bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of clinical and pathologic staging in esophageal cancer.
Authors: Scholer Anthony Joseph , Uppal Abhineet , Ghosh Debopriya , Kledzik Mary , Santamaria-Barria Juan , Khader Adam , Fischer Trevan D , Goldfarb Melanie 
Published: January 2019

31 Background: Randomized trials have demonstrated improved disease-free survival for more advanced esophageal cancer treated with neoadjuvant chemo radiation (NCXRT). However, accurately treating a patient relies on the accuracy of pre-treatment T and N staging with endoscopy ultrasound and cross-sectional imaging, which is unknown, and can lead to over or under-treatment. Therefore, the objective of this study is to compare the clinical and pathologic staging in patients with early esophageal cancer that would be impacted by inaccurate clinical staging. Methods: Primary, non-metastatic esophageal cancer patients who had upfront esophagectomy without neoadjuvant CXRT between 2004 and 2013 were identified in the National Cancer database. The Kappa index was used to determine patient and tumor characteristics that effected concordance between clinical and pathologic T and N staging (p > 0.05 shows discordance). Results: Of 1810, 43 % of clinical T2 tumors were upstaged compared to 38% of T1 and 13% of clinical T2 were downstaged. Clinically positive N1 disease had the greatest concordance (91%) between clinical and pathologically staging, compared to clinical N0, where 57% were upstaged. Some patient groups significantly impacted the concordance rates of staging. T-Stage was less accurate (more discordant) in females (68%, kappa 0.41, p = 0.057) and Blacks (59%, kappa 0.023, p = 0.069) whereas overall N-stage was more discordant in Hispanics (83%, kappa, 0.67, p = 0.165). Conclusions: Accurate staging for esophageal adenocarcinoma can significantly impact the course of treatment. Upfront surgical resection of clinical T1 lesions and node negative tumors are at risk for under-treatment due to poor concordance with pathological stage, which may lead to decreased survival compared to a regimen of NCXRT. Clinicians should be aware of patient and tumor characteristics that increase the likelihood of discordance between clinical and pathologic staging when discussing treatment options for patients with esophageal cancer.
An updated retrospective review of the safety and efficacy of sorafenib for recurrent hepatocellular carcinoma post-liver transplantation.
Authors: Feng Sophie , Fallah-Rad Nazanin , Cao Yanshuo , Knox Jennifer J. , Jang Raymond Woo-Jun , Dhani Neesha C. , Sapisochin Gonzalo , Grant David , Greig Paul D , Lilly Leslie , Gorgen Andre , Chen Eric Xueyu 
Published: January 2019

313 Background: Orthotopic liver transplantation (OLT) is a potentially curative treatment for hepatocellular carcinoma (HCC). Despite an estimated recurrence rate between 15%-20%, there is currently no proven systemic therapy for the treatment of HCC relapse post OLT. Sorafenib has been a standard therapy for advanced HCC however data is lacking for the safety and efficacy of sorafenib in the setting of concurrent immunosuppressive agents. Methods: A retrospective review was performed of patients who received sorafenib for HCC relapse after OLT. Data on patient characteristics, treatment toxicity and efficacy was collected. The primary objectives were to evaluate toxicity and safety of sorafenib when used in combination with immunosuppressive therapies such as calcineurin and mTOR inhibitors. Secondary objectives were objective response rate, progression free survival (PFS), and time on therapy. Results: 35 patients over the last 11 years received sorafenib for HCC recurrence following OLT. 54.3% of patients received concurrent immunosuppression with tacrolimus. Toxicity from sorafenib was as expected, with no cases of acute or chronic organ rejection whilst on treatment. The median maximum tolerated dose was 400 mg a day with 40% of patients requiring dose reductions. The incidence of any adverse events (AEs) was 88.6%, with 17.1% having Grade 3-4 toxicity. Incidence of Grade 3-4 liver dysfunction was higher than historical studies at 6%. The overall response rate was 2.8% with a median PFS of 2.8 months. Median time on sorafenib was 3.1 months. Conclusions: There is a paucity of evidence guiding treatment of HCC recurrence following OLT. This retrospective review is one of the largest in the literature and shows that sorafenib used concurrently with immunosuppressive therapy for organ transplant is safe, with no precipitation of acute or chronic rejection, although liver function should be monitored closely. The median PFS in our cohort was shorter than expected. The efficacy of other agents should be explored in this population.[Table: see text]
Gemcitabine/nab-paclitaxel (G/A) alternating with 5-FU/leucovorin/irinotecan (FOLFIRI) in first-line metastatic pancreatic cancer (MPC): Updated results.
Authors: Picozzi Vincent J. , Lin Bruce Shih-Li , Mandelson Margaret T. 
Published: January 2019

314 Background: Both gemcitabine- and 5-FU-based chemotherapy (chemoRx) have demonstrated efficacy in MPC. Alternating these two regimens may 1) decrease toxicity 2) slow emergence of resistant cancer biology, and 3) provide a broader platform for addition of other (non)chemotherapeutic (CT) agents to the base regimen. The strategy using alternating G/A and FOLFIRI in MPC was first tested in the SEENA-1 trial (Picozzi et.al. GI Cancer Symposium 2017) and further suggested to be of benefit both at our own institution (Picozzi et.al. ASCO 2018 ) and elsewhere (Assenat et.al. ASCO 2018). We extend and update our observations here. Methods: Eligible patients (pts) had the following characteristics: 1) bx proven de novo MPC, 2) chemoRx naive, 3) ECOG PS 0/1, and 4) bi-dimensionally measurable disease. Treatment (Rx) consisted of 1) gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/2d 1,(8),15 alternating every 8 weeks (2 cycles) with FOLFIRI. Pts were radiographically restaged every 8 weeks. Rx was continued for up to 48 weeks, at which time additional Rx was given per physician/patient decision. Results: As of 9/2018, 61 pts have been treated at our institution via this method. Median age is 67; ECOG PS 0/1 58/42%. Disease site involvement included liver, lung, peritoneum 79%, 39%, and 23% respectively. Toxicity is less than typical with either individual regimen (e.g. no ≥ grade 3 neuropathy or diarrhea has been seen to date). Of pts followed for ≥ 4 months , 45/51 (88%) received ≥ 4 cycles Rx. Median number Rx cycles received was 9; 15/34 (44%) pts followed for > 1 year completed 48 weeks Rx. Disease control rate at 16 weeks in 45 evaluable patients is 89% (47% PR, 42% SD, 11% PD). 27/61 pts (44%) are currently on Rx (4 transferred care from region, 30 deceased). Currently, median f/u is 11.8 mo; median OS is 14.1 mo ( 95% CI 10.6-20.3 mo) 6,12, 18 and 24 mo OS are 88%,57 %, 34%, and 15% respectively. Conclusions: 1) Alternating G/A and FOLFIRI in MPC appears to have a more favorable toxicity profile than either individual regimen. 2) Median OS in MPC using this Rx is at least competitive with other reports. 3) The above method has potential to integrate other therapeutic agents/ treatment approaches.
Efficacy and safety of nivolumab in first-line or further treatment of advanced metastatic biliary tract cancer.
Authors: Gou Miaomiao , Zhang Yong , Si Haiyan , Dai Guanghai 
Published: January 2019

315 Background: PD-1 inhibitors have improved efficacy in many cancers. There are few report of nivolumab for metastatic biliary tract cancer (MBTC). This study reviewed the efficacy and safety of nivolumab for MBTC to improve efficacy and survival. Methods: Thirty patients with MBTC were voluntarily treated with non-clinical nivolumab at the PLA General Hospital. Nivolumab 200 mg or 180 mg was administered according to patient tolerance. Progression free survival (PFS), overall survival (OS) was evaluated by kaplan-meier and univariate analysis were carried out among clinical characteristics. Objective response rates (ORR), disease control rates (DCR), and treatment-related adverse events (AEs) were also evaluated. Results: The median treatment cycle is 4 cycles. One case was complete response (CR), 5 cases partial response (PR), 12 cases stable (SD). ORR was 20%, DCR was 60%. PFS was 3.1m (95% CI: 2.13~4.06 months). The AEs of nivolumab monothrapy were fatigue (3 cases), fever (2 cases), hypothyroidism (1 case), skin reaction (1 case). Nivolumab combined with chemotherapy related 1-2 hematologic toxicity were leukopenia (5 cases), thrombocytopenia (2 cases), and grade 3-4 were leukopenia (3 cases). Non-hematologic toxicity grade 1-2 were nausea and vomiting (4 cases), fatigue (4 cases), fever (3 cases), peripheral neurotoxicity (3 cases), and hypothyroidism (1 case). Univariate analysis showed that PFS was 4.20m in patients older than 53 years, slightly higher than those younger than 53 years (3.0 m, P = 0.047). PFS of nivolumab combined with chemotherapy was statistically significant compared with nivolumab monothrapy (4.1 m vs 2.3 m, p = 0.031). Patients with metastatic number > 2 had a shorter PFS than those < 2 (1.4 m vs 4.1 m, P = 0.05). PD-L1 expression positive have no better PFS compared with PD-L1 negative (3.6 m vs 3.1 m , p = 0.801). Multivariate analysis show nivolumab combined with chemotherapy was only independent factor for longer PFS (HR: 0.432, P < 0.05). Conclusions: the safety of nivolumab in MBTC is controllable. Subgroup analysis suggests that further selection of superior populations is needed and sample size need to be expanded to improve the efficacy of nivolumab in MBTC.
Safety and efficacy of lenvatinib by starting dose (8 mg or 12 mg) based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT.
Authors: Okusaka Takuji , Ikeda Kenji , Kudo Masatoshi , Finn Richard S. , Qin Shukui , Han Kwang-Hyub , Cheng Ann-Lii , Piscaglia Fabio , Kobayashi Masahiro , Sung Max W. , Chen Minshan , Wyrwicz Lucjan , Yoon Jung-Hwan , Ren Zhenggang , Stepan Daniel E. , Dutcus Corina E. , Tamai Toshiyuki , Ren Min , Hayato Seiichi , Kumada Hiromitsu 
Published: January 2019

316 Background: Lenvatinib (LEN) demonstrated statistical confirmation of noninferiority versus sorafenib (SOR) for overall survival (OS), and improved progression-free survival (PFS), time to progression, and objective response rate (ORR) in pts with uHCC in REFLECT (Kudo M et al, Lancet 2018). We report the efficacy and safety of LEN by starting dose, which was based on body weight (BW). Methods: In REFLECT, a multicenter, open-label, noninferiority trial, pts with uHCC were randomized 1:1 to LEN (BW < 60 kg: 8 mg/d; BW ≥ 60 kg: 12 mg/d; QD) or SOR (400 mg BID). Efficacy was analyzed by intention-to-treat; safety was analyzed in pts who received treatment, in each dose group. Results: Of 478 pts randomized to LEN, 151 (male, 70%; median age, 65 y) and 327 (male, 91%; median age, 62 y) were included in the LEN starting dose groups of 8 mg/d or 12 mg/d, respectively. In the 8-mg group, 14% of pts were from Western regions; 86% from Asia-Pacific. In the 12-mg group, 42% were from Western regions; 58% from Asia-Pacific. Median OS was 13.4 (95% CI: 10.5–15.7) and 13.7 months (95% CI: 12.0–15.6); ORR was 22.2% and 24.9% for pts with BW < 60 kg and ≥ 60 kg, respectively. Median PFS was 7.4 months in both groups. Median duration of treatment: 8-mg group, 5.6 months; 12-mg group, 6.3 months. Mean LEN relative dose intensity: 8-mg group, 87.7%; 12-mg group, 87.5%. Most common any-grade adverse events (AEs; 8-mg vs 12-mg) were hypertension (43% vs 42%), diarrhea (35% vs 40%), decreased appetite (33% vs 35%), weight loss (29% vs 32%), and fatigue (28% vs 31%). Adjusted by treatment duration, AE rates (episodes/patient-year) were similar for 8-mg versus 12-mg: hypertension (0.79 vs 0.78), diarrhea (1.06 vs 0.99), decreased appetite (0.63 vs 0.59), weight loss (0.50 vs 0.51), and fatigue (0.52 vs 0.47). Pharmacokinetic profiles were similar between groups. Conclusions: LEN efficacy was comparable between groups. Exposure to LEN was greater for the 12-mg versus 8-mg group. When AEs were adjusted by treatment duration, no notable differences in the AE profiles between the starting doses were observed. Altogether, these results support the 8-mg and 12-mg starting doses based on BW of < 60 kg and ≥ 60 kg, respectively, in REFLECT. Clinical trial information: NCT01761266.
A multicenter, phase Ib/2 study of varlitinib plus gemcitabine and cisplatin (gem/cis) for treatment of naïve, advanced, or metastatic biliary tract cancer (BTC).
Authors: Oh Do-Youn , Yong Wei-Peng , Chen Li-Tzong , Kim Ji-Won , Chang Alex Yuang-Chi , Park Jin Hyun , Hsieh Chih-Yi , Shih Hsuan-Jen , McIntyre Nicola , Chen Ying-Chen , Chang Wei-Ling , McHale Mark , Lindmark Bertil 
Published: January 2019

319 Background: BTC is a rapidly progressing cancer with limited response to chemotherapy. First line therapy (gem/cis) was defined in the ABC-02 study (Valle et al), where a 26% response was seen. HER family receptors are overexpressed and may be involved in tumour proliferation and survival in BTC. Varlitinib, a reversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, shows potent activity as monotherapy in preclinical BTC models and clinical activity in BTC patients (pts) in phase (ph) 1 trials. We conducted a ph Ib/2 study of varlitinib plus gem/cis in BTC to understand the safety profile and determine the maximum tolerated dose (MTD) of the combination. Methods: A modified 3+3+3 escalation design was used in Ph1b, with 2 varlitinib dose levels (200 and 300 mg BID) plus gem/cis on Day 1 and 8 in a 3 week cycle. The primary objectives are to determine the MTD and to characterize the safety profile. Secondary objectives are to assess the preliminary efficacy and to evaluate the pharmacokinetics of varlitinib and any circulating metabolites. Results: As of 10 Sep 2018, 21 pts were enrolled (11 in 200 mg cohort and 10 in 300 mg cohort, with 9 and 4 evaluable for MTD, respectively). Dose limiting toxicities (DLTs) were observed in 3 pts (1 G3 unconjugated hyperbilirubinemia and 1 G3 ALT transaminitis/G4 AST transaminitis in 200 mg cohort; 1 G4 thrombocytopenia/G3 febrile neutropenia/G3 AST elevation in 300 mg cohort). In 19 pts who were on varlitinib ≥ 1 month, 7 had partial response and 10 achieved stable disease (all > 12 weeks), giving the overall response rate of 37% and the disease control rate of 89%. The median PFS for the 200 mg cohort was 248 days and was not reached for the 300 mg cohort. The most common (≥ 30%) all-grade adverse events (AEs) regardless of causality were thrombocytopenia (62%), neutropenia (52%), anorexia (38%), nausea (38%), diarrhoea (38%), and anaemia (33%); the most common (≥ 15%) grade ≥ 3 AEs were neutropenia (48%), thrombocytopenia (33%), and anaemia (19%). Conclusions: Varlitinib plus gem/cis was well tolerated in the 200 mg cohort; the 300 mg cohort is ongoing. Preliminary anti-tumour activity was observed. Data will be updated at the time of presentation. Clinical trial information: NCT02992340.
Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer treated with gemcitabine and nab-paclitaxel.
Authors: Kan Motoyasu , Imaoka Hiroshi , Ikeda Masafumi , Mitsunaga Shuichi , Ohno Izumi , Hashimoto Yusuke , Sasaki Mitsuhito , Takahashi Hideaki , Watanabe Kazuo , Umemoto Kumiko , Kimura Gen , Shibuki Taro 
Published: January 2019

324 Background: Chemotherapy-induced neutropenia (CIN) has been reported to be associated with a longer survival in patients with various cancers. The aim of our study was to assess whether CIN could also be a prognostic factor in patients with unresectable pancreatic cancer receiving treatment with gemcitabine (GEM) and nab-paclitaxel (nab-PTX). Methods: We retrospectively analyzed the medical records of pancreatic cancer patients who had been treated with GEM and nab-PTX as first-line chemotherapy. CIN was categorized on the basis of the worst WHO grade during chemotherapy: absent/mild (≦ grade 2), or severe (≧ grade 3). The background characteristics and CIN as time-varying covariates (TVCs) were analyzed as potential prognostic factors using a Cox proportional hazards model. Results: We analyzed a total of 291 patients (absent/mild CIN: 116 patients; severe CIN: 174 patients). The median time to severe CIN was 14 days (interquartile range: 10–39 days). The median overall survival (OS) was significantly longer in the severe CIN group than in the absent/mild CIN group (19.2 vs. 11.3 months; p < 0.001) After adjustments, severe CIN was identified as an independent predictor of the OS (HR, 0.54; 95% CI, 0.38–0.77; p = 0.001). In the TVC model also, severe CIN was identified as an independent factor (HR, 0.79; 95% CI, 0.68–0.92; p = 0.002). Conclusions: Severe CIN was associated with a longer survival in patients with pancreatic cancer treated with GEM and nab-PTX.
External beam radiotherapy for hepatocellular carcinoma with right atrium tumor thrombus.
Authors: Bitterman Danielle Sara , Edgington Samantha K. , Noe Bridget N. , Kim Daniel W. , Eyler Christine E. , Goyal Lipika , Zhu Andrew X. , Wo Jennifer Yon-Li , Hong Theodore S. 
Published: January 2019

328 Background: Hepatocellular carcinoma (HCC) with right atrium tumor thrombus (RATT) via progression through hepatic veins into the inferior venal cava is a challenging entity with limited treatment options. Given the significant clinical sequelae of RATT, improved locoregional treatments are needed. We examined our experience with palliative right atrium-directed radiotherapy for HCC RATT. Methods: We conducted a retrospective study of 10 patients with HCC RATT treated with radiotherapy between 2011-2018. Patients with localized (n = 5) and metastatic (n = 5) disease were included. Clinical and treatment factors were collected. Results: Median follow-up was 3 mos. Baseline Childs Pugh score was A in 3 patients and B in 7 patients. The table below shows prescription and dosimetric data. No patients experienced grade ≥ 3 toxicity. The only major adverse cardiac event observed after radiotherapy was heart failure in 2 patients, and it was difficult to determine the contribution of treatment versus RATT. Three months post-radiation, 2 patients experienced a Childs Pugh score decline of > 2 points. At last follow-up, 5 patients were deceased, 4 patients were alive without progression, and 1 patient was alive with progression. Median progression free and overall survival was 3 mos (0.5-7 mos) and 3.5 mos (range 0.5-13 mos), respectively. RATT progression occurred in 1 patient, hepatic progression outside the treatment field occurred in 1 patient, and distant progression occurred in 2 patients. Causes of death included RATT progression (n = 1), HCC progression elsewhere (n = 2), hepatic decompensation (n = 1), and aspiration (n = 1). Conclusions: This unique series suggests HCC RATT-directed radiotherapy may be safe and locally effective. Prospective study is needed to understand the optimal treatment of these patients. [Table: see text]
Patterns of care and outcomes of definitive external beam radiotherapy and radioembolization for localized hepatocellular carcinoma: A propensity score-adjusted analysis.
Authors: Bitterman Danielle Sara , Sanford Nina Niu , Niemierko Andrzej , Mahal Brandon Arvin Virgil , Qadan Motaz , Ganguli Suvranu , Blaszkowsky Lawrence Scott , Zhu Andrew X. , Hong Theodore S. , Devlin Phillip M. , Goyal Lipika , Wo Jennifer Yon-Li 
Published: January 2019

329 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Most patients with localized HCC are not surgically operable or transplantation candidates, thus there is an increasing role for nonsurgical locoregional therapies. Ablative external beam radiotherapy (XRT) and transarterial radioembolization (TARE) are two emerging radiotherapeutic treatments for localized HCC. However, there are little data comparing their efficacy. We therefore sought to evaluate their utilization and efficacy in a large nationwide cohort. Methods: We conducted an observational study of 2,685 patients from the National Cancer Database diagnosed with American Joint Committee on Cancer 7th edition clinical stage I-III HCC between 2004-2015, treated with definitive-intent XRT delivered in 1-15 fractions or TARE. The association between treatment modality (XRT versus TARE [referent]) and overall survival (OS) was defined using propensity score-weighted Kaplan-Meier estimators and propensity score-weighted multivariable Cox regressions. Results: Among 2,685 patients, 2,007 (74.7%) received TARE and 678 (25.3%) received XRT, with increasing usage for both from 2004-2015 ( Ptrend < 0.001), but with overall greater uptake and absolute usage of TARE. Patients who received TARE were more likely to have elevated alpha fetoprotein and more advanced stage ( P < 0.05 for all). Median OS was 14.5 months for the entire cohort. XRT was associated with an OS advantage compared to TARE on propensity score-unadjusted analysis (adjusted hazard ratio [AHR] 0.80, 95% CI 0.67-0.95, P = 0.013), but not on propensity score-adjusted analysis (AHR 0.93, 95% CI 0.76-1.14, P = 0.491). Conclusions: Our study demonstrates that while both XRT and TARE usage have increased with time, there was greater uptake and absolute use of TARE, especially in advanced disease. Nevertheless, we found no difference in survival between XRT and TARE after propensity score-adjustment. Given their equivalence on retrospective study, prospective trials are necessary.
Lower risk of gastric atrophy and intestinal metaplasia in MALT lymphoma patients despite of H. pylori infection.
Authors: Lee San Min , Cheung Dae Young , Kim Jin Il , Park Soo-Heon 
Published: January 2019

33 Background: Atrophic gastritis and intestinal metaplasia are sequential consequences of chronic H. pylori infection. H. pylori infection is a well-known risk factor for gastric adenocarcinoma and MALT lymphoma of stomach. Atrophic gastritis and intestinal metaplasia increase the risk of gastric adenocarcinoma development. The relationship between gastric MALT lymphoma and atrophic gastritis-intestinal metaplasia has not been on the spot of interest. We investigated the clinical characteristics of gastric MALT lymphoma and co-presence of atrophic gastritis and intestinal metaplasia. Methods: Study was conducted by review of electronic medical record of patients who were diagnosed with gastric MALT lymphoma at an academic institute, the Yeouido St. Mary's Hospital, Seoul, Korea, from January 2001 to March 2018. Results: A total of 51 subjects were enrolled consecutively during the study period and analyzed retrospectively. The mean age was 57.5-year-old. The male to female ratio was 1.04 (26/25). On histologic examination, background atrophic gastritis was accompanied in 64.7% (33/51). Serum pepsinogen I, II and gastrin level, as serological marker for atrophy, were evaluated in 21 subjects. Thirteen out of 21 (61.9%) were compatible with serological atrophic gastritis (pepsinogen I / II ratio of less than three or pepsinogen I < 70 ng/mL). Conclusions: Prevalence of background mucosal atrophy or intestinal metaplasia was around 60% in patients with gastric MALT lymphoma. This is comparable to that of general population and lower than that of patients with gastric adenocarcinoma. Even though age can be a confounding factor, this result suggests different carcinogenic pathway of gastric MALT lymphoma from adenocarcinoma.