Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low and Intermediate Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy

Inclusion Criteria:

- Newly diagnosed, previously untreated participants with localized rhabdomyosarcoma
(RMS).

- Must have either low- or intermediate-risk disease, defined as:

- Low-risk: Embryonal, botryoid, spindle cell tumors only (Subset 1: Stage 1,
Group I; Stage 1 Group I; Stage 1 Group III orbital only; Stage 2 Group I; Stage
2 Group II) (Subset 2: Stage 1 Group III non orbit; Stage 3 Group I, II)

- Intermediate-risk: Embryonal, botryoid, or spindle cell RMS: Stage 2 or 3 and
Group III; Alveolar, undifferentiated, or anaplastic RMS: stage 1-3, group
I-I; I)

- Age < 22 years (eligible until 22nd birthday)

- Performance level corresponding to ECOG score of 0, 1, or 2. The Lansky performance
score should be used for participants < 16 years

- Participant has received no prior radiotherapy or chemotherapy (excluding steroids).
Prior biopsy, surgical resection and lymph node sampling is allowed.

- Initiation of chemotherapy is planned within 6 weeks (42 days) of the definitive
biopsy or surgical resection.

- Adequate bone marrow function defined as:

- Peripheral absolute neutrophil count (ANC) ≥ 750/μL

- Platelet count ≥ 75,000/μL (transfusion independent)

- Adequate liver function defined as total bilirubin < 1.5 x upper limit of normal
(ULN) for age. Participants with biliary or hepatic primaries with bilirubin values
greater than 1.5 x ULN may be enrolled on study if all other eligibility criteria are
met.

- Adequate renal function defined as:

- Creatinine clearance or radioisotope GFR > 70 mL/min/1.732 or

- Serum creatinine based on age and gender

- Participants with urinary tract obstruction by tumor must meet the renal
function criteria listed above AND must have unimpeded urinary flow established
via decompression of the obstructed portion of the urinary tract.

- Females of child-bearing potential cannot be pregnant or breast-feeding. Female
participants > 10 years of age or post-menarchal must have a negative serum or urine
pregnancy test within 24 hours prior to beginning treatment. Female participants who
are breast feeding must agree to stop breast feeding.

- Sexually active patients of childbearing potential must be willing to use effective
contraception during therapy and for at least 1 month after treatment is completed.

- No evidence of active, uncontrolled infection.

- All participants and/or their parents or legal guardians must sign a written informed
consent.

Exclusion Criteria:

- Participants who fail to meet one or more of the inclusion criteria will be excluded.