A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma

Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma
treatment regimen will be eligible to enroll prior to surgical resection of the primary
tumor. Following implantation of fiducial markers within the tumor bed and autologous
hematopoietic rescue, patients will begin the planning process for abdominal irradiation;
this requires multiple baseline studies, including computed tomography (CT), magnetic
resonance imaging (MRI), renal scintigraphy, and bloodwork. Most of these tests will be
repeated on a varying schedule over the five year follow-up period of the protocol, in order
to evaluate the impact of conformal radiotherapy on intra-abdominal tissues.

Intensity modulated radiation therapy (IMRT) delivery will follow current conventional
volume-targeting guidelines, however, appropriate application within the abdomen will be
determined by ascertaining intra-abdominal organ motion and the potential for reducing
normal tissue dose, while simultaneously increasing dose delivered to target tissues,
particularly when dose escalation for gross residual disease is required. Concurrent
neuro-hormonal tests, cytokine analyses, functional and morphologic imaging will generate
novel data describing the acute and chronic effects of radiotherapy within the abdomen.

NOTE: This study is currently closed to accrual, however, it is expected to re-open to
accrual later in 2015.

Inclusion Criteria:

- Mucositis ≤ Grade 2

- Patient stable on room air

- Albumin > 3 g/dL without albumin infusions for 1 week

- Serum creatinine should be < 1.5 x normal for age

- Lansky score >60

- Risk Strata Eligibility: Patients between 6 months and 18 years of age with newly
diagnosed abdominal primary, high-risk neuroblastoma defined as one of the following:

- International agreement on staging (INSS) stage 2a or 2b with N-myc (MYCN)
amplification (greater than four-fold increase in (MYCN) signals as compared to
reference signals), regardless of age or additional biologic features

- INSS stage 3 with either MYCN amplification (greater than four-fold increase in
MYCN signals as compared to reference signals), regardless of age or additional
biologic features, or for age > 18 months with unfavorable pathology, regardless
of MYCN status

- INSS stage 4 with MYCN amplification (greater than four-fold increase in MYCN
signals as compared to reference signals), regardless of age or additional
biologic features, or for age >18 months with unfavorable pathology, regardless
of MYCN status

- INSS stage 4S with MYCN amplification (greater than four-fold increase in MYCN
signals as compared to reference signals), regardless of additional biologic
features

- Exceptional Cases Still Considered Eligible:

- Prior palliative radiotherapy if not related to the primary site, however,
children receiving definitive radiotherapy as a part of the pre-enrollment
regimen are ineligible. Prior treatment regimen must follow the guidelines of an
applicable high-risk neuroblastoma regimen. Slight variations from this
timeframe are acceptable based on recovery of blood counts or other concerns
left to the discretion of the treating radiation oncologist.

- Patients receiving surgical management elsewhere are still considered eligible
to enroll on protocol therapy for assessment of the primary local control
objective, renal motion and toxicity assessment. Target motion objectives may be
excluded from the analysis of these patients.

Exclusion Criteria

- Patients who have received prior definitive radiotherapy at or adjacent to the
primary abdominal tumor bed.

- Patients who are unable to cooperate with acquisition of 4-dimensional computed
tomography (4DCT), computed tomography (CT) or magnetic resonance imaging-
(MRI)-based imaging procedures.

- Patients with known brain metastases.

- Any evidence of severe or uncontrolled systemic disease (e.g., unstable or
uncompensated respiratory, cardiac, hepatic, or renal disease).

- Pregnant women.

- Mediastinal primary tumors.

- Patients receiving surgery elsewhere, or at St. Jude within 3 months prior to study
activation, are excluded from assessment of target and motion objectives. However
they are still eligible to enroll for assessment of the primary objective, renal
motion and toxicity.