Journal of Neuro-Oncology

, Volume 116, Issue 3, pp 617–623 | Cite as

Surveillance imaging in children with malignant CNS tumors: low yield of spine MRI

  • Sébastien Perreault
  • Robert M. Lober
  • Anne-Sophie Carret
  • Guohua Zhang
  • Linda Hershon
  • Jean-Claude Décarie
  • Hannes Vogel
  • Kristen W. Yeom
  • Paul G. Fisher
  • Sonia Partap
Clinical Study

Abstract

Magnetic resonance imaging (MRI) is routinely obtained in patients with central nervous system (CNS) tumors, but few studies have been conducted to evaluate this practice. We assessed the benefits of surveillance MRI and more specifically spine MRI in a contemporary cohort. We evaluated MRI results of children diagnosed with CNS tumors from January 2000 to December 2011. Children with at least one surveillance MRI following the diagnosis of medulloblastoma (MB), atypical teratoid rhabdoid tumor (ATRT), pineoblastoma (PB), supratentorial primitive neuroectodermal tumor, supratentorial high-grade glioma (World Health Organization grade III–IV), CNS germ cell tumors or ependymoma were included. A total of 2,707 brain and 1,280 spine MRI scans were obtained in 258 patients. 97 % of all relapses occurred in the brain and 3 % were isolated to the spine. Relapse was identified in 226 (8 %) brain and 48 (4 %) spine MRI scans. The overall rate of detecting isolated spinal relapse was 9/1,000 and 7/1,000 for MB patients. MRI performed for PB showed the highest rate for detecting isolated spinal recurrence with 49/1,000. No initial isolated spinal relapse was identified in patients with glioma, supratentorial primitive neuroectodermal tumor and ATRT. Isolated spinal recurrences are infrequent in children with malignant CNS tumors and the yield of spine MRI is very low. Tailoring surveillance spine MRI to patients with higher spinal relapse risk such as PB, MB with metastatic disease and within 3 years of diagnosis could improve allocation of resources without compromising patient care.

Keywords

MRI imaging Brain neoplasms Child Childhood medulloblastoma Pineoblastoma Primitive neuroectodermal tumor 

Introduction

Standard care for patients with central nervous system (CNS) tumors now includes surveillance neuro-imaging and clinical evaluations at regular interval. Magnetic resonance imaging (MRI) has become the modality of choice over the last two decades due to relative high-resolution images and increased accessibility. However, there is no consensus on the optimal frequency of surveillance MRI. Furthermore, the benefits of including spine MRI as part of surveillance remains controversial, even for highly malignant tumors such as medulloblastoma (MB) [1]. Therefore, current practice varies considerably between providers, institutions and protocols. Since most studies on surveillance imaging were conducted between 1980 and 2000, a period during which various changes were made with regards to treatment and MRI application, we evaluated the utility of surveillance MRI in children with CNS malignant tumors in a recent cohort.

Methods

After approval by the institutional review board, we retrospectively identified a cohort of children diagnosed with malignant CNS tumors from January 2000 to December 2011 at two pediatric neuro-oncology centers. The study included patients of 21 years of age or less who underwent at least one surveillance MRI. Patients with a diagnosis of MB, atypical teratoid rhabdoid tumor (ATRT), pineoblastoma (PB), supratentorial primitive neuroectodermal tumor (sPNET), supratentorial high-grade glioma (World Health Organization [WHO] grade III–IV), or CNS germ cell tumor and ependymoma (WHO II and III) were included. Patients were included regardless of their treatment. Patients with a malignant CNS tumor involving only the spine at diagnosis were excluded. Clinical characteristics, including age at diagnosis and relapse, tumor type, overall survival, relapse or progression time and site were recorded.

The total number of brain and spine MRI per patients was calculated. Brain and spine MRI studies conducted within a week to each other were considered as combined study. All MRI with report or clinical note suggesting relapses were individually reviewed to confirm the recurrence. Relapse was defined as the detection of a new lesion, new leptomeningeal disease, or a significant increase (more than 25 %) in size of a previously known lesion. When tumor recurrence was equivocal, relapse was confirmed by radiological follow-up, clinical evolution, and, when possible, pathology reports from relapse surgery. Patients were categorized as symptomatic if they had new symptoms or new clinical signs at the time of their MRI, and as asymptomatic if there was no apparent change in their clinical status.

Statistical analyses were performed using the Fisher’s exact test two-tailed and unpaired t test. Survival was calculated by the Kaplan–Meier made curves and comparisons were conducted using the log-rank (Mantel Cox) test. p values of <0.05 were considered significant for this study. SPSS Statistics, version 20.0 (IBM, Armonk, NY) was used for all analyses.

Results

At total of 258 patients met inclusion criteria, with median age 8 years (range 0.3–21 years). 159 (62 %) patients were male and 99 (38 %) were female. Patients with MB represented the largest population in the cohort comprising 89 patients (34 %), followed by ependymomas (20 %), germ cell tumors (15 %), gliomas (13 %), sPNET (10 %), ATRT (4 %) and PB (4 %) (Table 1). During the observation period, a total of 2,707 brain MRI and 1,280 spine MRI exams were conducted (Table 1). Since all spine MRI were conducted at the same time or within a week after brain MRI, 1,280 were considered combined. On average, a patient underwent 10 (range 1–40) brain MRI and 3 (range 0–25) spine MRI exams with an average of 7.5 spine MRIs for MB and less than one spine MRI for glioma patients (p < 0.001).
Table 1

Patient demographics and total number of MRIs obtained

 

Total

High grade glioma

Ependymoma

Germ cell

MB

sPNET

ATRT

PB

Number of patients

N = 258

N = 34

N = 52

N = 39

N = 89

N = 25

N = 10

N = 9

Brain MRI obtained

2,707

245

565

433

990

313

64

97

Spine MRI obtained

1,280

35

92

126

758

185

23

61

Median # of brain MRI per patient (range)

10 (1–40)

6 (1–18)

10 (1–34)

12 (2–30)

11 (1–25)

11 (1–40)

4 (2–18)

10 (5–19)

Median # of spine MRI per patient (range)

3 (0–25)

0 (0–5)

1 (1–11)

3 (0–12)

7.5 (1–25)

6 (0–19)

3 (1–4)

6 (1–15)

Age at dx (years)

        

 Median

8

11

3.5

13.7

7.3

5.6

1.3

9.7

 Range

0.3–21

0.8–17.8

0.3–17.3

5.9–19.8

0.9–21

2.3–18.4

0.8–5.2

3.5–18.9

Total follow-up (months)

       

 Median

37.5

15

47.5

51

52

45

6.5

25

 Range

(1.5–142)

(1.5–133)

(6–133)

(2–151)

(3–142)

(3–137)

(2–65)

(4–96)

MB medulloblastoma, sPNET supratentorial primitive neuroectodermal tumor, ATRT atypical teratoid/rhabdoid tumor, PB pineoblastoma, # numbers, N number of patients

Detection rate of relapse

A total of 226 brain MRI and 48 spine MRIs identified relapse with a detection rate of 8 and 4 % respectively. Glioma was associated with the highest rate of relapse detected by brain MRI at 22 %, and germ cell tumors showed the lowest rate at 2 % (p < 0.0001). With regards to spinal relapse, PB had the highest yield at 20 % for detection rate of spinal relapse and sPNET the lowest at 2 % (p < 0.0001). Of 1,280 spine MRI exams conducted, 12 exams identified isolated spinal relapse, with a detection rate of 9/1,000. For MB, 5 of 758 spine MRI exams identified isolated spinal relapse with a detection rate of 7/1,000. PB had the highest detection rate at 49/1,000. No isolated spinal recurrence was identified by surveillance spine MRI in patients with sPNET and ATRT (Table 2).
Table 2

Surveillance MRI identifying relapse

 

Total

High grade glioma

Ependymoma

Germ cell

MB

sPNET

ATRT

PB

Identification of relapse

        

 Brain MRI

        

  N (%)

226 (8.3)

53 (21.6)

64 (11.3)

9 (2.1)

51 (5.2)

33 (10.5)

7 (10.9)

9 (9.3)

 Spine MRI

        

  N (%)

48 (3.8)

4 (11.4)

4 (4.3)

3 (2.4)

19 (2.5)

3 (1.6)

3 (13)

12 (19.7)

 Spine MRI onlya

        

  N (%)

12 (0.9)

1 (2.8)

1 (1.1)

2 (1.6)

5 (0.7)

0 (0)

0 (0)

3 (4.9)

MB medulloblastoma, sPNET supratentorial primitive neuroectodermal tumor, ATRT atypical teratoid/rhabdoid tumor, PB pineoblastoma, N number of MRI, (%) percentage of MRI identifying relapse

aIsolated spinal relapses identified on spine MRI

Site of relapse

Of 258 patients, 113 (44 %) had at least one relapse (Table 3). High-grade glioma patients had the highest relapse rate (82 %), compared to other tumor types (p < 0.0001). Out of 113 initial relapses, 77 % involved the brain only, 16 % the brain and spine and 7 % of relapses involved only the spine (Table 3). No patient with glioma, sPNET and ATRT had an isolated spinal relapse at first recurrence. In contrast, all PB had relapses that involved the spine and 40 % had isolated spinal recurrence. Out of the four patients with MB and isolated spine relapses, two of them had metastases at diagnosis. One patient had classic MB without metastasis and received dose-reduced craniospinal radiation. One patient with a subtotal resection of posterior fossa ependymoma relapsed with an isolated spinal lesion. Finally, one patient with a germinoma had an isolated relapse in the cervical spinal cord.
Table 3

Site of relapses

 

Total

High grade glioma

Ependymoma

Germ cell

MB

sPNET

ATRT

PB

First relapse (N)

113

28

26

9

27

14

4

5

 Site of relapse (%)

        

  Brain only

77.3

89.3

88.5

77.8

59.3

100

50

0

  Brain/spine

15.9

10.7

7.7

11.1

25.9

0

50

60

  Spine only

6.8

0

3.8

11.1

14.8

0

0

40

All relapse (N)

238

54

65

11

56

33

7

12

 Site of relapse (%)

        

  Brain only

81.5

92.5

93.9

72.7

66.1

90.9

57.1

0

  Brain/Spine

15.1

5.5

4.6

9.1

25

9.1

42.9

75

  Spine only

3.4

2.0

1.5

18.2

8.9

0

0

25

Time to relapse (months)

       

 Median

12

10.5

16

38

16

11.5

5.5

20

 Range

(0.3–137)

(0.8–38)

(1–65)

(1–137)

(0.5–76)

(0.3–54)

(5–9)

(11–30)

 >90 % of relapse (months)

34

27

36

97

26

29

9

30

MB medulloblastoma, sPNET supratentorial primitive neuroectodermal tumor, ATRT atypical teratoid/rhabdoid tumor, PB pineoblastoma, N number of patient

Similar results were observed when considering all relapses (total 238). One patient with a known relapse of metastatic glioma had a further progression identified only in the spine; none of the patients with sPNET and ATRT had an isolated relapse occurring in the spine. Relapsed PB was associated with spinal involvement in all cases, with a quarter involving the spine only and detected by spinal MRI.

Timing of relapse

Relapses usually occurred during the first year with a median time of 12 months (range 0.3–137 months). Ninety percent of relapses occurred within 34 months (Table 3). Median time to relapse was significantly different between tumors type (p < 0.001). Germ cell tumors had the longest median time to relapse with 38 months and ATRT the shortest with 5.5 months. Median time to relapse in patients with isolated spinal recurrence was 23 months (range 9–137). Except for the one patient with germinoma, all other patients presented their spinal relapse within 3 years.

Clinical features

In 14 (12 %) patients clinical status at relapse was unknown whereas in 99 the information could be retrieved. At initial relapse, 52 patients (46 %) were asymptomatic, compared with 47 patients (42 %) who were symptomatic (Appendix 1 in Electronic Supplementary Material). Only one patient out of 12 (8 %) with isolated spinal recurrence was clearly symptomatic and complained about leg pain. Nine were asymptomatic and in two patients with isolated spinal recurrence no information was available. Patients who were symptomatic did not have a longer interval since their last MRI (mean 3.9 vs 4.8 months, p = 0.14), nor did they have earlier relapses (median time to relapse 12 vs 11 months, p > 0.8) or worse outcome when compared to asymptomatic patients (median overall survival 23 vs 27 months, p > 0.3). Patients with glioma more frequently had symptoms than those with other tumor types (68 vs 38 %, respectively, p < 0.003).

Management

After their first relapse, 67 (59 %) patients underwent new treatments: chemotherapy (29 including 4 high-dose chemotherapy with autologous stem-cell support), surgery (6), radiosurgery (2), radiation therapy (7) and multimodal therapy (23). In 18 patients the decision was made to transition toward palliative care, 12 patients continued with treatment, eight were followed with closer interval MRI, and in eight patients no clear information on management could be found.

Discussion

This study demonstrates that the vast majority of relapses are detected on brain MRI and that the overall detection rate of isolated spinal relapses is extremely low. The benefits of spine surveillance MRI depend on tumor type and specific risk characteristics. Few studies on surveillance neuro-imaging of CNS tumors have been conducted. Most have limited their evaluation to MB, and included patients who underwent MRI but also CT-scans or even myelography [2, 3]. Several studies have reported that relapses were associated with symptoms [3, 4, 5]. Saunders et al. [6] observed that only 19.6 % of patients were asymptomatic at relapse. In our cohort, most initial recurrences were actually asymptomatic (46 %). This discrepancy could be explained by differences in imaging modalities, as all the patients in the current study underwent MRI which can detect tumor progression earlier than CT-scan and myelography before the patient becomes symptomatic [7].

While surveillance MRI now allows early detection of relapse, some authors have argued that the clinical benefits are marginal [1]. In our cohort, most relapse detection led to a change in patient management and, in more than half of the cases, a direct intervention was made. Patients with relapse can also be eligible for experimental treatment (phase I or II studies) when no standard curative treatment exists.

Even though surveillance neuro-imaging with scheduled MRI is now integrated to clinical and research practice, the rate of relapse detection is generally low. Two prior studies based on a heterogeneous population of low grade CNS tumors and CT imaging reported relapse detection rates of 1.59 and 2.8 % [5, 8]. In our study, the overall detection rate of relapse was higher at 8 % for brain MRI and 4 % for spine MRI. This can partly be explained by the exclusion of WHO grade I tumors that have a lower rate of recurrence [5].

Since the vast majority of relapses had intracranial progression (97 %) and isolated spinal relapses were rare, the benefit of surveillance spine MRI is low. Bartels et al. conducted a study were they evaluated the yield of spinal MRI for MB and sPNET patients treated with CSI [1]. In their cohort of 73 patients from 1985 to 2004 no isolated spinal recurrence was detected, in accordance with two previous reports [6, 9], and therefore they questioned the usefulness of spinal MRI in this population. In our study, we did observe five cases of isolated spinal relapse or progression in patients with MB. Even though MB represent 42 % of isolated spinal relapses in our study, the detection rate was very low (7/1,000) due to the large number of spine MRI exams conducted as part of their neuro-imaging surveillance. Limiting spinal surveillance MRI to the first 3 years for patients without risk factors such as spinal metastasis at the time of diagnosis could possibly increase the detection rate. Yao et al. [10] observed a low incidence of isolated spinal relapse (2 %) in patients without metastasis at diagnosis, in contrast to those with positive CSF fluid and/or metastasis at diagnosis (9 %). One of the patients who received low dose craniospinal radiation had an isolated spinal relapse, suggesting that patients who received dose reduced radiation might be at higher risk and may benefit from surveillance spine MRI.

The majority of high-grade gliomas relapse locally [11, 12]. Spinal metastasis is rare and has been reported to occur in 0.4–2 % of adult patients with glioblastoma. This percentage might be higher in children. Heideman et al. reported that nine (26 %) patients out of 41 high-grade glioma had disseminated disease at relapse. Of those, three (7 %) had isolated spinal recurrence [13]. Another study observed isolated spinal relapse in 6 % of their cohort [14]. While some experts have recommended conducting regular spine surveillance MRI in patient with high-grade glioma, data from different studies including ours does not support this practice [15].

In a study on sPNET without metastasis at diagnosis, Hong et al. [16] reported a treatment failure rate of 48 %, with 42 % involving the primary site and only 3 % with isolated CSF and/or spinal relapse. Timmermann et al. [17] reported similar findings, in which sPNET patients had 35 (92 %) relapses involving the primary site. Only four patients developed isolated distant metastases, all of which had metastatic disease at time of diagnosis. Those reports are similar to our observations which suggest that sPNET relapse locally and the benefit of conducting regular spine MRI is low. Limited data are available with regards to relapses pattern of PB. Spinal relapses have been described but most studies reported patients who did not undergo spine MRI at the time of recurrence [18, 19]. Despite the small number of patients with PB, our study supports the use of spine MRI in patients with PB since all had involvement of the spine at relapse and 40 % had isolated spinal recurrence.

Among our small cohort of ATRT patients, we observed that half failed locally and half had a diffuse leptomeningeal relapse. Similarly, Chi et al. [20] reported that out of eight patients, three failed locally, two had distant metastases and three had disseminated disease. In a meta-analysis including ATRT patients, 42 patients (58 %) had diffuse leptomeningeal relapse involving the spine and three (4 %) appears to have presented isolated spinal relapse [21]. However, due to a heterogeneous population and imaging modalities conclusion on the benefice of spine MRI is limited for ATRT patient. As observed previously and demonstrated in our study, ATRT relapsed within 3 years [20]. Therefore, spine surveillance MRI after 3 years may not be useful.

Most ependymomas and germ cell tumors relapse locally, and as such, we observed a low detection rate of isolated spinal relapse (1 and 2 %, respectively). The benefits therefore, appear low but based on the current literature, the usefulness of surveillance spine MRI in this population remains unclear. Messahel et al. studied more than 100 cases of relapsed pediatric ependymomas and reported that 84 % had local progression at time of relapse. In their study, isolated spinal relapses represent 5 % of treatment failure. It is, however, unknown if those patients had metastatic disease or positive cerebrospinal fluid cytology at diagnosis [22]. Spinal relapse in germ cell tumors is rare but has been described. In a study including 60 patients, one had an isolated spinal relapse [23]. Kamoshima et al. [24] reported a series of 25 patients with relapsed germ cell tumors, six had isolated spinal relapse and the latest relapse occurred 109 months after diagnosis. They, therefore, recommended performing yearly brain and spine for at least 10 years.

Given the rarity of ATRT and PB, our sample size is small and limits the extend of our conclusion. Despite this, our study offers valuable information. In the context where detection rate of isolated spinal relapse is very low, systematic use of brain and spine MRI as part of surveillance neuro-imaging may be carefully considered. Financial impacts on health care system and individual are not negligible as a brain combined with a spine MRI can cost up to three times more than a brain MRI. The cost of a brain and spine MRI can vary from 1,000 USD to 30,000 USD depending on the institution not including anesthesia. Furthermore, long scan times (90 min) of combined brain and spinal MRI could increase risk of patient motion, particularly during the contrast-portion that occurs at the end of the study. Risks associated with sedation during an MRI study is generally low, but complication range from drowsiness in 20 % of children in the following days to more serious complications such as cardio-pulmonary arrest [25]. Concerns have also been raised with regards to sedation and possible long-term cognitive sequelae in young children undergoing anesthesia [26]. Based on our study, selecting high-risk patient groups could improve the yield of surveillance spine MRI without compromise in identifying relapse. Patients with PB, patients with metastasis at diagnosis, and patients within 3 years of tumor diagnosis could benefit from surveillance spine MRI. However, blanket spine surveillance MRI in all patients with CNS tumors, particularly those with a diagnosis of high-grade gliomas and sPNET, may not be efficacious. In these cases, a brain MRI could be conducted followed by a spine MRI if an intracranial recurrence is identified.

Conclusion

Our study demonstrates the utility of surveillance MRI in detecting isolated spinal relapse in asymptomatic patients is low. Based on our findings, a subset of patients with PB and MB with metastatic disease and within 3 years of initial tumor diagnosis may benefit most from routine surveillance spine MRI. However, routine spine surveillance MRI of all patients with CNS tumors, and in particular, those with high-grade glioma and sPNET, may not be warranted. In this group, spinal MRI could be considered in the event an intracranial recurrence is detected by surveillance brain MRI. Tailoring surveillance spine MRI to patients with higher spinal relapse risk could improve allocation of resources and reduce iatrogenic risks without compromising patient care.

Notes

Acknowledgments

Sébastien Perreault is a Beverly and Bernard Wolfe Pediatric Neuro-Oncology fellow at Lucile Packard Children’s Hospital at Stanford University. He received Grants from Justine Lacoste Fundation and Fonds de Recherche en Santé du Québec (FRSQ) (Bourses de formation en recherche post-diplôme professionnel/Fellowship).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11060_2013_1347_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 12 kb)

References

  1. 1.
    Bartels U, Shroff M, Sung L et al (2006) Role of spinal MRI in the follow-up of children treated for medulloblastoma. Cancer 107:1340–1347PubMedCrossRefGoogle Scholar
  2. 2.
    Torres CF, Rebsamen S, Silber JH et al (1994) Surveillance scanning of children with medulloblastoma. N Engl J Med 330:892–895PubMedCrossRefGoogle Scholar
  3. 3.
    Yalcin B, Buyukpamukcu M, Akalan N et al (2002) Value of surveillance imaging in the management of medulloblastoma. Med Pediatr Oncol 38:91–97PubMedCrossRefGoogle Scholar
  4. 4.
    Minn AY, Pollock BH, Garzarella L et al (2001) Surveillance neuroimaging to detect relapse in childhood brain tumors: a Pediatric Oncology Group study. J Clin Oncol 19:4135–4140PubMedGoogle Scholar
  5. 5.
    Steinbok P, Hentschel S, Cochrane DD, Kestle JR (1996) Value of postoperative surveillance imaging in the management of children with some common brain tumors. J Neurosurg 84:726–732PubMedCrossRefGoogle Scholar
  6. 6.
    Saunders DE, Hayward RD, Phipps KP et al (2003) Surveillance neuroimaging of intracranial medulloblastoma in children: how effective, how often, and for how long? J Neurosurg 99:280–286PubMedCrossRefGoogle Scholar
  7. 7.
    Seute T, Leffers P, ten Velde GP, Twijnstra A (2008) Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI). Cancer 112:1827–1834PubMedCrossRefGoogle Scholar
  8. 8.
    Kovanlikaya A, Karabay N, Çakmakçi H et al (2003) Surveillance imaging and cost effectivity in pediatric brain tumors. Eur J Radiol 47:188–192PubMedCrossRefGoogle Scholar
  9. 9.
    Brand WN, Schneider PA, Tokars RP (1987) Long-term results of a pilot study of low dose cranial-spinal irradiation for cerebellar medulloblastoma. Int J Radiat Oncol Biol Phys 13:1641–1645PubMedCrossRefGoogle Scholar
  10. 10.
    Yao MS, Mehta MP, Boyett JM et al (1997) The effect of M-stage on patterns of failure in posterior fossa primitive neuroectodermal tumors treated on CCG-921: a phase III study in a high-risk patient population. Int J Radiat Oncol Biol Phys 38:469–475PubMedCrossRefGoogle Scholar
  11. 11.
    Uehara K, Sasayama T, Miyawaki D et al (2012) Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index. Radiat Oncol 7:104PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Sherriff J, Tamangani J, Senthil L et al (2013) Patterns of relapse in glioblastoma multiforme following concomitant chemoradiotherapy with temozolomide. Br J Radiol 86:20120414PubMedCrossRefGoogle Scholar
  13. 13.
    Heideman RL, Kuttesch J Jr, Gajjar AJ et al (1997) Supratentorial malignant gliomas in childhood: a single institution perspective. Cancer 80:497–504PubMedCrossRefGoogle Scholar
  14. 14.
    Vaidya SJ, Hargrave D, Saran F et al (2007) Pattern of recurrence in paediatric malignant glioma: an institutional experience. J Neurooncol 83:279–284PubMedCrossRefGoogle Scholar
  15. 15.
    Grabb PA, Albright AL, Pang D (1992) Dissemination of supratentorial malignant gliomas via the cerebrospinal fluid in children. Neurosurgery 30:64–71PubMedCrossRefGoogle Scholar
  16. 16.
    Hong TS, Mehta MP, Boyett JM et al (2004) Patterns of failure in supratentorial primitive neuroectodermal tumors treated in Children’s Cancer Group Study 921, a phase III combined modality study. Int J Radiat Oncol Biol Phys 60:204–213PubMedCrossRefGoogle Scholar
  17. 17.
    Timmermann B, Kortmann RD, Kuhl J et al (2002) Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol 20:842–849PubMedCrossRefGoogle Scholar
  18. 18.
    Jakacki RI, Zeltzer PM, Boyett JM et al (1995) Survival and prognostic factors following radiation and/or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a report of the Childrens Cancer Group. J Clin Oncol 13:1377–1383PubMedGoogle Scholar
  19. 19.
    Friedrich C, von Bueren AO, von Hoff K et al (2013) Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy. Neuro Oncol 15:224–234PubMedCrossRefGoogle Scholar
  20. 20.
    Chi SN, Zimmerman MA, Yao X et al (2009) Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27:385–389PubMedCrossRefGoogle Scholar
  21. 21.
    Athale UH, Duckworth J, Odame I, Barr R (2009) Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J Pediatr Hematol Oncol 31:651–663PubMedCrossRefGoogle Scholar
  22. 22.
    Messahel B, Ashley S, Saran F et al (2009) Relapsed intracranial ependymoma in children in the UK: patterns of relapse, survival and therapeutic outcome. Eur J Cancer 45:1815–1823PubMedCrossRefGoogle Scholar
  23. 23.
    Alapetite C, Brisse H, Patte C et al (2010) Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience. Neuro Oncol 12:1318–1325PubMedCentralPubMedGoogle Scholar
  24. 24.
    Kamoshima Y, Sawamura Y, Ikeda J et al (2008) Late recurrence and salvage therapy of CNS germinomas. J Neurooncol 90:205–211PubMedCrossRefGoogle Scholar
  25. 25.
    Edwards AD, Arthurs OJ (2011) Paediatric MRI under sedation: is it necessary? What is the evidence for the alternatives? Pediatr Radiol 41:1353–1364PubMedCrossRefGoogle Scholar
  26. 26.
    Mellon RD, Simone AF, Rappaport BA (2007) Use of anesthetic agents in neonates and young children. Anesth Analg 104:509–520PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sébastien Perreault
    • 1
    • 7
  • Robert M. Lober
    • 2
  • Anne-Sophie Carret
    • 8
  • Guohua Zhang
    • 8
  • Linda Hershon
    • 8
  • Jean-Claude Décarie
    • 9
  • Hannes Vogel
    • 3
  • Kristen W. Yeom
    • 4
  • Paul G. Fisher
    • 1
    • 2
    • 5
    • 6
  • Sonia Partap
    • 1
  1. 1.Division of Child Neurology, Department of Neurology, Lucile Packard Children’s Hospital at StanfordStanford UniversityPalo AltoUSA
  2. 2.Department of Neurosurgery, Lucile Packard Children’s Hospital at StanfordStanford UniversityPalo AltoUSA
  3. 3.Department of Pathology, Lucile Packard Children’s Hospital at StanfordStanford UniversityPalo AltoUSA
  4. 4.Department of Radiology, Lucile Packard Children’s Hospital at StanfordStanford UniversityPalo AltoUSA
  5. 5.Department of Pediatrics, Lucile Packard Children’s Hospital at StanfordStanford UniversityPalo AltoUSA
  6. 6.Department of Human Biology, Lucile Packard Children’s Hospital at StanfordStanford UniversityPalo AltoUSA
  7. 7.Division of NeurologyCHU Sainte-JustineMontrealCanada
  8. 8.Division of Hematology-OncologyCHU Sainte-JustineMontrealCanada
  9. 9.Department of RadiologyCHU Sainte-JustineMontrealCanada

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