Accuracy of robotic radiosurgery in renal cell carcinoma.

PURPOSE: Although emerging clinical evidence supports robotic radiosurgery as a highly effective treatment option for renal cell carcinoma (RCC) less than 4 cm in diameter, delivery uncertainties and associated target volume margins have not been studied in detail. We assess intrafraction tumor motion patterns and accuracy of robotic radiosurgery in renal tumors with real-time respiratory tracking to optimize treatment margins. METHODS: Delivery log files from 165 consecutive treatments of RCC were retrospectively analyzed. Five components were considered for planning target volume (PTV) margin estimation: (a) The model error from the correlation model between patient breath and tumor motion, (b) the prediction error from an algorithm predicting the patient breathing pattern, (c) the targeting error from the treatment robot, (d) the inherent total accuracy of the system for respiratory motion tracking, and (e) the margin required to cover potential target rotation, simulated with PTV rotations up to 10°. RESULTS: The median tumor motion was 10.5 mm, 2.4 mm and 4.4 mm in the superior-inferior, left-right, and anterior-posterior directions, respectively. The root of the sum of squares of all contributions to the system's inaccuracy results in a minimum PTV margin of 4.3 mm, 2.6 mm and 3.0 mm in the superior-inferior, left-right and anterior-posterior directions, respectively, assuming optimal fiducial position and neglecting target deformation. CONCLUSIONS: We have assessed kidney motion and derived PTV margins for the treatment of RCC with robotic radiosurgery, which helps to deliver renal treatments in a more consistent manner and potentially further improve outcomes.

Stereotactic ablative radiotherapy for treating primary head and neck cancer and locoregional recurrence: A comprehensive review of the literature.

Introduction: Although stereotactic ablative radiotherapy (SABR) has advance to standard-of-care for many different indications like lung and liver malignancies, it still remains in its infancy for treating head and neck cancer. Nevertheless there is a growing body of experience and evidence, which is summarized in this review Methods A thorough search of the literature was performed and critically reviewed both for SABR as a primary treatment as well as for treating locoregionally recurrent disease in a pre-irradiated field. Results: There exist only few prospective data published so far for treating head and neck cancer with SABR. In the primary situation especially implementing SABR as a boost after definitive radiotherapy or a single-modality for locally limited, small glottic cancer appear promising. On the other hand, SABR can be a useful modality for treating local recurrence in a pre-irradiated field. However, caution is needed in the case of proximity to a pre-irradiated carotid artery or other serial organs at risk. Usually only limited gross volumes are treated with 3-6 fractions every other day and a cumulative dose of 24-44 Gy in dedicated radiosurgery platforms or modern linacs with the possibility of online image-guidance and adequate immobilsation. Conclusions: SABR is an innovative, effective and promising treatment modality for small targets, especially in near proximity to organs at risk or in a pre-irradiated region. Prospective trials are further needed for this technique to become standard-of care.

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma.

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

End-to-end validation of fiducial tracking accuracy in robotic radiosurgery using MRI-only simulation imaging.

BACKGROUND: Image-guided radiation-therapy (IGRT)-based robotic radiosurgery using magnetic resonance imaging (MRI)-only simulation could allow for improved target definition with highly conformal radiotherapy treatments. Fiducial marker (FM)-based alignment is used with robotic radiosurgery treatments of sites such as the prostate because it aids in accurate target localization. Synthetic CT (sCT) images are generated in the MRI-only workflow but FMs used for IGRT appear as signal voids in MRIs and do not appear in MR-generated sCTs, hindering the ability to use sCTs for fiducial-based IGRT. PURPOSE: In this study we evaluate the fiducial tracking accuracy for a novel artificial fiducial insertion method in sCT images that allows for fiducial marker tracking in robotic radiosurgery, using MRI-only simulation imaging (MRI-only workflow). METHODS: Artificial fiducial markers were inserted into sCT images at the site of the real marker implantation as visible in MRI. Two phantoms were used in this study. A custom anthropomorphic pelvis phantom was designed to validate the tracking accuracy for a variety of artificial fiducials in an MRI-only workflow. A head phantom containing a hidden target and orthogonal film pair inserts was used to perform end-to-end tests of artificial fiducial configurations inserted in sCT images. The setup and end-to-end targeting accuracy of the MRI-only workflow were compared to the computed tomography (CT)-based standard. Each phantom had six FMs implanted with a minimum spacing of 2 cm. For each phantom a bulk-density sCT was generated, and artificial FMs were inserted at the implantation location. Several methods of FM insertion were tested including: (1) replacing HU with a fixed value (10000HU) (voxel-burned); (2) using a representative fiducial image derived from a linear combination of fiducial templates (composite-fiducial); (3) computationally simulating FM signal voids using a digital phantom containing FMs and inserting the corresponding signal void into sCT images (simulated-fiducial). All tests were performed on a CyberKnife system (Accuray, Sunnyvale, CA). Treatment plans and digital-reconstructed-radiographs were generated from the original CT and sCTs with embedded fiducials and used to align the phantom on the treatment couch. Differences in the initial phantom alignment (3D translations/rotations) and tracking parameters between CT-based plans and sCT-based plans were analyzed. End-to-end plans for both scenarios were generated and analyzed following our clinical protocol. RESULTS: For all plans, the fiducial tracking algorithm was able to identify the fiducial locations. The mean FM-extraction uncertainty for the composite and simulated FMs was below 48% for fiducials in both the anthropomorphic pelvis and end-to-end phantoms, which is below the 70% treatment uncertainty threshold. The total targeting error was within tolerance (<0.95 mm) for end-to-end tests of sCT images with the composite and head-on simulated FMs (0.26, 0.44, and 0.35 mm for the composite fiducial in sCT, head-on simulated fiducial in sCT, and fiducials in original CT, respectively. CONCLUSIONS: MRI-only simulation for robotic radiosurgery could potentially improve treatment accuracy and reduce planning margins. Our study has shown that using a composite-derived or simulated FM in conjunction with sCT images, MRI-only workflow can provide clinically acceptable setup accuracy in line with CT-based standards for FM-based robotic radiosurgery.

Meningioma involving the superior sagittal sinus: long-term outcome after robotic radiosurgery in primary and recurrent situation.

Objective: Treatment for meningiomas involving the superior sagittal sinus (SSS) is challenging and proved to be associated with higher risks compared to other brain locations. Therapeutical strategies may be either microsurgical (sub-)total resection or adjuvant radiation, or a combination of both. Thrombosis or SSS occlusion following resection or radiosurgery needs to be further elucidated to assess whether single or combined treatment is superior. We here present tumor control and side effect data of robotic radiosurgery (RRS) in combination with or without microsurgery. Methods: From our prospective database, we identified 137 patients with WHO grade I meningioma involving the SSS consecutively treated between 2005 and 2020. Treatment decisions were interdisciplinary. Patients underwent RRS as initial/solitary treatment (group 1), as adjuvant treatment after subtotal resection (group 2), or due to recurrent tumor growth after preceding microsurgery (group 3). Positive tumor response was assessed by MRI and defined as reduction of more than 50% of volume. Study endpoints were time to recurrence (TTR), time to RRS, risk factors for decreased survival, and side effects. Overall and specific recurrence rates for treatment groups were analyzed. Side effect data included therapy-related morbidity during follow-up (FU). Results: A total of 137 patients (median age, 58.3 years) with SSS meningiomas WHO grade I were analyzed: 51 patients (37.2%) in group 1, 15 patients (11.0%) in group 2, and 71 patients (51.8%) in group 3. Positive MR (morphological response) to therapy was achieved in 50 patients (36.4%), no response was observed in 25 patients (18.2%), and radiological tumor progression was detected in 8 patients (5.8%). Overall 5-year probability of tumor recurrence was 15.8% (median TTR, 41.6 months). Five-year probabilities of recurrence were 0%, 8.3.%, and 21.5% for groups 1-3 (p = 0.06). In multivariate analysis, tumor volume was significantly associated with extent of SSS occlusion (p = 0.026) and sex (p = 0.011). Tumor volume significantly correlated with TTR (p = 0.0046). Acute sinus venous thrombosis or venous congestion-associated bleedings did not occur in any of the groups. Conclusion: RRS for grade I meningiomas with SSS involvement represents a good option as first-line treatment, occasionally also in recurrent and adjuvant scenarios as part of a multimodal treatment strategy.

Prospective Evaluation of Response to Treatment, Survival Functions, Recurrence Pattern and Toxicity Profile in Indian Patients with Oligo-Brain Metastasis Treated with Only SRS.

Background: Prospective analysis of oligo-brain metastasis in Indian patients treated with SRS-only treatment. Methods: Between January 2017 and May 2022, 235 patients were screened and 138 histologically proven and radiologically confirmed. One to five brain metastasis patients aged more than 18 years with good Karnofsky performance status (KPS >70) accrued in ethical and scientific committee-approved prospective observational study protocol for treatment with only radiosurgery (SRS) with robotic radiosurgery (CyberKnife, CK) [AIMS IRB: 2020-071; CTRI No: REF/2022/01/050237]. Immobilization was performed with a thermoplastic mask, contrast CT simulation was performed with 0.625 mm slices, fused with T1 contrast/T2 FLAIR MRI images for contouring. Planning target volume (PTV) margin of 2-3 mm and a dose of 20-30 Gy in 1-5 fractions. Response to treatment, new brain lesions free survival, overall survival, and toxicity profile after CK were evaluated. Results: In total,: 138 patients with 251 lesions were accrued (median age 59 years (interquartile range [IQR] 49-67 years; female 51%; headache in 34%, motor deficit in 7%, KPS >90 in 56%; lung primary in 44%, breast in 30%; oligo-recurrence in 45%; synchronous oligo-metastases in 33%; adenocarcinoma primary in 83%). One hundred seven patients (77%) received upfront Stereotactic radiotherapy (SRS), 15 (11%) received postoperative SRS, 12 (9%) received whole brain radiotherapy (WBRT) before SRS, and 3 (2%) received WBRT plus SRS boost. The majority had solitary (56%) brain metastasis, 28% had two to three lesions, and 16% had four to five brain lesions. Frontal (39%) was the most common site. Median PTV was 15.5 mL (IQR - 8.1-28.5 mL). Seventy-one (52%) patients were treated with single fractions, 14% with three, and 33% with five fractions. Fraction schedules were 20-2 4 Gy/1fr; 27 Gy/3fr, and 25 Gy/5 fractions (mean BED 74.6 Gy [SD ± 48.1; mean MU 16608], mean treatment time was 49 min (range 17-118 min]. Twelve Gy normal brain volume was 40.8 mL (3.2%) (range 19.3-73.7 mL). At a mean follow-up of 15 months (SD 11.9 months; max 56 months), the mean actuarial OS after SRS-only treatment was 23.7 months (95% confidence interval [CI] 20-28). Further 124 (90%) patients had >3 months, 108 (78%) had >6 months, 65 (47%) had >12 months, and 26 (19%) had >24 months follow-up. Intracranial disease and extracranial disease were controlled in 72 (52.2%) and 60 (43.5%), respectively. "In-field" recurrence, "out-of-field," and "both in and out-of-field" recurrences were in 11%, 42%, and 46%, respectively. At the last follow-up, 55 patients (40%) were alive, 75 (54%) died due to disease progression, and the status of 8 (6%) patients was not known. Among 75 patients who died, 46 (61%) had extracranial disease progression, 12 (16%) had only intracranial progression, and 8 (11%) had unrelated causes. Also, 12/117 (9%) had radiological confirmation of radiation necrosis. Prognostication based on western patients (primary tumor type, number of lesions extracranial disease) showed similar outcomes. Conclusions: SRS alone in brain metastasis is feasible in the Indian subcontinent with similar survival outcomes, recurrence patterns, and toxicity as published in the western literature. Patient selection, dose schedule, and planning need to be standardized to have similar outcomes. WBRT can be safely omitted in Indian patients with oligo-brain metastasis. Western prognostication nomogram is applicable in the Indian patient population.

Long-term follow-up results of spine tumor treatment using high-dose radiotherapy after 3-dimensional-printed vertebral bodies implantation.

OBJECTIVE: To investigate the long-term safety and efficacy of high-dose radiotherapy after 3D-printed vertebral body implantation in the treatment of spinal tumors. METHODS: Thirty-three participants were recruited between July 2017 and August 2019. 3D-printed vertebral bodies were implanted in each participant, followed by postoperative robotic stereotactic radiosurgery at a dose of 35-40 Gy/5f. The tolerance of the 3D-printed vertebral body and the participant to the high-dose radiotherapy were evaluated. In addition, the local control of tumor and the local progression-free survival of the study participants following 3D-printed vertebral body implantation and high-dose radiotherapy were measured as indexes of effectiveness. RESULTS: Of the 33 participants included in the study, 30, including three participants (10%) with esophagitis of grade 3 or above and two participants (6.7%) with advanced radiation nerve injury, successfully underwent postoperative high-dose radiotherapy. The median follow-up was 26.7 months, and IQR was 15.9 months. Most participants had primary bone tumors with 27 cases (81.8%), and the rest had bone metastases in six cases (18.2%). After high-dose radiotherapy, the 3D-printed vertebrae maintained good vertebral stability and exhibited histocompatibility, without implant fractures. The local control rates were 100%, 88%, and 85% 6 months, 1 year, and 2 years after high-dose radiotherapy, respectively. Tumors recurred in four participants (12.1%) during the follow-up period. The median local progression-free survival after treatment was 25.7 months, with a range of 9.6-33.0 months. CONCLUSION: High-dose radiotherapy for spinal tumors after 3D-printed vertebral body implantation is feasible, elicits low toxicity, and yields satisfactory tumor control.

Robotic Radiosurgical Boost After Whole-Brain Radiotherapy for 12 Brain Metastases: En Bloc Consecutive Irradiation With Comprehensively Optimized Single Plan for Eight Lesions Totaling 118 cc.

General radiotherapeutic management for >10 brain metastases (BMs) totaling >100 cm3, including multiple large lesions (>10-30 cm3) in close proximity, demonstrated limited efficacy and/or safety. We describe a case of 12 BMs, summating 122.2 cm3, including a 39.6 cm3 maximum lesion and adjacent ones. The patient had an 8.1-year treatment history for recurrent/metastatic breast cancer refractory to endocrine and chemotherapy. BMs were treated with conventional whole-brain radiotherapy (WBRT) with 30 Gy/10 fractions (fr), followed by an immediate stereotactic radiosurgery (SRS) boost with 27 Gy/5 fr (52-64% isodoses) which covers the gross tumor boundaries of selected eight lesions (total 118.4 cm3). The SRS dose was defined to ensure the cumulative biologically effective dose (BED10) of just ≥80 Gy while minimizing the risk of radiation injury. The SRS was performed using a CyberKnife (CK) robotic system (Accuray Incorporated, Sunnyvale, California, United States) with a variable-sized collimator (10-40 mm), for which en bloc consecutive irradiation, using 215 beams based on a comprehensively optimized single plan (path), was adopted. The treatment time per fraction was ≤45 min (mean 5.6 min per lesion). Afterward, BMs demonstrated remarkable regression over six months, causing the total residual visible lesions of 12.6 cm3 (10.3%) at 11.4 months, despite the absence of obvious lesion shrinkage during the radiotherapy. WBRT, followed by an immediate 5-fr SRS boost with a total BED10 of 80 Gy to large and/or culprit lesions, can be an efficacious and safe treatment option for multiple BMs, totaling >120 cm3. En bloc consecutive irradiation with a single path provides overwhelmingly more efficient delivery for treating multiple lesions using CK in terms of irradiation time and comprehensive reduction of normal brain dose compared to individual planning. Volumetric-modulated arc-based >10-fr SRS with simultaneously integrated reduced-dose WBRT may be an alternative to further enhance efficacy and safety.

Preoperative robotic radiosurgery for early breast cancer: Results of the phase II ROCK trial (NCT03520894).

Background and purpose: Preoperative partial breast irradiation (PBI) has got the advantage of treating a well-defined target. We report the results of the phase II ROCK trial (NCT03520894), enrolling early breast cancer (BC) patients treated with preoperative robotic radiosurgery (prRS), in terms of acute and early late toxicity, disease control, and cosmesis. Material and methods: The study recruited between 2018 and 2021 at our Radiation Oncology Unit. Eligible patients were 50 + years old BC, hormonal receptors positive/human epidermal growth factor receptor 2 negative (HR+/HER2-), sized up to 25 mm. The study aimed to prospectively assess the toxicity and feasibility of a robotic single 21 Gy-fraction prRS in preoperative setting. Results: A total of 70 patients were recruited and 22 patients were successfully treated with pRS. Overall, three G1 adverse events (13.6 %) were recorded within 7 days from prRS. Three events (13.6 %) were recorded between 7 and 30 days, one G2 breast oedema and two G1 breast pain. No acute toxicity greater than G2 was recorded. Five patients experienced early late G1 toxicity. One patient reported G2 breast induration. No early late toxicity greater than G2 was observed. At a median follow up of 18 months (range 6-29.8), cosmetic results were scored excellent/good and fair in 14 and 5 patients, respectively, while 3 patients experienced a poor cosmetic outcome. Conclusions: ROCK trial showed that a single 21 Gy dose prRS represents a feasible technique for selected patients affected by early BC, showing an acceptable preliminary toxicity profile.

Dynamic 18F-FET PET/CT to differentiate recurrent primary brain tumor and brain metastases from radiation necrosis after single-session robotic radiosurgery.

OBJECTIVE: Cyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion correction. Although RRS appears to cause more radiation necrosis (RN), the radiometabolic changes after RRS have not been fully clarified. 18F-FET-PET/CT is used to differentiate recurrent tumor (RT) from RN after radiosurgery when MRI findings are indecisive. We explored the usefulness of dynamic parameters derived from 18F-FET PET in differentiating RT from RN after Cyberknife treatment in a single-center study population. METHODS: We retrospectively identified brain tumor patients with static and dynamic 18F-FET-PET/CT for suspected RN after Cyberknife. Static (tumor-to-background ratio) and dynamic PET parameters (time-activity curve, time-to-peak) were quantified. Analyses were performed for all lesions taken together (TOTAL) and for brain metastases only (METS). Diagnostic accuracy of PET parameters (using mean tumor-to-background ratio >1.95 and time-to-peak of 20 min for RT as cut-offs) and their respective improvement of diagnostic probability were analyzed. RESULTS: Fourteen patients with 28 brain tumors were included in quantitative analysis. Time-activity curves alone provided the highest sensitivities (TOTAL: 95%, METS: 100%) at the cost of specificity (TOTAL: 50%, METS: 57%). Combined mean tumor-to-background ratio and time-activity curve had the highest specificities (TOTAL: 63%, METS: 71%) and led to the highest increase in diagnosis probability of up to 16% p. - versus 5% p. when only static parameters were used. CONCLUSIONS: This preliminary study shows that combined dynamic and static 18F-FET PET/CT parameters can be used in differentiating RT from RN after RRS.

Applications of Frameless Image-Guided Robotic Stereotactic Radiotherapy and Radiosurgery in Pediatric Neuro-Oncology: A Systematic Review.

BACKGROUND: CyberKnife-based robotic radiosurgery (RRS) is a widely used treatment modality for various benign and malignant tumors of the central nervous system (CNS) in adults due to its high precision, favorable safety profile, and efficacy. Although RRS is emerging in pediatric neuro-oncology, scientific evidence for treatment indications, treatment parameters, and patient outcomes is scarce. This systematic review summarizes the current experience and evidence for RRS and robotic stereotactic radiotherapy (RSRT) in pediatric neuro-oncology. METHODS: We performed a systematic review based on the databases Ovid Medline, Embase, Cochrane Library, and PubMed to identify studies and published articles reporting on RRS and RSRT treatments in pediatric neuro-oncology. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied herein. Articles were included if they described the application of RRS and RSRT in pediatric neuro-oncological patients. The quality of the articles was assessed based on their evidence level and their risk for bias using the original as well as an adapted version of the Newcastle Ottawa Quality Assessment Scale (NOS). Only articles published until 1 August 2021, were included. RESULTS: A total of 23 articles were included after final review and removal of duplicates. Articles reported on a broad variety of CNS entities with various treatment indications. A majority of publications lacked substantial sample sizes and a prospective study design. Several reports included adult patients, thereby limiting the possibility of data extraction and analysis of pediatric patients. RRS and RSRT were mostly used in the setting of adjuvant, palliative, and salvage treatments with decent local control rates and acceptable short-to-intermediate-term toxicity. However, follow-up durations were limited. The evidence level was IV for all studies; the NOS score ranged between four and six, while the overall risk of bias was moderate to low. CONCLUSION: Publications on RRS and RSRT and their application in pediatric neuro-oncology are rare and lack high-quality evidence with respect to entity-related treatment standards and long-term outcomes. The limited data suggest that RRS and RSRT could be efficient treatment modalities, especially for children who are unsuitable for surgical interventions, suffer from tumor recurrences, or require palliative treatments. Nevertheless, the potential short-term and long-term adverse events must be kept in mind when choosing such a treatment. Prospective studies are necessary to determine the actual utility of RRS and RSRT in pediatric neuro-oncology.

The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas-A Multicenter Analysis and Review of the Literature.

BACKGROUND: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. METHODS: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. RESULTS: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. CONCLUSIONS: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery.

Image-Guided Robotic Radiosurgery for the Treatment of Lung Metastases of Renal Cell Carcinoma-A Retrospective, Single Center Analysis.

Pulmonary metastases are the most frequent site of metastases in renal cell carcinoma (RCC). Metastases directed treatment remains an important treatment option despite advances in systemic therapies. However, the safety and efficacy of robotic radiosurgery (RRS) for the treatment of lung metastases of RCC remains unclear. Patients with metastatic RCC and lung metastases treated by RRS were retrospectively analyzed for overall survival (OS), progression-free survival (PFS), local recurrence free survival (LRFS) and adverse events. The Kaplan-Meier method was used for survival analysis and the common terminology criteria for adverse events (CTCAE; Version 5.0) classification for assessment of adverse events. A total of 50 patients were included in this study. Median age was 64 (range 45-92) years at the time of RRS. Prior to RRS, 20 patients (40.0%) had received either tyrosine kinase inhibitors or immunotherapy and 27 patients (54.0%) were treatment naïve. In our patient cohort, the median PFS was 13 months (range: 2-93). LRFS was 96.7% after two years with only one patient revealing progressive disease of the treated metastases 13 months after RRS. Median OS was 35 months (range 2-94). Adverse events were documented in six patients (12%) and were limited to grade 2. Fatigue (n = 4) and pneumonitis (n = 2) were observed within 3 months after RRS. In conclusion, RRS is safe and effective for patients with metastatic RCC and pulmonary metastases. Radiation induced pneumonitis is specific in the treatment of pulmonary lesions, but not clinically relevant and survival rates seem favorable in this highly selected patient cohort. Future directions are the implementation of RRS in multimodal treatment approaches for oligometastatic or oligoprogressive disease.

Analysis of normal lung irradiation in radiosurgery treatments: a comparison of lung optimized treatment (LOT) on cyberknife, 4D target volume on helical tomotherapy, and DIBH on linear accelerator.

Quantitative retrospective analysis of the normal lung irradiation due to the variations of the ITV volume based on the techniques used for upper lobe (UL), mid lobe (ML), and lower lobe (LL) lung tumours when used with 2-view, 1-view, 0-view based LOT technique on Cyberknife, AveIP on Helical Tomotherapy, and DIBH on VMAT systems. In the treatment of lung tumours, patients medically inoperable or those who are unwilling to undergo surgery have the option to be treated using radiation therapy. There are many motion control techniques available for the treatment of the moving target, such as movement encompassment, respiratory gating, breath-hold, motion reduction, and tumour monitoring. ITV generation is dependent on technique and hence the volume of the PTVs will differ based on the technique used. This study aimed to determine the influence of these ITVs on the irradiated normal lung volume for UL, ML, and LL lung tumours for 23 patients. The mean difference in the PTV volumes generated with the 0-view technique was significant with that of 2-view and DIBH techniques (p-value < 0.04). The mean difference in the PTV volumes generated by 2-view and DIBH was small for UL, ML, and LL tumours. V5 of the combined lung with the 0-view method was 5% compared to the 2-view method for UL tumours (p-value = 0.04) and the same was 9.5%, and 16.8% for ML and LL tumours (p-value < 0.04). In contrast to all other techniques, lung volume parameters V5, V10, V20, and V30 for the 0-view technology were consistently higher irrespective of the tumour location in the lung. The observed maximum mean lung dose (MLD) was 6.2 Gy ± 2.7 Gy with the 0-view technique and the minimum was 3.85 Gy ± 1.75 Gy with the DIBH technique. The difference in MLD between DIBH and 2-view was negligible (p-value = 0.67). The MLD increased for LL tumours from 4 Gy to 6.5 Gy from the 2-view to 0-view technique (p-value = 0.009). There was a significant increase in MLD for LL tumours with the 0-view technique compared to AveIP (1.9 Gy, p-value = 0.04) and DIBH (2.0 Gy, p-value = 0.003) technique. For ML and UL tumours, except for 0-view and 1-view, the difference in the MLD between the rest of the methods was not significant (p-value > 0.11). In the treatment of lung tumour patients with SBRT, this study has demonstrated 2-view with Cyberknife and DIBH with VMAT treatment techniques have optimal normal lung tissue sparing. There was a significant increase in the average lung volume receiving 5%,10%, 20%, and 30% dose when comparing the 1-view, 0-view, AveIP, and DIBH techniques to the 2-view technique. However, DIBH with VMAT was dosimetrically advantageous for ML and LL tumours, while providing significantly shorter treatment times than any other technique studied.

Hepatocellular carcinoma patients with portal vein thrombosis treated with robotic radiosurgery: Interim results of a prospective study.

BACKGROUND: This is a prospective study evaluating the role of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) in Indian patients suffering from hepatocellular carcinoma with portal vein thrombosis (HCC-PVT). METHODS: Patients with inoperable HCC-PVT, good performance score (PS), and liver function are accrued for treatment on CK (version M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring, and the gross tumor volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per-risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy, and the duodenum max of ≤24 Gy). RESULTS: Seventy-two HCC-PVT accrued till date (mean age 63 years [38-76 years], 96% male; Child-Pugh [CP] A 84%, B 9%; Barcelona-Clinic Liver Cancer [BCLC] C 96%; PS0-1: 80%, Karnofsky performance score [KPS]>70: 88%; co-morbidities 42%; infective 12%, alcohol intake 31%, adjuvant sorafenib 39%). CP scores 5, 6, 7, and 8 were in 35%, 32%, 8%, and 18%, respectively. Focal disease with portal vein thrombus (PVT) in 21%, liver involvement >50% and <50% in 46% and 32%. Liver cancer study group of Japan staging-based portal vein invasion VP2, VP3, and VP4 in 22%, 29%, and 40%. Cancer of the Liver Italian Programm (CLIP) scores 1, 2, 3, 4, and 5 were in 8%, 26%, 31%, 26%, and 7%, respectively. Mean follow-up was 7.3 months (median 6 months, standard deviation [SD] 6; range 3-30 months). Mean actuarial overall survival (OS) was 11.4 months (SE 1.587; 95% CI: 8-14.2 months). Six months and 12 months actuarial OS 55% and 38%, respectively. At last follow-up, 25/69 (36%) were alive and 44/69 (64%) were dead. Among 54 patients evaluated for response assessment, 23 (30%) had radiological confirmed PVT response, 1 (3%) had response of IVC thrombus, and 30 (42%) had no or minimal response to SBRT. Actuarial OS in responders and non-responders were 14.4 months (95% CI 9.4-19.2) and 7.4 months (95% CI 4.9-9.7), p-value: 0.022. Six and 12 months survival in responders and non-responders were 65.7% and 37% and 49% and 24.6%, respectively. Post-SBRT, 4 (12%) patients underwent transarterial chemoembolization (TACE) 3 patients (8%) and 1 patient (4%) transarterial radioembolization (TARE). Post-CK, (<4 weeks) 2 patients (4%) had decompensation. CONCLUSIONS: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Risks and Benefits of Fiducial Marker Placement in Tumor Lesions for Robotic Radiosurgery: Technical Outcomes of 357 Implantations.

Fiducial markers (FM) inserted into tumors increase the precision of irradiation during robotic radiosurgery (RRS). This retrospective study evaluated the clinical complications, marker migration, and motion amplitude of FM implantations by analyzing 288 cancer patients (58% men; 63.1 ± 13.0 years) who underwent 357 FM implantations prior to RRS with CyberKnife, between 2011 and 2019. Complications were classified according to the Society of Interventional Radiology (SIR) guidelines. The radial motion amplitude was calculated for tumors that moved with respiration. A total of 725 gold FM was inserted. SIR-rated complications occurred in 17.9% of all procedures. Most complications (32.0%, 62/194 implantations) were observed in Synchrony®-tracked lesions affected by respiratory motion, particularly in pulmonary lesions (46.9% 52/111 implantations). Concurrent biopsy sampling was associated with a higher complication rate (p = 0.001). FM migration occurred in 3.6% after CT-guided and clinical FM implantations. The largest motion amplitudes were observed in hepatic (20.5 ± 11.0 mm) and lower lung lobe (15.4 ± 10.5 mm) lesions. This study increases the awareness of the risks of FM placement, especially in thoracic lesions affected by respiratory motion. Considering the maximum motion amplitude, FM placement remains essential in hepatic and lower lung lobe lesions located >100.0 mm from the spine.

68Ga-DOTATOC-PET/MRI-A Secure One-Stop Shop Imaging Tool for Robotic Radiosurgery Treatment Planning in Patients with Optic Nerve Sheath Meningioma.

Optic nerve sheath meningiomas (ONSM) are rare but can lead to irreversible blindness. Hybrid imaging may enhance tumor delineation and diagnostic accuracy via receptor binding. However, relevant clinical data for ONSM are lacking. We evaluated the feasibility of receptor-based hybrid imaging prior to robotic radiosurgery (RRS). We retrospectively analyzed all of our institution's patients with suspected ONSM who underwent combined positron emission tomography and magnetic resonance imaging (PET/MRI) with gallium-68-labeled (DOTA0-Phe1-Tyr3) octreotide (Ga68-DOTATOC) before RRS between 2018 and 2019. Eight patients with ten suspected ONSM (female = 7; median age, 51.2 years; IQR, 43.0-66.0) were included. Nine out of ten ONSM were deemed PET-positive with a median standard uptake value (SUV) max of 5.6 (IQR, 2.6-7.8). For all nine ONSM that presented 68Ga-DOTATOC uptake, hybrid PET/MRI was used for target volume contouring prior to RSS. At a median follow-up of 11.7 months (IQR, 9.4-16.4), tumor control was achieved in all patients. Radiosurgery resulted in the improvement of visual acuity in two of eight patients, whereas six showed stable vision. Ga68-DOTATOC-PET/MRI can be used for target volume contouring prior to RRS for ONSM as it enables safe treatment planning and improves diagnostic accuracy.

Effectiveness and Safety of Robotic Radiosurgery for Optic Nerve Sheath Meningiomas: A Single Institution Series.

The role of robotic radiosurgery (RRS) in the treatment of optic nerve sheath meningiomas (ONSM) remains controversial and it is only performed in specialized institutions due to tight dose constraints. We evaluated the effectiveness and safety of RRS in the management of ONSM. Twenty-five patients with 27 ONSM lesions who underwent RRS using the Cyberknife (CK) system were retrospectively analyzed (median age, 47.9 years; 84.0% women). Multisession RRS was used with 4-5 fractions with a cumulative dose of 20.0-25.0 Gy in 84.0% of patients and a single fraction at a dose of 14.0-15.0 Gy in 16% of patients. Prior to RRS, seven (28%) patients experienced blindness on the lesion side. In those patients with preserved vision prior to radiosurgery, the visual acuity remained the same in 90.0% and improved in 10.0% of the patients. Overall local tumor control was 96.0% (mean follow-up period; 37.4 ± 27.2 months). Neither patient age, previous surgery, or the period from the initial diagnosis to RRS showed a dependency on visual acuity before or after radiosurgery. RRS is a safe and effective treatment for the management of ONSM. Hypofractionation of radiosurgery in patients with preserved vision before CK treatment results in stable or improved vision.

Robotic Radiosurgery for Persistent Postoperative Acromegaly in Patients with Cavernous Sinus-Invading Pituitary Adenomas-A Multicenter Experience.

BACKGROUND: The rates of incomplete surgical resection for pituitary macroadenomas with cavernous sinus invasion are high. In growth hormone-producing adenomas, there is a considerable risk for persistent acromegaly. Thus, effective treatment options are needed to limit patient morbidity and mortality. This multicenter study assesses the efficacy and safety of robotic radiosurgery (RRS) for patients with cavernous sinus-invading adenomas with persistent acromegaly. METHODS: Patients who underwent RRS with CyberKnife for postoperative acromegaly were eligible. RESULTS: Fifty patients were included. At a median follow-up of 57 months, the local control was 100%. The pretreatment insulin-like growth factor 1 (IGF-1) levels and indexes were 381 ng/mL and 1.49, respectively. The median dose and prescription isodose were 18 Gy and 70%, respectively. Six months after RRS, and at the last follow-up, the IGF-1 levels and indexes were 277 ng/mL and 1.14, as well as 196 ng/mL and 0.83, respectively (p = 0.0001 and p = 0.0002). The IGF-1 index was a predictor for biochemical remission (p = 0.04). Nine patients achieved biochemical remission and 24 patients showed biochemical disease control. Three patients developed a new hypopituitarism. CONCLUSIONS: RRS is an effective treatment for this challenging patient population. IGF-1 levels are decreasing after treatment and most patients experience biochemical disease control or remission.

Safety and Efficacy of Robotic Radiosurgery for Visceral and Lymph Node Metastases of Renal Cell Carcinoma: A Retrospective, Single Center Analysis.

Despite rapid advances of systemic therapy options in renal cell carcinoma (RCC), local tumor or metastases treatment remains important in selected patients. Here, we assess the safety and efficacy of robotic radiosurgery (RRS) as an ablative therapy for visceral and lymph node metastases of RCC. Patients with histologically confirmed RCC and radiologically confirmed progression of visceral or lymph node metastases underwent RRS and were retrospectively analyzed. Overall survival and progression free survival were calculated by the Kaplan-Meier method and log-rank test. Sixty patients underwent RRS and were included in the analysis. Patients presented for RRS treatment with a median age at RRS treatment of 64 years (range 42-83), clear cell histology (88.3%) and favorable international metastatic renal cell carcinoma database (IMDC) risk score (58.3%). Treatment parameters differed for the number of fractions (median visceral metastases: 1, range 1-5; median lymph node metastases: 1, range 0-5; p = 0.003) and prescription dose (median visceral metastases 24 Gy, range 8-26; median lymph node metastases 18 Gy, range 7-26, p < 0.001). The median overall survival was 65.7 months (range: 2.9-108.6), the median progression free survival was 17.4 months (range: 2.7-70.0) and local tumor control was achieved in 96.7% of patients. Adverse events were limited to 8.3% of patients, with one grade 4 toxicity within 6 weeks after RRS therapy. RRS is a safe and effective treatment option in selected patients with metastatic RCC in a multimodal approach. Further research is warranted to confirm our findings prospectively.