Early outcomes and patterns of failure following proton therapy for nonmetastatic intracranial nongerminomatous germ cell tumors

Pediatr Blood Cancer. 2018 Jun;65(6):e26997. doi: 10.1002/pbc.26997. Epub 2018 Jan 30.


Background: Although dosimetric comparisons demonstrate the advantage of proton therapy (PT) over conventional radiotherapy for nongerminomatous germ cell tumors (NGGCT), clinical outcome data for this rare tumor are lacking. We sought to evaluate outcomes for children with NGGCT treated with PT.

Methods: Between 2007 and 2016, 14 children (median age 11, range, 5-19 years) with nonmetastatic NGGCT were treated with PT after induction chemotherapy. Most (8/14) were mixed germ cell. Five of 14 patients had complete resection of their primary tumor before radiation. Off study, eight patients received 36 Gy (RBE [relative biological effectiveness]) craniospinal irradiation (CSI). On study, two patients received 30.6 Gy (RBE) whole-ventricle irradiation and four received focal radiation alone. All patients received a total dose of 54 Gy (RBE) to the tumor/tumor bed.

Results: At a median follow-up of 2.8 years, all patients were alive with no local recurrences. Three-year progression-free survival was 86%. Both metastatic recurrences occurred in patients treated with focal radiation alone; one with an immature teratoma developed an isolated spinal recurrence 5 months after treatment. Another with a mixed germ cell tumor developed a multifocal ventricular and shunt tract recurrence 7 months after treatment. Serious toxicity was minimal, including cataracts and hormone deficiency, and limited to children who received CSI.

Conclusion: Early outcomes in children treated for NGGCT suggest the high conformality of PT does not compromise disease control and yields low toxicity. This pattern of failure data adds to growing evidence suggesting chemotherapy followed by focal radiotherapy alone is inadequate in controlling localized NGGCT.

Keywords: central nervous system; choriocarcinoma; embryonal carcinoma; germ cell; neoplasms; pediatric; proton therapy; radiation oncology; teratoma; yolk sac tumor.

MeSH terms

  • Adolescent
  • Adult
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cranial Irradiation / mortality*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / radiotherapy
  • Neoplasms, Germ Cell and Embryonal / mortality*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Neoplasms, Germ Cell and Embryonal / radiotherapy
  • Prognosis
  • Proton Therapy / mortality*
  • Radiotherapy Dosage
  • Retrospective Studies
  • Survival Rate
  • Testicular Neoplasms / mortality*
  • Testicular Neoplasms / pathology
  • Testicular Neoplasms / radiotherapy
  • Treatment Failure
  • Young Adult

Supplementary concepts

  • Nonseminomatous germ cell tumor