A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses

Anton C conceived the study, collected the data, participated in the samples analysis, drafted the manuscript and performed the statistical analysis. Carvalho FM conceived the study and participated in its design, coordination and blueprint. Oliveira EI participated in the samples psychoanalysis and rendition. Maciel GA participated in the sample distribution analysis. Baracat EC reviewed the manuscript. Carvalho JP conceived the study and participated in its design, coordination and enlist. All authors have read and approved the concluding manuscript. There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method acting. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential gear diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy electric potential were considered low-risk, which may be used as an acceptable assessment method acting for referring patients to reference centers. The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4 %, 79.6 %, 74.1 %, and 63 %, respectively. Among carcinoma, the sensitivities of CA125, HE4, ROMA ( pre- and post-menopausal ), and RMI were 93.5 %, 87.1 %, 80 %, 95.2 %, and 87.1 %, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent. Patients who had been diagnosed with ovarian masses through image analyses ( north = 128 ) were assessed for their formula of the tumor markers CA125 and HE4. The ROMA and RMI values were besides determined. The sensitivity and specificity of each argument were calculated using telephone receiver operating characteristic curves according to the area under the curl ( AUC ) for each method acting.

Reading: A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses

Over 90 % of all ovarian masses detected in pre-menopausal women and improving to 60 % of masses found in post-menopausal women are benign ( 3 ). frankincense, it is crucial to assess risk for women who present with pelvic masses, as this process should optimize health policies without overburdening reference point centers. presently, the tumor markers CA125 and human epididymis protein 4 ( HE4 ) deoxyadenosine monophosphate well as the risk ovarian malignancy algorithm ( ROMA ) and risk malignancy index ( RMI ) values are used as tools for differentiating between low- and bad patients with ovarian cancer. In more than 85 % of advanced-stage ovarian carcinoma cases, the levels of CA125 have been found to be elevated above the cutoff respect for bad patients ( > 35 U/ml ). In contrast, the levels of CA125 are elevated in merely 50 % of early-stage ovarian carcinoma cases ( 4 ). furthermore, in post-menopausal women, CA125 values greater than 95 U/ml are associated with a cocksure predictive value of 95 % ( 5 ). HE4 is a recently discovered tumor marker that has been shown to have a sensitivity of 72.9 % and a specificity of 95 % for differentiating between types of ovarian masses, and these values are higher than those related to the habit of CA125 ( 6 ). In 2009, Moore et alabama. ( 7 ) proposed that the ROMA value, which takes into account the levels of CA125 and HE4 together with menopausal status, could be used to evaluate ovarian masses using merely quantitative and objective parameters. The use of this algorithm in cohorts of pre- and post-menopausal women resulted in a sensitivity of 88.7 % and a specificity of 74.7 % ( 7 ). Almost 20 years anterior to the development of the ROMA, Jacobs et alabama. ( 8 ) created the RMI, which takes into account the CA125 value, menopausal condition, and sonography parameters. RMI values greater than 200 were shown to be associated with a higher risk of malignancy and demonstrated a sensitivity of 85.4 % and a specificity of 96.9 % ( 8 ). ovarian cancer is the seventh most common cancer in women and is not diagnosed before reaching an advance stage in approximately 70 % of all cases. As a consequence, the 5-year survival rate associated with ovarian cancer is less than 30 % ( 1, 2 ). consequently, both surgical staging and the performance of optimum cytoreduction procedures in address centers may have a substantial impact on patient survival. The sensitivity and specificity for CA125, HE4, ROMA, and RMI were calculated. The ROC curves and area under the crook ( AUC ) values were calculated to compare the accuracy of each method for predicting malignant ovarian masses. The statistical analyses were performed using MedCalc v11.1.1.0 ( MedCalc Software, Mariakerke, Belgium ) ( 10 ). For all of the statistical comparisons, a level of phosphorus < 0.05 was accepted as statistically significant. The cutoff values for CA125 and HE4 were 35 U/ml ( as recommended by the manufacturer ) and 70 autopsy [ as used by Moore, et alabama. ( 9 ) ], respectively. These cutoff values were the lapp as those used for the establishment of the ROMA ( 7 ). The ROMA cutoff values for bad patients were ≥13.1 % and ≥27.7 % for pre-menopausal and post-menopausal women, respectively, as suggested by Moore et alabama. ( 7 ). The shortcut RMI measure for differentiating between benign versus malignant masses was 200, as proposed by Jacobs et aluminum. ( 8 ) We determined the optimum cutoff value for the CA125 and HE4 tumor markers a well as the ROMA and RMI by analyzing the point of greatest accuracy in the recipient operating characteristic ( ROC ) curves. where U = 0 for an ultrasound score of 0, U = 1 for an ultrasound score of 1, and U = 3 for an ultrasound mark of 2-5 and M = 1 for pre-menopausal women and M = 3 for post-menopausal women. If the affected role undergo CT or MR anterior to ultrasound, the parameters for the sonographic evaluations were identical to those described by Jacobs et alabama. ( 8 ) and Moore et alabama. ( 9 ). Although the RMI parameters had been validated with ultrasound parameters, we used the lapp ultrasound parameters for CT and RM as those used by Moore et aluminum. ( 9 ). On the day of operating room or imaging-guided biopsy, two lineage samples ( 3-5 ml each ) were collected before the routine. One sample was analyzed for the CA125 floor using a Cobas® 4000 analyzer series and the 411 module for immunoassays ( Roche®, USA ). The second sample was centrifuged and stored at -80°C, and the flat of HE4 was subsequently determined using an HE4 enzyme immunoassay ( EIA ) ( Fujirebio Diagnostics Inc., Goteborg, Sweden ). A total of 128 patients between the ages of 15 and 90 years were referred to our hospital with pelvic masses, which were thought to be of ovarian origin as diagnosed by sonography, computed imaging ( CT ), or magnetic resonance ( MR ). The women included in the report undergo surgery or imaging-guided biopsy when they presented signs of carcinomatosis. The levels of CA125 and HE4 were measured, and the ROMA and RMI scores were calculated as previously described ( 7, 8 ). The pre-menopausal patients were evaluated outside of the menstrual period. We considered post-menopausal patients to be those over 50 years of age or those over 40 years of age who had not experienced menses for at least one class. The exception criteria included pregnancy, peritoneal dialysis, any previously diagnosed disease normally associated with an increase in CA 125 ( such as mesothelioma ), and non-ovarian tumors. This was a prospective learn conducted at the Department of Obstetrics and Gynecology of the Universidade de São Paulo and the Instituto do Câncer do Estado de São Paulo ( São Paulo, Brazil ) between June 2008 and January 2011. The sketch was approved by the Ethical Committee for Research Projects of the Hospital district attorney Clínicas district attorney Faculdade de Medicina da Universidade de São Paulo ( CAPPesq ) ( protocol 1067/08 ), and all of the patients provided inform consent. Twelve ( 92.3 % ) of the 13 patients diagnosed with endometrioma had elevated values of CA125, and alone three ( 23.1 % ) had increased HE4 values. The ROC curves for CA125, HE4, ROMA, and RMI were calculated to compare the accuracy of the four methods. The greatest united self-defense force of colombia was associated with the RMI values ( 0.861 ), as compared to the ROC values for the ROMA ( 0.824 ), HE4 ( 0.777 ), and CA125 ( 0.802 ). The ROC curves were compared using a pairwise comparison method acting ( 10 ), and no differences were detected between the four methods. In summation, no differences were observed in the ROC curves of CA125 and HE4 as compared to the ROMA and RMI. however, differences were observed between the HE4 and ROMA values ( p = 0.03 ) in the overall assessment ( ) and among post-menopausal women ( p = 0.05 ).

When the LMP tumors were classified as low-risk, the sensitivities for CA125, HE4, ROMA, and RMI increased to 83.8 %, 86.5 %, 83.8 %, and 75.7 %, respectively. In accession, the sensitivities associated with the discrimination between primary coil carcinoma of the ovary for CA125, HE4, ROMA, and RMI were 93.5 %, 87.1 %, 95.2 %, and 87.1 %, respectively. provides the sensitivity and specificity values established for CA125, HE4, ROMA, and RMI in both pre-and post-menopausal women. The optimum shortcut values for these data were besides calculated. The characteristics of the study population, including long time, menopausal status, and the mean and median levels of CA125 and HE4 a well as the RMI and ROMA values, are shown in. The tumors in this cohort were classified into two groups consisting of those with a low- or bad for ovarian malignity. The low-risk tumors included teratoma ( n = 16 ), endometriomas ( normality = 13 ), fibromas ( nitrogen = 4 ), mucinous cystadenomas ( newton = 11 ), serous cystadenomas ( north = 14 ), Brenner tumors ( newton = 2 ), and bare cysts ( newton = 6 ). The bad tumors included low-malignant-potential ( LMP ) serous ( north = 6 ) and mucinous ( north = 11 ) tumors, serous carcinoma ( n = 16 ), endometrioid adenocarcinoma ( normality = 3 ), mucinous adenocarcinoma ( newton = 3 ), carcinosarcoma ( newton = 1 ), metastatic adenocarcinoma of the breast ( newton = 1 ), metastatic adenocarcinoma of the gastrointestinal tract ( normality = 5 ), metastatic adenocarcinoma of the colon ( n = 1 ), clear cell carcinoma ( n = 1 ), granulosa cell tumor ( n = 4 ), Leydig cell tumor ( north = 1 ), and steroid cell tumor ( n = 1 ). The sensitivities associated with CA125, HE4, ROMA, and RMI for this age group of cases were 70.4 %, 79.6 %, 74.1 %, and 63 %, respectively. Eight patients were excluded from this report for the follow reasons : technical foul problems were encountered with the samples from five patients, one affected role had a subserosal leiomyoma rather of an ovarian aggregate, one patient was being treated with peritoneal dialysis, and one patient had been diagnosed with mesothelioma .

DISCUSSION

Our results indicate that the tumor markers CA125 and HE4 angstrom well as ROMA and RMI values are useful methods for differentiating ovarian masses according to whether they are associated with a high or low risk for developing into ovarian cancer, and this type of assessment which will ultimately optimize the referral of patients to reference centers. We intentionally modified the above methods to perform an analysis using the available tools in act practice. For the ROMA, we used the CA125 kit from Roche® even though this algorithm had been validated using the Fujiribios CA125 kit, as we routinely use the Roche® kit for our services. Although we wanted to ensure that the stream study provided an accurate representation of the tools available at our hospital, we applied the same numeric cutoff values proposed by Moore et aluminum. ( 7 ). furthermore, we believe that the small deviations observed in the analysis presented here did not compromise the overall findings of the analyze. The RMI method acting in the first place described by Jacobs et aluminum. ( 8 ) used ultrasound judgment as the sole imagination parameter, although we included both CT and MRI in our study ( as did Moore et alabama. ) ( 9 ). It would be expected that this modification would improve the results for the RMI than those presented by Jacobs et al., as CT and MR technologies can more accurately buttocks adnexal tumors. however, our study found that this modification did not provide more accurate results. In the study by Jacobs et aluminum. ( 8 ), the sensitivity and specificity reached 85.4 % and 96.9 %, respectively, using a shortcut respect of 200. In the present study, the sensitivity and specificity values associated with the RMI were 66.7 % and 87.9 %, respectively, which are lower than those demonstrated by Jacobs et aluminum. ( 8 ). One likely explanation for these unlike results may have been the greater heterogeneity of histological types observed in our analyze. however, the samples we analyzed demonstrated a profile identical similar to that observed in clinical practice. To evaluate the accuracy of the four ovarian cancer risk stratification methods, an AUC was calculated for each ROC. We calculated ROC values of 80.2 % and 77.7 % for CA125 and HE4, respectively, and found no statistical remainder between these values ( p = 0.67 ). In contrast, an evaluation of the lapp tumor markers by Moore et aluminum . ( 9 ) found ROC values of 83.6 % and 90.8 %, respectively, and no statistically significant differences were observed for these ROMA and RMI curves either ( p = 0.50 ). however, the study by Moore et aluminum . ( 9 ) reported the AUCs for the ROMA and RMI to be 91.3 % and 84.4 %, as compared to the values of 82.4 % and 85.5 % obtained in our cogitation, respectively. These differences may besides be explained by the more heterogeneous quality of the tumors evaluated in our study. In the current study, the optimum cutoff values associated with the ROMA were 13.97 % and 39.68 % for pre- and post-menopausal women, respectively. The pre-menopausal ROMA cutoff value in our cogitation was similar that reported by Moore et alabama . ( 9 ), whereas the post-menopausal value was higher ( 13.1 % and 27.7 %, respectively ). The shortcut values reported by Van Gorp et aluminum . ( 11 ) were 16.6 % and 35.9 % for pre- and post-menopausal women, respectively, which were besides like to those identified in our study. The authors of this former cogitation besides found an overall shortcut prize for the post-menopausal ROMA of 22.2 %, which was similar to the measure of 23.3 % identified in our sketch. The use of unlike CA125 kits may have resulted in these differences, and the inclusion of CT and MRI methods may explain the higher shortcut RMI value obtained in the stream study as compared to the study by Jacobs et alabama . ( 8 ) ( 275.7 vs. 200, respectively ). One major problem associated with the pre-operative evaluation of pelvic masses concerns the recognition of LMP tumors and the diagnosis of endometriosis. We found that the four methods of risk evaluation demonstrated better performance when LMP tumors were classified as low-risk tumors. The sensitivity value for CA125 detection was 83.8 % with a specificity of 71.1 %, whereas these values were 70.4 % and 74.2 %, respectively, when the tumors were classified as bad. In addition, HE4 sensitivity increased from 79.65 to 86.5 %, ROMA sensitivity increased from 74.1 % to 83.8 %, and RMI sensitivity increased from 63 % to 75.7 % when these tumors were classified as low-risk. Although the classification of LMP tumors remains controversial, clinical and biological evidence suggests that these tumors can be classified as low-risk. LMP tumors are associated with a good prognosis, and 5-year survival rates are approximately 98 % for stage I tumors and 90 % for stage III tumors with non-invasive implants ( 12 ). In accession, BRAF and KRAS mutations characterize the low-grade nerve pathway of ovarian carcinogenesis, and borderline tumors are identified as harbinger lesions of this nerve pathway ( 13 ). Although it is outside the setting of the current sketch to discuss the nature and treatment options for LMP tumors, these types of tumors represent an crucial differential gear diagnosis for pelvic masses. In our cohort, these tumors were found in 17 ( 14.2 % ) cases, which mirrors the frequency of these tumors observed in common clinical rehearse. Because these tumors are low-grade and in most cases do not require surgical biopsy as a first-line approach, their inclusion in the low-risk category appears to be satisfactory. therefore, patients receiving care from non-specialized centers may besides be referred to reference centers for appropriate staging without compromising their prognosis ( 12 ). furthermore, if LMP tumors are classified as low-risk, the load related to an inflow of lower-risk patients at specialize centers may be reduced.