Dosimetric evaluation in Helical TomoTherapy for lung SBRT using Monte Carlo-based independent dose verification software.

PURPOSE: To elucidate the dosimetric errors caused by a model-based algorithm in lung stereotactic body radiation therapy (SBRT) with Helical TomoTherapy (HT) using Monte Carlo (MC)-based dose verification software. METHODS: For 38 plans of lung SBRT, the dose calculation accuracy of a treatment planning system (TPS) of HT was compared with the results of DoseCHECK, the commercial MC-based independent verification software. The following indices were extracted to evaluate the correlation of dosimetric errors: (1) target volume, (2) average computed tomography (CT) value of the planning target volume (PTV) margin, and (3) average CT value of surrounding 2-mm area of the PTV (PTV ring). Receiver operating characteristic (ROC) analyses determined the threshold for 5% of differences in PTV D95%. Then, the 38 plans were classified into two groups using the cutoff values of ROC analysis for these three indices. Dosimetric differences between groups were statistically compared using the Mann-Whitney U test. RESULTS: TPS of HT overestimated by more than 5% in the PTV D95% in 16 of 38 plans. The PTV ring showed the strongest correlation with dosimetric differences. The cutoff value for the target volume, the PTV margin, and the PTV ring was 14.7 cc, -754 HU, and -708 HU, respectively. The area under the curve (AUC) for the target volume, the PTV margin, and the PTV ring were 0.835, 0.878, and 0.932, respectively. Dosimetric errors more than 5% were observed when the PTV volume was less than 15 cc or when the CT value around the target was less than -700 HU. CONCLUSION: The TPS of HT might overestimate the PTV dose by more than 5% if any the three indices in this study were below threshold. Therefore, independent verification with an MC-based algorithm should be strongly recommended for lung SBRT in HT.

Effects of muscular endurance and tendon extensibility on endurance of joint stiffness.

In some sporting events (e.g., long-distance running), the ability to maintain joint stiffness is considered an essential physical ability. However, the determinants of joint stiffness endurance remain unclear. This study aimed to examine the effects of muscular endurance and tendon extensibility on joint stiffness endurance. Thirteen males performed the fatigue task (5 sets of 50 hopping). Ankle joint stiffness during drop jump was measured before and after fatigue task. The maximum number of repetitions at 30% of one repetition maximum for plantar flexion was measured as muscular endurance. Maximal elongation of the Achilles tendon was measured during ramp (with a low strain rate of tendon) and ballistic (with a high strain rate of tendon) contractions as tendon extensibility. Joint stiffness significantly decreased by 7.5% after the fatigue task (p = 0.033). The maximum number of repetitions at 30% of 1RM (79.6 ± 48.7 repetitions) was not significantly correlated with the relative change in joint stiffness (r = 0.283, p = 0.348). The maximal elongation of the Achilles tendon measured during ramp and ballistic contractions were not significantly associated with the relative change in joint stiffness (r = 0.326, p = 0.277 for ramp contraction; r = 0.438, p = 0.135 for ballistic contraction). These results suggest that muscular endurance and tendon extensibility were unrelated to joint stiffness endurance.

Strontium-89 chloride delivery for painful bone metastases in patients with a history of prior irradiation.

BACKGROUND: Re-irradiation of a previously irradiated site must be done with careful consideration to minimize dose to organs at risk. AIMS: To evaluate pain response and safety of Sr-89 administration for painful bone metastases after prior irradiation. METHODS: We retrospectively reviewed patients with Sr-89 injection for painful bone metastasis in a previously irradiated site. All patients were seen in follow-up at 1, 2, 3, and 4 months after injection and every 6 months thereafter. Pain control, toxicity, and pain progression-free survival were analyzed. Correlation of pain relapse with the following characteristics was analyzed: gender, age, primary tumor, tumor pathology, baseline performance status, and baseline verbal rating scale. RESULTS: Among 25 patients analyzed (10 male, 15 female), median age was 68 (range, 50-81) years. Primary tumor sites included lung (n = 11), breast (n = 3), uterine cervix (n = 3), prostate (n = 3), and others (n = 5). Median follow-up was 25 (range, 1-76) months. Pain relief was observed in 24 patients (96.0%). One- and 2-year pain progression-free survival rates in these patients were 54.5% and 48.4%, respectively. Median time to pain progression was 5 (range, 2-16) months. Statistically significantly lower pain progression-free survival was observed in patients with osteolytic bone metastases (p < 0.01). No grade 3 or worse adverse events were observed. CONCLUSION: Sr-89 injection showed pain relief in most of our patients with painful bone metastases in a previously irradiated site and caused no grade 3 or worse adverse events. Sr-89 is an option for patients with a painful bone metastasis in a previously irradiated site.

Effective clinical applications of Monte Carlo-based independent secondary dose verification software for helical tomotherapy.

PURPOSE: To investigate the scope of the effective clinical application of Monte Carlo (MC)-based independent dose verification software for helical tomotherapy. METHODS: DoseCHECK was selected as the MC-based dose calculation software. First, the dose calculation accuracy of DoseCHECK was evaluated with film and chamber measurements in a water-equivalent phantom. Second, the dose calculation accuracy was examined in several heterogeneous materials. Finally, dosimetric comparisons between DoseCHECK and the treatment planning system (TPS) were performed for clinical patient plans. Prostate IMRT, head and neck IMRT (HN), total body irradiation (TBI), and brain stereotactic radiotherapy (SRT) were evaluated. RESULT: The DoseCHECK calculations agreed with the chamber and film measurements in the homogenous phantom. For heterogeneous phantom cases, the dose differences between DoseCHECK and TPS were within 3 %, except in air, in which large dose differences of 20 % were observed. In clinical patient plans, the median dose differences between the lung Dmean in TBI cases and the normal brain Dmean in brain SRT cases were significantly >3 %. For HN and brain SRT cases, the median target dose differences were >3 %. CONCLUSION: Our results show that independent dose verification with the MC algorithm can detect systematic errors caused by the lack of heterogeneity correction in the TPS. In particular, MC-based independent dose verification is required for HN, TBI, and brain SRT cases in helical tomotherapy.

Bioorthogonal Photoreactive Surfaces for Single-Cell Analysis of Intercellular Communications.

Methods to construct single-cell pairs of heterogeneous cells attract attention because of their potential in cell biological and medical applications for analyzing individual intercellular communications such as immune and nerve synaptic interactions. Photoactivatable substrate surfaces for cell anchoring are promising tools to achieve single-cell pairing. However, conventional surfaces that photoactivate a single type of cell anchoring moiety restrict the combination of cell pair types and their applications. We developed a photoresponsive material comprising a bioorthogonal photoreactive moiety and non-cell adhesive hydrophilic polymer. The material-coated surface allows conjugation with various cell anchoring molecules in response to light at specific timings and consequently achieves light-induced anchoring of a variety of cells at defined regions. Using the platform surface, an array of cancer cell and natural-killer (NK) cell pairs was constructed on a flat substrate surface and the dynamic morphological changes of the cancer cells were monitored by cytotoxic interaction with NK cells at a single-cell level. The photoreactive surface is a useful tool for image-based investigation of the communications between a variety of cell types.

Chemoenzymatic Labeling to Visualize Intercellular Contacts Using Lipidated SortaseA.

Methods to label intercellular contact have attracted attention because of their potential in cell biological and medical applications for the analysis of intercellular communications. In this study, a simple and versatile method for chemoenzymatic labeling of intercellularly contacting cells is demonstrated using a cell-surface anchoring reagent of a poly(ethylene glycol)(PEG)-lipid conjugate. The surface of each cell in the cell pairs of interest were decorated with sortase A (SrtA) and triglycine peptide that were lipidated with PEG-lipid. In the mixture of the two-cell populations, the triglycine-modified cells were enzymatically labeled with a fluorescent labeling reagent when in contact with SrtA-modified cells on a substrate. The selective labeling of the contacting cells was confirmed by confocal microscopy. The method is a promising tool for selective visualization of intercellularly contacting cells in cell mixtures for cell-cell communication analysis.

Photoactivatable Materials for Versatile Single-Cell Patterning Based on the Photocaging of Cell-Anchoring Moieties through Lipid Self-Assembly.

Versatile methods for patterning multiple types of cells with single-cell resolution have become an increasingly important technology for cell analysis, cell-based device construction, and tissue engineering. Here, we present a photoactivatable material based on poly(ethylene glycol) (PEG)-lipids for patterning a variety of cells, regardless of their adhesion abilities. In this study, PEG-lipids bearing dual fatty acid chains were first shown to perfectly suppress cell anchoring on their coated substrate surfaces whereas those with single-chain lipids stably anchored cells through lipid-cell membrane interactions. From this finding, a PEG-lipid with one each of both normal and photocleavable fatty acid chains was synthesized as a material that could convert the chain number from two to one by exposure to light. On the photoconvertible PEG-lipid surface, cell anchoring was activated by light exposure. High-speed atomic force microscopy measurements revealed that this photocaging of the lipid-cell membrane interaction occurs because the hydrophobic dual chains self-assemble into nanoscale structures and cooperatively inhibit the anchoring. Light-induced dissociation of the lipid assembly achieved the light-guided fine patterning of multiple cells through local photoactivation of the anchoring interactions. Using this surface, human natural killer cells and leukemia cells could be positioned to interact one-by-one. The cytotoxic capacity of single immune cells was then monitored via microscopy, showing the proof-of-principle for applications in the high-throughput analysis of the heterogeneity in individual cell-cell communications. Thus, the substrate coated with our photoactivatable material can serve as a versatile platform for the accurate and rapid patterning of multiple-element cells for intercellular communication-based diagnostics.

Photo-responsive materials with strong cell trapping ability for light-guided manipulation of nonadherent cells.

We report a photo-cleavable material for tight trapping of nonadherent cells to substrate surfaces. Model immunocytes were selectively trapped in a non-irradiated area as single cells after the projection of a light pattern and withstood high-speed laminar flow, achieving light-guided cell release from the substrates.

Reversible and Photoresponsive Immobilization of Nonadherent Cells by Spiropyran-Conjugated PEG-Lipids.

Spatiotemporal control of cell-material interactions contributes to our understanding of cell biology and the development of cell engineering. Here, we first report the reversible and spatio-selective immobilization of nonadherent cells through the use of photoswitchable polymeric materials. The substrate coated with spiropyran-conjugated poly(ethylene glycol) (PEG) lipids, which bind to cell membranes via the lipid moiety only in their merocyanine form, enabled rapid cell immobilization and release in an on-off manner by irradiation with ultraviolet and visible light, respectively. Our work has the potential to improve the performance of cell manipulations on chips and to enable rapid cell arrangement/sorting on various surfaces.