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Purpose: Stereotactic radiosurgery (SRS) has been increasingly used to treat intracranial pathologies in elderly patients. The treatment efficiency of SRS has been demonstrated in meningiomas, with excellent local control. We aimed to analyze the safety of robotic SRS in elderly patients with meningiomas. Methods: We searched for patients with suspected WHO °I meningioma ≥ 60 years old, who underwent CyberKnife (CK) SRS from January 2011 to December 2021. Tumor localization was categorized using the "CLASS" algorithmic scale. Tumor response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria for meningiomas. Adverse effects were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and a cox regression was performed to investigate possible predictors. Results: We identified 82 patients with 102 CK-treated lesions that matched the criteria for the first SRS. The median age was 70 [IQR 64-75] years, and 24.3% of the patients were aged > 75 years. Multiple lesions (up to six) were treated in 14.1% of the SRS-sessions. A previous surgery was performed in 57.3% of lesions, with a median time interval of 41 [IQR 10 - 58] months between the initial surgical procedure and the SRS treatment. In 47.9% of cases, CLASS 3 meningiomas at high-risk locations were irradiated. Single fraction radiosurgery was applied to 62.5% of the lesions, while in the remaining cases multi-session SRS with three to five fractions was used. During the median follow-up period of 15.9 months, lesion size progression was observed in 3 cases. Karnofsky Performance Status (KPS) declined by ≥ 20 points in four patients. Adverse effects occurred in 13 patients, while only four patients had CTCAE ≥2 toxicities. Hereby only one of these toxicities was persistent. The occurrence of complications was independent of age, planned target volume (PTV), high-risk localization, and surgery before SRS. Conclusion: The data indicates that SRS is a safe, efficient, and convenient treatment modality for elderly patients with meningioma, even at high-risk locations.
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[This corrects the article DOI: 10.3389/fonc.2023.1056330.].
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Introduction: Neoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT). Methods: We identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0 mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials. Results: We included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm3 were smaller tumors (pre-GTV < 15.0 cm3), whereas larger tumors greater than 25.0 cm3 showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2-84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview. Conclusion: Patients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.
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Melanoma brain metastases (MBM) variably respond to therapeutic interventions; thus determining patient's prognosis. However, the mechanisms that govern therapy response are poorly understood. Here, we use a multi-OMICS approach and targeted sequencing (TargetSeq) to unravel the programs that potentially control the development of progressive intracranial disease. Molecularly, the expression of E-cadherin (Ecad) or NGFR, the BRAF mutation state and level of immune cell infiltration subdivides tumors into proliferative/pigmented and invasive/stem-like/therapy-resistant irrespective of the intracranial location. The analysis of MAPK inhibitor-naive and refractory MBM reveals switching from Ecad-associated into NGFR-associated programs during progression. NGFR-associated programs control cell migration and proliferation via downstream transcription factors such as SOX4. Moreover, global methylome profiling uncovers 46 differentially methylated regions that discriminate BRAFmut and wildtype MBM. In summary, we propose that the expression of Ecad and NGFR sub- classifies MBM and suggest that the Ecad-to-NGFR phenotype switch is a rate-limiting process which potentially indicates drug-response and intracranial progression states in melanoma patients.