SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease

Abstract

Background. We conducted a nonrandomized international study for intracranial germinoma that compared chemotherapy followed by local radiotherapy with reduced-dose craniospinal irradiation (CSI) alone, to determine whether the combined treatment regimen produced equivalent outcome and avoided irradiation beyond the primary tumor site(s). Methods. Patients with localized germinoma received either CSI or 2 courses of carboplatin and etoposide alternating with etoposide and ifosfamide, followed by local radiotherapy. Metastatic patients received CSI with focal boosts to primary tumor and metastatic sites, with the option to be preceded with chemotherapy. Results. Patients with localized germinoma (n ¼ 190) received either CSI alone (n ¼ 125) or combined therapy (n ¼ 65), demonstrating no differences in 5-year event-free or overall survival, but a difference in progression-free survival (0.97 + 0.02 vs 0.88 + 0.04; P ¼ .04). Seven of 65 patients receiving combined treatment experienced relapse (6 with ventricular recurrence outside the primary radiotherapy field), and only 4 of 125 patients treated with CSI alone experienced relapse (all at the primary tumor site). Metastatic patients (n ¼ 45) had 0.98 + 0.023 event-free and overall survival. Conclusions. Localized germinoma can be treated with reduced dose CSI alone or with chemotherapy and reduced-field radiotherapy. The pattern of relapse suggests inclusion of ventricles in the radiation field. G erminomas contribute to about 60% of all intracranial germ cell tumors located in the pineal gland, suprasellar region, basal ganglia, and hypothalamus.1 Intracranial germinomas are highly radiosensitive, with a tendency to spread via cerebrospinal fluid (CSF), and systemic craniospinal radiation therapy has been the standard treatment for many decades.2,3 With this treatment approach, the majority of patients have been cured. 4 Concerns have long been raised about the potential adverse effects of radiotherapy.4 -6 Therefore, other treatment approaches were introduced to evaluate craniospinal irradiation alone, but with reduced doses, compared with previous practice, or chemotherapy either in combination with radiotherapy or alone. 7,8 In the German MAKEI 89 trial, 30 Gy were applied to the craniospinal axis (CSI) with an additional tumor boost of 15 Gy. 9 With this regimen, 88% of the patients remained relapse-free at 5 years. In 1990, the French Society of Paediatric Oncology initiated a trial using chemotherapy and local field radiotherapy in localized germinomas with favorable results. 10 In 1998, Matsutani et al 11,12 reported excellent survival for germinomas treated with surgery, followed by extended field or whole brain radiotherapy. Patients who received chemotherapy before reduced radiotherapy (30 Gy) were all alive at a median follow-up of 4.3 years. Aoyama et al 13 presented promising excellent results in a second Japanese series including 16 germinomas treated with surgery, followed by chemotherapy and low-dose involved-field radiotherapy. Approaches using c...

Cerebral germinoma revealed through a polydipsic polyuric syndrome in a 10-year-old girl: case report

“…Th ey occur mostly in the testes (25%), ovaries (25%), sacrococcygeal region (20%), and the central nervous system (20%) (Calaminus et al 2013). Th e germ cell tumors of the central nervous system are rare and usually arise from the midline structures (Hayashi et al 2009).…”

“…As illustrated by our observation, the young girl presented low levels of TSH, GH, cortisol, and ADH, which can be explained by a compression of the infundibulum, stalk and/or pituitary gland by the tumor. Regarding the diff erential diagnosis, some authors have described pubertal delay due to the hypogonadism and hyperprolactinemia (Echevarria et al 2008). However, the tumor can also lead to an early onset of puberty (before 8 years for girls).…”

“…It may be a non-specifi c marker of malignancy. A mild elevation of β-HCG has been noted in the syncytiotrophoblastic form of the germinoma (Echevarria et al 2008). Increased alfafetoprotein levels may indicate the presence of cancer, most commonly liver cancer, cancer of the ovary, or the germ cell tumor.…”

Treatment Outcome in Patients with Primary Central Nervous System Germ Cell Tumour: Clinical Experience from a Regional Cancer Centre in North India

“…The authors concluded that reduced-volume radiotherapy plus boost should replace CSI when a radiotherapy-only approach is used in patients with intracranial germinoma [20] . In the SIOP CNS GCT 96 trial, reduced-dose CSI (24 Gy in 15 fractions over 3 weeks) followed by local boost (16 fractions over 2 weeks) or chemotherapy (4 cycles of alternating carboplatin, etoposide and ifosfamide, etoposide) followed by local radiotherapy (40 Gy in 25 fractions over 5 weeks) led to equivalent 5-year overall and event-free survival in patients with localized germinoma [21] . However, a high incidence of ventricular relapse outside the primary radiation field in patients receiving local RT (9.2%) underlines the necessity of including the entire ventricular system in the radiation portal and whole ventricular RT (24 Gy in 15 fractions over 3 weeks) followed by local boost (16 Gy in 10 fractions over 2 weeks in patients with partial response or stable disease after pre-irradiation chemotherapy) is currently being evaluated in patients with localized germinoma in the SIOP CNS GCT II study [6,21] .…”

Proton Radiotherapy for Childhood Tumors: an Overview of Early Clinical Results

“…Chemotherapy followed by local irradiation showed promising results in early institutional trials, [21,22]. However, recent publications have demonstrated a high risk of ventricular relapse [23,24] and therefore WVRT remains a component of treatment when chemotherapy is also used. For patients with disseminated disease, CSI is standard.…”