Laser-heated needle for biopsy tract ablation: In vivo study of rabbit liver biopsy

PurposeTo investigate the efficacy of a newly-developed laser-heated core biopsy needle in the thermal ablation of biopsy tract to reduce hemorrhage after biopsy using in vivo rabbit’s liver model.Materials and methodsFive male New Zealand White rabbits weighed between 1.5 and 4.0 kg were anesthetized and their livers were exposed. 18 liver biopsies were performed under control group (without tract ablation, n = 9) and study group (with tract ablation, n = 9) settings. The needle insertion depth (~3 cm) and rate of retraction (~3 mm/s) were fixed in all the experiments. For tract ablation, three different needle temperatures (100, 120 and 150 °C) were compared. The blood loss at each biopsy site was measured by weighing the gauze pads before and after blood absorption. The rabbits were euthanized immediately and the liver specimens were stained with hematoxylin-eosin (H&E) for further histopathological examination (HPE).ResultsThe average blood loss in the study group was reduced significantly (p < 0.05) compared to the control group. The highest percentage of bleeding reduction was observed at the needle temperature of 150 °C (93.8%), followed by 120 °C (85.8%) and 100 °C (84.2%). The HPE results show that the laser-heated core biopsy needle was able to cause lateral coagulative necrosis up to 14 mm diameter along the ablation tract.ConclusionThe laser-heated core biopsy needle reduced hemorrhage up to 93.8% and induced homogenous coagulative necrosis along the ablation tract in the rabbits’ livers. This could potentially reduce the risk of tumor seeding in clinical settings.     

Potential interest of developing an integrated boost dose escalation for stereotactic irradiation of primary prostate cancer

IntroductionThe stereotactic irradiation is a new approach for low-risk prostate cancer. The aim of the present study was to evaluate a schema of stereotactic irradiation of the prostate with an integrated-boost into the tumor.Material and methodsThe prostate and the tumor were delineated by a radiologist on CT/MRI fusion. A 9-coplanar fields IMRT plan was optimized with three different dose levels: 1) 5 × 6.5 Gy to the PTV1 (plan 1), 2) 5 × 8 Gy to the PTV1 (plan 2) and 3) 5 × 6.5 Gy on the PTV1 with 5 × 8 Gy on the PTV2 (plan 3). The maximum dose (MaxD), mean dose (MD) and doses received by 2% (D2), 5% (D5), 10% (D10) and 25% (D25) of the rectum and bladder walls were used to compare the 3 IMRT plans.ResultsA dose escalation to entire prostate from 6.5 Gy to 8 Gy increased the rectum MD, MaxD, D2, D5, D10 and D25 by 3.75 Gy, 8.42 Gy, 7.88 Gy, 7.36 Gy, 6.67 Gy and 5.54 Gy. Similar results were observed for the bladder with 1.72 Gy, 8.28 Gy, 7.01 Gy, 5.69 Gy, 4.36 Gy and 2.42 Gy for the same dosimetric parameters. An integrated SBRT boost only to PTV2 reduced by about 50% the dose difference for rectum and bladder compared to a homogenous prostate dose escalation. Thereby, the MD, D2, D5, D10 and D25 for rectum were increased by 1.51 Gy, 4.24 Gy, 3.08 Gy, 2.84 Gy and 2.37 Gy in plan 3 compared to plan 1.ConclusionsThe present planning study of an integrated SBRT boost limits the doses received by the rectum and bladder if compared to a whole prostate dose escalation for SBRT approach.     

Simple low-cost approaches to semantic segmentation in radiation therapy planning for prostate cancer using deep learning with non-contrast planning CT images

PurposeDeep learning has shown great efficacy for semantic segmentation. However, there are difficulties in the collection, labeling and management of medical imaging data, because of ethical complications and the limited number of imaging studies available at a single facility.This study aimed to find a simple and low-cost method to increase the accuracy of deep learning semantic segmentation for radiation therapy of prostate cancer.MethodsIn total, 556 cases with non-contrast CT images for prostate cancer radiation therapy were examined using a two-dimensional U-Net. Initially, all slices were used for the input data. Then, we removed slices of the cranial portions, which were beyond the margins of the bladder and rectum. Finally, the ground truth labels for the bladder and rectum were added as channels to the input for the prostate training dataset.ResultsThe highest mean dice similarity coefficients (DSCs) for each organ in the test dataset of 56 cases were 0.85 ± 0.05, 0.94 ± 0.04 and 0.85 ± 0.07 for the prostate, bladder and rectum, respectively. Removal of the cranial slices from the original images significantly increased the DSC of the rectum from 0.83 ± 0.09 to 0.85 ± 0.07 (p < 0.05). Adding bladder and rectum information to prostate training without removing the slices significantly increased the DSC of the prostate from 0.79 ± 0.05 to 0.85 ± 0.05 (p < 0.05).ConclusionsThese cost-free approaches may be useful for new applications, which may include updated models and datasets. They may be applicable to other organs at risk (OARs) and clinical targets such as elective nodal irradiation.     

Focal Laser Ablation of Prostate Cancer: Numerical Simulation of Temperature and Damage Distribution

Background

The use of minimally invasive ablative techniques in the management of patients with low grade and localized prostate tumours could represent a treatment option between active surveillance and radical therapy. Focal laser ablation (FLA) could be one of these treatment modalities. Dosimetry planning and conformation of the treated area to the tumor remain major issues, especially when, several fibers are required. An effective method to perform pre-treatment planning of this therapy is computer simulation. In this study we present an in vivo validation of a mathematical model.

Methods

The simulation model is based on finite elements method (FEM) to solve the bio-heat and the thermal damage equations. Laser irradiation was performed with a 980 nm laser diode system (5 W, 75 s). Light was transmitted using a cylindrical diffusing fiber inserted inside a preclinical animal prostate cancer model induced in Copenhagen rats. Non-enhanced T2-weighted and dynamic gadolinium-enhanced T1-weighted MR imaging examinations were performed at baseline and 48 hours after the procedure. The model was validated by comparing the simulated necrosis volume to the results obtained in vivo on (MRI) and by histological analysis. 3 iso-damage temperatures were considered 43° C, 45° C and 50° C.

Results

The mean volume of the tissue necrosis, estimated from the histological analyses was 0.974 ± 0.059 cc and 0.98 ± 0.052 cc on the 48 h MR images. For the simulation model, volumes were: 1.38 cc when T = 43° C, 1.1 cc for T = 45°C and 0.99 cc when T = 50 C°.

Conclusions

In this study, a clear correlation was established between simulation and in vivo experiments of FLA for prostate cancer.Simulation is a promising planning technique for this therapy. It needs further more evaluation to allow to FLA to become a widely applied surgical method.

     

A comparative study of prostate PTV margins for patients using hydrogel spacer or rectal balloon in proton therapy

PurposeTo compare the planning target volume (PTV) margins needed for prostate patients who have used hydrogel spacer or rectal balloon during proton treatments.MethodTotal of 190 prostate patients treated with proton therapy during 2017 were selected for this study. Of these patients, 96 had hydrogel spacer injection and 94 patients had only rectal balloons insertion. All patients had implanted gold markers inside the prostate for daily target alignment. Post-treatment radigraphs were obtained to evaluate prostate intrafraction motion. The systematic and random components of patient setup residual error and prostate intrafraction motion error were obtained. PTV margins were calculated using the van Herk formula for both patient groups.ResultsFor setup residual error, the mean values in the superior-inferior (SI) direction and the variances in the left–right (LR) direction were statistically different between the two groups. For intrafraction motion, there were significant differences of the mean values in the SI direction and of the variances in both LR and anterior-posterior (AP) directions. The population PTV margins for hydrogel spacer group were 2.6 mm, 3.3 mm, and 1.6 mm in LR, SI, AP directions, respectively. For the rectal balloon group, the PTV margins were 2.1 mm, 3.1 mm, and 2.0 mm in LR, SI, AP directions, respectively.ConclusionStatistically significant differences were observed in the patient setup and prostate intrafraction motion errors of the two patient groups. However, under the current protocol of bladder preparation and daily marker-based x-ray image-guidance, population PTV margins were comparable between the two patient groups.     

Quality assurance-based optimization (QAO): Towards improving patient-specific quality assurance in volumetric modulated arc therapy plans using machine learning

IntroductionPrevious literature has shown general trade-offs between plan complexity and resulting quality assurance (QA) outcomes. However, existing solutions for controlling this trade-off do not guarantee corresponding improvements in deliverability. Therefore, this work explored the feasibility of an optimization framework for directly maximizing predicted QA outcomes of plans without compromising the dosimetric quality of plans designed with an established knowledge-based planning (KBP) technique.Materials and MethodsA support vector machine (SVM) was developed – using a database of 500 previous VMAT plans – to predict gamma passing rates (GPRs; 3%/3mm percent dose-difference/distance-to-agreement with local normalization) based on selected complexity features. A heuristic, QA-based optimization (QAO) framework was devised by utilizing the SVM model to iteratively modify mechanical treatment features most commonly associated with suboptimal GPRs. Specifically, leaf gaps (LGs) <50 mm were widened by random amounts, which impacts all aperture-based complexity features. 13 prostate KBP-guided VMAT plans were optimized via QAO using user-specified maximum LG displacements before corresponding changes in predicted GPRs and dose were assessed.ResultsPredicted GPRs increased by an average of 1.14 ± 1.25% (p = 0.006) with QAO using a 3 mm maximum random LG displacement. There were small differences in dose, resulting in similarly small changes in tumor control probability (maximum increase = 0.05%) and normal tissue complication probabilities in the bladder, rectum, and femoral heads (maximum decrease = 0.2% in the rectum).ConclusionThis study explored the feasibility of QAO and warrants future investigations of further incorporating QA endpoints into plan optimization.     

Dual energy computed tomography thermometry during hepatic microwave ablation in an ex-vivo porcine model

BackgroundMicrowave thermoablation (MTA) is a treatment method used to destroy hepatic tumors.ObjectiveTo investigate temperature changes during MTA of ex-vivo porcine liver using dual-energy computed tomography (DECT) imaging.MethodsThree MTA experiments were performed using ex-vivo porcine liver (15 × 15 × 15 cm³) and DECT imaging with 80/Sn140 kVp spectral and 0.5-weighted reconstructions. Images were acquired from basic organ temperature to 100 °C with 10 °C difference during microwave heating and cooling phases. Three fluoro-optic thermometers were used for temperature measurements; two were placed at 1 cm and third one positioned at 2 cm distance from the applicator. Tissue temperature, ablation-region-conspicuity (ARC), ablation-region dimensions and image quality were determined. Regression analysis was performed determining thermal sensitivity during heating and cooling phases.ResultsDetermined thermal sensitivities during heating phase were: −0.59 Hounsfield Unit/°C (80 kVp), −0.60HU/°C (0.5-weighted) and −0.59HU/°C (140 kVp); furthermore, during cooling: −0.56HU/°C (80 kVp), −0.55HU/°C (0.5-weighted) and −0.55HU/°C (140 kVp). ARC showed significantly higher (all P < 0.05) values for thermometer positions −1 and −2 compared to −3; however, comparison between positions −1 and −2 was insignificant (P > 0.05). Signal-to-noise ratios were higher for 0.5-weighted but ARC values were higher for 80 kVp images.ConclusionMicrowave thermal sensitivity on tissue was inversely linear with DECT image datasets. Heating phase showed higher influence of temperature on HU compared to cooling; ARC and ablation-region were increased with increase in temperature.     

Assessment of daily dose accumulation for robustly optimized intensity modulated proton therapy treatment of prostate cancer

PurposeTo implement a daily CBCT based dose accumulation technique in order to assess ideal robust optimization (RO) parameters for IMPT treatment of prostate cancer.MethodsTen prostate cancer patients previously treated with VMAT and having daily CBCT were included. First, RO-IMPT plans were created with ± 3 mm and ± 5 mm patient setup and ± 3% proton range uncertainties, respectively. Second, the planning CT (pCT) was deformably registered to the CBCT to create a synthetic CT (sCT). Both daily and weekly sampling strategies were employed to determine optimal dose accumulation frequency. Doses were recalculated on sCTs for both ± 3 mm/±3% and ± 5 mm/±3% uncertainties and were accumulated back to the pCT. Accumulated doses generated from ± 3 mm/±3% and ± 5 mm/±3% RO-IMPT plans were evaluated using the clinical dose volume constraints for CTV, bladder, and rectum.ResultsDaily accumulated dose based on both ± 3mm/±3% and ±5 mm/±3% uncertainties for RO-IMPT plans resulted in satisfactory CTV coverage (RO-IMPT_3mm/3% CTV_V95 = 99.01 ± 0.87% vs. RO-IMPT_5mm/3% CTV_V95 = 99.81 ± 0.2%, P = 0.002). However, the accumulated dose based on ± 3 mm/3% RO-IMPT plans consistently provided greater OAR sparing than ±5 mm/±3% RO-IMPT plans (RO-IMPT_3mm/3% rectum_V65Gy = 2.93 ± 2.39% vs. RO-IMPT_5mm/3% rectum_V65Gy = 4.38 ± 3%, P < 0.01; RO-IMPT_3mm/3% bladder_V65Gy = 5.2 ± 7.12% vs. RO-IMPT_5mm/3% bladder_V65Gy = 7.12 ± 9.59%, P < 0.01). The gamma analysis showed high dosimetric agreement between weekly and daily accumulated dose distributions.ConclusionsThis study demonstrated that for RO-IMPT optimization, ±3mm/±3% uncertainty is sufficient to create plans that meet desired CTV coverage while achieving superior sparing to OARs when compared with ± 5 mm/±3% uncertainty. Furthermore, weekly dose accumulation can accurately estimate the overall dose delivered to prostate cancer patients.     

Dodecaborate lipid liposomes as new vehicles for boron delivery system of neutron capture therapy

closo-Dodecaborate lipid liposomes were developed as new vehicles for boron delivery system (BDS) of neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in combination with neutron irradiation. The liposomes composed of closo-dodecaborate lipids DSBL and DPBL displayed high cytotoxicity with thermal neutron irradiation. The closo-dodecaborate lipid liposomes were taken up into the cytoplasm by endocytosis without degradation of the liposomes. Boron concentration of 22.7 ppm in tumor was achieved by injection with DSBL-25% PEG liposomes at 20 mg B/kg. Promising BNCT effects were observed in the mice injected with DSBL-25% PEG liposomes: the tumor growth was significantly suppressed after thermal neutron irradiation (1.8 × 10¹² neutrons/cm²).     

Investigation of temperature-dependent viscoelastic properties of thermal lesions in ex vivo animal liver tissue

The viscoelastic characteristics of thermal lesions in ex vivo animal liver are investigated in this paper. Characterization of the moduli of thermal lesions prepared at several temperatures will provide additional information for the elastographic monitoring of radio frequency ablation of hepatic tumors. In this study, the frequency-dependent complex modulus of thermal lesions prepared at temperatures ranging from 60 to 90 °C over a frequency range from 0.1 to 50 Hz are presented. Lesions were prepared using either radio frequency ablation or double immersion boiling. It was found that both the magnitude and phase of the modulus increase with frequency, a behavior that has been noted in the literature. A new result reported shows that the modulus dependence on temperature reveals a local maximum around 70–75 °C corresponding to the temperature at which tissue has released most of its water content. The modulus values at temperatures higher than 70 °C continued to increase, but the extent of increase depend on animal species and other factors.     

Sex difference in cerebral blood flow velocity during exercise hyperthermia

IntroductionCerebral blood flow and thermal perception during physical exercise under hyperthermia conditions in females are poorly understood. Because sex differences exist for blood pressure control, resting middle cerebral artery velocity (MCA_Vmean), and pain, we tested the hypothesis that females would have greater reductions in MCAv_mean and increased thermal perceptual strain during exercise hyperthermia compared to males.MethodsTwenty-two healthy active males and females completed 60 min of matched exercise metabolic heat production in a 1) control cool (24.0 ± 0.0 °C; 14.4 ± 3.4% Rh) and 2) hot (42.3 ± 0.3 °C; 28.4 ± 5.2% Rh) conditions in random order, separated by at least 3 days while MCAv_mean, thermal comfort, and preference was obtained during the exercise.ResultsCompared to 36 °C mean body temperature (M^bt), as hyperthermia increased to 39 °C Mbt, females had a greater reduction in absolute (MCAv_mean), and relative change (%Δ MCAv_mean) and conductance (%Δ MCAv_mean conductance) in MCA_Vmean compared to males (Interaction: Temperature x Sex, P ≤ 0.002). During exercise in cool conditions, absolute and conductance MCAv_mean was maintained from rest through exercise; however, females had greater MCA_Vmean compared to males (Main effect: Sex, P < 0.0008). We also found disparities in females' perceptual thermal comfort and thermal preference. These differences may be associated with a greater reduction in partial pressure of end-tidal CO₂, and different cardiovascular and blood pressure control to exercise under hyperthermia.ConclusionsIn summary, females exercise cerebral blood flow velocity is reduced to a greater extent (25% vs 15%) and the initial reduction occurs at lower hyperthermia mean body temperatures (~38 °C vs ~39 °C) and are under greater thermal perceptual strain compared to males.     

Utilization of cone-beam CT for offline evaluation of target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment

AimTo assess target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment and to assess possibility of safety margin reduction.BackgroundImplementation of IGRT should influence safety margins. Utilization of cone-beam CT provides current 3D anatomic information directly in irradiation position. Such information enables reconstruction of the actual dose distribution.Materials and methodsSeventeen prostate patients were treated with daily bony anatomy image-guidance. Cone-beam CT (CBCT) scans were acquired once a week immediately after bony anatomy alignment. After the prostate, seminal vesicles, rectum and bladder were contoured, the delivered dose distribution was reconstructed. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed a 1 cm safety margin. Alternative plans assuming a smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with the initial ones. Rectal and bladder volumes irradiated with doses higher than 75 Gy, 70 Gy, 60 Gy, 50 Gy and 40 Gy were analyzed.ResultsIn 12% of reconstructed plans the prostate coverage was not sufficient. The prostate underdosage was observed in 5 patients. Coverage of seminal vesicles was not satisfactory in 3% of plans. Most of the target underdosage corresponded to excessive rectal or bladder filling. Evaluation of alternative plans assuming a smaller 7 mm margin revealed 22% and 11% of plans where prostate and seminal vesicles coverage, respectively, was compromised. These were distributed over 8 and 7 patients, respectively.ConclusionSufficient dose coverage of target volumes was not achieved for all patients. Reducing of safety margin is not acceptable. Initial rectal and bladder volumes cannot be considered representative for subsequent treatment.     

Clinical impact of dosimetric changes for volumetric modulated arc therapy in log file-based patient dose calculations

PurposeA log file-based method cannot detect dosimetric changes due to linac component miscalibration because log files are insensitive to miscalibration. Herein, clinical impacts of dosimetric changes on a log file-based method were determined.Methods and materialsFive head-and-neck and five prostate plans were applied. Miscalibration-simulated log files were generated by inducing a linac component miscalibration into the log file. Miscalibration magnitudes for leaf, gantry, and collimator at the general tolerance level were ±0.5 mm, ±1°, and ±1°, respectively, and at a tighter tolerance level achievable on current linac were ±0.3 mm, ±0.5°, and ±0.5°, respectively. Re-calculations were performed on patient anatomy using log file data.ResultsChanges in tumor control probability/normal tissue complication probability from treatment planning system dose to re-calculated dose at the general tolerance level was 1.8% on planning target volume (PTV) and 2.4% on organs at risk (OARs) in both plans. These changes at the tighter tolerance level were improved to 1.0% on PTV and to 1.5% on OARs, with a statistically significant difference.ConclusionsWe determined the clinical impacts of dosimetric changes on a log file-based method using a general tolerance level and a tighter tolerance level for linac miscalibration and found that a tighter tolerance level significantly improved the accuracy of the log file-based method.     

Synthesis and characterization of pHLIP® coated gold nanoparticles

Novel approaches in synthesis of spherical and multispiked gold nanoparticles coated with polyethylene glycol (PEG) and pH Low Insertion Peptide (pHLIP^®) were introduced. The presence of a tumor-targeting pHLIP^® peptide in the nanoparticle coating enhances the stability of particles in solution and promotes a pH-dependent cellular uptake. The spherical particles were prepared with sodium citrate as a gold reducing agent to form particles of 7.0±2.5 nm in mean metallic core diameter and ～43 nm in mean hydrodynamic diameter. The particles that were injected into tumors in mice (21 µg of gold) were homogeneously distributed within a tumor mass with no staining of the muscle tissue adjacent to the tumor. Up to 30% of the injected gold dose remained within the tumor one hour post-injection. The multispiked gold nanoparticles with a mean metallic core diameter of 146.0±50.4 nm and a mean hydrodynamic size of ~161 nm were prepared using ascorbic acid as a reducing agent and disk-like bicelles as a template. Only the presence of a soft template, like bicelles, ensured the appearance of spiked nanoparticles with resonance in the near infrared region. The irradiation of spiked gold nanoparticles by an 805 nm laser led to the time- and concentration-dependent increase of temperature. Both pHLIP^® and PEG coated gold spherical and multispiked nanoparticles might find application in radiation and thermal therapies of tumors.     

Thermoregulation in premature infants: A mathematical model

PurposeIn 2010, approximately 14.9 million babies (11.1%) were born preterm. Because preterm infants suffer from an immature thermoregulatory system they have difficulty maintaining their core body temperature at a constant level. Therefore, it is essential to maintain their temperature at, ideally, around 37 °C. For this, mathematical models can provide detailed insight into heat transfer processes and body-environment interactions for clinical applications.MethodsA new multi-node mathematical model of the thermoregulatory system of newborn infants is presented. It comprises seven compartments, one spherical and six cylindrical, which represent the head, thorax, abdomen, arms and legs, respectively. The model is customizable, i.e. it meets individual characteristics of the neonate (e.g. gestational age, postnatal age, weight and length) which play an important role in heat transfer mechanisms. The model was validated during thermal neutrality and in a transient thermal environment.ResultsDuring thermal neutrality the model accurately predicted skin and core temperatures. The difference in mean core temperature between measurements and simulations averaged 0.25±0.21 °C and that of skin temperature averaged 0.36±0.36 °C. During transient thermal conditions, our approach simulated the thermoregulatory dynamics/responses. Here, for all infants, the mean absolute error between core temperatures averaged 0.12±0.11 °C and that of skin temperatures hovered around 0.30 °C.ConclusionsThe mathematical model appears able to predict core and skin temperatures during thermal neutrality and in case of a transient thermal conditions.     

Applying radiobiological plan ranking methodology to VMAT prostate SBRT

The impact of a rectal spacer and an increased near maximum target dose in VMAT prostate SBRT is studied.For a group of 11 patients (35 Gy-in-five-fractions VMAT prostate SBRT) a set of 4 plans were generated, namely two VMAT plans, with D2% ⩽ 37.5 Gy (Hom) and with D2% ⩽ 40.2 Gy (Het), were created for each of two CT scans taken before (NoSpc) and after (Spc) transperineal spacer insertion. Consequently the methodology for parameter invariant TCP (tumor control probability) plan ranking was applied for comparison of the plans in terms of tumor control. NTCPs (normal tissue complication probabilities) were calculated for rectum and bladder using Lyman’s model.For all 11 patients the TCP plan ranking has shown that the Het plans would perform considerably better in TCP terms than the Hom ones. The plans without rectal spacer were ranked worse compared to those with rectal spacer except for one set of Hom plans. The calculated NTCPs for rectum produced by the Het plans were quite similar to the NTCPs of the Hom ones. The rectal NTCPs of the Hom Spc plans were always lower than the NTCPs of the Hom NoSpc plans. The NTCP values for bladder were extremely low in all cases.The use of rectal spacer leads in general to lower risk of rectal complications, as expected, and even to better tumor control. Plans with increased near maximum target dose (D2% ⩽ 40.2 Gy) are expected to perform much better in terms of tumor control than those with D2% ⩽ 37.5 Gy.     

Cone-beam CT-based inter-fraction localization errors for tumors in the pelvic region

PurposeTo evaluate inter-fraction tumor localization errors (TE) in the RapidArc® treatment of pelvic cancers based on CBCT. Appropriate CTV-to PTV margins in a non-IGRT scenario have been proposed.MethodsData of 928 patients with prostate, gynecological, and rectum/anal canal cancers were retrospectively analyzed to determine systematic and random localization errors. Two protocols were used: daily online IGRT (d-IGRT) and weekly IGRT. The latter consisted in acquiring a CBCT for the first 3 fractions and subsequently once a week. TE for patients who underwent d-IGRT protocol were calculated using either all CBCTs or the first 3.ResultsThe systematic (and random) TE in the AP, LL, and SI direction were: for prostate bed 2.7(3.2), 2.3(2.8) and 1.9(2.2) mm; for prostate 4.2(3.1), 2.9(2.8) and 2.3(2.2) mm; for gynecological 3.0(3.6), 2.4(2.7) and 2.3(2.5) mm; for rectum 2.8(2.8), 2.4(2.8) and 2.3(2.5) mm; for anal canal 3.1(3.3), 2.1(2.5) and 2.2(2.7) mm. CTV-to-PTV margins determined from all CBCTs were 14 mm in the AP, 10 mm in the LL and 9–9.5 mm in the SI directions for the prostate and the gynecological groups and 9.5–10.5 mm in AP, 9 mm in LL and 8–10 mm in the SI direction for the prostate bed and the rectum/anal canal groups. If assessed on the basis of the first 3 CBCTs, the calculated CTV-to-PTV margins were slightly larger.Conclusionswithout IGRT, large CTV-to-PTV margins up to 15 mm are required to account for inter-fraction tumor localization errors. Daily IGRT should be used for all hypo-fractionated treatments to reduce margins and avoid increased toxicity to critical organs.     

Quantification of residual dose estimation error on log file-based patient dose calculation

PurposeThe log file-based patient dose estimation includes a residual dose estimation error caused by leaf miscalibration, which cannot be reflected on the estimated dose. The purpose of this study is to determine this residual dose estimation error.Methods and materialsModified log files for seven head-and-neck and prostate volumetric modulated arc therapy (VMAT) plans simulating leaf miscalibration were generated by shifting both leaf banks (systematic leaf gap errors: ±2.0, ±1.0, and ±0.5 mm in opposite directions and systematic leaf shifts: ±1.0 mm in the same direction) using MATLAB-based (MathWorks, Natick, MA) in-house software. The generated modified and non-modified log files were imported back into the treatment planning system and recalculated. Subsequently, the generalized equivalent uniform dose (gEUD) was quantified for the definition of the planning target volume (PTV) and organs at risks.ResultsFor MLC leaves calibrated within ±0.5 mm, the quantified residual dose estimation errors that obtained from the slope of the linear regression of gEUD changes between non- and modified log file doses per leaf gap are in head-and-neck plans 1.32 ± 0.27% and 0.82 ± 0.17 Gy for PTV and spinal cord, respectively, and in prostate plans 1.22 ± 0.36%, 0.95 ± 0.14 Gy, and 0.45 ± 0.08 Gy for PTV, rectum, and bladder, respectively.ConclusionsIn this work, we determine the residual dose estimation errors for VMAT delivery using the log file-based patient dose calculation according to the MLC calibration accuracy.     

Ablation index-guided 50W radiofrequency ablation for left atrial posterior wall isolation in atrial fibrillation

BackgroundAblation index (AI)-guided ablation for posterior wall isolation (PWI) using high-power, short-duration remains untested. We sought to evaluate the acute outcomes of AI-guided 50 W ablation vs. conventional ablation, and investigate the differences in relationship between contact force (CF), time and AI in both groups.MethodsConsecutive patients undergoing first-time AI-guided ablation with PWI using either 50 W or 35–40 W ablation were enrolled. Acute procedural metrics and individual lesion level ablation data were compared between groups.Results40 patients (50 W: n = 20, 35–40 W: n = 20) with atrial fibrillation were included. Total procedure time was significantly reduced with 50 W (120 vs. 143 mins, p = 0.004) and there was a trend toward decreased ablation time (22 vs. 28 mins, p = 0.052). First pass and acute success of PWI were comparable between the 50 W and 35–40 W groups (10 vs. 8 patients, p = 0.525 and 20 vs. 19 patients, p = 1.000, respectively). Individual lesion analysis of all 959 RF applications (50 W: n = 458, 35–40 W: n = 501) demonstrated that 50 W ablation led to lower ablation time per lesion (10.4 vs. 13.0s, p < 0.001), and increased AI (471 vs. 461, p < 0.001) and impedance drop (7.4 vs. 6.9ohms, p = 0.007). Excessive ablations (AI>600 for roof line; AI>500 elsewhere) were more frequently observed in the 50 W group (9.0% vs. 4.6%, p = 0.007). CF had very good discriminative capability for excessive ablation in both groups. At 50 W, limiting the CF to <10 g reduced the number of excessive ablations on the floor line and within the posterior box to 12% and 4%,respectively. Recurrence of atrial arrhythmias at 12 months were comparable between the groups.ConclusionAI-guided 50 W RF ablation reduces the ablation time of individual lesions and total procedure time without compromising first pass and acute success rates of PWI or 12-month outcomes compared to conventional powers.     

The effect of two cryopreservation methods on human sperm DNA damage

Several methods are currently available for selection when conducting sperm cryopreservation, however, these methods might cause different degrees of damage on sperm DNA. The aim of the this study is to compare the effects of storage at −80 °C (in ultra-low temperature refrigerator) and at −196 °C (in liquid nitrogen) on sperm DNA damage, thus to provide a reference for choosing the right method according to different aims. We randomly collected 28 semen samples from college students of Chongqing city. The samples stored at −80 °C were neat semen samples and the samples stored at −196 °C were mixed with additional cryoprotectants. Each sample was subjected to two freezing-thawing cycles, and the sperm DNA damage levels of fresh and thawed samples were measured by single cell gel electrophoresis (SCGE) and sperm chromatin structure assay (SCSA). Both SCGE and SCSA assays showed cryopreservation induced significant damage to sperm DNA. However, storage at −196 °C lead to more severe damage to sperm DNA than storage at −80 °C measured by SCSA. Sperm DNA damage increased simultaneously with the higher frequency of freezing-thawing cycles. We concluded that storage of neat semen samples at −80 °C had milder damage to sperm DNA than storage at −196 °C mixed with cryoprotectants. To avoid additional sperm DNA damage, repeated freezing and thawing should be prevented.