bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective evaluation of a developed S-1 dosage formula based on renal function.
Authors: Mizukami Takuro , Takeuchi Masashi , Imamura Chiyo K. , Booka Eisuke , TAKEUCHI HIROYA , Kawakami Takeshi , Funakoshi Taro , Wakuda Kazushige , Aoki Yu , Hamamoto Yasuo , Kitago Minoru , Kawakubo Hirofumi , Boku Narikazu , Tanigawara Yusuke , Kitagawa Yuko 
Published: January 2019

86 Background: S-1 is an oral anticancer drug, containing tegafur (a prodrug of 5-FU), 5-chloro-2,4-dihydroxypyridine (CDHP, inhibitor of dihydoropyrimidine dehydrogenase) and potassium oxonate. Because CDHP is excreted in urine, renal dysfunction increases incidence of severe adverse drug reactions due to higher exposure of 5-FU. As approved dose of S-1 is determined by body surface area (BSA) for patients with normal renal function, dose of S-1 is practically reduced according to renal function of creatinine clearance (CLcr) estimated by the Cockcroft-Gault equation. In a previous pharmacokinetic study (n = 16), we had developed an S-1 dosage formula based on renal function achieving the target area under the concentration-time curve (AUC) of 5-FU: Dose = target AUC x (21.9 + 0.375 x CLcr) x BSA. We conducted a prospective study to evaluate and refine this formula if necessary. Methods: Thirty patients with various renal function received S-1 at dose determined by our developed formula. A series of blood samples were obtained at predefined times after the first dose to calculate the AUC of 5-FU. Predictability of the formula was evaluated by comparison between the observed and the target AUCs. Results: The observed daily AUC was ranged from 712.6 to 2868.7 ng‧h/mL in 30 patients with BSA in the range of 1.14-1.84 m2 and CLcr in the range of 23.8-96.4 mL/min. Eighteen patients of them achieved the target AUC (1447.8 ± 545.4 ng‧h/mL). Since population pharmacokinetic analysis using combined pharmacokinetic data of 30 patients in this study and 16 patients in the previous study demonstrated that clearance of 5-FU is significantly lower in female than in male, the S-1 dosage formula was refined including gender as an additional factor: Dose = target AUC × (14.5 + 8.23 x GENDER [0 for female and 1 for male] + 0.301 × CLcr) × BSA. Revised nomograms showing recommended daily dose of S-1 were proposed for males and females taking into account tablet strengths. Conclusions: The refined formula for determining S-1 dosage on the basis of renal function, BSA and gender can be applied to clinical practice to ensure efficacy and safety for cancer patients treated with S-1. Clinical trial information: UMIN 000023880.
Feasibility of endoscopic resection in early gastric cancer with lymphovascular invasion.
Authors: Lee Jun Haeng , Lee Hyuk , Kim Jae J 
Published: January 2019

87 Background: Lymphovascular invasion (LVI) is associated with the risk of lymph node metastasis (LNM) and poor survival in gastric cancer patients. However, it is unclear whether LVI is a noncurative criteria component in all patients. We evaluated the risk factors of LNM in LVI-positive early gastric cancer (EGC) patients and identified a subgroup with a negligible LNM risk to assess the feasibility of endoscopic resection in these patients. Methods: The clinicopathologic and survival data of patients undergoing surgery for gastric cancer were reviewed; LVI-positive EGC patients were selected. Logistic regression analysis was used to test the associations of potential risk factors with LNM; Kaplan-Meier analysis was used to compare survival curves. Results: LVI was detected in 1,243 (15.5%) patients. In the multivariate logistic analysis, larger tumor size (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.16-1.31; P < 0.001), presence of ulcer (OR, 1.80; 95% CI, 1.15-2.82, P = 0.010), undifferentiated histology (OR, 1.64; 95% CI, 1.25-2.16; P < 0.001), submucosal invasion (OR, 2.28, 95% CI, 1.38-3.76, P = 0.001), middle (OR, 2.12; 95% CI, 1.26-3.55, P = 0.004) or lower third location (OR, 2.28; 95% CI, 1.32-3.60, P = 0.002), and younger age (OR, 0.98; 95% CI, 0.97-0.99; P = 0.002) independently predicted LNM in LVI-positive EGC patients. LVI-positive patients fulfilling the absolute endoscopic resection criteria did not have LNM, and there was no significant difference in the overall (P = 0.928) and disease-specific survival (P = 0.821) between these patients and those with LVI-negative EGC. Conclusions: Additional surgery after endoscopic resection might be unnecessary in LVI-positive patients meeting the absolute criteria for endoscopic resection.
Nutrition and exercise patterns in survivors of esophageal and gastroesophageal junction (EGEJ) cancers.
Authors: Jain Rishi , Ramamurthy Chethan , Sheng Jennifer Y. , Granina Evgenia , Lu Xiaoning , Yu Daohai , Abbas Abbas E. , Meyer Joshua E. , Dotan Efrat , Fang Carolyn Y , Denlinger Crystal S. 
Published: January 2019

89 Background: While obesity is a risk factor for EGEJ, malnutrition is common at diagnosis (dx) and can be exacerbated by neoadjuvant therapy (NAT) and esophagectomy. Little is known regarding nutrition and exercise patterns of EGEJ cancer survivors. Methods: A survey of EGEJ survivors > 12 months from esophagectomy was conducted. Pts were identified using institutional tumor registry. The Dillman mailed survey method was used. Questionnaires regarding health behaviors were employed: Godin Leisure-Time Exercise [GLTQ], Cancer Appetite and Symptom [CASQ], Nutritional Self-Efficacy (NSEQ). Chart review included demographics, pt characteristics and therapy received. Spearman correlation, Wilcoxon and Fisher’s tests assessed relationships between groups or variables. Results: Forty one of 140 eligible pts (29%) returned questionnaires and had surgery between 1991-2014. Median age was 69 and 78% were male. Most (83%) had adenocarcinoma. On presentation, 73% had clinical stage II or III disease and 76% received NAT. Median time from dx was 5 years (range 2-25). Mean weight loss from dx to current was 38 lbs. Mean BMI (kg/m2) was 29.52 at dx and 24.15 at most recent clinic visit. Obesity was present in 37% of pts at dx, but only 7% of survivors. Mean health behavior scores (SD): GLTQ 22.10 (22.93), CASQ 31.74 (6.66), and NSEQ 11.39 (4.03). Age, marital status, gender, education, and income were not associated with GLTQ, CASQ or NSEQ. Sedentary lifestyle (SL) with GTLQ score < 14 was present in 46% of survivors and associated with overweight BMI (mean 26.7 for SL vs 23.7 for non-SL; p = 0.04). There was a significant positive correlation between current BMI and NSEQ score (r = 0.68; p = 0.03). Conclusions: Many EGEJ cancer pts present with obesity but subsequently lose weight after curative therapy. The mean CASQ score in our population is similar to other GI cancer populations, suggesting that residual symptoms persist years after treatment ends. There is a high prevalence of SL in survivors which is associated with being overweight. Higher levels of nutrition self-efficacy were also associated with a higher current BMI. Future studies should define strategies to optimize nutrition and exercise habits in EGEJ cancer survivors.
Multicenter prospective observational study of QoL after palliative surgery for patients with bowel obstruction caused by peritoneal dissemination of gastric cancer.
Authors: Ito Yuichi , Fujitani Kazumasa , Sakamaki Kentaro , Ando Masahiko , Kawabata Ryohei , Tanizawa Yutaka , Yoshikawa Takaki , Yamada Takanobu , Hirao Motohiro , Yamada Makoto , Hihara Jun , Fukushima Ryoji , Choda Yasuhiro , Kodera Yasuhiro , Teshima Shin , Shinohara Hisashi , Kondo Masato 
Published: January 2019

90 Background: Patients with peritoneal dissemination of gastric cancer have poor oral intake caused by bowel obstruction. Palliative surgery has often been undertaken to improve quality of life (QoL), but there is no prospective study on palliative surgery. Methods: We prospectively examined the significance of palliative surgery for patients with poor oral intake caused by peritoneal dissemination of gastric cancer using a patient-reported QoL measures. Eligibility criteria included histologically proven primary gastric adenocarcinoma presenting with bowel obstruction caused by peritoneal dissemination; presence of non-curable factors; extremely poor or no oral intake requiring parenteral nutrition. Patients underwent palliative surgery by small intestine/colon resection, small intestine/colon bypass or ileostomy/colostomy for bowel obstruction. The primary endpoint was change in QoL assessed at baseline, 14 days, 1 month and 3 months following surgical palliation by means of the Euro QoL Five Dimensions (EQ-5D) questionnaire and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications. Results: Between May 2013 and March 2018, 63 patients (33 bypass and 28 stoma, 3 exploratory laparotomy) were enrolled from 14 institutions. The mean EQ-5D utility index baseline score of 0.6 remained consistent. Gastric-specific symptoms mostly showed statistically significant improvement from baseline. 42 patients (67%) were able to eat solid food 2 weeks after palliative surgery and 36 patients (57%) tolerated it for 3 months. The rate of overall morbidity of grade III or more according to the Clavien–Dindo classification was 15.8 per cent (10 patients) and the 30-day postoperative mortality rate was 3.2 per cent (2 patients). Conclusions: In patients with bowel obstruction caused by peritoneal dissemination of gastric cancer, palliative surgery maintained QoL while improving solid food intake, with acceptable operative morbidity and mortality rate. Clinical trial information: 000023495.
Long-term effects of an oral elemental nutritional supplement on post-gastrectomy body weight loss in gastric cancer patients.
Authors: Nishikawa Kazuhiro , Kimura Yutaka , Kishi Kentaro , Inoue Kentaro , Matsuyama Jin , Akamaru Yusuke , Tamura Shigeyuki , Kawabata Ryohei , Kawada Junji , Yanagimoto Yoshitomo , Kawase Tomono , Takagi Mari , Fukui Junichi , Takeno Atsushi , Fujii Chika , Yamada Takeshi , Shimokawa Toshio , Imamura Hiroshi 
Published: January 2019

94 Background: Postoperative weight loss could have a negative effect on quality of life and prognosis of gastric cancer patients. We have already shown that daily nutritional intervention with an oral elemental diet (ED) attenuated the short-term postoperative percentage of body weight loss (% BWL) in post-gastrectomy patients, especially in underwent total gastrectomy (TG). This study was conducted to evaluate the postoperative long-term BWL of nutritional intervention. Methods: This study was conducted in a cohort of consecutive patients which were randomly allocated to receive the control or ED diet in the original trial. Control group received the regular diet alone after gastrectomy, while ED group received 300 kcal of ED plus their regular diet for 6–8 weeks. The primary endpoint was the % BWL from the presurgical bodyweight to that at 1 year after surgery by surgical type. Secondary endpoints were changes in nutrition-related blood parameters. Results: One hundred six of registered patients in the original trial were eligible for efficacy analyses. There was not significant difference in the % BWL between the two groups (9.13 ± 7.72 % vs. 7.09 ± 7.49 %, respectively; p = 0.171). The % BWL at one year after surgery was significantly lower in ED group than in control group among patients who underwent TG (n = 19 and 17, respectively; 9.66 ± 5.98% vs. 15.11 ± 6.78%, respectively; p = 0.015), but not in patients who underwent distal gastrectomy (DG) (n = 38 and 32, respectively; 5.81 ± 7.91% vs. 5.96 ± 6.20%, respectively; p = 0.933). A multivariate analysis revealed that only type of gastrectomy was independently associated with % BWL at 1 year after surgery. And in total gastrectomy, ED administration was independently associated with % BWL. Total lymphocyte count in ED group increased more than that in control group at 1 year after surgery. Conclusions: Nutritional intervention with ED at 300 kcal per day for 6–8 weeks reduced body weight loss at 1 year as well as 6-8 weeks after surgery in patients who underwent total gastrectomy. Clinical trial information: 000023455.
Predictors of distress among individuals with gastric cancer.
Authors: Olson Julie , McManus Shauna , Miller Melissa F. , Yuen Eva , Denlinger Crystal S. , Stein Kevin 
Published: January 2019

96 Background: With improving survival, gastric cancer patients face long-term quality of life concerns, including management of persistent symptoms and maintenance of social activity. We examined psychosocial distress and areas of concern in a national sample of gastric patients. Methods: Using data from the Cancer Support Community’s Cancer Experience Registry, our sample included 72 patients with a primary diagnosis of stomach (54%), esophageal (36%), or GIST (11%) cancer. Participants reported cancer-related distress using CancerSupportSource®, a 25-item tool with a 2-item anxiety risk subscale, 2-item depression risk subscale, and four additional subscales measuring symptom burden, body/healthy lifestyle, healthcare team communication, and relationship concerns. We used logistic regression to estimate which of these subscales influence risk for clinically significant anxiety and depression controlling for demographic/clinical variables that were associated with anxiety and depression risk in bivariate analysis. Results: Our sample was 62% female, 80% White, and averaged 58 years of age ( SD = 13). 24% were diagnosed less than one year before participating. 33% were ever diagnosed as metastatic. 42% had received surgery. 60% were at risk for clinically significant anxiety and 50% for clinically significant depression. In regression models, relationship concerns were significantly associated with greater risk for anxiety ( OR = 1.5; p < .05) and depression ( OR = 1.7; p < .05). Greater concern with healthcare team communication was associated with anxiety risk in bivariate analysis ( r = .41, p < .01), but the association was only a trend in the multivariate model ( OR = 1.4; p = .06). Similarly symptom burden concern was associated with depression risk in bivariate analysis ( r = .57, p < .01) but only a trend in multivariate analysis ( OR = 1.2; p = .06). Conclusions: Relationship concerns predicted risk for clinically significant anxiety and depression among stomach, esophageal, and GIST patients. Healthcare team communication and symptom burden concerns were also associated with anxiety and depression risk. Results highlight the need for constructive patient-provider communication, particularly around relationships and symptoms. Clinical trial information: NCT02333604.
Locally advanced gastric cancer (LAGC): Does histology suggest strategy in PAN-cancer Era?
Authors: Zurlo Ina Valeria , Calegari Maria Alessandra , Orlandi Armando , Strippoli Antonia , Pozzo Carmelo , Bagalà Cinzia , Garufi Giovanna , Di Dio Carmela , Barone Carlo , Bria Emilio , Basso Michele 
Published: January 2019

97 Background: Surgery is the only potentially curative treatment for LAGC. Evidences suggest that perioperative CT (pCT) plus surgery is superior to surgery alone, whereas studies on adjuvant CT (aCT) are controversial. Guidelines recommend a pCT approach in pts with stage II/III, nevertheless in real-life many pts receive immediate surgery followed by aCT. Histology influences both survival and pathological response with worse prognosis among diffuse LAGC. No trial has compared pCT and aCT or investigated the impact of histology on the outcome of these different approaches. We hypothesized that histology may predict a different benefit from CT administered in the two settings, allowing to define the optimal strategy. We performed a study comparing the two approaches according to histology. Methods: We retrospectively analyzed pts with stage II/III LAGCs treated at our Institution between Jan-09 and Jan-17. The objective of the study was to evaluate the impact of histology (intestinal and diffuse) on survival according to strategy approach (pCT vs aCT). Primary endpoints were DFS and OS. Results: 81 pts had diffuse LAGC (29 received pCT, 52 aCT) and 60 had intestinal LAGC (32 received pCT, 29 aCT). In the intestinal cohort both DFS and OS were significantly higher in pts treated with pCT compared to aCT (DFS: HR 0.3, p = 0.02; OS: HR 0.3, p = 0.03). On the contrary in the diffuse cohort both DFS and OS were significantly lower in pts receiving pCT compared to those receiving aCT (DFS: HR 2.4, p = 0.0014; OS: HR 2.6, p = 0.0012). Conclusions: Our study, although retrospective and small-sized, shows that the survival benefit of pCT is limited to intestinal LAGC, whereas in diffuse LAGC the administration of pCT appears detrimental. Indeed, diffuse LAGC is known to be chemoresistant and pCT might delay surgery allowing metastasization. Despite the arising of recent molecular classification, still far from modifying clinical practice, histotype might represent an easy factor to discriminate pts benefitting from pCT (intestinal) to those in whom upfront surgery might be recommended (diffuse). Our hypothesis needs to be confirmed in prospective trials.
Dose escalation and expansion cohort study for DS-8895a in patients with advanced solid tumors.
Authors: Satoh Taroh , Shitara Kohei , Iwasa Satoru , Yamaguchi Kensei , Muro Kei , Komatsu Yoshito , Nishina Tomohiro , Esaki Taito , Hasegawa Jun , Kakurai Yasuyuki , Kamiyama Emi , Nakata Tomoko , Nakamura Kota , Hyodo Ichinosuke 
Published: January 2019

99 Background: Erythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface of many tumors and is associated with poor prognosis, suggesting EPHA2 as a target for cancer therapy. DS-8895a is an afucosylated, humanized anti-EPHA2 IgG1 monoclonal antibody with potent cytotoxicity. We report results from a phase I clinical trial to determine safety, tolerability, and pharmacokinetics (PK) of DS-8895a in Japanese patients with advanced solid tumors (NCT02004717). Methods: Step 1 (dose escalation cohort) had patients with advanced solid tumors and comprised of six dose levels (0.1–20 mg/mL, intravenous infusion, every 2 weeks [Q2W]) with a 28-day dose limiting toxicity (DLT) evaluation period. Step 2 (expansion cohort) patients had gastric or esophageal cancer confirmed to be EPHA2 positive by immunohistochemistry. Dose level in Step 2 was determined based on results obtained in Step 1. We evaluated safety, PK, potential biomarkers including circulating NK cells and cytokines, and tumor response. Results: Maximum tolerated dose was not reached in Step 1 (n = 22). DS-8895a was administered at 20 mg/kg Q2W in Step 2 (n = 15). Among 37 patients in the safety analysis set, adverse events (AEs) were reported in 97.3% (64.9% drug-related); 35.1% presented grade ≥ 3 AEs (8.1% drug-related). Dose delay and study discontinuation due to AEs (treatment related: grade 4 platelet decrease, hypoesthesia, hypotension, peripheral coldness, nausea, and vomiting) were observed in one and four patients (20 mg/kg), respectively. Infusion-related reactions occurred in 51.4% of patients resulting in 10 dose interruptions with one discontinuation. Serum inflammatory cytokines were transiently increased 4 h from the end of infusion drug administration. Serum DS-8895a maximum and trough concentrations increased dose-dependently. Biomarkers had no apparent relationship to best overall response. Seven patients in Step 1 achieved stable disease; in Step 2, six patients achieved stable disease and one patient achieved partial response. Conclusions: DS-8895a was safe and well tolerated up to 20 mg/kg. The PK of DS-8895a was dose-dependent as expected. Clinical trial information: NCT02004717.
Multicenter open-label phase II trial to evaluate nivolumab and ipilimumab for second line therapy in elderly patients with advanced esophageal squamous cell cancer (RAMONA).
Authors: Meindl-Beinker Nadja M , Hartel Nicolai , Maenz Martin , Betge Johannes , Ebert Matthias Philip 
Published: January 2019

TPS174 Background: Advanced esophageal squamous cell cancer (ESCC) is frequently diagnosed in elderly patients (pts) and impact of 2nd line chemotherapy is poorly defined. In line with recent data demonstrating effectiveness of checkpoint inhibitors Nivolumab (Nivo) and Ipilimumab (Ipi) in squamous cell carcinoma pts, combined Nivo/Ipi therapy will be assessed as 2nd line therapy of advanced ESCC in elderly pts. Methods: RAMONA is a multicenter open-label phase II trial (NCT03416244). Eligibility and geriatric status of the pts will be assessed by the G8 screening tool and the Deficit Accumulation Frailty Index (DAFI). Upon safety assessment after a three cycle run-in phase of Nivo (240 mg Q2W), eligible pts will be escalated to Nivo (240 mg Q2W)/Ipi (1 mg/kg Q6W) combination therapy. The other pts will remain on Nivo only. The primary objective of this trial is to demonstrate a significant survival benefit of the Nivo/Ipi combination therapy in advanced ESCC compared to historical data of standard chemotherapy regimens. Primary endpoint is overall survival (OS); secondary endpoints are tumor response, PFS, safety and quality of life (QoL). The trial has a 90% Power to detect a hazard ratio of 0.68 at a one-side significance level of alpha = 0.05 under the assumption of exponential survival. This corresponds to an increase of the 1-year OS rate by a margin of 13% compared to historical controls for standard chemotherapy (i.e. 30% vs 17%). Subjects are accrued for a period of 12 month. Follow-up continues for 24 month after the last subject is added. Including a sample size increase to compensate for uninformative drop-outs a total of n = 75 subjects will be recruited. The primary endpoint will be assessed using a one-sample log-rank test. A particular study objective is the evaluation of the tolerability of Nivo as single agent and in combination with Ipi in terms of QoL. Therefore time to QoL deterioration will be determined. 18 pts have been enrolled by mid of September 2018. RAMONA also includes translational research to identify predictive biomarkers, establish organoid cultures from tumor tissues and assess the utility of microbiome analyses for response prediction. Clinical trial information: NCT03416244.