Low-dose Craniospinal Irradiation Research Articles

GCT-08. Patients with Metastatic Central Nervous System Germinoma Involving the Basal Ganglia and Thalami, a Case Series

BACKGROUND: Central nervous system (CNS) germinomas are commonly located in the suprasellar and/or pineal regions. Current treatment strategies include irradiation (RT) alone or chemotherapy with RT to reduce the dose and field of RT. However, given their rarity and poorly defined imaging characteristics, germinomas originating in the basal ganglia/thalami (BGTG) have proven challenging to treat. We present a case series of six patients with metastatic BGTG, given the paucity of published research on patients with metastatic CNS BGTG. METHODS: A retrospective multi-institutional review was performed across four institutions in two countries. RESULTS: Two patients were females, and four were males. The median age at presentation was 14.9 years. Biopsies were performed in all patients except for one patient who underwent subtotal surgical resection of her primary tumor. Three patients received RT only, while the remaining three received chemotherapy with RT. Carboplatin and etoposide were used in all three patients who received chemotherapy. All six patients received craniospinal irradiation (CSI). For patients who received RT only, the CSI dose ranged between (24 – 27.2 Gy) with a total dose to the primary site ranging between (36 – 40 Gy). For patients who received chemotherapy, one patient received 36 Gy with a total dose of 54 Gy to the primary site. The second patient received 24 Gy with a total dose of 40 Gy to the primary site. The CSI dose was not available for the third patient. All patients remain alive with a median event-free survival (EFS) and overall survival (OS) of 49 months (range: 14.3 – 168 months). CONCLUSION: In our series, patients with metastatic CNS BGTG treated with CSI with or without chemotherapy had excellent outcomes. Future larger studies are needed to compare the outcomes between CSI only and chemotherapy with low-dose CSI among patients with metastatic CNS BGTG.

Medulloblastoma

Current treatment protocols for medulloblastomas(MBs)stratify patients into high and average risk groups according to their age, metastatic status, and residual tumor volume after resection. Recent genetic and molecular biological reserach revealed that MBs are classified into at least four core subgroups - WNT, SHH, Group 3, and Group 4 - based on differences in their cytogenetics, mutational spectra, and gene expression signatures, as well as in their clinical phenotypes and prognosis. Latest studies suggest more distinct subtypes of MBs by DNA methylation profiles. In addition to conventional clinical risk stratification, new molecular risk stratification using molecular subgroups/subtypes, cytogenetic features and copy number aberrations help understand the outcome of current standard and/or experimental therapies. To achieve further improvement in prognosis and reduce treatment-related adverse events, the efficiency and safety of low-dose craniospinal irradiation and novel molecular targeted drugs, including SMO inhibitors, cyclin-dependent kinases 4/6, or checkpoint kinase 1/2 inhibitors, have been examined with respect to the molecular properties of each tumor. The molecular information of each MB is indispensable for precision medicine of MBs, strongly promoting the development of advanced therapeutic strategies of MBs.

A Pilot Study of Low-Dose Craniospinal Irradiation in Patients With Newly Diagnosed Average-Risk Medulloblastoma.

PurposeMedulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. Prior to advances in molecular subgrouping, we sought to reduce the late effects of radiation in patients with average-risk medulloblastoma.MethodsWe performed a single-arm, multi-institution study, reducing the dose of craniospinal irradiation by 25% to 18 Gray (Gy) with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy.ResultsTwenty-eight (28) patients aged 3-30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93% (95% CI 74% to 98%), respectively. The 5-year RFS and OS were 71% (95% CI 50% to 85%) and 86% (95% CI 66% to 94%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities.ConclusionsGiven the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from a reduced craniospinal radiation dose of 18 Gy without impacting relapse-free or overall survival.Clinical Trial RegistrationClinicalTrials.gov identifier: NCT00031590

Results of COG ACNS0331: A Phase III Trial of Involved-Field Radiotherapy (IFRT) and Low Dose Craniospinal Irradiation (LD-CSI) with Chemotherapy in Average-Risk Medulloblastoma: A Report from the Children's Oncology Group

Results of COG ACNS0331: A Phase III Trial of Involved-Field Radiotherapy (IFRT) and Low Dose Craniospinal Irradiation (LD-CSI) with Chemotherapy in Average-Risk Medulloblastoma: A Report from the Children's Oncology Group

Chronic Residual Lesions in Metastatic Medulloblastoma Patients

In a retrospective review of 24 metastatic medulloblastoma patients whose treatment included craniospinal irradiation, 5 patients presented with gross residual abnormalities at completion of therapy. This report describes 2 medulloblastoma patients with persistent residual abnormalities on serial follow-up imaging studies. The patients aged 2 and 2.5 years old at the time of diagnosis underwent surgery followed by multiagent chemotherapy. One patient progressed on therapy and underwent salvage craniospinal radiation. The second showed residual tumor on end of treatment imaging and received low-dose craniospinal irradiation. Despite persistent magnetic resonance imaging findings, the patients are alive and well 13 and 7 years after diagnosis with no further treatment applied. The nature of these residual abnormalities is discussed.

Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma

Purpose: To determine the optimal radiotherapy (RT) dose and volume for treatment of intracranial germinoma. Materials and methods: Eighty-one intracranial germinoma patients (33 pathologically-verified; 48 presumed by radiosensitivity testing) treated with RT alone between 1971 and 2002 were analyzed. The RT volume varied from focal (13) to whole brain (8), or to the entire neuraxis (60). All the cases after 1982 received craniospinal irradiation (CSI). Radiation dose was reduced gradually during the study period from 59 to 39.3 Gy for primary tumors, and from 34.2 to 19.5 Gy for the neuraxis. The median follow-up time was 120 months (48–260 months). Results: Five- and ten-year relapse-free survival rates were 98.8% and 94.1%, respectively. All the recurrences occurred in the patients who received local (4/13) or whole brain RT (1/8). None of the patients who received CSI suffered from a recurrence. Forty-six patients received 45 Gy or less to the primary site and 22 patients received less than 20 Gy to the spinal axis. Conclusion: Low-dose CSI-based RT should remain the standard treatment for intracranial germinoma. The RT dose can be reduced to 39.3 Gy for primary tumor sites and to 19.5 Gy for the spinal axis.

Low-dose Craniospinal Irradiation and Ifosfamide, Cisplatin and Etoposide for Non-metastatic Embryonal Tumors in the Central Nervous System

The current study was conducted to evaluate the effects of low-dose craniospinal irradiation (CSI) combined with chemotherapy on non-metastatic embryonal tumors in the central nervous system (CNS), including medulloblastoma and supra-tentorial primitive neuroectodermal tumors (ST-PNET). All patients were treated according to the following protocol. After surgery, the patients < or =5 years old received 18 Gy and the patients >5 years old received 24 Gy CSI. The dose to the primary tumor bed was 39.6-54 Gy. Chemotherapy consisted of ifosfamide, cisplatin and etoposide (ICE chemotherapy). Sixteen patients aged 0.5-20.4 (median 6.1) years were enrolled and followed for 11-165 (median 112) months. Both 5-year actuarial overall survival (OAS) and progression-free survival (PFS) were 81% (95% confidence interval (CI): 62-100%) for the 16 patients. Both 5-year OAS and PFS were 82% (CI: 59-100%) for the patients with medulloblastoma and 80% (CI: 45-100%) for the patients with ST-PNET. Both 5-year OAS and PFS were 75% for the eight patients < or =5 years old and 88% for the eight patients >5 years old. Both 5-year OAS and PFS were 100% for six average-risk patients (3 years or older, total resection and posterior fossa) and 70% for 10 poor-risk patients (others). The median total intellectual quotient at the last follow-up was 85 (ranging from 48 to 103) in 12 patients who were followed for 3-145 (median 49) months. Eight patients received hormone replacement therapy. Low-dose CSI and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the CNS.

Whole neuraxis irradiation to address central nervous system (CNS) relapse in high-risk neuroblastoma (NB)

10050 Background: CNS relapse in high-risk NB is on the rise as extracranial disease control improves. Management of CNS relapse with radiotherapy (RT) that does not address the entire neuraxis has been ineffective in preventing further progression and ultimate death. The purpose of the present study is to describe the use of craniospinal irradiation (CSI) for CNS relapse in high-risk NB and compare outcomes to a historical cohort of patients who did not receive CSI. Methods: A retrospective query identified 24 children with high- risk NB treated at MSKCC since 1987 who received RT for CNS relapse. All patients received appropriate initial therapies and were in remission at the time of CNS recurrence. 14 patients received CSI, and 10 received focal RT that did not address the entire neuraxis. CSI was delivered to a median dose of 2160 cGy, and 10 patients received a boost to a median dose of 2520 cGy. Of those who underwent CSI, 13 (93%) received intrathecal (IT) immunotherapy with 131I-8H9 or 131I-3F8. None of the patients in the non-CSI cohort received IT immunotherapy. Results: The demographic and relapse characteristics were similar between the two groups with the exception that patients who underwent CSI represented a more modern cohort. The age at and time to CNS relapse was 5 and 1.5 years, respectively, in both cohorts. At a median follow-up of 18.3 months (range 1.5–53) after CNS relapse, 10 (71%) patients in the CSI group are alive without evidence of disease. In contrast, all 10 patients in the non-CSI cohort died of disease at a median of 8.1 months (range 4.2–12.9). One patient in the CSI cohort died 1.5 years after CNS relapse of progressive leptomeningeal disease; this was also the only patient in that cohort who did not receive IT immunotherapy. One patient in the CSI cohort died 22 months after CNS relapse of unrelated causes. Two patients developed bone recurrence, but remain free of CNS disease. Conclusions: Based on this small cohort of patients, low-dose CSI in conjunction with IT immunotherapy provides durable CNS remissions and improved survival relative to the experience with focal RT and conventional therapies alone. Further evaluation of long-term NB survivors after CSI is warranted to determine the unique long-term treatment consequences for this young patient cohort. No significant financial relationships to disclose.

Feasibility and outcome of patients with medulloblastoma treated with pre-irradiation chemotherapy and reduced dose craniospinal radiotherapy (csrh) using mycc as a molecular marker for prognosis

10040 Background: Children with medulloblastoma are more susceptible to the deleterious effects of craniospinal irradiation (CSRT) and have a higher relapse rate when treated with low-dose CSRT alone. Cytogenetic abnormalities that have been described in childhood medulloblastoma include loss of 17p, amplification of MYCC, amplification of MYCN and isochromosome 17q. This study was undertaken to determine the feasibility and efficacy of treating children with medulloblastoma with pre-irradiation chemotherapy and reduced-dose craniospinal radiotherapy and investigated the frequency and prognostic significance of MYCC amplification. Methods: 65 patients received 3 cycles of alternating chemotherapy (vincristine, etoposide and carboplatin and vincristine, etoposide and cyclophosphamide). All patients received radiotherapy to the craniospinal axis (25 Gy followed by a boost to posterior fossa with 30 Gy). After completion of CSRT, the patients received additional 3 cycles of alternating chemotherapy. Fluorescence in situ hybridization (FISH) was used to detect amplification of the MYCC oncogene. Results: Among the 65 patients, the median survival time was 21.0 months (3–52.0 months) from the date of diagnosis. The overall response rate was 89%. The estimated four-year progression-free survival was 78 percent and the four-year overall survival was 84 percent. The most predominant toxicity with post-irradiation chemotherapy was myelosuppression. Grade III neutropenia occurred in ≥60% of patients in each cycle. MYCC amplification was founded in 4 positive cases (6%). Estimate of the survival distributions for patients with and without MYCC amplification, reveals sufficient evidence to conclude that survival among MYCC-amplified patients is poorer than among non-amplified patients (P < .0001). Conclusions: This study has demonstrated the feasibility and benefits of administering pre-irradiation chemotherapy with reduced dose craniospinal irradiation in patients with medulloblastoma and confirmed the frequency of MYCC amplification in a large cohort of patients and further suggest that MYCC amplification may be a marker of poor prognosis. No significant financial relationships to disclose.

Low-Dose Craniospinal Irradiation (CSI) With Computed Tomographic (CT) Simulation and Ifosfamide, Cisplatin, and Etopiside for Non-Metastatic Embryonal Tumors in the Central Nervous System

Purpose/Objective(s): To evaluate the effects of low-dose cranio-spinal irradiation (CSI) with CT simulation combined with chemotherapy for non-metastatic embryonal tumors in the central nervous system. Materials/Methods: All patients were treated with CTsimulation with the help of MRI information. After surgery, patients 5 years received 24Gy/12Fr/3wks CSI. The dose to the primary tumor bed was 39.6-54Gy/22 27Fr/6-7wks. Chemotherapy consisted of ifosfamide (900 mg/m2, day 1-5), cisplatin (20 mg/m2, days 1-5), and etoposide (60 mg/m2, days 1-5). Dose of each agent was modified according to pre-determined dose reduction criteria after second course of chemotherapy. Patients younger than 2.5 years old received the chemotherapy after surgery and radiotherapy was given when they became 2.5 years old. For older patients, the chemotherapy was given once before radiotherapy and subsequently after radiotherapy. Results: Sixteen patients aged 0.5 to 20.4 (median 6.1) years were enrolled and followed for 11 to 172 months with the median of 118 months. Overall survival and progression-free survival for the 8 patients who received 18Gy CSI were both 75 % (CI: 45 100%). Overall survival and progression-free survival for the 8 patients who received 24 Gy CSI were 88% (CI: 64100%) and 75% (CI: 44-100%) respectively. In total, both 5-years actuarial overall survival and progression-free survival were 81 % (CI: 62 100 %) for the 16 patients. Both 5-year actuarial overall and progression-free survival rate were 100% for 6 average risk patients (3 years or older, total resection, posterior fossa) and 70 % (95% confidence interval, CI: 4298%) for 10 poor-risk group (others) (p=0.14). Total intellectual quotient (IQ) was measured in 12 patients with the median follow-up period of 49 months ranged from 3 to 145 months. Total IQ was distributed from 48 103 with the median of 83 at the last follow-up. There was no apparent discrepancy between verbal IQ (median 86, 48 119) and performance IQ (92, 58 113) in 9 patients who could receive the examination for verbal IQ and performance IQ. Apparent deterioration in total IQ more than 10 points was not observed in 6 patients whose total IQ was measured more than 2 times during the follow-up with the median interval of 69 ranged from 19 to 125 months. Deficiency in thyroid hormone, corticosteroid hormone, and growth hormone was observed in 1, 1, and 2 patients, respectively. All were treated with hormonal supplementation. No patients suffered from symptomatic hearing deficiency or required hearing aids. One patient experienced hemangioma in the skull in the irradiated region and received surgical removal of the tumor. Conclusions: Low-dose CSI with CT simulation and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the central nervous system.

Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element.

Concurrent chemotherapy and low-dose craniospinal irradiation followed by conformal posterior fossa tumor bed boost for average risk medulloblastoma: efficacy and patterns of failure

Concurrent chemotherapy and low-dose craniospinal irradiation followed by conformal posterior fossa tumor bed boost for average risk medulloblastoma: efficacy and patterns of failure

Hypothyroidism in children with medulloblastoma: a comparison of 3600 and 2340 cGy craniospinal radiotherapy

Purpose : To determine if low-dose craniospinal irradiation (2340 cGy) with chemotherapy is associated with a lower incidence of hypothyroidism compared to standard dose (3600 cGy) with or without chemotherapy in children with medulloblastoma. Patients and Methods : Between 1980 and 1999, 32 patients ≤20 years old survived after craniospinal irradiation with or without chemotherapy. Twenty patients received 3600 cGy craniospinal irradiation (CSI), whereas 12 had 2340 cGy CSI; all patients received a posterior fossa boost to a total dose 5040–5580 cGy. The median ages at the time of CSI for those receiving 2340 cGy and 3600 cGy were 7.2 and 10.2 years, respectively. Chemotherapy (CT) was employed in 22 children. All children who received 2340 cGy had CT consisting of vincristine, CCNU, and either cisplatin or cyclophosphamide. Ten of 20 (50%) patients receiving 3600 cGy had CT; the most common regimen was vincristine, CCNU, and prednisone. Serum-free thyroxine and thyroid-stimulating hormone concentrations were measured in all children at variable times after radiotherapy. Thyroid-stimulating hormone responses to i.v. thyrotrophin-releasing hormone were assessed in those suspected of having central hypothyroidism. Median follow-up for children receiving 2340 cGy was 5 years (range: 2–11.2 years), whereas for those receiving 3600 cGy, follow-up was 12.5 years (range: 2.4–20 years). Results : Eighteen patients (56%) developed hypothyroidism at a median time after radiotherapy of 41 months (range: 10 months to 18 years). Primary hypothyroidism was more common than central hypothyroidism (38% and 19%). All 7 children <5 years developed hypothyroidism, whereas 9 of 15 (60%) ages 5–10 and 2 of 10 (20%) age >10 years had hypothyroidism ( p < 0.001). Hypothyroidism was documented in 10 of 12 (83%) who had 2340 cGy + CT, 6 of 10 (60%) who had 3600 cGy + CT, and 2 of 10 (20%) who had 3600 cGy without CT ( p < 0.025). Conclusions : Current treatment regimens consisting of chemotherapy and 2340 cGy craniospinal irradiation followed by a posterior fossa boost for medulloblastoma do not show a reduction of hypothyroidism. Young age and use of chemotherapy were associated with a higher incidence of hypothyroidism.

Updated results of a pilot study of low dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma)

Children under 5 years old with medulloblastoma (MB) have a poor prognosis. They are more susceptible to the deleterious effects of craniospinal irradiation (CSART) and have a higher relapse rate when treated with low-dose CSART alone. We, thus, embarked on a prospective trial testing the usefulness of very low dose CSART and adjuvant chemotherapy. This is an update of a previous report on these patients. Between January 1988 and March 1990, 10 patients with medulloblastoma were treated using 18 Gy radiation therapy (RT) to the craniospinal axis, a posterior fossa (PF) boost to 50.4-55.8 Gy and chemotherapy consisting of vincristine (VCR) weekly during RT. This was followed by VCR, cis-diamminedichloroplatinum (CDDP), and lomustine (CCNU) for eight, 6-week cycles. Patients between 18 and 60 months of age without evidence of tumor dissemination were eligible for study. Follow-up was available until September 1994 with a median follow-up for living patients of 6.3 years from diagnosis. Actuarial survival at over 6 years is 70 +/- 20%. Three of the 10 patients relapsed and died. In one patient, the relapse developed in the spine and brain outside the posterior fossa, in the second, concurrently in the posterior fossa, brain and spine, and the third, only in the spine. One surviving child developed a brain stem infarct 4.8 years after diagnosis and has since almost fully recovered. A mean intelligence quotient (IQ) score of 103 in six patients surviving at least 1 year is unchanged from the baseline group score of 107. Five children tested at baseline and 2 years following treatment had IQ scores of 101 and 102, respectively. Six children tested at baseline and at 3 years had IQ scores of 106 and 96, respectively. Excluding the child tested shortly after his brain stem infarct, baseline and 3 year IQ scores were 103 and 97, respectively. Five of the seven long-term survivors grew at rates significantly below their expected velocities during the follow-up period, while the others grew normally. Three patients have received growth hormone, and none have required thyroid replacement. These data suggest that medulloblastoma patients can be cured with chemotherapy and reduced doses of craniospinal irradiation. The low doses of CSART given by us in conjunction with cis-platin-based chemotherapy produce minimal neurocognitive damage. Growth velocities in very young children so treated are, however, dramatically reduced. Better means of improving the therapeutic ratio are still needed.

Pattern of recurrence of medulloblastoma after low-dose

Purpose: We retrospectively evaluated relapse of medulloblastoma after low- or high-dose craniospinal radiotherapy, and after conventional or hyperfractionated posterior fossa irradiation. Methods and Materials: Ninety-two pediatric patients were treated postoperatively since 1970 at the University of California, San Francisco. Until 1989, we employed conventional fractionation with low (≤ 30 Gy) or high-dose craniospinal fields and low-dose (≤ 56 Gy) posterior fossa boosts. Recently, hyperfractionation delivered low- or high-dose to the craniospinal axis and high-dose to the posterior fossa. Most patients treated after 1979 received chemotherapy. Results: Median follow-up was 70 months. Five-year disease-free survival was 36% (22% for poor-risk vs. 59% for good-risk patients). Five-year overall survival was 52% (43% for poor vs. 68% for good-risk). Neither the dose to the posterior fossa nor the craniospinal axis was statistically related to recurrence. Failure in the posterior fossa occurred despite boosts greater than 56 Gy. Females, over the age of 6 years, had significantly better relapse-free survival than males of the same age. Six of the 54 patients who relapsed were long-term survivors. Conclusions: Low-dose craniospinal radiotherapy, where the majority of patients received chemotherapy, was not associated with increased failure. High-dose posterior fossa hyperfractionation did not improve control. Long-term survival was noted in a number of patients after relapse. We recommend 60 Gy or greater with conventional fractions to the primary area, and continued study of low-dose craniospinal irradiation with adjuvant chemotherapy.

Results of a pilot study of very low dose craniospinal irradiation plus chemotherapy for children under five with medulloblastoma: An update

Results of a pilot study of very low dose craniospinal irradiation plus chemotherapy for children under five with medulloblastoma: An update

Low-dose craniospinal radiation therapy for medulloblastoma

At the University of California, San Francisco, 65 children with medulloblastoma of the posterior fossa were treated postoperatively with craniospinal irradiation; the dose to the posterior fossa was 54 Gy. The 26 children initially treated had only radiation therapy, receiving 30 to 40 Gy to the spine and 40 to 50 Gy to the brain. Subsequently, 39 children were treated with low-dose craniospinal irradiation and chemotherapy; 24 to 30 Gy was directed to the whole brain and 24 to 26 Gy to the spinal axis. Chemotherapy generally consisted of procarbazine just before, and hydroxyurea during, radiation therapy. Poor-risk and good-risk patients (defined by tumor resection < 75% or >75%, positive or negative myelogram, positive or negative cerebrospinal fluid analysis, age < or >2 years, respectively) were evenly distributed between the low-dose and high-dose craniospinal radiation therapy groups. Median follow-up was 51 months (range, 24 to 228 months). Kaplan-Meier actuarial survival for all patients was 73% at 5 years, 70% at 10 years. Freedom from disease progression was 68% at 5 years, 65% at 10 years. Whereas poor-risk patients treated with low-dose craniospinal irradiation and chemotherapy had a 5-year survival of 58% and a 5-year freedom from disease progression of 39%, those figures in the comparable good-risk patients were 83% and 77%, respectively. For both good-risk and poor-risk patients, the posterior fossa was the primary site of recurrence. Tumors recurred in the frontal region, probably under blocks, in three patients receiving low-dose irradiation and in two receiving the higher dose. Reducing the dose of whole-brain and spinal irradiation and giving chemotherapy did not result in a higher rate of recurrence in the brain or spinal cord. Intellectual and social function appeared better in patients receiving the lower dose. We did not study whether chemotherapy benefitted good-risk patients. Craniospinal axis irradiation at a lower dose than conventionally used does not compromise local control or survival in patients with medulloblastoma, and may reduce toxicity.