bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Detection and Accurate Description of Extent of Metastatic Bone Disease in Breast Cancer With Fluoride Ion and Positron Emission Tomography
Authors: Schirrmeister Holger , Guhlmann Albrecht , Kotzerke Jörg , Santjohanser Claudia , Kühn Thorsten , Kreienberg Rolf , Messer Peter , Nüssle Karin , Elsner Klaus , Glatting Gerhard , Träger Harald , Neumaier Bernd , Diederichs Christoph , Reske Sven N. 
Published: February 2017

PURPOSE: Previous studies have shown that bone metastases are revealed by magnetic resonance imaging (MRI) or bone marrow scintigraphy several months before they are visible by conventional bone scintigraphy (BS). We present a new approach for detecting bone metastases in patients with breast cancer. We compared findings obtained with fluoride ion (F-18) and positron emission tomography (PET) with those obtained with conventional BS. PATIENTS AND METHODS: Thirty-four breast cancer patients were prospectively examined using F-18–PET and conventional BS. F-18–PET and BS were performed within 3 weeks of each other. Metastatic bone disease was previously known to be present in six patients and was suspected (bone pain or increasing levels of tumor markers, Ca2+, alkaline phosphatase) in 28 patients. Both imaging modalities were compared by patient-by-patient analysis and lesion-by-lesion analysis, using a five-point scale for receiver operating characteristic (ROC) curve analysis. A panel of reference methodswas used, including MRI (28 patients), planar x-ray (17 patients), and spiral computed tomography (four patients). RESULTS: With F-18–PET, 64 bone metastases were detected in 17 patients. Only 29 metastases were detected in 11 patients with BS. As a result of F-18–PET imaging, clinical management was changed in four patients (11.7%). For F-18–PET, the area under the ROC curve was 0.99 on a lesion basis (for BS, it was 0.74; P < .05) and 1.00 on a patient basis (for BS, it was 0.82; P < .05). CONCLUSION: F-18–PET demonstrates a very early bone reaction when small bone marrow metastases are present, allowing accurate detection of breast cancer bone metastases. This accurate detection has a significant effect on clinical management, compared with the effect on management brought about by detection with conventional BS.
Hyper-CVAD Program in Burkitt's-Type Adult Acute Lymphoblastic Leukemia
Authors: Thomas Deborah A. , Cortes Jorge , O'Brien Susan , Pierce Sherry , Faderl Stefan , Albitar Maher , Hagemeister Frederick B. , Cabanillas Fernando F. , Murphy Sharon , Keating Michael J. , Kantarjian Hagop 
Published: February 2017

PURPOSE: To evaluate response and outcome with a front-line intensive multiagent chemotherapy regimen in adults with Burkitt's-type acute lymphoblastic leukemia (B-ALL). PATIENTS AND METHODS: From September 1992 to June 1997, 26 consecutive adults with newly diagnosed untreated B-ALL received hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD). Their median age was 58 years (range, 17 to 79 years), and 46% were ≥ 60 years. Patients received Hyper-CVAD alternated with courses of high-dose methotrexate and cytarabine. Granulocyte colony-stimulating factor and prophylactic antibiotics were administered for all eight planned courses. CNS prophylaxis alternated intrathecal methotrexate and cytarabine on days 2 and 7 of each course. RESULTS: Complete remission (CR) was obtained in 21 patients (81%). There were five induction deaths (19%). The median time to CR was 22 days (range, 15 to 89 days); 70% achieved CR within 4 weeks. The 3-year survival rate was 49% (± 11%); the 3-year continuous CR rate was 61% (± 11%). Twelve CR patients (57%) were in continuous CR at a median follow-up of 3+ years (range, 13+ months to 6.5+ years). Characteristics predicting for worse survival were age ≥ 60 years, poor performance status, anemia, thrombocytopenia, peripheral blasts, and increased lactate dehydrogenase level. The 3-year survival rate was 77% for 14 patients younger than 60 years and 17% for 12 patients ≥ 60 years (P < .01). Regression analysis identified older age, anemia, and presence of peripheral blasts as independent factors associated with shorter survival. Patients could be stratified according to (1) no or one adverse feature, (2) two adverse features, and (3) all adverse features. The 3-year survival rates were 89%, 47%, and 0%, respectively (P < .01). CONCLUSION: Hyper-CVAD is effective in adult B-ALL. Identification of patients with high risk for relapse and improved methods to detect residual disease may result in risk-oriented approaches.
Marginal Zone B-Cell Lymphoma: A Clinical Comparison of Nodal and Mucosa-Associated Lymphoid Tissue Types
Authors: Nathwani Bharat N. , Anderson James R. , Armitage James O. , Cavalli Franco , Diebold Jacques , Drachenberg Milton R. , Harris Nancy L. , MacLennan Kenneth A. , Müller-Hermelink H. Konrad , Ullrich Fred A. , Weisenburger Dennis D. 
Published: February 2017

PURPOSE: In the International Lymphoma Study Group classification of lymphoma, extranodal marginal zone B-cell lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) type is listed as a distinctive entity. However, nodal MZL is listed as a provisional entity because of questions as to whether it is truly a disease or just an advanced stage of MALT-type MZL. To resolve the issue of whether primary nodal MZL without involvement of mucosal sites exists and whether it is clinically different from extranodal MALT-type lymphoma, we compared the clinical features of these two lymphomas. PATIENTS AND METHODS: Five expert hematopathologists reached a consensus diagnosis of MZL in 93 patients. Seventy-three were classified as having MALT-type MZL because of involvement of a mucosal site at the time of diagnosis, and 20 were classified as having nodal MZL because of involvement of lymph nodes without involvement of a mucosal site. RESULTS: A comparison of the clinical features of nodal MZL and MALT-type MZL showed that more patients with nodal MZL presented with advanced-stage disease (71% v 34%; P = .02), peripheral lymphadenopathy (100% v 8%; P < .001), and para-aortic lymphadenopathy (56% v 14%; P < .001) than those with MALT-type MZL. However, fewer patients with nodal MZL had a large mass (≥ 5 cm) than those with MALT-type MZL (31% v 68%; P = .03). The 5-year overall survival of patients with nodal MZL was lower than that for patients with MALT-type MZL (56% v 81%; P = .09), with a similar result for failure-free survival (28% v 65%; P = .01). Comparisons of patients with International Prognostic Index scores of 0 to 3 showed that those with nodal MZL had lower 5-year overall survival (52% v 88%; P = .025) and failure-free survival (30% v 75%; P = .007) rates than those with MALT-type MZL. CONCLUSION: Nodal MZL seems to be a distinctive disease entity rather than an advanced stage of MALT-type MZL because the clinical presentations and survival outcomes are different in these two types of MZL. Clinically, nodal MZL is similar to other low-grade, node-based B-cell lymphomas, such as follicular and small lymphocytic lymphomas.
Assessment and Significance of Mediastinal Bulk in Hodgkin's Disease: Comparison Between Computed Tomography and Chest Radiography
Authors: Bradley A. J. , Carrington B. M. , Lawrance J. A.L. , Ryder W. D.J. , Radford J. A. 
Published: February 2017

PURPOSE: In Hodgkin's disease (HD), mediastinal bulk is currently defined from chest radiograph (CXR) measurements as a ratio of the maximum transverse mass diameter to the internal thoracic diameter at T5/6 level ≥ 0.33. We evaluated how computed tomographic (CT) measurements of bulk correspond to those obtained from the CXR and correlated nodal mass long axis diameter with freedom from progression. METHODS: Ninety-five adult patients who had a CXR thoracic ratio of greater than 0.3 and a CT scan within 28 days of the CXR were included in the study, provided that both investigations were performed before the start of treatment. Measurements of the widest mediastinal diameter and internal thoracic diameter were made on both CXR and CT scan. The thoracic ratio (TR) was calculated for each modality and compared using paired t tests. The longest diameter of the largest individual nodal mass (LIMCT) was also measured from the CT and correlated with freedom from progression using Cox regression. RESULTS: There was excellent correlation between CT and CXR for measurement of TR, with TRCT greater than TRCXR (mean difference of 2%). A TRCT of 0.35 was found to be equivalent to a TRCXR of 0.33. No single measurement of nodal size correlated with the current definition of bulk. However LIMCT greater than 10 cm did correlate with increased risk of progressive HD (P = .03), even after adjustment for other prognostic variables (chemotherapy regimen and Hasenclever Prognostic Index). CONCLUSION: Excellent correlation was observed between assessment of TR by CXR and CT scan. The longest diameter of the LIMCT greater than 10 cm was found to be associated with an increased risk of disease progression.
Low-Grade Stage III-IV Follicular Lymphoma: Multivariate Analysis of Prognostic Factors in 484 Patients—A Study of the Groupe d'Etude des Lymphomes de l'Adulte
Authors: Decaudin Didier , Lepage Eric , Brousse Nicole , Brice Pauline , Harousseau Jean-Luc , Belhadj Karim , Tilly Hervé , Michaux Lucienne , Chèze Stéphane , Coiffier Bertrand , Solal-Céligny Philippe 
Published: February 2017

PURPOSE: To identify the prognostic factors that influence overall survival (OS) in patients with stage III-IV follicular lymphomas and evaluate the clinical usefulness and the prognostic value of the International Prognostic Index (IPI). PATIENTS AND METHODS: Four hundred eighty-four patients with Ann Arbor stage III-IV follicular lymphomas treated in two phase III trials from 1986 to 1995 were screened for this study. All histologic slides were reviewed by two hematopathologists. The influence of the initial parameters on survival was defined by univariate (log-rank test) and multivariate (Cox model) analyses. RESULTS: The poor prognostic factors for OS (age > 60 years, “B” symptom(s), ≥ two extranodal sites, stage IV disease, tumor bulk > 7 cm, at least three nodal sites > 3 cm, liver involvement, serous effusion-compression or orbital/epidural involvement, and erythrocyte sedimentation rate > 30 mm/h) that were significant in univariate analysis were subjected to multivariate analysis. Three factors remained significant: B symptom(s) (risk ratio = 1.80), age greater than 60 years (risk ratio = 1.60), and at least three nodal sites greater than 3 cm (risk ratio = 1.71). When the IPI was applied to these patients, the score was 1, 2, 3, and 4-5 in 49%, 39%, 11%, and 2%, respectively, and it was significant for progression-free survival (P = .002) and OS (P = .0001). CONCLUSION: Three prognostic factors for poor OS were identified: B symptoms, age greater than 60 years, and at least three nodal sites greater than 3 cm. The IPI was prognostic for OS, but in this population, a very low number of patients belonged to the high-risk groups.
Survival and Prognostic Stratification of 670 Patients With Advanced Renal Cell Carcinoma
Authors: Motzer Robert J. , Mazumdar Madhu , Bacik Jennifer , Berg William , Amsterdam Alison , Ferrara Joseph 
Published: February 2017

PURPOSE: To identify prognostic factors and a model predictive for survival in patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 670 patients with advanced RCC treated in 24 Memorial Sloan-Kettering Cancer Center clinical trials between 1975 and 1996. Clinical features were first examined univariately. A stepwise modeling approach based on Cox proportional hazards regression was then used to form a multivariate model. The predictive performance of the model was internally validated through a two-step nonparametric bootstrapping process. RESULTS: The median survival time was 10 months (95% confidence interval [CI], 9 to 11 months). Fifty-seven of 670 patients remain alive, and the median follow-up time for survivors was 33 months. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status (<80%), high serum lactate dehydrogenase (> 1.5 times upper limit of normal), low hemoglobin (< lower limit of normal), high “corrected” serum calcium (> 10 mg/dL), and absence of prior nephrectomy. These were used as risk factors to categorize patients into three different groups. The median time to death in the 25% of patients with zero risk factors (favorable-risk) was 20 months. Fifty-three percent of the patients had one or two risk factors (intermediate-risk), and the median survival time in this group was 10 months. Patients with three or more risk factors (poor-risk), who comprised 22% of the patients, had a median survival time of 4 months. CONCLUSIONS: Five prognostic factors for predicting survival were identified and used to categorize patients with metastatic RCC into three risk groups, for which the median survival times were separated by 6 months or more. These risk categories can be used in clinical trial design and interpretation and in patient management. The low long-term survival rate emphasizes the priority of clinical investigation to identify more effective therapy.
Multi-Institutional Study of the Angiogenesis Inhibitor TNP-470 in Metastatic Renal Carcinoma
Authors: Stadler Walter M. , Kuzel Timothy , Shapiro Charles , Sosman Jeffery , Clark Joseph , Vogelzang Nicholas J. 
Published: February 2017

PURPOSE: Renal cell carcinoma is resistant to most chemotherapy, and only a minority of patients respond to immunotherapy. Its highly vascular nature suggests that antiangiogenesis therapy might be useful. We thus performed a phase II study of the fumigillin analog TNP-470 in previously treated patients with metastatic renal cell carcinoma.PATIENTS AND METHODS: Metastatic renal cell carcinoma patients with good organ function were entered onto the study through five separate institutions. There were no exclusion criteria for prior therapy. All patients were treated at a dose of 60 mg/m2of TNP-470 infused over 1 hour three times per week.RESULTS: Thirty-three patients were enrolled. Therapy was generally well tolerated, but asthenia, fatigue, vertigo, dizziness, sense of imbalance, and loss of concentration were common and severe enough to lead to therapy discontinuation in five patients. There was only one partial response of short duration (response rate, 3%, 95% confidence interval, 0% to 16%), but six patients (18%) remained on study for 6 or more months without toxicity or disease progression.CONCLUSION: Long-term therapy with TNP-470 has manageable toxicities and is feasible in patients with metastatic renal cell carcinoma but does not lead to any significant objective responses. Further studies in this population using TNP-470 schedules that produce more prolonged drug levels and clinical trial end points other than objective tumor regression may be indicated.
Activity and Pharmacodynamics of 21-Day Topotecan Infusion in Patients With Ovarian Cancer Previously Treated With Platinum-Based Chemotherapy
Authors: Hochster Howard , Wadler Scott , Runowicz Carolyn , Liebes Leonard , Cohen Henry , Wallach Robert , Sorich Joan , Taubes Beth , Speyer James 
Published: February 2017

PURPOSE: Twenty-one–day topotecan infusion was administered as second-line therapy in patients with previously treated ovarian cancer (based on our prior favorable phase I experience) to determine its activity, time to progression, and pharmacodynamics. PATIENTS AND METHODS: Ovarian cancer patients with measurable lesions and one prior platinum-containing regimen were eligible. Topotecan 0.4 mg/m2/d 21-day continuous ambulatory intravenous infusion, with appropriate dose modifications for toxicity, was administered every 28 days. Weekly blood levels of topotecan and topoisomerase-1 (topo-1) levels in peripheral-blood mononuclear cells (PBMCs) were determined for pharmacodynamic correlation. RESULTS: Twenty-four patients were entered onto the study (six cisplatin-refractory, five relapsing within < 6 months and 13 relapsing > 6 months after platinum-based therapy). A total of 128 cycles of topotecan (median, four cycles per patient; range, one to 12 cycles) were administered. The major toxicity was neutropenia (29% grade 3 in all cycles and 4% grade 4). One episode of grade 4 thrombocytopenia (4%) occurred. Fifty-two percent of the patients had anemia that required transfusions. Eight of 23 patients with measurable disease (35%; 95% confidence interval [CI], 15% to 54%) had partial responses (PRs) lasting longer than 1 month. Two of these patients had minor residual computed tomographic changes but had clinical complete remissions that lasted up to 53 weeks while they were not undergoing further therapy. One patient with nonmeasurable disease had a PR (by CA-125 criteria) that lasted 6 months, for an overall response rate of 38% in nine of 24 patients (95% CI, 18% to 57%). The median time to progression was 26 weeks. Pharmacodynamic analysis demonstrated a statistically significant decrease in free PBMC topo-1 level at weeks 2 and 3 of drug administration. There was a strong statistical correlation between the decrease in free topo-1 levels and increasing area under the curve (AUC) for topotecan. This was confirmed in a pharmacodynamic model. CONCLUSION: Twenty-one–day infusion is a well-tolerated method of administering topotecan. Pharmacodynamic studies demonstrate correlations between (1) the week of infusion and the PBMC topo-1 level, (2) the AUC of topotecan and the decrease in topo-1 levels, and (3) the change in topo-1 level and the neutrophil nadir. The objective response rate of 35% to 38% (95% CI, 15% to 57%) in this small multicenter study is at the upper level for topotecan therapy in previously treated ovarian cancer. Prolonged topotecan administration therefore warrants further investigation in larger, randomized studies comparing this 21-day schedule with the once-daily-for-5-days schedule.
KRN8602 (MX2-Hydrochloride): An Active New Agent for the Treatment of Recurrent High-Grade Glioma
Authors: Clarke Kerrie , Basser Russell L. , Underhill Craig , Mitchell Peter , Bartlett Jane , Cher Lawrence , Findlay Michael , Dalley David , Pell Malcolm , Byrne Michael , Geldard Howard , Hill John S. , Maher Darryl , Fox Richard M. , Green Michael D. , Kaye Andrew H. 
Published: February 2017

PURPOSE: To assess the efficacy and toxicity of KRN8602 when administered as an intravenous bolus to patients with recurrent high-grade malignant glioma. PATIENTS AND METHODS: Patients with recurrent or persistent anaplastic astrocytoma or glioblastoma multiforme who had not received recent chemotherapy or radiotherapy and were of good performance status (Eastern Cooperative Oncology Group score ≤ 2) were treated with an intravenous bolus of 40 mg/m2 KRN8602 every 28 days. Tumor responses were assessed radiologically and clinically after every second cycle of therapy. Treatment was continued until documented progression or a total of six cycles. RESULTS: A median of three cycles (range, one to six cycles) of KRN8602 was administered to 55 patients, 49 of whom received at least two cycles and were, therefore, assessable for response. The overall response rate (disease stabilization or better) was 43% (95% confidence interval, 29% to 58%). There were three complete responses, one partial response, seven minor responses, and 10 patients with stable disease. The median time to progression was 2 months (range, 1.5 to 37 months) and overall survival was 11 months (range, 1.5 to 40 months). Neutropenia was the most common toxicity, although it was generally of brief duration, and there were only seven episodes of febrile neutropenia in 176 cycles delivered. Nonhematologic toxicity was mostly gastrointestinal (nausea and vomiting, diarrhea) and events were grade 2 or lower except for a single episode of grade 3 vomiting. CONCLUSION: KRN8602 is an active new agent with minimal toxicity in the treatment of relapsed or refractory high-grade glioma. Further studies with KRN8602 in combination with other cytotoxics and in adjuvant treatment of gliomas are warranted.
Frequency of First Metastatic Events in Breast Cancer: Implications for Sequencing of Systemic and Local-Regional Treatment
Authors: Thames Howard D. , Buchholz Thomas A. , Smith Cynthia D. 
Published: February 2017

PURPOSE: The sequencing of treatment for early breast cancer is controversial. The purpose of this study was to quantify the risk of delaying surgery, using estimates of the frequency of first metastases from breast primary tumors. PATIENTS AND METHODS: The probability that 560 (node-negative), 657 (with one to three positive nodes), and 505 (with more than three positive nodes) women treated without adjuvant chemotherapy would be free of distant disease at presentation was fit to a mathematical model of the seeding of distant metastases and combined with estimates of the growth rate to calculate the frequency of first distant disseminations per month. RESULTS: Frequencies of first distant metastases were approximately 1% to 2% per month, 2% to 4% per month, and 3% to 6% per month in T1 patients who were node-negative, had one to three positive nodes, or more than three positive nodes, respectively. As a result, the typical patient with T1 disease, who has a 70% to 80% chance of being free of distant disease, runs a 1% to 4% risk of distant dissemination for each month surgery is delayed. Assuming a 30% reduction in mortality caused by adjuvant chemotherapy, the model predicts that T1 patients treated with neoadjuvant chemotherapy would potentially have a higher rate of distant metastasis development than those treated with an initial surgical resection followed by adjuvant chemotherapy. CONCLUSION: We formulate the hypothesis that optimal sequencing of surgery and systemic treatment of breast cancer may be size-dependent, with a disadvantage or no benefit from neoadjuvant treatment for T1 patients but an increasing benefit with increasing size of the primary tumor.
Health-Related Quality of Life and Tamoxifen in Breast Cancer Prevention: A Report From the National Surgical Adjuvant Breast and Bowel Project P-1 Study
Authors: Day Richard , Ganz Patricia A. , Costantino Joseph P. , Cronin Walter M. , Wickerham D. Lawrence , Fisher Bernard 
Published: February 2017

PURPOSE: This is the initial report from the health-related quality of life (HRQL) component of the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. This report provides an overview of HRQL findings, comparing tamoxifen and placebo groups, and advice to clinicians counseling women about the use of tamoxifen in a prevention setting. PATIENTS AND METHODS: This report covers the baseline and the first 36 months of follow-up data on 11,064 women recruited over the first 24 months of the study. Findings are presented from the Center for Epidemiological Studies–Depression Scale (CES-D), the Medical Outcomes Study 36-Item Short Form Health Status Survey (MOS SF-36) and sexual functioning scale, and a symptom checklist. RESULTS: No differences were found between placebo and tamoxifen groups for the proportion of participants scoring above a clinically significant level on the CES-D. No differences were found between groups for the MOS SF-36 summary physical and mental scores. The mean number of symptoms reported was consistently higher in the tamoxifen group and was associated with vasomotor and gynecologic symptoms. Significant increases were found in the proportion of women on tamoxifen reporting problems of sexual functioning at a definite or serious level, although overall rates of sexual activity remained similar. CONCLUSION: Women need to be informed of the increased frequency of vasomotor and gynecologic symptoms and problems of sexual functioning associated with tamoxifen use. Weight gain and depression, two clinical problems anecdotally associated with tamoxifen treatment, were not increased in frequency in this trial in healthy women, which is good news that also needs to be communicated.