Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors: Long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy

Pediatr Blood Cancer. 2017 Nov;64(11). doi: 10.1002/pbc.26637. Epub 2017 Jul 11.

Abstract

Purpose: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs).

Materials and methods: We retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014.

Results: Thirty-four patients received induction chemotherapy followed by radiation with or without surgery. Median follow-up was 11.1 years (0.8-23.3). Outcomes were significantly improved in these 34 patients (5-year overall survival [OS]: 88% versus 50%, P = 0.0092), so analysis is restricted to that subset. Disease-free survival (DFS) was 67, 60, and 54% at 5, 10, and 15 years, respectively. Elevated cerebrospinal fluid-α-fetoprotein (CSF-AFP) at diagnosis was associated with poorer DFS (37 vs. 89% at 10 years; P = 0.01). There was no statistically significant difference in OS, or DFS, or patterns of failure for limited radiotherapy volumes versus larger volumes; however, patients receiving initial local radiotherapy had 32% distant central nervous system (CNS) recurrence at 10 years compared to 0% for those receiving initial larger field irradiation (P = 0.09). Fifteen patients recurred. All four patients who relapsed in the spine had received local radiotherapy and had elevated serum and CSF-AFP at baseline. All three patients with ventricular relapse received local radiation therapy.

Conclusions: NGGCT patients continue to relapse beyond 5 years. Late ventricular relapse occurred even in patients without clear evidence of germinoma component. Elevated CSF-AFP at diagnosis is associated with poor DFS and risk for distant CNS relapse. Patients with residual radiographic disease after chemotherapy or residual malignant histologies after second-look surgery have inferior outcomes. Our data support consideration of treatment intensification for these patients.

Keywords: extensive radiotherapy; germ cell tumor; local radiotherapy; nongerminomatous germ cell tumor; radiotherapy.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / cerebrospinal fluid
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation / standards*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Neoplasm Staging
  • Neoplasms, Germ Cell and Embryonal / cerebrospinal fluid
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Neoplasms, Germ Cell and Embryonal / therapy*
  • Prognosis
  • Radiotherapy Dosage
  • Retrospective Studies
  • Second-Look Surgery
  • Survival Rate
  • Young Adult
  • alpha-Fetoproteins / cerebrospinal fluid

Substances

  • alpha-Fetoproteins