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

William G. Breen, Miran J. Blanchard, Amulya Nageswara Rao, David Daniels, Jan Craig Buckner, Nadia N Laack

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5 Citations (Scopus)

Abstract

Purpose: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs). Materials and methods: We retrospectively reviewed records of 3,440 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.

Original languageEnglish (US)
JournalPediatric Blood and Cancer
DOIs
StateAccepted/In press - 2017

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Germ Cell and Embryonal Neoplasms
Radiotherapy
Drug Therapy
Disease-Free Survival
Recurrence
Second-Look Surgery
Central Nervous System
Germinoma
Fetal Proteins
Induction Chemotherapy
Survival
Cerebrospinal Fluid
Histology
Spine
Radiation

Keywords

  • Extensive radiotherapy
  • Germ cell tumor
  • Local radiotherapy
  • Nongerminomatous germ cell tumor
  • Radiotherapy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

@article{b6047f84523941ec8d59f120444270b3,
title = "Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors: Long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy",
abstract = "Purpose: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs). Materials and methods: We retrospectively reviewed records of 3,440 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",
author = "Breen, {William G.} and Blanchard, {Miran J.} and Rao, {Amulya Nageswara} and David Daniels and Buckner, {Jan Craig} and Laack, {Nadia N}",
year = "2017",
doi = "10.1002/pbc.26637",
language = "English (US)",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors

T2 - Long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy

AU - Breen, William G.

AU - Blanchard, Miran J.

AU - Rao, Amulya Nageswara

AU - Daniels, David

AU - Buckner, Jan Craig

AU - Laack, Nadia N

PY - 2017

Y1 - 2017

N2 - Purpose: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs). Materials and methods: We retrospectively reviewed records of 3,440 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.

AB - Purpose: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs). Materials and methods: We retrospectively reviewed records of 3,440 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.

KW - Extensive radiotherapy

KW - Germ cell tumor

KW - Local radiotherapy

KW - Nongerminomatous germ cell tumor

KW - Radiotherapy

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U2 - 10.1002/pbc.26637

DO - 10.1002/pbc.26637

M3 - Article

C2 - 28695992

AN - SCOPUS:85022322794

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

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