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      Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2)

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          Abstract

          This randomized, open-label, multi-center phase 2 study (NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemotherapy in patients with esophageal squamous cell carcinoma after first-line chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with efficacy. The median OS in the sintilimab group was significantly improved compared with the chemotherapy group (median OS 7.2 vs.6.2 months; P = 0.032; HR = 0.70; 95% CI, 0.50–0.97). Incidence of treatment-related adverse events of grade 3–5 was lower with sintilimab than with chemotherapy (20.2 vs. 39.1%). Patients with high T-cell receptor (TCR) clonality and low molecular tumor burden index (mTBI) showed the longest median OS (15.0 months). Patients with NLR < 3 at 6 weeks post-treatment had a significantly prolonged median OS (16.6 months) compared with NLR ≥ 3. The results demonstrate a significant improvement in OS of sintilimab compared to chemotherapy as second-line treatment for advanced or metastatic ESCC.

          Abstract

          Patients with advanced esophageal cancer have poor prognosis and limited treatment options. This randomized, phase II trial compares the efficacy and safety of the anti-PD-1 antibody sintilimab versus chemotherapy in Chinese patients with esophageal squamous cell carcinoma after first-line therapy

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Trimmomatic: a flexible trimmer for Illumina sequence data

            Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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              STAR: ultrafast universal RNA-seq aligner.

              Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.
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                Author and article information

                Contributors
                jmxu2003@yahoo.com
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                14 February 2022
                14 February 2022
                2022
                : 13
                : 857
                Affiliations
                [1 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Gastrointestinal Oncology, The Fifth Medical Center, , Chinese PLA General Hospital, ; Beijing, China
                [2 ]GRID grid.412633.1, ISNI 0000 0004 1799 0733, Department of Oncology, , The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, China
                [3 ]GRID grid.412676.0, ISNI 0000 0004 1799 0784, Department of Oncology, , The First Affiliated Hospital of Nanjing Medical University, ; Nanjing, China
                [4 ]GRID grid.410730.1, ISNI 0000 0004 1799 4363, Department of Radiotherapy, , Nantong Tumor Hospital, ; Nantong, China
                [5 ]GRID grid.415108.9, ISNI 0000 0004 1757 9178, Department of Medical Oncology, , Fujian Provincial Hospital, ; Fuzhou, China
                [6 ]GRID grid.412679.f, ISNI 0000 0004 1771 3402, Department of Oncology, , The First Affiliated Hospital of Anhui Medical University, ; Hefei, China
                [7 ]GRID grid.429222.d, ISNI 0000 0004 1798 0228, Department of Oncology, , The First Affiliated Hospital of Soochow University, ; Suzhou, China
                [8 ]GRID grid.452402.5, ISNI 0000 0004 1808 3430, Department of Chemotherapy, , Qilu Hospital of Shandong University, ; Jinan, China
                [9 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Department of Medical Oncology, Cancer Hospital, , Chinese Academy of Medical Sciences and Peking Union Medical College, ; Beijing, China
                [10 ]GRID grid.452661.2, ISNI 0000 0004 1803 6319, Department of Medical Oncology, , The First Affiliated Hospital of Zhejiang University, ; Hangzhou, China
                [11 ]GRID grid.452438.c, ISNI 0000 0004 1760 8119, Department of Medical Oncology, , The First Affiliated Hospital of Xi’an Jiaotong University, ; Xi’an, China
                [12 ]GRID grid.414008.9, ISNI 0000 0004 1799 4638, Department of Immunotherapy, , Henan Cancer Hospital, ; Zhengzhou, China
                [13 ]GRID grid.412636.4, ISNI 0000 0004 1757 9485, Department of Oncology, , The First Hospital of China Medical University, ; Shenyang, China
                [14 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Cancer Center, , Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, ; Wuhan, China
                [15 ]GRID grid.412651.5, ISNI 0000 0004 1808 3502, Department of Gastrointestinal Oncology, , Harbin Medical University Cancer Hospital, ; Harbin, China
                [16 ]GRID grid.430605.4, ISNI 0000 0004 1758 4110, Cancer Center, , The First Hospital of Jilin University, ; Changchun, China
                [17 ]GRID grid.417397.f, ISNI 0000 0004 1808 0985, Department of Thoracic Oncology, , Zhejiang Cancer Hospital, ; Hangzhou, China
                [18 ]GRID grid.414252.4, ISNI 0000 0004 1761 8894, Department of Oncology, , Chinese People’s Liberation Army General Hospital, ; Beijing, China
                [19 ]GRID grid.413405.7, ISNI 0000 0004 1808 0686, Department of Gastrointestinal Oncology, , Guangdong Provincial People’s Hospital, ; Guangzhou, China
                [20 ]GRID grid.459742.9, ISNI 0000 0004 1798 5889, Department of Gastroenterology, , Liaoning Cancer Hospital, ; Shenyang, China
                [21 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Department of Medical Oncology, Peking Union Medical College Hospital, , Chinese Academy of Medical Sciences, ; Beijing, China
                [22 ]Department of Thoracic Surgery I, Yunnan Cancer Hospital, Kunming, China
                [23 ]GRID grid.284723.8, ISNI 0000 0000 8877 7471, Department of Oncology, Nanfang Hospital, , Southern Medical University, ; Guangzhou, China
                [24 ]GRID grid.410622.3, ISNI 0000 0004 1758 2377, Departmentof Thoracic Medical Oncology, , Hunan Cancer Hospital, ; Changsha, China
                [25 ]Department of Oncology, No. 900 Hospital of The Joint Logistic Support Force, Fuzhou, China
                [26 ]GRID grid.461867.a, ISNI 0000 0004 1765 2646, Department of Gastrointestinal Oncology, , Gansu Provincial Cancer Hospital, ; Lanzhou, China
                [27 ]GRID grid.452252.6, ISNI 0000 0004 8342 692X, Department of Oncology, , Affiliated Hospital of Jining Medical University, ; Jining, China
                [28 ]Innovent Biologics, Inc., Suzhou, China
                Author information
                http://orcid.org/0000-0003-4467-6021
                http://orcid.org/0000-0002-1364-8442
                Article
                28408
                10.1038/s41467-022-28408-3
                8844279
                35165274
                a18600fe-9f28-480d-9d81-040e67ea48bd
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 April 2021
                : 17 January 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 82072613
                Award Recipient :
                Funded by: This study was supported by Innovent Biologics, Inc., and co-funded by Eli Lilly and Company.
                Categories
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                © The Author(s) 2022

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                oesophageal cancer
                Uncategorized
                oesophageal cancer

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