Risk Management for Radiation-Induced Cardiovascular Disease (RICVD): The 2022 Consensus Statement of the Taiwan Society for Therapeutic Radiology and Oncology (TASTRO) and Taiwan Society of Cardiology (TSOC).

Advances in cancer management have significantly improved survival in patients with cancers. Cardiovascular complications of cancer treatment are becoming significant competing causes of death in these patients. Radiotherapy is an indispensable component of cancer treatment, and irradiation of the heart and vasculature during cancer radiotherapy is now recognized as a new risk factor for cardiovascular diseases. It is important to involve multidisciplinary expertise and provide practical recommendations to promote awareness, recognize risks, and provide adequate interventions without jeopardizing cancer control. In this consensus paper, experts from the Taiwan Society for Therapeutic Radiology and Oncology and Taiwan Society of Cardiology provide a focused update on the clinical practice for risk stratification and management of radiation-induced cardiovascular disease (RICVD). We believe that implementing RICVD care under a collaborative cardio-oncology program will significantly improve cancer treatment outcomes and will facilitate high quality clinical investigations.

Health care needs of elderly patients with lung, liver, or colon cancer in Taiwan.

BACKGROUND: Globally, different age groups in the elderly population have experienced major shifts over time. Human life expectancy doubled from the 19th to the twentieth century and has increased to 80 years in the twenty-first century. These conditions imply economic challenges and the increasing prevalence of certain health conditions. Old age is associated with increased care needs in various aspects of daily life. This study assessed the health care needs of elderly patients with lung, liver, and colorectal cancer in Taiwan and analyzed the factors underlying their needs. METHODS: This cross-sectional descriptive survey assessed 234 elderly patients with diagnosis of lung, liver, and colorectal cancer in Taiwan. We investigated their health care needs and daily living functions by using the Supportive Care Needs Survey and Karnofsky Performance Status, respectively. RESULTS: Patients required the most assistance in physical functioning and daily living. Patients aged ≥85 years required more care than those aged 65-74 years in terms of information access and sexuality needs. Patients with poor functional status required more care than those capable of undertaking normal activities. Patients diagnosed as having liver cancer required more care than those with lung or colorectal cancer. Patients with advanced cancer required more physical and daily care than those with early-stage cancer. CONCLUSIONS: Patients' health care needs differed with age, primary cancer site, and functional status. Patients aged ≥85 years and those with poor function, primary liver cancer, and advanced cancer had higher care needs.

The Effectiveness of Bereavement Support for Adult Family Caregivers in Palliative Care: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: This meta-analysis aimed to summarize and synthesize the effectiveness of bereavement support for adult family caregivers in palliative care. METHODS: Meta-analysis was conducted. The databases of the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, Medline, PubMed, Scopus, and Web of Science were comprehensively searched from inception until January 2020. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and standard methods for conducting a meta-analysis. Data analysis was performed using Comprehensive Meta-analysis version 3.0, and the random-effects model was adopted. FINDINGS: In total, 19 randomized controlled trials with an overall sample size of 2,690 participants met the inclusion criteria. The study showed that bereavement support had a significant effect on reducing grief (Hedges' g score = -0.198; 95% confidence interval [CI] -0.310 to -0.087), depression (Hedges' g score = -0.252; 95% CI -0.406 to -0.098), and anxiety (Hedges' g score = -0.153; 95% CI -0.283 to -0.023); however, high heterogeneity was present. No statistically significant difference was shown for traumatic feelings. Based on moderator analysis, a group format was more effective for grief, a combined individual and group format for depression, and an individual format for anxiety. Bereavement support was more effective when delivered by professionals, when delivered in more than six sessions, and need to be evaluated within 6 months. CONCLUSIONS: Bereavement support was effective in reducing grief, depression, and anxiety. The majority of the included studies had moderate heterogeneity, which limited the comparability of the evidence. Therefore, more robust randomized controlled trials are needed to confirm these study results. CLINICAL RELEVANCE: This meta-analysis provides evidence that bereavement support delivered in the palliative care setting is effective for reducing grief, depression, and anxiety. Nurses and other healthcare professionals can make recommendations for adult family caregivers based on this study in reducing psychological symptoms due to a loss in the palliative care domain.

Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound.

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.

Prognostic and predictive factors for clinical and radiographic responses in patients with painful bone metastasis treated with magnetic resonance-guided focused ultrasound surgery.

Background: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an alternative local therapy for patients with painful bone metastasis. However, little is known about the prognostic and predictive factors of MRgFUS in treating bone metastasis. Materials and methods: This retrospective study analyzed the performance status, treated site, pretreatment pain score, pretreatment tumor volume and lesion coverage volume factor (CVF) of 31 patients who underwent MRgFUS. A numerical rating scale for pain was used at the same time to assess the clinical response. Radiographic responses were evaluated using a modified version of The University of Texas MD Anderson Cancer Center criteria and reference to the MR imaging or computed tomography scans obtained 3 months after treatment. Univariate and multivariate logistic regression analyses were conducted to examine the effect of variables on clinical and radiographic responses. Results: The overall clinical response rate was 83.9% and radiographic response rate was 67.7%. Multivariate logistic regression analysis revealed that the better pretreatment Karnofsky performance status (KPS) (odds ratio: 1.220, 95% confidence interval (CI): 1.033-1.440; p = 0.019) was significantly associated with a more positive clinical response, and that the lesion CVF (odds ratio: 1.183, 95% CI: 1.029-1.183; p = 0.0055) was an independent prognostic factor for radiographic responses. The radiographic response of patients with lesion CVF ≥70% and CVF <70% were 91.7% and 52.6%, respectively (p = 0.0235). Conclusion: The pretreatment KPS was an independent prognostic factor for clinical responses, and lesion CVF was an independent prognostic factor for radiographic responses.

Psychometric properties of the Chinese mainland version of the Palliative Care Spiritual Care Competency Scale (PCSCCS-M) in nursing: a cross-sectional study.

BACKGROUND: Spiritual care competencies are among the primary professional skills that enable best practices in nursing. Assessing these competencies and identifying those that are insufficient are important tasks. The traditional Chinese version of the Palliative Care Spiritual Care Competency Scale (PCSCCS) used in Taiwan is a well-validated tool to measure palliative caregivers' competencies in providing spiritual care. However, whether this scale is valid and reliable for use with nurses in other health-care contexts is unknown. The purpose of this study is to determine this version's validity and reliability for use with nurses in mainland China. METHODS: The PCSCCS was first converted into a simplified Chinese version (PCSCCS-M) from the traditional Chinese version used in Taiwan such that mainland nurses could read and understand it easily. Then, the validity and reliability of the PCSCCS-M was evaluated with 400 Chinese nurses recruited using convenience sampling from three university-affiliated comprehensive hospitals, two cancer hospitals, one psychiatric hospital, two traditional Chinese medicine hospitals, one marital and child service care center, and one community health service center. Concurrent validity was assessed using Pearson's correlation coefficients of the PCSCCS-M and the Chinese version of the Spiritual Care-Giving Scale (C-SCGS). Exploratory factor analysis (EFA) was performed to determine the construct validity. Confirmatory factor analysis (CFA) was conducted using another sample of 351 nurses to verify the quality of the factor structures of the PCSCCS-M. An internal consistency test based on Cronbach's alpha coefficient and a stability test based on the Guttman split-half coefficient were also conducted. RESULTS: Useful data were obtained from 356 participants (response rate: 89%). EFA confirmed a three-dimensional structure of the scale after one item was deleted, and the three factors explained 63.839% of the total variance. Cronbach's alpha coefficients of the three subscales were 0.811, 0.889 and 0.896, and the Guttman split-half coefficient for the PCSCCS-M was 0.862. Modified CFA indicated a well-fitting model. The correlation between the PCSCCS-M and C-SCGS was 0.340 (p < 0.01). CONCLUSIONS: The PCSCCS-M is a brief, easy-to-understand, and psychometrically sound measurement tool to evaluate spiritual care competencies in nurses from mainland China.

Adaptive control of phase leading compensator parameters applied to respiratory motion compensation system.

PURPOSE: This study evaluates the feasibility of our previously developed Respiratory Motion Compensation System (RMCS) combined with the Phase Lead Compensator (PLC) to eliminate system delays during the compensation of respiration-induced tumor motion. The study objective is to improve the compensation effect of RMCS and the efficay of radiation therapy to reduce its side effects to the patients. MATERIAL AND METHODS: In this study, LabVIEW was used to develop the proposed software for calculating real-time adaptive control parameters, combined with PLC and RMCS for the compensation of total system delay time. Experiments of respiratory motion compensation were performed using 6 pre-recorded human respiration patterns and 7 sets of different sine waves. During the experiments, a respiratory simulation device, Respiratory Motion Simulation System (RMSS), was placed on the RMCS, and the detected target motion signals by the Ultrasound Image Tracking Algorithm (UITA) were transmitted to the RMCS, and the compensation of respiration induced motion was started. Finally, the tracking error of the system is obtained by comparing the encoder signals bwtween RMSS and RMCS. The compensation efficacy is verified by the root mean squared error (RMSE) and the system compensation rate (CR). RESULTS: The experimental results show that the calcuated CR with the simulated respiration patterns is between 42.85% ∼3.53% and 33.76% ∼2.62% in the Right-Left (RL) and Superior-Inferior (SI), respectively, after the RMCS compensation of using the adaptive control parameters in PLC. For the compensation results of human respiration patterns, the CR is between 58.95% ∼8.56% and 62.87% ∼9.05% in RL and SI, respectively. CONCLUSIONS: During the respiratory motion compensation, the influence of the delay time of the entire system (RMCS+RMSS+UITA) on the compensation effect was improved by adding an adaptive control PLC, which reduces compensation error and helps improve efficacy of radiation therapy.

Effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma receiving definitive radiotherapy or concurrent chemoradiotherapy through intensity-modulated radiation therapy techniques.

BACKGROUND: Few large, prospective, randomized studies have investigated the effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma (TESCC) who receive definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through modern, intensity modulated-RT (IMRT) techniques. The therapeutic effects of esophagectomy in patients with TESCC were evaluated using modern clinical staging and RT techniques and suitable RT doses. METHODS: The authors analyzed data from patients with TESCC from the Taiwan Cancer Registry database. Patients were categorized into the following groups on the basis of treatment modality to compare their outcomes: group 1 received definitive CCRT, group 2 received neoadjuvant RT followed by esophagectomy (total IMRT dose, ≥50 grays [Gy]), and group 3 receiving neoadjuvant CCRT followed by esophagectomy (total IMRT dose, ≥ 50 Gy). The median total RT dose and fraction size were 50.4 Gy and 1.8 Gy per fraction, respectively. Group 1 was used as the control arm for investigating the risk of mortality after treatment. RESULTS: In total, 3123 patients who had TESCC without distant metastasis were enrolled. Patient ages 65 years and older, Charlson comorbidity index scores ≥3, advanced clinical stages (IIA-IIIC), alcohol consumption, and cigarette smoking were identified as significant, independent poor prognostic risk factors for overall survival in multivariate Cox regression analyses. In group 3, after adjustment for confounders, the adjusted hazard ratios (95% confidence intervals [CIs]) for overall mortality were 0.62 (95% CI, 0.41-0.93) for patients with clinical stage IIA disease, 0.61 (95% CI, 0.41-0.91) for those with clinical stage IIB disease, 0.47 (95% CI, 0.38-0.55) for those with clinical stage IIIA disease, 0.47 (95% CI, 0.39-0.56) for those with clinical stage IIIB disease, and 0.46 (95% CI, 0.37-0.57) for those with clinical stage IIIC disease. CONCLUSIONS: Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043-2053. © 2017 American Cancer Society.

Garcinol downregulates Notch1 signaling via modulating miR-200c and suppresses oncogenic properties of PANC-1 cancer stem-like cells.

Pancreatic cancer represents one of the most aggressive types of malignancy due to its high resistance toward most clinically available treatments. The presence of pancreatic cancer stem-like cells (CSCs) has been attributed to the intrinsically high resistance and highly metastatic potential of this disease. Here, we identified and isolated pancreatic CSCs using the side population (SP) method from human pancreatic cancer cell line, PANC-1. We then compared the SP and non-SP PANC-1 cells genetically. PANC-1 SP cells exhibited CSC properties including enhanced self-renewal ability, increased metastatic potential, and resistance toward gemcitabine treatment. These cancer stem-like phenotypes were supported by their enhanced expression of ABCG2, Oct4, and CD44. A traditional plant-derived antioxidant, garcinol, has been implicated for its anticancer properties. Here, we found that garcinol treatment to PANC-1 SP cells significantly suppressed the stem-like properties of PANC-1 SP cells and metastatic potential by downregulating the expression of Mcl-1, EZH2, ABCG2, Gli-1, and Notch1. More importantly, garcinol treatment led to the upregulation of several tumor suppressor microRNAs, and miR-200c increased by garcinol treatment was found to target and downregulate Notch1. Thus, PANC-1 SP cells may serve as a model for studying drug-resistant pancreatic CSCs, and garcinol has the potential as an antagonist against pancreatic CSCs.

An autotuning respiration compensation system based on ultrasound image tracking.

The purpose of this study was to develop an ultrasound image tracking algorithm (UITA) for extracting the exact displacement of internal organs caused by respiratory motion. The program can track organ displacements in real time, and analyze the displacement signals associated with organ displacements via a respiration compensating system (RCS). The ultrasound imaging system is noninvasive and has a high spatial resolution and a high frame rate (around 32 frames/s), which reduces the radiation doses that patients receive during computed tomography and X-ray observations. This allows for the continuous noninvasive observation and compensation of organ displacements simultaneously during a radiation therapy session.This study designed a UITA for tracking the motion of a specific target, such as the human diaphragm. Simulated diaphragm motion driven by a respiration simulation system was observed with an ultrasound imaging system, and then the induced diaphragm displacements were calculated by our proposed UITA. These signals were used to adjust the gain of the RCS so that the amplitudes of the compensation signals were close to the target movements. The inclination angle of the ultrasound probe with respect to the surface of the abdomen affects the results of ultrasound image displacement tracking. Therefore, the displacement of the phantom was verified by a LINAC with different inclination-angle settings of the ultrasound probe. The experimental results indicate that the best inclination angle of the ultrasound probe is 40 degrees, since this results in the target displacement of the ultrasound images being close to the actual target motion. The displacement signals of the tracking phantom and the opposing displacement signals created by the RCS were compared to assess the positioning accuracy of our proposed ultrasound image tracking technique combined with the RCS.When the ultrasound probe was inclined by 40 degrees in simulated respiration experiments using sine waves, the correlation between the target displacement on the ultrasound images and the actual target displacement was around 97%, and all of the compensation rates exceeded 94% after activating the RCS. Furthermore, the diaphragm movements on the ultrasound images of three patients could be captured by our image tracking technique. The test results show that our algorithm could achieve precise point locking and tracking functions on the diaphragm. This study has demonstrated the feasibility of the proposed ultrasound image tracking technique combined with the RCS for compensating for organ displacements caused by respiratory motion.This study has shown that the proposed ultrasound image tracking technique combined with the RCS can provide real-time compensation of respiratory motion during radiation therapy, without increasing the overall treatment time. In addition, the system has modest space requirements and is easy to operate.

Clinical outcomes of robot-assisted intersphincteric resection for low rectal cancer: comparison with conventional laparoscopy and multifactorial analysis of the learning curve for robotic surgery.

BACKGROUND: This study evaluated the feasibility of robot-assisted intersphincteric resection (ISR) for low rectal cancer. Further, we attempted to analyze the learning curve for robotic surgery. METHODS: A total of 64 patients were retrospectively chart-reviewed. Patients were classified into a laparoscopic procedure (n = 28) group and a robot-assisted (n = 36) group. Comparisons of age, gender, clinical staging, operating time, complications, and pathologic status were analyzed. Besides, we used a seventh-order moving average method for the construction of a learning curve in robotic surgery. RESULTS: Operating time was 374.3 min (range, 210-570 min) in the laparoscopic group and 485.8 min (range, 315-720 min) in the robotic group, with statistical difference between these two groups (P < 0.001). Thirteen patients (46.4 %) received diverting stoma in the laparoscopic group and seven patients (19.4 %) in the robotic group, with statistical difference between these two groups (P = 0.021). Operative experience of robotic ISR showed that the mean operating time was 519.5 min (range, 360-720 min) in the first stage and 448.2 min (range, 315-585 min) in the second stage, with statistical difference between these two stages (P = 0.02). Multifactorial analysis showed that protective diverting stoma creation or neorectum necrosis was not associated with age, sex, pretreatment T stage, or surgeons' experience. CONCLUSIONS: Our data shows that robot-assisted ISR for low rectal cancer is feasible and safe with no compromising oncological outcomes. The surgeons' experience improves operating time in robotic surgery.

Biomedical nanostructured coating for minimally invasive surgery devices applications: characterization, cell cytotoxicity evaluation and an animal study in rat.

BACKGROUND: Thermal injury and tissue sticking, which influence wound remodeling, are major concerns in electrosurgery. In this study, the effect of lateral thermal injury caused by different electrosurgical electrodes on hepatic remodeling was investigated. METHODS: A monopolar electrosurgical unit equipped with untreated stainless steel (SS) and chromium nitride coated stainless steel (CrN-SS) electrodes was used to create lesions on the liver lobes of adult rats. Animals were sacrificed for evaluations at 0, 3, 7, and 28 days postoperatively. RESULTS: CrN-SS needles generated lower levels of sticking tissue, and the thermographs showed that recorded highest temperature in liver tissue from the CrN-SS needle group was significantly lower than in the SS needle group. The total injury area of livers treated with CrN-SS needles was significantly lower than livers treated with SS needles at each time point. Moreover, the CrN-SS needles caused a relatively smaller area of lateral thermal injury, a smaller area of fibrotic tissue, and a faster process of hepatic remodeling in rat liver than the SS needles. Immunofluorescence staining and Western blot analysis showed that rats treated with CrN-SS needles expressed lower levels of NF-κB and caspase-3 postoperatively. CONCLUSIONS: This study reveals that the plating of electrodes with a CrN film is an efficient method for improving the performance of electrosurgical units and should benefit wound remodeling. However, more tests must be performed to confirm these promising findings in human patients.

Photothermal Temperature-Modulated Cancer Metastasis Harnessed Using Proteinase-Triggered Assembly of Near-Infrared II Photoacoustic/Photothermal Nanotheranostics.

Here we demonstrate that cancer metastasis could be modulated by the judicious tuning of physical parameters such as photothermal temperature in nanoparticle-mediated photothermal therapy (PTT). This is supported by theranostic nanosystem design and characterization, in vitro and in vivo analyses, and transcriptome-based gene profiling. In this work, the highly efficient near-infrared II (NIR-II) photoacoustic image (PA)-guided PTT are selectively activated using our developed matrix metalloproteinase (MMP)-triggered in situ assembly of gold nanodandelions (GNDs@gelatin). Unlike other "always-on" NIR PTT agents lacking specific bioactivation and suffering from the intrinsic nonspecific pseudosignals and treatment-related side effects such as metastasis, our GNDs@gelatin possesses important advantages while deployed in cancer PTT that include the following: (1) The theranostic effects could be "turned on" only after specific MMP-2/-9 activity and with acidity in the tumor microenvironment. (2) The quantitative PA diagnosis allows for precise PTT planning for better cancer treatment. (3) GNDs@gelatin could noninvasively quantify MMP activity and efficiently harness NIR-I (808 nm) and NIR-II (1064 nm) energies for tumor ablation. (4) The multibranched nanostructures reabsorb scattered laser photons, thus enhancing the surface plasmons for the pronounced photothermal conversion of aggregated GNDs@gelatin in situ. (5) It is noteworthy that in situ tumor eradication at higher PTT temperature (>55 °C) mediated by GNDs@gelatin could induce subsequent metastasis, which could be otherwise abolished at lower PTT temperatures (50 °C > T > 43 °C). (6) Furthermore, the gene profiling using transcriptome-based microarray including GO and KEGG analyses revealed that 315 differentially expressed genes were identified in higher PTT temperature treated tumors compared with lower PTT temperature ones. These were enriched into some well-known cancer-related pathways, such as cell migration pathway, signal transductions, cell proliferation, wound healing, PPAR signaling, and metabolic pathways. These observations suggest a new perspective of "moderate-is-better" in nanoparticle-mediated PTT for maximizing its therapeutic/prognosis benefits and translational potential with metastasis inhibition.

Trifluoperazine, an antipsychotic agent, inhibits cancer stem cell growth and overcomes drug resistance of lung cancer.

RATIONALE: Cancer stem cell (CSC) theory has drawn much attention, with evidence supporting the contribution of stem cells to tumor initiation, relapse, and therapy resistance. OBJECTIVES: To screen drugs that target CSCs to improve the current treatment outcome and overcome drug resistance in patients with lung cancer. METHODS: We used publicly available embryonic stem cell and CSC-associated gene signatures to query the Connectivity Map for potential drugs that can, at least in part, reverse the gene expression profile of CSCs. High scores were noted for several phenothiazine-like antipsychotic drugs, including trifluoperazine. We then treated lung CSCs with different EGFR mutation status with trifluoperazine to examine its anti-CSC properties. Lung CSCs resistant to epidermal growth factor receptor-tyrosine kinase inhibitor or cisplatin were treated with trifluoperazine plus gefitinib or trifluoperazine plus cisplatin. Animal models were used for in vivo validation of the anti-CSC effect and synergistic effect of trifluoperazine with gefitinib. MEASUREMENTS AND MAIN RESULTS: We demonstrated that trifluoperazine inhibited CSC tumor spheroid formation and down-regulated the expression of CSC markers (CD44/CD133). Trifluoperazine inhibited Wnt/ß-catenin signaling in gefitinib-resistant lung cancer spheroids. The combination of trifluoperazine with either gefitinib or cisplatin overcame drug resistance in lung CSCs. Trifluoperazine inhibited the tumor growth and enhanced the inhibitory activity of gefitinib in lung cancer metastatic and orthotopic CSC animal models. CONCLUSIONS: Using in silico drug screening by Connectivity Map followed by empirical validations, we repurposed an existing phenothiazine-like antipsychotic drug, trifluoperazine, as a potential anti-CSC agent that could overcome epidermal growth factor receptor-tyrosine kinase inhibitor and chemotherapy resistance.

Recent Advances in Metal-Based NanoEnhancers for Particle Therapy.

Radiotherapy is one of the most common therapeutic regimens for cancer treatment. Over the past decade, proton therapy (PT) has emerged as an advanced type of radiotherapy (RT) that uses proton beams instead of conventional photon RT. Both PT and carbon-ion beam therapy (CIBT) exhibit excellent therapeutic results because of the physical characteristics of the resulting Bragg peaks, which has been exploited for cancer treatment in medical centers worldwide. Although particle therapies show significant advantages to photon RT by minimizing the radiation damage to normal tissue after the tumors, they still cause damage to normal tissue before the tumor. Since the physical mechanisms are different from particle therapy and photon RT, efforts have been made to ameliorate these effects by combining nanomaterials and particle therapies to improve tumor targeting by concentrating the radiation effects. Metallic nanoparticles (MNPs) exhibit many unique properties, such as strong X-ray absorption cross-sections and catalytic activity, and they are considered nano-radioenhancers (NREs) for RT. In this review, we systematically summarize the putative mechanisms involved in NRE-induced radioenhancement in particle therapy and the experimental results in in vitro and in vivo models. We also discuss the potential of translating preclinical metal-based NP-enhanced particle therapy studies into clinical practice using examples of several metal-based NREs, such as SPION, Abraxane, AGuIX, and NBTXR3. Furthermore, the future challenges and development of NREs for PT are presented for clinical translation. Finally, we propose a roadmap to pursue future studies to strengthen the interplay of particle therapy and nanomedicine.

Comparison of local ablative therapies, including radiofrequency ablation, microwave ablation, stereotactic ablative radiotherapy, and particle radiotherapy, for inoperable hepatocellular carcinoma: a systematic review and meta-analysis.

Surgical intervention is the first-line treatment in well-selected hepatocellular carcinoma (HCC) patients. However, only a few patients are suitable to receive radical surgery. We conducted a systematic review and meta-analysis to evaluate local control among four local ablative therapies in inoperable HCC patients, including radiofrequency ablation therapy (RFA), microwave ablation therapy (MWA), stereotactic ablative radiotherapy (SABR), and particle radiotherapy. The primary outcome was the local control rate and the secondary were regional and distant progression rates, overall survival rate, and adverse events. We included twenty-six studies from PubMed, EMBASE, and Cochrane Library databases. MWA (p < 0.001) and particle radiotherapy (p < 0.001) showed better performance of local control compared to RFA, while SABR (p = 0.276) showed a non-significant trend. However, SABR (p = 0.002) and particle radiotherapy (p < 0.001) showed better performance than RFA in HCCs of ≥ 30 mm in size. MWA showed a similar result to RFA while SABR and particle radiotherapy showed a lower survival rate in the 2-, 3-, and 4-year overall survival rates. Our results indicate that MWA, SABR and particle radiotherapy were safe and no inferior to RFA in local control rate. Besides, the local control rates of SABR and particle radiotherapy are better than RFA in HCC of ≥ 30 mm in size. As a result, we suggested that MWA, SABR and particle radiotherapy to be effective alternatives to RFA for inoperable HCC. Moreover, the tumor size should be taken into consideration for optimal treatment selection between local ablative therapies.

Entecavir versus tenofovir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative hepatectomy.

BACKGROUND: There is still controversy about whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have different effects on the outcomes of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). AIMS: The aim of this study was to compare the prognoses between ETV and TDF treatment among patients with HBV-related HCC after hepatectomy. METHODS: An analysis was done on data from the Taiwan Cancer Registry, which was linked to Taiwan National Health Insurance Research Database, for the years 2011-2016. We identified 7107 patients with HBV-related HCC after curative hepatectomy, and 25.3% of them used ETV or TDF after surgery. After propensity score overlap weighting, 1797 patients treated with ETV (n = 1365) or TDF (n = 432) were included for analyses. Cox proportional hazards models were used to compare the efficacy of ETV and TDF for recurrence and overall survival (OS). RESULTS: After hepatectomy, the recurrence rate per 100 person-years was 14.87 for the ETV group and 9.25 for the TDF group. The risk of recurrence was similar in the TDF group and the ETV group (HR [95% CI]: 0.91 [0.69-1.19; p = 0.479]), as was the risk of all-cause mortality (HR [95% CI]: 0.67 [0.42-1.07]; p = 0.091). When considering early recurrence (<2 years) and late recurrence (≧2 years), the TDF and ETV groups showed no significant differences. Subgroup analyses and sensitivity analyses demonstrated consistent results. CONCLUSION: Both TDF and ETV showed similar health benefits in terms of recurrence and OS in patients with HBV-related HCC patients after hepatectomy.

Development and evaluation of ultrasound image tracking technology based on Mask R-CNN applied to respiratory motion compensation system.

Background: For respiration induced tumor displacement during a radiation therapy, a common method to prevent the extra radiation is image-guided radiation therapy. Moreover, mask region-based convolutional neural networks (Mask R-CNN) is one of the state-of-the-art (SOTA) object detection frameworks capable of conducting object classification, localization, and pixel-level instance segmentation. Methods: We developed a novel ultrasound image tracking technology based on Mask R-CNN for stable tracking of the detected diaphragm motion and applied to the respiratory motion compensation system (RMCS). For training Mask R-CNN, 1800 ultrasonic images of the human diaphragm are collected. Subsequently, an ultrasonic image tracking algorithm was developed to compute the mean pixel coordinates of the diaphragm detected by Mask R-CNN. These calculated coordinates are then utilized by the RMCS for compensation purposes. The tracking similarity verification experiment of mask ultrasonic imaging tracking algorithm (M-UITA) is performed. Results: The correlation between the input signal and the signal tracked by M-UITA was evaluated during the experiment. The average discrete Fréchet distance was less than 4 mm. Subsequently, a respiratory displacement compensation experiment was conducted. The proposed method was compared to UITA, and the compensation rates of three different respiratory signals were calculated and compared. The experimental results showed that the proposed method achieved a 6.22% improvement in compensation rate compared to UITA. Conclusions: This study introduces a novel method called M-UITA, which offers high tracking precision and excellent stability for monitoring diaphragm movement. Additionally, it eliminates the need for manual parameter adjustments during operation, which is an added advantage.

Personalized cancer avatars for patients with thymic malignancies: A pilot study with circulating tumor cell-derived organoids.

BACKGROUND: Systemic therapy is the primary treatment for advanced thymic malignancies. However, there is an urgent need to improve clinical outcome. Personalized treatment based on predictive biomarkers is a potential approach to address this requirement. In this study, we aimed to show the correlation between drug sensitivity tests on CTCs-derived organoids and clinical response in patients with thymic malignancies. This approach carries the potential to create personalized cancer avatars and improve treatment outcome for patients. METHODS: We previously reported potential treatment outcome prediction with patient-derived organoids (cancer avatars) in patients with pancreatic ductal adenocarcinoma. To further investigate the feasibility of this approach in advanced thymic malignancies, we conducted a study in which 12 patients were enrolled and 21 liquid biopsies were performed. RESULTS: Cancer avatars were successfully derived in 16 out of 21 samples (success rate 76.2%). We found a sensitivity of 1.0 and specificity of 0.6 for drug sensitivity tests on the cancer avatars, and a two-tailed Fisher's exact test revealed a significant correlation between drug sensitivity tests and clinical responses (p = 0.0275). CONCLUSION: This study supports the potential of circulating tumor cell-derived organoids to inform personalized treatment for advanced thymic malignancies. Further validation of this proof of concept finding is ongoing.