Tumor burden monitoring using cell-free tumor DNA could be limited by tumor heterogeneity in advanced breast cancer and should be evaluated together with radiographic imaging.

BACKGROUND: Accurate measurement of tumor burden in breast cancer disease is essential to improve the clinical management of patients. In this study, we evaluate whether the fluctuations in the fraction of PIK3CA mutant allele correlates with tumor response according to RECIST criteria and tumor markers quantification. METHODS: Eighty six plasma samples were analyzed by digital PCR using Rare Mutation Assays for E542K, E545K and H1047R. Mutant cfDNA and tumor markers CA15-3 and CEA were compared with radiographic imaging. RESULTS: The agreement between PIK3CA mutation status in FFPE samples and circulating tumor DNA (ctDNA) was moderate (K = 0.591; 95% IC = 0.371-0.811). Restricting the analysis to the metastatic patients, we found a good agreement between PIK3CA mutation status assessed in liquid and solid biopsy (K = 0.798 95%; IC = 0.586-1). ctDNA showed serial changes with fluctuations correlating with tumor markers 15.3 and CEA in 7 out of 8 cases with Pearson correlation coefficients ranging from 0.99 to 0.46 and from 0.99 to 0.38 respectively. Similarly, fluctuations in the fraction of PIK3CA mutant allele always correlated with changes in lesion size seen on images, although in two cases it did not correlate with treatment responses as defined by RECIST criteria. CONCLUSION: oncogenic mutation quantification in plasma samples can be useful to monitor treatment outcome. However, it might be limited by tumor heterogeneity in advanced disease and it should be evaluated together with radiographic imaging.

Life Cycle Assessment of Rare Earth Elements-Free Permanent Magnet Alternatives: Sintered Ferrite and Mn-Al-C.

Permanent magnets are fundamental constituents in key sectors such as energy and transport, but also robotics, automatization, medicine, etc. High-performance magnets are based on rare earth elements (RE), included in the European list of critical raw materials list. The volatility of their market increased the research over the past decade to develop RE-free magnets to fill the large performance/cost gap existing between ferrites and RE-based magnets. The improvement of hard ferrites and Mn-Al-C permanent magnets plays into this important technological role in the near future. The possible substitution advantage was widely discussed in the literature considering both magnetic properties and economic aspects. To evaluate further sustainability aspects, the present paper gives a life cycle assessment quantifying the environmental gain resulting from the production of RE-free magnets based on traditional hexaferrite and Mn-Al-C. The analysis quantified an advantage of both magnets that overcomes the 95% in all the considered impact categories (such as climate change, ozone depletion, human toxicity) compared to RE-based technologies. The benefit also includes the health and safety of working time aspects, proving possible reduction of worker risks by 3-12 times. The results represent the fundamentals for the development of green magnets that are able to significantly contribute to an effective sustainable transition.