Hypofractionated Stereotactic Radiotherapy Research Articles

Comprehensively evaluating the performance of Elekta high-definition dynamic radiosurgery for hypofractionated stereotactic radiotherapy of multiple brain metastases

PurposeTo evaluate the dosimetric and delivery performance of Elekta high-definition dynamic radiosurgery (HDRS) in hypofractionated stereotactic radiotherapy (HSRT) for multiple brain metastases (BMs) by comparison with a conventional single-isocenter noncoplanar volumetric modulated arc therapy (VMAT) technique using the RayStation treatment planning system (TPS). Materials and methodsFrom June 2022 to October 2023, thirty-two patients (a total of 140 BMs) treated with HSRT (30–48 Gy/3-6f) via HDRS-based single-isocenter noncoplanar VMAT (HDRS-VMAT) were retrospectively selected for this study. Each patient was replanned using RayStation TPS-based single-isocenter noncoplanar VMAT (RayStation-VMAT). HDRS-VMAT and RayStation-VMAT plans were compared in terms of the gradient index (GI), conformity index (CI), normal brain tissue (NBT) dose exposure, monitor units (MUs), homogeneity index (HI), delivery accuracy, and beam-on time (BOT). ResultsCompared with the RayStation-VMAT plan, the HDRS-VMAT plan achieved superior CI (1.14 ± 0.09 vs. 1.23 ± 0.12, P < 0.001) and GI (5.23 ± 1.18 vs. 7.83 ± 2.75, p < 0.001) but had greater HI values. Compared with the RyaStation-VMAT plan, the HDRS-VMAT plan also yielded significantly lower NBT dose exposures (V23Gy, V21Gy, V18Gy, V12Gy and Dmean) but at the cost of increased MUs (3659.16 ± 1225.28 vs. 2536.23 ± 785.80, p < 0.001). The difference in BOTs was minimal (<1 min), which was not considered clinically significant. Furthermore, the HDRS-VMAT exhibited a higher gamma passing rate across all criteria (P < 0.001), particularly under stricter criteria (2%/1 mm), achieving an approximately 3% increase. ConclusionCompared with RaySation-VMAT, HDRS-VMAT offers superior target conformity, better NBT sparing, and higher delivery accuracy while maintaining comparable delivery efficiency. This represents a promising approach for HSRT of multiple BMs.

Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy

BackgroundThe role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. MethodsPatients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. ResultsFifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19–78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10−20 Gy), 27 Gy (range, 18−33 Gy) and 25 Gy (range, 25−30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. ConclusionOur findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

Hypofractionated stereotactic radiotherapy in Spetzler Martin grades 4 and 5 arteriovenous malformations in the pediatric population: Is it a viable alternative?

To analyze the outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for Spetzler Martin grades 4 and 5 arteriovenous malformations (AVMs) in a pediatric population. Fourteen patients with Spetzler Martin (SM) grades IV and V large AVMs who underwent HFSRT between January 2013 and July 2019 were retrospectively reviewed. All patients received HFSRT at a dose of 30-36Gy in 5 to 6 fractions. They were followed up annually with clinical and imaging assessments to evaluate obliteration rates. The median age at presentation was 15years (range 8-21years). Ten (71%) were SM grade 4 AVMs and the rest were SM grade 5 AVMs. The majority presented with headache (8 [57%]), and 3 (21%) presented with bleeding. The median nidus volume was 39.4cc (IQR, 31.4-52.4). Two (14%) patients had infratentorial AVMs. All of them had deep venous drainage. The median clinical follow-up duration was 75months (range 31-107months). There was complete obliteration of the nidus in 3 (21%) patients with a median time to obliteration of 39months. HFSRT resulted in a reduction of the AVM volume to 12cc or less in nearly 70% of patients. None of the patients experienced re-bleeding. 79% reported an improvement in their symptoms. HFSRT is a highly effective treatment for high-grade AVMs in children, which can result in either complete elimination or significant reduction of the nidus volume or make it suitable for additional treatment, such as single-session stereotactic radiosurgery (SRS).

Going from 3D/3D to 2D/3D registration for noncoplanar setup verification in intracranial single-isocenter multiple-target hypofractionated stereotactic radiotherapy: comparison between kilo-voltage/mega-voltage image pairs and noncoplanar cone-beam computed tomography.

Single-isocenter (SI) noncoplanar volumetric modulated arc therapy (NC-VMAT) has been widely used in stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HSRT) for multiple brain metastases (BMs). However, it is critical to verify patient positioning at a noncoplanar couch angle. This study aimed to compare the noncoplanar setup discrepancies between kilo-voltage/mega-voltage image (kV/MV) orthogonal image pairs with a 2-dimensional/3-dimensional (2D/3D) matching mode and noncoplanar cone-beam computed tomography (NC-CBCT) with a 3D/3D matching mode in SI NC-VMAT HSRT for multiple BMs. Twenty patients with multiple BMs [2-5] who underwent SI NC-VMAT HSRT were enrolled in this study. Prior to each noncoplanar field delivery, both kV/MV orthogonal image pairs and NC-CBCT were used to determine setup errors. The setup error values reported by NC-CBCT were defined as the gold standard and compared to those reported by kV/MV orthogonal image pairs. The Bland-Altman analysis method was utilized to assess the agreement of the two positioning modalities. In total, 104 kV/MV image pairs and NC-CBCT scans were acquired. The mean setup error differences (SEDs; absolute values) between the two positioning systems were 0.17 mm, 0.21 mm, 0.16 mm, 0.22°, 0.18°, and 0.17° in the vertical, longitudinal, lateral, yaw, pitch, and roll directions, respectively. The maximum SEDs regarding translation and rotation occurred in the longitudinal and yaw directions at 0.60 mm and 0.8°, respectively. Bland-Altman analysis showed excellent agreement between the two positioning modalities, and the 95% limits of agreement (LOAs) never exceeded 0.6 mm and 0.6° in the translational and rotational directions, respectively. Only 4.80% of SEDs exceeded the tolerance of 0.5 mm/0.5°. Orthogonal kV/MV image pairs with 2D/3D matching mode could provide comparable accuracy for noncoplanar positioning as NC-CBCT with 3D/3D matching mode.

Long-term clinical outcomes of hypofractionated stereotactic radiotherapy using the CyberKnife robotic radiosurgery system for jugular foramen schwannomas.

Jugular foramen schwannomas (JFSs) are rarely seen, benign tumors with slow growth. Today, management options for JFSs include observation, surgery, and radiation. However, the optimal treatment strategy remains controversial. Stereotactic radiosurgery serves as a minimally invasive alternative or adjuvant therapeutic regimen of microsurgery. Gamma Knife radiosurgery is suitable for patients with JFS who have small- and medium-sized tumors and normal cranial nerve (CN) function. Hypofractionated stereotactic radiotherapy (HSRT) offers a potential radiobiological advantage and may result in better preservation of normal structures compared to single-fraction stereotactic radiosurgery. The aim of the article was to review the clinical and radiographic outcomes of patients with JFS who were treated using HSRT. The authors retrospectively analyzed 74 patients with JFS who received HSRT between January 2009 and January 2020 in the authors' center. Among them, 53 patients were newly diagnosed with JFS, 19 patients had a previous history of microsurgical resection, and the other 2 patients underwent CyberKnife because of tumor recurrence after Gamma Knife radiosurgery. A total of 73 patients had preexisting CN symptoms and signs. The median tumor volume was 14.8 cm3 (range 0.5-41.2 cm3), and most of them (70.3%) were ≥ 10 cm3. The radiation dose regimen was prescribed depending on the tumor size, and more fractions were used in larger tumors. The median margin doses prescribed were 18.2 Gy/2 fractions, 21.0 Gy/3 fractions, and 21.6 Gy/4 fractions. The median follow-up was 103 months (range 18-158 months). After treatment, 42 (56.8%) patients had tumor regression, 27 (36.5%) patients had stable tumors, and 5 (6.8%) experienced tumor progression. Among them, MRI revealed that 1 patient had a complete response. Three patients received surgery at a median of 25 months because of tumor progression. One patient underwent ventriculoperitoneal shunt insertion for hydrocephalus that developed after HSRT independent of tumor progression. The 5-year progression-free survival rate was 93.2%. Preexisting cranial neuropathies improved in 46 patients, remained stable in 14, and worsened in 14. HSRT proved to be a safe and effective primary or adjuvant treatment strategy for JFSs, although 14 patients (18.9%) experienced some degree of delayed symptomatic deterioration posttreatment. This therapeutic option was demonstrated to provide both excellent tumor control and improvement in CN function.

Promising Outcomes in Acromegaly Patients Receiving CyberKnife Stereotactic Hypofractionated Radiotherapy.

The primary treatment for patients with acromegaly has traditionally been transsphenoidal surgery, with decreasing reliance on radiotherapy (RT) due to advancements in pharmacotherapy (PT). Despite these advancements, a substantial portion of patients still face persistent acromegaly, necessitating novel treatment approaches. This study investigates the role of CyberKnife Stereotactic Hypofractionated Radiotherapy (CK-HFRT) in persistent acromegaly. The primary objective was to assess the impact of CK-HFRT on endocrine remission (ER) rates while maintaining acceptable toxicity levels. The study retrospectively analyzed 31consecutive patients with acromegaly who received CK-HFRT following multiple unsuccessful surgeries and prolonged PT without ER. Various CK-HFRT dose fractionation regimes were administered, and dose volume histograms were evaluated. Tumor control, cured disease (CD), endocrine remission (ER) rates, and overall survival were estimated at a median follow-up of 62 months. Acute and late toxicity, including pituitary insufficiency and radiation-induced optic neuropathy (RION), were also assessed. At 62 months of follow-up, the study group demonstrated excellent tumor control with 100% nonprogressive adenomas. Endocrine remission was achieved in 86.7% of patients, with a 22.4% CD rate at five years. Pituitary insufficiency occurred in 32.3% of patients, and no cases of RION were reported. The study observed three deaths related to cardiovascular diseases, all in patients receiving PT. Overall survival at five years was 79.2%. CyberKnife stereotactic hypofractionated radiotherapy, as an adjunct to PT, provides a viable treatment option for patients with persistent acromegaly following unsuccessful surgeries. The therapy results in substantial ER rates and tumor control while minimizing the risk of permanent radiation-induced optic neuropathy. However, the decision to administer CK-HFRT should be individualized, considering the patient's overall condition and treatment history.

Hypofractionated Stereotactic Radiotherapy (HFSRT) of the Resection Cavity vs. Whole-Brain Radiotherapy (WBRT) Following Brain Metastasis Resection – Results of the ESTRON Randomized Phase 2 Trial

Hypofractionated Stereotactic Radiotherapy (HFSRT) of the Resection Cavity vs. Whole-Brain Radiotherapy (WBRT) Following Brain Metastasis Resection – Results of the ESTRON Randomized Phase 2 Trial

Role of hypofractionated stereotactic radiotherapy for primary optic nerve sheath meningioma.

Optic nerve sheath meningiomas (ONSM) are rare tumors potentially causing visual deficits. This study aims to report the anatomic and visual outcomes of patients with primary ONSM treated with hypofractionated stereotactic radiotherapy (HF-SRT). Data of 36 patients treated with HF-SRT between 2008 and 2019 were retrospectively collected. The clinical target volume (CTV) was equal to the gross tumor volume and a 2 mm was added for the planning target volume. All responses other than progression were accepted as local control (LC). The VA grading was performed under 3 groups to provide an even distribution; 20/400 or worse, 20/40-20/400, and 20/40 or better. Median HF-SRT dose was 25 Gy and the median CTV was 1.94 cc. After a median of 106 months of follow-up, the tumor regressed in 23 (64%), was stable in 9 (25%), and progressed in 4 (11%) eyes. The overall rate of LC was 89% with 2-, 5-, 10-, and 15-year rate of 100%, 94%, 84%, and 84%, respectively. Treatment-related late toxicity rate was 11%. The VA was stable in 27 (75%) eyes, improved in 5 (14%) eyes, and worsened in 4 (11%) eyes, respectively, after HF-SRT. Female gender was the only independent predictor of an improved VA. Hypofractionated stereotactic radiotherapy is a safe and satisfactory treatment option for primary ONSM without severe toxicity. It may be advisable to commence treatment before an established visual deficit of 20/400 or worse occurs, to make the most of the functional benefit.

Hypofractionated Stereotactic Radiotherapy vs. Single Fraction Stereotactic Radiosurgery to the Resection Cavity of Brain Metastases after Surgical Resection (SATURNUS trial): A Prospective, Randomized Phase III Trial

The brain is a common site for metastases. Resection of large or symptomatic metastases is followed by stereotactic radiotherapy to prevent local recurrence. The optimal fractionation scheme is subject of ongoing research. Supported by emerging retrospective data, we hypothesize that hypofractionated stereotactic radiotherapy (HFSRT) is superior to single-fraction stereotactic radiosurgery (SRS) in terms of local control (LC). We designed the SATURNUS trial to prospectively demonstrate the superiority of HFSRT over SRS after resection of brain metastases in terms of LC. The SATURNUS trial is a prospective, randomized phase III trial, currently recruiting patients at a single institution. Patients are 1:1 allocated to HFSRT or SRS using permuted block randomization. Affiliation to the treatment arm is solely blinded to the neuroradiologist assessing therapy response. HFSRT will be delivered with 6 - 7 x 5 Gy and SRS with 1 x 12-20 Gy, prescribed to the surrounding isodose, depending on cavity size and proximity to structures at risk. For SRS, doses do not exceed the maximum doses according to RTOG 90-05. Case number calculation was based on own institutional data on HFSRT (mean LC rate of 88% at 12 months) and data from large phase III trials on SRS (pooled mean LC rate of 66% at 12 months). Using a Chi-squared test of equal proportions (odds ratio = 1), setting test significance level (α) to 0.05, and allocating an equal number of patients to both treatment arms, 114 patients are needed to detect the superiority of HFSRT in terms of LC at 12 months (primary endpoint) with a power of at least 80%. Estimating a dropout rate of 10%, the case number was set to 126. The trial was registered with clinicaltrials.gov (NCT05160818). The first patient was enrolled in May 2021 and recruitment is ongoing. Patients with up to three resected brain metastases are considered for study participation. Further eligibility criteria are histologically confirmed solid tumor disease, resection cavity diameter ≤ 4 cm, consent to perform adjuvant radiotherapy by an interdisciplinary tumor board, completed wound healing, resection within the last six weeks at the time of study inclusion, age ≥ 18 years, KPS ≥ 60%, adequate contraceptive measures for fertile women / men and written informed consent. Patients are followed up clinically and with MRI at 6 weeks and 3, 6, 9 and 12 months after treatment. LC is assessed according to RANO-BM. Toxicity (CTCAE v4.03) is assessed as a secondary endpoint. The rather broad dose corridors allowed within the trial do justice to clinical reality, however, may represent a limitation of the trial. They are therefore addressed with a predefined subgroup analysis, as will be cavity size, among others. Participation of further study centers is desired. To the best of our knowledge, the SATURNUS trial is the only randomized phase III trial adequately powered to detect the superiority of HFSRT over SRS with regard to LC for resected brain metastases. To be determined. To be determined.

Outcomes of 30 Gy/5 Fr Hypofractionated Stereotactic Radiation Therapy for Small Brain Metastases (≤2 cm).

Stereotactic radiosurgery (SRS)-used for brain metastases (BMs) with a tumor diameter of ≤2 cm-has a high local control rate, however, it can cause symptomatic radiation-induced brain necrosis. Hypofractionated stereotactic radiation therapy (HFSRT) is not commonly used for such lesions and its effectiveness remains unknown. Herein, the efficacy of 30 Gy 5-fraction HFSRT for treating BMs of <2 cm was retrospectively evaluated. Patients who received HFSRT and had a gross tumor volume (GTV) of ≤2 cm in maximum diameter were included in the study (49 patients; 179 BMs; median follow-up period, 11.9 months). The mean GTV Peripheral Dose (D95) was 36.2 Gy. The local control (LC) rates at 1 and 2 years were 93.0% and 81.5%, respectively, for all lesions. The 1-year LC rates were 93.6% and 92.0% for ≤1.0-cm and 1.0-2.0-cm lesions, respectively. Multivariate analysis revealed that the only significant difference was in GTV maximal tumor diameter (HR=1.961, p=0.0002). Notably, only one patient had asymptomatic radiation necrosis. Owing to the high toxicity of SRS, 5-fraction HFSRT can be an effective treatment strategy for BMs of <2 cm.

Post-Operative Stereotactic Radiotherapy for Resected Brain Metastases: Results of the Multicenter Analysis (AURORA) of the German Working Group "Stereotactic Radiotherapy"

While the results of prospective studies support the use of postoperative stereotactic radiotherapy (RT) to the resection cavity (RC) as the standard of care after surgery, there are several issues that need to be investigated such as factors for improving local control, risk of leptomeningeal disease and radiation necrosis. Further, the optimal dose and fractionation is still under debate. The working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology (DEGRO) analyzed its multi-institutional database with 661 patients who received postoperative stereotactic RT to the RC. Treatment was performed at 13 centers between 2008 and 2021. Patient characteristics, treatment details, and follow-up data including overall survival (OS), local control (LC) were evaluated. Cox Regression and Kaplan-Meier curves with Log-rank Tests were calculated for selected variables. In this retrospective study, overall survival was 61.5% at 1 year, 47.6% at 2 years, and 35.5% at 3 years, and local control was 84.6% at 1 year, 74.8% at 2 years, and 72.8% at 3 years. 96% of patients were treated with hypofractionated stereotactic radiotherapy (HSRT), only 26 patients received single fraction radiosurgery (4%). Prognostic factors associated with overall survival were Karnofsky Performance Status, RPA and GPA class, controlled primary tumor and absence of extracranial metastases, whereas prognostic factor associated with local control was planning target volume (23 mL or less). HSRT is the most common fractionation form in the treatment of RCs in this multicenter analysis. This approach results in excellent OS and LC outcomes. OS in patients with resected brain metastases is mainly influenced by performance status. In regard to local control, RT of large cavities remain a challenge with significantly worse outcome.

Hyperbaric Oxygen Therapy plus Hypofractionated Stereotactic Radiotherapy in Recurrent Glioblastoma

Hypoxia is thought to play a role in tumor development, angiogenesis and growth, and resistance to chemotherapy, antiangiogenic therapy and radiotherapy (RT) in a large number of human cancers. Brain tumors, especially highly aggressive GBM with its necrotic tissue, are more likely to be affected by hypoxia. The median partial pressure of oxygen (PO2) of high-grade gliomas in patients under anesthesia was approximately 5-7 mmHg, with a significant proportion of PO2 values <2.5 mmHg. The radiosensitivity of brain tumors could potentially be increased by performing hyperbaric oxygenation (HBO) before the RT session. We propose an innovative approach to improve the efficacy of accelerated hypofractionated Stereotactic Radiotherapy (HSRT) after HBO (HBO-RT) for the treatment of recurrent HGG (rHGG). The primary objective of this study is to evaluate the disease control rate (DCR) at 3 months. The secondary Objectives are: - Safety assessment (acute and late toxicity). - Overall Survival (OS), - Progression Free Survival (PFS). We enrolled 14 patients (aged >18 years) with rHGG detected using MRI. A total dose of 15-25 Gy was administered in daily 5-Gy fractions for 3-5 consecutive days after daily HBO. Median follow-up from re-irradiation was 22.8 months (range: 2.0-24.2 months). The disease control rate 3-months after HBO-RT was 50% (23.0-76.9). Six- and 12-month Progression-free survival was 35.7% (95% CI: 13-59.4) and 10.7% (95% CI: 0.8-35.4), respectively. Median overall survival of HBO-RT was 10.7 months (95% CI: 6.6-24.2). No acute or late neurologic toxicity >grade (G)2 was observed. HSRT combined to HBO seems effective and safe in the treatment of rHGG.

Assessment of interfraction dose variation in pancreas SBRT using daily simulation MR images

Pancreatic Cancer is associated with poor treatment outcomes compared to other cancers. High local control rates have been achieved by using hypofractionated stereotactic body radiotherapy (SBRT) to treat pancreatic cancer. Challenges in delivering SBRT include close proximity of several organs at risk (OARs) and target volume inter and intra fraction positional variations. Magnetic resonance image (MRI) guided radiotherapy has shown potential for online adaptive radiotherapy for pancreatic cancer, with superior soft tissue contrast compared to CT. The aim of this study was to investigate the variability of target and OAR volumes for different treatment approaches for pancreatic cancer, and to assess the suitability of utilizing a treatment-day MRI for treatment planning purposes. Ten healthy volunteers were scanned on a Siemens Skyra 3 T MRI scanner over two sessions (approximately 3 h apart), per day over 5 days to simulate an SBRT daily simulation scan for treatment planning. A pretreatment scan was also done to simulate patient setup and treatment. A 4D MRI scan was taken at each session for internal target volume (ITV) generation and assessment. For each volunteer a treatment plan was generated in the Raystation treatment planning system (TPS) following departmental protocols on the day one, first session dataset (D1S1), with bulk density overrides applied to enable dose calculation. This treatment plan was propagated through other imaging sessions, and the dose calculated. An additional treatment plan was generated on each first session of each day (S1) to simulate a daily replan process, with this plan propagated to the second session of the day. These accumulated mock treatment doses were assessed against the original treatment plan through DVH comparison of the PTV and OAR volumes. The generated ITV showed large variations when compared to both the first session ITV and daily ITV, with an average magnitude of 22.44% ± 13.28% and 25.83% ± 37.48% respectively. The PTV D95 was reduced by approximately 23.3% for both plan comparisons considered. Surrounding OARs had large variations in dose, with the small bowel V30 increasing by 128.87% when compared to the D1S1 plan, and 43.11% when compared to each daily S1 plan. Daily online adaptive radiotherapy is required for accurate dose delivery for pancreas cancer in the absence of additional motion management and tumour tracking techniques.

Can Optical Surface Imaging Replace Non-coplanar Cone-beam Computed Tomography for Non-coplanar Set-up Verification in Single-isocentre Non-coplanar Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Single and Multiple Brain Metastases?

AimsTo conduct a direct comparison regarding the non-coplanar positioning accuracy between the optical surface imaging system Catalyst HDTM and non-coplanar cone-beam computed tomography (NC-CBCT) in intracranial single-isocentre non-coplanar stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HSRT). Materials and methodsTwenty patients with between one and five brain metastases who underwent single-isocentre non-coplanar volumetric modulated arc therapy (NC-VMAT) SRS or HSRT were enrolled in this study. For each non-zero couch angle, both Catalyst HDTM and NC-CBCT were used for set-up verification prior to beam delivery. The set-up error reported by Catalyst HDTM was compared with the set-up error derived from NC-CBCT, which was defined as the gold standard. Additionally, the dose delivery accuracy of each non-coplanar field after using Catalyst HDTM and NC-CBCT for set-up correction was measured with SRS MapCHECKTM. ResultsThe median set-up error differences (absolute values) between the two positioning methods were 0.30 mm, 0.40 mm, 0.50 mm, 0.15°, 0.10° and 0.10° in the vertical, longitudinal, lateral, yaw, pitch and roll directions, respectively. The largest absolute set-up error differences regarding translation and rotation were 1.5 mm and 1.1°, which occurred in the longitudinal and yaw directions, respectively. Only 35.71% of the pairs of measurements were within the tolerance of 0.5 mm and 0.5° simultaneously. In addition, the non-coplanar field with NC-CBCT correction yielded a higher gamma passing rate than that with Catalyst HDTM correction (P < 0.05), especially for evaluation criteria of 1%/1 mm with a median increase of 12.8%. ConclusionsCatalyst HDTM may not replace NC-CBCT for non-coplanar set-up corrections in single-isocentre NC-VMAT SRS and HSRT for single and multiple brain metastases. The potential role of Catalyst HDTM in intracranial SRS/HSRT needs to be further studied in the future.

Impact of Choroidal Melanoma Characteristics on Progression-Free Survival in Patients Undergoing Hypofractionated Stereotactic Photon Radiotherapy.

In an effort to replace ultrasonography-based thickness measurements, we investigated whether choroidal melanoma characteristics are related to progression-free survival (PFS) in patients monitored after linear accelerator (LINAC)-based hypofractionated stereotactic photon radiotherapy. In a retrospective dataset, we used a linear mixed model to assess the associations between PFS and tumor characteristics; in particular, thickness, largest basal diameter (LBD), base area and volume. Thickness and LBD are statistically significantly associated with PFS. In a subgroup of 16 patients undergoing enucleation due to melanoma recurrence or progression, there were statistically significant changes in mean thickness and LBD before surgery. Mean PFS was 42 ± 30months. Ultrasonography-based thickness measurements may not be necessary for treated choroidal melanoma monitoring; instead, we propose sequential LBD assessments, which should preferably be performed using fundus photography in future.

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

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. We retrospectively analyzed 25 NF2 patients with 48 VSs who were treated using Robotic HSRT at Ramathibodi Hospital from January 2009 to January 2020. 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 18Gy (range, 18-25Gy) 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. 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.

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

BackgroundThe 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.MethodsIn 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.DiscussionAlthough 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 registrationThe 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.

Opportunities and Alternatives of Modern Radiation Oncology and Surgery for the Management of Resectable Brain Metastases.

Postsurgical radiotherapy (RT) has been early proven to prevent local tumor recurrence, initially performed with whole brain RT (WBRT). Subsequent to disadvantageous cognitive sequalae for the patient and the broad distribution of modern linear accelerators, focal irradiation of the tumor has omitted WBRT in most cases. In many studies, the effectiveness of local RT of the resection cavity, either as single-fraction stereotactic radiosurgery (SRS) or hypo-fractionated stereotactic RT (hFSRT), has been demonstrated to be effective and safe. However, whereas prospective high-level incidence is still lacking on which dose and fractionation scheme is the best choice for the patient, further ablative techniques have come into play. Neoadjuvant SRS (N-SRS) prior to resection combines straightforward target delineation with an accelerated post-surgical phase, allowing an earlier start of systemic treatment or rehabilitation as indicated. In addition, low-energy intraoperative RT (IORT) on the surgical bed has been introduced as another alternative to external beam RT, offering sterilization of the cavity surface with steep dose gradients towards the healthy brain. This consensus paper summarizes current local treatment strategies for resectable brain metastases regarding available data and patient-centered decision-making.

Optimal timing of hypofractionated stereotactic radiotherapy for epidermal growth factor receptor-mutated non-small-cell lung cancer patients with brain metastases.

For epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients with limited brain metastases (BMs), who eventually receive both tyrosine kinase inhibitors (TKIs) treatment and brain radiotherapy, the optimal timing of radiotherapy is not clear. The present retrospective analysis aimed to partly solve this problem. In total 84 EGFR-mutated NSCLC patients with limited BMs, who received both TKI treatment and brain hypofractionated stereotactic radiotherapy (HSRT), were enrolled. Patients were divided into three groups based on whether the HSRT was administrated 2 weeks before or after the beginning of TKI treatment (upfront HSRT), when intracranial lesions stabilized after TKI treatment (consolidative HSRT), or when the intracranial disease progressed after TKI treatment (salvage HSRT). The clinical efficacy and toxicities were evaluated. The median intracranial progression-free survival (iPFS) and overall PFS calculated from the initiation of HSRT (iPFS1 and PFS1) of all patients were 17.5 and 13.1 months, respectively. The median iPFS and PFS calculated from the initiation of TKI treatment (iPFS2 and PFS2) of all patients were 24.1 and 18.4 months, respectively. Compared to consolidative and salvage HSRT, upfront HSRT improved iPFS1 (not reached vs. 17.5 months vs. 11.0 months, p<0.001) and PFS1 (18.4 months vs. 9.1 months vs. 7.9 months, p<0.001), and reduced the initial intracranial failure rate (12.5%vs. 48.1%vs. 56%, p<0.001). However, there were no significant differences between the three groups for iPFS2, PFS2, and overall survival. Hepatic metastases and diagnosis-specific Graded Prognostic Assessment (ds-GPA) at 2-3 were poor prognostic factors. For patients who receive both TKI treatment and brain HSRT, the timing of HSRT does not seem to influence the eventual therapeutic effect. Further validation in prospective clinical studies is needed.