Clinical implication of tumor mutational burden in patients with HER2-positive refractory metastatic breast cancer.

This study explored the clinical implications of tumor mutational burden (TMB) in a well-defined HER2-positive metastatic breast cancer (MBC) patient population who had been previously treated but had subsequent disease progression. Whole exome sequencing was performed on formalin-fixed paraffin-embedded tumor samples and matched normal tissue. Among the 46 patients, 13 (28.3%) were estrogen receptor-positive and nine (19.6%) were progesterone receptor-positive by immunohistochemistry analysis. Twenty patients (43.5%) had recurrent MBC compared with de novo MBC (n = 26, 56.5%). Sixteen patients (34.6%) demonstrated more than 100 somatic non-synonymous SNV mutations, which was predefined as a high TMB. The median follow-up duration was 57.5 months. The median overall survival (mOS) differed significantly between low and high TMB status (44.9 months vs. 85.8 months, respectively, p = 0.016). In a multivariate Cox regression analysis, TMB was the only independent prognostic factor for good metastatic overall survival after adjusting for age and recurrence (Hazard ratio [HR] = 0.32, 95% confidence interval [CI], 0.103-0.998, p = 0.049). These data suggest that high TMB may be a prognostic marker for predicting good overall survival for patients undergoing conventional HER2-directed treatments and chemotherapy. Further, future clinical trials harnessing TMB may benefit by identifying an appropriate population who may have a favorable response to immunotherapy after recurrence following HER2-directed treatments.

Geometric attack resistant watermarking in wavelet transform domain.

In this paper, we propose an autocorrelation function (ACF) based watermarking scheme in the discrete wavelet transform (DWT) domain. Conventional ACF-based watermarking embeds a watermark in the spatial domain due to its detection mechanism.We show that the autocorrelation (AC) peaks, which play an important role in estimating the applied geometric attacks in ACF-based watermarking, can also be extracted by embedding the watermark in the DWT domain. In the proposed scheme, a periodic watermark is embedded in the DWT domain by considering the AC peak strength and noise visibility. The proposed scheme also deals efficiently with the image shift problem in the detection process by using the undecimated DWT. Experimental results show that the proposed scheme yields stronger AC peaks than the spatial domain scheme does and, as a result, shows improved robustness against combined geometric-removal.