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Objective: Brain arteriovenous malformations (BAVMs) represent an ongoing clinical challenge because of their complex nature. The long-term outcomes of BAVMs patients treated with stereotactic radiosurgery (SRS) alone are unclear. Methods: We conducted a retrospective analysis of 201 patients treated for BAVMs from January 2010 to December 2019. The identified predictors of obliteration or hemorrhage in the multivariate analysis were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 201 patients treated with gamma knife radiosurgery (GKRS) alone as the primary treatment for BAVMs were included. The mean age at GKRS treatment was 31.4 ± 1.1 years, and 61.2% of the patients were male. Multivariate logistic regression revealed that a higher radiosurgery-based AVM score (OR 1.847, 95% CI = 1.292–2.641; p = 0.001) was significantly associated with worse obliteration, and a higher margin dose significantly favored obliteration (OR 0.352, 95% CI = 0.189–0.658; p = 0.001). Multivariate analysis revealed that an increased lesion volume of 1 cm3 (OR 1.279, 95% CI = 1.023–1.600; p = 0.031) and a high margin dose (OR 0.363, 95% CI = 0.134–0.983; p = 0.046) were significant prognostic factors for post-SRS hemorrhage. Conclusions: In conclusion, our study investigated the available clinical and radiological prognostic factors for BAVMs and revealed that a higher margin dose significantly improved both the obliteration rate and nonhemorrhagic outcomes. Currently, the most appropriate candidates, Spetzler-Martin grade, and optimal radiation dose are still being defined by prospective trials. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the incidence and risk factors of new-onset hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenomas in a single center. Methods: In this retrospective study, 241 pituitary adenoma patients who underwent GKRS from 1993 to 2016 were enrolled. These patients had complete endocrine, imaging, and clinical data before and after GKRS. The median follow-up time was 56.0 (range, 12.7–297.6) months. Results: Fifty patients (20.7%) developed new-onset hypopituitarism after GKRS, including hypogonadism (n = 22), hypothyroidism (n = 29), hypocortisolism (n = 20), and growth hormone deficiency (n = 4). The median time to new-onset hypopituitarism was 44.1 (range, 13.5–141.4) months. The rates of new-onset hypopituitarism were 7%, 16%, 20%, 39%, and 45% at 1, 3, 5, 10, and 15 years, respectively. For those patients treated with a single GKRS, sex (p = 0.012), suprasellar extension (p = 0.048), tumor volume (≥ 5 cm3) (p < 0.001), tumor progression (p = 0.001), pre-existing hypopituitarism (p = 0.011), and previous surgery (p = 0.009) were significantly associated with new-onset hypopituitarism in univariate analysis. In the multivariate analysis, tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism (hazard ratio [HR] = 3.401, 95% confidence interval [CI] = 1.708–6.773, p < 0.001 and HR = 3.594, 95% CI = 1.032–12.516, p = 0.045, respectively). For patients who received 2 or more times GKRS, no risk factors associated with new-onset hypopituitarism were found. Conclusion: New-onset hypopituitarism was not uncommon after GKRS for pituitary adenomas. In this study, large tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism after a single GKRS. [ABSTRACT FROM AUTHOR]

Introduction: The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). Methods: In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. Discussion: This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. Trial registration: Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the indications and efficacy of gamma knife radiosurgery (GKRS) as a salvage treatment for recurrent low-and high-grade glioma. Methods: This retrospective study of 107 patients with recurrent glioma treated with GKRS between 2009 and 2022, including 68 high-grade glioma (HGG) and 39 low-grade glioma (LGG) cases. The Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). The log-rank test was used to analyze the multivariate prognosis of the Cox proportional hazards model. Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. The prognostic value of main clinical features was estimated, including histopathology, Karnofsky performance status (KPS), recurrence time interval, target location, two or more GKRS, surgery for recurrence, site of recurrence, left or right side of the brain and so on. Results: The median follow-up time was 74.5 months. The median OS and PFS were 17.0 months and 5.5 months for all patients. The median OS and PFS were 11.0 months and 5.0 months for HGG, respectively. The median OS and PFS were 49.0 months and 12.0 months for LGG, respectively. Multivariate analysis showed that two or more GKRS, left or right side of the brain and brainstem significantly affected PFS. Meanwhile, the KPS index, two or more GKRS, pathological grade, and brainstem significantly affected OS. Stratified analysis showed that surgery for recurrence significantly affected OS and PFS for LGG. KPS significantly affected OS and PFS for HGG. No serious adverse events were noted post-GKRS. Conclusion: GKRS is a safe and effective salvage treatment for recurrent glioma. Moreover, it can be applied after multiple recurrences with tolerable adverse effects. [ABSTRACT FROM AUTHOR]

Background: So far, only limited studies exist that evaluate patients with brain metastases (BM) from GI cancer and associated primary cancers who were treated by Gamma Knife Radiosurgery (GKRS) and concomitant immunotherapy (IT) or targeted therapy (TT). Methods: Survival after GKRS was compared to the general and specific Graded Prognostic Assessment (GPA) and Score Index for Radiosurgery (SIR). Further, the influence of age, sex, Karnofsky Performance Status Scale (KPS), extracranial metastases (ECM) status at BM diagnosis, number of BM, the Recursive Partitioning Analysis (RPA) classes, GKRS1 treatment mode and concomitant treatment with IT or TT on the survival after GKRS was analyzed. Moreover, complication rates after concomitant GKRS and mainly TT treatment are reported. Results: Multivariate Cox regression analysis revealed IT or TT at or after the first Gamma Knife Radiosurgery (GKRS1) treatment as the only significant predictor for overall survival after GKRS1, even after adjusting for sex, KPS group, age group, number of BM at GKRS1, RPA class, ECM status at BM diagnosis and GKRS treatment mode. Concomitant treatment with IT or TT did not increase the rate of adverse radiation effects. There was no significant difference in local BM progression after GKRS between patients who received IT or TT and patients without IT or TT. Conclusion: Good local tumor control rates and low rates of side effects demonstrate the safety and efficacy of GKRS in patients with BM from GI cancers. The concomitant radiosurgical and targeted oncological treatment significantly improves the survival after GKRS without increasing the rate of adverse radiation effects. To provide local tumor control, radiosurgery remains of utmost importance in modern GI BM management. [ABSTRACT FROM AUTHOR]

Background: Tentorial dural arteriovenous fistulas (TDAVFs) are abnormal shunts between meningeal arteries and the intradural venous system located in the tentorial dura mater, which typically manifest with haemorrhage or progressive neurological disorders. TDAVFs with pure ocular presentation have been rarely reported. Case Presentations: The case of a 56-year-old man presented with unilateral eye redness, proptosis and elevated intraocular pressure was reported herein, which was caused by a TDAVF. The fistula was fed by the left posterior cerebral artery and posterior meningeal artery. The drainage was into the basal vein and internal cerebral veins, which led the arterial blood flow forward to the left superior ophthalmic vein directly. The redundant blood flow caused the rise of episcleral venous pressure, leading to the clinical presentations. Gamma knife radiosurgery was performed then considering the delicate vascular structure and its deep location. The corkscrew hyperaemia was gradually alleviated after the surgery, but the intraocular pressure remained elevated at follow-ups. Conclusion: Dural arteriovenous fistulas which are not directly connected to cavernous sinus could cause ocular presentations like proptosis, eye redness and ocular hypertension. [ABSTRACT FROM AUTHOR]

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

Background: Stereotactic body radiotherapy (SBRT) is a novel radio-therapeutic technique that has recently emerged as standard-of-care treatment for medically inoperable, early-stage non-small cell lung cancer (NSCLC). In this study, we compared the cost-effectiveness of SBRT with that of conventional fractionated radiotherapy (CFRT) in patients with medically inoperable, early-stage NSCLC from the perspective of the Chinese health system. Methods: A Markov model was developed to describe health states of patients after treatment with SBRT and CFRT. The recurrence risks, treatment toxicities, and utilities inputs were obtained from the literature. The costs were based on listed prices and real-world evidence. A simulation was conducted to determine the post-treatment lifetime years. For each treatment, the total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) per QALY were calculated. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of the model parameters. Results: In the base case analysis, SBRT was associated with a mean cost of USD16,933 and 2.05 QALYs, whereas CFRT was associated with a mean cost of USD17,726 and 1.61 QALYs. SBRT is a more cost-effective strategy compared with CFRT for medically inoperable, early-stage NSCLC, with USD 1802 is saved for every incremental QALY. This result was validated by DSA and PSA, in which SBRT remained the most cost-effective option. Conclusions: The findings suggested that, compared to CFRT, SBRT may be considered a more cost-effective strategy for medically inoperable, early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Background: Studies of novel microsurgical adjuncts, such as 5-aminolevulinic acid (5-ALA) fluorescence have shown various fluorescence patterns within meningiomas, opening new avenues for complete microsurgical resection. Here, we present a recurrent, radiation-induced meningioma, previously operated on two occasions (initial gross total resection and subtotal 12 years later) and also irradiated by Gamma Knife radiosurgery (GKR, 6 years after the first surgery). We thought to assess the usefulness of 68−Ga Dotatoc in surgical target planning and of 5-ALA as an adjunct for maximal microsurgical excision. Case report: We report on a 43 years-old Caucasian male diagnosed with atypical, radiation induced WHO II meningioma, with left basal temporal bone implantation. Hodgkin lymphoma treated with cranial and mediastinal radiation during infancy marked his personal history. He underwent a first gross total microsurgical resection, followed 6 and 12 years later by Gamma Knife radiosurgery (GKR) and second subtotal microsurgical resection, respectively. Magnetic resonance imaging (MRI) displayed new recurrence 13 years after initial diagnosis. He was clinically asymptomatic but routine Magnetic resonance imaging showed constant progression. There was strong 68−Ga Dotatoc uptake. We used 5-ALA guided microsurgical resection. Intraoperative views confirmed strong fluorescence, in concordance with both preoperative Magnetic resonance imaging enhancement and 68−Ga Dotatoc. The tumor was completely removed, with meningeal and bone resection. Conclusion: The authors conclude that fluorescence-guided resection using 5-ALA is useful for recurrent atypical, radiation-induced meningioma even despite previous irradiation and multiple recurrences. [ABSTRACT FROM AUTHOR]

Background: Data on acute toxicities after stereotactic radiotherapy (SRT) for brain metastases, including multiple and large lesions, are lacking. We aimed to evaluate the incidence and nature of toxicities immediately after SRT using a linear accelerator. Methods: This retrospective study reviewed the medical records of 315 patients with brain metastases treated with SRT at our institution between May 2019 and February 2022. In total, 439 SRT sessions were performed for 2161 brain metastases. The outcome of interest was immediate side effects (ISEs), defined as new or worsening symptoms occurring during SRT or within 14 days after the end of SRT. Results: Grade ≥ 2 and ≥ 3 ISEs occurred in 16 (3.6%) and 7 (1.6%) cases, respectively. Among 63 treatments for 10 or more lesions (range: 10–40), 1 (1.6%) ISE occurred. Among 22 treatments for lesions with a maximum tumor volume of > 10 cc, 2 (9.1%) ISEs occurred. Grade ≥ 3 ISEs included 1, 4, 1, and 1 cases of grade 3 nausea, grade 3 new-onset partial and generalized seizures, grade 3 obstructive hydrocephalus, and grade 5 intracranial hemorrhage, respectively. ISEs were more common in patients with a larger maximum tumor volume, primary sites other than lung and breast cancer, and pre-treatment neurological symptoms. Conclusion: SRT using a linear accelerator for brain metastases, including multiple and large lesions, is safe, with a low incidence of ISEs. Serious complications immediately after SRT are rare but possible; therefore, careful follow-up is necessary after treatment initiation. [ABSTRACT FROM AUTHOR]

Background: Long-term follow-up using volumetric measurement could significantly assist in the management of vestibular schwannomas (VS). Manual segmentation of VS from MRI for treatment planning and follow-up assessment is labor-intensive and time-consuming. This study aims to develop a deep learning technique to fully automatically segment VS from MRI. Methods: This study retrospectively analyzed MRI data of 737 patients who received gamma knife radiosurgery for VS. Treatment planning T1-weighted isotropic MR and manually contoured gross tumor volumes (GTV) were used for model development. A 3D convolutional neural network (CNN) was built on ResNet blocks. Spatial attenuation and deep supervision modules were integrated in each decoder level to enhance the training for the small tumor volume on brain MRI. The model was trained and tested on 587 and 150 patient data, respectively, from this institution (n = 495) and a publicly available dataset (n = 242). The model performance were assessed by the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), average symmetric surface (ASSD) and relative absolute volume difference (RAVD) of the model segmentation results against the GTVs. Results: Measured on combined testing data from two institutions, the proposed method achieved mean DSC of 0.91 ± 0.08, ASSD of 0.3 ± 0.4 mm, HD95 of 1.3 ± 1.6 mm, and RAVD of 0.09 ± 0.15. The DSCs were 0.91 ± 0.09 and 0.92 ± 0.06 on 100 testing patients of this institution and 50 of the public data, respectively. Conclusions: A CNN model was developed for fully automated segmentation of VS on T1-Weighted isotropic MRI. The model achieved good performance compared with physician clinical delineations on a sizeable dataset from two institutions. The proposed method potentially facilitates clinical workflow of radiosurgery for VS patient management. [ABSTRACT FROM AUTHOR]

Background: Adrenal insufficiency is a life-threatening condition, and advanced gastric cancer is associated with very poor prognosis. Adrenalectomy and/or metastatic invasion of the adrenal glands can cause primary adrenal insufficiency, which in turn can present with symptoms mimicking advanced cancer. Case presentation: Herein we report of a 68-year-old White male with a history of left adrenalectomy in conjunction with distal gastrectomy due to gastric adenocarcinoma. At the 2-year follow-up visit after cancer surgery, the patient presented with fatigue, unintentional weight loss, hyperkalemia, and a computed tomography scan with a right adrenal mass. Primary adrenal insufficiency caused by gastric cancer metastatic invasion of the remaining right adrenal gland was established and glucocorticoid therapy initiated. The patient received first line palliative chemotherapy with systemic disease control and subsequent stereotactic body radiotherapy to the right adrenal gland. More than 17 months after pathology-confirmed gastric cancer relapse, there is no clinical nor radiological evidence of active malignant disease and the patient is doing well on glucocorticoid replacement therapy. Conclusions: This case does not only illustrate the importance of prompt and correct clinical management of adrenal insufficiency, but also that selected patients with advanced gastric cancer can gain from and achieve long-term survival using a multimodal treatment approach. [ABSTRACT FROM AUTHOR]

Background: Comparative prospective data regarding different radiosurgery (SRS) modalities for treating brain metastases (BMs) from solid tumors are not available. To investigate with a single institute phase III randomized trial whether SRS executed with linac (Arm-B) is superior to a dedicated multi-source gamma-ray stereotactic platform (Arm-A). Methods: Adults patients with 1–4 BMs from solid tumors up to 30 mm in maximum diameter were randomly assigned to arms A and B. The primary endpoint was cumulative incidence of symptomatic (grade 2–3) radionecrosis (CIRN). Secondary endpoints were local progression cumulative incidence (CILP), distant brain failure, disease-free survival (DFS), and overall survival (OS). Results: A total of 251 patients were randomly assigned to Arm-A (121) or Arm-B (130). The 1-year RN cumulative incidence was 6.7% in whole cohort, 3.8% (95% CI 1.9–7.4%) in Arm-B, and 9.3% (95% CI 6.2–13.8%) in the Arm-A (p = 0.43). CIRN was influenced by target volume irradiated only for the Arm-A (p << 0.001; HR 1.36 [95% CI 1.25–1.48]). Symptomatic RN occurred in 56 cases at a median time of 10.3 months (range 1.15–54.8 months), 27 in the Arm-B at a median time of 15.9 months (range 4.9–54.8 months), and 29 in the Arm-A at a median time of 6.9 months (1.2–32.3 months), without statistically significant differences between the two arms. No statistically significant differences were recorded between the two arms in CILP, BDF, DFS or OS. The mean beam-on time to deliver SRS was 49.0 ± 36.2 min in Arm-A, and 3.1 ± 1.6 min in Arm-B. Conclusions: Given the technical differences between the treatment platforms investigated in this single-institution study, linac-based SRS (Arm-B) did not lead to significantly lower grade 2–3 RN rates versus the multi-source gamma-ray system (Arm-A) in a population of patients with limited brain metastases of small volume. No significant difference in local control was observed between both arms. For Arm-B, the treatment delivery time was significantly lower than for Arm-A. Trial registration: ClinicalTrials.gov Identifier NCT02355613. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative radiotherapy (SABR) is recommended as first-choice treatment to inoperable early-stage non-small cell lung cancer (NSCLC). However, it is not widely adopted in developing countries, and its cost-effectiveness is unclear. We aimed to perform a systematic review of full economic evaluations (EE) that compared SABR with other radiotherapy or surgical procedures to assess the results and methodological approach. Methods: The protocol was registered on PROSPERO (CRD42021241640). We included full EE studies with early-stage NSCLC in which one group was submitted to SABR. Studies that were partial EE, included advanced NSCLC or other neoplasm were excluded. We performed the last search on June 2021 in Medline, EMBASE and other databases. The reporting quality were assessed by CHEERS checklist. The main characteristics of each study were tabulated, and the results were presented by a narrative synthesis. Results: We included nine studies. Three compared radiotherapy techniques, in which SABR was found to be dominant or cost-effective. Six compared SABR with surgery, and in this group, there was not a unanimous decision. All included only direct healthcare costs but varied about categories included. The parameters used in the model-based studies were highly heterogeneous using mixed data from various sources. The items properly reported varied from 29 to 67%. Conclusions: The studies were all from developed countries and lacked in reporting quality. We recommend that developing countries produce their own studies. More strict alignment to reporting guidelines and use of robust evidence as model parameters are also advised. [ABSTRACT FROM AUTHOR]

Background: Stereotactic radiosurgery (SRS) is the preferred treatment for vestibular schwannoma (VS) in patients with preserved hearing and tumour diameter < 3 cm. Emerging evidence suggests restricting cochlear dose could preserve hearing. This retrospective replanning study aims to compare dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for superiority of cochlear dose sparing without compromising tumour coverage. Methods: Eligibility criteria included sporadic VS, serviceable hearing and availability of CT and MRI for planning. The original gross tumour volume and brainstem OAR volume were retained; the cochlea was newly contoured on the planning CT scan (bone window). Each case was replanned using the three above techniques, prescribing 12 Gy to the 80% isodose line. No dose constraint was applied to the cochlea. Results: Eighteen patients were replanned. Mean tumour volume was 2.25 cc. Tumour coverage and tumour mean dose (DCAT: 14.2, IMRT: 14.6, VMAT: 14.5 Gy) were comparable. Paddick and RTOG conformity indices were better for DCAT (0.66 and 1.6) and VMAT (0.69 and 1.5) compared to IMRT (0.56 and 1.9). DCAT had superior gradient index (3.0) compared to VMAT (3.4) and IMRT (3.4). VMAT delivered the lowest mean brainstem maximum dose (8.3 Gy) and decreased the mean cochlear dose (3.4 Gy) by 2.3 and 2.1 Gy, and the mean cochlear maximum dose (3.6 Gy) by 2.4 and 2.5 Gy relative to DCAT and IMRT, respectively. Conclusion: LINAC-based SRS treatment using VMAT can achieve better cochlear dose sparing than DCAT or IMRT while maintaining tumour coverage. [ABSTRACT FROM AUTHOR]

Background: Vestibular schwannomas are benign tumours for which various treatments are available. We performed a systematic review of prospective controlled trials comparing the patient-relevant benefits and harms of single-fraction stereotactic radiosurgery (sfSRS) with microsurgical resection (MR) in patients with vestibular schwannoma. Methods: We searched for randomized controlled trials (RCTs) and non-randomized prospective controlled trials in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: 09/2021) and also screened reference lists of relevant systematic reviews. Manufacturers were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome. We assessed the risk of bias (high or low) at the study and outcome level. If feasible, meta-analyses were performed. We graded the results into different categories (hint, indication, or proof of greater benefit or harm). Results: We identified three non-randomized prospective controlled trials of generally low quality with evaluable data on 339 patients with unilateral vestibular schwannoma. There was an indication of greater benefit of sfSRS compared with MR for facial palsy (OR 0.06, 95% CI 0.02–0.21, p < 0.001, 2 studies), hearing function (no pooled estimate available, 2 studies), and length of hospital stay (no pooled estimate available, 2 studies). We found no clinically relevant differences for mortality, vertigo, headaches, tinnitus, balance function, work disability, adverse events, and health-related quality of life. Conclusions: Our systematic review indicates that sfSRS has greater benefits than MR in patients with unilateral vestibular schwannoma. However, it is unclear whether this conclusion still holds after 2 years, as long-term studies are lacking. It is also unclear whether the effects of sfSRS are similar in patients with bilateral vestibular schwannomas. Long-term prospective studies including patients with this condition would therefore be useful. Systematic review registration: The full (German language) protocol and report (Commission No. N20-03) are available on the institute's website: www.iqwig.de/en/projects/n20-03.html [ABSTRACT FROM AUTHOR]

Background: Primary treatment of central neurocytomas is surgical resection. Gamma Knife surgery is considered a valuable therapeutic option in case of residual (after subtotal resection) or recurrent central neurocytomas. Here, we focused on the role of F-18 fluroethyltyrosine as a marker to document tumor progression after initial resection, in the context of an atypical central neurocytoma. We also describe MIB-1's role in evaluating therapeutic decision-making.Case Presentation: Two patients with central neurocytomas were treated by Gamma Knife surgery in our center. The first case (31-year-old Caucasian male) had atypical central neurocytoma. Four and a half years after surgical resection, magnetic resonance imaging and F-18 fluroethyltyrosine documented clear progression of residual central neurocytoma, further treated by Gamma Knife surgery (18 Gy at 50%, target volume 1.4 cc, and prescription isodose volume 1.8 cc). The initial post-Gamma Knife surgery clinical course was uneventful, with progressive volumetric reduction of residual tumor up to 4.5 years, when out-of-field recurrence was suspected and confirmed by local F-18 fluroethyltyrosine hyperactivity. Second single-fraction Gamma Knife surgery was performed (18 Gy at 50%, target volume 0.49 cc, prescription isodose volume 0.72 cc). The second (32-year-old Caucasian female) had previous subtotal resection and typical central neurocytoma. Seven years later, she had residual tumor progression. Single-fraction Gamma Knife surgery was performed (16 Gy at 50% isodose line, target volume 1.7 cc, and prescription isodose volume 2.5 cc). Last follow-up showed tumor volume reduction. Follow-up magnetic resonance imaging showed important volumetric reduction of both treated lesions.Conclusions: In atypical central neurocytomas, F-18 fluroethyltyrosine could be used as postoperative examination to detect small tumor remnants, follow-up evaluation following the Gamma Knife surgery or, in select cases, following surgical resection. The role of MIB-1 is important in therapeutic decision-making, as tumors with MIB-1 exceeding 2% are characterized by more aggressive clinical course. Single-fraction Gamma Knife surgery remains a valuable therapeutic option for postoperative residual atypical central neurocytomas and central neurocytoma recurrences. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to evaluate the curative effect and safety of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC) patients with inferior vena cava (IVCTT) and right atrial tumor thrombus (RATT).Methods: This retrospective study included fifteen advanced HCC patients with IVCTT and RATT who were treated with SBRT between 2013 and 2020. The prescribed dose delivered to the tumor was 45-50 Gy/7-10 fx. We report their treatment responses according to survival time and toxicities.Results: For these patients, the median follow-up time was 15 months (2-52 months). Local tumor control rates of the treated area were 80% at the time of death or at the last follow-up. The 6-month, 12-month, 18-month and 24-month OS rates were 80.0%, 60.0%, 33.3% and 26.7%, respectively. None of these patients died from the toxicity outcomes and complications of SBRT.Conclusion: SBRT is an effective option for advanced HCC patients with IVCTT and RATT. [ABSTRACT FROM AUTHOR]

Purpose: Gamma knife radiosurgery (GK) is a commonly used approach for the treatment of intracranial lesions. Its radiation response is typically not immediate, but delayed. In this study, we analyzed cases from a prospectively collected database to assess the influence of COVID-19 pandemic on the decision making in patients treated by gamma knife radiosurgery. Methods: From January 2019 to August 2021, 540 cases of intracranial lesions were treated by GK with 207 cases before COVID-19 pandemic as a control. During the COVID-19 pandemic, 333 cases were similarly treated on patients with or without the COVID-19 vaccination. All the GK treated parameters as well as time profile in the decision making were analyzed. The parameters included age, sex, characteristic of lesion, targeted volume, peripheral radiation dose, neurological status, Karnofsky Performance Status (KPS), time interval from MRI diagnosis to consultation, time interval from the approval to treatment, frequency of outpatient department (OPD) visit, and frequency of imaging follow-up. Results: Longer time intervals from diagnosis to GK consultation and treatment were found in the pandemic group (36.8 ± 25.5/54.5 ± 27.6 days) compared with the pre-COVID control (17.1 ± 22.4/45.0 ± 28.0 days) or vaccination group (12.2 ± 7.1/29.6 ± 10.9 days) (p < 0.001, and p < 0.001, respectively). The fewer OPD visits and MRI examinations also showed the same trends. High proportion of neurological deficits were found in the pandemic group (65.4%) compared with the control (45.4%) or vaccination group (58.1%) (p < 0.001). The Charlson comorbidity in the pandemic group was 3.9 ± 3.3, the control group was 4.6 ± 3.2, and the vaccination group was 3.1 ± 3.1. There were similar inter-group difference (p < 0.001). In multiple variant analyses, longer time intervals from the diagnosis to consultation or treatment, OPD frequency and MRI examination were likely influenced by the status of the COVID-19 pandemic as they were alleviated by the vaccination. Conclusions: The decision making in patients requiring gamma knife treatment was most likely influenced by the status of the COVID-19 pandemic, while vaccination appeared to attenuate their hesitant behaviors. Patients with pre-treatment neurological deficits and high co-morbidity undergoing the gamma knife treatment were less affected by the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with overall survival remaining poor despite ongoing efforts to explore new treatment paradigms. Given these outcomes, efforts have been made to shorten treatment time. Recent data report on the safety of CyberKnife (CK) fractionated stereotactic radiosurgery (SRS) in the management of GBM using a five-fraction regimen. The latest Gamma Knife (GK) model also supports frameless SRS, and outcomes using GK SRS in the management of primary GBM have not yet been reported.Objective: To report on the feasibility of five-fraction SRS with the GammaKnife ICON in the management of newly diagnosed GBM.Methods: In this single institutional study, we retrospectively reviewed all patients from our medical center from January 2017 through December 2021 who received fractionated SRS with Gamma Knife ICON for newly diagnosed GBM. Patient demographics, upfront surgical margins, molecular subtyping, radiation treatment volumes, systemic therapies, and follow-up imaging findings were extracted to report on oncologic outcomes.Results: We identified six patients treated within the above time frame. Median age at diagnosis was 73.5 years, 66% were male, and had a median Karnofsky Performance Status (KPS) of 70. All tumors were IDH wild-type, and all but one were MGMT methylated and received concurrent temozolomide (TMZ). Within this group, progression free survival was comparable to that of historical data without significant radiation-induced toxicities.Conclusion: Gamma Knife ICON may be discussed as a potential treatment option for select GBM patients and warrants further investigation in the prospective setting. [ABSTRACT FROM AUTHOR]

Background: Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke in young adults, which can lead to severe neurological impairment. The registry of Multimodality treatment for brain ArTeriovenous malformation in mainland CHina (MATCH) is a national prospective registry to identify the natural history of AVMs in Asian population; to investigate traditional and emerging hemorrhagic predictors; and to explore the superiority of the multidisciplinary assessment in improving the long-term outcomes. Methods: Consecutive AVM patients will be enrolled from 52 participating hospitals in mainland China. Baseline demographic, clinical and imaging data will be collected prospectively. Conservation, microsurgery, embolization, stereotactic radiosurgery (SRS), and multimodal strategies are all included in this study. Patients will be divided into experimental and control group according to whether the treatment protocols are formulated by multidisciplinary team. Neurofunctional status, subsequent hemorrhage, seizure, and novel neurofunctional deficit will be queried at 3 months, annually (1 and 2 years), 3 years, and 10 years follow-up. Results: Between August 2011 and April 2021, 3241 AVMs were enrolled in 11 participating sites. Among them, 59.0% were male with an average age of 28.4 ± 14.6 years, 61.2% had rupture history and 2268 hemorrhagic events occurred before admission. The median Spetzler-Martin grade and Lawton-Young grade was 3 and 5, respectively. Microsurgery is the dominant strategy (35.7%), with a similar proportion of embolization, SRS, and a combination of both (12.7%; 14.8%; 11.8%; respectively). Among them, 15.43% underwent multidisciplinary assessment and received standardized treatment. At the most recent follow-up, 7.8% were lost and the median follow-up duration was 5.6 years. Conclusions: The MATCH study is a large-sample nationwide prospective registry to investigate multimodality management strategy for AVMs. Data from this registry may also provide the opportunity for individualized risk assessment and the development of optimal individual management strategies. Trial registration: ClinicalTrials.gov Registry (NCT04572568). [ABSTRACT FROM AUTHOR]

Purpose: Linac stereotactic radiosurgery (SRS) is gaining popularity as a form of radiation treatment for cerebral arteriovenous malformations (AVMs) since the theory of combined radiosurgical and endovascular treatment poses much uncertainty and due to significant technical progress for SRS. This study focuses on how to evaluate obliteration and re-bleeding rates, and to determine factors and adverse effects influencing obliteration after linac-based SRS for cerebral AVMs.Material and Methods: From a statistical record of 71 patients, 31 had partial embolisation, five surgery and 29 had no prior treatment. Using Kaplan-Meier survival and life table analyses, actuarial obliteration and annual bleeding hazard rates were calculated after SRS.Results: After a follow up of 1, 2 and 3 years the actual obliteration rates were 22, 59 and 66%, respectively whereby it was noted that prior embolization had no effect on the obliteration rate. Annual bleeding hazard rates were further analyzed after stereotactic radiosurgery to be 2.1% and 1.4% for the first and second year respectively. Asymptomatic abnormalities were detected after imaging in 33.9% of patients. A dose of less than 18 Gy significantly reduced the obliteration probability.Conclusion: SRS is a therapeutic option for intracerebral AVM. In general, there is a low rate of morbidity and a high probability of nidus obliteration. [ABSTRACT FROM AUTHOR]

Background: The standard therapy for brain metastasis was surgery combined with whole brain radiotherapy (WBRT). The latter is however, associated with important neurocognitive toxicity. To reduce this toxicity, postoperative stereotactic radiosurgery (SRS) is a promising technique. We assessed the efficacy and the tolerance to postoperative Gamma Knife radiosurgery (GK) on the tumor bed after resection of brain metastases.Methods: Between February 2011 and December 2016, following macroscopic complete surgical resection, 64 patients and 65 surgical cavities were treated by GK in our institution. The indication for adjuvant radiosurgery was a multidisciplinary decision. The main assessment criteria considered in this study were local control, intracranial metastasis-free survival (ICMFS), overall survival and toxicity.Results: Median follow-up: 11.1 months. Median time between surgery and radiosurgery: 35 days. Median dose was 20 Gy prescribed to the 50% isodose line, for a median treated volume of 5.6 cc. Four patients (7%) suffered from local recurrence. Local recurrence-free, intracranial recurrence-free and overall survival at 1 year were 97.5%, 57.6% and 62.4% respectively. In total, 23 patients (41%) suffered from intracranial recurrence outside the tumor bed. In univariate analysis: concomitant GK treatment of multiple lesions and the tumor bed was associated with a decrease in ICMFS (HR = 1.16 [1.005-1.34] p = 0.04). In multivariate analysis: a non-lung primary tumor was significantly associated with a decrease in ICMFS (HR = 8.04 [1.82-35.4] p = 0.006). An increase in performance status (PS) and in the initial number of cerebral metastases significantly reduced overall survival (HR = 5.4 [1.11-26.3] p = 0.037, HR = 2.7 [1.004-7.36] p = 0.049, respectively) and One radiation necrosis histologically proven.Conclusion: Our study confirmed that postoperative GK after resection of cerebral metastases is an efficient and well-tolerated technique, to treat volumes of all sizes (0.8 to 40 cc). Iterative SRS or salvage WBRT can be performed in cases of intracranial relapse, postponing WBRT with its potential side effects. [ABSTRACT FROM AUTHOR]

Background: The CyberKnife Xsight lung-tracking system (XLTS) provides an alternative to fiducial-based target-tracking systems (FTTS) for non-small-cell lung cancer (NSCLC) patients without invasive fiducial insertion procedures. This study provides a method for 3D independent dosimetric verification of the accuracy of the FTTS compared to the XLTS without relying on log-files generated by the CyberKnife system.Methods: A respiratory motion trace was taken from a 4D-CT of a real lung cancer patient and applied to a modified QUASAR™ respiratory motion phantom. A novel approach to 3D dosimetry was developed using Gafchromic EBT3 film, allowing the 3D dose distribution delivered to the moving phantom to be reconstructed. Treatments were planned using the recommended margins for one and three fiducial markers and XLTS 2-view, 1-view and 0-view target-tracking modalities. The dose delivery accuracy was analysed by comparing the reconstructed dose distributions to the planned dose distributions using gamma index analysis.Results: For the 3%/2 mm gamma criterion, gamma passing rates up to 99.37% were observed for the static deliveries. The 3-fiducial and 1-fiducial-based deliveries exhibited passing rates of 93.74% and 97.82%, respectively, in the absence of target rotation. When target rotation was considered, the passing rate for 1-fiducial tracking degraded to 91.24%. The passing rates observed for XLTS 2-view, 1-view and 0-view target-tracking were 92.78%, 96.22% and 76.08%, respectively.Conclusions: Except for the XLTS 0-view, the dosimetric accuracy of the XLTS was comparable to the FTTS under equivalent treatment conditions. This study gives us further confidence in the CyberKnife XLTS and FTTS systems. [ABSTRACT FROM AUTHOR]

Background: Stereotactic irradiation is one of the treatment modalities for intraocular uveal melanoma. The study's purpose was to describe the background of stereotactic one-day session radiosurgery, how the comparison in the difference between the tumor volume measured values from the magnetic resonance imaging (MRI) method and the ultrasound method was related to it, and which method was more precise to be used for tumor regression after irradiation.Methods: The group of 147 patients with choroidal melanoma was treated by stereotactic irradiation on the linear accelerator with a single dose of 35.0 Gy. During the standard treatment process the uveal melanoma volumes, needed for dose calculation, were obtained using MRI from the individual stereotactic planning scheme and by ultrasound from the ultrasound device. All volumes were statistically compared using the paired t-test, and for the visualization purpose, the Bland-Altman plot was used.Results: In the group of patients, it was 70 (47.6%) males and 77 (52.4%) females. The tumor volume median was from MRI equal to 0.44 cm3 and from ultrasound equal to 0.53 cm3. The difference between the ultrasound and the MRI volume measured values was statistically significant. However, the Bland-Altman plot clearly documents that the two methods are in agreement and can be used interchangeably. In most of the cases, the measured values of the ultrasound-calculated volume achieved slightly higher measured values.Conclusions: The calculation of the intraocular uveal tumor volume is a crucial part of the stereotactic irradiation treatment. The ultrasound volume measured values were in most of the cases higher than the measured values from the MRI. Although the methods are comparable and can be used interchangeably, we are recommending using the more precise MRI method not only during the treatment but also on later regular medical checks of tumor regression or progression. [ABSTRACT FROM AUTHOR]

Purpose: To report the use of short-term perfluorocarbon liquid (ST-PFCL) tamponade following choroidal melanoma endoresection. Methods: Patients with medium to large choroidal melanomas not amenable to primary Ruthenium-106 brachytherapy underwent choroidal melanoma endoresection following gamma knife radiosurgery. During surgery, a complete vitrectomy was performed followed by PFCL injection, then a retinectomy with endoresection of the melanoma and underlying choroid was done. Complete PFCL filling was then achieved, and laser barrage surrounding the retinectomy was done. A Ruthenium-106 plaque was then inserted. Postoperatively, supine positioning was maintained for three days followed by plaque and PFCL removal with silicone oil injection. Several months later, silicone oil was removed. Results: Four eyes of 4 patients underwent endoresection with ST-PFCL tamponade. Mean height of tumor was 8.6 ± 0.85 mm, while mean maximal basal diameter was 11.5 ± 1.1 mm. Mean preoperative logMAR best corrected visual acuity (BCVA) was 1.76 ± 0.18. All patients underwent preoperative gamma knife radiosurgery and postoperative brachytherapy. There were no major intraoperative or postoperative complications. All patients underwent silicone oil injection with PFCL/plaque removal after 3 days, while silicone oil was removed after 4 ± 1.2 months. Mean postoperative logMAR BCVA 3 months following oil removal was 0.89 ± 0.22 (p = 0.02). Mean follow-up duration was 17 ± 2.8 months. No patient developed local tumor recurrence, distant metastases, or vitreoretinal complications by final visit. Conclusion: ST-PFCL tamponade may reduce the risk of intraoperative and postoperative complications associated with choroidal melanoma endoresection. [ABSTRACT FROM AUTHOR]

Background: Unplanned reoperation (UR) after radical surgery for oral cancer (OC) is a health threat for the patients. The aim of the study was to identify the incidence of and risk factors for unplanned reoperation following oral cancer radical surgery, and to explore a potential role for long-term survival. Methods: The present study followed a retrospective study design. Univariate and multivariate analyses were used to identify risk factors for demographic and clinical characteristics of patients. Survival analysis was performed by the Kaplan–Meier method. The data was analyzed statistically between November and December 2021. Results: The incidence of UR was 15.7%. The primary cause of UR was reconstructed flap complications. Multivariate logistic regression analyses revealed that diabetes, tumor size, type of reconstruction, and nodal metastasis were independent risk factors for UR. Patients undergoing UR had a longer hospitalization, more post-operative complications, and a higher mortality compared with the non-UR group. UR is negatively correlated with the cancer-specific survival rate of patients (Log-rank test, P = 0.024). Conclusion: Diabetes, tumor size, pedicled flap reconstruction and cervical nodal metastasis (N2) as independent risk factors for UR was discovered. UR was positively correlated with perioperative complications prolong hospital stay, and increased early mortality, but negatively correlated with the cancer-specific survival rate survival rate. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To report results from our phase II study of stereotactic body radiotherapy (SBRT) delivering 36 Gy in 4 fractions for patients with localized prostate cancer.Materials/methods: We enrolled 55 patients treated with SBRT delivering 36 Gy in 4 fractions between 2015 to 2018. All patients were categorized as low-risk (n = 4), intermediate-risk (n = 31) or high-risk (n = 20) according to National Comprehensive Cancer Network criteria. Median age was 73 years (range 54-86 years). Two-thirds of patients (n = 37) had received androgen-deprivation therapy for 3-46 months (median, 31 months). Median duration of follow-up was 36 months (range 1-54 months). We used Radiation Therapy Oncology Group and National Cancer Institute-Common Toxicity Criteria version 4 for toxicity assessments. Quality of life (QOL) outcomes were also evaluated using the Expanded Prostate Cancer Index Composite (EPIC).Results: Protocol treatments were completed for all patients. Six patients experienced biochemical failures. Among these six patients, three patients experienced clinical failure. One patient showed bone metastasis before biochemical failure. One patient died of gastric cancer. The 3-year biochemical control rate was 89.8%. Acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were observed in 5 patients (9%) and 6 patients (11%), respectively. No grade 3 or higher acute toxicities were observed. Late grade 2 GU and GI toxicities were observed in 7 patients (13%) and 4 patients (7%), respectively. Late grade 3 GU and GI toxicities were observed in 1 patient (1.8%) each. EPIC scores decreased slightly during the acute phase and recovered within 3 months after treatment.Conclusion: Our phase II study showed that SBRT delivering 36 Gy in 4 fractions was safe and effective with favorable QOL outcomes, although this regimen showed slightly more severe toxicities compared to current standards. [ABSTRACT FROM AUTHOR]

Background: Treatment decision for recurrent symptomatic brain metastases (BM) is challenging with scarce data regarding surgical resection. We therefore evaluated the efficacy of surgery for pretreated, recurrent BM in a comprehensive multidisciplinary treatment setting.Methods: In a retrospective single center study, patients were analyzed, who underwent surgical resection of recurrent BM between 2007 and 2019. Intracranial event-free survival (EFS) and overall survival (OS) were evaluated by Kaplan-Maier and Cox regression analysis.Results: We included 107 patients with different primary tumor entities and individual previous treatment for BM. Primary tumors comprised non-small cell lung cancer (NSCLC) (37.4%), breast cancer (19.6%), melanoma (13.1%), gastro-intestinal cancer (10.3%) and other, rare entities (19.6%). The number of previous treatments of BM ranged from one to four; the adjuvant treatment modalities comprised: none, focal or whole brain radiotherapy, brachytherapy and radiosurgery. The median pre-operative Karnofsky Performance Score (KPS) was 70% (range 40-100) and improved to 80% (range 0-100) after surgery. The complication rate was 26.2% and two patients died during the perioperative period. Sixty-seven (62.6%) patients received postoperative local radio-oncologic and/or systemic therapy. Median postoperative EFS and OS were 7.1 (95%CI 5.8-8.2) and 11.1 (95%CI 8.4-13.6) months, respectively. The clinical status (postoperative KPS ≥ 70 (HR 0.27 95%CI 0.16-0.46; p < 0.001) remained the only independent factor for survival in multivariate analysis.Conclusions: Surgical resection of recurrent BM may improve the clinical status and thus OS but is associated with a high complication rate; therefore a very careful patient selection is crucial. [ABSTRACT FROM AUTHOR]

Background: The abscopal effect is a phenomenon in which a tumor located far from irradiated lesions regresses. We have experienced a case in which both intracranial and extracranial lesions showed an abscopal effect after radiotherapy for spinal metastases of unknown primary. We report the differential abscopal effect in extracranial and intracranial lesions. Case presentation: A 57-year-old Japanese man was diagnosed with multiple lung nodules, bone metastases, and brain metastases. The results of pathological examination at the previous hospital he visited suggested adenocarcinoma of the lung. However, there was a possibility that the biopsy specimen was inadequate. Radiation therapy was performed on the ninth thoracic vertebra for a total dose of 39 Gy in 13 fractions because the lesion in the ninth thoracic vertebra was destructively extending. After thorough examination, the primary lesion could not be identified, and we made diagnosis of cancer of unknown primary. The patient did not want to receive systemic chemotherapy; however, all of the lesions except for the brain metastases had spontaneously shrunk 2 months after radiation therapy. Although the brain metastases had partially shrunk, whole-brain radiotherapy for a total dose of 36 Gy in 12 fractions was performed. Fifteen months after initial radiation therapy, the brain metastasis recurred, and Gamma Knife radiosurgery was additionally performed. The brain metastases disappeared after the radiosurgery. During a period of 30 months after radiation therapy for the ninth vertebra, the lesions of the trunk all maintained their shrinkage without systemic chemotherapy. Right cervical lymph node metastasis and brain metastases occurred 30 months after the initial radiation therapy. A biopsy of the right cervical lymph node led to the diagnosis of clear cell carcinoma. Although we considered additional radiation therapy or chemotherapy, the patient died 3 months after the progression of recurrence lesions. Discussion and conclusions: We report a rare case in which radiotherapy alone for an extracranial metastatic lesion of a vertebra resulted in an abscopal effect on both extracranial and intracranial lesions. Notably, the abscopal effect in the intracranial lesions was weaker than that in the extracranial lesions. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to investigate the long-term outcomes of primary versus postoperative Gamma Knife radiosurgery (GKRS) for benign meningiomas.Methods: Three hundred and forty meningioma patients underwent GKRS were retrospectively reviewed. Patients in the postoperative GKRS group were matched to those in the primary GKRS group, in a 1:1 ratio.Results: The study consisted of 122 patients, including primary (n = 61) and postoperative (n = 61) GKRS group. Thirty-four patients (27.9%) occurred radiological progression after a median follow-up of 72.5 (range, 24.2-254.5) months. The median time to radiological progression was 85.1 (range, 20.7-205.1) months. The radiological progression-free survival (PFS) was 100%, 93%, 87%, and 49%, at 1, 3, 5, and 10 years respectively. Thirty-one patients (25.4%) occurred clinical progression. The clinical PFS was 92%, 89%, 84%, and 60%, at 1, 3, 5, and 10 years. In combined group, only max diameter ≥ 50 mm was associated with radiological (p = 0.020) and clinical PFS (hazard ratio [HR] = 2.896, 95% confidence interval [CI] = 1.280-6.553, p = 0.011). Twenty-five patients (20.5%) developed GKRS related adverse effects, including radiation-induced edema (n = 21). Non-skull base tumors (HR = 3.611, 95% CI = 1.489-8.760, p = 0.005) and preexisting peritumoral edema (HR = 3.571, 95% CI = 1.167-10.929, p = 0.026) were significantly related to radiation-induced edema in combined group. There was no significant difference in radiological PFS (p = 0.403), clinical PFS (p = 0.336), and GKRS related adverse effects (p = 0.138) between primary and postoperative GKRS groups.Conclusions: Primary GKRS could provide similar radiological and clinical outcomes, as well as similar complication rate compared with postoperative GKRS. For selective benign meningioma patients (asymptomatic or mildly symptomatic tumors; unfavorable locations for surgical resection; comorbidities or an advanced age), GKRS could be an alternative primary treatment. [ABSTRACT FROM AUTHOR]

Background: Subependymal giant cell astrocytoma is a benign brain tumor that occurs in patients with tuberous sclerosis complex. Surgical removal is the traditional treatment, and expert opinion is strongly against the use of radiotherapy. Recently, success has been reported with the mTor inhibitor everolimus in reducing tumor volume, but regrowth has been observed after dose reduction or cessation., Case Report: We present the case of a 40-year-old Asian female patient treated successfully for growing bilateral subependymal giant cell astrocytoma with fractionated stereotactic radiotherapy before everolimus became available. After a follow-up of 8 years, everolimus was administered for renal angiomyolipoma and the patient was followed up until 13 years after radiotherapy. Successive magnetic resonance imaging demonstrated an 80% volume reduction after radiotherapy that increased to 90% with everolimus. A review of the literature was done leveraging Medline via PubMed, and we assembled a database of 1298 article references and 780 full-text articles in search of evidence for contraindicating radiotherapy in subependymal giant cell astrocytoma. Varying results of single-fraction radiosurgery were described in a total of 13 cases. Only in two published cases was the radiation dose of fractionated radiotherapy mentioned. One single publication mentions an induced secondary brain tumor 8 years after whole-brain radiotherapy., Conclusion: There is no evidence of contraindication and exclusion of fractionated radiotherapy in treating subependymal giant cell astrocytoma. Our experience demonstrates that subependymal giant cell astrocytoma, as other benign intracranial tumors, responds slowly but progressively to radiotherapy and suggests that fractionated stereotactic radiotherapy holds promise to consolidate responses obtained with mTor inhibitors avoiding regrowth after cessation., (© 2024. The Author(s).)

Purpose/objective(s): To communicate our institutional experience with single isocenter radiosurgery treatments for multiple brain metastases, including challenges with determining planning target volume (PTV) margins and resulting consequences, image-guidance translational and rotational tolerances, intra-fraction patient motion, and prescription considerations with larger PTV margins.Materials/methods: Eight patient treatments with 51 targets were planned with various margins using Elements Multiple Brain Mets SRS treatment planning software (Brainlab, Munich, Germany). Forty-eight plans with 0 mm, 1 mm and 2 mm margins were created, including plans with variable margins, where targets more than 6 cm away from the isocenter were planned with larger margins. The dosimetric impact of the margins were analyzed with V5Gy, V8Gy, V10Gy, V12Gy values. Additionally, 12 patient motion data were analyzed to determine both the impact of the repositioning threshold and the distributions of the patient translational and rotational movements.Results: The V5Gy, V8Gy, V10Gy, V12Gy volumes approximately doubled when margins change from 0 to 1 mm and tripled when change from 0 to 2 mm. With variable margins, the aggregated results are similar to results from plans using the lower of two margins, since only 12.2% of the targets were more than 6 cm away from the isocenter. With 0.5 mm re-positioning threshold, 57.4% of the time the patients are repositioned. Reducing the threshold to 0.25 mm results in 91.7% repositioning rate, due to limitations of the fusion algorithm and actual patient motion. The 90th percentile of translational movements in all directions is 0.7 mm, while the 90th percentile of rotational movements in all directions is 0.6 degrees. Median translations and rotations are 0.2 mm and 0.2 degrees, respectively.Conclusions: Based on the data presented, we have switched our modus operandi from 2 to 1 mm PTV margins, with an eventual goal of using 0.5 and 1.0 mm variable margins when an automated margin assignment method becomes available. The 0.5 mm and 0.5 degrees repositioning thresholds are clinically appropriate with small residual patient movements. [ABSTRACT FROM AUTHOR]

Background: Main purpose was to describe procedures and identify challenges in the implementation process of adaptive and non-adaptive MR-guided radiotherapy (MRgRT), especially new risks in workflow due to the new technique. We herein report the single center experience for the implementation of (MRgRT) and present an overview on our treatment practice.Methods: Descriptive statistics were used to summarize clinical and technical characteristics of treatment and patient characteristics including sites treated between April 2019 and end of March 2020 after ethical approval. A risk analysis was performed to identify risks of the online adaptive workflow.Results: A summary of the processes on the MR-Linac including workflows, quality assurance and possible pitfalls is presented. 111 patients with 124 courses were treated during the first year of MR-guided radiotherapy. The most commonly treated site was the abdomen (42% of all treatment courses). 73% of the courses were daily online adapted and a high number of treatment courses (75%) were treated with stereotactic body irradiation. Only 4/382 fractions could not be treated due to a failing online adaptive quality assurance. In the risk analysis for errors, the two risks with the highest risk priority number were both in the contouring category, making it the most critical step in the workflow.Conclusion: Although challenging, establishment of MRgRT as a routinely used technique at our department was successful for all sites and daily o-ART was feasible from the first day on. However, ongoing research and reports will have to inform us on the optimal indications for MRgRT because careful patient selection is necessary as it continues to be a time-consuming treatment technique with restricted availability. After risk analysis, the most critical workflow category was the contouring process, which resembles the need of experienced staff and safety check paths. [ABSTRACT FROM AUTHOR]

Background: Intramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature.Methods: We included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined.Results: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed.Conclusion: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients. [ABSTRACT FROM AUTHOR]

Objectives: The SWORD trial is the first multicenter, single arm, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony stimulating factor (GM-CSF) in advanced non-small cell lung cancer (NSCLC) without sensitizing driver mutations. A safety run-in phase was conducted to determine the tolerability of the experimental treatment.Materials and Methods: Twenty metastatic NSCLC patients who failed first-line chemotherapy were enrolled, and they received SBRT (8 Gy × 3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks, until disease progression, unacceptable toxicity, or up to 35 cycles) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 2 weeks after SBRT. In addition, blood and tissue samples were serially collected for translational research.Results: Median age of the patients was 61 and all of them had more than 5 lesions at baseline. The sites of SBRT included lung (n = 11), mediastinal lymph node (n = 5), liver (n = 1), abdominal lymph node (n = 1), pleural nodule (n = 1) and vertebra (n = 1). No patients had dose-limiting toxicities (DLTs) and 18 patients experienced treatment-related adverse event (TRAE). The most common TRAEs were fatigue (50%), fever (30%), and ostealgia (20%), and they all were grade 1. Only 2 grade 3 TRAEs were observed, including elevation of liver enzymes in one and transient acute heart failure in another. No grade 4 or 5 AE was observed.Conclusion: Sintilimab, SBRT and GM-CSF for advanced NSCLC is safe with manageable TRAEs and the trial continues to recruit participants. Trial registration ClinicalTrials.gov, NCT04106180. Registered 26 September 2019, SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC-Tabular View-ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Background: The benefit and the risk profile of Gamma Knife radiosurgery (GKRS) for intracerebral cavernoma remains incompletely defined in part due to the natural history of low incidence of bleeding and spontaneous regression of this vascular malformation. In this study, we retrieved cases from a prospectively collected database to assess the outcome of intracerebral cavernoma treated with GKRS using a double blinded review process for treatment.Methods: From 2003 to 2018, there were 94 cases of cavernoma treated by GKRS in the doubly blinded assessments by two experienced neurological and approved for GKRS treatment. All the patients received GKRS with margin dose of 11-12 (Gray) Gy and afterwards were assessed for neurological outcome, radiologic response, and quality of life.Results: The median age of the patients was 48 (15-85) years with median follow up of 77 (26-180) months post SRS. The mean target volume was 1.93 ± 3.45 cc. In those who has pre-SRS epilepsy, 7 of 16 (43.7%) achieved seizure freedom (Engel I/II) and 9 of 16 (56.3%) achieved decreased seizures (Engel III) after SRS. Rebleeding occurred in 2 cases (2.1%) at 13 and 52 months post SRS. The radiologic assessment demonstrated 20 (21.3%) cases of decreased cavernoma volume, 69 (73.4%) were stable, and 5 (7.3%) increased size. Eighty-seven of 94 (92.5%) cases at the last follow up achieve improvement in their quality of life, but 7 cases (7.4%) showed a deterioration. In statistical analysis, the effective seizure control class (Engel I/II) was highly correlated with patient harboring a single lesion (p < 0.05) and deep seated location of the cavernoma (p < 0.01). New neurological deficits were highly correlated with decreased mental (p < 0.001) and physical (p < 0.05) components of quality of life testing, KPS (p < 0.001), deep seated location (p < 0.01), and increased nidus volume (p < 0.05). Quality of life deterioration either in physical component (p < 0.01), mental component (p < 0.01), and KPS (p < 0.05) was highly correlated with increased cavernoma volume.Conclusion: Low margin dose GKRS for intracerebral cavernoma offers reasonable seizure control and improved quality of life while conferring a low risk of treatment complications including adverse radiation effect. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to analyze the treatment efficacy and safety of stereotactic ablative body radiotherapy (SABR) boost for cervical cancer patients not amenable to brachytherapy.Methods: A retrospective review of the medical records from single institution of 25 eligible patients was performed. The patients underwent pelvic radiotherapy (RT) in 25 or 28 fractions with a median dose of 45 Gy (range 44-50.4 Gy). SABR boost was delivered after pelvic RT, with a median dose of 25 Gy (range 20-33 Gy), and a median fraction number of 5 (range 4-6). 21 patients with a follow-up period of more than one year were included in the toxicity analysis, and hematuria and hematochezia that occurred later than 3 months after the RT were graded.Results: The median follow-up period after radiotherapy was 2.85 years (range 0.33-6.60). The 3-year local control, locoregional control, disease-free survival, and overall survival rates were 80.9%, 75.8%, 40.9%, and 77.1%, respectively. 5 patients experienced grade 3 toxicity (3 genitourinary, 3 gastrointestinal), and no grade 4-5 toxicity was reported. Univariate analysis showed that cumulative D2cc in equivalent dose in 2 Gy fractions (EQD2) of rectum was marginally predictive for any grade of hematochezia (P = 0.051). Cumulative D2cc EQD2 of bladder was not predictive for hematuria. In the receiver operating characteristic (ROC) curve analysis, the optimal threshold of cumulative rectal D2cc EQD2 was 81.2 Gy for any grade of hematochezia.Conclusion: SABR boost for cervical cancer was effective and tolerable. Although it cannot substitute brachytherapy, it can be a treatment option when brachytherapy is not possible. [ABSTRACT FROM AUTHOR]

The role of radiotherapy in advanced medullary thyroid carcinoma (MTC) is confined to patients in whom surgical treatment or the administration of tyrosine kinase inhibitors are not possible or contraindicated. High fractionated radiation doses during radiosurgery or fractionated stereotactic radiotherapy are applied to reduce cancer-related symptoms and stabilize irradiated lesions. This study aimed to retrospectively evaluate the therapeutic effect of stereotactic radiotherapy in MTC patients. Material and methods: The study group involved 11 MTC patients, treated due to 16 cancer lesions, mainly bone metastases (10 lesions), lymph node (2 lesions) metastases, or liver metastases (2 lesions), one primary thyroid tumor, and one MTC recurrence in the thyroid bed. The fractionated and total radiation doses ranged between 5 and 12 Gy and 8–44 Gy, respectively. Six lesions were treated with a single radiation fraction, three lesions with 2 fractions, another 6 lesions with 3 fractions, whereas the remaining one metastatic lesion with 9 fractions of stereotactic radiosurgery. Results: The beneficial effect of stereotactic radiosurgery was obtained in all treated lesions. None of treated lesions progressed in the further disease course. Fourteen lesions were stable (87.5 %), including eight lesions showing progression before radiosurgery (good response). Disease control was obtained in all soft-tissue metastases. Regarding bone metastases, partial regression was achieved in 20 % lesions, whereas in 30 % lesions progressive before radiotherapy, the treatment led to disease stabilization. Conclusions: Our data pointed to the effectiveness of high-dose fractionated radiotherapy in MTC. However, an observation of a larger group of patients is required to confirm it. [ABSTRACT FROM AUTHOR]

Background: Treating chordoma through surgery alone is often ineffective. Thus, surgery often performed with irradiation, with a reported 5-year survival rate of 60-75%. The clinical course varies, and disease rarity prevents larger number of clinical investigations.Methods: In total, 19 patients with clival chordomas were retrospectively extracted from our institutional database. They were initially treated with maximal tumor removal using the extended transsphenoidal approach between March 2006 and January 2021. When total tumor removal was achieved, prophylactic irradiation was not performed. If tumor remnants or recurrence were confirmed, Gamma Knife (GK) radiosurgery was performed. The mean follow-up period was 106.7 months (ranged 27-224 months). The clinical course and prognostic factors were investigated.Results: Total removal was achieved in 10 patients, whereas 4 patients suffered recurrence and required GK. GK was applied to 11 patients with a 50% isodose of 13-18 Gy (mean: 15.4 Gy), and eight patients remained progression free, whereas three patients suffered repeated local recurrence and died of tumor-related complications. The mean overall progression-free interval was 57.2 months (range: 6-169 months). One male patient died of tumor un-related lung cancer 36 months after the initial treatment, and other patients survived throughout the observational periods. The mean overall survival was 106.7 months (range: 27-224 months). Thus, the 5-year survival rate was 94.7%. Statistical analysis indicated that sex (men), > 15 Gy of 50% isodose by GK, and screening brain examinations as prophylactic medicine were significant favorable prognostic factors.Conclusions: The favorable outcomes in this investigation suggest the importance of early detection and treatment. Surgery may enable better conditions for sufficient GK doses. [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma (ACC) is a rare malignant tumor involving mostly the head and neck region, and frequently the salivary glands. The development of lung metastasis after treatment of the primary tumor is a common occurrence in ACC. Although lung metastases show a slow rate of growth, approximately 10% of patients die from distant metastases. The radioresistance of ACC limits the efficacy of conventional radiotherapy for lung metastases, and the optimal dose remains to be determined. Stereotactic body radiotherapy (SBRT) using CyberKnife can deliver a high dose to the lung tumor, while sparing the surrounding normal lung tissues, leading to favorable local control in non-squamous cell lung cancer and metastatic lung tumors. We report a case of lung metastases from ACC treated successfully with SBRT using CyberKnife.Case Presentation: A 76-year-old Japanese man with ACC who was treated with carbon ion radiotherapy for a primary oropharynx tumor presented with three metastatic lesions in the lung. The tumor masses were located in the right upper, right lower, and left lower lobes of the lungs. Surgical resection was not indicated because of the presence of multiple tumors. The patient underwent SBRT at 60 Gy in 10 sequential fractions for each tumor. The biologically effective dose based on an alpha/beta ratio of 2 Gy was 240 Gy per tumor. The percentage of the total lung volume irradiated with >20 Gy was 4.9%, 3.2%, and 2.6% for each tumor. The patient developed acute radiation pneumonitis during the initial therapy, which resolved at 6 months after the CyberKnife treatment. At 21 months after the first CyberKnife treatment, three tumors showed no signs of recurrence. No late toxicity was observed.Conclusions: SBRT using CyberKnife is an effective and feasible approach to the management of multiple lung metastases of ACC. [ABSTRACT FROM AUTHOR]

Background: Complete surgical remission (CSR) is the best predictor of overall survival (OS) for patients with metastatic osteosarcoma. However, metastasectomy has not been widely implemented in China in the last decade due to various factors, and instead, most physicians choose hypofractionated radiotherapy to treat pulmonary lesions. This study aimed to retrospectively evaluate the outcomes of different local treatments for pulmonary lesions and identify the best local therapy strategies for these patients.Methods: We reviewed the clinical courses of osteosarcoma patients with pulmonary metastases who were initially treated in two sarcoma centres in Beijing, China, from June 1st, 2009, to March 26th, 2020. With a median follow-up of 32.4 (95% confidence interval (CI): 30.8, 36.1) months, a total of 127 patients with 605 pulmonary nodules, all of whom had received local therapy and firstly achieved CSR or complete radiated/metabolic remission (CRR), were included in the analysis. A total of 102 patients with 525 nodules were initially diagnosed with resectable lung metastases, while 25 patients had 80 indeterminate nodules at presentation and relapsed with pulmonary metastases within 6 months after the completion of adjuvant chemotherapy.Results: Eighty-eight of 127 (69.3%) patients had fewer than 5 nodules at the time of local therapy, with 48 of 127 (37.8%) located in the unilateral pleura. No patient underwent thoracotomy, and 42 of 127 patients (85 nodules) received video-assisted thoracoscopic surgery (VATS). In addition, 79 of 127 patients (520 nodules) received hypofractionated stereotactic body radiotherapy (RT), such as Gamma Knife radiosurgery or CyberKnife radiosurgery. The twelve-month event-free survival (EFS) (from local therapy to progression) rate of this entire study cohort was 35.6% (95% CI: 26.8, 44.4%), without a significant difference between the two groups (44.7% for VATS vs. 28.4% for RT, P = 0.755). Radiation-induced pneumonitis was observed in 62 of 86 (72.1%) patients, with one patient (1/86, 1.2%) in grade 4.Conclusions: Our past data showed a similar prognosis with the use of hypofractionated radiotherapy and VATS for the treatment of pulmonary metastasis and no inferiority to thoracotomy regarding historical outcomes. Currently, high-resolution chest computed tomography (CT) provides sufficient information on nodules, and less invasive modalities can thus be considered for treatment. [ABSTRACT FROM AUTHOR]

Background: Stereotactic radiosurgery (SRS) has been recognized as a first-line treatment option for small to moderate sized vestibular schwannoma (VS). Our aim is to evaluate the impact of SRS doses and other patient and disease characteristics on vestibular function in patients with VS.Methods: Data on VS patients treated with single-fraction SRS to 12 Gy were retrospectively reviewed. No dose constraints were given to the vestibule during optimization in treatment planning. Patient and tumor characteristics, pre- and post-SRS vestibular examination results and patient-reported dizziness were assessed from patient records.Results: Fifty-three patients were analyzed. Median follow-up was 32 months (range, 6-79). The median minimum, mean and maximum vestibular doses were 2.6 ± 1.6 Gy, 6.7 ± 2.8 Gy, and 11 ± 3.6 Gy, respectively. On univariate analysis, Koos grade (p = 0.04; OR: 3.45; 95% CI 1.01-11.81), tumor volume (median 6.1 cm3; range, 0.8-38; p = 0.01; OR: 4.85; 95% CI 1.43-16.49), presence of pre-SRS dizziness (p = 0.02; OR: 3.98; 95% CI 1.19-13.24) and minimum vestibular dose (p = 0.033; OR: 1.55; 95% CI 1.03-2.32) showed a significant association with patient-reported dizziness. On multivariate analysis, minimum vestibular dose remained significant (p = 0.02; OR: 1.75; 95% CI 1.05-2.89). Patients with improved caloric function had received significantly lower mean (1.5 ± 0.7 Gy, p = 0.01) and maximum doses (4 ± 1.5 Gy, p = 0.01) to the vestibule.Conclusions: Our results reveal that 5 Gy and above minimum vestibular doses significantly worsened dizziness. Additionally, mean and maximum doses received by the vestibule were significantly lower in patients who had improved caloric function. Further investigations are needed to determine dose-volume parameters and their effects on vestibular toxicity. [ABSTRACT FROM AUTHOR]

Objective: To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT).Methods and Materials: From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ''In-Field (IF)'', "Marginal recurrence" or ''Out-of-Field (OF)'' if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose.Results: We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6-28.9 cc), while the mean MTVrec was 4.3 cc (1.1-12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61-91%) and 4 recurrences were marginal to MTVpre (1-33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5-69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV).Conclusion: Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse. [ABSTRACT FROM AUTHOR]

Purpose: To compare linac-based mono-isocentric radiosurgery with Brainlab Elements Multiple Brain Mets (MBM) SRS and the Gamma Knife using a specific statistical method and to analyze the dosimetric impact of the target volume geometric characteristics. A dose fall-off analysis allowed to evaluate the Gradient Index relevancy for the dose spillage characterization.Material and Methods: Treatments were planned on twenty patients with three to nine brain metastases with MBM 2.0 and GammaPlan 11.0. Ninety-five metastases ranging from 0.02 to 9.61 cc were included. Paddick Index (PI), Gradient Index (GI), dose fall-off, volume of healthy brain receiving more than 12 Gy (V12Gy) and DVH were used for the plan comparison according to target volume, major axis diameter and Sphericity Index (SI). The multivariate regression approach allowed to analyze the impact of each geometric characteristic keeping all the others unchanged. A parallel study was led to evaluate the impact of the isodose line (IDL) prescription on the MBM plan quality.Results: For mono-isocentric linac-based radiosurgery, the IDL around 70-75% was the best compromise found. For both techniques, the GI and the dose fall-off decreased with the target volume. In comparison, PI was slightly improved with MBM for targets < 1 cc or SI > 0.78. GI was improved with GP for targets < 2.5 cc. The V12Gy was higher with MBM for lesions > 0.4 cc or SI < 0.84 and exceeded 10 cc for targets > 5 cc against 6.5 cc with GP. The presence of OAR close to the PTV had no impact on the dose fall off values. The dose fall-off was higher for volumes < 3.8 cc with GP which had the sharpest dose fall-off in the infero-superior direction up to 30%/mm. The mean beam-on time was 94 min with GP against 13 min with MBM.Conclusions: The dose fall-off and the V12Gy were more relevant indicators than the GI for the low dose spillage assessment. Both evaluated techniques have comparable plan qualities with a slightly improved selectivity with MBM for smaller lesions but with a healthy tissues sparing slightly favorable to GP at the expense of a considerably longer irradiation time. However, a higher healthy tissue exposure must be considered for large volumes in MBM plans. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiation therapy (SBRT) is an established therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). Many elderly patients are medically inoperable owing to comorbidities. Therefore, SBRT may be a useful therapy for elderly patients. However, the application of SBRT for patients aged ≥ 80 years has not been completely elucidated. Therefore, this study aimed to assess the clinical utility of SBRT for elderly patients aged ≥ 80 years with pathologically proven early-stage NSCLC.Methods: We retrospectively evaluated the data of patients aged ≥ 80 years with pathologically proven primary NSCLC who underwent SBRT at our institution between January 2009 and March 2020. Treatment outcomes and toxicities were analyzed. We used the Kaplan-Meier method to estimate survival curves and the log-rank test to compare the survival curves. We performed univariate and multivariate Cox regression analyses. p-values < 0.05 were regarded significant.Results: Sixty-four patients (65 lesions) were included, and the median follow-up period was 38.7 (range 3.5-95.7) months. The median age was 82.9 (range 80.0-94.8) years. Sixteen patients were medically operable, and 48 patients were medically inoperable. The prescribed dose of SBRT was either 48 Gy in four fractions or 60 Gy in 10 fractions. The median survival time was 60.0 months (95% confidence interval, 43.5-71.1). The 1-, 3-, and 5-year local control, cancer-specific survival, progression-free survival, and overall survival rates were 98.4%, 98.4%, 81.0%, and 88.9%; 90.1%, 93.7%, 58.9%, and 68.3%; and 87.4%, 83.5%, 38.2%, and 47.5%, respectively. Multivariate analysis revealed that inoperability and solid nodules were the predictors of poor overall survival after SBRT in elderly patients. Two patients (3.1%) had grade 3 radiation pneumonitis, and one patient (1.6%) had grade 5 radiation pneumonitis.Conclusions: SBRT was feasible in patients aged ≥ 80 years with NSCLC. It achieved good local control with minimal toxicity. SBRT may be beneficial in elderly patients with early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Background: Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone.Methods: This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis.Discussion: The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts.Trials Registration: ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study. [ABSTRACT FROM AUTHOR]

Background: Stereotactic radiosurgery (SRS) has been increasingly applied for up to 10 brain metastases instead of whole brain radiation therapy (WBRT) to achieve local tumor control while reducing neurotoxicity. Furthermore, brain-metastasis incidence is rising due to the increasing survival of patients with cancer. Our aim was to analyze the efficacy and safety of CyberKnife (CK) radiosurgery for elderly patients. Methods: We retrospectively identified all patients with brain metastases ≥ 65 years old treated with CK-SRS at our institution since 2011 and analyzed data of primary diseases, multimodality treatments, and local therapy effect based on imaging follow-up and treatment safety. Kaplan–Meier analysis for local progression-free interval and overall survival were performed. Results: We identified 97 patients (233 lesions) fulfilling the criteria at the first CK-SRS. The mean age was 73.2 ± 5.8 (range: 65.0–87.0) years. Overall, 13.4% of the patients were > 80 years old. The three most frequent primary cancers were lung (40.2%), kidney (22.7%), and malignant melanoma (15.5%). In 38.5% (47/122 treatments) multiple brain metastases were treated with the CK-SRS, with up to eight lesions in one session. The median planning target volume (PTV) was 1.05 (range: 0.01–19.80) cm3. A single fraction was applied in 92.3% of the lesions with a median prescription dose of 19 (range: 12–21) Gy. The estimated overall survivals at 3-, 6-, and 12 months after SRS were 79, 55, and 23%, respectively. The estimated local tumor progression-free intervals at 6-, 12-, 24-, 36-, and 72 months after SRS were 99.2, 89.0, 67.2, 64.6, and 64.6%, respectively. Older age and female sex were predictive factors of local progression. The Karnofsky performance score remained stable in 97.9% of the patients; only one patient developed a neurological deficit after SRS of a cerebellar lesion (ataxia, CTCAE Grade 2). Conclusions: SRS is a safe and efficient option for the treatment of elderly patients with brain metastases with good local control rates without the side effects of WBRT. Older age and female sex seem to be predictive factors of local progression. Prospective studies are warranted to clarify the role of SRS treatment for elderly patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patients with locally advanced oropharynx squamous cell carcinoma have suboptimal outcomes with standard chemoradiation. Here, we evaluated toxicity and oncologic outcomes of dose escalation using radiosurgical boost for patients with unfavorable oropharynx squamous cell carcinoma.Materials and Methods: Between 2010-2017, Thirty four patients with intermediate- or high-risk oropharynx squamous cell carcinoma were enrolled onto this prospective phase I trial. Each patient received concurrent cisplatin and fractionated radiotherapy totaling 60 Gy or 66 Gy followed by radiosurgery boost to areas of residual gross tumor: single fraction of 8 Gy or 10 Gy, or two fractions of 5 Gy each. Primary endpoint was treatment toxicity. Secondary endpoints were local, regional, and distant disease control.Results: Eleven, sixteen and seven patients received radiosurgery boost with 8 Gy in 1 fraction, 10 Gy in 1 fraction, and 10 Gy in 2 fractions respectively. Acute toxicities include 4 patients with tumor necrosis causing grade 3 dysphagia, of which 3 developed grade 4 pharyngeal hemorrhage requiring surgical intervention. At 24 months after treatment, 7%, 9%, and 15% had grade 2 dysgeusia, xerostomia, and dysphagia, respectively, and two patients remained feeding tube dependent. No grade 5 toxicities occurred secondary to treatment. Local, regional, and distant control at a median follow up of 4.2 years were 85.3%, 85.3% and 88.2%, respectively. Five patients died resulting in overall survival of 85.3%.Conclusions: This study is the first to report the use of radiosurgery boost dose escalation in patients with unfavorable oropharynx squamous cell carcinoma. Longer follow-up, larger cohorts, and further refinement of boost methodology are needed prior to implementation in routine clinical practice.Trial Registration: Northwell Health Protocol #09-309A (NCT02703493) ( https://clinicaltrials.gov/ct2/show/NCT02703493 ). [ABSTRACT FROM AUTHOR]

Background: Local hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity is emerging as the standard of care in the treatment of patients with a limited number of brain metastases as it warrants less neurological impairment compared to whole brain radiotherapy. In periventricular metastases surgical resection can lead to an opening of the ventricles and subsequently carries a potential risk of cerebrospinal tumour cell dissemination. The aim of this study was to assess whether local radiotherapy of the resection cavity is viable in these cases.Methods: From our institutional database we analyzed the data of 125 consecutive patients with resected brain metastases treated in our institution with HFSRT between 2009 and 2017. The incidence of LMD, overall survival (OS), local recurrence (LC) and distant recurrence were evaluated depending on ventricular opening (VO) during surgery.Results: From all 125 patients, the ventricles were opened during surgery in 14 cases (11.2%). None of the patients with VO and 7 patients without VO during surgery developed LMD (p = 0.371). OS (p = 0.817), LC (p = 0.524) and distant recurrence (p = 0.488) did not differ in relation to VO during surgical resection. However, the incidence of distant intraventricular recurrence was slightly increased in patients with VO (14.3% vs. 2.7%, p < 0.01).Conclusion: VO during neurosurgical resection did not affect the outcome after HFSRT of the resection cavity in patients with brain metastases. Particularly, the incidence of LMD was not increased in patients receiving local HFSRT after VO. HFSRT can therefore be offered independently of VO as a local treatment of tumor bed after resection of brain metastases. [ABSTRACT FROM AUTHOR]