A Monte Carlo study on dose distribution validation of GZP6 60Co stepping source

Aim

Stepping source in brachytherapy systems is used to treat a target lesion longer than the effective treatment length of the source. Cancerous lesions in the cervix, esophagus and rectum are examples of such a target lesion.

Background

In this study, the stepping source of a GZP6 afterloading intracavitary brachytherapy unit was simulated using Monte Carlo (MC) simulation and the results were used for the validation of the GZP6 treatment planning system (TPS).

Materials and methods

The stepping source was simulated using MCNPX Monte Carlo code. Dose distributions in the longitudinal plane were obtained by using a matrix shift method for esophageal tumor lengths of 8 and 10 cm. A mesh tally has been employed for the absorbed dose calculation in a cylindrical water phantom. A total of 5 × 10⁸ photon histories were scored and the MC statistical error obtained was at the range of 0.008–3.5%, an average of 0.2%.

Results

The acquired MC and TPS isodose curves were compared and it was shown that the dose distributions in the longitudinal plane were relatively coincidental. In the transverse direction, a maximum dose difference of 7% and 5% was observed for tumor lengths of 8 and 10 cm, respectively.

Conclusion

Considering that the certified source activity is given with ±10% uncertainty, the obtained difference is reasonable. It can be concluded that the accuracy of the dose distributions produced by GZP6 TPS for the stepping source is acceptable for its clinical applications.     

Evaluation of rectal dose discrepancies between planned and in vivo dosimetry using MOSkin detector and PTW 9112 semiconductor probe during 60Co HDR CT-based intracavitary cervix brachytherapy

PurposeDose to the rectum during brachytherapy treatment may differ from an approved treatment plan which can be quantified with in vivo dosimetry (IVD). This study compares the planned with in vivo doses measured with MOSkin and PTW 9112 rectal probe in patients undergoing CT based HDR cervical brachytherapy with Co-60 source.MethodsDose measurement of a standard pear-shaped plan carried out in phantom to verify the MOSkin dose measurement accuracy. With MOSkin attached to the third diode, RP3 of the PTW 9112, both detectors were inserted into patients’ rectum. The RP3 and MOSkin measured doses in 18 sessions as well as the maximum measured doses from PTW 9112, RP_max in 48 sessions were compared to the planned doses.ResultsPercentage dose differences ΔD (%) in phantom study for two MOSkin found to be 2.22 ± 0.07% and 2.5 ± 0.07%. IVD of 18 sessions resulted in ΔD(%) of −16.3% to 14.9% with MOSkin and ΔD(%) of −35.7% to −2.1% with RP3. In 48 sessions, RP_max recorded ΔD(%) of −37.1% to 11.0%. MOSkin_measured doses were higher in 44.4% (8/18) sessions, while RP3_measured were lower than planned doses in all sessions. RP_max_measured were lower in 87.5% of applications (42/47).ConclusionsThe delivered doses proven to deviate from planned doses due to unavoidable shift between imaging and treatment as measured with MOSkin and PTW 9112 detectors. The integration of MOSkin on commercial PTW 9112 surface found to be feasible for rectal dose IVD during cervical HDR ICBT.     

Comparison of planned and measured rectal dose in-vivo during high dose rate Cobalt-60 brachytherapy of cervical cancer

Cobalt-60 (Co-60) is a relatively new source for the application of high-dose rate (HDR) brachytherapy. Radiation dose to the rectum is often a limiting factor in achieving the full prescribed dose to the target during brachytherapy of cervical cancer. The aim of this study was to measure radiation doses to the rectum in-vivo during HDR Co-60 brachytherapy. A total of eleven HDR brachytherapy treatments of cervical cancer were recruited in this study. A series of diodes incorporated in a rectal probe was inserted into the patient's rectum during each brachytherapy procedure. Real-time measured rectal doses were compared to calculated doses by the treatment planning system (TPS). The differences between calculated and measured dose ranged from 8.5% to 41.2%. This corresponds to absolute dose differences ranging from 0.3 Gy to 1.5 Gy. A linear relationship was observed between calculated and measured doses with linear regression R² value of 0.88, indicating close association between the measured and calculated doses. In general, absorbed doses for the rectum as calculated by TPS were observed to be higher than the doses measured using the diode probe. In-vivo dosimetry is an important quality assurance method for HDR brachytherapy of cervical cancer. It provides information that can contribute to the reduction of errors and discrepancies in dose delivery. Our study has shown that in-vivo dosimetry is feasible and can be performed to estimate the dose to the rectum during HDR brachytherapy using Co-60.     

Fetal dose measurements and shielding efficiency assessment in a custom setup of 192Ir brachytherapy for a pregnant woman with breast cancer

PurposeTo assess the radiation dose to the fetus of a pregnant patient undergoing high-dose-rate (HDR) ¹⁹²Ir interstitial breast brachytherapy, and to design a new patient setup and lead shielding technique that minimizes the fetal dose.MethodsRadiochromic films were placed between the slices of an anthropomorphic phantom modeling the patient. The pregnant woman was seated in a chair with the breast over a table and inside a leaded box. Dose variation as a function of distance from the implant volume as well as dose homogeneity within a representative slice of the fetal position was evaluated without and with shielding.ResultsWith shielding, the peripheral dose after a complete treatment ranged from 50 cGy at 5 cm from the caudal edge of the breast to <0.1 cGy at 30 cm. The shielding reduces absorbed dose by a factor of two near the breast and more than an order of magnitude beyond 20 cm. The dose is heterogeneous within a given axial plane, with variations from the central region within 50%. Interstitial HDR ¹⁹²Ir brachytherapy with breast shielding can be more advantageous than external-beam radiotherapy (EBRT) from a radiation protection point of view, as long as the distance to the uterine fundus is higher than about 10 cm. Furthermore, the weight of the shielding here proposed is notably lower than that needed in EBRT.ConclusionsShielded breast brachytherapy may benefit pregnant patients needing localized radiotherapy, especially during the early gestational ages when the fetus is more sensitive to ionizing radiation.     

Dosimetric comparison of MRI-based HDR brachytherapy and stereotactic radiotherapy in patients with advanced cervical cancer: A virtual brachytherapy study

AimTo evaluate the treatment plans of 3D image-guided brachytherapy (BT) and stereotactic robotic radiotherapy with online image guidance – CyberKnife (CK) in patients with locally advanced cervix cancer.Methods and materialsTen pairs of plans for patients with locally advanced inoperable cervical cancer were created using MR based 3D brachytherapy and stereotaxis CK. The dose that covers 98% of the target volume (HR CTV D98) was taken as a reference and other parameters were compared.ResultsOf the ten studied cases, the dose from D100 GTV was comparable for both devices, on average, the BT GTV D90 was 10–20% higher than for CK. The HR CTV D90 was higher for CK with an average difference of 10–20%, but only fifteen percent of HR CTV (the peripheral part) received a higher dose from CK, while 85% of the target volume received higher doses from BT. We found a significant organ-sparing effect of CK compared to brachytherapy (20–30% lower doses in 0.1 cm³, 1 cm³, and 2 cm³).ConclusionBT remains to be the best method for dose escalation. Due to the significant organ-sparing effect of CK, patients that are not candidates for BT could benefit from stereotaxis more than from classical external beam radiotherapy.     

Thermoluminescence dosimetry of the dose received by scrotum and testes in radiotherapy of rectal cancer,compared to the point doses calculated by 3D-planning software

PurposeRadiation received by the testes in the course of radiotherapy for rectal cancer may cause oligospermia and azospermia. We sought to determine the dose to the scrotum and testes with thermoluminescence dosimetry (TLD), and compare it to the dose calculated by 3D planning software.MethodsThe TLDs were fixed to the scrotum in six points anteriorly and posteriorly in two fractions of radiotherapy. All patients received a 50–50.4 Gy total dose in prone position with 3D-planning. The average dose of TLD measurements was compared to the average of 6 relevant point doses calculated by the planning software.ResultsThe mean scrotal dose of radiation in 33 patients as measured by TLD was 3.77 Gy (7.5% of the total prescribed dose), and the mean of point doses calculated by the planning software was 4.11 Gy (8.1% of the total dose), with no significant difference. A significant relationship was seen between the position of the inferior edge of the fields and the mean scrotal dose (P = .04). Also body mass index (BMI) was inversely related with the scrotal dose (P = .049).ConclusionWe found a dose of about 4 Gy received by the scrotum and testes from a total prescribed dose of 50 Gy in the radiotherapy of rectal carcinoma patients, with TLD measurements confirming testicular dose estimations by the planning software. This dose could be significantly harmful for spermatogenesis. Thus careful attention to the testicular dose in radiotherapy of rectal cancer for men desiring continued fertility is a necessity.     

A retrospective comparison of organ dose and effective dose in percutaneous vertebroplasty performed under CT guidance or using a fixed C-arm with a flat-panel detector

PurposeTo compare the organ-dose and effective-dose (E) delivered to the patient during percutaneous vertebroplasty (PVP) of one thoracic or lumbar vertebra performed under CT guidance or using a fixed C-arm.MethodsConsecutive adult patients undergoing PVP of one vertebra under CT-guidance, with optimized protocol and training of physicians, or using a fixed C-arm were retrospectively included from January 2016 to June 2017. Organ-doses were computed on 16 organs using CT Expo 2.4 software for the CT procedures and PCXMC 2.0 for the fixed C-arm procedures. E was also computed with both software. Dosimetric values per anatomic locations for all procedures were compared using the paired Mann-Whitney-Wilcoxon test.ResultsIn total, 73 patients were analysed (27 men and 46 women, mean age 78 ± 10 years) among whom 35 (48%) underwent PVP under CT guidance and 38 (52%) PVP using a fixed C-arm. The median E was 11.31 [6.54; 15.82] mSv for all PVPs performed under CT guidance and 5.58 [3.33; 8.71] mSv for fixed C-arm and the differences was significant (p<0.001). For lumbar PVP, the organ doses of stomach, liver and colon were significantly higher with CT-scan than with the fixed C-arm: 97% (p=0.02); 21% (p=0.099) and 375% (p=0.002), respectively. For thoracic PVP, the lung organ dose was significantly higher with CT-scan than with the fixed C-arm (127%; p<0.001) and the oesophagus organ doses were not significantly different (p = 0.626).ConclusionThis study showed that the E and the organ dose on directly exposed organs were both higher for PVP performed under CT-guidance than with the fixed C-arm.     

Construction and application of urinary system model with functional bladder module

In order to study the construction and application of urinary system model with functional bladder module, bladder model was designed, and appropriate materials was selected to make it, and its performance was studied. The results showed that in the analysis of pressure performance of bladder model, more detrusor instability was found in the model than in the urodynamic test, and there was significant statistical difference (P < 0.01). In the analysis of bladder safety capacity, it was found that the bladder safety capacity in the model was much larger than that measured by urodynamics, and there was significant statistical difference (P < 0.01). In the analysis of detrusor workmanship and contraction rate, it was found that the normal model group was significantly smaller than the obstruction group, and there was significant statistical difference (P < 0.01). Comparing the detrusor contraction rate of the two groups, it was found that the normal group and the obstruction group had significant difference at t3, and there was no statistical difference between the other two groups. Therefore, through this study, it is found that the understanding of urinary system can be enhanced by building bladder model, and the basic operating skills of medical staff can be improved more easily by using bladder model, which achieves the expected results of the experiment. Although some shortcomings have been found in the course of the study, it still provides experimental reference for the clinical study of bladder in the future.     

Comparison of manual and inverse optimisation techniques in high dose rate intracavitary brachytherapy of cervical cancer: A dosimetric study

Aims and objectivesTo compare dosimetrically the manual optimisation with IPSA using dose volume histograms (DVH) among patients treated for carcinoma of cervix with intracavitary brachytherapy.BackgroundWith the advent of advanced imaging modalities, there has been a shift from conventional X-ray based planning to three-dimensional planning. Manual optimisation is widely used across various institutions but it is time consuming and operator dependant. Inverse planning simulated annealing (IPSA) is now available in various brachytherapy planning systems. But there is a paucity of studies comparing manual optimisation and IPSA in treatment of carcinoma cervix with intracavitary brachytherapy and hence this study.Materials and methodsFifteen consecutive patients treated between December 2013 and March 2014 with intracavitary brachytherapy for carcinoma of cervix were selected for this study. All patients were initially treated with external beam radiotherapy followed by intracavitary brachytherapy. The DVH was evaluated and compared between manually optimised plans and IPSA in the same set of patients.ResultsThere was a significant improvement in the HRCTV coverage, mean V100 of 87.75% and 82.37% (p = 0.001) and conformity index 0.67 and 0.6 (p = 0.007) for plans generated using IPSA and manual optimisation, respectively. Homogeneity index and dose to the OARs remained similar between the two groups.ConclusionThe use of inverse planning in intracavitary brachytherapy of cervix has shown a significant improvement in the target volume coverage when compared with manual planning.     

A new m6A methylation-related gene signature for prognostic value in patient with urothelial carcinoma of the bladder

Background: Bladder cancer (BC) is one of the most common malignant urological cancer in the world. Because of its characteristic of easy-recurrence and muscle-invasive, advances in our genetic understanding of bladder cancer should be translated into prognostic indicators.Methods: We investigated 16 m⁶A RNA methylation regulators from The Cancer Genome Atlas (TCGA) database and The Human Protein Atlas (HPA) database. The expression profile, clinical application as well as prognostic value of these genes in UC were investigated. Moreover, we further explored the correlation between RNA methylation genes and biological functions, pathways and immune status.Results: Five m⁶A-related genes (HNRNPC, YTHDF2, YTHDF1, HNRNPA2B1, METTL3) up-regulated in UC tissues, while three regulators (ZC3H13, METTL16, FTO) down-regulated in UC. FTO and YTHDF2 show biomarker potential for the prognosis of UC patients. In addition, these identified genes may related with essential functions and core molecular pathways.Conclusions: Our research shows that two m⁶A RNA methylation regulators can serve as reliable prognostic biomarkers of UC, which might be exerted as potential targets of therapeutic strategies.     

Phenotypic,functional and molecular analysis of lymphocytes associated with bladder cancer

 Bladder-washing-derived lymphocytes (BWDL) from 67 patients with bladder cancer were studied. The large majority of samples contained a pure population of T lymphocytes, whereas B and NK cells were absent. A comparative analysis of bladder lymphocytes and peripheral blood lymphocytes (PBL), collected in parallel, showed that BWDL significantly differed from PBL. In vitro cultures of bladder lymphocytes were attempted on 21 samples but in vitro expansion was only possible on six patients treated with bacillus Calmette-Guérin (BCG). This finding indicates that BWDL are characterized by a severe proliferative defect. Nevertheless, the addition of BCG on bladder lymphocytes expanded in vitro enhanced their proliferation, suggesting that this population is sensitized against BCG antigen(s). The analysis of T cell receptor restriction patterns showed that bladder lymphocytes from patients under BCG treatment were oligoclonal. A possible explanation for the efficiency of the immune response and good clinical outcome in patients treated with BCG could be found in the high homology between some BCG antigens and human heat-shock proteins, which are overexpressed in transformed cells. Received: 8 June 1995 / Accepted: 22 November 1995     

Compliance with bladder protocol during concurrent chemoradiation for cancer of the cervix and its impact on enteritis: A prospective observational study

Aim

This prospective study aims to assess the compliance with bladder protocol and the correlation with enteritis during pelvic radiation.

一种简单快速克隆IL-6信号转导相关基因的方法

细胞因子作用于受体时的一个重要结果是诱导基因表达。为了克隆与IL-6诱导相关的基因,我们利用一个快速的改良DD-PCR方法,分离并检测了IL-6诱导和未诱导的U937细胞的差异表达基因。用三个完全变性的6—mer引物进行反转录,用2或3个较长的随机引物进行PCR扩增,扩增产物很在2%琼脂糖凝胶电泳上分离,之后回收差异片段并直接用于克隆和测序。在研究中,获得了7个不同的EST,序列分析表明其中2个EST可能是与细胞信号转导相关的新基因片段;反向Northern杂交证实它们是与IL-6作用相关的差异表达基因。     

Comparison of different treatment planning optimization methods for vaginal HDR brachytherapy with multichannel applicators: A reduction of the high doses to the vaginal mucosa is possible

PurposeA direct planning approach with multi-channel vaginal cylinders (MVCs) used for HDR brachytherapy of vaginal cancers is particularly challenging. Purpose of this study was to compare the dosimetric performances of different forward and inverse methods used for the optimization of MVC-based vaginal treatments for endometrial cancer, with a particular attention to the definition of strategies useful to limit the high doses to the vaginal mucosa.MethodsTwelve postoperative vaginal HDR brachytherapy treatments performed with MVCs were considered. Plans were retrospectively optimized with three different methods: Dose Point Optimization followed by Graphical Optimization (DPO + GrO), Inverse Planning Simulated Annealing with two different class solutions as starting conditions (surflPSA and homogIPSA) and Hybrid Inverse Planning Optimization (HIPO). Several dosimetric parameters related to target coverage, hot spot extensions and sparing of organs at risk were analyzed to evaluate the quality of the achieved treatment plans. Dose homogeneity index (DHI), conformal index (COIN) and a further parameter quantifying the proportion of the central catheter loading with respect to the overall loading (i.e., the central catheter loading index: CCLI) were also quantified.ResultsThe achieved PTV coverage parameters were highly correlated with each other but uncorrelated with the hot spot quantifiers. HomogIPSA and HIPO achieved higher DHIs and CCLIs and lower volumes of high doses than DPO + GrO and surflPSA.ConclusionsWithin the investigated optimization methods, HIPO and homoglPSA showed the highest dose homogeneity to the target. In particular, homogIPSA resulted also the most effective in reducing hot spots to the vaginal mucosa.     

Preclinical pharmacokinetics of MHAA4549A,a human monoclonal antibody to influenza A virus,and the prediction of its efficacious clinical dose for the treatment of patients hospitalized with influenza A

MHAA4549A is a human immunoglobulin G1 (IgG1) monoclonal antibody that binds to a highly conserved epitope on the stalk of influenza A hemagglutinin and blocks the hemagglutinin-mediated membrane fusion in the endosome, neutralizing all known human influenza A strains. Pharmacokinetics (PK) of MHAA4549A and its related antibodies were determined in DBA/2J and Balb-c mice at 5 mg/kg and in cynomolgus monkeys at 5 and 100 mg/kg as a single intravenous dose. Serum samples were analyzed for antibody concentrations using an ELISA and the PK was evaluated using WinNonlin software. Human PK profiles were projected based on the PK in monkeys using species-invariant time method. The human efficacious dose projection was based on in vivo nonclinical pharmacological active doses, exposure in mouse infection models and expected human PK. The PK profiles of MHAA4549A and its related antibody showed a linear bi-exponential disposition in mice and cynomolgus monkeys. In mice, clearance and half-life ranged from 5.77 to 9.98 mL/day/kg and 10.2 to 5.76 days, respectively. In cynomolgus monkeys, clearance and half-life ranged from 4.33 to 4.34 mL/day/kg and 11.3 to 11.9 days, respectively. The predicted clearance in humans was ～2.60 mL/day/kg. A single intravenous dose ranging from 15 to 45 mg/kg was predicted to achieve efficacious exposure in humans. In conclusion, the PK of MHAA4549A was as expected for a human IgG1 monoclonal antibody that lacks known endogenous host targets. The predicted clearance and projected efficacious doses in humans for MHAA4549A have been verified in a Phase 1 study and Phase 2a study, respectively.     

A mathematical model for reconstitution of granulopoiesis after high dose chemotherapy with autologous stem cell transplantation

High dose chemotherapy supported with hematopoietic progenitor cells gives a characteristic neutropenic period (blood neutrophils <0.510⁹ c/l) ranging from 10 to 16 days. The question of a correlation between the CFU-GM content of the transplanted CD34+ cells and time to neutrophil recovery by patients having been given high-dose chemotherapy (HD-CT) with stem cell support was addressed by means of a mathematical model of granulopoiesis. The model utilizes a convection-reaction partial differential equation (PDE) with feedback from a cytokine compartment on proliferation, maturation, and mobilization of granulocytes from bone marrow to blood. The observed number of CFU-GM cells in the transplanted CD34+ cell autograft was used as input to the model. Using this approach, the observed gross relationship between CFU-GM content in the reinfused blood product and engraftment time could be reproduced. At the same time, the effects of assumed physiological mechanisms, especially some of the effects of G-CSF on proliferation rate, maturation rate, mobilization, and cell death, could be investigated and discussed relative to observed engraftment. The model makes it possible to explain how cytokines interfere with progenitor cell mobilization from bone marrow to blood, and it points out the implications of a regulating mechanism for the granulocyte maturation rate.     

The influence of indoor lighting with low blue light dose on urine 6-sulphatoxymelatonin concentrations and sleep efficiency of healthy volunteers

Light, especially its blue component, is the main synchronizer of circadian rhythms. We investigated effects of suppressed blue band of the spectrum on melatonin production and sleep efficiency in 18 young volunteers. During control days, participants lived in their home environment, and next five days in a room lit only by daylight with windows equipped with a filter blocking the blue band of the light spectrum. Light intensity, circadian stimulus and light irradiance were monitored. No significant changes in the daily pattern and total urinary 6-sulphatoxymelatonin excretion were found between control and experimental conditions. Parameters of sleep efficiency measured by wrist actigraphy were not worsened, but neutral chronotypes exhibited shortened sleep duration under light-modified conditions. We conclude that young healthy people can compensate for negative effects of transitory-worsened lighting conditions on their daily rhythms, but chronotypes and other personal characteristics may modify biological responses and should be considered.     

Functional analysis of Rfx6 and mutant variants associated with neonatal diabetes

Mutations in rfx6 were recently associated with Mitchell–Riley syndrome, which involves neonatal diabetes, and other digestive system defects. To better define the function of Rfx6 in early endoderm development we cloned the Xenopus homologue. Expression of rfx6 begins early, showing broad expression throughout the anterior endoderm; at later stages rfx6 expression becomes restricted to the endocrine cells of the gut and pancreas. Morpholino knockdown of rfx6 caused a loss of pancreas marker expression, as well as other abnormalities. Co-injection of exogenous wild-type rfx6 rescued the morpholino phenotype in Xenopus tadpoles, whereas attempts to rescue the loss-of-function phenotype using mutant rfx6 based on Mitchell–Riley patients were unsuccessful. To better define the pleiotropic effects, we performed microarray analyses of gene expression in knockdown foregut tissue. In addition to pancreatic defects, the microarray analyses revealed downregulation of lung, stomach and heart markers and an upregulation of kidney markers. We verified these results using RT-PCR and in situ hybridization. Based on the different rfx6 expression patterns and our functional analyses, we propose that rfx6 has both early and late functions. In early development Rfx6 plays a broad role, being essential for development of most anterior endodermal organs. At later stages however, Rfx6 function is restricted to endocrine cells.