In present study, we firstly found that there was more desmoplastic nodular medulloblastoma cases (20.9%) in patients < 3 years (Fig. 1 and Table 1), however, which is lower than 44% in the previous reports . Secondly, radiation was less frequently applied in patients < 3 years, which is consistent to the clinical practice of reduced or delayed application of radiation in those patients due to concerns of neurocognitive impairment [19, 20]. Thirdly, we identified that patients < 3 years was really in high risk compared to patients ≥ 3 years with lower 6-month, 1-year, 3-year and 5-year survival rate. Differential epidemiological characteristics, such as age and histology, and application of radiation as shown in Table 1 might account for survival difference between patients < 3 years old and ≥ 3 years old. Indeed, before use of CSI, medulloblastoma remains incurable in older children even with GTR [4, 21].
In the literature, the benefit of GTR remains controversial. Albright et al  and Zeltzer et al  reported survival benefit of GTR over PR or biopsy in patients > 3 years old, however, no significance was found in Akyuz’s study with patients age of 0 to 18 years old  and in Evans’s study with patients age of 2 to 16 years old . The above studies implied that age might affect significance of GTR in survival. In a large retrospective study, Thompson et al found significant interaction between age and extent of resection, however, they did report overall and progress-free survival benefit of GTR compared to near total resection and subtotal resection in patients < 3 years old . Notably, the prognostic benefit of increased extent of resection was attenuated when molecular subgroup affiliation is taken into account . Similarly, the present study demonstrated that GTR did not confer OS and PFS benefit in patients < 3 years old (Table 2). However, GTR showed OS benefit but no PFS benefit in ≥ 3 years old group (Table 3).
It is well established that radiation alone could largely improve patient perspective and cure the disease [4, 21]. Early studies elicited that chemotherapy alone could prolong tumor free survival in younger children less than 18 months of age . For those patients aged < 5 years old, Grill et al proved that conventional chemotherapy alone was sufficient to cure patients who had GTR, but not those with incompletely resection or metastatic medulloblastoma . The present study identified that chemotherapy but not radiation significantly improved OS and PFS in younger patients < 3 years old (Table 2), however, the OS and PFS benefit of chemotherapy and radiation was inverted in those patients ≥ 3 years old (Table 3). Different sensitivity of histological subtypes to chemotherapy might account for the difference between patients < 3 years old and ≥ 3 years old [23, 24], since there are more desmoplastic nodular medulloblastoma cases in < 3 years old patients. Furthermore, in those patients ≥ 3 years old and underwent surgical procedures, the benefit of radiation alone largely depends on the extent of resection (Tables 4 and 5). It is worth noting that adjuvant radiation together with chemotherapy largely improves patient outcome even in those underwent partial resection (Tables 4 and 5).
With the introduction of molecular diagnosis by the 2016 WHO classification of central nervous system tumor , different molecular subtype and origin of medulloblastoma determine the sensitivity to chemo-, radio- or targeting therapy [4, 5, 26, 27]. Hence, pathological diagnosis from surgical procedures is highly recommended in the treatment of pediatric medulloblastoma. Due to apparent reasons, the epidemiology of molecular subtype and its impact on the outcome of pediatric medulloblastoma is out of the scope of the study.
Due to limited cases, we were unable to further investigate the survival benefit of radiation and chemotherapy in medulloblastoma patients less than 3 years old who received biopsy, PR or GTR. Also, the study is subject to inherent limitations of retrospective study. The treatment patterns might vary from each patient and doctor, and the “standard” treatments including radio- and chemo- therapy differ from each year or each version of guideline. Moreover, the further details of radiation or chemotherapy are largely unknown and might impact the results of present studies and cause bias.
Notwithstanding these limitations, data from present study demonstrates that the extent of surgical resection confer overall survival benefit in those ≥ 3 years old patients but not in those < 3 years old. Chemotherapy shows OS and PFS benefit in those ≥ 3 years old patients but not in those < 3 years old, however, radiation shows inverted effect between those two populations. Moreover, adjuvant radiation plus chemotherapy largely is the most effective adjuvant treatment for those underwent tumor resection. In conclusion, the extent of resection should be differentially considered and applied between pediatric medulloblastoma patients < 3 years old and ≥ 3 years old, so are the adjuvant treatments.