bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Simple Stratification Factor Prognostic for Survival in Advanced Cancer: The Good/Bad/Uncertain Index
Authors: Sloan Jeff A. , Loprinzi Charles L. , Laurine John A. , Novotny Paul J. , Vargas-Chanes Delfino , Krook James E. , O’Connell Michael J. , Kugler John W. , Tirona Maria Tria , Kardinal Carl G. , Wiesenfeld Martin , Tschetter Loren K. , Hatfield Alan K. , Schaefer Paul L. 
Published: February 2017

PURPOSE: This article summarizes the third step of a research program to identify variables that supplement the predictive power of the the Eastern Cooperative Oncology Group (ECOG) performance status (PS) for survival. The objective was to produce a simple, practical, stratification factor for phase III oncology clinical trials involving patients with advanced malignant disease. PATIENTS AND METHODS: A questionnaire was administered to 729 patients with metastatic colorectal or lung cancers. Patients provided a Karnofsky index and appetite rating while physicians provided a survival estimate and the ECOG-PS. Scores for each item were categorized as having a positive, neutral, or negative indication for survival. A patient was classified as having a relatively good prognosis if three or more of the four items showed a positive indication, a bad prognosis if three or more items were negative, and an uncertain prognosis otherwise (Good/Bad/Uncertain [GBU] index). RESULTS: The GBU index improved on the prognostic power of a Cox model quartile index and PS alone and increased the accuracy of survival classification estimates by 5% to 10% more than ECOG-PS alone. For patients with PS of 0 or 1, significant survival patterns exist between GBU groups (P= .002 and .0001, respectively). CONCLUSION: The GBU index may be recommended as a supplementary stratification factor for certain future phase III trials in metastatic lung or colorectal cancer where patient heterogeneity is a particular concern. The GBU represents a relatively modest increase to the cost and patient burden of a clinical trial given the additional control that is achieved over the potentially confounding concomitant to the treatment variable.
Randomized Clinical Trials in Oncology: Understanding and Attitudes Predict Willingness to Participate
Authors: Ellis Peter M. , Butow Phyllis N. , Tattersall Martin H.N. , Dunn Stewart M. , Houssami Nehmat 
Published: February 2017

PURPOSE: To explore the association at different time points in the trajectory of breast cancer care, between anxiety, knowledge, and attitudes, on women’s willingness to participate in randomized clinical trials. MATERIALS AND METHODS: A cross-sectional survey was undertaken among women attending a breast clinic for screening mammography or diagnostic assessment plus women with newly diagnosed breast cancer to assess attitudes toward and willingness to participate in randomized clinical trials of breast cancer treatment. RESULTS: Five hundred forty-five women completed questionnaires assessing knowledge of and attitudes toward randomized clinical trials. The mean age of respondents was 48.9 years (SD, 11.3 years). Thirty-three percent of women would consider participating in a clinical trial if they had breast cancer. Women with breast cancer (31%) were significantly more likely to decline to participate than women attending for screening mammography (15%) or diagnostic assessment (15%, P = .0002). Women who might consider participating in a randomized clinical trial were more knowledgeable about randomized trials (mean difference, 0.7; 95% confidence interval [CI], 0.2 to 1.2; P = .003). In a multivariate analysis, women who would consider participating in a randomized trial were younger (odds ratio [OR], 0.96; 95% CI, 0.93 to 0.99), more likely to want an active role in decision-making (OR, 3.2; 95% CI, 1.3 to 7.6), and reported a greater impact from the positive aspects of clinical trials (OR, 2.2; 95% CI, 1.3 to 3.8) and less impact from the negative aspects of clinical trials (OR, 2.2; 95% CI, 1.3 to 3.2). CONCLUSION: These findings suggest that women who have a better understanding of issues about clinical trials have more favorable attitudes toward randomized trials and are more willing to consider participation in a clinical trial.
Acute and Chronic Graft-Versus-Host Disease After Allogeneic Peripheral-Blood Stem-Cell and Bone Marrow Transplantation: A Meta-Analysis
Authors: Cutler Corey , Giri Satyendra , Jeyapalan Suriya , Paniagua David , Viswanathan Akila , Antin Joseph H. 
Published: February 2017

PURPOSE: Controversy exists as to whether the incidence of graft-versus-host disease (GVHD) is increased after peripheral-blood stem-cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta-analysis of all trials comparing the incidence of acute and chronic GVHD after PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse rates after the two procedures. METHODS: An extensive MEDLINE search of the literature was undertaken. Primary authors were contacted for clarification and completion of missing information. A review of cited references was also undertaken. Sixteen studies (five randomized controlled trials and 11 cohort studies) were included in this analysis. Data was extracted by two pairs of reviewers and analyzed for the outcomes of interest. Meta-analyses, regression analyses, and assessments of publication bias were performed. RESULTS: Using a random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P= .006) when compared with traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI, 1.25 to 1.88; P < .001) when compared with BMT. The RR of developing clinically extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P < .001). The excess risk of chronic GVHD was explained by differences in the T-cell dose delivered with the graft in a meta-regression model that did not reach statistical significance. There was a trend towards a decrease in the rate of relapse after PBSCT (RR = 0.81; 95% CI, 0.62 to 1.05). CONCLUSION: Both acute and chronic GVHD are more common after PBSCT than BMT, and this may be associated with lower rates of malignant relapse. The magnitude of the transfused T-cell load may explain the differences in chronic GVHD risk.
Body-Surface Area–Based Dosing Does Not Increase Accuracy of Predicting Cisplatin Exposure
Authors: de Jongh Felix E. , Verweij Jaap , Loos Walter J. , de Wit Ronald , de Jonge Maja J.A. , Planting André S.T. , Nooter Kees , Stoter Gerrit , Sparreboom Alex 
Published: February 2017

PURPOSE: Most anticancer drugs are dosed based on body-surface area (BSA) to reduce interindividual variability of drug effects. We evaluated the relevance of this concept for cisplatin by analyzing cisplatin pharmacokinetics obtained in prospective studies in a large patient population. PATIENTS AND METHODS: Data were obtained from 268 adult patients (163 males/105 females; median age, 54 years [range, 21 to 74 years]) with advanced solid tumors treated in phase I/II trials with cisplatin monotherapy or combination chemotherapy with etoposide, irinotecan, topotecan, or docetaxel. Cisplatin was administered either weekly (n = 93) or once every 3 weeks (n = 175) at dose levels of 50 to 100 mg/m2 (3-hour infusion). Analysis of 485 complete courses was based on measurement of total and non–protein-bound cisplatin in plasma by atomic absorption spectrometry. RESULTS: No pharmacokinetic interaction was found between cisplatin and the anticancer drugs used in combination therapies. A linear correlation was observed between area under the curves of unbound and total cisplatin (r = 0.63). The mean plasma clearance of unbound cisplatin (CLfree) was 57.1 ± 14.7 L/h (range, 31.0 to 116 L/h), with an interpatient variability of 25.6%. BSA varied between 1.43 and 2.40 m2 (mean, 1.86 ± 0.19 m2), with an interpatient variability of 10.4%. When CLfree was corrected for BSA, interindividual variability remained in the same order (23.6 v 25.6%). Only a weak correlation was found between CLfree and BSA (r = 0.42). Intrapatient variability in CLfree, calculated from 90 patients was 12.1% ± 7.8% (range, 0.30% to 32.7%). CONCLUSION: In view of the high interpatient variability in CLfree relative to variation in observed BSA, no rationale for continuing BSA-based dosing was found. We recommend fixed-dosing regimens for cisplatin.
Primary Chemotherapy for Operable Breast Cancer: Incidence and Prognostic Significance of Ipsilateral Breast Tumor Recurrence After Breast-Conserving Surgery
Authors: Rouzier Roman , Extra Jean-Marc , Carton Mathieu , Falcou Marie-Christine , Vincent-Salomon Anne , Fourquet Alain , Pouillart Pierre , Bourstyn Edwige 
Published: February 2017

PURPOSE: To determine the incidence and the prognostic value of ipsilateral breast tumor recurrence (IBTR) in patients treated with primary chemotherapy and breast-conserving surgery. PATIENTS AND METHODS: Between January 1985 and December 1994, 257 patients with invasive T1 to T3 breast carcinoma were treated with primary chemotherapy, lumpectomy, and radiation therapy. The median follow-up time was 93 months. To evaluate the role of IBTR in metastase-free survival, a Cox regression multivariate analysis was performed using IBTR as a time-dependent covariate. RESULTS: The IBTR rates were 16% (± 2.4%) at 5 years and 21.5% (± 3.2%) at 10 years. Multivariate analysis showed that the probability of local control was decreased by the following independent factors: age ≤ 40 years, excision margin ≤ 2 mm, S-phase fraction more than 4%, and clinical tumor size more than 2 cm at the time of surgery. In patients with excision margins of more than 2 mm, the IBTR rates were 12.7% at 5 years and 17% at 10 years. Nodal status, age ≤ 40 years, and negative estrogen receptor status were predictors of distant disease in the Cox multivariate model with fixed covariates. The contribution of IBTR was highly significant (relative risk = 5.34) when added to the model, whereas age ≤ 40 years was no longer significant. After IBTR, 31.4% (± 7.0%) of patients developed metastases at 2 years and 59.7% (± 8.1%) at 5 years. Skin involvement, size at initial surgery, and estrogen receptor status were predictors of metastases after IBTR. CONCLUSION: IBTR is a strong predictor for distant metastases. There are implications for conservative surgery after downstaging of the tumor and therapy at the time of IBTR.
United States Multicenter Study of Arsenic Trioxide in Relapsed Acute Promyelocytic Leukemia
Authors: Soignet Steven L. , Frankel Stanley R. , Douer Dan , Tallman Martin S. , Kantarjian Hagop , Calleja Elizabeth , Stone Richard M. , Kalaycio Matt , Scheinberg David A. , Steinherz Peter , Sievers Eric L. , Coutré Steven , Dahlberg Steve , Ellison Ralph , Warrell Raymond P. 
Published: February 2017

PURPOSE: To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Forty patients experiencing first (n = 21) or ≥ second (n = 19) relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study. RESULTS: Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/μL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes. CONCLUSION: This study establishes ATO as a highly effective therapy for patients with relapsed APL.
Primary Gastrointestinal Non-Hodgkin’s Lymphoma: II. Combined Surgical and Conservative or Conservative Management Only in Localized Gastric Lymphoma—Results of the Prospective German Multicenter Study GIT NHL 01/92
Authors: Koch Peter , del Valle Francisco , Berdel Wolfgang E. , Willich Normann A. , Reers Berthold , Hiddemann Wolfgang , Grothaus-Pinke Bernward , Reinartz Gabriele , Brockmann Jens , Temmesfeld Altfried , Schmitz Rudolf , Rübe Christian , Probst Andreas , Jaenke Gert , Bodenstein Heinrich , Junker Arved , Pott Christiane , Schultze Jürgen , Heinecke Achim , Parwaresch Reza , Tiemann Markus ,   for the German Multicenter Study Group
Published: February 2017

PURPOSE: The aim of the study was to obtain data on anatomic and histologic distribution, clinical features, and treatment results of patients with primary gastrointestinal non-Hodgkin’s lymphomas, particularly combined surgical and conservative treatment (CSCT) versus conservative treatment (CT) alone for primary gastric lymphoma (PGL) in localized stages. PATIENTS AND METHODS: Whether the treatment included surgery was left to the discretion of each participating center. Radiotherapy (Rx) and chemotherapy were stratified according to histologic grading, stage, and the inclusion or omission of surgery as follows: patients with low-grade PGL were treated with extended-field (EF) Rx (30 Gy). In case of residual tumor after surgery or in case of CT only (in stage IIE after six cycles of cyclophosphamide, vincristine, and prednisone), an additional boost of 10 Gy was given. All patients with high-grade PGL were treated with four (stage IE) or six (stage IIE) cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by EF Rx (stage IE) or involved-field (IF) Rx (stage IIE). Rx dosage corresponded to low-grade NHL. RESULTS: Between October 1992 and November 1996, 106 patients had CT only. The survival rate (SR) after 5 years was 84.4% and was influenced neither by patients’ characteristics nor by stage or histologic grade. Seventy-nine patients had CSCT. Their SR was 82.0%. Complete resection of the tumor (R0) was prognostic for the overall survival (P = .0165) as compared with incomplete resection. CONCLUSION: Although the study was not randomized, a stomach-conserving approach may be favored.
Quality of Life in Palliative Cancer Care: Results From a Cluster Randomized Trial
Authors: Jordhøy Marit S. , Fayers Peter , Loge Jon Håvard , Ahlner-Elmqvist Marianne , Kaasa Stein 
Published: February 2017

PURPOSE: To assess the impact of comprehensive palliative care on patients’ quality of life. The intervention was based on cooperation between a palliative medicine unit and the community service and was compared with conventional care. PATIENTS AND METHODS: A cluster randomized trial was carried out, with community health care districts defined as the clusters. Patients from these districts who had malignant disease and survival expectancy between 2 to 9 months were entered onto the trial. The main quality-of-life end points were physical and emotional functioning, pain, and psychologic distress assessed monthly by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire and Impact of Event scale (IES). In total, 235 intervention patients and 199 controls were included. RESULTS: During the initial 4 months of follow-up, the compliance was good (72%) and comparable among treatment groups. No significant differences on any of the quality-of-life scores were found. At later assessments and for scores that were made within 3 months before death, there was also no consistent tendency in favor of any treatment group on the main outcomes or other EORTC QLQ-C30 scales/items. CONCLUSION: A general program of palliative care may be important to ensure flexibility and to meet the needs of terminally ill patients. However, to achieve improvements on a group level of the various dimensions of quality of life, specific interventions directed toward specific symptoms or problems may have to be defined, evaluated, and included in the program.
Efficacy of Contralateral Prophylactic Mastectomy in Women With a Personal and Family History of Breast Cancer
Authors: McDonnell Shannon K. , Schaid Daniel J. , Myers Jeffrey L. , Grant Clive S. , Donohue John H. , Woods John E. , Frost Marlene H. , Johnson Joanne L. , Sitta Diana L. , Slezak Jeffrey M. , Crotty Thomas B. , Jenkins Robert B. , Sellers Thomas A. , Hartmann Lynn C. 
Published: February 2017

PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.
Molecular Screening for Hereditary Nonpolyposis Colorectal Cancer: A Prospective, Population-Based Study
Authors: Percesepe Antonio , Borghi Francesca , Menigatti Mirco , Losi Lorena , Foroni Moira , Di Gregorio Carmela , Rossi Giuseppina , Pedroni Monica , Sala Elisa , Vaccina Fabiana , Roncucci Luca , Benatti Piero , Viel Alessandra , Genuardi Maurizio , Marra Giancarlo , Kristo Paula , Peltomäki Paivi , Ponz de Leon Maurizio 
Published: February 2017

PURPOSE: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. PATIENTS AND METHODS: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. RESULTS: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P < .01), high mucinous component (P < .01), and poor differentiation (P = .002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. CONCLUSION: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.
K-ras and p16 Aberrations Confer Poor Prognosis in Human Colorectal Cancer
Authors: Esteller M. , González S. , Risques R. A. , Marcuello E. , Mangues R. , Germà J. R. , Herman J. G. , Capellà G. , Peinado M. A. 
Published: February 2017

PURPOSE: Mutations in the K-ras gene are frequent in human cancer. ras activation in primary cells results in a cellular senescence phenotype that is precluded by inactivation of p16. At the clinical level, this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways. PATIENTS AND METHODS: We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospectively collected colorectal carcinomas. p53 mutations and p14 alternative reading frame methylation status were also assessed. Associations with survival were investigated. RESULTS: K-ras mutations were present in 44 (38%) of 115 cases, and p16 methylation was present in 42 (37%) of 113 cases. p53 mutations were detected in 50% (56 of 115) and p14 methylation in 29% (32 of 112) of cases. K-ras and p16 alterations were independent genetic events. Presence of K-ras or p16 genetic alterations (analyzed independently) was associated with shorter survival, although differences were not statistically significant. Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras. Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis. Differences were maintained when cases undergoing radical surgery and without distant metastases were considered. CONCLUSION: These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer.