bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recommendations for Cancer Prevention Trials Using Potentially Ototoxic Test Agents
Authors: Shotland Lawrence I. , Ondrey Frank G. , Mayo Kristen A. , Viner Jaye L. 
Published: February 2017

PURPOSE: Preventive oncology applies pharmacologic agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy, a process that may require administration of agents over long periods of time. Although ototoxicity may be a tolerable side effect of anticancer or antimicrobial therapy, even modest ototoxicity may not be acceptable in agents developed for preventive oncology that are routinely administered to subjects who neither are, nor necessarily will become, clinically ill. MATERIALS AND METHODS: Age-related shifts in hearing may occur over the course of longterm or open-ended therapy; consequently, age-adjusted norms enable researchers to better distinguish hearing loss caused by drugs from that caused by aging. Norms for hearing sensitivity are derived from the Baltimore Longitudinal Study of Aging and are the basis for the proposed audiologic monitoring recommendations. RESULTS: Audiologic monitoring recommendations are presented that standardize patient selection, adverse event reporting, posttreatment follow-up, and audiologic testing for potentially ototoxic investigational agents. CONCLUSION: These recommendations are applicable to trials of investigational agents as well as various classes of drugs used in routine clinical care.
Decision Support for Patients With Early-Stage Breast Cancer: Effects of an Interactive Breast Cancer CDROM on Treatment Decision, Satisfaction, and Quality of Life
Authors: Molenaar Sjaak , Sprangers Mirjam AG , Rutgers Emiel J. Th. , Luiten Ernest JT , Mulder Jan , Bossuyt Patrick MM , van Everdingen Jannes JE , Oosterveld Paul , de Haes Hanneke CJM 
Published: February 2017

PURPOSE: To investigate the effects of the Interactive Breast Cancer CDROM as a decision aid for breast cancer patients with a choice between breast conserving therapy (BCT) and mastectomy (MT). PATIENTS AND METHODS: Consecutive patients with stage I and II breast cancer were enrolled. A quasi-experimental, longitudinal, and pretest/posttest design was used. Follow-up was scheduled 3 and 9 months after discharge from the hospital. Control patients (n = 88) received standard care (oral information and brochures). The CDROM was provided to patients in the experimental condition (n = 92) as a supplement to standard procedures. Outcome variables were treatment decision, satisfaction, and quality of life (QoL). RESULTS: No effect on treatment decision was found. CDROM patients expressed more general satisfaction with information at 3 and 9 months (95% confidence interval for the difference (d) between the means (d: 4.1 to 12.5 and 5.7 to 14.2 respectively). CDROM patients were also more satisfied with their treatment decision at 3 and at 9 months (d: 0.1 to 0.4; 0.2 to 0.5). Moreover, at 9 months, CDROM patients were more satisfied with breast cancer–specific information (d: 0.9 to 16.5), the decision-making process (d: 0.1 to 0.4), and communication (d: 0.2 to 11.0). At 3 and 9 months, a positive effect was found on general health (d: 0.2 to 14.5 and 0.3 to 15.0). Moreover, at 9 months, CDROM patients reported better physical functioning (d: 5.1 to 19.8), less pain (d: -17.9 to -4.5), and fewer arm symptoms (d: -14.1 to -0.5). CONCLUSION: The Interactive Breast Cancer CDROM improved decision making in patients with early-stage breast cancer with a choice between BCT and MT, as evaluated in terms of patients’ satisfaction and QoL.
Discussing Adjuvant Cancer Therapy
Authors: Leighl Natasha , Gattellari Melina , Butow Phyllis , Brown Richard , Tattersall Martin H.N. 
Published: February 2017

PURPOSE: To document the adequacy of patient information in oncology consultations concerning adjuvant therapy and explore predictors of physician communication patterns, treatment decisions, patient information recall, and satisfaction. PATIENTS AND METHODS: Retrospective analysis of audiotapes and verbatim transcripts of 101 initial adjuvant therapy consultations with medical and radiation oncologists was undertaken. Content analysis, data on communication patterns, treatment decisions, patient anxiety, satisfaction, and information recall were collected. Predictors of physician communication, treatment decisions, recall, and satisfaction with the consultation were identified. RESULTS: The majority of patients were well informed of their prognosis, benefits and risks of therapy, and alternative management options. Only half were asked about preferences for information or decision-making involvement. Predictors of information detail given include patient sex, age, occupation, and education. Radiation and medical oncologists express prognosis and treatment benefit using similar phrases. When offered the chance to delay decision-making, most patients do so (P < .01). Final treatment decisions appear to be influenced by the presentation of choice in treatment options by the oncologist and whether the treatment decision was made during the initial consultation (P < .01). Information recall was not influenced by communication factors. Patients receiving less detailed information had slightly higher satisfaction with the consultation (P = .03). More anxious patients tended to be less satisfied (P = .07). CONCLUSION: The optimal way to discuss adjuvant therapy is undefined. More emphasis can be placed on soliciting patient preferences for information and decision-making involvement and tailoring both to the needs of the individual patient. Providing choice in treatment and delaying decision-making may affect the patient’s treatment decision.
Circulating Neuroblastoma Cells Detected by Reverse Transcriptase Polymerase Chain Reaction for Tyrosine Hydroxylase mRNA Are an Independent Poor Prognostic Indicator in Stage 4 Neuroblastoma in Children Over 1 Year
Authors: Burchill Susan A. , Lewis Ian J. , Abrams Keith R. , Riley Richard , Imeson John , Pearson Andrew D.J. , Pinkerton Ross , Selby Peter 
Published: February 2017

PURPOSE: In this prospective, multicenter study, the independent prognostic power of neuroblastoma cells detected by reverse transcriptase polymerase chain reaction (RT-PCR) for tyrosine hydroxylase (TH) mRNA was evaluated. PATIENTS AND METHODS: The clinical significance of disease detected by RT-PCR in peripheral blood from children at diagnosis was compared with established prognostic markers [ie, age, lactate dehydrogenase (LDH), neuron-specific enolase, ferritin, and MYCN gene amplification] by multivariate analysis. The value of disease detection by RT-PCR during treatment and follow-up was also examined. RESULTS: TH mRNA was detected in peripheral blood from 33 of 49 (67%) children with stage 4 neuroblastoma > 1 year old at diagnosis and was a significant predictive factor for overall survival [hazard ratio (HR) = 2.40, 95% confidence interval (CI) 1.19 to 4.84, P = .014) and event-free survival (HR = 2.09, 95% CI 1.06 to 4.17, P = .034) in a multivariate analysis. Detection of disease in blood from clinically disease-free children was related to increased risk of death (HR 2.54, 95% CI 1.42 to 4.55, P = .0014). CONCLUSION: TH mRNA in peripheral blood of children with neuroblastoma is a poor prognostic indictor, reflecting the propensity for dissemination via the bloodstream. When combined with a serum LDH > 1500 IU/L, this is the most powerful poor prognostic model at diagnosis for children > 1 year old with stage 4 disease. The detection of TH mRNA in peripheral blood from clinically disease-free children is related to increased risk of relapse and death.
Immediate Neurocognitive Effects of Methylphenidate on Learning-Impaired Survivors of Childhood Cancer
Authors: Thompson Stephen J. , Leigh Laurie , Christensen Robbin , Xiong Xiaoping , Kun Larry E. , Heideman Richard L. , Reddick W. Eugene , Gajjar Amar , Merchant Thomas , Pui Ching-Hon , Hudson Melissa M. , Mulhern Raymond K. 
Published: February 2017

PURPOSE: To test if methylphenidate (MPH) has an objective beneficial effect on immediate performance on tests of neurocognitive functions among learning-impaired survivors of childhood acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT). PATIENTS AND METHODS: From July 1, 1997 through December 31, 1998, 104 long-term survivors of childhood ALL or a malignant BT completed neurocognitive screening for learning impairments and concurrent problems with sustained attention. Eligibility criteria for the MPH trial included an estimated intelligence quotient greater than 50, academic achievement in the 16th percentile or lower for age in reading, math, or spelling, and an ability to sustain attention on a computerized version of the Conners’ Continuous Performance Test (CPT) in the 16th percentile or lower for age and sex. Of the 104, 32 (BT, n = 25; ALL, n = 7) were eligible on the basis of these a priori criteria for a randomized, double-blinded, placebo-controlled trial of MPH. The patients ingested a placebo (lactose) or MPH (0.6 mg/kg; 20 mg maximum) and repeated selected portions of the screening battery 90 minutes later. RESULTS: Compared to the 17 patients randomized to the placebo group, the 15 patients randomized to the MPH group had a significantly greater improvement on the CPT for sustained attention (errors of omission, P = .015) and overall index (P = .008) but not for errors of commission (indicative of impulsiveness) nor reaction times. A trend for greater improvement in the MPH group on a measure of verbal memory failed to reach statistical significance. No trend was observed for MPH effectiveness in improving learning of a word association task. No significant side effects from MPH were observed. CONCLUSION: MPH resulted in a statistically significant improvement on measures of attention abilities that cannot be explained by placebo or practice effects.
Phase I Trial of Oral Green Tea Extract in Adult Patients With Solid Tumors
Authors: Pisters Katherine M.W. , Newman Robert A. , Coldman Brenda , Shin Dong M. , Khuri Fadlo R. , Hong Waun Ki , Glisson Bonnie S. , Lee Jin S. 
Published: February 2017

PURPOSE: This trial was designed to determine the maximum-tolerated dose, toxicity, and pharmacology of oral green tea extract (GTE) once daily or three times daily. PATIENTS AND METHODS: Cohorts of three or more adult cancer patients were administered oral GTE with water after meals one or three times daily for 4 weeks, to a maximum of 6 months, depending on disease response and patient tolerance. Pharmacokinetic analyses were encouraged but optional. RESULTS: Dose levels of 0.5 to 5.05 g/m2 qd and 1.0 to 2.2 g/m2 tid were explored. A total of 49 patients were studied. Patient characteristics: median age, 57 years (range, 27 to 77 years); 23 patients were women (47%); 98% had a Zubrod PS of 1%; 98% had PS of 1; and 21 had non–small-cell lung, 19 had head & neck cancer, three had mesothelioma, and six had other. Mild to moderate toxicities were seen at most dose levels and promptly reversed on discontinuation of GTE. Dose-limiting toxicities were caffeine related and included neurologic and gastrointestinal effects. The maximum-tolerated dose was 4.2 g/m2 once daily or 1.0 g/m2 three times daily. No major responses occurred; 10 patients with stable disease completed 6 months of GTE. Pharmacokinetic analyses found accumulation of caffeine levels that were dose dependent, whereas epigallocatechin gallate levels did not accumulate nor appear dose related. CONCLUSION: A dose of 1.0 g/m2 tid (equivalent to 7 to 8 Japanese cups [120 mL] of green tea three times daily) is recommended for future studies. The side effects of this preparation of GTE were caffeine related. Oral GTE at the doses studied can be taken safely for at least 6 months.
No Downstaging After Short-Term Preoperative Radiotherapy in Rectal Cancer Patients
Authors: Marijnen C.A.M. , Nagtegaal I.D. , Kranenbarg E. Klein , Hermans J. , van de Velde C.J.H. , Leer J.W.H. , van Krieken J.H.J.M. ,   for the Pathology Review Committee and the Cooperative Clinical Investigators
Published: February 2017

PURPOSE: In retrospective studies, total mesorectal excision (TME) surgery has been demonstrated to result in a reduction in the number of local recurrences of rectal cancer. Reports on improved local control after preoperative, hypofractionated radiotherapy have led to the introduction of a randomized multicenter trial to evaluate the effect of TME surgery with and without preoperative radiotherapy. Treatment with preoperative radiotherapy might have an effect on the pathologic characteristics that determine staging of rectal cancer. We investigated the occurrence of downstaging in rectal cancer patients treated with and without preoperative radiotherapy.PATIENTS AND METHODS: We analyzed the differences in tumor size, number of examined lymph nodes, tumor-node-metastasis stage, and histopathologic features in 1,321 patients entered onto a randomized trial. The trial compared preoperative radiotherapy (5 × 5 Gy) followed by TME surgery with TME surgery alone. Patients who had an interval of more than 10 days between the start of radiotherapy and surgery were excluded from analysis.RESULTS: Differences were observed in tumor size (P < .001) and total number of examined lymph nodes (P < .001). No difference in tumor or node classification was detected. The irradiated group demonstrated more poorly differentiated tumors as well as more mucinous tumors.CONCLUSION: In rectal cancer patients, short-term, preoperative radiotherapy with 5 × 5 Gy does not lead to downstaging if the interval between the start of radiotherapy and surgery does not exceed 10 days.
Phase II Study of the Cyclin-Dependent Kinase Inhibitor Flavopiridol Administered to Patients With Advanced Gastric Carcinoma
Authors: Schwartz Gary K. , Ilson David , Saltz Leonard , O’Reilly Eileen , Tong William , Maslak Peter , Werner Jeanine , Perkins Pam , Stoltz Maxine , Kelsen David 
Published: February 2017

PURPOSE: Flavopiridol is the first cyclin-dependent kinase inhibitor to enter clinical trials. Activity in gastric cancer xenografts and in a patient with gastric cancer on the phase I trial led to this phase II study of flavopiridol in patients with metastatic gastric cancer. PATIENTS AND METHODS: Sixteen patients were entered onto the study, and 14 were assessable for response. Flavopiridol was administered initially at a dose of 50 mg/m2/d by continuous infusion for 72 hours every 2 weeks. Assessment of plasma pharmacokinetics was performed in all patients. Peripheral mononuclear cells were collected throughout the 72-hour infusion for determinants of apoptosis. RESULTS: There were no major objective responses (exact confidence interval 0% to 23%). One patient achieved a minor response in his liver metastases, though the primary progressed. Other patients exhibited histologic and radiographic evidence of tumor necrosis. Common toxicities included fatigue in 93% of patients (grade 3 or 4 in 27%) and diarrhea in 73% of patients (grade 3 or 4 in 20%). Five patients (33%) developed venous thromboses at the central catheter tip. The studies performed on peripheral mononuclear cells indicated no induction of apoptosis. CONCLUSION: Flavopiridol administered as a single agent for 72 hours every 14 days is inactive in the treatment of gastric cancer. The drug also induced an unexpected higher incidence of vascular thrombosis and fatigue than was anticipated from the phase I trials. Future development of flavopiridolwill depend on other doses and schedules in combination with chemotherapy.
Self-Reported Quality of Life of Individual Cancer Patients: Concordance of Results With Disease Course and Medical Records
Authors: Velikova Galina , Wright Penny , Smith Adam B. , Stark Daniel , Perren Timothy , Brown Julia , Selby Peter 
Published: February 2017

PURPOSE: To investigate the applicability of a standard quality of life (QL) questionnaire to individual cancer patients and to explore the potential for impact of QL information on the process of care by comparing at group level the QL results with the medical records. PATIENTS AND METHODS: One hundred fourteen consecutive patients at the oncology clinics at St James’s Hospital, Leeds, United Kingdom, completed the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 on a touch-screen computer over a 6-month period. The QL results were compared with the corresponding medical records at individual and group level. RESULTS: For individual patients, the serial measurement of QL allowed recognition of patterns over time corresponding to disease course. At group level, a higher proportion of patients reported problems on EORTC QLQ-C30 than were mentioned in the medical records (McNemar paired test, P < .01). Most often clinicians mentioned pain (22% to 39%), and at the initial visit role (66%), and social issues (77%). For the rest of the symptoms and functions, the problems were recorded in between 1% and 25% of the notes, but 20% to 76% of the patients reported QL impairment. Problems that were not recorded in the medical notes tended to be of low severity, with a significant trend observed for pain, fatigue, nausea/vomiting, dyspnea, loss of appetite, and physical function scale (χ2 test, 11.55 to 34.42, df = 1, P < .001). CONCLUSION: The QL data on individual patients was consistent with the clinical records, thus providing evidence for the validity of these measures in assessment of the individual. The QL profiles had more information on symptoms and particularly on functional issues, such as emotional distress and physical performance.
Natural Killer/Natural Killer-Like T-Cell Lymphoma, CD56+, Presenting in the Skin: An Increasingly Recognized Entity With an Aggressive Course
Authors: Mraz-Gernhard Serena , Natkunam Yasodha , Hoppe Richard T. , LeBoit Philip , Kohler Sabine , Kim Youn H. 
Published: February 2017

PURPOSE: To describe and identify the clinical and pathologic features of prognostic significance for natural killer (NK) and NK-like T-cell (NK/T-cell) lymphoma presenting in the skin.PATIENTS AND METHODS: This study was a retrospective review of 30 patients with CD56+ lymphomas initially presenting with cutaneous lesions, with analysis of clinical and histopathologic parameters.RESULTS: The median survival for all patients was 15 months. Those with extracutaneous manifestations at presentation (11 patients) had a shorter median survival of 7.6 months as compared with those without extracutaneous involvement (17 patients), who had a more favorable median survival of 44.9 months (P = .0001). Age, gender, extent of cutaneous involvement, and initial response to therapy had no statistically significant effect on survival. Seven patients (24%) had detectable Epstein-Barr virus (EBV) within neoplastic cells. The patients with tumor cells that coexpress CD30 (seven patients) have not yet reached a median survival after 35 months of follow-up as compared with those with CD30− tumor cells (20 patients), who had a median survival of 9.6 months (P < .02). Routine histopathologic characteristics had no prognostic significance nor did the presence of CD3ε, EBV, or multidrug resistance.CONCLUSION: NK/T-cell lymphoma is an aggressive neoplasm; however, a subset with a more favorable outcome is identified in this study. The presence of extracutaneous disease at presentation is the most important clinical variable and portends a poor prognosis. The extent of initial skin involvement does not reliably predict outcome. Patients from the United States with NK/T-cell lymphoma presenting in the skin have a low incidence of demonstrable EBV in their tumor cells. Patients with coexpression of CD30 in CD56 lymphomas tend to have a more favorable outcome.
Oral Mucositis and the Clinical and Economic Outcomes of Hematopoietic Stem-Cell Transplantation
Authors: Sonis Stephen T. , Oster Gerry , Fuchs Hank , Bellm Lisa , Bradford Williamson Z. , Edelsberg John , Hayden Vanessa , Eilers June , Epstein Joel B. , LeVeque Francis G. , Miller Carole , Peterson Douglas E. , Schubert Mark M. , Spijkervet Frederik K.L. , Horowitz Mary 
Published: February 2017

PURPOSE: To explore the relationship between oral mucositis and selected clinical and economic outcomes in blood and marrow transplant patients. PATIENTS AND METHODS: Subjects consisted of 92 transplant patients from eight centers who participated in a multinational pilot study of a new oral mucositis scoring system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients were evaluated for erythema and ulceration/pseudomembrane formation beginning on the first day of conditioning and continuing for 28 days. We examined the relationship between patients’ peak OMAS scores and days with fever (body temperature > 38.0°C), the occurrence of significant infection, days of total parenteral nutrition (TPN), and days of injectable narcotic therapy (all over 28 days), days in hospital (over 60 days), total hospital charges for the index admission, and vital status at 100 days. RESULTS: Patients’ peak OMAS scores spanned the full range of possible values (0 to 5) and were significantly (P < .05) correlated with all of the outcomes of interest except days with fever (P = .21). In analyses controlling for type of graft (autologous v allogeneic) and study center, a 1-point increase in peak OMAS score was associated with (1) 1.0 additional day with fever (P < .01), (2) a 2.1-fold increase in risk of significant infection (P < .01), (3) 2.7 additional days of TPN (P < .0001), (4) 2.6 additional days of injectable narcotic therapy (P < .0001), (5) 2.6 additional days in hospital (P < .01), (6) $25,405 in additional hospital charges (P < .0001), and (7) a 3.9-fold increase in 100-day mortality risk (P < .01). Mean hospital charges were $42,749 higher among patients with evidence of ulceration compared with those without (P = .06). CONCLUSION: Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.
Clinical and Pharmacologic Study of the Epirubicin and Paclitaxel Combination in Women With Metastatic Breast Cancer
Authors: Grasselli Giacomo , Viganò Lucia , Capri Giuseppe , Locatelli Alberta , Tarenzi Emiliana , Spreafico Carlo , Bertuzzi Alexia , Giani Antonio , Materazzo Carlo , Cresta Sara , Perotti Antonella , Valagussa P. , Gianni Luca 
Published: February 2017

PURPOSE: A pharmacokinetic interaction may cause increased cardiotoxicity of paclitaxel (PTX) and high cumulative dose of doxorubicin. We tested antitumor activity, tolerability, and pharmacokinetics of the lesser cardiotoxic epirubicin (EPI) and PTX (ET combination). PATIENTS AND METHODS: Twenty-seven women with untreated metastatic breast cancer, median age of 56 years, and prominent visceral involvement (74%) were studied. Three-weekly EPI (90 mg/m2) and PTX (200 mg/m2 over 3 hours) were given for a maximum nine cycles. EPI was administered 24 hours before PTX (E → T) in cycle 1, and 15 minutes before PTX (ET) thereafter. EPI, epirubicinol (EOL), EPI-glucuronide (EPI-glu), EOL-glucuronide (EOL-glu), PTX, and 6α-OH-PTX were measured in plasma and urine in 14 women. RESULTS: Patients received 205 cycles of ET and a median EPI dose of 720 mg/m2. Grade 4 neutropenia (49% of cycles) was the most frequent toxicity. Cardiac contractility was decreased in five patients. Mild congestive heart failure occurred in two (7.4%). Response rate was 76% (28% complete). Median overall survival was 29 months. On the basis of intrapatient comparison in the first 24 hours of E → T and ET cycles, PTX did not affect EPI disposition, but significantly increased plasma exposure to EOL (by 137%), EPI-glu (threefold) and EOL-glu (twofold). Urinary excretion of EPI dose went from 8.2% in E → T to 11.8% in ET cycles. Clearance of PTX was 30% slower in ET than E → T. ET cycles caused lower neutrophil nadir than E → T (644 ± 327 v 195 ± 91, P < .05) CONCLUSION: ET is feasible, devoid of excessive cardiac toxicity, and active. A reciprocal pharmacokinetic interference between the two drugs has pharmacodynamic consequences, and suggests a direct effect of PTX on EPI metabolism requiring ad hoc investigation.