Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study

Hiroyuki Shimizu MD, Kazuya Motomura MD, PhD, Fumiharu Ohka MD, PhD, Kosuke Aoki MD, PhD, Kuniaki Tanahashi MD, PhD, Masaki Hirano MD, PhD, Lushun Chalise MD, PhD, Tomohide Nishikawa MD, Junya Yamaguchi MD, Jun Yoshida MD, PhD, Atsushi Natsume MD, PhD and Toshihiko Wakabayashi MD, PhD
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  • Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan
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OBJECTIVE

The current study aimed to evaluate the treatment outcomes and toxicities of patients with intracranial germ cell tumors (GCTs).

METHODS

This study retrospectively included 110 consecutive patients (70 patients in the germinomatous group and 40 patients in the nongerminomatous GCT [NGGCT] groups) receiving surgery, platinum-based chemotherapy, and radiotherapy for newly diagnosed primary intracranial GCTs. In the authors’ protocol, patients with GCTs were further divided into the following four groups: the germinomatous group and the NGGCT groups (mature teratoma, intermediate prognosis, or poor prognosis).

RESULTS

The median overall survival (OS) and progression-free survival (PFS) rates of the patients in the germinomatous group were significantly higher than those in the NGGCT group (p < 0.001). The 5-, 10-, and 20-year OS rates in the germinomatous group were 97.1%, 95.7%, and 93.2%, respectively, with a median follow-up of 11.0 years. On the contrary, the 5-, 10-, and 20-year OS rates in the NGGCT group were 67.3%, 63.4%, and 55.4%, respectively. The 5-, 10-, and 20-year PFS rates were 91.4%, 86.6%, and 86.6%, respectively, in the germinomatous group, whereas those of the NGGCT group were approximately 67.4%, 60.2%, and 53.5%, respectively. Based on the four types of classification in our study, the 5-, 10-, and 20-year OS rates in the NGGCT intermediate prognosis group were 78.9%, 71.8%, and 53.8%, respectively. On the contrary, the 3- and 5-year OS rates in the NGGCT poor prognosis group were 42.9% and 34.3%, respectively. Moreover, toxicities with the treatment of intracranial GCTs were found to be tolerable in the present study population. The multivariate survival models for OS in the NGGCT intermediate prognosis and poor prognosis groups demonstrated that only the alpha-fetoprotein status was significantly associated with worsened OS (HR 3.88, 95% CI 1.29–11.66; p = 0.02).

CONCLUSIONS

The authors found that platinum-based chemotherapy and radiotherapy result in favorable survival outcomes in patients with germinomatous GCTs. Clinical outcomes were still unfavorable in the NGGCT intermediate prognosis and poor prognosis groups; therefore, a new protocol that increases the survival rate of patients belonging in both groups should be considered.

ABBREVIATIONS AFP = alpha-fetoprotein; β-hCG = beta–human chorionic gonadotropin; CBDCA+VP-16 = carboplatin and etoposide; CDDP+VP-16 = cisplatin and etoposide; GCT = germ cell tumor; GTR = gross-total resection; ICE = carboplatin, etoposide, and ifosfamide; NGGCT = nongerminomatous GCT; OS = overall survival; PFS = progression-free survival; STGC = syncytiotrophoblastic giant cell; TICS-J = Japanese version of the Telephone Interview for Cognitive Status.

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Contributor Notes

Correspondence Kazuya Motomura: Nagoya University School of Medicine, Nagoya, Japan. kmotomura@med.nagoya-u.ac.jp.

INCLUDE WHEN CITING Published online October 2, 2020; DOI: 10.3171/2020.6.JNS20638.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

  • 1

    Brain Tumor Registry of Japan (2005–2008). Neurol Med Chir (Tokyo). 2017;57(1 Suppl):9102.

  • 2

    Ostrom QT, Cioffi G, Gittleman H, CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012–2016. Neuro Oncol. 2019;21(suppl 5):v1v100.

    • Search Google Scholar
    • Export Citation
  • 3

    McCarthy BJ, Shibui S, Kayama T, Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries. Neuro Oncol. 2012;14(9):11941200.

    • Search Google Scholar
    • Export Citation
  • 4

    Louis DN, Ohgaki H, Wiestler OD, The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97109.

    • Search Google Scholar
    • Export Citation
  • 5

    Louis DN, Perry A, Reifenberger G, The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803820.

    • Search Google Scholar
    • Export Citation
  • 6

    Murray MJ, Bartels U, Nishikawa R, Consensus on the management of intracranial germ-cell tumours. Lancet Oncol. 2015;16(9):e470e477.

  • 7

    Dufour C, Guerrini-Rousseau L, Grill J. Central nervous system germ cell tumors: an update. Curr Opin Oncol. 2014;26(6):622626.

  • 8

    Kong Z, Wang Y, Dai C, Central nervous system germ cell tumors: a review of the literature. J Child Neurol. 2018;33(9):610620.

  • 9

    Matsutani M. Combined chemotherapy and radiation therapy for CNS germ cell tumors—the Japanese experience. J Neurooncol. 2001;54(3):311316.

    • Search Google Scholar
    • Export Citation
  • 10

    Aoyama H, Shirato H, Ikeda J, Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors. J Clin Oncol. 2002;20(3):857865.

    • Search Google Scholar
    • Export Citation
  • 11

    Bouffet E, Baranzelli MC, Patte C, Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Société Française d’Oncologie Pédiatrique. Br J Cancer. 1999;79(7–8):11991204.

    • Search Google Scholar
    • Export Citation
  • 12

    Matsutani M, Sano K, Takakura K, Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg. 1997;86(3):446455.

    • Search Google Scholar
    • Export Citation
  • 13

    Calaminus G, Kortmann R, Worch J, 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. Neuro Oncol. 2013;15(6):788796.

    • Search Google Scholar
    • Export Citation
  • 14

    Acharya S, DeWees T, Shinohara ET, Perkins SM. Long-term outcomes and late effects for childhood and young adulthood intracranial germinomas. Neuro Oncol. 2015;17(5):741746.

    • Search Google Scholar
    • Export Citation
  • 15

    Foo AS, Lim C, Chong DQ, Primary intracranial germ cell tumours: experience of a single South-East Asian institution. J Clin Neurosci. 2014;21(10):17611766.

    • Search Google Scholar
    • Export Citation
  • 16

    Kochi M, Itoyama Y, Shiraishi S, Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors. J Neurosurg. 2003;99(1):106114.

    • Search Google Scholar
    • Export Citation
  • 17

    Cheng S, Kilday JP, Laperriere N, Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation. J Neurooncol. 2016;127(1):173180.

    • Search Google Scholar
    • Export Citation
  • 18

    Kanamori M, Kumabe T, Saito R, Optimal treatment strategy for intracranial germ cell tumors: a single institution analysis. J Neurosurg Pediatr. 2009;4(6):506514.

    • Search Google Scholar
    • Export Citation
  • 19

    Yoshida J, Sugita K, Kobayashi T, Prognosis of intracranial germ cell tumours: effectiveness of chemotherapy with cisplatin and etoposide (CDDP and VP-16). Acta Neurochir (Wien). 1993;120(3-4):111117.

    • Search Google Scholar
    • Export Citation
  • 20

    Konagaya Y, Washimi Y, Hattori H, Validation of the telephone interview for cognitive status (TICS) in Japanese. Int J Geriatr Psychiatry. 2007;22(7):695700.

    • Search Google Scholar
    • Export Citation
  • 21

    Fetcko K, Dey M. Primary central nervous system germ cell tumors: a review and update. Med Res Arch. 2018;6(3):1719.

  • 22

    Kawabata Y, Takahashi JA, Arakawa Y, Long term outcomes in patients with intracranial germinomas: a single institution experience of irradiation with or without chemotherapy. J Neurooncol. 2008;88(2):161167.

    • Search Google Scholar
    • Export Citation
  • 23

    Jennings MT, Gelman R, Hochberg F. Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg. 1985;63(2):155167.

  • 24

    Calaminus G, Frappaz D, Kortmann RD, Outcome of patients with intracranial non-germinomatous germ cell tumors—lessons from the SIOP-CNS-GCT-96 trial. Neuro Oncol. 2017;19(12):16611672.

    • Search Google Scholar
    • Export Citation
  • 25

    Goldman S, Bouffet E, Fisher PG, Phase II trial assessing the ability of neoadjuvant chemotherapy with or without second-look surgery to eliminate measurable disease for nongerminomatous germ cell tumors: a Children’s Oncology Group study. J Clin Oncol. 2015;33(22):24642471.

    • Search Google Scholar
    • Export Citation
  • 26

    Packer RJ, Gurney JG, Punyko JA, Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: childhood cancer survivor study. J Clin Oncol. 2003;21(17):32553261.

    • Search Google Scholar
    • Export Citation
  • 27

    Takada A, Ii N, Hirayama M, Long-term follow-up of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumor. J Neurosurg Pediatr. 2018;23(3):317324.

    • Search Google Scholar
    • Export Citation
  • 28

    Lee DS, Lim DH, Kim IH, Upfront chemotherapy followed by response adaptive radiotherapy for intracranial germinoma: prospective multicenter cohort study. Radiother Oncol. 2019;138:180186.

    • Search Google Scholar
    • Export Citation
  • 29

    Al-Hussaini M, Sultan I, Abuirmileh N, Pineal gland tumors: experience from the SEER database. J Neurooncol. 2009;94(3):351358.

  • 30

    Fukushima S, Otsuka A, Suzuki T, Mutually exclusive mutations of KIT and RAS are associated with KIT mRNA expression and chromosomal instability in primary intracranial pure germinomas. Acta Neuropathol. 2014;127(6):911925.

    • Search Google Scholar
    • Export Citation
  • 31

    Fukushima S, Yamashita S, Kobayashi H, Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol. 2017;133(3):445462.

    • Search Google Scholar
    • Export Citation

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