Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma: Analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data

Martin Mynarek, Barry Pizer, Christelle Dufour, Dannis Van Vuurden, M. Garami, Maura Massimino, Jason Fangusaro, Tom Davidson, Maria Joao Gil-Da-Costa, Jaroslav Sterba, Martin Benesch, Nicolas Gerber, B. Ole Juhnke, Robert Kwiecien, Torsten Pietsch, Marcel Kool, Steve Clifford, David W. Ellison, Felice Giangaspero, Pieter WesselingFloyd Gilles, Nicholas Gottardo, Jonathan L. Finlay, Stefan Rutkowski, Katja Von Hoff

Research output: Contribution to journalArticle

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Abstract

Background. Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors. Patients and Methods. Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-dependent covariates. Results. Data on 135 patients with pineoblastoma aged 0.01-20.7 (median 4.9) years were analyzed. Median observation time was 7.3 years. Favorable prognostic factors were age ≥4 years (hazard ratio [HR] for progression-free survival [PFS] 0.270, P < .001) and administration of radiotherapy (HR for PFS 0.282, P < .001). Metastatic disease (HR for PFS 2.015, P = .006), but not postoperative residual tumor, was associated with unfavorable prognosis. In 57 patients <4 years old, 5-year PFS/overall survival (OS) were 11 ± 4%/12 ± 4%. Two patients survived after chemotherapy only, while 3 of 16 treated with craniospinal irradiation (CSI) with boost, and 3 of 5 treated with high-dose chemotherapy (HDCT) and local radiotherapy survived. In 78 patients aged ≥4 years, PFS/OS were 72 ± 7%/73 ± 7% for patients without metastases, and 50 ± 10%/55 ± 10% with metastases. Seventy-three patients received radiotherapy (48 conventionally fractionated CSI, median dose 35.0 [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local radiotherapy), with (n = 68) or without (n = 6) chemotherapy. The treatment sequence had no impact; application of HDCT had weak impact on survival in older patients. Conclusion. Survival is poor in young children treated without radiotherapy. In these patients, combination of HDCT and local radiotherapy may warrant further evaluation in the absence of more specific or targeted treatments. CSI combined with chemotherapy is effective for older non-metastatic patients.

Original languageEnglish
Pages (from-to)576-585
Number of pages10
JournalNeuro-Oncology
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

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Pinealoma
Young Adult
Pediatrics
Craniospinal Irradiation
Radiotherapy
Disease-Free Survival
Drug Therapy
Therapeutics
Survival
Brain Neoplasms
Neoplasm Metastasis
Residual Neoplasm
Proportional Hazards Models
Observation

Keywords

  • High-dose chemotherapy
  • Pediatric
  • Pineoblastoma
  • Radiotherapy
  • Treatment

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma : Analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data. / Mynarek, Martin; Pizer, Barry; Dufour, Christelle; Van Vuurden, Dannis; Garami, M.; Massimino, Maura; Fangusaro, Jason; Davidson, Tom; Gil-Da-Costa, Maria Joao; Sterba, Jaroslav; Benesch, Martin; Gerber, Nicolas; Juhnke, B. Ole; Kwiecien, Robert; Pietsch, Torsten; Kool, Marcel; Clifford, Steve; Ellison, David W.; Giangaspero, Felice; Wesseling, Pieter; Gilles, Floyd; Gottardo, Nicholas; Finlay, Jonathan L.; Rutkowski, Stefan; Von Hoff, Katja.

In: Neuro-Oncology, Vol. 19, No. 4, 01.04.2017, p. 576-585.

Research output: Contribution to journalArticle

Mynarek, M, Pizer, B, Dufour, C, Van Vuurden, D, Garami, M, Massimino, M, Fangusaro, J, Davidson, T, Gil-Da-Costa, MJ, Sterba, J, Benesch, M, Gerber, N, Juhnke, BO, Kwiecien, R, Pietsch, T, Kool, M, Clifford, S, Ellison, DW, Giangaspero, F, Wesseling, P, Gilles, F, Gottardo, N, Finlay, JL, Rutkowski, S & Von Hoff, K 2017, 'Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma: Analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data', Neuro-Oncology, vol. 19, no. 4, pp. 576-585. https://doi.org/10.1093/neuonc/now234
Mynarek, Martin ; Pizer, Barry ; Dufour, Christelle ; Van Vuurden, Dannis ; Garami, M. ; Massimino, Maura ; Fangusaro, Jason ; Davidson, Tom ; Gil-Da-Costa, Maria Joao ; Sterba, Jaroslav ; Benesch, Martin ; Gerber, Nicolas ; Juhnke, B. Ole ; Kwiecien, Robert ; Pietsch, Torsten ; Kool, Marcel ; Clifford, Steve ; Ellison, David W. ; Giangaspero, Felice ; Wesseling, Pieter ; Gilles, Floyd ; Gottardo, Nicholas ; Finlay, Jonathan L. ; Rutkowski, Stefan ; Von Hoff, Katja. / Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma : Analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data. In: Neuro-Oncology. 2017 ; Vol. 19, No. 4. pp. 576-585.
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abstract = "Background. Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors. Patients and Methods. Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-dependent covariates. Results. Data on 135 patients with pineoblastoma aged 0.01-20.7 (median 4.9) years were analyzed. Median observation time was 7.3 years. Favorable prognostic factors were age ≥4 years (hazard ratio [HR] for progression-free survival [PFS] 0.270, P < .001) and administration of radiotherapy (HR for PFS 0.282, P < .001). Metastatic disease (HR for PFS 2.015, P = .006), but not postoperative residual tumor, was associated with unfavorable prognosis. In 57 patients <4 years old, 5-year PFS/overall survival (OS) were 11 ± 4{\%}/12 ± 4{\%}. Two patients survived after chemotherapy only, while 3 of 16 treated with craniospinal irradiation (CSI) with boost, and 3 of 5 treated with high-dose chemotherapy (HDCT) and local radiotherapy survived. In 78 patients aged ≥4 years, PFS/OS were 72 ± 7{\%}/73 ± 7{\%} for patients without metastases, and 50 ± 10{\%}/55 ± 10{\%} with metastases. Seventy-three patients received radiotherapy (48 conventionally fractionated CSI, median dose 35.0 [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local radiotherapy), with (n = 68) or without (n = 6) chemotherapy. The treatment sequence had no impact; application of HDCT had weak impact on survival in older patients. Conclusion. Survival is poor in young children treated without radiotherapy. In these patients, combination of HDCT and local radiotherapy may warrant further evaluation in the absence of more specific or targeted treatments. CSI combined with chemotherapy is effective for older non-metastatic patients.",
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T1 - Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma

T2 - Analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data

AU - Mynarek, Martin

AU - Pizer, Barry

AU - Dufour, Christelle

AU - Van Vuurden, Dannis

AU - Garami, M.

AU - Massimino, Maura

AU - Fangusaro, Jason

AU - Davidson, Tom

AU - Gil-Da-Costa, Maria Joao

AU - Sterba, Jaroslav

AU - Benesch, Martin

AU - Gerber, Nicolas

AU - Juhnke, B. Ole

AU - Kwiecien, Robert

AU - Pietsch, Torsten

AU - Kool, Marcel

AU - Clifford, Steve

AU - Ellison, David W.

AU - Giangaspero, Felice

AU - Wesseling, Pieter

AU - Gilles, Floyd

AU - Gottardo, Nicholas

AU - Finlay, Jonathan L.

AU - Rutkowski, Stefan

AU - Von Hoff, Katja

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background. Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors. Patients and Methods. Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-dependent covariates. Results. Data on 135 patients with pineoblastoma aged 0.01-20.7 (median 4.9) years were analyzed. Median observation time was 7.3 years. Favorable prognostic factors were age ≥4 years (hazard ratio [HR] for progression-free survival [PFS] 0.270, P < .001) and administration of radiotherapy (HR for PFS 0.282, P < .001). Metastatic disease (HR for PFS 2.015, P = .006), but not postoperative residual tumor, was associated with unfavorable prognosis. In 57 patients <4 years old, 5-year PFS/overall survival (OS) were 11 ± 4%/12 ± 4%. Two patients survived after chemotherapy only, while 3 of 16 treated with craniospinal irradiation (CSI) with boost, and 3 of 5 treated with high-dose chemotherapy (HDCT) and local radiotherapy survived. In 78 patients aged ≥4 years, PFS/OS were 72 ± 7%/73 ± 7% for patients without metastases, and 50 ± 10%/55 ± 10% with metastases. Seventy-three patients received radiotherapy (48 conventionally fractionated CSI, median dose 35.0 [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local radiotherapy), with (n = 68) or without (n = 6) chemotherapy. The treatment sequence had no impact; application of HDCT had weak impact on survival in older patients. Conclusion. Survival is poor in young children treated without radiotherapy. In these patients, combination of HDCT and local radiotherapy may warrant further evaluation in the absence of more specific or targeted treatments. CSI combined with chemotherapy is effective for older non-metastatic patients.

AB - Background. Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors. Patients and Methods. Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-dependent covariates. Results. Data on 135 patients with pineoblastoma aged 0.01-20.7 (median 4.9) years were analyzed. Median observation time was 7.3 years. Favorable prognostic factors were age ≥4 years (hazard ratio [HR] for progression-free survival [PFS] 0.270, P < .001) and administration of radiotherapy (HR for PFS 0.282, P < .001). Metastatic disease (HR for PFS 2.015, P = .006), but not postoperative residual tumor, was associated with unfavorable prognosis. In 57 patients <4 years old, 5-year PFS/overall survival (OS) were 11 ± 4%/12 ± 4%. Two patients survived after chemotherapy only, while 3 of 16 treated with craniospinal irradiation (CSI) with boost, and 3 of 5 treated with high-dose chemotherapy (HDCT) and local radiotherapy survived. In 78 patients aged ≥4 years, PFS/OS were 72 ± 7%/73 ± 7% for patients without metastases, and 50 ± 10%/55 ± 10% with metastases. Seventy-three patients received radiotherapy (48 conventionally fractionated CSI, median dose 35.0 [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local radiotherapy), with (n = 68) or without (n = 6) chemotherapy. The treatment sequence had no impact; application of HDCT had weak impact on survival in older patients. Conclusion. Survival is poor in young children treated without radiotherapy. In these patients, combination of HDCT and local radiotherapy may warrant further evaluation in the absence of more specific or targeted treatments. CSI combined with chemotherapy is effective for older non-metastatic patients.

KW - High-dose chemotherapy

KW - Pediatric

KW - Pineoblastoma

KW - Radiotherapy

KW - Treatment

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