Immune checkpoint inhibitors in ovarian cancer: where do we stand?

Numerous retrospective studies have demonstrated that the density of intra-tumoral immune cell infiltration is prognostic in epithelial ovarian cancer (OC). These observations together with reports of programmed death ligand-1 (PD-L1) expression in advanced OC provided the rationale for investigating the benefit of programmed death-1 (PD1) or PD-L1 inhibition in OC. Unfortunately clinical trials to date evaluating PD1/PD-L1 inhibition in patients with relapsed OC have been disappointing. In this review we will discuss early results from single agent PD1/PD-L1 inhibitors and the strategies to enhance benefit from immune-oncology agents in OC, including proposing anti-PD-L1 in combination with other agents (cytotoxics, anti-angiogenics, poly(ADP-ribose) polymerase. (PARP) inhibitors, targeted therapies or other immunotherapies), as well as evaluating these agents earlier in the disease course, or in biomarker selected patients

Diagonal and Low-Rank Matrix Decompositions, Correlation Matrices, and Ellipsoid Fitting

In this paper we establish links between, and new results for, three problems that are not usually considered together. The first is a matrix decomposition problem that arises in areas such as statistical modeling and signal processing: given a matrix $X$ formed as the sum of an unknown diagonal matrix and an unknown low rank positive semidefinite matrix, decompose $X$ into these constituents. The second problem we consider is to determine the facial structure of the set of correlation matrices, a convex set also known as the elliptope. This convex body, and particularly its facial structure, plays a role in applications from combinatorial optimization to mathematical finance. The third problem is a basic geometric question: given points $v_1,v_2,...,v_n\in \R^k$ (where $n > k$) determine whether there is a centered ellipsoid passing \emph{exactly} through all of the points. We show that in a precise sense these three problems are equivalent. Furthermore we establish a simple sufficient condition on a subspace $U$ that ensures any positive semidefinite matrix $L$ with column space $U$ can be recovered from $D+L$ for any diagonal matrix $D$ using a convex optimization-based heuristic known as minimum trace factor analysis. This result leads to a new understanding of the structure of rank-deficient correlation matrices and a simple condition on a set of points that ensures there is a centered ellipsoid passing through them.Comment: 20 page

The kink Casimir energy in a lattice sine-Gordon model

The Casimir energy of quantum fluctuations about the classical kink configuration is computed numerically for a recently proposed lattice sine-Gordon model. This energy depends periodically on the kink position and is found to be approximately sinusoidal.Comment: 10 pages, 4 postscript figure

Kondo effect in a one dimensional d-wave superconductor

We derive a solvable resonant-level type model, to describe an impurity spin coupled to zero-energy bound states localized at the edge of a one dimensional d-wave superconductor. This results in a two-channel Kondo effect with a quite unusual low-temperature thermodynamics. For instance, the local impurity susceptibility yields a finite maximum at zero temperature (but no logarithmic-divergence) due to the splitting of the impurity in two Majorana fermions. Moreover, we make comparisons with the Kondo effect occurring in a two dimensional d-wave superconductor.Comment: 9 pages, final version; To be published in Europhysics Letter

Fermi surface renormalization in Hubbard ladders

We derive the one-loop renormalization equations for the shift in the Fermi-wavevectors for one-dimensional interacting models with four Fermi-points (two left and two right movers) and two Fermi velocities v_1 and v_2. We find the shift to be proportional to (v_1-v_2)U^2, where U is the Hubbard-U. Our results apply to the Hubbard ladder and to the t_1-t_2 Hubbard model. The Fermi-sea with fewer particles tends to empty. The stability of a saddle point due to shifts of the Fermi-energy and the shift of the Fermi-wavevector at the Mott-Hubbard transition are discussed.Comment: 5 pages, 4 Postscript figure

Theory of anomalous magnetic interference pattern in mesoscopic SNS Josephson junctions

The magnetic interference pattern in mesoscopic SNS Josephson junctions is sensitive to the scattering in the normal part of the system. In this paper we investigate it, generalizing Ishii's formula for current-phase dependence to the case of normal scattering at NS boundaries in an SNS junction of finite width. The resulting flattening of the first diffraction peak is consistent with experimental data for S-2DEG-S mesoscopic junctions.Comment: 6 pages, 5 figures. Phys. Rev. B 68, 144514 (2003

Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy

BACKGROUND: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. METHODS: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). RESULTS: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. CONCLUSIONS: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients