Thirty-year clinical experience in gamma knife radiosurgery for trigeminal schwannomas.

We aimed to evaluate the radiographic and clinical outcomes after gamma knife radiosurgery (GKRS) for trigeminal schwannomas (TSs). A total of 87 patients who underwent GKRS for TSs between 1990 and 2020 were enrolled. The mean tumor volume was 4.3 cm3. The median prescribed dose for the margins of the tumor was 13 Gy. The median follow-up duration was 64.3 months (range 12.0-311.5 months). The overall local tumor control rate was 90%, and the symptom response rate was 93%. The response rate for each symptom was 88% for facial pain, 97% for facial sensory change, and 86% for cranial nerve deficits. Nineteen (22%) patients showed transient swelling, which had regressed at the time of the last follow-up. Cystic tumors were associated with transient swelling (p = 0.04). A tumor volume of < 2.7 cm3 was associated with local tumor control in univariable analysis. Transient swelling was associated with symptom control failure in both univariable and multivariable analyses (p = 0.04, odds ratio 14.538). GKRS is an effective treatment for TSs, both for local control and symptom control.

Outcomes after gamma knife radiosurgery for intraventricular meningiomas.

BACKGROUND: Intraventricular meningiomas (IVMs) are rare tumors with considerable treatment-associated morbidity due to their challenging location. Treatment with stereotactic radiosurgery (SRS) is sparsely reported in the literature. We describe our experience over the last 35 years using Gamma knife radiosurgery (GKRS) for IVMs. METHODS: We retrospectively reviewed the GKRS database identifying 2501 meningiomas treated at the University of Pittsburgh Medical Center over the last 35 years. Nineteen patients with (12 males, mean age = 53.2 years, range 14-84) 20 IVMs were identified. Headache was the most frequent presenting symptom (N = 12), and the trigone of the lateral ventricle was the most common location (N = 18). The median tumor volume was 4.8 cc (range, 0.8-17). The median margin dose was 14 Gy (range, 12-25) delivered at 50% isodose line. RESULTS: At a median follow-up of 63.1 months (range, 6-322.4) symptom control was achieved in 18 (94.7%) patients. The overall progression-free survival (PFS) was 95% at 5 years, and 85% at 10-years. After Log-rank test, patients who underwent GKRS within 12 months after diagnosis (vs. ≥ 12 months, X2: 4.455, p = 0.035), patients treated with primary GKRS without prior biopsy (vs. prior biopsy, X2: 4.000, p = 0.046), and patients with WHO grade I meningioma (vs. WHO II, X2: 9.000, p = 0.003) had a longer PFS. Imaging showed peritumoral edema in seven cases at a median of 10.5 (range, 6.13-24.3) months after GKRS. Only three of these patients were symptomatic and were successfully managed with oral medications. Cox´s regression revealed that a V12Gy ≥ 10 cc [HR: 10.09 (95% CI: 2.11-48.21), p = 0.004], and tumor volume ≥ 8 cc [HR: 5.87 (95% CI: 1.28-26.97), p = 0.023] were associated with a higher risk of peritumoral edema. CONCLUSION: GKRS is an effective and safe management option for intraventricular meningiomas. Early GKRS should be considered as a primary management modality for small and medium sized IVM and adjuvant management for residual IVMs.

Simultaneous integrated boost (SIB) to dominant intra-prostatic lesions during extreme hypofractionation for prostate cancer: the impact of rectal spacers.

PURPOSE: Boosting dominant intra-prostatic lesions (DILs) has the potential to increase the therapeutic ratio in prostate cancer radiotherapy. In this study, employing 5-fraction stereotactic ablative radiotherapy (SABR) volumetric modulated arc therapy (VMAT) to deliver 40 Gy to the prostate clinical target volume (CTV) while boosting the DIL up to 50 Gy was evaluated for patients before and after rectal spacer insertion. MATERIALS AND METHODS: 24 Computed Tomography (CT) scans of 12 prostate cancer patients with unfavourable intermediate or high risk prostate cancer were employed in this study. At least two treatment plans were generated for each patient to compare pre- and post-spacer insertion plans. Plans were evaluated for target coverage, organs-at-risk doses, and the achievable boost dose level. RESULTS: The CTV coverage was significantly better in plans with a spacer, V40Gy 98.4% versus 97.0% (p = 0.012). Using spacers significantly reduced rectal dose in all 12 patients in this study. It was possible to boost DIL to 50 Gy to without violating dose constraints in 6 of 12 patients and to 47.5 Gy in 3 patients post-spacer insertion. For 3 patients (25%) it was not possible to boost DIL above 45 Gy even with a spacer in situ. Without a spacer, for 6 patient (50%) clinically acceptable plan were only achieved when the DIL dose was lowered to 45 Gy. In five of these 6 patients the dose limiting structure was the urethra (urethra planning risk volume V45Gy [cc] ≤ 0.1 cc constraint). CONCLUSIONS: Clinically acceptable plans for 5 fraction SABR, 40 Gy to the prostate CTV, with a SIB to DIL (45-50 Gy) were achieved. The boost dose achieved was DIL location dependent and primarily affected by DIL's proximity to the urethra. Compared to plans before spacer insertion, higher DIL dose were achieved with spacer in situ for 25% of the patients. Moreover, significant reduction in rectal dose and better target coverage were also achieved for all patients with spacers in situ.

Determination of Collimator Helmet Factors for Leksell Gamma Knife 4C Unit Using GAF Chromic EBT3 Film and ImageJ Software.

BACKGROUND: Measurement of Collimator helmet factors (CHF) is an important quality assurance procedure to be performed on Leksell Gamma Knife unit at regular interval to make sure that the interchangeable collimator helmet fit into the source channels without any positional inaccuracy which leads to major treatment error. The primary aim of this study is to measure the CHFs for Elekta Leksell Gamma knife 4C helmets using GafChromic EBT3 film and Image J software. METHODS: GafChromic EBT3 film, EPSON expression 10000 XL scanner and Image J analysis software was used for this study. The calibration curve of GafChromic EBT3 film was generated with known dose values for 14 mm collimator helmet using ImageJ software. The collimator helmet factor (CHF) for 4mm, 8mm and 14 mm collimator helmets were measured by normalizing dose rates of 4mm, 8mm and 14 mm to the dose rate of 18 mm collimator helmet using the previously generated calibration curve. The measured CHF was compared to Elekta reference value and previously published mean values. RESULTS: The measured CHFs were 0.896, 0.958, and 0.986 for 4mm, 8mm and 14mm collimators respectively. The percentage difference obtained was 1.7 %, 0.21 %, 0.1 % between measured values and reference values. CONCLUSION: The measurement of CHFs in LGK 4C unit using GafChromic EBT3 film and ImageJ software is a reliable method to verify the manufacturer quoted CHFs in routine quality assurance procedures.

Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy.

Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of combined therapy. Methods: TTFields arrays were attached to a warm saline water bath and salt was added until the TTFields generator reached the maximal 2000 mA peak-to-peak current. A ball cube phantom containing 2 orthogonal films surrounded by fiducials was placed in the water phantom, CT scanned, and a radiation treatment plan with 58 isocentric beams was created using a 3 cm circular collimator. Fiducial tracking was used to deliver radiation, the films were scanned, and end-to-end targeting error was measured with vendor-supplied software. In addition, radiation effects on electric fields generated by the TTFields system were assessed by examining logfiles generated from the field generator. Results: With TTFields arrays in place and powered on, the robotic radiosurgery system achieved a final targeting result of 0.47 mm, which was well within the submillimeter specification. No discernible effects on TTFields current output beyond 0.3% were observed in the logfiles when the radiation beam pulsed on and off. Conclusion: A robotic radiosurgery system was used to verify that radiation targeting was not adversely affected when the TTFields arrays were in place and the TTFields delivery device was powered on. In addition, this study verified that radiation delivered simultaneously with TTFields did not interfere with the generation of the electric fields.

A priori quality assurance using a benchmark case of the randomized phase 2 GORTEC 2014-14 in oligometastatic head and neck cancer patients.

PURPOSE: A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT. MATERIAL AND METHODS: Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices. RESULTS: Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices. CONCLUSION: A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality.

Output factor measurements with multiple detectors in CyberKnife® Robotic Radiosurgery System.

AIM: The aim of this study was to measure and compare the output factor (OF) of a CyberKnife Robotic Radiosurgery System with eight different small field detectors and validate with Technical Report Series (TRS) report 483. BACKGROUND: Accurate dosimetry of CyberKnife system is limited due to the challenges in small field dosimetry. OF is a vital dosimetric parameter used in the photon beam modeling and any error would affect the dose calculation accuracy. MATERIALS AND METHODS: In this study, the OF was measured with eight different small-field detectors for the 12 IRIS collimators at 800 mm SAD setup at 15 mm depth. The detectors used were PTW 31016 PinPoint 3D, IBA PFD shielded diode, IBA EFD unshielded diode, IBA SFD unshielded diode (stereotactic), PTW 60008 shielded diode, PTW 60012 unshielded diode, PTW 60018 unshielded diode (stereotactic), and PTW 60019 CVD diamond detector. OF was obtained after correcting for field output correction factors from IAEA TRS No. 483. RESULTS: The field OFs in CyberKnife are derived from the measured data by applying the correction factors from Table 23 in TRS 483 for the eight small field detectors. These field OFs matched within 2% of peer-reviewed published values. The range and standard deviation showed a decreasing trend with collimator diameter. CONCLUSION: The field OF obtained after applying the appropriate correction factor from TRS 483 matched well with the peer-reviewed published OFs. The inter-detector variation showed a decreasing trend with increasing collimator field size. This study gives physicists confidence in measuring field OFs while using small field detectors mentioned in this work.

Evaluation of inter- and intra-fraction 6D motion for stereotactic body radiation therapy of spinal metastases: influence of treatment time.

BACKGROUND: The objective of this study was to analyze the amplitude of translational and rotational movements occurring during stereotactic body radiotherapy (SBRT) of spinal metastases in two different positioning devices. The relevance of intra-fractional imaging and the influence of treatment time were evaluated. METHODS: Twenty patients were treated in the supine position either (1) on a body vacuum cushion with arms raised and resting on a clegecel or (2) on an integrated SBRT solution consisting of a SBRT table top, an Orfit™ AIO system, and a vacuum cushion. Alignments between the cone beam computed tomography (CBCT) and the planning computed tomography allowed corrections of inter- and intra-fraction positional shifts using a 6D table. The absolute values of the translational and rotational setup errors obtained for 329 CBCT were recorded. The translational 3D vector, the maximum angle, and the characteristic times of the treatment fractions were calculated. RESULTS: An improvement in the mean (SD) inter-fraction 3D vector (mm) from 7.8 (5.9) to 5.9 (3.8) was obtained by changing the fixation devices from (1) to (2) (p < 0.038). The maximum angles were less than 2° for a total of 87% for (1) and 96% for (2). The mean (SD) of the intra-fraction 3D vectors (mm) was lower for the new 1.1 (0.8) positioning fixation (2) compared to the old one (1) 1.7 (1.7) (p = 0.004). The angular corrections applied in the intra-fraction were on average very low (0.4°) and similar between the two systems. A strong correlation was found between the 3D displacement vector and the fraction time for (1) and (2) with regression coefficients of 0.408 (0.262-0.555, 95% CI) and 0.069 (0.010-0.128, 95% CI), respectively. An accuracy of 1 mm would require intra-fraction imaging every 5 min for both systems. If the expected accuracy was 2 mm, then only system (2) could avoid intra-fractional imaging. CONCLUSIONS: This study allowed us to evaluate setup errors of two immobilization devices for spine SBRT. The association of inter- and intra-fraction imaging with 6D repositioning of a patient is inevitable. The correlation between treatment time and corrections to be applied encourages us to move toward imaging modalities which allow a reduction in fraction time.

The Long-Term Outcome of CyberKnife-Based Stereotactic Radiotherapy for Head and Neck Paragangliomas: A Single-Center Experience.

OBJECTIVE: To assess long-term outcomes of hypofractionated stereotactic radiotherapy (hSRT) for head and neck paragangliomas (HNPGs). METHODS: Patients who underwent hSRT with CyberKnife for HNPGs from 2010 to 2019 were retrospectively reviewed. RESULTS: A total of 34 HNPGs in 29 patients were identified. Mean patient age was 50 ± 16 years, and 15 patients (52%) were female. Fifteen patients (55%) had undergone previous procedures. Four cases (14%) were functional in hormone production. According to the Fisch classification, 1 (3%) case was B, 12 (42%) cases were C, 14 (48%) cases were D, and 2 (7%) cases were unclassified.1 The median prescribed dose covering 95% of the planning target volume was 2500 cGy (interquartile range 2100-2600 cGy), and the median target volume was 10 cm3 (interquartile range 6.0-18.3 cm3). The local control rate was 97%. The median progression-free survival was 66 months (interquartile range 28-95 months), and 96% of patients were free of tumor progression at 8 years. During follow-up, 1 case (3%) resulted in permanent facial nerve palsy (House-Brackmann grade II), and another case (3%) resulted in asymptomatic cerebellar radiation necrosis. Univariate and multivariate analysis showed that no previous surgical history (odds ratio 8.58, 95% confidence interval 1.2-59.7, P = 0.03) was a positive predictor of symptomatic improvement. CONCLUSIONS: hSRT for HNPGs was an effective treatment with minimal side effects over the long term and may have a role as first-line therapy, especially for symptomatic nonfunctional HNPGs, for better symptom control.

Efficacy and safety of hypofractionated stereotactic radiotherapy for brain metastases using three fractions: A single-centre retrospective study.

PURPOSE: Hypofractionated stereotactic radiotherapy (HFSRT) has become a standard of care for patients with a limited number of brain metastases (BM). An increasing number of linear accelerators (LA) are able to accurately perform HFSRT including VersaHD® (Elekta®) LA. The main aim of this study was to report clinical outcomes of BM treated by HFSRT using 3×7.7Gy on 70% isodose line in terms of local control (LC). PATIENTS AND METHODS: Between November 2016 and October 2018, all patients suffering from histologically-proven primary with one or several newly diagnosed BM treated by HFSRT were retrospectively included and evaluated. Patients who had received prior treatment by neurosurgery or cerebral radiotherapy were excluded. RESULTS: Among 44 patients, 61 BM were treated. With a median follow-up of 31.9 months, LC rates at 6 and 12 months were 93.2% and 90.9, respectively. Single-BM was independently predictive of LC (P=0.025) and overall survival (P=0.013). Acute toxicity rates were acceptable: 65.9% of patients had grade 1 and 2 and no acute grade 3 toxicity according to the NCI-CTCAE (version 5.0). Regarding delayed toxicity, one case (2.3%) of radionecrosis was confirmed by magnetic resonance spectroscopy. CONCLUSION: In our single-centre retrospective analysis, BM treatment by HFSRT delivered in three fractions showed a 12-month LC rate of 90.9% without major toxicities, which suggests safety and efficiency of this technique. However, longer-term follow-up and prospective studies are still needed to confirm these results.

Organ motion in linac-based SBRT for glottic cancer.

PURPOSE: The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. METHODS AND MATERIALS: Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. RESULTS: For the population systematic (Æ©) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Æ©) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). CONCLUSIONS: In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.

5-year results of accelerated partial breast irradiation (APBI) with SBRT (stereotactic body radiation therapy) and exactrac adaptive gating (Novalis®) for very early breast cancer patients: was it all worth it?

PURPOSE: To explore the feasibility of image-guided and respiratory-gated Stereotactic Body Radiation Therapy (SBRT) for Accelerated Partial Breast Irradiation (APBI) in patients with very early breast cancer. MATERIAL AND METHODS: Selected patients with early breast carcinoma after breast-conserving surgery were enrolled in this phase II trial. A fiducial marker was percutaneously placed close to surgical bed and five external fiducials were set on the skin. A CT scan for planning was acquired at free breathing. The treatment was planned and DVH were assessed according to international recommendations. Prescription dose was 30 Gy in five consecutive fractions of 6 Gy. A 6MV monoenergetic LINAC (linear accelerator) that combines stereoscopic X-ray imaging system and ExacTrac Adaptive Gating technique was used. PTV (planning target volume) intrafraction motion was controlled and PTV was irradiated in a selected gated area of the respiratory cycle. Shifts for a correct, gated set-up were calculated and automatically applied. RESULTS: Between April 2013 and October 2015, a total of 23 patients were included. The median tumor size was 12 mm. The mean PTV volume was 114 cc. The mean ipsilateral lung V9 Gy was 2.2% and for left-sided breast cancers, the volume of the heart receiving 1.5 Gy was 11.5%. Maximum skin dose was 30.8 Gy. Acute toxicity was grade1 in all the patients and 100% experienced excellent/good breast cosmesis outcomes. With a median follow-up of 66 months (range 8-99 months) local-relapse-free-survival reaches 100%. One patient developed a second breast cancer outside the treated quadrant after 25.1 months. CONCLUSION: APBI with SBRT and ExacTrac Adaptive Gating System was feasible. The acute and late toxicities were almost null and cosmesis was excellent. We also found that the margins of 5 mm applied from CTV to PTV were sufficient to compensate for geometric uncertainties.

Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

Computation of epistemic uncertainty due to limited data samples in small field dosimetry using Fuzzy Set Theory.

OBJECTIVE: To estimate the epistemic (or fuzzy) uncertainty, arising due to limited data samples in the measurement of the output factors (OFs) of the small fields using Fuzzy Set Theory (FST). METHODS: EBT3 film samples of size 50 × 50 mm2 were used for the measurement of the OF of stereotactic radiosurgery (SRS) cones of size 4, 6, 7.5, 10, 12.5 and 15 mm diameter, normalized with respect to the output of 100 × 100 mm2 open field size. Three measurements were done per cone/field size. Red color channel was chosen for the dosimetry purpose, net optical density (NOD) was converted to the dose using non-linear relation. To estimate the epistemic uncertainty associated with the measured OFs due to limited number of data samples, a triangular fuzzy number (TFN) was assumed as the fuzziness in the dose delivered by the individual SRS cone/field. Uncertainty in the OF was estimated by applying the Fuzzy Vertex Method (FVM). The membership functions of the OF were constructed for each cone size and the nature of the uncertainty in the OF of the cones was expressed in the terms of its fuzziness. For the sake of completeness of the study, the statistical uncertainty involved in the procedure has also been calculated. RESULTS: The statistical and fuzzy uncertainties in the measurement of OF of cones range from 3.28 to 6.25% and 2.58 to 5.44% respectively. The smallest cone of 4 mm has the largest values of statistical and fuzzy uncertainties. The membership functions of the OF for the studied cones were triangular in nature. CONCLUSION: The epistemic uncertainty arising due to limited number of data samples holds a significant fraction of the prescribed dose, and therefore, should not be ignored in the total uncertainty estimation. ADVANCES IN KNOWLEDGE: This study highlights the significance of epistemic component of measurement uncertainty arising out due to the insufficient/limited number of measurements of a quantity.

Clinical outcome after CyberKnife® radiosurgery re-irradiation for recurrent brain metastases.

PURPOSE: The objective of this study was to elucidate the impact on clinical outcomes resulting from re-irradiation for locally recurrent (LR) brain metastases (BM) using CyberKnife® stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Seventy-seven patients with 254 LR BM lesions treated using SRS re-irradiation between January 2014 and December 2018 were analysed in this retrospective study. The local control (LC), overall survival (OS) rates, and adverse events were assessed. The adverse events were classified according to the Common terminology for adverse event (CTCAE) v5.0. RESULTS: The median follow-up duration was 8.9 months. The median age of the patients was 55 years (IQR: 47-62). The 3, 6, and 9-month LC and OS rates were 92.2%, 73.4%, and 73.4% and 79.2%, 61.0%, and 48.1%, respectively. On multivariate analysis the gender (male vs. female; HR, 1.79; 95% CI, 1.06-3.01; P=0.028), type of first brain radiation (WBI vs. SRS) followed by re-irradiation using SRS (HR, 9.32; 95% CI, 2.77-15.27; P<0.001) tumour volume (>12cc vs. ≤12cc; HR, 1.84; 95% CI, 1.10-3.11; P=0.02), and recursive partitioning analysis (RPA) (I vs. II & III; HR, 0.38; 95% CI, 0.19-0.70; P=0.001) were independent predictive factor for OS. Radionecrosis was reported in 3 patients. CONCLUSION: With acceptable toxicity, SRS re-irradiation for LR BM showed a favourable rate for LC and OS and reported better OS for the female gender, a patient undergoing first brain radiation with SRS, tumour volume ≤12cc, and RPA-I. This result needs to be further evaluated in future clinical studies.

Impact of field number and beam angle on ERE for lung stereotactic body radiotherapy with 1.5T MR-Linac.

PURPOSE: To investigate the impact of field number and beam angle on ERE during IMRT planning with 1.5T MR-Linac for lung stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: IMRT plans for three representative lung cases who treated with 1.5T MR-Linac were generated using TPS Monaco 5.40.01. In each case, five types of plans were generated: (1) the "original plan" generated using 5-fields and beam angles manually optimized in ipsilateral tumor side, with no transverse magnetic field (TMF); (2) the plans generated by reoptimizing and recalculating the original plan, with a 1.5T TMF; (3) the plans generated with 5-fields, with beam angles manually optimized in anterior-posterior (AP) direction; (4) the plans generated with equidistant 5-fields; and (5) the plans generated with equidistant 9-fields. These plans were compared using a variety of dose-volume-parameters (DVPs). RESULTS: The DVPs under TMF showed the presence of 1.5T TMF can slightly change for all lung cases studied. When the plans generated with beam angles manually optimized in anterior-posterior direction, results showed that the plans improved conformity and homogeneity for PTV and reduced the dose to tissue surface. Furthermore, the results showed that the equidistant/non-equidistant comparison of the previous target anatomy result in a more favourable dose distribution for the equidistant beam setting. At last, the results showed the dose distributions for PTV with 9 and 5 equidistant beams were not significantly different. CONCLUSION: The plan quality can be significantly changed by the presence of a 1.5T TMF for lung SBRT with MR-Linac. The selection of optimal fields number and beam angle can substantially reduce or even eliminate these changes, without deteriorating overall plan quality.

Predictive factors of radio-induced complications in 194 eyes undergoing gamma knife radiosurgery for uveal melanoma.

BACKGROUND AND PURPOSE: To report the factors predictive of radio-induced complications (i.e. radiation retinopathy [RR], radiation papillopathy [RP] and neovascular glaucoma [NVG]) in uveal melanoma (UM) patients undergoing gamma knife radiosurgery (GKR). MATERIALS AND METHODS: Longitudinal cohort study on patients with UM treated at the Ocular Oncology Service, San Raffaele Scientific Institute, Milan, between June 1994 and November 2018. Data were retrospectively reviewed. Rates of GKR-related complications were reported. Variables associated with each complication were investigated using multivariable Cox models and confirmed by logistic regression analysis. Hazard ratio (HR) and 95% confidence intervals (CI) were reported for significant associations. RESULTS: One hundred ninety-four patients (99 males, 51%) were included, and 184 tumours were primarily located in the choroid (95%). Median follow-up was 57 months (range 6-286). Local control was achieved in 182 eyes (94%), and 152 eyes (78%) experienced at least one radiation-induced complication. Radiation retinopathy was documented in 67 eyes (35%) after a median of 23 months. Older age (HR = 0.97, 95% CI = 0.95-0.99, p = 0.02) had a protective effect for RR. Radiation papillopathy was diagnosed in 35 eyes (18%) after a median of 14 months after GKR. Macular or peripapillary location (HR = 3.06, 95% CI = 1.52-6.16, p = 0.002) was associated with increased risk of RP, while older age was protective (HR = 0.95, 95% CI = 0.93-0.98, p = 0.001). New-onset NVG was found in 53 eyes (27%), and median onset was 28 months. Tumour thickness (HR = 4.41, 95% CI = 2.23-8.72, p < 0.001) and peripapillary location (HR = 2.78, 95% CI = 1.46-5.27, p = 0.002) were the main risk factors associated with NVG. CONCLUSION: Understanding factors predictive for radiation-related complications in patients undergoing GKR might help for better counselling and treatment planning.

Dosimetric and radiobiological comparison of treatment plan between CyberKnife and EDGE in stereotactic body radiotherapy for pancreatic cancer.

To perform a comparison of the different stereotactic body radiotherapy (SBRT) plans between the Varian EDGE and CyberKnife (CK) systems for locally advanced unresectable pancreatic cancer. Fifteen patients with pancreatic cancer were selected in this study. The median planning target volume (PTV) was 28.688 cm3 (5.736-49.246 cm3). The SBRT plans for the EDGE and CK were generated in the Eclipse and Multiplan systems respectively with the same contouring and dose constrains for PTV and organs at risk (OARs). Dose distributions in PTV were evaluated in terms of coverage, conformity index (CI), new conformity index (nCI), homogeneity index (HI), and gradient index (GI). OARs, including spinal cord, bowel, stomach, duodenum and kidneys were statistically evaluated by different dose-volume metrics and equivalent uniform dose (EUD). The volume covered by the different isodose lines (ISDL) ranging from 10 to 100% for normal tissue were also analyzed. All SBRT plans for EDGE and CK met the dose constraints for PTV and OARs. For the PTV, the dosimetric metrics in EDGE plans were lower than that in CK, except that D99 and GI were slightly higher. The EDGE plans with lower CI, nCI and HI were superior to generate more conformal and homogeneous dose distribution for PTV. For the normal tissue, the CK plans were better at OARs sparing. The radiobiological indices EUD of spinal cord, duodenum, stomach, and kidneys were lower for CK plans, except that liver were higher. The volumes of normal tissue covered by medium ISDLs (with range of 20-70%) were lower for CK plans while that covered by high and low ISDLs were lower for EDGE plans. This study indicated that both EDGE and CK generated equivalent plan quality, and both systems can be considered as beneficial techniques for SBRT of pancreatic cancer. EDGE plans offered more conformal and homogeneous dose distribution for PTV, while the CK plans could minimize the exposure of OARs.

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique.

PURPOSE: Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. METHODS: patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. RESULTS: 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2-22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2-7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. CONCLUSION: Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.

Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases.

PURPOSE: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature. METHODS AND MATERIALS: PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference. RESULTS: Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter. CONCLUSIONS: TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS.