<h3>Purpose/Objective(s)</h3> Post-operative flank radiotherapy (RT) is standard for many children with renal tumors for treatment of microscopic disease in the retroperitoneal (RP) renal bed/ para-aortic lymph nodes (PALN). Standard APPA X-ray (XRT) fields include normal tissues (NT) within abdomen not at risk for malignant contamination, and do not conform to RP region. We report results of planned interim analysis from a study evaluating use of conformal pencil beam scanned proton therapy (PBS) for RT of RP. <h3>Materials/Methods</h3> Patients (pts) were enrolled on Phase II trial with IRB approval; eligibility included Wilms tumor or clear cell sarcoma of kidney (CCSK) requiring flank-only RT according to Children's Oncology Group guidelines. Primary endpoint: toxicity (CTCv4.0). Secondary endpoints: patient reported outcomes (PRO), NT dosimetry, local recurrence (LR), and overall survival (OS). After 4D simulation, pre-operative images were fused. Superior/ inferior/ lateral GTV were determined by pre-op disease extent, with 1cm tool used to contour RP space; GTV was expanded 1cm to create CTV; PALN included when involved. Standard RT (10.8 Gy/6 fx) was condensed to 10 Gy/5 fx. Normal tissue constraints (NTC) included kidney (CK) (V80<10Gy), cord (max 12Gy), heart (max 11Gy, V50<10Gy), liver (V70<20Gy). <h3>Results</h3> From 1/2018-12/2021, 11 pts enrolled with planned interim analysis after 10th: 8 boys/3 girls, 6 black/ 5 white, median age 3y (range 1-9 y), 2 with clinical Beckwith-Wiedemann syndrome, 7 requiring daily anesthesia. Nine had unilateral (UL) tumors (5 left-sided, 8 Wilms tumor (7 favorable histology, 2 diffuse anaplasia (DA)), 1 CCSK); 2 had bilateral Wilms with UL DA. Overall stage was I (1), II (2), III (4), IV (2), V (2) and local I (2), II (2), III (7). All had chemotherapy, 8 pre-operatively. Total dose was 10 Gy/ 5 fx for 9 pts given in one week; 2 required additional 9 Gy for unresected PALN (1) and positive margin (1). PBS was delivered to CTV using two energy-degraded beams from 230 MeV cyclotron (posterior and posterior oblique) with daily IGRT. Of 10 pts analyzed, none experienced LR (median follow-up 26 m (range 12-48 m). One fx to 1 pt was given with x-rays due to proton downtime; no other missed fx. No pt experienced G2+ toxicity; 2 had hypertension at diagnosis which has resolved. Most common PRO were constipation (n=3), nausea (n=2), vomiting (n=1). NTC and >=98% CTV receiving >=98% of planned dose were met for all pts. Median dose to 50% of liver was 0.7 Gy (R 0.09-10), CK 1.35 Gy (R 0.3-2.8 Gy), bowel 5.1 Gy (R 1.2-11.4 Gy), compared to expected 10 Gy, 2 Gy, and 10 Gy with XRT to flank. <h3>Conclusion</h3> Based on planned interim analysis, the use of conformal PBS proton fields to treat the RP space for children requiring RT for Wilms tumor appears feasible and safe, allowing reduction in exposure of NT compared to XRT flank fields. Change in regimen from 6 to 5 fx has been well-tolerated. These findings support continuation of the planned trial.