Long-term consequences of residual lesions after chemoradiotherapy in patients with germinoma at onset

Shigeru YamaguchiDepartments of Neurosurgery,

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Michinari OkamotoDepartments of Neurosurgery,

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Yukitomo IshiDepartments of Neurosurgery,

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Ryosuke SawayaDepartments of Neurosurgery,

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Hiroaki MotegiDepartments of Neurosurgery,

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Minako SugiyamaPediatrics,

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Taisuke HaradaDiagnostic Imaging,

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Noriyuki FujimaDiagnostic Imaging,

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Takashi MoriRadiation Oncology, and

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Takayuki HashimotoRadiation Oncology, and

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Emi TakakuwaSurgical Pathology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

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Atsushi ManabePediatrics,

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Kohsuke KudoDiagnostic Imaging,

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Hidefumi AoyamaRadiation Oncology, and

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Miki FujimuraDepartments of Neurosurgery,

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OBJECTIVE

In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis.

METHODS

The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated.

RESULTS

Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion.

CONCLUSIONS

End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.

ABBREVIATIONS

AFP = α-fetoprotein; CBDCA = carboplatin; CDDP = cisplatin; HR = hazard ratio; IFOS = ifosfamide; IGCT = intracranial germ cell tumor; NGGCT = nongerminomatous germ cell tumor; OS = overall survival; PFS = progression-free survival; PLAP = placental alkaline phosphatase; VP-16 = etoposide; β-hCG = β-subunit human chorionic gonadotropin.
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Illustration from Wang et al. (pp 538–546). © Ju-lei Wang, published with permission.

  • 1

    Sawamura Y, Shirato H, Ikeda J, et al. Induction chemotherapy followed by reduced-volume radiation therapy for newly diagnosed central nervous system germinoma. J Neurosurg. 1998;88(1):6672.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Sawamura Y, Ikeda J, Shirato H, Tada M, Abe H. Germ cell tumours of the central nervous system: treatment consideration based on 111 cases and their long-term clinical outcomes. Eur J Cancer. 1998;34(1):104110.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Takami H, Fukuoka K, Fukushima S, et al. Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium. Neuro Oncol. 2019;21(12):15651577.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Byun HK, Yoon HI, Cho J, et al. Optimization of intracranial germinoma treatment: radiotherapy alone with reduced volume and dose. Int J Radiat Oncol Biol Phys. 2020;108(3):657666.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Sawamura Y, de Tribolet N, Ishii N, Abe H. Management of primary intracranial germinomas: diagnostic surgery or radical resection? J Neurosurg. 1997;87(2):262266.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

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

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

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

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Kim CY, Choi JW, Lee JY, et al. Intracranial growing teratoma syndrome: clinical characteristics and treatment strategy. J Neurooncol. 2011;101(1):109115.

  • 9

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

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Kanamori M, Kumabe T, Watanabe M, et al. Indications for salvage surgery during treatment for intracranial germ cell tumors. J Neurooncol. 2018;138(3):601607.

  • 11

    Takami H, Perry A, Graffeo CS, Giannini C, Daniels DJ. Novel diagnostic methods and posttreatment clinical phenotypes among intracranial germ cell tumors. Neurosurgery. 2020;87(3):563572.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Ogiwara H, Kiyotani C, Terashima K, Morota N. Second-look surgery for intracranial germ cell tumors. Neurosurgery. 2015;76(6):658662.

  • 13

    Weiner HL, Lichtenbaum RA, Wisoff JH, et al. Delayed surgical resection of central nervous system germ cell tumors. Neurosurgery. 2002;50(4):727734.

  • 14

    Goldman S, Bouffet E, Fisher PG, et al. 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.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Calaminus G, Kortmann R, Worch J, et al. 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

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

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Okamoto M, Yamaguchi S, Ishi Y, et al. Diagnostic capability of cerebrospinal fluid-placental alkaline phosphatase value in intracranial germ cell tumor. Oncology. 2021;99(1):2331.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Aihara Y, Watanabe S, Amano K, et al. Placental alkaline phosphatase levels in cerebrospinal fluid can have a decisive role in the differential diagnosis of intracranial germ cell tumors. J Neurosurg. 2018;131(3):687694.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Watanabe S, Aihara Y, Kikuno A, et al. A highly sensitive and specific chemiluminescent enzyme immunoassay for placental alkaline phosphatase in the cerebrospinal fluid of patients with intracranial germinomas. Pediatr Neurosurg. 2012;48(3):141145.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Kamoshima Y, Sawamura Y. Update on current standard treatments in central nervous system germ cell tumors. Curr Opin Neurol. 2010;23(6):571575.

  • 21

    Sugiyama K, Arita K, Tominaga A, et al. Morphologic features of human chorionic gonadotropin- or alpha-fetoprotein-producing germ cell tumors of the central nervous system: histological heterogeneity and surgical meaning. Brain Tumor Pathol. 2001;18(2):115122.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

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

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Frappaz D, Dhall G, Murray MJ, et al. EANO, SNO and Euracan consensus review on the current management and future development of intracranial germ cell tumors in adolescents and young adults. Neuro Oncol. 2022;24(4):516527.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Nakagawa K, Aoki Y, Akanuma A, et al. Radiation therapy of intracranial germ cell tumors with radiosensitivity assessment. Radiat Med. 1992;10(2):5561.

  • 25

    Friedman JA, Lynch JJ, Buckner JC, Scheithauer BW, Raffel C. Management of malignant pineal germ cell tumors with residual mature teratoma. Neurosurgery. 2001;48(3):518523.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Khoo B, Ramakonar HH, Robbins P, Honeybul S. Intracranial monodermal teratoma presenting with growing teratoma syndrome. J Surg Case Rep. 2017;2017(5):rjx038.

  • 27

    Tsuyuguchi S, Sugiyama K, Kinoshita Y, et al. Primary and recurrent growing teratoma syndrome in central nervous system nongerminomatous germ cell tumors: case series and review of the literature. World Neurosurg. 2020;134:e360e371.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

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

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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