bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro and in vivo efficacy of the combined treatment of 150 khz tumor treating fields (TTFields) and sorafenib in hepatocellular carcinoma.
Authors: Weinberg Uri , Davidi Shiri , Gotlib Karnit , Zeevi Einav , Tempel- Brami Catherine , Schneiderman Rosa S. , Voloshin Tali , Giladi Moshe , Kinzel Adrian , Kirson Eilon David , Palti Yoram 
Published: January 2019

333 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer related mortality and the primary cause of cancer death. Sorafenib, an oral multikinase inhibitor is approved for patients with advanced HCC, yet its survival benefit is still limited. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. The aim of this work is to explore the potential of the use of TTFields alone and in combination with Sorafenib as a treatment for HCC. Methods: HepG2 and Huh-7D12 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Sorafenib (36-3000 nM) was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, cell cycle and clonogenic potential were determined. N1S1 HCC cells were injected to the left lobe of the liver of SD rats. After 1 week, TTFields (1.2 V/cm) and Sorafenib (10 mg/kg) were applied for 6 days and tumor growth was followed using MRI. Healthy rats were used to study safety of the use of TTFields (150 kHz) applied to the abdomen. Results: The optimal TTFields frequency was found to be 150 kHz for both cell lines. TTFields application (1.0 - 1.7 V/cm, 72 hours) at 150 kHz led to 53-64% reduction in cell counts and to additional reduction of over 70% in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number cells (2-way ANOVA, p < 0.001) as compared to each treatment alone. Tumor growth was significantly reduced by the combined group compared to the control group (student t test, p < 0.01). Safety studies did not reveal any adverse event associated with TTFields application to the rat abdomen. Conclusions: The results presented in this work demonstrate that TTFields can be a safe and effective treatment against HCC cells and that the combination with Sorafenib may further enhance treatment efficacy.
Impact of glycemic control on treatment efficacy and safety during nabpaclitaxel plus gemcitabine therapy in unresectable pancreatic cancer.
Authors: Tauchi Junko , Shinohara Akira , Ohashi Ken , Shibuki Taro , Kimura Gen , Umemoto Kumiko , Watanabe Kazuo , Sasaki Mitsuhito , Takahashi Hideaki , Hashimoto Yusuke , Imaoka Hiroshi , Ohno Izumi , Mitsunaga Shuichi , Ikeda Masafumi , Kawasaki Toshikatsu 
Published: January 2019

337 Background: Diabetes mellitus (DM) and hyperglycemia have been widely considered to be associated with the risk of pancreatic cancer. However, the aim of this study was to evaluate the relationship between glycemic control and the efficacy or safety in pancreatic cancer pts receiving treatment with nab-Paclitaxel (nab-PTX) plus Gemcitabine (GEM). Methods: We retrospectively reviewed 285 pts with unresectable pancreatic cancer with nab-PTX plus GEM as the first-line chemotherapy from December 2014 to March 2017 at the National Cancer Center Hospital East, Kashiwa, Japan. The pts were divided into two groups, average blood glucose level during the period of chemotherapy was less than 160 mg/dL (Group GC: Good glycemic control group) and more than 160 mg/dL (Group PC: Poor glycemic control group). Results: A total of 285 pts were enrolled. Median age was 66 years (range: 26-84) and males/females: 180/105, PS (0-1/2-3): 272/13, stage (III/IV): 77/208. There were 226 pts in GC group and 59 pts in PC group. No significant differences were seen in the overall survival between Group GC and PC (median: 16.1 months vs. 13.8 months, p = 0.344) and in the progression free survival between the two groups (median: 7.5 months vs. 8.2 months, p = 0.862). The incidence rate of grade 2-3 chemotherapy-induced peripheral neuropathy (CIPN) was significantly higher in Group PC compared with Group GC (Group GC 28.3%, Group PC 45.8%, p = 0.010). Univariate and multivariate analyses identified glycemic control as significant independent factors associated with the incidence of grade 2-3 of CIPN (Odds ratio 2.182, 95% CI 1.20-3.96, p = 0.010). There was no significant difference in the relative dose intensity of nab-PTX between two groups (median, 56.6% in group GC, 56.5% in group PC, p = 0.952). Conclusions: Glycemic control during the chemotherapy with nab-PTX plus GEM in unresectable pancreatic cancer was not associated with OS. The incidence of severe CIPN was higher in pts with poor glycemic control compared with good glycemic control.
Liver injury by immune checkpoint inhibitors in patients with hepatocellular carcinoma.
Authors: Personeni Nicola , Pressiani Tiziana , Capogreco Antonio , Dal Buono Arianna , D'Alessio Antonio , Prete Maria Giuseppina , Smiroldo Valeria , Bozzarelli Silvia , Giordano Laura , Aghemo Alessio , Santoro Armando , Rimassa Lorenza 
Published: January 2019

341 Background: In patients with hepatocellular carcinoma (HCC) and baseline liver dysfunction, hepatic immune-related adverse events (HIRAEs) during immunotherapy have not been adequately characterized and their impact on subsequent treatment outcomes is not known. Methods: 40 patients with advanced/unresectable HCC and Child Pugh score A have been enrolled in first and second-line clinical trials of anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs). HCC etiologies were: hepatitis C (32.5%), hepatitis B (7.5%), alcohol abuse (27.5%), other (32.5%). 7 received anti-PD-1 mAbs alone and 33 received combined regimens that included anti-PD-1 mAbs plus either anti-cytotoxic T lymphocyte antigen 4 (30.4%) or tyrosine kinase inhibitors (TKIs) (54.5%), or both (15.1%). We reviewed their liver function tests and HIRAEs onset was related to time to treatment failure (TTF). Results: Overall, 12 patients (30%) developed grade ≥ 3 hepatitis according to Common Toxicity Criteria for Adverse Events v. 4.03, resulting in 4 cases of grade 2 drug-induced liver injury per DILI Working Group criteria. Time between therapy initiation and hepatitis onset was 1.4 months (0.4-2.8) and median peak aminotransferase (AT) level was 258 IU/L (85-869). Out of 6 permanent treatment discontinuations due to adverse events (AEs), 4 were linked to hepatitis. Higher AT median levels at baseline were significantly linked to grade ≥ 3 hepatitis compared with lower grades (95 IU/L vs. 36 IU/L, respectively; p = 0.008). Etiology, age, treatment did not predict HIRAEs onset. TTF in patients in patients with grade ≥ 3 hepatitis was shorter than in the whole cohort (1.4 vs. 3.8 months, p = 0.041), while overall survival did not differ (p = 0.125). Conclusions: We observed a 30% incidence of clinically significant HIRAEs. HIRAEs represent the most frequent AEs leading to treatment discontinuation in patients with HCC undergoing treatments with immune checkpoint inhibitors. Baseline AT levels may identify patients at increased risk of grade ≥ 3 hepatitis.
The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: An exploratory subgroup analysis of JCOG1113.
Authors: Yamada Ikuhiro , Morizane Chigusa , Okusaka Takuji , Ogawa Gakuto , Sato Yuya , Ueno Makoto , Ikeda Masafumi , Sugimori Kazuya , Fukutomi Akira , Shimizu Satoshi , Mizuno Nobumasa , Yanagimoto Hiroaki , Sano Keiji , Tobimatsu Kazutoshi , Yane Kei , Nakamori Shoji , Sata Naohiro , Nishina Tomohiro , Ishii Hiroshi , Furuse Junji 
Published: January 2019

349 Background: JCOG1113 is a randomized phase III trial to confirm the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for advanced biliary tract cancer (BTC) in overall survival (OS). In the final analysis, GS demonstrated non-inferiority to GC in OS and was considered as a new option of standard of care for advanced BTC. However, there are few reports on the efficacy and safety of combination chemotherapy in elderly patients with advanced BTC. Therefore, this study aimed to explore the clinical outcomes of combination chemotherapy in elderly patients with advanced BTC. Methods: Among all enrolled patients in JCOG1113, ≥ 75 years old patients were included in this exploratory subgroup analysis. Cox regression analysis was performed to investigate the influence of age at baseline on OS and PFS. Clinically relevant adverse events (AEs) were defined as any of grade 2 or more fatigue, appetite loss, nausea, vomiting, oral mucositis, and diarrhea, and were compared using Fisher’s exact test. Results: Among all enrolled patients, 155 patients in GC and 139 patients in GS were included in < 75 years old cohort and 20 patients in GC and 40 patients in GS were included in ≥ 75 years old cohort.The HR of ≥ 75 years old cohort to < 75 years old cohort for OS was 0.96 (95% CI 0.71–1.30) in all enrolled patients. The HR of ≥ 75 years old cohort to < 75 years old cohort for OS was 1.26 (95% CI 0.77–2.04) in GC, and 0.84 (95% CI 0.56–1.24) in GS. The HR of ≥ 75 years old cohort to < 75 years old cohort for PFS was 1.01 (95% CI 0.63–1.61) in GC, and 0.78 (95% CI 0.54–1.12) in GS. Clinically relevant AEs were 36.1% in < 75 years old cohort and 25.0% in ≥ 75 years old cohort in GC, and 29.5% in < 75 years old cohort and 32.5% in ≥ 75 years old cohort in GS. Conclusions: The clinical outcomes of combination chemotherapy in elderly patients were comparable to non-elderly patients. Clinical trial information: 000010667.
Effectiveness of laparoscopic surgery in patients with large gastric GIST (diameter > 5cm).
Authors: Li Fei , Gao Chongchong 
Published: January 2019

35 Background: Recently, the application of laparoscopic or DaVinci surgery in relatively small gastrointestinal stromal tumors (GIST) has been increasingly recognized. However, the use in large stromal tumors, especially with a diameter greater than 5 cm, remains controversial for fear of tumor rupture. The aim of our study is to observe the effectiveness of laparoscopic approach in treatment of large gastric GIST. Methods: Patients who were diagnosed with gastric GIST (diameter > 5cm) at Xuanwu Hospital, China and underwent laparoscopic surgery from May 2011 to May 2018 were assessed. We set intraoperative tumor rupture as primary outcome. Secondly outcomes were conversion rate, operating time, estimated blood loss, length of postoperative hospital stay and recurrence rate at the end of the follow-up. Results: Fourty patients were included in our study with tumor size (7.54 ty-tw) cm (range, 5.0~13.8 cm). There was no intraoperative tumor rupture occurred. The median duration of operation was (76.3±29.9) minutes with estimated blood loss (28.7±15.2) mL. The median time for length of postoperative hospital stay was (5.8±4.1) days. The follow-up period for all the patients was 23.1 months (range, 2.4~51months). No local or distant recurrence was observed. Conclusions: Laparoscopic resection for large gastric GIST is feasible and effective. Laparoscopic surgery can substitute for open surgery as standard approach for gastric stromal tumors.
Provider-volume associated with variable receipt of therapy and outcomes for noncurative pancreas adenocarcinoma: A population-based analysis.
Authors: Hallet Julie I. , Davis Laura , Mavros Michail , Mahar Alyson L. , Beyfuss Kaitlyn , Liu Ying , Kennedy Erin Diane , Earle Craig , Coburn Natalie G. 
Published: January 2019

352 Background: While high-volume providers for pancreatic adenocarcinoma (PA) surgery yield better outcomes, variation in practice and the role of provider-volume has not been investigated for systemic therapy. We examined variation in practice and outcomes in the management of non-curative PA, based on medical oncology provider-volume. Methods: We conducted a population based retrospective cohort study of non-resected PA over 2005-2016 by linking administrative healthcare datasets. High-volume (HV) medical-oncology providers were defined as the 5th quintile of number of PA seen per provider per year. Outcomes were receipt of chemotherapy and overall survival (OS). Brown Forsythe Levene (BFL) test for equality of variances assessed outcomes variability between provider-volume quintiles (Q1 to 5). Multivariate regressions examined the association between management by HV provider and receipt of systemic therapy and OS. Results: Of 10,881 non-curative PA patients, 7,062 consulted with medical oncology. Among 341 medical oncology providers, 3% were HV, defined as > 16 patients/year. There was variability in receipt of chemotherapy based on provider-volume, with 44% (IQR: 25-54) for Q1 and 47% (IQR: 43-54) for Q5, and in median survival, with 4.1 months (IQR: 2.7-6.2) for Q1 and 7.5 months (IQR: 6.6-8.0) for Q5. Variability between provider-volume quintiles was significant for receipt of chemotherapy and median survival (both BFL p < 0.001). After adjusting for age, sex, comorbidity burden, rurality, income quintile, and diagnosis year, HV provider was independently associated with higher odds of receiving chemotherapy (OR 1.19 [1.05-1.34]), and superior OS (HR 0.79 [0.74-0.84]). Conclusions: There was significant variation in non-curative management and outcomes of PA based on provider-volume. Management by a HV provider was independently associated with higher odds of receiving chemotherapy and superior OS, after adjusting for case-mix. This information is important to inform disease care pathways and care organization. Cancer care systems could consider initiatives to increase the number of HV providers to reduce variation and improve outcomes.
Real-world treatment characteristics for first-line therapy (1L) of advanced hepatocellular carcinoma (HCC) in Canada and Europe.
Authors: Gill Sharlene , Jaffe Dena H , DeCongelio Marc , DuBell Arnold N. , Shi Jing , Wisniewski Tami , Thompson Gwilym 
Published: January 2019

353 Background: Sorafenib is indicated for the treatment of HCC. This study captures and describes real-world use of 1L therapy for advanced unresectable or metastatic HCC across Canada and Europe. Methods: A retrospective, non-interventional survey of 278 physicians in Canada (7.5%) and Europe (92.5%) (France, Germany, Italy, Spain and UK) was conducted between Feb-Mar 2018. Clinical and treatment data were collected from medical charts for patients aged ≥18y, who initiated and completed systemic 1L treatment for HCC within 2 years of data collection, and a Child-Pugh [CP] A/B at 1L initiation. Descriptive statistics compared 1L systemic therapy, sorafenib vs. other. Results: 706 patients were included (n = 504 sorafenib; n = 202 other [83% chemotherapy; 10% targeted therapy; 7% checkpoint inhibitors]) with a mean age at 1L of 62.7±9.3y and 79% males. Comorbidities did not differ by sorafenib vs. other for alcoholism (33%), Hepatitis C (14%), and nonalcoholic steatohepatitis and/or nonalcoholic fatty liver disease (9%) but did for Hepatitis B (12% vs. 6%) and cirrhosis (31% vs. 18%) (both p < 0.05). At diagnosis, more patients treated with sorafenib vs. other had portal vein invasion (56% vs. 35%, p < 0.001). At 1L initiation, sorafenib patients had better performance status (PS) (ECOG 0-1: 80% vs. 67%, p < 0.05) and preserved liver function (CP A: 58% vs. 47%, p < 0.05). The results indicated that sorafenib was used less compared to other systemic therapies among those with poor performance (ECOG 2-4) and poor liver function (CP B) (71% vs. 83%, p = 0.068). Median treatment duration was shorter for sorafenib (2 vs. 4 months, p < 0.001). The most common grade 3 adverse events were fatigue (9%), diarrhea (5%), and hand/foot skin reaction (4%). Conclusions: In this real-world chart survey of Canadian and European physicians, sorafenib remains the most commonly used 1L systemic therapy for advanced HCC. Patients treated with sorafenib were more likely to have cirrhotic liver disease, portal vein invasion, better PS and preserved liver function, but sorafenib use was not limited to CP A. Understanding determinants of 1L therapy is important as the treatment landscape of HCC is evolving to address unmet need.
Toxicity of FOLFOX-abraxane (FOLFOX-A) on phase II Brown University Oncology Group (BrUOG) trials.
Authors: Safran Howard , Breakstone Rimini , Charpentier Kevin , Vatkevich John , Marks Eric I , Cavanagh Lindsey , Mitchell Kristen , Renaud Jen , Beard Rachel , Rosati Kayla 
Published: January 2019

354 Background: FOLFIRINOX increases survival in pancreatic cancer. The Brown University Oncology Group developed the FOLFOX-A regimen in a phase I study. (Am J Clin Oncol, 2016). We subsequently opened phase II studies of FOLFOX-A in patients with metastatic pancreatic cancer (BrUOG 292), locally advanced/borderline pancreatic cancer (BrUOG 318) and adjuvant disease following resection (BrUOG 295). The BrUOG Data Safety Monitoring Committee met on May 22, 2018. Toxicity of FOLFOX-A reviewed at the May meeting aligned with data lock in April on phase II FOLFOX-A studies and is summarized. Methods: Patients received oxaliplatin, 85mg/m2 day 1, nab-paclitaxel, 150mg/m2 and leucovorin 400mg/m2 day 1 and fluorouracil 2400mg/m2 by continuous IV infusion over 46 hours. Myeloid growth factor support was optional. Cycles were repeated every 14 days for up to 10-12 cycles. Oxaliplatin was dose reduced to 68mg/m2 for grade 2 neurotoxicity. CTCAE version 4 toxicity scales were utilized. Results: A total of 81 patients were accrued, (22 adjuvant, 36 metastatic, 23 locally advanced disease). Cumulative fatigue was the most common toxicity and required dose reduction in 50% of patients. The incidences of grade 2, 3 and 4 neutropenia were 26%, 17% and 6%, respectively. Grade 2,3 and 4 diarrhea were 9%, 15% and 0%. The rates of grade 2,3 and 4 neuropathy were 29%, 2% and 0%. Conclusions: FOLFOX-A is well tolerated with low incidences of grade 3 neuropathy and gastrointestinal toxicity. Toxicities were less frequent in patients treated in the adjuvant setting. Clinical trial information: NCT02080221, NCT02022033, NCT02578732.
Hepatic arterial infusion chemotherapy after sorafenib treatment in patients with advanced hepatocellular carcinoma who are unfit for regorafenib.
Authors: Terashima Takeshi , Yamashita Tatsuya , Takata Noboru , Arai Kuniaki , Mizukoshi Eishiro , Kaneko Shuichi 
Published: January 2019

355 Background: The RESORCE trial proved survival benefit of regorafenib on advanced hepatocellular carcinoma (aHCC) in the limiting cohort. This study aimed to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) as second-line treatment in patients with aHCC who are unfit for regorafenib. Methods: We studied consecutive 159 patients with aHCC treated with sorafenib in our institution from June 2009 to March 2018. We divided them into two groups according to the eligibility for RESORCE trial (Rego or non-Rego group) and investigated the efficacy of HAIC as post-sorafenib treatment. Moreover, we also analyzed the prognostic factors in each group. Results: When sorafenib treatment failed, 63 patients (39.6%) fulfilled key inclusion criteria of the RESORCE trial and were considered as fit for regorafenib treatment (Rego group). Among 96 remaining patients (non-Rego group), 34 patients (35.4%) were treated with HAIC after sorafenib. The objective response and the median progression-free survival of HAIC were 38.2% and 3.9 months, which were independent of the efficacy or treatment duration of sorafenib. The median survival of HAIC after sorafenib was 11.3 months which was significantly longer than that of 62 patients without HAIC (4.7 months; P = 0.023). Four factors, HAIC (HR 0.516), Child-Pugh A (HR 0.362), tumor size ≥35mm (HR 1.959), and AFP ≥200 (HR 1.728), were identified as independent prognostic factors after sorafenib in multivariate analysis. In Rego group, 14 patients were actually treated with regorafenib and their survival after sorafenib was longer than that of the patients without regorafenib and with HAIC (P < 0.01 and P < 0.01, respectively). In Rego group, regorafenib (HR 0.152), extrahepatic lesions (HR 2.160), and ≥10 intra-hepatic lesions (HR 2.099) were identified as prognostic factors after sorafenib in multivariate analysis. Conclusions: HAIC showed promising tumor response and patients’ outcome for the patients who are unfit for regorafenib. Further investigation is needed to compare HAIC with ramucirumab, cabozantinib or nivolumab.
Results of conversion surgery after the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic cancer.
Authors: Ikeda Naoya , Akahori Takahiro , Satoi Sohei , Yanagimoto Hiroaki , Nagai Minako , Nakagawa Kenji , Nishiwada Satoshi , Nakamura Kota , Takagi Tadataka , Hirooka Satoshi , Yamamoto Tomohisa , Yamaki So , Sho Masayuki 
Published: January 2019

366 Background: Recent improvements in chemotherapy for initially unresectable pancreatic ductal adenocarcinoma (UPDAC) occasionally show remarkable antitumor effect and lead to conversion surgery (CS). However, the optimal indication and clinical impact of CS remains unknown. We have recently developed a new regimen consisted of biweekly S-1, oxaliplatin, and irinotecan (SOXIRI). In this regimen, we used S-1 in alternate-day administration instead of 5-FU, that can be more feasible than FOLFIRINOX. The aim of this study was to evaluate the clinical impact of CS after SOXILI treatment for initially UPDAC. Methods: We conducted an open-label, single-arm, phase II study that was carried out at Nara Medical University and Kansai Medical University in Japan. Patients with untreated metastatic and locally advanced PDAC were enrolled. They received 80 mg/m2 twice a day of S-1 for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results: The 35 enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8%; median OS, 17.7 months; and median PFS, 7.4 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). Twenty-three out of 35 patients of UR-PDAC were unresectable locally advanced pancreatic cancer (UR-LAPA). Seven out of 23 patients with UR-LAPA underwent CS. Distal pancreatectomy with celiac axis resection was performed in three patients, central pancreatectomy was performed in one patient. Pancreatoduodenectomy (PD) was performed in two patients, and PD with portal vein resection in one patient. Two out of seven patients had postoperative complications. One case had grade B pancreatic fistula, and the other case underwent cholecystectomy due to acute cholecystitis. The median OS in patients who received CS was 31.4 months. Conclusions: SOXIRI regimen has shown promising clinical efficacy with acceptable tolerability in patients with unresectable pancreatic cancer. Furthermore, it may be a potent first-line treatment when considering conversion surgery. Clinical trial information: UMIN000014339.