Necrosis after craniospinal irradiation

Results from a prospective series of children with central nervous system embryonal tumors

Erin S. Murphy, Thomas E. Merchant, Shengjie Wu, Xiaoping Xiong, Renin Lukose, Karen D. Wright, Ibrahim Qaddoumi, Gregory Armstrong, Alberto Broniscer, Amar Gajjar

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Abstract

Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series. Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis. Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% ± 1.3% (n = 236) for the entire cohort and 4.4% ± 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ≥50 Gy (92.12% ± 4.58% vs 72.89% ± 1.96%; P=.0337), ≥52 Gy (88.95% ± 5.50% vs 69.16% ± 1.97%; P=.0275), and ≥54 Gy (82.28% ± 7.06% vs 63.37% ± 1.96%; P=.0488), respectively. Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.

Original languageEnglish (US)
JournalInternational Journal of Radiation Oncology Biology Physics
Volume83
Issue number5
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

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Craniospinal Irradiation
Central Nervous System Neoplasms
central nervous system
necrosis
Necrosis
tumors
irradiation
incidence
Medulloblastoma
Incidence
death
brain
Infratentorial Neoplasms
dosage
Brain
Vincristine
Cyclophosphamide
Cisplatin
Cause of Death
margins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

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Necrosis after craniospinal irradiation : Results from a prospective series of children with central nervous system embryonal tumors. / Murphy, Erin S.; Merchant, Thomas E.; Wu, Shengjie; Xiong, Xiaoping; Lukose, Renin; Wright, Karen D.; Qaddoumi, Ibrahim; Armstrong, Gregory; Broniscer, Alberto; Gajjar, Amar.

In: International Journal of Radiation Oncology Biology Physics, Vol. 83, No. 5, 01.08.2012.

Research output: Contribution to journalArticle

Murphy, Erin S. ; Merchant, Thomas E. ; Wu, Shengjie ; Xiong, Xiaoping ; Lukose, Renin ; Wright, Karen D. ; Qaddoumi, Ibrahim ; Armstrong, Gregory ; Broniscer, Alberto ; Gajjar, Amar. / Necrosis after craniospinal irradiation : Results from a prospective series of children with central nervous system embryonal tumors. In: International Journal of Radiation Oncology Biology Physics. 2012 ; Vol. 83, No. 5.
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abstract = "Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series. Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis. Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7{\%} ± 1.3{\%} (n = 236) for the entire cohort and 4.4{\%} ± 1.5{\%} (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ≥50 Gy (92.12{\%} ± 4.58{\%} vs 72.89{\%} ± 1.96{\%}; P=.0337), ≥52 Gy (88.95{\%} ± 5.50{\%} vs 69.16{\%} ± 1.97{\%}; P=.0275), and ≥54 Gy (82.28{\%} ± 7.06{\%} vs 63.37{\%} ± 1.96{\%}; P=.0488), respectively. Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7{\%} at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.",
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T2 - Results from a prospective series of children with central nervous system embryonal tumors

AU - Murphy, Erin S.

AU - Merchant, Thomas E.

AU - Wu, Shengjie

AU - Xiong, Xiaoping

AU - Lukose, Renin

AU - Wright, Karen D.

AU - Qaddoumi, Ibrahim

AU - Armstrong, Gregory

AU - Broniscer, Alberto

AU - Gajjar, Amar

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N2 - Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series. Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis. Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% ± 1.3% (n = 236) for the entire cohort and 4.4% ± 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ≥50 Gy (92.12% ± 4.58% vs 72.89% ± 1.96%; P=.0337), ≥52 Gy (88.95% ± 5.50% vs 69.16% ± 1.97%; P=.0275), and ≥54 Gy (82.28% ± 7.06% vs 63.37% ± 1.96%; P=.0488), respectively. Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.

AB - Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series. Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis. Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% ± 1.3% (n = 236) for the entire cohort and 4.4% ± 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ≥50 Gy (92.12% ± 4.58% vs 72.89% ± 1.96%; P=.0337), ≥52 Gy (88.95% ± 5.50% vs 69.16% ± 1.97%; P=.0275), and ≥54 Gy (82.28% ± 7.06% vs 63.37% ± 1.96%; P=.0488), respectively. Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.

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