J Neurosurg Pediatrics 13:170–177, 2014 ©AANS, 2014
Quality of life after surgical treatment of primary intramedullary spinal cord tumors in children Clinical article Christian Schneider, M.D.,1 Eveline Teresa Hidalgo, M.D.,1 Thomas Schmitt-Mechelke, M.D., 2 and Karl F. Kothbauer, M.D.1,3 Divisions of 1Neurosurgery and 2Pediatric Neurology, Cantonal Hospital of Lucerne; and 3Department of Neurosurgery, University of Basel, Switzerland Object. Presently, the best available treatment for intramedullary spinal cord tumors (IMSCTs) in children is microsurgery with the objective of maximal tumor removal and minimal neurological morbidity. The latter has become manageable with the development and standard use of intraoperative neurophysiological monitoring. Traditionally, the perioperative neurological evaluation is based on surgical or spinal cord injury scores focusing on sensorimotor function. Little is known about the quality of life after such operations; therefore, this study was designed to investigate the impact of surgery for IMSCTs on the quality of life in children. Methods. Twelve consecutive pediatric patients treated for IMSCT were included in this retrospective fixed cohort study. A multidimensional questionnaire-based quality of life instrument, the Pediatric Quality of Life Questionnaire version 4 (PedsQL 4.0), was chosen to analyze follow-up data. This validated instrument particularly allows for a comparison between a patient cohort and a healthy pediatric sample population. Results. Of 11 mailed questionnaires (1 patient had died of progressive disease), 10 were returned, resulting in a response rate of 91%. There were 8 low-grade lesions (5 pilocytic astrocytomas, 1 ganglioglioma, 1 hemangioblastoma, and 1 cavernoma) and 4 high-grade lesions (2 anaplastic gangliogliomas, 1 glioblastoma, and 1 glioneuronal tumor). The mean age at diagnosis was 7.5 years, the mean follow-up was 4.2 years, and 83% of the patients were male. Total resection was achieved in 5 patients and subtotal resection in 7. Four patients had undergone 2 or more resections. The 4 patients with high-grade tumors and 2 with incompletely resected low-grade tumors underwent adjuvant treatment (2 chemotherapy and 4 both radiotherapy and chemotherapy). The mean modified McCormick Scale score at the time of diagnosis was 1.7; at the time of follow-up, 1.5. The mean PedsQL 4.0 total score in the low-grade group was 78.5; in the high-grade group, 82.6. There was no significant difference in PedsQL 4.0 scores between the patient cohort and the normal population. Conclusions. In a small cohort of children who had undergone surgery for IMSCTs with a mean follow-up of 4.2 years, quality of life scores according to the PedsQL 4.0 instrument were not different from those in a normal sample population. (http://thejns.org/doi/abs/10.3171/2013.11.PEDS13346)
Key Words • quality of life • PedsQL 4.0 • intramedullary spinal cord tumor • children • surgical treatment • follow-up • oncology
I
ntramedullary spinal cord tumors (IMSCTs) are rare,
composing about 10% of all neoplasms of the CNS in children.20 Presently, the best available treatment for IMSCTs is microsurgery with the objective of maximal tumor removal and minimal neurological morbidity. It has been shown that the oncological outcome for low-grade glial tumors depends on the extent of resection. However, once near-total resection is achieved, further removal of small remnants appears to provide no additional benefit.7 Furthermore, this “last remnant” resection would logically carry the highest risk of surgery-induced neurological Abbreviations used in this paper: CSR = Child Self Report; IMSCT = intramedullary spinal cord tumor; mMS = modified McCormick Scale; PedsQL 4.0 = Pediatric Quality of Life Questionnaire version 4.0; PPR = Parent Proxy Report; QOL = quality of life.
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damage. The ability to avoid such neurological damage during surgery has improved with the development and standard use of intraoperative neurophysiological monitoring.12,14,21 To evaluate neurological function pre- and postoperatively or to compare neurological function between groups, the McCormick Scale (often modified for pediatric needs) is widely used.7,16 The modified McCormick Scale (mMS) as well as other spinal cord injury scales focuses on more or less detailed neurological assessment (Table 1). The more comprehensive question of patient quality of life (QOL)—particularly in the long term—is less well delineated by such functional scores and has not been studied in much detail. Any significant adverse effects of surgery upon a broader measure of QOL cannot be studJ Neurosurg: Pediatrics / Volume 13 / February 2014
Quality of life in pediatric IMSCT TABLE 1: Modified McCormick Scale for grading neurological function in spinal cord conditions Grade
Explanation
I
neurologically intact, ambulates normally, may have minimal dysesthesia mild motor or sensory deficit; patient maintains functional in dependence moderate deficit, limitation of function, independent w/ ex ternal aid severe motor or sensory deficit, limit of function w/ a depen dent patient paraplegic or quadriplegic, even if there is flickering move ment
II III IV V
ied in group comparisons, as there cannot be any studies comparing surgery with no surgery or comparing surgery with other isolated treatments such as radiation and/or chemotherapy. To overcome this limitation, we sought a tool to compare QOL in surgically treated patients with that in a normal group. It was assumed that considering the impact of the tumor itself and the additional effects of intramedullary resection, the QOL in the former patients would be worse than in the healthy population. After reviewing available questionnaires, we determined that the Pediatric Quality of Life Questionnaire version 4 (PedsQL 4.0) seemed to be ideal for our purposes. It provides an overview of different dimensions of QOL, has adapted formulations for all age groups, utilizes parents or proxies for young or disabled children, and can also be used for adolescents and young adults.26,31 Most importantly, the instrument is validated for internal consistency over all age groups and is validly translated into different languages. Furthermore, normative data have been published to evaluate the impact of a specific disease compared with a healthy status. This latter aspect is especially useful given that the current study design is necessarily retrospective.4,9,10,15,26–31
Methods
The ethics committee of the Canton of Lucerne approved this retrospective fixed cohort study, which included 12 consecutive patients under the age of 18 years. They had all undergone microsurgical removal of an IMSCT performed by the senior author between 2005 and 2013 at the Cantonal Hospital of Lucerne. Intraoperative neurophysiological monitoring had been used in all cases. Patients with intradural extramedullary tumors and those with dysraphic conditions were excluded from analysis. The mMS had been routinely used to evaluate neurological outcome (Table 1) in all patients at the time of diagnosis and at the follow-up.16 The QOL study described in this paper was performed using the PedsQL 4.0, developed by Dr. James W. Varni (http://www.pedsql.org).4,26–31 The German, Spanish, and Croatian translations of the PedsQL 4.0 were used.9,10,15 Table 2 summarizes the 23 items calculated into the final QOL scores. Each item was scored as a number from 0 to 4 by the patient and/or the proxy, with 0 meaning no disJ Neurosurg: Pediatrics / Volume 13 / February 2014
TABLE 2: Structure of the PedsQL 4.0 instrument Exemplary Item Description (0–4 points)* physical functioning 1. It is hard for me to walk more than one block 2. It is hard for me to run 3. It is hard for me to do sports activity or exercise 4. It is hard for me to lift something heavy 5. It is hard for me to take a bath or shower by myself 6. It is hard for me to do chores around the house 7. I hurt or ache 8. I have low energy psychosocial functioning emotional functioning 1. I feel afraid or scared 2. I feel sad or blue 3. I feel angry 4. I have trouble sleeping 5. I worry about what will happen to me social functioning 1. I have trouble getting along w/ others 2. Others do not want to be my friend 3. Others tease me 4. I cannot do things others my age can do 5. It is hard to keep up w/ my peers school functioning 1. It is hard to pay attention at work/school 2. I forget things 3. I have trouble keeping up w/ my work or studies 4. I miss work or school because of not feeling well 5. I miss work or school to go to the doctor or hospital * Wording of items is adapted to the age groups of the PedsQL 4.0.
ability at all and 4 indicating maximal disability. These raw scores were transformed to a 0–100 scale (algorithm: 0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0) with 100 indicating the best possible function. Missing items were replaced by the arithmetic mean to calculate a subscore, provided that at least 50% of the items for each subscore were answered. Quality of life was assessed in 4 dimensions: 1) physical functioning, 2) emotional functioning, 3) social functioning, and 4) school functioning. The latter 3 dimensions were summarized as psychosocial functioning. The arithmetic mean over all 4 dimensions constituted the total score of the PedsQL 4.0. In older children and adolescents, the QOL data were reported by the patient him- or herself (Child Self Report [CSR]); in younger or severely disabled children, by the parents or proxies (Parent Proxy Report [PPR]). For children between 5 and 7 years, an adapted CSR questionnaire provided visual analog pictograms of weeping and smiling faces to be pointed at. In these patients, an additional PPR was mandatory to complete the questionnaire, which explains why some patients had both CSR and PPR data. Questions varied a little according to age group; for example, other items replaced school func171
C. Schneider et al. tioning items for infants and toddlers. Nevertheless, the instrument has proved to be reasonably consistent for assessing QOL over all age groups.30 Of the 12 patients eligible for this study, one boy had died of progressive disease; therefore, the PedsQL 4.0 was mailed to 11 patients and families. An informed consent form was mailed together with the questionnaire to be signed by the parents for children under 14 years of age, by the patient and parents for children over 14 but under 18 years, and by the patient if he or she was over 18 years at the time of follow-up. Nonresponders to the first mailing were sent a written reminder; nonresponders to this second mailing were contacted personally by telephone. To evaluate the impact of an IMSCT on QOL, we used data from a large (more than 5000 individuals) healthy population sample.26 Authors of the normative collective data give a certain value difference for each PedsQL 4.0 subscore that, when surpassed, delineates a “clinically important difference.” Using the GraphPad Prism software (version 6.02), we performed an unpaired t-test to compare patients and the healthy collective, assuming a level of significance of a = 5%. The same procedure was repeated for the subgroups of patients with low-grade and high-grade IMSCTs. On the basis of the abovementioned clinically important difference, a power calculation was performed to assess the number of patients ideally included in the study to reach a power of 0.8 using the 1-sample Z-test for a sample mean.
Results
Demographic and Clinical Data
Of the 12 patients eligible for analysis, 10 were male
and 2 were female, with a mean age of 7.5 years (Table 3). Histological diagnosis was high-grade tumor in 4 patients (1 glioblastoma, 2 anaplastic gangliogliomas, and 1 glioneuronal tumor) and low-grade tumor in 8 patients (5 pilocytic astrocytomas, 1 ganglioglioma, 1 hemangioblastoma, and 1 cavernoma). Patients in the low-grade group were slightly older at diagnosis with a mean age of 9.6 years as compared with a mean age of 5.3 years in the high-grade group. One patient in the high-grade group had died of progressive disease. Total resection was achieved in 5 patients and subtotal resection in 7. Four patients underwent 2 or more surgeries, 4 patients received adjuvant radiotherapy, and 6 patients received adjuvant chemotherapy. The mean mMS score for all patients at the time of diagnosis was 1.7; at the time of follow up, it was 1.5. No clinically important difference was calculated for either the low-grade or the high-grade group.26 Collection of QOL Data
Ten patients returned the questionnaire, resulting in a response rate of 91% (Table 3). The one nonresponder was contacted by telephone but gave no specific reason for not participating. All returned questionnaires were sufficiently completed to process the PedsQL 4.0 scores. Therefore, demographic and clinical data could be reported for 12 patients, whereas the QOL data refer to 10 patients (1 patient deceased and 1 nonresponder). The mean follow-up from the time of initial diagnosis to the date of a returned questionnaire was 4.2 years (2.4 years in the high-grade group, 5.9 years in the low-grade group).
Results of QOL Assessment
Table 4 provides a detailed description of the indi-
TABLE 3: Overview of data in 12 patients with IMSCTs* No. (%) Parameter
Low-Grade Lesions
High-Grade Lesions
Total or Mean
patients sex (male/female) death from progressive disease mean age at Dg in yrs patients in whom total resection was achieved patients w/ multiple interventions for tumor resection patients w/ adjuvant radiotherapy patients w/ adjuvant chemotherapy mean mMS score at Dg/at FU nonresponder to QOL questionnaire mean FU time from Dg to QOL assessment in yrs mean PedsQL 4.0 score in patients/mean score in normative population clinically important difference‡
8 (67) 7/1 (58/8) 0 (0) 9.6 4 (33) 3 (25) 1 (8) 2 (17) 1.7/1.7 1 (8) 5.9 78.50/82.11
4 (33) 3/1 (25/8) 1 (8) 5.3 1 (8) 1 (8) 3 (25) 4 (33) 1.8/1.3 0 (0) 2.4 82.64/82.11
12 10/2 1 7.5† 5 4 4 6 1.7/1.5† 1 4.2 80.57/82.11†
no
no
no
* Dg = diagnosis; FU = follow-up. † Mean values. ‡ The clinically important difference value was published by authors of the PedsQL 4.0 normative data (Varni et al., 2003). It describes the standard error of measurement and was derived by multiplying the standard deviation of 1-alpha (Cronbach’s alpha reliability coefficient) of the normative data. Transformed to the PedsQL 4.0 scores, it describes the minimal difference between a patient’s score and the normative data that has a probability of less than 5% of being coincidental.
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1) pA WHO I; 2) recurrent pA WHO I 1) pA WHO I; 2) recurrent pA WHO I 1) pA WHO I; 2) recurrent pA WHO I; 3) recurrent pA WHO I pA WHO I 1) AC WHO II; 2) recurrent AC WHO II; 3) recurrent AC WHO IV GG WHO I AGG WHO III
2: 4 yrs, M
abnormal motor de velopment
Initial Symptoms TR
Surgery
C5–6 & T2–3
HB WHO I
CH WHO I
11: 18 yrs, M
12: 13 yrs, M
C3–5
T8–L1 C6–T10
T8–10 T6–12
incidental (cutaneous TR lesions)
RT no
Chemo
Remarks
no
no
no
yes no
no yes
no
no
yes yes
no yes
von Hippel-Lindau disease, un der surveillance secondary kyphosis after lam inectomy
rare case of AGG —
— rare case of AGG
no no nonresponder to QOL mailing 1) no; 2) yes; 1) yes; 2) no; malignant transformation, death 3) no 3) no at 84 mos after Dg
1) no; 2) yes possible recurrence, under sur veillance no —
severe spasticity, intrathecal baclofen therapy in evalua tion 1) no; 2) yes 1) yes; 2) no proton beam RT
no
1) PR; 2) PR; no 3) PR
1) TR; 2) TR
PR, S 1) B, PR, & S; 2) PR & S; 3) PR scoliosis PR paraparesis, gait dis- PR turbance back pain at night TR scoliosis, gait distur- PR bance paresthesias TR
T8–11 scoliosis 1) T9–11; 2) T8–12; gait disturbance 3) L4–S1
nuchal pain, gait dis turbance 1) T8–12; 2) T8–12; leg paresis 3) T8–12
1) C3–6; 2) C2–7
1) C3–T2; 2) C3–T2 nuchal pain, torticollis 1) PR; 2) PR
T1–4
Spinal Level
9: 14 yrs, F AGG WHO III 10: 30 mos, M GNT
7: 13 yrs, F 8: 19 mos, M
5: 11 yrs, M 6: 3 yrs, M
4: 8 yrs, M
3: 6 yrs, M
pA WHO I
Histological Dg
1: 3 yrs, M
Case No.: Age at Dg, Sex
1
1
1 2
1 3
1 1
2
1
3
3
1
1
1 2
1 1
2 —
2
1
2
3
at FU
mMS Score at Dg
* AC = astrocytoma; AGG = anaplastic ganglioglioma; B = biopsy; CH = cavernous hemangioma; Chemo = chemotherapy; GG = ganglioglioma; GNT = glioneuronal tumor; HB = hemangioblastoma; pA = pilocytic astrocytoma; PR = partial resection; RT = radiotherapy; S = correction of scoliosis; TR = total resection; — = not applicable.
Other
GG
AC
Tumor
TABLE 4: Clinical features and individual PedsQL 4.0 data*
Quality of life in pediatric IMSCT
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C. Schneider et al. vidual patients, including histological diagnosis, initial symptoms, spinal level of tumor occurrence, and treatment regimen as well as mMS scores and PedsQL 4.0 scores for each patient (Table 5). For some of the PedsQL 4.0 subscores, a clinically important difference was noted in individual patients (Table 5), but these small differences did not affect overall QOL scores in the whole group (Figs. 1–3). Figure 1 compares data from the normal collective with data in all patients with IMSCTs across the PedsQL 4.0 scores for CSR and PPR. There was no statistically significant difference between the study cohort and the normal sample population. When the patients were stratified into low-grade (Fig. 2) and high-grade (Fig. 3) groups, there was only one significant difference—in the physical functioning subscore of the CSR, not the PPR, indicating a slightly worse physical functioning situation in the low-grade group. When performing the power calculation, assuming the
clinically important difference as the minimal difference and the predefined level of significance of a = 5%, the following statements can be made: For the CSR total score, a sample size of 57 patients would be needed to reach a power of 0.8, and for the PPR total score, a sample size of 78 patients would be needed to reach a power of 0.8.
Discussion
Regarding the demographics of and histological diagnoses in the patients in this study, the findings were about as expected in the low-grade group. Pilocytic astrocytomas are the tumors most commonly found in the pediatric population. They can recur, and patients with such a recurrence usually undergo a second surgery and/ or receive adjuvant treatment. Based on original data presented by Constantini in 2000 and confirmed by McGirt in 2008, subtotal resection is oncologically sufficient for long-term survival, and thus adjuvant treatment would
TABLE 5: Individual PedsQL 4.0 data in 12 patients with with IMSCTs* PedsQL 4.0 Data Case No.
Age at QOL Assessment (yrs)
Scale
CSR
1
13
2
9
3
11
4
19
5 6 7
— — 14
8
7
9
14
75.21 68.75 81.67 79.59 87.50 71.67 93.34 100.00 86.67 57.50 50.00 65.00 — — 71.15 65.63 76.67 72.29 81.25 63.33 92.50 75.32 92.50
10
3
11
24
12
15
TS PH PsH TS PH PsH TS PH PsH TS PH PsH — — TS PH PsH TS PH PsH TS PH PsH TS PH PsH TS PH PsH TS PH PsH
— 87.09 75.32 92.50 75.32 65.63 85.00
Clinically Important Difference† PPR — 74.68 84.36 65.00 95.00 100.00 90.00 — — — — 93.54 93.75 93.33 — 72.50 62.50 82.50 — —
CSR yes yes no no no yes no no no yes yes yes — — yes yes no yes no yes no yes no — no no no yes yes no
PPR — yes no yes no no no — — — — no no no — yes yes no — —
* PH = Physical Health Score; PsH = Psychosocial Health Score; TS = Total Score. † See Table 3 footnote for explanation.
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Quality of life in pediatric IMSCT
Fig. 1. Comparison of PedsQL 4.0 scores in all patients with IMSCTs (gray) and in a healthy population (black). Left: Child Self Report. Right: Parent Proxy Report. No significant difference was demonstrated between the two groups.
be the exception rather than the rule.7,18 It must be noted that every other patient in this series—even those with a low-grade tumor—received adjuvant treatment. This high proportion of patients with adjuvant treatment is amplified by the occurrence of 2 cases of a particularly rare tumor type, the anaplastic ganglioglioma in the highgrade group.23 The occurrence of these rare tumors in our cohort may be due to a referral bias of complex cases to the senior author. The role of adjuvant radiotherapy is debated. It must be noted that in retrospective studies, there is some evidence of prolonged progression-free and overall survival, especially in high-grade IMSCTs and in ependymomas.3,11,13,24 A series of publications have already reported good outcomes (using the mMS) and determined the safety and efficacy of the best possible microsurgical tumor removal
with the aid of intraoperative neurophysiological monitoring.1,2,5–8,12,14,17,18,21,25 No significant overall impact on reported QOL can be measured using the PedsQL 4.0 when comparing children with IMSCT and a healthy collective. There is only one minor exception to this conclusion: in the physical health item of the CSR score in the low-grade subgroup (Fig. 2), the t-test revealed a significant impact of the disease at an error level of 5%. This significance disappeared when combining CSR and PPR in this group. However, this finding indicates a potential tendency for the physical health item to be the first to be affected by IMSCT surgery if a larger patient group could be studied. A 2009 Canadian study by Scheinemann et al., including 29 patients with low-grade spinal cord gliomas and a mean follow-up of 8.2 years, reported an 83% rate
Fig. 2. Comparison of PedsQL 4.0 scores in patients with a low-grade IMSCT (gray) and in a healthy population (black). Left: Child Self Report. Right: Parent Proxy Report. Asterisk indicates the subscore with a significant (p < 0.05) difference between patients and the normal collective (physical health in the CSR form).
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Fig. 3. Comparison of PedsQL 4.0 scores in patients with a high-grade IMSCT (gray) and in a healthy population (black). Left: Child Self Report. Right: Parent Proxy Report. No significant difference was demonstrated between the two groups.
of significant neurological and orthopedic sequelae.22 Even though these authors did not report a formal QOL assessment, the data indicated either the possibility of later deterioration or some other bias in the patient group as determined by disease, surgery, or adjuvant treatment. Particularly, late spinal deformities can occur after multilevel laminectomies.19,32 The retrospective nature, small patient group, referral bias, group inhomogeneity, and high number of patients needed to reach a power of 0.8 are certainly weaknesses of this study. To include 50–70 patients is impossible, as these cases are simply not treated within a reasonable time frame given the low incidence of the disease. That is precisely one important reason to use a standardized and validated instrument to assess a multidimensional issue such as QOL to compare even a small patient group with a healthy collective and still have a meaningful study design with known numerical power. Such an assessment has not been reported. Since the value of surgery for diagnosis and its documented oncological benefit are established, no prospective study comparing surgery with adjuvant treatments is conceivable. Therefore, particular aspects of treatment, such as QOL in the present report, must be studied in other ways. Comparing the study cohort—with its common denominator of surgical treatment—with a normal sample appeared to be logical. It is somewhat surprising that no differences were found in the QOL of patients compared with that in the normal collective. With a serious disease and a serious operation as in IMSCTs, it would have been intuitively obvious to expect a less than normal QOL. Furthermore, the study cohort was fixed by the surgery, which all patients had in common. And the fact that many patients underwent additional treatments, which may well have adversely affected QOL, did not push the results toward a worse status. It is possible though that in a larger study population, a small impact on QOL data would have reached statistical significance, as delineated in the power calculation. 176
Moreover, there may be a proxy bias. Parents sometimes take great efforts to obtain specialized surgical treatment, even abroad, and may tend to have a more positive view of their children’s QOL status. It is also very probable that patients with a long interval from diagnosis to QOL assessment report a better clinical status (a “happy to have survived” bias). Finally, the high response rate for a questionnairebased mail-in study is unusual.26 It may be explained by the close interaction among patients, families, and caregivers for the management of a complex condition.
Conclusions
In children with surgically treated IMSCT, QOL measured with the PedsQL 4.0 is not different from that in a healthy collective after a mean follow-up of 4.2 years. This conclusion is drawn with an awareness of the small patient group, but still is an encouraging finding and can be emphasized when surgery is discussed with patients and parents confronted with this disorder. Acknowledgment The authors thank Ms. Vanessa Martel from the MAPI Research Trust for providing the PedsQL 4.0 questionnaire in different translations and her support in scoring the instrument. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Schneider, Hidalgo, Kothbauer. Acquisition of data: Schneider. Analysis and interpretation of data: Schneider, Schmitt-Mechelke, Kothbauer. Drafting the article: Schneider, Kothbauer. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Schneider. Statistical analysis: Schneider. Administrative/technical/ material support: all authors. Study supervision: Kothbauer.
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Quality of life in pediatric IMSCT References 1. Bansal S, Ailawadhi P, Suri A, Kale SS, Sarat Chandra P, Singh M, et al: Ten years’ experience in the management of spinal intramedullary tumors in a single institution. J Clin Neurosci 20:292–298, 2013 2. Bansal S, Suri A, Borkar SA, Kale SS, Singh M, Mahapatra AK: Management of intramedullary tumors in children: analysis of 82 operated cases. Childs Nerv Syst 28:2063–2069, 2012 3. Benesch M, Weber-Mzell D, Gerber NU, von Hoff K, Deinlein F, Krauss J, et al: Ependymoma of the spinal cord in children and adolescents: a retrospective series from the HIT database. Clinical article. J Neurosurg Pediatr 6:137–144, 2010 4. Chan KS, Mangione-Smith R, Burwinkle TM, Rosen M, Varni JW: The PedsQL: reliability and validity of the short-form generic core scales and asthma module. Med Care 43:256–265, 2005 5. Choi GH, Oh JK, Kim TY, You NK, Lee HS, Yoon DH, et al: The clinical features and surgical outcomes of pediatric patients with primary spinal cord tumor. Childs Nerv Syst 28: 897–904, 2012 6. Constantini S, Houten J, Miller DC, Freed D, Ozek MM, Rorke LB, et al: Intramedullary spinal cord tumors in children under the age of 3 years. J Neurosurg 85:1036–1043, 1996 7. Constantini S, Miller DC, Allen JC, Rorke LB, Freed D, Epstein FJ: Radical excision of intramedullary spinal cord tumors: surgical morbidity and long-term follow-up evaluation in 164 children and young adults. J Neurosurg 93 (2 Suppl): 183–193, 2000 8. de Amoreira Gepp R, Couto JM, Silva MD, Silva RT, Neri EA: Intramedullary tumors in children: analysis of 24 operated cases. Arq Neuropsiquiatr 68:396–399, 2010 9. Felder-Puig R, Frey E, Proksch K, Varni JW, Gadner H, Topf R: Validation of the German version of the Pediatric Quality of Life Inventory (PedsQL) in childhood cancer patients off treatment and children with epilepsy. Qual Life Res 13:223–234, 2004 10. González-Gil T, Mendoza-Soto A, Alonso-Lloret F, CastroMurga R, Pose-Becerra C, Martín-Arribas MC: The Spanish version of the health-related quality of life questionnaire for children and adolescents with heart disease (PedsQL™). Rev Esp Cardiol (Engl Ed) 65:249–257, 2012 11. Guss ZD, Moningi S, Jallo GI, Cohen KJ, Wharam MD, Terezakis SA: Management of pediatric spinal cord astrocytomas: outcomes with adjuvant radiation. Int J Radiat Oncol Biol Phys 85:1307–1311, 2013 12. Jallo GI, Kothbauer KF, Epstein FJ: Intrinsic spinal cord tumor resection. Neurosurgery 49:1124–1128, 2001 13. Katoh N, Shirato H, Aoyama H, Onimaru R, Suzuki K, Hida K, et al: Hypofractionated radiotherapy boost for dose escalation as a treatment option for high-grade spinal cord astrocytic tumor. J Neurooncol 78:63–69, 2006 14. Kothbauer KF, Deletis V, Epstein FJ: Motor-evoked potential monitoring for intramedullary spinal cord tumor surgery: correlation of clinical and neurophysiological data in a series of 100 consecutive procedures. Neurosurg Focus 4(5):E1, 1998 15. Lusić I, Dzamonja G, Titlić M, Bilić I, Sodić L, Lusić L, et al: Psychometric validation of the Croatian version of the Quality of Life in Epilepsy Inventory (QOLIE-31). Coll Antropol 35: 1177–1184, 2011 16. McCormick PC, Stein BM: Intramedullary tumors in adults. Neurosurg Clin N Am 1:609–630, 1990 17. McGirt MJ, Chaichana KL, Atiba A, Attenello F, Woodworth GF, Jallo GI: Neurological outcome after resection of intramedullary spinal cord tumors in children. Childs Nerv Syst 24:93–97, 2008 18. McGirt MJ, Chaichana KL, Atiba A, Attenello F, Yao KC, Jallo GI: Resection of intramedullary spinal cord tumors in
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children: assessment of long-term motor and sensory deficits. J Neurosurg Pediatr 1:63–67, 2008 19. McGirt MJ, Chaichana KL, Atiba A, Bydon A, Witham TF, Yao KC, et al: Incidence of spinal deformity after resection of intramedullary spinal cord tumors in children who underwent laminectomy compared with laminoplasty. J Neurosurg Pediatr 1:57–62, 2008 20. Nadkarni TD, Rekate HL: Pediatric intramedullary spinal cord tumors. Critical review of the literature. Childs Nerv Syst 15: 17–28, 1999 21. Sala F, Palandri G, Basso E, Lanteri P, Deletis V, Faccioli F, et al: Motor evoked potential monitoring improves outcome after surgery for intramedullary spinal cord tumors: a historical control study. Neurosurgery 58:1129–1143, 2006 22. Scheinemann K, Bartels U, Huang A, Hawkins C, Kulkarni AV, Bouffet E, et al: Survival and functional outcome of childhood spinal cord low-grade gliomas. Clinical article. J Neurosurg Pediatr 4:254–261, 2009 23. Schneider C, Vosbeck J, Grotzer MA, Boltshauser E, Kothbauer KF: Anaplastic ganglioglioma: a very rare intramedullary spinal cord tumor. Pediatr Neurosurg 48:42–47, 2012 24. Tendulkar RD, Pai Panandiker AS, Wu S, Kun LE, Broniscer A, Sanford RA, et al: Irradiation of pediatric high-grade spinal cord tumors. Int J Radiat Oncol Biol Phys 78:1451–1456, 2010 25. Tobias ME, McGirt MJ, Chaichana KL, Goldstein IM, Kothbauer KF, Epstein F, et al: Surgical management of long intramedullary spinal cord tumors. Childs Nerv Syst 24:219–223, 2008 26. Varni JW, Burwinkle TM, Seid M, Skarr D: The PedsQL 4.0 as a pediatric population health measure: feasibility, reliability, and validity. Ambul Pediatr 3:329–341, 2003 27. Varni JW, Limbers CA: The PedsQL 4.0 Generic Core Scales Young Adult Version: feasibility, reliability and validity in a university student population. J Health Psychol 14:611–622, 2009 28. Varni JW, Limbers CA, Neighbors K, Schulz K, Lieu JE, Heffer RW, et al: The PedsQL™ Infant Scales: feasibility, internal consistency reliability, and validity in healthy and ill infants. Qual Life Res 20:45–55, 2011 29. Varni JW, Seid M, Knight TS, Uzark K, Szer IS: The PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and impact on clinical decision-making. J Behav Med 25:175–193, 2002 30. Varni JW, Seid M, Kurtin PS: PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care 39:800–812, 2001 31. Varni JW, Seid M, Rode CA: The PedsQL: measurement model for the pediatric quality of life inventory. Med Care 37:126– 139, 1999 32. Yao KC, McGirt MJ, Chaichana KL, Constantini S, Jallo GI: Risk factors for progressive spinal deformity following resection of intramedullary spinal cord tumors in children: an analysis of 161 consecutive cases. J Neurosurg 107 (6 Suppl): 463–468, 2007
Manuscript submitted July 9, 2013. Accepted November 18, 2013. Parts of this material were presented in abstract and poster form at the 2nd Congress of the Swiss Federation of Clinical Neuro-Socie ties held in Montreux, Switzerland, on June 5–7, 2013. Please include this information when citing this paper: published online December 20, 2013; DOI: 10.3171/2013.11.PEDS13346. Address correspondence to: Christian Schneider, M.D., Division of Neurosurgery, Cantonal Hospital of Lucerne, 6000 Lucerne 16, Switzerland. email: [email protected].
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Quality of life after surgical treatment of primary intramedullary spinal cord tumors in children Clinical article Christian Schneider, M.D.,1 Eveline Teresa Hidalgo, M.D.,1 Thomas Schmitt-Mechelke, M.D., 2 and Karl F. Kothbauer, M.D.1,3 Divisions of 1Neurosurgery and 2Pediatric Neurology, Cantonal Hospital of Lucerne; and 3Department of Neurosurgery, University of Basel, Switzerland Object. Presently, the best available treatment for intramedullary spinal cord tumors (IMSCTs) in children is microsurgery with the objective of maximal tumor removal and minimal neurological morbidity. The latter has become manageable with the development and standard use of intraoperative neurophysiological monitoring. Traditionally, the perioperative neurological evaluation is based on surgical or spinal cord injury scores focusing on sensorimotor function. Little is known about the quality of life after such operations; therefore, this study was designed to investigate the impact of surgery for IMSCTs on the quality of life in children. Methods. Twelve consecutive pediatric patients treated for IMSCT were included in this retrospective fixed cohort study. A multidimensional questionnaire-based quality of life instrument, the Pediatric Quality of Life Questionnaire version 4 (PedsQL 4.0), was chosen to analyze follow-up data. This validated instrument particularly allows for a comparison between a patient cohort and a healthy pediatric sample population. Results. Of 11 mailed questionnaires (1 patient had died of progressive disease), 10 were returned, resulting in a response rate of 91%. There were 8 low-grade lesions (5 pilocytic astrocytomas, 1 ganglioglioma, 1 hemangioblastoma, and 1 cavernoma) and 4 high-grade lesions (2 anaplastic gangliogliomas, 1 glioblastoma, and 1 glioneuronal tumor). The mean age at diagnosis was 7.5 years, the mean follow-up was 4.2 years, and 83% of the patients were male. Total resection was achieved in 5 patients and subtotal resection in 7. Four patients had undergone 2 or more resections. The 4 patients with high-grade tumors and 2 with incompletely resected low-grade tumors underwent adjuvant treatment (2 chemotherapy and 4 both radiotherapy and chemotherapy). The mean modified McCormick Scale score at the time of diagnosis was 1.7; at the time of follow-up, 1.5. The mean PedsQL 4.0 total score in the low-grade group was 78.5; in the high-grade group, 82.6. There was no significant difference in PedsQL 4.0 scores between the patient cohort and the normal population. Conclusions. In a small cohort of children who had undergone surgery for IMSCTs with a mean follow-up of 4.2 years, quality of life scores according to the PedsQL 4.0 instrument were not different from those in a normal sample population. (http://thejns.org/doi/abs/10.3171/2013.11.PEDS13346)
Key Words • quality of life • PedsQL 4.0 • intramedullary spinal cord tumor • children • surgical treatment • follow-up • oncology
I
ntramedullary spinal cord tumors (IMSCTs) are rare,
composing about 10% of all neoplasms of the CNS in children.20 Presently, the best available treatment for IMSCTs is microsurgery with the objective of maximal tumor removal and minimal neurological morbidity. It has been shown that the oncological outcome for low-grade glial tumors depends on the extent of resection. However, once near-total resection is achieved, further removal of small remnants appears to provide no additional benefit.7 Furthermore, this “last remnant” resection would logically carry the highest risk of surgery-induced neurological Abbreviations used in this paper: CSR = Child Self Report; IMSCT = intramedullary spinal cord tumor; mMS = modified McCormick Scale; PedsQL 4.0 = Pediatric Quality of Life Questionnaire version 4.0; PPR = Parent Proxy Report; QOL = quality of life.
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damage. The ability to avoid such neurological damage during surgery has improved with the development and standard use of intraoperative neurophysiological monitoring.12,14,21 To evaluate neurological function pre- and postoperatively or to compare neurological function between groups, the McCormick Scale (often modified for pediatric needs) is widely used.7,16 The modified McCormick Scale (mMS) as well as other spinal cord injury scales focuses on more or less detailed neurological assessment (Table 1). The more comprehensive question of patient quality of life (QOL)—particularly in the long term—is less well delineated by such functional scores and has not been studied in much detail. Any significant adverse effects of surgery upon a broader measure of QOL cannot be studJ Neurosurg: Pediatrics / Volume 13 / February 2014
Quality of life in pediatric IMSCT TABLE 1: Modified McCormick Scale for grading neurological function in spinal cord conditions Grade
Explanation
I
neurologically intact, ambulates normally, may have minimal dysesthesia mild motor or sensory deficit; patient maintains functional in dependence moderate deficit, limitation of function, independent w/ ex ternal aid severe motor or sensory deficit, limit of function w/ a depen dent patient paraplegic or quadriplegic, even if there is flickering move ment
II III IV V
ied in group comparisons, as there cannot be any studies comparing surgery with no surgery or comparing surgery with other isolated treatments such as radiation and/or chemotherapy. To overcome this limitation, we sought a tool to compare QOL in surgically treated patients with that in a normal group. It was assumed that considering the impact of the tumor itself and the additional effects of intramedullary resection, the QOL in the former patients would be worse than in the healthy population. After reviewing available questionnaires, we determined that the Pediatric Quality of Life Questionnaire version 4 (PedsQL 4.0) seemed to be ideal for our purposes. It provides an overview of different dimensions of QOL, has adapted formulations for all age groups, utilizes parents or proxies for young or disabled children, and can also be used for adolescents and young adults.26,31 Most importantly, the instrument is validated for internal consistency over all age groups and is validly translated into different languages. Furthermore, normative data have been published to evaluate the impact of a specific disease compared with a healthy status. This latter aspect is especially useful given that the current study design is necessarily retrospective.4,9,10,15,26–31
Methods
The ethics committee of the Canton of Lucerne approved this retrospective fixed cohort study, which included 12 consecutive patients under the age of 18 years. They had all undergone microsurgical removal of an IMSCT performed by the senior author between 2005 and 2013 at the Cantonal Hospital of Lucerne. Intraoperative neurophysiological monitoring had been used in all cases. Patients with intradural extramedullary tumors and those with dysraphic conditions were excluded from analysis. The mMS had been routinely used to evaluate neurological outcome (Table 1) in all patients at the time of diagnosis and at the follow-up.16 The QOL study described in this paper was performed using the PedsQL 4.0, developed by Dr. James W. Varni (http://www.pedsql.org).4,26–31 The German, Spanish, and Croatian translations of the PedsQL 4.0 were used.9,10,15 Table 2 summarizes the 23 items calculated into the final QOL scores. Each item was scored as a number from 0 to 4 by the patient and/or the proxy, with 0 meaning no disJ Neurosurg: Pediatrics / Volume 13 / February 2014
TABLE 2: Structure of the PedsQL 4.0 instrument Exemplary Item Description (0–4 points)* physical functioning 1. It is hard for me to walk more than one block 2. It is hard for me to run 3. It is hard for me to do sports activity or exercise 4. It is hard for me to lift something heavy 5. It is hard for me to take a bath or shower by myself 6. It is hard for me to do chores around the house 7. I hurt or ache 8. I have low energy psychosocial functioning emotional functioning 1. I feel afraid or scared 2. I feel sad or blue 3. I feel angry 4. I have trouble sleeping 5. I worry about what will happen to me social functioning 1. I have trouble getting along w/ others 2. Others do not want to be my friend 3. Others tease me 4. I cannot do things others my age can do 5. It is hard to keep up w/ my peers school functioning 1. It is hard to pay attention at work/school 2. I forget things 3. I have trouble keeping up w/ my work or studies 4. I miss work or school because of not feeling well 5. I miss work or school to go to the doctor or hospital * Wording of items is adapted to the age groups of the PedsQL 4.0.
ability at all and 4 indicating maximal disability. These raw scores were transformed to a 0–100 scale (algorithm: 0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0) with 100 indicating the best possible function. Missing items were replaced by the arithmetic mean to calculate a subscore, provided that at least 50% of the items for each subscore were answered. Quality of life was assessed in 4 dimensions: 1) physical functioning, 2) emotional functioning, 3) social functioning, and 4) school functioning. The latter 3 dimensions were summarized as psychosocial functioning. The arithmetic mean over all 4 dimensions constituted the total score of the PedsQL 4.0. In older children and adolescents, the QOL data were reported by the patient him- or herself (Child Self Report [CSR]); in younger or severely disabled children, by the parents or proxies (Parent Proxy Report [PPR]). For children between 5 and 7 years, an adapted CSR questionnaire provided visual analog pictograms of weeping and smiling faces to be pointed at. In these patients, an additional PPR was mandatory to complete the questionnaire, which explains why some patients had both CSR and PPR data. Questions varied a little according to age group; for example, other items replaced school func171
C. Schneider et al. tioning items for infants and toddlers. Nevertheless, the instrument has proved to be reasonably consistent for assessing QOL over all age groups.30 Of the 12 patients eligible for this study, one boy had died of progressive disease; therefore, the PedsQL 4.0 was mailed to 11 patients and families. An informed consent form was mailed together with the questionnaire to be signed by the parents for children under 14 years of age, by the patient and parents for children over 14 but under 18 years, and by the patient if he or she was over 18 years at the time of follow-up. Nonresponders to the first mailing were sent a written reminder; nonresponders to this second mailing were contacted personally by telephone. To evaluate the impact of an IMSCT on QOL, we used data from a large (more than 5000 individuals) healthy population sample.26 Authors of the normative collective data give a certain value difference for each PedsQL 4.0 subscore that, when surpassed, delineates a “clinically important difference.” Using the GraphPad Prism software (version 6.02), we performed an unpaired t-test to compare patients and the healthy collective, assuming a level of significance of a = 5%. The same procedure was repeated for the subgroups of patients with low-grade and high-grade IMSCTs. On the basis of the abovementioned clinically important difference, a power calculation was performed to assess the number of patients ideally included in the study to reach a power of 0.8 using the 1-sample Z-test for a sample mean.
Results
Demographic and Clinical Data
Of the 12 patients eligible for analysis, 10 were male
and 2 were female, with a mean age of 7.5 years (Table 3). Histological diagnosis was high-grade tumor in 4 patients (1 glioblastoma, 2 anaplastic gangliogliomas, and 1 glioneuronal tumor) and low-grade tumor in 8 patients (5 pilocytic astrocytomas, 1 ganglioglioma, 1 hemangioblastoma, and 1 cavernoma). Patients in the low-grade group were slightly older at diagnosis with a mean age of 9.6 years as compared with a mean age of 5.3 years in the high-grade group. One patient in the high-grade group had died of progressive disease. Total resection was achieved in 5 patients and subtotal resection in 7. Four patients underwent 2 or more surgeries, 4 patients received adjuvant radiotherapy, and 6 patients received adjuvant chemotherapy. The mean mMS score for all patients at the time of diagnosis was 1.7; at the time of follow up, it was 1.5. No clinically important difference was calculated for either the low-grade or the high-grade group.26 Collection of QOL Data
Ten patients returned the questionnaire, resulting in a response rate of 91% (Table 3). The one nonresponder was contacted by telephone but gave no specific reason for not participating. All returned questionnaires were sufficiently completed to process the PedsQL 4.0 scores. Therefore, demographic and clinical data could be reported for 12 patients, whereas the QOL data refer to 10 patients (1 patient deceased and 1 nonresponder). The mean follow-up from the time of initial diagnosis to the date of a returned questionnaire was 4.2 years (2.4 years in the high-grade group, 5.9 years in the low-grade group).
Results of QOL Assessment
Table 4 provides a detailed description of the indi-
TABLE 3: Overview of data in 12 patients with IMSCTs* No. (%) Parameter
Low-Grade Lesions
High-Grade Lesions
Total or Mean
patients sex (male/female) death from progressive disease mean age at Dg in yrs patients in whom total resection was achieved patients w/ multiple interventions for tumor resection patients w/ adjuvant radiotherapy patients w/ adjuvant chemotherapy mean mMS score at Dg/at FU nonresponder to QOL questionnaire mean FU time from Dg to QOL assessment in yrs mean PedsQL 4.0 score in patients/mean score in normative population clinically important difference‡
8 (67) 7/1 (58/8) 0 (0) 9.6 4 (33) 3 (25) 1 (8) 2 (17) 1.7/1.7 1 (8) 5.9 78.50/82.11
4 (33) 3/1 (25/8) 1 (8) 5.3 1 (8) 1 (8) 3 (25) 4 (33) 1.8/1.3 0 (0) 2.4 82.64/82.11
12 10/2 1 7.5† 5 4 4 6 1.7/1.5† 1 4.2 80.57/82.11†
no
no
no
* Dg = diagnosis; FU = follow-up. † Mean values. ‡ The clinically important difference value was published by authors of the PedsQL 4.0 normative data (Varni et al., 2003). It describes the standard error of measurement and was derived by multiplying the standard deviation of 1-alpha (Cronbach’s alpha reliability coefficient) of the normative data. Transformed to the PedsQL 4.0 scores, it describes the minimal difference between a patient’s score and the normative data that has a probability of less than 5% of being coincidental.
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1) pA WHO I; 2) recurrent pA WHO I 1) pA WHO I; 2) recurrent pA WHO I 1) pA WHO I; 2) recurrent pA WHO I; 3) recurrent pA WHO I pA WHO I 1) AC WHO II; 2) recurrent AC WHO II; 3) recurrent AC WHO IV GG WHO I AGG WHO III
2: 4 yrs, M
abnormal motor de velopment
Initial Symptoms TR
Surgery
C5–6 & T2–3
HB WHO I
CH WHO I
11: 18 yrs, M
12: 13 yrs, M
C3–5
T8–L1 C6–T10
T8–10 T6–12
incidental (cutaneous TR lesions)
RT no
Chemo
Remarks
no
no
no
yes no
no yes
no
no
yes yes
no yes
von Hippel-Lindau disease, un der surveillance secondary kyphosis after lam inectomy
rare case of AGG —
— rare case of AGG
no no nonresponder to QOL mailing 1) no; 2) yes; 1) yes; 2) no; malignant transformation, death 3) no 3) no at 84 mos after Dg
1) no; 2) yes possible recurrence, under sur veillance no —
severe spasticity, intrathecal baclofen therapy in evalua tion 1) no; 2) yes 1) yes; 2) no proton beam RT
no
1) PR; 2) PR; no 3) PR
1) TR; 2) TR
PR, S 1) B, PR, & S; 2) PR & S; 3) PR scoliosis PR paraparesis, gait dis- PR turbance back pain at night TR scoliosis, gait distur- PR bance paresthesias TR
T8–11 scoliosis 1) T9–11; 2) T8–12; gait disturbance 3) L4–S1
nuchal pain, gait dis turbance 1) T8–12; 2) T8–12; leg paresis 3) T8–12
1) C3–6; 2) C2–7
1) C3–T2; 2) C3–T2 nuchal pain, torticollis 1) PR; 2) PR
T1–4
Spinal Level
9: 14 yrs, F AGG WHO III 10: 30 mos, M GNT
7: 13 yrs, F 8: 19 mos, M
5: 11 yrs, M 6: 3 yrs, M
4: 8 yrs, M
3: 6 yrs, M
pA WHO I
Histological Dg
1: 3 yrs, M
Case No.: Age at Dg, Sex
1
1
1 2
1 3
1 1
2
1
3
3
1
1
1 2
1 1
2 —
2
1
2
3
at FU
mMS Score at Dg
* AC = astrocytoma; AGG = anaplastic ganglioglioma; B = biopsy; CH = cavernous hemangioma; Chemo = chemotherapy; GG = ganglioglioma; GNT = glioneuronal tumor; HB = hemangioblastoma; pA = pilocytic astrocytoma; PR = partial resection; RT = radiotherapy; S = correction of scoliosis; TR = total resection; — = not applicable.
Other
GG
AC
Tumor
TABLE 4: Clinical features and individual PedsQL 4.0 data*
Quality of life in pediatric IMSCT
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C. Schneider et al. vidual patients, including histological diagnosis, initial symptoms, spinal level of tumor occurrence, and treatment regimen as well as mMS scores and PedsQL 4.0 scores for each patient (Table 5). For some of the PedsQL 4.0 subscores, a clinically important difference was noted in individual patients (Table 5), but these small differences did not affect overall QOL scores in the whole group (Figs. 1–3). Figure 1 compares data from the normal collective with data in all patients with IMSCTs across the PedsQL 4.0 scores for CSR and PPR. There was no statistically significant difference between the study cohort and the normal sample population. When the patients were stratified into low-grade (Fig. 2) and high-grade (Fig. 3) groups, there was only one significant difference—in the physical functioning subscore of the CSR, not the PPR, indicating a slightly worse physical functioning situation in the low-grade group. When performing the power calculation, assuming the
clinically important difference as the minimal difference and the predefined level of significance of a = 5%, the following statements can be made: For the CSR total score, a sample size of 57 patients would be needed to reach a power of 0.8, and for the PPR total score, a sample size of 78 patients would be needed to reach a power of 0.8.
Discussion
Regarding the demographics of and histological diagnoses in the patients in this study, the findings were about as expected in the low-grade group. Pilocytic astrocytomas are the tumors most commonly found in the pediatric population. They can recur, and patients with such a recurrence usually undergo a second surgery and/ or receive adjuvant treatment. Based on original data presented by Constantini in 2000 and confirmed by McGirt in 2008, subtotal resection is oncologically sufficient for long-term survival, and thus adjuvant treatment would
TABLE 5: Individual PedsQL 4.0 data in 12 patients with with IMSCTs* PedsQL 4.0 Data Case No.
Age at QOL Assessment (yrs)
Scale
CSR
1
13
2
9
3
11
4
19
5 6 7
— — 14
8
7
9
14
75.21 68.75 81.67 79.59 87.50 71.67 93.34 100.00 86.67 57.50 50.00 65.00 — — 71.15 65.63 76.67 72.29 81.25 63.33 92.50 75.32 92.50
10
3
11
24
12
15
TS PH PsH TS PH PsH TS PH PsH TS PH PsH — — TS PH PsH TS PH PsH TS PH PsH TS PH PsH TS PH PsH TS PH PsH
— 87.09 75.32 92.50 75.32 65.63 85.00
Clinically Important Difference† PPR — 74.68 84.36 65.00 95.00 100.00 90.00 — — — — 93.54 93.75 93.33 — 72.50 62.50 82.50 — —
CSR yes yes no no no yes no no no yes yes yes — — yes yes no yes no yes no yes no — no no no yes yes no
PPR — yes no yes no no no — — — — no no no — yes yes no — —
* PH = Physical Health Score; PsH = Psychosocial Health Score; TS = Total Score. † See Table 3 footnote for explanation.
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Quality of life in pediatric IMSCT
Fig. 1. Comparison of PedsQL 4.0 scores in all patients with IMSCTs (gray) and in a healthy population (black). Left: Child Self Report. Right: Parent Proxy Report. No significant difference was demonstrated between the two groups.
be the exception rather than the rule.7,18 It must be noted that every other patient in this series—even those with a low-grade tumor—received adjuvant treatment. This high proportion of patients with adjuvant treatment is amplified by the occurrence of 2 cases of a particularly rare tumor type, the anaplastic ganglioglioma in the highgrade group.23 The occurrence of these rare tumors in our cohort may be due to a referral bias of complex cases to the senior author. The role of adjuvant radiotherapy is debated. It must be noted that in retrospective studies, there is some evidence of prolonged progression-free and overall survival, especially in high-grade IMSCTs and in ependymomas.3,11,13,24 A series of publications have already reported good outcomes (using the mMS) and determined the safety and efficacy of the best possible microsurgical tumor removal
with the aid of intraoperative neurophysiological monitoring.1,2,5–8,12,14,17,18,21,25 No significant overall impact on reported QOL can be measured using the PedsQL 4.0 when comparing children with IMSCT and a healthy collective. There is only one minor exception to this conclusion: in the physical health item of the CSR score in the low-grade subgroup (Fig. 2), the t-test revealed a significant impact of the disease at an error level of 5%. This significance disappeared when combining CSR and PPR in this group. However, this finding indicates a potential tendency for the physical health item to be the first to be affected by IMSCT surgery if a larger patient group could be studied. A 2009 Canadian study by Scheinemann et al., including 29 patients with low-grade spinal cord gliomas and a mean follow-up of 8.2 years, reported an 83% rate
Fig. 2. Comparison of PedsQL 4.0 scores in patients with a low-grade IMSCT (gray) and in a healthy population (black). Left: Child Self Report. Right: Parent Proxy Report. Asterisk indicates the subscore with a significant (p < 0.05) difference between patients and the normal collective (physical health in the CSR form).
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Fig. 3. Comparison of PedsQL 4.0 scores in patients with a high-grade IMSCT (gray) and in a healthy population (black). Left: Child Self Report. Right: Parent Proxy Report. No significant difference was demonstrated between the two groups.
of significant neurological and orthopedic sequelae.22 Even though these authors did not report a formal QOL assessment, the data indicated either the possibility of later deterioration or some other bias in the patient group as determined by disease, surgery, or adjuvant treatment. Particularly, late spinal deformities can occur after multilevel laminectomies.19,32 The retrospective nature, small patient group, referral bias, group inhomogeneity, and high number of patients needed to reach a power of 0.8 are certainly weaknesses of this study. To include 50–70 patients is impossible, as these cases are simply not treated within a reasonable time frame given the low incidence of the disease. That is precisely one important reason to use a standardized and validated instrument to assess a multidimensional issue such as QOL to compare even a small patient group with a healthy collective and still have a meaningful study design with known numerical power. Such an assessment has not been reported. Since the value of surgery for diagnosis and its documented oncological benefit are established, no prospective study comparing surgery with adjuvant treatments is conceivable. Therefore, particular aspects of treatment, such as QOL in the present report, must be studied in other ways. Comparing the study cohort—with its common denominator of surgical treatment—with a normal sample appeared to be logical. It is somewhat surprising that no differences were found in the QOL of patients compared with that in the normal collective. With a serious disease and a serious operation as in IMSCTs, it would have been intuitively obvious to expect a less than normal QOL. Furthermore, the study cohort was fixed by the surgery, which all patients had in common. And the fact that many patients underwent additional treatments, which may well have adversely affected QOL, did not push the results toward a worse status. It is possible though that in a larger study population, a small impact on QOL data would have reached statistical significance, as delineated in the power calculation. 176
Moreover, there may be a proxy bias. Parents sometimes take great efforts to obtain specialized surgical treatment, even abroad, and may tend to have a more positive view of their children’s QOL status. It is also very probable that patients with a long interval from diagnosis to QOL assessment report a better clinical status (a “happy to have survived” bias). Finally, the high response rate for a questionnairebased mail-in study is unusual.26 It may be explained by the close interaction among patients, families, and caregivers for the management of a complex condition.
Conclusions
In children with surgically treated IMSCT, QOL measured with the PedsQL 4.0 is not different from that in a healthy collective after a mean follow-up of 4.2 years. This conclusion is drawn with an awareness of the small patient group, but still is an encouraging finding and can be emphasized when surgery is discussed with patients and parents confronted with this disorder. Acknowledgment The authors thank Ms. Vanessa Martel from the MAPI Research Trust for providing the PedsQL 4.0 questionnaire in different translations and her support in scoring the instrument. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Schneider, Hidalgo, Kothbauer. Acquisition of data: Schneider. Analysis and interpretation of data: Schneider, Schmitt-Mechelke, Kothbauer. Drafting the article: Schneider, Kothbauer. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Schneider. Statistical analysis: Schneider. Administrative/technical/ material support: all authors. Study supervision: Kothbauer.
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Manuscript submitted July 9, 2013. Accepted November 18, 2013. Parts of this material were presented in abstract and poster form at the 2nd Congress of the Swiss Federation of Clinical Neuro-Socie ties held in Montreux, Switzerland, on June 5–7, 2013. Please include this information when citing this paper: published online December 20, 2013; DOI: 10.3171/2013.11.PEDS13346. Address correspondence to: Christian Schneider, M.D., Division of Neurosurgery, Cantonal Hospital of Lucerne, 6000 Lucerne 16, Switzerland. email: [email protected].
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