Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Evaluation of Air-Kerma and Absorbed Dose to Water for External Radiotherapy Beam Using Ionization Chamber

Radiotherapy is the most widely applied oncologic treatment modality utilizing ionizing radiation. A high degree of accuracy, reliability and reproducibility is required for a successful treatment outcome. Measurement using ionization chamber is a prerequisite for absorbed dose determination for external beam radiotherapy. Calibration coefficient is expressed in terms of air kerma and absorbed dose to water traceable to Secondary Standards Dosimetry Laboratory. The objective of this work was to evaluate the level of accuracy of ionization chamber used for clinical radiotherapy beam determination. Measurement and accuracy determination were carried out according to IAEA TRS 398 protocol. Clinical farmers type ionization chamber measurement and National Reference standard from Secondary Standards Dosimetry Laboratory were both exposed to cobalt-60 beam and measurement results compared under the same environmental conditions. The accuracy level between National Reference Standard and clinical radiotherapy standard was found to be −1.92% and −2.02% for air kerma and absorbed dose to water respectively. To minimize the effect of error and maximize therapeutic dose during treatment in order to achieve required clinical outcome, calibration factor was determined for air kerma (Nk) as 49.7 mGy/nC and absorbed dose to water ND, as 52.9 mGy/nC. The study established that radiotherapy beam measurement chain is prone to errors. Hence there is a need to independently verify the accuracy of radiation dose to ensure precision of dose delivery. The errors must be accounted for during clinical planning by factoring in calibration factor to minimize the systematic errors during treatment, and thereby providing enough room to achieve ±5% dose delivery to tumor target as recommended by ICRU.

Correlation between dose-volume parameters and rectal bleeding after 12 fractions of carbon ion radiotherapy for prostate cancer

BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate cancer.Rectal bleeding is a major cause of toxicity even with CIRT.However,to date,a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown.Similarly,the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT.AIM To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer.METHODS Among 259 patients who received 51.6 Gy[relative biological effectiveness(RBE)],in 12 fractions of CIRT,15 had grade 1(5.8%)and nine had grade 2 rectal bleeding(3.5%).The dose-volume parameters included the volume(cc)of the rectum irradiated with at least x Gy(RBE)(Vx)and the minimum dose in the most irradiated x cc normal rectal volume(Dx).RESULTS The mean values of D6cc,D2cc,V10 Gy(RBE),V20 Gy(RBE),V30 Gy(RBE),and V40 Gy(RBE)were significantly higher in the patients with rectal bleeding than in those without.The cutoff values were D6cc=34.34 Gy(RBE),D2cc=46.46 Gy(RBE),V10 Gy(RBE)=9.85 cc,V20 Gy(RBE)=7.00 cc,V30 Gy(RBE)=6.91 cc,and V40 Gy(RBE)=4.26 cc.The D2cc,V10 Gy(RBE),and V20 Gy(RBE)cutoff values were significant predictors of grade 2 rectal bleeding.CONCLUSION The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.

Evaluation of Dosimetric Impact of Uncertainty of Measurement in Estimating External Radiotherapy Dose

Cancer is a major societal public health and economic problem, responsible for one in every six deaths. Radiotherapy is the main technique of treatment for more than half of cancer patients. To achieve a successful outcome, the radiation dose must be delivered accurately and precisely to the tumor, within ± 5% accuracy. Smaller uncertainties are required for better treatment outcome. The objective of the study is to investigate the uncertainty of measurement of external radiotherapy beam using a standard ionization chamber under reference conditions. Clinical farmers type ionization chamber measurement was compared against the National Reference standard, by exposing it in a beam 60Co gamma source. The measurement set up was carried out according to IAEA TRS 498 protocol and uncertainty of measurement evaluated according to GUM TEDDOC-1585. Evaluation and analysis were done for the identified subjects of uncertainty contributors. The expanded uncertainty associated with 56 mGy/nC ND,W was found to be 0.9% corresponding to a confidence level of approximately 95% with a coverage factor of k = 2. The study established the impact of dosimetry uncertainty of measurement in estimating external radiotherapy dose. The investigation established that the largest contributor of uncertainty is the stability of the ionization chamber at 36%, followed by temperature at 22% and positioning of the chamber in the beam at 8%. The effect of pressure, electrometer, resolution, and reproducibility were found to be minimal to the overall uncertainty. The study indicate that there is no flawless measurement, as there are many prospective sources of variation. Measurement results have component of unreliability and should be regarded as best estimates of the true value. .

Simultaneous integrated dose reduction intensity-modulated radiotherapy effectively reduces cardiac toxicity in limited-stage small cell lung cancer

Objective:To assess the clinical outcomes and toxicities of once daily(QD)simultaneous dose reduction intensity-modulated radiotherapy(SDR-IMRT-QD;SDR-QD)versus conventional QD IMRT(C-QD)and twice daily(BID)IMRT in patients with limited-stage small cell lung cancer(LS-SCLC).Methods:After propensity score matching(PSM),a retrospective analysis involving 300 patients with LS-SCLC treated using SDR-QD,C-QD,or BID was performed from January 1,2014 to December 31,2019.The prescribed irradiation dose in the SDR-QD cohort was 60 Gy/PGTV and 54 Gy/PTV QD.The radiation dose was 60 Gy for both PGTV and PTV QD in the C-QD cohort.The radiation dose was 45 Gy for both PGTV and PTV in the BID cohort.Toxicities,short-term effects,and survival outcomes were recorded.A meta-analysis on the protective effects of pharmaceuticals for cardiac toxicities induced by anti-tumor therapy was performed.Results:The median overall survival time(MST)in the 3 cohorts were 32.7 months(SDR-QD),26.3 months(C-QD),and 33.6 months(BID);the differences between groups were statistically significant.Lower toxicities and doses to organs-at-risk(OARs)occurred in the SDR-QD and BID cohorts.Further,the cardiac dose dosimetric parameter Vheart40 was negatively associated with survival(r=-0.35,P=0.007).A Vheart40 value of 16.5%was recommended as a cut-off point,which yielded 54.7%sensitivity and 85.7%specificity for predicting negative survival outcomes.The meta-analysis indicated that pharmaceuticals significantly reduced the cardiac toxicities induced by chemotherapy,but not radiotherapy.Conclusions:SDR-QD was shown to have similar toxicities and survival compared with BID,but fewer toxicities and better survival than C-QD.In addition,cardiac dose exposure was negatively associated with survival.Thus,16.5%of the cardiac dosimetric parameter Vheart40 is recommended as the cut-off point,and a Vheart40>16.5%predicts poor survival.

Effect of low dose laser cycloplasty on deepening anterior chamber in chronic angle-closure glaucoma

AIM:To describe the outcome of using low-dose laser cycloplasty(LCP)in chronic angle-closure glaucoma(CACG).METHODS:A retrospective case series.Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed.The main outcomes included intraocular pressure(IOP),the number of glaucoma medication,anterior segment parameters and surgery-related complications.RESULTS:A total of 7 eyes of 7 CACG patients(age 38.9±11.0y)underwent LCP with a mean follow-up of 27.1±13.7mo(range 16-48mo).Following LCP,mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg(P=0.027)with 0.4±1.1 glaucoma medications(P=0.001)at final follow-up.The anterior chamber depth(ACD),angle opening distance500 and trabecular-iris angle increased from 1.65±0.33 mm,0.05 mm(range 0-0.30 mm)and 5.1°(range,0-31.97°)at baseline to 1.98±0.43 mm(P=0.073),0.53 mm(range 0.42-0.91 mm,P=0.015),45.9°(range,40.2°-59.4°),(P=0.015)in the long-term follow-up,respectively.The deepening of ACD and reopening of anterior chamber angle(ACA)was observed in 6 eyes(85.7%).CONCLUSION:LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications.In addition,LCP can bring a significant deepening in ACD and reopening of ACA.

Variant Wasserstein Generative Adversarial Network Applied on Low Dose CT Image Denoising

Computed Tomography(CT)images have been extensively employed in disease diagnosis and treatment,causing a huge concern over the dose of radiation to which patients are exposed.Increasing the radiation dose to get a better image may lead to the development of genetic disorders and cancer in the patients;on the other hand,decreasing it by using a Low-Dose CT(LDCT)image may cause more noise and increased artifacts,which can compromise the diagnosis.So,image reconstruction from LDCT image data is necessary to improve radiologists’judgment and confidence.This study proposed three novel models for denoising LDCT images based on Wasserstein Generative Adversarial Network(WGAN).They were incorporated with different loss functions,including Visual Geometry Group(VGG),Structural Similarity Loss(SSIM),and Structurally Sensitive Loss(SSL),to reduce noise and preserve important information on LDCT images and investigate the effect of different types of loss functions.Furthermore,experiments have been conducted on the Graphical Processing Unit(GPU)and Central Processing Unit(CPU)to compare the performance of the proposed models.The results demonstrated that images from the proposed WGAN-SSIM,WGAN-VGG-SSIM,and WGAN-VGG-SSL were denoised better than those from state-of-the-art models(WGAN,WGAN-VGG,and SMGAN)and converged to a stable equilibrium compared with WGAN and WGAN-VGG.The proposed models are effective in reducing noise,suppressing artifacts,and maintaining informative structure and texture details,especially WGAN-VGG-SSL which achieved a high peak-signalto-noise ratio(PNSR)on both GPU(26.1336)and CPU(25.8270).The average accuracy of WGAN-VGG-SSL outperformed that of the state-ofthe-art methods by 1 percent.Experiments prove that theWGAN-VGG-SSL is more stable than the other models on both GPU and CPU.

Efficacy of Low Dose Naltrexone on Pain Reduction in Chronic Pain Syndromes: A Meta Analysis

Chronic pain is a multifaceted debilitating experience often associated with significant physical and emotional burden. Low dose naltrexone (LDN) has gained attention in recent years for its potential utility in the management of fibromyalgia, irritable bowel syndrome, multiple sclerosis, and painful diabetic neuropathy. LDN’s analgesic effects have been associated with its ability to increase the production of endorphins while reducing the production of tumor necrosis factor-alpha, interleukin-6, reactive oxygen species and nitric oxide. This meta-analysis aims to systematically review and synthesize the available evidence on efficacy of LDN as an analgesic in pain syndromes, with a focus on chronic (neuro) inflammatory diseases. The goal is to provide clinicians with a more comprehensive estimate of the effectiveness of LDN as a non-opioid option for managing chronic pain and guide future research in the area. Thirteen randomized control trials, published from 1990 to 2022, were selected for the analysis that satisfied inclusion criteria. The overall effects in these studies were calculated using the standardized mean difference (SMD) between the LDN and placebo groups. We found an overall SMD of -10.77 (95% CI: -13.96 to -7.58) with a p-value of 0.002. This indicated that the LDN group experienced a statistically significant reduction in pain compared to placebo. This meta-analysis provides evidence for the potential efficacy of low dose naltrexone in reducing pain and enhancing analgesia in various pain syndromes. LDN may be a useful treatment option for patients suffering from chronic pain, particularly with fibromyalgia, multiple sclerosis, or diabetic neuropathy. However, further research is needed to confirm the efficacy and safety of low dose naltrexone for chronic pain conditions, especially with larger sample sizes, standardized dosing regimens and treatment durations.

The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound （HIFU） combined with （＋） low-dose external beam radiotherapy （LRT） as supplemental therapy for advanced prostate cancer （PCa） following hormonal therapy （HT）. Our definition of HIFU＋LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy （CRT）. We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU＋LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU ＋LRT treatment. There were significant differences among four groups with regard to overall survival （OS） and disease-specific survival （DSS） curves （P=0.018 and 0.015）. Further comparison between each pair of groups suggested that the long-term DSS of the H IFU ＋ LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU＋LRT group and the CRT group. Multivariable Cox＇s proportional hazard model showed that both HIFU＋LRT and CRT were independently associated with DSS （P=0.001 and 0.035） and had protective effects with regard to the risk of death. Compared with CRT, HIFU ＋LRT significantly decreased incidences of radiation-related late gastrointestinal （GI） and genitourinary （GU） toxicity grade ≥ II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and reRional lymph node metastases after HT. As an alternative to CRT, HIFU＋LRT showed Rood efficacy and better safety.

Effective Dose Screening of Low Level Red Light in Different Cell Indexes

The low level red light irradiation dose that produced positive response on different cell indexes was selected through experiments.In fibroblast detection model,the low level red light irradiation dose that had positive response to the four indicators of mitochondrial membrane potential,ATP release,cell migration and collagen synthesis was screened.The experimental results showed that low level red light with a irradiation dose of 2 J/cm^(2) had a positive response to the above four indexes in fibroblast.The test model on fibroblast was later transferred to dermal papilla cells for further experimental verification.The results showed that low level red light with a irradiation dose of 2 J/cm^(2) also had a positive response to the four indicators of dermal papilla cells,namely,mitochondrial membrane potential,ATP release,cell proliferation rate and collagen synthesis.It is proved that the low level red light with a irradiation dose of 2 J/cm^(2) could improve the mitochondrial function,cell migration and collagen synthesis of fibroblast and dermal papilla cell,thus providing energy for cell activities,improving cell repair ability and cell anti-aging ability.

Systematic analysis and modeling of the FLASH sparing effect as a function of dose and dose rate

Ultrahigh-dose-rate radiotherapy(FLASH-RT)is a revolutionary radiotherapy technology that can spare normal tissues without compromising tumor control.Although qualitative experimental results have been reported,quantitative and systematic analysis of data is necessary.Particularly,the FLASH effect response model to the dose or dose rate is still unclear.This study investigated the relationships between the FLASH effect and experimental parameters,such as dose,dose rate,and other factors by analyzing published in vivo experimental data from animal models.The data were modeled based on logistic regression analysis using the sigmoid function.The model was evaluated using prediction accuracy,receiver operating characteristic(ROC)curve,and area under the ROC curve.Results showed that the FLASH effect was closely related to the dose,mean dose rate,tissue type,and corresponding biological endpoints.The dose rate corresponding to a 50% probability of triggering cognitive protection in the brain was 45 Gy s^(-1).The dose rate corresponding to a 50% probability of triggering intestinal crypt survival and regeneration was 140 Gy s^(-1).For the skin toxicity effect,the dose corresponding to a 50% probability of triggering the FLASH effect was 24 Gy.This study helps to characterize the conditions underlying the FLASH effect and provides important information for optimizing experiments.

Is Escalated Radiation Dose in Definitive Chemoradiotherapy Better for Inoperable Esophageal Carcinoma? A Meta-Analysis and Systematic Review

Purpose: This study aimed to compare the survival benefits between different total radiation doses in definitive chemoradiotherapy (dCRT) for inoperable esophageal carcinoma (EC) based on modern radiotherapy techniques. Methods: A systematic review was performed by searching the databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. All studies published prior to November 30, 2022, comparing radiation dose and disease-related outcomes in EC patients. The hazard ratio (HR) and odds ratio (OR) were used to describe the risk of outcomes and toxicities. Results: Seven prospective trials involving 1124EC patients were enrolled for analyses. The results revealed that the effect on overall survival (HR = 0.99, 95% CI = 0.85 - 1.16, P = 0.94), local progression-free survival (HR = 0.83, 95% CI = 0.58 - 1.17, P = 0.29), local regional progression-free survival (HR = 0.94, 95% CI = 0.76 - 1.17, P = 0.61), progression-free survival (HR = 0.90, 95% CI = 0.71 - 1.13, P = 0.35) was similar in the high-dose and standard-dose groups. Additionally, a high radiation dose exhibited a potential disadvantage in respiratory toxicities when compared with a standard dose (4.8% vs 2.2%, OR 2.11, P = 0.06). Conclusions: The efficacy of the HD group (≥60 Gy) and the SD group (approximately 50 Gy) for inoperable local advanced EC was similar. However, the HD group exhibited a high radiation dose exhibited a potential disadvantage in respiratory toxicities when compared with a standard dose. Simultaneously, the final results of several ongoing prospective trials regarding the optimal radiation dose in dCRT are awaited.

Uninvolved liver dose prediction in stereotactic body radiation therapy for liver cancer based on the neural network method

BACKGROUND The quality of a radiotherapy plan often depends on the knowledge and expertise of the plan designers.AIM To predict the uninvolved liver dose in stereotactic body radiotherapy(SBRT)for liver cancer using a neural network-based method.METHODS A total of 114 SBRT plans for liver cancer were used to test the neural network method.Sub-organs of the uninvolved liver were automatically generated.Correlations between the volume of each sub-organ,uninvolved liver dose,and neural network prediction model were established using MATLAB.Of the cases,70%were selected as the training set,15%as the validation set,and 15%as the test set.The regression R-value and mean square error(MSE)were used to evaluate the model.RESULTS The volume of the uninvolved liver was related to the volume of the corresponding sub-organs.For all sets of Rvalues of the prediction model,except for D_(n0)which was 0.7513,all R-values of D_(n10)-D_(n100)and D_(nmean)were>0.8.The MSE of the prediction model was also low.CONCLUSION We developed a neural network-based method to predict the uninvolved liver dose in SBRT for liver cancer.It is simple and easy to use and warrants further promotion and application.

Validation of the TOPAS Monte-Carlo Code of the Off-Field Dose of a 6 MV Synergy Linac

The risk of radiation-induced second cancer and the late tissue loss due to Off-field doses in radiotherapy remain a serious concern. Monte Carlo (MC) simulation is currently one of the most accurate methods for calculating these doses. MC simulation model based on the Particle Simulation Tool (TOPAS) has been developed to simulate the off-field dose of an Elekta Synergy linear accelerator (Linac) emitting 6 MV photons. Measurements were taken in a water phantom using an ionization chamber to validate this model. The Percentage Depth Dose (PDD) at the depth of 0.0, 5.0, 10.0 and 15.0 cm from the beam axis for a 10 × 10 cm2 field size was measured and simulated. Off-field dose profiles at the depth of 1.5 (dmax), 5.0 and 10.0 cm for field sizes of 5 × 5, 10 × 10, 15 × 15, and 20 × 20 cm2 respectively were measured and simulated. Comparison of measured and simulated off-field dose values showed a good agreement. The average gamma passing rate of the PDDs and profiles curves for off-field doses were 87.5% and 98.11% respectively. The local dose difference based on the PDD curve between the measured and simulated was less than 6.0 % for all locations. For all field size considered in this study, the average difference between profile curves for off-field dose measured and simulated was 9.1%. PDDs and Profiles curves for off-field dose simulation uncertainties were less than 2.0% and 1.0% respectively. TOPAS-MC simulation model developed is a good representation of our 6 MV Linac Elekta Synergy for assessing off-field dose, which would be the primary cause of some secondary cancers.

Enhancing Precision in Radiotherapy Delivery: Validating Monte Carlo Simulation Models for 6 MV Elekta Synergy Agility LINAC Photon Beam Using Two Models of the GAMOS Code

The most crucial requirement in radiation therapy treatment planning is a fast and accurate treatment planning system that minimizes damage to healthy tissues surrounding cancer cells. The use of Monte Carlo toolkits has become indispensable for research aimed at precisely determining the dose in radiotherapy. Among the numerous algorithms developed in recent years, the GAMOS code, which utilizes the Geant4 toolkit for Monte Carlo simula-tions, incorporates various electromagnetic physics models and multiple scattering models for simulating particle interactions with matter. This makes it a valuable tool for dose calculations in medical applications and throughout the patient’s volume. The aim of this present work aims to vali-date the GAMOS code for the simulation of a 6 MV photon-beam output from the Elekta Synergy Agility linear accelerator. The simulation involves mod-eling the major components of the accelerator head and the interactions of the radiation beam with a homogeneous water phantom and particle information was collected following the modeling of the phase space. This space was po-sitioned under the X and Y jaws, utilizing three electromagnetic physics mod-els of the GAMOS code: Standard, Penelope, and Low-Energy, along with three multiple scattering models: Goudsmit-Saunderson, Urban, and Wentzel-VI. The obtained phase space file was used as a particle source to simulate dose distributions (depth-dose and dose profile) for field sizes of 5 × 5 cm2 and 10 × 10 cm2 at depths of 10 cm and 20 cm in a water phantom, with a source-surface distance (SSD) of 90 cm from the target. We compared the three electromagnetic physics models and the three multiple scattering mod-els of the GAMOS code to experimental results. Validation of our results was performed using the gamma index, with an acceptability criterion of 3% for the dose difference (DD) and 3 mm for the distance-to-agreement (DTA). We achieved agreements of 94% and 96%, respectively, between simulation and experimentation for the three electromagnetic physics models and three mul-tiple scattering models, for field sizes of 5 × 5 cm2 and 10 × 10 cm2 for depth-dose curves. For dose profile curves, a good agreement of 100% was found between simulation and experimentation for the three electromagnetic physics models, as well as for the three multiple scattering models for a field size of 5 × 5 cm2 at 10 cm and 20 cm depths. For a field size of 10 × 10 cm2, the Penelope model dominated with 98% for 10 cm, along with the three multiple scattering models. The Penelope model and the Standard model, along with the three multiple scattering models, dominated with 100% for 20 cm. Our study, which compared these different GAMOS code models, can be crucial for enhancing the accuracy and quality of radiotherapy, contributing to more effective patient treatment. Our research compares various electro-magnetic physics models and multiple scattering models with experimental measurements, enabling us to choose the models that produce the most reli-able results, thereby directly impacting the quality of simulations. This en-hances confidence in using these models for treatment planning. Our re-search consistently contributes to the progress of Monte Carlo simulation techniques in radiation therapy, enriching the scientific literature.

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

Low-Dose Involved-Field Radiotherapy in Relapsed Low-Grade Non-Hodgkin's Lymphoma in Elderly Patients (Mansoura University Experience)

Purpose: To assess the response rate, duration of response and prognostic factors affecting response after low-dose involved-field radiotherapy in patients with relapsed low-grade B-cell non-Hodgkin lymphoma. Patients and Methods: Forty-four patients were included. Patients were treated with a total dose of 4 Gy (2 × 2 Gy) using 6 - 15 Mv photon or electron beam. Results: most patients were above age of 60 years (59%) with male predominance. Follicular lymphoma was the most common pathological type;bulky disease (>5 cm) was presented in 61.4%. Patients who received only 2 regimens were 63.7% and 31.8% had >2 involved sites. No treatment related toxicity was observed. The overall response rate was 88.7%;complete response was reached in 59.1% and stable disease in 6.8%, progressive disease in 4.5%. Median time to local progression was 33 months (95% CI 23.70 - 42.29);2-year local progression free survival was 78%. Response rate was found to be dependent on age, number of involved sites and lymph node size but independent on sex, pathological type, number of prior regimens, LDH level and time since diagnosis. Conclusion: Short-course-low dose palliative radiotherapy (2 × 2 Gy) affords an attractive option for treatment of relapsed low-grade non-Hodgkin’s lymphoma due to high response rates. However, these results had to be confirmed in a larger number of patients.

Effects of Low Dose Radiation on Tumor Apoptosis, Cell Cycle and Apoptosis-Related Protein Bcl-2 in Tumor-Bearing Mice

To study the effects of low dose radiation (LDR) on tumor apoptosis, cellcycle progression and changes of apoptosis-related protein Bcl-2 in tumor-bearing mice. Methods:Male mice of Kunming strain were implanted subcutaneously with S180 sarcoma cells in the left inguenas an in situ experimental animal model. Seven days later, the mice were subjected to 75 mGywhole-body γ-irradiation. At 24 and 48 h after the irradiation, all mice were sacrificed. The tumorsizes were measured, and tumor cell apoptosis and cell cycle progression were analyzed by flowcytometry. The expression of apoptosis-related protein Bcl-2 and the apoptotic rate of tumor cellswere observed by immunohistochemistry and electron microscopy. Results: Tumors grew significantlyslower after LDR (P 【 0.05). The tumor cells were arrested in G1 phrase and the expression of Bcl-2protein decreased at 24 h. Apoptotic rate of tumor cells was increased significantly at 48 h afterLDR (P 【 0.01). Conclusion: LDR could cause a G1-phase arrest and increase the apoptosis of tumorcells through the low level of apoptosis-related protein bcl-2 in the tumor-bearing mice. Theorganized immune function and anti-tumor ability are markedly increased after LDR. Our studyprovides practical evidence of clinical application to cancer treatment.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.

Involvement of Endoplasmic Reticulum Stress in Apoptosis of Testicular Cells Induced by Low-dose Radiation

Summary： The study examined the role of endoplasmic reticulum stress （ERS） and signaling pathways of inositol-requiring enzyme-1 （IRE1）, RNA-activated protein kinase-like ER kinase （PERK） and activating transcription factor-6 （ATF6） in apoptosis of mouse testicular cells treated with low-dose radiation （LDR）. In the dose-dependent experiment, the mice were treated with whole-body X-ray irradiation at different doses （25, 50, 75, 100 or 200 mGy） and sacrificed 12 h later. In the time-dependent experiment, the mice were exposed to 75 mGy X-ray irradiation and killed at different time points （3, 6, 12, 18 or 24 h）. Testicular cells were harvested for experiments. H202 and NO concentrations, and Ca2＋-ATPase activity were detected by biochemical assays, the calcium ion concentration （[Ca2＋]i） by flow cytometry using fluo-3 probe, and GRP78 mRNA and protein expressions by quantitative real-time RT-PCR （qRT-PCR） and Western blotting, respectively. The mRNA expressions of S-XBP1, JNK, caspase-12 and CHOP were measured by qRT-PCR, and the protein expressions of IREla, S-XBP1, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP by Western blot- ting. The results showed that the concentrations of H202 and NO, the mR_NA expressions of GRP78, S-XBP1, JNK, caspase-12 and CHOP, and the protein expressions of GRP78, S-XBP1, IREla, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP were significantly increased in a time- and dose-dependent manner after LDR. But the [Ca2]i and Ca2-ATPase activities were sig nificantly decreased in a time and dose-dependent manner. It was concluded that the ERS, regulated by IRE 1, PERK and ATF6 pathways, is involved in the apoptosis of testicular cells in LDR mice, which is associated with ERS-apoptotic signaling molecules of JNK, caspase-12 and CHOP.