Published papers

We studied the band structure of NdFeAs$_{1-x}$P$_{x}$O$_{0.9}$F$_{0.1}$ ($x$ = 0, 0.2, 0.4 and 0.6) using angle-resolved photoemission spectroscopy (ARPES) measurements. Two of the hole bands, $α_1$ $(d_{xz})$ and $α_3$ $(d_{z^2})$, were observed at the Brillouin zone center in the $P$-polarized light configuration, while the other two hole bands, $α_2$ $(d_{yz})$ and $γ$ $(d_{xy})$, were observed in the $S$-polarized alternative. The observed $γ$ band shifts downwards as $x$ increases, which is consistent with the theoretical prediction for the change in bond angle of As/P-Fe-As/P. Furthermore, a small amount of the $d_{xy}$ orbital component was observed at the same binding energy as that of the top of the $α_1$ band, thus indicating the band reconstruction of the originally degenerate $α_1$ and $α_2$ $(d_{xz}/d_{yz})$ bands by the unoccupied $d_{xy}$ band. The change in the energy level of the $α_1$ band top with $d_{xy}$ orbital character is accompanied by a $T_{c}$ upturn at $0.2 < x < 0.4$. The $T_{c}$ continues to increase as the $α_1$ band shifts downward, crossing the Fermi level. The incipient band with the $d_{xy}$ orbital character on its top could be an important ingredient for high $T_{c}$ 1111-type iron-based superconductors.

Oxaliplatin-based chemotherapy with a regimen such as FOLFOX with or without targeted therapy is a standard of care option for advanced colorectal cancer; however, long-term exposure to oxaliplatin is associated with cumulative toxicity. Growing evidence suggests maintenance therapy with a less intensive regimen after platinum-based induction therapy can provide continuing benefit with reduced toxicity. We describe the rationale and design of the Phase III LYNK-003 trial, which will evaluate the efficacy and safety of olaparib with or without bevacizumab compared with 5-fluoruracil plus bevacizumab in patients with unresectable or metastatic colorectal cancer that has not progressed on an induction course of FOLFOX plus bevacizumab. The primary end point is progression-free survival by independent central review; secondary end points include overall survival, objective response, duration of response and safety. Clinical trial registration: NCT04456699.

BACKGROUND: The randomized, open-label, phase III LYNK-003 study assessed the efficacy of first-line maintenance olaparib, alone or in combination with bevacizumab, versus bevacizumab plus a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer (mCRC). We present results of the prespecified interim futility analysis. METHODS: Eligible participants were ≥18 years of age with unresectable or mCRC that had not progressed after induction with first-line bevacizumab plus 5-fluorouracil plus oxaliplatin plus leucovorin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). Participants were randomly assigned 1:1:1 to olaparib plus bevacizumab, olaparib alone, or bevacizumab plus a fluoropyrimidine (5-fluorouracil or capecitabine). The primary end point was progression-free survival (PFS) per RECIST v1.1 by central review. RESULTS: Between August 2020 and May 2022, 309 participants were assigned to olaparib plus bevacizumab (n = 104), olaparib (n = 107), or bevacizumab plus fluoropyrimidine (n = 98). At interim analysis, with a median follow-up of 7.6 months (range 0.1-19.7 months), the median PFS was 3.7 months (95% CI 2.8-5.3) with olaparib plus bevacizumab (HR 1.52; 95% CI 1.02-2.27; P = 0.982) and 3.5 months (95% CI 2.0-3.7) with olaparib (HR 2.11; 95% CI 1.39-3.18; P = 0.999) versus 5.6 months (95% CI 3.8-5.9) with bevacizumab plus fluoropyrimidine. Treatment-related adverse events occurred in 64 (62%), 52 (50%), and 57 (59%) participants, respectively. There were no treatment-related deaths. CONCLUSION: The LYNK-003 study was stopped prematurely as criteria for futility were met. Maintenance olaparib with or without bevacizumab did not demonstrate clinical efficacy compared with bevacizumab plus a fluoropyrimidine. GOV REGISTRATION: NCT04456699.

We obtain a lower bound of the degree of irrationality of very general complete intersections over the complex field from the recent results of the first author and Chen--Stapleton. For combining these results, we make a minor adjustment of Chen--Stapleton's method using the trace map of differential modules.

We demonstrate size selective optical trapping and transport for nanoparticles near an optical nanofiber taper. Using a two-wavelength, counter-propagating mode configuration, we show that 100 nm diameter and 150 nm diameter gold nanospheres (GNSs) are trapped by the evanescent field in the taper region at different optical powers. Conversely, when one nanoparticle species is trapped the other may be transported, leading to a sieve-like effect. Our results show that sophisticated optical manipulation can be achieved in a passive configuration by taking advantage of mode behavior in nanophotonics devices.

We construct the marginal loosely trapped surface (marginal LTS) for the Kerr spacetime with a small Kerr parameter perturbatively, where the LTS condition is saturated. An LTS is a surface that specifies the strong gravity region, which is a generalization of the photon sphere in the Schwarzschild spacetime. It turns out that there are an infinite number of marginal LTSs. At the leading order of the small Kerr parameter, all of the marginal LTSs have the same area. However, one can see that the maximal marginal LTS among them is uniquely determined at the higher order.

Colorectal cancer is the second leading cause of cancer deaths worldwide, with a 5-year relative survival of 14% in patients with metastatic colorectal cancer (mCRC). Patients with BRAF V600E mutations, which occur in ∼10%-15% of patients with mCRC, have a poorer prognosis compared with those with wild-type BRAF tumours. The combination of the BRAF inhibitor encorafenib with the epidermal growth factor receptor inhibitor cetuximab currently represents the only chemotherapy-free targeted therapy approved in the USA and Europe for previously treated patients with BRAF V600E-mutated mCRC. As a class, BRAF inhibitors are associated with dermatologic, gastrointestinal, and renal events, as well as pyrexia and secondary skin malignancies. Adverse event (AE) profiles of specific BRAF inhibitors vary, however, and are affected by the specific agents given in combination. In patients with mCRC, commonly reported AEs of cetuximab monotherapy include infusion reactions and dermatologic toxicities. Data from the phase III BEACON CRC study indicate that the combination of encorafenib with cetuximab has a distinct safety profile. Here we review the most frequently reported AEs that occurred with this combination in BEACON CRC and best practices for managing and mitigating AEs that require more than standard supportive care.

Background The selection of biologic therapies in metastatic colorectal cancer (mCRC) is traditionally guided by right–left classification; however, this binary classification may not fully capture heterogeneity in responsiveness to anti–epidermal growth factor receptor (EGFR) therapy. We evaluated whether treatment efficacy varies across detailed anatomical tumour segments. Methods Individual patient-level data from 12 randomised controlled trials in the ARCAD database were analysed. Patients with RAS wild-type (RAS-WT) mCRC receiving first-line doublet chemotherapy plus anti-EGFR therapy or bevacizumab were included. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). Results A total of 2867 patients were included (815 right-sided colon cancer [RSC]; 2052 left-sided colorectal cancer [LSC]). In RAS-WT RSCs, anti-EGFR therapy was not associated with improved OS or PFS versus bevacizumab. In RAS/BRAF-WT RSCs, anti-EGFR therapy was associated with inferior PFS. In contrast, in RAS-WT LSCs, anti-EGFR therapy significantly improved OS and ORR, without a significant difference in PFS. Segment-level analyses (N = 1491) showed no significant heterogeneity within RSCs, although median OS numerically varied across subsites. Within LSCs, the OS benefit was most pronounced in the rectum. Conclusions The efficacy of anti-EGFR therapy in mCRC appears to exhibit additional intraregional heterogeneity beyond the conventional right–left classification. These findings suggest that anatomical tumour location may reflect underlying biological differences not fully captured by this binary classification.