Hypofractionated Stereotactic Radiotherapy Research Articles

Adaptive stereotactic radiosurgery for cerebral metastases of non-small cell lung cancer: a retrospective study

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cause of brain metastases (BM). Adaptive stereotactic radiosurgery (ASRS) may be a useful option in the treatment of patients with large unresectable brain metastases (BM), but to date there are only a limited number of studies evaluating the effectiveness of this method.OBJECTIVE: To analyze the effectiveness of ASRS in patients with large BM NSCLC not subject to surgical resection.MATERIAL AND METHODS: We retrospectively analyzed data from 37 patients suffering from NSCLC with 45 large (>2 cm in diameter, volume >4 cm3) unresectable BM treated with the Gamma Knife Perfexion model using two- and three-fraction ASRS. Of these, 14 foci (31.1%) were metastases of squamous cell lung cancer, 31 (68.9%) were metastases of adenocarcinoma. The median volume of lesions treated with ASRS was 9.8 (range 4.6–30.6 cm3). The dynamics of volume changes between fractions and the cumulative incidence of local relapses (CILR) were studied, and ROC analysis was performed for the tumor volume parameter. Intracranial progression-free survival (iPFS) and overall survival (OS) were assessed. Statistics: To establish statistical significance of differences for related variables, the Wilcoxon test for pairwise comparisons and the Friedman test for three or more groups were used. The Kaplan-Meier method was used to calculate local control, PFS, and OS rates. The log-rank test was used to compare survival data in two groups.RESULTS: The median follow-up period was 19.4 months. With two-fraction ASRS, the median volume of metastasis decreased by 28.6% by the second session, with three-fraction — by 40.0% by the third session. The 1-year and 2-year CILR rates were 8.6±6.1%, respectively; 26.1±12.3%. In ROC analysis, the area under the curve (AUC) for tumor volume was 0.80 (95% CI 0.6– 1.0) with an optimal cutoff of 18.5 cm3. The differences in CILR between the groups with metastasis volume <18.5 cm3 and ≥18.5 cm3 were statistically significant (p<0.001). Median iPFS was 8.3 (95% CI 5.9–10.7) months, 1-year iPFS was 33.5±8.1%;2-year — 7.8±5.2%. Median OS was 13.2 (95% CI 9.0–17.4) months; 1-year OS — 52.9±8.7%, 2-year — 22.4±8.8%.DISCUSSION: Using two- and three-fraction ASRS, we delivered doses to large BM sufficient for a high level of local control with an acceptable risk of neurotoxicity: 1-year local control was 91.4%; 2-year — 73.9%; the incidence of radionecrosis is 8.5%. A statistically significant effect of lesion volume ≥18.5 cm3 on the risk of local recurrence was found. The iPFS and OS indicators after ASRS can be considered satisfactory for this group of patients.CONCLUSION: ASRS is an effective and perhaps optimal strategy for the treatment of large unresectable BM in patients with NSCLC, but comparison with other modern radiotherapy modalities such as stereotactic hypofractionated radiotherapy and WBRT with simultaneous integrated boost is needed.

Clinical implementation of real time motion management for prostate SBRT: A radiation therapist’s perspective

Background and purposeThe adoption of hypo-fractionated stereotactic body radiotherapy (SBRT) for treating prostate cancer has led to an increase in specialised techniques for monitoring prostate motion. The aim of this study was to comprehensively review a radiation therapist (RTT) led treatment process in which two such systems were utilised, and present initial findings on their use within a SBRT prostate clinical trial. Materials and Methods18 patients were investigated, nine were fitted with the Micropos RayPilotTM (RP) system (Micropos Medical, Gothenburg, SE) and nine were fitted with the Micropos Raypilot Hypocath TM (HC) system. 36.25 Gray (Gy) was delivered in 5 fractions over 7 days with daily pre- and post-treatment cone beam computed tomography (CBCT) images acquired. Acute toxicity was reported on completion of treatment at six- and 12-weeks post-treatment, using the Radiation Therapy Oncology Group (RTOG) grading system and vertical (Vrt), longitudinal (Lng) and lateral (Lat) transmitter displacements recorded. ResultsA significant difference was found in the Lat displacement between devices (P=0.003). A more consistent bladder volume was reported in the HC group (68.03 cc to 483.7 cc RP, 196.11 cc to 313.85 cc HC). No significant difference was observed in mean dose to the bladder, rectum and bladder dose maximum between the groups. Comparison of the rectal dose maximum between the groups reported a significant result (P=0.09). Comparing displacements with toxicity endpoints identified two significant correlations: Grade 2 Genitourinary (GU) at 6 weeks, P=0.029; and no toxicity, Gastrointestinal (GI) at 12 weeks P=0.013. ConclusionBoth the directly implanted RP device and the urinary catheter-based HC device are capable of real time motion monitoring. Here, the HC system was advantageous in the SBRT prostate workflow.

Hypofractionated stereotactic radiotherapy for brain metastases in lung cancer patients: dose‒response effect and toxicity

BackgroundLung cancer is a common cause of brain metastases, approximately 40% of patients with lung cancer will develop brain metastases at some point during their disease. Hypofractionated stereotactic radiotherapy (HSRT) has been demonstrated to be effective in controlling limited brain metastases. However, there is still no conclusive on the optimal segmentation of HSRT. The aim of our study was to explore the correlation between the HSRT dosage and its treatment effect and toxicity.MethodsA retrospective analysis was conducted on patients with non-small cell lung cancer (NSCLC) brain metastasis at Hangzhou Cancer Hospital from 1 January 2019 to 1 January 2021. The number of brain metastases did not exceed 10 in all patients and the number of fractions of HSRT was 5. The prescription dose ranges from 25 to 40 Gy. The Kaplan–Meier method was used for estimation of the localised intracranial control rate (iLC). Adverse radiation effects (AREs) were evaluated according to CTCAE 5.0. This study was approved by the Institutional Ethics Review Board of the Hangzhou Cancer Hospital (#73/HZCH-2022).ResultsForty eligible patients with a total of 70 brain metastases were included in this study. The 1-year iLC was 76% and 89% in the prescribed dose ≤ 30 Gy and > 30 Gy group, respectively (P < 0.05). For patients treated with HSRT combined with targeted therapy, immunotherapy and chemotherapy, the 1-year iLC was 89%, 100%, and 45%, respectively. No significant associations were observed between the number, maximum diameter, location, and type of pathology of brain metastases. The rate of all-grade AREs was 33%. Two patients who received a total dose of 40 Gy developed grade 3 headache, the rest of the AREs were grade 1–2.ConclusionsIncreasing the prescription dose of HSRT improves treatment effect but may also exacerbate the side effects. Systemic therapy might impact the iLC rate, and individualized treatment regimens need to be developed.

Biological Insights and Radiation-Immuno-Oncology Developments in Primary and Secondary Brain Tumors.

Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts, they often cause significant mortality and morbidity across all ages. Radiotherapy (RT) remains the main treatment for brain cancers, improving associated symptoms, improving tumor control, and inducing a cure in some. However, the ultimate goal of cancer treatment, to improve a patient's survival, remains elusive for many CNS cancers, especially primary tumors. Over the years, there have thus been many preclinical studies and clinical trials designed to identify and overcome mechanisms of resistance to improve outcomes after RT and other therapies. For example, immunotherapy delivered concurrent with RT, especially hypo-fractionated stereotactic RT, is synergistic and has revolutionized the clinical management and outcome of some brain tumors, in particular brain metastases (secondary brain tumors). However, its impact on gliomas, the most common primary malignant CNS tumors, remains limited. In this review, we provide an overview of radioresistance mechanisms, the emerging strategies to overcome radioresistance, the role of the tumor microenviroment (TME), and the selection of the most significant results of radiation-immuno-oncological investigations. We also identify novel therapeutic opportunities in primary and secondary brain tumors with the purpose of elucidating current knowledge and stimulating further research to improve tumor control and patients' survival.

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.

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.

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.

Prospective Randomized Phase 2 Trial of Hypofractionated Stereotactic Radiation Therapy of 25 Gy in 5 Fractions Compared With 35 Gy in 5 Fractions in the Reirradiation of Recurrent Glioblastoma

The aim of this work was to investigate whether reirradiation of recurrent glioblastoma with hypofractionated stereotactic radiation therapy (HSRT) consisting of 35 Gy in 5 fractions (35 Gy/5 fx) compared with 25 Gy in 5 fractions (25 Gy/5 fx) improves outcomes while maintaining acceptable toxicity. We conducted a prospective randomized phase 2 trial involving patients with recurrent glioblastoma (per the 2007 and 2016 World Health Organization classification). A minimum interval from first radiation therapy of 5 months and gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS). We used a randomized phase 2 screening design with a 2-sided α of 0.15 for the primary endpoint. From 2011 to 2019, 40 patients were randomized and received HSRT, with 20 patients in each group. The median age was 50 years (range, 27-71); a new resection before HSRT was performed in 75% of patients. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P = .23). Six-month PFS was similar at 40% (85% CI, 24%-55%) for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P = .201). Grade ≥3 necrosis was numerically higher in the 35 Gy/5 fx group (3 [16%] vs 1 [5%]), but the difference was not statistically significant (P = .267). In an exploratory analysis, median OS of patients who developed treatment-related necrosis was 14.1 months, and that of patients who did not was 8.7 months (P = .003). HSRT alone with 35 Gy/5 fx was not superior to 25 Gy/5 fx in terms of PFS or OS. Due to a potential increase in the rate of clinically meaningful treatment-related necrosis, we suggest 25 Gy/5 fx as the standard dose in HSRT alone. During follow-up, attention should be given to differentiating tumor progression from potentially manageable complications.

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.

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.