bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and risk factors for cholangitis during systemic chemotherapy among patients with advanced biliary tract cancer.
Authors: Hashimoto J. , Morizane C. , Kondo S. , Ueno H. , Mitsunaga S. , Nakachi K. , Ikeda M. , Arai Y. , Okusaka T. 
Published: February 2017

313 Background: Patients with biliary tract cancer (BTC) have a high risk of developing cholangitis. In patients with advanced BTC receiving systemic chemotherapy, cholangitis might interfere with the execution of the treatment. Furthermore, cholangitis during severe immunosuppression might develop into lethal complications such as sepsis or shock. Purpose: To determine the incidence of cholangitis among patients with advanced BTC undergoing systemic chemotherapy and to identify risk factors for the development of cholangitis. Methods: We reviewed the records of 301 patients with advanced BTC who received systemic chemotherapy at our hospital between February 2002 and July 2009. The clinical data of patients treated with gemcitabine monotherapy (GEM) as a first-line chemotherapy was retrieved. Results: One hundred and thirty-one patients were successfully followed up throughout the entire GEM treatment. Forty-three patients had intrahepatic BTC (32.8%), 28 had extrahepatic BTC (21.4%), 11 had hilar BTC (8.4%), 7 had ampullary cancer (5.3%), and 42 had gallbladder cancer (32.1%). Interventional radiological treatment or biliary reconstruction for biliary obstruction was performed in 50 patients (37.9%) prior to the start of chemotherapy. The median time to GEM treatment failure was 126 days. Cholangitis developed in 30 patients (22.9%) during GEM, and severe cholangitis developed in 10 patients (7.6%). The median time to the first episode of cholangitis from the start of chemotherapy was 65 days. Chemotherapy was discontinued because of cholangitis in 4 patients (3.1%), but no deaths as a result of cholangitis occurred. A multivariate analysis using a logistic regression model demonstrated that the presence of hilar obstruction (p=0.0002, OR: 10.748), the loss of sphincter of Oddi function (p=0.0005,OR: 8.960), and the presence of internal biliary drainage (p=0.007, OR: 4.472) were independent risk factors of cholangitis. Conclusions: The incidence of cholangitis during GEM treatment was 22.9% among the advanced BTC patients in this study. Hilar obstruction, the loss of sphincter of Oddi function, and internal biliary drainage may be risk factors of cholangitis. No significant financial relationships to disclose.
The potential of shape-based treatment plan optimization for pancreatic IMRT treatments to spare organs at risk and allow for dose escalation to the tumor PTV.
Authors: Petit S. F. , Wu B. , Kazhdan M. , Dekker A. , Simari P. , Kumar R. , Taylor R. H. , Herman J. M. , McNutt T. 
Published: February 2017

316 Background: Due to the low dose tolerance of the organs at risk (OARs) in the abdomen the tumor dose for pancreatic cancer patient is restricted to 50-60 Gy in 1.8-2.0 Gy fractions when combined with chemotherapy. The goal of this study was to develop a system that can determine the minimal radiation dose to the OARs of each individual patient that is achievable while maintaining adequate tumor coverage. This could guide treatment planners to spare the OARs to the fullest extent. When the minimal doses to the OAR are achieved, the total plan can be upscaled until the normal tissue dose constraints are met, allowing for an increase in tumor dose without increased normal tissue toxicity. Methods: The minimal achievable dose to the OARs depends on its proximity to the planning target volume (PTV). The overlap volume histogram (OVH) was used to describe the spatial relation of each OAR to the PTV. A database of 33 patients, treated with IMRT, was queried to find the lowest achieved dose to an organ for any of the prior patients with less favorable PTV-OAR configurations than the current patient. This minimal dose must also be achievable for the OAR of the new patient. For 25 randomly chosen patients the lowest achievable dose to the liver and kidneys was predicted this way. Then the patients were replanned to verify if this dose could be achieved. The new plans were compared to the original clinical plans. Results: After replanning the predicted achievable dose to the liver was realized within 1 and 2 Gy for more than 86% and 96% of the patients respectively. For the kidneys these numbers were 83% and 96%. The average improvement in terms of mean dose was 1.4 Gy (range 0 – 4.6 Gy) for the liver and 1.7 Gy (range 0 – 6.3 Gy) for the kidneys. This would have allowed an increase in PTV dose of on average 5 Gy (range 0-13 Gy) based on the liver and 8.5 Gy (range 0-38 Gy) based on the kidneys compared to the original plan, without an increase in dose to the bowel, cord, and stomach. Conclusions: The lowest achievable dose to the OARs could accurately be predicted for pancreatic cancer patients within seconds. This can guide dosimetrists to spare the OARs or increase the PTV dose by 5 Gy without increased toxicity. [Table: see text]
Early experience of combination treatment of sorafenib and radiotherapy in patients with advanced hepatocellular carcinoma (HCC).
Authors: Seong J. 
Published: February 2017

320 Background: Although sorafenib has been recognized as a standard therapy for advanced HCC, its antitumor effect as a single modality seems unsatisfactory. In this study, we report our early experience of combination treatment of sorafenib and radiation in locally advanced or metastatic HCC. Methods: From 2007 to 2009, a total of 22 HCC patients were treated with concurrent sorafenib (400 mg/day) and radiation. Nine patients received local radiotherapy 45-54 Gy in 1.8-5 Gy/fraction on the primary tumor with sorafenib (primary group). In the primary group, number of patients in stage III, IVA, and IVB was 1, 4, and 4, respectively. The remaining 13 patients received local radiotherapy 30-58.4 Gy in 1.8-6 Gy/fraction on the metastatic tumor with sorafenib (metastatic group). The metastatic sites involved bones (8 patients), lymph nodes (3 patients), chest wall (1 patient) and pelvic cavity (1 patient). Toxicity and tumor response were evaluated. Results: In toxicity, the primary group presented hand-foot syndrome in 3 patients, grade 2 GI toxicity in 1 patient, and grade 2 thrombocytopenia in 1 patient. The metastatic group showed hand-foot syndrome in 2 patients and grade 1-2 GI toxicity in 4 patients. Grade 3 thrombocytopenia was observed in 2 patients, in whom the initial platelet count was less than 100,000/mm3. In tumor response, the primary group presented partial response and stable disease in 6 patients and 1 patient, respectively, among 8 assessable patients (PR rate; 6/8, 75%). Tumor marker AFP decreased from pretreatment 9,710±19,208 ng/mL to post- treatment 1,410±2,866 ng/mL. In the metastatic group, significant pain palliation was shown in 7 among 8 patients (87.5%) in Visual Analogue Scale. In the remaining 5 patients, tumor response was shown as partial response and stable disease in 4 patients and 1 patient, respectively (PR rate; 4/5, 80%). Conclusions: In combination treatment of sorafenib and radiation, toxicity was acceptable. The substantial tumor response was also observed. Although this is the limited experience, the results of this study urge the initiation of a controlled clinical trial to verify the effect of combination treatment of sorafenib and radiotherapy. No significant financial relationships to disclose.
Risk of metastatic spread in patients with early-stage, surgically resected pancreatic neuroendocrine tumors.
Authors: Strosberg J. R. , Cheema A. , Weber J. , Kvols L. K. 
Published: February 2017

338 Background: The risk of metastatic spread among patients with early-stage surgically resected pancreatic neuroendocrine tumors has not been well established. Methods: Patients with surgically resected localized or locally advanced pancreatic neuroendocrine tumors treated at the H. Lee Moffitt Cancer Center between 1999 and 2010 were assigned a stage (I-III) based on the new AJCC classification. Recurrence-free survival was measured for each stage. A separate analysis was performed excluding patients who had been referred to Moffitt Cancer Center after metastatic recurrence. Results: 123 patients with nonmetastatic, surgically resected pancreatic neuroendocrine tumors were identified. 5-year recurrence-free survival correlated with AJCC stage (p=0.01; Table). Conclusions: The novel AJCC 7th edition TNM classification for pancreatic neuroendocrine tumors is highly prognostic for recurrence in patients with surgically resected nonmetastatic tumors. [Table: see text] No significant financial relationships to disclose.
Effect of bridging therapy for hepatocellular carcinoma prior to orthotopic liver transplantation on disease control and response.
Authors: Chuy J. W. , Kinkhabwala M. , Reinus J. , Tanaka K. , Kaubisch A. 
Published: February 2017

343 Background: Orthotopic liver transplantation (OLT) is curative for both hepatocellular carcinoma (HCC) and underlying cirrhosis, but this option is limited by lengthy waiting times and donor organ shortages. Various bridging therapies have been employed to slow tumor progression, with reported results radiographically confirming local control with variable rates of tumor necrosis on pathologic examination of explants. Methods: We retrospectively studied 11 patients who underwent a total of 26 locoregional therapies prior to OLT for HCC. One patient was also maintained on sorafenib. The effectiveness of bridging therapies was assessed by radiologic response and histopathological examination of the explanted livers. Results: Sixteen tumor nodules identified in liver explants were evaluated. Pretransplant treatments included: TACE alone (5), TACE + sorafenib (2), RFA alone (1), TACE + RFA (6), or TACE + alcohol ablation (2) prior to OLT. Two nodules (13%) achieved complete tumor necrosis on explant analysis; these had been treated with TACE + RFA. Among 11 patients who underwent bridging therapies, 5 patients (45%) had no radiologic evidence of viable tumor prior to OLT. Among these patients, explant examination showed 2 patients with partial necrosis, 2 patients with at least 90% necrosis, and one patient with no evidence of viable tumor. Three patients with enhancing lesions on imaging prior to OLT had 100% concordance rate on pathological examination of the liver explant with respect to number of nodules identified. Conclusions: Although bridging therapy prior to OLT is effective in achieving disease control, most patients have viable tumor present upon assessment of explanted livers. Absence of viable tumor by radiologic evaluation following bridging therapy does not correspond to complete tumor necrosis. [Table: see text] No significant financial relationships to disclose.
Randomized phase III study of 5-fluorouracil/folinate/oxaliplatin given continuously or intermittently with or without cetuximab, as first-line treatment of metastatic colorectal cancer: The NORDIC VII study (NCT00145314), by the Nordic Colorectal Cancer Biomodulation Group.
Authors: Tveit K. , Guren T. , Glimelius B. , Pfeiffer P. , Sorbye H. , Pyrhonen S. , Kure E. , Ikdahl T. , Skovlund E. , Christoffersen T. 
Published: February 2017

365 Background: The role of anti-EGFR therapy in first-line treatment of metastatic colorectal cancer (mCRC) is not established. In the present study pts were randomized to FLOX or FLOX + cetuximab until progression or FLOX intermittently + cetuximab continuously. Methods: Treatment arm A: Nordic FLOX (q2w): oxaliplatin 85 mg/m2day 1, 5-FU bolus 500 mg/m2 and FA 60 mg/m2 day 1-2; B: FLOX + cetuximab, initial dose 400 mg/m2, then 250 mg/m2/week; C: FLOX for 16 weeks + cetuximab continuously, with FLOX added at progression. Primary endpoint was progression-free survival (PFS). Results: Between May 05-Oct 07, 571 pts were randomized, 566 pts evaluable in intention to treat (ITT) analyses. Median age was 61 (24-74). ECOG status: 0=67%, 1=29%, 2=4%. KRAS and BRAF mutation (mut) analyses were obtained in 498 (87%) and 457 pts (81%), respectively. 40% of tumors had KRAS mut, 12% had BRAF mut. Cetuximab combined with Nordic FLOX did not significantly improve RR, PFS or OS compared to FLOX. KRAS mutation was not predictive for cetuximab effect. OS was similar for patients treated with FLOX intermittently and cetuximab continuously as for patients treated until progression. BRAF mutation was a strong negative prognostic factor (median OS 7.6 vs. 20.4 mo). Conclusions: Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC, irrespective of KRAS-mut. [Table: see text] [Table: see text]
Analysis of preoperative CT and peroperative evaluation as predictors of involvement of hepatic pedicle LN in patients operated for CRLM.
Authors: Belghiti J. , Rau C. , Blanc B. , Ronot M. , Dokmak S. , Fuks D. , Paradis V. , Vilgrain V. , Faivre S. J. 
Published: February 2017

375 Background: Approximately 20% of patients who undergo resection for colorectal liver metastases (CLM) have additional metastases present in hepatic pedicle lymph nodes (HPLN). Although LN status is a major prognostic factor, routine LN dissection is controversial. We evaluated the accuracy of preoperative CT scans and peroperative surgical assessment to determine if these methods could help determining which patients are at high risk for nodal metastases and should undergo lymphadenectomy. Methods: Between 01-2008 and 06-2010, 76 consecutive patients who underwent liver resection and lymphadenectomy for CLM after neoadjuvant chemotherapy were enrolled in a prospective study. All patients had recent (<1 month) preoperative CT to evaluate their liver metastases and the presence, location, size and radiologic characteristics of LN were assessed. Peroperatively, the size and consistency of LN were evaluated by the surgeon. Surgeons and radiologists independently assessed LN involvement. Results were compared to the definitive pathologic examination. Results: Among the 76 patients, 241 nodes were analyzed with a mean number of 3 (± 2) nodes removed per patient. Lymphadenectomy increased the surgical procedure by 20 minutes (12-25 min) and there was no specific morbidity or mortality related to LN clearance. Pathologic HPLN involvement was observed in 15 (20%) patients with a median number of 2 (1-6) metastatic nodes per patient. Peroperative assessment had a high negative predictive value (NPV) = 91% with a low positive predictive value (PPV) = 43%. CT scan assessment had also a NPV and PPV of 85% and 56%, respectively. When considering both peroperative and radiologic data, 27% of patients with pathologic LN involvement were not anticipated and 25% of patients who were node negative on pathologic examination had suspected LN involvement. Conclusions: A selective strategy limiting HPLN clearance to high risk patients relies on information from preoperative CT scans and eroperative surgical assessment. Given that both modalities cannot accurately predict nodal pathologic status, routine HPLN dissection should be performed in patients who undergo resection of CRLM. No significant financial relationships to disclose.
Association of race and socioeconomic status and outcomes with patients with rectal cancer.
Authors: Nitzkorski J. R. , Willis A. I. , Farma J. M. , Cohen S. J. , Zhu F. , Nick D. M. , Sigurdson E. R. 
Published: February 2017

376 Background: Few studies have evaluated disparities of race and SES with outcomes in RC patients. We hypothesize that disparities exist in treatment and outcomes of RC. Methods: Medical records were retrospectively reviewed of RC patients treated from 2000-2009 at an NCI cancer center and an urban academic center. SES was estimated using census data. Quartiles of income and education based on zip codes were calculated. Lowest vs. other quartiles were compared. Clinicopathologic variables included: initial stage, chemotherapy refusal, sphincter preservation, and overall survival (OS). Results: 748 patients were included (581 white, 135 black, 6 other, 26 unknown). Patients with Medicaid were more likely to present with advanced disease (Table). Initial stage did not differ by race, income, or education. Non-white (NW) patients and low education were more likely to refuse chemotherapy. 7 patients refused radiation. After excluding stage IVpatients; sphincter preservation was higher among those with higher income. Median OS for all stages was worse for NW patients (31 months vs. 50 months, p<0.001), low income and education and most pronounced among NW patients with advanced disease. Insurance was not associated with survival difference. Advanced age, stage, and NW race (HR 1.49, 95% CI 1.10-2.02, p=0.01) were independent predictors of survival. Conclusions: Disparity exists in treatment acceptance and outcomes in patients with RC. NW race and lower SES is associated with advanced disease, lower rates of sphincter preservation, chemotherapy refusal, and worse OS in patients with RC. [Table: see text] [Table: see text]
Relative impact of chemotherapy with or without bevacizumab on cytokines and angiogenic factors (CAFs) in metastatic colorectal cancer.
Authors: Lieu C. H. , Tran H. T. , Fiorentino S. , Jiang Z. , Mao M. , Overman M. J. , Eng C. , Ellis L. M. , Heymach J. , Kopetz S. 
Published: February 2017

401 Background: CAFs were previously shown to be modulated in patients (pts) with metastatic colorectal cancer (mCRC) after bevacizumab-containing chemotherapy. Validation of these prior findings is warranted. In addition, the relative impact of bevacizumab and the cytotoxic chemotherapy components on CAFs has not been previously described. Methods: Plasma samples from 403 mCRC pts were obtained prior to any chemotherapy (Group A) or after progression on a regimen without or with bevacizumab (Group B and C, respectively) between 2002 and 2008. Samples were matched for number of metastatic disease sites (Groups A, B, C) and for prior chemotherapy duration, and time from last chemotherapy dose to sample collection (Groups B, C). Levels of 48 CAFs were measured by suspension bead multiplex assays (BioRad and EMD). Comparisons of Groups A v C (n=169 pairs) and Groups B v C (n=65 pairs) were by the two-sided, nonparametric Wilcoxon paired test, with p<0.05 significance for confirmation of previous CAF results. Results: Prior chemotherapy duration (6.5mo, 6.7mo), and time from last chemotherapy dose to sample collection (1.3mo, 1.2 mo) were similar for Groups B and C, respectively. Results were available for 80% of the samples. Compared to Group A, Group B had reductions in multiple CAFs, including IL-8 (-38%, p<0.0001) and PDGF (-62%, p<0.0001). Commensurate with prior results, PlGF, Eotaxin and TRAIL were increased in Group C by 30% (p<0.0001), 23% (p=0.024) and 19% (p=0.008) respectively. Most CAF changes were attributable to chemotherapy alone. However, PlGF (-31%, p<0.0001) and TRAIL (+26%, p=0.037) significantly differed in Groups B v C. In group C compared to A, multiple changes were seen in the EGFR-axis including decreases in EGF (-52%, p=0.032), epiregulin (-25%, p=0.0023), and HB-EGF (-40%, p<0.0001) as well as an increase in sEGFR (+10%, p=0.004). Conclusions: Most changes in CAFs after treatment with bevacizumab-containing chemotherapy appear to be due to chemotherapy alone and not attributable to anti-VEGF therapy, with several notable exceptions. Chemotherapy-induced changes in the EGFR-axis have not previously been described in mCRC and warrant further investigation. [Table: see text]
Effect of neuropilin-2 expression on TGF-β1-epithelial-mesenchymal transition in colorectal cancer cells.
Authors: Grandclement C. , Bedel R. , Kantelip B. , Viel E. , Remy Martin J. , Ferrand C. , Pivot X. B. , Tiberghien P. , Borg C. 
Published: February 2017

414 Background: Initially characterized as neuronal receptors, Neuropilins (NRPs) were also found to be expressed in endothelial cells and subsequently were shown to play a role in the development of the vascular system. NRP family consists of two genes, neuropilin-1 (NRP1) and neuropilin-2 (NRP2).The multiple functions of NRPs were recently highlighted by the identification of NRP role in oncogenesis. In this study, we first confirmed the role of NRP2 in tumor progression. We also extended the understanding of NRP2 oncogenic functions by investigating the ability of NRP2 to orchestrate epithelial-mesenchymal transition (EMT) in colorectal cancer cells. Methods: We have generated human colon cancer cell lines transfected with NRP2 transgene or siRNA to investigate NRP2 involvement in EMT. First, the oncogenic functions of NRP2 were studied in vitro by MTT, soft agar, invasion assays and in vivo using xenografts experiments. Ability of NRP2 to orchestrate EMT was then investigated by flow cytometry, immunohistochemical (IHC) staining, western-blotting and quantitative real-time PCR. Results: IHC staining revealed that NRP2 is expressed in human colon and breast carcinomas while it is not expressed in healthy tissues. Then, we confirmed that NRP2 increases tumor proliferation, colony formation, invasion and xenograft formation. Moreover, NRP2-expressing cells displayed an immunohistochemical phenotype of EMT characterized by the loss of E-Cadherin and an increase of vimentin. Furthermore, NRP2 expression promotes transforming-growth factor-β1 (TGF- β1) signaling, leading to an increased phosphorylation of the Smad2/3 complex in colorectal cancer cell lines. Specific inhibition of NRP2 using siRNA or treatment with specific TGFβRI kinase inhibitors prevented this phosphorylation and the EMT, suggesting that NRP2 cooperates with TGFRI to promote EMT in colorectal carcinoma. Conclusions: Our findings have reinforced the essential role of NRP2 in cancer progression and demonstrated that NRP2 expression confers to tumor cell lines the hallmarks of EMT. Moreover, in the current work, we present evidence for the therapeutic value of NRP2 targeting. No significant financial relationships to disclose.