Treatment and outcomes of UK and German patients with relapsed intracranial germ cell tumors following uniform first-line therapy

We aimed to retrospectively assess treatments/outcomes, including the value of high-dose-chemotherapy and autologous-stem-cell-rescue (HDC+AuSCR) and re-irradiation, in a large, European patient-cohort with relapsed intracranial germ-cell-tumors (GCTs) receiving uniform first-line therapy, including radiotherapy as standard-of-care. Fifty-eight UK/German patients (48 male/10 female) with relapsed intracranial-GCTs [13 germinoma/45 non-germinomatous GCT (NGGCT)] treated 1996-2010 as per the SIOP-CNS-GCT-96 protocol were evaluated. For germinoma, six patients relapsed with germinoma and five with NGGCT (one palliative, one teratoma patient excluded). Five-year overall-survival (OS) for the whole-group (n=11) was 55%. Four of six germinoma relapses and two of five relapsing with NGGCT were salvaged; patients were salvaged with either standard-dose-chemotherapy (SDC) and re-irradiation or HDC+AuSCR with/without re-irradiation. Of 45 relapsed NGGCT patients, 13 were excluded (three non-protocol adherence, five teratoma, five palliation). Five-year OS for the remaining 32 relapsed malignant NGGCT patients treated with curative intent was 9% (95%CI: 2-26%). By treatment received, 5-year OS for the 10 patients receiving SDC and 22 patients treated with intention for HDC+AuSCR was 0% (0-0%) and 14% (3-36%), respectively. The three relapsed NGGCT survivors had raised HCG markers alone; two received additional irradiation. Patients with relapsed germinoma had better 5-year OS than those with relapsed NGGCT (55 vs. 9%; p=0.007). Patients with relapsed germinoma were salvaged both with SDC and re-irradiation or HDC+AuSCR with/without re-irradiation; both represent valid treatment options. Outcomes for malignant relapse following initial diagnosis of NGGCT were exceptionally poor; the few survivors received thiotepa-based HDC+AuSCR, which is a treatment option at first malignant relapse for such patients, with further surgery/irradiation where feasible. What's new? What's the optimal approach to treating a certain type of relapsed brain tumor? The authors looked at a rare type of cancer called intracranial germ cell tumors (GCTs), which fall into two categories, germinomas and non-germinomatous tumors. They evaluated data from 58 European patients, the largest cohort of relapsed GCTs studied to date, all of whom received uniform first-line treatment. Patients with relapsed germinoma could survive after standard-dose chemotherapy with additional radiotherapy or high-dose chemotherapy plus autologous-stem-cell-rescue (HDC + AuSCR), with or without additional radiotherapy. Those who relapsed with non-germinomatous GCTs had a poor prognosis; only those receiving HDC + AuSCR had any possibility of cure.