Background

Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases.

Methods

In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (10⁶ then 10⁸ PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg was given on day 1 and every 21 (±3) days thereafter. Treatment continued until patients experienced dose-limiting toxicity (DLT), had complete response, progressive disease, needed alternative anticancer treatment, or withdrew due to an adverse event (AE). The primary endpoint was DLT incidence, and secondary endpoints included efficacy and AEs.

Results

Between 19 March 2018 and 6 November 2020, 11 patients with TNBC were enrolled (safety analysis set: n = 10); between 19 March 2018 and 16 October 2019, 25 patients with CRC were enrolled (safety analysis set: n = 24). For the 5 patients in the TNBC DLT analysis set, no patient had DLT; for the 18 patients in the CRC DLT analysis set, 3 (17%) had DLT, all serious AEs. AEs were reported by 9 (90%) TNBC and 23 (96%) CRC patients, the majority with grade ≥3 [TNBC, 7 (70%); CRC, 13 (54%)], and 1 was fatal [CRC, 1 (4%)]. Evidence of efficacy was limited. Overall response rate was 10% (95% confidence interval 0.3-44.5) for TNBC; one (10%) patient had a partial response. For CRC, no patients had a response; 14 (58%) were unassessable.

Conclusions

The safety profile reflected known risks with T-VEC including risks of intrahepatic injection; no unexpected safety findings from addition of atezolizumab to T-VEC were observed. Limited evidence of antitumor activity was observed.

This White Paper presents an overview of the current status and future perspective of QCD research, based on the community inputs and scientific conclusions from the 2022 Hot and Cold QCD Town Meeting. We present the progress made in the last decade toward a deep understanding of both the fundamental structure of the sub-atomic matter of nucleon and nucleus in cold QCD, and the hot QCD matter in heavy ion collisions. We identify key questions of QCD research and plausible paths to obtaining answers to those questions in the near future, hence defining priorities of our research over the coming decades.

This White Paper presents the community inputs and scientific conclusions from the Hot and Cold QCD Town Meeting that took place September 23-25, 2022 at MIT, as part of the Nuclear Science Advisory Committee (NSAC) 2023 Long Range Planning process. A total of 424 physicists registered for the meeting. The meeting highlighted progress in Quantum Chromodynamics (QCD) nuclear physics since the 2015 LRP (LRP15) and identified key questions and plausible paths to obtaining answers to those questions, defining priorities for our research over the coming decade. In defining the priority of outstanding physics opportunities for the future, both prospects for the short (~ 5 years) and longer term (5-10 years and beyond) are identified together with the facilities, personnel and other resources needed to maximize the discovery potential and maintain United States leadership in QCD physics worldwide. This White Paper is organized as follows: In the Executive Summary, we detail the Recommendations and Initiatives that were presented and discussed at the Town Meeting, and their supporting rationales. Section 2 highlights major progress and accomplishments of the past seven years. It is followed, in Section 3, by an overview of the physics opportunities for the immediate future, and in relation with the next QCD frontier: the EIC. Section 4 provides an overview of the physics motivations and goals associated with the EIC. Section 5 is devoted to the workforce development and support of diversity, equity and inclusion. This is followed by a dedicated section on computing in Section 6. Section 7 describes the national need for nuclear data science and the relevance to QCD research.

We report on new measurements of elliptic flow (v2) of electrons from heavy-flavor hadron decays at mid-rapidity (|y|<0.8) in Au+Au collisions at sNN = 27 and 54.4 GeV from the STAR experiment. Heavy-flavor decay electrons (eHF) in Au+Au collisions at sNN = 54.4 GeV exhibit a non-zero v2 in the transverse momentum (pT) region of pT< 2 GeV/c with the magnitude comparable to that at sNN=200 GeV. The measured eHF v2 at 54.4 GeV is also consistent with the expectation of their parent charm hadron v2 following number-of-constituent-quark scaling as other light and strange flavor hadrons at this energy. These suggest that charm quarks gain significant collectivity through the evolution of the QCD medium and may reach local thermal equilibrium in Au+Au collisions at sNN=54.4 GeV. The measured eHF v2 in Au+Au collisions at sNN= 27 GeV is consistent with zero within large uncertainties. The energy dependence of v2 for different flavor particles (π,ϕ,D0/eHF) shows an indication of quark mass hierarchy in reaching thermalization in high-energy nuclear collisions.

We report the measurement of K∗0 meson at midrapidity (|y|< 1.0) in Au+Au collisions at sNN=7.7, 11.5, 14.5, 19.6, 27, and 39 GeV collected by the STAR experiment during the Relativistic Heavy Ion Collider (RHIC) beam energy scan program. The transverse momentum spectra, yield, and average transverse momentum of K∗0 are presented as functions of collision centrality and beam energy. The K∗0/K yield ratios are presented for different collision centrality intervals and beam energies. The K∗0/K ratio in heavy-ion collisions are observed to be smaller than that in small-system collisions (e+e and p+p). The K∗0/K ratio follows a similar centrality dependence to that observed in previous RHIC and Large Hadron Collider measurements. The data favor the scenario of the dominance of hadronic rescattering over regeneration for K∗0 production in the hadronic phase of the medium.

We measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au+Au collisions at the BNL Relativistic Heavy Ion Collider. A significant v3 signal for protons is observed, which increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a slope at midrapidity, dv3/dy|(y=0), opposite in sign compared to the slope for directed flow. No significant v3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.

Abstract: The ratio of branching ratios of the W boson to muons and electrons, $$R^{\,\mu /e}_W={{\mathcal {B}}(W\rightarrow \mu u )}$$ R W μ / e = B ( W → μ ν ) /$${{\mathcal {B}}(W\rightarrow e u )}$$ B ( W → e ν ) , has been measured using $$140\,\text{ fb}^{-1}\,$$ 140 fb - 1 of pp collision data at $$\sqrt{s}=13$$ s = 13  $$\text {T}\text {e}\hspace{-1.00006pt}\text {V}$$ Te V collected with the ATLAS detector at the LHC, probing the universality of lepton couplings. The ratio is obtained from measurements of the $$t\bar{t}$$ t t ¯ production cross-section in the ee, $$e\mu $$ e μ and $$\mu \mu $$ μ μ dilepton final states. To reduce systematic uncertainties, it is normalised by the square root of the corresponding ratio $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e for the Z boson measured in inclusive $$Z\rightarrow ee$$ Z → e e and $$Z\rightarrow \mu \mu $$ Z → μ μ events. By using the precise value of $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e determined from $$e^+e^-$$ e + e - colliders, the ratio $$R^{\,\mu /e}_W$$ R W μ / e is determined to be $$\begin{aligned} R^{\,\mu /e}_W&= 0.9995\pm 0.0022\,\mathrm {(stat)}\,\pm 0.0036\,\mathrm {(syst)}\ &\quad \pm 0.0014\,\mathrm {(ext)} . \end{aligned}$$ R W μ / e = 0.9995 ± 0.0022 ( stat ) ± 0.0036 ( syst ) ± 0.0014 ( ext ) . The three uncertainties correspond to data statistics, experimental systematics and the external measurement of $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e , giving a total uncertainty of 0.0045, and confirming the Standard Model assumption of lepton flavour universality in W-boson decays at the 0.5% level.