Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)]. PATIENTS AND METHODS: c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSIONS: c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.

Hyper pure quartz as a promising material for retrospective and radiation processing dosimetry using ESR technique.

Samples of highly purified naturally occurring silicon dioxide (SiO(2)) commercially named clear fused quartz (CFQ), both in bulk and in powder form were exposed to 4 and 8 MeV electrons from a linear accelerator (radiotherapy unit) at doses between 0.5 and 60 Gy (minimum and maximum attainable dose, respectively). After irradiation, the samples were subjected to electron spin resonance (ESR) analysis readout to test their use as a mean of measuring absorbed doses in the samples. A good linearity between the absorbed dose (from 2 Gy up to the maximum dose applied of 60 Gy) and the ESR intensity of the samples was observed while a poor linearity at low doses (between the absorbed dose from 0.5 to 10 Gy and the ESR intensity) is seen. The background intensity in the case of the powder was higher than for the cylindrical samples and the ESR intensity was also lower in the former case, which gave rise to a dose curve response with a lower slope for the powders. No energy dependence was apparent for electrons of 4 and 8 MeV energy. The thermal fading of CFQ at room temperature showed a relatively sharp decay of approximately 30% over a period of 10 days after which the decay rate was negligible for a measured period of 80 days. The results in this study plus the previous work done (gamma irradiation of the samples) by the authors suggest that the materials could, by using the ESR technique, be a suitable candidate for alternative dose measurements in radiation processing and retrospective dosimetry.

The determination of calcium in faecal samples by instrumental fast neutron activation analysis.

A method is described for the determination of calcium in faecal material by a purely instrumental technique, namely fast neutron activation analysis. The major advantage of the technique over existing methods is that it requires minimal sample preparation. In addition, only a single standard is used and the method is also fairly rapid and simple. The method is well suited to the routine analysis of large numbers of samples and the results are shown to be comparable with atomic absorption spectrophotometry in accuracy. Finally, the technique can be extended to include the determination of several other elements providing a standard for each element is included.

Instrumental neutron activation analyses of lunar specimens.

Ten Apollo 11 specimnens were divided into 24 samtples. Sodillim contents of 8 diverse specimens clluster tightly abolit 0.3 percent. Plagioclase separated from sample 10044 contains aboltt 1.09 percent Na; barium is not enriched in the plagioclase separate. Contents of the rare earths are strikingly high, and relative abtmndances resemble those of calcium-rich achondrites or abyssal basalts but are depleted in Eu by factors of 2 to 3 and in La by about 20 percent. The plagioclase separate is enriched in Eu and pyroxenes (and opaqtte minerals are Eu-depleted. Fine fractions of 10044 are abotit 20 to 40 percent richer in most rare earths (50 percent for Eu) than coarse fractions, probably becaitse of the presence of small grains in which rare earths are mnarkedly concentrated. "Microgabbro" 10045 is imnpoverished, relative to the soil, in rare eartlhs and Hf. Ratios by mass of Zr to Hf are comlparatively low. Abttndances of Mn, Co, Fe, Sc and Cr stiggest systematic differences between igneous rocks on one hanid and breccias and "soil" on the other. Fromn the Co abuindances, no more than about 3 percent of the present "soil" can consist of chondritic mleteorite conitamination.