bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ability of integrated positron emission and computed tomography to detect significant colonic pathology
Authors: Weston Brian R. , Iyer Revathy B. , Qiao Wei , Lee Jeffrey H. , Bresalier Robert S. , Ross William A. 
Published: February 2010

AbstractBACKGROUND:The ability of integrated positron emission tomography and computed axial tomography (PET‐CT) to detect colonic pathology is not fully defined. The purpose of this study was to assess the ability of PET‐CT to detect colonic pathology and to determine the significance of (18F)2‐fluoro‐2‐deoxyglucose (18F‐FDG) activity noted incidentally in the colon on PET‐CT.METHODS:Records for all patients who underwent PET‐CT and colonoscopy at our institution were reviewed. Patients with history of colonic malignancy or colon surgery were excluded.RESULTS:Fifty‐eight patients had incidental colonic 18F‐FDG activity on PET (Group A) and 272 had none (Group B). In Group A, 65% of patients had pathologic findings detected on colonoscopy that corresponded to the site of PET activity. Standardized uptake value (SUV) readings were not helpful in distinguishing true‐positives from false‐positives. In Group B, 11.8% of patients were found to have significant colonic findings. Lesions not detected by PET‐CT included 4 colon cancers, 7 advanced adenomas, and 10 patients with colonic lymphoma. Overall, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET‐CT for detecting significant pathology were 53%, 93%, 65%, 89%, and 85%, respectively. For detecting colon cancer and adenomas 10 mm or more, the sensitivity, specificity, PPV, NPV, and accuracy of PET‐CT were 72%, 90%, 45%, 96%, and 88%, respectively.CONCLUSIONS:Incidental colonic activity detected by PET‐CT warrants further evaluation with colonoscopy. However, negative PET‐CT does not rule out significant colonic pathology including colon cancer, advanced adenomas, or lymphoma. Cancer 2010. © 2010 American Cancer Society.
Differential methylation of cell‐free circulating DNA among patients with pancreatic cancer versus chronic pancreatitis
Authors: Liggett Thomas , Melnikov Anatoliy , Yi Qi‐long , Replogle Charles , Brand Randall , Kaul Karen , Talamonti Mark , Abrams Ross A. , Levenson Victor 
Published: February 2010

AbstractBACKGROUND:Although patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer (PanCa), the timely detection of PanCa often is difficult, because the symptoms of CP and PanCa are very similar. Moreover, secondary inflammation may be identified in PanCa, further complicating diagnosis. To improve the survival of patients with PanCa, a reliable test to differentiate CP from PanCa is needed. In this article, the authors describe a methylation profile of cell‐free plasma DNA that distinguished CP from PanCa with >90% accuracy.METHODS:Methylation in cell‐free, plasma DNA was compared among 30 samples from patients with CP, 30 samples from patients with PanCa, and 30 samples from healthy controls (N) using a microarray‐mediated methylation analysis of 56 fragments in each sample (MethDet56). Statistical analysis was done by using the Fisher exact test, a naive Bayes algorithm, and 25 rounds of 5‐fold cross‐validation.RESULTS:The MethDet56 methylation analysis technique identified 17 gene promoters as informative (8 for distinguishing N from CP and 14 for distinguishing CP from PanCa). It achieved 81.7% sensitivity and 78% specificity (P<.01) in the detection of CP (N vs CP) and 91.2% sensitivity and 90.8% specificity (P<.01) in the differential detection of PanCa (PanCa vs CP).CONCLUSIONS:The current data suggested that, among patients with pancreatic disease, the methylation profiles of inflammatory disease and cancer are different and open a new venue for the development of biomarkers for differential diagnosis. Further investigation of diagnostic biomarkers for pancreatic cancer based on methylation in cell‐free, circulating DNA appears to be warranted. Cancer 2010. © 2010 American Cancer Society.
Tumor cell expression of programmed cell death‐1 ligand 1 is a prognostic factor for malignant melanoma
Authors: Hino Ryosuke , Kabashima Kenji , Kato Yu , Yagi Hiroaki , Nakamura Motonobu , Honjo Tasuku , Okazaki Taku , Tokura Yoshiki 
Published: February 2010

AbstractBACKGROUND:Melanoma tends to be refractory to various immunotherapies because of tumor‐induced immunosuppression. To investigate the mechanism underlining the immunosuppression of melanoma patients, the authors focused on programmed cell death‐1 (PD‐1)/PD‐1 ligand 1 (PD‐L1) interaction between tumor cells and T cells.METHODS:Melanoma specimens were collected from 59 primary tumors, 16 lymph nodes, and 4 lesions of in‐transit metastasis. Specimens stained with anti‐PD‐L1 monoclonal antibodies were digitalized to jpg files. To evaluate the intensity of PD‐L1 expression, histograms were used, and the red density (RD) was measured. PD‐1 expression on T cells was analyzed in blood samples from 10 patients who had stage IV melanoma and in 4 samples of in‐transit metastases.RESULTS:Twenty‐five patients comprised the “low” PD‐L1 expression group (RD value, <90), and 34 patients comprised the “high” group (RD value, ≥90). Breslow tumor thickness in the high‐expression group was significantly higher than in the low‐expression group. Univariate and multivariate analyses revealed that the overall survival rate of the high‐expression group was significantly lower than that of the low‐expression group. In all patients with stage IV disease who were examined, both CD8‐positive and CD4‐positive T cells had significantly higher PD‐1 expression levels in the peripheral blood. Tumor‐infiltrating T cells expressed high levels of PD‐1, and its expression was elevated further during the clinical course.CONCLUSIONS:The current results indicated that there is a correlation between the degree of PD‐L1 expression and the vertical growth of primary tumors in melanoma. Multivariate analysis demonstrated that PD‐L1 expression is an independent prognostic factor for melanoma. Cancer 2010. © 2010 American Cancer Society.
In‐hospital mortality from liver resection for hepatocellular carcinoma
Authors: Simons Jessica P. , Ng Sing Chau , Hill Joshua S. , Shah Shimul A. , Zhou Zheng , Tseng Jennifer F. 
Published: February 2010

AbstractBACKGROUND:There is a wide spectrum of disease burden in hepatocellular carcinoma accompanied by several options for surgical management. However, the associated mortality of such procedures is not well defined. Accurate predictions of patients' perioperative risk would be helpful to guide decision making.METHODS:The Nationwide Inpatient Sample was queried for data from 1998 to 2005. A cohort of patients who were discharged for hepatic procedures with a diagnosis of primary liver neoplasm was assembled. Procedures were categorized as hepatic lobectomy, wedge resection, or enucleation/ablation. Logistic regression and bootstrap methods were used to create an integer risk score for estimating the risk of in‐hospital mortality using procedure type, patient demographics, comorbidities, and hospital type. A randomly selected sample of 80% of the cohort (n = 2263) was used to create the score with validation conducted in the remaining 20% (n = 571).RESULTS:In total, 2834 patient discharges were identified. Overall in‐hospital mortality was 6.52%. Factors that were included in the final model were age, sex, Charlson comorbidity score, procedure type, and teaching hospital status. Integer values were assigned to these characteristics and were used to calculate an additive score. Four clinically relevant score groups were assembled to stratify the risk of in‐hospital mortality, with a 19‐fold gradient of mortality that ranged from 1.5% to 28.3%. In the derivation set, as in the validation set, the score discriminated well with c‐statistics of 0.75 and 0.73, respectively.CONCLUSIONS:The current results indicated that an integer‐based risk score can be used to predict in‐hospital mortality after surgery for hepatocellular carcinoma, and it may be useful for preoperative risk stratification and patient counseling. Cancer 2010. © 2010 American Cancer Society.
Inhibition of tumor growth and angiogenesis by a lysophosphatidic acid antagonist in an engineered three‐dimensional lung cancer xenograft model
Authors: Xu Xiaoyu , Prestwich Glenn D. 
Published: February 2010

AbstractBACKGROUND:We developed an engineered three‐dimensional (3D) tumor xenograft model of nonsmall cell lung cancer (NSCLC) in nude mice, and we used this model to evaluate a dual‐activity inhibitor of lysophosphatidic acid (LPA) biosynthesis and receptor activation.METHODS:First, BrP‐LPA, a pan‐antagonist for 4 LPA receptors and inhibitor of the lyosphospholipase D activity of autotaxin, was examined for inhibition of cell migration and cell invasion by human NSCLC A549 cells. Second, A549 cells were encapsulated in 3D in 3 semisynthetic extracellular matrices (ECMs) based on chemically modified glycosaminoglycans, and injected subcutaneously in nude mice. Tumor volume and vascularity were determined as a function of semisynthetic ECMs composition. Third, engineered NSCLC xenografts were formed from A549 cells in either Extracel‐HP or Matrigel, and mice were treated with 4 intraperitoneal injections of 3 mg/kg of BrP‐LPA.RESULTS:First, BrP‐LPA inhibited cell migration and invasiveness of A549 cells in vitro. Second, tumor growth and microvessel formation for 3D encapsulated A549 cells in vivo in nude mice increased in the following order: buffer only < Extracel < Extracel‐HP < Extracel‐HP containing growth factorss plus laminin. Third, tumor volumes increased rapidly in both Matrigel and Extracel‐HP encapsulated A549 cells, and tumor growth was markedly inhibited by BrP‐LPA treatment. Finally, tumor vascularization was dramatically reduced in the A549 tumors treated with BrP‐LPA.CONCLUSIONS:Engineered A549 lung tumors can be created by 3D encapsulation in an ECM substitute with user controlled composition. The engineered tumors regress and lose vascularity in response to a dual activity inhibitor of the LPA signaling pathway. Cancer 2010. © 2010 American Cancer Society.
Trimodality therapy without a platinum compound for localized carcinoma of the esophagus and gastroesophageal junction
Authors: Ajani Jaffer A. , Correa Arlene M. , Walsh Garrett L. , Komaki Ritsuko , Lee Jeffrey H. , Vaporciyan Ara A. , Rice David C. , Yao James C. , Maru Dipen M. , Hofstetter Wayne L. , Phan Alexandria T. , Swisher Stephen G. 
Published: February 2010

AbstractBACKGROUND:The use of platinum‐based chemoradiation for esophageal cancer is routine, but it is unclear which class of cytotoxic are optimum. It was hypothesized that chemoradiotherapy with fluoropyrimidine, taxane, and camptothecin would have preserved or improved efficacy with no compromise in safety.METHODS:Patients with histologically confirmed, resectable esophageal carcinoma were eligible. In addition to other tests, a baseline endoscopic ultrasonography (EUS) was obtained. Patients were medically fit and had near–normal organ functions. Patients received docetaxel and irinotecan, plus 5–fluorouracil as induction therapy and then the same cytotoxics with 50.4 grays of radiotherapy followed by an attempted surgery. Pathologic complete response (pathCR) at a rate of ≥20% was the primary endpoint. The pathCR and R0 resection were correlated with overall survival (OS). Safety was documented.RESULTS:Fifty‐five patients were enrolled. Seven were women, and the median age was 56 years. Fifty‐three (96%) patients had EUST3, and 41 (75%) had EUSN1 disease. Forty‐three (78%) patients underwent surgery, 20% achieved a pathCR, and 76.4% underwent an R0 resection. The median survival (n = 55 patients) was 43.3 months (range, 19‐75 months). Baseline clinical parameters were not found to be predictive of OS; however, patients with a pathCR (P = .005) and who underwent R0 resection (P ≤ .0001) had an improved OS. There was 1 treatment‐related postsurgical death reported. Grade 3 or 4 toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 62% of patients.CONCLUSIONS:The results of the current study documented that this 3‐drug, noncisplatin‐based chemoradiotherapy was feasible, safe, and active but not better than the published cisplatin‐based chemoradiotherapy. A fluoropyrimidine and another cytotoxic (from any class) may be adequate to establish a baseline chemoradiotherapy regimen to combine biologics. Cancer 2010. © 2010 American Cancer Society.
Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study
Authors: Thomas Xavier , Raffoux Emmanuel , Renneville Aline , Pautas Cecile , de Botton Stephane , Terre Christine , Gardin Claude , Hayette Sandrine , Preudhomme Claude , Dombret Herve 
Published: February 2010

AbstractBACKGROUND:Priming with granulocytic hematopoietic growth factors may modulate cell cycle kinetics of leukemic cells and render them more susceptible to phase‐specific chemotherapeutic agents. In a first report, we have shown that priming with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) may enhance complete remission (CR) rate and event‐free survival (EFS) in younger adults with acute myeloid leukemia (AML).METHODS:In this randomized trial, 259 patients with AML were randomized at baseline to receive or not receive GM‐CSF concurrently with all cycles of chemotherapy. The effects of GM‐CSF on survival were reported herein with a long‐term follow‐up and studied according to distinct biological subgroups defined on cytogenetics and molecular markers.RESULTS:The EFS rate was better in the GM‐CSF group (43% vs 34%; P = .04). GM‐CSF did not improve the outcome in patients from good risk subgroups, while patients from poor risk subgroups benefited from GM‐CSF therapy. In this population, the difference in terms of EFS probability was mainly observed in patients with high initial white blood cell count and in those with FLT3‐ITD or MLL rearrangement. When combining these 2 molecular abnormalities for comparison of the effect of GM‐CSF priming, the difference in terms of EFS was highly significant (5‐year EFS, 39% with GM‐CSF vs 8% without GM‐CSF; P = .007).CONCLUSIONS:Sensitization of leukemic cells and their progenitors by GM‐CSF appears as a plausible strategy for improving the outcome of patients with newly diagnosed AML. Patients with poor‐prognosis FLT3‐ITD or MLL rearrangement might be a good target population to further investigate priming strategies. Cancer 2010. © 2010 American Cancer Society.
Reduced incidence of infusion‐related reactions in metastatic colorectal cancer during treatment with cetuximab plus irinotecan with combined corticosteroid and antihistamine premedication
Authors: Siena Salvatore , Glynne‐Jones Robert , Adenis Antoine , Thaler Josef , Preusser Peter , Aguilar Enrique Aranda , Aapro Matti S. , Loos Anja H. , Esser Regina , Wilke Hansjochen 
Published: February 2010

AbstractBACKGROUND:The multinational MABEL study of 1147 patients with metastatic colorectal cancer (mCRC) who had recently failed an irinotecan‐containing regimen confirmed in a community practice setting the efficacy and safety of cetuximab combined with irinotecan.METHODS:This report describes a post hoc analysis of the influence of prophylactic premedication on the incidence of infusion‐related reactions (IRRs) in the MABEL study. The analysis was focused on the subpopulation of patients premedicated with antihistamines either with (n = 700) or without (n = 422) corticosteroids. Stepwise Cox regression modeling was used to examine the explanatory value of the type of premedication on progression‐free survival (PFS) and overall survival (OS) times.RESULTS:The incidence of IRRs was lower in the group of patients who received antihistamine plus corticosteroid (9.6%) compared with those who received antihistamine alone (25.6%). A similar trend was seen for grade 3 or 4 IRRs (1.0% vs 4.7%, respectively). The 12‐week PFS rates (61% vs 60%), median PFS (16.1 vs 13.1 weeks) and OS (9.2 vs 9.0 months) times for patients who received, respectively, antihistamines with and without corticosteroids were similar. Cox regression modeling did not identify any impact of type of premedication used (antihistamine with or without corticosteroids) on the efficacy of treatment in relation to PFS or OS.CONCLUSIONS:Prophylactically premedicating mCRC patients with both antihistamine and a corticosteroid appeared to reduce the frequency of cetuximab‐associated IRRs. Given that this was a post hoc analysis, caution must be exercised in the interpretation of these data, which require formal confirmation in a randomized study. Cancer 2010. © 2010 American Cancer Society.
Single‐institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting
Authors: Ku Geoffrey Y. , Yuan Jianda , Page David B. , Schroeder Sebastian E. A. , Panageas Katherine S. , Carvajal Richard D. , Chapman Paul B. , Schwartz Gary K. , Allison James P. , Wolchok Jedd D. 
Published: February 2010

AbstractBACKGROUND:Ipilimumab is a monoclonal antibody that antagonizes cytotoxic T lymphocyte antigen‐4, a negative regulator of the immune system. The authors report on advanced refractory melanoma patients treated in a compassionate use trial of ipilimumab at the Memorial Sloan‐Kettering Cancer Center.METHODS:Patients with advanced refractory melanoma were treated in a compassionate use trial with ipilimumab 10 mg/kg every 3 weeks for 4 doses. Those with evidence of clinical benefit at Week 24 (complete response [CR], partial response [PR], or stable disease [SD]) then received ipilimumab every 12 weeks.RESULTS:A total of 53 patients were enrolled, with 51 evaluable. Grade 3/4 immune‐related adverse events were noted in 29% of patients, with the most common immune‐related adverse events being pruritus (43%), rash (37%), and diarrhea (33%). On the basis of immune‐related response criteria, the response rate (CR + PR) was 12% (95% confidence interval [CI], 5%‐25%), whereas 29% had SD (95% CI, 18%‐44%). The median progression‐free survival was 2.6 months (95% CI, 2.3‐5.2 months), whereas the median overall survival (OS) was 7.2 months (95% CI, 4.0‐13.3 months). Patients with an absolute lymphocyte count (ALC) ≥1000/μL after 2 ipilimumab treatments (Week 7) had a significantly improved clinical benefit rate (51% vs 0%; P = .01) and median OS (11.9 vs 1.4 months; P < .001) compared with those with an ALC <1000/μL.CONCLUSIONS:The results confirm that ipilimumab is clinically active in patients with advanced refractory melanoma. The ALC after 2 ipilimumab treatments appears to correlate with clinical benefit and OS, and should be prospectively validated. Cancer 2010. © 2010 American Cancer Society.
Phase 1/2 study of preoperative docetaxel and mitoxantrone for high‐risk prostate cancer
Authors: Garzotto Mark , Higano Celestia S. , O'Brien Catherine , Rademacher Brooks L. S. , Janeba Nicole , Fazli Ladan , Lange Paul H. , Lieberman Stephen , Beer Tomasz M. 
Published: February 2010

AbstractBACKGROUND:A study was conducted to determine the 5‐year recurrence‐free survival in patients with high‐risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence.METHODS:Fifty‐seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m2 and escalating mitoxantrone to 4 mg/m2 before prostatectomy. Patients were treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week schedule. A tissue microarray, constructed from the prostatectomy specimens, served to facilitate the exploratory evaluation of biomarkers. The primary endpoint was recurrence‐free survival. Disease recurrence was defined as a confirmed serum prostate‐specific antigen (PSA) >0.4 ng/mL.RESULTS:Of the 57 patients, 54 received 4 cycles of docetaxel and mitoxantrone before radical prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67% of cases. Lymph node involvement was detected in 18.5% of cases. With a median follow‐up of 63 months, 27 of 57 (47.4%) patients recurred. The Kaplan‐Meier recurrence‐free survival at 2 years was 65.5% (95% confidence interval [CI], 53.0%‐78.0%) and was 49.8% at 5 years (95% CI, 35.5%‐64.1%). Pretreatment serum PSA, lymph node involvement, and postchemotherapy tissue vascular endothelial growth factor expression were independent predictors of early recurrence.CONCLUSIONS:Preoperative chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of the high‐risk patients remain free of disease recurrence at 5 years, and clinical and molecular predictors of early recurrence were identified. Cancer 2010. © 2010 American Cancer Society.
Effectiveness of a patient‐ and practice‐level colorectal cancer screening intervention in health plan members
Authors: Lewis Carmen , Pignone Michael , Schild Laura A. , Scott Tracy , Winquist Andrea , Rimer Barbara K. , Glanz Karen 
Published: February 2010

AbstractBACKGROUND:Evidence‐based interventions have been found effective in increasing colorectal cancer (CRC) screening. Translating these successful interventions into real world settings, such as health plans, can be challenging.METHODS:CHOICE (Communicating Health Options through Information and Cancer Education) is a controlled trial to test the effectiveness of a patient‐ and practice‐level intervention to increase use of recommended CRC screening tests. The patient‐level intervention was a patient decision aid and stage‐targeted brochures, mailed to eligible health plan members, to provide information about CRC, available screening tests, and how to obtain CRC screening at their physicians' practices. The practice‐level intervention was academic detailing to prepare practices to facilitate CRC testing once the patient was activated by the decision aid. Surveys and claims data will be used to assess CRC screening test completion.RESULTS:Thirty‐two primary care practices in Florida and Georgia participated. The authors recruited 443 participating health plan members for the trial; 211 were patients in intervention practices, and 232 were in usual care practices. Study participants reflected an insured population; the majority were white and aged <60 years. The authors also mailed the intervention to 343 people from intervention practices who did not respond to the eligibility or baseline survey. Receipt of screening in that group will be compared with screening among 319 people from usual care practices who did not respond to these surveys using claims data.CONCLUSIONS:The CHOICE study will demonstrate the effect of 2 combined evidence‐based interventions on CRC screening test completion among health plan members. Cancer 2010. © 2010 American Cancer Society.