Utility of Long-Term Surveillance Neuroimaging Five Years Post-Diagnosis in the Management of Pediatric Brain Tumours

  

    
LGG    (N=77) 
    
MB    (N=12) 
    
EP    (N=4) 
    
PNET    (N=1) 
    
Total    (N=94) 
  
  

    
Age    at diagnosis (years; mean ± 95% CI) 
    
8.1 ±    1.1 
    
11.5 ±    3.3 
    
12.5 ±    10.0 
    
10 
    
8.4 ±    1.0 
  
  

    
Sex 
  
  

    
Male 
    
33 (43%) 
    
9 (75%) 
    
3 (75%) 
    
1 (100%) 
    
46 
  
  

    
Female 
    
44 (57%) 
    
3 (25%) 
    
1 (25%) 
    
0 
    
48 
  
  

    
Extent    of Surgical Resection* 
  
  

    
Gross    total resection 
    
35 (45%) 
    
7 (58%) 
    
2 (50%) 
    
1 (100%) 
    
45 (48%) 
  
  

    
Subtotal    resection (>75%) 
    
8 (10%) 
    
2 (17%) 
    
1 (25%) 
    
0 
    
11 (12%) 
  
  

    
Partial    resection 
    
12 (16%) 
    
2 (17%) 
    
1 (25%) 
    
0 
    
15 (16%) 
  
  

    
Biopsy* 
    
3 (4%) 
    
0 
    
0 
    
0 
    
3 (3%) 
  
  

    
No    surgical intervention 
    
19 (25%) 
    
1 (8%) 
    
0 
    
0 
    
20 (21%) 
  
  

    
Relapse 
    
(N=13) 
    
(N=0) 
    
(N=0) 
    
(N=0) 
    
(N=13) 
  
  

    
Time    to relapse (years; mean ± 95% CI) 
    
3.2 ±    1.7 
    
N/A 
    
N/A 
    
N/A 
    
3.2 ±    1.7 
  
  

    
No.    relapse 5 years post Dx 
    
2 
    
N/A 
    
N/A 
    
N/A 
    
2 
  
  

    
Vascular    abnormalities (Cavernomas) 
    
(N=3) 
    
(N=5) 
    
(N=0) 
    
(N=1) 
    
(N=9) 
  
  

    
Time    to diagnosis (years; mean ± 95% CI) 
    
12.3 ±    6.9 
    
16.4 ±    3.5 
    
N/A 
    
2 
    
13.4 ±    4.2 
  

Table 1: Patient characteristics.

Two patients (15.4% of relapses), one with suprasellar LGG and another with right Optic Pathway Glioma (OPG) progressed after a period of five years from diagnosis. They were both detected clinically. Patient one, initially treated with subtotal surgical resection, presented at 12 years from initial diagnosis, with a two-week history of severe headaches four months prior to their yearly surveillance MRI. An MRI done at the time and six months later confirmed progression of LGG. The patient was treated with vinblastine monotherapy for 70 weeks and since has stable disease with no recurrence of symptoms four years later. Patient two, who was initially treated with vincristine and carboplatin, was also being followed with yearly surveillance MRIs. This patient presented at five-and-a-half years from initial diagnosis with deterioration in vision along with diplopia and nystagmus. These symptoms were noted one month prior to the next scheduled neuroimaging. An urgent MRI confirmed progression of LGG. The patient was also treated with vinblastine monotherapy for 70 weeks following which she has stable disease and stable vision two years later.

11 patients were diagnosed with vascular abnormalities during follow-up. Nine patients had radiation-induced Cavernous Malformations (CM), while two patients were diagnosed with developmental venous anomaly. CM was diagnosed incidentally in all patients during routine surveillance neuroimaging. The latency interval between radiation treatment and the detection of CM was 13.4 ± 4.2 years (range: 2-22 years). Six patients had multiple lesions. Majority of patients (67%) with CM had an underlying diagnosis of MB/PNET, while the remaining 33% had LGGs (who were treated with radiation).

Discussion

In this study, we investigated patients diagnosed with LGG, MB, PNET or EP to assess the incidence of recurrences, progressions and vascular abnormalities five years from diagnosis and their primary mode of detection, whether clinical or radiologic. The observed rate of recurrences and progressions among LGG patients of 17% was comparable to published literature [6-10]. Furthermore, the incidence of recurrences and progressions five years from diagnosis of 2.6% observed in this study was in accordance previous reports. In a study describing relapses amongst children with low-grade astrocytoma, 2.1% of patients (one cerebellar and two midline in location) relapsed after five years from diagnosis. Their mode of detection, however, clinical or radiologic, was not described [8]. Another study investigating recurrence in low-grade pediatric brain tumours reported diagnosing one asymptomatic patient (1.5%) on routine surveillance neuroimaging 10 years from diagnosis [9]. However, it is difficult to ascertain whether the patient’s outcome would be different if they were diagnosed with clinical symptoms. In our study, despite routine surveillance neuroimaging, both patients presented with clinical symptoms between their scheduled MRI scans. Also, their outcomes were not compromised due to diagnosis by clinical symptoms. Our data, thus, questions the utility of routine surveillance neuroimaging after five years from diagnosis in LGG patients if regular clinical follow-up and contact is maintained.

vascular abnormalities five years from diagnosis and their primary mode of detection, whether clinical or radiologic. The observed rate of recurrences and progressions among LGG patients of 17% was comparable to published literature [6-10]. Furthermore, the incidence of recurrences and progressions five years from diagnosis of 2.6% observed in this study was in accordance previous reports. In a study describing relapses amongst children with low-grade astrocytoma, 2.1% of patients (one cerebellar and two midline in location) relapsed after five years from diagnosis. Their mode of detection, however, clinical or radiologic, was not described [8]. Another study investigating recurrence in low-grade pediatric brain tumours reported diagnosing one asymptomatic patient (1.5%) on routine surveillance neuroimaging 10 years from diagnosis [9]. However, it is difficult to ascertain whether the patient’s outcome would be different if they were diagnosed with clinical symptoms. In our study, despite routine surveillance neuroimaging, both patients presented with clinical symptoms between their scheduled MRI scans. Also, their outcomes were not compromised due to diagnosis by clinical symptoms. Our data, thus, questions the utility of routine surveillance neuroimaging after five years from diagnosis in LGG patients if regular clinical follow-up and contact is maintained. diagnosed with clinical symptoms had a 12-times greater risk of death in that particular cohort [12]. In another series of 159 children with CNS tumours, ependymoma patients (19 children) were the only group that showed improved outcome when recurrences were identified by surveillance rather than symptoms [13]. Hence, there is adequate evidence in literature to support routine surveillance neuroimaging of EP patients even after five years from diagnosis.

In this study, the observed rate of radiation-associated CM was 9.6%, of which the majority was found in MB/PNET patients, likely a function of prior irradiation and not tumour type. In a recent study investigating the natural history of radiation-associated vascular abnormalities, 34% of patients were diagnosed with CMs. Notably, a majority of their cohort (54.6%) was comprised of MB patients and did not include any LGG patients. While none of the patients experienced symptoms from CM or had hemorrhage in this study, one of 34 patients had extra-lesional hemorrhage, diagnosed clinically due to new-onset headaches [14]. In another study examining cavernous malformations in children and young adults, the hemorrhage rate for incidentally discovered asymptomatic CM was very low at 0.2% per patient-year [15]. Given such low likelihood of secondary complications (i.e. hemorrhage), asymptomatic discovery of CMs does not seem to warrant routine surveillance neuroimaging.

Surveillance neuroimaging poses extensive costs and undue burden on the individual and the health care system. First, the institutional cost of neuroimaging per recurrence at five years is estimated to be $104,094 [9]. Second, the patients and families experience significant anxiety around the timing of neuroimaging. Third, there are added risks of general anesthetic for the younger patients who require sedation.

The limitations of our study include its retrospective design and prolonged time period over which patients were treated. This may have introduced treatment bias from evolving adjuvant chemotherapy and radiotherapy. Furthermore, our study lacks a central imaging review as well as a central pathological review to confirm the exact histopathological diagnoses. Therefore, our conclusions require validation in larger scale studies with even longer follow-up as the nature of some of these pathologies may make early conclusions about disease recurrence or progression spurious.

Conclusion

This study provides precursory evidence for further investigation into the utility of routine surveillance neuroimaging in LGG patients after five years from diagnosis. There is clearly a need for a larger prospective study in patients with LGG and other CNS tumours to decisively determine the value, timing and frequency of long-term surveillance neuroimaging.

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