Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning ...convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this study was to report a list of accepted fractionation schemes for high-dose-rate (HDR) brachytherapy for gynecological cancers in a definitive, neoadjuvant, or adjuvant setting.
...Members of the American Brachytherapy Society (ABS) Task Force with expertise in gynecological brachytherapy reviewed the literature and existing ABS guidelines regarding various dose-fractionation schedules for HDR brachytherapy to create this compendium. Other resources include current guidelines published by medical societies, clinical trials, the published medical literature, and the clinical experience of the ABS Task Force members. The ABS consensus statements for HDR brachytherapy practice were reviewed for these fractionation schemes and form the major source for this report. Specific recommendations for therapy and recommendations for further investigations were made when there was agreement.
A variety of dose-fractionation schedules for HDR brachytherapy alone or integrating brachytherapy with external-beam radiation exist. The choice of a given fractionation schedule may be appropriate depending on the practice situation for the patient and the resources available. While there is no single optimal dose-fractionation scheme for any disease site or clinical situation, higher doses per fraction with fewer fractions per regimen have been known to increase toxicity. The corresponding 2-Gray (Gy) per fraction radiobiologic equivalent doses have been provided (normalized therapy dose) to compare the various regimens where indicated and can be used to estimate isoeffective schedules.
This compendium of HDR brachytherapy fractionation schedules provides various options to the gynecologic brachytherapist and a ready reference for clinical use in the management of gynecological cancer treatments.
Better knowledge of the dose-toxicity relationship is essential for safe dose escalation to improve local control in cervical cancer radiotherapy. The conventional dose-toxicity model is based on the ...dose volume histogram, which is the parameter lacking spatial dose information. To overcome this limit, we explore a comprehensive rectal dose-toxicity model based on both dose volume histogram and dose map features for accurate radiation toxicity prediction.
Forty-two cervical cancer patients treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT) were retrospectively studied, including 12 with Grade ≥ 2 rectum toxicity and 30 patients with Grade 0-1 toxicity (non-toxicity patients). The cumulative equivalent 2-Gy rectal surface dose was deformably summed using the deformation vector fields obtained through a recent developed local topology preserved non-rigid point matching algorithm. The cumulative three-dimensional (3D) dose was flattened and mapped to a two-dimensional (2D) plane to obtain the rectum surface dose map (RSDM). The dose volume parameters (DVPs) were calculated from the 3D rectum surface, while the texture features and the dose geometric parameters (DGPs) were extracted from the 2D RSDM. Representative features further computed from DVPs, textures and DGPs by principle component analysis (PCA) and statistical analysis were respectively fed into a support vector machine equipped with a sequential feature selection procedure. The predictive powers of the representative features were compared with the GEC-ESTRO dosimetric parameters D
.
Satisfactory predictive accuracy of sensitivity 74.75 and 84.75%, specificity 72.67 and 79.87%, and area under the receiver operating characteristic curve (AUC) 0.82 and 0.91 were respectively achieved by the PCA features and statistical significant features, which were superior to the D
(AUC 0.71). The relative area in dose levels of 64Gy, 67Gy, 68Gy, 87Gy, 88Gy and 89Gy, perimeters in dose levels of 89Gy, as well as two texture features were ranked as the important factors that were closely correlated with rectal toxicity.
Our extensive experimental results have demonstrated the feasibility of the proposed scheme. A future large patient cohort study is still needed for model validation.
The spinal nerves have been observed to have a similar single-session dose tolerance to that of the spinal cord in pigs. Small-animal studies have shown that spinal cord dose tolerance depends on the ...length irradiated. This work aims to determine whether a dose-length effect exists for spinal nerves.
Twenty-seven Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 0.5 cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. The pigs were distributed into 6 groups with prescription doses of 16 Gy (n = 5), 18 Gy (n = 5), 20 Gy (n = 5), 22 Gy (n = 5), 24 Gy (n = 5), or 36 Gy (n = 2) and corresponding maximum doses of 16.7, 19.1, 21.3, 23.1, 25.5, and 38.6 Gy, respectively. Neurologic status was assessed with a serial electrodiagnostic examination and daily observation of gait for approximately 52 weeks. A histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff's staining was also performed.
Marked gait change was observed in 8 of 27 irradiated pigs. The latency for responding pigs was 11 to 16 weeks after irradiation. The affected animals presented with a limp in the left front limb, and 62.5% of these pigs had electrodiagnostic evidence of denervation in the C6 and C7 innervated muscles. A probit analysis showed the dose associated with a 50% incidence of gait change is 23.9 Gy (95% confidence interval, 22.5-25.8 Gy), which is 20% higher than that reported in a companion study where a 1.5 cm length was irradiated. All symptomatic pigs had demyelination and fibrosis in the irradiated nerves, but the contralateral nerves and spinal cord were normal.
A dose-length effect was observed for single-session irradiation of the spinal nerves in a Yucatan minipig model.
Purpose
The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human ...cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single‐fraction doses common to stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) treatments. This work describes the development of a system to evaluate local hypothermia for a radioprotective effect of the rat rectum during a large dose of radiation relevant to prostate SBRT. This includes the evaluation of a 3D‐printed small animal rectal cooling device and the integration with a small animal irradiator.
Methods
A 3‐cm long, dual‐lumen rectal temperature control apparatus (RTCA) was designed in SOLIDWORKS CAD for 3D printing. The RTCA was capable of recirculating flow in a device small enough for insertion into the rat rectum, with a metal support rod for strength as well as visibility during radiation treatment planning. The outer walls of the RTCA comprised of thin heat shrink plastic, achieving efficient heat transfer into adjacent tissues. Following leak‐proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within the rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. Integration with an image‐guided small animal irradiator and associated treatment planning system included evaluation for imaging artifacts and effect of brass tubing on dose calculation.
Results
The rectal temperature adjacent to the cooling device decreased from body temperature to 15°C within 10–20 min from device insertion and was maintained at 15 ± 3°C during active cooling for the evaluated time of one hour. MR thermometry revealed a steep temperature gradient with increasing distance from the cooling device with the desired temperature range maintained within the surrounding few millimeters.
Conclusions
A 3D‐printed rectal cooling device was fabricated for the purpose of inducing local hypothermia in the rat rectum. The RTCA was simply integrated with an image‐guided small animal irradiator and Monte Carlo‐based treatment planning system to facilitate an in vivo investigation of the radioprotective effect of hypothermia for late rectal toxicity following a single large dose of radiation.
To compare the single-fraction dose-related incidence of rectal obstruction and/or bleeding in normothermic and hypothermic rectums of a rat model.
A 1.9-cm length of rectum was irradiated with a ...single fraction in 57 Sprague-Dawley rats using a dedicated image-guided small animal irradiator and Monte Carlo-based treatment planning system. All rats had a rectal temperature control apparatus placed during irradiation and were stratified to achieve either a normothermic (37°C) or hypothermic (15°C) rectal wall temperature. Radiation was delivered to a 1-cm-diameter cylindrical volume about the cooling device and rectal wall. The radiation dose was escalated from 16 Gy up to 37 Gy to assess the dose response in each arm. The primary endpoint of this study was rectal obstruction and/or bleeding during a follow-up of 180 to 186 days. Histologic scoring was performed on all study rats.
Probit analysis showed a dose associated with a 50% incidence of rectal obstruction of 24.6 Gy and 40.8 Gy for normothermic and hypothermic arms, respectively. The occurrence of obstruction and/or bleeding correlated with the posttreatment histologic score for normothermic rats; however, there was no difference in histologic score between normothermic and hypothermic rats at the highest dose levels evaluated.
A significant radioprotective effect was observed using local hypothermia during a single large dose of radiation for the functional endpoint of rectal obstruction and/or bleeding. A confirmatory study in a large animal model with anatomic and physiologic similarities to humans is suggested.
To determine risk factors for fistula formation after interstitial brachytherapy (ISBT) in patients with advanced gynecologic cancers.
We performed an Institutional Review Board (IRB) approved ...retrospective review of 44 patients treated with transperineal template-based ISBT from 2011 to 2017 at a major metropolitan county and university health system. All patients were treated with image-guided high-dose-rate ISBT. Statistical analysis was performed using the χ
test to identify factors correlated with fistula formation. Survival and tumor control outcomes were calculated using Kaplan Meier analyses.
Patients had a mean age of 53 years (range, 28-81 years), a mean external beam dose of 43.1 Gy (range, 42.5-51.3 Gy), and a mean brachytherapy dose of 22.8 Gy (range, 21.3-30 Gy). Two of 44 patients had fistulas that could be definitively attributed to therapy for a fistula rate of 4.5%. Six additional patients (13.6%) developed fistula after treatment with associated recurrent disease but were included in the causality analysis. We analyzed patient tumor and treatment factors, and on univariate analyses we found that age ≥ 60 years, Hispanic ethnicity, bladder involvement, rectal D2 cc ≥ 70 Gy, and whether patients had post-radiation biopsies were predictors for fistula formation. The 1-year overall survival (OS), progression-free survival (PFS), and local control (LC) were 85%, 58.5%, and 76.9%, respectively, with a mean follow-up time 23 months (range, 4.0-68.8 months).
We identified factors that predict fistula formation in patients with advanced gynecologic tumors treated with ISBT. These factors can be used to stratify patients into a high-risk group, with potential for modification of brachytherapy planning to reduce their risk of fistula formation.
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•Auto-segmented contours generally provided sufficient nodal coverage.•Avoid auto-segmentation in all-fraction adaptation, later fractions, and larger nodes.•Rigid propagation and ...manual review recommended as second nodal contour checks.
Online cone-beam-based adaptive radiotherapy (ART) adjusts for anatomical changes during external beam radiotherapy. However, limited cone-beam image quality complicates nodal contouring. Despite this challenge, artificial-intelligence guided deformation (AID) can auto-generate nodal contours. Our study investigated the optimal use of such contours in cervical online cone-beam-based ART.
From 136 adaptive fractions across 21 cervical cancer patients with nodal disease, we extracted 649 clinically-delivered and AID clinical target volume (CTV) lymph node boost structures. We assessed geometric alignment between AID and clinical CTVs via dice similarity coefficient, and 95% Hausdorff distance, and geometric coverage of clinical CTVs by AID planning target volumes by false positive dice. Coverage of clinical CTVs by AID contour-based plans was evaluated using D100, D95, V100%, and V95%.
Between AID and clinical CTVs, the median dice similarity coefficient was 0.66 and the median 95 % Hausdorff distance was 4.0 mm. The median false positive dice of clinical CTV coverage by AID planning target volumes was 0. The median D100 was 1.00, the median D95 was 1.01, the median V100% was 1.00, and the median V95% was 1.00. Increased nodal volume, fraction number, and daily adaptation were associated with reduced clinical CTV coverage by AID-based plans.
In one of the first reports on pelvic nodal ART, AID-based plans could adequately cover nodal targets. However, physician review is required due to performance variation. Greater attention is needed for larger, daily-adapted nodes further into treatment.
Purpose
Radiosurgery is an established technique to treat cerebral arteriovenous malformations (AVMs). Obliteration of larger AVMs (> 10–15 cm3 or diameter > 3 cm) in a single session is challenging ...with current radiosurgery platforms due to toxicity. We present a novel technique of multistage stereotactic radiosurgery (SRS) for large intracranial arteriovenous malformations (AVM) using the Gamma Knife system.
Materials/Methods
Eighteen patients with large (> 10–15 cm3 or diameter > 3 cm) AVMs, which were previously treated using a staged SRS technique on the Cyberknife platform, were retrospectively selected for this study. The AVMs were contoured and divided into 3–8 subtargets to be treated sequentially in a staged approach at half to 4 week intervals. The prescription dose ranged from 15 Gy to 20 Gy, depending on the subtarget number, volume, and location. Gamma Knife plans using multiple collimator settings were generated and optimized. The coordinates of each shot from the initial plan covering the total AVM target were extracted based on their relative positions within the frame system. The shots were regrouped based on their location with respect to the subtarget contours to generate subplans for each stage. The delivery time of each shot for a subtarget was decay corrected with 60Co for staging the treatment course to generate the same dose distribution as that planned for the total AVM target. Conformality indices and dose–volume analysis were performed to evaluate treatment plans.
Results
With the shot redistribution technique, the composite dose for the multistaged treatment of multiple subtargets is equivalent to the initial plan for total AVM target. Gamma Knife plans resulted in an average PTV coverage of 96.3 ± 0.9% and a PITV of 1.23 ± 0.1. The resulting Conformality indices, V12Gy and R50 dose spillage values were 0.76 ± 0.05, 3.4 ± 1.8, and 3.1 ± 0.5 respectively.
Conclusion
The Gamma Knife system can deliver a multistaged conformal dose to treat large AVMs when correcting for translational setup errors of each shot at each staged treatment.
Most diagnosed early stage breast cancer cases are treated by lumpectomy and adjuvant radiation therapy, which significantly decreases the locoregional recurrence but causes inevitable toxicity to ...normal tissue. By using a technique of preparing liposomes carrying technetium-99m (99mTc), rhenium-186 (186Re), or rhenium-188 (188Re) radionuclides, as well as chemotherapeutic agents, or their combination, for cancer therapy with real time image-monitoring of pharmacokinetics and prediction of therapy effect, this study investigated the potential of a novel targeted focal radiotherapy with low systemic toxicity using radioactive immunoliposomes to treat both the surgical cavity and draining lymph nodes in a rat breast cancer xenograft positive surgical margin model. Immunoliposomes modified with either panitumumab (anti-EGFR) or bevacizumab (anti-VEGF) were remote loaded with 99mTc diagnostic radionuclide, and injected into the surgical cavity of female nude rats with positive margins postlumpectomy. Locoregional retention and systemic distribution of 99mTc-immunoliposomes were investigated by nuclear imaging, stereofluorescent microscopic imaging, and gamma counting. Histopathological examination of excised draining lymph nodes was performed. The locoregional retention of 99mTc-immunoliposomes in each animal was influenced by the physiological characteristics of the surgical site of individual animals. Panitumumab- and bevacizumab-liposome groups had higher intracavitary retention compared with the control liposome groups. Draining lymph node uptake was influenced by both the intracavitary radioactivity retention level and metastasis status. The panitumumab-liposome group had higher accumulation on the residual tumor surface and in the metastatic lymph nodes. Radioactive liposomes that were cleared from the cavity were metabolized quickly and accumulated at low levels in vital organs. Therapeutic radionuclide-carrying specifically targeted panitumumab- and bevacizumab-liposomes have increased potential compared to non-antibody targeted liposomes for postlumpectomy focal therapy to eradicate remaining breast cancer cells inside the cavity and draining lymph nodes with low systemic toxicity.
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