Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype

BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

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.

Feasibility of Integrating Leprosy Post-Exposure Prophylaxis with Single-Dose Rifampicin (LPEP) into Routine Leprosy Control Program in Bukedi and Teso Regions in Uganda

Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendation, a cross-sectional study among contacts of leprosy patients was conducted to investigate the feasibility of integrating leprosy systematic contact tracing and post-exposure prophylaxis (PEP) into the routine leprosy control program. Methods: This was a mixed methods cross-sectional study. The study was implemented in Kumi, Ngora, Serere, Soroti, Budaka and Kibuku Districts. Results: The 45 enrolled index patients (97.8% of the registered) identified a total of 135 contacts, of which 134 (99·2%) consented and were screened. Among them, one new leprosy patient was identified and started on treatment with multidrug therapy (MDT). All the eligible contacts, received the prophylactic treatment with Single Dose Rifampicin (SDR). Overall, SDR was administered to 133(98.5% of the listed contacts) with no adverse event reported. Factors associated with successful contact investigation and management included: Involvement of index patients, health care workers during the contact screening and SDR A administration, counselling of the index patients and contacts by the health care works, LPEP being administered as Directly observed Therapy (DOT) among others. Results Interpretation: The integration of leprosy post-exposure prophylaxis with administration of SDR and contact tracing is feasible, generally accepted by the patient, their contacts and health workers and can be integrated into the National Leprosy control programmes with minimal additional efforts once contact tracing has been established. Therefore, we recommend integration of administration of SDR in to the routine leprosy control program.

Role of high-dose amoxicillin dual therapy for Helicobacter pylori eradication in an Irish cohort:A prospective study

Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.

Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?

Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.

Helicobacter pylori:High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.

Determination of Timer Error and Evaluation of Its Effect on Dose for OB6, GammaBeam X200 and X-Ray Irradiators at the Secondary Standard Dosimetry Laboratory in Nigeria

Timer error as well as its convention is very important for dose accuracy during irradiation. This paper determines the timer error of irradiators at Secondary Standard Dosimetry Laboratory (SSDL) in Nigeria. The irradiators are Cs-137 OB6 irradiator and X-ray irradiators at the Protection level SSDL;and Co-60 irradiator at the Therapy Level SSDL. PTW UNIDOS electrometer and LS01 Ionization chamber were used at the Protection Level to obtain doses for both Cs-137 OB6 and X-ray irradiators while an IBA farmer type ionization chamber and an IBA DOSE 1 electrometer were used at the Protection Level SSDL. Single/multiple exposure method and graphical method were used in the determination of the timer error for the three irradiators. The timer error obtained for Cs-137 OB6 irradiator was 0.48 ± 0.01 s, the timer error for the X-ray irradiator was 0.09 ± 0.01 s while the timer error obtained for GammaBeam X200 was 1.21 ± 0.04 s. It was observed that the timer error is not affected by source to detector distance. It was also observed that the timer error of Co-60 Gamma X200 irradiator is increasing with the age of the machine. Source to detector distance and field size do not contribute towards the timer error of the irradiators. The timer error of the Co-60 Gamma X200 irradiator (the only irradiator among the irradiators with a pneumatic system) increases with the age of the irradiator.

A Bioequivalence Study of Empagliflozin/Metformin Fixed-Dose Combination in Healthy Subjects under Fasting Conditions

Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.

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.

Life Time Attributable Cancer Risk Estimated Using Scanner Reported Dose Length Product during Chest Computed Tomography Imaging in Young Children

This study aims to estimate the lifetime attributable cancer risk (LAR) for pediatric chest computed tomography (CT) examinations in five age groups using recently published age and region-specific conversion coefficients multiplying the widely available scanner registered dose length products (DLP) displayed on the CT console and hence calculating the Effective Dose (ED). The ED is then multiplied by the International Commission on Radiological Protection (ICRP) published risk factor for LAR. The obtained LAR values are compared with the international literature. Factors that may affect the LAR value are reported and discussed. The study included one hundred twenty five chest CT examinations for both males and females aged from less than one year to fifteen years. The patients reported data are from one single medical institution and using two CT scanners from June 2022 to December 2023. The results of this study may serve as benchmark for institutional radiation dose reference levels and risk estimation.

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.

Assessment of Dose and Lifetime Risk of Exposure Induced Cancer in Adult Common Computed Tomography Scans in Douala-Cameroon

Background: Among medical technologies that use ionizing radiation, CT is currently the radio diagnostic technic that can deliver the highest radiation to the Patient compared with other conventional procedures. In developing countries, the uses and risks of CT have not been well characterized. Objective: To estimate the lifetime attributable risk (LAR) incidence and mortality for cancer for each procedure for adult’s patients who had Computed Tomography examinations in 10 imaging centers in the city of Douala-Cameroon so as to provide a reference data. Materials and Methods: We conducted a cross-sectional study describing radiation dose associated with the 8 most common types of diagnostic CT studies performed on 1287 consecutive adult patients at 10 Douala radiology department. We estimated lifetime attributable risks of cancer by study type from these measured doses. Estimation of LAR for cancer incidence and mortality was based on the effective dose, patient’s sex and age at exposure using the BIER VII preferred models. Results: Mean effective dose from CT scans examinations varied from: 0.30 and 8.81 mSv. The highest doses were observed for lumbar spine CT (8.81 mSv), followed by abdomen-pelvis procedure (6.46 mSv), chest-abdomen-pelvic CT (6.61 mSv), chest CT (3.90 mSv), cervical Spine CT (3.05 mSv), head CT (1.7 mSv) and lower for sinus CT (0.30 mSv). The LAR values of all cancer from patients’ CT scans obtained vary from 67.13 excess per 100,000 (about 1 in 1489) and 0.45 excess per 100,000 (about 1 in 222,222). All cancer risk was high for lumbar spine CT in women 20 years old (67.13 excess deaths in 100,000 scans) followed by chest-abdomen-pelvic CT (50.36 excess deaths in 100,000 scans) and abdomen-pelvic CT (49.22 excess deaths in 100,000 scans) for the same age group. The LAR of incidence and mortality values were higher from female’s patients than males and higher for younger than older patients. Conclusion: This study was set out to estimate the LAR values associated with adult common CT scans procedures. The data indicates, LAR risks related to induced cancer from CT exposures were estimated to be low. This risk can be relatively significant for younger age group compared to older age group. The LAR values obtained will help to better evaluate radiation exposure risk, before ordering a CT scans examinations.

Total ionizing dose effect modeling method for CMOS digital-integrated circuit

Simulating the total ionizing dose(TID)of an electrical system using transistor-level models can be difficult and expensive,particularly for digital-integrated circuits(ICs).In this study,a method for modeling TID effects in complementary metaloxide semiconductor(CMOS)digital ICs based on the input/output buffer information specification(IBIS)was proposed.The digital IC was first divided into three parts based on its internal structure:the input buffer,output buffer,and functional area.Each of these three parts was separately modeled.Using the IBIS model,the transistor V-I characteristic curves of the buffers were processed,and the physical parameters were extracted and modeled using VHDL-AMS.In the functional area,logic functions were modeled in VHDL according to the data sheet.A golden digital IC model was developed by combining the input buffer,output buffer,and functional area models.Furthermore,the golden ratio was reconstructed based on TID experimental data,enabling the assessment of TID effects on the threshold voltage,carrier mobility,and time series of the digital IC.TID experiments were conducted using a CMOS non-inverting multiplexer,NC7SZ157,and the results were compared with the simulation results,which showed that the relative errors were less than 2%at each dose point.This confirms the practicality and accuracy of the proposed modeling method.The TID effect model for digital ICs developed using this modeling technique includes both the logical function of the IC and changes in electrical properties and functional degradation impacted by TID,which has potential applications in the design of radiation-hardening tolerance in digital ICs.

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.

Normalized glandular dose coefficients for digital breast tomosynthesis using detailed Chinese breast models

The rise in breast cancer diagnoses among Chinese women has necessitated the use of X-ray breast screening,which carries a radiation risk.This study aimed to provide a dosimetry protocol for the Chinese female population to replace the traditional standard that utilizes simplified breast models,for the accurate estimation of the mean glandular dose of a patient undergoing digital breast tomosynthesis(DBT).The first set of detailed Chinese female breast models and representative breast parameters was constructed.Considering backscatter radiation and computational efficiency,we improved the combination of these models and the Chinese reference adult female whole-body voxel phantom.Image acquisition for four commercial DBT systems that are widely employed in China was simulated using the Monte Carlo method to obtain the normalized glandular dose coefficients of DBT(D_(gN)^(DBT))and the glandular depth dose(D_(g)^(dep)(z))for different breast characteristics and X-ray spectra.We calculated a series of D_(gN)^(DBT) values for breasts with different percentage mass glandularities(5%,25%,50%,75%,and 100%)and compressed breast thicknesses(2,3,4,5,6,and 7 cm)at various tube potentials(25,28,30,32,35,and 49 kV)and target/filter combinations(W/Rh,W/Al,Mo/Mo,Rh/Rh,and Rh/Ag).The parameter dependence of the breast characteristics and beam conditions on D_(gN)^(DBT) in detailed breast models was investigated.The D_(gN)^(DBT) results were 14.6-51.0%lower than those of the traditional dosimetry standard in China.The difference in D_(gN)^(DBT) was mainly due to a decrease in the depth of the main energy deposition area caused by the glandular distribution along the depth direction.The results obtained in this study may be used to improve breast dosimetry in China and provide more detailed information on risk assessment during DBT.

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.

利用Batch Implant机台离子注入dose梯度分布调控注入均匀性的技术分析

阐述发现batch implant机台所作业的wafer状况,在wafer面内存在规律性梯度差异的dose分布。基于wafer processing过程中的形变现象,通过fine tune beam line及优化diskangle条件,可以定量设计dose梯度分布情况。通过优化离子注入在wafer面内分布的dose对称性,可以有效改善离子注入均匀性。

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.

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.

Predicting 3D Radiotherapy Dose-Volume Based on Deep Learning

Cancer is one of the most dangerous diseaseswith highmortality.One of the principal treatments is radiotherapy by using radiation beams to destroy cancer cells and this workflow requires a lot of experience and skill from doctors and technicians.In our study,we focused on the 3D dose prediction problem in radiotherapy by applying the deeplearning approach to computed tomography(CT)images of cancer patients.Medical image data has more complex characteristics than normal image data,and this research aims to explore the effectiveness of data preprocessing and augmentation in the context of the 3D dose prediction problem.We proposed four strategies to clarify our hypothesis in different aspects of applying data preprocessing and augmentation.In strategies,we trained our custom convolutional neural network model which has a structure inspired by the U-net,and residual blocks were also applied to the architecture.The output of the network is added with a rectified linear unit(Re-Lu)function for each pixel to ensure there are no negative values,which are absurd with radiation doses.Our experiments were conducted on the dataset of the Open Knowledge-Based Planning Challenge which was collected from head and neck cancer patients treatedwith radiation therapy.The results of four strategies showthat our hypothesis is rational by evaluating metrics in terms of the Dose-score and the Dose-volume histogram score(DVH-score).In the best training cases,the Dose-score is 3.08 and the DVH-score is 1.78.In addition,we also conducted a comparison with the results of another study in the same context of using the loss function.