Single-fraction Stereotactic Radiosurgery Research Articles

Tumor Control Probability and Time-Dose Response Modeling for Stereotactic Radiosurgery of Uveal Melanoma

IntroductionUveal melanoma (UM), while a rare malignancy, stands as the most prevalent intraocular malignancy in adults. Controversies persist regarding the dose dependency of local control (LC) through radiotherapy. This study seeks to elucidate the significance of the prescription dose by employing time-dose response models for UM patients receiving photon-based stereotactic radiosurgery (SRS). Materials and MethodsInclusion criteria comprised UM patients treated between 2005 and 2019. All patients underwent single-fraction SRS. Datapoints were separated into three dose groups, with Kaplan-Meier analysis performed on each group, from which time-dose response models for LC were created at 2, 4, and 7 years using maximum-likelihood fitted logistic models. ResultsOutcomes from 594 patients with 594 UM were used to create time-dose response models. The prescribed doses and the number of patients were as follows: 17-19 Gy (24 patients), 20 Gy (122 patients), 21 Gy (442 patients), and 22 Gy (6 patients). Averaged over all patients and doses, LC rates at 2, 4, and 7 years were 94.4%, 88.2%, and 69.0%, respectively. Time-dose response models for LC demonstrated a dose-dependent effect, showing 2-year LC rates of more than 90% with 20 Gy and 95% with 22 Gy. For four years and a LC of 90%, a dose of approximately 21 Gy was required. After seven years, the 21 Gy prescription dose is predicted to maintain a LC above 70%, sharply declining to less than 60% LC with 19 Gy and less than 40% with 18 Gy. ConclusionIn contrast to prior findings, the time-dose response models for UM undergoing photon-based SRS emphasize the critical role of the prescription dose in achieving lasting LC. The dose selection must be carefully balanced against toxicity risks, considering tumor geometry and individual patient characteristics to tailor treatments accordingly.

Pattern of recurrence after stereotactic body radiotherapy of nodal lesions: a single-institution analysis.

Stereotactic body radiotherapy (SBRT) and/or single fraction stereotactic body radiosurgery (SRS) are effective treatment options for the treatment of oligometastatic disease of lymph nodes. Despite the encouraging local control rate, progression-free survival remains unfair due to relapses that might occur in the same district or at other sites. The recurrence pattern analysis after nodal local ablative RT (laRT) in oligometastatic patients is presented in this study. The pattern of failure of patients with nodal metastases who were recruited and treated with SBRT in the Destroy-1 or SRS in the Destroy-2 trials was investigated in this single-institution, retrospective analysis. The different relapsed sites following laRT were recorded. Data on 190 patients who received SBRT or SRS on 269 nodal lesions were reviewed. A relapse rate of 57.2% (154 out of 269 nodal lesions) was registered. The pattern of failure was distant in 88 (57.4%) and loco-regional in 66 (42.6%) patients, respectively. The most frequent primary malignancies among patients experiencing loco-regional failure were genitourinary and gynaecological cancers. Furthermore, the predominant site of loco-regional relapse (62%) was the pelvic area. Only 26% of locoregional relapses occurred contra laterally, with 74% occurring ipsilaterally. The recurrence rates after laRT for nodal disease were more frequent in distant regions compared to locoregional sites. The most common scenarios for locoregional relapse appear to be genitourinary cancer and the pelvic site. In addition, recurrences often occur in the same nodal station or in a nodal station contiguous to the irradiated nodal site. Local ablative radiotherapy is an effective treatment in managing nodal oligometastasis. Despite the high local control rate, the progression free survival remains dismal with recurrences that can occur both loco-regionally or at distance. To understand the pattern of failure could aid the physicians to choose the best treatment strategy. This is the first study that reports the recurrence pattern of a significant number of nodal lesions treated with laRT.

Response of treatment-naive brain metastases to stereotactic radiosurgery

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Improving the Efficiency of Single-Isocenter Multiple Metastases Stereotactic Radiosurgery Treatment

PurposeMultiple brain metastases can be treated efficiently with Stereotactic Radio Surgery (SRS) using a Single Isocenter Dynamic Conformal Arc (SIDCA) technique. Currently plans are manually optimized, which may lead to unnecessary table angles and arcs being used. This study aimed to evaluate an automatic 4π-optimization SIDCA algorithm for treatment efficiency and plan quality.Methods and MaterialsAutomatic 4π-optimized SIDCA plans were created and compared to the manually optimized clinical plans for 54 patients who received single-fraction SRS to 2-10 metastases. The number of table angles and arcs were compared with a paired t-test using a Bonferroni-corrected significance level of p<0.05/4=0.0125. The reduction in treatment time was estimated from the difference in the number of table angles and arcs. Plan quality was assessed through the volume-averaged inverse Paddick Conformity Index (CI) and Gradient Index (GI), and the volume of normal brain surrounding each metastasis receiving 12 Gy (local V12 Gy). For a five-patient subset the automatic plans were manually adjusted further. CI and GI were assessed for non-inferiority using a one-sided t-test with the non-inferiority limit equal to the 95% inter-observer reproducibility limit from a separate planning study (corrected significance level p<0.05/(4−1)=0.017).ResultsThe automatic plans significantly improved treatment efficiency with a mean reduction in the number of table angles and arcs of −0.5±0.1 and −1.3±0.2 respectively (± standard error, both p<0.001). Estimated treatment time saving was −2.7±0.5minutes, 14% of the total. The volume-averaged CI and GI were non-inferior to the clinical plans (both p<0.001), although there was a small systematic shift in CI of 0.07±0.01. The resulting difference in local V12 Gy, 0.25±0.04cm3, was not clinically significant. Minor manual adjustment of the automatic plans removed these slight differences whilst preserving the improved treatment efficiency.ConclusionsAutomatic 4π-optimization can generate SIDCA SRS plans with improved treatment efficiency and non-inferior plan quality.

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.

Stereotactic radiosurgery for brain metastasis from cholangiocarcinoma.

Accounting for approximately 15% of primary liver cancers and 3% of gastrointestinal malignancies, cholangiocarcinoma (CCA) poses a serious health concern given its high mortality rate. Managing brain metastases (BMs) from CCA is challenging because of their rarity and poor prognosis, with little guidance on treatment from the literature. In this study, the authors aimed to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in managing BMs from CCA. This multicenter retrospective study included 13 CCA patients with 41 BMs treated with SRS from October 2006 to April 2022 at eight institutions affiliated with the International Radiosurgery Research Foundation. Inclusion criteria were a CCA diagnosis, an age over 18 years, no other malignancies, single-fraction SRS treatment for BMs, and at least one follow-up image. Data on demographics, tumor characteristics, treatment details, and outcomes were collected. The primary endpoints were local control (LC), intracranial progression-free survival (PFS), and overall survival (OS). The secondary endpoint was the development of adverse radiation effects (AREs). The median radiological follow-up was 5 months (range 1-18 months). At the last follow-up, LC was achieved in 39 (95.1%) of 41 BMs. New distant metastases were observed in 3 patients (23.1%), and the mean intracranial PFS was 9.4 months (95% CI 6.5-12.3 months). Six-month and 1-year OS rates were 38.5% and 11.5%, respectively, and the median OS was 6 months (95% CI 4.9-7.2 months). Concurrent immunotherapy was associated with a high risk of local failure (HR 29.665, 95% CI 1.799-489.206, p = 0.018), and the absence of systemic chemotherapy before SRS was linked to reduced OS (HR 6.658, 95% CI 1.173-37.776, p = 0.032). Regarding AREs, only 1 patient (7.7%) experienced right hemiparesis and was treated with corticosteroid therapy. SRS is an effective option for managing BMs in CCA patients, showing promise in LC and a high safety profile.

220 Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

INTRODUCTION: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients [254 (50.3%) males; median (IQR) age, 34 (15) years] from 14 centers. The median clinical and MRI follow-up was 52 (61) months and 47 (52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability = 50%, 95% CI = 45%-55%). Obliteration was achieved by 300 (59.4%) patients (5-year probability = 56%, 95% CI = 51%-61%). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4cm3, subdistribution hazard [SDH] 0.61, 95% CI 0.44-0.86, p = 0.005; &gt;4 cm3, SDH 0.47, 95% CI 0.32-0.7, p &lt; 0.001) and brainstem/basal ganglia involvement (SDH = 0.6, 95% CI = 0.45-0.81, p &lt; 0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat stereotactic radiosurgery confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first three years, extending the latency period to 5 years generally increases the rate favorable patient outcomes and reduces the necessity of a third intervention.

Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas: A Multicenter Study (STORM)

PurposeThe role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM, a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas. Methods and MaterialsData on patients with recurrent grade 2 and 3 meningioma treated with SRS at first recurrence were retrospectively collected from eight academic centers in the United States. Patients with multiple lesions at the time of initial diagnosis or more than two lesions at the time of first recurrence were excluded from this analysis. Patient demographics and treatment parameters were extracted at time of diagnosis, first recurrence, and second recurrence. Oncologic outcomes including progression-free survival (PFS) and overall survival (OS) as well as toxicity outcomes were reported at the patient level. ResultsFrom 2000-2022, 108 patients were identified (94% grade 2, 6.0% grade 3). 106 patients (98%) had upfront surgical resection (60% gross-total resection) with 18% receiving adjuvant radiotherapy (RT). Median time to first progression was 2.5 years (IQR 1.34-4.30). At first recurrence, patients were treated with single or fractionated SRS to a median marginal dose of 16 Gy to a maximum of two lesions (87% received single fraction SRS). Median follow-up time after SRS was 2.6 years. 1-, 2-, and 3-year PFS was 90%, 75%, and 57%, respectively after treatment with SRS. 1-, 2-, and 3-year OS was 97%, 94%, and 92%, respectively. On multivariable analysis, grade 3 disease (HR 6.80; 95% CI 1.61-28.6), male sex (HR 3.48; 95% CI 1.47-8.26), and receipt of prior RT (HR 2.69; 95% CI 1.23-5.86) were associated with worse PFS. SRS dose and tumor volume were not correlated with progression. Treatment was well-tolerated, with a 3.0% incidence of grade 2+ radiation necrosis. ConclusionsThis is the largest multi-center study to evaluate salvage SRS in recurrent grade 2 and 3 meningiomas. In this select cohort of patients with primarily grade 2 meningioma with potentially more favorable natural history of delayed, localized first recurrence amenable to salvage SRS, local control rates and toxicity profiles were favorable, warranting further prospective validation.

Stereotactic Radiosurgery for WHO Grade 2 and 3 Oligodendroglioma: An International Multicenter Study

INTRODUCTION: Oligodendrogliomas are primary brain tumors classified as IDH-mutant and 1p19q co-deleted in the 2021 WHO Classification. Surgery, fractionated radiotherapy and chemotherapy are well established treatments for these tumors, but there are few studies evaluating the efficacy of stereotactic radiosurgery (SRS). As these tumors are less infiltrative than astrocytomas and typically recur locally, they could be appropriate for local therapy such as SRS. METHODS: This was a retrospective multicenter study performed through the International Radiosurgery Research Foundation (IRRF). Adult patients were included if they underwent single-fraction SRS for a grade 2 or 3 oligodendroglioma. The primary endpoints were overall survival and progression-free survival. Secondary endpoints included clinical evolution and occurrence of adverse radiation events or other complications. RESULTS: Eight institutions submitted data for a total of 55 patients with a median clinical follow-up of 24 months. Median age at treatment was 46 years old and median pre-treatment KPS was 90. Median treatment volume was 4cc and median marginal dose delivered was 15Gy. The KPS remained stable post-SRS in 51% and worsened in 46.7% of patients, most often due to tumor progression (73.1%). Radiation-induced changes occurred in 29.6% of which 4 patients were symptomatic. Median progression-free survival was 17 months, with actuarial rates of 60.1% at 1 year, 31% at 2 years and 24.4% at 5 years after SRS. Median overall survival post-SRS was 58 months, with actuarial rates of 91.5% at 1 year, 83.4% at 2 years and 49.3% at 5 years post-SRS. Factors significantly associated with worsened survival were WHO grade 3 and prior radiotherapy and chemotherapy. Factors significantly associated with worsened PFS were WHO grade 3, prior radiotherapy and chemotherapy and higher treatment marginal dose. CONCLUSIONS: SRS appears to be a valuable management option for oligodendrogliomas.

Hypofractionated Stereotactic Radiosurgery in the Management of Brain Metastases.

Stereotactic radiosurgery (SRS) is an important weapon in the management of brain metastases. Single-fraction SRS is associated with local control rates ranging from approximately 70% to 100%, which are largely dependent on lesion and postoperative cavity size. The rates of local control and improved neurocognitive outcomes compared with conventional whole-brain radiation therapy have led to increased adoption of SRS in these settings. However, when treating larger targets and/or targets located in eloquent locations, the risk of normal tissue toxicity and adverse radiation effects within healthy brain tissue becomes significantly higher. Thus, hypofractionated SRS has become a widely adopted approach, which allows for the delivery of ablative doses of radiation while also minimizing the risk of toxicity. This approach has been studied in multiple retrospective reports in both the postoperative and intact settings. While there are no reported randomized data to date, there are trials underway evaluating this paradigm. In this article, we review the role of hypofractionated SRS in the management of brain metastases and emerging data that will serve to validate this treatment approach. Pertinent articles and references were obtained from a comprehensive search of PubMed/MEDLINE and clinicaltrials.gov.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

31LBA (PB-012) LBA Poster - Pre-operative single-fraction stereotactic radiosurgery for early-stage breast cancer: pathological results

31LBA (PB-012) LBA Poster - Pre-operative single-fraction stereotactic radiosurgery for early-stage breast cancer: pathological results

Initial Experience With 6D Skull Tracking and Intrafractional Motion Monitoring in the United Arab Emirates' First CyberKnife® Radiosurgery Center.

Introduction The introduction of the CyberKnife® system has marked a significant advancement in the field of radiosurgery, offering unparalleled precision in targeting and treating cranial and extracranial lesions. This paper details the first experience from the United Arab Emirates in implementing 6D skull tracking and intrafractional motion monitoring in CyberKnife® radiosurgery. The study aims to evaluate the system's efficacy in tracking and adjusting patient movement during treatment, enhancing treatment accuracy and patient safety. Methods and materials This retrospective study analyzed 732 images from six patients treated at the UAE's first CyberKnife® center. Patients were divided into two groups based on their treatment regimens: Patients 1 to 4 (P1 to P4) received multifractionated stereotactic radiotherapy, while Patients 5 and 6 (P5 and P6) underwent single-fraction stereotactic radiosurgery (SRS). The movements recorded included supero-inferior, lateral, antero-posterior, roll, pitch, and yaw. Statistical tools were employed to interpret the data, including heat maps, box-and-whisker plots, and correlation analysis. Results The study's results indicate varied patterns of intrafractional movement across the different axes and between the two treatment groups. Multifractionated therapy patients exhibited a specific range and frequency of movements compared to those undergoing single-fraction treatment. The most significant movements were observed in the supero-inferior and lateral axes. Discussion The findings suggest that the CyberKnife® system's real-time tracking and adaptive capabilities are crucial in managing patient movements, especially in prolonged treatment sessions. The differences in movement patterns between multifractionated and single-fraction treatments underscore the need for tailored approaches in intrafractional motion monitoring. Conclusion The initial experience of the UAE's first CyberKnife® center demonstrates the system's effectiveness in addressing intrafractional movements, enhancing the precision and safety of radiosurgery treatments. This study contributes valuable insights into optimizing treatment protocols and underscores the importance of continuous monitoring and adaptive strategies in advanced radiosurgery.

Treatment outcomes of single-fraction stereotactic radiosurgery for adenoid cystic carcinoma: a case series of 55 patients.

This study aimed to analyze the treatment outcomes of single-fraction stereotactic radiosurgery (SRS) for adenoid cystic carcinoma patients. Retrospective analysis was conducted for 55 patients with 66 lesions. SRS intentions were categorized as definitive, adjuvant, salvage, and palliative. Tumor control was defined as local (within 50% isodose line), marginal (outside 50% isodose line), and distant (metastasis outside head/neck). The median age was 60 years (range 21-85), with 53% males. Tumor origin was head/neck for 88% and trachea/lung for 12%. 61% were recurrent lesions. Median interval from diagnosis to SRS was 14 months. Preceding surgery was performed in 30%. SRS was administered as definitive (30 lesions), adjuvant (13), salvage (19), and palliative (4). SRS was used as a boost to external beam radiation therapy (EBRT) in 39%. Concurrent chemotherapy was administered in 26%. 5-, 10-, and 15-year local control rates were 60%, 33%, and 27%, respectively; local/marginal control rates were 29%, 13%, and 10%. For recurrent lesions treated with SRS without EBRT, 5-year local control rate was 14%, and local/marginal control rate was 5%. For recurrent lesions treated with SRS and EBRT, 5-year local control rate was 100%, and local/marginal control rate was 40%. The rate of distant failure after SRS was 40%. Older age and distant metastasis before SRS were negative factors for overall survival. SRS provided a high rate of local tumor control, but marginal failure was frequent. Integrating SRS with added EBRT exhibits potential for enhancing local and local/marginal tumor control, particularly in recurrent cases.

Radiation-Induced Sensorineural Hearing Loss and Potential Management

The cochlear apparatus is one of the major organs at risk when considering radiation therapy (RT) for brain, head, and neck tumors. Radiation oncologists currently consider mean dose constraints of <35 Gy for conventionally fractioned radiation therapy (RT), <4 Gy for single fraction stereotactic radiosurgery, and <17.1 or 25 Gy for 3- or 5-fraction stereotactic radiosurgery, respectively, as the standard of care. Indeed, dose adjustments are made in the setting of concurrent platinum-based chemotherapy or when prioritizing tumor coverage during treatment planning. Despite guidelines, in many patients, RT to the cochlea may still cause sensorineural hearing loss through progressive degeneration and ossification of the inner ear. There are several audiologic and otolaryngologic interventions for incident RT-induced hearing loss, including hearing aids, cochlear implants, or, in the context of vestibular schwannoma due to neurofibromatosis type 2, auditory brain stem implantation. Cochlear implants are the most effective at restoring hearing and improving quality of life for those with an intact cochlear nerve. An early multidisciplinary approach is essential to optimally manage RT-induced hearing loss, and this topic discussion serves as a guide for radiation oncologists on cochlear dosimetric considerations as well as how to address potential RT-induced adverse effects.

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

RADT-05. SINGLE VERSUS MULTI-FRACTION STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES: RATES OF LOCAL PROGRESSION AND NECROSIS

Abstract PURPOSE For large brain metastases, it is unknown whether single fraction stereotactic radiosurgery (sSRS) or multi-fraction stereotactic radiosurgery (fSRS) is optimal. We aimed to compare rates of local progression and necrosis between sSRS and fSRS for large brain metastases. METHODS Patients with intact or resected brain metastases with a target volume ≥ 4.2 cc (corresponding to a diameter ≥ 2 cm) treated with Gamma Knife (GK) or linear accelerator-based SRS from 2014-2022 were included in this retrospective review. RESULTS A total of 343 large brain metastases in 276 patients were included; 171 lesions were treated with sSRS (96% with GK) and 172 lesions with fSRS (100% with linear accelerator). Median lesion volume was 19.8 cc and 8.4 cc for fSRS and sSRS, respectively. Resection was performed prior to SRS in 228 (66%), with the remaining 115 metastases treated intact. There was no difference in rate of local progression between sSRS versus fSRS, or between resected versus intact targets (p &amp;gt;0.8 for both). Cumulative incidence of local progression (with death as a competing risk) at 1 and 3 years for patients receiving sSRS was 24% and 30%, respectively, compared to 22% and 34% for fSRS. FSRS was associated with significantly higher rates of necrosis than sSRS (HR 5.58, 2.38-13.08, p &amp;lt; 0.001). This association remained significant after controlling for target volume. Cumulative incidence of necrosis (with death as a competing risk) at 1 and 3 years for patients receiving sSRS was 1% and 3%, respectively, compared to 10% and 18% for fSRS. Necrosis rates were significantly higher with fSRS for both intact and resected targets (P &amp;lt; 0.02 for both). CONCLUSION While local control for large resected or intact brain metastases appears similar after sSRS or fSRS, this retrospective study shows higher rates of necrosis after fSRS. Prospective validation is needed.

Single fraction and hypofractionated radiosurgery for perioptic meningiomas-tumor control and visual outcomes: a systematic review and meta-analysis.

Perioptic meningiomas, defined as those that are less than 3mm from the optic apparatus, are challenging to treat with stereotactic radiosurgery (SRS). Tumor control must be weighed against the risk of radiation-induced optic neuropathy (RION), as both tumor progression and RION can lead to visual decline. We performed a systematic review and meta-analysis of single fraction SRS and hypofractionated radiosurgery (hfRS) for perioptic meningiomas, evaluating tumor control and visual preservation rates. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed articles published between 1968 and December 8, 2022. We retained 5 studies reporting 865 patients, 438 cases treated in single fraction, while 427 with hfRS. For single fraction SRS, the overall rate of tumor control was 95.1%, with actuarial rates at 5 and 10years of 96% and 89%, respectively; tumor progression was 7.7%. The rate of visual stability was 90.4%, including visual improvement in 29.3%. The rate of visual decline was 9.6%, including blindness in 1.2%. For hfRS, the overall rate of tumor control was 95.6% (range 92.1-99.1, p < 0.001); tumor progression was 4.4% (range 0.9-7.9, p = 0.01). Overall rate of visual stability was 94.9% (range 90.9-98.9, p < 0.001), including visual improvement in 22.7% (range 5.0-40.3, p = 0.01); visual decline was 5.1% (range 1.1-9.1, p = 0.013). SRS is an effective and safe treatment option for perioptic meningiomas. Both hypofractionated regimens and single fraction SRS can be considered.

Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients.

Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently. A retrospective study was conducted through the International Radiosurgery Research Foundation. Logistic regression models and competing risks analyses were utilized to identify predictors of any grade RN and symptomatic RN (SRN). The study included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI across 11 institutions in four countries with a median follow-up of 14.2months. The median age was 67years. The median margin SRS dose was 19Gy; 36.5% of patients had a V12 Gy ≥ 10 cm3. On multivariable analysis, V12 Gy ≥ 10 cm3 was a significant predictor of developing any grade RN (OR: 2.18) and SRN (OR: 3.95). At 1-year, the cumulative incidence of any grade and SRN for all patients was 4.8% and 3.8%, respectively. For concurrent and non-concurrent groups, the cumulative incidence of any grade RN was 3.8% versus 5.3%, respectively (p = 0.35); and for SRN was 3.8% vs. 3.6%, respectively (p = 0.95). The risk of any grade RN and symptomatic RN following single fraction SRS and ICI for NSCLC brain metastases increases as V12 Gy exceeds 10 cm3. Concurrent ICI and SRS do not appear to increase this risk. Radiosurgical planning techniques should aim to minimize V12 Gy.

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.