Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Long-term survival in patients with brain metastases-clinical characterization of a rare scenario.

PURPOSE: This study aimed to assess clinical, treatment, and prognostic features in patients with brain metastases (BM) from solid tumors achieving long-term survival (LTS). Further, the accuracy of diagnosis-specific Graded Prognostic Assessment scores (ds-GPA) to predict LTS was evaluated. METHODS: Patients admitted for radiotherapy of BM between 2010 and 2020 at a large tertiary cancer center with survival of at least 3 years from diagnosis of BM were included. Patient, tumor, treatment characteristics and ds-GPA were compiled retrospectively. RESULTS: From a total of 1248 patients with BM, 61 (4.9%) survived ≥ 3 years. In 40 patients, detailed patient charts were available. Among LTS patients, median survival time from diagnosis of BM was 51.5 months. Most frequent primary tumors were lung cancer (45%), melanoma (20%), and breast cancer (17.5%). At the time of diagnosis of BM, 11/40 patients (27.5%) had oligometastatic disease. Estimated mean survival time based on ds-GPA was 19.7 months (in 8 cases estimated survival < 12 months). Resection followed by focal or whole-brain radiotherapy (WBRT) was often applied (60%), followed by primary stereotactic radiotherapy (SRT) (20%) or WBRT (20%). 80% of patients received systemic treatment, appearing particularly active in specifically altered non-small lung cancer (NSCLC), melanoma, and HER2-positive breast cancer. Karnofsky performance score (KPS) and the presence of oligometastatic disease at BM diagnosis were persisting prognostic factors in LTS patients. CONCLUSION: In this monocentric setting reflecting daily pattern of care, LTS with BM is heterogeneous and difficult to predict. Effective local treatment and modern systemic therapies often appear crucial for LTS. The impact of concomitant diseases and frailty is not clear.

Quality requirements for MRI simulation in cranial stereotactic radiotherapy: a guideline from the German Taskforce "Imaging in Stereotactic Radiotherapy".

Accurate Magnetic Resonance Imaging (MRI) simulation is fundamental for high-precision stereotactic radiosurgery and fractionated stereotactic radiotherapy, collectively referred to as stereotactic radiotherapy (SRT), to deliver doses of high biological effectiveness to well-defined cranial targets. Multiple MRI hardware related factors as well as scanner configuration and sequence protocol parameters can affect the imaging accuracy and need to be optimized for the special purpose of radiotherapy treatment planning. MRI simulation for SRT is possible for different organizational environments including patient referral for imaging as well as dedicated MRI simulation in the radiotherapy department but require radiotherapy-optimized MRI protocols and defined quality standards to ensure geometrically accurate images that form an impeccable foundation for treatment planning. For this guideline, an interdisciplinary panel including experts from the working group for radiosurgery and stereotactic radiotherapy of the German Society for Radiation Oncology (DEGRO), the working group for physics and technology in stereotactic radiotherapy of the German Society for Medical Physics (DGMP), the German Society of Neurosurgery (DGNC), the German Society of Neuroradiology (DGNR) and the German Chapter of the International Society for Magnetic Resonance in Medicine (DS-ISMRM) have defined minimum MRI quality requirements as well as advanced MRI simulation options for cranial SRT.

SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. METHODS: 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. DISCUSSION: This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. TRIAL REGISTRATION: This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Hypofractionated stereotactic re-irradiation for progressive glioblastoma: twelve years' experience of a single center.

PURPOSE: We aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma. METHODS: The records of 77 previously irradiated glioblastoma patients who progressed and received second course hypofractionated SRT (1-5 fractions) between 2009 and 2022 in our department were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for all statistical analyses. RESULTS: The median time to progression from the end of initial radiotherapy was 14 months (range, 6-68 months). The most common SRT schedule was 30 Gy (range, 18-50 Gy) in 5 fractions (range, 1-5 fractions). The median follow-up after SRT was 9 months (range, 3-80 months). One-year overall (OS) and progression-free survival (PFS) rates after SRT were 46% and 35%, respectively. Re-irradiation dose and the presence of pseudoprogression were both significant independent positive prognostic factors for both OS (p = 0.009 and p = 0.04, respectively) and PFS (p = 0.008 and p = 0.04, respectively). For PFS, progression-free interval > 14 months was also a prognostic factor (p = 0.04). The treatment was well tolerated without significant acute toxicity. During follow-up, radiation necrosis was observed in 17 patients (22%), and 14 (82%) of them were asymptomatic. CONCLUSION: Hypofractionated SRT is an effective treatment approach for patients with progressive glioblastoma. Younger patients who progressed later than 14 months, received higher SRT doses, and experienced pseudoprogression following SRT had improved survival rates.

Fractionated stereotactic radiotherapy in craniopharyngiomas: A systematic review and single arm meta-analysis.

INTRODUCTION: Numerous studies have demonstrated Fractionated Stereotactic Radiotherapy's (FSRT) effectiveness in tumor control post-resection for craniopharyngiomas. Nevertheless, past literature has presented conflicting findings particularly regarding endocrine and visual function outcomes. This study aims to elucidate FSRT's efficacy and safety for this population. METHODS: Adhering to PRISMA, a systematic review and meta-analyses was conducted. Included studies had to report the effects of FSRT for treating craniopharyngiomas in a sample greater than four patients, addressing at least one of the outcomes of interest: improvement in visual acuity or field, new-onset hypopituitarism, effectiveness, and tumor progression. Relative risk with 95% confidence intervals were used to assess the outcomes. RESULTS: After retrieving a total of 1292 studies, 10 articles met the predefined criteria and thus were finally selected, amounting to a total of 256 patients. The improvement in visual acuity was estimated at 45% (95% CI: 6-83%), while the improvement in the visual field was 22% (95% CI: 0-51%). Regarding endocrine function, the new-onset hypopituitarism rate was found to be 5% (95% CI: 0-11%). Relative to FSRT effectiveness, the pooled estimate of the complete tumor response rate was 17% (95% CI: 4-30%), and the tumor progression rate was 7% (95% CI: 1-13%). Also, a 3-year progression-free survival rate of 98% (95% CI: 95-100%) was obtained. CONCLUSION: Despite limitations and risks, FSRT shows promise as a viable therapeutic option for craniopharyngiomas, offering notable benefits for visual functions and tumor control. Further research is required to better understand the associated risks, benefits, and clinical utility.

Evaluating contouring accuracy and dosimetry impact of current MRI-guided adaptive radiation therapy for brain metastases: a retrospective study.

BACKGROUND: Magnetic resonance imaging (MRI) guided adaptive radiotherapy (MRgART) has gained increasing attention, showing clinical advantages over conventional radiotherapy. However, there are concerns regarding online target delineation and modification accuracy. In our study, we aimed to investigate the accuracy of brain metastases (BMs) contouring and its impact on dosimetry in 1.5 T MRI-guided online adaptive fractionated stereotactic radiotherapy (FSRT). METHODS: Eighteen patients with 64 BMs were retrospectively evaluated. Pre-treatment 3.0 T MRI scans (gadolinium contrast-enhanced T1w, T1c) and initial 1.5 T MR-Linac scans (non-enhanced online-T1, T2, and FLAIR) were used for gross target volume (GTV) contouring. Five radiation oncologists independently contoured GTVs on pre-treatment T1c and initial online-T1, T2, and FLAIR images. We assessed intra-observer and inter-observer variations and analysed the dosimetry impact through treatment planning based on GTVs generated by online MRI, simulating the current online adaptive radiotherapy practice. RESULTS: The average Dice Similarity Coefficient (DSC) for inter-observer comparison were 0.79, 0.54, 0.59, and 0.64 for pre-treatment T1c, online-T1, T2, and FLAIR, respectively. Inter-observer variations were significantly smaller for the 3.0 T pre-treatment T1c than for the contrast-free online 1.5 T MR scans (P < 0.001). Compared to the T1c contours, the average DSC index of intra-observer contouring was 0.52‒0.55 for online MRIs. For BMs larger than 3 cm3, visible on all image sets, the average DSC indices were 0.69, 0.71 and 0.64 for online-T1, T2, and FLAIR, respectively, compared to the pre-treatment T1c contour. For BMs < 3 cm3, the average visibility rates were 22.3%, 41.3%, and 51.8% for online-T1, T2, and FLAIR, respectively. Simulated adaptive planning showed an average prescription dose coverage of 63.4‒66.9% when evaluated by ground truth planning target volumes (PTVs) generated on pre-treatment T1c, reducing it from over 99% coverage by PTVs generated on online MRIs. CONCLUSIONS: The accuracy of online target contouring was unsatisfactory for the current MRI-guided online adaptive FSRT. Small lesions had poor visibility on 1.5 T non-contrast-enhanced MR-Linac images. Contour inaccuracies caused a one-third drop in prescription dose coverage for the target volume. Future studies should explore the feasibility of contrast agent administration during daily treatment in MRI-guided online adaptive FSRT procedures.

Real-world experience of using stereotactic radiotherapy combined with anti-vascular endothelial growth factor to treat neovascular AMD.

INTRODUCTION: Adjunctive treatment or longer-acting drugs are required to treat nAMD to help ease burdens for patients and hospital clinics alike. Stereotactic therapy is one such option, providing a reduction in the number of injections over time. OBJECTIVE: To determine the clinical outcomes in a cohort of patients with nAMD receiving a combination therapy of stereotactic radiotherapy (SRT) with intravitreal anti-VEGF injections (IVI). METHOD: A retrospective analysis of 74 patients with nAMD, who had received IVI and SRT (16 Gray maximum dose to the macula) at a large tertiary university eye hospital, between March 2018 and September 2019 was performed. The number of IVIs, visual acuity (VA), and central retinal thickness (CRT) were evaluated at 12, 24, and 36 months after patients received SRT and compared to the same time interval prior to SRT. RESULTS: Follow-up data at 12, 24, and 36 months following and prior to SRT was available for 74, 48, and 22 patients respectively. Overall there was a significant reduction in the number of injections post-SRT. Twelve months following SRT, the median number of IVI was reduced by 1 (p < 0.05). The reduction in the median number of IVI was significantly reduced by 3 and 6 injections at 24- and 36-month follow-up respectively (p < 0.05). The CRT was significantly reduced post-SRT compared to the baseline values at all time periods. There was no statistically significant difference in VA at 12-month follow-up compared to baseline. The VA, however, significantly decreased at 24- and 36-month follow-up (p < 0.05). CONCLUSION: A therapy combining SRT with IVI has shown an overall reduction in the number of injections required in nAMD patients at 12, 24, and 36 months following SRT compared to IVI treatment alone. These real-world outcomes are comparable to other studies while also confirming the maintenance of the reduced frequency of required IVI for patients with nAMD.

Long-term outcomes of neuroendoscopic cyst partial resection combined with stereotactic radiotherapy for craniopharyngioma.

PURPOSE: The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas. METHODS: In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated. RESULTS: ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87 months (median, 33 months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension. CONCLUSION: Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation.

The impact of multiple deprivation on the management of vestibular schwannomas.

PURPOSE: While some factors have been well-shown to affect the decision-making in treating patients with vestibular schwannomas (VS), little is known on the role of deprivation. Our objective was to assess the effect of socioeconomic background on the management of patients with VS. METHODS: This retrospective cohort study included 460 patients with sporadic VS from West of Scotland. The postcode-based, multifactorial Scottish Index of Multiple Deprivation (SIMD) was used to assess the socioeconomic background of each patient. We performed a multivariate analysis including tumour size, growth and patient age with management modality (observation, stereotactic radiotherapy, microsurgery) being the main outcome measure and outcome (need for additional treatment) an additional measure. RESULTS: We found no significant difference in the demographics, tumour characteristics and primary treatment choice between patients with different SIMD scores. In addition, there was no statistically significant difference in the growth occurrence rates following first-line treatment (p = 0.964) and in the second-line treatment choice (p = 0.460). CONCLUSIONS: Multiple deprivation does not affect decision making in patients with VS in the examined cohort. This is probably linked to the centralisation and uniformity of the service and might not necessarily be applicable to other health services without centralisation.

Impact of abdominal compression on heart and stomach motion for stereotactic arrhythmia radioablation.

PURPOSE: To evaluate the effectiveness of abdominal compression (AC) as a respiratory motion management method for the heart and stomach during stereotactic arrhythmia radioablation (STAR). METHODS: 4D computed tomography (4DCT) scans of patients imaged with AC or without AC (free-breathing: FB) were obtained from ventricular-tachycardia (VT) (n = 3), lung cancer (n = 18), and liver cancer (n = 18) patients. Patients treated for VT were imaged both FB and with AC. Lung and liver patients were imaged once with FB or with AC, respectively. The heart, left ventricle (LV), LV components (LVCs), and stomach were contoured on each phase of the 4DCTs. Centre of mass (COM) translations in the left/right (LR), ant/post (AP), and sup/inf (SI) directions were measured for each structure. Minimum distances between LVCs and the stomach over the respiratory cycle were also measured on each 4DCT phase. Mann-Whitney U-tests were performed between AC and FB datasets with a significance of α = 0.05. RESULTS: No statistical difference (all p values were >0.05) was found in COM translations between FB and AC patient datasets for all contoured cardiac structures. A reduction in COM translation with AC relative to FB was patient, direction, and structure specific for the three VT patients. A significant decrease in the AP range of motion of the stomach was observed under AC compared to FB. No statistical difference was found between minimum distances to the stomach and LVCs between FB and AC. CONCLUSIONS: AC was not a consistent motion management method for STAR, nor does not uniformly affect the separation distance between LVCs and the stomach. If AC is employed in future STAR protocols, the motion of the target volume and its relative distance to the stomach should be compared on two 4DCTs: one while the patient is FB and one under AC.

A comparison of three-film analysis software for stereotactic radiotherapy patient-specific quality assurance.

AIM: The aim of this study was to investigate the suitability of three radiochromic film analysis software for stereotactic radiotherapy patient-specific quality assurance (PSQA): FilmQA Pro v5.0, SNC Patient v6.2, and eFilmQA v5.0. METHODS: Film calibration was conducted for each software followed by three sets of measurements. The first set assessed calibration accuracy by comparing measured and delivered doses at increments different from those used for calibration. The second set used each software to conduct PSQA through gamma analysis on 10 stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) patients. The third set utilized SNC Patient and eFilmQA to carry out gamma analysis on a collection of four digital test images, eliminating delivery and scanning uncertainties from impacting the analysis. Key supporting features within each software for conducting gamma analysis were identified. RESULTS: Overall, FilmQA Pro and eFilmQA were deemed comparable and favoured over SNC Patient due to the presence of key features such as triple-channel dosimetry, auto-optimization, and dose scaling. FilmQA Pro has a substantial user base and established reputation. eFilmQA, having been introduced more recently, serves as a viable alternative to FilmQA Pro, having been further refined for stereotactic radiotherapy PSQA. CONCLUSION: This study investigated the suitability of three film analysis software (FilmQA Pro, eFilmQA, and SNC Patient) for stereotactic radiotherapy PSQA. Results from the investigation indicated that both FilmQA Pro and eFilmQA are comparably suitable and are preferred over SNC Patient. Both FilmQA Pro and eFilmQA are recommended for radiotherapy clinics.

What is the optimal isodose line for stereotactic radiotherapy for single brain metastases using HyperArc?

PURPOSE: The study aimed to investigate the optimal isodose line (IDL) in linear accelerator-based stereotactic radiotherapy for single brain metastasis, using HyperArc. We compared the dosimetric parameters for target and normal brain tissue among six plans with different IDLs. METHODS: This study included 30 patients with single brain metastasis. We retrospectively generated six plans for each tumor with different IDLs (80%, 70%, 60%, 50%, 40%, and 33%) using HyperArc. All treatment plans were normalized to the prescription dose of 35 Gy in five fractions which was covered by 95% of the planning target volume (PTV), defined by adding a 1.0 mm margin to the gross tumor volume (GTV). The dosimetric parameters were compared among the six plans. RESULTS: For GTV > 0.1 cm3, the ratio of brain-GTV volumes receiving 25 Gy to PTV (V25Gy/PTV) was significantly lower at IDL 40%-70% than at IDL 80% and 33% (p < 0.01, retrospectively). For GTV < 0.1 cm3, V25Gy/PTV decreased continuously as IDL decreased. The values of D99% and D80% for GTV increased with decreasing IDL. An IDL of 50% or less was required to achieve D99% of greater than 43 Gy and D80% of greater than 50 Gy. The mean values of D99% and D80% for IDL 50% were 44.3 and 51.9 Gy. CONCLUSION: The optimal IDL is 40%-50% for GTV > 0.1 cm3. These lower IDLs could increase D99% and D80% of GTV while lowering V25Gy of normal brain tissue, which may help reduce the risk of radiation necrosis and improve local control.

SGRT-based stereotactic body radiotherapy for lung cancer setup accuracy and margin of the PTV.

OBJECTIVE: Surface-guided radiation therapy (SGRT, AlignRT) was used to analyze motion during stereotactic body radiotherapy (SBRT) in lung cancer patients and to explore the margin of the planning target volume (PTV). METHODS: The residual errors of the AlignRT were evaluated based on grayscale cone-beam computed tomography registration results before each treatment. AlignRT log file was used to analyze the correlation between the frequency and longest duration of errors larger than 2 mm and lasting longer than 2 s and maximum error with age and treatment duration. The displacement value at the end of treatment, the average displacement value, and the 95% probability density displacement interval were defined as intrafraction errors, and PTV1, PTV2, PTV3 were calculated by Van Herk formula or Z score analysis. Organ dosimetric differences were compared after the experience-based margin was replaced with PTV3. RESULTS: The interfraction residual errors were Vrt0 , 0.06 ± 0.18 cm; Lng0 , -0.03 ± 0.19 cm; Lat0 , 0.02 ± 0.15 cm; Pitch0 , 0.23 ± 0.7°; Roll0 , 0.1 ± 0.69°; Rtn0 , -0.02 ± 0.79°. The frequency, longest duration and maximum error in vertical direction were correlated with treatment duration (r = 0.404, 0.353, 0.283, p < 0.05, respectively). In the longitudinal direction, the frequency was correlated with age and treatment duration (r = 0.376, 0.283, p < 0.05, respectively), maximum error was correlated with age (r = 0.4, P < 0.05). Vertical, longitudinal, lateral margins of PTV1, PTV2, PTV3 were 2 mm, 4 mm, 2 mm; 2 mm, 2 mm, 2 mm, 3 mm, 5 mm, 3 mm, respectively. After replacing the original PTV, mean lung dose (MLD), 2-cm3 chest wall dose (CD), lung V20 decreased by 0.2 Gy, 2.1 Gy, 0.5%, respectively (p < 0.05). CONCLUSION: AlignRT can be used for interfraction setup and monitoring intrafraction motion. It is more reasonable to use upper and lower limits of the 95% probability density interval as an intrafraction error.

Cycle-generative adversarial network-based bone suppression imaging for highly accurate markerless motion tracking of lung tumors for cyberknife irradiation therapy.

PURPOSE: Lung tumor tracking during stereotactic radiotherapy with the CyberKnife can misrecognize tumor location under conditions where similar patterns exist in the search area. This study aimed to develop a technique for bone signal suppression during kV-x-ray imaging. METHODS: Paired CT images were created with or without bony structures using a 4D extended cardiac-torso phantom (XCAT phantom) in 56 cases. Subsequently, 3020 2D x-ray images were generated. Images with bone were input into cycle-consistent adversarial network (CycleGAN) and the bone suppressed images on the XCAT phantom (BSIphantom ) were created. They were then compared to images without bone using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). Next, 1000 non-simulated treatment images from real cases were input into the training model, and bone-suppressed images of the patient (BSIpatient ) were created. Zero means normalized cross correlation (ZNCC) by template matching between each of the actual treatment images and BSIpatient were calculated. RESULTS: BSIphantom values were compared to their paired images without bone of the XCAT phantom test data; SSIM and PSNR were 0.90 ± 0.06 and 24.54 ± 4.48, respectively. It was visually confirmed that only bone was selectively suppressed without significantly affecting tumor visualization. The ZNCC values of the actual treatment images and BSIpatient were 0.763 ± 0.136 and 0.773 ± 0.143, respectively. The BSIpatient showed improved recognition accuracy over the actual treatment images. CONCLUSIONS: The proposed bone suppression imaging technique based on CycleGAN improves image recognition, making it possible to achieve highly accurate motion tracking irradiation.

Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities.

PURPOSE: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.

Hypofractionated stereotactic radiotherapy (HFSRT) versus single fraction stereotactic radiosurgery (SRS) to the resection cavity of brain metastases after surgical resection (SATURNUS): study protocol for a randomized phase III trial.

BACKGROUND: The brain is a common site for cancer metastases. In case of large and/or symptomatic brain metastases, neurosurgical resection is performed. Adjuvant radiotherapy is a standard procedure to minimize the risk of local recurrence and is increasingly performed as local stereotactic radiotherapy to the resection cavity. Both hypofractionated stereotactic radiotherapy (HFSRT) and single fraction stereotactic radiosurgery (SRS) can be applied in this case. Although adjuvant stereotactic radiotherapy to the resection cavity is widely used in clinical routine and recommended in international guidelines, the optimal fractionation scheme still remains unclear. The SATURNUS trial prospectively compares adjuvant HFSRT with SRS and seeks to detect the superiority of HFSRT over SRS in terms of local tumor control. METHODS: In this single center two-armed randomized phase III trial, adjuvant radiotherapy to the resection cavity of brain metastases with HFSRT (6 - 7 × 5 Gy prescribed to the surrounding isodose) is compared to SRS (1 × 12-20 Gy prescribed to the surrounding isodose). Patients are randomized 1:1 into the two different treatment arms. The primary endpoint of the trial is local control at the resected site at 12 months. The trial is based on the hypothesis that HFSRT is superior to SRS in terms of local tumor control. DISCUSSION: Although adjuvant stereotactic radiotherapy after resection of brain metastases is considered standard of care treatment, there is a need for further prospective research to determine the optimal fractionation scheme. To the best of our knowledge, the SATURNUS study is the only randomized phase III study comparing different regimes of postoperative stereotactic radiotherapy to the resection cavity adequately powered to detect the superiority of HFSRT regarding local control. TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov, number NCT05160818, on December 16, 2021. The trial registry record is available on  https://clinicaltrials.gov/study/NCT05160818 . The presented protocol refers to version V1.3 from March 21, 2021.

Retrospective non-inferiority study of stereotactic radiosurgery for more than ten brain metastases.

AIM: This study aimed to investigate the clinical benefits of stereotactic radiosurgery (SRS) in patients with > 10 brain metastases (BM) compared to patients with 2-10 BM. METHODS: The study included multiple BM patients who underwent SRS between 2014 and 2022, excluding patients who underwent whole brain radiotherapy, had a Karnofsky Performance Status score < 60, suspected leptomeningeal disease, or a single BM lesion. Patients were divided into two groups (2-10 and > 10 BM groups) and matched 2:1 based on propensity scores. The primary endpoint was overall survival (OS) in the matched dataset, with intracranial progression-free survival (PFS) as the secondary endpoint. Non-inferiority was established if the upper limit of the 95% confidence interval (CI) of the adjusted hazard ratio was below 1.3. RESULTS: Of the 1042 patients identified, 434 met eligibility criteria. After propensity score matching, 240 patients were analyzed (160 in the BM 2-10 group and 80 in the > 10 BM group). The median OS was 18.2 months in the 2-10 BM group and 19.4 months in the > 10 BM group (P = 0.60). The adjusted hazard ratio was 0.86 (95% CI: 0.59-1.24), indicating non-inferiority. PFS was not significantly different between the groups (4.8 months vs. 4.8 months, P = 0.94). The number of BM did not significantly impact OS or PFS. CONCLUSIONS: SRS for selected patients with > 10 BM was non-inferior in terms of OS compared to those with 2-10 BM in a propensity score-matched dataset.

Long-term clinical outcomes of stereotactic radiotherapy for bilateral vestibular schwannomas in neurofibromatosis type 2 patients.

PURPOSE: The evidence for treating patients with neurofibromatosis 2-related vestibular schwannoma (VS-NF2) using hypofractionated stereotactic radiation therapy (HSRT) is limited. This study aimed to investigate clinical outcomes in patients with VS-NF2 treated with Robotic HSRT. METHODS: We retrospectively analyzed 25 NF2 patients with 48 VSs who were treated using Robotic HSRT at Ramathibodi Hospital from January 2009 to January 2020. RESULTS: Median follow-up was 98 months (range, 24-155 months). Median tumor volume was 2.3 cm3 (range, 0.4-28.3 cm3). Median prescribed dose was 18 Gy (range, 18-25 Gy) in three fractions (range, 3-5). The 5- and 10-year local control rates were 87% and 80%, respectively. The 5- and 10-year hearing preservation rates were 59% and 35%, respectively. Three patients developed new symptoms associated with transient volume expansion after treatment: hydrocephalus in one, facial weakness in one, and ataxia in one. No patient developed worsening of trigeminal nerve function. No histologically confirmed of radiation induced malignancy was reported in the study. CONCLUSIONS: Robotic HSRT demonstrated excellent long-term tumor control with a low non-auditory complication rate in patients with VS-NF2. However, preservation of hearing remains a major concern.

Intraoperative or postoperative stereotactic radiotherapy for brain metastases: time to systemic treatment onset and other patient-relevant outcomes.

PURPOSE: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time. METHODS: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups. RESULTS: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001). CONCLUSION: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.