Nguyen-Xuan Ht

How to predict para-aortic node involvement in advanced cervical cancer? Development of a predictive score. A FRANCOGYN study

Keywords: advanced cervical cancer, predictive model, para-aortic lymph node

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Node involvement is one of the main prognostic factor for cervical cancer, along with histological tumor size, depth of stromal invasion and presence of emboli [START_REF] Bhatla | Cancer of the cervix uteri[END_REF].

Para-aortic lymph node (PALN) assessment is essential in treating advanced cervical cancer. Patients with positive lymph nodes can benefit from an extended-field radiation on the PALN [START_REF] Marth | Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[END_REF][START_REF] Meng | Evaluation of the efficacy of prophylactic extended field irradiation in the concomitant chemoradiotherapy treatment of locally advanced cervical cancer, stage IIIB in the 2018 FIGO classification[END_REF] and it is of paramount importance to select patients who would most benefit from aortic irradiation. However, systematic irradiation of these nodes is associated with a significant increase in morbidity, with a risk of grade 3 and 4 toxicity according to Common Terminology Criteria For Adverse Events (CTCAE) classification of 15% (especially digestive toxicity) [START_REF] Frumovitz | Lymphadenectomy in locally advanced cervical cancer study (LiLACS): Phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA cervical cancer[END_REF]. Two options, still debated, can be used for PALN assessment: surgical para-aortic lymphadenectomy, or the use of positron emission tomography-coupled computed tomography (PET-CT) imaging. However, these two techniques have several limitations. The main risk of PET-CT is its low sensitivity, estimated around 33% according to a multicentric study [START_REF] Leblanc | Accuracy of 18-fluoro-2-deoxy-D-glucose positron emission tomography in the pretherapeutic detection of occult paraaortic node involvement in patients with a locally advanced cervical carcinoma[END_REF]. Due to the high risk of false negative, patients with a negative PET-CT should undergo a surgical para-aortic node staging. Current recommendations state that patients should undergo a PET-CT. In case of a PALN involvement, patients benefit from an extended field radiotherapy. In case of a negative PET-CT, patients should undergo a surgical paraaortic staging lymphadenectomy [START_REF] Marth | Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[END_REF][START_REF] Cibula | The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients With Cervical Cancer[END_REF]. Surgical node staging is not devoid of risk and is associated with a high per-operative and post-operative morbidity [START_REF] Smits | Pretreatment retroperitoneal para-aortic lymph node staging in advanced cervical cancer: a review[END_REF]. Moreover, the benefit of removal of metastatic PALN on overall survival and recurrence-free survival has not been clearly demonstrated [START_REF] Delpech | Lymph node surgical staging for locally advanced cervical cancer[END_REF].

The current trend in the management of gynecological cancers is towards therapeutic de-escalation. The use of predictive models could be useful in predicting invasion of PALN, avoiding staging surgery in low-risk patients and helping in the decision-making process of extended irradiation.

The objective of this study was to develop a score predicting PALN involvement in patients with advanced cervical cancer.

Patients and method

Population

We conducted a multicenter, retrospective study in 9 French centers (FRANCOGYN

Definitions

Patients were considered node-positive (N+) if the PET-CT was positive for the paraaortic area and/or had positive PALN at surgical staging. Suspected positive pelvic node on PET-CT were not considered as positive on PALN. Node-negative patients (N-) were defined as patients with negative nodes at surgical staging after PET-CT negative. Patients were considered to have an advanced cervical cancer if they had a stage Ib2 to IV 2009 FIGO cervical cancer. The 2009 classification was used since it does not depend on the node status.

Statistical analysis

Development of the model: Factors associated with a risk of para-aortic node involvement were determined by univariate analysis.

A student-t test and chi 2 test were used to compare the continuous and categorical values, respectively. Continuous variables were transformed into categorical variables according to the optimal threshold on the ROC curve.

Multivariate analysis was carried out using a logistic regression model, including significant variables upon univariate analysis to select the best combination of predictors. A ρ-value less than or equal to 0.05 was considered significant. A score was developed from the odds ratio (OR) of the logistic regression model. A stepwise selection method was used to select the best combination of predictors. Missing data were considered as negative. In the final model, only factors with a significant ρ-value (ρ ≤ 0.05) were selected.

Accuracy of the model: The performance of the model was tested by its discrimination and calibration [START_REF] Harrell | Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors[END_REF][START_REF] Steyerberg | Prognostic modelling with logistic regression analysis: a comparison of selection and estimation methods in small data sets[END_REF]. The discrimination was assessed using the area under the curve (AUC) of the receiver operating curve (ROC) [START_REF] Hanley | The meaning and use of the area under a receiver operating characteristic (ROC) curve[END_REF]. Calibration was studied using a graphical plot which showed the difference between the predicted outcome and the actual outcome. The mean and maximal error was calculated. The performance of the model was evaluated by its AUC. Sensitivity, specificity, negative and positive likelihood ratios were also assessed.

Validation of the model: An internal validation was performed with 1000 bootstrap resamples to obtain relatively unbiased estimates. The bootstrapping method provides an estimate of the average optimism of the AUC-ROC [START_REF] Harrell | Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors[END_REF].

All statistical analyses were carried out using an Excel database and Rstudio version 1.1.447.

Results

General results

Between 2000 and 2015, 1446 patients treated for cervical cancer were included. Of these, 498 had an advanced squamous cell cervical cancer (i.e. with a FIGO 2009 stage greater than or equal to IB2) (Figure 1). Ninety-one patients had positive PALN (18.3 %): 51 had positive nodes on PET-CT and 43 on definitive histology.

Patient characteristics

Patient characteristics are summarized in Table 1. The mean age of patients at diagnosis was 53 (± 14) and 54 (± 14) years old for N+ and N-patients, respectively. Of the 498 patients included in the study, 267 (53.6%) had not had a pap-smear test within 3 years and 11% (n=55) had a normal pap-smear less than 3 years before the cancer.

Two hundred and eighty-nine patients had both a lymphadenectomy and a PET-CT, 126 had only a PET-CT and 83 had only a lymphadenectomy.

Pre-operative assessment and surgical staging (Table 1)

The mean tumor size on pelvic MRI was 59.5 mm (± 25.5) in N+ versus 48.4 mm (±15.8) in N-patients and was significantly different (ρ<0.001). Suspicious pelvic lymph nodes on pelvic MRI were present in 42.6% (n=212) of the patients, of whom 29.7% (63/212) were N+.

The squamous cell carcinoma (SCC) tumor marker had a median value of 15.2 μg/L (range: 0 -317 μg/L) in N+ and 4.9 µg/L (range: 0 -153 µg/L) in N-patients (ρ = 0.02). After analyzing the ROC curve, the optimal threshold for differentiating positive and negative PALN for the SCC tumor marker was 8µ/L. PET-CT was performed in 90.1% (n=82) of N+ patients and 81.6% (n=332) of Npatients. Of the 91 patients with positive para-aortic nodes, 34% (31/91) had positive lymph node staging with negative PET-CT. Positive pelvic lymph nodes (PLN) on PET-CT was present in 54.9% (n=50) of N+ patients and 26.3% (n=107) of N-patients (ρ<0.001). The mean standard uptake value (SUV max) at the cervix was 12.78 (range: 0 -42.9).

Primary PALN staging was performed in 300 patients (60%) and was positive in 43 cases.

Predictive factors of para para-aortic lymph node involvement (Table 2)

After univariate analysis, the predictive factors for PALN involvement were tumor size greater than 60mm (OR 2.69, 95%CI [1.60 -4.52]), SCC marker > 8µ/L (OR 4.6, 95%CI [2.14 -9.90]), positive PLN on PET-CT (OR 3.27, 95%CI [1.98 -5.39]) and body mass index (BMI) > 25 kg/m² (OR 0.5, 95%CI [0.29 -0.84], ρ<0.01). Patients with a retroperitoneal lymphadenectomy had a statistically significant lower BMI (mean 24.6kg/m2) than patients without (mean 25.7kg/m2) (p=0.04).

In multivariate analysis, factors associated with node involvement were: tumor size greater than 60 mm (aOR=5.27 (95%IC = 1.96 -14.16)), SCC marker > 8µ/L (aOR=2.55 (95%IC = 0.97 -6.73)) and positive PLN on PET-CT (aOR=2.91 (95%IC = 1.07 -7.90)).

Development of the score (Figure 2)

All variables significant on multivariate analysis were included in our model. Points assigned to each criterion corresponded to the round of their respective odds ratios. Five points were given if the tumor size was greater than 6 cm on pelvic MRI, 3 points were given if PLN involvement was suspected on PET-CT, and 2 points were given if the SCC rate was greater than 8 µg/L. Thus, the model had a total of 10 points. This model allowed the population to be divided into 3 risk groups. Patient with a score inferior to 3 were considered at low risk with a 9% probability of PALN involvement with a sensitivity of 69% (95% CI = 0.58 -0.78) and a negative predictive value of 90% (95% CI = 0.87 -0.93). A score between 3 and 5 placed the patients in an intermediate risk population with a 26% probability of PALN involvement. Patients with a score greater than 5 were considered at high risk with a 43% probability of PALN involvement with a high specificity 0.92 (95%CI = 0.89 -0.94).

Performance of this score, determined by the area under the ROC curve (AUC), was 0.81 (95% CI= 0.72 -0.90). After 1000 bootstrap validation, the AUC was 0.80 (95%IC = 0.71-0.89). This suggests that the model is robust and well discriminating in this population.

The calibration curve showed no significant difference (ρ=0.93) between the predicted probabilities and the observed proportions with a mean error of 0.007 and a maximum error of 0.016.

Discussion

This study presents a simple score that can be used in clinical practice to predict PALN invasion in locally advanced cervical cancer (LACC). We included variables that are part of the routine extension assessment of advanced cervical cancer, such as tumor size, positive PLN on PET-CT and high SCC rate, into our score. A low risk group of patients (score < 3) with a predicted probability of para-aortic lymph node involvement of 9% was then defined. Patients in the high-risk group (score >5) had a predicted probability of 43%.

The benefit of surgical staging in terms of survival is still debated [START_REF] Gouy | Nodal-staging surgery for locally advanced cervical cancer in the era of PET[END_REF][START_REF] Gonzalez-Benitez | Lack of Survival Benefit of Para-Aortic Lymphadenectomy in Advanced Cervical Cancer[END_REF][START_REF] Brockbank | Pre-treatment surgical para-aortic lymph node assessment in locally advanced cervical cancer[END_REF][START_REF] Gold | Surgical versus radiographic determination of para-aortic lymph node metastases before chemoradiation for locally advanced cervical carcinoma: a Gynecologic Oncology Group Study[END_REF]. Indeed, some believe that PALN staging surgery improves the prognosis and in particular the overall survival and recurrence-free survival [START_REF] Leblanc | Therapeutic value of pretherapeutic extraperitoneal laparoscopic staging of locally advanced cervical carcinoma[END_REF]. Others find that the prognosis is deteriorated [START_REF] Lai | Randomized trial of surgical staging (extraperitoneal or laparoscopic) versus clinical staging in locally advanced cervical cancer[END_REF].

This surgical staging may induce intraoperative complications such as vascular, digestive or postoperative wounds and delay concomitant radio-chemotherapy. One review reported a complication rate between 4 and 24% with a predominance of lymphoceles [START_REF] Smits | Pretreatment retroperitoneal para-aortic lymph node staging in advanced cervical cancer: a review[END_REF].

The false-negative (FN) rate of the PET-CT varies between 12 and 17% [START_REF] Gouy | Prospective multicenter study evaluating the survival of patients with locally advanced cervical cancer undergoing laparoscopic para-aortic lymphadenectomy before chemoradiotherapy in the era of positron emission tomography imaging[END_REF][START_REF] De Cuypere | Added value of para-aortic surgical staging compared to 18F-FDG PET/CT on the external beam radiation field for patients with locally advanced cervical cancer: An ONCO-GF study[END_REF]. In our study, the rate of false negatives of PET-CT was 15.3%, concordant with these findings. The PLN on PET-CT is of particular interest. Indeed, Gouy et al suggested that positive PLN on PET-CT, increased the FN rate to 22% whereas, negative pelvic nodes decreased it to 9% [START_REF] Gouy | Nodal-staging surgery for locally advanced cervical cancer in the era of PET[END_REF]. PLN involvement is therefore a determining factor in assessing the risk of para-aortic involvement. Likewise, we found that the false-negative rate of PET-CT for para-aortic evaluation was 22.9% in case of positive pelvic node and 10.9% for negative pelvic node on PET-CT. Importance of PLN involvement in predicting PALN involvement has been previously showed in several studies, concordant with our findings [START_REF] Martinez | Tumour and pelvic lymph node metabolic activity on FDG-PET/CT to stratify patients for para-aortic surgical staging in locally advanced cervical cancer[END_REF]. Nevertheless, this imaging technique is not available in all centers, especially in developing countries, which could limit the wide use of our score.

Regarding the SCC marker, its dosage is not part of the recommendations for initial cervical cancer assessment [START_REF] Marth | Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[END_REF] but can be used in follow-up if it is initially informative. An initial elevation of SCC is frequently associated with advanced stage, large tumor volume, lymph node and lymphovascular involvement [START_REF] Fu | The role of squamous cell carcinoma antigen (SCC Ag) in outcome prediction after concurrent chemoradiotherapy and treatment decisions for patients with cervical cancer[END_REF]. In our study, a SCC rate greater than 8 μg/L was a predictive factor of PALN involvement. This rate may seem high since the rate associated with distant injury or recurrence is generally between 2 and 4 μg/L [START_REF] Choi | Significance of elevated SCC-Ag level on tumor recurrence and patient survival in patients with squamous-cell carcinoma of uterine cervix following definitive chemoradiotherapy: a multi-institutional analysis[END_REF][START_REF] Hong | Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone[END_REF].

However, this threshold presented the most accurate discrimination for differentiating positive and negative PALN.

The final predictive factor of our score was tumor size greater than 6 cm on pelvic MRI. Evaluation by pelvic MRI is part of the standard local-regional spread assessment for locally advanced cervical cancers. The risk of pelvic and PALN involvement increases with tumor size [START_REF] Delpech | Lymph node surgical staging for locally advanced cervical cancer[END_REF][START_REF] Havrilesky | Radical hysterectomy and pelvic lymphadenectomy for stage IB2 cervical cancer[END_REF][START_REF] Berman | Survival and patterns of recurrence in cervical cancer metastatic to periaortic lymph nodes (a Gynecologic Oncology Group study)[END_REF][START_REF] Wang | Nomogram for predicting para-aortic lymph node metastases in patients with cervical cancer[END_REF].

BMI was significant only upon univariate analysis. It must be noted however that this characteristic can be biased. Indeed, patients with a higher BMI were more likely to not undergo a para-aortic lymphadenectomy due to a potentially added morbidity. Patients with a higher BMI could therefore have more negative PALN since they did not benefit from a retroperitoneal lymphadenectomy. However, the BMI remained low in our population (patients with a retro-peritoneal lymphadenectomy mean BMI 24.6 kg/m 2 and patients without, mean BMI 25.7 kg/m 2 ).

In the era of personalized medicine, it is essential to provide a tailored treatment for each patient. Pre-therapeutic identification of an at-risk population is the cornerstone of this personalization. Our score allowed us to classify patients into 3 risk groups. A low risk (9% predicted probability of para-aortic involvement) group, an intermediate risk (26%) and a high-risk group (43%). This score presents a satisfactory discriminatory power (AUC = 0.81 95%CI = 0.71 -0.90) and an excellent calibration. In clinical practice, it could therefore be estimated that patients with a low risk of para-aortic involvement could avoid extended field irradiation to these lymph node areas. The question arises for patients with a high or intermediate risk. It could be argued that high-risk patients could be expected to have extended irradiation to the para-aortic areas. However, this group had a risk of only 43%. This would imply an unjustified risk of irradiation in up to half of the patients and extended field irradiation to para-aortic area is not without risk [START_REF] Frumovitz | Lymphadenectomy in locally advanced cervical cancer study (LiLACS): Phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA cervical cancer[END_REF]. Staging surgery would therefore still have a place for intermediate and high risks. To reduce morbidity, an infra-mesenteric lymphadenectomy could be discussed, as proposed by some [START_REF] Azaïs | Pretherapeutic staging of locally advanced cervical cancer: Inframesenteric paraaortic lymphadenectomy accuracy to detect paraaortic metastases in comparison with infrarenal paraaortic lymphadenectomy[END_REF][START_REF] Petitnicolas | Morbidity of Staging Inframesenteric Paraaortic Lymphadenectomy in Locally Advanced Cervical Cancer Compared With Infrarenal Lymphadenectomy[END_REF] and European Guidelines [START_REF] Marth | Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[END_REF]. Ideally, our score would have been able to indicate surgical staging only to patients with an intermediate risk and to perform prophylactic irradiation of the para-aortic areas in case of high risk.

Several predicting models have been previously developed. Wang et al developed a nomogram to predict PALN involvement. However, all stages of cervical cancer were included. PALN was only assessed by imaging (TEP-CT or CT) [START_REF] Wang | Nomogram for predicting para-aortic lymph node metastases in patients with cervical cancer[END_REF]. As previously stated, assessment of node involvement by imaging is far from perfect. A Korean team developed a score based on tumor size and PALN involvement on PET-CT with patient who underwent para-aortic lymphadenectomy in LACC [START_REF] Shim | Prediction model for paraaortic lymph node metastasis in patients with locally advanced cervical cancer[END_REF]. Likewise, the main limitation of this study is that patients with LACC did not undergo surgical staging. These two studies may have underestimated the FIGO stage and may have included patients with an initially advanced cervical cancer. Our study included patients assessed by imaging and/or surgery.

Limitations of our study include its retrospective design and the absence of an external validation of the score. Despite our large population size, the small number of events (91 positive para-aortic nodes) rendered it impossible to divide the population into a training and validation set. Moreover, the high number of missing information on PALN involvement could have biased our results. As discussed above, the predictive SCC threshold used in our score is very high compared to the literature. A systematic SCC dosage in the initial assessment could help to refine this threshold. Furthermore, the score was developed only in patients with squamous cell carcinoma of the cervix because of the small proportion of other histological types. Therefore, the score results cannot be extrapolated to these patients. Our score cannot be used in daily clinical practice in its current form due to the absence of an external validation. However, it can be used in complex situations to help weigh the decision.

As this score is based on imaging data, the addition of more efficient imaging to determine lymph node involvement could be of interest such as pelvic MRI with diffusionweight imaging (DWI-RMI) [START_REF] Choi | Node-by-node correlation between MR and PET/CT in patients with uterine cervical cancer: diffusion-weighted imaging versus size-based criteria on T2WI[END_REF][START_REF] Liu | A Comprehensive Comparison of CT, MRI, Positron Emission Tomography or Positron Emission Tomography/CT, and Diffusion Weighted Imaging-MRI for Detecting the Lymph Nodes Metastases in Patients with Cervical Cancer: A Meta-Analysis Based on 67 Studies[END_REF][START_REF] Perucho | Diffusionweighted magnetic resonance imaging of primary cervical cancer in the detection of subcentimetre metastatic lymph nodes[END_REF][START_REF] Lin | Detection of lymph node metastasis in cervical and uterine cancers by diffusion-weighted magnetic resonance imaging at 3T[END_REF][START_REF] Whittaker | Diffusion-weighted MR imaging of female pelvic tumors: a pictorial review[END_REF]. Likewise, the use of the SUVmax at the tumor and PLN seems promising [START_REF] Martinez | Tumour and pelvic lymph node metabolic activity on FDG-PET/CT to stratify patients for para-aortic surgical staging in locally advanced cervical cancer[END_REF][START_REF] Onal | Prognostic value of 18F-fluorodeoxyglucose uptake in pelvic lymph nodes in patients with cervical cancer treated with definitive chemoradiotherapy[END_REF].

Conclusion

We developed a simple score predicting PALN involvement in advanced cervical For patients with a low risk score (<3), the predicted probability of positive para-aortic node was 9.0% (IC95%=0.06-0.14). This threshold had a sensibility of 0.69 (IC95%=0.58-0.78) and a negative predictive value of 0.90 (IC95%=0.87-0.93).

Patients with a score > 5 were considered high-risk and had a positive likelihood ratio of 3.13 (IC95%=1.88-5.21) with a high specificity 0.92 (IC95%=0.89-0.94). A. Abbreviations: SCC = squamous cell carcinoma, MRI = magnetic resonance imaging, PET = positron emission tomography, 95%CI = 95% confidence interval

B

  group) from 2000 to 2015 (Creteil University Hospital, Tenon University Hospital, Poissy University Hospital, Reims University Hospital, Lille University Hospital, Tours University Hospital, Bondy University Hospital, Rennes University Hospital, and Marseille Public Hospital North). Adult patients with advanced squamous cell carcinoma of the cervix (International federation of gynecology and obstetrics, FIGO 2009 Ib2 to IV stage), who had PALN status evaluated by imaging and/or by surgery staging between 2000 and 2015 were included. Patients with other histologic type, localized cervical cancer or without information on PALN involvement were excluded. The research protocol was approved by the Institutional Review Board (IRB) of the French College of Obstetrics and Gynaecology (CEROG 2020-GYN-0601).

  cancers. Patients can be classified into 3 risk groups depending on their probability of lymph node invasion. Patients considered to be at low risk may avoid para-aortic staging as well as extensive field irradiation to these lymph nodes. This score is simple to use because the factors are part of the standard extension assessment of this pathology: tumor size on pelvic MRI, pelvic lymph node involvement on PET-CT and finally the SCC dosage. A prospective study and external validation are needed to confirm the performance and clinical value of such a model.

Figure 1 .

 1 Figure 1. Flow chart

Figure 3 :

 3 Figure 3: Discrimination and validation of the model predicting the invasion of para-aortic lymph nodes in patients presenting an advanced squamous cervical cancer A. ROC curve of the model. The predictive model had a AUC of 0,81 (95% CI 0.71-0.90) B. Calibration of the model. The horizontal axis represents the predicted probability of para-aortic lymph node invasion and the vertical axis represents the actual probability. Perfect prediction would correspond to the 45-degree broken line. The dotted and solid lines indicate the observe (apparent) nomogram performance before and after bootstrapping.

Table 1 .

 1 Population characteristicsAbbreviations: SD= standard deviation, BMI= body mass index, SCC = squamous cell carcinoma, MRI = magnetic resonance imaging, PET = positron emission tomography, PAL= para-aortic lymph nodes

	Characteristics	Positive PAL	Negative PAL	p
			N=91 (18.3%)	N=407 (81.7%)
		Mean (+/-SD)	53 +/-14	54 +/-14
	Age	Range	26-94	23-96	0.31
	Menopause	47 (51.65)	230 (56.51)	0.42
	BMI	Mean (+/-SD) Range	23.75 +/-5.21 15-36	25.35 +/-5.81 12-46	0.02
	Previous pregnancies	72 (79.12)	342 (84.02)	0.35
		1	16 (17.58)	63 (15.48)
	Grade	3 2	24 (26.37) 24 (26.37)	113 (27.76) 114 (28.01)	0.64
		NA	27 (29.68)	117 (28.75)
	Lympho-	Invasion	12 (13.18)	27 (6.63)	0.09
	vascular
	invasion
	Positive pelvic nodes on PET	50 (54.94)	107 (26.29)	<0.001
	scanner
	SCC	Mean (+/-SD) Range	38.77 +/-64.98 0-317	13.29 +/-23.04 0-153	0.02
		IB2	5 (5.49)	47 (11.55)
		IIA	1 (1.1)	9 (2.21)
		IIA1	0 (0)	9 (2.21)
	2009 FIGO stage	IIIA IIB IIA2	2 (2.2) 47 (51.65) 2 (2.2)	3 (0.74) 241 (59.21) 9 (2.21)	0.04
		IIIB	9 (9.89)	22 (5.41)
		IVA	18 (19.78)	59 (14.50)
		IVB	7 (7.6)	8 (1.96)
	MRI tumor size	Mean (+/-SD)	59.52 +/-25.52	48.40 +/-15.84	<0.001
	(mm)	Range	29-220	0-110

Table 2 .

 2 Multivariate analysis of factors associated with positive para-aortic lymph nodes in patients with advanced squamous cervical cancer.

	Variables		Multivariate analysis
			Adjusted	95% CI
			Odds ratio
	Tumor size on	4.93	2.59-10.72
	MRI (≤60 mm
	versus > 60 mm)
	SCC (≤8 versus	3.18	1.29-7.79
	>8)
	Positive	pelvic	2.45	1-6.01
	nodes on TEP

Conflict of interest

The authors declare that they have no conflicts of interest that might be relevant to the contents of this article.

Author contribution

Wrote