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Purpose: We investigated the safety and efficacy profile of intensity-modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, cisplatin (GDP), plus chidamide in the first-line setting for intermediate- and high-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL).Methods: This was an open-label, randomized phase 2 trial performed at 2 centers in China. Patients were eligible if they were newly-diagnosed with intermediate- and high-risk early-stage ENKTCL with at least one risk factor based on a nomogram-revised risk index: >60 years old, elevated serum lactate dehydrogenase, invasion of the primary tumor, stage II or Eastern Cooperative Oncology Group performance status >1 or stage II disease. Patients were treated with IMRT followed by GDP, with or without chidamide, in the first-line setting. Two-year progression-free survival (PFS) comprised the primary endpoint. Toxicities, the 2-year overall survival (OS), and the response rate comprised the secondary endpoints.Results: Eligible patients (N = 74) were enrolled between May 2015 and December 2019. Among them, 37 patients were treated with IMRT + GDP + chidamide (chidamide group), whereas 37 cases were treated with IMRT + GDP (control group). Follow-up comprised a median of 43.4 months (range, 1.0-74.6 months). The objective response rate was 86.5% in the chidamide group and 78.4% in the control group (P = .359) at the end of treatment completion. The 2 year OS and PFS rates were 89.2% and 75.2% in the chidamide group versus 83.8% (P = .388) and 70.2% (P = .821) in the control group. The main adverse events were hematological toxicities and mucositis, with similar rates in the 2 groups (P > .05).Conclusions: The addition of chidamide to IMRT + GDP as first-line treatment achieved similar treatment outcomes and tolerable toxicities compared with IMRT + GDP in patients with intermediate- and high-risk early-stage ENKTCL. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Dongguashan porphyry-skarn-stratabound deposit were formed in Early Cretaceous magmatic-hydrothermal system. • Pyrite Re-Os dating yielded ages of 135.8 ± 2.8 Ma, which provide constraints on the mineralization of stratabound orebodies. • Formation mechanism and hydrothermal fluids for Dongguashan pyrite were constrained. Stratabound deposits are widely distributed along the Middle-Lower Yangtze River metallogenic belt (Eastern China). The stratabound mineralization system in these stratabound deposits remains enigmatic as to whether it is associated with late Mesozoic intrusions or late Carboniferous sedimentary exhalative processes. Dongguashan is a typical stratabound deposit and is characterized by pyrite that formed in porphyry-skarn-stratabound orebodies, which makes it ideal for comparing porphyry, skarn, and stratabound mineralization systems by pyrite study. We classify pyrite types according to occurrence and generation. Specifically, the pyrite in the porphyry orebodies is composed of Py-p1 (potassic zone) and Py-p2 (propylitic and phyllic zone). Py-s, among garnet grains, occurs in the skarn orebodies. From top to bottom, the pyrite in the stratabound orebodies is composed of macrocrystalline pyrite (Py-m) in the massive mineralization zone, Py-l in the laminated mineralization zone, and coarse-grained pyrite (Py-v1) and microcrystalline pyrite (Py-v2) in the vein-like mineralization zone. Co, Ni, Se, As, and Au are most likely to occur as solid solutions in the Dongguashan pyrite. Pb and Bi are likely distributed in Dongguashan pyrite homogeneously as nanoinclusions. The Zn, Cu, and Mo in Dongguashan pyrite indicate that these elements occur as micromineral inclusions. The positive correlation between S and Fe, high Co/Ni ratios (mostly > 2), and coexistence with hydrothermal minerals imply a magmatic-hydrothermal origin for the Dongguashan pyrite. Py-m yields a Re–Os isochron age of 135.8 ± 2.8 Ma (MSWD = 1.8), which is interpreted as the stratabound ore-forming age. Combined with previous results, the porphyry-skarn-stratabound mineralization is the product of the same hydrothermal fluid system related to Early Cretaceous magmatic activity. [ABSTRACT FROM AUTHOR]

• The Dongguashan mineralization may have formed from magmatic-hydrothermal fluids. • Garnet LA-ICP-MS U-Pb dating yielded ages of 135.9 ± 2.1 Ma, 135.6 ± 2.2 Ma, and 134.6 ± 1.4 Ma, which provide constraints on the alteration initiation. • Physicochemical conditions of hydrothermal fluids for Dongguashan garnet were constrained. Dongguashan is one of the largest Cu-Au deposits in eastern China, with ubiquitous garnet in the stratiform and skarn orebodies. The stratiform ore-formation remains enigmatic. In this study, we describe the diverse textures and present new U-Pb age and chemical data for the Dongguashan garnet. Garnet in the skarn orebody can be divided into three generations (Grt-1, Grt-2, and Grt-3). Grt-1 and Grt-2 show three zones from core to inner rim to outer rim (a-b-c). Garnet in the stratiform orebody is homogeneous (Grt-s). All garnet types have low MnO, a wide range of Y/Ho ratios, and visible fluid inclusions, indicating that they formed from hydrothermal replacement. Grt-1a, Grt-1b, Grt-2a, Grt-2c, and Grt-3 are oscillatory-zoned, low-Sn, and HREE-rich grandite, which may have formed from reduced HREE-rich fluids. Meanwhile, Grt-1c and Grt-2b are high-Sn, LREE-rich andradite, and may have formed from oxidized LREE-rich fluids. Grt-s is pure, low-Sn, LREE-rich andradite, and that may have formed from oxidized LREE-rich fluids. The Eu behaviors are sensitive to the fluid physicochemical conditions and Cl content. Grt-1, Grt-2, and Grt-s have positive Eu anomalies, and may have formed from acidic and Cl-rich fluids. Grt-3 has negative Eu anomalies and was possibly formed from neutral and Cl-poor fluids. All garnet types at Dongguashan may have formed by infiltration metasomatism in an open system with multiple metasomatic pulses. Grt-1, Grt-2, and Grt-s yielded nearly the same in-situ U-Pb ages of 135.9 ± 2.1 Ma, 135.6 ± 2.2 Ma, and 134.6 ± 1.4 Ma, respectively. We propose that both ore types at Dongguashan deposit are closely related to the Early Cretaceous plutonism. [ABSTRACT FROM AUTHOR]