Nomogram based on multimodal magnetic resonance combined with B7-H3mRNA for preoperative lymph node prediction in esophagus cancer.

BACKGROUND: Accurate preoperative prediction of lymph node metastasis (LNM) in esophageal cancer (EC) patients is of crucial clinical significance for treatment planning and prognosis. AIM: To develop a clinical radiomics nomogram that can predict the preoperative lymph node (LN) status in EC patients. METHODS: A total of 32 EC patients confirmed by clinical pathology (who underwent surgical treatment) were included. Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy, and its correlation with LNM was analyzed. Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python. Feature extraction, data dimensionality reduction, and feature selection were performed using XGBoost model and leave-one-out cross-validation. Multivariable logistic regression analysis was used to establish the prediction model, which included radiomics features, LN status from computed tomography (CT) reports, and B7-H3 mRNA expression, represented by a radiomics nomogram. Receiver operating characteristic area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical application value of the model. RESULTS: The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis, and the difference was statistically significant (P < 0.05). The AUC value in the receiver operating characteristic (ROC) curve was 0.718 (95%CI: 0.528-0.907), with a sensitivity of 0.733 and specificity of 0.706, indicating good diagnostic performance. The individualized clinical prediction nomogram included radiomics features, LN status from CT reports, and B7-H3 mRNA expression. The ROC curve demonstrated good diagnostic value, with an AUC value of 0.765 (95%CI: 0.598-0.931), sensitivity of 0.800, and specificity of 0.706. DCA indicated the practical value of the radiomics nomogram in clinical practice. CONCLUSION: This study developed a radiomics nomogram that includes radiomics features, LN status from CT reports, and B7-H3 mRNA expression, enabling convenient preoperative individualized prediction of LNM in EC patients.

Self-etching assembly of designed NiFeMOF nanosheet arrays as high-efficient oxygen evolution electrocatalyst for water splitting.

2D metal-organic frameworks (MOFs) have emerged as potential candidates for electrocatalytic oxygen evolution reactions (OER) due to their inherent properties like abundant coordination unsaturated active sites and efficient charge transfer. Herein, a versatile and massively synthesizable self-etching assembly strategy wherein nickel-iron foam (NFF) acts as a substrate and a metal ion source. Specifically, by etching the nickel-iron foam (NFF) surface using ligands and solvents, Ni/Fe metal ions are activated and subsequently reacted under hydrothermal conditions, resulting in the formation of self-supporting nanosheet arrays, eliminating the need for external metal salts. The obtained 33 % NiFeMOF/NFF exhibits remarkable OER performance with ultra-low overpotentials of 188/231 mV at 10/100 mA cm-2 , respectively, outperforming most recently reported catalysts. Besides, the built 33 % NiFeMOF/NFF(+) ||Pt/C(-) electrolyzer presents low cell voltages of 1.55/1.83 V at 10/100 mA cm-2 , superior to the benchmark RuO2 (+) ||Pt/C(-) , implying good industrialization prospects. The excellent catalytic activity stems from the modulation of the electronic spin state of the Ni active site by the introduction of Fe, which facilitates the adsorption process of oxygen-containing intermediates and thus enhances the OER activity. This innovative approach offers a promising pathway for commercial-scale sustainable energy solutions.

Synergistic vacancy engineering of Co/MnO@NC catalyst for superior oxygen reduction reaction in liquid/solid zinc-air batteries.

The pursuit of efficient and economically viable catalysts for liquid/solid-state zinc-air batteries (ZABs) is of paramount importance yet presents formidable challenge. Herein, we synthesized a vacancy-rich cobalt/manganese oxide catalyst (Co/MnO@NC) stabilized on a nitrogen-doped mesoporous carbon (NC) nanosphere matrix by leveraging hydrothermal and high-temperature pyrolysis strategy. The optimized Co/MnO@NC demonstrates fast reaction kinetics and large limiting current densities comparable to commercial Pt/C in alkaline electrolyte for oxygen reduction reaction (ORR). Moreover, the Co/MnO@NC serves as an incredible cathode material for both liquid and flexible solid-state ZABs, delivering impressive peak power densities of 217.7 and 63.3 mW cm-2 and robust long-term stability (459 h), outperforming the state-of-the-art Pt/C and majority of the currently reported catalysts. Research indicates that the superior performance of the Co/MnO@NC catalyst primarily stems from the synergy between the heightened electrical conductivity of metallic Co and the regulatory capacity of MnO on adsorbed oxygen intermediates. In addition, the abundance of vacancies regulates the electronic configuration, and superhydrophilicity facilitates efficient electrolyte diffusion, thereby effectively ensuring optimal contact between the active site and reactants. Besides, the coexisting NC layer avoids the shedding of active sites, resulting in high stability. This work provides a viable approach for designing and advancing high-performance liquid/solid-state ZABs, highlighting the great potential of energy storage technology.

Synergistic Co-N/V-N dual sites in N-doped Co3V2O8 nanosheets: pioneering high-efficiency bifunctional electrolysis for high-current water splitting.

Developing affluent dual-metal active sites bifunctional electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is essential to achieve large-scale water electrolysis, whereas still remains challenging. Herein, a novel nitrogen-doped cobalt-vanadium oxide with abundant Co-N and V-N dual active sites supported on nickel foam (N-Co3V2O8@NF) is constructed by a controllable impregnation-thermal nitridation strategy. The staggered nanosheet structure ensures optimal exposure of active sites. More importantly, N doping effectively regulates the electronic structure of the metal centers and induces the formation of Co-N and V-N dual active sites, which is conducive to improving the conductivity and hydrophilicity, thus synergistically enhancing the electrocatalytic efficiency. Consequently, the optimized N-Co3V2O8@NF exhibits prominent HER (63 mV@10 mA cm-2) and OER (256 mV@10 mA cm-2) activities, surpassing most contemporary bifunctional electrocatalysts. In practical application, the assembled N-Co3V2O8@NF(+/-) electrolyzer consistently achieved ultra-low cell voltages of 1.97 and 2.03 V at 500 and 1000 mA cm-2, respectively, superior to the benchmark RuO2@NF(+) || Pt/C@NF(-) and showcasing robust durability. This paves the way for its prospective adoption in industrial water electrolysis applications.

Analysis of inpatient cost burden and influencing factors of seniors' patients with mental illness in Dalian, China.

BACKGROUND: As China's aging population continues to grow, the prevalence of mental illness among the seniors has been steadily increasing. The aim of this study is to reveal the changing trends and characteristics of economic burden among seniors patients with long-term hospitalization for mental illness, and to analyze the influencing factors. METHODS: The data for this study were gathered from seniors' patients with mental illness who were hospitalized and aged 60 years or older. The patients were admitted to four specialized and general hospitals located in Dalian city between January 2018 and December 2020. The types of diseases include affective mental disorders (mood disorders), Schizophrenia, schizotypal, and delusional disorders, Organic (including symptomatic) mental disorders, Neurotic, stress-related and somatoform disorders, Mental retardation, Mental and behavioral disorders due to substance use. (Identify the main diagnosis at discharge using ICD-10 coding). This study analyzed the basic characteristics and disease-related information of seniors patients with long-term psychiatric disorders who were hospitalized, and explored the factors influencing hospitalization costs among patients with different illnesses. RESULTS: Among the 3871 study subjects, the average length of hospital stay was 127.51 days. The average hospitalization expenses per case were 33,656.07 yuan. Seniors' patients with mental illness who receives treatment in specialized hospitals have higher hospitalization costs. Long-term hospitalization increases the total hospitalization costs. Age has an impact on hospitalization costs for patients with organic mental disorders. Patients with affective disorders (mood disorders) and neurotic, stress-related, and somatoform disorders who are covered by urban employee medical insurance have higher hospitalization costs.Patients with severe psychiatric disorders who have a 31-day readmission plan, as well as senior patients with somatoform disorders comorbid with other illnesses, incur higher hospitalization costs. CONCLUSIONS: We should take corresponding measures to reduce the number of readmissions for patients with severe mental illnesses. The impact of treatment methods and differences in healthcare institutions on total hospitalization costs deserves further research. It is necessary to strengthen the prevention and diagnosis of comorbid physical illnesses in patients with mental disorders. The burden of mental illnesses in the seniors is significant, and medical insurance policies should be inclined towards providing support.

Pancancer analysis of the correlations of HS6ST2 with prognosis, tumor immunity, and drug resistance.

HS6ST2 has ability to encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS and a crucial regulator of cell growth, differentiation, adhesion, and migration. Although mounting evidence supports a vital role for HS6ST2 in tumorigenesis of some cancers, no pan-cancer analysis of HS6ST2 has been reported. Therefore, we aimed to explore the prognostic value of HS6ST2 in 33 cancer types and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Lines Encyclopedia, Genotype Tissue Expression, and GSCA, we used a range of bioinformatics approaches to explore the potential carcinogenic role of HS6ST2, analysis of HS6ST2 and prognosis, DNA methylation, RNA methylation, microsatellite instability (MSI), tumor mutation burden (TMB), and immune cell infiltration in different tumors. The results show that HS6ST2 was highly expressed in most cancers but lower in Breast invasive carcinoma, Kidney Chromophobe, Kidney renal clear cell carcinoma, Kidney renal papillary cell carcinoma, and Uterine Corpus Endometrial Carcinoma. Moreover, HS6ST2 is positively or negatively associated with prognosis in different cancers. HS6ST2 expression was not only associated with MSI in 5 cancer types and associated with TMB in 10 cancer types, and it's significantly correlated with DNA methylation in 13 types of cancer, but it's correlated with RNA methylation related genes in most cancer. HS6ST2 expression was correlated with immune cell infiltration, immune-related genes, tumor immune microenvironment, and drug resistance in various cancers. Eventually, HS6ST2 was validated in human lung adenocarcinoma tissues. Our study reveals that HS6ST2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

Progress of magnetic resonance imaging radiomics in preoperative lymph node diagnosis of esophageal cancer.

Esophageal cancer, also referred to as esophagus cancer, is a prevalent disease in the cardiothoracic field and is a leading cause of cancer-related mortality in China. Accurately determining the status of lymph nodes is crucial for developing treatment plans, defining the scope of intraoperative lymph node dissection, and ascertaining the prognosis of patients with esophageal cancer. Recent advances in diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging (MRI) have improved the effectiveness of MRI for assessing lymph node involvement, making it a beneficial tool for guiding personalized treatment plans for patients with esophageal cancer in a clinical setting. Radiomics is a recently developed imaging technique that transforms radiological image data from regions of interest into high-dimensional feature data that can be analyzed. The features, such as shape, texture, and waveform, are associated with the cancer phenotype and tumor microenvironment. When these features correlate with the clinical disease outcomes, they form the basis for specific and reliable clinical evidence. This study aimed to review the potential clinical applications of MRI-based radiomics in studying the lymph nodes affected by esophageal cancer. The combination of MRI and radiomics is a powerful tool for diagnosing and treating esophageal cancer, enabling a more personalized and effectual approach.

Synergistic Promotion of Large-Current Water Splitting through Interfacial Engineering of Hierarchically Structured CoP-FeP Nanosheets with Rich P Vacancies.

The development of hydrogen evolution reaction (HER) catalysts with high performance under large current density is still a challenge. Introducing P vacancies in heterostructure is an appealing strategy to enhance HER kinetics. This study investigates a CoP-FeP heterostructure catalyst with abundant P vacancies (Vp-CoP-FeP/NF) on nickel foam (NF), which was prepared using dipping and phosphating treatment. The optimized Vp-CoP-FeP catalyst exerted prominent HER catalytic capability, requiring an ultra-low overpotential (58 mV @ 10 mA cm-2 ) and displaying robust durability (50 h @ 200 mA cm-2 ) in 1.0 M KOH solution. Furthermore, the catalyst demonstrated superior overall water splitting activity as cathode, demanding only cell voltage of 1.76 V at 200 mA cm-2 , outperforming Pt/C/NF(-) || RuO2 /NF(+) . The catalyst's outstanding performance can be attributed to the hierarchical structure of porous nanosheets, abundant P vacancies, and synergistic effect between CoP and FeP components, which promote water dissociation and H* adsorption and desorption, thereby synergically accelerating HER kinetics and enhancing HER activity. This study demonstrates the potential of HER catalysts with phosphorus-rich vacancies that can work under industrial-scale current density, highlighting the importance of developing durable and efficient catalysts for hydrogen production.

Oxygen vacancy engineering of mesoporous Bi-Fe2O3@NC multi-channel microspheres for remarkable oxygen reduction and aqueous/flexible Zn-air batteries.

Designing multi-channel mesoporous structure and introducing oxygen vacancies to synergistically enhance oxygen reduction reaction (ORR) activity is crucial for the practical application of zinc-air batteries (ZABs) in the field of energy storage and conversion. Herein, a novel multi-channel mesoporous Bi-Fe2O3 microsphere with abundant oxygen vacancies supported on nitrogen-doped carbon (denoted as Bi-Fe2O3@NC) is constructed and the designated catalyst demonstrates a higher half-wave potential (0.88 V), large limiting current density (5.8 mA cm-2@0.4 V), and superior stability. Besides, the aqueous ZAB utilizing Bi-Fe2O3@NC cathode achieves a high power density of 198.6 mW cm-2 and maintains exceptional stability for 459 h at 5 mA cm-2, superior to most previously reported catalysts. Furthermore, a solid-state ZAB assembled with Bi-Fe2O3@NC shows a power density of 55.9 mW cm-2, highlighting its potential for flexible ZAB applications. The prominent ORR performance of Bi-Fe2O3@NC can be ascribed to its unique multi-channel mesoporous structure and abundant oxygen vacancies, which increase the exposure of active sites and facilitate efficient electron/mass transport. This work provides valuable insights for the rational design of advanced ORR catalysts for the practical requirements of aqueous/flexible ZABs in energy storage and conversion.

The Patient With Right Atrial Thrombus With a Previous History of Double-Chambered Right Ventricular Surgery and Atrial Fibrillation: A Rare Association.

Right atrial thrombosis, which occurs alone, is rare in clinical practice. Its incidence and mechanism are unclear, but susceptibility factors are usually present at its occurrence: ischemic heart disease, heart failure, atrial fibrillation, and chronic kidney disease. Complete isolated right atrial thrombosis rarely occurs. We report here a 47-year-old male patient with a right atrial mass on cardiac ultrasound and chest computed tomography (CT) and a history of previous right heart surgery with type 2 diabetes mellitus and atrial fibrillation, complaining of "chest tightness and shortness of breath after activity for half a month." The patient was admitted to the hospital and underwent right atrial mass resection, and the postoperative pathology showed "right atrial thrombus." As right atrial thrombus is very rare and can be a serious threat to life when it occurs in the heart, the prevention and treatment of right atrial thrombus are very important. Based on the analysis of this case, we believe that for patients with special medical history such as "post right heart surgery and atrial fibrillation," we need to be vigilant for atrial thrombosis.

Over-expression of USP15/MMP3 predict poor prognosis and promote growth, migration in non-small cell lung cancer cells.

Aberrant ubiquitin modifications caused by an imbalance in the activities of ubiquitinases and de-ubiquitinases are emerging as important mechanisms underlying non-small cell lung cancer (NSCLC) progression. The deubiquitinating enzyme ubiquitin-specific peptidase 15 (USP15) has been identified as an important factor in oncogenesis and a potential therapeutic target. However, the expression profile and function of USP15 in NSCLC remain elusive. In the present study, we investigated the expression pattern and the potential biological functions of USP15 in NSCLC both in cells and animal models. Our data revealed that USP15 was highly expressed in NSCLC tissues and cells compared with normal counterpart. We subsequently knocked down USP15 expression in two NSCLC cell lines, which significantly suppressed cell proliferation. In addition, knocking down USP15 expression reduced NSCLC cell migration and invasion according to the results from Matrigel-Transwell analysis. NSCLC animal model results showed that USP15 knockdown also reduced NSCLC size. Biochemical analysis revealed that USP15 knockdown inhibited matrix metalloproteinase (MMP)3 and MMP9 expression. Furthermore, high levels of USP15 and MMP3 expression were associated with poor prognosis in NSCLC. In conclusion, the results from the present study suggest that the high expression of USP15 promotes NSCLC tumorigenesis. Therefore, it is proposed that USP15 and MMPs may represent novel biomarkers for NSCLC progression and prognosis.

Effect of different surgical approaches on the prognosis of patients with postoperative radiotherapy for stage IIB-IVA esophageal squamous cancer.

OBJECTIVE: To investigate the effect and clinical significance of different thoracic surgical approaches for patients with stage IIB-IVA esophageal squamous cell carcinoma on the survival and prognosis of postoperative radiotherapy patients. METHODS: One hundred thirty-two patients with stage IIB-IVA esophageal squamous cancer who received radiotherapy after surgery were screened for baseline characteristics and survival analysis. The Kaplan-Meier method was used to draw the survival curve for the follow-up data, and the log-rank test was used to compare the difference in survival rate between the two groups. The Cox regression model was used for multivariate survival analysis. RESULT: For stage IIB-IVA esophageal squamous cell carcinoma, the results of multivariate analysis showed that different surgical methods and clinical staging were independent factors affecting the survival and prognosis of patients after radiotherapy. The 1-, 3-, and 5-year survival rates of patients with advanced esophageal cancer through the left chest approach were 84.2%, 61.4%, and 36.8% respectively. The 1-, 3-, and 5-year survival rates of patients with advanced esophageal cancer through the right chest approach were 73.3%, 40.0%, and 21.3% respectively. There was no significant difference in the 1-year survival rate (P = 0.135) between the two surgical procedures. The 3-year survival rate (P < 0.05) and the 5-year survival rate (P < 0.05) were significantly different. CONCLUSION: For patients with stage IIB-IVA esophageal squamous cell carcinoma undergoing radiotherapy after surgery, the long-term survival prognosis of patients after the left thoracic approach is significantly higher than that of the right thoracic approach.

The relationship among social support, experienced stigma, psychological distress, and quality of life among tuberculosis patients in China.

The complex relationships among social support, experienced stigma, psychological distress, and quality of life (QOL) among tuberculosis (TB) patients are insufficiently understood. The purpose of this study was to explore the interrelationships among social support, experienced stigma, psychological distress, and QOL and to examine whether experienced stigma and psychological distress play a mediating role. A cross-sectional survey was conducted between November 2020 and March 2021 in Dalian, Liaoning Province, Northeast China. Data were obtained from 473 TB patients using a structured questionnaire. Structural equation modelling was used to examine the hypothetical model. The research model provided a good fit to the measured data. All research hypotheses were supported: (1) social support, experienced stigma and psychological distress were associated with QOL; (2) experienced stigma fully mediated the effect of social support on psychological distress; (3) psychological distress fully mediated the effect of experienced stigma on QOL; and (4) experienced stigma and psychological distress were sequential mediators between social support and QOL. This study elucidated the pathways linking social support, experienced stigma, and psychological distress to QOL and provides an empirical basis for improving the QOL of TB patients.

Oxidative stress transforms 3CLpro into an insoluble and more active form to promote SARS-CoV-2 replication.

3CLpro is a key proteinase for SARS-CoV-2 replication and serves as an important target for antiviral drug development. However, how its activity is regulated intracellularly is still obscure. In this study, we developed a 3CLpro protease activity reporter system to examine the impact of various factors, including nutrient supplements, ions, pHs, or oxidative stress inducers, on 3CLpro protease activity. We found that oxidative stress could increase the overall activity of 3CLpro. Not altering the expression, oxidative stress decreased the solubility of 3CLpro in the lysis buffer containing 1% Triton-X-100. The Triton-X-100-insoluble 3CLpro was correlated with aggregates' formation and responsible for the increased enzymatic activity. The disulfide bonds formed between Cys85 sites of 3CLpro protomers account for the insolubility and the aggregation of 3CLpro. Besides being regulated by oxidative stress, 3CLpro impaired the cellular antioxidant capacity by regulating the cleavage of GPx1 at its N-terminus. This cleavage could further elevate the 3CLpro-proximate oxidative activity, favor aggregation and activation of 3CLpro, and thus lead to a positive feedback loop. In summary, we reported that oxidative stress transforms 3CLpro into a detergent-insoluble form that is more enzymatically active, leading to increased viral replication/transcription. Our study provided mechanistic evidence that suggests the therapeutic potential of antioxidants in the clinical treatment of COVID-19 patients.

Prevalence and associated factors of psychological distress in tuberculosis patients in Northeast China: a cross-sectional study.

BACKGROUND: Psychological distress, a major comorbidities of tuberculosis (TB) patients, has posed a serious threat to the progress being made in global TB programs by affecting treatment adherence and health outcomes. However, the magnitude and associated factors of psychological distress have not been fully studied in China. The aim of the current study was to assess the prevalence of psychological distress in TB patients and to further determine the effects of socio-demographic characteristics, health-related variables, substance use status, social support, and experienced stigma on psychological distress. METHODS: A cross-sectional survey was conducted among TB patients attending three medical institutions in Dalian, Liaoning Province, Northeast China from November 2020 to March 2021. A structured questionnaire was developed to collect data on patients' socio-demographic characteristics, health-related information, substance use status, psychological distress, family function, doctor-patient relationship, policy support, experienced stigma and so on. The binary logistics regression model was used to determine the associated factors of psychological distress. RESULTS: A total of 473 TB patients were enrolled in this study, and the prevalence of psychological distress was 64.1%. Binary logistic regression analysis revealed that patients with a middle school education level or above (OR: 0.521, 95%CI: 0.279-0.974), no adverse drug reactions (OR: 0.476, 95%CI: 0.268-0.846), and regular physical exercise (OR: 0.528, 95%CI: 0.281-0.993) were more likely to stay away from psychological distress. However, patients who had a high economic burden (OR: 1.697, 95%CI: 1.014-2.840), diabetes (OR: 2.165, 95%CI: 1.025-4.573), self-rated illness severe (OR: 3.169, 95%CI: 1.081-9.285), perceived poor resistance (OR: 2.065, 95%CI: 1.118-3.815), severe family dysfunction (OR: 4.001, 95%CI: 1.158-13.823), perceived need for strengthen psychological counseling (OR: 4.837, 95%CI: 2.833-8.258), and a high experienced stigma (OR: 3.253, 95%CI: 1.966-5.384) tended to have a psychological distress. CONCLUSIONS: The study found that the proportion of psychological distress among TB patients was high in Northeast China, and it was influenced by a variety of factors. Effective interventions to reduce psychological distress in TB patients urgently need to be developed, and greater attention should be given to patients with risk factors.

Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT).

OBJECTIVE: Approximately 70 patients with large and bulky tumors refractory to prior treatments were treated with photon spatially fractionated GRID radiation (SFGRT). We identified 10 additional patients who clinically needed GRID but could not be treated with photons due to adjacent critical organs. We developed a proton SFGRT technique, and we report treatment of these 10 patients. METHODS: Subject data were reviewed for clinical results and dosimetric data. 50% of the patients were metastatic at the time of treatment and five had previous photon radiation to the local site but not via GRID. They were treated with 15-20 cobalt Gray equivalent using a single proton GRID field with an average beamlet count of 22.6 (range 7-51). 80% received an average adjuvant radiation dose to the GRID region of 40.8Gy (range 13.7-63.8Gy). Four received subsequent systemic therapy. RESULTS: The median follow-up time was 5.9 months (1.1-18.9). At last follow-up, seven patients were alive and three had died. Two patients who had died from metastatic disease had local shrinkage of tumor. Of those alive, four had complete or partial response, two had partial response but later progressed, and one had no response. For all patients, the tumor regression/local symptom improvement rate was 80%. 50% had acute side-effects of grade1/2 only and all were well-tolerated. CONCLUSION: In circumstances where patients cannot receive photon GRID, proton SFGRT is clinically feasible and effective, with a similar side-effect profile. ADVANCES IN KNOWLEDGE: Proton GRID should be considered as a treatment option earlier in the disease course for patients who cannot be treated by photon GRID.

Technical Note: Spot characteristic stability for proton pencil beam scanning.

PURPOSE: The spot characteristics for proton pencil beam scanning (PBS) were measured and analyzed over a 16 month period, which included one major site configuration update and six cyclotron interventions. The results provide a reference to establish the quality assurance (QA) frequency and tolerance for proton pencil beam scanning. METHODS: A simple treatment plan was generated to produce an asymmetric 9-spot pattern distributed throughout a field of 16 × 18 cm for each of 18 proton energies (100.0-226.0 MeV). The delivered fluence distribution in air was measured using a phosphor screen based CCD camera at three planes perpendicular to the beam line axis (x-ray imaging isocenter and up/down stream 15.0 cm). The measured fluence distributions for each energy were analyzed using in-house programs which calculated the spot sizes and positional deviations of the Gaussian shaped spots. RESULTS: Compared to the spot characteristic data installed into the treatment planning system, the 16-month averaged deviations of the measured spot sizes at the isocenter plane were 2.30% and 1.38% in the IEC gantry x and y directions, respectively. The maximum deviation was 12.87% while the minimum deviation was 0.003%, both at the upstream plane. After the collinearity of the proton and x-ray imaging system isocenters was optimized, the positional deviations of the spots were all within 1.5 mm for all three planes. During the site configuration update, spot positions were found to deviate by 6 mm until the tuning parameters file was properly restored. CONCLUSIONS: For this beam delivery system, it is recommended to perform a spot size and position check at least monthly and any time after a database update or cyclotron intervention occurs. A spot size deviation tolerance of <15% can be easily met with this delivery system. Deviations of spot positions were <2 mm at any plane up/down stream 15 cm from the isocenter.

A method for modeling laterally asymmetric proton beamlets resulting from collimation.

PURPOSE: To introduce a method to model the 3D dose distribution of laterally asymmetric proton beamlets resulting from collimation. The model enables rapid beamlet calculation for spot scanning (SS) delivery using a novel penumbra-reducing dynamic collimation system (DCS) with two pairs of trimmers oriented perpendicular to each other. METHODS: Trimmed beamlet dose distributions in water were simulated with MCNPX and the collimating effects noted in the simulations were validated by experimental measurement. The simulated beamlets were modeled analytically using integral depth dose curves along with an asymmetric Gaussian function to represent fluence in the beam's eye view (BEV). The BEV parameters consisted of Gaussian standard deviations (sigmas) along each primary axis (σ(x1),σ(x2),σ(y1),σ(y2)) together with the spatial location of the maximum dose (µ(x),µ(y)). Percent depth dose variation with trimmer position was accounted for with a depth-dependent correction function. Beamlet growth with depth was accounted for by combining the in-air divergence with Hong's fit of the Highland approximation along each axis in the BEV. RESULTS: The beamlet model showed excellent agreement with the Monte Carlo simulation data used as a benchmark. The overall passing rate for a 3D gamma test with 3%/3 mm passing criteria was 96.1% between the analytical model and Monte Carlo data in an example treatment plan. CONCLUSIONS: The analytical model is capable of accurately representing individual asymmetric beamlets resulting from use of the DCS. This method enables integration of the DCS into a treatment planning system to perform dose computation in patient datasets. The method could be generalized for use with any SS collimation system in which blades, leaves, or trimmers are used to laterally sharpen beamlets.

Onset time of tumor repopulation for cervical cancer: first evidence from clinical data.

PURPOSE: Accelerated tumor repopulation has significant implications in low-dose rate (LDR) brachytherapy. Repopulation onset time remains undetermined for cervical cancer. The purpose of this study was to determine the onset time of accelerated repopulation in cervical cancer, using clinical data. METHODS AND MATERIALS: The linear quadratic (LQ) model extended for tumor repopulation was used to analyze clinical data and magnetic resonance imaging-based three-dimensional tumor volumetric regression data from 80 cervical cancer patients who received external beam radiotherapy (EBRT) and LDR brachytherapy. The LDR dose was converted to EBRT dose in 1.8-Gy fractions by using the LQ formula, and the total dose ranged from 61.4 to 99.7 Gy. Patients were divided into 11 groups according to total dose and treatment time. The tumor control probability (TCP) was calculated for each group. The least χ(2) method was used to fit the TCP data with two free parameters: onset time (T(k)) of accelerated repopulation and number of clonogens (K), while other LQ model parameters were adopted from the literature, due to the limited patient data. RESULTS: Among the 11 patient groups, TCP varied from 33% to 100% as a function of radiation dose and overall treatment time. Higher dose and shorter treatment duration were associated with higher TCP. Using the LQ model, we achieved the best fit with onset time T(k) of 19 days and K of 139, with uncertainty ranges of (11, 22) days for T(k) and (48, 1822) for K, respectively. CONCLUSION: This is the first report of accelerated repopulation onset time in cervical cancer, derived directly from clinical data by using the LQ model. Our study verifies the fact that accelerated repopulation does exist in cervical cancer and has a relatively short onset time. Dose escalation may be required to compensate for the effects of tumor repopulation if the radiation therapy course is protracted.

When tumor repopulation starts? The onset time of prostate cancer during radiation therapy.

PURPOSE: To analyze published clinical data and provide a preliminary estimate of tumor repopulation rate and its onset time during radiation therapy for prostate cancer. METHODS: Data on prostate cancer treated with external beam radiotherapy (EBRT) by Perez et al. (2004), Amdur et al. (1990) and Lai et al. (1991) were analyzed in this study. The stage-combined pelvic control rate from Perez et al. was calculated to be 0.95±0.01, 0.87±0.02, and 0.72±0.04 for patients treated ≤7 weeks, 7.1-9 weeks, and >9 weeks respectively. Based on the Linear-Quadratic model, extended to account for tumor repopulation, the least χ² method was used to fit the clinical data and derive the onset time (T(k)) and effective doubling time (T(d)) for prostate cancer. Similar analysis was performed for the other two datasets. RESULTS: Best fit was achieved with onset time T(k)=34±7 days and doubling time T(d)=12±2 days. These parameters were independent of the choice of the α/ß values currently published in the literature. Analyses of the other two datasets showed T(k)=42±7 days with T(d)=9 ± 3 days, and T(k)=34±6 days with T(d)=34±5 days, respectively. T(k) was found to be dependent on tumor stage. CONCLUSIONS: Consistent values for onset time T(k) were obtained from different datasets, while the range of doubling time T(d) was large. Tumor repopulation starts no later than 58 days (at 90% confidence level) in the course of EBRT for prostate cancer.