A Wilcoxon signed rank sum test for nonparametric paired data was used to compare the 3DCRT and IMRT plans with the proton plans for the various dosimetric points, and to establish statistical significance, P≤0.05 (WinStat Microsoft Excel, Microsoft, Redmond,

WA). Results Target volume coverage All 3DCRT, IMRT, and proton plans met all normal-tissue constraints and were isoeffective in terms of PTV coverage. Pelvic bone Inhibitors,research,lifescience,medical marrow dosimetry The results for median pelvic bone marrow dosimetry comparing the 3 plans are shown in Table 1. At all dose levels evaluated, proton plans offered significantly reduced pelvic bone marrow exposure over 3DCRT and IMRT. Table 1 Median pelvic bone marrow exposure for 3DCRT versus IMRT versus proton therapy plans (range in parentheses) Small bowel and bladder dosimetry The results for small bowel and bladder dosimetry are shown in Table 2. Proton therapy was statistically superior to 3DCRT with regard to small bowel exposure at Inhibitors,research,lifescience,medical all evaluated dose levels and with regard to the urinary bladder at the V40Gy level. The superiority of proton therapy over IMRT Inhibitors,research,lifescience,medical with regard to small bowel exposure was

limited to the V10Gy and V20Gy levels. There was no significant improvement with protons compared to IMRT with regard to urinary bladder exposure. Table 2 Median small bowel and bladder normal-tissue exposures for each planning technique Discussion We present the first known dosimetric study comparing 3DCRT, IMRT, and proton therapy plans for neoadjuvant CRT for resectable rectal cancer. The results show superior bone marrow sparing for proton therapy over IMRT and 3DCRT and better sparing of small bowel with proton therapy, Inhibitors,research,lifescience,medical particularly at low-dose thresholds. As a result of its dosimetric advantages in certain tumors, such as childhood cancers (5-10)

and skull base tumors Inhibitors,research,lifescience,medical (11-13), proton therapy is a well-established radiotherapy Volasertib chemical structure treatment technique. Furthermore a growing body of evidence is emerging indicating superior dosimetric profiles and sparing of normal mafosfamide tissue over 3DCRT, IMRT, or both in various other tumor sites, including lung tumors (14-16), lymphoma (17,18) and upper gastrointestinal (GI) tumors (19,20). While radiation therapy for rectal cancer is a long-established practice and neoadjuvant CRT is a standard of care in the management of operable locally advanced rectal cancer (2,3,21,22), preoperative radiation is still delivered in most cancer centers using 3DCRT. Neoadjuvant CRT with 3DCRT, however, results in non-trivial rates of acute and late treatment toxicity from treatment as well as significant local and distant recurrence rates. In the German study (3) comparing pre- and postoperative CRT in which preoperative CRT was given to a dose of 50.