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.