High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial).

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

Assessment of stereotactic high-resolution detectors for stereotactic body radiotherapy: comparative analysis between myQA® SRS and Gafchromic EBT-XD films.

The study aimed to evaluate dosimetry systems used for stereotactic body radiotherapy (SBRT), specifically 2D array dosimetry and film dosimetry systems, for exploring their characteristics and clinical suitability. For this, high-resolution myQA SRS detectors and Gafchromic EBT-XD films were employed. Film analysis included net optical density (OD) values depending on energy, dose rate, scanner orientation, scanning side, and post-exposure growth. For myQA SRS, signal values were evaluated in terms of dose rate (400-1400 MU/min) and angular dependence (0-180° at 30° intervals) along with couch angles of 0°, 45°, and 90°. Pre-treatment verification included 32 SBRT patients for whom myQA SRS results were compared with those obtained with Gafchromic EBT-XD films. Analysis revealed less than 1% deviation in net OD for energy and dose rate dependence. Scanner orientation caused 2.5% net OD variation, with minimal differences between film front and back scan orientations (variance < 1.0%). A rapid OD rise occurred within six hours post-exposure, followed by gradual increase. The myQA SRS detector showed - 3.7% dose rate dependence (400 MU/min), while the angular dependence at 90° was - 26.7%. A correction factor effectively reduced these differences to < 1%. For myQA SRS, gamma passing rates were-93.6% (2%/1 mm), while those for EBT-XD films were-92.8%. Improved rates were observed with 3%/1 mm: for myQA SRS-97.9%, and for EBT-XD film-98.16%. In contrast, for 2%/2 mm with 10% threshold, for myQA SRS-97.7% and for EBT-XD film-98.97% were obtained. It is concluded that both myQA SRS detectors and EBT-XD films are suitable for SBRT pre-treatment verification, ensuring accuracy and reliability. However, myQA SRS detectors are preferred over EBT-XD film due to the fact that they offer real-time measurements and user-friendly features.

Assessment of minimum target dose as a predictor of local failure after spine SBRT.

OBJECTIVES: Metastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. METHODS: Spine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20-24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27-36 Gy and 21-24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. RESULTS: 522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3-54.4). The cumulative incidence of local failure was 10.5 % (7.4-13.4) at 1 year and 16.3 % (12.6-19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 - 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6-9.4) vs. 14.2 % (8.3-19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). CONCLUSIONS: Spine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14-15.3 Gy with single fraction SBRT is recommended whenever possible.

Left ventricle segment-specific motion assessment for cardiac-gated radiosurgery.

Purpose.Cardiac radiosurgery is a non-invasive treatment modality for ventricular tachycardia, where a linear accelerator is used to irradiate the arrhythmogenic region within the heart. In this work, cardiac magnetic resonance (CMR) cine images were used to quantify left ventricle (LV) segment-specific motion during the cardiac cycle and to assess potential advantages of cardiac-gated radiosurgery.Methods.CMR breath-hold cine images and LV contour points were analyzed for 50 controls and 50 heart failure patients with reduced ejection fraction (HFrEF, EF < 40%). Contour points were divided into anatomic segments according to the 17-segment model, and each segment was treated as a hypothetical treatment target. The optimum treatment window (one fifth of the cardiac cycle) was determined where segment centroid motion was minimal, then the maximum centroid displacement and treatment area were determined for the full cardiac cycle and for the treatment window. Mean centroid displacement and treatment area reductions with cardiac gating were determined for each of the 17 segments.Results.Full motion segment centroid displacements ranged between 6-14 mm (controls) and 4-11 mm (HFrEF). Full motion treatment areas ranged between 129-715 mm2(controls) and 149-766 mm2(HFrEF). With gating, centroid displacements were reduced to 1 mm (controls and HFrEF), while treatment areas were reduced to 62-349 mm2(controls) and 83-393 mm2(HFrEF). Relative treatment area reduction ranged between 38%-53% (controls) and 26%-48% (HFrEF).Conclusion.This data demonstrates that cardiac cycle motion is an important component of overall target motion and varies depending on the anatomic cardiac segment. Accounting for cardiac cycle motion, through cardiac gating, has the potential to significantly reduce treatment volumes for cardiac radiosurgery.

Dosimetric evaluation in Helical TomoTherapy for lung SBRT using Monte Carlo-based independent dose verification software.

PURPOSE: To elucidate the dosimetric errors caused by a model-based algorithm in lung stereotactic body radiation therapy (SBRT) with Helical TomoTherapy (HT) using Monte Carlo (MC)-based dose verification software. METHODS: For 38 plans of lung SBRT, the dose calculation accuracy of a treatment planning system (TPS) of HT was compared with the results of DoseCHECK, the commercial MC-based independent verification software. The following indices were extracted to evaluate the correlation of dosimetric errors: (1) target volume, (2) average computed tomography (CT) value of the planning target volume (PTV) margin, and (3) average CT value of surrounding 2-mm area of the PTV (PTV ring). Receiver operating characteristic (ROC) analyses determined the threshold for 5% of differences in PTV D95%. Then, the 38 plans were classified into two groups using the cutoff values of ROC analysis for these three indices. Dosimetric differences between groups were statistically compared using the Mann-Whitney U test. RESULTS: TPS of HT overestimated by more than 5% in the PTV D95% in 16 of 38 plans. The PTV ring showed the strongest correlation with dosimetric differences. The cutoff value for the target volume, the PTV margin, and the PTV ring was 14.7 cc, -754 HU, and -708 HU, respectively. The area under the curve (AUC) for the target volume, the PTV margin, and the PTV ring were 0.835, 0.878, and 0.932, respectively. Dosimetric errors more than 5% were observed when the PTV volume was less than 15 cc or when the CT value around the target was less than -700 HU. CONCLUSION: The TPS of HT might overestimate the PTV dose by more than 5% if any the three indices in this study were below threshold. Therefore, independent verification with an MC-based algorithm should be strongly recommended for lung SBRT in HT.

Assessment of Radiation Dosage to the Hippocampi during Treatment of Multiple Brain Metastases Using Gamma Knife Therapy.

Background and Objectives: Brain metastases (BMs) pose significant clinical challenges in systemic cancer patients. They often cause symptoms related to brain compression and are typically managed with multimodal therapies, such as surgery, chemotherapy, whole brain radiotherapy (WBRT), and stereotactic radiosurgery (SRS). With modern oncology treatments prolonging survival, concerns about the neurocognitive side effects of BM treatments are growing. WBRT, though widely used for multiple BMs, has recognized neurocognitive toxicity. SRS, particularly Gamma Knife (GK) therapy, offers a minimally invasive alternative with fewer side effects, suitable for patients with a quantifiable number of metastases and better prognoses. Materials and Methods: A retrospective analysis was conducted on 94 patients with multiple BMs treated exclusively with GK at an academic medical center. Patients with prior WBRT were excluded. This study focused on the mean radiation dose received by the hippocampal area, estimated according to the 'Hippocampal Contouring: A Contouring Atlas for RTOG 0933' guidelines. Results: The precision of GK equipment results in mean doses of radiation that are lower than those suggested by RTOG 0933 and observed in other studies. This precision may help mitigate cognitive dysfunction and other side effects of hippocampal irradiation. Conclusions: GK therapy facilitates the administration of smaller, safer radiation doses to the hippocampi, which is advantageous even for lesions in the temporal lobe. It is feasible to treat multiple metastases, including cases with more than 10, but it is typically reserved for patients with fewer metastases, with an average of 3 in this study. This underlines GK's potential for reducing adverse effects while managing BMs effectively.

Plan quality assessment of modern radiosurgery technologies in the treatment of multiple brain metastases.

Stereotactic radiosurgery (SRS) of multiple brain metastases has evolved over the last 40 years allowing centres to treat an increasing number of brain metastases in a single treatment fraction. HyperArcTMplanning optimisation technique is one such development that streamlines the treatment of multiple metastases with a single isocentre. Several studies have investigated the plan quality of HyperArc compared to CyberKnife or Gamma Knife, however there are limited number of studies that include all three modalities. It is the aim of this study to provide an assessment of plan quality between the three SRS platforms across ten patients with multiple brain metastases ranging from three to eight metastases per patient. Strict planning workflows were established to avoid bias towards any particular treatment platform. Plan quality was assessed through dose to organs at risk, Paddick conformity index (PCI), gradient index (GI), global efficiency index (Gη) and dose to normal brain tissue. Results from this study found mean PCI observed across Gamma Knife plans was significantly lower than HyperArc and CyberKnife. HyperArc plans observed significantly shorter beam-on times which were 10 to 20 times faster than CyberKnife and Gamma Knife plans. Gamma Knife and CyberKnife were found to produce plans with significantly superior GI, global efficiency index and the volume of healthy brain receiving greater than 12 Gy (V12Gy) when compared to HyperArc plans. Lesion volume was seen to influence the relative difference in dose metrics between systems. The study revealed that all three treatment modalities produced high quality plans for the SRS treatment of multiple brain metastases, each with respective benefits and limitations.

Prospective Longitudinal Assessment of Quality of Life After Stereotactic Ablative Radiotherapy for Oligometastases: Analysis of the Population-based SABR-5 Phase II Trial.

AIMS: To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). RESULTS: All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: -8.76, 90% confidence interval -11.29 to -6.24; POSI mean difference: -4.61, 90% confidence interval -6.09 to -3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. CONCLUSIONS: Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL.

Toward an improved assessment of dose conformity in radiotherapy.

BACKGROUND: Evaluation of dose conformity is important to ensure minimum dose to normal tissue and sufficient dose coverage of the planning target volume (PTV). The existing conformity indices depend on the PTV volume and do not differentiate between two different scenarios: overdosing normal tissue and underdosing PTV. PURPOSE: In this study, we introduce a novel index to assess conformity of dose distributions in radiotherapy. METHODS: The suggested conformity index C I d e x p $C{I_{{d_{exp}}}}$ is defined by the ratio of the volume representing actual "non-conformity" of the planned dose and the volume representing acceptable "non-conformity." The latter volume is produced by expanding the PTV. If both the average distance ( d ¯ $\overline d $ ) between the reference isodose surface and planning target volume and arbitrarily selected PTV expansion margin ( d e x p ${d_{exp}}$ ) are much smaller than the size of the PTV, C I d e x p $C{I_{{d_{exp}}}}$ approximately equals the ratio d ¯ d e x p $\dfrac{{\bar d}}{{{d_{exp}}}}$ . In this work, C I d e x p $C{I_{{d_{exp}}}}$ was utilized to analyze 90 cases of brain metastases treated with stereotactic radiation therapy (SRS) and 102 cases of lung cancer treated with stereotactic body radiation therapy (SBRT). RESULTS: For d e x p ${d_{exp}}$  = 0.1 cm, all considered SRS treatment plans were characterized by C I d e x p < 1 $C{I_{{d_{exp}}}} < 1$ while 2 out of 102 SBRT plans had C I d e x p > 1 $C{I_{{d_{exp}}}} > 1$ . The average values of C I d e x p $C{I_{{d_{exp}}}}$ for SRS and SBRT plans were 0.31 and 0.43, respectively. For d e x p ${d_{exp}}$  = 0.2 cm, all studied treatment plans had C I d e x p < 1 $C{I_{{d_{exp}}}} < 1$ , and the average values of C I d e x p $C{I_{{d_{exp}}}}$ for SRS and SBRT plans were 0.15 and 0.25, respectively. CONCLUSIONS: The suggested conformity index C I d e x p $C{I_{{d_{exp}}}}$ varies less with PTV volume than the RTOG and Riet-Paddick indices frequently used for evaluation of dose conformity. In addition, C I d e x p $C{I_{{d_{exp}}}}$ can be expressed as a sum of two terms which describe "over-coverage" and "under-coverage" of the treatment target. The results confirm that C I d e x p $C{I_{{d_{exp}}}}$ can be used for evaluation of dose conformity in SRS and SBRT.

Insurance Denial of Care for Randomized Controlled Trial-Eligible Patients: Incidence and Success Rate of Peer-To-Peer Authorization in Allowing Patients to Remain Trial-Eligible.

INTRODUCTION: Insurance denials for clinical trials serve as a pertinent barrier for patients to remain trial-eligible, thus hindering the development of therapies and the overall advancement of health care. We present results from an ongoing oncology randomized clinical trial regarding insurance denials and peer-to-peer authorization (P2PA) success rate in allowing patients to remain trial-eligible. METHODS: The ongoing Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms Phase II trial randomizes spine cancer patients to treatment with spine radiosurgery/stereotactic body radiation therapy (SBRT) versus conventional external beam radiation therapy (EBRT). Trial-eligible patients during the first 3 months of enrollment are examined to determine whether the option of SBRT was denied by their insurance. Advocacy for overcoming SBRT denial in P2PA centered on SBRT being recommended as a preferred treatment modality in the National Comprehensive Cancer Network guidelines, and the recent level I evidence demonstrating the advantages of SBRT over EBRT for symptomatic spine cancer. RESULTS: Of 15 trial-eligible patients, 3 (20%) experienced insurance denials for SBRT. P2PA resulted in the reversal of denials in all 3 patients, allowing each to remain trial-eligible for randomization between SBRT and cEBRT. CONCLUSIONS: Despite a clinical oncologic treatment modality for which recent Level 1 evidence is available, the insurance denial rate was 20%. A vigilant P2PA strategy focusing on highlighting National Comprehensive Cancer Network guidelines and the supporting Level 1 evidence resulted in a very high rate of reversing initial denial.

Early Treatment of Ruptured Cerebral Arteriovenous Malformations: Analysis of Neurological Outcomes and Health Care Costs.

BACKGROUND: The timing of surgical resection is controversial when managing ruptured arteriovenous malformations (AVMs) and varies considerably among centers. OBJECTIVE: To retrospectively analyze clinical outcomes and hospital costs associated with delayed treatment in a ruptured cerebral AVM patient cohort. METHODS: Patients undergoing surgical treatment for a ruptured cerebral AVM (January 1, 2015-December 31, 2020) were retrospectively analyzed. Patients who underwent emergent treatment of a ruptured AVM because of acute herniation were excluded, as were those treated >180 days after rupture. Patients were stratified by the timing of surgical intervention relative to AVM rupture into early (postbleed days 1-20) and delayed (postbleed days 21-180) treatment cohorts. RESULTS: Eighty-seven patients were identified. The early treatment cohort comprised 75 (86%) patients. The mean (SD) length of time between AVM rupture and surgical resection was 5 (5) days in the early cohort and 73 (60) days in the delayed cohort ( P < .001). The cohorts did not differ with respect to patient demographics, AVM size, Spetzler-Martin grade, frequency of preoperative embolization, or severity of clinical presentation ( P ≥ .15). Follow-up neurological status was equivalent between the cohorts ( P = .65). The associated mean health care costs were higher in the delayed treatment cohort ($241 597 [$99 363]) than in the early treatment cohort ($133 989 [$110 947]) ( P = .02). After adjustment for length of stay, each day of delayed treatment increased cost by a mean of $2465 (95% CI = $967-$3964, P = .002). CONCLUSION: Early treatment of ruptured AVMs was associated with significantly lower health care costs than delayed treatment, but surgical and neurological outcomes were equivalent.

Response Assessment in Brain Metastases Managed by Stereotactic Radiosurgery: A Reappraisal of the RANO-BM Criteria.

BACKGROUND: Brain metastases (BM) are increasingly being treated using stereotactic radiosurgery (SRS). Standardized response criteria are necessary to improve research and treatment protocols. This study's goal was to validate the RANO-BM criteria thresholds for tumor progression in a cohort of patients with brain metastases managed using SRS. METHODS: We performed a retrospective analysis of patients treated at least twice with SRS for brain metastases. Local progression, as defined by RANO-BM criteria, was compared to our multidisciplinary tumor board's treatment recommendation. A ROC curve was generated using varying diameter thresholds to assess the sensitivity and specificity of current RANO-BM criteria. RESULTS: 249 metastases in 67 patients were included in the analysis. RANO-BM criteria current progression thresholds yielded a sensitivity of 38%, a specificity of 95%, a positive predictive value of 71%, and a negative predictive value of 84% relative to our tumor board's treatment recommendation. Modified RANO-BM criteria using absolute diameter differences of 2.5 mm yielded a sensitivity of 83%, a specificity of 87%, a positive predictive value of 67% and a negative predictive value of 94%. CONCLUSIONS: Current RANO-BM criteria unreliably identifies clinically relevant tumor progression. The use of absolute diameter differences thresholds appears superior in our BM cohort.

Development and adaptations of the Graded Prognostic Assessment (GPA) scale: a systematic review.

The Graded Prognostic Assessment (GPA) score has the best accuracy among prognostic scales for patients with brain metastases (BM). A wide range of GPA-derived scales have been established to different types of primary tumor BM. However, there is a high variability between them, and their characteristics have not been described altogether yet. We aim to summarize the features of the existent GPA-derived scales and to compare their predictor factors and their uses in clinical setting. Medline was searched from inception until January 2023 to identify studies related to the development, update, or validation of GPA. The initial search yielded 1,083 results. 16 original studies and 16 validation studies were included, comprising a total of 33,348 patients. 13 different scales were assessed, including: GPA, Diagnosis-Specific GPA, Extracranial Score, Lung-molGPA, Updated Renal GPA, Updated Gastrointestinal GPA, Modified Breast GPA, Integrated Melanoma GPA, Melanoma Mol GPA, Sarcoma GPA, Hepatocellular Carcinoma GPA, Colorectal Cancer GPA, and Uterine Cancer GPA. The most prevalent prognostic predictors were age, Karnofsky Performance Status, number of BM, and presence or absence of extracranial metastases. Treatment modalities consisted of whole brain radiation therapy, stereotactic radiosurgery, surgery, cranial radiotherapy, gamma knife radiosurgery, and BRAF inhibitor therapy. Median survival rates with no treatment and with a specific treatment ranged from 6.1 weeks to 33 months and from 3.1 to 21 months, respectively. Original GPA and GPA-derived scales are valid prognostic tools, but with heterogeneous survival results when compared to each other. More studies are needed to improve scientific evidence of these scales.

Generalisation of radiotherapy dose calculation for Monte Carlo algorithm combined with 3D Swin-Unet: a multi-institutional IMRT evaluation.

Objective.Accurate dose calculations are essential prerequisites for precise radiotherapy. The integration of deep learning into dosimetry could consider computational accuracy and efficiency and has potential applicability to clinical dose calculation. The generalisation of a deep learning dose calculation method (hereinafter referred to as TERMA-Monte Carlo network, T-MC net) was evaluated in clinical practice using intensity-modulated radiotherapy (IMRT) plans for various human body regions and multiple institutions, with the Monte Carlo (MC) algorithm serving as a benchmark.Approach. Sixty IMRT plans were selected from four institutions for testing the head and neck, chest and abdomen, and pelvis regions. Using the MC results as the benchmark, the T-MC net calculation results were used to perform three-dimensional dose distribution and dose-volume histogram (DVH) comparisons of the entire body, planning target volume (PTV) and organs at risk (OARs), respectively, and calculate the mean ±95% confidence interval of gamma pass rate (GPR), percentage of agreement (PA) and dose difference ratio (DDR) of dose indices D95, D50, and D5.Main results. For the entire body, the GPRs of 3%/3 mm, 2%/2 mm, 2%/1 mm, and the PA were 99.62 ± 0.32%, 98.50 ± 1.09%, 95.60 ± 2.90% and 97.80 ± 1.12%, respectively. For the PTV, the GPRs of 3%/3 mm, 2%/2 mm, 2%/1 mm and the PA were 98.90 ± 1.00%, 95.78 ± 2.83%, 92.23 ± 4.74% and 98.93 ± 0.62%, respectively. The absolute value of average DDR was less than 1.4%.Significance. We proposed a general dose calculation framework based on deep learning, using the MC algorithm as a benchmark, performing a generalisation test for IMRT treatment plans across multiple institutions. The framework provides high computational speed while maintaining the accuracy of MC and may become an effective dose algorithm engine in treatment planning, adaptive radiotherapy, and dose verification.

Quality assessment of automatically planned O-Ring linac SBRT plans for pelvic lymph node metastases, finding the optimal minimum target size by comparison with robotic SBRT.

PURPOSE: The purpose of this study is to assess the quality of automatic planned O-Ring Halcyon linac SBRT plans for pelvic lymph node metastases and to establish an absolute PTV volume threshold as a plan quality prediction criterion. Compliance of the plans to institutional SBRT plan evaluation criteria and differences in plan quality and treatment delivery times between Halcyon Linac and CyberKnife robotic SBRT were evaluated. METHODS: Twenty-one CyberKnife treatment plans were replanned for Halcyon. Prescription doses range was 26-40 Gy in mean three fractions. The mean/median planning target volume was 4.0/3.6 cm3 . Institutional criteria for the plan evaluation were: New Conformity Index (NCI), Conformity Index (CI), Modified Gradient Index (MGI), selectivity index reciprocal (PIV/TVPIV ), and the target coverage by prescription isodose (%PIV). Statistical analysis based on the receiver operating characteristic (ROC) curve was used to determine a plan quality predictor threshold of the PTV volume. Comparative analysis of normal tissue complication probabilities (NTCP) was used to assess the risk of toxicity in healthy tissues. RESULTS: Seventy-one percent (n = 15)/95% (n = 20) of Halcyon and 81% (n = 17)/100% (n = 21) of CK plans fulfilled all ideal/tolerance criteria. For PTVs above a found optimal threshold of 2.6 cm3 (71%, n = 15), no statistically significant difference was observed between the CI, NCI, PIV/TVPIV , and MGI indexes of both groups, while the coverage (%PIV) was statistically but not clinically significantly different between cohorts. Significantly shorter delivery times are expected with Halcyon. No significant differences in NTCP were observed. CONCLUSION: All but one automatically optimized Halcyon treatment plans demonstrated ideal or acceptable performance. PTV threshold of 2.6 cm3 can be used as decision criteria in clinical settings. The results of our study demonstrated the promising performance of the Halcyon for pelvic SBRT, although plan-specific QA is required to verify machine performance during plan delivery.

Determination of volume averaging correction factors using an elliptical absorbed dose model for Gamma Knife Perfexion.

PURPOSE: The purpose of this study is to calculate volume averaging correction factors for detectors used in the dosimetry of Gamma Knife's narrow photon beams, and to determine the impact of volume averaging on the field output correction factor. METHODS: Simulations of different Gamma Knife fields were done using elliptical dose model formalism with newly introduced fit functions. To determine volume averaging correction factors a calculation of the absorbed dose over the volume of the detector was performed. The elliptical dose model was tested with respect to absorbed dose distribution for different volumes and compared with the calculations of Leksell GammaPlan v.11.3.1. RESULTS: The largest differences in absorbed dose calculated by the elliptical model and Leksell GammaPlan are 2.25%, 1.5%, and 0.6% for 16, 8, and 4 mm field sizes, respectively. Volume averaging correction factors were determined for six ionization chambers, five semiconductor detectors, a diamond, and two plastic scintillator detectors. In general, for all examined detectors the impact of volume averaging is more pronounced for smaller field sizes. All studied ionization chambers had a larger volume than other detectors, therefore the volume averaging correction factors for ionization chambers are larger for all investigated field sizes. Besides the fact that plastic scintillator detectors can be considered tissue-equivalent, volume averaging correction factor should be applied. CONCLUSION: Volume averaging correction factors for different detectors are determined and suitable detectors for dosimetry of Gamma Knife's narrow photon beams are recommended. It is shown that volume averaging has a dominant contribution to a field output correction factor.

Measuring dose in lung identifies peripheral tumour dose inaccuracy in SBRT audit.

PURPOSE: Stereotactic Body Radiotherapy (SBRT) for lung tumours has become a mainstay of clinical practice worldwide. Measurements in anthropomorphic phantoms enable verification of patient dose in clinically realistic scenarios. Correction factors for reporting dose to the tissue equivalent materials in a lung phantom are presented in the context of a national dosimetry audit for SBRT. Analysis of dosimetry audit results is performed showing inaccuracies of common dose calculation algorithms in soft tissue lung target, inhale lung material and at tissue interfaces. METHODS: Monte Carlo based simulation of correction factors for detectors in non-water tissue was performed for the soft tissue lung target and inhale lung materials of a modified CIRS SBRT thorax phantom. The corrections were determined for Gafchromic EBT3 Film and PTW 60019 microDiamond detectors used for measurements of 168 SBRT lung plans in an end-to-end dosimetry audit. Corrections were derived for dose to medium (Dm,m) and dose to water (Dw,w) scenarios. RESULTS: Correction factors were up to -3.4% and 9.2% for in field and out of field lung respectively. Overall, application of the correction factors improved the measurement-to-plan dose discrepancy. For the soft tissue lung target, agreement between planned and measured dose was within average of 3% for both film and microDiamond measurements. CONCLUSIONS: The correction factors developed for this work are provided for clinical users to apply to commissioning measurements using a commercially available thorax phantom where inhomogeneity is present. The end-to-end dosimetry audit demonstrates dose calculation algorithms can underestimate dose at lung tumour/lung tissue interfaces by an average of 2-5%.

Volumetric Assessment of Nonfunctional Pituitary Adenoma Treated With Stereotactic Radiosurgery: An Assessment of Long-Term Response.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is widely used to manage recurrent or residual nonfunctioning pituitary adenomas (NFPAs). Studies on the long-term volumetric response of NFPAs to SRS are lacking. Such a post-SRS volumetric study will allow us to set up appropriate radiographic follow-up protocols and predict tumor volumetric response. METHODS: Two providers independently performed volumetric analyses on 54 patients who underwent single-session SRS for a recurrent/residual NFPA. In the case of discrepancy between their results, the final volume was confirmed by an independent third provider. Volumetry was performed on the 1-, 3-, 5-, 7-, and 10-year follow-up neuroimaging studies. RESULTS: Most patients showed a favorable volumetric response, with 87% (47/54) showing tumor regression and 13% (7/54) showing tumor stability at 10 years. Year 3 post-SRS volumetric results correlated (R 2 = 0.82, 0.63, 0.56) with 5-, 7-, and 10-year outcomes. The mean interval volumetric reduction was 17% on year 1; further interval volumetric reduction was 17%, 9%, 4%, and 9% on years 3, 5, 7, and 10, respectively. CONCLUSION: Year 3 post-SRS volumetric response of patients with residual or recurrent NFPAs is predictive of their 7-10-year follow-up response. For patients demonstrating NFPA regression in the first 1-3 years, interval follow-up MRI's can likely be performed at 2-year periods unless otherwise clinically indicated. Further studies are needed to better define the volumetric response to adenomas more than a decade after SRS.

Commissioning and validation of a Monte Carlo algorithm for spine stereotactic radiosurgery.

PURPOSE: A 6FFF Monte Carlo (MC) dose calculation algorithm was commissioned for spine stereotactic radiosurgery (SRS). Model generation, validation, and ensuing model tuning are presented. METHODS: The model was generated using in-air and in-water commissioning measurements of field sizes between 10 and 400 mm2 . Commissioning measurements were compared to simulated water tank MC calculations to validate output factors, percent depth doses (PDDs), profile sizes and penumbras. Previously treated Spine SRS patients were re-optimized with the MC model to achieve clinically acceptable plans. Resulting plans were calculated on the StereoPHAN phantom and subsequently delivered to the microDiamond and SRSMapcheck to verify calculated dose accuracy. Model tuning was performed by adjusting the model's light field offset (LO) distance between physical and radiological positions of the MLCs, to improve field size and StereoPHAN calculation accuracy. Following tuning, plans were generated and delivered to an anthropomorphic 3D-printed spine phantom featuring realistic bone anatomy, to validate heterogeneity corrections. Finally, plans were validated using polymer gel (VIPAR based formulation) measurements. RESULTS: Compared to open field measurements, MC calculated output factors and PDDs were within 2%, profile penumbra widths were within 1 mm, and field sizes were within 0.5 mm. Calculated point dose measurements in the StereoPHAN were within 0.26% ± 0.93% and -0.10% ± 1.37% for targets and spinal canals, respectively. Average SRSMapcheck per-plan pass rates using a 2%/2 mm/10% threshold relative gamma analysis was 99.1% ± 0.89%. Adjusting LOs improved open field and patient-specific dosimetric agreement. Anthropomorphic phantom measurements were within -1.29% ± 1.00% and 0.27% ± 1.36% of MC calculated for the vertebral body (target) and spinal canal, respectively. VIPAR gel measurements confirmed good dosimetric agreement near the target-spine junction. CONCLUSION: Validation of a MC algorithm for simple fields and complex SRS spine deliveries in homogeneous and heterogeneous phantoms has been performed. The MC algorithm has been released for clinical use.