BackgroundThere is no standard neoadjuvant therapy for locally advanced esophageal cancer in China. The role of neoadjuvant chemotherapy plus immunotherapy for locally advanced esophageal cancer is still being explored.MethodsThis open-label, randomized phase II study was conducted at a single center between July 2019 and September 2020; 30 patients with locally advanced esophageal squamous cell carcinoma (ESCC) (T3, T4, or lymph-node positive) were enrolled. Patients were randomized according to the enrollment order at a 1:1 ratio to receive chemotherapy on day 1 and toripalimab on day 3 (experimental group) or chemotherapy and toripalimab on day 1 (control group). The chemotherapeutic regimen was paclitaxel and cisplatin. Surgery was performed 4 to 6 weeks after the second cycle of chemoimmunotherapy. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoint was safety and disease-free survival.ResultsThirty patients completed at least one cycle of chemoimmunotherapy; 11 in the experimental group and 13 in the control group received surgery. R0 resection was performed in all these 24 patients. Four patients (36%) in the experimental group and one (7%) in the control group achieved pCR. The experimental group showed a statistically non-significant higher pCR rate (p = 0.079). PD-L1 combined positive score (CPS) examination was performed in 14 patients; one in the control group had a PD-L1 CPS of 10, and pCR was achieved; the remaining 13 all had ≤1, and 11 of the 13 patients received surgery in which two (in the experimental group) achieved pCR. Two patients endured ≥grade 3 adverse events, and one suffered from grade 3 immune-related enteritis after one cycle of chemoimmunotherapy and dropped off the study. Another patient died from severe pulmonary infection and troponin elevation after surgery.ConclusionsAlthough the primary endpoint was not met, the initial results of this study showed that delaying toripalimab to day 3 in chemoimmunotherapy might achieve a higher pCR rate than that on the same day, and further large-sample clinical trials are needed to verify this.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT 03985670.
Current web search engines focus on searching only the most recent snapshot of the web. In some cases, however, it would be desirable to search over collections that include many different crawls and versions of each page. One important example of such a collection is the Internet Archive, though there are many others. Since the data size of such an archive is multiple times that of a single snapshot, this presents us with significant performance challenges. Current engines use various techniques for index compression and optimized query execution, but these techniques do not exploit the significant similarities between different versions of a page, or between different pages.In this paper, we propose a general framework for indexing and query processing of archival collections and, more generally, any collections with a sufficient amount of redundancy. Our approach results in significant reductions in index size and query processing costs on such collections, and it is orthogonal to and can be combined with the existing techniques. It also supports highly efficient updates, both locally and over a network. Within this framework, we describe and evaluate different implementations that trade off index size versus CPU cost and other factors, and discuss applications ranging from archival web search to local search of web sites, email archives, or file systems. We present experimental results based on search engine query log and a large collection consisting of multiple crawls.
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