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Background: Patients with advanced type B3 thymoma and thymic carcinoma resistant to chemotherapy have few treatment options. We report the efficacy and safety results of the combination of the anti-PD-L1 inhibitor avelumab with the anti-angiogenesis drug axitinib in patients with advanced type B3 thymoma and thymic carcinoma. Methods: CAVEATT was a single-arm, multicentre, phase 2 trial, conducted in two Italian centres (the European Instituteof Oncology and the Humanitas Institute, Milan) in patients with histologically confirmed type B3 thymoma or thymic carcinoma, with advanced stage of disease who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis drug was allowed but not with immune checkpoint inhibitors. Other inclusion criteria were age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0–2, progressive disease, and presence of measurable disease according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Patients received avelumab 10 mg/kg intravenously every 2 weeks and axitinib 5 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was the centrally assessed overall response rate according to RECIST version 1.1. Patients who received at least one cycle of treatment and had at least one CT scan after treatment start at scheduled time point by protocol were judged assessable for response and were included in efficacy and safety analyses. This study is registered with EUDRACT, 2017–004048–38; enrolment is completed and follow-up is ongoing. Findings: Between April 22, 2019, and June 30, 2021, 32 patients were enrolled. 27 patients had a thymic carcinoma, three a type B3 thymoma, and two a mixed type B3 thymoma and thymic carcinoma. 29 (91%) of 32 patients had stage IVB disease and 13 (41%) of 32 had been pretreated with an anti-angiogenesis drug. 11 of 32 patients had an overall response; thus the overall response rate was 34% (90% CI 21–50); no patients had a complete response, 11 (34%) had a partial response, 18 (56%) had stable disease, and in two patients (6%) progressive disease was the best response. The most common grade 3 or 4 adverse event was hypertension (grade 3 in six [19%] of 32 patients). Four (12%) of 32 patients developed serious adverse events that were new-onset immune-related adverse events, including one grade 3 interstitial pneumonitis, one grade 4 polymyositis, and two grade 3 polymyositis. There were no treatment-related deaths. Interpretation: Avelumab combined with axitinib has promising anti-tumour activity and acceptable toxicity in patients with advanced type B3 thymoma and thymic carcinoma progressing after chemotherapy, and could emerge as a new standard treatment option in this setting. Funding: Pfizer.

Non-Hermitian photonics has attracted increasing attention especially for sensing applications. Two coupled optical systems, designed to work at the “exceptional point”, exhibit a strong spectral response to perturbations. Due to the enhanced sensitivity of exceptional points, they have been usually suggested as perfect candidates for high resolution sensing. The drawback of these configurations is their undesired sensitivity also to external fluctuations and noise that could eliminate the advantages of exceptional points. Recently, the concept of exceptional surface has been proposed to overcome this problem. In particular, coupling two counterpropagating modes in the same structure prevents differential noise in distinct cavities from affecting the exceptional-point condition. In this work we present a new configuration based on exceptional surfaces to design an optical accelerometer. The strong spectral response guaranteed by exceptional surfaces is used here to demonstrate the enhancement of the sensitivity of a Bragg grating-based optical accelerometer, reaching a value of 3 nm/g at 0.5 g.

We propose an innovative optomechanical device, exploiting the force enhancement due to a quasi-PT symmetry in resonant coupled optical cavities. In order to perform the study, we develop a generalized modeling of the response theory of optical forces, including the loss and the gain effects in optical systems. The enhancement of optical force appears to be limited only by non-linearity and by the resolution of the gain/loss mechanism.

11575 Background: To further explore the activity of T as second/further line treatment in retroperitoneal leiomyosarcoma (LMS) and well differentiated/dedifferentiated liposarcoma (LPS). The primary endpoint of the study was the growth modulation rate (GMR) defined as the ratio between the time to progression under T (TTP) and during previous chemotherapy treatment (TTP-1). The secondary end-points were objective response rate as per RECIST and PFS. Methods: This was a multicenter, single-arm Phase 2 study, conducted in 20 Italian centers. Patients with locally relapsed or metastatic disease, already treated with one or more previous systemic treatments with anthracyclines and/or ifosfamide, were enrolled. T was administered at a dose of 1.3-1.5 mg/mq with a top dose of 2.6 mg per cycle. T was administered as a 24h continuous infusion until progressive disease, major toxicity, patient’s intolerance or medical decision. As per protocol, patients were considered responders if the GMR was > 1.33, non-responders if < 0.75 and neither if 0.76-1.32. Eighty evaluable patients were needed to detect an odds of trabectedin response ≥ 2.5, corresponding to 71.4% of patients with a GMR > 1.33 (80% power, one-sided alpha 2.5%). Results: From August 2014 to February 2019, 104 patients were registered and 91 were evaluable for the primary endpoint (32 pts with LMS and 59 with LPS). Overall, the median number of cycles received was 6.0 (q1-q3 3.0-12.0), the main reason for treatment discontinuation was disease progression in 72% of patients, followed by medical decision (8%). The median TTP was 6.0 months (6.2 and 6.0 for LMS and LPS), while the median TTP-1 was 7.5 months (8.1 and 6.4 for LMS and LPS). Thirty three patients (52% 95%CI: 36-58, p = 0.674, odds of response = 1.1) had a GMR > 1.33 (LMS: 46%, 95%CI 26-67,odds = 0.85; LPS 56%, 95%CI 40-72, odds = 1.3).Overall, response rate (CR+PR) was 16% (24% for LMS and 12% for LPS). Overall, in LPS we observed 15/47 patients with GMR < 0.5 and 15/47 with GMR > 2. Among LMS patients, 9/26 had a GMR < 0.5 and 10/26 > 2. Between LPS six patients had a GMR > 5. Previous treatment had been based on anthracyclines and/or ifosfamide in 85% of patients (91% in LPS population). Conclusions: While the primary end point of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with T in comparison to previous therapy (GMR < 0.5 or > 2, the latter including some pts with a long TTP with T). Efforts are ongoing to assess the pathologic counterparts of such discrepancies. T seems to be selectively active in poorly understood subgroups, with a pattern of activity distinct from other available agents. Clinical trial information: 2012-005428-14.

The U.S. Department of Justice/Federal Trade Commission Horizontal Merger Guidelines describes the hypothetical monopolist test (HMT) and significant and nontransitory increase in price (SSNIP) as tools to define antitrust markets. However, the discussion leaves some ambiguities with regards to the implementation of such tools. In this article, we present a methodology for quantitatively delineating geographic markets that is consistent with the Guidelines. In particular, for geographic markets that are based on the locations of customers, the market boundaries encompass the region into which sales are made from the merging parties’ plants, and competitors in the market are firms that sell to customers in the specified region. We use two approaches to identify the competitive reach of a plant—one based on actual shipping distances, which reflect the areas where the plant actually sells; and the other based on distances at which the plant’s product can be shipped profitably, which reflect all areas where the plant can potentially compete for customers. These distances are used to “draw circles” around plants to identify areas where one merging party plant’s competitive reach overlaps with the reach of another plant belonging to the merging partner, thus identifying the overlap customers. For each identified overlap customer area, the HMT is implemented using the critical loss analysis following a SSNIP by the hypothetical monopolist. We explain how to calculate the critical loss as well as the likely actual loss from the SSNIP.

Parity-time-symmetric optical gyroscopes are gaining interest for the enhanced sensitivity shown by exceptional points. The real splitting of anti-PT-symmetric gyroscopes is more reliable for stability and readout scheme than the complex splitting of parity-time-symmetric gyroscopes.

Anti-parity-time induced by Four Wave Mixing is theoretically demonstrated and numerically evaluated in a Silicon Nitride integrated platform. The existence of the exceptional point which separates a broken and an unbroken anti-PT-symmetric phases can be exploited for sensing applications.

Quartz enhanced photo acoustic spectroscopy (QEPAS) has gained a growing interest in recent years for gas sensing technology because of the high sensitivity provided by sharp resonant tuning forks (QTFs) exploited as piezoelectric sound wave detectors; and the modularity, compactness, and robustness of the sensors. The currently used experimental configurations of the QEPAS sensors still rely on free space optics, which are potentially subject to misalignment and require a relatively high space occupation. Here we propose the modelling and the design of a QEPAS sensor with the laser source and optical components for beam delivery bonded together and semi-integrated with the tuning fork. In particular, we propose a configuration in which an optical resonator placed between the prongs of the QTF is coupled with the laser source through a waveguide (OMRSI-QEPAS). For this setup design, COMSOL simulations provided pressure values of the acoustic wavefront comparable with the standard on-beam configuration employing acoustic resonator tubes. Therefore, the design here proposed aims to package the opto-acoustic core of a QEPAS sensor in a single module of few cubic centimeters to definitively address the misalignment issues and pave the way to a further level of miniaturization, integration and deployment for application like mobile and on-drone sensing.

IN03106 Poḷonnaruva Laṅkātilaka Guard-Stone Inscription of Vijaya-Bāhu IV - Transcript and Translation Source: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 42. (Reg. No. 3.) Kantaläi Gal-Āsana Inscription of Kitti Nissaṅka-Malla (1187–1196 A.D.),’ Epigraphia Zeylanica 2, pp. 283-290.

IN03105 Kantaläi Gal-Āsana Inscription of Kitti Nissaṅka-Malla - Transcript and Translation Source: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 42. (Reg. No. 3.) Kantaläi Gal-Āsana Inscription of Kitti Nissaṅka-Malla (1187–1196 A.D.),’ Epigraphia Zeylanica 2, pp. 283-290.

IN03104 Poḷonnaruva Gal-Vihāra Rock Inscription of Parakkama-Bāhu I - Transcript and Translation Source: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 41. (Reg. No. 278.) Poḷonnaruva, Gal-Vihāra: Rock-Inscription of Parakkama-Bāhu I (1153–1186 A.D.),’ Epigraphia Zeylanica 2, pp. 256-283.

Diagram of the Kantaläi gal-āsana. Published in: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 42. (Reg. No. 3.) Kantaläi Gal-Āsana Inscription of Kitti Nissaṅka-Malla (1187–1196 A.D.),’ Epigraphia Zeylanica 2, p. 283.

IN03103 Poḷonnaruva Slab Inscription of the Vēḷäikkāṟas - Transcript and Translation Source: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 40. (Reg. No. 2.) Poḷonnaruva: Slab-Inscription of the Vēḷäikkāṟas (circa 1138–1153 A.D.),’ Epigraphia Zeylanica 2, pp. 242-255.

IN03101 Poḷonnaruva Ānaulundāva Slab Inscription - Transcript and Translation Source: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 38. Poḷonnaruva: Ānaulundāva Slab-Inscription,’ Epigraphia Zeylanica 2, pp. 235-237.

IN03102 Poḷonnaruva Pot-Gul Vehera Inscription - Transcript and Translation Source: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 39. Poḷonnaruva: Pot-Gul Vehera Inscription,’ Epigraphia Zeylanica 2, pp. 238-241.

IN03100 Alutväva Pillar Inscription - Transcript and Translation Source: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 37. Alutväva Pillar-Inscription,’ Epigraphia Zeylanica 2, pp. 229-235.

IN03099 Poḷonnaruva Slab Inscription of Sāhasa-Malla - Transcript and Translation Source: Wickremasinghe, Don Martino de Zilva. (1912-27). ‘No. 36. Poḷonnaruva: Slab-Inscription of Sāhasa-Malla,’ Epigraphia Zeylanica 2, pp. 219-229.