e20530 Background: SMLPs are detected more commonly due to advancements in screening technology. Their workup and classification; however, are still lacking a clear standard. T stage of the largest lesion has been used as the major prognostic marker. This; however, does not take the number of SMLPs and their genomic drivers into consideration. This study aims to identify and review common risk factors associated with SMLPs and determine whether the number of primaries influence the prognosis. Methods: A systematic review of the literature published between 2000 and 2021 was conducted through PubMed and Medline by using the combination of keywords, including: “synchronous multiple primary lung cancer”, “simultaneous multifocal lung cancer”, “synchronous solitary lung metastasis”, “risk factor” and “prognosis”. A total of fifty studies were identified, among them only sixteen retrospective research articles and two review articles were relevant to the study at hand. Results: Sixteen retrospective studies including a total of 1685 eligible patients were reviewed. Thirteen of these studies reported the main histology type to be adenocarcinoma with a ratio ranging from 35% to 96.8%. Eight studies have reported the numbers of synchronous primary lung cancers, including one study found 11 SMLPs. Among these, one study by van Rens found number of SMLPs impact prognosis adversely compared to a single lung cancer. However, three other studies demonstrated multiple SMPLs do not adversely affect survival (Finley et al, 2010; Kocaturk et al, 2011; Li et al, 2020). Four of the sixteen studies analysed the effect of multiple lobes involvement and distance between tumors, with varying conclusions; two studies reported no difference in prognosis while one study revealed worse survival with multiple lobe involvement and one study found favorable outcome. Most studies confirm the usual prognostic factors for SMLPs, including: gender, smoking, type of surgery, comorbidities and adjuvant therapy. The median 5 year OS reported for SMLPs is 66%, with a wide range from 19% to 95.8%.The 3 year OS is 75% in most studies. Conclusions: The data on how the number of SMLPs affects the prognosis is uncertain. The current recommendation to base the decision for adjuvant therapy on the highest T stage is not supported by prospective evidence or consistent among published case series. Considering the recent approval of targeted therapies in early stage lung cancers, a better prognostic scoring system for SMLPs is required.
e16003 Background: Genomic instability from 20q amplification is an oncogenic pathway in colorectal cancer (CRC). Several genes have been implicated, including BCL2L1, AURKA, SRC, ASXL1, GNAS and TOP1. There is a lack of data regarding 20q amplified group and one study implicating these genes suggested these patients have better overall survival. Next Generation Sequencing (NGS) has become widely used in metastatic CRC (mCRC) and easily identifies patients with 20q amplification. Nevertheless, most oncologists do not routinely consider 20q amplification status and this subgroup remains underinvestigated. This study aims to investigate genomic and clinical characteristics of 20q amplified mCRC using a single-center retrospective cohort and a multi-center genomic dataset. Methods: A cohort was identified comprising patients with mCRC who had NGS testing of tumor DNA and were treated between 2014-2019. Cases with and without 20q amplification were identified. Genomic, clinical and survival data were analyzed. Significant genomic findings were compared with all-stage CRC data using the AACR Genomic Evidence Neoplasia Information Exchange (GENIE) and The Cancer Genome Atlas (TCGA) databases. Results: Of the mCRC cohort ( n= 72), 15% ( n= 11) had 20q amplification. Amplified and non-amplified groups had no significant differences in age, sex or follow-up time. Patients with 20q amplification were more likely to have never smoked, and less likely to have treatment with targeted therapy. Survival analysis showed clear separation with longer overall survival for the amplified group. Eight genes at loci 20q11 to 20q13 were amplified - in order of frequency: ASXL1, GNAS, ARFRP1, ZNF217, AURKA, BCL2L1, SRC and TOP1. 20q amplification was significantly associated with wild-type RAS and BRAF, microsatellite stability, mutant TP53 and mutant APC. Using the GENIE and TCGA databases, it was found that metastatic disease had increased prevalence of all 20q amplified genes except TOP1, when compared to all-stage CRC. Conclusions: Clinical use of NGS identifies the 20q amplification subgroup that has increased prevalence in mCRC (compared to all CRC). Compared to non-20q amplified mCRC, this group had better survival, suggesting genomic pattern in mCRC is a novel independent prognostic marker. We believe mCRC patients would benefit from further studies defining a genomic prognostication model and development of therapy targeting the 20q amplification pathway.
e16266 Background: Malignant biliary obstruction (MBO) is commonly associated with pancreaticobiliary cancers (PBCa). It increases the risk for cholangitis, hepatic failure, and deconditioning, which delays systemic therapy. This study aims to identify predictors associated with MBO outcomes after biliary decompression. Methods: This single-center, retrospective study analyzed patients with MBO from 2016-2020 who underwent biliary drainage. Patient demographics, cancer history, intervention type, and date of last follow up were obtained. Descriptive statistics were used to summarize relevant variables. Baseline characteristics were compared using Chi squared tests. Kruskal Wallis test was used to identify whether there were significant difference among multiple groups. Results: Of the 59 patients included, mean age was 62 years and 75% had PBCa. Baseline characteristics were presented in Table. The mean survival time from MBO diagnosis was 227 days (range: 16-1446). Overall, 39% survived at the end of 6 months follow up. Of the 29 patients who received chemotherapy after decompression, they were younger (57 vs 66 years old, p = 0.004). History of prior chemotherapy was significantly associated with increased 180-day mortality (OR 0.75, CI 0.58-0.97, p = 0.033). There were no differences based on sex, race, primary cancer, stage, intervention type or bilirubin levels in chemotherapy initiation or 6-month survival. In those with MBO as initial presentation of cancer, they were older, had pancreatic or biliary cancer, non-metastatic disease, unresected primary tumors, treatment-naïve, and no survival difference compared to later MBO presentation. Conclusions: Diagnosis of MBO is significantly associated with mortality (61% at 6-months) in our patient population, similar to historical controls of 40-60%. This data suggests that younger patients and those treatment naïve were associated with receipt of subsequent therapy and better 6-month survival, respectively.[Table: see text]
TPS235 Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker for non-invasive longitudinal monitoring of tumor progression in cancer management. Through the recent advances in next generation sequencing (NGS) technologies and personalized assays, ctDNA has been heralded as a promising tool to detect residual disease, relapse, and monitor treatment response in hematologic malignancies and solid tumors. Our study aims to determine whether treatment related ctDNA dynamics can be used as a reliable indicator to predict pathologic complete response (pCR) in patients with rectal cancer receiving neoadjuvant treatment. Methods: This is a prospective observational cohort study. The primary aim is to estimate the sensitivity and specificity of ctDNA clearance in predicting pCR in patients undergoing neoadjuvant therapy. The secondary aim is to evaluate the feasibility of using ctDNA as a surveillance method to detect progression of rectal cancer during neoadjuvant therapy and relapse in the subsequent follow up period. ctDNA levels are collected from newly diagnosed rectal cancer patients at 7 discrete time points: at diagnosis or screening, during neoadjuvant therapy, after completion of neoadjuvant therapy and 1 month, 2 months, 4 months, 6 months after surgery. This will be followed by every 3 months ctDNA testing for surveillance for up to 2 years. We expect to enroll approximately 30 patients at our institution. The subjects will be sorted into two groups: responders and non-responders based on whether they achieve pCR. ctDNA level between two groups will subsequently be compared. The use of ctDNA to predict pCR in rectal cancer patients may allow for many of these patients to safely avoid surgery if undetectable ctDNA at the end of neoadjuvant therapy strongly correlates with pCR. We are actively enrolling patients into this prospective observational study and expect to report the data in the near future. The data we obtain will be combined with those from several institutions around the US doing similar studies with the same test. Data analysis will subsequently be conducted. [Table: see text]
Pancreatic cancer is a highly lethal malignancy and one of the leading causes of cancer-related death. During the development and progression of cancer, tumor angiogenesis plays a crucial role. A great deal of evidence has revealed that human mast cells (MCs) contributed to tumor angiogenesis through releasing several pro-angiogenetic factors, among which tryptase is one of the most active. However, the role of mast cell tryptase (MCT) in human pancreatic cancer angiogenesis is still not well documented. In this study, we examined the MCT levels in serum from pancreatic cancer patients and evaluated the correlationship of the MCT level and tumor angiogenesis. In addition, the effect of MCT on endothelial cell proliferation and tube formation was investigated both in vitro and in nude mice bearing pancreatic tumor. It was found that MCT contributes to endothelial cell growth and tube formation via up-regulation of angiopoietin-1 expression. Moreover, using the MCT inhibitor nafamostat, tryptase-induced angiogenesis was obviously suppressed both in vitro and in vivo. Our findings suggest that MCT plays an important role in pancreatic cancer angiogenesis and tumor growth via activating the angiopoietin-1 pathway, and tryptase inhibitors may be evaluated as an effective anti-angiogenetic approach in pancreatic cancer therapy.
This paper tries to conduct a comprehensive evaluation of higher education in China. Although there are many factors affecting the quality of the higher education, this paper attempts to explain the condition in a simple way. We use the students' individual abilities, students' grades, and the employment rate as the standards to judge the quality of higher education. We found out the factors that influence higher education. At last we carry out some structural advice to improve the higher education quality.
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