Qin Xu, Yi-Bin Lin, Xian Lin, Jing Liu, Li Li, Peng Zheng, Bin Liu, H. Shi
{"title":"Clinical factors associated with comprehensive genomic variation profiling of cervical cancer.","authors":"Qin Xu, Yi-Bin Lin, Xian Lin, Jing Liu, Li Li, Peng Zheng, Bin Liu, H. Shi","doi":"10.1200/jgo.2019.5.suppl.62","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.62","url":null,"abstract":"62 Background: To better understand the mechanism contributing to cervical carcinogenesis, we perform a comprehensive analysis of genomic alterations in cervical cancer (CC). Methods: We conducted whole-exome sequencing of 43 CCs and established strict integrated workflow of genomic analysis. Correlation analysis was performed to measure the relationships between gene mutations and clinical characteristics of CC patients. Results: Genomic analysis revealed 28 genes frequently mutated in CC including BRD4 (4/43), AXL (4/43), MED12 (4/43), which are undetermined genomic features in CC, and identified recurrent genetic mutations in PIK3CA (16/43), KMT2D (11/43), KMT2C (6/43), FBXW7 (5/43), FAT1 (5/43), ERBB2 (4/43), EP300 (3/43) and NFE2L2 (3/43). Intriguingly, CC patients harbored high frequent mutations in BRCA2 (7/43), but not in BRCA1. The relationship between BRCA2 mutations and clinical factors is yet to be determined. The identified mutations predominately resulted in the dysregulation of the PI3K/AKT/mTOR pathway. Interestingly, we found that AXL mutations were positively correlated with FIGO stage ( P = 0.028), regional lymph node metastasis ( P = 0.011) and distant metastasis ( P = 0.022). KMT2C mutations were positively correlated with FIGO stage ( P = 0.004) and distant metastasis ( P = 0.009). SF3B1 mutations were positively correlated with regional lymph node metastasis ( P = 0.027) and distant metastasis ( P< 0.001). NFE2L2, ERBB2, RAC1, MED12, MET, BAP1, PTPRD and HNF1Amutations were positively correlated with distant metastasis ( P = 0.045, P = 0.004, P = 0.022, P = 0.001, P< 0.001, P< 0.001, P = 0.014, P< 0.001, respectively). POLD1 mutations were positively associated with regional lymph node metastasis ( P = 0.029). However, NOTCH1 mutations were negatively associated with regional lymph node metastasis ( P = 0.047). STK11 mutations were negatively associated with FIGO stage ( P = 0.013). Conclusions: Our results highlight the application of deep sequencing for understanding the molecular mechanisms and uncovering potential diagnostic and therapeutic targets of CC.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44581691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive analysis of maintenance therapy after first-line treatment with pemetrexed and platinum-containing double drug regimen combined by bevacizumab in EGFR wild type advanced non-squamous NSCLC.","authors":"Xianghua Zhang, Li-xia Ma, Ying Cheng, H. Cui","doi":"10.1200/jgo.2019.5.suppl.133","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.133","url":null,"abstract":"133 Background: Pemetrexed combined with platinum was the standard treatment for first-line EGFR wild type non-squamous NSCLC , but further research is needed to confirm the safety of pemetrexed and bevacizumab treatment in maintenance therapy after first-line treatment in advenced non-squamous NSCLC. Methods: Total 60 patients with newly diagnosed advanced non-squamous NSCLC admitted to the hospital from June 2015 to June 2017, which were ARMS confirmed the EGFR wild type. In the observation group, bevacizumab +pemetrexed+ platinum was maintained with bevacizumab (BAP-B group). Control group: bevacizumab + pemetrexed + platinum was maintained with pemetrexed (BAP-A group). 60 patients completed 4- 6 cycles of chemotherapy and maintenance therapy for more than 4 cycles. The curative effect was evaluated According to Recis 1.1.The toxic reaction was evaluated WHO chemotherapeutic drug toxicity. The quality of life of patients were evaluated by EORTC QLQ-LC43. All the data were processed by SPSS19.0. P < 0.05 was statistically significant. Results: 33 cases in BAP-B and 27 cases in BAP-A . In this study, BAP-B & BAP-A : ORR 61.0% & 50.0% (P > 0.05);DCR 73.5 & 64.8 % ( P>0.05), median PFS 9.6 m & 7.2 m (P < 0.05), OS:18.2 m & 12.6 m (P < 0.05). Adverse incidence: BAP-B & BAP-A: leukopenia rate 43.0% & 41.2% hemoglobin reduction 40.0% & 38.5%; The reaction rate of digestive tract was 35.3% & 34.5%. There was no significant difference between the two groups. The incidence of hypertension in BAP-B (18.8%) was higher than that in BAP-A (0%) (P < 0.05). The incidence of proteuria in BAP-B (8.8%) was higher than that in BAP-A (2.0%) (P < 0.05), BAP-A and BAP-B (P < 0.05). The quality of life score of EORTC QLQ-C43 was (73.17 ±2.75) & (59.68 ±2.52), which was higher than that before treatment (52.75 ±2.02) & (53.01 ±1.98), and the score of BAP-A was higher than that of BAP-B(P < 0.05). Conclusions: The first line treatment of advanced EGFR wild type non-squamous NSCLC needs comprehensive consideration of curative effect, survival time, safety, quality of life and economic problems in order to choose the most suitable treatment.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48292548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What Filipinos, the world’s number one Internet users, want to know about cancer: A Google search analysis from 2015 to 2019.","authors":"L. Catedral, L. Leones, C. M. Berba","doi":"10.1200/jgo.2019.5.suppl.23","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.23","url":null,"abstract":"23 Background: Filipinos were the world’s heaviest Internet users in 2018. It has been shown that they use the Internet to actively search for health-related information, but it has not yet been determined what kinds of information are sought. There is a gap in our present understanding of the information needs of the Filipino population in relation to cancer. The study assessed the cancer-related information needs of Filipinos using Internet search data from March 2015 to May 2019. Methods: A retrospective longitudinal study was done using Google AdWords Keyword Planner to identify search terms related to cancer from Internet users from the Philippines from June 2015 to May 2019. The identified search terms were assessed descriptively using Microsoft Excel version 16.26. The search terms were qualitatively categorized and described. Results: A total of 806 cancer-related search terms were identified, with 13,632,890 Google web searches, during the period under review. The top ten search terms with the highest monthly search volume in the Philippines (n=4,741,600, 34.78%) were “cancer,” “breast cancer,” “cervical cancer,” “prostate cancer,” “colon cancer,” “breast cancer symptoms,” “lung cancer,” “lung cancer symptoms,” “colon cancer symptoms,” and “lungs.” In this time period, Filipinos sought information on cancer-related signs and symptoms (n=3,307,640, 24.26%) and cancer treatment (n=604,070, 4.43%). Filipinos also searched for alternative, herbal, and natural cancer treatments, but the search volume accounted for a low percentage of the total searches (n=8,710, 0.06%). Searches for the search term, “cancer,” were highest on January to February, a trend observed from January 2016 to 2019. Conclusions: Our study provides insight into the cancer-related information needs of the Filipino population. This information may inform the development of targeted, cost-effective awareness campaigns through the Internet, which may be more effective if launched at the beginning of each year.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42454233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. French, D. Kurbegov, D. Spigel, M. Makowski, Samantha R. Terker, P. Clark
{"title":"Automate incidental findings in radiology reports using natural language processing and machine learning to identify and classify lung nodules.","authors":"C. French, D. Kurbegov, D. Spigel, M. Makowski, Samantha R. Terker, P. Clark","doi":"10.1200/jgo.2019.5.suppl.49","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.49","url":null,"abstract":"49 Background: Pulmonary nodule incidental findings challenge providers to balance resource efficiency and high clinical quality. Incidental findings tend to be under evaluated with studies reporting appropriate follow-up rates as low as 29%. The efficient identification of patients with high risk nodules is foundational to ensuring appropriate follow-up and requires the clinical reading and classification of radiology reports. We tested the feasibility of automating this process with natural language processing (NLP) and machine learning (ML). Methods: In cooperation with Sarah Cannon, the Cancer Institute of HCA Healthcare, we conducted a series of experiments on 8,879 free-text, narrative CT radiology reports. A representative sample of health system ED, IP, and OP reports dated from Dec 2015 - April 2017 were divided into a development set for model training and validation, and a test set to evaluate model performance. A “Nodule Model” was trained to detect the reported presence of a pulmonary nodule and a rules-based “Size Model” was developed to extract the size of the nodule in mms. Reports were bucketed into three prediction groups: ≥ 6 mm, <6 mm, and no size indicated. Nodules were placed in a queue for follow-up if the nodule was predicted ≥ 6 mm, or if the nodule had no size indicated and the report contained the word “mass.” The Fleischner Society Guidelines and clinical review informed these definitions. Results: Precision and recall metrics were calculated for multiple model thresholds. A threshold was selected based on the validation set calculations and a success criterion of 90% queue precision was selected to minimize false positives. On the test dataset, the F1 measure of the entire pipeline was 72.9%, recall was 60.3%, and queue precision was 90.2%, exceeding success criteria. Conclusions: The experiments demonstrate the feasibility of technology to automate the detection and classification of pulmonary nodule incidental findings in radiology reports. This approach promises to improve healthcare quality by increasing the rate of appropriate lung nodule incidental finding follow-up and treatment without excessive labor or risking overutilization.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46212648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhenwei Peng, Shuling Chen, Han Xiao, Yuanqi Wang, M. Kuang
{"title":"Microvascular invasion guiding selection of candidates for combination treatment with sorafenib and TACE for intermediate recurrent hepatocellular carcinoma.","authors":"Zhenwei Peng, Shuling Chen, Han Xiao, Yuanqi Wang, M. Kuang","doi":"10.1200/jgo.2019.5.suppl.105","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.105","url":null,"abstract":"105 Background: To investigate the role of sorafenib combined with transarterial chemoembolization (TACE) for the treatment of intermediate recurrent hepatocellular carcinoma (rHCC) after initial hepatectomy and whether the status of microvascular invasion (MVI) could help screen out the appropriate candidates for the combination treatment. Methods: The study was approved by the ethics committee of two tertiary medical centers in China. From Jan 2010 to Dec 2016, 260 consecutive patients with intermediate rHCC after initial hepatectomy who underwent combination treatment or TACE were enrolled. Overall survival (OS) and progression-free survival (PFS) were compared between these two treatments according to MVI status. Results: The 1-, 3-, 5-year OS (77.1% vs. 62.0%, 49.3% vs. 35.2%, 38.9% vs. 20.5%, P = 0.011) and PFS (74.2% vs. 56.5%, 37.5% vs. 18.7%, 37.5% vs. 18.7%, P = 0.003) rates were significantly higher in the combination group than those in the TACE group for intermediate rHCC. For MVI-positive patients, the median OS (17.2 months vs. 12.1 months, P = 0.024) and PFS (17.0 months vs. 11.0 months, P = 0.022) after combination treatment (n = 55) were significantly longer than those after TACE alone (n = 72). For MVI-negative patients, the median OS (42.7 months vs. 32.6 months, P = 0.247) and PFS (24.6 months vs. 17.2 months, P = 0.113) were comparable between combination therapy (n = 73) and TACE alone (n = 60). Multivariate analysis revealed that tumor number, MVI status and treatment allocation were significant predictors of OS and PFS, while the tumor size was another prognostic factor for PFS. Conclusions: Patients with intermediate rHCC can benefit from sorafenib plus TACE treatment, while MVI-positive patients were good candidates for combination treatment.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46420316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Fleck, R. Preger, L. Venegas, H. D. A. V. Trasel
{"title":"Multidimensional integrative medicine applied to outpatient cancer treatment in southern Brazil: Preliminary cost-effectiveness analysis.","authors":"J. Fleck, R. Preger, L. Venegas, H. D. A. V. Trasel","doi":"10.1200/jgo.2019.5.suppl.5","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.5","url":null,"abstract":"5 Background: Cost-effective analysis as part of cancer treatment decision-making. Methods: We reviewed deaths of 52 metastatic cancer patients treated with multidimensional integrative medicine (MIM) approach. Patients received standard oncologic treatment plus a MIM predefined program of emotional, cognitive and social support. The method included empathy improvement, changes on physician attitude and office environment, modulation of staff behavior supporting patient’s needs and rights, promotion of belongingness, increasing on patient’s protagonism using multimedia interactive narrative and shared decision-making. Patients were categorised according to the tumor site, pathologic, molecular and IHC characteristics, clinical stage and treatment. Observed survival was defined as the time elapsed between the detection of first metastasis and death. The observed survival for each patient was compared with the median expected survival previously reported on prospective randomised trials which had accrued patients with similar prognostic factors based on a best fit model. Treatment monthly cost for each patient was converted in American dollars (USD) on a daily exchange basis. Cost of the treatment periods were compared with those analysed in four large USA commercial managed care plans. Results: Treatment of metastatic cancer patients using MIM showed a 44% increase in median survival and a 48% decrease in cost. The estimated ICER/QALY was of 32304 USD, which represented 2.0 of Brazilian PPP. Conclusions: Despite methodological limitations, this is the first study to indicate a cost-effective survival increase in metastatic cancer patients using a MIM-behavioral modulation model. [Table: see text]","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48205770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Belhadj-Tahar, Jindde Chen, P. Song, Jun Zhao, M. Quan, Caixin Li, Xingjian Gu, Guanghua Yang, Yong Gao
{"title":"Novel CT-guided 188-rhenium brachytherapy device for local primary and secondary lung malignancies.","authors":"H. Belhadj-Tahar, Jindde Chen, P. Song, Jun Zhao, M. Quan, Caixin Li, Xingjian Gu, Guanghua Yang, Yong Gao","doi":"10.1200/jgo.2019.5.suppl.96","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.96","url":null,"abstract":"96 Background: Stereotactic brachytherapy for extensive local tumors offers a very effective treatment option locally without significant complications in medically impaired patients. In this context, we have recently developed a new potential anticancer agent from Poly-L-Lysins dendrimer as a delivery nano system loaded with diffusible Imidazolic probes complexed with 188-Rhenium for targeting in particular hypoxic tumors resistant to conventional cancer treatments. The aim of the study is assessment the safety profile and therapeutic efficacy of anticancer agent derived from [188Re]rhenium-ligand as radioactive ligand loaded 5th generation poly-L-lysine dendrimer in patients with unresectable Lung Malignancies. Methods: The experiment agent “ 188Re-ImDendrim” is consisting of 5th generation poly-L-lysine dendrimer (20 nM) mixed with nitro-imidazole-methyl-1,2,3-triazol-methyl-di-(2-pycolyl) amine at GMP grade and labelled with [188Re]-rhenium. The study was approved by Shanghai East Hospital ethics committee. 5 patients received “188Re-ImDendrim” directly into lung tumors under CT-guidance, at an activity level of 162 MBq/cc of tumor (range 2 to 7 cm; mean diameter, 4 cm) . For voluminous tumors ( > 65 cc) the dose is given in divided injection spaced 2 weeks apart (Tumor of 115cc: 2 administrations, Tumor of 180 cc: 3 administrations). At H0.5, H 4, H24, H36 , H72 post-administration, the patient get a SPECT control. The response to treatment is evaluated thanks to PET/CT Standardized Uptake Values (SUVs). Results: Stereotactic administrations of “188-Rhenium-ImDendrim” were successfully carried out in all patients under local anesthesia. The radioactive product diffuses homogeneously in the tumor volume and remains 72 hours post-administration with no significant diffusion out site of injection. The One of the 5 patients reported discrete transitive hemoptysis as adverse events. All targeted tumors were responding at 12 weeks, with two complete responses. Conclusions: Percutaneous single and iterative administrations of this novel 188-Rhenium-Imdendrim brachytherapy device into lung cancers are safe and well tolerated. The initial data on therapeutic response are promising. Clinical trial information: EC.D (BG) 016.03.1.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41344584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adjuvant nab-paclitaxel plus gemcitabine versus gemcitabine in resected pancreatic ductal adenocarcinoma: A Chinese single institution experience.","authors":"Z. Yin, Rong Liu","doi":"10.1200/jgo.2019.5.suppl.85","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.85","url":null,"abstract":"85 Background: Adjuvant chemotherapy with gemcitabine (GEM) is standard care for resected pancreatic ductal adenocarcinoma (PDAC). Nab-paclitaxel plus gemcitabine (AG) vs gemcitabine (GEM) have shown better survival and tumor response with in advanced or metastatic PDAC. We aimed to determine the efficacy and safety of AG compared with GEM for resected PDAC. Methods: We retrospectively reviewed resectable PDAC patients (pts) who received AG or GEM as adjuvant chemotherapy from January 2013 to December 2016 at the Chinese PLA General Hospital, Bei Jing, China. Pts received nab-paclitaxel (125mg/m2) followed by GEM (1,000 mg/m2) on days 1, 8 every 3 weeks or GEM (1,000 mg/m2) alone on days 1, 8 every 3 weeks for 6 cycles unless disease progression or there was unacceptable level of adverse events. Disease free survival (DFS), overall survival (OS) and toxicity were analyzed. Results: Among 70 pts received AG or GEM as adjuvant chemotherapy, 10 pts were excluded due to the serious complication or R2 resection. The analysis was based on 30 pts in each group undergone complete macroscopic (R0 or R1) resection. Median DFS was 15.8 months (95% CI 13.1-18.5) in AG group (6 pts not arrived) compared with 12.2 months in GEM group (95% CI 9.6-14.8, P = 0.039, 3 pts not arrived). Median OS was 28.3 months (95% CI 21.9-34.6) in AG group (11 pts not arrived) as compared with 20.6 months in GEM group (95% CI 11.2-29.9, P= 0.028, 7 pts not arrived). The 2 years survival rate was 63.3% versus 43.3% in AG group versus GEM group. The most common adverse events of grade 3 or higher were leukopenia (32.3% in AG group vs. 20.7% in GEM group, P= 0.387), neutropenia (45.2% vs.31%, P= 0.298), G-CSF use (41.9% vs. 24.1%, P= 0.177), sensory peripheral neuropathy (51.6% vs. 24.1%, P= 0.036) and fatigue (3.2% vs. 3.4%, P= 0.737). Conclusions: Our results provide the evidence that the adjuvant combination of nab-paclitaxel plus gemcitabine significantly improved DFS and OS of resected PDAC.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43753742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth Ding, Zhilong Zhao, Hongsheng Xue, Jianxin Li, T. Lei, Xuezhen Ma, Jianlin Wu, Qin Huang
{"title":"CancerScreen: A novel ultrasensitive liquid biopsy for early-stage cancer detection by ctDNA Duplex Sequencing and Tissue of Origin identification with supervised machine learning.","authors":"Elizabeth Ding, Zhilong Zhao, Hongsheng Xue, Jianxin Li, T. Lei, Xuezhen Ma, Jianlin Wu, Qin Huang","doi":"10.1200/jgo.2019.5.suppl.60","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.60","url":null,"abstract":"60 Background: Circulating tumor DNA (ctDNA) in blood holds promise as a cancer-specific biomarker for early-stage cancer diagnosis. However, detection of ultra-low mutation allelic frequency (MAF) of ctDNA at early stages of cancer is infeasible by conventional next generation sequencing (NGS). Using duplex sequencing with unique molecular identifiers (UMIs) and custom-designed probes, we tested the hypothesis that ctDNA duplex sequencing with UMIs was able to detect ultra-low MAF of ctDNA in patients with early-stage cancers. Methods: A 128-gene panel that contains probes targeted to clinical relevant genome variations in cancers of the lung, stomach, and esophagus was designed and validated with reference DNA and controls using ctDNA duplex sequencing with UMIs. A data analysis pipeline was implemented withimproved algorithms for variant calling, blood tumor mutational burden (bTMB) calculation, and supervised machine learning for tissue-of-origin primary cancer identification. Results: We designed and validated a ctDNA duplex sequencing with UMIs assay that enables simultaneous detection of 128 clinical relevant geneswith SNPs, indels, amplifications, and fusions in a single blood test. Compared to conventional ctDNA NGS, our assay achieved high sensitivity (over 82%) and specificity (over 96%) with LOD at 0.1% MAF for stage I lung, gastric and esophageal cancers with the sequencing depth at 30,000x from a cohort of 136 clinical samples. Results also showed significant concordance of MAF and TMB between DNA from tumor tissues and plasma ctDNA. Our deep learning predictive model with novel algorithms and features for tumor tissue-of-origin classification achieved an overall 85% accuracy. Conclusions: In this study, a novel ultrasensitive assay was designed and validated for accurate detection of MAF at 0.1% from plasma ctDNA of multiple tumors, and accurate classification on tissue-of-origin for major primary cancers using supervised deep learning. The results of this liquid biopsy study from initial clinical testing showed its promise on clinical applications for early-stage cancer diagnosis.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43770950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Nozawa, Hiroshi Shiratori, K. Kawai, K. Hata, Toshiaki Tanaka, T. Nishikawa, Y. Shuno, K. Sasaki, M. Kaneko, S. Emoto, K. Murono, H. Sonoda, H. Ishii, S. Ishihara
{"title":"Risk factors and therapeutic significance for inguinal lymph node metastasis in advanced lower rectal cancer.","authors":"H. Nozawa, Hiroshi Shiratori, K. Kawai, K. Hata, Toshiaki Tanaka, T. Nishikawa, Y. Shuno, K. Sasaki, M. Kaneko, S. Emoto, K. Murono, H. Sonoda, H. Ishii, S. Ishihara","doi":"10.1200/jgo.2019.5.suppl.120","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.120","url":null,"abstract":"120 Background: Which patients with lower rectal cancer are at risk of inguinal lymph node metastasis (ILNM) and how to treat ILNM remain unclear. This study aimed to clarify the predictors of ILNM and clinical significance of treatment for ILNM. Methods: Consecutive patients with rectal adenocarcinoma invading the anal canal who underwent curative surgery between 2003 and 2019 at a single institution were retrospectively reviewed. The pathological nodal involvement in mesorectal, lateral pelvic or inguinal lymph nodes (ILN) at the time of rectal surgery and of later onset were collectively defined as final nodal metastasis (f-LNM) in this study. Factors associated with f-LNM were analyzed. Moreover, the ‘modified therapeutic value index’ defined by the 5-year overall survival rate of patients treated against f-LNM multiplied by their frequency was calculated for each lymph node area. Results: A total of 145 patients were enrolled, among whom16 patients developed ILNM. For predicting f-ILNM, the cutoff 8.5 mm of ILN diameter gave area under the curve of 0.889. Dentate line involvement and ILN larger than a simplified cutoff of 8 mm were independently associated with the development of ILNM (odds ratio: 33.4 and 11.9, respectively). The modified therapeutic value indice of inguinal, lateral pelvic and mesorectal LNs in the entire population were 6.1, 8.2 and 20.3 points, respectively. In patients with dentate line invaded by cancer, they were 11.7, 5.8 and 16.2 points, respectively. Moreover, the index of ILN was 21.1 points when confined to patients with ILN larger than 8 mm. Conclusions: Dentate line involvement and ILN larger than 8 mm were predictive of developing ILNM in patients with rectal cancer invading the anal canal. Treatment of ILNM may be recommended for patients manifesting the above predictors, given the significant therapeutic outcomes.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42383042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}