Faculty Bibliography

Purpose: The purpose of this study is to assess the dosimetric equivalence of MR-generated synthetic CT and conventional CT for treatment planning in radiotherapy of rectal cancer. Methods: This study was conducted on eleven patients who underwent whole-body PET/MR and PET/CT examination in a prospective IRB-approved study. MR data were obtained on a 3T Siemens PET/MR hybrid scanner using a 2-point Dixon sequence. Synthetic CT (synCT) was generated from Dixon MR using a model-based method and then registered to CT using a deformable registration. Rectal tumors were artificially contoured in the synCT by a physician to define a planning tumor volume (PTV) for treatment planning comparison. Standard treatment planning directives were used to create a four-field box (4F), an oblique four-field box (O4F) and a volumetric modulated arc therapy (VMAT) plans on synCT for each PTV. The plans were recalculated on registered planCT with the same MUs as on synCT. Dose-volume metrics and gamma analysis were evaluated between synCT and CT plans. Results: Differences in PTV Dmin, D95% and Dmax between synCT and CT plans across all patients were 0.02 +/- 0.82% for 4F, -0.16 +/- 0.78% for O4F and -0.31 +/- 0.97% for VMAT plans. In any of the treatment techniques, no significant differences were observed in organs at risk (OAR) dose metrics including small bowel (V45 Gy), bladder (V40 Gy) and femoral head (V30 Gy). Gamma Analysis with 2%/2 mm dose difference/distance to agreement showed percentage pass rates of 98.7 +/- 3.1, 98.0 +/- 3.6, and 98.8 +/- 2.7 for 4F, O4F and VMAT, respectively between SynCT and CT plan. Conclusion: Planning on synCT agreed well with the dose recalculated on planning CT for conventional treatment techniques in rectal cancer radiotherapy. These results suggest the potential of MR-only radiotherapy using MR generated synCT

BACKGROUND & AIMS: The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. METHODS: We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2-12 Gy and analyzed by flow cytometry. RESULTS: Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. CONCLUSIONS: Radiation exposure causes macrophages in PDAs of mice to acquire an immune-suppressive phenotype and reduce T-cell mediated anti-tumor responses. Agents that block MCSF prevent this effect, allowing radiation to have increased efficacy in slowing tumor growth.