Journal of Pediatric Surgery (2011) 46, 11821185

www.elsevier.com/locate/jpedsurg

Tumor volume to fetal weight ratio as an early prognostic classification for fetal sacrococcygeal teratoma
Manuel A. Rodriguez a , Darrell L. Cass a,b , David A. Lazar a,b , Christopher I. Cassady b , Kenneth J. Moise b , Anthony Johnson b , Oren P. Mushin a , Saif F. Hassan a , Bella Belleza-Bascon b , Oluyinka O. Olutoye a,b,
a

Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA b Texas Children's Fetal Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA
Received 15 March 2011; accepted 26 March 2011

Key words:
Sacrococcygeal teratoma; SCT; Fetal surgery; Tumor volume to fetal weight ratio; TFR; Outcome

Abstract Purpose: This study was designed to develop a prognostic factor for fetuses with sacrococcygeal teratoma (SCT) that may be useful to predict outcome and guide counseling early in pregnancy. We hypothesize that, in fetuses with SCT, the ratio of tumor size to estimated fetal weight in the second trimester predicts outcome. Methods: We retrospectively reviewed charts of all patients evaluated at our Fetal Center for SCT between 2004 and 2009. Estimated fetal weight and tumor volume were calculated based on prenatal ultrasound or fetal magnetic resonance imaging. Patients were stratified based on tumor volume to fetal weight ratio (TFR), and their outcomes were analyzed by Fisher's Exact test. Results: Tumor volume to fetal weight ratio before 24 weeks' gestation was predictive of outcome. Those with a TFR less than or equal to 0.12 (n = 5) had a significantly better outcome than patients with a TFR greater than 0.12 (n = 5, P b .05). All patients with poor outcomes had a TFR greater than 0.12 by 24 weeks' gestation. A TFR greater than 0.12 predicted poor outcome with 100% sensitivity and 83% specificity. All 4 patients who developed hydrops had a TFR greater than 0.12. Conclusion: In our series of fetuses with SCT, TFR before 24 weeks' gestation correlates with outcome. This novel, prenatal diagnostic tool may be useful in prenatal counseling and for early identification of high-risk fetuses. 2011 Elsevier Inc. All rights reserved.

Sacrococcygeal teratoma (SCT) is the most common congenital tumor in newborns, with a reported incidence of 1 in 27,000 to 40,000 births [1,2]. The outcome of fetuses with
Corresponding author. Texas Children's Hospital, 6701 Fannin St., Clinical Care Center CC650, Houston, TX 77030, USA. Tel.: +1 832 822 3135(Office); fax: +1 832 825 3141. E-mail address: oolutoye@bcm.edu (O.O. Olutoye). 0022-3468/$ see front matter 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2011.03.051

SCT is quite variable. Whereas some fetuses have an uncomplicated prenatal course, about one half of those diagnosed by the second trimester die before birth because of complications of the tumor [3]. As a result, fetuses with SCT require close in utero surveillance for rapid tumor growth and secondary physiologic effects [4]. This variability in outcome has created a dilemma in family counseling; and several prognostic factors have been studied including tumor

SCT tumor volume ratio size, rate of growth, intratumoral calcifications, solid vs cystic component, vascularity, presence of hydronephrosis or bladder displacement, and polyhydramnios [5-7]. The objective of this study was to develop a simple and sensitive prognostic factor that may be useful to predict outcome and guide counseling early in pregnancy. We hypothesized that in fetuses with SCT, the tumor volume to fetal weight ratio (TFR) in the second trimester will predict outcome.

1183 analyzed by Fisher's Exact test. Statistical analysis was performed using Prism 4.0 (GraphPad Software, La Jolla, CA). A P value of b .05 was considered significant.

2. Results
Twelve fetuses presented with SCT during the study period. One patient with a history of Ebstein anomaly and another who underwent elective termination of pregnancy owing to psychosocial issues were excluded from this analysis (Table 1). Twenty-one ultrasounds and 10 MRI studies were available to obtain measurements of tumor size and estimated fetal weight. Nine pregnancies were singletons, and one was a twin pregnancy. Serial evaluations were not possible for all patients because of individual differences in the timing of the referral, fetal intervention, delivery, or termination of pregnancy secondary to fetal hydrops or mirror syndrome. The PMA at the time of initial imaging ranged from 16 and 6/7 weeks to 32 weeks (median, 23 weeks). In 6 cases, serial evaluations were available; in 4 cases, only the initial evaluation was obtained. The calculated tumor volume ranged from 21 to 1136 mL (median, 221 mL), and the estimated fetal weight ranged from 400 to 2444 g (median, 850 g). The TFR ranged from 0.01 to 1.31 (median, 0.58). In all cases with multiple measurements, both tumor volume and TFR increased with PMA. The TFR before 24 weeks PMA was predictive of outcome. Using receiver operating characteristic analysis (Fig. 1), a cutoff of the TFR greater than 0.12 predicted poor outcome with a sensitivity of 100%, a specificity of 83%, a negative predictive value of 100%, and a positive predictive value of 80%. All fetuses with a TFR less than or equal to 0.12 (n = 5) had a good outcome compared with only 20% of those with a TFR greater than 0.12 (n = 5, P b .05). Those patients with TFR less than or equal to 0.12 before 24 weeks PMA that subsequently increased to greater than 0.12 with advancing age and tumor size still had a good outcome. In those patients whose initial evaluation was after 24 weeks PMA and had TFR less than or equal to

1. Methods
Following approval by the Institutional Review Board of Baylor College of Medicine (H-26009), the medical records of all patients evaluated at the Texas Children's Fetal Center for SCT between 2004 and 2009 were retrospectively reviewed. Data were collected, including postmenstrual age (PMA) at diagnosis, tumor size on prenatal imaging, estimated fetal weight, and maternal and fetal outcome. All 3-dimensional ultrasound and ultrafast magnetic resonance imaging (MRI) studies were performed and/or interpreted by experienced Fetal Center radiologists blinded to the fetuses' clinical outcome. Fetal weight was estimated by ultrasound using the Hadlock formula; and tumor volume was measured by ultrasound or MRI using the greatest dimensions of length, width, and depth to calculate a prolate ellipsoid [8-10]. With these 2 parameters, the TFR was obtained by dividing the calculated total tumor volume by the estimated fetal weight. The earliest available TFR was used for analysis. Two variables were taken into account to analyze this group: TFR and outcome. A good outcome was defined as successful tumor resection after delivery and survival to greater than 6 months of age. A poor outcome was defined as the development of fetal hydrops, fetal demise, or neonatal death. Fetal hydrops was defined as integumentary edema, presence of effusion in at least 1 body cavity, and echocardiographic evidence of cardiac compromise. Receiver operating characteristic analysis was used to select a cutoff value for TFR based on optimum sensitivity and specificity. Patients were stratified by TFR, and their outcomes were

Table 1

TFR and outcome of fetuses with SCT TFR 0.01 0.03 0.06 0.09 0.10 0.14 0.18 0.38 0.44 1.31 Hydrops No No No No No Yes No Yes Yes Yes PMA at birth 32 39 35 38 34 27 36 27 25 34 Outcome Survival Survival Survival Survival Survival Neonatal death Survival Neonatal death Neonatal death Survival Comments Postnatal resection Postnatal resection Postnatal resection Postnatal resection Postnatal resection Emergent C-section for mirror syndrome Twin gestation, postnatal resection Emergent C-section for hydrops Emergent C-section for mirror syndrome Fetal tumor debulking

PMA at diagnosis 28 25 27 23 25 20 24 23 21 22

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M.A. Rodriguez et al. sensitivity and negative predictive value that would be simple to calculate and useful for counseling as early as the second trimester. In our series of fetuses with SCT, a TFR less than or equal to 0.12 predicted an uncomplicated perinatal course with 100% survival. Patients with a TFR greater than 0.12 before 24 weeks PMA had an increased risk of complicated pregnancy and perinatal demise. Fetal demise in cases of SCT has been explained through several mechanisms. Massive hemorrhage into the tumor with fetal exsanguination may occur spontaneously in utero or be precipitated by labor and delivery. Alternatively, high output cardiac failure may develop owing to a vascular steal phenomenon secondary to either high flow requirements of the tumor or arteriovenous fistulization [3,7]. This cardiac failure is often followed by mirror syndrome and/or fetal demise. Attempted fetal interventions for the treatment of SCT have encountered varying degrees of success and have ranged from in utero resection to percutaneous laser or radiofrequency ablation of the tumor or drainage of cystic SCTs [17-20]. Postnatal adjuncts to surgical tumor resection include laparoscopic ligation of the median sacral artery or preoperative angiography with embolization of the tumor vessels [18-25]. The TFR may help identify fetuses at risk for poor outcome that may benefit from close monitoring for the onset of hydrops. Furthermore, this modality provides an objective comparison of the size of the mass to the fetus. We propose that the term giant SCT be reserved for patients with TFR greater than 0.12 who are more likely to require in utero intervention or advanced perinatal management. Our study is limited by the small number of patients with this rare anomaly. A large multicenter study to further evaluate and validate the TFR in other patient populations is already in progress. We propose TFR as a novel diagnostic tool that, once validated, may be useful in prenatal counseling and for identifying high-risk fetuses with SCTs in the second trimester who may benefit from advanced perinatal management.

Fig. 1 Receiver operating characteristic curve illustrating sensitivities and specificities of TFR. A cutoff value of TFR greater than 0.12 predicted poor outcome with 100% sensitivity and 83% specificity. Area under the curve = 0.958.

0.12, we estimated that the TFR before 24 weeks would have been less than the value at initial evaluation; and they all had a good outcome. The fetus with the greatest TFR (1.31) developed hydrops at 25 weeks PMA and subsequently underwent fetal surgical resection of the extrapelvic tumor. The remaining intrapelvic component was resected after birth; and at 2-year follow-up, the child is neurodevelopmentally normal but yet to be potty trained. Four fetuses in our series developed hydrops, although only one developed hydrops before 24 weeks PMA. All fetuses who eventually went on to develop hydrops had a TFR greater than 0.12 by 24 weeks PMA. Without fetal surgical resection, those with hydrops died. There was no significant difference in the Altman classification type [11] between patients with good and poor outcome (Table 2).

3. Discussion
Advances in prenatal care and obstetric ultrasound over the past 2 decades have allowed for early detection of fetal malformations, among them SCT. Once diagnosed, fetuses with these anomalies can be further evaluated with ultrafast MRI and fetal echocardiogram [12-16]. This study focused on the development of a prognostic factor with high
Table 2 Distribution of patient outcome by Altman classification Type I Good outcome Poor outcome 1 0 Type II 4 3 Type III 1 1 Type IV 0 0

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