Martin Mynarek1, Barry Pizer2, Christelle Dufour3, Dannis van Vuurden4, Miklos Garami5, Maura Massimino6, Jason Fangusaro7, Tom Davidson8, Maria Joao Gil-da-Costa9, Jaroslav Sterba10, Martin Benesch11, Nicolas Gerber12, B Ole Juhnke1, Robert Kwiecien13, Torsten Pietsch14, Marcel Kool15, Steve Clifford16, David W Ellison17, Felice Giangaspero18,19, Pieter Wesseling20,21, Floyd Gilles22, Nicholas Gottardo23, Jonathan L Finlay24, Stefan Rutkowski1, Katja von Hoff1. 1. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 2. Oncology Unit, Alder Hey Children's Hospital, Liverpool, UK. 3. Brain Tumor Programme, Department of Pediatric and Adolescent Oncology, Institut Gustave Roussy, Villejuif, France. 4. Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, Netherlands. 5. Second Department of Pediatrics, School of Medicine, Semmelweis University, Budapest, Hungary. 6. Department of Pediatrics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 7. Department of Hematology, Oncology and Stem Cell Transplant, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA. 8. Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA. 9. Department of Pediatric Hematoncology, University Hospital de São João, Porto, Portugal. 10. Pediatric Oncology Department, University Hospital Brno, Brno, Czech Republic. 11. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical University of Graz, Graz, Austria. 12. Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland. 13. Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany. 14. Department of Neuropathology, University of Bonn, Bonn, Germany. 15. Division of Pediatric Neurooncology, German Cancer Research Center, Heidelberg, Germany. 16. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK. 17. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. 18. Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy. 19. IRCCS Neuromed, Pozzilli, Italy. 20. Department of Pathology, VU University Medical Center, Amsterdam, Netherlands. 21. Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands. 22. Department of Pathology (Neuropathology), Children's Hospital Los Angeles and the University of Southern California, Los Angeles, California, USA. 23. Telethon Kids Institute, Subiaco, Western Australia. 24. Department of Pediatrics, Division of Hematology, Oncology and BMT, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio, USA.
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.
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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