Phase II Study of Proton Radiation Therapy for Neuroblastoma

Proton radiation will be delivered daily for 3-4 weeks, depending on the dose prescribed by
study doctor. Treatment is delivered (Monday - Friday) for 5 days (no weekends or holidays).
Each treatment the participant will lie on a table for 30-45 minutes.

The radiation therapy will be outpatient at Massachusetts General Hospital.

During radiation therapy, the participant will have the following weekly assessments and
procedures:

- Physical Exam

- Assess for any side effects

- Routine blood tests (weekly or at least every other week)

Post-treatment Follow Up Visit (s):

The participant will be asked to return to the clinic 3-6 months after their last dose of
radiation therapy and then annually for up to 5 years for the following procedures:

- Medical History

- Physical Exam

- Diagnostic Imaging

- Assess for side effects

- Lung Function Tests (if required)

- MUGA or ECHO (if required)

Inclusion Criteria:

- Participants must have histologically confirmed neuroblastoma or ganglioneuroblastoma
or elevated urinary catecholamine metabolites. If tumor tissue was obtained,
pathological review of surgical specimen at the Massachusetts General Hospital or
other DF/HCC institution is required, but preliminary report only required prior to
enrollment. If no tumor tissue was obtained, urinary catecholamine metabolites are
required.

- Participants do not need to have measurable disease at the time of radiation. Age ≥ 3
and ≤ 25 years at the time of diagnosis because this study evaluates this disease
entity in the pediatric population which may differ from the adult population.

- Life expectancy of greater than 12 months.

- ECOG performance status ≤2 (Karnofsky ≥60%, Lansky ≥60%, see Appendix A).

- Diagnostic Imaging MRI and/or CT of the area to be treated within 8 weeks of any
treatment. Baseline bone marrow biopsy and bone scan (with 99mTc-diphosphonate or MIBG
scan (131I-MIBG or 123I-MIBG) from time of original diagnosis is required.

- Because radiation is known to be teratogenic, women of child-bearing potential and men
must agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation. Should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.

- Ability of the patient or the patient's legal guardian to understand and the
willingness to sign a written informed consent document.

- Participants or their legal guardian must sign consent prior to the initiation of
radiation therapy.

Exclusion Criteria:

- Patients will be ineligible if any prior therapeutic radiation therapy > 500 cGy has
been delivered.

- Patients will be ineligible if chemotherapy was completed ≥ 1 year from the planned
start date of radiation therapy or if the patient is referred for radiation therapy
after a relapse following a regimen with chemotherapy alone.

- Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 5 years and are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer
in situ, and basal cell or squamous cell carcinoma of the skin.

- Pregnant females are excluded. Women of childbearing age/menstruating must have a
negative pregnancy test prior to initiation of radiation therapy.