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This study evaluated segmentation accuracy, efficiency, and radiomic feature stability for manual (MD), artificial intelligence-based (AI), and hybrid (MD + AI) contouring of pelvic organs on planning CT (pCT) and HyperSight cone-beam CT (hCBCT) for adaptive radiotherapy. Dice similarity and 95th percentile Hausdorff distance (HD95) quantified segmentation agreement, while radiomic feature stability was assessed using the concordance correlation coefficient (CCC). Agreement between segmentation approaches was highest for bladder and femora (median Dice 0.95–0.96; HD95 1.88–2.17 mm), intermediate for prostate and rectum (median Dice 0.92; HD95 2.22–2.62 mm), and lowest for seminal vesicles and penile bulb (median Dice 0.76–0.83; HD95 3.01–3.41 mm). AI and MD + AI reduced contouring times by about 90% and 60% compared to MD. Radiomic feature stability differed significantly between segmentation modes (all p adj ≤ 0.05). GLRLM features exhibited significantly higher stability than other features, whereas morphological features showed lower stability. Median radiomic feature stability was highest for bladder and femora, and intermediate for prostate and rectum. In conclusion, AI-based and hybrid contouring achieved high accuracy and substantial time savings, while texture- and intensity-based radiomic features showed robustness with AI segmentation. This study demonstrated feasibility of extracting distinct, reliable quantitative parameters based on AI-only contouring of pelvic structures.

CT-guided adaptive radiotherapy (aRT) based on HyperSight TM -CBCT provides high-quality imaging, allowing quantitative radiomic feature analysis as a monitoring tool. This study comprehensively evaluates the stability of radiomic features, as potential imaging biomarkers, in pelvic structures of prostate cancer patients treated with adaptive stereotactic body radiation therapy (SBRT). Between December 2023 and July 2024, 32 patients with localized prostate cancer underwent adaptive SBRT at the Ethos ® linear accelerator (Varian, Siemens Healthineers) with HyperSight-CBCT imaging. Longitudinal stability was assessed by intraclass correlation coefficient (ICC) over five fractions of aRT for target structures and non-hollow organs at risk. In pooled organs at risk, 93.0% of features showed very high stability (ICC > 0.9) compared to 67.4% in pooled target structures, indicating significantly lower stability for target structures ( p  = 0.00009129). Second-order features demonstrated greater stability than conventional and shape-based features ( p  = 0.0433, p  = 0.0252). Fraction number significantly affected longitudinal prostate feature variability ( p  = 0.0135). This study comprehensively analyzed HyperSight-CBCT imaging to evaluate longitudinal stability of radiomic features during adaptive SBRT for prostate cancer. The trends observed will provide a framework for future CT-guided aRT studies, facilitating quantitative imaging analysis of radiological biomarkers for clinical translation and improving personalized treatment.

Background Although glioblastoma (GB) is associated with a devastating prognosis, a small proportion of patients achieve long-term survival rates. We herein present a matched-pair analysis of molecular factors found in long- and short-term survivors (LTS, STS). Methods We performed a cross-institutional analysis of 262 patient records and matched a group of 91 LTS (≥ 3 years) with two groups of STS (STS-1, n = 91; STS-2, n = 80). Matching was performed according to age, Karnofsky Performance Status, initial therapy and adjuvant therapy. Molecular factors were compared between LTS (total of 91 patients) v. STS-1, and LTS (subgroup of 80 patients) v. STS-2. We included glial fibrillary acidic protein (GFAP), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase 1 (IDH-1); furthermore, the proliferation index was analyzed (Ki-67/MIB-1). Results IDH-1 and decreased Ki-67 were numerically associated with LTS but the difference was only significant compared to STS-1 (n.s. v. STS-2). LTS was associated with MGMT promoter hypermethylation ( p  = 0.013 and p  = 0.022) and GFAP expression ( p  < 0.001 and p  = 0.001). Positivity for both factors combined compared to negativity for one factor occurred more often in the LTS group ( p  = 0.002 and p  = 0.006); negativity for both factors combined did not occur in the LTS group. Conclusion In this retrospective analysis, GFAP expression and MGMT promoter methylation were associated with LTS. Given the hypothesis-generating nature of our study, these observations should be confirmed in prospective clinical trials.

Background Daily adaptive radiation therapy (ART) of patients with non-small cell lung cancer (NSCLC) lowers organs at risk exposure while maintaining the planning target volume (PTV) coverage. Thus, ART allows an isotoxic approach with increased doses to the PTV that could improve local tumor control. Herein we evaluate daily online ART strategies regarding their impact on relevant dose-volume metrics. Methods Daily cone-beam CTs (1 × n = 28, 1 × n = 29, 11 × n = 30) of 13 stage III NSCLC patients were converted into synthetic CTs (sCTs). Treatment plans (TPs) were created retrospectively on the first-fraction sCTs (sCT 1 ) and subsequently transferred unaltered to the sCTs of the remaining fractions of each patient (sCT 2−n ) (IGRT scenario). Two additional TPs were generated on sCT 2−n : one minimizing the lung-dose while preserving the D 95% (PTV) (isoeffective scenario), the other escalating the D 95% (PTV) with a constant V 20Gy (lung ipsilateral ) (isotoxic scenario). Results Compared to the original TPs predicted dose, the median D 95% (PTV) in the IGRT scenario decreased by 1.6 Gy ± 4.2 Gy while the V 20Gy (lung ipsilateral ) increased in median by 1.1% ± 4.4%. The isoeffective scenario preserved the PTV coverage and reduced the median V 20Gy (lung ipsilateral ) by 3.1% ± 3.6%. Furthermore, the median V 5% (heart) decreased by 2.9% ± 6.4%. With an isotoxic prescription, a median dose-escalation to the gross target volume of 10.0 Gy ± 8.1 Gy without increasing the V 20Gy (lung ipsilateral ) and V 5% (heart) was feasible. Conclusions We demonstrated that even without reducing safety margins, ART can reduce lung-doses, while still reaching adequate target coverage or escalate target doses without increasing ipsilateral lung exposure. Clinical benefits by means of toxicity and local control of both strategies should be evaluated in prospective clinical trials.

Background This study examined the longitudinal changes in metabolic liver function and MR-morphological dilatation of intrahepatic bile ducts in patients with stereotactic body radiation therapy (SBRT) for liver metastases. Methods This retrospective study included 64 patients with SBRT of 84 liver metastases between February 2005 and January 2019. To evaluate hepatobiliary toxicity, the laboratory parameters albumin, alanine-transaminase (ALAT), aspartate-transaminase (ASAT), bilirubin and gamma-glutamyltransferase (GGT) and the qualitative dilatation of MR-morphological peritumoural, intrahepatic bile ducts were analyzed from pre- up to 12 months post-SBRT. Results The liver metastases were irradiated with a median D50 to the GTV of BED α/β=10 Gy = 134 Gy (range 51–219 Gy) resulting in a median mean dose D mean -L-EQD2 α/β=3 Gy = 11.8 Gy (range 0.4–65.6 Gy) to the total liver. The central hepatobiliary tract (cHBT) was exposed to a median D mean -cHBT-BED α/β=10 Gy = 8.3 Gy (range 0.1–81.6 Gy). Significant decreases in albumin and increases in GGT and bilirubin were observed up to 12 months post-SBRT. D mean -L-EQD2 α/β=3 Gy , D mean -cHBT-BED α/β=10 Gy and VBED α/β=10Gy 66Gy-cHBT and VBED α/β=10Gy 72Gy-cHBT were significant cofactors influencing the course of GGT, ASAT and bilirubin, but not for albumin and ALAT. MR-morphological, short- and long-term dilatation of peritumoural bile ducts were associated with significant higher VBED α/β=10Gy 66Gy-cHBT and VBED α/β=10Gy 72Gy-cHBT values and were significantly more frequent for SBRT of target volumes with < 3 cm distance to the cHBT. Conclusion SBRT of liver metastases was associated with minor alterations in metabolic liver function. High dose exposure and proximity of the liver metastases to the cHBT may lead to locoregional bile duct dilatation after SBRT. Further evaluation of metabolic and MR-morphological changes in liver function is recommended in personalised oncological treatment approaches for liver-directed therapies.

Background Cone-beam computed tomography (CBCT)-based adaptive radiotherapy (ART) at the Ethos ® linear accelerator (eLinac) allows for daily anatomical and dosimetric adjustments and relies on robust image quality. This study evaluated the longitudinal image quality of the novel HyperSight TM -CBCT (hCBCT) compared to planning CT (pCT), using phantoms and data of prostate cancer patients undergoing adaptive stereotactic body radiotherapy (SBRT). Building on this, the longitudinal contour sharpness of the organs in fractional hCBCT and their usability for ART workflow across fractions was evaluated. Methods Between December 2023 and May 2024, 26 prostate cancer patients receiving ART at the eLinac with hCBCT technology were enrolled. Phantom studies assessed pCT and hCBCT image quality. Patient based analyses of all 156 imaging scans (pCT and each of the fractional hCBCT) analyzed, longitudinally examined firstly image quality, secondly contour sharpness of prostate, seminal vesicles, and rectal wall, and thirdly confidence to delineate the structures for the ART workflow. Time required for the ART based parameters were recorded. Quantitative metrics included CT number changes in the fat adjacent to the prostate and seminal vesicles. Friedman’s test with Bonferroni correction, Spearman and Intraclass Correlation Coefficient (ICC) were used for statistics. Results hCBCT scans showed robust image quality parameters in the phantom and patient based analysis across fractions. Inter-observer agreement was moderate, with lower rating score for resident compared to the experienced radiation oncologist ( p  < 0.001). Patient based analysis showed no significant differences of the contour sharpness of the prostate and seminal vesicles between pCT and initial hCBCT scan, but contour sharpness ratings declined across treatment fractions. Confidence for the delineation of prostate and seminal vesicles during ART was significantly decreased at later fractions (each p adj <0.05) and this correlated significantly with longer assessment times (p adj ≤0.05). The CT attenuation of the fat tissue adjacent to the prostate and seminal vesicles significantly increased across the fractions (p adj <0.05). Conclusions High-quality imaging for adaptive SBRT in prostate cancer is provided by hCBCT, which offers equivalent tissue visualization compared to pCT. Fraction-dependent decreases in contour sharpness can be detected using longitudinal hCBCT imaging. These decreases are likely related to treatment-induced tissue changes and may impact ART workflow. The rating of the observed effects may potentially be influenced by the observer’s experience.

Background Patient-reported health-related quality of life (HRQOL) differs between treatment options for prostate carcinoma. Long-term HRQOL data in brachytherapy series are scarce. Therefore, we analyzed prostate-specific and general HRQOL in patients treated with brachytherapy for prostate carcinoma after long-term follow-up. Methods Two hundred ninety-six patients with prostate carcinoma were treated with brachytherapy (01/1998–11/2003). General and prostate-specific HRQOL were measured using EORTC-QLQ-C30 and EORTC-QLQ-PR25, respectively. Patients were asked to complete the questionnaires after a median follow-up of 141 (119–181) months. QLQ-C30 results were compared to the German reference population. QLQ-PR25 results were compared to an earlier follow-up after a median of 51 months (no published QLQ-PR25 reference population for comparison). Additionally, a literature review on HRQOL data in brachytherapy series was performed. Results One hundred six (35.8%) patients were lost to follow-up, 70 (23.6%) had died. 120 (40.5%) patients were contacted. 80 questionnaires were returned (27% of the original cohort; 91% of alive patients were ≥70 years). Sexual activity declined over time (mean scores: 40.5 vs. 45.5; p  = 0.006), hormonal treatment-related symptoms, problems associated with incontinence aids, and burden of obstructive urinary symptoms did not differ significantly compared to the 51-month follow-up. General HRQOL was numerically better in our cohort as compared to the German reference population (> 16% relative difference for both age strata; < 70 and ≥70 years). Conclusions Our results indicate that symptom-burden after long-term follow-up and associated prostate-specific HRQOL remains relatively stable from 51 to 141 months. General HRQOL in surviving patients was numerically better compared to the reference population.

Cancer is a complex disease process that evolves as a consequence of multiple malfunctions in key regulatory molecular networks. Understanding these networks will be essential to combat cancer. In this study, we focussed on central players in such networks. In a series of colon and breast cancer cell lines, we found that CD24 activates Src, and induces the activation of c-Jun and expression of c-Jun and c-Fos. Thereby CD24 increases the promoter activity and expression of miR-21, which in turn suppresses expression of Pdcd4 and PTEN. Co-transfection of a CD24 expression construct and an siRNA that silences Src showed that CD24-dependent upregulation of miR-21 is mediated by Src. Additionally, we found that miR-34a post-transcriptionally downregulates CD24 and Src expression, leading to the deactivation of c-Jun, reduced expression of c-Jun and c-Fos, inhibition of miR-21, and upregulation of Pdcd4 and PTEN. Furthermore, miR-34a-mediated inhibition of Src expression reduced migration and invasion of colorectal cancer cells. Resected tumor tissues from 26 colorectal patients showed significantly lower expression of Pdcd4 and miR-34a, and higher expression of CD24, Src and miR-21 compared to the corresponding normal tissues. Moreover, CD24 positively correlated with the amount of Src protein in tumor tissues, and a trend towards an inverse correlation between miR-34a and Src protein levels was also observed. Our results reveal essential players in the complex networks that regulate the progression of solid tumors such as colorectal cancer. These findings therefore identify novel therapeutic approaches for combating tumor growth and progression.

Background Postoperative/adjuvant radiotherapy of advanced gastric cancer involves a large planning target volume (PTV) with multi-concave shapes which presents a challenge for volumetric modulated arc therapy (VMAT) planning. This study investigates the advantages of automated VMAT planning for this site compared to manual VMAT planning by expert planners. Methods For 20 gastric cancer patients in the postoperative/adjuvant setting, dual-arc VMAT plans were generated using fully automated multi-criterial treatment planning (autoVMAT), and compared to manually generated VMAT plans (manVMAT). Both automated and manual plans were created to deliver a median dose of 45 Gy to the PTV using identical planning and segmentation parameters. Plans were evaluated by two expert radiation oncologists for clinical acceptability. AutoVMAT and manVMAT plans were also compared based on dose-volume histogram (DVH) and predicted normal tissue complication probability (NTCP) analysis. Results Both manVMAT and autoVMAT plans were considered clinically acceptable. Target coverage was similar (manVMAT: 96.6 ± 1.6%, autoVMAT: 97.4 ± 1.0%, p  = 0.085). With autoVMAT, median kidney dose was reduced on average by > 25%; (for left kidney from 11.3 ± 2.1 Gy to 8.9 ± 3.5 Gy ( p  = 0.002); for right kidney from 9.2 ± 2.2 Gy to 6.1 ± 1.3 Gy ( p  <  0.001)). Median dose to the liver was lower as well (18.8 ± 2.3 Gy vs. 17.1 ± 3.6 Gy, p  = 0.048). In addition, Dmax of the spinal cord was significantly reduced (38.3 ± 3.7 Gy vs. 31.6 ± 2.6 Gy, p  <  0.001). Substantial improvements in dose conformity and integral dose were achieved with autoVMAT plans (4.2% and 9.1%, respectively; p  <  0.001). Due to the better OAR sparing in the autoVMAT plans compared to manVMAT plans, the predicted NTCPs for the left and right kidney and the liver-PTV were significantly reduced by 11.3%, 12.8%, 7%, respectively ( p  ≤ 0.001). Delivery time and total number of monitor units were increased in autoVMAT plans (from 168 ± 19 s to 207 ± 26 s, p  = 0.006) and (from 781 ± 168 MU to 1001 ± 134 MU, p  = 0.003), respectively. Conclusions For postoperative/adjuvant radiotherapy of advanced gastric cancer, involving a complex target shape, automated VMAT planning is feasible and can substantially reduce the dose to the kidneys and the liver, without compromising the target dose delivery.

Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT). This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent ([less than or equai to]30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS. One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0-40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03). The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.