In this study, we sought to compare Epigenetic inhibitor in vivo proton therapy plans for patients treated with neoadjuvant CRT to IMRT and 3DCRT plans in an attempt to quantify the dosimetric benefit of proton therapy in a cohort of patients receiving neoadjuvant CRT. Materials and methods Under an institutional review board-approved study, 8 consecutive patients with resectable rectal cancers underwent treatment planning with

3DCRT, IMRT, and conformal proton therapy. All patients were simulated in the prone position with a full bladder and imaged on a Phillips Brilliance (Phillips Healthcare, Andover, MA) Inhibitors,research,lifescience,medical large-bore computed tomography (CT) scanner with a 60-cm field-of-view and 1-mm slices. Target volumes and dose constraints Initial target volumes (PTV1) were contoured using the guidelines in the Radiation Therapy Oncology Group (RTOG) anorectal atlas (4). The initial clinical target volume (CTV) consisted of the gross tumor volume (GTV) as determined by a combination of physical examination, colonoscopy, and diagnostic CT and/or magnetic Inhibitors,research,lifescience,medical resonance imaging (MRI) scan plus the entire mesorectum, including the perirectal fat and presacral space

along with the internal iliac lymph nodes. Boost target volumes (PTV2) consisted of the GTV plus a 2-cm uniform expansion. The dose delivered to the PTV1 was 45 Gray (Gy) or Cobalt Gray Equivalent (CGE) in 25 fractions with Inhibitors,research,lifescience,medical a boost of 5.4 CGE in 3 fractions to the PTV2, resulting in a total dose of 50.4 CGE over 28 fractions. Target goals were similar to those used in the RTOG 0822 protocol for resectable rectal cancer. For each treatment phase, 95% of the PTV received 100% of the target dose and 100% of the PTV received 95% of the target dose. Per the normal-tissue constraints, no more than Inhibitors,research,lifescience,medical 180 cm3 of small bowel received greater than 35 Gy, while no more than 40% of the femoral heads received greater than 40 Gy; V40Gy for the bladder was less than 40%. 3DCRT plans delivered the target doses via a standardized 3-field (posterior/anterior, right lateral, and left lateral) approach with a 2-to-1 field weighting by dose contributed to the Inhibitors,research,lifescience,medical target volume. IMRT plans delivered the initial 45 Gy following the planning

and dose delivery guidelines of the RTOG 0822 protocol and a 5.4-Gy boost by following the same field before angles as the initial plan. PT plans utilized a 3-field approach similar to the 3DCRT plans with a heavier weighting of the posterior field relative to the right and left lateral fields (3.1 to 1 to 1). To avoid excess skin toxicity, the maximum dose permitted to 1 cm2 of skin was 35 Gy. To account for air within the rectum when designing the proton plan, the Hounsfield units were overridden for the circumferential air-filled portion of the rectum. Representative colorwash dose distributions for typical proton therapy, IMRT and 3DCRT plans are shown in Figure 1. Figure 1 Colorwash dose distributions for typical proton therapy, IMRT and 3DCRT plans for a patient with resectable rectal cancer.