Tracking plasma DNA mutation dynamics in estrogen receptor positive metastatic breast cancer with dPCR-SEQ

Serial monitoring of plasma DNA mutations in estrogen receptor positive metastatic breast cancer (ER + MBC) holds promise as an early predictor of therapeutic response. Here, we developed dPCR-SEQ, a customized assay that utilizes digital PCR-based target enrichment followed by next-generation sequencing to analyze plasma DNA mutations in ESR1, PIK3CA, and TP53. We validated dPCR-SEQ in a prospective cohort of 58 patients with ER + MBC and demonstrate excellent concordance with hotspot ESR1 mutation abundance measured by conventional digital PCR. The dPCR-SEQ assay revealed ESR1, PIK3CA, and TP53 plasma ctDNA mutations in 55%, 32%, and 32% of the study patients, respectively. We also observed dynamic changes in ESR1, PIK3CA, and TP53 ctDNA mutant allele fraction (MAF) that were frequently discordant between the different genes. Thus, monitoring plasma DNA mutation dynamics using a dPCR-SEQ assay is feasible, accurate, and may be investigated as a biomarker of therapeutic response in ER + MBC

Rapid clearance profile of plasma circulating tumor HPV type 16 DNA during chemoradiotherapy correlates with disease control in HPV-associated oropharyngeal cancer

Purpose: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Experimental Design: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16- positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non-HPV-associated malignancy was also analyzed. Results: Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (>200 copies/mL) and >95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or >10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049). Conclusions: A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPVassociated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy

Search for the Rare Decays J/Psi --> Ds- e+ nu_e, J/Psi --> D- e+ nu_e, and J/Psi --> D0bar e+ e-

We report on a search for the decays J/Psi --> Ds- e+ nu_e + c.c., J/Psi --> D- e+ nu_e + c.c., and J/Psi --> D0bar e+ e- + c.c. in a sample of 5.8 * 10^7 J/Psi events collected with the BESII detector at the BEPC. No excess of signal above background is observed, and 90% confidence level upper limits on the branching fractions are set: B(J/Psi --> Ds- e+ nu_e + c.c.)<4.8*10^-5, B(J/Psi --> D- e+ nu_e + c.c.) D0bar e+ e- + c.c.)<1.1*10^-5Comment: 10 pages, 4 figure

Study of J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar

The branching ratios and Angular distributions for J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar are measured using BESII 58 million J/psi.Comment: 11 pages, 5 figure

Measurement of \chi_cJ--> K+K-K+K-

Using 14M psi(2S) events taken with the BES-II detector, chi_cJ-->K+K-K+K- decays are studied. For the four-kaon final state, the branching fractions are B(chi_c0,1,2 -->K+K-K+K-)=(3.48\pm 0.23\pm 0.47)\times 10^{-3}, (0.70\pm 0.13\pm 0.10)\times 10^{-3}, and (2.17\pm 0.20\pm 0.31)\times 10^{-3}. For the \phi K+K- final state, the branching fractions, which are measured for the first time, are B(chi_c0,1,2-->\phi K+K-)=(1.03\pm 0.22\pm 0.15)\times 10^{-3}, (0.46\pm 0.16\pm 0.06)\times 10^{-3}, and (1.67\pm 0.26\pm 0.24)\times 10^{-4}. For the \phi\phi final state, B(chi_{c0,2}-->\phi\phi)=(0.94\pm 0.21\pm 0.13)\times 10^{-3} and (1.70\pm 0.30\pm 0.25)\times 10^{-3}.Comment: 7 pages, 7 figure

Partial wave analyses of J/psi to gamma pi^+ pi^- and gamma pi^0 pi^0

Results are presented on J/psi radiative decays to pi^+pi^- and pi^0pi^0 based on a sample of 58M J/psi events taken with the BESII detector. Partial wave analyses are carried out using the relativistic covariant tensor amplitude method in the 1.0 to 2.3 GeV/c^2 pipi mass range. There are conspicuous peaks due to the f_2(1270) and two 0^++ states in the 1.45 and 1.75 GeV/c^2 mass regions. The first 0^++ state has a mass of 1466\pm 6\pm 20 MeV/c^2, a width of 108^{+14}_{-11}\pm 25 MeV/c^2, and a branching fraction B(J/psi \to \gamma f_0(1500) \to\gamma \pi^+\pi^-) = (0.67\pm0.02\pm0.30) \times 10^{-4}. Spin 0 is strongly preferred over spin 2. The second 0^++ state peaks at 1765^{+4}_{-3}\pm 13 MeV/c^2 with a width of 145\pm8\pm69 MeV/c^2. If this 0^++ is interpreted as coming from f_0(1710), the ratio of its branching fractions to pipi and K\bar K is 0.41^{+0.11}_{-0.17}.Comment: 9 pages, 6 figure

Evidence for kappa Meson Production in J/psi -> bar{K}^*(892)^0K^+pi^- Process

Based on 58 million BESII J/psi events, the bar{K}^*(892)^0K^+pi^- channel in K^+K^-pi^+pi^- is studied. A clear low mass enhancement in the invariant mass spectrum of K^+pi^- is observed. The low mass enhancement does not come from background of other J/psi decay channels, nor from phase space. Two independent partial wave analyses have been performed. Both analyses favor that the low mass enhancement is the kappa, an isospinor scalar resonant state. The average mass and width of the kappa in the two analyses are 878 +- 23^{+64}_{-55} MeV/c^2 and 499 +- 52^{+55}_{-87} MeV/c^2, respectively, corresponding to a pole at (841 +- 30^{+81}_{-73}) - i(309 +- 45^{+48}_{-72}) MeV/c^2.Comment: 17 pages, 5 figure

Measurements of the cross sections for e+e−→hadronse^+e^- \to {\rm hadrons} at 3.650, 3.6648, 3.773 GeV and the branching fraction for ψ(3770)→non−DDˉ\psi(3770)\to {\rm non-}D\bar D

Using the BES-II detector at the BEPC Collider, we measured the lowest order cross sections and the $R$ values ($R=\sigma^0_{e^+e^- \to {\rm hadrons}}/\sigma^0_{e^+e^- \to \mu^+\mu^-}$) for inclusive hadronic event production at the center-of-mass energies of 3.650 GeV, 3.6648 GeV and 3.773 GeV. The results lead to $\bar R_{uds}=2.224\pm 0.019\pm 0.089$ which is the average of these measured at 3.650 GeV and 3.6648 GeV, and $R=3.793\pm 0.037 \pm 0.190$ at $\sqrt{s}=3.773$ GeV. We determined the lowest order cross section for $\psi(3770)$ production to be $\sigma^{\rm B}_{\psi(3770)} = (9.575\pm 0.256 \pm 0.813)~{\rm nb}$ at 3.773 GeV, the branching fractions for $\psi(3770)$ decays to be $BF(\psi(3770) \to D^0\bar D^0)=(48.9 \pm 1.2 \pm 3.8)$, $BF(\psi(3770) \to D^+ D^-)=(35.0 \pm 1.1 \pm 3.3)$ and $BF(\psi(3770) \to D\bar{D})=(83.9 \pm 1.6 \pm 5.7)$, which result in the total non-$D\bar D$ branching fraction of $\psi(3770)$ decay to be $BF(\psi(3770) \to {\rm non}-D\bar D)=(16.1 \pm 1.6 \pm 5.7)$.Comment: 11 pages, 5 figure

Precison Measurements of the Mass, the Widths of ψ(3770)\psi(3770) Resonance and the Cross Section σ[e+e−→ψ(3770)]\sigma[e^+e^-\to \psi(3770)] at Ecm=3.7724E_{\rm cm}=3.7724 GeV

By analyzing the $R$ values measured at 68 energy points in the energy region between 3.650 and 3.872 GeV reported in our previous paper, we have precisely measured the mass, the total width, the leptonic width and the leptonic decay branching fraction of the $\psi(3770)$ to be ${M}_{\psi(3770)}=3772.4 \pm 0.4 \pm 0.3$ MeV, $\Gamma_{\psi(3770)}^{\rm tot} = 28.6 \pm 1.2 \pm 0.2$ MeV, $\Gamma_{\psi(3770)}^{ee} = 279 \pm 11 \pm 13$ eV and $B[\psi(3770)\to e^+e^-]=(0.98\pm 0.04\pm 0.04)\times 10^{-5}$, respectively, which result in the observed cross section $\sigma^{\rm obs}[e^+e^-\to \psi(3770)]=7.25\pm 0.27 \pm 0.34$ nb at $\sqrt{s}=3772.4$ MeV. We have also measured $R_{\rm uds}=2.121\pm 0.023 \pm 0.084$ for the continuum light hadron production in the region from 3.650 to 3.872 GeV.Comment: 5 pages, 2 figure