bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost of Outpatient Blood Transfusion in Cancer Patients
Authors: Crémieux Pierre-Yves , Barrett Barbara , Anderson Kenneth , Slavin Mitchell B. 
Published: February 2017

PURPOSE: To determine the cost of outpatient RBC transfusion from the provider’s perspective at a major urban, academic cancer center. PATIENTS AND METHODS: We retrospectively studied 517 cancer patients with hematologic or solid tumors who received blood during fiscal year 1995 to 1996. A process-flow diagram was developed, and cost and utilization data for 12 months were collected and analyzed. A structured interview process was used to identify all direct and indirect costs from within the inpatient unit, blood bank, and outpatient clinic. Average costs were computed for the entire sample and for specific subgroups. RESULTS: In 1998 dollars, the average cost per RBC unit was $469 for adults and $568 for pediatric cancer patients. Adults and children generally received two and one RBC units per transfusion, respectively. Therefore, the average cost of a two-unit transfusion was $938 for adults. Patients with hematologic tumors required more RBC units (7.1 RBC units per year) at a higher average cost ($512 per RBC unit) than patients with solid tumors (4.7 RBC units per year, $474 per RBC unit). Further variations across tumor types were observed. Overhead, direct material, and direct labor represented 46%, 19%, and 35% of total costs respectively. CONCLUSION: The cost of outpatient RBC transfusions in cancer patients is higher than previously reported, in part because overhead costs and fixed costs might have been underestimated in previous studies. Furthermore, age, tumor type, and geographic variations in the cost of fixed assets and labor have a substantial impact on the cost of blood. The results indicate that the cost-effectiveness of alternatives to transfusions in the management of cancer patients may have been underestimated in the existing literature.
Increased Risk of Acute Leukemia After Adjuvant Chemotherapy for Breast Cancer: A Population-Based Study
Authors: Chaplain Gilles , Milan Chantal , Sgro Catherine , Carli Paule-Marie , Bonithon-Kopp Claire 
Published: February 2017

PURPOSE: To quantify the risk of acute leukemia after adjuvant therapy, especially chemotherapy with topoisomerase II inhibitors. PATIENTS AND METHODS: We performed a population-based study in a cohort of 3,093 women younger than 85 years who resided in the French administrative area of the Côte d’Or, who were given a first diagnosis of primary breast cancer between 1982 and 1996, and who received a curative treatment. Information about therapy and follow-up events was obtained from records of cancer registries that covered this area. RESULTS: Until December 1998, 10 cases of acute leukemia, including nonlymphoid acute leukemia and refractory anemia with excess of blasts, occurred in patients before any local or distant recurrence. All cases developed in the first 4 years of follow-up. Compared with the general female population, the incidence rate of leukemia was significantly increased in women who received radiotherapy and chemotherapy (standardized incidence ratio, 28.5; P < .0001). A dose-dependent increase in the risk of leukemia was observed in women treated with mitoxantrone. Cox regression analysis showed that the risk of leukemia was significantly lower in patients treated with anthracyclines than in those treated with mitoxantrone at cumulative doses ≥ 13 mg/m2. CONCLUSION: The combination of adjuvant radiotherapy and chemotherapy with mitoxantrone induces a high risk of acute leukemia in patients with breast cancer. A leukemogenic effect of chemotherapy with anthracyclines cannot be ruled out with certainty. However, there are some suggestions that these topoisomerase II inhibitors might be less leukemogenic than mitoxantrone and could be preferred in an adjuvant setting.
Low-Stage Medulloblastoma: Final Analysis of Trial Comparing Standard-Dose With Reduced-Dose Neuraxis Irradiation
Authors: Thomas Patrick R. M. , Deutsch Melvin , Kepner James L. , Boyett James M. , Krischer Jeffrey , Aronin Patricia , Albright Leland , Allen Jeffrey C. , Packer Roger J. , Linggood Rita , Mulhern Raymond , Stehbens James A. , Langston James , Stanley Philip , Duffner Patricia , Rorke Lucy , Cherlow Joel , Friedman Henry S. , Finlay Jonathan L. , Vietti Teresa J. , Kun Larry E. 
Published: February 2017

PURPOSE: To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. PATIENTS AND METHODS: The Pediatric Oncology Group and Children’s Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed tomography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. RESULTS: The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuraxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuraxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P = .080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P = .141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. CONCLUSION: Reduced-dose neuraxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement.
Treatment for Primary CNS Lymphoma: The Next Step
Authors: Abrey Lauren E. , Yahalom Joachim , DeAngelis Lisa M. 
Published: February 2017

PURPOSE: The use of preradiotherapy (RT) methotrexate (MTX) has improved disease control and survival in patients with primary CNS lymphoma (PCNSL). The reported protocol was designed to optimize and enhance the chemotherapeutic component of treatment. PATIENTS AND METHODS: Fifty-two patients were treated with five cycles of high-dose MTX 3.5 g/m2, procarbazine 100 mg/m2/d, and vincristine 1.4 mg/m2. Thirty patients received whole-brain RT (45 Gy). Twenty-two older patients deferred RT to diminish the risk of delayed neurotoxicity; these patients are compared with 12 older patients who completed the entire treatment regimen. Most patients (n = 35) received high-dose cytarabine after RT. RESULTS: Objective response rate to the induction chemotherapy regimen was 90%; overall median survival is 60 months. Grade 3 or 4 myelosuppression was seen in 30 patients, primarily in association with cytarabine; grade 3 nephrotoxicity due to MTX was seen in two patients. Older patients had similar median survival with or without the addition of RT: 32 versus 33 months, respectively. However, late neurotoxicity was significantly more common in those older patients who received RT (P = .00004). Patients younger than 60 years who received the complete treatment regimen have not reached median disease-free or overall survival. CONCLUSION: Increasing the dose of MTX and adding procarbazine and vincristine improved disease control and overall survival in patients with newly diagnosed PCNSL. Younger patients in particular fared extremely well with this treatment regimen. In older patients, deferring whole-brain RT did not compromise overall survival but did reduce treatment-related toxicity.
Utility of Positron Emission Tomography for the Staging of Patients With Potentially Operable Esophageal Carcinoma
Authors: Flamen P. , Lerut A. , Van Cutsem E. , De Wever W. , Peeters M. , Stroobants S. , Dupont P. , Bormans G. , Hiele M. , De Leyn P. , Van Raemdonck D. , Coosemans W. , Ectors N. , Haustermans K. , Mortelmans L. 
Published: February 2017

PURPOSE: A prospective study of preoperative tumor-node-metastasis staging of patients with esophageal cancer (EC) was designed to compare the accuracy of 18-F-fluoro-deoxy-d-glucose (FDG) positron emission tomography (PET) with conventional noninvasive modalities. PATIENTS AND METHODS: Seventy-four patients with carcinomas of the esophagus (n = 43) or gastroesophageal junction (n = 31) were studied. All patients underwent attenuation-corrected FDG-PET imaging, a spiral computed tomography (CT) scan, and an endoscopic ultrasound (EUS). RESULTS: FDG-PET demonstrated increased activity in the primary tumor in 70 of 74 patients (sensitivity: 95%). False-negative PET images were found in four patients with T1 lesions. Thirty-four patients (46%) had stage IV disease. FDG-PET had a higher accuracy for diagnosing stage IV disease compared with the combination of CT and EUS (82% v 64%, respectively; P = .004). FDG-PET had additional diagnostic value in 16 (22%) of 74 patients by upstaging 11 (15%) and downstaging five (7%) patients. Thirty-nine (53%) of the 74 patients underwent a 2- or 3-field lymphadenectomy in conjunction with primary curative esophagectomy. In these patients, tumoral involvement was found in 21 local and 35 regional or distant lymph nodes (LN). For local LN, the sensitivity of FDG-PET was lower than EUS (33% v 81%, respectively; P = .027), but the specificity may have been higher (89% v 67%, respectively; P = not significant [NS]). For the assessment of regional and distant LN involvement, compared with the combined use of CT and EUS, FDG-PET had a higher specificity (90% v 98%, respectively; P = .025) and a similar sensitivity (46% v 43%, respectively; P = NS). CONCLUSION: PET significantly improves the detection of stage IV disease in EC compared with the conventional staging modalities. PET improves diagnostic specificity for LN staging.
Expression of Interferon Regulatory Factor 4 in Chronic Myeloid Leukemia: Correlation With Response to Interferon Alfa Therapy
Authors: Schmidt Manuel , Hochhaus Andreas , König-Merediz Sven A. , Brendel Cornelia , Proba Jutta , Hoppe Georg J. , Wittig Burghardt , Ehninger Gerhard , Hehlmann Rüdiger , Neubauer Andreas 
Published: February 2017

PURPOSE: Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-α) treatment in CML.MATERIALS AND METHODS: Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro–stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-α therapy and in 47 additional CML samples taken during IFN-α therapy. IRF4 expression was then correlated with cytogenetic response to IFN-α.RESULTS: IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-α therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-α therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-α, a good response was associated with high IRF4 expression.CONCLUSION: IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-α therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-α in CML.
Phase I Assessment of the Pharmacokinetics, Metabolism, and Safety of Emitefur in Patients With Refractory Solid Tumors
Authors: Nemunaitis J. , Eager R. , Twaddell T. , Corey A. , Sekar K. , Tkaczuk K. , Thompson J. , Hoff P.M. , Pazdur R. 
Published: February 2017

PURPOSE: To determine the toxicities, dose-limiting toxicities (DLT), maximum-tolerated dose, and pharmacokinetic profile of emitefur (BOF-A2) in patients with advanced solid tumors. METHODS: This was a phase I dose-escalating trial in which cohorts of patients received BOF-A2 (cohort 1, 300 mg/m2 orally [PO] tid; cohort 2, 200 mg/m2 PO tid; cohort 3, 200 mg/m2 bid; and cohort 4, 250 mg/m2 bid) for 14 consecutive days followed by 1 week of rest (cycle 1). Pharmacokinetics, toxicity, and tumor response were monitored. RESULTS: Nineteen patients received 110 cycles (three patients in cohort 1, three patients in cohort 2, 10 patients in cohort 3, and three patients in cohort 4). DLT (grade 3 stomatitis, diarrhea, leukopenia) was observed in cohorts 1, 2, and 4. Pharmacokinetics indicated that prolonged systemic expression of fluorouracil (5-FU) is maintained after administration of BOF-A2 at a dose of 200 mg bid for 14 days. The mean steady-state concentration of plasma 5-FU was ≥ 24 ng/mL, which was 184-fold greater than the minimum effective cytotoxic concentration in vitro. Lack of variation of 5-FU trough levels within a day at steady-state indicates suppression of circadian variation. One patient in cohort 3 achieved a partial response and five patients maintained stable disease in excess of 6 months. CONCLUSION: BOF-A2 at a dose of 200 mg PO bid for 14 days followed by 7 days of rest is well tolerated. Prolonged exposure to 5-FU above the predicted preclinical minimum effective concentration is maintained, without evidence of circadian variation. Furthermore, evidence of antitumor activity is suggested.
Results and Outcome of Retroperitoneal Lymph Node Dissection for Clinical Stage I Embryonal Carcinoma–Predominant Testis Cancer
Authors: Sweeney Christopher J. , Hermans Benoit P. , Heilman Douglas K. , Foster Richard S. , Donohue John P. , Einhorn Lawrence H. 
Published: February 2017

PURPOSE: To determine the incidence of metastatic disease and usage of chemotherapy (adjuvant or metastatic) after primary retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I embryonal carcinoma (EC)–predominant testicular cancer. EC predominance was defined as the presence of EC at a level greater than that of any other histologic diagonsis. PATIENTS AND METHODS: All CS I patients with nonseminomatous germ cell tumors who underwent RPLND at Indiana University from 1990 to 1995 were reviewed retrospectively. RESULTS: Two-year follow-up was available for 292 of 320 patients. EC-predominant disease was found in 125 (42.8%) of 292. Eighty-five (68.0%) of 125 patients with EC-predominant disease had pathologic stage (PS) I, and 18 (21.2%) of this group of 85 relapsed. A significantly lower PS I relapse rate of 3% was found for patients who had non–EC-predominant disease (P < .0001). PS II disease was more frequent in patients with EC predominance, as 40 (32.0%) of 125 had retroperitoneal metastases, compared with 26 (15.6%) of 167 patients with a non–EC-predominant histologic diagnosis (P = .0024). Chemotherapy was administered to 48 (38.4%) of the 125 patients with CS I EC-predominant disease after RPLND. This included 25 CS I patients with PS II disease who received adjuvant chemotherapy in addition to 23 patients who subsequently required chemotherapy for relapse after RPLND. Ten (66.6%) of 15 PS II EC-predominant patients were cured by surgery alone. Currently, all 125 EC-predominant patients are disease-free. CONCLUSION: Patients with CS I EC-predominant disease are at a relatively high risk for metastatic disease.
Phase I/II Study of Gemcitabine Plus Vinorelbine as First-Line Chemotherapy of Non–Small-Cell Lung Cancer
Authors: Lorusso Vito , Carpagnano Francesco , Frasci Giuseppe , Panza Nicola , Di Rienzo Gaetano , Cisternino Mario Luigi , Napoli Gaetano , Orlando Silvio , Cinieri Saverio , Brunetti Cosimo , Palazzo Salvatore , De Lena Mario 
Published: February 2017

PURPOSE: To determine the maximum-tolerated dose of gemcitabine when combined with a fixed dose of vinorelbine in the treatment of non–small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the activity of this combination. PATIENTS AND METHODS: Sixty-eight patients with stage IIIB/IV NSCLC were treated with vinorelbine at fixed dose of 30 mg/m2 intravenously and gemcitabine at increasing dose levels from 800 to 1,500 mg/m2 intravenously on days 1 and 8 every 3 weeks. RESULTS: In phase I, dose-limiting toxicity occurred at the dosage of 1,500 mg/m2 gemcitabine, with three of five patients developing grade 4 thrombocytopenia. In phase II, with gemcitabine at 1,200 mg/m2, 19 (36%) of 52 assessable patients responded. Objective response was observed in 11 (39%) of 28 patients with stage IIIB disease and in eight (33%) of 24 patients with stage IV. The median time to progression was 29 weeks (range, 2 to 41 weeks; 35 weeks and 16 weeks for stages IIIB and IV, respectively), and median survival was 54 weeks (range, 2 to 84+ weeks; 63 weeks and 42 weeks for stages IIIB and IV, respectively). One-year survival was 64% for patients with stage IIIB disease and 29% for those with stage IV. Clinical benefit response was observed in 29 (59%) of 49 assessable patients. Grade 4 leukopenia and thrombocytopenia were uncommon (6% and 8% of cases, respectively); however, grade 3/4 leukothrombocytopenia occurred more frequently in patients aged more than 70 years (52% and 24%, respectively). CONCLUSION: The combination of vinorelbine and gemcitabine is effective and tolerable in the treatment of NSCLC, thus deserving randomized trials with cisplatin combination regimens.
Content and Quality of Currently Published Phase II Cancer Trials
Authors: Mariani Luigi , Marubini Ettore 
Published: February 2017

PURPOSE: A number of statistical methods have been proposed for the design and analysis of phase II studies based on dichotomous outcomes. To investigate to what extent such methods are in current use, we conducted a survey of published studies. Materials and Methods: We identified studies by conducting a computerized literature search of MEDLINE. We considered trials on systemic antineoplastic treatments described as phase II or pilot. The search was limited to articles written in English and published in 1997. RESULTS: Three hundred eight trials were identified. The majority, ie, 295 (95.8%), had been conducted as single-arm studies, with objective tumor response as the primary efficacy end point. An identifiable statistical design was reported for only 58 (19.7%) of these trials. The quality in reporting the statistical design and compliance with the design in carrying out the study or results interpretation were frequently poor. The frequency of reporting the statistical design was not shown to increase over the years of study start and was not associated with sample size or study duration. Instead, a significant association was found with trial results (which were less frequently positive among studies with a statistical design) and with the impact factor of the publishing journal. CONCLUSION: This survey shows that the quality of the statistical component of published phase II cancer trials is generally poor and raises suspicion that low quality is likely to bias study findings. Journals might improve the methodologic standard of published articles through a more vigilant reviewing policy.
Dietary Fat Intake and Endogenous Sex Steroid Hormone Levels in Postmenopausal Women
Authors: Holmes Michelle D. , Spiegelman Donna , Willett Walter C. , Manson JoAnn E. , Hunter David J. , Barbieri Robert L. , Colditz Graham A. , Hankinson Susan E. 
Published: February 2017

PURPOSE: To examine the relationship between plasma levels of reproductive sex steroid hormones in postmenopausal women and their reported fat intake. METHODS: We measured plasma sex steroid hormones levels in plasma collected in 1989 and 1990 from 381 healthy postmenopausal women. For each woman, we measured fat intake in 1986 and 1990 by a food-frequency questionnaire. The cross-sectional associations between the percentage of energy from total and specific types of dietary fat intake and plasma hormone levels were assessed by linear regression, controlling for energy intake, obesity, and protein intake. RESULTS: The plasma estradiol level was 4.3% lower (95% confidence limits, −8.3%, −0.2%) for a substitution of 5% of energy from fat intake for an equivalent amount of energy from carbohydrate when adjusted for obesity and other covariates. Estradiol was also inversely associated with all other fat types except trans fat; the inverse associations with vegetable fat and marine omega-3 fats were statistically significant. CONCLUSION: We observed an inverse association between total fat intake averaged over 4 to 5 years and estradiol levels. This result is inconsistent with the hypothesis that fat intake predisposes to breast cancer risk by raising endogenous estrogen levels.
Cisplatin, Doxorubicin, and Delayed Surgery for Childhood Hepatoblastoma: A Successful Approach—Results of the First Prospective Study of the International Society of Pediatric Oncology
Authors: Pritchard Jon , Brown Julia , Shafford Elizabeth , Perilongo Giorgio , Brock Penelope , Dicks-Mireaux Claire , Keeling Jean , Phillips Angela , Vos Anton , Plaschkes Jack 
Published: February 2017

PURPOSE: Hepatoblastoma (HB) is a rare malignant liver tumor which occurs almost exclusively in childhood. In the 1970s, survival was approximately 20% to 30%. Since the introduction of cisplatin (PLA) and doxorubicin (DO) into the chemotherapy regimens used to treat these patients, the survival rate has improved dramatically. In most recent studies, primary surgery preceded chemotherapy. In this study by the liver group of the International Society of Pediatric Oncology the aim was to improve survival and reduce operative morbidity and mortality by using preoperative chemotherapy. PATIENTS AND METHODS: After biopsy and assessment of pretreatment extent of disease all patients were treated with continuous 24-hour intravenous infusion of PLA 80 mg/m2 followed by DO 60 mg/m2 over 48 hours (PLADO). After four courses of this chemotherapy, patients were reassessed. Where possible, the primary tumor was resected and treatment completed with two more courses of chemotherapy. RESULTS: One hundred fifty-four patients were registered in the study, and 138 received preoperative chemotherapy. One hundred thirteen (82%) showed a partial response with tumor shrinkage and serial decrease of serum alpha-fetoprotein levels. One hundred fifteen patients had delayed surgery, and 106 (including six with liver transplants) had complete resection of primary tumor. Five-year event-free survival was 66%, and overall survival was 75%. CONCLUSION: This study demonstrates that international collaboration on a large scale is feasible. The toxicity of chemotherapy and morbidity of surgery were acceptable and the overall survival gratifyingly high. We now regard PLADO chemotherapy and delayed surgery to be the best available treatment for children with HB. Other treatment programs should be measured against this standard.