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Purpose: To report planning and acute toxicity data of the first 60 patients treated within a Phase I–II study with moderate hypofractionation by image-guided helical tomotherapy. Methods and Materials: Various clinical target volumes (CTVs) were defined: CTV1—pelvic nodes; CTV2—upper portion of seminal vesicles; CTV3—lower portion of SV; CTV4—prostate; overlap between planning target volume (PTV) 4 and rectum. Different doses to each PTV were simultaneously delivered in 28 fractions. For 31 low-risk patients: 56.0, 61.6, and 71.4 Gy for PTV2–4, respectively; for 20 intermediate-risk patients: 51.8, 61.6, 65.5, and 74.2 Gy for PTV1–4, respectively; for 9 high-risk patients: 51.8 and 65.5 Gy for PTV1–2 and 74.2 Gy for PTV3–4. For all patients, the dose to overlap was 65.5 Gy. Results: The mean fraction of rectum receiving more than 65 Gy (V65) and rectal Dmax were 10% and 70.8 Gy respectively. In cases of pelvic node irradiation, the intestinal cavity (outside PTV) receiving > 45 and 50 Gy was 86 and 12 cc, respectively. A homogeneous dose distribution within each PTV was guaranteed. Acute genitourinary toxicity according to RTOG scoring system was as follows: 21/60 (35%) Grade 1, 12/60 (20%) Grade 2, 2/60 (3%) Grade 3. Acute rectal toxicities were: 18/60 (30%) Grade 1. Twelve (20%) patients showed Grade 1 upper intestinal toxicity (uGI). No patients experienced ≥ Grade 2 acute rectal or uGI side effects. Conclusions: This study shows excellent results with regard to acute toxicity. Further research is necessary to assess definitive late toxicity and tumor control outcome. [Copyright &y& Elsevier]