bluuebunny/crossref_metadata_2025_split huggingface dataset:
PET-directed combined modality therapy for gastroesophageal junction cancer: First results of the prospective MEMORI trial.
Authors: Lorenzen Sylvie , Quante Michael , Rauscher Isabel , Slotta-Huspenina Julia , Becker Karl Friedrich , Weichert Wilko , Feith Marcus , Friess Helmut , Combs Stephanie E , Weber Wolfgang , Haller Bernhard , Angele Martin K , Albertsmeier Markus , Blankenstein Christiane , Kasper Stefan , Zimmermann Jens Peter , Algül Hana , Schmid Roland M. , Schwaiger Markus , Siveke Jens T 
Published: May 2019

4018 Background: We evaluated a PET-guided treatment stratification for improvement in obtaining negative surgical margins (R0) in resectable gastroesophageal junction (GEJ) adenocarcinoma. According to sequential 18F-FDG PET, only 40–50% of patients (pts) respond to neoadjuvant chemotherapy (CTX). Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). Methods: 75 pts with resectable GEJ adenocarcinomas were enrolled in this interventional, prospective, non-randomized multicenter trial. Pts underwent baseline 18F-FDG PET scan followed by 1 cycle of CTX (physicians’ choice, e.g. EOX, XP, mFOLFOX6). PET was repeated at day 14-21 and responders (P-R), defined as ≥ 35% decrease in SUVmax from baseline, continued with CTX. P-NR switched to CRT (41.4 Gy/23 fractions with weekly carboplatin/paclitaxel). Pts underwent surgery 4-6 weeks post-CTX/CRT. Primary objective was an improvement of R0 resection rates in P-NR above a proportion of 70% based on results from the MUNICON1/2 trials. Secondary endpoints include disease-free survival (DFS), overall survival (OS), measured from randomization to death from any cause, and translational endpoints. Results: Between 12/2014 and 07/ 2018 160 pts with resectable GEJ adenocarcinomas were prospectively screened with PET in three German university centers. Overall, 85 pts (53%) could not be included due to previously undetectable metastases (40/25%), no or too low FDG uptake of the primary tumor (21/13%), other reasons (24/15%). 75 eligible pts were enrolled in the study and 69 were evaluable. Based on PET criteria, 47 (68%) and 22 (32%) were P-R and P-NR, respectively. R0 resection rates were 94% (44/47) for P-R and 91% (20/22) for P-NR. Pathologic complete remission (pCR; < 10% vital tumor cells), was 33% (15/46) in P-R and 55% (12/22) in P-NR. With a median follow-up time of 19 months (mo), estimated 18 mo DFS was 71%/61% for P-R/P-NR, respectively. Observed median 18 mo OS was 95% for P-R and 75% for P-NR. Conclusions: Alternative CRT for GEJ adenocarcinoma improved R0- and pCR rates among pts who were P-NR after induction CTX. PET response was prognostic for a prolonged OS and DFS. Clinical trial information: 2014-000860-16.
Randomized phase III trial of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric cancer (JCOG0912).
Authors: Katai Hitoshi , Mizusawa Junki , Katayama Hiroshi , Morita Shinji , Yamada Takanobu , Bando Etsuro , Misawa Kazunari , Takagi Masakazu , Takagane Akinori , Teshima Shin , Koeda Keisuke , Nunobe Souya , Yoshikawa Takaki , Terashima Masanori , Sasako Mitsuru ,   Stomach Cancer Study Group of Japan Clinical Oncology Group
Published: May 2019

4020 Background: The number of patients undergoing laparoscopy-assisted distal gastrectomy (LADG) has been increasing worldwide. Several retrospective studies have demonstrated equivalent survival after LADG compared to open distal gastrectomy (ODG). However, no confirmatory randomized controlled trials has been published in a peer review journal to evaluate the efficacy of LADG compared with ODG, ensuring strict surgical skill and quality control of surgery. We conducted phase III study to confirm that LADG is not inferior to ODG in efficacy. Methods: Eligibility criteria included histologically proven adenocarcinoma in the middle or lower third of the stomach; clinical stage I tumor (T1N0, T1N1, T2(MP)N0). Patients were preoperatively randomized to ODG or LADG. LADG was performed by accredited surgeon. The extent of nodal dissection was decided according to Japanese gastric cancer treatment guidelines. The primary endpoint is relapse-free survival (RFS) and the secondary endpoints are overall survival (OS), short-term clinical outcomes, and postoperative quality of life. Planned sample size was 920 patients in total, which was determined with at least 80% power, a one-sided alpha of 5%, and a non-inferiority margin for a hazard ratio of 1.54. Before the 1st interim analysis, the primary endpoint was amended from OS to RFS in 2015 because the surrogacy of RFS for OS was demonstrated and the predicted number of events for OS was smaller than expected. Results: A total of 921 patients were randomized (ODG 459, LADG 462) between Mar. 2010 and Nov. 2013. Among 921 patients, 912 patients (99%) underwent assigned surgery. Conversion to ODG was needed for 16 patients (3.5%) in LADG arm mainly due to advanced disease. 5-year RFS was 94.0% (95% CI: 91.4-95.9%) in ODG and 95.1% (92.7-96.8%) in LADG. LADG was non-inferior to ODG for RFS. (HR: 0.84 [90% CI: 0.56-1.27 ( < 1.54)], p for non-inferiority = 0.008). 5-year OS was 95.2% (92.7-96.8) in ODG and 97.0% (94.9-98.2) in LADG (HR: 0.83 [95% CI: 0.49-1.40]). Conclusions: The non-inferiority of LADG to ODG in RFS was confirmed. LADG has been established as one of the standard treatments for clinical stage I gastric cancer. Clinical trial information: UMIN000003319.
Perioperative chemotherapy alone versus preoperative chemoradiotherapy for locally advanced distal esophageal and gastroesophageal junction cancer: A 10-year review of the British Columbia (BC) Cancer Registry.
Authors: Liu Shiru Lucy , Yu Irene S. , Lau Sally CM , Zhao Yizhou , Schellenberg Devin , Gill Sharlene , Lim Howard John 
Published: May 2019

4028 Background: The optimal treatment strategy for resectable cancer of the distal esophagus (ESOPH) and gastroesophageal junction (GEJ) remains controversial. This study evaluates patterns of practice in BC, rates of complete surgical resection, and survival outcomes of patients treated with perioperative chemotherapy alone (CA), per MAGIC or FLOT4 protocol, versus preoperative chemoradiotherapy (CRT), per CROSS protocol. Methods: We undertook a provincial analysis of initially resectable, locally advanced, cancer of the ESOPH and/or GEJ who underwent surgery in BC, from 2008 to 2018. Baseline patient, tumor, treatment, and clinical outcome data were collected from the BC Cancer Registry. Kaplan-Meier survival and multivariate regression analyses were conducted. Results: Among 575 patients, 468 underwent surgery and were included (Table). More surgeries were aborted intraoperatively in the CA cohort compared to CRT (12% vs 2%, p<0.001). There was no difference in age, sex, or ECOG performance status among the cohorts, and 83% were adenocarcinoma. While 82% of ESOPH involving GEJ (N = 251, 54%) is treated with CRT, only 53% of GEJ alone (N=217, 46%) is treated with CRT (p<0.001). CRT is associated with a higher rate of complete or partial pathologic response compared to CA (59% vs 39%, p=0.002). R0 resection rate was 90% and 94% in the CA and CRT cohort, respectively (p=0.383). There is no statistically significant difference in overall survival, with medians of 29.6 and 26.0 months for patients treated with CA and CRT, respectively (p=0.723). Cancer-specific survival is also not significantly different (p=0.565). In the CA cohort, 37% of patients complete all 8 cycles of FLOT and 52% of patients complete all 6 cycles of MAGIC (p=0.396). Conclusions: Patients treated with CRT have higher rates of complete resection and pathologic response, but their survival is not significantly different compared to those treated with CA. [Table: see text]
Phase 2 study of camrelizumab (anti-PD-1 antibody) combined with apatinib and chemotherapy for the first-line treatment of advanced esophageal squamous cell carcinoma.
Authors: Zhang Bo , Qi Ling , Wang Xi , Jiang Jun , Zhang Xin , Liu Yun , Mu Lan , Huang Jing 
Published: May 2019

4033 Background: Both anti-PD-1 antibodies and molecular antiangiogenic agents have shown promising anti-tumor activities in patients with advanced esophageal cancer. We conducted this single-center phase 2 study to evaluate the efficacy and safety of camrelizumab (anti-PD-1 antibody) plus apatinib (VEGFR2-TKI) in combination with liposomal paclitaxel and nedaplatin in the first-line treatment of patients with esophageal squamous cell carcinoma (ESCC). Methods: Patients with unresectable locally advanced or metastatic ESCC received camrelizumab 200mg d1, liposomal paclitaxel 150mg/m2 d1, nedaplatin 50mg/m2 d1 and apatinib 250mg d1-14. Treatments were repeated every 14 days for up to 6-9 cycles, followed by maintenance therapy with camrelizumab, apatinib, or both. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. PD-L1 positivity, defined as a combined positive score (CPS) ≥1, was evaluated by immunohistochemistry (IHC). Results: Between Aug 6th 2018 and Feb 6th 2019, a total of 29 patients were enrolled. The median age was 62 years (43-70). Most patients were male (22/29, 75.9%) with metastatic disease (25/29, 86.2%). Response evaluation by independent central review was available in 26 patients, with 19 achieving a best response of PR, 6 with SD, and 1 with PD. The ORR and DCR were 73.1% (19/26) and 96.2% (25/26), respectively. Data for PFS and OS were not matured. The most common grade 3/4 adverse events were leucopenia (21/29, 72.4%) and neutropenia (15/29, 51.7%). Two cases of treatment-related SAEs occurred, both led to hospitalization: one patient developed grade 3 febrile neutropenia, grade 4 leucopenia and grade 3 anorexia; another patient developed grade 4 toxic epidermal necrolysis. Conclusions: Camrelizumab plus apatinib in combination with liposomal paclitaxel and nedaplatin could be a new treatment option for patients with unresectable locally advanced or metastatic ESCC. Clinical trial information: NCT03603756.
Prognostic value of serum soluble programmed death-ligand 1 (sPDL1) and dynamics during chemotherapy in advanced gastric cancer patients.
Authors: Park Woochan , Bang Ju-Hee , Nam Ah-Rong , Park Ji Eun , Kim Mei Hua , Oh Kyoung Seok , Bang Yung-Jue , Oh Do-Youn 
Published: May 2019

4034 Background: The soluble form Programmed Death-Ligand 1(sPDL1) is suggested to have immunosuppressive activity and under investigation as candidate biomarker for immuno-oncology drug development. In this study, we measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). Methods: We prospectively enrolled 68 GC patients who were candidates for palliative standard 1st-line chemotherapy, and blood was serially collected at pre-and post-one cycle of chemotherapy, at best response and disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progression-free survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off values of sPDL1 levels and changes for survivals were found using C-statistics. Results: The median baseline sPDL1 was 0.8ng/mL(range, 0.06 - 6.06ng/mL). The median OS and PFS were 14.9 months (95% CI: 7.33-22.47) and 8.0 months (95% CI: 5.96-10.0), respectively. sPDL1 and NLR showed a positive correlation. Patients with low levels of sPD-L1 at diagnosis ( < 1.92 ng/mL) showed a better OS and PFS than the patients with a high sPDL1 (OS: 18.3 vs. 95 months, P = 0.057, PFS: 8.9 vs. 6.0 months, P = 0.04). The baseline sPDL1 before treatment were higher in the PD group than in the SD and PR groups (mean:2.91, 1.17, 1.19, P = 0.019). Patients whose sPDL1 increased after 1st cycle of chemotherapy showed the tendency of worse PFS and OS. When disease progressed, sPDL1 increased compared with baseline (mean:1.31, 1.45, P = 0.029). Conclusions: sPDL1 at pre-chemotherapy confers the prognostic value for PFS and OS in GC patients under palliative 1st-line chemotherapy. The dynamics of sPDL1 during chemotherapy correlates with disease courses.
POF (paclitaxel plus FOLFOX) versus IP PAC (intraperitoneal paclitaxel plus FOLFOX) versus FOLFOX as a first-line treatment in advanced gastric cancer (AGC): Update from a multicenter, randomized phase II trial, FNF-004 trial.
Authors: Lin Rongbo , Chen Yigui , Zhu Jinfeng , Lin Peicheng , Chen Wujin , Fang Wenzheng , Li Hui , Liu Jie , Zhao Shen , Fan Nan-Feng 
Published: May 2019

4035 Background: The PFS with POF was statistically significantly improved and IP PAC was trending to improve compared to FOLFOX in first-line setting in AGC were reported in 2019 ASCO-GI (abstract 6). Update and subgroup analysis were released herein. Methods: The patients with AGC were randomized to three groups. The POF or IP PAC was paclitaxel 135 mg/m2intravenously (POF) or paclitaxel 80 mg/m2 intraperitoneally (IP PAC) followed by mFOLFOX6 omitted 5-Fu bolus. Every 14 days repeated for all three regimens. Up to 9 cycles of treatment were administered, followed by S-1 until disease progression. The primary endpoint was PFS. Results: Between Nov 2015 and May 2018, 89 pts (30 POF, 29 IP PAC, 30 FOLFOX) were randomly allocated. PFS, OS and RR were seen in the table below. Either POF or IP PAC was statistically significantly better than FOLFOX in PFS. In subgroup with female, peritoneal metastasis, ascites, lymphadenopathy in peritoneal cavity, number of organs involved > 2, POF was statistically significantly better than FOLFOX in PFS. In subgroup with female, gastrium of primary tumor site, peritoneal metastasis, ascites, no lymphadenopathy out of peritoneal cavity, IP PAC was statistically significantly better than FOLFOX in PFS. Intravenously docetaxel plus S-1 still saw response after IP PAC. Conclusions: either POF or IP PAC improved survival compared to FOLFOX, especially in patients with female or peritoneum metastasis. Only POF, not IP PAC, improved response rate compared to FOLFOX. Clinical trial information: NCT02845908. [Table: see text]
Health-related quality of life (HRQoL) of pembrolizumab (pembro) versus physician choice single-agent paclitaxel, docetaxel, or irinotecan in subjects with advanced/metastatic adenocarcinoma (ACC) or squamous cell carcinoma (SCC) of the esophagus that has progressed after first-line standard therapy (KEYNOTE-181).
Authors: Adenis Antoine , Kulkarni Amit , Girotto Gustavo Colagiovanni , De La Fouchardiere Christelle , Senellart Helene , Van Laarhoven Hanneke W.M. , Hochhauser Daniel , Mansoor Wasat , Al-Rajabi Raed , Norquist Josephine , Suryawanshi Shailaja , Bhagia Pooja , Metges Jean-Philippe 
Published: May 2019

4048 Background: KEYNOTE-181 (NCT02564263) is an open-label, randomized, phase 3 trial in ACC and SCC of the esophagus that evaluated IV pembro 200 mg Q3W for up to 2 years vs investigator choice of single-agent paclitaxel/docetaxel/irinotecan (control). Pembro was superior to control for OS in patients with PD-L1 CPS ≥10 (N = 222; median 9.3 vs 6.7 months; P= 0.0074). Here we present results of prespecified HRQoL analyses in this population. Methods: The EORTC QLQ-C30 and EORTC QLQ-OES18 were administered at baseline; weeks 2, 3, 4, 6, 9, 12, 18; every 9 weeks up to 1 year/end of treatment; and 30-day safety follow-up visit. Data from patients receiving ≥1 dose of study treatment and completing ≥1 HRQoL assessment were analyzed. Least squares mean (LSM) score change from baseline to week 9, 95% CI, and nominal P values were calculated. Time to deterioration (TTD) (≥10-point decline from baseline) was assessed by Kaplan-Meier method and Cox regression model. HRs, 95% CIs, and nominal P values are provided. Results: The HRQoL population included 218 PD-L1 CPS ≥10 patients (107 pembro, 111 control). QLQ-C30 compliance at week 9 was 88.9% for pembro and 83.9% for control. There was no significant difference in LSM between arms (3.68; 95% CI –2.28, 9.64; P= 0.2248) in global health status (GHS)/QoL score. Week 9 QLQ-OES18 compliance was 88.4% for pembro and 83.3% for control. QLQ-OES18 scores were not significantly different between arms. TTD for pain (HR 1.02; 95% CI 0.58, 1.81; P= 0.5282), reflux (HR 1.69; 95% CI 0.83, 3.47; P= 0.9254), and dysphagia (HR 1.81; 95% CI 0.97, 3.37; P= 0.9693) subscales were not significantly different between arms. Conclusions: Over 9 weeks, patients treated with pembro had stable GHS/QoL scores similar to those of patients treated with single-agent docetaxel/paclitaxel/irinotecan. Combined with the superior OS and lower rate of treatment-related AEs seen with pembro, these data support clinically meaningful benefit of pembro in esophageal cancer patients with PD-L1 CPS ≥10. Clinical trial information: NCT02564263.
A pilot study of neoadjuvant FOLFIRINOX followed by chemoradiation for gastric and gastroesophageal cancer: Preliminary results.
Authors: Wo Jennifer Yon-Li , Clark Jeffrey William , Allen Jill N. , Blaszkowsky Lawrence Scott , Keane Florence , Drapek Lorraine C. , Ryan David P. , Corcoran Ryan Bruce , Roeland Eric , Parikh Aparna Raj , Khandekar Melin Janardan , Heist Rebecca Suk , Morse Christopher , Yeap Beow Y. , Ulysse Christine A , Christopher Benjamin , Lanuti Michael , Berger David L. , Mullen John Thomas , Hong Theodore S. 
Published: May 2019

4057 Background: We performed a single-arm pilot study of total neoadjuvant approach including FOLFIRINOX and chemoradiation (CRT) with concurrent carboplatin/taxol (C/T) followed by surgery in patients with locally advanced gastric or gastroesophageal junction (GEJ) cancer. Methods: Patients were enrolled on a NCI sponsored, prospective, single arm study (NCT03279237). Key eligibility criteria included: histologically confirmed T3/4 or lymph node (LN) positive gastric or GEJ cancer, ECOG PS ≤1, age 18+, life expectancy > 3 months. Exclusion criteria included: visceral metastases, prior chemotherapy or RT, or prior targeted therapy. Extensive LN disease beyond the surgical field (supraclavicular or para-aortic) was permitted if deemed feasible to be encompassed within a RT field. Laparoscopy was not required. Pts were treated with neoadjuvant FOLFIRINOX x 8, restaging, CRT (45 Gy for gastric, 50.4 Gy for GEJ) with concurrent C/T, restaging, followed by surgical resection. Dose reductions were at discretion of the treating physician. The primary objective was to determine the rate of completion of FOLFIRINOX x 8 followed by CRT delivered in the preoperative setting. Secondary endpoints included: 1) acute toxicity and 2) pathologic complete response (pCR). Results: From Oct 2017 to June 2018, 25 pts were enrolled. Median age was 60 (range:30-76), 17 pts were male (68%). All pts started FOLFIRINOX; 23 (92%) pts completed all 8 planned cycles. Two pts did not complete the planned 8 cycles due to metastatic progression. Rates of grade 3+ overall, gastrointestinal, and hematologic toxicities were 28%, 12%, and 28% respectively. Of the entire cohort, 23 (92%) pts started chemoRT and 22 (88%) pts completed chemoRT (1 pt died during CRT due to pulseless electrical activity arrest). All 22 pts (88%) who completed CRT went for surgical exploration, of whom 2 pts were found with intraoperative metastases. Therefore, 20 (80%) pts underwent surgical resection. At time of abstract, 1 pt’s pathology is in process; 7 pts had a pCR (37% in resected cohort, 28% in ITT cohort), all with R0 resection. Conclusions: Total neoadjuvant FOLFIRINOX followed by CRT is feasible with acceptable rates of treatment completion and grade 3+ toxicity. In our small series, the rate of pCR is promising and a follow-up study is currently planned. Clinical trial information: NCT03279237.
Safety and efficacy of durvalumab following multimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Results from Big Ten Cancer Research Consortium study.
Authors: Mamdani Hirva , Schneider Bryan J. , Abushahin Laith I. , Birdas Thomas J , Kesler Kenneth , Burney Heather , Perkins Susan M. , Jalal Shadia Ibrahim 
Published: May 2019

4058 Background: Concurrent chemoradiation (CRT) followed by esophagectomy is a standard of care for locally advanced esophageal (LA-EAC) and GEJ adenocarcinoma. Approximately 50% of patients (pts) experience disease relapse within the 1st yr after treatment(tx) completion. No adjuvant tx has been shown to improve survival in these pts. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown upregulation of PD-1/PD-L1 pathway with RT +/- chemotherapy. Methods: We conducted a phase II trial evaluating safety and efficacy of durvalumab (durva), a monoclonal antibody against PD-L1, in pts with LA-EAC and GEJ adenocarcinoma who have viable tumor in surgical specimen after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1yr. Results: 24 pts were enrolled from 4/2016-1/2018 (median age: 60yrs (range, 43-70). 18 received carbo/paclitaxel and 6 received cis/5-FU concurrently with radiation. Staging at diagnosis: T2N0 (n=3, 12.5%), T2N2 (n=3, 12.5%),T3N0 (n=6, 25%), T3N1 (n=6, 25%), T3N2 (n=4, 17%), T3N3 (n=1, 4%), T3Nx (n=1, 4%).19 pts (79%) had positive lymph nodes (LNs) at the time of surgery following CRT. 12 pts completed 1yr of tx, 12 came off tx before 1yr because of relapse(6), AEs(5), and consent withdrawal (1). Median number of tx cycles was 12.5 (range, 2-13). Most common AEs were fatigue (n=8, 33.3%) and nausea (n=6, 25%). 3pts (12.5%) developed grade 3 irAEs: pneumonitis (1), hepatitis (1), colitis (1). At median follow up of 14.5 mo (range, 1.7-24mo), 17 are disease free (including 5 who came off tx before 1yr). 7pts (29%) have relapsed (3 alive, 4 died). 6/7pts had distant relapse (lung, brain, bone, cervical LNs) and 1 had locoregional relapse. 1-yr RFS and OS were 79.2% and 95.5%, respectively. 2-yr OS was 59.2%. RFS probability at 26 mo was 67.9%. Median survival after relapse was 11.1 mo (range, 0.1-11.3mo). Conclusions: Adjuvant durvalumab following trimodality therapy for LA-EAC and GEJ adenocarcinoma was safe and feasible with improvement in 1-yr RFS to 79.2% compared to historical rate of 50%. OS results are encouraging in this high risk pt population. Clinical trial information: NCT02639065.