A matched-pair analysis comparing stereotactic radiosurgery with whole-brain radiotherapy for patients with multiple brain metastases.

INTRODUCTION: Stereotactic radiosurgery (SRS) is an emerging treatment for patients with multiple brain metastases (BM). The present work compares the SRS of multiple brain metastases with whole-brain radiotherapy (WBRT). METHODS: We performed a matched-pair analysis for 128 patients with multiple BM treated with either SRS or WBRT over a 5-year period. Patients were matched pairwise for seven potential prognostic factors. A mixed Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS). Distant intracranial progression-free survival (icPFS) and local control were assessed using a Fine and Gray subdistribution hazard model and considering death as competing event. RESULTS: Patients undergoing SRS had a median of 4 BM (range 3-16). 1-year local control of individual BM following SRS was 91.7%. Median OS in the SRS subgroup was 15.7 months (IQR 9.7-36.4) versus 8.0 months (interquartile range, IQR 3.8-18.0) in the WBRT subgroup (HR 2.25, 95% CI [1.5; 3.5], p < 0.001). Median icPFS was 8.6 (IQR 3.4-18.0) versus 22.4 (IQR 5.6-28.6) months, respectively (HR for WBRT 0.41, 95% CI [0.24; 0.71], p = 0.001). Following SRS, synchronous BM diagnosis (HR 2.51, 95% CI [1.30; 4.70], p = 0.004), higher initial number of BM (HR 1.21, 95% CI [1.10; 1.40], p = 0.002) and lung cancer histology (HR 2.05, 95% CI [1.10; 3.80], p = 0.024) negatively impacted survival. Excellent clinical performance (KPI 90%) was a positive prognosticator (HR 0.38, 95% CI [0.20; 0.72], p = 0.003), as was extracerebral tumor control (HR 0.48, 95% CI [0.24; 0.97], p = 0.040). Higher initial (HR 1.19, 95% CI [1.00; 1.40], p < 0.013) and total number of BM (HR 1.23, 95% CI [1.10; 1.40], p < 0.001) were prognostic for shorter icPFS. CONCLUSION: This is the first matched-pair analysis to compare SRS alone versus WBRT alone for multiple BM. OS was prolonged in the SRS subgroup and generally favorable in the entire cohort. Our results suggest SRS as a feasible and effective treatment for patients with multiple BM.

Transformation or replacement - Effects of hormone therapy on cardiovascular risk.

Hormone therapy (HT) is important and frequently used both regarding replacement therapy (HRT) and gender affirming therapy (GAHT). While HRT has been effective in addressing symptoms related to hormone shortage, several side effects have been described. In this context, there are some studies that show increased cardiovascular risk. However, there are also studies reporting protective aspects of HT. Nevertheless, the exact impact of HT on cardiovascular risk and the underlying mechanisms remain poorly understood. This article explores the relationship between diverse types of HT and cardiovascular risk, focusing on mechanistic insights of the underlying hormones on platelet and leukocyte function as well as on effects on endothelial and adipose tissue cells.

Are patients with rheumatic diseases on immunosuppressive therapies protected against preventable infections? A cross-sectional cohort study.

OBJECTIVE: To evaluate the prevalence of infections, prevalence of hospitalisation due to infections, the vaccination status and perceived screening of infections prior to the start of biologic disease modifying antirheumatic drugs (bDMARDs) of a patient cohort with chronic inflammatory rheumatic diseases (CIRD). METHODS: Consecutive CIRD patients reporting to our specialised centre were prospectively included (n=975) in this cross-sectional study. Data on comorbidities including infections, treatment, vaccination status, screening for latent tuberculosis infection (LTBI) and hepatitis B (HepB) were collected. Antibodies against measles and HepB were measured by ELISA. The vaccination status was assessed by a predefined vaccination score (0-26) categorising patients into four immunisation states: low (0-6), moderate (7-13), good (14-20), high (21-26). RESULTS: All patients on bDMARDs (n=499) were screened for LTBI, and 469 for HepB (94%). All LTBI patients (n=16) received isoniazid (3.2%) and 16 chronic HepB patients received lamivudine (3.4%). Protective measles specific IgG-antibodies were found in 901 patients (92.4%). Although 629 patients were educated about vaccination strategies (64.5%), only 540 showed a vaccination card (55.4%). Only 49% of patients had undergone pneumococcal vaccination and less than 30% were protected against HepB and influenza, while 7.6% have not protective antibody titres against measles. No patient met the German national vaccination recommendations requiring a complete documentation of vaccines. The mean vaccination score was 13.3±4.2 with 5.7% of patients having a low, 43.9% a moderate, 47.0% a good and 3.3% a high score. CONCLUSIONS: The majority of CIRD patients are n0t sufficiently vaccinated against pneumococci, HepB, influenza and measles. Although CIRD patients and general practitioners regularly receive professional information about the need of vaccination, vaccination rates were low to moderate. Interdisciplinary quality projects should be planned to change that inacceptable result.

Single-Isocenter Volumetric Modulated Arc Therapy vs. CyberKnife M6 for the Stereotactic Radiosurgery of Multiple Brain Metastases.

Introduction: Stereotactic radiosurgery (SRS) is becoming more frequently used for patients with multiple brain metastases (BMs). Single-isocenter volumetric modulated arc therapy (SI-VMAT) is an emerging alternative to dedicated systems such as CyberKnife (CK). We present a dosimetric comparison between CyberKnife M6 and SI-VMAT, planned at RayStation V8B, for the simultaneous SRS of five or more BM. Patients and Methods: Twenty treatment plans of CK-based single-session SRS to ≥5 brain metastases were replanned using SI-VMAT for delivery at an Elekta VersaHD linear accelerator. Prescription dose was 20 or 18 Gy, conformally enclosing at least 98% of the total planning target volume (PTV), with PTV margin-width adapted to the respective SRS technique. Comparatively analyzed quality metrics included dose distribution to the healthy brain (HB), including different isodose volumes, conformity, and gradient indices. Estimated treatment time was also compared. Results: Median HB isodose volumes for 3, 5, 8, 10, and 12 Gy were consistently smaller for CK-SRS compared to SI-VMAT (p < 0.001). Dose falloff outside the target volume, as expressed by the gradient indices GI_high and GI_low, was consistently steeper for CK-SRS compared to SI-VMAT (p < 0.001). CK-SRS achieved a median GI_high of 3.1 [interquartile range (IQR), 2.9-1.3] vs. 5.0 (IQR 4.3-5.5) for SI-VMAT (p < 0.001). For GI_low, the results were 3.0 (IQR, 2.9-3.1) for CK-SRS vs. 5.6 (IQR, 4.3-5.5) for SI-VMAT (p < 0.001). The median conformity index (CI) was 1.2 (IQR, 1.1-1.2) for CK-SRS vs. 1.5 (IQR, 1.4-1.7) for SI-VMAT (p < 0.001). Estimated treatment time was shorter for SI-VMAT, yielding a median of 13.7 min (IQR, 13.5-14.0) compared to 130 min (IQR, 114.5-154.5) for CK-SRS (p < 0.001). Conclusion: SI-VMAT offers enhanced treatment efficiency in cases with multiple BM, as compared to CyberKnife, but requires compromise regarding conformity and integral dose to the healthy brain. Additionally, delivery at a conventional linear accelerator (linac) may require a larger PTV margin to account for delivery and setup errors. Further evaluations are warranted to determine whether the detected dosimetric differences are clinically relevant. SI-VMAT could be a reasonable alternative to a dedicated radiosurgery system for selected patients with multiple BM.

Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases-Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept.

BACKGROUND: Pre-operative radiosurgery (SRS) preceding the resection of brain metastases promises to circumvent limitations of post-operative cavity SRS. It minimizes uncertainties regarding delineation and safety margins and could reduce dose exposure of the healthy brain (HB). METHODS: We performed a systematic treatment plan comparison on 24 patients who received post-operative radiosurgery of the resection cavity at our institution. Comparative treatment plans were calculated for hypofractionated stereotactic radiotherapy (7 × 5 Gray (Gy)) in a hypothetical pre-operative (pre-op) and two post-operative scenarios, either with (extended field, post-op-E) or without the surgical tract (involved field, post-op-I). Detailed volumetric comparison of the resulting target volumes was performed, as well as dosimetric comparison focusing on targets and the HB. RESULTS: The resection cavity was significantly smaller and different in morphology from the pre-operative lesion, yielding a low Dice Similarity Coefficient (DSC) of 53% (p = 0.019). Post-op-I and post-op-E targets showed high similarity (DSC = 93%), and including the surgical tract moderately enlarged resulting median target size (18.58 ccm vs. 22.89 ccm, p < 0.001). Dosimetric analysis favored the pre-operative treatment setting since it significantly decreased relevant dose exposure of the HB (Median volume receiving 28 Gy: 6.79 vs. 10.79 for pre-op vs. post-op-E, p < 0.001). Dosimetrically, pre-operative SRS is a promising alternative to post-operative cavity irradiation that could furthermore offer practical benefits regarding delineation and treatment planning. Comparative trials are required to evaluate potential clinical advantages of this approach.