Person:

Wang, Yi

Purpose

To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and set-up approaches employed in proton therapy.

Methods

We used series of CT data, which included the pre-treatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription iso-dose were evaluated.

Results

In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7–3.6 mm for individual patients, variations of over 5 mm from the planning CT observed in all series), and femur rotation angle (standard deviation between 1.3–4.8°, with the maximum excursion exceeding 10° in 6 out of 10 datasets). Shifts in the position of treated volume (98% iso-dose) were correlated with the variations in the lateral tissue thickness.

Conclusions

Analysis suggests that, combined with image-guided set-up verification, the range compensator expansion technique prevents loss of dose to target due to femur rotation and soft tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer.

Abstract Basic fibroblast growth factor (bFGF), which plays an important role in tumour angiogenesis and progression, provides a potential target for cancer therapy. Here we screened a phage display heptapeptide library with bFGF and identified 11 specific bFGF-binding phage clones. Two of these clones had identical sequence and the corresponding peptide (referred to as P7) showed high homology to the immunoglobulin-like (Ig-like) domain III (D3) of high-affinity bFGF receptors, FGFR1 (IIIc) and FGFR2 (IIIc). The P7 peptide and its corresponding motif in D3 of FGFRs both carried negative charges and shared similar hydrophobic profiles. Functional analysis demonstrated that synthetic P7 peptides mediate strong inhibition of bFGF-induced cell proliferation and neovascularization. Our results demonstrate that the P7 peptide is a potent bFGF antagonist with strong antiangiogenetic activity, and might have therapeutic potential in cancer therapy.

Abstract The development of non-invasive ocular drug delivery systems is of practical importance in the treatment of retinal disease. In this study, we evaluated the efficacy of transactivator of transcription protein transduction domain (TAT-PTD, TAT49–57) as a vehicle to deliver acidic FGF (aFGF) to retina in rats. TAT-conjugated aFGF-His (TAT-aFGF-His) exhibited efficient penetration into the retina following topical administration to the ocular surface. Immunochemical staining with anti-His revealed that TAT-aFGF-His proteins were readily found in the retina (mainly in the ganglion cell layer) at 30 min. and remained detectable for at least 8 hrs after administration. In contrast, His+ proteins were undetectable in the retina after topical administration of aFGF-His, indicating that aFGF-His cannot penetrate the ocular barrier. Furthermore, TAT-aFGF-His, but not aFGF-His, mediated significant protection against retinal ischemia–reperfusion (IR) injury. After IR injury, retina from TAT-aFGF-His-treated rats showed better-maintained inner retinal layer structure, reduced apoptosis of retinal ganglion cells and improved retinal function compared to those treated with aFGF-His or PBS. These results indicate that conjugation of TAT to aFGF-His can markedly improve the ability of aFGF-His to penetrate the ocular barrier without impairing its biological function. Thus, TAT49–57 provides a potential vehicle for efficient drug delivery in the treatment of retinal disease.

Hypertension has become a significant global public health concern and is also one of the most common risk factors of cardiovascular disease. Recent studies have shown the promising result of peptides inhibiting angiotensin converting enzyme (ACE) in lowering the blood pressure in both animal models and humans. However, the oral bioavailability and continuous antihypertensive effectiveness require further optimization. Novel nanoparticle-based drug delivery systems are helpful to overcome these barriers. Therefore, a poly-(lactic-co-glycolic) acid nanoparticle (PLGANPs) oral delivery system, of the antihypertensive small peptides Val-Leu-Pro-Val-Pro (VLPVP, VP5) model, was developed in this study and its antihypertensive effect was investigated in spontaneously hypertensive rats (SHRs) for the first time. The obtained VP5 nanoparticles (VP5-NPs) showed a small particle size of 223.7 ± 2.3 nm and high entrapment efficiency (EE%) of 87.37% ± 0.92%. Transmission electronic microscopy (TEM) analysis showed that the nanoparticles were spherical and homogeneous. The optimal preparation of VP5-NPs exhibited sustained release of VP5 in vitro and a 96 h long-term antihypertensive effect with enhanced efficacy in vivo. This study illustrated that PLGANPs might be an optimal formulation for oral delivery of antihypertensive small peptides and VP5-NPs might be worthy of further development and use as a potential therapeutic strategy for hypertension in the future.

This study evaluates the implementation of volumetric‐modulated arc therapy (VMAT) using multicriteria optimization (MCO) in the RayStation treatment planning system (TPS) for complex sites, namely extremity and body sarcoma. The VMAT‐MCO algorithm implemented in RayStation is newly developed and requires an integrated, comprehensive analysis of plan generation, delivery, and treatment efficiency. Ten patients previously treated by intensity‐modulated radiation therapy (IMRT) with MCO were randomly selected and replanned using VMAT‐MCO. The plan quality was compared using homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV) and dose sparing of organs at risk (OARs). Given the diversity of the tumor location, the 10 plans did not have a common OAR except for skin. The skin D50 and Dmean was directly compared between VMAT‐MCO and IMRT‐MCO. Additional OAR dose points were compared on a plan‐by‐plan basis. The treatment efficiency was compared using plan monitor units (MU) and net beam‐on time. Plan quality assurance was performed using the Sun Nuclear ArcCHECK phantom and a gamma criteria of 3%/3 mm. No statistically significant differences were found between VMAT‐ and IMRT‐MCO for HI and CI of the PTV or D50 and Dmean to the skin. The VMAT‐MCO plans showed general improvements in sparing to OARs. The VMAT‐MCO plan set showed statistically significant improvements over the IMRT‐MCO set in treatment efficiency per plan MU (p<0.05) and net beam‐on time (p<0.01). The VMAT‐MCO plan deliverability was validated. Similar gamma passing rates were observed for the two modalities. This study verifies the suitability of VMAT‐MCO for sarcoma cancer and highlighted the comparability in plan quality and improvement in treatment efficiency offered by VMAT‐MCO as compared to IMRT‐MCO. PACS number(s): separated by commas 87.55.D, 87.55.de, 87.55.Qr

Abstract This study compared the dosimetric performance of (a) volumetric modulated arc therapy (VMAT) with standard optimization (STD) and (b) multi‐criteria optimization (MCO) to (c) intensity modulated radiation therapy (IMRT) with MCO for hippocampal avoidance whole brain radiation therapy (HA‐WBRT) in RayStation treatment planning system (TPS). Ten HA‐WBRT patients previously treated with MCO‐IMRT or MCO‐VMAT on an Elekta Infinity accelerator with Agility multileaf collimators (5‐mm leaves) were re‐planned for the other two modalities. All patients received 30 Gy in 15 fractions to the planning target volume (PTV), namely, PTV30 expanded with a 2‐mm margin from the whole brain excluding hippocampus with margin. The patients all had metastatic lesions (up to 12) of variable sizes and proximity to the hippocampus, treated with an additional 7.5 Gy from a simultaneous integrated boost (SIB) to PTV37.5. The IMRT plans used eight to eleven non‐coplanar fields, whereas the VMAT plans used two coplanar full arcs and a vertex half arc. The averaged target coverage, dose to organs‐at‐risk (OARs) and monitor unit provided by the three modalities were compared, and a Wilcoxon signed‐rank test was performed. MCO‐VMAT provided statistically significant reduction of D100 of hippocampus compared to STD‐VMAT, and Dmax of cochleas compared to MCO‐IMRT. With statistical significance, MCO‐VMAT improved V30 of PTV30 by 14.2% and 4.8%, respectively, compared to MCO‐IMRT and STD‐VMAT. It also raised D95 of PTV37.5 by 0.4 Gy compared to both MCO‐IMRT and STD‐VMAT. Improved plan quality parameters such as a decrease in overall plan Dmax and total monitor units (MU) were also observed for MCO‐VMAT. MCO‐VMAT is found to be the optimal modality for HA‐WBRT in terms of PTV coverage, OAR sparing and delivery efficiency, compared to MCO‐IMRT or STD‐VMAT.