An investigation into the impact of volumetric rescanning and fractionation treatment on dose homogeneity in liver cancer proton therapy.

The Pencil Beam Scanning (PBS) technique in modern particle therapy offers a highly conformal dose distribution but poses challenges due to the interplay effect, an interaction between respiration-induced organ movement and PBS. This study evaluates the effectiveness of different volumetric rescanning strategies in mitigating this effect in liver cancer proton therapy. We used a Geant4-based Monte Carlo simulation toolkit, 'TOPAS,' and an image registration toolbox, 'Elastix,' to calculate 4D dose distributions from 5 patients' four-dimensional computed tomography (4DCT). We analyzed the homogeneity index (HI) value of the Clinical Tumor Volume (CTV) at different rescan numbers and treatment times. Our results indicate that dose homogeneity stabilizes at a low point after a week of treatment, implying that both rescanning and fractionation treatments help mitigate the interplay effect. Notably, an increase in the number of rescans doesn't significantly reduce the mean dose to normal tissue but effectively prevents high localized doses to tissue adjacent to the CTV. Rescanning techniques, based on statistical averaging, require no extra equipment or patient cooperation, making them widely accessible. However, the number of rescans, tumor location, diaphragm movement, and treatment fractionation significantly influence their effectiveness. Therefore, deciding the number of rescans should involve considering the number of beams, treatment fraction size, and total delivery time to avoid unnecessary treatment extension without significant clinical benefits. The results showed that 2-3 rescans are more clinically suitable for liver cancer patients undergoing proton therapy.

Higher complication risk of totally implantable venous access port systems in patients with advanced cancer - a single institution retrospective analysis.

BACKGROUND: Totally implantable port systems are generally recommended for prolonged central venous access in diverse settings, but their risk of complications remains unclear for patients with advanced cancer. AIM: The aim of this study was to assess the risk of port system failure in patients with advanced cancer. DESIGN: We conducted a retrospective cohort study in a comprehensive cancer centre. SETTING/PARTICIPANTS: A detailed chart review was conducted among 566 patients with 573 ports inserted during January-June, 2009 (average 345.3 catheter-days). Cox regression analysis was applied to evaluate factors during insertion and early maintenance that could lead to premature removal of the port systems due to infection or occlusion. RESULTS: Port system-related infection was significantly associated with receiving palliative care immediately after implantation (hazard ratio, HR = 7.3, 95% confidence interval, 95% CI = 1.2-46.0), after adjusting for probable confounders. Primary cancer site also impacted the occurrence of device-related infection. Receiving oncologic/palliative care (HR = 3.0, P = 0.064), advanced cancer stage (HR = 6.5, P = 0.077) and body surface area above 1.71 m(2) (HR = 3.4, P = 0.029) increased the risk of port system occlusion. CONCLUSIONS: Our study indicates that totally implantable port systems yield a higher risk of complications in terminally ill patients. Further investigation should be carefully conducted to compare outcomes of various central venous access devices in patients with advanced cancer and to develop preventive strategies against catheter failure.

Safrole-2',3'-oxide induces cytotoxic and genotoxic effects in HepG2 cells and in mice.

Safrole-2',3'-oxide (SAFO) is a reactive electrophilic metabolite of the hepatocarcinogen safrole, the main component of sassafras oil. Safrole occurs naturally in a variety of spices and herbs, including the commonly used Chinese medicine Xi xin (Asari Radix et Rhizoma) and Dong quai (Angelica sinensis). SAFO is the most mutagenic metabolite of safrole tested in the Ames test. However, little or no data are available on the genotoxicity of SAFO in mammalian systems. In this study, we investigated the cytotoxicity and genotoxicity of SAFO in human HepG2 cells and male FVB mice. Using MTT assay, SAFO exhibited a dose- and time-dependent cytotoxic effect in HepG2 cells with TC(50) values of 361.9µM and 193.2µM after 24 and 48h exposure, respectively. In addition, treatment with SAFO at doses of 125µM and higher for 24h in HepG2 cells resulted in a 5.1-79.6-fold increase in mean Comet tail moment by the alkaline Comet assay and a 2.6-7.8-fold increase in the frequency of micronucleated binucleated cells by the cytokinesis-block micronucleus assay. Furthermore, repeated intraperitoneal administration of SAFO (15, 30, 45, and 60mg/kg) to mice every other day for a total of twelve doses caused a significant dose-dependent increase in mean Comet tail moment in peripheral blood leukocytes (13.3-43.4-fold) and in the frequency of micronucleated reticulocytes (1.5-5.8-fold). Repeated administration of SAFO (60mg/kg) to mice caused liver lesions manifested as a rim of ballooning degeneration of hepatocytes immediately surrounding the central vein. Our data clearly demonstrate that SAFO significantly induced cytotoxicity, DNA strand breaks, micronuclei formation both in human cells in vitro and in mice. More studies are needed to explore the role SAFO plays in safrole-induced genotoxicity.

A bi-tapered and air-gapped beam shaping assembly used for AB-BNCT.

The 7Li(p,n)7Be reaction, which leads to a soft neutron field, is often chosen as the neutron producing reaction used for accelerator-based boron neutron capture therapy (AB-BNCT). This study aims to design a compact beam shaping assembly (BSA) and auxiliary system for a 7Li(p,n)7Be reaction-based neutron source and to evaluate the relationship between the BSA design and the consequent neutron beam quality for further optimization. In this study, five types of moderator shapes for the BSA model were designed. Both the in-air and in-phantom figures of merit were considered to evaluate the performance of the BSA designs. It was found that the BSA with a bi-tapered and air-gapped design could generate a high-intensity epithermal neutron beam, which could be used to treat deep-seated brain tumors within a reasonable time.

Radiation-Induced Emesis (RIE) in Extended-Field Radiotherapy for Gynecological Malignancies: Dosimetric and Non-Dosimetric Factors.

Radiation-induced emesis (RIE) is usually noted during abdominal-pelvic radiotherapy. In gynecological malignancies, it is usually noted in para-aortic but not whole-pelvic irradiation. Irradiated small bowel (SB) may be associated with RIE. The significance of SB dosimetry remains unclear. Dosimetric and non-dosimetric factors were evaluated and correlated with RIE in 45 patients with gynecological malignancies undergoing extended-field radiotherapy (EFRT) (median 45 Gy) from 2006 to 2021. Early-onset RIE (within 72 h after the first fraction of EFRT) was noted in 10 of 12 RIE patients. RIE was significantly associated with the SB mean dose. The RIE rates were 58.3% and 15.2% (p = 0.007) in patients with a low (<63%) and high (≥63%) SB mean dose. Logistic regression revealed that the SB mean dose remained the independent factor of overall RIE (p = 0.049) and early-onset RIE (p = 0.014). Therefore, constraint of the SB mean dose limited to less than 63% of the prescribed dose is suggested to decrease RIE.

Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Effects of parent-based social media and moderate exercise on the adherence and pulmonary functions among asthmatic children.

Our previous study showed Tai-Chi-Chuan (TCC) training, a moderate exercise, at school improved pulmonary function and inflammation profiles in children with mild asthma. However, habitual practice is hard to maintain with the lack of continuous family and peer support. We investigated whether parental intervention with social media could enhance children's adherence to exercise at home and improve asthmatic outcome measures. Parents were opted to attend a 12-week TCC classroom training, supervise home practice, and report to a four-step web-based social media platform to stay updated and motivated through logging activity and tracking competition. Fractional exhaled nitric oxide (FeNO), FEV1/FVC and peak expiratory flow (PEF) were measured before and after 12 weeks of training. Fifty-three asthmatic children were allocated into non-TCC (control, n = 12), TCC groups with moderate-to-severe (TCC-S, n = 26) and mild-to-moderate (TCC-M, n = 15) asthma. We found both TCC groups exhibited better pulmonary function than the non-TCC control. TCC increased FVC in mild-to-moderate asthma children while more pronounced improvement in FEV1, FEV1/FVC, PEF and FeNO was noticed in moderate-to-severe asthmatic children. All TCC subjects retained greater participation and better interaction online except for low-ranking families who dramatically dropped their practice 9 weeks later. For asthmatic children, moderate exercise improves pulmonary functions in a severity-dependent fashion. Parent-based Learn-Practice-Persuade-Award wheel is a useful platform to motivate children engagement in physical activity. Classical social persuasive skills could enhance general parent-child relationship but tend to decrease in persuasiveness over time in low-ranking families.

The Chinese Version of the Brief Assessment of Cognition in Schizophrenia: Data of a Large-Scale Mandarin-Speaking Population.

OBJECTIVE: The Brief Assessment of Cognition in Schizophrenia (BACS) is a cognitive assessment tool used to measure the broad aspects of cognition that are most frequently impaired in patients with schizophrenia. This study aims to develop the normative data of the Chinese version of the BACS among the Mandarin-speaking population. METHOD: This cross-sectional study included 382 healthy participants (age range: 19-79 years; mean age: 48.0 ± 16.7 years, 47.6% men) in Taiwan, who were evaluated with the BACS. Means and standard deviations of subtests and composite scores were arranged by age group and gender. The Z-scores calculated based on the U.S. norms were compared to our scores based on the norms established in this study. RESULTS: The raw scores of all the BACS tests (verbal memory, digit sequencing, token motor test, verbal fluency, symbol coding, and Tower of London) were negatively correlated with participants' age. Women were superior to men in verbal memory, but inferior to them in executive function. Furthermore, applying the U.S. norms of the BACS to determine the performance of the Chinese BACS results in bias with regard to verbal memory, token motor test, verbal fluency, symbol coding, Tower of London and composite score. CONCLUSIONS: These findings demonstrate that directly applying western cognitive norms to a Mandarin-speaking population can cause biased interpretations. The results of this study can be an important reference for clinical settings and research related to cognitive assessments in Mandarin-speaking Chinese populations.

Application of integrative information system improves the quality and effectiveness of cancer case management.

Cancer case management provides consecutive care during the entire process through diagnosis to treatment and follow-up. We established an integrative information system with integration of the health information system. This integrative information system shortened the time spent on case screening, follow-up data management, and monthly data summarization of case managers. It also promoted the case follow-up rate. This integrative information system may improve the quality and effectiveness for cancer case management, one important part of cancer nursing.

Isolation of bona fide differentially expressed genes in the 18-hour sepsis liver by suppression subtractive hybridization.

In late sepsis, it has been established that the liver plays a major role in the initiation of multiorgan failure, which is the most lethal complication in hospitals. The molecular mechanism underlying liver failure that results from sepsis remains elusive. This study was undertaken to identify the bona fide differentially expressed genes in the 18-h septic liver by suppression subtractive hybridization, and the data were corroborated by Northern blot analysis. The differential gene expression profile renders a clue as to the genes involved in septic liver failure. The cecal ligation and puncture (CLP) model of a polymicrobial septic rat was used, with the late sepsis referring to animals sacrificed at 18 h after CLP. We have identified three upregulated genes (TII-kininogen, serine protease inhibitor 2.2 [Spi2.2], and alpha 2 macroglobulin [alpha M]) and six down-regulated genes (hydroxysteroid dehydrogenase [3 alpha HSD], EST189895/mouse RNase4, bile acid-CoA-amino acid N-acyltransferase [kan-1/rBAT], IF1, albumin, and alpha 2u-globulins [alpha 2u-G PGCL1]). Among these genes, the 3 alpha HSD and kan-1/rBAT are involved in bile acid metabolism. The IF1 plays a crucial role in any disease that involves ATP hydrolysis by F1F0-ATPase. The alpha 2M, TII-kininogen, and Spi2.2 are protease inhibitors. The functions of the alpha 2u-G PGCL1 and EST189895/mouse RNase4 genes are unknown. The present results suggest that the roles of disturbance of bile acid metabolism/synthesis and the abolishment of ATP production may contribute to liver failure during late sepsis.

Are high energy proton beams ideal for AB-BNCT? A brief discussion from the viewpoint of fast neutron contamination control.

High energy proton beam (>8MeV) is favorable for producing neutrons with high yield. However, the produced neutrons are of high energies. These high energy neutrons can cause severe fast neutron contamination and degrade the BNCT treatment quality if they are not appropriately moderated. Hence, this study aims to briefly discuss the issue, from the viewpoint of fast neutron contamination control, whether high energy proton beam is ideal for AB-BNCT or not. In this study, D2O, PbF4, CaF2, and Fluental(™) were used standalone as moderator materials to slow down 1-, 6-, and 10-MeV parallelly incident neutrons. From the calculated results, we concluded that neutrons produced by high energy proton beam could not be easily moderated by a single moderator to an acceptable contamination level and still with reasonable epithermal neutron beam intensity. Hence, much more complicated and sophisticated designs of beam shaping assembly have to be developed when using high energy proton beams.

Dosimetric performance evaluation regarding proton beam incident angles of a lithium-based AB-BNCT design.

The (7)Li(p,xn)(7)Be nuclear reaction, based on the low-energy protons, could produce soft neutrons for accelerator-based boron neutron capture therapy (AB-BNCT). Based on the fact that the induced neutron field is relatively divergent, the relationship between the incident angle of proton beam and the neutron beam quality was evaluated in this study. To provide an intense epithermal neutron beam, a beam-shaping assembly (BSA) was designed. And a modified Snyder head phantom was used in the calculations for evaluating the dosimetric performance. From the calculated results, the intensity of epithermal neutrons increased with the increase in proton incident angle. Hence, either the irradiation time or the required proton current can be reduced. When the incident angle of 2.5-MeV proton beam is 120°, the required proton current is ∼13.3 mA for an irradiation time of half an hour.

Dose estimation of animal experiments at the THOR BNCT beam by NCTPlan and Xplan.

Dose estimation of animal experiments affects many subsequent derived quantities, such as RBE and CBE values. It is important to ensure the trustiness of calculated dose of the irradiated animals. However, the dose estimation was normally calculated using simplified geometries and tissue compositions, which led to rough results. This paper introduces the use of treatment planning systems NCTplan and Xplan for the dose estimation. A mouse was taken as an example and it was brought to hospital for micro-PET/CT scan. It was found that the critical organ doses of an irradiated mouse calculated by simplified model were unreliable in comparison to Xplan voxel model. The difference could reach the extent of several tenths percent. It is recommended that a treatment planning system should be introduced to future animal experiments to upgrade the data quality.

Efficiency of drug delivery enhanced by acoustic pressure during blood-brain barrier disruption induced by focused ultrasound.

PURPOSE: We evaluated the delivery efficiency of intravenously injected large molecular agents, before and after disruption of the blood-brain barrier (BBB-D), induced by focused ultrasound (FUS) using various acoustic parameters. MATERIALS AND METHODS: Male Sprague-Dawley rats were injected intravenously with Evans blue (EB) before or after BBB-D induction by pulsed FUS. We used a 1.0 MHz pulsed FUS with four acoustic power settings and an ultrasound contrast agent (UCA) at four different doses to induce BBB-D resulting from cavitation. The permeability of the BBB was assessed quantitatively based on the extravasation of EB. Contrast enhanced magnetic resonance imaging (MRI) was used to monitor the gadolinium deposition associated with FUS. Histological analysis was performed to examine tissue damage. RESULTS: The accumulation of EB in rat brain was found to be dependent on acoustic power and UCA dosage, regardless of whether EB administration occurred before or after FUS-induced BBB-D. Administration of EB followed by sonication resulted in greater EB extravasation than that for rats subjected to sonication prior to EB injection. To reduce tissue damage, EB extravasation was enhanced by first administering EB by intravenous injection, followed by sonication at reduced acoustic power or UCA dosage. The normalized signal intensity change in rat brains that received the same dose of UCA and sonicated after gadolinium injection was significantly greater than in rats undergoing sonication followed by gadolinium administration. Moreover, contrast enhanced MRI showed a more precise distribution of gadolinium in the brain when gadolinium was administered before sonication. CONCLUSION: We demonstrated that a compound administered prior to sonication treatment promotes extravasation of the sonicated region. Thus, it is possible to optimize ultrasound parameters for lower sonication and reduced UCA doses, to induce BBB-D while minimizing damage to normal brain tissue.