bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparoscopic sentinel node navigation surgery versus laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer: Final three-year survival results of multicenter randomized controlled phase III trial (SENORITA trial).
Authors: Ryu Keun Won , Kim Young Woo , Min Jae Seok , An Ji Yeong , Yoon Hong Man , Eom Bang Wool , Hur Hoon , Lee Young Joon , Cho Gyu Seok , Park Youngkyu , Jung Mi Ran , Park Ji-Ho , Hyung Woo Jin , Jeong Sang-Ho , Han Mira , Nam Byung-Ho 
Published: May 2020

4510 Background: The benefits and hazards of laparoscopic sentinel node navigation surgery (LSNNS), compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection in early gastric cancer (EGC), are unknown. The SENORITA trial investigated the clinical impact of LSNNS in EGC in terms of short-term surgical outcomes, long-term survival and quality of life. Methods: This study is a prospective, multicenter, randomized controlled, non-inferiority trial. Patients with preoperatively diagnosed gastric adenocarcinoma with T1N0 of 3 cm or less in diameter, regardless of histology, except absolute indication for endoscopic resection were eligible. Patients were randomized to LSG or LSNNS using dual tracers. The primary endpoint is 3-year disease-free survival (3yDFS). Planned sample size per arm is 290 patients with the non-inferiority margin of 2.737 in hazard ratio (HR) assuming that LSG achieve 97% 3yDFS, 5% of type 1 error and 80% of power. Three-year recurrence-free survival (3yRFS), overall survival (3yOS) and disease specific death rate (3yDSDR) were evaluated as secondary endpoints. Results: From March 2013 to December 2016, 580 patients were randomized (LSG arm 292 vs. LSNNS arm 288). After 53 patients dropped out before surgery, operation was performed in 527 patients (269 vs. 258), representing the full analysis set. LSG was performed in 266 according to the protocol excluding 3 open conversion. After exclusion of 13 without LSNNS due to various reasons, LSNNS was performed in 245 patients according to the protocol. After median follow up of 47.5 months, 3yDFS were 95.5% and 91.8% (HR 1.901, CI 0.911 – 3.967), respectively. The 3yRFS was 98.9% and 95.2% (p=0.019), and 3yOS was 99.2% and 97.6% (p=0.166), and 3yDSDR was 99.5% and 99.1% (p=0.591), respectively. Conclusion: LSNNS in EGC did not show non-inferiority compared with LSG in terms of 3yDFS. However, 3yOS and 3yDSDR of LSNNS were comparable to LSG by the rescue surgery of recurrence. LSNNS might be an alternative surgical option instead of LSG in selected EGC patients. Clinical trial information: NCT01804998 .
FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel: Results from the phase II RAMIRIS Study of the AIO.
Authors: Lorenzen Sylvie , Thuss-Patience Peter C. , Pauligk Claudia , Goekkurt Eray , Ettrich Thomas Jens , Lordick Florian , Stahl Michael , Reichardt Peter , Soekler Martin , Pink Daniel , Probst Stephan , Hinke Axel , Goetze Thorsten Oliver , Al-Batran Salah-Eddin 
Published: May 2020

4514 Background: Ramucirumab (Ram) as monotherapy or plus paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. These pts may benefit more from another, non-cross resistant chemotherapy backbone regimen. This trial evaluates the addition of Ram to FOLFIRI as second line treatment. Methods: This is a multicenter, randomized, investigator initiated, phase II trial. Pts with GEA who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomized 2:1 to either FOLFIRI plus Ram every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus Ram every two weeks (Arm B). Major endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and toxicity. Results: 111 pts (median age 61 years, 65% of pts had prior docetaxel therapy) were enrolled and 110 analyzed within intention to treat population (ITT, Arm A, 72; Arm B, 38). In the ITT, there was no significant difference in median OS (A, 6.8 vs. B, 7.6 months, HR 0.94, p = 0.77) and median PFS (A, 4.6 vs. B, 3.6 months, HR 0.72, p = 0.12). For pts with prior docetaxel use (71/110), median PFS was A, 4.3 vs. B, 2.0 months, HR 0.49, p = 0.008 and median OS was A, 7.5 vs. B, 6.4 months, HR 0.71, p = 0.25. In 101 pts with tumor assessment and included in the response analysis, ORR and DCR was 23% and 65% in Arm A and 11% and 60% in Arm B, respectively. 67 pts assessable for response were pre-treated with docetaxel. In these pts, ORR was 24% in Arm A and 9% in Arm B. Disease control rate (DCR) was 67% and 41% for Arm A and B respectively. Both therapies were similarly tolerable, final safety results will be shown. Conclusions: The RAMIRIS trial demonstrated feasibility of the combination of FOLFIRI and Ram. With a response rate of 24% and a median PFS of 4.3 months, docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial, which is currently ongoing. Clinical trial information: NCT03081143 .
ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma: Five year follow-up.
Authors: Neoptolemos John P. , Palmer Daniel H. , Ghaneh Paula , Valle Juan W. , Cunningham David , Wadsley Jonathan , Meyer Tim , Anthoney Alan , Glimelius Bengt , Falk Stephen , Segersvard Ralf , Middleton Gary William , Ross Paul J. , Wasan Harpreet Singh , McDonald Alec , Crosby Tom David Lewis , Psarelli Eftychia Eirini , Hammel Pascal , Hackert Thilo , Buchler Markus W. ,   European Study Group for Pancreatic Cancer (ESPAC)
Published: May 2020

4516 Background: The ESPAC-4 trial demonstrated that adjuvant GEM/CAP for pancreatic cancer significantly improved survival compared to GEM monotherapy. The aim of this study is to evaluate the long-term outcomes in the ESPAC-4 trial. Methods: Patients with pancreatic ductal adenocarcinoma were randomized within 12 weeks of surgery (stratified for R0/R1 resection margin status and country) to have either six 4-week cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was five-year survival; secondary endpoints were toxicity and relapse free survival. 722 patients (480 expected events), 361 in each arm, were needed to detect a 10% difference in 2-year survival rates with 90% power (log-rank test with 5% two-sided alpha). Results: Between Nov 10 2008 and Sep 11 2014, 732 patients were randomized with 730 included in the full analysis set (366 GEM, 364 GEM/CAP). Median age was 65 years, 57% were men. WHO performance status was 0, 1 or 2 in 42% 55% and 3% respectively. Postoperative median CA19-9 was 19 kU/L. Median maximum tumor size was 30 mm, 61% were R1 resections, 80% were node positive and 40% were poorly differentiated. The data freeze was on 24 February 2020; median follow up was 60 months with 531 overall deaths, 280 in GEM, and 251 in GEM/CAP. Median (95% CI) survival (months) for patients treated with GEM/CAP was 27.7 23.3 – 31.2) and 26.0 (22.7 – 28.4) for GEM. Five-year (95% CI) survival rates were 20 (16 – 25) % for GEM and 28 (23 – 33) % for GEM/CAP. Stratified log-rank analysis revealed an HR=0.84 [95% CI, 0.70 – 0.99]; χ2 (1) = 3.87, P=0.049. 70 out of 366 GEM patients in the safety set reported 101 grade 3/4 serious adverse events, while 65 out of 359 GEM/CAP patients reported 97 grade 3/4 serious adverse events ( P=0.724). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: 96397434 .
A prospective randomized controlled trial of selective transarterial chemoembolization using drug-eluting beads loaded with epirubicin versus selective conventional transarterial chemoembolization using epirubicin-lipiodol for hepatocellular carcinoma: The JIVROSG-1302 PRESIDENT study.
Authors: Ikeda Masafumi , Inaba Yoshitaka , Tanaka Toshihiro , Sugawara Shunsuke , Kodama Yoshihisa , Aramaki Takeshi , Anai Hiroshi , Morita Shinichi , Tsukahara Yoshinori , Seki Hiroshi , Sato Mikio , Kamimura Kenya , Azama Kimei , Tsurusaki Masakatsu , Sugihara Eiji , Miyazaki Masaya , Sone Miyuki , Arai Yasuaki 
Published: May 2020

4518 Background: Transarterial chemoembolization (TACE) with selective catheterization into the segmental or subsegmental hepatic arteries supplying HCC is often performed to achieve the complete local control of HCC in the patients with a limited number of small sized nodules. To clarify which of TACE with drug-eluting beads loaded with epirubicin (DEB-TACE) or conventional TACE with epirubicin-lipiodol (cTACE) can achieve the complete response (CR) more frequently, we performed a randomized controlled trial of DEB-TACE vs. cTACE. Methods: Between March 2016 and May 2019, unresectable HCC patients with Child-Pugh class A or B who were scheduled to receive selective TACE were randomly assigned 1:1 to the DEB-TACE group and the cTACE group. The primary endpoint was the CR rate at 3 months, and the secondary endpoints were the CR rate at 1 month and rate of adverse events (AEs). The response and AEs were assessed according to the modified RECIST by an independent review committee and the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0., respectively. Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE 101 patients) were enrolled from 22 Japanese institutions. The patient characteristics were well-balanced between the two groups. The median number of tumors was one in both groups and the median tumor size was 20.0 mm in the DEB-TACE group and 20.5 mm in the cTACE group. The table shows the CR rates and frequencies of AEs. The CR rates of cTACE at 3 and 1 months were significantly higher than those of DEB-TACE. The frequency of AEs (all grades), including pyrexia, malaise, increased serum total bilirubin (T-Bil) and increased serum alanine transaminase (ALT), was significantly higher in the cTACE group than in the DEB-TACE group. Conclusions: Selective cTACE appeared to have greater efficacy for local tumor control as compared to selective DEB-TACE, however, the frequencies of post-embolization syndromes were higher in the cTACE group than in the DEB-TACE group. Clinical trial information: UMIN000021250 . [Table: see text]
A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC).
Authors: Zhu Andrew X. , Finn Richard S. , Ikeda Masafumi , Sung Max W. , Baron Ari David , Kudo Masatoshi , Okusaka Takuji , Kobayashi Masahiro , Kumada Hiromitsu , Kaneko Shuichi , Pracht Marc , Mamontov Konstantin , Meyer Tim , Mody Kalgi , Kubota Tomoki , Dutcus Corina E. , SAITO KENICHI , Siegel Abby B. , Dubrovsky Leonid , Llovet Josep M 
Published: May 2020

4519 Background: LEN is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT, approved for first line (1L) treatment of uHCC. PEMBRO, an anti-PD-1 monoclonal antibody, was granted accelerated approval for the treatment of patients (pts) with HCC after sorafenib therapy. We assessed the safety and efficacy of LEN + PEMBRO in uHCC. Methods: In this phase 1b trial (NCT03006926), pts received LEN 12 mg/day (bodyweight [BW] ≥60 kg) or 8 mg/day (BW <60 kg) orally + PEMBRO 200 mg IV on Day 1 of a 21-day cycle. Primary endpoints were safety and tolerability for Part 1 and objective response rate (ORR) and duration of response (DOR) by mRECIST and RECIST v1.1 per independent imaging review (IIR) in the 1L setting for Part 2. Results: 104 pts (part 1, n=6; part 2, n=98) were enrolled. No DLTs were reported in Part 1; 100 pts were included in the 1L analysis of LEN + PEMBRO–4 pts (part 1) excluded due to prior sorafenib. At data cutoff (October 31, 2019) and median follow-up of 10.6 months, 37 pts continued treatment (LEN only, n=3; both drugs, n=34); median duration of treatment was 7.9 months (LEN, 7.6 months; PEMBRO, 7.4 months). Median OS was 22.0 months (95% CI 20.4–not estimable [NE]), median PFS was 8.6 months (95% CI 7.1–9.7), and ORR was 36% (95% CI 26.6–46.2) (RECIST v1.1 per IIR). Additional efficacy outcomes are shown in the table. Treatment-emergent adverse events (TEAEs) occurred in 99% of pts (grade ≥3, 85%; grade ≥4, 23%). The most common grade ≥3 TEAE was hypertension (18% of pts). Treatment-related AEs (TRAEs) occurred in 95% of pts (grade ≥3, 67%; grade ≥4, 4%). The most common grade ≥3 TRAE was hypertension (17% of pts). 36% of pts had serious TRAEs and 3 pts died from a TRAE (acute respiratory failure/acute respiratory distress syndrome, n=1; intestinal perforation, n=1; abnormal hepatic function, n=1). Conclusions: LEN + PEMBRO has promising antitumor activity with a tolerable safety profile. An ongoing phase 3 trial (NCT03713593) is assessing LEN + PEMBRO vs LEN alone as 1L therapy for uHCC. Clinical trial information: NCT03006926 . [Table: see text]
First-in-human phase I study of BVAC-B cell therapy in HER2-positive advanced gastric cancer.
Authors: Lee Jii Bum , Kwon Woo Sun , Kim Hyo Song , Jung Minkyu , Kim Sinyoung , Park Myunghwan , Kim Wuhyun , Choi Ki-Young , Oh Taegwon , Kang Chang-Yuil , Chung Hyun Cheol , Rha Sun Young 
Published: May 2020

4534 Background: BVAC-B is an autologous B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HER2/neu gene and loaded with alpha-galactosyl ceramide, a natural killer T cell ligand. It may have activity against HER2/neu positive cancer. Preclinical data in mouse models have shown promising anti-tumor activity by eliciting broad spectrum of immune responses against HER2/neu positive tumor cells. We report here the results of phase 1 study of BVAC-B in HER2 positive advanced gastric cancer. Methods: Metastatic gastric cancer with IHC > 1+ of HER2/neu were eligible for enrollment. Two weeks before treatment, subjects were admitted to hospital for collection of PBMC and plasma by lymphapheresis. The PBMC were sent to Cellid for vaccine manufacturing which took a day. BVAC-B was given intravenously at 0, 4, 8, and 12 weeks. Subjects received low (2.5X 107 cells/dose), medium (5.0X 107 cells/dose) or high dose (1.0X 108 cells/dose). Endpoints included safety, tolerability and MTD for phase 2 trial. Exploratory outcomes included immune responses after BVAC-B administration. Results: As of January 29, 2020, 8 subjects were treated with BVAC-B at doses of 2.5X 107 cells/dose (n=1), 5.0X 107 cells/dose (n=1) and 1.0X 108 cells/dose (n=6). Median line of therapy at which BVAC-B was administered was 4 (range, 2-9). Mean duration treatment was 1.8 (range 1-4) cycles. The most common treatment related adverse events were fever (n=4, 50%). One subject enrolled in medium dose experienced cytokine release syndrome (G2) with high fever (39.3℃) and hypotension 8 hours after first administration, but was manageable with hydration and supportive management. Other adverse events included increase of AST and ALT (G1, n=1 and G2, n=2), and hypotension (G1, n=1). There were no adverse events which led to treatment discontinuation. Immunologic response analysis showed that BVAC-B induced activation of natural killer T cells, natural killer cells, HER2/neu specific T cells, and release of HER2/neu specific antibody upon vaccinations in few patients who were evaluated. Conclusions: BVAC B is feasible and has acceptable toxicity profile. We considered all dose evaluated in this study available for phase 2 study, given that the maximum tolerated dose is expected to exceed the maximum dose administered in this study. For clinically relevant effect, further studies are warranted, including earlier line of exposure to BVAC-B as well as combination treatments. Clinical trial information: NCT03425773 .
Impact of body measurements (BM) on overall survival (OS) and quality of life (QoL) in real-world patients (pts) with metastatic esophageal cancer.
Authors: Soriano Joelle , Hueniken Katrina , Bajwa Jaspreet K. , Dong George , Wang Wanning , Soberano Tyler , Taylor Kirsty , Brown M. Catherine , Chen Eric Xueyu , Knox Jennifer J. , Jang Raymond Woo-Jun , Wong Rebecca , Darling Gail Elizabeth , Xu Wei , Elimova Elena , Liu Geoffrey , Rozenberg Dmitry , McInnis Micheal , Fares Aline Fusco 
Published: May 2020

4544 Background: Body fat and muscle influence prognosis in many cancer types. However, this association is unclear for real-world MEC pts, who are often in worse performance status than their previous baseline. In addition, the relationship of BM at presentation and QoL is unknown. We used real-world MEC pts to assess the importance of BM in OS and QoL. Methods: BM were done at baseline computed tomography in MEC pts, treated from 2006-2014 at the Princess Margaret Cancer Centre. Two radiologists (correlation 0.9-1.0) assessed L3 level using SliceOMatic to determine Skeletal Muscle Index (SMI - muscle area at L3 normalized by height), Visceral Adiposity Tissue (VAT), and Subcutaneous Adiposity Tissue (SAT). We used previously published cut-offs for sarcopenia based on sex and BMI, and the highest tertile as the cut-off for adiposity. We used prospectively collected QoL surveys including EuroQol 5D-5L (EQ5D) and the Functional Assessment of Cancer Therapy – Esophageal (FACT-E). Results: Of 200 pts, 164 (82%) were male, 180 (92%) were non-Asian; mean age was 62 y; ECOG: 0-1 = 142 (71%), 2 = 58 (29%); 69% had adenocarcinoma; 5% were underweight, 44% normal weight, 30% overweight, and 21% obese. 40 (20%) pts completed QoL measures. We found that 104 (52%) were sarcopenic at baseline, 66 (33%) had high VAT, and 67 (34%) had high SAT. A multivariable Cox model showed that sarcopenia and VAT were independent prognostic variables for three-year OS: sarcopenia increased the risk of death by 50% (adjusted hazard ratio, aHR 1.50, p 0.02), whereas every 100-cm2 increase in VAT improved OS by 24% (aHR 0.76, p 0.03). Finally, sarcopenic pts had significantly worse physical well-being (p 0.01) on FACT-E after adjusting for sex and age. Numerically, the EQ5D also showed lower scores in sarcopenic pts but this was not statistically significant (p 0.18). Conclusions: In MEC pts, sarcopenia and low visceral adiposity result in worse OS; sarcopenia is also significantly associated with poor QoL. Future work will need to focus on potential rehabilitation strategies such as nutritional support and exercise training to offset the poor prognosis associated with sarcopenia and reduced adiposity. [Table: see text]
Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma.
Authors: Ma Lucy Xiaolu , Taylor Kirsty , Espin-Garcia Osvaldo , Suzuki Chihiro , Anconina Reut , Allen Michael J , Honório Marta , Bach Yvonne , Allison Frances , Chen Eric Xueyu , Yeung Jonathan , Darling Gail Elizabeth , Wong Rebecca , Kalimuthu Sangeetha , Jang Raymond Woo-Jun , Veit-Haibach Patrick , Elimova Elena 
Published: May 2020

4557 Background: Malnutrition and sarcopenia (defined as low skeletal muscle mass) are recognized as poor prognostic factors in many cancers. Studies to date in gastroesophageal cancer have largely focused on patients (pts) undergoing curative intent surgery. This study aims to evaluate the prognostic utility of nutritional markers and sarcopenia in pts with de novo metastatic gastric and esophageal adenocarcinoma (GEA). Methods: Pts with de novo metastatic GEA seen at the Princess Margaret Cancer Centre from 2010-2016 with available pre-treatment abdominal computed tomography imaging were identified from an institutional database. Nutritional index (NRI) was calculated using weight and albumin, with moderate/severe malnutrition defined as NRI < 97.5. Skeletal muscle index (SMI) normalized by height was calculated at the L3 level using Slice-O-Matic software. Sarcopenia was defined as SMI < 34.4cm2/m2 in women and < 45.4cm2/m2 in men based on previously established consensus. Results: Of 175 consecutive pts, median age was 61, 69% were male, 79% had ECOG performance status 0-1, and 71% received chemotherapy. Median BMI was 24.2 (range 15.7-39.8), 70% of pts had > 5% weight loss in the preceding 3 months, and 29% had moderate/severe malnutrition. 68 pts (39%) were sarcopenic, of whom 46% were malnourished. Median overall survival (OS) was 9.3 months (95% CI 7.3-11.4) for all pts. OS was significantly worse in malnourished pts (5.5 vs 10.9 months, p = 0.000475) and displayed a non-significant trend in sarcopenic pts (7.8 vs 10.6 months, p = 0.186). On univariable Cox proportional hazards (PH) analysis, ECOG (p < 0.001), number of metastatic sites (p = 0.029) and NRI (p < 0.001) were significant prognostic factors, while BMI (p = 0.57) and sarcopenia (p = 0.19) were not. On multivariable Cox PH analysis, ECOG (p < 0.001) and NRI (p = 0.025) remained significant as poor prognostic factors for OS. Conclusions: This study demonstrates in a large cohort of de novo metastatic GEA pts that ECOG and NRI were significantly associated with poor OS. NRI was superior to BMI alone. Early identification of malnourished pts using NRI may allow for supportive interventions to optimize nutritional status. Further study is needed to determine whether these factors can be modified to improve prognosis in these pts.