Trial Outcomes & Findings for Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor (NCT NCT00085202)

Last Updated: 2024-02-08

Results Overview

The relationship between ERBB2 protein expression in tumors and progression-free survival was assessed in 122 participants with a diagnosis of medulloblastoma and with ERBB2 protein assessments. If the ERBB2 value was greater than zero, the ERBB2 was defined as positive for the participant. If the ERBB2 value was zero, the ERBB2 was defined as negative. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

416 participants

Primary outcome timeframe

2 years after tumor cell analysis in 122 participants

Results posted on

2024-02-08

Participant Flow

416 participants were enrolled between 9/9/2003 and 3/7/2013.

Of the 416 participants enrolled, three were ineligible and taken off study.

Participant milestones

Participant milestones
Measure	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	Average-Risk Group Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET's/ATRT). Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).
Overall Study STARTED	144	269
Overall Study COMPLETED	120	251
Overall Study NOT COMPLETED	24	18

Reasons for withdrawal

Reasons for withdrawal
Measure	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	Average-Risk Group Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET's/ATRT). Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).
Overall Study Still on therapy	0	2
Overall Study Bone involvement confirmed by bone scan	1	0
Overall Study Excessive toxicity	5	6
Overall Study Non-specified	5	3
Overall Study Withdrawal by Subject	1	2
Overall Study Physician Decision	1	4
Overall Study Progressive disease	11	1

Baseline Characteristics

Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Average-Risk Group n=269 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET's/ATRT). Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group n=144 Participants Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	Total n=413 Participants Total of all reporting groups
Age, Continuous	8.42 years n=5 Participants	7.87 years n=7 Participants	8.33 years n=5 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	56 Participants n=7 Participants	161 Participants n=5 Participants
Sex: Female, Male Male	164 Participants n=5 Participants	88 Participants n=7 Participants	252 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years after tumor cell analysis in 122 participants

Population: Analysis included the first 122 participants with a diagnosis of medulloblastoma and with fresh tissue and ERBB2 protein assessments. Participants with a diagnosis of PNET, PNET variants, or ATRT were not included in this analysis.

Outcome measures

Outcome measures
Measure	Average Risk Group n=122 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=85 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group n=37 Participants Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors Negative ERBB2	86.7 probability of PFS at 2 years Interval 76.9 to 96.5	93.5 probability of PFS at 2 years Interval 85.1 to 100.0	71.4 probability of PFS at 2 years Interval 48.9 to 93.9	—	—	—	—	—
Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors Positive ERBB2	79.2 probability of PFS at 2 years Interval 70.4 to 88.0	83.3 probability of PFS at 2 years Interval 73.5 to 93.1	69.6 probability of PFS at 2 years Interval 50.8 to 88.4	—	—	—	—	—

PRIMARY outcome

Timeframe: 2 years after tumor cell analysis in 122 participants

Population: Analysis was completed for the first 122 participants with a diagnosis of medulloblastoma and with fresh tissue and ERBB2 protein assessments. Participants with a diagnosis of PNET, PNET variants, or ATRT were not included in this analysis.

122 participants with a diagnosis of medulloblastoma were grouped by ERBB2 positive/negative assessment and risk group into 4 groups. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.

Outcome measures

Outcome measures
Measure	Average Risk Group n=54 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=23 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group n=31 Participants Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk n=14 Participants 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group.	83.3 probability of PFS at 2 years Interval 73.5 to 93.1	69.6 probability of PFS at 2 years Interval 50.8 to 88.4	93.5 probability of PFS at 2 years Interval 85.1 to 100.0	71.4 probability of PFS at 2 years Interval 48.9 to 93.9	—	—	—	—

PRIMARY outcome

Timeframe: within 3.5 years following completion of accrual

Population: Only patients with WNT and SHH tumors with available tissue for targeted sequencing were analyzed for frequency of mutation. WNT and SHH subgroups were identified by methylation profiling.

The frequency of mutations for the main genes associated with SHH and WNT tumors identified via targeted sequencing based on formalin fixed paraffin embedded material is provided.

Outcome measures

Outcome measures
Measure	Average Risk Group n=20 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=18 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group n=20 Participants Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk n=18 Participants 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic n=20 Participants Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic n=18 Participants Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline n=20 Participants Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline n=18 Participants Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Frequency of Mutations Associated With SHH and WNT Tumors FBXW7	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	4 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors GSE1	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors CTNNB1	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	18 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors SMARCA4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	4 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors APC	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Frequency of Mutations Associated With SHH and WNT Tumors EPHA7	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors ARID1A	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors ATM	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors BRCA2	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors PTCH1	7 Participants	0 Participants	0 Participants	0 Participants	4 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors DDX3X	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants	7 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors TP53	0 Participants	0 Participants	0 Participants	0 Participants	5 Participants	3 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors KMT2D	2 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors SUFU	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors CREBBP	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors GLI2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors TCF4	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors PTEN	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors KMT2C	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors PIK3CA	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants
Frequency of Mutations Associated With SHH and WNT Tumors ARID2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 5 years postdiagnosis

Population: Of the 126 MB patients enrolled, 41 were not eligible. This left 85 patients considered eligible for the randomization study. Of the 85 eligible patients,81 were randomized to either SOC (n= 38) or to RI (n =43). The parents of only four patients did not consent to the intervention study. Two patients randomized to the RI group, and four patients in the SOC group, were excluded due to having only a single assessment, which resulted in 75 patients (RI=41, SOC=34) over a 5-year follow-up period.

SOC is standard-of-Care control group. Patients randomly assigned to the control group received the current standard of care. RI is Reading Intervention Group. Patients randomly assigned to Reading Intervention Group which is with The Fast ForWord program. Assessment of reading decoding was completed using the Woodcock Johnson, Third Edition (WJIII) Tests of Achievement (Woodcock, McGraw, \& Mather, 2001), with particular attention given to the reading and reading-related abilities. Two subtests were completed: (1) Letter-Word Identification, and (2) Word Attack, a test requiring the patient to read phonologically regular nonwords. The combination of these two subtests provided a standardized composite score of overall reading decoding ability with a population mean of 100 and a standard deviation of 15. Scores of 90-110 are considered to be in the average range, while those 80-89 are considered low-average (refer: Journal of Pediatric Psychology 39(4) pp. 450-458, 2014).

Outcome measures

Outcome measures
Measure	Average Risk Group n=41 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=34 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Reading Decoding Composite Scores in the Intervention and Standard of Care Groups Baseline	104.1 score on a scale Standard Error 1.902	102.4 score on a scale Standard Error 2.604	—	—	—	—	—	—
Reading Decoding Composite Scores in the Intervention and Standard of Care Groups Change over time	-1.51 score on a scale Standard Error 0.4849	-1.17 score on a scale Standard Error 0.4883	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Annually for 6 years post irradiation

Population: Analysis included 100 average risk participants with a diagnosis of medulloblastoma who had cumulative radiotherapy dose profiles and treatment failure volumes data available. All participants included in analysis who were still at risk and on-study were followed for a minimum of 6 years. Participants with a diagnosis of PNET, PNET variants, or ATRT were not included in this analysis.

To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.

Outcome measures

Outcome measures
Measure	Average Risk Group n=100 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa	6 Participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At enrollment

Population: Children with medulloblastoma who were age 3-21 years at diagnosis and were enrolled on SJMB03 at St Jude Children's Research Hospital. Patients were excluded if the cumulative RT plan (Craniospinal Irradiation (CSI) and boost) could not be retrieved; if the baseline preRT Magnetic Resonance Image (MRI) scan was of poor quality, preventing delineation of brain substructures ; or if the patient had completed fewer than two specific neurocognitive evaluations for this objective.

Assessment of associative memory at enrollment. Associate memory score is a representative measurement of learning and recalling pictograph representations of words. It measures associative memory (Long-Term Retrieval). Mean=100, SD=15, Average Range 85-115. Higher is better.

Outcome measures

Outcome measures
Measure	Average Risk Group n=51 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=23 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Associative Memory for Two Risk Group at Enrollment	93.61 score on a scale Standard Error 22.25	98.04 score on a scale Standard Error 18.56	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At 5 years after enrollment

Population: Children with medulloblastoma who were age 3-21 years at diagnosis and were enrolled on SJMB03 at St Jude Children's Research Hospital. Patients were excluded if the cumulative RT plan (Craniospinal Irradiation (CSI) and boost) could not be retrieved; if the baseline preRT Magnetic Resonance Image (MRI) scan was of poor quality, preventing delineation of brain substructures; or if the patient had completed fewer than two specific neurocognitive evaluations for this objective.

Assessment of associative memory at 5 years after enrollment. Assessment of associative memory score at enrollment. Associate memory score is a representative measurement of learning and recalling pictograph representations of words. It measures associative memory (Long-Term Retrieval). Mean=100, SD=15, Average Range 85-115. Higher is better.

Outcome measures

Outcome measures
Measure	Average Risk Group n=59 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=24 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Associative Memory for Two Risk Group at 5 Years After Enrollment	98.73 score on a scale Standard Error 16.94	93.58 score on a scale Standard Error 13.7	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At enrollment

Population: Children with medulloblastoma who were age 3-21 years at diagnosis and were enrolled on SJMB03 at St Jude Children's Research Hospital. Patients were excluded if the cumulative RT plan (Craniospinal Irradiation (CSI) and boost) could not be retrieved; if the baseline preRT Magnetic Resonance Image (MRI) scan was of poor quality, preventing delineation of brain substructures; or if the patient had completed fewer than two specific neurocognitive evaluations for this objective.

Assessment of Processing Speed at enrollment. This score measure of Processing Speed based on Visual Matching and Decision Speed tests. Mean=100, SD=15, Average Range 85-115. Higher is better.

Outcome measures

Outcome measures
Measure	Average Risk Group n=48 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=21 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Processing Speed for Two Risk Group at Enrollment	83.98 score on a scale Standard Error 18.53	87.29 score on a scale Standard Error 19.73	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At 5 years after enrollment

Population: Children with medulloblastoma who were age 3-21 years at diagnosis and were enrolled on SJMB03 at St Jude Children's Research Hospital. Patients were excluded if the cumulative RT plan (Craniospinal Irradiation (CSI) and boost) could not be retrieved; if the baseline preRT Magnetic Resonance Image (MRI) scan was of poor quality, preventing delineation of brain substructures; or if the patient had completed fewer than two specific neurocognitive evaluations for this objective.

Assessment of Processing Speed at 5 years after enrollment. This score measure of Processing Speed based on Visual Matching and Decision Speed tests. Mean=100, SD=15, Average Range 85-115. Higher is better.

Outcome measures

Outcome measures
Measure	Average Risk Group n=57 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=24 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Processing Speed for Two Risk Group at 5 Years After Enrollment	84.21 score on a scale Standard Error 24.36	75.71 score on a scale Standard Error 25.71	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At enrollment

Population: Children with medulloblastoma who were age 3-21 years at diagnosis and were enrolled on SJMB03 at St Jude Children's Research Hospital. Patients were excluded if the cumulative RT plan (Craniospinal Irradiation (CSI) and boost) could not be retrieved; if the baseline preRT Magnetic Resonance Image (MRI) scan was of poor quality, preventing delineation of brain substructures; or if the patient had completed fewer than two specific neurocognitive evaluations for this objective.

Assessment of Perceptual Speed at enrollment. It measures rapidly locating and circling identical numbers from a set of numbers which reflects perceptual speed. Mean=100, SD=15, Average Range 85-115. Higher is better.

Outcome measures

Outcome measures
Measure	Average Risk Group n=49 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=23 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Perceptual Speed for Two Risk Group at Enrollment	82.06 score on a scale Standard Error 19.99	90.04 score on a scale Standard Error 18.23	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At 5 years after enrollment

Population: Children with medulloblastoma who were age 3-21 years at diagnosis and were enrolled on SJMB03 at St Jude Children's Research Hospital. Patients were excluded if the cumulative RT plan (Craniospinal Irradiation (CSI) and boost) could not be retrieved; if the baseline preRT Magnetic Resonance Image (MRI) scan was of poor quality, preventing delineation of brain substructures; or if the patient had completed fewer than two specific neurocognitive evaluations for this objective.

Assessment of Perceptual Speed at 5 years after enrollment. It measures rapidly locating and circling identical numbers from a set of numbers which reflects perceptual speed. Mean=100, SD=15, Average Range 85-115. Higher is better.

Outcome measures

Outcome measures
Measure	Average Risk Group n=59 Participants Average-Risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	Average-Risk Group n=24 Participants Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa. Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.	ERBB2 Negative & High Risk 14 participants who were ERBB2 negative and in the high risk group	SHH Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	WNT Pathway - SNV Somatic Tissue from this subgroup of patients was analyzed for somatic single nucleotide variation (SNV).	SHH Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).	WNT Pathway - SNV Germline Tissue from this subgroup of patients was analyzed for germline single nucleotide variation (SNV).
Perceptual Speed for Two Risk Group at 5 Years After Enrollment	78.68 score on a scale Standard Error 21.58	72.29 score on a scale Standard Error 27.32	—	—	—	—	—	—

Adverse Events

Average-Risk Group

Serious events: 17 serious events

Other events: 236 other events

Deaths: 0 deaths

High-Risk Group

Serious events: 17 serious events

Other events: 118 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Amar Gajjar, MD

St. Jude Children's Research Hospital

Phone: 866-278-5833

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Average-Risk Group n=269 participants at risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET's/ATRT). Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group n=144 participants at risk Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Cardiac disorders Supraventricular and nodal arrhythmia - sinus bradycardia	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Cardiac disorders Cardiac general - other	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Cardiac disorders Pericardial effusion (non-malignant)	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Vascular disorders Thrombotic microangiopathy	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
General disorders Death not associated with CTCAE term, death NOS	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Vascular disorders Hemorrhage/bleeding - other	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Hepatobiliary disorders Cholecystitis	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Hepatobiliary disorders Pancreatitis	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Febrile neutropenia	0.74% 2/269 • Number of events 2 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection, blood	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, blood	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	1.4% 2/144 • Number of events 2 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, lung (pneumonia)	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, meninges (meningitis)	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, wound	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with unknown ANC, meninges (meningitis)	0.74% 2/269 • Number of events 2 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with unknown ANC, wound	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Metabolism and nutrition disorders Acidosis (metabolic or respiratory)	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Musculoskeletal and connective tissue disorders Musculoskeletal/soft tissue - other	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Apnea	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders CNS cerebrovascular ischemia	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders CNS necrosis/cystic progression	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	2.1% 3/144 • Number of events 3 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Cognitive disturbance	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Confusion	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Encephalopathy	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Leak, cerebrospinal fluid (CSF)	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	1.4% 2/144 • Number of events 2 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Leukoencephalopathy (radiographic findings)	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Neuropathy	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Personality/behavioral	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Seizure	1.1% 3/269 • Number of events 3 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	2.1% 3/144 • Number of events 3 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Somnolence/depressed level of consciousness	0.00% 0/269 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Nervous system disorders Syncope (fainting)	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome (ARDS)	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	0.74% 2/269 • Number of events 2 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis (radiographic changes)	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.00% 0/144 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Respiratory, thoracic and mediastinal disorders Pulmonary/upper respiratory - other	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
General disorders Syndromes - other	0.37% 1/269 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	0.69% 1/144 • Number of events 1 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.

Other adverse events
Measure	Average-Risk Group n=269 participants at risk Participants assigned to the average-risk arm had localized tumor without overt evidence of invasion beyond the posterior fossa (or supratentorial compartment for PNET's/ATRT). Participants with T4 disease met the following criteria: gross total resection defined as residual tumor or imaging abnormality whose size was \<1.5 cm\^2 on postoperative CT or MR images, no evidence of CNS or extraneural metastasis, and brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \<1.5 cm\^2).	High-Risk Group n=144 participants at risk Participants assigned to the high-risk arm were determined to have the presence of metastatic disease within the neuraxis (i.e., evidence of subarachnoid dissemination), OR presence of residual disease (≥1.5 cm\^2) at the primary site after surgery.
Infections and infestations Febrile neutropenia	63.9% 172/269 • Number of events 383 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	53.5% 77/144 • Number of events 148 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection, blood	20.4% 55/269 • Number of events 76 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	16.7% 24/144 • Number of events 28 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Gastrointestinal disorders Vomiting	19.7% 53/269 • Number of events 63 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	14.6% 21/144 • Number of events 29 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	14.5% 39/269 • Number of events 54 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	16.0% 23/144 • Number of events 32 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
General disorders Pain, abdomen NOS	12.3% 33/269 • Number of events 37 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	11.8% 17/144 • Number of events 30 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Gastrointestinal disorders Nausea	10.0% 27/269 • Number of events 30 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	13.9% 20/144 • Number of events 23 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection - other	9.3% 25/269 • Number of events 33 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	11.1% 16/144 • Number of events 19 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Gastrointestinal disorders Diarrhea	8.6% 23/269 • Number of events 36 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	9.7% 14/144 • Number of events 16 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Colitis, infectious (e.g., Clostridium difficile)	8.2% 22/269 • Number of events 28 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	4.9% 7/144 • Number of events 8 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, blood	7.8% 21/269 • Number of events 30 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	6.2% 9/144 • Number of events 11 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Gastrointestinal disorders Anorexia	6.3% 17/269 • Number of events 17 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	8.3% 12/144 • Number of events 13 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with unknown ANC, blood	6.3% 17/269 • Number of events 23 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	9.0% 13/144 • Number of events 19 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, catheter-related	5.9% 16/269 • Number of events 21 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	2.1% 3/144 • Number of events 3 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Cardiac disorders Hypotension	5.9% 16/269 • Number of events 17 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	9.7% 14/144 • Number of events 19 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Cardiac disorders Hypertension	5.6% 15/269 • Number of events 25 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	6.9% 10/144 • Number of events 12 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Infections and infestations Infection, catheter-related	5.2% 14/269 • Number of events 15 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	3.5% 5/144 • Number of events 7 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Vascular disorders Hemorrhage, pulmonary/upper respiratory, nose	5.2% 14/269 • Number of events 20 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	7.6% 11/144 • Number of events 16 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
General disorders Pain, head/headache	4.8% 13/269 • Number of events 13 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	6.9% 10/144 • Number of events 14 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.
Ear and labyrinth disorders Hearing: patients with/without baseline audiogram and enrolled in a monitoring program	4.1% 11/269 • Number of events 12 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.	6.2% 9/144 • Number of events 9 • Adverse events (AEs) are reported through 9/17/2013 and include all grade 3, 4 and 5 events occurring during treatment to 30 days after treatment end, and events occurring >30 days after treatment end and felt to be possibly related to protocol treatment. Per protocol, Grade 3 and 4 hematologic toxicities, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected if they occurred from the beginning of radiation therapy through the end of 4 courses of high dose chemotherapy.