bluuebunny/crossref_metadata_2025_split huggingface dataset:
SBRT outcomes for primary and metastatic liver lesions.
Authors: Stenmark M. H. , Liu E. , Schipper M. J. , Ben-Josef E. , Lawrence T. S. , Feng M. U. 
Published: February 2017

262 Background: Stereotactic body radiation therapy (SBRT) permits precise delivery of 1-5 high doses of radiation to liver tumors with low risk of toxicity. This study aims to evaluate local control and overall survival (OS) in patients treated with SBRT for primary and metastatic liver lesions. Methods: From 2006 to 2010, 62 patients with 106 liver lesions (71 metastatic, 35 primary) were treated with SBRT. Lesions were most commonly from primary hepatocellular carcinoma (29%), or colorectal (23%), breast (8%), or esophageal metastases (8%). Patients were heavily pretreated: 51% received ≥1 prior form of liver-directed therapy and 54% received ≥1 prior systemic therapy regimen. The number of active hepatic lesions at the time of SBRT was 1 in 49%, 2 in 23%, 3 in 22%, and ≥4 in 7%. Of the metastatic lesions, 42% were accompanied by active extrahepatic disease. Of the primary liver lesions, 69% were Child-Pugh class A, 26% class B, and 6% class C. Median gross tumor volume (GTV) was 8.8 cm3 (range 0.2-222.4). Median biological equivalent prescription dose (BED10) was 100 Gy (42.6-180). The majority of patients received either 3 or 5 fractions (47% and 48%, respectively). Results: Median follow-up for all lesions was 18 months (4.6-46.8). Local tumor control was observed in 92/106 treated lesions with 1- and 2-yr local control rates of 88% and 74%. No correlation was found between local control and lesion type (primary vs metastatic), lesion size, or prior liver directed therapy. Median survival for all patients was 25.2 months, with 1- and 2-year OS of 81% and 52%. Survival was longer among patients with metastatic lesions compared to primary lesions (2-yr OS 63% vs 29%, HR 0.46, p=0.02). The number of active hepatic lesions was an independent prognostic factor for survival (HR 1.77, p=0.002). For patients with metastatic liver lesions, the presence of active extrahepatic disease yielded significantly worse survival (2-yr OS 37% vs 83%). Among HCC patients, a lower CLIP score was associated with improved survival with 2-yr OS of 55% for CLIP score 0, 44% for score 1, 17% for score 2, and 0% for score 3. No patients experienced RILD. Conclusions: Treatment of liver tumors with SBRT provides excellent local control, necessitating further improvements in systemic therapy. No significant financial relationships to disclose.
Neoadjuvant intensity-modulated radiotherapy (IMRT) in pancreatic adenocarcinoma: The Dartmouth experience.
Authors: Palmeri M. , Pipas J. M. , Ripple G. H. , McGowan M. , Smith K. D. , Zaki B. I. 
Published: February 2017

274 Background: Neoadjuvant chemoradiation may play a role in improving the resectability and overall survival (OS) of patients with pancreatic adenocarcinoma. IMRT allows higher radiation doses to regions within a tumor while minimizing the dose to surrounding normal structures. Methods: Eighty-one patients with pancreatic adenocarcinoma completed neoadjuvant IMRT from 2003-2008. All were staged by CT scan, endoscopic ultrasound and laparoscopy. Based on defined resectability criteria, 14 were resectable (R), 38 considered borderline resectable (B) and 29 unresectable (U). Patients were categorized into 3 groups based on their neoadjuvant treatment. All patients received concurrent IMRT with gemcitabine (50mg/m2) twice weekly for 12 doses. IMRT prescription dose was 54 Gy in 28 fractions with a biologically effective dose of 64.47Gy10. All resected patients received intra-operative radiation (mean dose 14 Gy). Group 1 received neoadjuvant chemotherapy involving gemcitabine and docetaxel on days 1, 15, and 29 followed by IMRT. Group 2 received concurrent weekly cetuximab in addition to bi-weekly gemcitabine and IMRT. Group 3 received only concurrent gemcitabine twice weekly and IMRT. Four weeks after treatment completion, patients were evaluated with a CT scan in preparation for surgery. Results: Median OS for all patients was 22 months. The overall resectability rate after neoadjuvant IMRT was 63%. 78% of B and 39% of U patients underwent resection. 80% of all patients had an R0 resection. Median OS was 23 months for R, 28 months for B and 14 months for U patients (P = 0.002). Median OS was 18 months, 27 months and 18 months respectively for patients receiving gemcitabine-IMRT, gemcitabine-cetuximab and neoadjuvant gemcitabine/docetaxel plus concurrent gemcitabine-IMRT (P = 0.20). Median OS for R0 resections were 28 months compared to 24.3 months for patients with positive margins and 11.7 months for unresectable patients (P < 0.001). Conclusions: IMRT as part of a neoadjuvant treatment strategy for pancreatic adenocarcinoma is feasible and well tolerated. Neoadjuvant IMRT rendered a significant percentage of B patients resectable with an OS comparable to patients who were R at presentation. [Table: see text]
A phase II study of capecitabine in combination with erlotinib as first-line therapy in patients with metastatic pancreatic cancer (stage IV).
Authors: Candamio Folgar S. , Méndez Méndez C. , Jorge Fernández M. , Romero Reinoso C. , Quintero-Aldana G. , Salgado Fernández M. , de la Cámara Gómez J. , Reboredo López M. , Ramos Vazquez M. , Lopez R. 
Published: February 2017

277 Background: Patients with metastatic pancreatic cancer (mPC) have poor prognosis. Given the activity of both capecitabine and erlotinib in pancreatic cancer, we hypothesized that combination use of two drugs in first-line therapy would improve clinical outcomes in these patients. Methods: A prospective, single arm, open-label, phase II study. Patients received capecitabine 1,000mg/m2 twice daily on days 1-14 in 3-week cycles combined with erlotinib 150 mg po daily for 18 weeks, until disease progression, unacceptable toxicity or withdrawal, with a follow-up visit performed at 30-days post-treatment. The primary endpoint was objective response rate measured with RECIST criteria. Results: A total of 32 patients were evaluated. Baseline characteristics: median age was 64 years (56-70), male: 50%, Karnofsky PS ≥ 80%: 94%, tumor histology: 93.5% adenocarcinoma, 49% moderately differentiated. 11 (34%) patients had surgery, 2 (6%) had prior radiotherapy and 3 (9%) prior chemotherapy. Median treatment duration was 61 days (6-156). 3 (9%) patients required dose reduction of capecitabine and 8 (25%) of erlotinib. Of the 32 patients, 6 completed the treatment period, 22 discontinued the study prematurely due to disease progression and 4 due to AEs. Disease control rate (confirmed complete response [CR], partial response [PR] and stable disease [SD] according to RECIST criteria) was 28.2%. 2 (6.3%) patients achieved PR and 7 (21.9%) had SD. After a mean follow-up of 6.3 months, the median progression-free (PFS) and overall survival (OS) was 2.10 and 4.3 months, respectively, with a 6-months survival rate of 43.8%. Safety analysis revealed that the main grade 1/2 toxicities were rash (34%), asthenia (31%), diarrhea (31%), stomatitis (22%) and emesis (22%). Three cases of grade 3 hand-foot syndrome and 1 case of infection due to biliary stent were detected. No toxicity grade 4 occurred. Conclusions: Capecitabine administered in combination with erlotinib is an active regimen in patients with metastatic pancreatic cancer with a favourable safety profile. These results suggest that this regimen could represent a first-line treatment option for these patients. No significant financial relationships to disclose.
Survival by anatomic site, histologic type, and tumor stage in stomach and esophageal cancer patients from the U.S. SEER Cancer Registry.
Authors: Wang L. , Chu L. , Shing M. , Dong W. 
Published: February 2017

28 Background: Data on the association of tumor characteristics and survival for stomach cancer (SC) and esophageal cancer (EC) patients (pts) are limited. The objective of this study was to describe survival in United States. SC and EC pts by anatomic site, histologic type, and tumor stage. Methods: SC and EC pts were identified in the Surveillance, Epidemiology and End Results (SEER) Cancer Registry. SC was classified by anatomic site (cardia and non-cardia/other) and histologic type (intestinal, diffuse, other per Lauren criteria). EC was classified into anatomic site (middle/upper third, abdominal/lower third, overlapping lesions, NOS) and histologic type (adenocarcinoma (AC), squamous cell carcinoma (SQ), other). Frequency distribution and median survival were examined in these subgroups. Results: From 2004-2006, >15,500 SC and > 9,800 EC cases were diagnosed. SC: (29% cardia) and (24% diffuse, 66% intestinal, 10% other). Compared with non-cardia/other pts, cardia pts tended to be male (77% vs 56%), white (88% vs 66%), intestinal type (77% vs 61%) and present with earlier stage disease (stage I-IIIa: 48% vs 42%). With the exception of stage I/II pts, survival was longer in cardia than non-cardia/other pts. The difference was most striking in stage IIIb/IV pts (7 months (mos) cardia vs 4 mos non-cardia/other). Compared to intestinal type, diffuse type tended to be younger (median age: 64 vs 72 yrs), more female (49% vs 34%), and present with more stage IIIb/IV disease (50% vs 39%). No difference in survival by histologic type was observed when accounting for stage. EC: (26% middle/upper, 58% lower, 5% overlapping, 11% NOS) and (57% AC, 34% SQ, 9% other). Among pts with AC histology 78% occurred in the lower third; in SQ most occurred in upper/middle third (56%). Compared to SQ, AC tended to be male (85% vs 63%), white (95% vs 67%), and present with stage IV disease (34% vs 25%). For all stages combined, survival was longer for AC pts (11 mos AC, 9 mos SQ, 4 mos other). This difference was most apparent among early stage (I-III) pts. Conclusions: Survival in SC and EC was associated with staging, anatomic and histologic subtypes. Quantifying this provides insights for the design and interpretation of clinical development programs. [Table: see text]
A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC).
Authors: Czito B. G. , Willett C. , Kennedy-Newton P. , Tyler D. S. , Hurwitz H. , Uronis H. E. 
Published: February 2017

281 Background: Localized PC is commonly managed with chemoradiotherapy, with or without surgical resection. The optimal combination of agents and doses is the subject of continued investigation. This phase I study examines the combination of two targeted radiosensitizing agents in combination with radiation therapy. Methods: Eligible patients had resectable, borderline resectable or locally advanced adenocarcinoma. Patients received RT (1.8 Gy qd to 50.4 Gy) concurrent with bevacizumab and erlotinib. Dose-level 1 was bevacizumab 10 mg/kg weeks 1, 3 and 5 and erlotinib 100 mg daily, RT days only. Drug doses were escalated depending on encountered toxicity. The primary endpoint was determination of the maximally tolerated dose of this combination. Secondary endpoints included toxicity and activity assessment. Results: Nine patients were enrolled in the phase I study. Maximal EUS/CT stage was T2N0 (n=1), T3N0 (n=1), T3N1 (n=2) or T4N0 (n=5). Of 3 patients in dose-level 1, two had radiographic stable disease (SD) and one partial response (PR). One pt underwent exploratory laparotomy and found to be unresectable, experiencing prolonged postoperative incisional healing. Three patients were then enrolled at dose-level 2 (bevacizumab 10 mg/kg, erlotinib 125 mg). Two had SD and one progressive disease (PD). One pt underwent exploratory laparotomy, aborted due to previously undetected hepatic metastases. Three patients were then enrolled at dose-level 3 (bevacizumab 10 mg/kg, erlotinib 150 mg). One pt had SD and two PR. One pt underwent distal pancreatectomy, experiencing postoperative pancreatic leak and abscess formation. All patients with elevated CA 19-9 at baseline had a decrease, with amedian decrease of 69% (R:13-93%). Dose-limiting toxicity (DLT) was not encountered at any dose-level. Primary non-dose limiting toxicities in all cohorts included NCI CTCAE v3.0 grade 1-2 nausea/vomiting, rash, diarrhea, fatigue, and anorexia. Conclusions: Concurrent chemoradiotherapy utilizing erlotinib and bevacizumab is reasonably well-tolerated. The recommended phase II dose is bevacizumab 10 mg/kg weeks 1, 3, and 5 and erlotinib 150 mg RT days only. Phase II accrual is underway. [Table: see text]
A phase II feasibility study of sorafenib and gemcitabine combination therapy in advanced hepatocellular carcinoma.
Authors: Naqi N. , Ahmad S. , Murad S. , Khattak J. 
Published: February 2017

298 Background: Sorafenib is considered standard of care in advanced hepatocellular carcinoma (HCC) giving survival benefit of around 4 months. Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile, may improve results. The primary objective of this study was to evaluate the efficacy and safety of sorafenib and gemcitabine combination in advanced HCC. Methods: 30 patients of advanced HCC were enrolled in this non-randomized, open-label treatment protocol. Sorafenib 400 mg orally twice daily with gemcitabine 1,000mg/m2 intravenous on day 1 and 8 of a 4 week cycle for 4 months. Inclusion criteria: Child class A and B, adequate liver, marrow and renal functions, at least one uni-dimensional measureable lesion, Exclusion criteria: uncontrolled hypertension, serious infections, brain metastasis, bleeding diathesis, pregnant or lactating. National Cancer Institute criteria for adverse events (NCI CTCAE) Version 3.0, and Response evaluation criteria for solid tumors (RECIST) was used for assessment. Results: 30 patients: 23 male and 7 female. 24 (80%) Child class A and 6 (20%) class B. All had chronic liver disease. 22 (73.3%) had significantly high alfa-fetoprotein levels (≥ 500). 20 (66.7%) positive for hepatitis C, 4 (13.3%) for hepatitis B. 6 (20%) had no evidence of viral infection. 19 (63.3%) had multifocal lesions and 11 (36.7%) unifocal. 18 (60%) completing 4 cycles of treatment were assessed for response. 2 partial responses (PR) and 8 stable disease (SD) were seen. No complete response (CR) was observed. 8 patients had progressive disease, 4 progressing on interim assessment were taken off protocol. Toxicity: primarily hematological. Gemcitabine related thrombocytopenia being the most common (40%) requiring frequent dose modifications and delays. Sorafenib specific, hand foot skin reaction and anorexia were next most frequent. Conclusions: Sorafenib and gemcitabine combination is not feasible in advanced HCC due to its hematological toxicity especially thrombocytopenia, requiring frequent dose reductions and delays. No significant financial relationships to disclose.
Changes in imatinib plasma trough level during long-term treatment of patients with advanced gastrointestinal stromal tumors.
Authors: Kang Y. , Yoo C. , Ryoo B. , Chang H. , Lee J. , Beck M. , Kim T. , Ryu M. 
Published: February 2017

306 Background: Pharmacokinetic study in patients with gastrointestinal stromal tumors (GISTs) suggested that plasma concentrations of imatinib decrease following long-term exposure. We therefore measured changes in imatinib plasma trough levels (Cmin) after long-term exposure. Methods: Between November 2009 and May 2010, follow-up (FU) imatinib Cmin was measured in 65 patients who received the same dose of imatinib for at least 9 months after a previous baseline (BL) measurement. Total 244 blood samples were obtained (127 at BL and 117 at FU) and plasma level was measured by liquid chromatography-tandem mass spectrometry. Results: Median patient age was 54 years (range, 28–76 years) and 42 (64.6%) patients were male. Sixty-one (93.8%) patients were treated with 400 mg/day imatinib and 4 (6.2%) with 300 mg/day. The median interval from initiation of imatinib to BL test was 6.4 months (range, 0.5–66.6 months), and the median interval between BL and FU test was 13.1 months (range, 9.6–18.4 months). The mean ± standard deviation imatinib Cmin was significantly higher at FU than at BL (1442 ± 693 ng/mL vs 1221 ± 624 ng/mL, p<0.001). The mean inter- and intra-subject variabilities were 49.2% and 25.5%, respectively, at BL, and 44.2% and 20.4%, respectively, at FU. Multivariate analysis showed a significant correlation between the ratio of FU to BL imatinib Cmin and that of albumin (r=-0.397, p=0.001). In per-sample analysis, imatinib Cmin was significantly correlated with age, hemoglobin, albumin, creatinine clearance, previous major gastrectomy and time between initiation of imatinib and plasma level tests. Conclusions: Steady-state imatinib Cmin did not decrease but remained stable in most GIST patients during long-term treatment. Changes in imatinib Cmin were associated with changes in albumin concentration. Monitoring of imatinib Cmin only for concerns about time-dependent decreases in imatinib exposure is not necessary. [Table: see text]
Second-line chemotherapy with capecitabine (CAP) and oxaliplatin (OX) in patients with pancreatic or biliary tree adenocarcinoma (ADC).
Authors: Mane J. , Iruarrizaga E. , Rubio I. , Fonseca E. , Iza E. , Casas R. , Marrodan I. , Martinez M. , Fernandez R. , Carrera S. 
Published: February 2017

308 Background: Pancreatic and biliary tree ADC represent poor prognostic tumors. Gemcitabine is usually considered the first- line chemotherapy and after that no standard treatment has been established. CAP and OX have demonstrated some activity in metastatic (M1) and locally advanced (LA) pancreatic cancer, and the combination of these drugs confers additional benefit as well. We conducted this study in order to establish the efficacy of this schedule on pancreatic and biliary tree ADC. Methods: Pts with M1 or LA pancreatic or biliary tree ADC with progression to one previous chemotherapy treatment were included. Performance status≤2, age≥18 years and adequate renal and hepatic function were selected. Schedule of chemotherapy: CAP 1000 mg/m2 bid on days 2 to 15 and OX 130 mg/m2 on day 1 of a 3-week cycle. RECIST criteria were used for assessment of response and NCI-CTCAE v 3.0 for toxicity. Results: Between April 2006 and March 2010, 40 pt were included. Male/female: 29/11. Mean age: 60.7 years (37-74). Pancreatic/biliary: 23/17. PS 0/1/2: 3/27/10. LA/ M1: 1/39. Mean number of cycles: 2.50 (1-10). Disease response per pt, partial/ stable disease/progression/not evaluated: 1/9/21/9. Tumor control (partial/stable disease): 10 pt (22%). Hematologic toxicity (grade1/2/3/4) (%) per pt: neutropenia 5/2.5/7.5/0; thrombocytopenia 15/5/2.5/5; anemia 42.5/10/52.5/0. Nonhematologic toxicity (grade 1/2/3) (%) per pt: asthenia 10/45/17.5; emesis 22.5/15/2.5.; anorexia 12.5/35/7.5; diarrhea 7.5/12.5/5; neurotoxicity 42.5/17.5/2.5; hand-foot syndrome 5/2.5/2.5. One toxic death was reported. Median time to progression: 15 weeks (95% CI 6.6-23.3). Median survival time: 19 weeks (95% CI 10.4-27.5). For pts with PS0 or 1 median overall survival was 23 weeks (95% CI 6.3-39.6) and for pts with PS2 was 8 weeks (95% CI 5.3-1.6) (p 0.004). Conclusions: Advanced pancreatic and biliar ADC have unfavorable prognosis. After first-line treatment, CAPOX shows a tolerable toxicity and some activity and it can represent an alternative on selected pretreated pts. No significant financial relationships to disclose.
Do bisphosphonates increase esophageal cancer risk? A meta-analysis.
Authors: Ditah I. C. , Janarthanan S. , Tageja N. 
Published: February 2017

31 Background: Oral bisphosphonates are known to cause severe esophagitis in some users. This has lead to some authors speculating that they may also increase the risk of esophageal cancer. However, studies investigating the association have yielded inconsistent results. The aim of this work is to summarize available data on the magnitude and direction of the association in a meta-analysis. Methods: A standardized search was independently conducted by two investigators from January 1990 through September 2010 on Medline and PubMed. Identified articles that met the exposure and outcome definition were manually reviewed for any additional references. Only full articles that provided risk estimates for the association were eligible for inclusion. The most adjusted risk estimates were abstracted independently by the two authors and synthesized using the random-effects model. A stratified analysis by study design has also been done. All studies were evaluated for publication bias before analysis. Results: Five studies, three case-controls and two cohort studies were eligible for analysis. The combined risk estimate for esophageal cancer was 0.86 (95% CI: 0.62, 1.09). This result remained consistently nonsignificant among the case control studies with a risk estimate of 1.26 (95% CI: 0.94, 1.57). However, there was a significant decrease in the risk of esophageal cancer among the cohort studies with a risk ratio of 0.35 (95% CI: 0.00, 0.71). There was no heterogeneity among the studies by study design. No evidence of publication bias was found, even by study design. Conclusions: This meta-analysis shows that the evidence in support of an association between bisphosphonates and esophageal cancer is lacking. Large studies with appropriate comparison groups, adequate follow-up, robust characterization of the exposure and information on potential confounders are warranted to determine whether bisphosphonates increase esophageal cancer risk. No significant financial relationships to disclose.
Bleeding events and eligibility requirements in studies evaluating an antiangiogenic agent in hepatocellular carcinoma (HCC).
Authors: Duffy A. G. , Greten T. 
Published: February 2017

310 Background: The presence of cirrhosis means an increased baseline potential risk of bleeding in patients with HCC. With the establishment of sorafenib as a standard of care option this risk is further increased. Bleeding events might potentially become a bigger problem, when sorafenib is combined with other vascular targeting agents. Therefore standardized eligibility criteria across clinical trials are needed. Methods: We performed a review of all available studies evaluating an antiangiogenic agent either alone or in combination with another agent. The following variables were recorded: demographics, eligibility criteria re: platelet count, coagulation, CP status, endoscopic requirements, hemorrhagic events (any grade). Data tabulated and descriptive statistical analysis employed. Results: 30 studies were identified since 2005 involving a total of 2,416 pts. 19 studies were available as published manuscripts. 11 of the studies involved sorafenib, 8 bevacizumab, 4 sunitinib with the remainder involving other agents (brivanib, lenalidomide, TSU68, Linifanib, ramicirumab).Eligibility criteria range re: platelet count 40 – 150; INR 1 – 2.3; No study was identified which mandated endoscopy to outrule varices, apart from one study which did so after the occurrence of 2 variceal bleeds. Serious hemorrhagic event up to 13%. Conclusions: While the risk of hemorrhagic event in studies evaluating an antiangiogenic agent appears to be within an acceptable range, there are no standardized across-study eligibility criteria for this “at risk” population in terms of platelet count, prothrombin time, or endoscopic requirements. Future studies will need to address this issue in more detail, particularly when multiple vascular targeting agents are combined. No significant financial relationships to disclose.