Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

Thomas E. Merchant, Larry E. Kun, Matthew J. Krasin, Dana Wallace, Murali M. Chintagumpala, Shiao Y. Woo, David M. Ashley, Maree Sexton, Stewart J. Kellie, Verity Ahern, Amar Gajjar

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Purpose: Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation. Methods and Materials: Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). The planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine. Results: At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0% ± 5.3% and 4.9% ± 2.4% (± standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant. Conclusion: This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF.

Original languageEnglish (US)
Pages (from-to)782-787
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume70
Issue number3
DOIs
StatePublished - Mar 1 2008

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Craniospinal Irradiation
Medulloblastoma
chemotherapy
radiation therapy
Radiotherapy
Drug Therapy
dosage
irradiation
margins
Conformal Radiotherapy
hypothalamus
Research Ethics Committees
Cochlea
cochlea
Vincristine
Temporal Lobe
Ambulatory Surgical Procedures
Cyclophosphamide
Cisplatin
Hypothalamus

Keywords

  • Central nervous system neoplasm
  • Chemotherapy
  • Conformal radiotherapy
  • Pediatrics
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma. / Merchant, Thomas E.; Kun, Larry E.; Krasin, Matthew J.; Wallace, Dana; Chintagumpala, Murali M.; Woo, Shiao Y.; Ashley, David M.; Sexton, Maree; Kellie, Stewart J.; Ahern, Verity; Gajjar, Amar.

In: International Journal of Radiation Oncology Biology Physics, Vol. 70, No. 3, 01.03.2008, p. 782-787.

Research output: Contribution to journalArticle

Merchant, Thomas E. ; Kun, Larry E. ; Krasin, Matthew J. ; Wallace, Dana ; Chintagumpala, Murali M. ; Woo, Shiao Y. ; Ashley, David M. ; Sexton, Maree ; Kellie, Stewart J. ; Ahern, Verity ; Gajjar, Amar. / Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma. In: International Journal of Radiation Oncology Biology Physics. 2008 ; Vol. 70, No. 3. pp. 782-787.
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abstract = "Purpose: Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation. Methods and Materials: Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). The planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine. Results: At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0{\%} ± 5.3{\%} and 4.9{\%} ± 2.4{\%} (± standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13{\%} in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant. Conclusion: This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF.",
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AU - Merchant, Thomas E.

AU - Kun, Larry E.

AU - Krasin, Matthew J.

AU - Wallace, Dana

AU - Chintagumpala, Murali M.

AU - Woo, Shiao Y.

AU - Ashley, David M.

AU - Sexton, Maree

AU - Kellie, Stewart J.

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