Beyond surgical resection: evaluating stereotactic brachytherapy iodine-125 for low-grade gliomas: a systematic review and meta-analysis.

Stereotactic Brachytherapy Iodine-125 (SBT I-125) has been investigated by some studies for the treatment of lowgrade gliomas. We performed a meta-analysis to assess the efficacy and safety of SBT I-125 Brachytherapy for treatment of patients with Low-Grade Gliomas. PubMed, Cochrane, Web of Science, and EMBASE databases were searched for randomized and observational studies. This systematic review and meta-analysis was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. We used relative risk (RR) with 95% confidence intervals and random effects model to compare the effects of I-125 SBT treatment on the interest outcomes. We evaluated heterogeneity using I2 statistics; we considered heterogeneity to be significant if the p-value was less than 0.05 and I2 was higher than 35%. We performed statistical analysis using the software R (version 4.2.3). A total of 20 studies with a cohort of 988 patients with low grade gliomas who received SBT I-125 as a treatment option. The pooled analysis evidenced: (1) Complication rate of 10% (95% CI: 7-12%; I² = 60%); (2) 5-year PFS of 66% (99% CI: 45-86%; I²= 98%); (3) 10-year PFS was 66% (99% CI: 45-86%; I²= 98%); (4) Malignant transformation rate of 26% (95% CI: 8-45%; I²=0); (5) Mortality of 33% (95% CI: 15-51%; I² = 0%). Our systematic review and meta-analysis of SBT I-125 for low-grade gliomas have revealed significant concerns regarding its safety and efficacy. Despite a proportion of patients remaining progression-free, elevated rates of complications and mortality cast doubt on the intervention's reliability. Future research should prioritize long-term follow-up studies, standardized protocols, and comparative effectiveness research.

Short-term predictors of stereotactic radiosurgery outcome for untreated single non-small cell lung cancer brain metastases: a restrospective cohort study.

Stereotactic radiosurgery (SRS) is an option for brain metastases (BM) not eligible for surgical resection, however, predictors of SRS outcomes are poorly known. The aim of this study is to investigate predictors of SRS outcome in patients with BM secondary to non-small cell lung cancer (NSCLC). The secondary objective is to analyze the value of volumetric criteria in identifying BM progression. This retrospective cohort study included patients >18 years of age with a single untreated BM secondary to NSCLC. Demographic, clinical, and radiological data were assessed. The primary outcome was treatment failure, defined as a BM volumetric increase 12 months after SRS. The unidimensional measurement of the BM at follow-up was also assessed. One hundred thirty-five patients were included, with a median BM volume at baseline of 1.1 cm3 (IQR 0.4-2.3). Fifty-two (38.5%) patients had SRS failure at follow-up. Only right BM laterality was associated with SRS failure (p=0.039). Using the volumetric definition of SRS failure, the unidimensional criteria demonstrated a sensibility of 60.78% (46.11%-74.16%), specificity of 89.02% (80.18%-94.86%), positive LR of 5.54 (2.88-10.66) and negative LR of 0.44 (0.31-0.63). SRS demonstrated a 61.5% local control rate 12 months after treatment. Among the potential predictors of treatment outcome analyzed, only the right BM laterality had a significant association with SRS failure. The volumetric criteria were able to identify more subtle signs of BM increase than the unidimensional criteria, which may allow earlier diagnosis of disease progression and use of appropriate therapies.

Bevacizumab improved prognosis for advanced EGFR-mutant lung adenocarcinoma with brain metastasis receiving cerebral radiotherapy.

OBJECTIVE: This study aimed to determine whether the combined use of bevacizumab could improve overall survival (OS) in patients with brain metastasis (BM), epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) undergoing cerebral radiotherapy. MATERIALS AND METHODS: A total of 237 patients with EGFR-mutant lung adenocarcinoma and BM met the inclusion criteria for this retrospective study, including 102 patients in the bevacizumab treatment group and 135 in the non-bevacizumab group. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to identify EGFR-mutated BM prognostic factors for these patients. RESULTS: At the end of the last follow-up period, 176 patients (74.3%) had died, and the median overall survival (OS) was 34.2 months. We observed a significant difference in the median OS between the bevacizumab and non-bevacizumab groups (45.8 months vs 30.0 months, P < 0.0001). Among the 178 (75.1%) patients who received cerebral radiotherapy, the median OS of patients in the bevacizumab + cerebral radiotherapy group was 45.8 months versus 32.0 months in the non-bevacizumab + cerebral radiotherapy group, respectively (P = 0.0007). Patients treated with bevacizumab after cerebral radiotherapy had a longer median OS than patients treated with bevacizumab before cerebral radiotherapy (59.4 months vs 33.7 months, P = 0.0198). In the univariate analysis, smoking status, Lung-molGPA scores, and bevacizumab therapy showed correlations (HR = 1.450, P = 0.045; HR = 0.700, P = 0.023; HR = 0.499, P < 0.001). Multivariate analysis showed that bevacizumab therapy alone (hazard ratio [HR] = 0.514; P < 0.001) was independently associated with improved OS. CONCLUSION: In patients with BM from EGFR-mutated NSCLC, cerebral radiotherapy with bevacizumab markedly improved OS. This improvement was more evident after cerebral radiotherapy.

Efficacy and Safety of Intraoperative Radiotherapy for High-Grade Gliomas: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: High-grade gliomas (HGGs) are aggressive tumors of the central nervous system that cause significant morbidity and mortality. Despite advances in surgery and radiation therapy (RT), HGG still has a high incidence of recurrence and treatment failure. Intraoperative radiotherapy (IORT) has emerged as a promising therapeutic approach to achieve local tumor control while sparing normal brain tissue from radiation-induced damage. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the use of IORT for HGG. Eligible studies were included based on specific criteria, and data were independently extracted. Outcomes of interest included complications, IORT failure, survival rates at 12 and 24 months, and mortality. RESULTS: Sixteen studies comprising 436 patients were included. The overall complication rate after IORT was 17%, with significant heterogeneity observed. The IORT failure rate was 77%, while the survival rates at 12 and 24 months were 74% and 24%, respectively. The mortality rate was 62%. CONCLUSION: This meta-analysis suggests that IORT may be a promising adjuvant treatment for selected patients with HGG. Despite the high rate of complications and treatment failures, the survival outcomes were comparable or even superior to conventional methods. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation through prospective randomized controlled trials to better understand the specific patient populations that may benefit most from IORT. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation. Notably, the ongoing RP3 trial (NCT02685605) is currently underway, with the aim of providing a more comprehensive understanding of IORT. Moreover, future research should focus on managing complications associated with IORT to improve its safety and efficacy in treating HGG.

Surface guided radiation therapy with an innovative open-face mask and mouth bite: patient motion management in brain stereotactic radiotherapy.

INTRODUCTION: To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. METHODS: This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland-Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. RESULTS: The median of translation error between stages of the AlignRT positioning process was (0.03-0.07) cm, and the median of rotation error was (0.20-0.40)°, which were significantly better than those of the Fraxion positioning process (0.09-0.11) cm and (0.60-0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01 cm, - 0.07 cm, 0.03 cm, - 0.30°, - 0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10 cm and 0.50°. CONCLUSIONS: The application of the SGRT with an innovative open-face mask and mouth bite device could achieve precision positioning accuracy and stability, and the accuracy of the AlignRT system exhibits excellent constancy with the CBCT gold standard. The non-coplanar radiation field monitoring can provide reliable support for motion management in fractional treatment.

Radiotherapy for Brain Metastases Near the End of Life: Characterizing Patients and Tumor Features.

PURPOSE: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment. METHODS: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days. RESULTS: A total of 546 patients were included in the study. A KPS of <70 (P = .021), the number of brain metastases (P = .001), the lack of brain metastasectomy (P = .006), and the lack of systemic therapies after BrRT (P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 (P < .001), the lack of brain metastasectomy (P = .015), and the lack of systemic therapies after BrRT (P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days. CONCLUSION: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.

A Potential Boron Neutron Capture Therapy Agent Selectively Suppresses High-Grade Glioma: In Vitro and in Vivo Exploration.

Glioblastoma (GBM), as the most central nervous system (CNS) intractable disease, has spoiled millions of lives due to its high mortality. Even though several efforts have been made, the existing treatments have had limited success. In this sense, we studied a lead compound, the boron-rich selective epidermal growth factor receptor (EGFR)-inhibitor hybrid 1, as a potential drug for GBM treatment. For this end, we analyzed the in vitro activity of hybrid 1 in a glioma/primary astrocytes coculture, studying cellular death types triggered by treatment with this compound and its cellular localizations. Additionally, hybrid 1 concentrated boron in glioma cells selectively and more effectively than the boron neutron capture therapy (BNCT)-clinical agent 10B-l-boronophenylalanine and thus displayed a better in vitro-BNCT effect. This encouraged us to analyze hybrid 1 in vivo. Therefore, immunosuppressed mice bearing U87 MG human GBM were treated with both 1 and 1 encapsulated in a modified liposome (recognized by brain-blood barrier peptide transporters), and we observed a potent in vivo per se antitumor activity (tumor size decrease and animal survival increase). These data demonstrate that 1 could be a promising new targeted therapy for GBM.

Intraoperative radiotherapy for brain metastases: first-stage results of a single-arm, open-label, phase 2 trial.

OBJECTIVE: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM. METHODS: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage. RESULTS: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN. CONCLUSION: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies.

Brain radiotoxicity-related 15CAcBRT gene expression signature predicts survival prognosis of glioblastoma patients.

BACKGROUND: Glioblastoma is the most common and devastating primary brain cancer. Radiotherapy is standard of care; however, it is associated with brain radiation toxicity (BRT). This study used a multi-omics approach to determine whether BRT-related genes (RGs) harbor survival prognostic value and whether their encoded proteins represent novel therapeutic targets for glioblastoma. METHODS: RGs were identified through analysis of single-nucleotide variants associated with BRT (R-SNVs). Functional relationships between RGs were established using Protein-Protein Interaction networks. The influence of RGs and their functional groups on glioblastoma prognosis was evaluated using clinical samples from the Glioblastoma Bio-Discovery Portal database and validated using the Chinese Glioma Genome Atlas dataset. The identification of clusters of radiotoxic and putative pathogenic variants in proteins encoded by RGs was achieved by computational 3D structural analysis. RESULTS: We identified the BRT-related 15CAcBRT molecular signature with prognostic value in glioblastoma, by analysis of the COMT and APOE protein functional groups. Its external validation confirmed clinical relevance independent of age, MGMT promoter methylation status, and IDH mutation status. Interestingly, the genes IL6, APOE, and MAOB documented significant gene expression levels alteration, useful for drug repositioning. Biological networks associated with 15CAcBRT signature involved pathways relevant to cancer and neurodegenerative diseases. Analysis of 3D clusters of radiotoxic and putative pathogenic variants in proteins coded by RGs unveiled potential novel therapeutic targets in neuro-oncology. CONCLUSIONS: 15CAcBRT is a BRT-related molecular signature with prognostic significance for glioblastoma patients and represents a hub for drug repositioning and development of novel therapies.

The correlations between psychological distress, cognitive impairment and quality of life in patients with brain metastases after whole-brain radiotherapy.

BACKGROUND: Psychological distress and cognitive impairment are highly prevalent among patients with brain metastases after whole-brain radiotherapy (WBRT). Our purpose was to evaluate the correlations between psychological distress, cognitive impairment and quality of life in patients with brain metastases after WBRT. METHODS: Seventy-one patients with brain metastasis treated with WBRT were enrolled in this study and were investigated with several scales, including the Montreal Cognitive Assessment Scale (MoCA), the Functional Assessment of Cancer Therapy-Cognitive Function version 3 (FACT-Cog, version 3), the Functional Assessment of Cancer Therapy-Brain Module version 4 (FACT-Br, version 4) and the Psychological Distress Thermometer (DT), before and after WBRT. RESULTS: The MoCA, FACT-Cog and FACT-Br scores in patients with brain metastases were significantly decreased after WBRT compared with before WBRT (z = - 7.106, - 6.933 and - 6.250, respectively, P < 0.001), while the DT scores were significantly increased (z = 6.613, P < 0.001). There was an obvious negative correlation between the DT score and the FACT-Cog score (r = - 0.660, P < 0.001), a significant negative correlation between the DT score and the FACT-Br score (r = - 0.833, P < 0.001), and an obvious positive correlation between the FACT-Cog score and the FACT-Br score (r = 0.603, P < 0.001). These results suggest that WBRT can cause cognitive impairment in patients with brain metastases, increase their psychological distress and reduce their quality of life (QOL). CONCLUSION: After receiving WBRT, the cognitive function and QOL of patients with brain metastases were decreased, while psychological distress increased. The cognitive impairment and the decline of QOL after WBRT are associated with increased psychological distress, and that the decline of QOL is associated with cognitive impairment of patients.

Radioterapia intraoperatoria en tumores y metástasis cerebrales resecables / Intraoperative radiotherapy in resectable brain tumors and metastases

INTRODUCCIÓN: El tumor cerebral primario presenta una prevalencia global estimada en 10.8 casos por 100 000 habitantes con una tendencia creciente. El tipo más común de tumor cerebral primario es el glioma, que en la mayoría de casos (70-80%), se caracteriza por ser un tumor agresivo de alto grado (rápido crecimiento y diseminación local), con una supervivencia a los 5 años alrededor del 35% e inferior al 10% para el subtipo más agresivo, el glioblastoma, con una supervivencia media de 14 meses. Por su parte, el tumor cerebral secundario o metástasis cerebral es el tumor intracraneal más frecuente en personas adultas. En tumores donde es factible la extirpación quirúrgica del tumor (resección), además de la cirugía, la radioterapia externa adyuvante ha demostrado eficacia en el tratamiento de algunos tumores cerebrales primarios y metástasis cerebrales, aumentando la supervivencia global y el tiempo de supervivencia sin evidencia de progresión. La radioterapia intraoperatoria (RIO), en fase de estudio o ensayo clínico, surge como una alternativa o tratamiento adicinal a la radioterapia externa y consiste en administrar una dosis única de radiación durante la resección del tumor sobre las áreas de cerebro que estaban en contacto con éste antes de ser extirpado. Existen diferentes modalidades de RIO según el tipo de radiación administrada, como la

Plasmocitoma extramedular solitario rinosinusal: reporte de caso y revisión de literatura / Solitary extramedullary plasmacytoma of the rhinosinusal cavity: a case report and literature review

Resumen El plasmocitoma extramedular solitario (PES) es una neooplasia maligna infrecuente caracterizada por una proliferación aislada de células plasmáticas monoclonales en tejido extramedular. La localización más frecuente es en cabeza y cuello con predominio en el territorio rinosinusal, sin embargo, estas lesiones malignas representan menos del 1% de los tumores de esta región anatómica. El diagnostico requiere una alta sospecha clínica, análisis histopatológico acucioso, estudios serológicos y exámenes radiológicos sistémicos de acuerdo a los criterios diagnósticos establecidos en la literatura internacional. Se analiza el caso de un paciente masculino con un PES que se presentó como un tumor de fosa nasal derecha y obstrucción nasal de meses de evolución con hallazgos clínicos e imagenológicos inespecíficos. El diagnóstico definitivo se realizó mediante biopsia endoscópica nasal y estudio histopatológico. El tratamiento fue abordado de manera multidisciplinaria entre otorrinolaringología, hematología y radiooncología. De acuerdo a las guías internacionales, se decidió realizar radioterapia localizada con buen resultado clínico precoz. El PES requiere un abordaje multidisciplinario para lograr un diagnóstico y tratamiento oportuno, siendo imprescindible la exclusión del mieloma múltiple debido a las diferencias terapéuticas y en pronóstico clínico. El tratamiento puede realizarse con radioterapia y/o cirugía, siendo la radioterapia el pilar de tratamiento.

Abstract Solitary extramedullary plasmacytoma (SEP) is a rare malignant neoplasm characterized by isolated proliferation of monoclonal plasma cells in extramedullary tissue. The most frequent location is in the head and neck with a predominance in the rhinosinusal territory; however, these malignant lesions represent less than 1% of the tumors in this anatomical region. The diagnosis requires a high clinical suspicion, careful histopathological analysis, serological studies and systemic radiological examinations according to the diagnostic criteria established in the international literature. We analyze the case of a male patient with SEP that presented as a tumor of the right nostril and nasal obstruction of months of evolution with nonspecific clinical and imaging findings. The definitive diagnosis was made by nasal endoscopic biopsy and histopathological study. The treatment was approached by multidisciplinary teamwork. According to international guidelines, it was decided to perform localized radiotherapy with good early clinical results. SEP requires a multidisciplinary approach to achieve a timely diagnosis and treatment, being essential exclusion of multiple myeloma due to the therapeutic differences and prognosis. Treatment can be done with radiation therapy and/or surgery; radiation therapy is the mainstay of treatment.

Glioblastoma Treatment: State-of-the-Art and Future Perspectives.

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve overall survival, free-progression survival, and life quality in glioblastoma patients. (2) Methods: Our objective is to recap the actual state-of-the-art in glioblastoma treatment, resume the actual research and future perspectives on immunotherapy, as well as the new synthetic molecules and natural compounds that represent potential future therapies at preclinical stages. (3) Conclusions: Despite the great efforts in therapeutic research, glioblastoma management has suffered minimal changes, and the prognosis remains poor. Combined therapeutic strategies and delivery methods, including immunotherapy, synthetic molecules, natural compounds, and glioblastoma stem cell inhibition, may potentiate the standard of care therapy and represent the next step in glioblastoma management research.

Evaluation of the correlation between dosimetric, geometric, and technical parameters of radiosurgery planning for multiple brain metastases.

PURPOSE: To evaluate the correlation between dosimetric, geometric, and technical parameters for radiosurgery planning of multiple brain metastasis treatments treated with a linear accelerator with volumetric modulated arc therapy (VMAT) technique. MATERIALS AND METHODS: Data were collected retrospectively from 55 patients who underwent radiosurgery in a single institution from August 2017 to February 2020. Patients presented 4-21 brain metastases were treated with a single fraction with doses between 18 and 20 Gy. Dosimetric variables were collected including V5Gy, V8Gy, V10Gy, V12Gy, V14Gy, conformity index (CI), heterogeneity index (HI), maximum dose (Dmax), and the CI_R50. Geometric variables including the number of lesions, target volumes, the smallest target volume, the largest target volume, and the distance between the isocenter and the most distant lesion (DIL) and technical variables such as the numbers of total arcs, noncoplanar arcs, and isocenters were collected for analysis. RESULTS: The number of lesions had a moderate positive correlation with V5Gy, V8Gy, V10Gy, V12Gy, V14Gy, HI, Dmax, and with the number of total arcs. The target volumes had a positive medium-high correlation with V5Gy, V8Gy, V10Gy, V12Gy, V14Gy, and moderate positive correlation with HI, Dmax, number of arcs and noncoplanar arcs. The CI and CI_R50 had a negative correlation with all volumes related to the target: the target volumes, the smallest, and the largest lesion. A positive correlation was observed between the distance of the isocenter and the most DIL with V5Gy, V8Gy, V10Gy, V12Gy, V14Gy, HI, Dmax, and the number of isocenters. CONCLUSION: It was found that the number of lesions and the target volumes are good predictors of dosimetric indexes of plan evaluation and that the distance between the isocenter and the most DIL harms them.

Outcomes after stereotactic radiosurgery of brain metastases in patients with malignant melanoma and validation of the melanoma molGPA.

INTRODUCTION: Malignant melanoma is the third most common primary in the diagnosis of brain metastases. Stereotactic radiosurgery (SRS) is a well-established treatment option in limited brain disease. We analyzed outcomes of SRS with a particular focus on the graded prognostic assessment (GPA, melanoma molGPA), prognostic factors, and toxicity. METHODS: We evaluated 173 brain metastases in 83 patients with malignant melanoma. All were treated with SRS median dose of 20 Gy prescribed to the 80 or 100% isodose line between 2002 and 2019. All patients were followed-up regularly, including contrast-enhanced brain imaging as well as clinical examination, initially 6 weeks after treatment, then in quarterly follow-up. RESULTS: The median age was 61 years (range 27-80); 36 female and 47 male patients were treated. After a median follow-up of 5.7 months, median OS (overall survival) was 9.7 months 95%-KI 4.7-14.7). LC (local control) at 6 months, 12, 24 months was 89%, 86%, and 72%, respectively (median was not reached). Median DBC (distant brain control) was 8.2 months (95%-KI 4.7-11.7). For OS, a KPS ≥ 80%, a positive BRAF mutation status, a small PTV (planning target volume), the absence of extracranial metastases, as well as a GPA and melanoma molGPA > 2 were prognostic factors. In the MVA, a small PTV and a melanoma molGPA > 2 remained significant. CONCLUSION: The present survival outcomes support the use of the disease-specific melanoma molGPA as reliable prognostic score. Favorable outcomes for SRS compared to other studies were observed. In the treatment of brain metastases of malignant melanoma patients, a multidisciplinary approach consisting of surgery, SRS, chemotherapy, and immunotherapy should be considered.

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.

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.

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

PURPOSE: To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. METHODS: Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. RESULTS: A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3-7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6-7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4-55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6-109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan-Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis. Post-treatment changes were seen in 33 (30%) patients on follow-up imaging, with higher cumulative dose (EQD2 ≥ 104.3 Gy) being associated with increased risk of post-re-RT pseudo-progression. CONCLUSION: This clinical audit reports encouraging survival outcomes and identifies key prognostic factors associated with high-dose salvage re-RT in recurrent/progressive glioma.

Efficacy of salvage stereotactic radiotherapy (SRT) for locally recurrent brain metastases after initial SRT and characteristics of target population.

OBJECTIVES: Due to a steadily growing use of stereotactic radiotherapy (SRT) for treatment of brain metastases (BMs), the in-field failure after an initial stereotaxy is an increasingly frequent problem. Repeat stereotactic radiotherapy (re-SRT) shows encouraging results in terms of local control. However, the evidence on prognostic factors limiting the overall survival (OS) of re-treated patients is scarce. Here, we sought to analyze the patients' and treatment characteristics influencing the survival outcomes after re-SRT. METHODS: Data of all patients with local failure of initial SRT treated from 2012 to 2019 were retrospectively reviewed and cases treated with salvage SRT were analyzed. We analyzed the impact of patients' and treatment characteristics on overall survival after re-SRT by Kaplan-Meier method and Cox regression models. Local and distant brain control, cause of death, and radionecrosis rate were also assessed. RESULTS: Forty-seven patients with 55 BMs treated with re-SRT were evaluated. Median OS after re-SRT was 9.2 months and the overall local control was 83.6%. Nine BMs (16.4%) presented local relapse (LR), 12 (21.8%) radionecrosis, while 21 patients (44.7%) developed new BMs. Only absence of extracranial metastases at BMs diagnosis (HR 0.42, CI 95%; 0.18-0.97), extracranial disease progression (HR 2.39, CI 95%; 1.06-5.38) and distant brain failure (HR 3.94, CI 95%; 1.68-9.24) after re-SRT were significantly associated with patients' survival. Extracranial progression following re-SRT was an independent prognosticator of worse OS. CONCLUSION: Re-SRT after LR presented excellent local control with acceptable RN rate and improved patients' survival, limited mainly by extracranial and distant brain progression.

Síndrome del uno y medio asociado a parálisis facial: presentación de un caso / One and a half syndrome associated with facial paralysis. A case report

Introducción: el síndrome del uno y medio, descrito por primera vez por Miller Fisher en 1967, se caracteriza por la presencia de parálisis de la mirada conjugada horizontal y oftalmoplejía internuclear ipsilateral. Eggenberger descubrió la combinación del síndrome del uno y medio y la parálisis del nervio facial ipsilateral, y lo denominó síndrome del ocho y medio. Caso clínico: paciente de 36 años de edad con antecedentes de salud, que acude por desviación de la boca y visión doble con ambos ojos en mirada hacia la derecha e izquierda, con mareos. Al examen oftalmológico en ojo derecho presenta limitación de la abducción y aducción con movimientos verticales conservados. Ojo izquierdo: limitación de la aducción del ojo con abducción y movimientos verticales conservados, nistagmo en abducción y exotropia menor de 15 grados, dificultad para el cierre palpebral del ojo derecho con desviación de la comisura labial del lado izquierdo. Discusión: las causas más frecuentes son el infarto protuberancial y la esclerosis múltiple, siguiendo las hemorragias pontinas y los tumores del tallo cerebral. Se indicó imagen por resonancia magnética. Conclusiones: se diagnostica parálisis facial periférica derecha y síndrome del uno y medio, el estudio de imagen mostró tumor a nivel de tronco encefálico (puente). Se trató con radioterapia(AU)

Introduction: the one-and-a-half syndrome, first described by Miller Fisher in 1967, is characterized by the presence of horizontal conjugated gaze palsy and ipsilateral internuclear ophthalmoplegia. Eggenberger discovered the combination of one-and-a-half syndrome and ipsilateral facial nerve palsy, and named it eight-and-a-half syndrome. Clinical case: 36-year-old patient with a medical history, who comes to the hospital due to a deviation of the mouth and double vision with both eyes looking to the right and left, with dizziness. On ophthalmological examination in the right eye, he presented limited abduction and adduction with preserved vertical movements. Left eye: limitation of adduction of the eye with abduction and preserved vertical movements, nystagmus in abduction and exotropia less than 15 degrees, difficulty in closing the right eye with a deviation of the labial commissure on the left side. Discussion: the most frequent causes are pontine infarction and multiple sclerosis, followed by pontine hemorrhages and brain stem tumors. Magnetic resonance imaging was indicated. Conclusions: right peripheral facial palsy and one-and-a-half syndrome were diagnosed, the imaging study showed a tumor at the level of the brainstem (bridge). It was treated with radiotherapy(EU)