RESUMEN
PURPOSE: To evaluate the positive predictive value and factors predictive of malignancy of additional calcifications in the pre-therapeutic work-up of a synchronous breast cancer. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study and informed consent was waved. Consecutive patients referred to our center between January 1st 2018 and December 31st 2022 for a breast cancer and who presented additional calcifications detected during the pretreatment work-up were eligible for inclusion in this study. Morphology, distribution and BI-RADS category of the calcifications were assessed in consensus by 3 radiologists specialized in breast imaging. Side and distance from the cancer were collected. The predictive value of malignancy of the calcifications was calculated for each BI-RADS category. Factors associated with malignancy were evaluated by logistic non-conditional regression on univariate and multivariate analysis. RESULTS: One hundred and thirteen clusters of calcifications in 103 patients were included. Among the groups of calcifications 41 % were malignant, 31 % benign and 28 % were atypia on biopsy. After exclusion of the non-operated atypia, 50.5 % of additional calcifications were ultimately malignant and 49.5 % were benign. The predictive value of malignancy was 20.7 %; 40.7 %; 63 %; 85.7 % and 100 % for category BI-RADS 3, 4a, 4B, 4c and 5 respectively. On multivariate analysis, multifocality or centricity of the index tumour (P = 0.01), BI-RADS classifications (P = 0.0001) and location ipsilateral less than 35 mm to the index cancer (P = 0.008) of the additional calcifications were found to be independent predictors of malignancy. Sixty percent of calcifications were not described on the initial out-center diagnostic work-up. CONCLUSION: Additional calcifications detected during the pretreatment work-up of a breast cancer are associated with a higher probability of malignancy than in a screening population and require biopsy even when demonstrating probably benign (BI-RADS 3) features.
RESUMEN
Immune checkpoint inhibitors (ICIs) show limited clinical activity in patients with advanced soft-tissue sarcomas (STSs). Retrospective analysis suggests that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in these patients. PEMBROSARC is a multicohort phase 2 study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS (NCT02406781). The primary endpoint was the 6-month non-progression rate (NPR). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. The 6-month NPR and ORRs for cohorts in this trial enrolling all comers were previously reported; here, we report the results of a cohort enrolling patients selected based on the presence of TLSs (n = 30). The 6-month NPR was 40% (95% confidence interval (CI), 22.7-59.4), so the primary endpoint was met. The ORR was 30% (95% CI, 14.7-49.4). In comparison, the 6-month NPR and ORR were 4.9% (95% CI, 0.6-16.5) and 2.4% (95% CI, 0.1-12.9), respectively, in the all-comer cohorts. The most frequent toxicities were grade 1 or 2 fatigue, nausea, dysthyroidism, diarrhea and anemia. Exploratory analyses revealed that the abundance of intratumoral plasma cells (PCs) was significantly associated with improved outcome. These results suggest that TLS presence in advanced STS is a potential predictive biomarker to improve patients' selection for pembrolizumab treatment.
