bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomerase Activity and Prognosis in Primary Breast Cancers
Authors: Carey Lisa A. , Kim Nam W. , Goodman Steven , Marks Jeffrey , Henderson Gregory , Umbricht Christopher B. , Dome Jeffrey S. , Dooley William , Amshey Stefan R. , Sukumar Saraswati 
Published: February 2017

PURPOSE: Recent studies associate telomerase activity with prognostic factors and survival. We compared quantitative telomerase activity in primary tumors with traditional prognostic factors and outcome in a group of invasive but nonmetastatic breast cancers. PATIENTS AND METHODS: Telomerase activity was measured in 203 invasive breast cancers by the quantitative telomeric repeat amplification protocol method. Telomerase expression was compared with 28S rRNA level, tumor content, and clinical variables, including outcome. For clinical correlations, telomerase activity was standardized by two methods: (1) a correction for cellularity using 28S rRNA levels, and (2) a correction for the histologically determined invasive proportion of the specimen. RESULTS: Telomerase activity was found in 82% of breast cancers with measurable 28S rRNA levels. Telomerase activity was associated with the proliferative index (P < .01) of the tumor but not with any other prognostic variable. Neither uncorrected nor corrected telomerase activity was associated with relapse-free or overall survival in this study. CONCLUSION: Telomerase activity level was associated with the proliferative index of invasive breast cancers, but its measurement in samples from this group of nonmetastatic breast cancer patients did not predict survival.
Effect of Radiotherapy and Chemotherapy on Pulmonary Function After Treatment for Breast Cancer and Lymphoma: A Follow-Up Study
Authors: Theuws Jacqueline C.M. , Muller Sara H. , Seppenwoolde Yvette , Kwa Stefan L.S. , Boersma Liesbeth J. , Hart Guus A.M. , Baas Paul , Lebesque Joos V. 
Published: February 2017

PURPOSE: To determine the changes in pulmonary function tests (PFTs) 0 to 48 months after treatment for breast cancer and lymphoma.PATIENTS AND METHODS: The alveolar volume (VA), vital capacity, forced expiratory volume in 1 second, and corrected transfer factor of carbon monoxide (TL,COc) were measured in 69 breast cancer and 41 lymphoma patients before treatment and 3, 18, and 48 months after treatment with radiotherapy alone or radiotherapy in combination with chemotherapy (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine; cyclophosphamide, epidoxorubicin, fluorouracil; cyclophosphamide, thiotepa, carboplatin; cyclophosphamide, methotrexate, fluorouracil). The three-dimensional dose distribution in the lung of each patient was converted to the mean lung dose. Statistical analysis was used to evaluate the changes in PFT values over time in relation to age, sex, smoking, chemotherapy, and the mean lung dose.RESULTS: After an initial reduction in PFT values at 3 months, significant recovery was seen at 18 months for all patients. Thereafter, no further improvement could be demonstrated. Reductions in spirometry values and VAwere related to the mean lung dose only (0.9% per Gy at 3 months and 0.4% per Gy mean dose at 18 months). TL,COcdecreased 1.1% per Gy mean dose and additionally decreased 6% when chemotherapy was given after radiotherapy. Chemotherapy administered before radiotherapy reduced baseline TL,COcvalues by 8% to 21%. All patients showed an improvement of 5% at 18 months.CONCLUSION: On the basis of the mean lung dose and the chemotherapy regimen, the changes in PFT values can be estimated before treatment within 10% of the values actually observed in 72% to 85% of our patients with healthy lungs.
High-Dose Therapy and Autologous Stem-Cell Transplantation for Adult Patients With Hodgkin's Disease Who Do Not Enter Remission After Induction Chemotherapy: Results in 175 Patients Reported to the European Group for Blood and Marrow Transplantation
Authors: Sweetenham John W. , Carella Angelo M. , Taghipour Golnaz , Cunningham David , Marcus Robert , Volpe Aldo Della , Linch David C. , Schmitz Norbert , Goldstone Anthony H. 
Published: February 2017

PURPOSE: To investigate the results of high-dose therapy and autologous stem-cell transplantation (ASCT) in adults with Hodgkin's disease who do not enter remission after induction therapy, to determine overall survival (OS) and progression free survival (PFS), and to identify prognostic factors. PATIENTS AND METHODS: A retrospective analysis of 175 patients reported to the European Group for Blood and Marrow Transplantation between November 1979 and October 1995. One hundred were male and 75 were female, with a median age of 26.5 years. Responses to first-line therapy were defined as progressive disease (PD) in 88 and stable/minimally responsive disease (SD/MR) in 87. Seventy-five patients received ASCT after failure of one induction regimen. Second-line therapy was given to the remaining 100 patients. Response to second-line therapy was PD in 34 and SD/MR in 66. OS and PFS rates were determined, and prognostic factors were investigated using univariate and multivariate analyses. RESULTS: Responses to high-dose therapy and ASCT were complete response (30%), partial response (28%), no response (14%), PD (14%), and toxic death (14%). Actuarial 5-year OS and PFS rates were 36% and 32%, respectively. In univariate analysis for PFS and OS, adverse factors were use of a second-line chemotherapy regimen and interval of more than 18 months between diagnosis and ASCT. In multivariate analysis, the interval between diagnosis and ASCT maintained prognostic significance for OS. Response to the chemotherapy regimen given immediately before ASCT had no predictive value. CONCLUSION: High-dose therapy and ASCT is an effective treatment strategy for patients with Hodgkin's disease for whom induction chemotherapy fails. Outcome was equivalent for those with obvious PD or SD/MR in response to the regimen given immediately before high-dose therapy. Prospective randomized studies are required to compare this approach with conventional-dose salvage therapy.
Increased Incidence of Hodgkin's Disease After Allogeneic Bone Marrow Transplantation
Authors: Rowlings Philip A. , Curtis Rochelle E. , Passweg Jakob R. , Deeg H. Joachim , Socié Gérard , Travis Lois B. , Kingma Douglas W. , Jaffe Elaine S. , Sobocinski Kathleen A. , Horowitz Mary M. 
Published: February 2017

PURPOSE: Immune dysregulation associated with allogeneic bone marrow transplantation (BMT) is linked to an increased risk of posttransplant lymphoproliferative disorders (PTLD); however, reports of Hodgkin's disease (HD) after transplantation are rare. PATIENTS AND METHODS: We evaluated the risk of HD among 18,531 persons receiving allogeneic BMT between 1964 and 1992 at 235 centers. The number of HD cases was compared with that expected in the general population. Risk factors were identified using Poisson regression and a nested case-control study. RESULTS: Risk of HD was increased in the postBMT population compared with the general population with an observed-to-expected incidence ratio (O/E) of 6.2 (observed cases, n = 8; 95% confidence interval [CI], 2.7 to 12). A significantly increased risk of HD remained after excluding two human immunodeficiency virus–positive patients (observed cases, n = 6; O/E = 4.7, 95% CI, 1.7 to 10.3). Mixed cellularity subtype predominated (five of eight cases, 63%). Five of six assessable cases contained Epstein-Barr virus (EBV) genome. Posttransplant HD differed from PTLD by later onset (> 2.5 years) and lack of association with established risk factors (such as T-cell depletion and HLA disparity). Patients with HD were more likely than matched controls to have had grade 2 to 4 acute graft-versus-host disease (GVHD), required therapy for chronic GVHD, or both (P = .002), although analysis included small numbers of patients. CONCLUSION: The increased incidence of HD among BMT recipients adds support to current theories which link overstimulation of cell-mediated immunity and exposure to EBV with various subtypes of HD. The long latency of HD after transplant and lack of association with risk factors for PTLD is noteworthy and should be explored further for possible insights into pathogenesis.
Vinblastine Versus Vinblastine Plus Oral Estramustine Phosphate for Patients With Hormone-Refractory Prostate Cancer: A Hoosier Oncology Group and Fox Chase Network Phase III Trial
Authors: Hudes Gary , Einhorn Lawrence , Ross Eric , Balsham Andrew , Loehrer Patrick , Ramsey Harry , Sprandio John , Entmacher Michael , Dugan William , Ansari Rafat , Monaco Frank , Hanna Mark , Roth Bruce 
Published: February 2017

PURPOSE: To compare vinblastine versus the combination of vinblastine plus estramustine as treatment for patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: A total of 201 patients with metastatic prostate cancer, progressive after hormonal therapy and antiandrogen withdrawal (if prior antiandrogen treatment), were randomized to receive vinblastine (V) 4 mg/m2 by intravenous bolus weekly for 6 weeks followed by 2 weeks off, either alone or together with estramustine phosphate (EM-V) 600 mg/m2 PO days 1 through 42, repeated every 8 weeks. Of 193 eligible patients, 98 received V, and 95 received EM-V. RESULTS: Overall survival trended in favor of EM-V but was not significantly different as determined by Kaplan-Meier analysis (P = .08). Median survival was 11.9 months for EM-V and 9.2 months for V. EM-V was superior to V for secondary end points of time to progression (P < .001, stratified log rank test; median 3.7 v 2.2 months, respectively) and for proportion of patients with ≥ 50% prostate-specific antigen (PSA) decline sustained for at least 3 monthly measurements (25.2% v 3.2%, respectively; P < .0001). Granulocytopenia was significantly less for EM-V compared with V (grade 2, 3, and 4 = 7%, 7%, and 1% v 27%, 18% and 9%, respectively; P < .0001); however, grade 2 or worse nausea (26% v 7%, respectively; P = .0002) and extremity edema (22% v 8%, respectively; P = .005) were more frequent for EM-V. CONCLUSION: Although overall survival was not significantly greater for the combination, EM-V was superior to V for time to progression and PSA improvement. These results encourage further study of estramustine-based antimicrotubule drug combinations in HRPC.
Further Evaluation of Intensified and Increased Total Dose of Cyclophosphamide for the Treatment of Primary Breast Cancer: Findings From National Surgical Adjuvant Breast and Bowel Project B-25
Authors: Fisher Bernard , Anderson Stewart , DeCillis Arthur , Dimitrov Nikolay , Atkins James N. , Fehrenbacher Louis , Henry Patrick H. , Romond Edward H. , Lanier Keith S. , Davila Enrique , Kardinal Carl G. , Laufman Leslie , Pierce H. Irving , Abramson Neil , Keller Alan M. , Hamm John T. , Wickerham D.L. , Begovic Mirsada , Tan-Chiu Elizabeth , Tian Wei , Wolmark Norman 
Published: February 2017

PURPOSE: In 1989, the National Surgical Adjuvant Breast and Bowel Project initiated the B-22 trial to determine whether intensifying or intensifying and increasing the total dose of cyclophosphamide in a doxorubicin-cyclophosphamide combination would benefit women with primary breast cancer and positive axillary nodes. B-25 was initiated to determine whether further intensifying and increasing the cyclophosphamide dose would yield more favorable results. PATIENTS AND METHODS: Patients (n = 2,548) were randomly assigned to three groups. The dose and intensity of doxorubicin were similar in all groups. Group 1 received four courses, ie, double the dose and intensity of cyclophosphamide given in the B-22 standard therapy group; group 2 received the same dose of cyclophosphamide as in group 1, administered in two courses (intensified); group 3 received double the dose of cyclophosphamide (intensified and increased) given in group 1. All patients received recombinant human granulocyte colony-stimulating factor. Life-table estimates were used to determine disease-free survival (DFS) and overall survival. RESULTS: No significant difference was observed in DFS (P = .20), distant DFS (P = .31), or survival (P = .76) among the three groups. At 5 years, the DFS in groups 1 and 2 (61% v 64%, respectively; P = .29) was similar to but slightly lower than that in group 3 (61% v 66%, respectively; P = 08). Survival in group 1 was concordant with that in groups 2 (78% v 77%, respectively; P = .71) and 3 (78% v 79%, respectively; P = .86). Grade 4 toxicity was 20%, 34%, and 49% in groups 1, 2, and 3, respectively. Severe infection and septic episodes increased in group 3. The decrease in the amount and intensity of cyclophosphamide and delays in therapy were greatest in courses 3 and 4 in group 3. The incidence of acute myeloid leukemia increased in all groups. CONCLUSION: Because intensifying and increasing cyclophosphamide two or four times that given in standard clinical practice did not substantively improve outcome, such therapy should be reserved for the clinical trial setting.
Micrometastases of Bone Marrow in Localized Prostate Cancer: Correlation With Established Risk Factors
Authors: Weckermann Dorothea , Müller Peter , Wawroschek Friedhelm , Krawczak Gunnar , Riethmüller Gert , Schlimok Günter 
Published: February 2017

PURPOSE: The presence of cytokeratin 18–positive cells in bone marrow correlates with conventional risk factors in many tumors. We examined whether this was also valid for localized or lymphatically spread prostate cancer. PATIENTS AND METHODS: Immediately before radical prostatectomy, bone marrow aspirates from both sides of the iliac crest were taken from 287 patients. The presence of cells containing cytokeratin 18 was interpreted as micrometastasis. RESULTS: In patients with negative lymph nodes (n = 219), conventional risk factors (Gleason score, pathologic stage, ploidy, and preoperative prostate-specific antigen) did not correlate with the preoperative detection of cells containing cytokeratin 18. There was also no correlation with lymph node metastases. Furthermore, there was no interdependency between the preoperatively detected number of cells and the established risk factors. CONCLUSION: We assume the presence of epithelial cells in bone marrow to be an independent parameter, the clinical importance of which must be substantiated by further studies.
Eligibility and Response Guidelines for Phase II Clinical Trials in Androgen-Independent Prostate Cancer: Recommendations From the Prostate-Specific Antigen Working Group
Authors: Bubley Glenn J. , Carducci Michael , Dahut William , Dawson Nancy , Daliani Danai , Eisenberger Mario , Figg William D. , Freidlin Boris , Halabi Susan , Hudes Gary , Hussain Maha , Kaplan Richard , Myers Charles , Oh William , Petrylak Daniel P. , Reed Eddie , Roth Bruce , Sartor Oliver , Scher Howard , Simons Jonathan , Sinibaldi Vickie , Small Eric J. , Smith Matthew R. , Trump Donald L. , Vollmer Robin , Wilding George 
Published: February 2017

PURPOSE: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. RESULT: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. CONCLUSION: Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point.
Neurocognitive Development of Children After a Cerebellar Tumor in Infancy: A Longitudinal Study
Authors: Copeland Donna R. , deMoor Carl , Moore III Bartlett D. , Ater Joann L. 
Published: February 2017

PURPOSE: To assess the long-term neuropsychologic effects experienced by children who have tumors in the cerebellum that are diagnosed and treated during infancy. PATIENTS AND METHODS: Twenty-seven children with posterior fossa tumors diagnosed at less than 36 months of age were assessed prospectively with a comprehensive set of age-appropriate tests. Group means and SDs are reported for assessments conducted at diagnosis (analysis 1) and at the most recent follow-up appointment (analysis 2). Cognitive developmental growth curves were derived from the prospective data (analysis 3) using mixed model regression analyses and controlling for age at diagnosis and socioeconomic status. RESULTS: In the first analysis, eight of 11 infants at diagnosis scored within normal limits on all neuropsychologic domains, except for motor skills, which were impaired. In the second analysis, mean scores at the most recent follow-up of 21 of 27 patients were mostly in the normal range; however, group comparisons between those who had (n = 7) and had not (n = 14) been treated with cranial radiation therapy (CRT) showed that patients in the irradiated (CRT) group scored significantly lower than those in the nonirradiated (No-CRT) group on verbal intelligence quotient (IQ) and in the motor domain. In the third analysis (growth curves of CRT and No-CRT groups), statistically significant differences in slope were found on verbal IQ, performance IQ, perceptual-motor skills, language, and attention/executive skills. Slopes on the fine-motor domain were similar; both groups declined at approximately the same rate. CONCLUSION: Neurocognitive development and outcome of children with cerebellar tumors diagnosed in infancy is very positive among those who were treated with surgery and chemotherapy. Declines in performance across time were minimal, and scores tended to remain within normal limits. By itself, a cerebellar tumor in infancy does not seem to have a significant impact on children. However, those who received CRT as part of their treatment are likely to have neurocognitive and psychosocial deficits that require remediational interventions.
Gemcitabine and Cisplatin Versus Mitomycin, Ifosfamide, and Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Randomized Phase III Study of the Italian Lung Cancer Project
Authors: Crinò L. , Scagliotti G. V. , Ricci S. , De Marinis F. , Rinaldi M. , Gridelli C. , Ceribelli A. , Bianco R. , Marangolo M. , Di Costanzo F. , Sassi M. , Barni S. , Ravaioli A. , Adamo V. , Portalone L. , Cruciani G. , Masotti A. , Ferrara G. , Gozzelino F. , Tonato M. 
Published: February 2017

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non–small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m2 on days 1, 8, and 15 plus cisplatin 100 mg/m2 on day 2, every 28 days, or mitomycin 6 mg/m2, ifosfamide 3,000 mg/m2, and mesna on day 1 plus cisplatin 100 mg/m2 on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P = .029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P = .877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P < .001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P < .001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.
Multiple Courses of High-Dose Ifosfamide, Carboplatin, and Etoposide With Peripheral-Blood Progenitor Cells and Filgrastim for Small-Cell Lung Cancer: A Feasibility Study by the European Group for Blood and Marrow Transplantation
Authors: Leyvraz S. , Perey L. , Rosti G. , Lange A. , Pampallona S. , Peters R. , Humblet Y. , Bosquée L. , Pasini F. , Marangolo M. 
Published: February 2017

PURPOSE: To determine the feasibility and safety of multiple sequential courses of high-dose chemotherapy and peripheral-blood progenitor cells (PBPCs) administered in a multicenter setting to patients with small-cell lung cancer. PATIENTS AND METHODS: Sixty-nine patients (limited disease, n = 30; extensive disease, n = 39) treated at 15 European centers were scheduled to receive three courses of high-dose chemotherapy with ifosfamide 10 g/m2, carboplatin 1200 mg/m2, and etoposide 1200 mg/m2 (ICE) divided over 4 days at 28-day intervals. PBPCs were harvested before treatment and mobilized with epirubicin 150 mg/m2 administered via an intravenous bolus divided over 2 days and filgrastim 5 μg/kg/d administered subcutaneously. RESULTS: The performed leukaphereses (one to five per patient) yielded a median of 16.6 × 106/kg (range, 1.0 to 96.6 × 106/kg) CD34+ cells, which was sufficient for three reinfusions. Fifty patients (72%) completed the treatment according to schedule. Nine patients completed two courses, and six patients completed one course of treatment. The increase in dose-intensity was 290% that of a standard ICE regimen. The median duration of myelosuppression was similar between courses, namely 4 days (range, 1 to 12 days) for leukocytes less than 0.5 × 109/L and 4 days (range, 0 to 22 days) for thrombocytes less than 20 × 109/L. Febrile neutropenia developed in 66% of courses, severe diarrhea in 14%, mucositis in 10%, and nausea and vomiting in 21% of courses. There were six cases of toxic death (9%), most of which occurred in the first year of accrual and thus were attributable to the learning curve. The antitumor effect of the regimen was reflected in an 86% remission rate (95% confidence interval [CI], 74% to 93%), with 51% of patients achieving a complete response (95% CI, 38% to 63%). Median overall survival was 18 months for patients with limited disease and 11 months for patients with extensive disease. CONCLUSION: This multiple sequential high-dose ICE regimen could be safely administered on a multicenter basis to patients with small-cell lung cancer. The dose-intensity could be increased to 290% that of standard ICE regimen. The benefit of this approach is currently being tested in a randomized trial that aims to double the long-term rate of survival for patients with small-cell lung cancer.