CT-based dose recalculations in head and neck cancer radiotherapy: comparison of daily dose recalculations to less time-consuming approaches.

BACKGROUND: The goal of this study was to investigate if daily dose recalculations are necessary or if less time-consuming approaches can be used to identify dose differences to the planned dose in patients with head and neck cancers (H&N). METHODS: For 12 H&N patients treated with helical tomotherapy, daily dose calculations were performed retrospectively. Four different summation doses (SuDo) were calculated: DayDo (daily dose calculation), MVCTx2, MVCTx5, and MVCTx10 (dose calculations every second, fifth, and tenth fraction). Dose recalculations were depicted on the last contoured mega voltage CT (MVCT). The DayDo was compared to the planned dose and to the less time-consuming SuDo scenarios. The doses were assessed for the planning target volume (PTV) and the organs at risk (OARs): mandible (mand), spinal cord (SC), spinal cord +5 mm (SC+5 mm), parotid glands (PG). RESULTS: The ipsilateral PG, contralateral PG, and PTV volume decreased by -22.5% (range: -34.8 to 5.2%), -19.5% (-31.5 to 15.8%), and -2.6% (-16.7 to 0.2%), respectively. There was a significant median mean dose (Dmean) dose difference for DayDo compared to the planned dose for PG total of 1.9 Gy (-3.3 to 7.3 Gy). But less time-consuming SuDo compared to DayDo showed statistically significant but not clinically relevant (<2%) dose differences for several organs. Hence the small dose difference to the gold standard (DayDo), we recommend dose recalculations every fifth MVCT in order to identify the occurrence of dose differences compared to the planned dose. CONCLUSION: Daily dose calculations are the most precise to assess dose differences between actual and planned dose. Dose recalculations on every fifth MVCT (i. e., weekly control CTs) are an applicable and time-saving way of identifying patients with significant dose differences compared to the planned dose.

Fiducial markers: can the urologist do better?

INTRODUCTION: Radiotherapy to the bladder has a risk of toxicity to pelvic structures, which can be reduced by using fiducial markers for targeting. Injectable contrast offers an alternative marker to gold seeds, which may fall out or exacerbate scarring. Combining contrast agents with tissue glue can minimize dispersion through tissue, enhancing its utility. We evaluated combinations of contrast agents and tissue glue using porcine bladder, for feasibility and utility as fiducial markers to aid image-guided radiotherapy. METHODS: Different contrast agents (Lipiodol ultra or Urografin) were combined with different tissue glues (Histoacryl, Tisseal or Glubran2). The mixtures were endoscopically injected into porcine bladder submucosa to identify the area of interest with multiple fiducial markers. The porcine bladders were imaged within a phantom porcine pelvis using standard radiation therapy imaging modalities. The feasibility as an injectable fiducial marker and visibility of each fiducial marker on imaging were scored as binary outcomes by two proceduralists and two radiation therapists, respectively. RESULTS: Lipiodol-glue combinations were successfully administered as multiple fiducials that were evident on CT and CBCT. Lipiodol with Histoacryl or Glubran2 was visible on kV imaging. The Lipiodol Glubran2 combination was deemed subjectively easiest to use at delivery, and a better fiducial on KV imaging. CONCLUSION: This study demonstrates the feasibility of mixing contrast medium Lipiodol with Histoacryl or Glubran2 tissue glue, which, injected endoscopically, provides discrete and visible fiducial markers to aid image-guided radiotherapy. Although promising, further study is required to assess the durability of these markers through a course of radiotherapy.

[Comparison of vacuum bag fixation and Orfit rack with thermoplastic membrane fixation for image-guided cervical cancer radiotherapy].

Objective: To compare the difference of displacement between the vacuum bag fixation and the Orfit rack with thermoplastic membrane fixation of the cervical cancer patients, and to explore the individual fixation of the patients. Methods: We retrospectively analyzed the clinical data of 66 patients diagnosed as cervical cancer in Zhangzhou Municipal Hospital of Fujian Province from December 2014 to April 2016. Among them, 33 patients were fixed with vacuum bag, 33 patients were fixed with the Orfit rack with thermoplastic membrane. The cone-beam computed tomography (CBCT) images were acquired daily for the first three times of the radiotherapy, followed by once every other day for a total of 15 times. The CBCT scan images were matched with the CT scan images, and the matching results were recorded and analyzed. Results: The absolute value of the displacement in the left and right directions of the vacuum bag group was (0.28±0.30) cm, significantly lower than (0.38±0.46) cm in the Orfit rack with thermoplastic membrane group(P<0.001). The absolute value of the displacement in the anteroposterior direction of the vacuum bag group was (0.28±0.32) cm, with no significant difference of (0.27±0.23) cm in the Orfit rack with thermoplastic membrane group (P=0.580). The absolute value of the displacement in the up and down directions was (0.33±0.60) cm, with no statistically significant difference of (0.27±0.48) cm in the Orfit rack with thermoplastic membrane group (P=0.150). During the three times of CBCT scans, the differences of displacement in the left and right directions of the vacuum bag group were negligible, while apparently varied in the anteroposterior and up and down directions, however, the differences were not statistically significant (P>0.05). The change of the displacement in the three-dimensional direction in the Orfit rack with thermoplastic membrane group was marginal, and all of the differences were not significant(all P>0.05). Conclusions: Both the vacuum bag fixation and the Orfit rack with thermoplastic membrane fixation are suitable for the cone-beam CT image-guided radiotherapy of cervical cancer patients. However, the displacement in the left and right directions of the vacuum bag fixation is smaller than the Orfit rack with thermoplastic membrane fixation. During the period of treatment, the mean value of the difference of displacement in the anterior and posterior directions of the Orfit rack with thermoplastic membrane fixation is mild, which can be used individually by the patients with a flexible body and good tolerance.

A novel endoscopic marker for radiological localization and image-guided radiotherapy in esophageal and gastric cancers (with video).

BACKGROUND AND AIMS: Radiotherapy is an accepted modality in the treatment of esophageal cancers and is currently being evaluated in conjunction with chemotherapy for the neoadjuvant treatment of gastric cancers. Our aim was to assess whether a novel endoscopically inserted marker can be used to improve radiological assessment of the primary cancer and allow for image-guided radiotherapy. METHODS: A phase II feasibility study was conducted at a tertiary-care center. Twenty-six consecutive adult patients with esophagogastric cancers underwent endoscopic marking of the tumor margins with a novel radiopaque marker (mixture of lipiodol and n-butyl 2-cyanoacrylate). The main outcome measure was the successful insertion of the marker based on a combination of radiological, endoscopic, and histological assessment. RESULTS: A total of 92 markers were inserted in 26 patients. Twenty-two (88%) had follow-up imaging to assess the 81 markers inserted, 79 of which (97.5%) were visible. There were no postprocedural adverse events noted in our cohort. Radiological assessment of tumor size improved such that it was in line with the endoscopic evaluation after marker placement in 18 of 21 patients (85.7%) who had appropriate follow-up radiology imaging. Ten patients (38.5%) from our cohort underwent image-guided radiotherapy (IGRT) by using the endoscopically inserted markers. CONCLUSION: Within the limitations of our small pilot study, endoscopic placement of our novel marker was successful in the majority of our cohort without significant adverse events. Marker placement resulted in improved radiological localization in the majority of our cohort and allowed for IGRT. (Australian New Zealand Clinical Trials Registry: ACTRN12613000239763.).

Impact of hydrogel spacer injections on interfraction prostate motion during prostate cancer radiotherapy.

Background The dosimetric advantage of prostate-rectum spacers to displace the anterior rectal wall outside of the high-dose radiation regions has been clearly established in prostate cancer radiotherapy (RT). The aim of this study was to assess the impact of hydrogel spacer (HS) in the interfraction prostate motion in patients undergoing RT for prostate cancer. Material and methods Twenty prostate cancer patients implanted with three fiducial markers (FM) with (n = 10) or without (n = 10) HS were analyzed. Displacements between the prostate isocenter based on the FM's position and the bony anatomy were quantified in the left-right (LR), anterior-posterior (AP), superior-inferior (SI) axes by offline analyses of 122 cone beam computed tomography scans. Group systematic (M), systematic (Σ) and random (σ) setup errors were determined. Results In patients with or without HS, the overall mean interfraction prostate displacements were 0.4 versus -0.4 mm (p = 0.0001), 0.6 versus 0.6 mm (p = 0.85), and -0.6 mm versus -0.3 mm (p = 0.48) for the LR, AP, and SI axes, respectively. Prostate displacements >5 mm in the AP and SI directions were similar for both groups. No differences in M, Σ and σ setup errors were observed in the three axes between HS + or HS- patients. Conclusions HS implantation does not significantly influence the interfraction prostate motion in patients treated with RT for prostate cancer. The major expected benefit of HS is a reduction of the high-dose levels to the rectal wall without influence in prostate immobilization.

A retrospective study on improving the accuracy of radiotherapy for patients with breast cancer with lymph node metastasis using Styrofoam.

BACKGROUND: To retrospectively analyze the accuracy of radiotherapy using cone beam computed tomography (CBCT), Styrofoam fixation, and breast bracket fixation in the chest wall target area and supraclavicular lymphatic drainage area (supraclavicular target area) of patients with breast cancer.and compare the setting efficiency and comfort satisfaction. PATIENTS AND METHODS: A total of 65 patients with postoperative lymphatic metastasis of breast cancer, including 36 cases of Styrofoam fixation and 29 cases of breast bracket fixation, were recruited from March 2021 to August 2022 and retrospectively analyzed. All the patients underwent CBCT scans weekly, and the setup errors of the chest wall and supraclavicular target volume were compared and recorded. The planning target volume (PTV) margins of the two groups were calculated using the correlation MPTV = 2.5Σ + 0.7σ. The setup time and comfort satisfaction scores of the two groups were recorded and analyzed. The correlations among errors in each direction were analyzed using the Pearson correlation analysis. RESULTS: There was a significant difference in the left-right direction (X) axis of the chest wall target area between the Styrofoam and breast bracket groups (1.59 ± 1.47 mm vs. 2.05 ± 1.64 mm, P = 0.012). There were statistical differences in the ventrodorsal direction (Z) and bed angle of the supraclavicular target area, the data were (1.36 ± 1.27 mm vs. 1.75 ± 1.55 mm, P = 0.046; 0.47 ± 0.47° vs. 0.66 ± 0.59°, P = 0.006, respectively). In the X, Y, and Z directions, the respective PTV margins of the two groups in the chest wall target area were 5.01 mm, 5.99 mm, and 5.47 mm in the Styrofoam group, while those in the breast bracket group were 6.10 mm, 6.34 mm, and 6.10 mm, respectively. Moreover, the PTV margins of the supraclavicular target in the three directions were 3.69 mm, 3.86 mm, and 4.28 mm in the Styrofoam group, while those in the breast bracket group were 3.99 mm, 3.72 mm, and 5.45 mm, respectively. The setup time of the two groups was 3.4 ± 1.1 min and 5.5 ± 3.1 min (P = 0.007). The subjective comfort satisfaction scores of the two groups were 27.50 ± 1.24 and 25.44 ± 1.23 (P < 0.001). CONCLUSIONS: The application of Styrofoam fixation in radiotherapy of breast cancer in the supraclavicular lymph node area has several advantages as compared to breast bracket fixation, including higher positioning accuracy, smaller external expansion boundary, improved work efficiency, and patients' comfort, which might provide a reference for clinical work.

Surface guided radiation therapy with an innovative open-face mask and mouth bite: patient motion management in brain stereotactic radiotherapy.

INTRODUCTION: To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. METHODS: This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland-Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. RESULTS: The median of translation error between stages of the AlignRT positioning process was (0.03-0.07) cm, and the median of rotation error was (0.20-0.40)°, which were significantly better than those of the Fraxion positioning process (0.09-0.11) cm and (0.60-0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01 cm, - 0.07 cm, 0.03 cm, - 0.30°, - 0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10 cm and 0.50°. CONCLUSIONS: The application of the SGRT with an innovative open-face mask and mouth bite device could achieve precision positioning accuracy and stability, and the accuracy of the AlignRT system exhibits excellent constancy with the CBCT gold standard. The non-coplanar radiation field monitoring can provide reliable support for motion management in fractional treatment.

A framework for deformable image registration validation in radiotherapy clinical applications.

Quantitative validation of deformable image registration (DIR) algorithms is extremely difficult because of the complexity involved in constructing a deformable phantom that can duplicate various clinical scenarios. The purpose of this study is to describe a framework to test the accuracy of DIR based on computational modeling and evaluating using inverse consistency and other methods. Three clinically relevant organ deformations were created in prostate (distended rectum and rectal gas), head and neck (large neck flexion), and lung (inhale and exhale lung volumes with variable contrast enhancement) study sets. DIR was performed using both B-spline and diffeomorphic demons algorithms in the forward and inverse direction. A compositive accumulation of forward and inverse deformation vector fields was done to quantify the inverse consistency error (ICE). The anatomical correspondence of tumor and organs at risk was quantified by comparing the original RT structures with those obtained after DIR. Further, the physical characteristics of the deformation field, namely the Jacobian and harmonic energy, were computed to quantify the preservation of image topology and regularity of spatial transformation obtained in DIR. The ICE was comparable in prostate case but the B-spline algorithm had significantly better anatomical correspondence for rectum and prostate than diffeomorphic demons algorithm. The ICE was 6.5 mm for demons algorithm for head and neck case when compared to 0.7 mm for B-spline. Since the induced neck flexion was large, the average Dice similarity coefficient between both algorithms was only 0.87, 0.52, 0.81, and 0.67 for tumor, cord, parotids, and mandible, respectively. The B-spline algorithm accurately estimated deformations between images with variable contrast in our lung study, while diffeomorphic demons algorithm led to gross errors on structures affected by contrast variation. The proposed framework offers the application of known deformations on any image datasets, to evaluate the overall accuracy and limitations of a DIR algorithm used in radiation oncology. The evaluation based on anatomical correspondence, physical characteristics of deformation field, and image characteristics can facilitate DIR verification with the ultimate goal of implementing adaptive radiotherapy. The suitability of application of a particular evaluation metric in validating DIR is dependent on the clinical deformation observed.

Monte Carlo optimization and experimental validation of a prototype ionization chamber for accurate magnetic resonance image guided radiation therapy (MRgRT) daily output constancy measurements in solid phantoms.

PURPOSE: To optimize the design, develop and test a prototype ionization chamber for accurate daily output constancy measurements in solid phantoms in clinical magnetic resonance-guided radiation therapy (MRgRT) radiotherapy beams. Up to 4% variations in response using commercial ionization chambers have been previously reported; the prototype ionization chamber developed here aims to minimize these variations. METHODS: Monte Carlo simulations with the EGSnrc code system are used to optimize an ionization chamber design by increasing the thickness of a brass (high-density, nonferromagnetic, easy-to-machine) wall until results consistent with no air gap are produced for simulations with a 1.5 T and 0.35 T magnetic field, with a 0.2 mm air gap and varying the placement of the chamber model within the air gap. Based on the results of these simulations, prototype ionization chambers are manufactured and tested in conventional linac beams and in a 7 MV Elekta Unity MR-linac. The chambers are rotated about their axes, both parallel and perpendicular to the 1.5 T magnetic field, through 360º in a plastic phantom with measurements made at each cardinal angle. This reveals any variation in chamber response by varying the thickness of the air gap between the chamber and the phantom. RESULTS: Monte Carlo simulations demonstrate that the optimal thickness of the chamber wall to mitigate the effect of an asymmetric air gap between the chamber and the plastic phantom is 1.1 mm of brass. With this thickness, the differences between simulations with and without an air gap and with asymmetric placement of the chamber within the air gap are less than 0.2%. A prototype chamber constructed with a 1.1 mm brass wall thickness exhibits less than 0.3% variation in response when rotated about its axis in the plastic phantom in a beam from an MR-linac, independent of whether its axis is parallel or perpendicular to the magnetic field. CONCLUSION: The optimized ionization chamber design and validated prototype for accurate MR-linac daily output constancy measurements allows utilization of conventional phantoms and procedures in MRgRT systems. This can minimize disruption to clinical workflow for MR-linac quality assurance measurements.

Biodegradable Fiducial Markers for Bimodal Near-Infrared Fluorescence- and X-ray-Based Imaging.

This study aimed to evaluate, for the first time, implantable, biodegradable fiducial markers (FMs), which were designed for bimodal, near-infrared fluorescence-based (NIRF) and X-ray-based imaging. The developed FMs had poly(l-lactide-co-caprolactone)-based core-shell structures made of radiopaque (core) and fluorescent (shell) composites with a poly(l-lactide-co-caprolactone) matrix. The approved for human use contrast agents were utilized as fillers. Indocyanine green was applied to the shell material, whereas in the core materials, iohexol and barium sulfate were compared. Moreover, the possibility of tailoring the stability of the properties of the core materials by the addition of hydroxyapatite (HAp) was examined. The performed in situ (porcine tissue) and in vivo experiment (rat model) confirmed that the developed FMs possessed pronounced contrasting properties in NIRF and X-ray imaging. The presence of HAp improved the radiopacity of FMs at the initial state. It was also proved that, in iohexol-containing FMs, the presence of HAp slightly decreased the stability of contrasting properties, while in BaSO4-containing ones, changes were less pronounced. A comprehensive material analysis explaining the differences in the stability of the contrasting properties was also presented. The tissue response around the FMs with composite cores was comparable to that of the FMs with a pristine polymeric core. The developed composite FMs did not cause serious adverse effects on the surrounding tissues even when irradiated in vivo. The developed FMs ensured good visibility for NIRF image-supported tumor surgery and the following X-ray image-guided radiotherapy. Moreover, this study replenishes a scanty report regarding similar biodegradable composite materials with a high potential for application.

Randomised controlled trial on the effect of simethicone bowel preparation on rectal variability during image-guided radiation therapy for prostate cancer (SPoRT study).

INTRODUCTION: The purpose of this study was to assess whether simethicone reduces the rectal volume (RV) and gas volume (GV), to increase treatment accuracy and to decrease toxicity of prostate radiation therapy. METHODS: 30 patients were randomised to simethicone or no intervention. Cone-beam computed tomography (CBCT) scans were performed on Days 1-3 and weekly until completion of radiation. RV and GV were measured using volume delineation. Toxicity data were collected. RESULTS: 264 CBCTs were analysed. RV and GV were not significantly different in the simethicone group compared with the control group at each time point (P >0.05) after adjusting for Week 0 values as a covariate. The simethicone group showed an average reduction in RV and GV of 10% and 21%, respectively, compared with the control group (P >0.05). Standard deviations were calculated over 10 time points, which were grouped to represent the first 2-3 weeks of radiation therapy versus subsequent weeks. These were not significantly different between the simethicone and control group. However, there was a statistically significant decrease in the variability of RV at time points 6-10 compared with time points 1-5 within the simethicone group (P = 0.012), but no significant difference was found between these grouped time points in the control group (P = 0.581). The toxicity questionnaires showed no significant difference between the groups. CONCLUSIONS: Simethicone did not decrease the RV or GV overall. However, simethicone appeared to significantly decrease the RV variability from Week three onwards. This suggests that taking simethicone two to three weeks before starting radiation therapy may reduce RV variability, although a larger study is needed to confirm this.

Increased beam attenuation and surface dose by different couch inserts of treatment tables used in megavoltage radiotherapy.

The use of solid carbon fiber table materials in radiotherapy has become more common with the implementation of image-guided radiotherapy (IGRT), since the solid materials give less imaging artifacts than the so-called tennis racket couchtops. The downside of the solid carbon fiber couch inserts is that they increase the beam attenuation, resulting in increased surface doses and inaccuracies in determine the dose in the patient. The purpose of this study was to evaluate the interaction of 6 and 15 MV photons with eight different couch inserts. The presented results enable direct comparison of the attenuation properties of the studied couchtops. With a direct posterior beam the maximum attenuations reach 3.6% and 2.4% with 6 and 15 MV, respectively. The measured maximum attenuation by a couchtop with an oblique gantry angle was 10.8% and 7.4% at 6 and 15 MV energies, respectively. The skin-sparing effect was decreased substantially with every couchtop. The highest increases in surface doses were recorded to be four- and threefold, as compared to the direct posterior open field surface doses of 6 and 15 MV, respectively. In conclusion, the carbon fiber tabletops decrease the skin-sparing effect of megavoltage photon energies. The increased beam attenuation and skin doses should be taken into account in the process of treatment planning.

Head-and-neck organs-at-risk auto-delineation using dual pyramid networks for CBCT-guided adaptive radiotherapy.

Organ-at-risk (OAR) delineation is a key step for cone-beam CT (CBCT) based adaptive radiotherapy planning that can be a time-consuming, labor-intensive, and subject-to-variability process. We aim to develop a fully automated approach aided by synthetic MRI for rapid and accurate CBCT multi-organ contouring in head-and-neck (HN) cancer patients. MRI has superb soft-tissue contrasts, while CBCT offers bony-structure contrasts. Using the complementary information provided by MRI and CBCT is expected to enable accurate multi-organ segmentation in HN cancer patients. In our proposed method, MR images are firstly synthesized using a pre-trained cycle-consistent generative adversarial network given CBCT. The features of CBCT and synthetic MRI (sMRI) are then extracted using dual pyramid networks for final delineation of organs. CBCT images and their corresponding manual contours were used as pairs to train and test the proposed model. Quantitative metrics including Dice similarity coefficient (DSC), Hausdorff distance 95% (HD95), mean surface distance, and residual mean square distance (RMS) were used to evaluate the proposed method. The proposed method was evaluated on a cohort of 65 HN cancer patients. CBCT images were collected from those patients who received proton therapy. Overall, DSC values of 0.87 ± 0.03, 0.79 ± 0.10/0.79 ± 0.11, 0.89 ± 0.08/0.89 ± 0.07, 0.90 ± 0.08, 0.75 ± 0.06/0.77 ± 0.06, 0.86 ± 0.13, 0.66 ± 0.14, 0.78 ± 0.05/0.77 ± 0.04, 0.96 ± 0.04, 0.89 ± 0.04/0.89 ± 0.04, 0.83 ± 0.02, and 0.84 ± 0.07 for commonly used OARs for treatment planning including brain stem, left/right cochlea, left/right eye, larynx, left/right lens, mandible, optic chiasm, left/right optic nerve, oral cavity, left/right parotid, pharynx, and spinal cord, respectively, were achieved. This study provides a rapid and accurate OAR auto-delineation approach, which can be used for adaptive radiation therapy.

Gadolinium-Rose Bengal Coordination Polymer Nanodots for MR-/Fluorescence-Image-Guided Radiation and Photodynamic Therapy.

Combination therapy based on nanomedicine has gained momentum in oncology in recent years, offering superior safety and efficacy over monotherapies. It is critical to design theranostics that are composed of imaging and therapeutic agents already approved. Herein, gadolinium (Gd)-rose bengal coordination polymer nanodots (GRDs) are reported. The GRDs exhibit a unique absorption property and 7.7-fold luminescence enhancement, as well as a 1.9-fold increase in singlet oxygen generation efficiency over free rose bengal. Meanwhile, GRDs exhibit a twofold increase in r1 relaxivity over gadopentetic acid (Gd-DTPA) and have better X-ray absorption ability than rose bengal alone. These excellent properties of the GRDs are verified both in vitro and in vivo. The combination of photodynamic therapy (PDT) and radiation therapy (RT) more significantly inhibits tumor growth than monotherapies (i.e., PDT or RT). This work offers a new route to designing and synthesizing Gd-based nanotheranostics for image-guided cancer therapy.

Magnetic targeted near-infrared II PA/MR imaging guided photothermal therapy to trigger cancer immunotherapy.

Rationale: Photothermal therapy (PTT) alone is easy to cause cancer recurrence and fail to completely resist metastasis, yet recurrence and metastasis are two major difficulties in cancer treatment. Titanium disulfide (TiS2) nanosheet anchored iron oxide nanoparticles (IO NPs) with strong absorption in the second near-infrared (NIR-II) window and excellent magnetic properties is developed as therapeutic agent for NIR-II photoacoustic (PA) imaging and magnetic resonance (MR) imaging guided NIR-II PTT triggered immunotherapy. Methods: The TiS2 nanosheets were prepared through a modified colloidal chemistry approach, and TSIO nanoagents were prepared by using a one pot self-assembly technique. The magnetic targeting capability of TSIO nanoagents were monitored by NIR-II PA, MR and thermal imaging in vivo. The NIR-II PTT combined with immunotherapy effect was investigated in mouse breast cancer tumor-bearing mice. Results: The TSIO nanoplatform showed enhanced tumor accumulation when a magnetic field was applied and had the ability to real time monitor the treatment process via dual NIR-II PA and MR imaging. In addition, the magnetic targeted NIR-II PA/MR imaging guided PTT provides an effective way to reverse the immunosuppression inside a tumor and to cooperate with immunotherapy to improve therapeutic outcome of the primary, distal and metastatic tumors.

Hyaluronic acid spacer in focal prostate reirradiation: A single centre experience.

PURPOSE: The optimal management of locally recurrent prostate cancer after curative radiotherapy is still unknown. In this study, we evaluated the preliminary results of reirradiation using stereotactic body radiotherapy for locally recurrent prostate cancer after initial definitive local radiotherapy. MATERIALS AND METHODS: Between April 2016 and February 2019, 11 patients with recurrent disease at the previously irradiated prostate were treated. Local recurrence was detected by radiological with or without functional imaging modalities including prostate multiparametric/pelvic MRI or positron-emission tomography-computerised tomography with (68Ga)-labelled prostate-specific membrane antigen performed after rising prostate specific antigen serum level during follow-up. All patients received stereotactic body radiotherapy to the recurrent nodule to a total dose of 30Gy in five fractions. Hyaluronic acid spacer was injected between prostate and rectum in seven patients to decrease the rectal dose. Acute toxicity was evaluated by using Common Terminology Criteria for Adverse Events version 4.0, and late toxicity was evaluated by using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. RESULTS: At the diagnosis, the median age was 64 years, and the mean prostate specific antigen serum concentration was 17.7ng/mL. The median interval time between local recurrence and initial definitive radiotherapy was 63 months. Mean prostate specific antigen concentration nadir value during follow-up was 0.43ng/mL. With a median follow up of 19 months, three patients developed either local or distant relapse. One patient had grade 3 acute rectal toxicity, and one patient had grade 2 late urinary toxicity. We did not observe any acute or late toxicity due to hyaluronic acid spacer injection. CONCLUSION: Reirradiation after local recurrence following initial definitive radiotherapy together with hyaluronic acid spacer use seems to be effective and safe.

Variations of the Dose Distribution Between CT- and CBCT-based Plans for Oropharyngeal Cancer.

BACKGROUND/AIM: The parotid glands in the head and neck are organs at risks (OARs) adjacent to high dose region and dose of OARs might be increased during the course of radiotherapy. The influence factors of the dose distribution for the parotid glands were investigated in terms of weight loss and mandibular rotation for head and neck cancers treated with volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Ten oropharyngeal cancer patients (OPC) who underwent VMAT were enrolled. The dose volume histogram (DVH) parameters of the parotid glands and planning target volume (PTV) were compared between the planning computed tomography (CT) and the on board imager (OBI) at 1, 5, 10, 15, and 20 fractions. RESULTS: The variation of dose distribution in PTV was not observed in both factors. The relationship between the mandibular rotation and dose difference for the right and left parotid glands (linear regression, r2=0.1577 and -0.689) showed a slighty stronger correlation with dose difference than the weight loss (linear regression, r2=-0.079 and -0.547). CONCLUSION: The mandibular rotation tends to have a large influence on dose distribution of the parotid glands for head and neck cancers treated with VMAT.

Nanoliposomes Co-Encapsulating CT Imaging Contrast Agent and Photosensitizer for Enhanced, Imaging Guided Photodynamic Therapy of Cancer.

Fluorescence (FL) and X-ray computed tomography (CT) imaging-guided photodynamic therapy (PDT) can provide a powerful theranostic tool to visualize, monitor, and treat cancer and other diseases with enhanced accuracy and efficacy. Methods: In this study, clinically approved iodinated CT imaging contrast agent (CTIA) iodixanol and commercially available photosensitizer (PS) meso-tetrakis (4-sulphonatophenyl) porphine (TPPS4) were co-encapsulated in biocompatible PEGylated nanoliposomes (NL) for enhanced anticancer PDT guided by bimodal (FL and CT) imaging. Results: The NL co-encapsulation of iodixanol and TPPS4 (LIT) lead to an increase in singlet oxygen generation by PS via the intraparticle heavy-atom (iodine) effect on PS molecules, as it was confirmed by both direct and indirect measurements of singlet oxygen production. The confocal imaging and PDT of cancer cells were performed in vitro, exhibiting the cellular uptake of TPPS4 formulations and enhanced PDT efficacy of LIT. Meanwhile, bimodal (FL and CT) imaging was also conducted with tumor-bearing mice and the imaging results manifested high-efficient accumulation and retention of LIT in tumors. Moreover, PDT of tumor in vivo was shown to be drastically more efficient with LIT than with other formulations of TPPS4. Conclusion: This study demonstrated that LIT can serve as a highly efficient theranostic nanoplatform for enhanced anticancer PDT guided by bimodal (FL and CT) imaging.

Technical Note: Experimental verification of magnetic field-induced beam deflection and Bragg peak displacement for MR-integrated proton therapy.

PURPOSE: Given its sensitivity to anatomical variations, proton therapy is expected to benefit greatly from integration with magnetic resonance imaging for online anatomy monitoring during irradiation. Such an integration raises several challenges, as both systems mutually interact. The proton beam will experience quasi-continuous energy loss and energy-dependent electromagnetic deflection at the same time, giving rise to a deflected beam trajectory and an altered dose distribution with a displaced Bragg peak. So far, these effects have only been predicted using Monte Carlo and analytical models, but no clear consensus has been reached and experimental benchmark data are lacking. We measured proton beam trajectories and Bragg peak displacement in a homogeneous phantom placed inside a magnetic field and compared them to simulations. METHODS: Planar dose distributions of proton pencil beams (80-180 MeV) traversing the field of a 0.95 T NdFeB permanent magnet while depositing energy in a PMMA slab phantom were measured using EBT3 radiochromic films and simulated using the Geant4 toolkit. Deflected beam trajectories and the Bragg peak displacement were extracted from the measured planar dose distributions and compared against the simulations. RESULTS: The lateral beam deflection was clearly visible on the EBT3 films and ranged from 1 to 10 mm for 80 to 180 MeV, respectively. Simulated and measured beam trajectories and Bragg peak displacement agreed within 0.8 mm for all studied proton energies. CONCLUSIONS: These results prove that the magnetic field-induced Bragg peak displacement is both measurable and accurately predictable in a homogeneous phantom at 0.95 T, and allows Monte Carlo simulations to be used as gold standard for proton beam trajectory prediction in similar frameworks for MR-integrated proton therapy.

Image guided high-dose-rate brachytherapy versus volumetric modulated arc therapy for head and neck cancer: A comparative analysis of dosimetry for target volume and organs at risk.

Background The aim of the study was to present dosimetric comparison of image guided high-dose-rate brachytherapy (IGBT) with volumetric modulated arc therapy (VMAT) for head and neck cancer regarding conformity of dose distribution to planning target volume (PTV) and doses to organs at risk (OARs). Patients and methods Thirty-eight consecutive patients with T1-4 mobile tongue, floor of mouth and base of tongue cancer treated with IGBT were selected. For these patients additional VMAT treatment plans were also prepared using identical computed tomography data. OARs and PTV related parameters (e.g. V98, D0.1cm3, Dmean, etc.) were compared. Results Mean V98 of the PTV was 90.2% vs. 90.4% (p > 0.05) for IGBT and VMAT, respectively. Mean D0.1cm3 to the mandible was 77.0% vs. 85.4% (p < 0.05). Dmean to ipsilateral and contralateral parotid glands was 4.6% vs. 4.6% and 3.0% vs. 3.9% (p > 0.05). Dmean to ipsilateral and contralateral submandibular glands was 16.4% vs. 21.9% (p > 0.05) and 8.2% vs. 16.9% (p < 0.05), respectively. Conclusions Both techniques showed excellent target coverage. With IGBT dose to normal tissues was lower than with VMAT. The results prove the superiority of IGBT in the protection of OARs and the important role of this invasive method in the era of new external beam techniques.