Repeat single-session stereotactic radiosurgery for arteriovenous malformation: a systematic review and meta-analysis.

BACKGROUND: Stereotactic radiosurgery is the preferred option for treating brain arteriovenous malformation (AVM) when the risks associated with surgery outweigh the potential benefits. However, some patients require repeat radiosurgery due to residual AVM after the first procedure. This systematic review and meta-analysis aimed to investigate the safety and efficacy of repeated procedure of radiosurgery for AVM. METHOD: A systematic review was conducted according to the PRISMA guideline. The search was conducted on PubMed, Scopus, Embase, and Web of Science, using a pre-designed search string. Studies investigating the efficacy of repeat radiosurgery for residual AVM following initial single session radiosurgery were included. The risk of bias was assessed using the JBI tool. Meta-analysis and met-regression were performed to pool and inspect data. RESULTS: Our meta-analysis, with a mean follow-up of 45.57 months, reveals repeat radiosurgery as a viable option for arteriovenous malformations (AVMs), achieving a 60.82% obliteration rate with a mean time to obliteration of 33.18 months. Meta-regression identifies AVM volume and Spetzler-Martin (SM) grade as factors influencing obliteration, with smaller volume and lower SM grades associated with higher rates. Complications include 10.33% radiation-induced changes, 5.26% post-radiosurgery hemorrhage, 2.56% neurologic deficits, and 0.67% cyst formation. Heterogeneity in complications is primarily attributed to male proportion and SM grade, while factors influencing post-radiosurgery hemorrhage remain unclear. The type of radiosurgery, whether Gamma Knife Radiosurgery (GKRS) or LINAC, does not significantly impact outcomes. CONCLUSION: Repeat radiosurgery is a feasible, effective, and safe treatment for AVMs following failure of initial radiosurgery. When utilized in appropriate patient subgroups, it provides an acceptable risk-to-benefit profile. Feature studies are required to clarify its clear indications.

Functional imaging guided stereotactic ablative body radiotherapy (SABR) with focal dose escalation and bladder trigone sparing for intermediate and high-risk prostate cancer: study protocol for phase II safo trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer. METHODS: Patients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping. DISCUSSION: To the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL SPONSOR: IRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica). STUDY SETTING: Clinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023. TRIAL STATUS: Protocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

Long-term outcome of primary clival chordomas: a single-center retrospective study with an emphasis on the timing of recurrences based on the primary treatment.

OBJECTIVE: This study aimed to provide data on extended outcomes in primary clival chordomas, focusing on progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective single-center analysis was conducted on patients with clival chordoma treated between 1987 and 2022 using surgery, stereotactic radiosurgery, or proton radiation therapy (PRT). RESULTS: The study included 100 patients (median age 44 years, 51% male). Surgery was performed using the endoscopic endonasal approach in 71 patients (71%). Gross-total resection (GTR) or near-total resection (NTR) was attained in 39 patients (39%). Postoperatively, new cranial nerve deficits occurred in 7%, CSF leak in 4%, and meningitis in none of the patients. Radiation therapy was performed in 79 patients (79%), with PRT in 50 patients (50%) as the primary treatment. During the median follow-up period of 73 (interquartile range [IQR] 38-132) months, 41 recurrences (41%) and 31 deaths (31%) were confirmed. Patients with GTR/NTR had a median PFS of 41 (IQR 24-70) months. Patients with subtotal resection or biopsy had a median PFS of 38 (IQR 16-97) months. The median PFS of patients who received radiation therapy was 43 (IQR 26-86) months, while that of patients who did not receive radiation therapy was 18 (IQR 5-62) months. The Kaplan-Meier method showed that patients with GTR/NTR (p = 0.007) and those who received radiation therapy (p < 0.001) had longer PFS than their counterparts. The PFS rates following primary treatment at 5, 10, 15, and 20 years were 51%, 25%, 17%, and 7%, respectively. The OS rates at the same intervals were 84%, 60%, 42%, and 34%, respectively. Multivariate Cox regression analysis showed that age < 44 years (p = 0.02), greater extent of resection (EOR; p = 0.03), and radiation therapy (p < 0.001) were associated with lower recurrence rates. Another multivariate analysis showed that age < 44 years (p = 0.01), greater EOR (p = 0.04), and freedom from recurrence (p = 0.02) were associated with lower mortality rates. Regarding pathology data, brachyury was positive in 98%, pan-cytokeratin in 93%, epithelial membrane antigen in 85%, and S100 in 74%. No immunohistochemical markers were associated with recurrence. CONCLUSIONS: In this study, younger age, maximal safe resection, and radiation therapy were important factors for longer PFS in patients with primary clival chordomas. Preventing recurrences played a crucial role in achieving longer OS.

Stereotactic radiosurgery in the management of skull base chordomas: a comprehensive systematic review and meta-analysis.

OBJECTIVE: Chordoma is a primary bone tumor with limited literature on its management because of its rarity. Resection, while considered the first-line treatment, does not always provide adequate tumor control. In this systematic review, the authors aimed to provide comprehensive insights by managing these tumors with stereotactic radiosurgery (SRS). METHODS: A systematic review was conducted according to PRISMA guidelines using the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases. Search terms included chordoma and radiosurgery and their equivalent terms. Data on baseline characteristics, SRS details, and outcomes were extracted. The Joanna Briggs Institute checklist was used to assess risk of bias. A meta-analysis was performed on relevant variables. RESULTS: A total of 33 eligible studies encompassing 714 patients with skull base chordomas were included. Most studies had a low risk of bias. Patients, predominantly male (57.37%) with a mean age of 46.54 years, exhibited a conventional chordoma subtype (74.77%) and primary lesions (77.91%), mainly in the clivus (98.04%). The mean lesion volume was 13.49 cm3, and 96.68% of patients had undergone prior surgical attempts. Gamma Knife radiosurgery (88.76%) was the predominant SRS method. Radiologically, 27.19% of patients experienced tumor regression, while 55.02% showed no signs of disease progression at the latest follow-up. Progression occurred after a mean of 48.02 months. Symptom improvement was noted in 27.98% of patients. Radiosurgery was associated with a relatively low overall adverse event rate (11.94%), mainly cranial nerve deficits (8.72%). Meta-regression revealed that age and primary lesion type influenced symptom improvement, while factors like extent of resection, radiotherapy, and SRS type affected adverse event rates. CONCLUSIONS: This systematic review provides evidence on the safety and effectiveness of radiosurgery in the management of skull base chordomas. Local tumor control was achieved in the majority of patients treated with SRS. Various baseline characteristics and SRS features have been analyzed to identify modifying factors for each outcome to provide a framework for informed decision-making when managing these patients.

Optimizing radiotherapy strategies for skull base chordoma: a comprehensive meta-analysis and systematic review of treatment modalities and outcomes.

OBJECTIVE: In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC. METHODS: Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05. RESULTS: A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively. CONCLUSIONS: The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

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

Advances in Cranial Surgery.

The landscape of the cranial neurosurgery has changed tremendously in past couple of decades. The main frontiers including introduction of neuro-endoscopy, minimally invasive skull base approaches, SRS, laser interstitial thermal therapy and use of tubular retractors have revolutionized the management of intracerebral hemorrhages, deep seated tumors other intracranial pathologies. Introduction of these novel techniques is based on smaller incisions with maximal operative corridors, decreased blood loss, shorter hospital stays, decreased post-operative pain and cosmetically appealing scars that improves patient satisfaction and clinical outcomes. The sophisticated tools like neuroendoscopy have improved light source, and better visualization around the corners. Advanced navigated tools and channel-based retractors help us to target deeply seated lesions with increased precision and minimal disruption of the surrounding neurovascular tissues. Advent of stereotactic radiosurgery has provided us alternative feasible, safe and effective options for treatment of patients who are otherwise not medically stable to undergo complex cranial surgical interventions. This paper review advances in treatment of intracranial pathologies, and how the neurosurgeons and other medical providers at the University of Missouri-Columbia (UMC) are optimizing these treatments for their patients.

Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Treatment of Brain Arteriovenous Malformations.

Brain arteriovenous malformations (AVMs) are a rare entity of vascular anomalies, characteristic of anatomical shunting where arterial blood directly flows into the venous circulation. The main aim of the active treatment policy of brain AVMs is the prevention of haemorrhage. There are well-established treatment strategies that continually improve in their safety and efficacy, primarily due to the advances in imaging modalities, targeted and novel techniques, the development of alternative treatment approaches, and even better experience with the disease itself. There are interesting imaging novelties that may be prospectively applicable in the decision-making and planning of the most effective treatment approach for individual patients with intracranial AVM. Surgery is often considered the first-line treatment; however, each patient should be evaluated individually, and the risks of the active treatment policy should not overcome the benefits of the spontaneous natural history of the disease. All treatment modalities, i.e., surgery, radiosurgery, endovascular embolization, and observation, are justified but need to be meticulously selected for each individual patient in order to deliver the best treatment outcome. This chapter deals with historical and currently applied dogmas, followed by introductions of advances in each available treatment modality of AVM management.

SBRT for Cardiac Ablation in Patients With Refractory Ventricular Tachycardia.

BACKGROUND: This case details a 44-year-old man with end-stage ischemic cardiomyopathy with refractory ventricular tachycardia (VT). The patient has a single-chamber implantable cardioverter-defibrillator, has had 2 VT ablations, and uses medication to manage his VT. Despite these interventions, he continued to have episodes of VT. The patient underwent stereotactic body radiation therapy (SBRT) to help reduce the burden of his VT. The patient received a dose of 25 Gy to his right inferior lateral region of the heart and a dose of 15 Gy to the inferior portion of the heart closer to the stomach. The patient followed up 1 month later and reported that his energy levels improved and that no arrhythmias had occurred since his SBRT treatment. DISCUSSION: The options for treating end-stage VT are limited. However, a treatment option using SBRT has been introduced to reduce the VT burden in patients. Cardiac SBRT is a noninvasive outpatient procedure that, while still awaiting U.S. Food and Drug Administration approval, reduces arrhythmia episodes and offers favorable short-term benefits for patients who have not responded to traditional treatment modalities. CONCLUSION: Cardiac SBRT is a novel treatment for VT in patients where standard treatments have failed. This case study demonstrates that SBRT effectively reduced arrhythmias in a patient with VT. The long-term clinical outcomes are not known, but the opportunity SBRT offers for treatment-refractory patients is favorable and should be considered.

Surgical management of large lower cranial nerves schwannomas: long term results of a less aggressive resection strategy.

In an effort to reduce the high morbidity and life-threatening complications after radical resection in large schwannoma surgery, alternative strategies of nontotal resections have emerged. To evaluate the long term clinical and oncological outcome after lower cranial nerves (LCN) schwannoma surgery operated on with a cranial nerve-sparing technique. Single center retrospective cohort study of 8 consecutive patients harboring LCN schwannomas operated on between March 2005 and October 2021. The mean LCN schwannoma diameter was 33 mm (range 26-51). Seven patients (87,5%) underwent a modified retrosigmoid approach. Three patients underwent gross total resection (37,5%), 3 had received neartotal resection (mean tumor residue 0,25 cc) and subtotal resection in 2 patients who presented with an extracranial extension of the tumor (mean tumor residue 2,44 cc). Both patients had received upfront additional GKRS. The three patients who presented with preoperative CN IX & X injuries recovered within 6 months after surgery. All of the five patients freed from any preoperative CNs IX & X symptoms experienced transient (80%) or definitive (one patient) disturbances after surgery. They all improved within 6 months but one who required long term gastrostomy feeding tube. This patient harbored a schwannoma originating from the glossopharyngeal nerve, which could not be anatomically preserved during surgery. Tumor control was achieved in 100% of cases with a mean follow-up of 91 months. LCN schwannomas could be surgically removed through a less aggressive non-radical resection strategy with acceptable functional results and excellent tumor control.

Neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable hepatocellular carcinoma: the Notable-HCC phase 1b trial.

Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.

Markerless liver online adaptive stereotactic radiotherapy: feasibility analysisCervantes.

Objective. Radio-opaque markers are recommended for image-guided radiotherapy in liver stereotactic ablative radiotherapy (SABR), but their implantation is invasive. We evaluate in thisin-silicostudy the feasibility of cone-beam computed tomography-guided stereotactic online-adaptive radiotherapy (CBCT-STAR) to propagate the target volumes without implanting radio-opaque markers and assess its consequence on the margin that should be used in that context.Approach. An emulator of a CBCT-STAR-dedicated treatment planning system was used to generate plans for 32 liver SABR patients. Three target volume propagation strategies were compared, analysing the volume difference between the GTVPropagatedand the GTVConventional, the vector lengths between their centres of mass (lCoM), and the 95th percentile of the Hausdorff distance between these two volumes (HD95). These propagation strategies were: (1) structure-guided deformable registration with deformable GTV propagation; (2) rigid registration with rigid GTV propagation; and (3) image-guided deformable registration with rigid GTV propagation. Adaptive margin calculation integrated propagation errors, while interfraction position errors were removed. Scheduled plans (PlanNon-adaptive) and daily-adapted plans (PlanAdaptive) were compared for each treatment fraction.Main results.The image-guided deformable registration with rigid GTV propagation was the best propagation strategy regarding tolCoM(mean: 4.3 +/- 2.1 mm), HD95 (mean 4.8 +/- 3.2 mm) and volume preservation between GTVPropagatedand GTVConventional. This resulted in a planning target volume (PTV) margin increase (+69.1% in volume on average). Online adaptation (PlanAdaptive) reduced the violation rate of the most important dose constraints ('priority 1 constraints', 4.2 versus 0.9%, respectively;p< 0.001) and even improved target volume coverage compared to non-adaptive plans (PlanNon-adaptive).Significance. Markerless CBCT-STAR for liver tumours is feasible using Image-guided deformable registration with rigid GTV propagation. Despite the cost in terms of PTV volumes, daily adaptation reduces constraints violation and restores target volumes coverage.

An AI-based approach for modeling the synergy between radiotherapy and immunotherapy.

Personalized, ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) is designed to administer tumoricidal doses in a pulsed mode with extended intervals, spanning weeks or months. This approach leverages longer intervals to adapt the treatment plan based on tumor changes and enhance immune-modulated effects. In this investigation, we seek to elucidate the potential synergy between combined PULSAR and PD-L1 blockade immunotherapy using experimental data from a Lewis Lung Carcinoma (LLC) syngeneic murine cancer model. Employing a long short-term memory (LSTM) recurrent neural network (RNN) model, we simulated the treatment response by treating irradiation and anti-PD-L1 as external stimuli occurring in a temporal sequence. Our findings demonstrate that: (1) The model can simulate tumor growth by integrating various parameters such as timing and dose, and (2) The model provides mechanistic interpretations of a "causal relationship" in combined treatment, offering a completely novel perspective. The model can be utilized for in-silico modeling, facilitating exploration of innovative treatment combinations to optimize therapeutic outcomes. Advanced modeling techniques, coupled with additional efforts in biomarker identification, may deepen our understanding of the biological mechanisms underlying the combined treatment.

SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. METHODS: 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. DISCUSSION: This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. TRIAL REGISTRATION: This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Knowledge-based planning for Gamma Knife.

BACKGROUND: Current methods for Gamma Knife (GK) treatment planning utilizes either manual forward planning, where planners manually place shots in a tumor to achieve a desired dose distribution, or inverse planning, whereby the dose delivered to a tumor is optimized for multiple objectives based on established metrics. For other treatment modalities like IMRT and VMAT, there has been a recent push to develop knowledge-based planning (KBP) pipelines to address the limitations presented by forward and inverse planning. However, no complete KBP pipeline has been created for GK. PURPOSE: To develop a novel (KBP) pipeline, using inverse optimization (IO) with 3D dose predictions for GK. METHODS: Data were obtained for 349 patients from Sunnybrook Health Sciences Centre. A 3D dose prediction model was trained using 322 patients, based on a previously published deep learning methodology, and dose predictions were generated for the remaining 27 out-of-sample patients. A generalized IO model was developed to learn objective function weights from dose predictions. These weights were then used in an inverse planning model to generate deliverable treatment plans. A dose mimicking (DM) model was also implemented for comparison. The quality of the resulting plans was compared to their clinical counterparts using standard GK quality metrics. The performance of the models was also characterized with respect to the dose predictions. RESULTS: Across all quality metrics, plans generated using the IO pipeline performed at least as well as or better than the respective clinical plans. The average conformity and gradient indices of IO plans was 0.737 ± $\pm$ 0.158 and 3.356 ± $\pm$ 1.030 respectively, compared to 0.713 ± $\pm$ 0.124 and 3.452 ± $\pm$ 1.123 for the clinical plans. IO plans also performed better than DM plans for five of the six quality metrics. Plans generated using IO also have average treatment times comparable to that of clinical plans. With regards to the dose predictions, predictions with higher conformity tend to result in higher quality KBP plans. CONCLUSIONS: Plans resulting from an IO KBP pipeline are, on average, of equal or superior quality compared to those obtained through manual planning. The results demonstrate the potential for the use of KBP to generate GK treatment with minimal human intervention.

Prediction of the treatment response and local failure of patients with brain metastasis treated with stereotactic radiosurgery using machine learning: A systematic review and meta-analysis.

BACKGROUND: Stereotactic radiosurgery (SRS) effectively treats brain metastases. It can provide local control, symptom relief, and improved survival rates, but it poses challenges in selecting optimal candidates, determining dose and fractionation, monitoring for toxicity, and integrating with other modalities. Practical tools to predict patient outcomes are also needed. Machine learning (ML) is currently used to predict treatment outcomes. We aim to investigate the accuracy of ML in predicting treatment response and local failure of brain metastasis treated with SRS. METHODS: PubMed, Scopus, Web of Science (WoS), and Embase were searched until April 16th, which was repeated on October 17th, 2023 to find possible relevant papers. The study preparation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The statistical analysis was performed by the MIDAS package of STATA v.17. RESULTS: A total of 17 articles were reviewed, of which seven and eleven were related to the clinical use of ML in predicting local failure and treatment response. The ML algorithms showed sensitivity and specificity of 0.89 (95% CI: 0.84-0.93) and 0.87 (95% CI: 0.81-0.92) for predicting treatment response. The positive likelihood ratio was 7.1 (95% CI: 4.5-11.1), the negative likelihood ratio was 0.13 (95% CI: 0.08-0.19), and the diagnostic odds ratio was 56 (95% CI: 25-125). Moreover, the pooled estimates for sensitivity and specificity of ML algorithms for predicting local failure were 0.93 (95% CI: 0.76-0.98) and 0.80 (95% CI: 0.53-0.94). The positive likelihood ratio was 4.7 (95% CI: 1.6-14.0), the negative likelihood ratio was 0.09 (95% CI: 0.02-0.39), and the diagnostic odds ratio was 53 (95% CI: 5-606). CONCLUSION: ML holds promise in predicting treatment response and local failure in brain metastasis patients receiving SRS. However, further studies and improvements in the treatment process can refine the models and effectively integrate them into clinical practice.

The optimal treatment for patients with stage I non-small cell lung cancer: minimally invasive lobectomy versus stereotactic ablative radiotherapy - a nationwide cohort study.

OBJECTIVES: The aim of the Early-Stage LUNG cancer (ESLUNG) study was to compare outcomes after minimally invasive lobectomy (MIL) and stereotactic ablative radiotherapy (SABR) in patients with stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this retrospective cohort study, patients with clinical stage I NSCLC (according to TNM7), treated in 2014-2016 with MIL or SABR, were included. 5-year overall survival (OS) and recurrence-free survival (RFS) were calculated and compared between patients treated with MIL and a propensity score (PS)-weighted SABR population with characteristics comparable to those of the MIL group. RESULTS: 1211 MIL and 972 SABR patients were included. Nodal upstaging occurred in 13.0 % of operated patients. 30-day mortality was 1.0 % after MIL and 0.2 % after SABR. After SABR, the 5-year regional recurrence rate (18.1 versus 14.2 %; HR 0.74, 95 % CI 0.58-0.94) and distant metastasis rate (26.2 versus 20.2 %; HR 0.72, 95 % CI 0.59-0.88) were significantly higher than after MIL, with similar local recurrence rate (13.1 versus 12.1 %; HR 0.90, 95 % CI 0.68-1.19). Unadjusted 5-year OS and RFS were 70.2 versus 40.3 % and 58.0 versus 25.1 % after MIL and SABR, respectively. PS-weighted, multivariable analyses showed no significant difference in OS (HR 0.89, 95 % CI 0.65-1.20) and better RFS after MIL (HR 0.70, 95 % CI 0.49-0.99). CONCLUSION: OS was not significantly different between stage I NSCLC patients treated with MIL and the PS-weighted population of patients treated with SABR. For operable patients with stage I NSCLC, SABR could therefore be an alternative treatment option with comparable OS outcome. However, RFS was better after MIL due to fewer regional recurrences and distant metastases. Future studies should focus on optimization of patient selection for MIL or SABR to further reduce postoperative mortality and morbidity after MIL and nodal failures after SABR.