Discussion
Whilst most relapsed CNS germinomas can be salvaged, relapsed CNS NG-GCTs have a much worse prognosis8,11,12. There is no international consensus on salvage therapy for relapsed CNS NG-GCT and there are relatively few published case series with limited and heterogeneous cases13. Murray et al.15 reported a cohort of 32 relapsed CNS NG-GCT patients with a 5-year overall survival (OS) of 9% (95%CI: 2-26). Of the 16 patients who received high dose chemotherapy (HDC) and ASCT, 13 died (range 3-35 months), one was alive with stable disease (at 88 months follow-up), and another 2 survivors were disease-free. Interestingly, these 2 patients were the only ones who received irradiation after HDC and ASCT. Similarly, Callec et al.13 reported a retrospective multicenter study of 25 patients with relapsed CNS NG-GCT showing a 5-year OS of 72% (95%CI: 46-87) for patients who received HDC and 29% (95%CI: 4-61) for those who didn’t (P=0.006). These observations and others have led the Third International CNS Germ Cell Tumor Symposium to recommend HDC, surgery, and irradiation, if feasible, for the management of relapsed CNS NG-GCTs16.
Elevated serum AFP at initial diagnosis (>1000 ng/ml) was incorporated as a poor prognostic factor in the SIOP CNS GCT II trial (NCT01424839), following results of the SIOP CNS GCT 96 showing that among 19 patients with AFP >1000 ng/ml the 5-year progression-free survival (PFS) was 32% compared to 130 patients with AFP <1000 ng/ml, who had a 5-year EFS of 76%17. As a result of that, the SIOP CNS GCT II trial incorporated an experimental arm with two cycles of conventional PEI followed by 2 cycles of high-dose PEI with ASCT. The results of this trial have not been published at the time of this report.
As per the latest CCLG guidelines18, management of relapsed CNS NG-GCT includes conventional dose platinum-based chemotherapy, which may either be PEI, Carboplatin/Etoposide or Gemcitabine/Paclitaxel/Oxaliplatin. This should be followed by surgical resection, if feasible, then high dose carboplatin, etoposide and thiotepa followed by ASCT. Irradiation should then be considered as consolidation.
This case also illustrates the importance of close surveillance with tumour markers for early detection of recurrences in secreting GCTs, since the low volume of disease at the time of recurrence is likely to have played a role in his favourable long-term outcome. Additionally, our case could receive CSI because he had only had focal radiotherapy at initial diagnosis. However, those cases with metastatic disease at initial diagnosis who receive CSI upfront would not have this choice in case of a metastatic relapse. Of note, whilst this case was salvaged, this young man has to deal with with a number of late effects, including poor memory, cataracts, and hearing loss requiring hearing aids. Although he is able to live an independent live, the late effects associated with this intensive treatment should not be overlooked.
Relapsed CNS NG-GCTs have a dismal prognosis. Notwithstanding, this case with relapsed metastatic pineal YST illustrates the importance of close surveillance with tumour markers and that it is possible to achieve long-term survival with multimodal treatment, including induction chemotherapy, high dose chemotherapy with ASCT, and radiotherapy.