Child's Nerv Syst (1986) 2:238-241 M NS © Springer-Verlag 1986

A new staging method versus TNM staging in children with posterior fossa primitive neuroectodermal tumor (medulloblastoma) John P. Laurent and William R. Cheek

Department of Neurosurgery, Section of Pediatric Neurosurgery, Baylor College of Medicine, and Texas Children's Hospital, Houston., Texas, USA

Abstract. Prognostic factors were evaluated in 30 children with primitive neuroectodermal tumors of the posterior fossa (classical medulloblastoma or differentiated me- dulloblastoma). The preoperative TNM (Tumor, Node, Metastasis) staging system has been applied to estimate prognosis of patients with central nervous system tumors, but this system was not applicable in assessing the post- operative status of the tumor. To fill this need, a post- operative staging system was developed known as MAPS (Metastasis, Age, Pathology, Surgery), and in this report its efficacy is compared with that of the TNM system. The predictive values of MAPS staging in these 30 children were better than those obtained using the TNM method (MAPS r 2 = -0.90; TNM t a = -0.73; P < 0.05).

Key words: Primitive neuroectodermal tumors - Posterior fossa - Medulloblastoma - Staging - Pediatrics.

did not find the prognostic capability of the TNM classifi- cation to be entirely acceptable in our children, as was true in other reported series [3, 21, 24, 27].

Materials and methods

Both the TNM (Table 1) and MAPS (Table 2) systems were used in staging PNET-PF at the time of diagnosis in 30 consecutive children (1976-1983) treated in our institution. Staging was correlated, at 10-year follow-up, with death or living. Beginning in 1979, myelographic studies (plain myelogram, CT metrizimide myelogram, or both), cerebrospinal fluid analysis for tumor cells, and an enhanced CT cranial scan were performed within 10 days after surgery on each child. Age-related standard radiotherapy (craniospinal) was done on completion of these procedures, and booster doses were given to areas of spine in which there was positive myelographic evidence of tumor seeding. Chemotherapy was instituted on an individual basis.

Primitive neuroectodermal tumors of the posterior fossa (PNET-PF) constitute 15% to 20% of intracranial tumors found in children. Classically, the tumor originates in the posterior medullary velum and, in many instances, invades the brain stem. Metastasis can take place throughout the cerebrospinal fluid pathway [1, 7, 12, 14], and systemic metastases have been seen [17]. Age at the time of onset influences prognosis [1, 3, 7, 9-11, 15]. Children less than 1 year of age in whom PNET-PF has developed seldom survive beyond 3 years o f age.

Pathological studies indicate that the lack of cellular differentiation in PNET-PF improves prognosis [9, 23]. Total surgical removal has been associated with long-term survival [4, 5, 7, 22, 25, 28]. Proper tumor staging of these children should correlate with length of survival. The TNM classification was designed primarily to estimate prognosis in patients with tumors outside the central nervous system [2], but Chang and co-workers [8, 15] later adapted the method to include intracranial tumors. We

Offprint requests to: J.P. Laurent, Texas Children's Hospital, Suite 0-202, 6621 Fannin, Houston, TX 77030, USA

Table [151

1. Operative staging system for cerebellar medulloblastoma

T1 Tumor less than 3 cm diameter and limited to the classic midline position in the vermis, the roof of the IV ventricle, and less frequently to the cerebellar hemispheres.

T2 Tumor 3 cm or greater in diameter further invading one ad- jacent structure or partially filling the ventricle.

T3 This stage is divided into T3A and T3B. T3A Tumor further invading two adjacent structures or completely filling the IV ventricle with extension into the aqueduct of Sylvius, foramen of Magendie or foramen of Luschka, thus produc- ing marked internal hydrocephalus. T3B Tumor arising from the floor of the IV ventricle or brain stem and filling the IV ventricle.

T4 Tumor further spreading through the aqueduct of Sylvius to involve the III ventricle or midbrain, or tumor extending to the upper cervical cord.

M0 No evidence of gross subarachnoid or hematogenous me- tatasis.

M1 Microscopic tumor cells formed in cerebrospinal fluid. M2 Gross nodular seeding demonstrated in cerebellar, cerebral

subarachnoid space or in the III or lateral ventricles. M~ Gross nodular seeding in spinal subarachnoid space. M4 Metastasis outside the cerebrospinal axis.

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Table 2. MAPS staging system Table 3. Comparison of MAPS and TNM staging systems

Metastasis M=0 No evidence of metastases M= 1 Evidenceofmetastases

Age A = 0 Greater than 3 years old A= 1 Less than 3 years old

Pathology P = 0 Undifferentiated tumor P = 1 Differentiated tumor

Surgery S = 0 Total removal S = 1 Subtotal removal

Chang et al. [8] adapted the preoperative international TNM (Tumor, Node, Metastasis) staging system for solid tumors to central nervous system tumors by deleting the Node category (Table 1). The postoperative MAPS (Metastasis, Age, Pathology, Surgery) staging system is self-explanatory (Table 1). The sub- script values for each category (e.g., M0 = 0) were added to obtain values that could be analyzed statistically. For example, the MAPS value would be 4 in a child less than 3 years of age (A1 = 1) in whom a spinal mass is present (M1 =1), a differentiated PNET-PF is found on pathological examination (P1---1), and a subtotal surgical removal (S1 = 1).

R e s u l t s

Table 3 shows each child in whom both TNM and MAPS stagings were done and the length of t ime until death or i f the child is still living. The average length of follow-up was 5 years (range 1-10 years). The correlat ion coefficient at 5 years was r 2 = -0.90 for MAPS and R 2 = - 0 . 7 3 for TNM (Figs. 1, 2). Corre la t ion values for long-term prognosis were significantly more precise [ (P<0 .05) chi-square analysis] when the MAPS system was used in staging. Since each child provides its own comparison, differing radia t ion and chemotherapeut ic modal i t ies will not affect analysis.

The prognostic capabil i t ies o f the TNM and MAPS systems of staging were de te rmined at 3 and 5 years after tumor diagnosis. I f one assumes that the findings from both these staging methods are statistically acceptable at 1 year, then it would be possible to compare the prog- nostic capabi l i ty of each method at year ly intervals. After the 2nd year, the capabi l i ty o f TNM is less significant [(P > 0.05) pa i red t analysis], while the results of the MAPS system remain constant (P < 0.05).

In our series of 30 children, each category under both staging systems was evaluated to determine its prognost ic capabili ty. The correlat ion coefficients of TNM staging were r 2 = - 0 . 0 0 5 for T and r 2 = - 0 . 8 5 for M. Correla t ion coefficients for MAPS were: M, P = -0.85; A, P = - 0 . 8 5 ; P, r 2 = - 0 . 8 5 ; and S, r 2= -0 .75 . The correlat ion was good for all categories of MAPS, with metastasis, age, and pa thology being the best correlates.

Patient TNM TNM MAPS MAPS Years no. score total score total

Death Alive

1 3-0 3 0110 2 1 2 3-3 6 1111 4 1 3 2-2 4 1110 3 2 4 2-2 4 1111 4 2 5 2-3 5 1111 4 1 6 3-0 3 0111 3 1 7 2-0 2 0001 1 8 3-0 3 0001 1 9 2-0 2 0001 1

10 2-0 2 0001 1 3 11 3-0 3 0001 1 12 2-3 5 1001 2 1 13 2-0 2 0111 3 1 14 3-0 3 0001 1 15 2-0 2 0011 2 2 16 3-0 3 0011 2 1 17 2-0 2 0011 2 2 18 3-0 3 0111 3 3 19 2-2 4 1010 2 1 20 2-0 2 0101 2 3 21 2-0 2 0001 1 22 2-0 2 0100 1 23 2-0 2 0001 1 4 24 2-0 2 0011 2 25 3-0 3 0100 1 26 2-3 5 1011 3 1 27 2-0 2 0000 0 28 2-1 3 1011 3 2 29 3-0 3 0101 2 4 30 2-3 5 1011 3 3

100

80 >

6o g O

40 09 tA

a_ 20 0 •

1 2 3 4 5 -Total TNM score

Fig. 1. Percentage survival using TNM staging system. • 3 years data (r ~ = -0.72); [ ] - - •, 5 years data (t a =-0.71)

100 P

.>-6> 80 J ~ ~ ~ 60 i

g 13 Loi

I I 1 I I

00 1 2 3 4 Total NAPS score

Fig. 2. Percentage survival using maps staging system. • 3 years data (r ~ =-0.84); [ ] - - c z , 5 years data (r 2 =-0.90)

@,

@,

240

Discussion

Staging values for primitive neuroectodermal tumors of the posterior fossa (PNET-PF) in children should correlate with prognosis if one assumes that tumor growth charac- teristics are similar in all individuals. Since length of survival in adults with PNET-PF appears to differ from that in children [4, 9, 16, 18], staging criteria used for children may not be applicable for adults. This difference is probably related to attempts to utilize adult staging systems in children and to include staging categories that are not significant. Older category selections and defini- tions for staging have been outdated by more recent methods of testing (CT scanning, microneurosurgery, nuclear magnetic resonance, metrizimide CT myelograms, CSF polyamine levels, and others).

Metastasis (M)

Central nervous system or systemic metastases from PNET-PF decrease length of survival. Except in unusual cases, death is inevitable in 3 -5 years after such metastases are detected [4]. Bone scans, liver scans, myelography, enhanced brain CT scans, spinal metrizimide myelography, bone biopsies, leptomeningeal biopsy, and CSF polyamine levels are some of the a rmamenta r ium used to detect suspected metastases. In 2 children in our series, both supratentorial and spinal metastases were noted at the time of initial tumor diagnosis, while 7 had only spinal metastases.

Age (A)

In younger children with PNET-PF, the 5-year survival rates differ according to age. In those under 5 years of age, the survival rate at 5 years was 48% compared with a 60% survival rate in children older than 5 years [3]. Age-related prognosis has been noted by others [1, 9-11]. The location of postoperative residual tumor in younger children may affect their survival more than actual age [I, 13]. Because of the inconsistencies in age-related prognoses reported in the literature, staging was separated into two age cate- gories (Table 2). The correlation coefficient for age was r 2 = -0.85 with the MAPS system.

Pathology (P)

The prognostic significance of the pathology of medul- loblastoma has been reported in other studies [1, 19, 20]. Chatty and Earl [9], Packer et al. [23], and Rorke [26] showed that in children with medul loblas toma differen- tiated toward ependymal, neuronal, mesenchymal, or other cell lines, the long-term prognosis was worse than in children with the classical small-cell undifferentiated medulloblastoma. MAPS staging relates to the cellular

pattern of the tumor, i.e., differentiated or undifferentiated. The MAPS correlation of pathological staging with prog- nosis was excellent (r 2 = -0.85).

Surgery (S)

The T of the TNM grading system for medul loblastoma represents the status of the tumor prior to surgery (Ta- ble 1). Although TNM staging may be valuable as a tool in radiotherapeutic grading [8], it cannot be used to assess the effect of surgical resection and the remaining tumor burden [6]. The S of MAPS is the assessment of the surgeon following surgery, confirmed by a postoperative, preradiation, enhanced CT scan. MAPS is employed only to assess the postoperative status and location of the tumor. Invasion of the brain stem structures (mesencepha- lon, diencephalon, or myeloencephalon) are classified as S = 1 in the MAPS classification (unless tumor is removed). In patients with residual tumor in the brain stem (S), the incidence of death or recurrence of tumor within 3 years was 3 times that in those in whom the tumor was totally removed. Many investigators have reported an increase in survival rate with greater tumor resection of PNET-PF [5, 22, 24, 25]. Correlation coefficients to T (TNM) and

S (MAPS) were r ~ = - 0 . 5 0 and r 2 =-0 .85 , respectively. The value of the MAPS staging system is assessing the

prognostic impact of the extent and degree of tumor burden following the initial definitive surgery and in analyzing the data in a prospective manner. An enhanced postoperative CT scan is essential in confirming the extent of residual tumor, as well as the presence of intracranial metastasis. The data show that the amount of postopera- tive tumor burden was assessed more appropriately using MAPS than when the preoperative-perioperat ive TNM system was employed tbr this purpose.

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