.70
DISCUSSION

The present study determined the accuracy of IOTA Simple Rules and IOTA

ADNEX in discriminating between malignant and benign adnexal masses. The

results showed that both methods were good in ruling out malignancy as seen in

its high sensitivities. The former also exhibited high specificity. For the IOTA

simple rules, the sensitivity and specificity were 100% (95% CI: 51.0% - 100%)

and 81.0% (95% CI: 60.0% - 92.3%), respectively. The probability that a patient

had malignant histopath result given that she is malignant by IOTA simple rules

was 50.0% (95% CI: 21.5% - 78.5%). Moreover, the probability that a patient

had benign histopath result given that she is benign by IOTA simple rules was

100.0% (95% CI: 81.6% - 100%).

In an international cross-sectional cohort study done by Timmerman et al. from

2002 to 2012, the use of IOTA Simple Rules by standardized transvaginal

ultrasound examination in patients with adnexal tumors who were selected for

surgery was compared to histopathologic diagnosis which is the gold standard.

22 oncology centers, referral centers for ultrasonography, and general hospitals

were included in the study and data on 4848 patients were evaluated. The

investigators used the 5 Simple Rules for detecting benign tumor (B-features)

and the 5 features indicative of malignancy (M-features) based on the presence

of ascites, tumor morphology, and degree of vascularity at ultrasonography. The

malignancy rate was 43% (1402/3263) in oncology centers, higher as compared

to 17% (263/ 1585) in other centers. The area under the receiver operating

characteristic curve on validation data was almost the same in oncology centers

(0.917; 95% confidence interval, 0.901e0.931) and other centers (0.916; 95%

16
confidence interval, 0.873e0.945). Sensitivity was 99.7%, specificity 33.7%, LRþ

1.5, LRe 0.010, PPV 44.8%, and NPV 98.9% for the 1% risk cutoff while for the

30% risk cutoff, sensitivity was 89.0%, specificity 84.7%, LRþ 5.8, LRe 0.13, PPV

75.4%, and NPV 93.9%. They concluded that quantification of the risk of

malignancy based on the Simple Rules has good diagnostic performance both in

oncology centers and other centers10.

Table 1 showed the demographic data of patients with ovarian masses where

more than 59.6 % of patients who have ovarian masses are more than 35 years

old. Multigravid patients comprise more than 50% of patients with ovarian

masses. Also, 70.2% of multiparous women and 22.8% of nulliparous women

have ovarian masses, respectively. Other risk factors such as early menarche,

infertility, history of endometrial cancer or breast cancer, or menstrual

irregularities, late age of menopause, high BMI, long term use of hormone

replacement therapy, and genetic mutations 5,6 were not investigated in the

present study since records were only reviewed retrospectively, and did not show

these data.

The IOTA simple rules were validated in a prospective study in 19 ultrasound

centers with 1938 participants. The sensitivity and specificity were high at 92%

(95% CI 89-94%) and 96% (95% CI 94-97%), respectively. The investigators

concluded that preoperative diagnosis of ovarian masses using IOTA simple

rules has the potential to improve management of adnexal masses. Those

masses diagnosed as inconclusive underwent subjective assessment by

experienced ultrasound examiners and were diagnosed accurately with a

sensitivity of 91% (95% CI 88-93%) and specificity of 93% (95% CI 91-94%). In

the same study, the risk of malignancy index, LR1 and LR2 were found to be not

useful in diagnosis of ovarian masses11.

Alcazar et al did a prospective observational study from 2012-2014 in two tertiary

care universities to externally validate the diagnostic performance of a three-step

17
strategy proposed by the IOTA group, namely, use of simple descriptors (step 1),

use of simple rules (step 2), and subjective impression of an expert examiner

(step 3). The overall sensitivity and specificity of the three-step strategy were

high at 94.3% and 94.9%, respectively12.

Garg et al evaluated the efficacy of the IOTA simple rules in their case-control

prospective study from 2014 to 2016. 50 patients were included in the study and

IOTA simple rules were applicable in 45 out of 50 patients (90%). The sensitivity

of IOTA simple rules in this study in detecting malignant masses is 91.66%,

specificity of 84.84%, and accuracy of 86.66%. Conclusion was that IOTA simple

rules is highly sensitive and highly specific in predicting ovarian malignancy 13.

In a retrospective study done by Nowak and Soja et al from 2014-2015, 425

patients with ovarian tumors were evaluated using the IOTA Simple Rules and

compared it to histopathologic diagnosis which is the gold standard. The

investigators concluded that IOTA Simple Rules is highly sensitive in detecting

malignant ovarian masses14.

The main advantage of IOTA simple rules is its simplicity which can be an ideal

tool that can aid less experienced sonographers in discriminating between

malignant and benign adnexal masses. By just using simple tick box system, a

result can be produced rapidly. However, the disadvantage of IOTA simple rules

is that it can yield an inconclusive result. In the present study, inconclusive result

was noted in 4 (13.8%) of the 29 subjects with results in the IOTA simple rules. A

previous study by Timmerman, et al found 25% inconclusive results 10. For these

tumors that cannot be classified by the IOTA simple rules, ultrasound

examination by an expert examiner night be useful. In the present study, there

were 4 false positives noted. These four patients presented with pelvo-abdominal

mass in ultrasound.

Meanwhile, the IOTA adnex model showed a sensitivity and specificity of 84.6%

(95% CI: 57.8% - 95.7%) and 65.4% (95% CI: 46.2% - 80.6%), respectively. The

18
probability that a patient had malignant histopath result given that she is

malignant by IOTA adnex was 55.0% (95% CI: 34.2% - 74.2%). Moreover, the

probability that a patient had benign histopath result given that she is benign by

IOTA adnex was 89.5% (95% CI: 68.6% - 97.1%).

In 2016, a prospective validation study on the diagnostic accuracy of IOTA

Logistic Regression 1 and 2 (LR 1 and LR2) and the IOTA ADNEX model in

assessment of different neoplasias of the adnexa was done at the Philippine

General Hospital. 67 patients were included in the study and the investigators

concluded that IOTA LR1, LR2 and ADNEX model were all useful diagnostic

tools in differentiating benign from malignant adnexal masses obtaining an AUC

of 0.96, 0.88 and 0.96, respectively. For IOTA LR1, LR2, and ADNEX model, the

sensitivity was89% (95% CI 74-100), 61% (95% CI 39-84), 89% (95% CI, 74-

100), respectively while the specificity was 92% (95% CI 84-100), 96%(95%CI

90-100), 76% (95% CI 63-88), respectively15.

In a local retrospective study done in 2017 by Morales and San Juan, the

accuracy of IOTA, Sassone and Lerner scoring were compared to each other

and to histopathologic diagnosis, which is the gold standard. In the said study,

the three had sensitivity of 100% but IOTA had higher specificity at 85% when

compared with Sassone and Lerner, having specificities of 68% and 65%,

respectively16.

In another local study done by Duran-Ranada and Anzures from May 2017 to

March 2018, IOTA Simple Rules and IOTA Adnex Model were used in

assessment of adnexal masses against histopathological diagnosis at Dr. Jose

Fabella Memorial Hospital. 53 women were included in the said study which

obtained 90% sensitivity, 100% specificity, 100% negative predictive value, 100%

positive predictive value using IOTA Simple rules while IOTA Adnex Model

resulted to 96.88% sensitivity, 90.48% specificity, 93.94% positive predictive

value, and 95% negative predictive value17.

19
The IOTA ADNEX Model aside from predicting the stage of malignancy,

differentiates benign from malignant lesions. However, the superiority of this

model remains to be proven. In a combined retrospective and prospective study

by Nohuz from 2011 to 2016, postmenopausal women with ovarian masses were

evaluated using the ADNEX model obtaining sensitivity of 100% and specificity of

98%18.

Chen et al in 2017, made a retrospective study evaluating the diagnostic

accuracy of IOTA Adnex Model in the preoperative diagnosis of adnexal masses

in female patients from a gynecological oncology center in China. The

investigators concluded that the IOTA ADNEX model has good performance in

differentiating benign from malignant adnexal masses with and area under the

curve (AUC) of 0.94 (95% CI, 0.91-0.97) and excellent performance in

distinguishing between a benign ovarian tumor and Stages II-IV Ovarian Cancer

with an AUC of 0.99 (95% CI 0.97-1.00) in a Chinese setting 19.

Given the late detection, poor prognosis, and high mortality of women with

ovarian malignancy, it is of utmost importance to correctly diagnose them

preoperatively for proper management and improved survival rate. And in the

present study, it was shown that preoperative ultrasound examination is good in

discriminating malignant and benign adnexal masses. However, other ancillary

procedures are also recommended for further screening, like tumor markers, and

referral to gynecologic oncologist may be beneficial.

Although the research has reached its objectives, there are some limitations of

the study. One limitation is that, it was conducted only in one institution,

Valenzuela Medical Center. As such, the results can only be generalized to

women who consulted at Valenzuela Medical Center. Another limitation is the

retrospective nature of the study which simply relied on available records.

Therefore, the quality of data collected may be threatened. Still another limitation

was that the scoring system uses ultrasound variables that are subjective like the

20
evaluation of the regularity of solid tumors. The element of subjectivity may

account for the misclassification. However, the strength of this study is that all

ultrasound findings either by IOTA simple rules or IOTA adnex model were

verified by histopath which is considered the gold standard. Hence, verification

bias was addressed in this study.

CONCLUSION

The results of the study show that both IOTA simple rules and IOTA adnex model

were comparable with the histopath result in diagnosing benign and malignant

adnexal masses. IOTA simple rules showed a sensitivity and specificity of 100%

(95% CI: 51.0% - 100%) and 81.0% (95% CI: 60.0% - 92.3%), respectively. The

positive and negative predictive values were 50.0% (95% CI: 21.5% - 78.5%) and

100.0% (95% CI: 81.6% - 100%) respectively. The IOTA adnex model showed a

sensitivity and specificity of 84.6% (95% CI: 57.8% - 95.7%) and 65.4% (95% CI:

46.2% - 80.6%), respectively and positive and negative predictive values of

55.0% (95% CI: 34.2% - 74.2%) and 89.5% (95% CI: 68.6% - 97.1%)

respectively. Thus, these two methods can be used in differentiating between

malignant and benign adnexal masses.

RECOMMENDATION

Since the results of the study showed that both IOTA simple rules and IOTA

adnex model were comparable with the histopath result in diagnosing benign and

malignant adnexal masses, a multicenter study can be done to further evaluate

and validate the results of the present study. Other ancillary procedures are also

recommended for further screening, like tumor markers, and referral to

gynecologic oncologist may be beneficial.

21
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