bluuebunny/crossref_metadata_2025_split huggingface dataset:
The outcome of patients with advanced hepatocellular carcinoma (HCC) in pre- and post-sorafenib eras using the SEER database.
Authors: Tan Jiahuai , Choi Minsig , Philip Philip Agop , Dyson Gregory , Shields Anthony Frank , Kim Richard D. 
Published: February 2017

276 Background: HCC is the third most common cause of cancer-related death globally. Prognosis for advanced HCC is dismal due to lack of effective treatment options for the majority of patients who present with advanced disease. Sorafenib was the first agent reported to improve overall survival in patients with good liver function enrolled in phase III clinical trials. However, survival impact of sorafenib on the general population with advanced HCC has not been studied to date. Methods: Sorafenib was approved for patients with advanced HCC and Child-Pugh A liver disease in 2007. We analyzed 2005-2006 and 2008-2009 clinical outcome data from the SEER to compare the impact of this targeted therapy in the population based setting. The Kaplan-Meier method was used to estimate the median survival and 95% confidence intervals (CI). The log-rank test was used to test the difference in survival curves. Cox regression analyses were utilized for the estimation of hazard ratios. Results: We identified 2297 and 2808 stage III and IV HCC cases diagnosed in [2005, 2006] and [2008, 2009], respectively. Seventy-seven percent of the patients were male and the median age was 61 years old for males and 66 for females. The median survival estimates (95% CIs) are 3 (3, 4) months and 4 (4, 4) months for patients diagnosed in [2005, 2006] and [2008, 2009], respectively. The hazard ratio (95% CI) for overall survival comparing [2008, 2009] to [2005, 2006] was 0.92 (0.87, 0.98, p-value = 0.01). We performed multivariable Cox regression modeling and African American patients have a hazard ratio of death [1.14 (1.06, 1.23)] as compared to European American patients. Younger females have a decreased hazard of dying relative to younger men, while older females have an increase hazard of dying relative to older men. Conclusions: The approval of sorafenib treatment produced very modest median survival gain in advanced HCC patients based on SEER population study. However, the small benefit in hazard ratio may have been impacted by small number of patients with advanced HCC who are being treated or are able to be treated with sorafenib in this era.
Phase I trial of sorafenib in high-risk hepatocellular carcinoma (HCC) patients after liver transplantation.
Authors: Siegel Abby B. , El-Khoueiry Anthony B. , Finn Richard S. , Blanke Charles Davic , Hidalgo Rosa , Brown Robert S. 
Published: February 2017

280 Background: LT offers long-term survival for HCC patients within the Milan criteria. For those outside, rates of recurrence are higher. There are no known treatments which decrease risk of recurrence post-transplant. We began a multicenter Phase I study of sorafenib in high-risk HCC patients after LT. Methods: Eligible subjects had pathologically proven HCC that was either (1) outside Milan (pre- or post-transplant), (2) poorly differentiated (Edmondson and Steiner grade 4), or (3) had vascular invasion at explant. We used a standard phase I dose-escalation design, beginning drug between 4 and 16 weeks after LT, with a planned duration of treatment of 6 months. Cohort dosages are as follows: (1) 200 mg q day (6 enrolled), (2) 200 mg BID (3 enrolled), (3) 200 mg/400 mg (3 enrolled), and (4) 400 mg BID. Correlative studies include circulating endothelial cells (CECs) and plasma biomarkers which are being collected prior to treatment, at 1 month, and at recurrence. Results: We have enrolled 12 patients, 11 are reported here. Mean age is 62; 64% had underlying HCV, 27% HBV, and 9% ETOH. 45% were outside Milan based on preoperative imaging. On explant, 36% had high grade pathology, and 18% had vascular invasion. Grade 3-4 toxicities seen in >10% include: cytopenias (27% neutropenia), LFT abnormalities (T. bili 18%), HTN (18%), and diarrhea (18%). We are currently enrolling at the 3rd dose level. We had 1 episode acute rejection at the 3rd dose level. CEC data are available for 8 patients, with a baseline range from 15-91, and 1 month range from 2-254. Mean follow up time is 18.0 months. 3 patients have recurred, one who was on drug for < 1 month. Conclusions: To our knowledge, this is the only ongoing multicenter Phase I trial of sorafenib in the post-transplant setting in the US. Post-transplant sorafenib for high-risk patients is feasible, and toxicity has been manageable for the most part. DLT has not yet been defined. Clinical trial information: NCT00997022.
Cryoablation compared with radiofrequency ablation and microwave coagulation therapy for the local control of primary hepatocellular carcinoma.
Authors: Ei Shigenori , Tanabe Minoru , Hibi Taizo , Itano Osamu , Shinoda Masahiro , Kitago Minoru , Abe Yuta , Yagi Hiroshi , Okabayashi Koji , Odaira Masanori , Kadota Yoshie , Fujimura Tomonori , Katsuki Yusuke , Tanaka Masayuki , Tsutsui Rina , Wakabayashi Go , Kitagawa Yuko 
Published: February 2017

286 Background: Although cryoablation (Cryo) has been advocated as an effective local treatment for hepatocellular carcinoma (HCC), data are lacking regarding its outcomes in comparison with radiofrequency ablation (RFA) and microwave coagulation therapy (MCT). The aim of this study was to clarify the benefits and disadvantages of each modality for primary HCC. Methods: We reviewed outcomes of 120 patients with primary HCCs (< 5cm) who underwent local treatment (Cryo: n = 55 and RFA/MCT: n = 65) between 1998 and 2011. The primary endpoint was local recurrence free survival (LRFS). The secondary endpoints were complication rates and the length of hospital stay. Results: Age, sex, Child-Pugh score, and background liver disease were identical between both groups. The Cryo group had larger tumors (mean ± standard error tumor size: Cryo 2.55 ± 0.75 cm vs. RFA/MCT 1.96 ± 0.72cm, p < 0.001). The LRFS was higher in the Cryo group than in RFA/MCT group (2270.0 ± 240.8 days vs. 1940.7 ± 269.5 days: p = 0.116). The Cox proportional hazards multivariate analysis revealed that Cryo as the treatment of choice was an independent predictive indicator of improved LRFS (HR, 0.403 [95% CI: 0.202−0.807], P = 0.010). On the contrary, tumor size (for each 1 cm increase, HR, 1.635 [95% CI: 1.038–2.574], p = 0.034) and Child-Pugh score ≥ 6 (HR, 2.166 [95% CI: 1.179 – 3.979], p = 0.013) were negative prognostic factors for LRFS. Subgroup analysis showed that the LRFS for tumors ≤ 2 cm was similar between the 2 groups. However, if the tumor size was greater than 2 cm, the LRFS of the Cryo group was superior to RFA/MCT (2400.0 ± 287.4 days vs. 1177.9 ± 366.5 days: p = 0.004). The complication rates (Cryo 10.9% vs. RFA/MCT 10.8%: p = 0.980) and the length of hospital stay (9.45 ± 5.33 days vs. 9.52 ± 5.90 days: p = 0.947) were similar in both groups. No mortality was observed in the entire cohort. Conclusions: Cryo provides significantly higher chance of local control for primary HCCs compared with RFA/MCT, particularly if the tumor size exceeds 2 cm. Associated risks are at least equivalent to those of RFA/MCT even in patients with marginal to poor liver function. Cryo is a promising local ablative option in an era of rising incidence of HCC.
Postoperative radiotherapy for gallbladder cancer.
Authors: Park Jin-hong , Kim Jong Hoon , Yoon Sang Min , Jung Nuri Hyun , Lee Young-Joo , Park Kwang-Min , Chang Heung-Moon , Kim Kyu-Pyo 
Published: February 2017

289 Background: Gallbladder cancer (GBC) is a relatively uncommon malignancy with high recurrence rate and poor prognosis, even after curative resection. Although postoperative radiotherapy (RT) has been tried to improve the poor results of surgery alone, the benefit of postoperative RT for GBC is still a matter of debate. The present study aimed to evaluate the effect of postoperative RT on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) in patients with GBC. Methods: Between March 1998 and July 2009, 228 patients with GBC (T2-3 N0-2) underwent surgical resection with potentially curative aim (R0 or R1) at Asan Medical Center. Among the 228 patients, 86 received postoperative RT (RT group) with or without concurrent chemotherapy, and 142 did surgery alone (no-RT group). All patients with postoperative RT received three-dimensional conformal radiotherapy, and the median radiation dose was 50 Gy (range, 45-60 Gy) at 1.8 or 2.0 Gy/fraction daily. Among them, 57 patients (66.3%) had concurrent chemotherapy based on 5-fluorouracil. Results: The median follow-up time was 90 months (range, 35-96 months) for the surviving patients. Although RT group had significantly more advanced disease in overall stage (p = 0.005), T stage (p = 0.002), N stage (p = 0.010), and higher rate of R1 resection (p = 0.027), the 3-year LRC was 78% for RT group and 66% for no-RT group (p = 0.088). Also, there was no significant difference in the 3-year DFS and OS: 51% vs. 52% (p = 0.994) and 53% vs. 56% (p = 0.541), respectively. In multivariate analysis, postoperative RT was a significant predictive factor of improved LRC (p = 0.011), DFS (p = 0.016) and OS (p = 0.036). Conclusions: Although RT group had more adverse risk factors, the treatment outcomes of RT group were similar to those of no-RT group. Moreover, postoperative RT was a significant predictor of improved LRC, DFS and OS after adjusting these factors. These results suggest that postoperative RT might be effective in locoregional control and survival for patients with GBC.
A randomized, double-blind, placebo-controlled trial of trametinib, a MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas.
Authors: Infante Jeffrey R. , Somer Bradley G. , Park Joon Oh , Li Chung-Pin , Scheulen Max E. , Kasubhai Saifuddin M. , Oh Do-Youn , Liu Yuan , Lahiri Soumi , Steplewski Klaudia , Le Ngocdiep T. 
Published: February 2017

291 Background: Trametinib, an oral MEK1/2 inhibitor, holds promise for tumors that frequently harbor RAS activating mutations, such as pancreatic cancer. Trametinib monotherapy or in combination with gemcitabine showed preliminary activity in patients (pts) with advanced pancreatic cancer. Methods: Eligible pts with untreated metastatic pancreatic cancer were randomized (double-blind, 1:1) to receive gemcitabine 1000 mg/m2 intravenously weekly x 7 for 8 weeks, then weekly x 3 every 4 weeks, plus either trametinib 2 mg or placebo daily. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and duration of response (DoR). OS and ORR were also analyzed based on baseline KRAS status as determined in plasma cell free DNA (cfDNA). Results: Baseline characteristics for the 160 randomized and treated pts were similar across arms. Skin related events (73% vs. 34%), diarrhea (54% vs. 28%), thrombocytopenia (40% vs. 28%), and stomatitis (36% vs. 8%) were more frequent with trametinib, as was grade 3/4 anemia (22% vs. 11%). However, rates of grade ≥ 3 thrombocytopenia, neutropenia and febrile neutropenia were similar between the arms. More pts on trametinib arm required dose reduction or interruption due to AEs (68% vs. 49% and 74% vs. 43%, respectively). Median OS was 8.4 months with trametinib compared to 6.7 months with placebo [HR 0.98 (95% CI: 0.67, 1.44, p=0.453)]. Median PFS was 16 weeks on trametinib and 15 weeks on placebo arm. ORRs and median DoRs were 22% and 23.9 weeks and 18% and 16.1 weeks on trametinib and placebo arm, respectively. The median OS and ORR in the subgroup of pts with KRAS mutations (n=143) was similar to OS and ORR for all randomized pts. Conclusions: This is first randomized, placebo-controlled trial evaluating the combination of gemcitabine with a MEK inhibitor. There was an increased incidence of skin, GI, and hematologic toxicities with trametinib compared to placebo. The addition of trametinib did not improve OS, PFS, or response rate. These outcomes remained independent of KRAS mutations based on cfDNA. Clinical trial information: NCT01231581.
Phase I/II study of E7050 (golvantinib) in combination with sorafenib in patients (pts) with advanced hepatocellular carcinoma (HCC): Phase I results.
Authors: O'Neil Bert H. , Bendell Johanna C. , Modiano Manuel R. , Machiels Jean-Pascal H. , Versola Melissa Jo , Hodge Jeff Paul , Sawarna Karen , Tse Nielson 
Published: February 2017

294 Background: Golvatinib (G) is highly potent, small molecule ATP-competitive inhibitor of the c-Met receptor tyrosine kinase and multiple members of the Eph receptor family as well as c-Kit and Ron, based on isolated kinase assays. G plus sorafenib (S) had an additive cell killing effect in a HepG2 hepatocellular cell viability assay, thus warranting further evaluation of the combination in HCC. Methods: The study is an ongoing open-label phase I/II study. Eligible pts have advanced HCC, Child-Pugh (CP) A or B, up to 2 prior regimens, including S. A 3+3 dose escalation design was used to determine the maximum tolerated dose (MTD) with planned doses of G (200 mg, 300 mg, 400 mg) PO qd each in combination with S 400 mg bid in 28 day cycles.The dose limiting toxicity (DLT) evaluation period was the first 28 days. Treatment continued until disease progression or development of unmanageable toxicities. Response was assessed by RECIST 1.1. Phase I is complete and preliminary data are presented. Results: 13 pts (med age: 60; M/F: 83%/17%, CP A/B: 92%/8%) were enrolled in 2 cohorts and the MTD was declared as G 200 mg qd and S 400 mg bid. Median treatment duration, 112 days. Confirmed partial responses (PRs) were observed in 2/12 (17%) pts and durable SD was observed in 4/13 (31%) pts based on investigator assessment. Conclusions: G in combination with S appeared to demonstrate manageable toxicity in advanced HCC pts. The PRs and durable SD observed in this pretreated pt population appear favourable and support continued evaluation in phase II. Clinical trial information: NCT01271504. [Table: see text]
Survivorship care patterns and late effects after cancers of the pancreas and biliary tract.
Authors: Hill-Kayser Christine E. , Vachani Carolyn , Hampshire Margaret K. , Di Lullo Gloria A. , Metz James M. 
Published: February 2017

296 Background: Pancreas and biliary (PBT) cancers are generally associated with poor prognosis, despite aggressive, multimodality therapy. The population of cancer survivors after these diagnoses may be largely ignored, despite risk of late effects. This Internet-based study seeks to evaluate patient-reported toxicities and survivorship care patterns after treatment of PBT cancers. Methods: Patient-reported data were gathered via convenience sample from PBT survivors voluntarily utilizing a publically available Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and the OncoLink website, the tool asks survivors to enter data regarding diagnosis, demographics, and treatments, and provides customized guidelines for future care. During use of the tool, PBT survivors are queried regarding late effects associated with specific treatments. Results: 89 PBT survivors utilized the tool from 2010-2012, 66% with pancreas cancer, 20% biliary, and 13% liver. Of the entire group, 59% were female and 81% Caucasian. Median diagnosis age was 59 and median current age 61. Average time since diagnosis was 2 years (range <1-8). Most reported having had multimodality therapy - 71% surgery, 78% chemotherapy, and 46% radiation – although only 30% report continued care from an oncologist and 8% having received previous survivorship information. Of 17 patients queried, 3 had metastatic disease and 3 had recurrent disease. When the entire group was queried regarding possible side effects of treatment, 44% report persistent neuropathy, 24% chronic diarrhea, 21% bowel stricture or obstruction, and 15% chronic skin changes in the radiation portal. Conclusions: Although the prognosis after PBT cancers remains relatively poor, a small population of long-term survivors exists. Survivors using this tool have generally not received survivorship information and most are no longer followed by an oncologist despite having received multimodality treatment. Neuropathy and gastrointestinal side effects appear to be the most bothersome to this group. This tool represents a potential way to provide information to underrepresented survivorship groups such as PBT survivors in the future.
A public hospital experience with young gastric cancer patients.
Authors: Goldner Bryan S. , Velasquez Jonathan , Stabile Bruce E. , Chen Steven L. , Kim Joseph , Lin Matthew , Caton Amy , Lee Byrne 
Published: February 2017

30 Background: Recent literature has reported an increased incidence in the United States of node positive and metastatic disease in young patients with gastric adenocarcinoma. The purpose of this study was to investigate the effect of age (≤40 years) on patients with gastric adenocarcinoma at a large urban public institution. Methods: A total of 520 cases of gastric adenocarcinoma treated between 1995 and 2012 were identified. Information was gathered from the medical record including age at presentation, stage at presentation, pathological type of GC, treatment received, and mortality data. Descriptive statistics were used to analyze the data. Survival was analyzed using the Kaplan-Meier method. Comparisons were made using the log-rank test. Results: The mean age at diagnosis was 56 years. 64 patients (12%) were identified as ≤40 years old. 57 of 64 (89%) of the young age group presented with stage III or IV disease, compared with 75% of patients >40 years of age (p=0.014). For patients ≤40 years old, 38% underwent an operation with curative intent, which was comparable to 39% in patients >40 years old. Of patients who underwent surgery, only 33% (10 of 30) ≤40 years old received an R0 resection compared to 110 of 184 (60%) in those >40 years old (p=0.007). The overall median survival was 5 months with one-year survival of 24% for the young patients and a median of 7.8 months with 39% one-year survival for the older patients (p=0.016). Conclusions: There is a decreased awareness and therefore suspicion of the diagnosis of gastric cancer in young patients (≤40 years of age). For this reason, young patients with gastric adenocarcinoma may present with more advanced disease than older patients. Surgical exploration was often futile, and survival was especially poor in young patients likely due to the more advanced nature of their disease at diagnosis.
Characteristics and outcomes of adenosquamous carcinoma of the pancreas.
Authors: Simone Christine G. , Zuluaga Toro Tania , Chan Ellie , George Thomas J. 
Published: February 2017

311 Background: Adenosquamous carcinoma of the pancreas (ASCAP) is a rare pancreatic malignancy variant reported to have a worse prognosis than adenocarcinoma of the pancreas (ACP). Most reports demonstrate a survival rate of less than two years. This study was undertaken to characterize this subtype in the context of a contemporary ACP cohort. Methods: This retrospective analysis included all patients who underwent definitive pancreatic cancer resection at the University of Florida from 2001 to 2011. Central pathology review of suspected ASCAP cases was undertaken. Patient characteristics, tumor features, treatment, and outcomes were collected with t-test analysis for differences. Results: Eight of 237 patients (3.3%) were histologically confirmed as ASCAP. Differences between the ASCAP and ACP cohorts are listed in the Table. ASCAP patients were similar to patients with ACP with no differences in presentation, symptoms or reported tumor markers including CA19-9, CEA, or hypercalcemia. However, ASCAP patients were slightly older, smoked less, and had more involvement of the body and tail. None (0/8) of the ASCAP diagnoses were identified on fine needle aspiration, only surgical specimen review. Post-operative therapy was inconsistently provided to the ASCAP patient population. With a median f/u of 2.9 years, 31% of ACP and 37% of ASACP patients are alive with median overall survival favoring patients with ACP (0.6 vs. 1.7 years; p<0.006). Conclusions: In a contemporary cohort, ASCAP remains a rare malignancy with a relatively worse prognosis than ACP. Diagnostic biopsy may be non-confirmatory for ASCAP and may lead to under-reporting. Aggressive surgical resection is curative for a subset of ASCAP patients, but overall survival remains poor. Further investigation into the role of adjuvant therapy and risk factor modification for this variant may be valuable. [Table: see text]
Phase I/II trial of neoadjuvant chemoradiotherapy with 5-FU, cisplatin, mitomycin C, and heparin for borderline resectable pancreatic cancer.
Authors: Hibi Taizo , Kitago Minoru , Aiura Koichi , Tanabe Minoru , Itano Osamu , Shinoda Masahiro , Abe Yuta , Yagi Hiroshi , Kitagawa Yuko 
Published: February 2017

315 Background: Because of the high incidence of local recurrence and liver metastasis, long-term outcomes of patients following resection of advanced pancreatic cancer are extremely poor. Facilitation of curative resection and prevention of micrometastasis are the goals of neoadjuvant therapy. We evaluated the feasibility and efficacy of our neoadjuvant chemoradiotherapy (NACRT) protocol for borderline resectable pancreatic cancer patients. Methods: During the period between 2003 and 2011, 24 patients with borderline resectable pancreatic cancers underwent NACRT comprising 5-FU (300 mg/body/day, day 1−5/week for 4 weeks), cisplatin (10mg/body day2, 9, 16, 23), mitomycin C (4mg/body/day, day 1, 8, 15, and 22), heparin (6000 IU/body/day for 4 weeks), and radiation (2 Gy/day, day 1−5/week for 4 weeks, total 40 Gy). They were reevaluated for resectability after therapy. Primary endpoints were toxicity and overall patient and disease-free survivals. Secondary endpoint was the ratio of microscopically margin negative resection. Results: All 24 patients completedNACRT. Grade 3−4 hematological adverse events were observed in 9 (38%) patients but none developed severe gastrointestinal toxicity. In 7 (29%) patients, restaging revealed distant metastasis or local disease progression not amenable to curative resection. The remaining 17 patients (71%) underwent surgery (pancreatoduodenectomy, 13 and distal pancreatectomy, 4) with zero 30-day postoperative or in-hospital mortality. The 5-year overall all patient and disease-free survival rates after pancreatectomy were 52.6% and 36.3%, respectively. Postoperative histopathological evaluation demonstrated a marked degenerative change in the specimen, achieving negative surgical margins in 15/17 (88%) patients and pathological complete response in the remaining 2 (12%) patients. Conclusions: Our NACRT protocol is feasible with a low toxicity profile and an excellent curative resection rate in the treatment of borderline resectable pancreatic cancer. It is a promising regimen associated with improved long-term prognoses than historical controls.