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

Abstract

Purpose/Objective-Limiting neurocognitive sequelae of radiation therapy (RT) has been an objective in the treatment of medulloblastoma (MB). Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation (CSI) may reduce neurocognitive sequelae and requires evaluation. October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk MB were treated on a prospective, IRB-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of CSI (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 post-operative tumor bed surrounded by an anatomically confined margin of 2 cm which was then expanded with a geometric margin of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Materials/Methods-Between CONFLICT OF INTEREST NOTIFICATION:There are no conflicts of interest with the authors or materials in this manuscript. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included 4 cycles of high-dose cyclophosphamide, cisplatin and vincristine.Results-With a median follow-up of 61.2 months (5.2-115.0 months), the estimated 5-year eventfree survival and cumulative incidence of PF failure were 83.0% ± 5.3% and 4.9% ± 2.4% (±SE), respectively. Targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses above 55Gy compared to conventionally planned RT. Reductions in dose to the temporal lobes, cochleae and hypothalamus were statistically significant.Conclusions-This prospective trial demonstrates that irradiation of less than the entire PF after 23.4 Gy CSI for average-risk MB results in disease control comparable to treatment of the entire PF.

Medulloblastoma

“…The latter is indicated due to the high rate of relapse within the posterior fossa. Studies conducted by the International Society of Pediatric Oncology (SIOP) and the Children’s Oncology Group, among others, have supported a reduction in the CSI dose to 23.4-24 Gy with the addition of adjuvant chemotherapy [50, 51]. ACNS0331, a COG study of further CSI dose-reduction to 18 Gy in young children (aged 3 to 7 years) is currently underway.…”

“…ACNS0331, a COG study of further CSI dose-reduction to 18 Gy in young children (aged 3 to 7 years) is currently underway. Similarly, several studies have demonstrated that the posterior fossa radiation volume may be safely reduced through conformal treatment to the tumor bed, allowing for sparing of normal structures, including the temporal lobes, hypothalamus, and cochleae, although this is not a universally accepted practice [51-53]. Similarly, the use of IMRT or proton beam therapy can reduce exposure to the heart and liver during CSI [54-57].…”

Central Nervous System Cancers

“…The conventional dose is 30 to 36 Gy of craniospinal irradiation and a boost to a total of 55.8 Gy to the primary brain site. 113,115 A lower craniospinal dose of 23.4 Gy, combined with chemotherapy, has gained popularity for average-risk patients to lessen side effects while maintaining 55.8 Gy to the posterior fossa, 111,116,117 although one randomized trial found an increased relapse risk with dose reduction. 118 SRS demonstrated safety and efficacy in a small series of 12 adult patients with residual or recurrent disease.…”

“…The use of postirradiation chemotherapy to allow radiation dose reduction is becoming increasingly common especially for children, 116,117 but optimal use of adjuvant chemotherapy is still unclear for adult patients. 110–112,120,121 A phase III study that enrolled more than 400 patients between ages 3 and 21 years to receive postirradiation cisplatin-based chemotherapy regimens recorded an encouraging 86% 5-year survival.…”

Ototoxicity evaluation in medulloblastoma patients treated with involved field boost using intensity-modulated radiation therapy (IMRT): a retrospective review

“…Adjuvant cisplatin-based chemotherapy is also used. This approach results in a 5-year survival rate in up to 85% of standard risk (SR) cases [1-3]. …”