bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of the Synthetic Retinoid Fenretinide: Long-Term Results From a Controlled Clinical Trial for the Prevention of Contralateral Breast Cancer
Authors: Camerini Tiziana , Mariani Luigi , De Palo Giuseppe , Marubini Ettore , Di Mauro Maria Gaetana , Decensi Andrea , Costa Alberto , Veronesi Umberto 
Published: February 2017

PURPOSE: To describe the pattern of occurrence of adverse events commonly arising during treatment with fenretinide, a synthetic retinoid under investigation for cancer prevention. PATIENTS AND METHODS: The series includes 2,867 women accrued in a trial aimed at assessing the effect of fenretinide on the prevention of second breast malignancy. Women were randomly assigned to receive no treatment (1,435 patients) or 5-year fenretinide treatment (1,432 patients). In terms of disease recurrence in the breast, the trial showed a possible beneficial effect of the compound in premenopausal women, and an opposite trend in postmenopausal women. End points considered for safety assessment were the occurrence of diminished dark adaptation, dermatologic disorders, gastrointestinal symptoms, disorders of the ocular surface, and abnormal laboratory values. RESULTS: The most common adverse events were diminished dark adaptation (cumulative incidence, 19.0%) and dermatologic disorders (18.6%). Less common events were gastrointestinal symptoms (13.0%) and disorders of the ocular surface (10.9%). In comparison, incidence figures in the control arm were 2.9% for diminished dark adaptation, 2.9% for dermatologic disorders, 5.4% for gastrointestinal symptoms, and 3.2% for disorders of the ocular surface. Symptoms occurring during fenretinide treatment tended to recover with time. No between-group difference was observed for the occurrence of laboratory data abnormalities. Overall, 63 (4.4%) treatment discontinuations were caused by adverse events. CONCLUSION: Given the number of patients involved in the study and the prolonged intake of the drug, the experience on fenretinide tolerability can be considered sufficiently reassuring to justify further testing of the retinoid.
Reliability and Validity of the Functional Assessment of Cancer Therapy–Ovarian
Authors: Basen-Engquist Karen , Bodurka-Bevers Diane , Fitzgerald Mary A. , Webster Kimberly , Cella David , Hu Shaohua , Gershenson David M. 
Published: February 2017

PURPOSE: To report the reliability and validity of the Functional Assessment of Cancer Therapy–Ovarian (FACT-O) in a consecutive series of outpatients with epithelial ovarian cancer. PATIENTS AND METHODS: Two hundred thirty-two ovarian cancer patients attending an outpatient gynecologic oncology clinic completed questionnaires at baseline. The patients’ FACT-O scores were compared with their performance status, disease stage, treatment status, and other factors hypothesized to be related to quality of life. Patients received a second questionnaire either one week after baseline to assess the instrument’s test-retest reliability and/or two months after baseline to evaluate its sensitivity to change in performance status. RESULTS: Internal consistency and test-retest reliability of the FACT-O were adequate. Overall, the scales correlated with other measures as expected; all correlations were in the hypothesized direction. Patients with advanced disease, poor performance status, and who were receiving active treatment had lower scores on physical, functional, and ovarian cancer-specific scales. The total FACT-O and emotional well-being scores were lower for patients with poor performance status and patients in active treatment. The FACT-O total and all subscale scores except emotional well-being were sensitive to decreases in performance status. CONCLUSION: Overall, the FACT-O provides a reliable and valid assessment of the quality of life of women with ovarian cancer, and is appropriate as a brief quality of life assessment in clinical trials and descriptive studies.
Tamoxifen for the Prevention of Breast Cancer: Psychosocial Impact on Women Participating in Two Randomized Controlled Trials
Authors: Fallowfield Lesley , Fleissig Anne , Edwards Rob , West Andrea , Powles Trevor J. , Howell Anthony , Cuzick Jack 
Published: February 2017

PURPOSE: The purpose of this study was to evaluate the psychosocial implications of tamoxifen versus placebo in women who are at increased risk of breast cancer. PATIENTS AND METHODS: The 488 women in the psychosocial study were recruited from participants in two placebo-controlled, double-blind, randomized, controlled trials that investigated the efficacy of tamoxifen in the prevention of breast cancer in women who are at high familial risk. During a 5-year period, repeated assessments were made of anxiety, psychological distress, and sexual functioning using standardized questionnaires before treatment at baseline and at 6-month intervals during the trial. RESULTS: Questionnaire completion over 5 years was good, with 71.1% of women returning at least 8 of 10 follow-up assessments. Although scores from individuals showed considerable fluctuation and variation over time, changes in anxiety, mood, and sexual functioning were not associated with treatment group. The number of symptoms reported at 48 months via a self-report cheklist were not associated with treatment group, but vasomotor symptoms were more frequent among tamoxifen-treated women. Symptoms of low energy, breast sensitivity, and visual blurring were reported most frequently in the placebo group. CONCLUSION: In general, these results are comparable to those from the National Surgical Adjuvant Breast and Bowel Project psychosocial study despite differences in study populations, methodology, and instruments. The long-term use of tamoxifen and other selective estrogen response modulators as preventive agents in high-risk groups has been questioned, but we found no evidence of treatment-related side effects that affect women’s psychosocial and sexual functioning.
Clinical Evidence for Topotecan-Paclitaxel Non–Cross-Resistance in Ovarian Cancer
Authors: Gore Martin , ten Bokkel Huinink Wim , Carmichael James , Gordon Alan , Davidson Neville , Coleman Robert , Spaczynski Marek , Héron Jean-François , Bolis Giorgio , Malmström Henric , Malfetano John , Scarabelli Claudio , Vennin Phillipe , Ross Graham , Fields Scott Z. 
Published: February 2017

PURPOSE: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non–cross-resistance between these two compounds. PATIENTS AND METHODS: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m2/d) × 5 every 21 days (n = 112) or paclitaxel (175 mg/m2 over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. RESULTS: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P = .638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). CONCLUSION: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non–cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.
Accelerated Treatment of Breast Cancer
Authors: Vicini Frank A. , Baglan Kathy L. , Kestin Larry L. , Mitchell Chris , Chen Peter Y. , Frazier Robert C. , Edmundson Greg , Goldstein Neal S. , Benitez Pamela , Huang Raywin R. , Martinez Alvaro 
Published: February 2017

PURPOSE: Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS: Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS: No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P = .31 and 2% v 1%, P = .63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P = .24), disease-free survival (87% v 91%, P = .55), overall survival (90% v 93%, P = .66), or cause-specific survival (97% v 99%, P = .28). CONCLUSION: Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.
Non-Hodgkin’s Lymphoma After Primary Hodgkin’s Disease in the German Hodgkin’s Lymphoma Study Group: Incidence, Treatment, and Prognosis
Authors: Rueffer Ulrich , Josting Andreas , Franklin Jeremy , May Michael , Sieber Markus , Breuer Kai , Engert Andreas , Diehl for the German Hodgkin’s Lymphoma Study Group Volker 
Published: February 2017

PURPOSE: The cumulative incidence for non-Hodgkin lymphoma’s (NHL) after primary Hodgkin’s disease (HD) ranges between 1% and 6%. To investigate the course of disease for secondary NHL, we retrospectively analyzed patients treated within clinical trials of the German Hodgkin’s Lymphoma Study Group (GHSG) since 1981. PATIENTS AND METHODS: From 1981 to 1998, the GHSG conducted three generations of clinical trials for the treatment of primary HD involving a total of 5,406 patients. Reference histology by an expert panel was obtained for 4,104 of the patients. Data on incidence, treatment, and outcome of secondary NHL were updated in March 1999. RESULTS: At first diagnosis of HD, the pathologists rejected 114 (2.1%) of 5,520 cases initially diagnosed as HD and rediagnosed them as primary NHL. Fifty-two (0.9%) of the remaining 5,406 patients developed a secondary NHL. One patient was excluded from further analyses because of insufficient documentation. Six patients had no further therapy because of patient refusal (n = 1) or rapidly progressive disease (n = 5). For the remaining 45 patients, overall response rate was 43% (36% complete response and 7% partial response). The actuarial 2-year freedom from treatment failure (FFTF) and overall survival (OS) for all patients was 24% and 30%, respectively, and for patients with diffuse large-cell lymphoma, it was 28% and 35%, respectively. Time of occurrence of secondary NHL after first diagnosis of HD and variables employed in the age-adjusted International Prognostic Factor Index (IPFI) significantly influenced treatment outcome. CONCLUSION: In the GHSG, the incidence of secondary NHL with 0.9% is relatively low compared with previously reported series. The prognosis of secondary NHL seems dismal and is significantly influenced by time of occurrence and the age-adjusted IPFI. In a subset of patients with secondary NHL, long-term disease-free survival could be achieved.
Multicenter Phase Ib/II Trial of the Radiation Enhancer Motexafin Gadolinium in Patients With Brain Metastases
Authors: Carde Patrice , Timmerman Robert , Mehta Minesh P. , Koprowski Christopher D. , Ford Judith , Tishler Roy B. , Miles Dale , Miller Richard A. , Renschler Markus F. 
Published: February 2017

PURPOSE: Motexafin gadolinium is a magnetic resonance imaging (MRI)–detectable redox active drug that localizes selectively in tumor cells and enhances the effect of radiation therapy. This phase Ib/II trial of motexafin gadolinium, administered concurrently with 30 Gy in 10 fractions whole-brain radiation therapy (WBRT), was conducted to determine maximum-tolerated dose (MTD), dose-limiting toxicity, pharmacokinetics, and biolocalization in patients with brain metastases. Additional endpoints were radiologic response rate and survival. PATIENTS AND METHODS: Motexafin gadolinium was administered before each radiation treatment in this open-label, multicenter, international trial. In phase Ib, drug dose was escalated until the MTD was exceeded. In phase II, drug was evaluated in a narrow dose range. RESULTS: In phase Ib, the motexafin gadolinium dose was escalated in 39 patients (0.3 mg/kg to 8.4 mg/kg). In phase II, 22 patients received 5 mg/kg to 6.3 mg/kg motexafin gadolinium. Ten once-daily treatments were well tolerated. The MTD was 6.3 mg/kg, with dose-limiting reversible liver toxicity. Motexafin gadolinium’s tumor selectivity was established using MRI. The radiologic response rate was 72% in phase II. Median survival was 4.7 months for all patients, 5.4 months for recursive partitioning analysis (RPA) class 2 patients, and 3.8 months for RPA class 3 patients. One-year actuarial survival for all patients was 25%. CONCLUSION: Motexafin gadolinium was well tolerated at doses up to 6.3 mg/kg, was selectively accumulated in tumors, and, when combined with WBRT of 30 Gy in 10 fractions, was associated with a high radiologic response rate.
Phase I Clinical and Pharmacogenetic Study of Weekly TAS-103 in Patients With Advanced Cancer
Authors: Ewesuedo Reginald B. , Iyer Lalitha , Das Soma , Koenig Annette , Mani Sridhar , Vogelzang Nicholas J. , Schilsky Richard L. , Brenckman Wayne , Ratain Mark J. 
Published: February 2017

PURPOSE: TAS-103 is an inhibitor of both topoiso-merase I and II enzymes with broad antitumor activity. It is metabolized to TAS-103-glucuronide (TAS-103-G) predominantly by uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1). We conducted a phase I study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of TAS-103 when administered on a weekly schedule to patients with advanced cancer. In addition, we evaluated the influence of UGT1A1 genotype on the pharmacokinetics and toxicity of TAS-103. PATIENTS AND METHODS: Thirty-two patients were treated with escalating doses (50 to 200 mg/m2) of TAS-103, administered intravenously over 1 hour each week for 3 weeks. Pharmacokinetic analysis was performed at the 130-, 160-, and 200-mg/m2 dose levels. UGT1A1 genotypes were determined using reverse-transcription polymerase chain reaction techniques. RESULTS: DLT (grade 3 neutropenia) was observed in 5 of 12 patients at 160 mg/m2 and in 3 of 6 patients at 200 mg/m2. At 160 mg/m2, there was a significant correlation between areas under the curve (AUCs) for TAS-103 and TAS-103-G (r = 0.76, P < .05) and an apparent relationship between TAS-103 AUC and D 15 absolute neutrophil count (r = −0.63, P < .05, n = 11, one outlier excluded). UGT1A1 genotype did not influence clearance of TAS-103. CONCLUSION: We recommend a dose of 130 to 160 mg/m2, or 250 to 300 mg administered using the above weekly schedule for phase II studies. Further studies to characterize the pharmacodynamics and pharmacogenetics of TAS-103 are warranted.
Individualized Patient Education and Coaching to Improve Pain Control Among Cancer Outpatients
Authors: Oliver Jennifer Wright , Kravitz Richard L. , Kaplan Sherrie H. , Meyers Frederick J. 
Published: February 2017

PURPOSE: An estimated 42% of cancer patients suffer from poorly controlled pain, in part because of patient-related barriers to pain control. The objective of this study was to evaluate the effect of an individualized education and coaching intervention on pain outcomes and pain-related knowledge among outpatients with cancer-related pain. PATIENTS AND METHODS: English-speaking cancer patients (18 to 75 years old) with moderate pain over the past 2 weeks were randomly assigned to the experimental (n = 34) or control group (n = 33). Experimental patients received a 20-minute individualized education and coaching session to increase knowledge of pain self-management, to redress personal misconceptions about pain treatment, and to rehearse an individually scripted patient-physician dialog about pain control. The control group received standardized instruction on controlling pain. Data on average pain, functional impairment as a result of pain, pain frequency, and pain-related knowledge were collected at enrollment and 2-week follow-up. RESULTS: At baseline, there were no significant differences between experimental and control groups in terms of average pain, functional impairment as a result of pain, pain frequency, or pain-related knowledge. At follow-up, average pain severity improved significantly more among experimental group patients than among control patients (P = .014). The intervention had no statistically significant impact on functional impairment as a result of pain, pain frequency, or pain-related knowledge. CONCLUSION: Compared with provision of standard educational materials and counseling, a brief individualized education and coaching intervention for outpatients with cancer-related pain was associated with improvement in average pain levels. Larger studies are needed to validate these effects and elucidate their mechanisms.
T-Cell/Histiocyte–Rich Large B-Cell Lymphoma: A Distinct Clinicopathologic Entity
Authors: Achten R. , Verhoef G. , Vanuytsel L. , De Wolf-Peeters C. 
Published: February 2017

PURPOSE: Although it has proven difficult to delineate diagnostically reproducible and clinically relevant subgroups, the heterogeneity of diffuse large B-cell lymphomas (DLBCL) is widely acknowledged. In 1992, we reported on six cases that suggested that large B-cell lymphoma rich in stromal histiocytes and T cells may be identified as a distinct clinicopathologic entity within DLBCL. PATIENTS AND METHODS: An integrated clinicopathologic study of 40 cases of this DLBCL subtype is presented. RESULTS: Distinguishing a DLBCL rich in histiocytes and reactive T cells, designated T-cell/histiocyte–rich large B-cell lymphoma (THR-BCL), may be justified from a clinical point of view. The disease typically affects middle-aged male patients who usually present with advanced-stage disease that is not adequately managed with current therapeutic strategies. Whereas proliferation fraction and p53 overexpression, in addition to the clinical variables incorporated in the International Prognostic Index (IPI), significantly correlate with response to treatment and survival in a univariate analysis, only the IPI score identifies relevant prognostic THR-BCL subpopulations in a multivariate model. The morphologic and immunophenotypic profile of the neoplastic B cells in THR-BCL suggests that they may originate from a germinal center ancestor. CONCLUSION: THR-BCL constitutes a distinct clinicopathologic entity that is characterized by an aggressive behavior. Experimental therapeutic strategies may be indicated to obtain a more favorable response to treatment in this disease.
Quality-of-Life–Adjusted Survival Analysis of High-Dose Adjuvant Interferon Alfa-2b for High-Risk Melanoma Patients Using Intergroup Clinical Trial Data
Authors: Kilbridge Kerry L. , Cole Bernard F. , Kirkwood John M. , Haluska Frank G. , Atkins Michael A. , Ruckdeschel John C. , Sock Dana E. , Nease Robert F. , Weeks Jane C. 
Published: February 2017

PURPOSE: High-dose adjuvant interferon alfa-2b (IFNα2b) for high-risk melanoma is a 1-year regimen that improves relapse-free and overall survival but has significant toxicity. A quality-of-life–adjusted survival (QAS) analysis analysis of two cooperative group phase III trials, E1684 and E1690/S9111/C9190, was performed, incorporating patient values (utilities) for the toxicity of IFNα2b treatment and melanoma recurrence. PATIENTS AND METHODS: Quality-Adjusted Time Without Symptoms or Toxicity methodology was used with melanoma patient utilities and trial data to estimate the effect of IFNα2b on QAS. The increase or decrease in QAS that patients could expect from treatment was estimated based on their utilities. Eleven utility predictor questions were tested to identify patients with utilities that result in decreased QAS. RESULTS: Using E1684 data, IFNα2b would result in an increase in QAS for all sets of patient utilities. This benefit was significant (P < .05) for 16% of patients. Using E1690/S9111/C9190 data, 77% of patients would experience a benefit in QAS from IFNα2b and 23% would experience a decrease in QAS; neither of these effects was statistically significant. Using utility predictors and the E1690/S9111/C9190 analysis, a decision rule was formulated that helps identify patients in whom IFNα2b may detract from QAS. CONCLUSION: Most patients experienced improvement in QAS in both trials, but this benefit was statistically significant in only 16% of patients in E1684. Change in QAS depends more on the utility for IFNα2b toxicity than on the utility for melanoma recurrence. Cancer patients probably have higher utilities for IFNα2b toxicity than members of the general population and will tend to favor IFNα2b treatment as a result.
Treatment Decision Making in Early-Stage Breast Cancer: Should Surgeons Match Patients’ Desired Level of Involvement?
Authors: Keating Nancy L. , Guadagnoli Edward , Landrum Mary Beth , Borbas Catherine , Weeks Jane C. 
Published: February 2017

PURPOSE: To describe desired and actual roles in treatment decision making among patients with early-stage breast cancer, identify how often patients’ actual roles matched their desired roles, and examine whether matching of actual and desired roles was associated with type of treatment received and satisfaction. PATIENTS AND METHODS: We surveyed 1,081 women (response, 70%) diagnosed with early-stage breast cancer in Massachusetts or Minnesota about their desired and actual roles in treatment decision making with their surgeon and used logistic regression to assess whether matching of actual to desired roles was associated with type of surgery and satisfaction. RESULTS: Most patients (64%) desired a collaborative role in decision making, but only 33% reported actually having such a collaborative role when they discussed treatments with their surgeons. Overall, 49% of women reported an actual role that matched the desired role they reported, 25% had a less active role than desired, and 26% had a more active role than desired. In adjusted analyses, patients whose reported actual role matched their desired role were no more likely than others to undergo breast-conserving surgery (P > .2), but these women were more satisfied with their treatment choice (83.5% very satisfied; reference) than those whose role was less active than desired (72.9% very satisfied; P = .02) or more active than desired (72.2% very satisfied; P = .005). CONCLUSION: Only approximately half of patients reported an actual role in decision making that matched the desired role they reported. These patients were more satisfied with their treatment choice than other patients, suggesting that women with early-stage breast cancer may benefit from surgeons’ efforts to identify their preferences for participation in decisions and tailor the decision-making process to them.