A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma.

BACKGROUND: Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. METHODS: In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1-14, 135 mg/m2 intravenous paclitaxel on day 1, and 60-75 mg/m2 intravenous cisplatin on days 1-3 every 3 weeks for a maximum of 4-6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30-19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2-87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2-97.6%). The median duration of response was 6.80 months (95% CI, 4.52-9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002-0.606; P = 0.022). CONCLUSIONS: The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04063683. Registered 21 August 2019.

[Root architecture and fine root characteristics of Juglans mandshurica saplings in different habitats in the secondary forest on the west slope of Zhangguangcailing, China]. / å¼ å¹¿æ‰å²­è¥¿å¡æ¬¡ç”Ÿæž—ä¸åŒç”Ÿå¢ƒèƒ¡æ¡ƒæ¥¸å¹¼æ ‘æ ¹ç³»æž„åž‹åŠç»†æ ¹ç‰¹å¾.

The whole root excavation method was used to examine root configuration of Juglans mandshurica, with the age of 5-6 years in three habitats (forest edge, gap, and canopy) in a secondary forest on the western part of Zhangguangcailing Mountains. Root structure and fine root function were measured. The root topological index, average joint length, cross-sectional area ratio before and after root branching were calculated and fine root chemical compositions were analyzed. Roots of J. mandshurica at forest edge tended to be dichotomous branch (Topological index:TI=0.68), that under the canopy were herringbone-like branch (TI=0.79), and the gap was between the two (TI=0.72). The average connection length of roots among the three habitats was not significant. The cross-sectional area ratio of roots before and after root branching in three habitats was 1.06, 1.04 and 1.07, respectively, which was not affected by root diameter, in accordance with the Leonardo da Vinci rule. For the same order fine root in different habitats, its length and specific surface area gradually increased from the edge of the forest to the canopy. The N content decreased first and then increased, while the C content and C/N increased first and then decreased. From the forest edge to the gap and to the under canopy, roots tended to move from the dichotomous branch to the herringbone-like branch by reducing the overlap between the secondary branches and roots, increasing specific root length, specific surface area and changing the contents of C and N to cope with environmental change and improve nutrient absorption efficiency.

[Soil denitrification rates in different type riparian zones in maoershan mountainous region of China].

Soil samples were collected from forested, clear-cut, and grassy riparian zones under forest background and from forested and barren riparian zones under cropland background in the Maoershan mountainous region of China. The samples were incubated in laboratory, and their denitrification potentials were determined by nitrate-deduction method. The results showed that under crop-land background, soil denitrification rate was the highest in forested riparian zone and the lowest in barren riparian zone, with the deduction rate of nitrate varied from 46.79%-91.13% and 15.64% -81.84%, respectively. Under forest background, soil denitrification rate decreased in the order of clearcut > forested > grassy riparian zone, with the deduction rate of nitrate being 42.06%-90.39%, 28.24%-85.73% and 21.44%-83.11%, respectively. The denitrification rate was higher in subsurface layer than in deeper layer, and the denitrification potential was limited by the available carbon and nitrate, being the greatest in the forested riparian zone under cropland background.

[Lymphatic metastasis intensity of and lymphadenectomy for thoracic esophageal squamous cell carcinoma].

BACKGROUND & OBJECTIVE: The intensity of lymphatic metastasis consists of lymph node metastasis number (LMN) and lymph node metastasis ratio (LMR). LMR is the ratio of positive nodes to dissected nodes. LMN and LMR are 2 important prognostic factors of esophageal cancer, and are adopted in tumor staging. This study was to assess the lymphatic metastasis intensity of thoracic esophageal squamous cell carcinoma (ESCC), and explore the influential factors and lymphadenectomy pattern. METHODS: A total of 120 patients with ESCC had been operated in the Second Affiliated Hospital of Sun Yat-sen University from 1998 to 2000. The lymph nodes were dissected according to the mapping scheme of the American Thoracic Society (ATS) modified by Casson et al. RESULTS: A total of 2 631 lymph nodes were dissected with an average of 22 lymph nodes in each case. The cervical LMR was significantly higher in the upper thoracic ESCC than in the middle and lower thoracic ESCC (20.9% vs. 12.9% and 6.8%, P<0.05). The left gastric LMR was significantly higher in the lower thoracic ESCC than in the middle and upper thoracic ESCC (37.5% vs. 17.5% and 7.1%, P<0.05). Subcarinal metastatic lymph nodes were often found in the middle thoracic ESCC. T stage, histological differentiation, and circum wall involvement degree were correlated to lymphatic metastasis intensity (P<0.05); the length of esophageal lesion had no correlation to lymphatic metastasis intensity (P>0.05). The survival time of the patients received the right thoracic esophagectomy with 3-field lymphadenectomy (3-FL) was significantly longer than that of the patients received the left thoracic esophagectomy with 2-FL (P<0.05). CONCLUSIONS: During the operation on ESCC, the regions with high lymphatic metastasis intensity should be dissected. T stage, histological differentiation, and circum wall involvement degree are important influential factors of lymphatic metastasis intensity. The right thoracic esophagectomy with 3-FL is superior to the left thoracic esophagectomy with 2-FL.