Background:
While the role of stereotactic radiotherapy for brain metastases is increasing, evidence on the comparative efficacy and safety of fractionated stereotactic radiotherapy (FSRT) and ...single-session radiosurgery (SRS) is scarce.
Methods:
Longitudinal volumetric analysis was performed in a consecutive cohort of 120 patients and 190 brain metastases (>0.065 cm
3
in volume / > ~5 mm in diameter) treated exclusively with FSRT (
n
= 98) and SRS (
n
= 92), respectively. A total of 972 tumor segmentations was used, averaging 5.1 time points per metastasis. Progression was defined using a volumetric extension of the RANO-BM criteria. Local control and radionecrosis were compared for lesions treated with FSRT and SRS, respectively.
Results:
Metastases treated with FSRT were significantly larger at baseline (mean, 4.66 vs. 0.40 cm
3
,
p
< 0.001). Biologically effective dose (BED) for metastases (α/β = 12, linear-quadratic-cubic model) was significantly associated with local control, whereas BED for normal brain (α/β = 2, linear-quadratic model) was significantly associated with radionecrosis. Median time to local progression was 22.9 months in the FSRT group compared to 14.5 months in the SRS group (
p
= 0.022). Overall radionecrosis rate at 12 months was 3.4% for FSRT and 14.8% for SRS (
p
= 0.010). Radionecrosis °IV requiring resection with histologic proof of radiation necrosis also was significantly reduced in the FSRT group (FSRT 0.0% vs. SRS 3.9%,
p
= 0.041). In multivariate analysis, FSRT was associated with reduced risk of progression (HR 0.47,
p
= 0.015) and reduced risk of radionecrosis (HR 0.18,
p
= 0.045).
Conclusions:
This volumetric study provides initial evidence that the improvements in therapeutic ratio expected for FSRT in larger brain metastases, might equally extend into the domain of smaller metastases, traditionally less considered for fractionated treatment. FSRT might constitute an important tool to further increase local control and reduce radionecrosis risk in stereotactic radiotherapy for brain metastases, that should be assessed in randomized intervention trials.
Purpose
The potential of large language models in medicine for education and decision-making purposes has been demonstrated as they have achieved decent scores on medical exams such as the United ...States Medical Licensing Exam (USMLE) and the MedQA exam. This work aims to evaluate the performance of ChatGPT-4 in the specialized field of radiation oncology.
Methods
The 38th American College of Radiology (ACR) radiation oncology in-training (TXIT) exam and the 2022 Red Journal Gray Zone cases are used to benchmark the performance of ChatGPT-4. The TXIT exam contains 300 questions covering various topics of radiation oncology. The 2022 Gray Zone collection contains 15 complex clinical cases.
Results
For the TXIT exam, ChatGPT-3.5 and ChatGPT-4 have achieved the scores of 62.05% and 78.77%, respectively, highlighting the advantage of the latest ChatGPT-4 model. Based on the TXIT exam, ChatGPT-4’s strong and weak areas in radiation oncology are identified to some extent. Specifically, ChatGPT-4 demonstrates better knowledge of statistics, CNS & eye, pediatrics, biology, and physics than knowledge of bone & soft tissue and gynecology, as per the ACR knowledge domain. Regarding clinical care paths, ChatGPT-4 performs better in diagnosis, prognosis, and toxicity than brachytherapy and dosimetry. It lacks proficiency in in-depth details of clinical trials. For the Gray Zone cases, ChatGPT-4 is able to suggest a personalized treatment approach to each case with high correctness and comprehensiveness. Importantly, it provides novel treatment aspects for many cases, which are not suggested by any human experts.
Conclusion
Both evaluations demonstrate the potential of ChatGPT-4 in medical education for the general public and cancer patients, as well as the potential to aid clinical decision-making, while acknowledging its limitations in certain domains. Owing to the risk of hallucinations, it is essential to verify the content generated by models such as ChatGPT for accuracy.
While the treatment of squamous cell carcinoma of the head and neck (HNSCC) with radiotherapy (RT) is complemented more and more by immunotherapy in clinical trials, little is known about the impact ...of the human papillomavirus (HPV) status or the applied RT scheme on the immune phenotype of the tumor cells. Therefore, we aimed to examine the impact of the HPV status of four human HNSCC cell lines on cell death and the expression of immune checkpoint molecules (ICMs) after RT with either hypofractionation irradiation (5x3.0Gy) or a high single dose (1x19.3Gy) via multicolor flow cytometry and quantitative PCR at an early time point after therapy. In our study, 5x3.0Gy RT induced high numbers of early and late apoptotic cells independent of the HPV status, but necrosis was only increased in the HPV-positive UM-Scc-47 cells. Generally, the immune stimulatory ICMs (CD70, CD137-L, ICOS-L) were less affected by RT compared to the immune suppressive ones (PD-L1, PD-L2, and the herpesvirus entry mediator (HVEM)). A significant higher surface expression of the analyzed ICMs was found after hypofractionated RT compared to a single high dose; however, regardless of the HPV status, with the exception of ICOS-L. Here, HPV-positive HNSCC tumor cells showed a stronger response to 5x3.0Gy than HPV-negative ones. On the RNA level, only minor alterations of ICMs were observed following RT, with the exception of the HPV negative cell line CAL33 treated with 5x3.0Gy, where PD-L2, HVEM and CD70 were significantly increased. We conclude that the HPV status may not distinctly predict immunological responses following RT, and thus cannot be used as a single predictive marker for therapy responses in HNSCC. In contrast, the patient-specific individual expression of ICMs following RT is preferable for the targeted patient selection for immune therapy directed against distinct ICM.
Low-dose radiation therapy (LDRT) has been successfully established for decades as an alternative analgesic treatment option for patients suffering from chronic degenerative and inflammatory ...diseases. In this study, 483 patients were undergoing LDRT for degenerative joint disease of the fingers and thumb at the University Hospital Erlangen between 2004 and 2019. Radiotherapy was applied according to the German guidelines for LDRT. Several impact factors on therapeutic success, such as the age and gender, the number of affected fingers, the single and cumulative dose, as well as the number of series, were investigated. In summary, 70% of the patients showed an improvement of their pain following LDRT. No significant impact was found for the factors age, gender, the number of series or the cumulative dosage. Patients with an involvement of the thumb showed a significantly worse outcome compared to patients with an isolated affection of the fingers. In this cohort, patients receiving a single dose of 0.5 Gy reported a significantly better outcome than patients receiving 1.0 Gy, strongly suggesting a reduction in the total dose. In summary, LDRT is a good alternative treatment option for patients suffering from degenerative and inflammatory joint disease of the fingers.
Improvements of heat-delivery systems have led to hyperthermia (HT) being increasingly recognized as an adjunct treatment modality also for brain tumors. But how HT affects the immune phenotype of ...glioblastoma cells is only scarcely known.
We therefore investigated the effect of in vitro HT, radiotherapy (RT), and the combination of both (RHT) on cell death modalities, immune checkpoint molecule (ICM) expression and release of the danger signal HSP70 of two human glioblastoma cell lines (U87 and U251) by using multicolor flow cytometry and ELISA. Hyperthermia was performed once or twice for 60-minute sessions reaching temperatures of 39 °C, 41 °C, and 44 °C, respectively. RT was administered with 5 x 2 Gy.
A hyperthermia chamber for cell culture t-flasks regulating the temperature via a contact sensor was developed. While the glioblastoma cells were rather radioresistant, particularly in U251 cells, the combination of RT with HT significantly increased the percentage of apoptotic and necrotic cells for all temperatures examined and for both, single and double HT application. In line with that, an increased release of HSP 70 was seen only in U251 cells, mainly following treatment with HT at temperatures of 44 °C alone or in combination with RT. In contrast, immune suppressive (PD-L1, PD-L2, HVEM) and immune stimulatory (ICOS-L, CD137-L and Ox40-L) ICMs were significantly increased mostly on U87 cells, and particularly after RHT with 41 °C.
Individual assessment of the glioblastoma immune cell phenotype with regard to the planned treatment is mandatory to optimize multimodal radio-immunotherapy protocols including HT.
The treatment of chronic inflammatory and degenerative diseases by low dose radiation therapy (LDRT) is promising especially for patients who were refractory for classical therapies. LDRT aims to ...reduce pain of patients and to increase their mobility. Although LDRT has been applied since the late 19th century, the immunological mechanisms remain elusive. Within the prospective IMMO-LDRT01 trial (NCT02653079) the effects of LDRT on the peripheral blood immune status, as well as on pain and life quality of patients have been analyzed. Blood is taken before and after every serial irradiation with a single dose per fraction of 0.5Gy, as well as during follow-up appointments in order to determine a detailed longitudinal immune status by multicolor flow cytometry. Here, we report the results of an interim analysis of 125 patients, representing half the number of patients to be recruited. LDRT significantly improved patients' pain levels and induced distinct systemic immune modulations. While the total number of leukocytes remained unchanged in the peripheral blood, LDRT induced a slight reduction of eosinophils, basophils and plasmacytoid dendritic cells and an increase of B cells. Furthermore, activated immune cells were decreased following LDRT. Especially cells of the monocytic lineage correlated to LDRT-induced improvements of clinical symptoms, qualifying these immune cells as predictive biomarkers for the therapeutic success. We conclude that LDRT improves pain of the patients by inducing systemic immune modulations and that immune biomarkers could be defined for prediction by improved patient stratification in the future.
Deep learning-based head and neck lymph node level (HN_LNL) autodelineation is of high relevance to radiotherapy research and clinical treatment planning but still underinvestigated in academic ...literature. In particular, there is no publicly available open-source solution for large-scale autosegmentation of HN_LNL in the research setting.
An expert-delineated cohort of 35 planning CTs was used for training of an nnU-net 3D-fullres/2D-ensemble model for autosegmentation of 20 different HN_LNL. A second cohort acquired at the same institution later in time served as the test set (n = 20). In a completely blinded evaluation, 3 clinical experts rated the quality of deep learning autosegmentations in a head-to-head comparison with expert-created contours. For a subgroup of 10 cases, intraobserver variability was compared to the average deep learning autosegmentation accuracy on the original and recontoured set of expert segmentations. A postprocessing step to adjust craniocaudal boundaries of level autosegmentations to the CT slice plane was introduced and the effect of autocontour consistency with CT slice plane orientation on geometric accuracy and expert rating was investigated.
Blinded expert ratings for deep learning segmentations and expert-created contours were not significantly different. Deep learning segmentations with slice plane adjustment were rated numerically higher (mean, 81.0 vs. 79.6, p = 0.185) and deep learning segmentations without slice plane adjustment were rated numerically lower (77.2 vs. 79.6, p = 0.167) than manually drawn contours. In a head-to-head comparison, deep learning segmentations with CT slice plane adjustment were rated significantly better than deep learning contours without slice plane adjustment (81.0 vs. 77.2, p = 0.004). Geometric accuracy of deep learning segmentations was not different from intraobserver variability (mean Dice per level, 0.76 vs. 0.77, p = 0.307). Clinical significance of contour consistency with CT slice plane orientation was not represented by geometric accuracy metrics (volumetric Dice, 0.78 vs. 0.78, p = 0.703).
We show that a nnU-net 3D-fullres/2D-ensemble model can be used for highly accurate autodelineation of HN_LNL using only a limited training dataset that is ideally suited for large-scale standardized autodelineation of HN_LNL in the research setting. Geometric accuracy metrics are only an imperfect surrogate for blinded expert rating.
Total Skin Electron Irradiation (TSEI) is a method for treating malignant cutaneous T-cell lymphomas. This work aims to implement and optimize the total skin technique established at Strahlenklinik ...Erlangen, Germany on two new linear accelerators and to quantify the risks using failure mode and effects (FMEA) analysis.
TSEI is performed at a VersaHD accelerator (Elekta, Stockholm) with 6MeV in the “high dose rate mode” HDRE and a nominal field size of 40×40cm2. To reach the entire skin surface, the patients perform 6 different body positions at a distance of 330cm behind an acrylic scatter plate, with two overlapping irradiation fields being radiated at 2 gantry angles per position. The irradiation technique was commissioned according to the recommendation of AAPM report 23. With the help of a reference profile at 270°, 2 gantry angles were calculated, which in total resulted in an optimal dose distribution. This was metrologically verified with ion-chamber measurements in the patient's longitudinal axis. The influence of the shape of the acrylic scatter plate and the distance between the acrylic scatter plate and patient was determined by measurements. The dose homogeneity was verified using an anthropomorphic disc phantom equipped with GafChromic films. The workflows and failure modes of the total skin technique were described in a process map and subsequently quantified with a FMEA analysis.
An optimal dose distribution is achieved at a distance of SSD=330cm, using the gantry angles 289° and 251°. The previously used segmented acrylic scatter plate was replaced by a flat plate (200×120×0.5cm3), which is placed at a distance of 50cm in front of the patient. The densitometric evaluation of the GafChromic films in the anthropomorphic disc phantom revealed an expected dose distribution of 3Gy at a depth of up to 1.5cm below the skin surface, with a homogeneity of ±10% over the phantom's longitudinal axis. By FMEA a maximum risk priority number of 30 was determined.
Based on the calculations and measurements performed on the new accelerators as well as the risk analysis, we concluded that total skin therapy can be implemented clinically.
Purpose
To share our experiences in implementing a dedicated magnetic resonance (MR) scanner for radiotherapy (RT) treatment planning using a novel coil setup for brain imaging in treatment position ...as well as to present developed core protocols with sequences specifically tuned for brain and prostate RT treatment planning.
Materials and methods
Our novel setup consists of two large 18-channel flexible coils and a specifically designed wooden mask holder mounted on a flat tabletop overlay, which allows patients to be measured in treatment position with mask immobilization. The signal-to-noise ratio (SNR) of this setup was compared to the vendor-provided flexible coil RT setup and the standard setup for diagnostic radiology. The occurrence of motion artifacts was quantified. To develop magnetic resonance imaging (MRI) protocols, we formulated site- and disease-specific clinical objectives.
Results
Our novel setup showed mean SNR of 163 ± 28 anteriorly, 104 ± 23 centrally, and 78 ± 14 posteriorly compared to 84 ± 8 and 102 ± 22 anteriorly, 68 ± 6 and 95 ± 20 centrally, and 56 ± 7 and 119 ± 23 posteriorly for the vendor-provided and diagnostic setup, respectively. All differences were significant (
p
> 0.05). Image quality of our novel setup was judged suitable for contouring by expert-based assessment. Motion artifacts were found in 8/60 patients in the diagnostic setup, whereas none were found for patients in the RT setup. Site-specific core protocols were designed to minimize distortions while optimizing tissue contrast and 3D resolution according to indication-specific objectives.
Conclusion
We present a novel setup for high-quality imaging in treatment position that allows use of several immobilization systems enabling MR-only workflows, which could reduce unnecessary dose and registration inaccuracies.
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