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Abstract BACKGROUND Stereotactic radiosurgery (SRS) for benign intracranial meningiomas is an established treatment. OBJECTIVE To summarize the literature and provide evidence-based practice guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS Articles in English specific to SRS for benign intracranial meningioma, published from January 1964 to April 2018, were systematically reviewed. Three electronic databases, PubMed, EMBASE, and the Cochrane Central Register, were searched. RESULTS Out of the 2844 studies identified, 305 had a full text evaluation and 27 studies met the criteria to be included in this analysis. All but one were retrospective studies. The 10-yr local control (LC) rate ranged from 71% to 100%. The 10-yr progression-free-survival rate ranged from 55% to 97%. The prescription dose ranged typically between 12 and 15 Gy, delivered in a single fraction. Toxicity rate was generally low. CONCLUSION The current literature supporting SRS for benign intracranial meningioma lacks level I and II evidence. However, when summarizing the large number of level III studies, it is clear that SRS can be recommended as an effective evidence-based treatment option (recommendation level II) for grade 1 meningioma.

Hypo-fractionated radiotherapy (HF-RT) is increasingly used for elderly and frail glioblastoma patients. In countries with limited radiotherapy capacities, HF-RT is more widely applied. This allowed us to compare conventional fractionation (CF-RT) vs. HF-RT in patients of any age and performance status. We retrospectively analysed 277 patients [110 HF-RT (52.5 Gy in 15 fractions) vs. 167 CF-RT (54.0-60.0 Gy in 27-33 fractions)] for local control (LC) and overall survival (OS) including subgroups considering specific patient characteristics. On univariable comparisons, CF-RT was associated with significantly better LC and OS in patients with KPS ≤70 and unifocal glioblastoma, and with OS in the entire cohort. Trends were found for LC and OS in patients aged <60 years, and for OS in additional four subgroups. On multivariable analyses, improved LC and OS were significantly associated with CF-RT, KPS 80-100, unifocal glioblastoma, resection, and receipt of chemotherapy. Maximum diameter <45 mm was associated with improved OS. Given the limitations of this study, CF-RT appeared associated with better outcomes. Selected patients may benefit from HF-RT.

This study aimed to explore the effect of observation, microsurgery, and radiotherapy for patients with vestibular schwannoma (VS). We searched PubMed, Medline, Embase, Web of Science, and Cochrane library from their establishment to July 31, 2024. 34 non-RCTs and 1 RCT that included 6 interventions were analyzed. We found the MS, and different SRS all had better tumor local control rates. Regarding preserved hearing, the order from the highest to the lowest was FSRT 5 fractions, FSRT 3 fractions, SRS, ConFSRT, Observation, and MS. Regarding improvement in the rate of tinnitus, the order from the highest to the lowest was ConFSRT, FSRT 3 fractions, SRS, Observation, MS, and FSRT 5 fractions. In terms of improving the rate of disequilibrium/vertigo, the order from the highest to the lowest was SRS, Observation, FSRT 3 fractions, FSRT 5 fractions, MS, and ConFSRT. In terms of protection of the trigeminal nerve, the order from the highest to lowest was observation, SRS, ConFSRT, FSRT 3 fractions, FSRT 5 fractions, and MS. Lastly, in terms of protection of the facial nerve, the order from the highest to lowest was SRS, ConFSRT, Observation, FSRT 3 fractions, FSRT 5 fractions, and MS. In patients with VS, MS and radiosurgery showed better local tumor control rates; however, compared with MS, different SRS all provided better protection of nerve function and improved the symptoms of vestibular function and tinnitus, among which the best was SRS. Therefore, in these patients, SRS may be a promising alternative treatment.

Introduction We conducted a study to evaluate the dosimetric feasibility of mask‐based cobalt‐60 fractionated stereotactic radiotherapy (mcfSRT) with the Leksell Gamma Knife® Icon™ device. Methods Eleven patients with intracranial tumours were selected for this dosimetry study. These patients, previously treated with volumetric arc therapy (VMAT), were re‐planned using mcfSRT. Target volume coverage, conformity/gradient indices, doses to organs at risk and treatment times were compared between the mcfSRT and VMAT plans. Two‐sided paired Wilcoxon signed‐rank test was used to compare differences between the two plans. Results The V95 for PTV was similar between fractionated mcfSRT and VMAT (P = 0.47). The conformity index and gradient indices were 0.9 and 3.3, respectively, for mcfSRT compared to 0.7 and 4.2, respectively, for VMAT (P < 0.001 and 0.004, respectively). The radiation exposure to normal brain was lower for mcfSRT across V10, V25 and V50 compared with VMAT (P = 0.007, <0.001 and <0.001, respectively). The median D0.1cc for optic nerve and chiasm as well as the median D50 to the hippocampi were lower for mcfSRT compared to VMAT. Median beam‐on time for mcfSRT was 9.7 min per fraction, compared to 0.9 min for VMAT (P = 0.002). Conclusion mcfSRT plans achieve equivalent target volume coverage, improved conformity and gradient indices, and reduced radiation doses to organs at risk as compared with VMAT plans. These results suggest superior dosimetric parameters for mcfSRT plans and can form the basis for future prospective studies. In this comparative dosimetry study, fractionated cobalt‐60 radiosurgery plans (top panels) achieved equivalent target coverage but improved conformity and organ‐at‐risk sparing as compared to VMAT plans (bottom panels). Fractionated radiosurgery may be considered for future prospective study as a highly focused modality for photon radiation of intracranial tumours.

Palliative radiotherapy has a great role in the treatment of large tumor masses. However, treating a bulky disease could be difficult, especially in critical anatomical areas. In daily clinical practice, short course hypofractionated radiotherapy is delivered in order to control the symptomatic disease. Radiation fields generally encompass the entire tumor mass, which is homogeneously irradiated. Recent technological advances enable delivering a higher radiation dose in small areas within a large mass. This goal, previously achieved thanks to the GRID approach, is now achievable using the newest concept of LATTICE radiotherapy (LT-RT). This kind of treatment allows exploiting various radiation effects, such as bystander and abscopal effects. These events may be enhanced by the concomitant use of immunotherapy, with the latter being ever more successfully delivered in cancer patients. Moreover, a critical issue in the treatment of large masses is the inhomogeneous intratumoral distribution of well-oxygenated and hypo-oxygenated areas. It is well known that hypoxic areas are more resistant to the killing effect of radiation, hence the need to target them with higher aggressive doses. This concept introduces the “oxygen-guided radiation therapy” (OGRT), which means looking for suitable hypoxic markers to implement in PET/CT and Magnetic Resonance Imaging. Future treatment strategies are likely to involve combinations of LT-RT, OGRT, and immunotherapy. In this paper, we review the radiobiological rationale behind a potential benefit of LT-RT and OGRT, and we summarize the results reported in the few clinical trials published so far regarding these issues. Lastly, we suggest what future perspectives may emerge by combining immunotherapy with LT-RT/OGRT.

Abstract RADIOSURGERY VS OBSERVATION Question What are the indications for stereotactic radiosurgery (SRS) treatment vs observation for patients with intracanalicular vestibular schwannomas without evidence of radiographic progression? Recommendation Level 3: If tinnitus is not observed at presentation, it is recommended that intracanalicular vestibular schwannomas and small tumors (<2 cm) without tinnitus be observed as observation does not have a negative impact on tumor growth or hearing preservation compared to treatment. RADIOSURGERY TECHNOLOGY Question Is there a difference in outcome based on radiosurgery equipment used: Gamma Knife (Elekta, Stockholm, Sweden) vs linear accelerator-based radiosurgery vs proton beam? Recommendation There are no studies that compare 2 or all 3 modalities. Thus, recommendations on outcome based on modality cannot be made. RADIOSURGERY TECHNIQUE Question Is there a difference in outcome based on the dose delivered? Recommendation Level 3: As there is no difference in radiographic control using different doses, it is recommended that for single fraction SRS doses, <13 Gy be used to facilitate hearing preservation and minimize new onset or worsening of preexisting cranial nerve deficits. Question Is there a difference in outcome based on the number of fractions? Recommendation As there is no difference in radiographic control and clinical outcome using single or multiple fractions, no recommendations can be given. RADIOGRAPHIC FOLLOW-UP, RETREATMENT, AND TUMORIGENESIS AFTER RADIOSURGERY Question What is the best time sequence for follow-up images after SRS? Recommendation Level 3: Follow-up imaging should be obtained at intervals after SRS based on clinical indications, a patient's personal circumstances, or institutional protocols. Long-term follow-up with serial magnetic resonance imagings to evaluate for recurrence is recommended. No recommendations can be given regarding the interval of these studies. Question Is there a role for retreatment? Recommendation Level 3: When there has been progression of tumor after SRS, SRS can be safely and effectively performed as a retreatment. Question What is the risk of radiation-induced malignant transformation of vestibular schwannomas treated with SRS? Recommendation Level 3: Patients should be informed that there is minimal risk of malignant transformation of vestibular schwannomas after SRS. NEUROFIBROMATOSIS TYPE 2 Question What are the indications for SRS in patients with neurofibromatosis type 2? Recommendation Level 3: Radiosurgery is a treatment option for patients with neurofibromatosis type 2 whose vestibular schwannomas are enlarging and/or causing hearing loss.  The full guideline can be found at: https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_7.

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade.

Radiotherapy is involved in 50% of all cancer treatments and 40% of cancer cures. Most of these treatments are delivered in fractions of equal doses of radiation (Fractional Equivalent Dosing (FED)) in days to weeks. This treatment paradigm has remained unchanged in the past century and does not account for the development of radioresistance during treatment. Even if under-optimized, deviating from a century of successful therapy delivered in FED can be difficult. One way of exploring the infinite space of fraction size and scheduling to identify optimal fractionation schedules is through mathematical oncology simulations that allow for in silico evaluation. This review article explores the evidence that current fractionation promotes the development of radioresistance, summarizes mathematical solutions to account for radioresistance, both in the curative and non-curative setting, and reviews current clinical data investigating non-FED fractionated radiotherapy.

Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced (LA) at diagnosis. The combination of radiotherapy (RT), chemotherapy, targeted therapy, and immunotherapy are the primary LA-HNSCC treatment options. Nevertheless, the choice of optimal LA-HNSCC treatment remains controversial. We systematically searched public databases for LA-HNSCC-related studies and assess treatment effectiveness and safety by assessing the objective response rate (ORR), ≥3 adverse events (AEs), overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), local-region control (LRC), and disease-specific survival (DSS). 126 randomized controlled clinical trials (RCTs) were included in this study. We show that concurrent RT with nimotuzumab or conventional concurrent chemo-radiotherapy (CCRT) had significantly better efficacy and long-term survival without increasing AEs than RT alone. Accelerated fractionated radiotherapy (AFRT) showed better efficiency than conventional fractionated RT, although it had higher AEs. In addition, concurrent cetuximab combined with RT failed to show a significant advantage over RT alone. Trial registration: PROSPERO CRD42022352127.

Background Spatially fractionated radiotherapy (SFRT) intentionally creates spatially-modulated peak-valley dose patterns for improving the tumor control or/and the sparing of organs at risk, compared to conventional radiotherapy (CONV). Evaluating non-uniform dose distributions using conventional physical dose does not fully account for the biological effectiveness of SFRT. In this study, we adopt the equivalent uniform dose (EUD) as a surrogate metric to evaluate non-uniform dose distributions. Purpose This work will develop a SFRT treatment planning method with EUD optimization, which is the first-of-its-kind to the best of our knowledge. Methods The SFRT scenario of proton GRID with uniform target dose is considered in this work for dose-only optimization (DO) and joint dose and peak-valley-dose-ratio (PVDR) optimization (JDPO) respectively. In addition to dose and PVDR optimization, SFRT treatment planning also optimizes the EUD. The EUD used in this work is based on cell survival as modeled by the linear-quadratic model. The EUD optimization problem is solved by: (1) iterative convex relaxation to decouple the nonconvex dose-volume-histogram constraint; (2) linearized alternating direction method of multiplier to efficiently handle the nonconvex minimum-monitor-unit constraint and nonlinear EUD objective. Results EUD optimization reduced the EUD and increased survival fraction. For example, for a head-and-neck patient, EUD optimization decreased the brainstem EUD from 5.52% to 3.86% for DO, and from 5.78% to 4.82% for JDPO, and increased the brainstem survival fraction from 72.9% to 81.6% for DO, and from 71.5% to 76.6% for JDPO. Furthermore, EUD optimization preserved PVDR from DO or JDPO. Conclusions A novel EUD optimization method is proposed for SFRT that can reduce the EUD and increase the survival fraction.