Journal ofNeuro-Oncology 22: 67-76, 1994. �9 1994 Kluwer Academic Publishers. Printed in the Netherlands.

Clinical Study

Scale for assessing quality of life of children survivors of cranial posterior fossa tumors

Jose Martinez-Ciiment 1, Victoria Castel Sanchez, Carlos Esquembre Menor, Amparo Verdeguer Miralles and Josep Ferns Tortajada 'La Fe' Children's Hospital, Pediatric Oncology Unit, Avda. Campanar, 21, 46009 Valencia, Spain," l Current address: The University of Chicago Medical Center, Section of Hem/Oncology, Chicago, Il, USA

Key words: quality of life, children, brain tumors, posterior fossa tumors, long-term sequelae, astrocytoma, medulloblastoma, brain stem glioma, ependymoma

Abstract

Background. Evaluation of quality of life of survivors of brain tumors is an important aspect of outcome that must be included in clinical studies.

Methods. We have developed a new scale for assessing quality of life (QL) of pediatric long-term survivors of posterior fossa tumors based on their physical, psychointellectual~ and endocrine/growth status. We have studied 39 patients, with a median follow-up of 9 years. Twenty-five had cerebellar astrocytoma (CA), 6 medulloblastoma (MDB), 5 brain-stem glioma (BSG) and 3 ependymoma of IV ventricle (EPD).

Results. Sixty-six percent of children showed neurologic and/or visual sequelae. Little or no significant dis- ability (Bloom's levels I-II) were present in 66%. Psychointellectual dysfunction was present in 44%, with an IQ < 90 in 39%. Endocrine and growth disorders were ~ound in 26%, mostly stature anomalies. According to our scale, QL scores were high in 19 patients (49%), intermediate in 8 (20%), and low in the remaining 12 (31%). Unfavourable outcomes were related to age of less than 4 years, tumors other than CA (MDB, BSG, EPD), incomplete tumoral resection, and employment of radiotherapy and chemotherapy.

Conclusion. Our results are comparable to others pre~4eusly reported, and this supports the validity of our scale. We consider that this scale is applicable to evaluate QL of children survivors of cranial tumors.

Introduction

Intracranial tumors account for 20% of all child- hood cancers, exceeded only by leukemias. More than half are located in the posterior fossa, essen- tially low-grade cerebellar astrocytomas and me- dulloblastomas, and less frequently brain-stem gliornas and ependymomas [1, 2].

Survival of children with brain tumors has in- creased over the last two decades, due in part to ad-

vances in neurosurgery, radiation, and chemother- apy [2--4]. However, as a consequence of these aggressive therapies, the long term evolution of children cured of brain tumors is far from being sat- isfactory [5-9]. Studies assessing quality of life (QL) of these survivors are often difficult~ mainly be- cause of the broad spectrum of sequelae they de- velop [10-12].

The present study was designed to quantify these long-term sequelae and evaluate QL of pediatric

68

survivors of posterior fossa tumors (PFT). For this purpose, we have developed a new scale based on evaluation of functional, psychointellectual and en- docrine/growth status after treatment. We have based our scale on previously published papers and our own experience [13-23].

M e t h o d s : s t u d y d e s i g n

Phase L Subjects

Charts of all children survivors of PFT seen at our Unit from March 1971 to March 1988 were re- viewed. Details of tumor and patient characteristics were abstracted. Subjects who fulfilled the follow- ing criteria were included: - younger than 11 years at diagnosis. - no neurological, visual, psychointelectual or en-

docrine deficit before diagnosis. - at least 3 years of follow up from diagnosis when

evaluation was done, with no sign of tumor activ- ity since remission had been achieved.

- patient and families consent to participate in the study.

Phase II. Evaluation of patients

Thirty-nine patients were evaluated and included in the study. The following parameters were deter- mined:

l. Physical and neurological status Formal examination by a pediatric oncologist which included assessements of the patient's motor, soma- tosensory, oculomotor, auditory, and cerebellar functions was conducted. Ophthalmoscopic evalua- tion, quantification of visual acuity with the Snellen chart (in younger children picture optotypes were used), and visual field testing with Goldman visual field were performed in all patients by a pediatric ophthalmologist. Also investigated was whether patients had normal or handicapped physical activ- ity (sports, play, dance). Patients were classified ac- cording to their degree of disability as recommend- ed by Bloom (Table 1) [24].

2. Psychological functioning

All subjects, as well as one or both parents, were interviewed in person. Verbal, learning, perceptual and memory abilities of subjects were assessed. Educative or occupational levels were measured as Good-Fair-Poor. Mental disabilities, behavioral un- adaptability, emotional problems, or depression were registered. If any of these problems were de- tected, the patients were reevaluated by a pediatric psychologist. Practice of spare time activities (manual skills, music, reading, painting) were test- ed. Intelligence tests were performed: the Wesches- ler Intelligence Scale (WISC) was used in children from 4 to 15 years, the WISC for adults (WAIS-R) was used in older patients [25], and the Terman- Merril test was used test in children younger than 4 years [2@

3. Growth and endocrine status The following parameters were determined: - height, weight and height velocity according to

Tanner [27]. - upper/lower segment ratios, measured by deter-

mining total height and pubis-to-floor length [28].

- bone age by standards of Greulich-Pyle [29]. - puberal status (Tanner), menarche and sexual

development. According to these evaluations, patients were clas- sified into three levels of endocrine and growth sta- tus: * level 1: patients with no endocrine or growth se-

quelae. * Level 2: patients with one of the following en-

docrine or growth sequelae: normal stature with decreased height velocity, obesity with weight percentile > 90, reduced upper/lower segment of height ratio, or retarded bone age.

* Level 3: patients with precocious puberty, pa-

Table 1. Bloom's scale

Level I: Level II: Level III: Level IV:

No disabilities, active life Mild disability, active life Moderate disability, capable of self-care Total disability, incapable of self-care

tients with percentile of height < 3, or patients with two or more of the sequelae included in Level 2.

In cases of growlh or endocrine disorders, stimula- tion tests for measuring the pituitary function were performed: growth hormone (GH) provocation test with insulin (0,1 U/kg i.v.) (normal response: se- rum GH > 7 ng/mL at any time); FSH and LH levels afte~ LP/-RH infusion (lO9 mcgr i.v.) (non;na~ vM- ues LH: 15-55 ng/mL; FSH: 0-280 ng/mL; nmmal response: doubling the baseline LH, 0-30% rise in FSH); and T3, T4 and TSH concentrations after TRH infusion (200 mcgr i.v,) (normal value~ T3: 75-200 Ixg/dL; T4:5-11 ~g/dL; TSH: 0.5-3.8 i_tUt mL; normal response: TSH rinse of 5 gU/mL above baseline) [30].

Phase IlL Quality-of-l~fe scale

The scale for asgessing QL is represented in Table 2.

Table 2. Scale for assessing quality of life of children survivors of

brain tumors

L Functionalstgtus (Bloom's scale) - Level I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Points

- Level II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Points

- Level III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Point

- Level IV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Points

2 Psychointellectual functioning A. Scholar/occupalional level

- Good . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Points

- Fair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Point

- Poor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Points

B. Intelligence quotient (IQ)

- > 90 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Point5

- 7(~-g9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Feint

- < 70 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Poinls C. Mental disorders

- No . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Point

- Yes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Points

3~ Endocrine and growth evaluation - Lever l . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Potat~

- Level 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Petals

- Level 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Point

Score: 1 + 2 + 3 = * Group A = 13 Points.

Group B = 11, 12 Points.

* Group C = 8-10 Points.

* Group D = < 8 Point~.

69

The basis for differentiating the four groups of pa- tients was their degree of disability and their QL af- ter rehabilitation: * Group A (13 poinls): No disabiliw, very good

QL. * Group B (11,12 points): Minor disability, accept-

able or good QL. * Group C (8-10 points): Moderate disability, ac-

ceptable QL after adequate rehabilitation. + Group D (< 8 points): Severe disability, poor

QL. Finally, the QL scores were evaluated with respect to patient's characteristics, as well aa therapy.

Statistical methods

The association of the diverse sequelae and the QL scores among subgroups of patients were assessed by Fisher's exact test. All values were tested for one

Table J. Characteristics and therapy of 39 children survivors of

posterior fossa tumors

* Median age at diagnosis: 5 years (range 1-10 years)

* Median age at evaluation 14 y (range 4-23 years)

* Median foBow-up time: 9 y (r~nge 3-29 years)

* Sex: 17 males/22 females

* Type and location of tumor:

- Cerebellar astrocytoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

- Medulloblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

- Brain stem glioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

- Epe~dymoma IV -ventricle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

* Therapy:

Surgery: 37 (95%) - complete resection: 24 (66%)

- subtotal resection: 7 (18%)

- partial resection: 6 (16%)

Radiotherapy: 17 (44%)

Ftetd - Locat: t0 (5 BSG, 4 CA, l EPD)

- Craniospinal: 7 (6 MDB, ] EPD)

Dosage -25-35 Oy (gpine)

- 30-40 Gy (Cranium)

- 40-50 Oy (Posterior Fossa)

Chemotherapy: 8 (20%)

- MDB: 5 (VCR, MTX, CCNU/VCR~ MTX, PROC)

- CA: ~ (VCR, PROC, CCNU)

- EPD: 1 (VCR, PROC, CCNU)

- BSG: 1 (8 drugs in one day)

CA: Cerebellar Astrocytoma. MDB: Medulloblastoma. BSG:

Brain Stem Glioma. EPD: Ependymoma. CompLete Resection:

100% removal of tumor. 5~sb total Resection: 7 ~-99 % removal of

tumor. Parlial Resection: < 75% removal of l umor VCR: Vin-

cristine. MTX: Methotrexate. PROC: Procarbazine.

70

group of patients and compared with the remaining of patients except where i~dica~ed.

Results

Phase I

Data corresponding to the 39 subjects are shown in

Table 3. The median age at diagnosis was 5 years (range 1-10y); the median age at evaluation was 14 years (R: 4-23y), with a median follow-up time of 9

years (R: 3-20y). There were 17 males and 22 fe- males. Twenty-five children had cerebellar astrocy- toma (CA), 6 had medulloblastoma (MDB), 5 had brain s tem glioma (BSG), and 3 had ependymoma of the forth ventricle ( E P D )

Phase H

1. Neurologic and v&ual status

Twenty-six patients (66,6%) had neurological and/ or visual impairment. Cerebellar dysfunctions were

the most frequent (18 cases), manifested predom- inantly as intention t remor and ataxia. The second most frequent dysfunctions were visual abnormal- ities, including oculomotor nerve palsies (13 cases). The remaining dysabilities were motor deficits (7

cases), hearing losses (2 cases), and epilepsy (1 case).

According to Bloom's scale, 15 cases were classi-

fled as having Level I (38%), 11 cases as Level I I /28%), 8 cases as Level I I I (21%), and 5 cases as Level IV (13 %). Twenty-nine patients were practic-

ing physical activities, 16 of them without any diffi- culty.

2. Psychointellectual evaluation

Psycholointellectual sequelae were identified in 17 patients (44%). Scholar/occupational level was good in 22 cases (56 %), fair in 10 (26 %), and poor in the remaining 7 (18%). In 7 patients, mental disor-

ders were detected: severe anxiety in 3, depression in 2, and social inadaptation in 2. Enter ta inment ac-

tivities were per formed by 26 subjects (66,6%). IQ was determined in 33 patients: 9 of them had an IQ between 70 and 90, and 4 more had an IQ less than 70.

3, Growth and endocrine evaluation

Ten patients developed endocrine and growth dis-

orders: seven presented sequelae involving growth retardation, and three had precocious puber ty (Ta- ble 4). In 9 of these patients, stimulation endocrine tests were completed: all cases had normal results.

Four patients were included in endocrine level II and six in level III. In all seven patients with growth

retardation, growth hormone levels were normal, and G H therapy was not used in any of these cases. The 4 cases with decreased upper/ lower segment

ratios had been treated with high-dose cranio-spi- nal irradiation. We detected three girls with preco- cious puberty. No thyroid dysfunction was noted.

Table 4. Endocrine evaluation: patien{s with endocrine and/or growth sequelae

Case 1 2 3 4 5 6 7 8 9 10

Diagnosis SS SS + U/L SS U/L U/L U/L B/C PP PP PP Tumor CA EPD BSG MDB MDB MDB EPD BSG MDB MDB Age Dx 3 2 2 3 2 2 3 3 4 6 Present age 13 13 4 24 10 1i 10 8 tl 12 RT. NO CSI LOC CSI CSI CSI NO LOC CSI CSI CT. NO YES YES YES YES YES NO NO YES NO Surgery SUB PAR NO PAR PAR PAR TOT PAR TOT TOT Level 3 3 3 2 2 2 2 3 3 3

Diagnosis: SS = Short Stature, U/L = Reduced Upper/Lower Segment Ratio, B/C = Retardation in Bone Age with respecl to Chronolog- ical Age. PP = Precocious Puberty. CA = Cerebellar Astrocytoma. MDB = Medullo-blastoma, BSG = Brain Stem Glioma, EPD = Epen- dymoma. RT = Radiotherapy. CSI = Craniospinal Irradiation, LOC = Posterior Fossa Irradiation. CT = Chemotherapy. Surgery: TOT = Total resection, PAR = Partial resection. SUB = Subtotal resection. NO = No surgery. Level: Endocrine level.

71

Fig. 1. Children survivors of posterior fossa tumors. Long-term sequelae. Correlation with age at presentation of tumor. Neu- ral = neurologic sequelae. Psycho = pshychointellectual seque- lae. Endoc = endoeri~ologie and growth sequelae.

Phase III. Quality-of-life scores

The 39 children survivors of PFT were classified as follows: * Group A: 7 patients (18%). * Group B: 12 patients (31%)_ * Group C: 8 patients (20%). * Group D: 12 patients (31%).

Influence of tumor type, age, sex, and treatment on quality of life

Type of tumor. Total number of sequelae were less frequent in patients witla CA with respect to the re- maining children (p = 0.043), especially for endo- crine and growth sequelae (p < 0.0001). Despite pa- tients with CA had a lower number of all sequelae than patients with MDB, differences among these two groups were only significant for the visual and endocrine/growth dysfunctions (p = 0.013 and p = 0.0001 respectively). QL scores were better in the CA group when compared to the MDB group (p = 0.018), but the difference was not significant when compared to the rest of tumors (p = 0.1), Patients with MDB had the highest number of sequelae (p = 0,02), the lowest Bloom's scores (p = 0.002), and the worst QL scores (p = 0.02) with respect to the other groups. Patients with BSG and EPD had an inter- mediate number of sequelae and QL scores, Neur- olog~ca~ sequelae were frequent in a~l groups, espe- cially in MDB; however, differences were not sig-

Fig. 2. Children survivors of posterior fossa tumors. Long-term sequelae~ Correlation with type of surgery. Neurol = neurologic sequelae. Psycho = psychointellectual sequelae. Endocr = endo- crinologic and gro'~th sequelae.

nificant. Forty percent of patients with CA had neurological dysfunctions, but they were mostly mi- nor complications: 76% of patients were classified in the groups I-II in Bloom's scale.

Age. Poor QL were strongly related to young age. Children under 4 years of age at diagnosis had worse visual and endocrine functions than older pa- tients (p = 0.03 and p = 0.0015): lower QL scores were also noted in lhese young children (p = 0.02). Most of the visual dysfunctions were: impaired vi- sual acuity and reduced visual field. Intellectual dysfunctions were also more frequent in children under 4 years, and they had less neurologic late ef- fects; however, differences were not slatistica~y sig- nificant. If radiotherapy (RT) was employed in the young children, the consequences were devastat- ing: 5 of 6 survivors were classified in group D (p <

0.0001) (Fig. 1).

Sex. In our series, unfavorable outcomes were more frequent in female survivors than in males: 59% of girls vs. 41% of boys were in the C-D groups of QL. However, differences were not significant (p = 0.34). This results can be explained by the high number of aggressive tumors found in females and by the use of RT and CT in them.

Surgery. Patients who had tumors which were total- ly resected had better outcomes than patients with non-Iotaily resected tumors, bul the differences were only significant for the endocrine and growth

72

Table 5. Long-term sequelae and quality of life in children survivors of posterior fossa tumors, Correlation with type of tumor

Tumor CA (25) MDB (6) BSG (5) EPD (3)

Neurologic seq. 10 (40%) 5 (83%) 3 (60%) 1 (33%) Visual seq. 6 (24%) 5 (83%)** 2 (40%) 0 Psychointellect seq. 8 (32%) 5 (83%) 2 (40%) 2 (66%) Endocrine/growth seq. 1 (4%)*** 5 (83%)*** 2 (40%) 2 (66%) Bloom's scale: 1-11 19 1"** 4 2 Score QL: Group A 5 0 1 1

Group B 10 0 2 0 Group C 5 2* 0 1 Group D 5 4* 2 1

CA = Cerebellar Astrocytoma. MDB = Medulloblastoma. BSG = Brain Stem Glioma. EPD = Ependymoma. SEQ = Sequelae. (*) p < 0.05. (**) p < 0.01. (***) p < 0.001.

anomalies (p = 0.015). This is very probably related to the additional therapy they received as com- pared with patients with totally resected tumors (Fig. 2).

Radiotherapy (RT). Survivors who received radi- ation therapy had larger number of sequelae than patients not irradiated, especially visual and endo- crinological sequelae (p = 0.03 and p = 0.0004 re- spectively). In the RT group, QL scores were very unfavourable in patients who were treated with high-dose cranio-spinal RT (100% in C-D groups) as compared to patients who received only local RT (p = 0.19) or to patients not irradiated (p = 0.0081) (Table VI).

Chemotherapy (CT). The use of CT was related to poor QL, although all patients who underwent CT were also treated with high-dose RT. When com- paring patients treated with RT plus CT with those

treated only with RT, 100% (8 of 8 patients) vs. 33% (3 of 9) were classified in groups C or D (p = 0.009). Sequelae were more frequent in the RT plus CT group (p = 0,086) when compared to the remainder of patients.

Discussion

It is estimated that by the year 2.000, one in every 1.000 adults reaching the age of 20 will be a long- term survivor of childhood cancer. The manage- ment of these survivors, and the evaluation of their quality of life (QL) have been receiving increased attention during recent years [3-5, 7]. We report here the evaluation of 39 pediatric survivors of PFT with a new scale for assessing QL.

Astrocytomas of the cerebellum (CA) in children are mostly low-grade tumors, presenting a 10-year survival rate of nearly 90% /31-331. Complete re-

Table 6. Long-term sequelae and quality of life in children survivors of posterior fossa tumors. Correlation with radiotherapy

Type of sequelae CSI (n = 7) Local RT (n = 10) No RT (n = 22)

Neurologic 5 (71%) 4 (40%) 10 (45 %) Visual 5 (71%)* 1 (10%)* 7 (32%)* Psychointellectual 5 (71%) 4 (40%) 8 (36%) Endocrine/growth 6 (86%)*** 2 (20%)*** 2 (10%)*** Score QL: Group A 0 3 4

Group B 0 3 9 Group C 2** t 5** Group D 5** 3 4**

Local RT = Posterior Fossa Irradiation. CSI = Craniospinal Irradiation. No RT = No Radiotherapy. (*) p < 0.05. (**) p < 0.01. (***) p < 0.001.

section is often possible, but whether postoperative RT improves survival in subtotally excised tumors is still unclear [34]. Although half of our patients with CA had sequelaes, QL scores were high; these late effects were mainly minor neurological deficits that do not impair their normal lives. The incidence of other sequelae was low. These dysfunctions were directly related to the incomplete surgical resection and the subsequent use of RT.

Recently reported series indicate a 5-year dis- ease-free survival in childhood medulloblastoma (MDB) of 60-65 % following surgery and high-dose cranio-spinal irradiation (CSI) plus boost to the posterior fossa [35]. This rate can even improve with adjuvant CT [36, 37]. However, the QL in sur- vivors is generally disastrous. Hope-Hirsch and cols. reported an incidence of neurologic, intellec- tual and emotional sequelae of 50, 58 and 47% at 5 years of treatment, worsening in all cases: no pa- tient had normal employment at 10 years from diag- nosis [38]. Other authors are not so pessimistic [39- 44]. Many studies have been designed to maintain the high survival rate and at the same time to reduce the severe sequelae derived mainly from CSI [45- 47]. In our series children with MDB were the most impaired group, with an uniformly poor QL and sig- nificant sequelae present in all of them. These find- ings were directly related to: the use of CSI, the use of CT and the age less than 4 years.

tnfratentorial ependymomas (EPD) in child- hood are rare, and their prognosis is considered to be poor even after surgical resection, RT and CT [48-52]. Two of the 3 patients with EPD had a bad QL: one was treated with surgery alone and the other was treated with surgery, CSI RT, and CT. The third EPD was treated only with surgery, and was included in group A. On the other hand, brain stem gliomas (BSG), despite often being low-grade tu- mors, have the same bad evolution, due to their in- operable location [33, 53, 54]. In our study, the BSG group of patients had moderate number of sequelae and intermediate QL scores: three were included in groups A-B, treated with surgery and/or local RT; and two in group D, treated with surgery, local RT, and CT.

Our results can be compared to other series. Li and cols. reviewed 73 children survivors of PFT,

73

with a similar distribution of tumor types as ours [55]. They reported that 79% were in Bloom's levels I or II, presenting the same type of neurological se- quelae. As suggested by others, perhaps the longer evolution of these patients (18 years) explains their better performance with respect to our series (66%) [5, 7, 32]. Kun and cols. [7] found 33% of pa- tients with low IQ (< 80), and an incidence of emo- tional sequelae of 50%. In our serie, 39% of patients had IQ < 90, and only 18% developed emotional dysfunctions. Lannering and cols., in a study of 29 children with PFT with more than 5 years of evolu- tion, noted a moderate to severe disability in 21%, and an IQ lower than 90 in 35%; these proportions rose twice in the group of irradiated patients [12]. We have also found this direct relation between the neurodevelopmental and psychointellectual status in our patients when RT was used.

In our series, 26% of survivors had growth or en- docrine disorders, an incidence that is variable in other reports. Most of patients were younger than 4 years, had MDB, the tumor was not completely re- sected, and were treated with RT. Height anomalies were the most frequent disturbances. In many stud- ies, growth retardation is considered to be due to GH deficiency, which is secondary to hypothalamic- pituitary irradiation. However, other factors that can influence final height are: the effect of RT on the growing spine, causing abnormal upper/lower segment ratios; early puberty, which accelerates the skeletal maturation; and hypothyroidism [4, 22, 42, 45]. In patients of short stature and low levels of GH, GH treatment is clearly indicated [23, 42]. In all of our patients with growth retardation, GH lev- els were normal. Four subjects who had been treat- ed with CSI developed a decreased upper/lower segment ratio. Three girls had precocious puberty, and all of them had a normal final height. In spite of the published data, no thyroid dysfunction was de- tected by us.

Several recent reports include the term 'Quality of Life' as the quantification of the performance status in childhood survivors of cancer [5, 10, 12, 13, 15, 16]. However, in most of these reports this con- cept is analyzed in a single way: (1) by studying only one type of tumor (p.e. medullobtastomas); (2) by evaluating individualized aspects of treatment (p.e.

74

radiotherapy); or (3) by quantifying specific dys- functions (p.e. psycho-intellectual development, endocrine deficits). Furthermore, QL has been de- termined only by examining the neurological and psychointellectual status of the patient, overlook- ing in some cases the endocrine and developmental sequelae. The Karnofsky scale of performance sta- tus [20, 21] has been the most frequently employed measure of physical activity. It provides a quantifi- cation from 0 to 100 of the patients' disabilities, by rating their mobility, the degree of self-care, the em- ployment capacity and life at home. Obviously, it is not readily applicable to children. The scale em- ployed by us, established by Bloom [24], contains four categories of physical status, and is more easily applied to young children. Together with Bloom's scale, we have determinated the psychointellectual and endocrinological status of our patients, that way assessing QL of children survivors of posterior fossa tumors. The concordance of our results with those previously published does confirm the valid- ity of this scale. We consider that our numerical scale can be applied to childen and adolescents who are long-term survivors of cranial tumors of all ages.

Nineteen pediatric survivors of PFT (49%) had no or minimal sequelaes, performing well at school or at work, with a good QL. Eight more (20%) had moderate disability, with a QL that can be accept- able with an adequate rehabilitation. The remain- ing 12 subjects (31%) were classified as having a poor QL which can be improved slightly. These un- favourable outcomes were related to several fac- tors: tumoTs other than astrocytoma of the cerebel- lum, especially meduliobtastoma, age iess than 4 at the time of diagnosis, incomplete tumoral resec- tion, employment of RT (specially CSI) and CT. Currently, the great majority of our survivors are under specialized follow-up by the different sec- tions of our hospital, including periodic neurolog- ical and visual examinations, physical rehabilitation programs, psychoemotional support and special- ized education systems, as well as endocrine and de- velopmental evaluations.

Acknowledgement

We would like to acknowledge the contribution of Celia Ciscar, Pediatric Psychologist, for the psy- chointellectual evaluation of patients and Mike Harrison and Rita Sprudzs for their kind assistance in the preparation ol lhis manuscript.

References

1 Heideman RL, Packer RJ, Albright LA. Freeman CR, Rorke LB: Tumors of ~he central nervous system. I~: Pizzo PA, Poplack DG. Principles and practice of Pediatric Oncol- ogy. J.B. Lippincott Company, Philadelphia, pp 633-681, 1993

2. Duffner PK, Cohen ME, Meyers MH: Survival of children with brain tumors: SEER program 1973-1980. Neurology 36: 597-601, 1986

3. DaaoffBF, Cowchock S, Marquette C, Mulgrew L, Kramer S: Assessment of long-term effects of primary radiation therapy for brain tumors in children. Cancer 49: 1580-1586, 1982

4. Duffner PK, Cohen ME, Thomas PR, Lansky SB: The long- term effects of cranial irradiation on the central nervous sys- tem. Cancer 56: 1841-1846, 1985

5. Mostow EN, Byrne J, Connelly RR, Mulv/hil JJ: Quality of life in long-term survivors of CNS tumors of childhood and adolescence. J Clio Oncol 9: 592-599, 1991

6. Blatt J, Bleyer WA: Late effects of childhood cancer and its heatment. In: Pizzo PA, Poplack DG~ Principles and Prac- tice of Pediatric Ontology, J.B Lippincott Company, Phila- delphia, pp. 1003-1026, 1989

7. Kun LE, Mulhern RK, Crisco JJ: Quality of life in children treated for brain tumors. J Neurosurg 58: 1-6, 1983

8. Mulhern RK, Wasserman AL, Friedman AG, Fairclough D: Social competence and behavioral adjustment of children who are long-term survivors of cancer. Pediatrics 83(1): 1g- 25, 1989

9. Grrenberg HS, KazaR A, Meadows AT: P~ychologic func- tioning in 8-to-16-year-old cancer survivors and their par- ents. J Pediatr 114: 488493, 1989

10. Makipernaa A: Long-term quality of life and psychosocial coping after treatmenl of solid tumors in childhood. Acta Paediatr Scand 78: 728-735,1989

11. Packer RJ , Meadows AT, Rorke LB, Gotdwein JL, D' Angio G: Long-term sequelae of cancer treatment on the central nervous system in childhood. Med Pediatr Oncol 15: 241- 253, 1987

12. Lannering B, Murky I, Lundberg A, Olsson E: Long-term sequelae after pediatric brain tumors: their effect on disabil- ity and quality of life. Med Pediatr Onco118: 304-310,1990

13. Milstein JM, Cohen ME, Sinks LF: The iufluence and relia-

bility of neurologic assessment and Karofsky performance score on prognosis. Cancer 56: 1834-1836,1985

14. Lansky LL, List MA, Lansky SB, Cohen ME, Sinks LF: To- ward the development of a play performance scale for chil- dren (PPSC). Cancer 56: 1837-1840, 1985

15. Feldstein ML: Quality-of-life-adjusted survival for compar- ing cancer treatments. Cancer 67: 851-854, 1991

16. Bloom JR: Quality of life after cancer. Cancer 67: 855-859, 1991

17. Allen A, Malpas JS, Kingston JE: Educational achieve- ments of survivors of childhood cancer. Pediatr Hematol Oncol 7: 31-39, 1990

18. Michael BE, Copeland DR: Psychosocial issues in child- hood cancer. Am J Pediatr Hematol Oncol 9: 73-83, 1987

19. Christ GH: Social consequences of the cancer experience. Am J Pediatr Hematol Oncol 9: 84-88, 1987

20. Karnofsky DA, Burchenal JH: The clinical evaluation of chemotherapeutics in cancer. In: MacLeod CM (ed) Eval- uation of the chemotherapeutic agents. New York: Colum- bia University Press: 191-205,1949

21. Schang CC, Heinrich RL, Ganz PA: Karnofsky Perform- ance Status revisited: reliability, validity and guidelines. J Clin Oncot 2: 187-193,1984

22. Oberfield SE, Allen JC, Pollack J, New MI, levine LS: Long- term endocrine sequelae after treatment of medulloblasto- ma: prospective study of growth and thyroid function. J Pe- diatr 108: 219-223, 1986

23. Brauner R, Rappaport R, Prevot C, Czernichow R Zucker JM, B ataini Pet al.: A prospective study of the development of GH in children given cranial irradiation, and its relation to statural growth. J Clin Endocrinol Metab 68: 346-351, 1989

24. Bloom HJG, Wallace EN, Henk JM: The treatment and prognosis of medulloblastoma in children. A study of 82 ver- ified cases. Am J Roentgeno1105: 43-62, 1969

25. Weschesler intelligence scale for children manual. The psy- chologycal corporation, New York, 1949, revised. Standardi- zation manual 1971. Adaptaci6n espafiola de TEA, Ed, S.A.

26. Terman LM, Merrill MA: Medida de la intelligencia. M4to- do para el empleo de las Pruebas de Stanford-Binet. Espasa Calpe, Madrid, 1976, 9" Ed.

27. Tanner JM, Wbitehouse RH: Clinical longitudinal stan- dards for height, weight, height velocity and weight velocity and the stages of puberty. Arch Dis Child 51: 170-177, 1976

28. Wilkins L: Diagnosis and treatment of endocrine disorders in childhood and adolescence. Springfields, Charles C. To- mas, Publisher, 1965

29. Greulich WW, Pyle SI: Radiographic Atlas of skeletal devel- opment of the hand and wrist. 2d Ed, Standford Calif, Stand- ford University Press, 1959

30. Pediatric Endocrinology, pp 176-179. Ed: Nancy Collins, Williams & Williams; Baltimore

31. Garcia DM, Latifi HR, Simpson JR, Picker S: Astrocytomas of the cerebellum in children. J Neurosurg 71: 661-665.339- 345,1989

32. Mulhern RK, Horowitz ME, Kovnar EH, Langston J, San-

75

ford, Kun LE: Neurodevelopmental status of infants and young children treated for brain tumors with preirradiation chemotherapy. J Ciin Oncol 7: t660-1666, 1989

33. Mandigers CM, Lippens RJ, Hoogenhcut J, Meijer E, Wier- ingen PM, Theeuwes AG: Astrocytoma in childhood: sur- vival and performance. Pediatr Hematol Oncol 7: 121-128, 1990

34. North CA, North RB, Epstein JA, Piantadosi S, Wharam MD: Low-grade cerebral astrocytomas. Survival and quality of life after radiation therapy. Cancer 66: 6-14, t990

35. Kun LE, Constine LS: Medulloblastoma-caulion regarding new treatment approaches. Int J Radiat Oncol Biol Phys 20: 897-899, 1991

36. Hope-Hirsch E, Renier D, Lellouch-Tubiana A, Sainte- Rose C, Pierre-Kahn A, Hirsch JF: Medulloblastoma in childhood: progressive intellectual deterioration. Child's Nerv Sys 6: 60-65, t990

37. Clausen N, Garwics S, Glomstein A, Jonmundsson G, Kruus S, Yssing M: Medulloblastoma in nordic children. Incidence and mortality. Acta Paediatr Scand Suppl 371: 5-11, 1990

38. Bleyer WA, Fallavollita J, Robinson L, Balsom W, Meadows A, Heyn R et al.: Influence of age, sex, and concurrent in- trathecat methotrexate t~erapy on intellectual function af- ter cranial irradiation. Pediatr Hematol Oncol 7: 329-338, 1990

39. Yssing M, Garwicz S, Glomstein A, Jonmundsson G, Kruus S: Medulloblastoma in nordic children III: Neurologic and soctal prognosis in long term survivors. Acta Paediatr Scand Supp1371: 12.19, 1990

40. Silverman CL, Palkes H, Talent B, Kovnar E, Clouse JW, Thomas PR: Late effects of radiotherapy on patients with cerebellar medulloblastoma. Cancer 54: 825-829, 1984

41. Chin HW, Maruyama Y: Age at treatment and long-term performance results in medulloblastoma. Cancer 53: 1952- 1958, 1984

42. Rappaport R, Brauner R: Growth and endocrine disorders secondary to cranial irradiation. Pediatr Res 25: 561-567, 1989

43. Jacobsen BB, Garwicz S, Glomstein A, Jonmundsson G, Kruus S, Yssing M: Medulloblastoma in nordic children II. Long term growth and endocrine sequelae Acts Paediatr Scand Supp1371: 20-27, 1990

44. Halberg FE, Wara WM, Fippin LF, Edwards MS, Levin VA, Davis RL et al.: Low-dose craniospinal radiation therapy for medulloblastoma. Int J Radiat Oncol Biol Phys 20: 65t-654, 1991

45. Krischer JR Ragab AH, Kun L, Kim TH, Laurent JR Boyett JM, Cornell CA et al.: Nitrogen mustard, vincristine, procar- bazine and prednisone as adjuvant chemotherapy in the treatment or medulloblastoma. A Pediatric Oncology Group Study. J Neurosurg 74: 905-909, 199I

46. Packer RJ: Chemotherapy for medulloblastoma/primitive neuroectodermal tumors of the posterior fossa. Ann Neurol 28: 823-828, 1990

47. Gaspar LE, Dawson DJ, Tilley-Gulliford SA, Banerjee P: Medulloblastoma: long-term follow-up of patients treated

76

with electron irradiation of the spinal field. Radiology 180: 867-870, 1991

48. Nazar GB, Hoffman H J, Becker LE, Jenkin D, Humphreys RR Hendrick EB: Infratentorial ependymomas in child- hood: prognostic factors and treatment. J Neurosurg 72: 408-417, 1990

49. Vanuytsel L, Brada M: The role of prophylactic spinal irradi- ation in localized intracranial ependymoma. Int J Radiat Oncol Biol Phys 21: 825-830, 1991

50. Goldwein JW, Corn BW, Finlay JL, Packer RJ, Rorke LB, Schut L: Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas? Cancer 67: 2766-2771, 1991

51. Lyons MK, Kelly PJ: Posterior fossa ependymomas: report

of 30 cases and review of the Iiterature. Neurosurgery 28: 65%665, 1991

52. Undjian S, Marinov M: Intracranial ependymomas in chil- dren. Child's Nerv Sys 6: 131-134, 1990

53. Epstein F, McCleary EL: Intrinsec brain stem tumors of childhood: Surgical indications. J Neurosurg 64: 11-15, 1986

54. Freeman CR, Suissa S: Brain stem tumors in children: re- sults of a survey of 62 patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 12: 1823-1828, t986

55. Li FR Winston KR, Gimbrere K: Follow-up of children with brain tumors. Cancer 54: 135-138,1984

Address for offprints: V.C. Sanchez, Hospital Infantil La Fe, Uni- dad de Oncologia Pediatrica, Avda. Campanar, 21, 46009 Valen- cia, Spain