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Abstract The PATRICIA study (NCT02536339) examined the efficacy and safety of pertuzumab plus high-dose trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) with progressive central nervous system (CNS) metastases following radiotherapy. Primary analysis confirmed CNS objective response rate (ORR) was 11% (95% confidence interval [CI]: 3–25); clinical benefit rate (CBR) was 68% (4 months) and 51% (6 months). We report final efficacy data after a further 21-months of follow-up, updated safety, survival, and patient-reported outcomes (PROs). Patients received standard-dose pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Primary endpoint: confirmed ORR (CNS) per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary endpoints were response duration, CBR, progression-free survival (PFS), overall survival (OS), safety, and PROs. By clinical cut-off, 39 patients had completed or discontinued treatment. Confirmed ORR (CNS) was 11% (95% CI: 3.0–25.4). Median CNS-PFS was 4.6 months (95% CI: 4.0–8.9), as was median CNS-PFS or systemic PFS (95% CI: 4.0–8.9); median OS was 27.2 months (95% CI: 16.1–not reached). CBR in the CNS was 51% (19 patients, 95% CI: 34.4–68.1) at 6 months. Two patients remained on treatment until study closure, achieving stable disease for 4.1 and 4.8 years. Treatment-related grade 3/4 adverse events occurred in 7.7% of patients. Patients with confirmed partial response or stable disease (≥4 months) in the CNS had stable PROs over time. Pertuzumab plus high-dose trastuzumab represents a reasonable non-chemotherapeutic treatment option for selected patients with HER2-positive MBC with CNS metastases.

Femoral fractures due to sideways falls continue to be a major cause of concern for the elderly. Existing approaches for the prevention of these injuries have limited efficacy. Prophylactic femoral augmentation systems, particularly those involving the injection of ceramic-based bone cements, are gaining more attention as a potential alternative preventative approach. We evaluated the mechanical effectiveness of three variations of a bone cement injection pattern (basic ellipsoid, hollow ellipsoid, small ellipsoid) utilizing finite element simulations of sideways fall impacts. The basic augmentation pattern was tested with both high- and low-strength ceramic-based cements. The cement patterns were added to the finite element models (FEMs) of five cadaveric femurs, which were then subject to simulated sideways falls at seven impact velocities ranging from 1.0 m/s to 4.0 m/s. Peak impact forces and peak acetabular forces were examined, and failure was evaluated using a strain-based criterion. We found that the basic HA ellipsoid provided the highest increases in both the force at the acetabulum of the impacted femur (“acetabular force”, 55.0% ± 22.0%) and at the force plate (“impact force”, 37.4% ± 15.8%). Changing the cement to a weaker material, brushite, resulted in reduced strengthening of the femur (45.2% ± 19.4% acetabular and 30.4% ± 13.0% impact). Using a hollow version of the ellipsoid appeared to have no effect on the fracture outcome and only a minor effect on the other metrics (54.1% ± 22.3% acetabular force increase and 35.3% ± 16.0% impact force increase). However, when the outer two layers of the ellipsoid were removed (small ellipsoid), the force increases that were achieved were only 9.8% ± 5.5% acetabular force and 8.2% ± 4.1% impact force. These results demonstrate the importance of supporting the femoral neck cortex to prevent femoral fractures in a sideways fall, and provide plausible options for prophylactic femoral augmentation. As this is a preliminary study, the surgical technique, the possible effects of trabecular bone damage during the augmentation process, and the effect on the blood supply to the femoral head must be assessed further.