A phase II study of atezolizumab, pertuzumab, and high-dose trastuzumab for central nervous system metastases in patients with HER2-positive breast cancer.

PURPOSE: Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response. PATIENTS AND METHODS: This was a single-arm, multi-center, phase II trial of atezolizumab, pertuzumab, and high-dose trastuzumab for patients with HER2-positive breast cancer brain metastases. Participants received atezolizumab 1200 mg IV every 3 weeks (q3w), pertuzumab (loading dose 840 mg IV, then 420 mg IV q3w), and high-dose trastuzumab (6 mg/kg IV weekly for 24 weeks, then 6 mg/kg IV q3w). The primary endpoint was CNS overall response rate (ORR) per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Key secondary endpoints included CBR, overall survival (OS), and safety and tolerability of the combination. RESULTS: Among 19 enrolled participants, two had a confirmed intracranial partial response for a CNS-ORR of 10.5% (90% CI: 1.9%-29.6%). The study did not meet the prespecified efficacy threshold and was terminated early. The CBR was 42.1% at 18 weeks and 31.6% at 24 weeks. Seven patients (36.8%) required a dose delay or hold, and the most frequent any-grade adverse events were diarrhea (26.3%) and fatigue (26.3%). CONCLUSIONS: The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer brain metastases.

Multinucleated tumor cells in clear cell renal cell carcinoma.

OBJECTIVES: Multinucleated tumor cells (MTCs) in clear cell renal cell carcinoma (ccRCC) are not well understood. METHODS: Our study included ccRCC cases in a single institution between 2010 and 2019. We classified MTC as MTC with degenerative atypia (MTCD), MTC with no anaplasia (MTCNA), and MTC with anaplasia (MTCA). Clinicopathologic characteristics and outcomes were compared between MTC groups. RESULTS: In all, 92 of 256 people (36%) with ccRCC had MTC. People with ccRCC with MTCD and those with ccRCC but no MTC had similar clinicopathologic characteristics and outcomes. Also, MTCNA and MTCA were associated with larger tumor size, advanced pathologic tumor stage, higher World Health Organization/International Society of Urologic Pathologists nuclear grade, and higher metastatic potential (P < .001 for each parameter). Overall, MTCA was associated with an increased rate of recurrence (P = .004), higher metastatic potential (P < .001), and shorter time to metastasis (P = .033), regardless of tumor stage. Univariate Cox regression revealed MTCNA as a significant predictor of metastasis at 5 years (hazard ratio [HR], 4.171; 95% CI, 1.934-8.998); moreover, MTCA was a significant predictor of recurrence (HR, 5.723; 95% CI, 2.495-13.124), metastasis (HR, 12.024; 5.966-24.232), and death (HR, 5.661; 95% CI, 2.688-11.924) at 5 years. CONCLUSIONS: Although MTCD may not be relevant in tumor grading, MTCNA and MTCA are associated with adverse outcomes.

Diffusion tensor imaging and diffusion-weighted imaging on axillary lymph node status in breast cancer patients.

PURPOSE This article will examine the usefulness of diffusion tensor imaging (DTI) and diffusion-weighted imaging (DWI) on the assessment of axillary lymph nodes (ALN) of breast cancer patients. METHODS Axillary lymph nodes in 66 breast cancer patients were examined by DTI and DWI, and the largest lymph node with increased cortical thickness in axilla was selected. Morphological features, apparent diffusion coefficient (ADC), volume anisotropy, and fractional anisotropy values were measured by using a special software. Imaging findings and histopathological results were recorded. RESULTS Metastatic ALN were detected in 43 (65.1%) patients. Cortical thickness of the metastatic ALN was significantly higher than the non-metastatic ALNs (P < .001), and the long-axis-to-shortaxis ratio was significantly lower in metastatic ALNs (P < .001). There was a statistically significant difference between the ALN status and fatty hilum presence (P < .001). Apparent diffusion coefficient values of metastatic ALNs were statistically lower than those of non-metastatic ALNs (P < .001) using a cutoff value of 1.26 × 10-3 mm2 /s for b=500 ADC and 1.21 × 10-3 mm2 /s for b=800 ADC which had 97.7% sensitivity and 91.3% specificity. Fractional anisotropy and volume anisotropy values were significantly different between both groups. A cutoff value of 0.47 for b-500 fractional anisotropy had 83.7% sensitivity, 69.6% specificity 69.6% positive predictive value, and 83.7% negative predictive value. A cutoff value of 0.33 for b=500 volume anisotropy had 76.7% sensitivity, 78.3% specificity, 86.8% positive predictive value, and 64.3% negative predictive value. CONCLUSION Apparent diffusion coefficient value of metastatic ALNs was found to be significantly lower than those of non-metastatic ALN, and DTI metrics of metastatic ALN were found to be significantly higher than those of non-metastatic ALN. Overall, ADC had a better diagnostic performance than morphological features, fractional anisotropy, and volume anisotropy. Diffusion tensor imagingderived diffusion metrics may be used to complement breast magnetic resonance imaging in the future after further standardization of the imaging parameters.