The Dosimetric Outcome of a Rotational Planning Target Volume in Patients With Oropharyngeal Cancers.

An isotropic expanded Planning Target Volume (PTV) neglects patient's off-axis rotation. This study designs a rotational PTV that is used instead of the standard 3-mm Clinical Target Volume (CTV) expanded PTV in oropharyngeal cancers with the goal to reduce pharyngeal constrictor muscle (PCM) mean dose. 10 patients were retrospectively evaluated. For off-axis rotation, the image was rotated around the longitudinal axis (cervical spinal canal) ± 5 degrees. These new CTVs were combined to form the rotational PTV. The standard and rotational treatment plans were designed with the goal to keep the superior and middle PCM-CTV70 mean dose to less than 50 Gy. There were a 355 cGy reduction in the superior PCM mean dose (form 5332 to 4977 cGy) and a 506 cGy reduction in middle PCM mean dose (from 4185 to 3679 cGy). 60% of patients may have at least a 20% reduction in dysphagia probability based on a Normal Tissue Complication Probability (NTCP) formula. The superior and middle PCM mean dose were reduced to less than 50 Gy in 40 and 20% of cases. There was an association between superior PCM mean dose and overlap volume of PTV70 and superior PCM in both standard (r = 0.92, p = 0.001) and rotational (r = 0.84, p = 0.002) plans. This association was present for middle PCM and PTV70 (r = 0.52, p = 0.02 and r = 0.62, p = 0.006). Rotational PTV can lower the mean dose to superior and middle PCMs, ultimately leading to lower dysphagia rates.

Cholesterol-like Condensing Effect of Perfluoroalkyl Substances on a Phospholipid Bilayer.

To understand the potential cytotoxicity of perfluoroalkyl substances (PFAS), we study their interactions with a model phospholipid bilayer membrane using molecular dynamics (MD) simulations. Four typical PFAS molecules are investigated, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), and perfluorohexane sulfonate (PFHxS). All of these PFAS molecules are found to spontaneously penetrate the lipid bilayer within a short simulation time (a few nanoseconds). During the penetration process, further free-energy analysis reveals that a PFAS molecule encounters an energy barrier at the bilayer/water interface. To overcome this free-energy barrier, the PFAS molecule flips itself at the interface. We further investigate the influence of embedded PFAS molecules on the membrane properties. All of the embedded PFAS molecules are found to produce a cholesterol-like condensing effect on the lipid bilayer, which includes increases of the order parameters of lipid tails and the thickness of the lipid bilayer and a decrease of area per lipid. Moreover, the PFAS molecules are found to form hydrogen bonds with oxygen atoms at three different positions of a lipid molecule. Our work reveals the penetration pathway of PFAS molecules entering into a lipid bilayer. In addition, the cholesterol-like condensing effect induced by embedded PFAS molecules on model membranes is systematically investigated and discussed. Our simulations can help understand the physical mechanisms of PFAS cytotoxicity.