{"status":"ok","message-type":"work-list","message-version":"1.0.0","message":{"facets":{},"total-results":45751,"items":[{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:28:05Z","timestamp":1685939285512},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natera, Inc"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> TPS3634 <\/jats:p><jats:p> Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal\/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II\/III trial, up to 1,912 pts with resected stage III A, B (all pts) and stage II, IIIC (ctDNA+ only) CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (SignateraTM, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP) + oxaliplatin (Ox) for 3-6 mos per established guidelines vs. serial ctDNA monitoring. Patients who are ctDNA+ post-operatively or with serial monitoring (Cohort B) will be randomized to FP+Ox vs. more intensive AC with addition of irinotecan (I) for 6 mos. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate vs. delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox vs FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched\/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022. NCT#: NCT05174169. Support: U10-CA-180868, -180822; UG1CA-189867; Natera, Inc. Clinical trial information: NCT05174169 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.tps3634","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:36:10Z","timestamp":1685892970000},"page":"TPS3634-TPS3634","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US): NRG-GI008."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct05174169","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Arvind","family":"Dasari","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guan","family":"Yu","sequence":"additional","affiliation":[{"name":"The University of Pittsburgh, and NRG Oncology SDMC, Pittsburgh, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Kopetz","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel A.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"NSABP Foundation, Inc., Pittsburgh, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C.","family":"Lucas","sequence":"additional","affiliation":[{"name":"UMPC Hillman Cancer Center, The University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim Halil","family":"Sahin","sequence":"additional","affiliation":[{"name":"The University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dustin A.","family":"Deming","sequence":"additional","affiliation":[{"name":"University of Wisconsin, Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip Agop","family":"Philip","sequence":"additional","affiliation":[{"name":"Henry Ford Cancer Institute, Detroit, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore S.","family":"Hong","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yesenia","family":"Rojas-Khalil","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M.","family":"Loree","sequence":"additional","affiliation":[{"name":"BCCA, Vancouver Cancer Centre, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman","family":"Wolmark","sequence":"additional","affiliation":[{"name":"UPMC Hillman Cancer Center, The University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Yothers","sequence":"additional","affiliation":[{"name":"The University of Pittsburgh, and NRG Oncology SDMC, Pittsburgh, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"George","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Center, Gainesville, FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher Hanyoung","family":"Lieu","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center, Aurora, CO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.TPS3634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:38:14Z","timestamp":1685893094000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.TPS3634"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.TPS3634"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.tps3634","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:26:59Z","timestamp":1685939219086},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"None."}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> 3516 <\/jats:p><jats:p> Background: Several retrospective studies have previously demonstrated that a combination of adjuvant systemic chemotherapy and hepatic arterial infusion (HAI) could benefit patients following colorectal cancer liver metastases (CRLM) resection. This prospective clinical study aimed to determine whether adding HAI to adjuvant systemic chemotherapy could reduce the risk of recurrence following CRLM resection. Methods: The HARVEST study is an investigator-initiated, prospective, randomized controlled trial investigating the efficacy and safety of adjuvant intravenous chemotherapy with or without HAI floxuridine (FUDR) in CRLM patients that underwent liver metastasectomy. Patients in the systemic chemotherapy plus HAIC arm (HAI group) received systemic FOLFOX (q2w) plus HAI (FUDR, d1-14, q4w) for up to 6 months, while the systemic chemotherapy group without HAI (non-HAI group) received intravenous FOLFOX only. The primary study endpoint is the relapse-free survival in the modified intention-to-treat (mITT) population. Blood samples at different time points were also collected and circulating tumor DNA (ctDNA) was tested for NPY and SEPT9 methylation. Results: The study was prematurely terminated due to FUDR production halt in China. Ninety-two patients were randomized and seventy-seven patients (38 in the HAI group and 39 in the non-HAI group) were eventually included in our mITT analysis. After a median follow-up of 35.8 months, there were 22 (57.9%) and 25 (64.1%) recurrences in the HAI and non-HAI groups, respectively. The median relapse-free survival was 20.0 months in the HAI group and 11.7 months in the non-HAI group (p = 0.14; HR 0.65; 95% confidence interval [CI] 0.37 to 1.16). No significant difference was found in terms of overall survival between the two groups (p = 0.461). Our subgroup analysis revealed that patients with multiple liver metastases (p &lt; 0.01) and RAS\/BRAF mutation (p &lt; 0.01) could benefit from adjuvant HAI treatment. Based on ctDNA status, patients with positive postoperative ctDNA methylation benefited from adjuvant HAI treatment (p &lt; 0.01), while those with negative postoperative ctDNA methylation status (p = 0.95) did not. Chemotherapy-related adverse events were comparable between the two groups. Conclusions: Adjuvant chemotherapy intensification using HAI did not significantly reduce recurrence following CRLM resection. However, patients with multiple liver metastases, RAS\/BRAF mutation and those with positive postoperative ctDNA might benefit from adjuvant HAI treatment. Clinical trial information: NCT03500874 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.3516","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:36:10Z","timestamp":1685892970000},"page":"3516-3516","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Adjuvant systemic chemotherapy with or without hepatic arterial infusion of floxuridine in patients following colorectal cancer liver metastases resection (HARVEST): A prospective, randomized controlled trial."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct03500874","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Yu-hong","family":"Li","sequence":"first","affiliation":[{"name":"Sun Yat-sen University Cancer Center,  State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Shen","family":"Wang","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center,  State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang-Kui","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Fei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin-Kui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Rong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Department of Medical Oncology, Sun Yat-Sen University Cancer Center., Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Zhong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ren","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-Hai","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Sen","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui-Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.3516","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:40:56Z","timestamp":1685893256000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.3516"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.3516"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.3516","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:27:07Z","timestamp":1685939227119},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"DOI":"10.13039\/501100001809","name":"national natural science foundation of china","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing Medical Award Foundation"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> e16204 <\/jats:p><jats:p> Background: To determine the safety and efficacy of transcatheter arterial chemoembolization with CalliSpheres beads loaded with arsenic trioxide (CBATO-TACE) in the first-line treatment of patients with large (5 cm \u2264 maximum diameter\uff1c10 cm) or huge (maximum diameter \u226510 cm) hepatocellular carcinoma (HCC). Methods: Patients were randomly allocated to the CBATO-TACE group and the cTACE group. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS), treatment response, and treatment- related adverse events (TRAEs). The extrahepatic collateral arteries, liver function, and liver fibrosis after the first TACE were also evaluated. Results: From September 2018 to September 2020, a total of 207 patients underwent TACE were consecutively enrolled in this study. The median PFS was 9.5 months (range: 8.0-11.0) in the CBATO group, which was significantly longer than that in the cTACE group (6.0 months, range: 4.0-6.0) ( P&lt; 0.0001). Patients in the CBATO group had a median OS of 22 months (range: 20.0-27.0) compared with 16 months (range:15.0-20.0\uff09in the cTACE group ( P= 0.0084). The most common TRAEs were fever ( P= 0.043), nausea and vomiting ( P= 0.002), which were more observed in the cTACE group. In addition, the progressive disease time, pulmonary metastasis rate ( P= 0.01), the mean number of EHC arteries ( P= 0.01) and average number of TACE sessions ( P= 0.025) were significantly decreased in the CBATO group. Conclusions: CBATO-TACE achieved better therapeutic outcomes and similar safety profile compared to cTACE in large or huge HCC patients. Furthermore, CBATO-TACE was able to reduce extrahepatic collateral arteries production and extrahepatic lung metastasis. Clinical trial information: ChiCTR1800018418 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.e16204","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:38:35Z","timestamp":1685893115000},"page":"e16204-e16204","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Transcatheter arterial chemoembolization using CalliSpheres beads loaded with arsenic trioxide for unresectable large or huge hepatocellular carcinoma: A prospective study."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"chictr1800018418","registry":"10.18810\/chictr"}],"author":[{"given":"Xuhuan","family":"Duan","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donglin","family":"Kuang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huibin","family":"Lu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingbing","family":"Qiao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengjun","family":"Fan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianzhuang","family":"Ren","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinwei","family":"Han","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.e16204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:53:29Z","timestamp":1685894009000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.e16204"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.e16204"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.e16204","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:26:43Z","timestamp":1685939203843},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"Chugai Pharmaceutical Co., Ltd"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> 3111 <\/jats:p><jats:p> Background: Precision oncology using the comprehensive genomic profiling (CGP) test by next-generation sequencing has been introduced into clinical practice. In Japan, only 6.8% of patients accessed the precision treatment because it is only indicated after standard of care (SoC). FoundationOne CDx (F1CDx) is the software as a medical device for the detection of actionable and druggable genomic alterations in 324 genes. F1CDx has the function of both CGP test and companion diagnostics (CDx). Therefore, F1CDx could be ideally used in the early stages of treatments. In this study, we investigated the clinical utility of F1CDx in previously untreated patients with metastatic or recurrent solid tumors. Methods: We conducted a multi-institutional, prospective study in six hospitals in Japan (FIRST-Dx study). Chemotherapy-na\u00efve adult patients with advanced solid tumor (GI, Lung, Breast, GYN, Melanoma) and ECOG performance status of 0-1 were enrolled. Primary endpoint was the ratio of patients with actionable mutation. Secondary endpoints were the ratio of patients with druggable mutation, molecular-based recommended therapy (MBRT), gene alteration with CDx, CGP success rate, and patients who actually received MBRT. Results: 183 patients were enrolled between May 2021 and February 2022, 180 patients with median (range) age 64 (23-88) years underwent F1CDx test (92 men, lung [n=28], colon\/small intestine [n=27], pancreas [n=27], breast [n=25], biliary tract [n=20], gastric [n=19], uterus [n=12], esophagus [n=10], ovary [n=6], and skin melanoma [n=6]). 175 tests were successful (CGP success rate: 97%), and 172 patients were evaluable for endpoint analyses with follow-up through July 2022. Actionable and druggable cancer genomic alterations were found in 172 patients (100.0% [95% CI: 97.9-100.0%]) and 109 patients (63.4% [95% CI: 55.7-70.6%]), respectively. MBRT determined by molecular tumor board was found in 105 patients (61.0% [95% CI: 53.3-68.4%]). Genomic alterations included in the CDx list of F1CDx were found in 49 patients (28.5% [95%CI: 21.9-35.9%]) in the tumor-agnostic setting. After a median follow-up of 7.9 months, 34 patients (19.8 % [95%CI: 14.1-26.5%]) actually received MBRTs. Twenty-six patients received evidence level A MBRT, two received evidence level B MBRT, and six received evidence level C MBRT. Conclusions: We showed that 61% of the patients with previously untreated advanced cancer had MBRTs found by F1CDx and 20% of them actually received MBRTs early in their disease course. CGP test before SoC for advanced solid tumors could provide better opportunities for receiving MBRTs than after completion of SoC. Our data would recommend expanded approval with respect to the timing of CGP test for patients with previously untreated advanced solid tumors. Clinical trial information: UMIN000042408 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.3111","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:23:35Z","timestamp":1685892215000},"page":"3111-3111","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive genomic profiling before the first-line setting versus after the completion of standard of care in patients with previously untreated advanced solid tumors: The prospective FIRST-Dx study."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"umin000042408","registry":"10.18810\/umin-japan"}],"author":[{"given":"Junichi","family":"Matsubara","sequence":"first","affiliation":[{"name":"Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumi","family":"Mukai","sequence":"additional","affiliation":[{"name":"Kyoto University Hospital, Kyoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Kage","sequence":"additional","affiliation":[{"name":"Department of Next-Generation Precision Medicine Development Laboratory, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsutoshi","family":"Oda","sequence":"additional","affiliation":[{"name":"The University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Kudo","sequence":"additional","affiliation":[{"name":"Tokyo Medical and Dental University, Bunkyo-Ku, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadakatsu","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Tokyo Medical and Dental University, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Ebi","sequence":"additional","affiliation":[{"name":"Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Muro","sequence":"additional","affiliation":[{"name":"Aichi Cancer Center Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuji","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Toyama University Hospital, Toyama-Shi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahomi","family":"Tokudome","sequence":"additional","affiliation":[{"name":"Wakayama Medical University Hospital, Wakayama-Shi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Internal Medicine III, Wakayama Medical University, Wakayama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manabu","family":"Muto","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.3111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:34:10Z","timestamp":1685892850000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.3111"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.3111"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.3111","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:45Z","timestamp":1685939145767},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"Beyond Spring"},{"name":"Institutional Funds"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> 8023 <\/jats:p><jats:p> Background: Plinabulin is a selective immunomodulating microtubule-binding agent, which prevents chemotherapy induced neutropenia (CIN) via a mechanism of action different from that of G-CSF analogues. It has been studied for CIN and anti-solid tumor activity in phase 3 trials. To decrease the period of myelosuppression and obligate neutropenia after high dose melphalan with autologous hematopoietic stem cell transplantation (AHCT) for patients with multiple myeloma, we studied the addition of plinabulin to standard growth factors. Methods: To achieve the primary objective of reducing the duration of absolute neutropenia post AHCT, 40mg of intravenous plinabulin was given 1-3 hours after stem cell infusion (Day 0) with pegfilgrastim on Day +1 in this pilot trial (NCT05130827). Secondary objectives include the safety, tolerability, and toxicity profile of plinabulin in combination with pegfilgrastim, neutrophil and platelet engraftment rate, disease response, progression free and overall survival, patient reported outcome (PRO) assessment of symptom burden, and plinabulin pharmacokinetic profiling. Exploratory objectives include transfusion requirements, phenotypic characterization of neutrophil population through day 30, and analysis of cytokine levels early post AHCT. Results: Between January 2022 and February 2023, 15 patients with median age of 64 (range 54-74) and 33% female received plinabulin after melphalan 140 (n = 4) or 200mg\/m2 (n = 11). Median CD34+ cells\/kg infused was 4.12 x 10^6 (range 2.18 \u2013 7.85). Half of the patients had hypertension immediately after the plinabulin infusion, which is a known toxicity and resolved within a few hours. Median WBC on Day 0, 1, and 2 was 7.67(3.6 \u2013 11.5), 5.2 (3.2 \u2013 13.6), and 17.1 (5.1-59.1), respectively. Of the 14 patients who have engrafted to date, median time to ANC &gt; 0.5 x 10^9 cell\/L was 11 days (range 9-16) with median days from AHCT to ANC &lt; 0.5 of 5 days (range 5-6). The median number of days of ANC &lt; 0.1 and &lt; 0.5 were 2 (range 1-5) and 5 days (range 4-9), respectively. For the 7 patients who had a fever, the median time to fever was 8 days from AHCT (range 8-12), and all except one were peri-engraftment. Median length of stay was 17 days (range 15-21). Median pRBC and platelet transfusions were 0 (range 0-3) and 3 (range 0-11), respectively. Conclusions: Plinabulin appears well tolerated without additional major toxicities post AHCT and provided a high WBC on Day +2 and decreased rate of neutropenic fever. Plinabulin PK, quality of life data, and PROs will be presented. Adjusting the schedule of plinabulin to later post AHCT pre engraftment may further shorten the duration of neutropenia using this novel mechanism of action. Clinical trial information: NCT05130827 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.8023","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T16:11:56Z","timestamp":1685895116000},"page":"8023-8023","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Plinabulin to shorten neutropenia and improve quality of life peri-autologous hematopoietic cell transplant."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct05130827","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Gunjan L.","family":"Shah","sequence":"first","affiliation":[{"name":"Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Hanley","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ambika","family":"Datta","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyssa","family":"Kamrowski","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Chung","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaurav K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hani","family":"Hassoun","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Hoover","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malin","family":"Hultcrantz","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha","family":"Korde","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar Boutros","family":"Lahoud","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather Jolie","family":"Landau","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander M.","family":"Lesokhin","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Scordo","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urvi A","family":"Shah","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlyn Rose Co","family":"Tan","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad Zafar","family":"Usmani","sequence":"additional","affiliation":[{"name":"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon W.","family":"Mohanlal","sequence":"additional","affiliation":[{"name":"BeyondSpring Pharmaceuticals, Inc., New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Giralt","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.8023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T16:18:02Z","timestamp":1685895482000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.8023"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.8023"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.8023","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:57Z","timestamp":1685939157751},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"Merck & Co.; Merck Sharp & Dohme"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> TPS6111 <\/jats:p><jats:p> Background: Standard treatments for locally advanced larynx cancers include concurrent cisplatin\/radiation therapy, or induction chemotherapy followed by radiation therapy alone, with the goal of organ preservation. Both strategies have been shown to achieve similar laryngectomy-free survival (LFS), but failed to improve overall survival (OS) compared with radiation therapy alone or surgery followed by radiation therapy. Although cisplatin given concurrently with radiation therapy is commonly used for organ preservation, there are concerns regarding long-term outcomes, such as late toxicities. Pembrolizumab with chemotherapy has been shown to improve OS in recurrent\/metastatic head and neck squamous cell carcinomas (HNSCCs). Additionally, pembrolizumab combined with radiation therapy has been shown to be safe in locally advanced HNSCC. LACOG 0720 is designed to evaluate a pembrolizumab-based, cisplatin-free, and concurrent chemoradiation therapy-free regimen for larynx preservation, in an attempt to improve outcomes and avoid late toxicities. Methods: LACOG 0720 is a phase 2, single-arm, multicentric trial assessing patients with newly diagnosed squamous cell carcinoma of the larynx (glottic or supraglottic) and clinical stages III, IVA, or IVB (AJCC 8th Ed.). Patients with large volume T4 disease (invasion through the cartilage or extension &gt; 1 cm to the base of the tongue) or T1 disease are excluded. Patients receive 3 cycles of induction chemo-immunotherapy (carboplatin AUC6, paclitaxel 175 mg\/m\u00b2, and pembrolizumab 200 mg, IV every 21 days [q21D]), followed by concurrent radioimmunotherapy (Intensity-modulated radiation therapy with pembrolizumab 200 mg IV q21D for 3 cycles), followed by consolidation immunotherapy (pembrolizumab 200 mg IV q21D for 11 cycles). The primary endpoint is two-year LFS rate. Secondary endpoints include two-year larynx dysfunction-free survival, OS, overall response rate, short-term and long-term toxicities, causes of death, patterns of failure, and quality of life. Predictive biomarkers of response and survival will be evaluated as exploratory analysis. The sample size was calculated based on the primary endpoint. Using the Chi-square Test for One Proportion and considering a one-sided 10% significance level, 39 patients are needed to achieve 80% power to detect the difference between the null hypothesis; that the true laryngectomy-free survival at two years is 59%, and the alternative hypothesis that the laryngectomy-free survival at two years is 75%. From Feb 2022 to Feb 2023, 24 patients were enrolled in 10 Brazilian centers. Results are expected in July 2024. NCT04943445. Clinical trial information: NCT04943445 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.tps6111","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:58:27Z","timestamp":1685894307000},"page":"TPS6111-TPS6111","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A single-arm, multi-institutional, phase 2 study of a pembrolizumab-based organ preservation strategy for locally advanced larynx cancers: SMART-KEY (LACOG 0720) trial."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct04943445","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Thiago Bueno","family":"Oliveira","sequence":"first","affiliation":[{"name":"A.C. Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio Augusto","family":"Ferreira da Silva","sequence":"additional","affiliation":[{"name":"Hospital de Amor de Barretos, Barretos, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiane","family":"Motta","sequence":"additional","affiliation":[{"name":"Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto, Ribeir\u00e3o Preto, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea Juliana","family":"Gomes","sequence":"additional","affiliation":[{"name":"Liga Norte Riograndense Contra o C\u00e2ncer, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iane","family":"Pinto Figueiredo Lima","sequence":"additional","affiliation":[{"name":"Centro Regional Integrado de Oncologia (CRIO), Fortaleza, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda Bohns Pruski","family":"Ramos","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa em Oncologia (CPO) - HSL, Porto Alegre, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Henrique","family":"de Lima Araujo","sequence":"additional","affiliation":[{"name":"Instituto Nacional do C\u00e2ncer, Rio De Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena Perez","family":"Mak","sequence":"additional","affiliation":[{"name":"Instituto do Cancer do Estado de Sao Paulo - Hospital das Clinicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathia Cristina","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Faculdade Regional de S\u00e3o Jos\u00e9 do Rio Preto, S\u00e3o Jos\u00e9 Do Rio Preto, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo Nader","family":"Marta","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos Antonio","family":"Santos","sequence":"additional","affiliation":[{"name":"CONFIAR Radioterapia, Goi\u00e2nia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafaela Gomes","family":"de Jesus","sequence":"additional","affiliation":[{"name":"Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Werutsky","sequence":"additional","affiliation":[{"name":"Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiane Francieli","family":"Rebelatto","sequence":"additional","affiliation":[{"name":"Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William Nassib","family":"William","sequence":"additional","affiliation":[{"name":"Hospital Benefic\u00eancia Portuguesa, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.TPS6111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T16:01:45Z","timestamp":1685894505000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.TPS6111"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.TPS6111"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.tps6111","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:20Z","timestamp":1685939120869},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"ImmVira Co., Limited"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> 2640 <\/jats:p><jats:p> Background: T3011 is a genetically modified, next-generation oncolytic HSV-1 with 2 exogenous genes encoding the active heterodimer human IL-12 and the Fab fragment of an anti-human PD-1 antibody. T3011 intratumoral injection (IT) was reported to be well tolerated in patients (pts). IV therapy of OVs is rare and provides an attractive option to many pts with advanced cancers that are not candidates for IT therapy. Methods: It is a phase I\/IIa multi-center, open label, single ascending dose (SAD) \/multiple ascending dose (MAD) study to evaluate T3011 IV therapy. The primary objective is to evaluate the safety and tolerability. Dose cohort and regimen are shown in Table. PK and PD profiles are tested in samples of blood, saliva, urine, and tumor tissue. Results: As of 16 Dec 2022, 15 pts with stage IV disease were enrolled, 9 pts had received at least 3 lines of prior therapy. The median follow-up time is 1.58 months. Treatment-emergent adverse event (TEAE) occurred in 15 (100%) pts and treatment-related adverse event (TRAE) occurred in 10 (66.7%) pts. G3 TEAE in 3 (20%) pts (hypertriglyceridemia, dyspnea, lymphopenia) and G3 TRAE in 1 (6.7%) pt (lymphopenia), no\u2265 G4 AE reported. Dyspnea, the only reported SAE (1, 6.7%), is drug-unrelated. TRAEs were lymphopenia (5, 33.3%), anemia (1, 6.7%), diarrhea (1, 6.7%), malaise (1, 6.7%), urticaria (1,6.7%), rash (1, 6.7%), constipation (1, 6.7%), flu like symptoms (1, 6.7%), headache (1, 6.7%) and abnormal laboratory test results (incidence were all 6.7%), most of them are mild and manageable. No AEs led to drug withdrawal. No DLT occurred; MTD was not reached. 11\/15 pts achieved stable disease (SD) by RECIST v 1.1. DCR was 73.3%. 1 pt with colorectal cancer who experienced irinotecan-based chemotherapy, anti-VEGF and radiotherapy in Cohort 1 had a long-term SD for over 4 months. In SAD part, T3011 DNA in blood at 2 hours post-dose was detected in 0% (0\/3), 0% (0\/4), 66.7% (2\/3) and 100% (2\/2) pts in Cohort 1, 2, 3 and 4 respectively. The DNA copies in pts of Cohort 4 are significantly higher than those of Cohort 3 (Mean viral DNA copies\/ul 49.6 vs. 5.7). In cohort 2 of MAD part, T3011 DNA in blood at 2 hours post-dose was detected in 0% (0\/3), 66.7% (2\/3) and 100% (3\/3) pts at C1D1, C1D4 and C1D8 respectively. T3011 DNA was not detected in saliva or urine samples. Pre-existing HSV-1 IgG was shown to hardly affect T3011 activity. Conclusions: T3011 IV is safe and well tolerated, and unlikely to spread to close contacts. Preliminary efficacy is encouraging. T3011 DNA in blood is in a dose-dependent manner with additive effect from repeated doses supporting continued recruitment of pts to higher dose cohorts. Clinical trial information: NCT05598268 . [Table: see text] <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.2640","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:12:10Z","timestamp":1685891530000},"page":"2640-2640","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A phase I\/IIa study to assess the safety, tolerability, PK, and PD of T3011, a genetically modified oncolytic virus (OVs) administered intravenously (IV) in patients with advanced solid tumors."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct05598268","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ziming","family":"Li","sequence":"first","affiliation":[{"name":"Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhujiang Hospital of Southern Medical University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zheng","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiye","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junbin","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Bengbu Medical College, Bengbu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Hu","sequence":"additional","affiliation":[{"name":"Beijing Chest Hospital, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-xia","family":"Luo","sequence":"additional","affiliation":[{"name":"The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijia","family":"Pang","sequence":"additional","affiliation":[{"name":"ImmVira Co., Limited, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenmin","family":"Fu","sequence":"additional","affiliation":[{"name":"ImmVira Co., Limited, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanmei","family":"Qin","sequence":"additional","affiliation":[{"name":"ImmVira Co., Limited, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun","family":"Lu","sequence":"additional","affiliation":[{"name":"Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.2640","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:25:19Z","timestamp":1685892319000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.2640"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.2640"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.2640","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:25Z","timestamp":1685939125569},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"None."}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> 586 <\/jats:p><jats:p> Background: Black women with breast cancer have the highest breast cancer mortality (BCM) rates of any racial and ethnic group. The higher burden of triple negative breast cancer (TNBC) in Black women contributes to disparities in BCM, but the extent to which disparate outcomes exist in patients with similar tumor biology is uncertain. The objective of this study was to examine racial differences in disease outcomes and BCM between Black and White patients in a clinical trial population of high-risk TNBC with residual disease after neoadjuvant chemotherapy (NAC). Methods: From 2015-2021, the ECOG-ACRIN EA1131 clinical trial randomized 415 clinical stage II-III TNBC patients with residual disease after NAC to either adjuvant capecitabine or platinum. For this analysis, 366 patients with known self-reported Black or White race and follow-up data were included. The aim of this unplanned exploratory analysis was to examine locoregional recurrence (LRR), distant recurrence (DR), and BCM by race using Kaplan-Meier curves for unadjusted estimates and Cox modeling for adjusted analyses. Results: Racial distribution of the analysis population included 66 (18.0%) Black and 300 (82.0%) White patients. 239 (65.3%) patients presented with clinical stage II and 127 (34.7%) with stage III disease. All patients had residual pathological disease after NAC: 86 (23.5%) stage I, 176 (48.1%) stage II, and 102 (27.9%) stage III (n=2 unknown). Median age was 49 years in Black and 54 years in White patients, p=0.003. Disease presentation, response to chemotherapy, and treatment arm were similar by race. Median follow up was 20 months. 2-year estimated LRR occurred in 31.6% of Black and 18.6% of White patients although this was not statistically significant (p=0.387), and 2-year estimated DR and BCM were similar by race. Estimated 2-year outcomes are outlined. Models adjusted for race, age, stage, grade, treatment arm, and locoregional therapy did not identify race as an independent predictor of LRR, DR, or BCM. Higher pathologic stage was the only consistent independent predictor of recurrent disease or BCM (stage III with HR 6.14 for LRR; HR 5.16 for DR; HR 6.84 for BCM; all p&lt;0.001). Conclusions: In this population of high-risk patients with residual TNBC after NAC with similar tumor biology treated on a clinical trial, there was a trend towards increased LRR in Black patients and similar DR and BCM between Black and White patients at 2 years of follow-up. This suggests that differences in BCM in other breast cancer populations may be at least partially driven by differences in tumor biology. Clinical trial information: NCT02445391 . [Table: see text] <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.586","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T14:02:11Z","timestamp":1685887331000},"page":"586-586","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Disease outcomes by race in patients with high-risk triple negative breast cancer with residual disease after neoadjuvant chemotherapy: A post-hoc analysis of the EA1131 randomized clinical trial."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct02445391","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Olga","family":"Kantor","sequence":"first","affiliation":[{"name":"Brigham and Women's Hospital, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A.","family":"Newman","sequence":"additional","affiliation":[{"name":"Weill Cornell, Detroit, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren K","family":"Anderson","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charity","family":"Glass","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica L.","family":"Mayer","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther R.","family":"Ogayo","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Chavez-MacGregor","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel A.","family":"Freedman","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tari A.","family":"King","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Mittendorf","sequence":"additional","affiliation":[{"name":"Division of Breast Surgery, Department of Surgery, BWH, Breast Oncology Program, Dana-Farber\/Brigham and Women\u2019s Cancer Center, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.586","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T14:09:25Z","timestamp":1685887765000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.586"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.586"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.586","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:14Z","timestamp":1685939114953},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> e24173 <\/jats:p><jats:p> Background: Prophylactic use of rhG-CSF is routinely recommended in patients with a high risk of febrile neutropenia (FN) after chemotherapy. Currently, rhG-CSF is mostly used in clinical practice. However, PEG-rhG-CSF tends to be a substitute due to its convenience and long-acting effect. Regarding concerns about its efficacy and safety, whether PEG-rhG-CSF could be prophylactically used after these regimens with a high risk of FN is still in doubt. Doxorubicin combined with ifosfamide is commonly applied in sarcoma patients and is one of the most serious myelosuppressive chemotherapy regimens in solid tumors. We compared the efficacy and safety of PEG-rhG-CSF with rhG-CSF in the prevention of severe granulocytopenia and FN, in patients receiving this representative regimen. Methods: This was a single-center, prospective, randomized, crossover, non-inferiority phase II trial. Patients with sarcoma suitable for doxorubicin combined with ifosfamide treatment were enrolled. All patients received 2 cycles of chemotherapy and were randomly assigned to either the AOB group (PEG-rhG-CSF used in 1st cycle and rhG-CSF in 2nd cycle) or BOA group (rhG-CSF used in 1st cycle and PEG-rhG-CSF in 2nd cycle). Blood monitoring every other day until ANC \u2265 2\u00d710<jats:sup>9<\/jats:sup>\/L in two consecutive tests. The primary endpoints were the frequency and duration of grade 4 granulocytopenia after prophylactic use of PEG-rhG-CSF and rhG-CSF respectively, the secondary endpoints were the frequency and duration of febrile neutropenia, and proportion of antibiotic use. Results: From Jan 1, 2018 to Aug 31, 2021, 70 patients were enrolled, 35 each in AOB and BOA. There were no statistical differences in the incidence and duration of grade 4 granulocytopenia (85.7% vs. 77.0%, p = 0.1; 1.34d vs. 1.41d, p = 0.70), the proportion and duration of febrile neutropenia (12.8% vs. 8.2%, p = 0.77; 0.6d vs. 0.8d, p = 0.74), and the proportion of antibiotics used (19.1% vs. 14.9%, p = 0.79) when comparing PEG-rhG-CSF vs. rhG-CSF in prophylactical use. The incidence of grade 4 granulocytopenia in both groups was comparable in 1st cycle (90.9% vs. 96.0%, p = 0.47), but in 2nd cycle it was significantly lower in AOB than that in BOA (54.5% vs. 88.0%, p = 0.01). The lowest value of ANC was higher in AOB in 2nd cycle (0.32G\/L vs. 0.12G\/L, p = 0.03). Conclusions: This study demonstrated PEG-rhG-CSF could prevent granulocytopenia and FN in sarcoma patients receiving doxorubicin combined with ifosfamide, with comparable efficacy and toxicities as rhG-CSF. Considering the convenience in use and patient compliance, PEG-rhG-CSF could be an effective and reasonable alternative to rhG-CSF. Clinical trial information: ChiCTR1900021945 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.e24173","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T16:33:06Z","timestamp":1685896386000},"page":"e24173-e24173","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of PEG-rhG-CSF versus rhG-CSF in preventing granulocytopenia in sarcoma patients receiving doxorubicin combined with ifosfamide: A prospective, randomized, non-inferiority phase II study."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"chictr1900021945","registry":"10.18810\/chictr"}],"author":[{"given":"Li","family":"Fan","sequence":"first","affiliation":[{"name":"Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Ye","sequence":"additional","affiliation":[{"name":"Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Whhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rubo","family":"Cao","sequence":"additional","affiliation":[{"name":"Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bicheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Whhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Peng","sequence":"additional","affiliation":[{"name":"Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.e24173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T16:33:36Z","timestamp":1685896416000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.e24173"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.e24173"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.e24173","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:28Z","timestamp":1685939128179},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"Guardant Health"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> TPS3626 <\/jats:p><jats:p> Background: Asymptomatic screening is an effective method for detecting early cancers when prognosis strongly depends on stage at time of diagnosis. Unscreened individuals often have a basic understanding of the importance and availability of colorectal cancer (CRC) screening but have concerns regarding the collection method of the currently available stool-based options or the invasiveness of direct visualization options that deter test completion. We hypothesize that offering a blood-based CRC screening test during a routine healthcare visit can increase screening adherence, especially within hard-to-reach populations and those hesitant about completing CRC screening. Methods: The Ohio State University Guardant Shield Colorectal Cancer Screening Project (NCT05716477) is a prospective study in the United States designed to recruit individuals who are currently engaging with mobile health clinics and are not up to date with CRC screening, with the aim of improving health in hard-to-reach populations. The study\u2019s primary objective is to evaluate the acceptance of a commercially available blood-based CRC screening test (Shield, Guardant Health, USA) in individuals aged 45-84, who have existing appointments with a mobile health clinic, and are not up to date with guideline recommended CRC screening. The study team screens for eligibility criteria before the appointment and reaches out to the individual to begin the informed consent process. Positive blood-based test results will be triaged to colonoscopy for further evaluation. A post-study survey will be administered to consented individuals aimed to collect data on CRC screening knowledge which will be correlated to patient demographics and uptake. Acceptance will be defined as those approached and with completed specimen collection. Progress: The study initiated on October 25, 2022, with the first patient enrolled on December 20, 2022. Enrollment is expected to continue with a target enrollment of 300 individuals. Clinical trial information: NCT05716477 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.tps3626","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:36:10Z","timestamp":1685892970000},"page":"TPS3626-TPS3626","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["The Ohio State University Guardant Shield Colorectal Cancer Screening Project."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct05716477","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Peter","family":"Stanich","sequence":"first","affiliation":[{"name":"The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia R","family":"DeGraffinreid","sequence":"additional","affiliation":[{"name":"Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chasity M","family":"Washington","sequence":"additional","affiliation":[{"name":"Ohio State University James Cancer Hospital and Solove Research Institute, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oindrila","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Lontoc","sequence":"additional","affiliation":[{"name":"Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Electra D.","family":"Paskett","sequence":"additional","affiliation":[{"name":"Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.TPS3626","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:37:01Z","timestamp":1685893021000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.TPS3626"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.TPS3626"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.tps3626","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:02Z","timestamp":1685939102534},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"Pfizer and Jazz"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> 7024 <\/jats:p><jats:p> Background: Gemtuzumab ozogamicin (GO) is effective in favorable-risk acute myelogenous leukemia (AML), while its activity is limited in higher-risk AML in part due to multi-drug resistance (MDR) mechanisms, particularly P-glycoprotein efflux pumps. CPX-351 provides a survival benefit in secondary AML, a disease characterized by high MDR activity. The objective of this trial is to utilize CPX-351 as a bulk cytoreduction agent, to first reduce the high MDR leukemia clones, followed by sequential treatment with GO in a more favorable leukemia environment. Methods: This was a multicenter phase Ib trial of CPX-351 plus GO in relapsed\/refractory (R\/R) AML patients with standard 3+3 dose escalation design (NCT03904251). Cohort A was treated with CPX-351 100 u\/m<jats:sup>2<\/jats:sup> on days 1, 3, and 5 plus GO 3 mg\/m<jats:sup>2<\/jats:sup> (max 4.5 mg) on day 7. Cohort B was treated with the same regimen plus an additional dose of GO 3 mg\/m2 on day 4. The primary endpoint was the maximum tolerated dose (MTD), defined as &lt; 2 dose limiting toxicities (DLTs) in the highest dose cohort. Secondary endpoints were IWG complete remission (CR) rate at day 28-42, liver veno-occlusive disease (VOD) rate diagnosed by the Baltimore criteria, and time of hematologic recovery (defined as ANC &gt; 1000\/uL and platelet count &gt; 100,000\/uL). Patients were enrolled at 4 University of California Hematologic Malignancies Consortium (UCHMC) centers: UC Los Angeles, UC San Francisco, UC Davis, and UC Irvine. Results: Thirteen participants were enrolled. The median age was 63 years (range 29-75). Eleven had relapsed disease, and two had refractory disease. Most received one prior line of therapy (n = 9). Seven had ELN 2022 adverse-risk disease at initial diagnosis, and two had intermediate-risk disease. The MTD was not reached. DLTs were observed in 1\/6 participants in cohort A (grade 3 rash), and 1\/6 participants in cohort B (grade 5 intracranial hemorrhage in the setting of severe thrombocytopenia). There were no cases of liver VOD. Of 12 evaluable participants, 4 achieved CR (33%), of whom 3 were negative for measurable residual disease by multiparametric flow cytometry, and 1 one achieved partial remission. The median age of responders was 30 years (range 28-65). The median time to return of normal hematopoiesis in those who achieved remission was 37 days (range 36-43). Three participants received allogeneic hematopoietic cell transplant (alloHCT) following investigational therapy: one remains in remission 34 months post-transplant, one died of infectious complications shortly after alloHCT, and one relapsed at day +60. Conclusions: CPX-351 plus two doses of GO 3 mg\/m2 is a feasible treatment with acceptable toxicity and reasonable marrow recovery kinetics. However, only three participants went on to curative alloHCT. Further evaluation for efficacy in a larger patient population is needed to determine the utility of this regimen in R\/R AML. Clinical trial information: NCT03904251 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.7024","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T16:04:34Z","timestamp":1685894674000},"page":"7024-7024","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["UCHMC 1812: A phase 1b trial of CPX-351 plus gemtuzumab ozogamicin for relapsed\/refractory acute myeloid leukemia."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct03904251","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Daria Louise","family":"Gaut","sequence":"first","affiliation":[{"name":"University of California Los Angeles, Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley","family":"Callas","sequence":"additional","affiliation":[{"name":"University of California Los Angeles, Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lloyd Earl","family":"Damon","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian Andrew","family":"Jonas","sequence":"additional","affiliation":[{"name":"UC Davis Comprehensive Cancer Center, Sacramento, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepa","family":"Jeyakumar","sequence":"additional","affiliation":[{"name":"University of California, Irvine, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Borror","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Osorio","sequence":"additional","affiliation":[{"name":"University of California Irvine, Orange, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Ta","sequence":"additional","affiliation":[{"name":"University of California Davis, Sacramento, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunmin","family":"Park","sequence":"additional","affiliation":[{"name":"Ronald Reagan UCLA Medical Center, Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary J.","family":"Schiller","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine at UCLA, Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew Joseph","family":"Wieduwilt","sequence":"additional","affiliation":[{"name":"Wake Forest Univeristy, Winston-Salem, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caspian","family":"Oliai","sequence":"additional","affiliation":[{"name":"University of California Los Angeles, Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.7024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T16:11:06Z","timestamp":1685895066000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.7024"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.7024"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.7024","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:07Z","timestamp":1685939107896},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> TPS5101 <\/jats:p><jats:p> Background: 18F-DCFPyL PSMA PET imaging is now FDA approved for patients with high-risk prostate cancer and those with biochemically recurrent prostate cancer (BCR). BCR has been traditionally defined as a rising PSA after definitive surgery and\/or radiation have not been curative in patients without tumor findings on a CT or Tc99 bone scan. There are an estimated 25,000-50,000 new cases of BCR in the US annually. BCR patients are usually managed conservatively, often with surveillance since there is no data demonstrating interventions improve survival. Although 18F-DCFPyL will be able to detect disease at the micrometastatic\/subclinical level, there is limited prospective data on how these patients should be managed. While great enthusiasm exists to utilize radiation or ADT-based regimens extrapolated from a more advanced disease state, the natural history of subclinical disease seen on 18F-DCFPyL remains unclear (Madan RA et al. J Clin Oncol 2022). Methods: The primary objective of this study is to monitor patients with recurrent prostate cancer to learn about the natural history of 18F-DCFPyL PET positive disease in this patient population. Eligible patients include those who have had prior definitive surgery or radiation, current PSA \u22650.50 ng\/mL, testosterone &gt; 100 ng\/mL, no evidence of soft tissue disease on CT scan\/MRI and no bone lesions on bone scan. Patients will undergo initial imaging with 18F-DCFPyL scans. Those with negative findings on the initial scan will have annual repeat 18F-DCFPyL scans. Patients with positive initial scans will be scanned every 6 months. All patients will have PSA testing every 3 months and will undergo annual CT and Tc99 bone scans. Up to 250 patients will be followed for 5 years or until off-study criteria is met (including new findings on CT\/bone scans consistent with metastatic disease or continuous systemic prostate cancer therapy for more than 6 months). In addition to monitoring the imaging changes, we will evaluate patterns of progression on 18F-DCPyL scans over time, analyze PSA doubling time in context of 18F-DCFPyL changes and evaluate circulating biomarkers. ClinicalTrials.gov Identifier: NCT05588128. Clinical trial information: NCT05588128 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.tps5101","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:49:12Z","timestamp":1685893752000},"page":"TPS5101-TPS5101","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A study of prospective monitoring of patients with recurrent prostate cancer using serial PSMA imaging (18F-DCFPyL)."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct05588128","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Mohammad O.","family":"Atiq","sequence":"first","affiliation":[{"name":"Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liza","family":"Lindenberg","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Mena Gonzalez","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baris","family":"Turkbey","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatima","family":"Karzai","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, CCR, NCI, NIH, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Hausler","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, NCI, NIH, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa M.","family":"Cordes","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Program, CCR, NCI, NIH, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Williams","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Hankin","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, CCR, NCI, NIH, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L.","family":"Gulley","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William Douglas","family":"Figg","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, CCR, NCI, NIH, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter L.","family":"Choyke","sequence":"additional","affiliation":[{"name":"Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi Amrit","family":"Madan","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, NIC, NIH, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.TPS5101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:49:36Z","timestamp":1685893776000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.TPS5101"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.TPS5101"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.tps5101","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:25:15Z","timestamp":1685939115143},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"None."}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> 4086 <\/jats:p><jats:p> Background: The prognosis of biliary tract cancer (BTC) remains unsatisfactory. Thus, this study aimed to determine the efficacy, safety, and predictive biomarkers of the immune checkpoint inhibitor sintilimab in combination with gemcitabine and cisplatin (GemCis) in advanced BTCs. Methods: In this single-arm, phase II study (Trial registration number: ChiCTR2000036652), gemcitabine (1000 mg\/m\u00b2) plus cisplatin (25 mg\/m\u00b2) were administered on days 1 and 8, respectively, while 200 mg sintilimab was administered on day 1 of each 21-day cycle for 6\u20138 weeks, followed by sintilimab alone up to 2 years. The primary endpoint was overall survival (OS). The second endpoints were objective response rate (ORR), progression-free survival (PFS), and disease control rate, assessed using RECIST V.1.1. Multiomics biomarkers associated with clinical response were assessed as exploratory objectives. Results: Thirty patients were enrolled between August 2020 and May 2022. The median follow-up duration, OS, and PFS were 12.3 months (95% confidence interval [CI]: 9.1\u201316.0), 15.9 months (95% CI: 8.6\u2013not reached), and 5.1 months (95% CI: 4.3\u20138.7), respectively. Here, 36.7% of patients were found to achieve an objective response. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations (median, PFS: 9.8 vs. 4.5 months, p = 0.023; OS: NR vs. 9.0 months, p = 0.014; ORR: 77.8% vs. 19%, p = 0.004) or loss-of-function mutations in chromatin remodeling genes (median, PFS: 8.7 vs. 4.2 months, p = 0.021; ORR: 63.6% vs. 21.1%, p = 0.046) presented better tumor response and survival outcomes. Furthermore, transcriptome analysis of the tumor immune microenvironment revealed a markedly longer PFS, and tumor response were associated with higher expression of 3-gene effector T cell signature (median, PFS: 7.8 vs. 4.3 months, p = 0.02; ORR: 64.2% vs. 7.1%, p = 0.004) and 18-gene inflamed T cell signature (median, PFS: 8.6 vs. 4.3 months, p = 0.01; ORR: 64.2% vs. 7.1%, p = 0.004). Moreover, our findings highlighted the adverse predictive value of mast cells in immuno-chemotherapy for BTCs for the first time. Conclusions: Sintilimab plus GemCis displayed a promising antitumor activity and acceptable safety profile as a first-line treatment in patients with advanced BTC. Multiomics potential predictive biomarkers are identified and warrant further verification. Clinical trial information: ChiCTR2000036652 . <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.4086","type":"journal-article","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:37:26Z","timestamp":1685893046000},"page":"4086-4086","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Sintilimab plus gemcitabine and cisplatin as a first-line treatment for patients with advanced biliary tract cancer: A biomolecular exploratory, phase II clinical trial."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"chictr2000036652","registry":"10.18810\/chictr"}],"author":[{"given":"Zhen-gang","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Oncology, Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian-mei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Lou","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-jie","family":"Tao","sequence":"additional","affiliation":[{"name":"Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi-yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Han","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Oncology, Eastern Hepatobiliary Surgery Hospital, the Naval Medical University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-pei","family":"Shang","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-long","family":"Dong","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He-ming","family":"Xu","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lie-ping","family":"Guo","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunjie","family":"Song","sequence":"additional","affiliation":[{"name":"Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuang","family":"Qi","sequence":"additional","affiliation":[{"name":"Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanglong","family":"Deng","sequence":"additional","affiliation":[{"name":"Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.4086","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T15:47:43Z","timestamp":1685893663000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.4086"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.4086"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.4086","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T06:04:46Z","timestamp":1705903486557},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"NanOlogy, LLC"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p> e15187 <\/jats:p><jats:p> Background: The safety of local delivery of large surface area microparticle paclitaxel (LSAM-PTX) or docetaxel (LSAM-DTX) to solid tumors has been evaluated in Phase 1\/2 trials across 156 subjects with 43% (67\/156) on various concurrent standard of care (SOC) therapies. Local administration of LSAM-PTX or LSAM-DTX leads to a reduction in systemic drug exposure and drug-related adverse events (AE) and may reduce toxicities encountered in combination systemic treatment regimens. This report summarizes safety findings in subjects co-administered LSAM-PTX or LSAM-DTX and common SOC therapies for treatment of carcinomas. Methods: During the study follow-up periods, AE and serious AE (SAE) were coded (MedDRA 16.1 -23.1) and assessed (NCI CTCAE 3 - 5). Results: In 7 studies (median age 69 years (range 37-96), 61% male, 88% white) (Table), LSAM-PTX administrations occurred as follows: intraperitoneal (n = 31 subjects), intraprostatic (n = 17), and intratumoral (n = 72). A median of 1 cycle (range 1-6) of LSAM-PTX was administered. LSAM-DTX was injected once into bladder tissue after tumor resection followed by a median of 10 cycles (range 7-10) of intravesical instillation in 36 subjects. 59 subjects (median age 65 (range 48-86), 53% male, 88% white) received local LSAM-PTX and concomitant chemotherapy, immunotherapy, or radiation. Rates of subjects who had Grade 3 SAE possibly related to LSAM-PTX were 29%, 24%, 16%, 6.7% and 5.0% in paclitaxel, carboplatin, 5-FU, nab-paclitaxel, and gemcitabine combinations, respectively. Grade 4 SAE possibly related to LSAM-PTX were found in 1 subject each co-administered pembrolizumab (13%), carboplatin (5.9%), and paclitaxel (7.1%). Subjects treated with 5-FU, gemcitabine, and nab-paclitaxel reported no related Grade 4 SAE. No Grade 5 SAE were deemed possibly related to LSAM-PTX. 8 subjects (median age 78 (range 54-89), 100% male, 88% white) received local LSAM-DTX therapy in combination with SOC therapies. No Grade 3-5 AE were reported with LSAM-DTX in combination with gemcitabine, carboplatin, pembrolizumab, avelumab or radiation. Conclusions: Local treatment of solid tumors with LSAM-PTX or LSAM-DTX has the potential to overcome some limitations of SOC therapies by increasing tumor dwell time and reducing systemic toxicities which are often exacerbated in combinatorial treatment regimens. Clinical trial information: NCT00666991 , NCT03636256 , NCT03077659 , NCT04221828 , NCT03029585 , NCT03077685 , NCT04314895 . [Table: see text] <\/jats:p>","DOI":"10.1200\/jco.2023.41.16_suppl.e15187","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T16:48:12Z","timestamp":1686156492000},"page":"e15187-e15187","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Safety of locally administered large surface area microparticle paclitaxel and docetaxel in combination with standard of care cancer therapies."],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct00666991","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03077659","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03077685","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03029585","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03636256","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04314895","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04221828","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Shelagh","family":"Verco","sequence":"first","affiliation":[{"name":"US Biotest, Inc., San Luis Obispo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Maulhardt","sequence":"additional","affiliation":[{"name":"US Biotest, Inc., San Luis Obispo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyson","family":"Marin","sequence":"additional","affiliation":[{"name":"US Biotest, Inc., San Luis Obispo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antony","family":"Verco","sequence":"additional","affiliation":[{"name":"US Biotest, Inc., San Luis Obispo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2023.41.16_suppl.e15187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T16:51:27Z","timestamp":1686156687000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2023.41.16_suppl.e15187"}},"issued":{"date-parts":[[2023,6,1]]},"references-count":0,"journal-issue":{"issue":"16_suppl","published-print":{"date-parts":[[2023,6,1]]}},"alternative-id":["10.1200\/JCO.2023.41.16_suppl.e15187"],"URL":"https:\/\/doi.org\/10.1200\/jco.2023.41.16_suppl.e15187","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2023,6,1]]},"assertion":[{"value":"2023-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T20:40:20Z","timestamp":1716324020168},"reference-count":31,"publisher":"BMJ","issue":"4","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Evid Based Med"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>In what became a highly-publicised move, the American Heart Association (AHA) and American College of Cardiology (ACC) effectively dropped low-density lipoprotein cholesterol (LDL-C) goals from their most recent guidelines pertaining to the matter. However, due to developments since the AHA and ACC released their current guidelines, some have called for a return to focusing on LDL-C goals. This article puts forth an overview of the salient issues at hand, important evidence-based considerations, and a conclusion that shifting focus away from LDL-C goals is clearly an evidence-based step in the right direction. 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Ther"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>This article evaluates the efficacy and safety of baricitinib 4\u00a0mg versus placebo in United States including Puerto Rico (US) and rest of the world (ROW) subpopulations using data pooled from RA-BEAM and RA-BUILD, which enrolled patients with moderate-to-severe adult-onset rheumatoid arthritis (RA).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In RA-BEAM, patients with an inadequate response (IR) to methotrexate,\u2009at least one X-ray erosion, and high sensitivity C-reactive protein (hsCRP)\u2009\u2265\u20096\u00a0mg\/L were randomized to placebo or orally administered baricitinib 4\u00a0mg daily or subcutaneously administered adalimumab 40\u00a0mg every other week. In RA-BUILD, patients with an IR to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) and with hsCRP\u2009\u2265\u20093.6\u00a0mg\/L were randomized to placebo or baricitinib 2 or 4\u00a0mg daily. Patients in both trials were biologic naive. In this post hoc analysis, data from both studies were pooled (714 baricitinib 4\u00a0mg-treated, 716 placebo-treated patients).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Overall, 188 US and 1242 ROW patients were included. Subgroups differed in baseline characteristics including race, weight, age, time since RA diagnosis, current corticosteroid use, and previous csDMARD use. At weeks 12 and 24, baricitinib-treated patients had larger responses compared to placebo-treated patients for multiple efficacy outcomes: American College of Rheumatology 20\/50\/70 response, low disease activity, remission, Disease Activity Score 28-C-reactive protein, and Health Assessment Questionnaire-Disability Index. Overall, similar efficacy was observed in US and ROW subgroups with no notable safety differences between subgroups at weeks 12 or 24.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Baricitinib 4\u00a0mg was efficacious compared to placebo in US and ROW subpopulations. Safety was similar between subgroups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Funding<\/jats:title>\n                <jats:p>Eli Lilly &amp; Company and Incyte Corporation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial Registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov identifiers, NCT01721057; NCT01710358.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s40744-018-0110-x","type":"journal-article","created":{"date-parts":[[2018,4,21]],"date-time":"2018-04-21T06:44:13Z","timestamp":1524293053000},"page":"43-55","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs in United States and Rest of World: A Subset Analysis"],"prefix":"10.1007","volume":"5","clinical-trial-number":[{"clinical-trial-number":"nct01710358","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Alvin F.","family":"Wells","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Greenwald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Bradley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jahangir","family":"Alam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vipin","family":"Arora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia E.","family":"Kartman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,4,21]]},"reference":[{"key":"110_CR1","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/clpt.2011.325","volume":"91","author":"I Colmegna","year":"2012","unstructured":"Colmegna I, Ohata BR, Menard HA. 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The research comprised three workstreams (WSs) focused on older women.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Maximising survival<\/jats:title><jats:p>WS1 \u2013 to identify the role of older women\u2019s and surgeons\u2019 preferences in cancer treatment decisions and whether comorbidity or fitness for surgery has an impact on survival.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Minimising complications<\/jats:title><jats:p>WS2 \u2013 to assess multifrequency bioimpedance (BEA) compared with perometry in identifying women predisposed to develop lymphoedema after axillary node clearance (ANC) surgery. WS3 \u2013 to assess, in women at risk of lymphoedema, whether or not applying compression garments prevents the onset of lymphoedema.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Design<\/jats:title><jats:p>WS1 \u2013 a prospective, consecutive cohort of surgical consultations with women aged \u2265\u200970 years with operable breast cancer. Interviews and questionnaire surveys of surgeons\u2019 and women\u2019s perceptions of responsibility for treatment decisions (Controlled Preference Score), effects related to survival and secondary outcomes. WS2 \u2013 women undergoing ANC for cancer in 21 UK centres underwent baseline and subsequent BEA, and perometer arm measurements and quality-of-life (QoL) assessments. WS3 \u2013 a randomised controlled trial testing standard versus applying graduated compression garments to the affected arm, for 1 year, in WS2 patients developing arm swelling.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Setting<\/jats:title><jats:p>Breast outpatient clinics in hospitals with specialist lymphoedema clinics.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Participants<\/jats:title><jats:p>WS1 \u2013 patients aged \u2265\u200970 years with newly diagnosed, operable, invasive breast cancer. WS2 \u2013 women with node-positive cancer scheduled to undergo ANC. WS3 \u2013 WS2 participants developing a 4\u20139% increase in arm volume.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Interventions<\/jats:title><jats:p>WS1 \u2013 observational study. WS2 \u2013 observational study. WS3 \u2013 application of graduated compression garments to affected arm, compared with standard management, for 1 year.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Outcomes<\/jats:title><jats:p>WS1 \u2013 self-report and clinically assessed health, QoL, complications and survival. WS2 \u2013 perometer and bioimpedance spectroscopy (BIS) measurements, QoL and health utility; and sensitivity and specificity of BIS for detecting lymphoedema compared with perometer arm measurements; in addition, a health economics assessment was performed. WS3 \u2013 time to the development of lymphoedema [\u2265\u200910% relative arm-volume increase (RAVI)] from randomisation.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Results<\/jats:title><jats:p>WS1 \u2013 overall, 910 women were recruited, but numbers in the substudies differ depending on consent\/eligibility. In a study of patient\/surgeon choice, 83.0% [95% confidence interval (CI) 80.4% to 85.6%] had surgery. Adjusting for health and choice, only women aged &gt;\u200985 years had reduced odds of surgery [odds ratio (OR) 0.18, 95%CI 0.07 to 0.44]. Patient role in treatment decisions made no difference to receipt of surgery. A qualitative study of women who did not have surgery identified three groups: \u2018patient declined\u2019, \u2018patient considered\u2019 and \u2018surgeon decided\u2019. In a survival substudy, adjusting for tumour stage, comorbidity and functional status, women undergoing surgery had one-third the hazard of dying from cancer. Serious complications from surgery were low and not predicted by older age. In a substudy of the effect of surgical decision-making on HRQoL, 59 (26%) received preferred treatment decision-making style. In multivariate analyses, change in HRQoL was associated neither with congruence (<jats:italic>p<\/jats:italic>\u2009=\u20090.133) nor with receipt of surgery (<jats:italic>p<\/jats:italic>\u2009=\u20090.841). In a substudy of receipt of chemotherapy in women aged \u2265\u200965 years, adjusting for tumour characteristics, health measures and choice, women aged \u2265\u200975 years had reduced odds of chemotherapy (OR 0.06, 95%CI 0.02 to 0.16). WS2 \u2013 lymphoedema by 24 months was detected in 21.4% of women by perometry (24.4% sleeve application) and in 39.4% by BIS. Perometer and BIS measurements correlated at 6 months (<jats:italic>r<\/jats:italic>\u2009=\u20090.61). Specificity for sleeve application was greater for perometry (94% CI 93% to 96%) at 24 months, as was a positive predictive value of 59% (95% CI 48% to 68%). Lymphoedema diagnosis reduced QoL scores. Sleeve application in the absence of RAVI of &gt;\u20099% did not improve QoL or symptoms. A composite definition of lymphoedema was developed, comprising a 9% cut-off point for perometer and self-reported considerable swelling. Diagnostic accuracy was \u2265\u200994% at 6, 12 and 24 months. WS3 \u2013 the PLACE (Prevention of Lymphoedema After Clearance of External compression) trial recruited 143 patients, but recruitment was slow and closed early on the advice of the Independent Data Monitoring Committee. A qualitative substudy identified a number of barriers to recruitment.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-10\"><jats:title>Conclusions<\/jats:title><jats:p>Half of older patients felt that they influenced decisions about their treatment. No relationship between decision preference being fulfilled and HRQoL in elderly patients diagnosed with cancer occurred, and older age did not predict complications. Primary surgery reduced the hazard of dying of cancer by two-thirds, independent of age, health and tumour characteristics. Women aged \u2265\u200975 years have reduced odds of receiving chemotherapy. Lymphoedema (along with a BMI of &gt;\u200930\u2009kg\/m<jats:sup>2<\/jats:sup>, cigarette smoking and chemotherapy) reduces QoL. Changes in arm volume of &gt;\u20099% predicted lymphoedema requiring and benefiting from sleeve application. The PLACE trial qualitative work provides a number of insights into problems of recruitment that were specific to this trial (stigma of compression garments) but that are also generalisable to other RCTs.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-11\"><jats:title>Limitations<\/jats:title><jats:p>Both WS1 and WS2 were large, multicentre, UK cohort, observational studies. The WS3 PLACE trial has not reported yet but closed with approximately half of the patients originally planned.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-12\"><jats:title>Future work<\/jats:title><jats:p>Research producing objective measures for sleeve prescription in the NHS is required.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-13\"><jats:title>Trial registration<\/jats:title><jats:p>Current Controlled Trials ISRCTN48880939.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-14\"><jats:title>Funding<\/jats:title><jats:p>This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in<jats:italic>Programme Grants for Applied Research<\/jats:italic>; Vol. 7, No. 5. See the NIHR Journals Library website for further project information. Additional support for WS1 came from a Breast Cancer Campaign Grant and a NIHR Postdoctoral Fellowship. ImpediMed (Carslbad, CA, USA;<jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:role=\"web\" xlink:href=\"https:\/\/www.impedimed.com\">www.impedimed.com<\/jats:uri>) provided bioimpedance L-Dex<jats:sup>\u00ae<\/jats:sup>machines and electrodes for the study and Sigvaris provided the external compression garments free of charge for the (PLACE) trial.<\/jats:p><\/jats:sec>","DOI":"10.3310\/pgfar07050","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T09:54:03Z","timestamp":1566467643000},"page":"1-260","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Individualising breast cancer treatment to improve survival and minimise complications in older women: a research programme including the PLACE RCT"],"prefix":"10.3310","volume":"7","clinical-trial-number":[{"clinical-trial-number":"isrctn48880939","registry":"10.18810\/isrctn","type":"results"}],"author":[{"given":"Nigel","family":"Bundred","sequence":"first","affiliation":[{"name":"Department of Academic Surgery, Manchester University NHS Foundation Trust, Manchester, UK"},{"name":"Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Todd","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Academic Surgery, Manchester University NHS Foundation Trust, Manchester, UK"},{"name":"Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK"},{"name":"Clinical Trials Co-ordination Unit, The Christie NHS Foundation Trust, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3004-2821","authenticated-orcid":true,"given":"Vaughan","family":"Keeley","sequence":"additional","affiliation":[{"name":"Department of Palliative Medicine, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnie","family":"Purushotham","sequence":"additional","affiliation":[{"name":"Breast Unit, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2142-5767","authenticated-orcid":true,"given":"Adrian","family":"Bagust","sequence":"additional","affiliation":[{"name":"Management School, University of Liverpool, Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Foden","sequence":"additional","affiliation":[{"name":"Department of Academic Surgery, Manchester University NHS Foundation Trust, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Bramley","sequence":"additional","affiliation":[{"name":"Oncology Research, Pennine Acute Hospitals NHS Trust, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-1513","authenticated-orcid":true,"given":"Katie","family":"Riches","sequence":"additional","affiliation":[{"name":"Department of Palliative Medicine, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6221","published-online":{"date-parts":[[2019,8]]},"reference":[{"key":"key20190821104345024_ref1-bib1","unstructured":"Department of Health and Social Care. 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URL: www.nice.org.uk\/guidance\/mib111 (accessed 8 May 2019)."},{"key":"key20190821104345024_ref1-bib33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10549-015-3357-8","article-title":"Comparison of multi-frequency bioimpedance with perometry for the early detection and intervention of lymphoedema after axillary node clearance for breast cancer","volume":"151","author":"Bundred","year":"2015","journal-title":"Breast Cancer Res Treat"},{"volume-title":"Clinical Trial Protocol: Multi-frequency Bioimpedance in the Early Detection of Lymphoedema after Axillary Surgery","year":"2015","author":"Bundred","key":"key20190821104345024_ref1-bib34"},{"key":"key20190821104345024_ref1-bib35","volume-title":"An Introduction to Medical Statistics","author":"Bland","year":"2005","edition":"3rd edn."},{"key":"key20190821104345024_ref1-bib36","first-page":"26","article-title":"Reliability and limits of agreement of circumferential, water displacement, and optoelectronic volumetry in the measurement of upper limb lymphedema","volume":"40","author":"Deltombe","year":"2007","journal-title":"Lymphology"},{"key":"key20190821104345024_ref1-bib37","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1158\/1055-9965.EPI-06-0168","article-title":"The epidemiology of arm and hand swelling in premenopausal breast cancer survivors","volume":"16","author":"Paskett","year":"2007","journal-title":"Cancer Epidem Biomarkers"},{"key":"key20190821104345024_ref1-bib38","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1177\/096228029800700404","article-title":"Evaluation of diagnostic tests without gold standards","volume":"7","author":"Hui","year":"1998","journal-title":"Stat Methods Med Res"},{"issue":"50","key":"key20190821104345024_ref1-bib39","doi-asserted-by":"publisher","DOI":"10.3310\/hta11500","article-title":"Evaluation of diagnostic tests when there is no gold standard. 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Cancer Statistics Registrations: Registrations of Cancer Diagnosed in 2011, England. Series MB1 No. 42. Newport: ONS; 2011. 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Best Research for Best Health \u2013 A New National Health Research Strategy. London: Department of Health and Social Care; 2006."},{"key":"key20190821104345024_ref1-bib53","unstructured":"UK Clinical Trials Gateway. Public and Patient Survey. Southampton: NIHR; 2012. URL: www.nihr.ac.uk\/documents\/about-NIHR\/NIHR- Publications\/UKCTG-Report-Public-and-Patient-Survey-Report-2012.pdf (accessed 19 April 2018)."},{"key":"key20190821104345024_ref1-bib54","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1478-4505-13-8","article-title":"Barriers and opportunities for enhancing patient recruitment and retention in clinical research: findings from an interview study in an NHS academic health science centre","volume":"13","author":"Adams","year":"2015","journal-title":"Health Res Policy Syst"},{"key":"key20190821104345024_ref1-bib55","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1745-6215-15-5","article-title":"Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled 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Research"],"language":"en","link":[{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/publications\/pgfar07050\/pgfar07050.xml","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2030306","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2030306","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T15:47:39Z","timestamp":1692114459000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/pgfar\/pgfar07050"}},"issued":{"date-parts":[[2019,8]]},"references-count":62,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["10.3310\/pgfar07050"],"URL":"https:\/\/doi.org\/10.3310\/pgfar07050","ISSN":["2050-4322","2050-4330"],"issn-type":[{"type":"print","value":"2050-4322"},{"type":"electronic","value":"2050-4330"}],"published":{"date-parts":[[2019,8]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"}]},{"indexed":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:21:54Z","timestamp":1706574114791},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"4_suppl","funder":[{"name":"None."}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:p> 684 <\/jats:p><jats:p> Background: Preliminary results of the interim analysis of the ARCADIA trial have shown that combining multitargeted receptor tyrosine kinase inhibitor CABO with the checkpoint inhibitor DURVA has promising activity and a manageable safety profile in patients (pts) affected by UC recurred or progressed after failure of at least one line of platinum-based chemotherapy for metastatic disease in a phase II study (NCT03824691). To identify peripheral blood biomarkers potentially associated with clinical response, we carried out a quantitative profiling of innate and adaptive immune subsets from a subset of treated pts. Methods: From 09\/2019 and 08\/2023 blood samples from 65 pts were collected at baseline and before the third treatment cycle. Absolute cell counts for 29 innate and adaptive immune subsets were determined by multiparametric flow cytometry. Results: In pre-therapy samples a significant higher counts for all CD45+ leukocytes were found in non-responders compared to responders (p=0.0053, Mann Whitney test, n= 27 patients). This was, explained by higher counts for CD16+CD15+ neutrophils (p=0.0005), classical CD14+CD16- (p=0.0119) and CD14++CD16+ intermediate (p=0.0186) monocytes, CD56dim CD16+ NK cells (p=0.0365) and Lin-HLA-DR-\/LoCD33+CD14+CD15- M-MDSCs (p=0.0281). At baseline, higher neutrophils counts were associated with worse PFS (p=0.0117, log rank test), while higher eosinophils counts were associated with improved PFS (p=0.0158). Compared to responders, non-responders underwent a significant reduction in post-treatment counts for all CD45+ leukocytes (p=0,0024, Wilcoxon matched pair test), due to reduction of neutrophils (p=0.0068), CD15+CD16- eosinophils (p=0.0068), CD3+ T cells (p=0.0425) CD19+ B cells (p=0.0068), classical monocytes (p=0.0034), activated (HLA-DR+) CD56dim CD16- NK cells (p=0.0068), M-MDSCs (p=0.0161), Lin- HLA-DR-\/Lo CD33+ CD14- CD15+ PMN-MDSCs (p=0.001), Lin- HLA-DR+ CD33- pDCs (p=0.0269) and Lin- HLA-DR+ CD33+ mDCs (p=0.0005). Conclusions: These preliminary findings suggest that high baseline counts for granulocytes, monocytes and MDSCs may negatively impact on response in pts treated with CABO+DURVA. Moreover, baseline neutrophils and eosinophils counts show opposite impact on PFS. Grant support: NET-2016-02361632 from Italian Health Ministry to A. Anichini. Clinical trial information: NCT03824691 . <\/jats:p>","DOI":"10.1200\/jco.2024.42.4_suppl.684","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T21:06:41Z","timestamp":1706562401000},"page":"684-684","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral biomarker analysis in patients with advanced urothelial carcinoma (UC) after platinum chemotherapy treated with cabozantinib (CABO) plus durvalumab (DURVA): Preliminary analysis from the phase 2 ARCADIA trial."],"prefix":"10.1200","volume":"42","clinical-trial-number":[{"clinical-trial-number":"nct03824691","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Patrizia","family":"Giannatempo","sequence":"first","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Sgambelluri","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Stellato","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Guadalupi","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Raggi","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Rametta","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achille","family":"Bottiglieri","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Claps","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Medical Oncology Department, Fondaione IRCCS Istituto Nazionale Tumori, Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferrari Bravo","family":"Walter","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Oldani","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Zimatore","sequence":"additional","affiliation":[{"name":"Genitourinary Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Calareso","sequence":"additional","affiliation":[{"name":"Radiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Alessi","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Advanced Diagnostics Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Verzoni","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo G.","family":"De Braud","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Procopio","sequence":"additional","affiliation":[{"name":"Genitourinary Medical Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Necchi","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Anichini","sequence":"additional","affiliation":[{"name":"Human Tumors Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Mortarini","sequence":"additional","affiliation":[{"name":"Human Tumors Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2024.42.4_suppl.684","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T21:47:11Z","timestamp":1706564831000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2024.42.4_suppl.684"}},"issued":{"date-parts":[[2024,2,1]]},"references-count":0,"journal-issue":{"issue":"4_suppl","published-print":{"date-parts":[[2024,2,1]]}},"alternative-id":["10.1200\/JCO.2024.42.4_suppl.684"],"URL":"https:\/\/doi.org\/10.1200\/jco.2024.42.4_suppl.684","ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"published":{"date-parts":[[2024,2,1]]},"assertion":[{"value":"2024-01-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]},{"indexed":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:17:56Z","timestamp":1720484276986},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"16_suppl","funder":[{"name":"CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD"}],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:p> e16011 <\/jats:p><jats:p> Background: PD-1 inhibitor combined with chemotherapy are the standard first-line treatment for advanced ESCC. Anlotinib, a multitargeted tyrosine kinase inhibitor (TKI), has been demonstrated favorable efficacy and manageable toxicity as both first-line treatment when combined with TP and second-line monotherapy in advanced ESCC. TQB2450 is a novel humanized anti-PD-L1 monoclonal antibody. We conducted a phase II trial to evaluate the efficacy and safety of alotinib combined with TQB2450, cisplatin, and paclitaxel as first-line treatment for advanced ESCC. Here is the update results. Methods: Eligible patients (pts) with previously untreated unresectable locally advanced or metastatic ESCC received TQB2450 (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) combined with paclitaxel (135mg\/m<jats:sup>2<\/jats:sup>, iv, d1, q3w) and cisplatin (60~75mg\/m<jats:sup>2<\/jats:sup>, iv, d1~3, q3w) for 4 - 6 cycles as initial therapy. Patients without progressive disease (PD) continued to receive same dose of anlotinib plus TQB2450 as maintenance therapy until PD or unacceptable toxicity. The primary endpoint was PFS (RECIST version 1.1). Secondary endpoints included iPFS (iRECIST), ORR (RECIST version 1.1), DCR, DOR and safety. Results: At the data cutoff date of November 14, 2023, 50 pts were enrolled with a median age of 64 years (range 41-74), male (39\/50, 78%) and ECOG PS 1 (38\/50, 76%). Among 43 tumor response evaluable pts , 4 achieved complete response, 32 had partial response and 8 had stable disease. The ORR was 72.00% (95% CI: 57.51, 83.77) and the DCR was 84.0% (95% CI: 70.89, 92.83). The 12-month PFS rate was 66.84% (95% CI: 48.73, 79.79) and the 12-month OS rate was 74.22% (95% CI: 59.06, 84.46), but the median PFS and OS was not reached. The incidence of \u2265G3 treatment emergent adverse events was 78%, mainly included neutropenia (44%, 22\/50), leukopenia (24%, 12\/50) and hypertension (20%, 10\/50). 20 pts (48%, 24\/50) occurred serious AEs. Conclusions: The combination of TQB2450 plus anlotinib, paclitaxel and cisplatin, demonstrated encouraging efficacy and manageable toxicity in patients with advanced ESCC when used as first-line treatment. 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