bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective multicenter study evaluating the efficacy and safety of irinotecan in patients with advanced gastric cancer: Analysis of albumin-bilirubin (ALBI) grade.
Authors: Motoo Iori , Komatsu Yoshito , Yuki Satoshi , Nakano Shintaro , Nakatsumi Hiroshi , Kawamoto Yasuyuki , Muranaka Tetsuhito , Sawada Kentaro , Ando Takayuki , Miyagishima Takuto , Harada Kazuaki , Kobayashi Yoshimitsu , Hatanaka Kazuteru , Ishiguro Atsushi , Tanimoto Aya , Honda Takuya , Dazai Masayoshi , Sasaki Takahide , Sakamoto Naoya 
Published: February 2020

415 Background: It is important to predict prognosis and risk of adverse events in patients with advanced gastric cancer receiving chemotherapy. Albumin-bilirubin (ALBI) grade is recently used as liver function assessment and prognosticator in hepatocellular carcinoma. Irinotecan is metabolized in the liver, so ALBI score may be useful for predicting irinotecan efficacy and safety. Methods: We conducted a retrospective multicenter study and investigated association between efficacy and ALBI grade in patients who received irinotecan monotherapy between January 2010 and December 2017. All patients had to receive fluoropyrimidine and platinum as prior therapy. The ALBI score is calculated by the equation: ALBI score = (log10 bilirubin [µmol/L] × 0.66) + (albumin [g/L] × −0.0852). As a result, ALBI grades 1, 2, and 3 were developed as follows: ALBI score ≤ −2.60 (ALBI grade 1), > −2.60 to ≤ −1.39 (ALBI grade 2), and > −1.39 (ALBI grade 3). Results: The number of patients with ALBI grade 1/2/3 is 100/68/5. In ALBI 1/2-3 patients, performance status 0/1/≥2 was 37/57/6 and 17/43/14, treatment line 2nd/3rd or later was 58/42 and 21/53, HER2 positive/negative 14/86 and 16/58, respectively. In ALBI 1/2-3 patients, median PFS was 3.3 and 2.3 months (HR = 0.684, P = 0.018) and median OS was 11.7 and 6.7 months (HR = 0.492, P < 0.001), respectively. In ALBI 1/2-3 patients, median treatment cycle which was 6 and 4 ( P = 0.09) and RDI were significantly different was, and RDI was 0.80 vs 0.70( P = 0.027), respectively.Hematological AEs were observed in 88% and 87% ( P = 1.000), severe hematological AEs (≥G3) were 41% and 58%( P = 0.040). Non-hematological AEs were 87% and 86%( P = 1.000), severe non-hematological AEs (≥G3) were 11% and 18% ( P = 0.257), respectively. Severe AEs in more than 5% patients were leukopenia (12% and 18%), neutropenia (23% and 28%), anemia (16% and 31%), and anorexia (2% and 10%).In multivariate analysis, ALBI grade was associated with shorter OS (ALBI 1 and 2-3: HR 1.773 95%C.I. 1.184-2.654, p = 0.005). Conclusions: ALBI grade might be both prognostic factor and risk factor in treatment with irinotecan monotherapy for patients with AGC.
Development of a gene panel for 18F-FDG PET positivity prediction in gastric cancer.
Authors: Bae Seong-Woo , Berlth Felix , Choi Hongyoon , Jeong Kyoung-Yun , Min Jimin , Park Ji-Hyeon , Choi Jong-Ho , Park Shin-Hoo , Kong Seong-Ho , Park Do Joong , Lee Hyuk-Joon , Chung June-Key , Yang Han-Kwang 
Published: February 2020

420 Background: 18F-FDG PET is widely used in clinical cancer diagnostics. However, 18F-FDG PET scan in gastric cancer (GC) is still controversial because of its lower sensitivity in diagnosis and staging compared to other imaging modalities. The purpose of this study was to establish a gene panel for 18F-FDG PET positivity in GC by using patient-derived xenografts (PDXs). Methods: BALB/c nude mice were subcutaneously implanted with 30 cases of GC PDX tissues and underwent a simultaneous PET/MRI scanner. Using RNA-seq data of the 30 GC PDXs for training set, we constructed a gene co-expression network which was correlated with the maximal standardized uptake values (SUVmax). The least absolute shrinkage and selection operator (LASSO) was used for identification of genomic signature for the PET positivity and a prediction model was established. By using qRT-PCR, a gene panel (PredictionScore) based on the gene signature was developed. Results: We found that the PDXs could recapitulate FDG avidity of those parental tumors between 15 Patient-PDX pairs (Spearman r = 0.54, p-value = 0.04). The prediction model with the identified five genes ( PLS1, PYY, HBQ1, SLC6A5, NAT16) provided excellent prediction values compared with actual SUVmax for 15 patients as a validation set (Spearman r = 0.56, p-value = 0.03) and for 8 patients as a test set (Spearman r = 0.90, p-value = 0.005). The PredictionScore showed significant positive correlation with the actual SUVmax for 7 patients as an external validation set (Spearman r = 0.82, p-value = 0.03). Conclusions: PDX can be used to develop a gene panel for the PET positivity prediction in GC. Our results showed that the scoring system can be clinically applicable for developing a predicted stratification model. Future studies will aim to evaluate the panel for a higher number of PET-scanned GC patients to establish a rational patient selection for PET scan in clinical settings.
Comparison of immune-related gene expression between primary and metastatic site in advanced gastric cancer patients with peritoneal dissemination.
Authors: Takahashi Naoki , Matano Yutaka , Tsujibata Akihiko , Murayama Kozue , Miyazawa Shoichi , MATSUSHIMA TOMOHIRO , Shimizu Satoshi , Kumekawa Yosuke , Yoshii Takako , Asayama Masako , Hara Hiroki 
Published: February 2020

423 Background: Immune checkpoints inhibitor (ICI) is effective and approved in some solid tumors including advanced gastric cancer (GC). Peritoneal dissemination is known as a poor prognostic factor and was reported to be associated with the resistance to ICI according to the previous reports. The aim of our study is to compare the immune-related gene expression between primary site and peritoneal lesion in advanced GC patients. Methods: Among advanced GC patients, we selected those who underwent surgical resection for both primary and peritoneal lesions simultaneously. Formalin-fixed paraffin-embedded (FFPE) tumor tissues of primary and peritoneal lesions were prepared and RNA was extracted by Maxwell RSC RNA FFPE kit (Promega). Immune-related gene expression was evaluated by using nCounter Max Analysis System (NanoString). We used nCounter PanCancer Immune Profiling Panel Kit which includes 770 immune-related genes. Results: Immune-related gene expression was evaluated by using twenty-four FFPE tumor tissues in twelve GC patients. Scatter plot and hierarchical clustering analyses showed that the pattern of immune-related gene expression was not much different between primary and peritoneal lesions beyond the individual differences. Regarding the T cell function, high expression of Immune-related genes was widely detected in patients with EB virus-positive (n = 2) and HER2-positive (n = 1). Gene expressions such as CD70, FAS, MAF and IL-3 were higher in peritoneal lesion compared with primary lesion (p < 0.05). Whereas, expressions of F2RL1 and IL-11 were lower in peritoneal lesion compared with primary lesion (p < 0.05). Conclusions: Our study indicated that there was not much difference of Immune-related gene expression between primary and peritoneal lesion in advanced GC patients. Positive status of EB virus and HER2 may be associated with high expression of immune-related genes. Further analysis to evaluate immune-related gene expression between primary and metastatic site may contribute the further understanding of cancer immunity in advanced GC.
Tumor microenvironment evaluation to predict pembrolizumab benefit of metastatic gastric cancer: Results from phase II clinical trial.
Authors: Zeng Dongqiang , Liao Wangjun , Shi Min , Zhou Rui , Huang Na , Yu Yunfang , Peng Wenying , Wu Jiani , Ye Zilan 
Published: February 2020

425 Background: Clinical studies support the efficacy of immune checkpoint blockades (ICBs) in a subset of patients with metastatic gastric cancer (mGC). With the aim of identifying determinants of response to ICBs, we performed molecular characterization of tissues from 61 patients with mGC who were treated with pembrolizumab as salvage treatment in a prospective phase 2 clinical trial (NCT#02589496). Methods: Of 61 patients, 60 patients underwent pretreatment biopsy and 45 specimens were of sufficiently high quality for RNA sequencing. TMEscore, which was previously established to quantify the tumor microenvironment (TME), was used to estimated TME of pretreatment specimens. The predictive value and correlation of integrative molecular characterization were systematically explored. Results: We established a methodology (TMEscore) to evaluated the TME of GC patients, which was previously found to be a robust prognostic and predictive biomarker for patients treated with ICBs. By applying ROC curve analysis, the TMEscore was found to be a best predictive biomarker (TMEscore: AUC = 0.891; CPS: AUC = 0.830; TMB: AUC = 0.672; MSI status: AUC = 0.708; EBV status: AUC = 0.727; respectively). Moreover, TMEscore was the most significant gene signature that correlated with tumor response (TMEscore: P = 1.7 × 10 −5; GEPs: P = 0.00035; ImmunoScore: P = 0.29106; CD8+ T cell fraction: P = 0.00011; Immune checkpoint score: P = 0.00149; respectively). TMB was not correlated with TMEscore (Kruskal-Wallis test, P = 0.14). A higher TMEscore was significantly associated with EBV+ and high-MSI TCGA molecular subtypes (Kruskal-Wallis test, P = 0.002) which were reported to benefit from ICBs of GC. Conclusions: These findings indicate that the assessment of TMEscore via high throughput-sequencing and PCA algorithm provides a robust biomarker for the selection of GC patients who may derive greater benefit from pembrolizumab. Our data also suggest that TMEscore may be a more accurate predictive biomarker than TMB, MSI and EBV status, and this resource may help facilitate the development of precision immunotherapy. Clinical trial information: NCT#02589496.
The clinical prognostic significance of lymphovascular invasion in gastric cancer.
Authors: Fujikawa Hirohito , Yamada Takanobu , Koumori Keisuke , Watanabe Hayato , Kano Kazuki , Shimoda Yota , Rino Yasushi , Masuda Munetaka , Ogata Takashi , Oshima Takashi 
Published: February 2020

428 Background: Lymphovascular invasion (LVI) of malignant tumor is regarded as an initial state of metastasis, including the lymph nodes, and therefore may be a prognostic factor in many malignancies. However, in gastric cancer, according to the current Japanese guidelines, LVI is not clinically useful information, except for in predicting the curability of endoscopic resection, and its clinicopathological characteristics and biological behavior remain unclear. The present study explored the histopathological significance of LVI in gastric cancer and clarified its correlation with the prognosis. Methods: From January 2000 to December 2013, a total of 2090 cases of gastric cancer undergoing radical gastrectomy were enrolled in this study. The correlation of LVI and other histopathological factors with the prognosis was evaluated. Lymphatic vessel invasion (ly) and venous invasion (v) were diagnosed followed the current Japanese classification. LVI positivity (LVIP) and LVI negativity (LVIN) were defined as the presence of lymphatic vessel and/or venous invasion and the absence of LVI, respectively. Results: LVIP was noted in 894 cases (42.8%). The age (p < 0.001), depth of tumor invasion (pT) (p < 0.001), lymph node metastasis (pN) (p < 0.001), and maximum tumor size (p < 0.001) were significantly correlated with the presence of LVI. A multivariate analysis showed that pT (p < 0.001), pN (p < 0.001), and LVI (p = 0.03) were independent risk factors for the prognosis of all patients. On analyzing the significance of every T factor and N factor for the overall survival of LVIP and LVIN cases, no significant difference was recognized in the prognosis among all pT1 patients and pT2-4 patients without nodal metastasis. However, in pT2-4 patients with nodal metastasis, a significant difference was revealed, and the 5-year overall survival rates in LVIP cases were lower than those in LVIN (60.9% [95% confidence interval: 56.3-65.3] vs. 76.7% [95% confidence interval 65.2-84.8], p = 0.005). Conclusions: LVI in gastric cancer is an independent prognostic factor, and its effect tends to be particularly strong in advanced cancer with lymph node metastasis. These patients may therefore require more effective adjuvant therapy.
A clinical scoring system for survival prediction in advanced gastric cancer.
Authors: Kim Jinchul , Yeo Ja Hyun , Hong Jung Yong , Kim Seung Tae , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Lee Jeeyun 
Published: February 2020

436 Background: We established a scoring system using easily approachable clinical characteristics at the timing of initiating palliative chemotherapy to achieve accurate overall survival prediction to first-line treatment consisting of fluoropyrimidines in patients with advanced gastric cancer. Methods: A total of 1,733 patients were included in the study. The dataset was split into a training (n=1156, 67%) and validation set (n=577, 33%). Top-ranked variables were identified using the Random Forest for Survival algorithm and analyzed into a Cox regression model, thereby constructing the scoring system for predicting overall survival of advanced gastric cancer. Results: Five variables were finally included in the scoring system: serum neutrophil-lymphocyte ratio, alkaline phosphatase, albumin level, performance status, and histologic differentiation. The scoring system determined four distinct risk groups in validation dataset with median overall survival of 17.1 month (95% confidence interval [CI] = 14.9 to 20.5 month), 12.9 month (95% CI = 11.4 to 14.6 month), 8.1 month (95% CI = 5.3 to 12.3 month), and 3.9 month (95% CI = 1.5 to 8.2 month), respectively. AUC to estimate discrimination performance of the scoring system was 66.1 for one-year overall survival. Conclusions: We developed a simple and clinically useful predictive scoring model in a relatively homogenous population who initiate fluoropyrimidine-containing chemotherapy in advanced gastric cancer. Generalized application of the scoring model will require additional independent validation. [Table: see text]
Revisiting the value of drains after low anterior resection for rectal cancer: An analysis of 996 patients.
Authors: Lee Rachel M. , Gamboa Adriana C. , Turgeon Michael K. , Prasad Sanjana , Kwakye Gifty , Hrebinko Katherine , Holder-Murray Jennifer , Abdel-Misih Sherif , Kimbrough Charles , Soda Mosope , Hawkins Alexander , Chapman William C. , Silviera Matthew , Maithel Shishir K. , Balch Glen C. 
Published: February 2020

45 Background: Although potentially associated with increased infections, intraoperative pelvic drains are often placed during low anterior resection (LAR) to evacuate postoperative fluid collections and identify/control potential anastomotic leaks. Our aim was to assess the validity of this practice in a large dataset of patients undergoing LAR for rectal cancer. Methods: Patients from the US Rectal Cancer Consortium (2007-17) who underwent curative-intent LAR for a primary rectal cancer were included. Patients were categorized as receiving a closed suction drain intraoperatively or not. Primary outcomes were superficial surgical site infection(SSI), deep SSI, intraabdominal abscess, anastomotic leak, and need for secondary drain placement. Three subgroup analyses were conducted in patients who received neoadjuvant chemoradiation, had a diverting loop ileostomy (DLI), and had low tumors <6cm from the anal verge. Results: Of 996 pts, average age was 58 yrs, 61% were male, and 67% (n=551) received a drain. Drain patients were more likely to be male (64vs54%), have a smoking history (25vs19%), have received neoadjuvant chemoradiation (73vs61%), have low tumors within 6cm of the anal verge (56vs36%), and have received a DLI (80vs71%) (all p<0.05). Drains were associated with an increased anastomotic leak rate (14vs8%, p=0.041), although there was no difference in the need for a secondary drainage procedure to control the leak (82vs88%, p=0.924). These findings persisted in all subset analyses. Drains were not associated with increased superficial SSI, deep SSI, or intraabdominal abscess in the entire cohort or each subset analysis. Reoperation (12vs10%, p=0.478) and readmission rates (28vs31%, p=0.511) were similar. Conclusions: Although not associated with increased infectious complications, intraoperatively-placed pelvic drains after low anterior resection for rectal cancer are associated with an increase in anastomotic leak rate and no reduction in the need for secondary drain placement or reoperation. Routine drainage should be abandoned.
Conversion surgery for advancedgastric cancer with peritoneal metastasis.
Authors: Nakamura Masaki , Nakamori Mikihito , Ojima Toshiyasu , Katsuda Masahiro , Hayata Keiji , Kitadani Junya , Yamaue Hiroki 
Published: February 2020

450 Background: Patients with peritoneal metastasis have significantly poor prognosis. We have performed pretherapeutic staging laparoscopy (SL) to diagnose peritoneal metastasis for patients with large type 3, type 4 or serosa-invasive gastric cancer. When peritoneal metastasis disappears by chemotherapy for patients with positive peritoneal cytology (CY1) or peritoneal dissemination (P1), we perform the conversion surgery (CS). Methods: We retrospectively analyzed clinical outcomes of 134 patients with advanced gastric cancer who underwent SL between 2005 from 2016. We examined safety and usefulness of CS for patients with CY1 or P1. Results: CY0P0, CY1P0 and P1 were found in 67, 28 and 39 patients, respectively. The median survival time (MST) of patients with CY0P0, CY1P0 and P1 were 39, 21 and 11 months (CY0P0 vs CY1P0; p = 0.029, CY0P0 vs P1; p<0.001, CY1P0 vs P1; p<0.001). In patients with CY1P0, 20 of 26 patients who received chemotherapy underwent the second look SL, and 14 patients (54%) underwent CS (R0) as peritoneal cytology turned negative. These regimens of chemotherapy were S-1/CDDP (n = 9), Docetaxel/CDDP/S-1 (n = 2), SOX (n = 2) and S-1/Docetaxel (n = 1) and the median number of treatment courses was5courses. The MSTs of patients with or without CS were 40 months and 11 months (p<0.001). Then, there was no difference in overall survival between patients with CS and patients with CY0P0 at the first SL (p = 0.866). All patients with P1received chemotherapy, and 11 of these patients underwent the second look SL. As peritoneal metastasis of 7 patients (18%) disappeared by chemotherapy, they underwent CS (R0). The MSTs of patients with or without CS were 31 months and 9 months (p = 0.026). Regarding complications after CS, surgical-site infection and interstitial pneumonia each occurred in one patient (grade II), and intestinal obstruction (grade IIIa) occurred in one patient. There was no mortality. Conclusions: This study suggests that CS is probably safe and may contribute to improve the survival rate of patients with peritoneal metastasis. Moreover, we developed the NSOX regimen, comprised of a combination nab-paclitaxel, S-1 and oxaliplatin, and have performed a phase I/II trial using the NSOX regimen (UMIN000030909).
Nivolumab (NIVO) + ipilimumab (IPI) + cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.
Authors: Yau Thomas , Zagonel Vittorina , Santoro Armando , Acosta-Rivera Mirelis , Choo Su Pin , Matilla Ana , He Aiwu Ruth , Cubillo Gracián Antonio , El-Khoueiry Anthony B. , Sangro Bruno , Eldawy Tarek , Bruix Jordi , Frassineti Giovanni , Vaccaro Gina M. , Tschaika Marina , Scheffold Christian , Shen Yun , Neely Jaclyn , Piscaglia Fabio 
Published: February 2020

478 Background: The programmed death-1 inhibitor NIVO had durable responses and a manageable safety profile in pts with aHCC in CheckMate 040 (NCT01658878; El-Khoueiry et al. Lancet 2017) and is approved in the United States, Canada, Australia, and elsewhere for sorafenib (SOR)-treated pts with aHCC. In another CheckMate 040 cohort, NIVO + IPI combination therapy had durable responses in SOR-treated pts with aHCC, with objective response rates (ORRs) > 30% in each dosing arm (Yau et al. J Clin Oncol 2019). CABO is also approved for SOR-treated pts with aHCC; a pivotal phase 3 trial reported median overall survival (OS) of 10.2 mo (Abou-Alfa et al. N Engl J Med 2018). This is the first report of efficacy and safety of NIVO + CABO +/- IPI (doublet and triplet) combinations in pts with aHCC. Methods: SOR-naive or -experienced pts with aHCC were randomized to 2 arms: [1] NIVO 240 mg Q2W + CABO 40 mg daily or [2] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W + CABO 40 mg daily. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included ORR (investigator assessed using RECIST v1.1) and safety/tolerability. Data cutoff was January 2019. Results: 71 pts were randomized to NIVO + CABO (n = 36) or NIVO + IPI + CABO (n = 35). Investigator-assessed ORR was 17% (6 pts with partial response [PR]) in the NIVO + CABO arm and 26% (9 pts with PR) in the NIVO + IPI + CABO arm. Disease control rate was 81% for the NIVO + CABO arm and 83% for the NIVO + IPI + CABO arm; median progression-free survival was 5.5 mo for the NIVO + CABO arm and 6.8 mo for the NIVO + IPI + CABO arm. Median OS was not reached in either arm. Grade 3-4 treatment-related adverse events (TRAEs) were reported in 15 pts (42%) in the NIVO + CABO arm and 25 pts (71%) in the NIVO + IPI + CABO arm and led to discontinuation in 1 (3%) and 7 (20%) pts, respectively. No new safety signals were observed in either arm. Updated data describing the efficacy and safety of the combinations will be shown. Conclusions: In pts with aHCC, NIVO + CABO +/- IPI combination therapy led to clinically meaningful responses. Although the triplet had a higher rate of TRAEs observed than the doublet regimen, the majority of AEs were manageable and reversible. Clinical trial information: NCT01658878.