bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of diabetes mellitus on risk of major vessel invasion and distant metastasis in hepatocellular carcinoma.
Authors: Connolly G. C. , Safadjou S. , Kashyap R. , Chen R. , Ndauguba A. , Dunne R. , Maliakal B. , Khorana A. A. , Orloff M. , Hezel A. F. 
Published: February 2017

174 Background: Diabetes mellitus (DM) is identified as a negative prognostic indicator in hepatocellular carcinoma (HCC), though the basis for this is unknown. Methods: We conducted a retrospective review of 279 advanced and 191 transplanted HCC patients diagnosed between 1998 and 2008. Logistic regression analyses were conducted to assess the effect of clinical DM on clinical outcomes including distant metastasis and vascular invasion. Results: Eighty- four of 191 (44%) transplanted patients had DM at time of transplantation and 97 of 279 (34%) nontransplanted patients had DM at the time of diagnosis. The presence of DM was associated with an older age at time of diagnosis and a higher prevalence of hepatitis C virus (HCV) and nonalcoholic steatohepatitis (NASH). Also 30% (30/97) of diabetics compared to only 9.3% (17/182) of nondiabetics (p<0.0001) among the cohort with advanced disease had distant metastasis at the time of initial diagnosis, and this difference remained significant when adjusting for CLIP stage, age, and etiologic risk factors in a multivariate logistic regression analysis (OR=8.3, p<0.0001). The association of DM with invasive disease was echoed among early stage transplanted HCC patients in whom histologically confirmed macrovascular invasion was higher among patients with DM compared to those without (20.5% vs. 9.5%, p=0.032). The association of DM with increased risk of macrovascular invasion remained significant in a multivariate logistic regression analysis when adjusting for tumor size, number of nodules, age, obesity and etiologic risk factors (OR=3.2, p=0.025). Conclusions: DM was associated with significantly higher incidence of histological macrovascular invasion in a large cohort of HCC patients receiving liver transplantation and a significantly higher rate of distant metastatic disease at diagnosis in a large cohort of HCC patients with advanced disease. No significant financial relationships to disclose.
Clinical significance of serum alkaline phosphatase level in advanced pancreatic cancer.
Authors: Ohno I. , Mitsunaga S. , Nakachi K. , Shimizu S. , Takahashi H. , Okuyama H. , Kojima Y. , Ochiai A. , Okusaka T. , Ikeda M. 
Published: February 2017

183 Background: Alkaline phosphatase (ALP) is an enzyme that is elevated by various hepatobiliary diseases. Generally its elevation is thought to indicate bile stasis. There are some reports that show ALP is an important prognostic factor for several cancers such as colon, lung, and gastric cancer. Often it is speculated that ALP elevation indicates bile stasis caused by liver metastasis. However, the significance of ALP elevation in advanced pancreatic cancer (APC) patients is not well evaluated. The aim of this study was to determine the significance of elevated serum ALP as a prognostic factor in patients with APC even without jaundice and liver metastasis. Methods: Serum ALP levels were measured in 393 patients with APC receiving gemcitabine monotherapy before treatment, and according to those levels, patients were subgrouped (ALP<upper normal limit (UNL), UNL-500 U/L, 501-700 U/L, 701-1000 U/L, 1000U/L < ALP). The clinical data of each group were analyzed to see characteristics of elevated ALP patients. The relationship between ALP level and survival, response were also examined. Results: The elevated ALP group included poor performance status (PS>1) patients (41.3%, p=0.001), and associated with low serum albumin (3.31±0.38, p<0.01). The elevated ALP group (median survival time (MST) 112 days) showed significantly worse prognosis and lower disease control rate compared to the normal ALP group (MST 217days) (p<0.001, p<0.001). Multivariate analysis revealed ALP (p<0.001), CRP (p<0.001), ascites (p<0.001), distant metastasis (p=0.003), white blood cell count (p=0.005), PS (p=0.020), AST (p=0.020), and ALT (p=0.020) were independent prognostic factors. Similar results were seen in liver metastasis free patients without jaundice. Conclusions: Elevated serum ALP level correlated with poor performance status and low serum albumin. ALP was also the independent prognostic factor in liver metastasis free APC patients without jaundice. No significant financial relationships to disclose.
Bioluminescence image-guided irradiation and tumor monitoring in a preclinical pancreatic cancer mouse model.
Authors: Tuli R. , Surmak A. , Ford E. C. , Tryggestad E. , Wong J. , DeWeese T. L. , Herman J. M. 
Published: February 2017

192 Background: Preclinical pancreatic cancer animal models for radiation research are far from optimal because they utilize nonlocalized, single-beam irradiation of large fields due to lack of accurate targeting and delivery. We report on a novel preclinical pancreatic cancer research model that utilizes bioluminescence imaging (BLI)-guided irradiation (RT) of orthotopic xenograft tumors, sparing of surrounding normal tissues and quantitative, noninvasive longitudinal assessment of treatment response. Methods: In accordance with institutional guidelines, luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were used to generate orthotopic pancreatic tumors in nude mice. BLI of tumors were correlated to PET/CT and necropsy specimens using Pearson correlation. BLI was compared to cone-beam CT (CBCT) to determine the location of the tumor centroid and estimate an appropriate margin for radiation planning. Off-line fusion of BLI with CBCT was performed to guide radiation delivery to tumors using our small animal radiation research platform (SARRP). RT-induced DNA damage was assessed by γ-H2Ax and p-ATM foci. BLI was used to longitudinally monitor radiation treatment response and was correlated to necropsy specimen. Results: BLI accurately predicted tumor volume (R2 = 0.9961) and correlated well with PET/CT imaging of tumors (R2 = 0.97). BLI centroid accuracy was 3.5 mm relative to that of the CBCT. Irradiated pancreatic tumors stained positively for γ-H2Ax and p-ATM, while surrounding organs were spared. Longitudinal assessment of irradiated (5 Gy) tumors with BLI revealed a significant tumor growth delay of 20 days relative to untreated controls. This was also confirmed pathologically as mean tumor volume of irradiated mice was 30.2% that of unirradiated mice (p < 0.05). Conclusions: We have developed a bioluminescent, orthotopic preclinical pancreas cancer model that allows noninvasive 1) normalizing of pretreatment tumor burden; 2) treatment planning and image-guided focal RT therapy; and 3) longitudinal assessment of treatment response. This unique translational model offers a means to investigate targeted and systemic agents with focused RT for pancreatic cancer. No significant financial relationships to disclose.
Quantification of hypoxia-inducible factor-1α, vascular endothelial growth factor, and angiopoietin-2 expression in hepatocellular carcinoma using a real-time quantitative reverse transcription polymerase chain reaction.
Authors: Sharma B. , Srinivasan R. , Chawla Y. K. , Chakraborty A. , Kapil S. , Singla B. , Duseja A. , Dhiman R. K. , Kalra N. 
Published: February 2017

223 Background: Hepatocellular carcinoma (HCC) is characteristically a hypervascular tumor and its progression is closely related to angiogenesis. Hypoxia inducible factor-1α (HIF-1 α), vascular endothelial growth factor (VEGF), and angiopioetin-2 (Ang-2) are key angiogenic factors in HCC. In this study, expression of HIF-1α, VEGF, and Ang-2 were analyzed and correlated with clinicopathologic features of HCC. Methods: Expression of HIF-1α, VEGF, and Ang-2 were analyzed by real-time quantitative reverse transcription polymerase chain reaction in 67 HCC patients (23HBV, 22HCV, 22NBNC) with mean age 59.09 ± 11.13 years (60 M: 7 F), 9 cirrhosis patients (2HBV, 2HCV, 5ALD) with mean age 48.33 ± 11.31 years (8 M:1 F), and 14 chronic hepatitis patients (7HBV, 7HCV) with mean age 48.33 ± 7.17 years (10 M: 4 F), respectively. HCC was diagnosed on the basis of EASL (European Association for the Study of the Liver) criteria. Results: Expression of HIF-1α and VEGF were found to be significantly higher in patients with HCC compared with cirrhosis and chronic hepatitis. Although Ang-2 expression was higher in HCC compared to cirrhosis and chronic hepatitis but the difference was not statistically significant. The difference in the expression of HIF-1α, VEGF, and Ang-2 in cirrhosis and chronic hepatitis were not significant. Tumor size was positively correlated with HIF-1 α(p = 0.268, p = 0.030)and VEGF (p = 0.546, p = 0.0001). A positive correlation was also seen between the HIF-1α and VEGF expression (p = 0.347, p = 0.0001). However no correlation of HIF-1α, VEGF and Ang-2 was seen with portal vein thrombosis, cirrhosis, etiology, AST, ALT, and platelets. Conclusions: HIF-1α and VEGF were highly expressed in HCC patients and may be responsible for the HCC growth. Further studies with a larger number of patients need to be done. No significant financial relationships to disclose.
The reality of pancreas cancer care from access to delivery.
Authors: Abraham A. A. , Al-Refaie W. B. , Parsons H. M. , Dudeja V. , Vickers S. M. , Habermann E. B. 
Published: February 2017

241 Background: Prior literature has identified significant demographic differences in surgically treated patients with pancreas cancer (PC). Therefore, we hypothesized that disparities in socio-demographics exist in critical parameters throughout the continuum of PC care. Methods: We compiled a retrospective cohort of AJCC Stage I-IV PC from the California Cancer Registry. We used logistic regression to study sociodemographics as predictors of: 1) resectability at diagnosis or treatment (defined as absence of pre- or postoperative features of advanced or metastatic disease), 2) undergoing pancreatectomy, and 3) receipt of adjuvant chemotherapy (with/without radiotherapy) after surgery, while adjusting for confounders. Results: Of 20,312 patients with PC (1994-2008), 37% presented with resectable disease. Of those, only 40% received pancreatectomy. At multivariate analysis, race did not predict resectability, yet independently predicted undergoing pancreatectomy and receiving adjuvant therapies. Whites were 1.5 times as likely as blacks to undergo pancreatectomy and, following surgery, were more likely to receive chemotherapy with or without radiotherapy (for all, p <0.01). Blacks were more likely to carry Medicaid than whites (10% vs. 5%, p<0.01). Compared to those with other insurances, Medicaid recipients showed lower odds of undergoing pancreatectomy (Table). Conclusions: Our results suggest that race and insurance continue to influence the continuum of optimal PC care. Going forward, further policies and research should identify effective strategies to neutralize disparities in PC care. [Table: see text] No significant financial relationships to disclose.
Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: A phase II study of the Belgian Group of Digestive Oncology.
Authors: Borbath I. , Ceratti A. , Verslype C. , Demols A. , Delaunoit T. , Deleporte A. , Laurent S. , Vergauwe P. , Van Cutsem E. , Van Laethem J. ,   Belgian Group of Digestive Oncology
Published: February 2017

245 Background: Cholangiocarcinomas (CCK) are uncommon tumors with an increasing incidence and a poor prognosis. Epidermal growth factor receptor (EGFR) expression and activation in CCK have been demonstrated. Methods: We conducted a multicenter phase II trial combining cetuximab (Ctx), an anti-EGFR chimerized IgG1 monoclonal antibody, to gemcitabine (Gem). Patients with either locally advanced (LA) or metastatic (M) CCK (excluding gallbladder) were included; no prior systemic therapy was allowed. Ctx was administrated at the initial dose of 400 mg/m2 and further injections at 250 mg/m2 every 7 days, and Gem was administrated at 1000 mg/m2 on days 1, 8, and 15 every 4 weeks. The primary endpoint was the progression-free survival (PFS) rate at 6 months. A Simon 2-stage design was used. We hypothesized that Gem/Ctx would improve 6 month-PFS rate from 20% to 40%. We needed 3 patients with PFS ≥ 6 months from the first 13 to further include a total of 43 patients. Results: Forty-four patients with advanced CCK (41% LA/59%M) were enrolled from 09/2008 to 01/2010. Median age was 61.5 years (range 40-86) and baseline ECOG PS was 0 for 68% and 1 for 32% of the patients. Forty-three percent of the patients had prior surgery. Forty-six percent of the patients were free from progression at 6 months. Median PFS was 5.8 months (95% CI, 4.4-7.4 m) and median overall survival was 11.6 months (95% CI, 8.7-14.6 m). Nine patients (20.9%) had partial response with a median duration of 5 months (range 2-10 m). Disease control rate (PR + SD > 8 weeks) was 81.4%. The most common grades 3/4 related-toxicities were haematological abnormalities (47.7%), skin rash (13.6%) and fatigue (11.3%). Due to toxicity, 6 patients discontinued study treatment; 14 and 3 patients had a Gem and Ctx dose reduction respectively. Among the nine responders, 8 experienced a skin rash of at least grade 2, suggesting a relationship between skin toxicity and efficacy. Conclusions: Our study met its endpoint, i.e., a PFS rate of 46% at 6 months, suggesting that Gem-Ctx combination had promising activity with a manageable toxicity profile in advanced CCK. Adding Ctx to the new standard of care Gem-cisplatin deserves further investigations in CCK. [Table: see text]
Preoperative chemotherapy in patients undergoing resection of colorectal liver metastases: Assessment of pattern of tumor response using CT registration imaging.
Authors: Cai G. , van Vledder M. G. , Kamel I. R. , Diaz L. A. , Boctor E. , Pawlik T. M. , Choti M. A. 
Published: February 2017

252 Background: A significant radiologic response from preoperative chemotherapy may successfully convert some unresectable colorectal liver metastases (CRLM) to resectable disease. Understanding the pattern of tumor shrinkage in relation to the hepatic structures such as the liver capsule and vascular pedicles is important. We sought to determine the spatial relationship between individual liver metastases before and after chemotherapy, as well as to adjacent intrahepatic structures. Methods: Using nonrigid registration of temporally separated CT scans before and after preoperative chemotherapy, 42 CRLM were evaluated in 27 patients with radiologic partial response. The response pattern was determined by independent observers and scored as: (1) asymmetric toward the liver periphery, (2) asymmetric toward the liver center, and (3) symmetric response. In addition, the shrinking pattern was characterized in relation to the liver capsule and major vascular pedicles, as well as clinicopathologic features. Results: Among the tumors evaluated, 38/42 lesions (90%) responded asymmetrically, with only 10% undergoing a symmetric contraction. 43% shrank toward the periphery and 47% centrally. Tumors in proximity to the liver capsule were more likely to respond peripherally compared to deeper lesions (p=0.013). Unexpectedly, R1 resection was more common in tumors with peripherally directed response vs. those with central or symmetric response (p=0.027). In addition, tumors within 5 mm of a single major vascular pedicle were more likely to shrink toward (59%) and not away from the vessel. No difference in response pattern was observed in relation to tumor size, chemotherapy regimen, or presence of steatosis. Conclusions: Tumors were found to respond asymmetrically in the vast majority of cases, either toward or away from the liver center. In addition, tumors in proximity to major vascular pedicles less commonly move away from these structures. These findings may have important implications when planning curative-intent resection or anticipating the ability to convert patients to resectable disease using preoperative chemotherapy. No significant financial relationships to disclose.
A phase I trial of the monoclonal antibody FG-3019 to connective tissue growth factor (CTGF) in locally advanced or metastatic pancreatic cancer.
Authors: Heestand G. M. , Pipas J. M. , Valone F. , McMullen A. D. , Gadea P. , Williams D. , Zhong M. , Neff T. , Fisher G. A. , Koong A. 
Published: February 2017

269 Background: CTGF is highly expressed in pancreatic tumors and is thought to mediate local desmoplasia. FG-3019 is a fully human monoclonal antibody against CTGF. Studies using FG-3019 in murine xenograft models have shown reduced tumor growth and metastasis. Methods: This open-label, dose escalation study assessed the safety and pharmacokinetics of FG-3019 (3, 10, 15, and 25 mg/kg q14D). FG-3019 was initiated on D1 to assess single-agent toxicity. Standard gemcitabine and erlotinib were added on D15. Chemotherapy-naive patients with locally advanced or metastatic adenocarcinoma were eligible. Seventeen subjects (median age 66 yrs) were enrolled: n=4, 3, and 10 at 3, 10, and 15 mg/kg respectively. Enrollment is ongoing in the 25 mg/kg cohort. Seven subjects were female; four were stage 3, and 13 were stage 4. Results: No safety signals were detected with single-agent FG-3019. After beginning chemotherapy, four subjects experienced seven SAEs, which were deemed unrelated to FG-3019 including three deaths: sepsis, suicide, and disease progression. Nine subjects experienced grade 3 AEs, all of which were expected in patients with pancreatic cancer. There were no grade 4 hematologic abnormalities. AEs related to gemcitabine (hematologic, abnormal LFTs) and erlotinib (rash) occurred at a rate and severity consistent with the prescribing information (preliminary data). Steady-state Cmax (median 428, range 236-455 μg/mL), and T1/2 (median 6.6, range 6.3-6.7 days) at the 10 mg/kg dose level were comparable to PK data from subjects in non-oncological trials who received FG-3019 at the same dose level. One subject had a partial response by RECIST criteria for 9.7+ months. Another subject had a minor response for 7.7 months. Three of five subjects with PET scans at baseline and D15 experienced stable to reduced PET activity before starting chemotherapy. The median TTP across all cohorts was 3.7 months (95% CI 1.9-6.2), and the median OS was 9.4 months (95% CI 1.9-10.6). Conclusions: FG-3019 is well tolerated and dose escalation continues. Reduced PET activity after treatment with single-agent FG-3019 may indicate a biological effect of the agent. [Table: see text]
Outcomes of continuously infused 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) as salvage regimen in patients with biliary tract cancer.
Authors: Lim K. , Han S. , Oh D. , Im S. , Kim T. , Bang Y. 
Published: February 2017

282 Background: In advanced biliary tract cancer, after failure of first-line chemotherapy, salvage chemotherapy has not yet been established and the prognostic factors in salvage setting have not been widely known. The purpose of this study was to evaluate the efficacy and safety of iFAM as salvage chemotherapy in biliary tract cancer and to reveal the prognostic factors. Methods: Eligibility included: 1) age 18-75, 2) histologically confirmed biliary tract cancer, 3) previously treated with palliative first-line chemotherapy, 4) ECOG PS 0-2, 5) adequate organ function. iFAM consisted of 5-FU 800 mg/m2 over 12 hour on days 1-5, doxorubicin 30 mg/m2 on day 1, and mitomycin-C 8 mg/m2 on day 1, every 4 weeks. Results: Between February 2003 and August 2009, 50 patients (pts) were enrolled. The median age was 57.3 yrs (range: 26.0-71.5 yrs), and there were 33 men (66%). 32 pts (64%) had ECOG PS 0-1 and 18 pts (36%) had PS 2. Biliary tract cancers were extrahepatic cholangiocarcinoma (30%), intrahepatic cholangiocarcinoma (30%) and gallbladder cancer (40%). Previous chemotherapy mainly consisted of gemcitabine-based and 5-FU-based regimens. Median cycles of iFAM were 2 (range: 1-6). Best responses to iFAM were PR in 2 (4%) pts and SD in 9 (18%), that is response rate was 4% and disease control rate was 22% (95% CI: 7.35-28.65). The median PFS and OS were 2.2 (95% CI: 2.0–2.4) months and 5.0 (95% CI: 3.3–6.7) months, respectively. Grade 3/4 hematologic toxicities were neutropenia (10%), anemia (2%), and thrombocytopenia (8%). Frequent nonhematologic toxicities were alopecia (34%), stomatitis (28%), vomiting (24%), and diarrhea (12%), which were grade 1/2. ECOG PS (0-1 vs 2) was significant prognostic factor for both PFS (p=0.029) and OS (p=0.025). Poor response to previous chemotherapy (p=0.031) were poor prognostic factors for OS. Conclusions: iFAM is an effective and safe treatment option in refractory biliary tract cancer and can be considered as salvage regimen, especially for patients with good PS and good response to previous chemotherapy. No significant financial relationships to disclose.
Neoadjuvant stereotactic body radiation therapy (SBRT) for borderline resectable pancreas cancer: Moffitt Cancer Center initial experience.
Authors: Chuong M. D. , Shridhar R. , Patel M. , Klapman J. , Barthel J. S. , Vignesh S. , Hodul P. J. , Springett G. M. , Malafa M. P. , Hoffe S. E. 
Published: February 2017

302 Background: Our institution has reported a strategy of using neoadjuvant GTX (gemcitabine, docetaxel, and capecitabine) chemotherapy followed by 5FU-based intensity-modulated radiation therapy (IMRT) for borderline resectable pancreas cancer. We now report our early experience with induction chemotherapy followed by stereotactic body radiation therapy (SBRT). Methods: This retrospective review evaluates our initial 5 fraction SBRT experience in 15 patients following induction chemotherapy for borderline resectable pancreatic cancer. Staging included pancreatic protocol CT, endoscopic ultrasound, and PET/CT scan. Induction regimens consisted of GTX for 3 cycles in 12 patients and gemcitabine alone in 3. Daily SBRT was delivered to the pancreas at least 1 week after completing systemic chemotherapy. Endoscopically implanted fiducial markers and daily cone beam CT were used for image guidance. Treatment was delivered on a Varian Trilogy unit using 6-15 MV photons. Doses were selected based on dose painting the portion of tumor adjacent to the vasculature to a higher dose while meeting normal tissue constraints. The entire gross tumor received a dose of 5-6 Gy per fraction while the portion of the tumor adjacent to the vasculature resulting in the borderline designation received up to 8 Gy per fraction. Patients were re-imaged 3-4 weeks after SBRT for consideration of surgery. Results: There were no acute or late grade 3 toxicities. At the time of this analysis, not all treated patients have reached the restaging time point, but 9 of 15 (60%) were candidates for resection. Six patients have gone to resection with negative margins and without any increased complications. Two patients were found to have disease surrounding the vasculature preventing resection. One patient had cardiac issues at surgery and resection was aborted. One patient was explored and found to have liver metastases. Conclusions: Integration of SBRT in conjunction with systemic therapy is well-tolerated and appears to facilitate margin-negative resection in borderline resectable pancreatic cancer. No significant financial relationships to disclose.