Care Patterns for Stereotactic Radiosurgery in Small Cell Lung Cancer Brain Metastases.

INTRODUCTION: The historical standard of care for brain metastases (BMs) from small cell lung cancer (SCLC) has been whole-brain radiotherapy (WBRT). However, there is growing interest in upfront stereotactic radiosurgery (SRS) for select SCLC patients. MATERIALS AND METHODS: We invited United State-based Radiation Oncologists (ROs) via email to answer an anonymous survey using a branching logic system addressing their use of SRS and WBRT for SCLC BMs. Wilcoxon rank-sum test and Fisher's exact test were used to compare differences in continuous and categorical variables, respectively. Multivariable logistic regression analyses were fitted for outcome variables including covariates with P < .10 obtained on univariable analysis. RESULTS: In total, 309 ROs completed the survey and 290 (95.7%) reported that they would consider SRS for SCLC BMs under certain clinical circumstances. Across patient characteristics, the number of BMs was the most heavily weighted factor (mean 4.3/5 in importance), followed by performance status, cognitive function, and response to prior therapy. Fewer BMs were correlated with increased SRS use (55.8% offered SRS "very frequently" [>75% of cases] or "often" [51%-75% of cases] for 1 BM vs. 1.1% for >10 BM, P < .001). In situations where WBRT was preferred, concern for rapid intracranial progression (45.3%) and lack of high-level data (36.9%) were the most important factors. The majority (60.6%) were aware of a large recent international retrospective analysis (the FIRE-SCLC study) reporting similar OS between upfront SRS and WBRT; awareness of this study was the only respondent variable predictive of SRS use for limited BMs (19.2% of those aware of the study preferring SRS for limited [≤4] BMs before vs. 61% preferring SRS after the publication, P < .001). The majority of respondents (88.2%) expressed a willingness to enroll patients on a recently opened recently opened randomized trial, NRG-CC009, comparing SRS versus hippocampal-avoidance WBRT. CONCLUSIONS: In the first survey of SRS for SCLC BMs, we observed a high level of physician openness to upfront SRS in SCLC, particularly for patients with limited numbers of BMs, as well as significant interest in generating prospective randomized data to clarify the role of SRS in this population.

Optimal application of stereotactic body radiotherapy and radiofrequency ablation treatment for different multifocal hepatocellular carcinoma lesions in patients with Barcelona Clinic Liver Cancer stage A4-B1: a pilot study.

BACKGROUND: In clinical practice, many hepatocellular carcinoma (HCC) patients in Barcelona Clinical Liver Cancer (BCLC) stage A4-B1 cannot receive the curative treatments of liver transplantation, resection, and radiofrequency ablation (RFA), which are the recommended options according to liver cancer guidelines. Our aim is to study the feasibility of RFA and stereotactic body radiotherapy (SBRT) as a curative treatment for different multifocal HCCs in BCLC stage A4-B1 patients. METHODS: From September 2014 to August 2019, 39 multifocal HCC lesions (median diameter: 16.6 mm) from 15 patients (median age: 73 years) were retrospectively selected. Among them, 23 were treated by RFA and the other 16 by SBRT because of predictable insufficiency and/or risk related to RFA performance. The indicators for evaluating this novel therapy were the tumor response, prognosis (recurrence and survival), and adverse effects (deterioration of laboratory test values and severe complications). RESULTS: The median follow-up duration was 31.3 months (range: 15.1-71.9 months). The total patients with a one-year complete response, stable disease, or disease progression were 11, 1, and 3, respectively. In total, 8 and 2 patients had confronted intrahepatic or local recurrence, respectively. The one-year progression-free survival rate and local control rate were 80% (12/15 patients) and 97.4% (38/39 lesions), respectively. The median time to progression was 20.1 (2.8-45.1) months. The one- and two-year survival rates were 100 and 88.9%, respectively. In up to five months' observation, no patient showed severe complications. Seven, four, and two patients had slight changes in their white blood cells, platelet count, or albumin-bilirubin grade, respectively. CONCLUSIONS: For patients with BCLC stage A4-B1, RFA and SBRT treatment for different multifocal HCCs may be a potential option because of the favorable prognosis and safety. However, before its application in clinical practice, prospective, controlled, large-scale studies are needed to further confirm our conclusions.

Thoracic stereotactic body radiation therapy plus first-line tyrosine kinase inhibitors for patients with epidermal growth factor receptor-mutant polymetastatic non-small-cell lung cancer: A propensity-matched retrospective study.

ABSTRACT: The role of thoracic stereotactic body radiation therapy (SBRT) in addition to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant polymetastatic non-small-cell lung cancer (NSCLC) has not been well established. This retrospective study aimed to evaluate the efficacy and safety of EGFR-TKIs with thoracic SBRT for the treatment of this patient group.Polymetastatic NSCLC was defined as having >5 metastatic lesions. Patients with polymetastatic NSCLC harboring positive EGFR mutations after initial TKI therapy for at least 8 weeks were eligible for SBRT between August 2016and August 2019. Eligible patients were treated with thoracic SBRT, and TKIs were administered for the duration of SBRT and continued after SBRT until they were considered ineffective. The control group was treated with TKI monotherapy. Propensity score matching (ratio of 1:4) was used to account for differences in baseline characteristics. Progression-free survival (PFS), overall survival, and treatment safety were evaluated.In total, 136 patients were included in the study population. Among them, 120 patients received TKIs alone, and 16 patients received TKIs with thoracic SBRT. The baseline characteristics did not significantly differ between the two cohorts after propensity score matching. The median PFS was 17.8 months in the thoracic SBRT group and 10.8 months in the control group (P = .033). In the multivariate analysis, a Cox regression model showed that thoracic SBRT was an independent statistically significant positive predictor of improved survival, with a hazard ratio of 0.54 (P = .046). We recorded no severe toxic effects or grade 4 to 5 toxicities.Real-world data demonstrate that thoracic SBRT significantly extends PFS in EGFR-mutant polymetastatic NSCLC patients with tolerable toxicity. Given these results, randomized studies are warranted.

Hospitalization outcomes among brain metastasis patients receiving radiation therapy with or without stereotactic radiosurgery from the 2005-2014 Nationwide Inpatient Sample.

The purpose of this study was to compare hospitalization outcomes among US inpatients with brain metastases who received stereotactic radiosurgery (SRS) and/or non-SRS radiation therapies without neurosurgical intervention. A cross-sectional study was conducted whereby existing data on 35,199 hospitalization records (non-SRS alone: 32,981; SRS alone: 1035; SRS + non-SRS: 1183) from 2005 to 2014 Nationwide Inpatient Sample were analyzed. Targeted maximum likelihood estimation and Super Learner algorithms were applied to estimate average treatment effects (ATE), marginal odds ratios (MOR) and causal risk ratio (CRR) for three distinct types of radiation therapy in relation to hospitalization outcomes, including length of stay (' ≥ 7 days' vs. ' < 7 days') and discharge destination ('non-routine' vs. 'routine'), controlling for patient and hospital characteristics. Recipients of SRS alone (ATE = - 0.071, CRR = 0.88, MOR = 0.75) or SRS + non-SRS (ATE = - 0.17, CRR = 0.70, MOR = 0.50) had shorter hospitalizations as compared to recipients of non-SRS alone. Recipients of SRS alone (ATE = - 0.13, CRR = 0.78, MOR = 0.59) or SRS + non-SRS (ATE = - 0.17, CRR = 0.72, MOR = 0.51) had reduced risks of non-routine discharge as compared to recipients of non-SRS alone. Similar analyses suggested recipients of SRS alone had shorter hospitalizations and similar risk of non-routine discharge when compared to recipients of SRS + non-SRS radiation therapies. SRS alone or in combination with non-SRS therapies may reduce the risks of prolonged hospitalization and non-routine discharge among hospitalized US patients with brain metastases who underwent radiation therapy without neurosurgical intervention.

Late metastatic presentation is associated with improved survival and delayed wide-spread progression after ablative stereotactic body radiotherapy for oligometastasis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastatic disease (OMD), but the effect of metastasis timing on patient outcomes remains uncertain. METHODS: An international database of patients with OMD treated with SBRT was assembled with rigorous quality assurance. Early versus late metastases were defined as those diagnosed ≤24 versus >24 months from the primary tumor. Overall survival (OS), progression-free survival (PFS), and incidences of wide-spread progression (WSP) were estimated using multivariable Cox proportional hazard models stratified by primary tumor types. RESULTS: The database consists of 1033 patients with median follow-up of 24.1 months (0.3-104.7). Late metastatic presentation (N = 427) was associated with improved OS compared to early metastasis (median survival 53.6 vs. 33.0 months, hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.47-0.72, p < 0.0001). Patients with non-small cell lung cancer (NSCLC, N = 255, HR 0.49, 95% CI: 0.33-0.74, p = 0.0005) and colorectal cancer (N = 235, HR 0.50, 95% CI: 0.30-0.84, p = 0.008) had better OS if presenting with late metastasis. Late metastasis correlated with longer PFS (median 17.1 vs. 9.0 months, HR 0.71, 95% CI: 0.61-0.83, p < 0.0001) and lower 2-year incidence of WSP (26.1% vs. 43.6%, HR 0.60, 95% CI: 0.49-0.74, p < 0.0001). Fewer WSP were observed in patients with NSCLC (HR 0.52, 95% CI: 0.33-0.83, p = 0.006) and kidney cancer (N = 63, HR 0.37, 95% CI: 0.14-0.97, p = 0.044) with late metastases. Across cancer types, greater SBRT target size was a significant predictor for worse OS. CONCLUSION: Late metastatic presentation is associated with improved survival and delayed progression in patients with OMD treated with SBRT.

Daily waiting and treatment times at an advanced radiation oncology setup: A 4-year audit of consecutive patients from single institution.

PURPOSE: We present our data for every single fraction for every patient treated at our center for the past 4 years, analyzing the waiting and treatment times. MATERIALS AND METHODS: Between January 2014 and February 2018, all patients and their corresponding recorded measurements of waiting time and machine treatment time were analyzed. Times recorded included actual arrival time, designated arrival time, linac entry time, and last beam treatment time. The complete waiting time information was divided into two categories (1) first day treatments and (2) subsequent day treatments. SPSS version 18 was used for statistical calculations, correlations, and assessing significance. RESULTS: First day treatments - of 1982 patients following treatments were carried out; 1557 volumetric-modulated arc therapy (78.6%), 88 three-dimensional conformal radiotherapy (RT) (4.4%), 14 electron (0.7%), 10 intensity-modulated RT (0.5%), 264 stereotactic irradiation (13.3%), 17 stereotactic body RT (0.7%), and 32 total body irradiation (1.6%). The mean (± standard deviation) times for early/late time, total spent time (TST), wait time gross (WTG), and wait time net (WTN) were 11.0 ± 49.6 min, 74.7 ± 44.8 min, 47.46 ± 43.9 min, and 24.1 ± 44.4 min, respectively. Subsequent day treatments - a total of 34,438 sessions of treatment delivery were recorded. Overall average WTG was 37.4 ± 32.7 min. Overall WTN was 12.1 ± 62.7 min. Overall mean total spent time (TST) was 52.4 ± 33.0 min, overall mean setup and treatment time was 15.1 ± 10.9 min. CONCLUSION: We have presented our results of patient-related times during RT. Our study covers the daily waiting times before RT as well as the actual treatment times during modern-day RT. This consecutive patient data from a large series shall be an important resource tool for future planners and policymakers.

National variation in the delivery of radiation oncology procedures in the non-facility-based setting.

PURPOSE: Though utilization of medical procedures has been shown to vary considerably across the United States, similar efforts to characterize variation in the delivery of radiation therapy (RT) procedures have not been forthcoming. Our aim was to characterize variation in the delivery of common RT procedures in the Medicare population. We hypothesized that delivery would vary significantly based on provider characteristics. METHODS: The Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File was linked to the CMS Physician Compare (PC) database by physician NPI to identify and sum all treatment delivery charges submitted by individual radiation oncologists in the non-facility-based (NFB) setting in 2016. Multivariable logistic regression analysis was carried out to determine provider characteristics (gender, practice rurality, practice region, and years since graduation) that predicted for the delivery of 3D conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic body RT (SBRT), stereotactic radiosurgery (SRS), low dose rate (LDR) brachytherapy, and high dose rate (HDR) brachytherapy delivery in the Medicare patient population. The overall significance of categorical variables in the multivariable logistic regression model was assessed by the likelihood ratio test (LRT). RESULTS: In total, 1,802 physicians from the NFB practice setting were analyzed. Male gender predicted for greater LDR brachytherapy delivery (OR 8.19, 95% CI 2.58-26.05, p < 0.001), but not greater delivery of other technologies. Metropolitan practice was the only predictor for greater HDR brachytherapy utilization (OR 12.95, 95% CI 1.81-92.60, p = 0.01). Practice region was predictive of the delivery of 3DCRT, SRS and SBRT (p < 0.01, p < 0.001, and p < 0.001, respectively). With the Northeast as the reference region, 3DCRT was more likely to be delivered by providers in the South (OR 1.33, 95% CI 1.09-1.62, p < 0.01) and the West (OR 1.38, 95% CI 1.11-1.71, p < 0.01). At the same time, SRS use was less likely in the Midwest (OR 0.71, 95% CI 0.55-0.91, p < 0.01), South (OR 0.49, 95% CI 0.40-0.61, p < 0.001), and West (OR 0.43, 95% CI 0.34-0.55, p < 0.001). SBRT, on the other hand, was more commonly utilized in the Midwest (OR 2.63, 95% CI 1.13-6.13, p = 0.03), South (OR 3.44, 95% CI 1.58-7.49, p < 0.01), and West (OR 4.87, 95% CI 2.21-10.72, p < 0.001). HDR brachytherapy use was also more likely in the Midwest (OR 1.97, 95% CI 1.11-3.49, p = 0.02) and West (OR 1.87, 95% CI 1.08-3.24, p = 0.03). While the degree held by the billing physician did not predict for delivery of a given procedure, greater years since graduation was related to decreased likelihood of SBRT use (OR 0.98, 95% CI 0.96-0.99, p < 0.001) and increased likelihood of LDR brachytherapy use (OR 1.02, 95% CI 1.00-1.04, p = 0.02). CONCLUSIONS: Substantial geographic variation in the use of specific RT technologies was identified. The degree to which this variation reflects effective care, preference-sensitive care, or supply-sensitive care warrants further investigation.

Choice and Trade-offs: Parent Decision Making for Neurotechnologies for Pediatric Drug-Resistant Epilepsy.

This qualitative study investigated factors that guide caregiver decision making and ethical trade-offs for advanced neurotechnologies used to treat children with drug-resistant epilepsy. Caregivers with affected children were recruited to semi-structured focus groups or interviews at one of 4 major epilepsy centers in Eastern and Western Canada and the USA (n = 22). Discussions were transcribed and qualitative analytic methods applied to examine values and priorities (eg, risks, benefits, adherence, invasiveness, reversibility) of caregivers pertaining to novel technologies to treat drug-resistant epilepsy. Discussions revealed 3 major thematic branches for decision making: (1) features of the intervention-risks and benefits, with an emphasis on an aversion to perceived invasiveness; (2) decision drivers-trust in the clinical team, treatment costs; and (3) quality of available information about neurotechnological options. Overall, caregivers' definition of treatment success is more expansive than seizure freedom. The full involvement of their values and priorities must be considered in the decision-making process.

Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study.

BACKGROUND: Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. METHODS: IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. RESULTS: Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti-programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab-treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab-treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. CONCLUSIONS: With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01511913. Registered January 19, 2012 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913.

Capecitabine and stereotactic radiation in the management of breast cancer brain metastases.

BACKGROUND: Little is known about the safety and efficacy of concurrent capecitabine and stereotactic radiotherapy in the setting of breast cancer brain metastases (BCBM). METHODS: Twenty-three patients with BCBM underwent 31 stereotactic sessions to 90 lesions from 2005 to 2019 with receipt of capecitabine. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of stereotactic radiation. Imaging was independently reviewed by a neuro-radiologist. RESULTS: Median follow-up from stereotactic radiation was 9.2 months. Receptor types of patients treated included triple negative (n = 7), hormone receptor (HR)+/HER2- (n = 7), HR+/HER2+ (n = 6), and HR-/HER2+ (n = 3). Fourteen patients had stage IV disease prior to BCBM diagnosis. The median number of brain metastases treated per patient was 3 (1 to 12). The median dose of stereotactic radiosurgery (SRS) was 21 Gy (range: 15-24 Gy) treated in a single fraction and for lesions treated with fractionated stereotactic radiation therapy (FSRT) 25 Gy (24-30 Gy) in a median of 5 fractions (range: 3-5). Of the 31 stereotactic sessions, 71% occurred within 1 month of capecitabine. No increased toxicity was noted in our series with no cases of radionecrosis. The 1-year OS, LC, and DIC were 46, 88, and 30%, respectively. CONCLUSIONS: In our single institution experience, we demonstrate stereotactic radiation and capecitabine to be a safe treatment for patients with BCBM with adequate LC. Further study is needed to determine the potential synergy between stereotactic radiation and capecitabine in the management of BCBM.

Implications of Radiotherapy Utilization in Korea from 2010 to 2019.

BACKGROUND: This study was to assess the rate of radiotherapy (RT) utilization according to the modality in South Korea to identify the implications of contemporary RT patterns. METHODS: We collected information from claims and reimbursement records of the National Health Insurance Service from 2010 to 2019. We classified the location of each institution as capital (Seoul, Incheon, and Gyeonggi-do) and non-capital areas. RESULTS: The rate of RT utilization in total cancer patients nationwide was 24.5% in 2010, which consistently has increased to 36.1% in 2019 (annual increase estimate [AIE], 4.5%). There was an abrupt increase in patients receiving intensity-modulated RT (IMRT), with an AIE of 33.5%, and a steady decline in patients receiving three-dimensional conformal RT (3DCRT), with an AIE of -7.1%. The commonest RT modality was IMRT (44.5%), followed by 3DCRT and stereotactic RT (SRT) (37.2% and 13.5%) in 2019. An increasing trend of advanced RT (such as IMRT and SRT) utilization was observed regardless of the region, although the AIE in the capital areas was slightly higher than that in non-capital areas. CONCLUSION: The utilization of overall RT application and especially of advanced modalities remarkably increased from 2010 to 2019. We also found gaps in their AIEs between capital and non-capital areas. We should ensure that advanced RT is accessible to all cancer patients across South Korea.

First Asian population study of stereotactic body radiation therapy for ventricular arrhythmias.

We report the first Asian series on stereotactic body radiation (SBRT) for refractory ventricular arrhythmia (VA) in Taiwanese patients. Three-dimensional electroanatomic maps, delayed-enhancement magnetic resonance imaging (DE-MRI), and dual-energy computed tomography (CT) were used to identify scar substrates. The main target volume was treated with a single radiation dose of 25 Gy and the margin volume received 20 Gy using simultaneous integrated boost delivered by the Varian TrueBeam system. Efficacy was assessed according to VA events recorded by an implantable cardioverter-defibrillator (ICD) or a 24-h Holter recorder. Pre- and post-radiation therapy imaging studies were performed. From February 2019 to December 2019, seven patients (six men, one woman; mean age, 55 years) were enrolled and treated. One patient died of hepatic failure. In the remaining six patients, at a median follow-up of 14.5 months, the VA burden and ICD shocks significantly decreased (only one patient with one ICD shock after treatment). Increased intensity on DE-MRI might be associated with a lower risk for VA recurrence, whereas dual-energy CT had lower detection sensitivity. No acute or minimal late adverse events occurred. In patients with refractory VA, SBRT is associated with a marked reduction in VA burden and ICD shocks, and DE-MRI might be useful for monitoring treatment effects.

Stereotactic Radiosurgery after Subtotal Resection of Critically-Located Grade I Meningioma: A Single-Center Experience and Review of Literature.

AIM: To analyze the results of stereotactic radiosurgery in 295 patients with residual Grade I meningiomas located at parasellar region, petroclival region, cerebellopontine angle and parasagittal region. MATERIAL AND METHODS: A total of 295 patients with Grade 1 residual Meningiomas (197 women, 98 men), who were treated by adjuvant radiosurgery in Gazi University Gamma Knife Center between 2004-2015 were analyzed. WHO Grade 2 and 3 meningiomas were not included in our study. Minimum radiological follow-up was 24 months. The median follow-up was 54 months. The tumor volume, location, treatment dose, morbidity, progression free survival and tumor control rate were analyzed. RESULTS: The median tumor volume was 5.2 cm3 (0.04-39.7), median age was 50 (20-80), median dose was 14 Gy and tumor control rate was 94.5% (stationary in 85.0%, volume reduction in 9.5%). Increase in tumor volume was seen in 16 patients (5.5%) and re-operation was performed in 5 of them (1.6%). Stereotactic radiosurgery was performed again for 8 patients (2.7%).The location of the tumors was as follows: 39.3% parasellar region, 20% cerebellopontine angle, 13.6% petroclival and 27.1% was parasagittal, falcine or convexity. Major morbidities were detected in 6 (2%) patients. Minor morbidities were detected in 18 (6.1%) patients. CONCLUSION: Stereotactic radiosurgery is an effective and safe treatment modality for residual Grade I meningiomas.

Lung Cancer Radiotherapy: Simulation and Analysis Based on a Multicomponent Mathematical Model.

BACKGROUND: Lung cancer has been one of the most deadly illnesses all over the world, and radiotherapy can be an effective approach for treating lung cancer. Now, mathematical model has been extended to many biomedical fields to give a hand for analysis, evaluation, prediction, and optimization. METHODS: In this paper, we propose a multicomponent mathematical model for simulating the lung cancer growth as well as radiotherapy treatment for lung cancer. The model is digitalized and coded for computer simulation, and the model parameters are fitted with many research and clinical data to provide accordant results along with the growth of lung cancer cells in vitro. RESULTS: Some typical radiotherapy plans such as stereotactic body radiotherapy, conventional fractional radiotherapy, and accelerated hypofractionated radiotherapy are simulated, analyzed, and discussed. The results show that our mathematical model can perform the basic work for analysis and evaluation of the radiotherapy plan. CONCLUSION: It will be expected that in the near future, mathematical model will be a valuable tool for optimization in personalized medical treatment.

Focus on the expected quality of reporting in SBRT/radiosurgery prospective studies: how far have we come in 30 years?

OBJECTIVES: We aimed at describing and assessing the quality of reporting in all published prospective trials about radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). METHODS: The Medline database was searched for. The reporting of study design, patients' and radiotherapy characteristics, previous and concurrent cancer treatments, acute and late toxicities and assessment of quality of life were collected. RESULTS: 114 articles - published between 1989 and 2019 - were analysed. 21 trials were randomised (18.4%). Randomisation information was unavailable in 59.6% of the publications. Data about randomisation, ITT analysis and whether the study was multicentre or not, had been significantly less reported during the 2010-2019 publication period than before (respectively 29.4% vs 57.4% (p < 0.001), 20.6% vs 57.4% (p < 0.001), 48.5% vs 68.1% (p < 0.001). 89.5% of the articles reported the number of included patients. Information about radiation total dose was available in 86% of cases and dose per fraction in 78.1%. Regarding the method of dose prescription, the prescription isodose was the most reported information (58.8%). The reporting of radiotherapy characteristics did not improve during the 2010 s-2019s. Acute and late high-grade toxicity was reported in 37.7 and 30.7%, respectively. Their reporting decreased in recent period, especially for all-grade late toxicities (p = 0.044). CONCLUSION: It seems necessary to meet stricter specifications to improve the quality of reporting. ADVANCES IN KNOWLEDGE: Our work results in one of the rare analyses of radiosurgery and SBRT publications. Literature must include necessary information to first, ensure treatments can be compared and reproduced and secondly, to permit to decide on new standards of care.

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.

Upfront pembrolizumab as an effective treatment start in patients with PD-L1 ≥ 50% non-oncogene addicted non-small cell lung cancer and asymptomatic brain metastases: an exploratory analysis.

INTRODUCTION: The efficacy of immune checkpoint inhibitors in patients with brain metastases (BMs) from non-oncogene addicted non-small cell lung cancer (NSCLC) is under investigation. Here, we sought to determine the optimal management of NSCLCs with PD-L1 ≥ 50% and asymptomatic BMs who were treated with first-line pembrolizumab. METHODS: Thirty patients from 15 institutions with PD-L1 ≥ 50% NSCLC had asymptomatic BMs, and met inclusion criteria. Patients were classified based on whether they had undergone upfront local radiotherapy for BMs as well as on the type of brain radiotherapy received. RESULTS: Nine patients were treated with upfront pembrolizumab alone, 8 patients with whole-brain radiotherapy (WBRT) followed by pembrolizumab and 13 patients with stereotactic radiosurgery (SRS) followed by pembrolizumab. Patients' characteristics were similar among the three groups of patients except for a higher number of BMs ≥ 3 in the WBRT group. One complete and 4 partial intracranial responses were observed with upfront pembrolizumab alone. The median survival was not reached for the pembrolizumab and WBRT (n = 8) groups, and it was 7.6 months for the SRS (n = 13) group (P = 0.09), with 12-month survival rates being 55.5%, 62.5%, and 23.0%, respectively. Salvage WBRT was delivered in 1 patient in the upfront pembrolizumab group and in 4 patients in the SRS group. CONCLUSIONS: Upfront pembrolizumab showed efficacy in selected patients with PD-L1 ≥ 50% non-oncogene addicted NSCLC and asymptomatic BMs. Prospective studies should address whether pembrolizumab alone, and deferral of radiotherapy, could be pursued in this patient population.

Application of a multi-institutional nomogram predicting salvage whole brain radiation-free survival to patients treated with postoperative stereotactic radiotherapy for brain metastases.

PURPOSE: The ultimate goal of stereotactic radiotherapy (SRT) of brain metastases (BM) is to avoid or postpone whole brain radiotherapy (WBRT). A nomogram based on multi-institutional data was developed by Gorovets, et al. to estimate the 6 and 12-months WBRT-free survival (WFS). The aim of the current retrospective study was to validate the nomogram in a cohort of postoperative BM patients treated with adjuvant SRT. MATERIAL AND METHODS: We reviewed the data of 68 patients treated between 2008-2017 with postoperative SRT for BM. The primary endpoint was the WFS. The receiver operating characteristic curve and area under the curve (AUC) were calculated for both 6- and 12-months time points. RESULTS: After a median follow-up of 64 months, the 1-year cumulative incidence of local and distant brain relapse rates were 15% [95% CI=8-26%] and 34% [95% CI=24-48%], respectively. At recurrence, repeated SRT or salvage WBRT were applied in 33% and 57% cases, respectively. The WFS rates at 6 and 12 months were 88% [95% CI=81-97%] and 67% [95% CI=56-81%], respectively. Using the Gorovets nomogram, the 6 months rates were overestimated while they were accurate at 12 months. AUC values were 0.47 and 0.62 for the 6- and 12-months respectively. Overall, Harrell's concordance index was 0.54. CONCLUSION: This nomogram-predicted well the 12 months WFS but its discriminative power was quite low. This underlines the limits of this kind of predictive tool and leads us to consider the use of big data analysis in the future.

Management and Outcomes of Sporadic Vestibular Schwannoma: A Longitudinal Study Over 12 Years.

OBJECTIVES: To evaluate the management of sporadic vestibular schwannomas (VS) with a 12-year follow-up. STUDY DESIGN: Retrospective study of all VS patients initially treated in 2005 in a tertiary referent center. METHODS: Initial decision making for microsurgical resection (MSR) or wait-and-scan (WaS) was according to VS size and hearing; subsequently, MSR or stereotactic radiosurgery (SRS) was proposed dependent on VS growth and size, hearing, and patient's age or willingness. RESULTS: Two hundred and one sporadic VS were included. The first management apportionment was 120 WaS (61.5%), 72 MSR (37%), three SRS (1.5%), and six others refused MSR and were lost to follow-up (LFU). Within 1 year, 95 (47%) VS were surgically removed; 17 (8.5%) were treated by SRS; and 35 (17.5%) were LFU. The proportions for SRS and LFU were virtually unchanged for the following years, and the proportion under MSR increased slightly within 3 years and then remained stable. Finally, at 12 years, 104 (51.5%) cases had been operated on, 21 (10.5%) treated by SRS, 23 (11.5%) still under WaS, and 53 (26.5%) LFU, which were mainly intracanalicular. The initially and subsequently operated cases presented similar hearing preservation rates and good facial nerve function outcomes. CONCLUSION: This longitudinal study of a large number of VS, which were diagnosed over a short period of time and followed for 12 years, provides new information on both the natural history of these benign tumors and individual patient concerns. This study recommends use of the WaS policy for small and mid-sized VS before active therapeutic decision making. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E970-E976, 2021.

Stereotactic Body Radiation Therapy for Mediastinal and Hilar Lymph Node Metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) to metastatic mediastinal and hilar lymphadenopathy (MHL) is challenging owing to the proximity of centrally located organs-at-risk. As limited data exist on the safety and efficacy of SBRT for MHL, a retrospective review of clinical outcomes was conducted from a large academic center. METHODS AND MATERIALS: Eligible patients received SBRT to MHL between 2014 to 2019 for the following indications: oligometastases, oligoprogression, or local control of a dominant area of progression. The primary endpoint was grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). The cumulative incidence function evaluated local failure (LF) and starting or changing systemic therapy (SCST). Kaplan-Meier methodology estimated progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-two patients (84 metastases) were included. Median follow-up was 20 months. Primary cancer sites included kidney (53.8%), lung (13.4%), breast (7.7%), and other (25.1%). Indications for SBRT were oligoprogression (n = 35; 67.3%), oligometastases (n = 10; 19.2%), or local failure of a dominant area of progression (n = 7; 13.5%). The majority (n = 31; 59.6%) received SBRT to a single lymph node metastasis. Median SBRT dose was 35 Gy (range, 30-50 Gy) with a median biologically effective dose of 59.5 Gy (range, 48-100 Gy). All treatments were in 5 fractions. Seven grade ≥3 toxicities were experienced by 6 patients (11.5%) and were mostly transient (5/7; 71%). There was a single (1.9%) grade 5 toxicity (radiation pneumonitis). The cumulative incidence of LF was 9.0% at 2 years. The cumulative incidence of SCST was 33.2% and 57.1% at 1 and 2 years, respectively. Median PFS was 4.0 months (95% confidence interval, 2.8-7.3) and median OS was 31.7 months (95% confidence interval, 23.8-87.5). CONCLUSIONS: In one of the largest single institutional series of SBRT for MHL, moderate rates of grade ≥3 toxicity were observed, although the majority were transient. This treatment resulted in low LF rates and potentially delayed SCST for many patients.