bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic Features of Long-Term Survivors and Disease-Free Survivors After Resection of Hepatocellular Carcinoma: A Study of a Prospective Cohort
Authors: Poon Ronnie Tung-Ping , Ng Irene Oi-Lin , Fan Sheung-Tat , Lai Edward Cheuk-Sin , Lo Chung-Mau , Liu Chi-Leung , Wong John 
Published: February 2017

PURPOSE: This study aims to clarify the clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The clinicopathologic features of 5-year survivors and disease-free survivors were elucidated in a cohort of 230 patients prospectively observed for > 5 years (64 to 192 months) after curative resection of HCC. RESULTS: The incidence of 5-year overall and disease-free survivors were 37% (85 of 230) and 20% (45 of 230), respectively. Clinicopathologic features associated with 5-year survivors included female sex (P = .024), preoperative serum albumin ≥ 40 g/L (P = .033), AST < 50 u/L (P = .001), tumor < 5 cm (P = .001), solitary tumor (P = .035), encapsulated tumor (P = .021), no venous invasion (P = .001), no microsatellite nodule (P = .001), and early pathologic tumor-node-metastasis (pTNM) stage (I or II, P < .001). Features favoring 5-year disease-free survivors were preoperative serum AST < 50 u/L (P = .007), tumor < 5 cm (P = .005), encapsulated tumor (P = .007), no venous invasion (P < .001), no microsatellite nodule (P = .001), and early pTNM stage (I or II, P < .001). By multivariate analysis, pTNM stage was the only significant predictive factor for both overall and disease-free survival. CONCLUSION: This study shows that long-term disease-free survival > 5 years after resection of HCC can be achieved in patients with favorable tumor characteristics. Early pTNM stage was the most reliable predictor of both long-term overall and disease-free survivors.
Clinicopathologic Re-Evaluation of 100 Malignant Fibrous Histiocytomas: Prognostic Relevance of Subclassification
Authors: Fletcher Christopher D.M. , Gustafson Pelle , Rydholm Anders , Willén Helena , Åkerman Måns 
Published: February 2017

PURPOSE: Malignant fibrous histiocytoma (MFH) has been regarded as the most common soft tissue sarcoma (STS) in adults. Yet its true nature and the validity of this diagnostic concept have increasingly been questioned. Available data suggest that most patients with MFH can be subclassified into specific STS types, but the clinical relevance of such categorization has been argued. In a retrospective study, we reclassified 100 tumors of the extremity and trunk wall primarily diagnosed as MFH and analyzed the outcome. PATIENTS AND METHODS: Patients were adults (median age, 70 years; range, 32 to 94 years). The median tumor size was 8 cm (range, 1 to 30 cm), and the thigh was the most common tumor location (n = 31). Median follow-up was 8 years (range, 3 to 16 years). The overall 5-year metastasis-free survival rate was 0.64. The tumors were reanalyzed histologically, immunohistochemically, and, where available, ultrastructurally, and were classified according to strict diagnostic criteria. Patients were staged according to the American Joint Committee on Cancer system, and prognoses were compared among different groups of the reclassified diagnoses, paying special attention to myogenic tumors. RESULTS: In 84 of 100 tumors, a specific line of differentiation was either proved or strongly suggested. The most common diagnoses were myxofibrosarcoma (n = 22) and leiomyosarcoma (n = 20). Overall, 30 tumors could be grouped as some form of myogenic sarcoma. These tumors had a worse prognosis, even within the same American Joint Committee on Cancer stage, and a shorter time to metastasis than nonmyogenic tumors. CONCLUSION: This retrospective study confirms that most so-called MFH can be subclassified by defined criteria; it provides evidence that such classification is clinically important. Specifically, pleomorphic STS showing myogenic differentiation are significantly more aggressive, a finding that allows planning future therapeutic trials.
Prediction of Response to Preoperative Chemotherapy in Adenocarcinomas of the Esophagogastric Junction by Metabolic Imaging
Authors: Weber Wolfgang A. , Ott Katja , Becker Karen , Dittler Hans-Joachim , Helmberger Hermann , Avril Norbert E. , Meisetschläger Günther , Busch Raymonde , Siewert Jörg-Rüdiger , Schwaiger Markus , Fink Ulrich 
Published: February 2017

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean ± 1 SD) after 14 days of therapy was significantly different between responding (−54% ± 17%) and nonresponding tumors (−15% ± 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P = .01) and shorter overall survival (P = .04). CONCLUSION: PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.
Indicators of Lifetime Estrogen Exposure: Effect on Breast Cancer Incidence and Interaction With Raloxifene Therapy in the Multiple Outcomes of Raloxifene Evaluation Study Participants
Authors: Lippman Marc E. , Krueger Kathryn A. , Eckert Stephen , Sashegyi Andreas , Walls Erin L. , Jamal Sophie , Cauley Jane A. , Cummings Steven R. 
Published: February 2017

PURPOSE: To test the hypothesis that risk factors related to lifetime estrogen exposure predict breast cancer incidence and to test if any subgroups experience enhanced benefit from raloxifene. PATIENTS AND METHODS: Postmenopausal women with osteoporosis (N = 7,705), enrolled onto the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, were randomly assigned to receive placebo, raloxifene 60 mg/d, or raloxifene 120 mg/d for 4 years. Breast cancer risk was analyzed by the following baseline characteristics indicative of estrogen exposure: previous hormone replacement therapy, prevalent vertebral fractures, family history of breast cancer, estradiol level, bone mineral density (BMD), body mass index, and age at menopause. Therapy-by-subgroup interactions were assessed using a logistic regression model. RESULTS: Overall, women with the highest one-third estradiol levels (≥ 12 pmol/L) had a 2.07-fold increased invasive breast cancer risk compared with women with lower levels. Raloxifene significantly reduced breast cancer risk in both the low- and high-estrogen subgroups for all risk factors examined (P < .05 for each comparison). The women with the highest BMD and those with a family history of breast cancer experienced a significantly greater therapy benefit with raloxifene, compared with the two thirds of patients with lower BMD or those without a family history, respectively; the subgroup-by-therapy interactions were significant (P = .005 and P = .015, respectively). CONCLUSION: The MORE trial confirms that increased lifetime estrogen exposure increases breast cancer risk. Raloxifene therapy reduces breast cancer risk in postmenopausal osteoporotic women regardless of lifetime estrogen exposure, but the reduction is greater in those with higher lifetime exposure to estrogen.
Relapse of TEL-AML1–Positive Acute Lymphoblastic Leukemia in Childhood: A Matched-Pair Analysis
Authors: Seeger Karl , Stackelberg Arend V. , Taube Tillmann , Buchwald Dirk , Körner Gabriele , Suttorp Meinolf , Dörffel Wolfgang , Tausch Werner , Henze Günter 
Published: February 2017

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor. PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL–negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse. RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 ± 0.10 versus 0.38 ± 0.10 (P = .09) and 0.82 ± 0.09 versus 0.42 ± 0.19 (P = .10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P < .001) but not of TEL-AML1 expression (P = .09). CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.
Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of Patients With Advanced Non–Small-Cell Lung Cancer: A Southwest Oncology Group Trial
Authors: Kelly Karen , Crowley John , Bunn Paul A. , Presant Cary A. , Grevstad Patra K. , Moinpour Carol M. , Ramsey Scott D. , Wozniak Antoinette J. , Weiss Geoffrey R. , Moore Dennis F. , Israel Valerie K. , Livingston Robert B. , Gandara David R. 
Published: February 2017

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non–small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m2 over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P = .002) and neutropenia (P = .008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P = .001, P = .007), and grade 3 peripheral neuropathy was higher on the PC arm (P < .001). More patients on the VC arm discontinued therapy because of toxicity (P = .001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non–small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.
Estimating the Cost of Informal Caregiving for Elderly Patients With Cancer
Authors: Hayman James A. , Langa Kenneth M. , Kabeto Mohammed U. , Katz Steven J. , DeMonner Sonya M. , Chernew Michael E. , Slavin Mitchell B. , Fendrick A. Mark 
Published: February 2017

PURPOSE: As the United States population ages, the increasing prevalence of cancer is likely to result in higher direct medical and nonmedical costs. Although estimates of the associated direct medical costs exist, very little information is available regarding the prevalence, time, and cost associated with informal caregiving for elderly cancer patients.MATERIALS AND METHODS: To estimate these costs, we used data from the first wave (1993) of the Asset and Health Dynamics (AHEAD) Study, a nationally representative longitudinal survey of people aged 70 or older. Using a multivariable, two-part regression model to control for differences in health and functional status, social support, and sociodemographics, we estimated the probability of receiving informal care, the average weekly number of caregiving hours, and the average annual caregiving cost per case (assuming an average hourly wage of $8.17) for subjects who reported no history of cancer (NC), having a diagnosis of cancer but not receiving treatment for their cancer in the last year (CNT), and having a diagnosis of cancer and receiving treatment in the last year (CT).RESULTS: Of the 7,443 subjects surveyed, 6,422 (86%) reported NC, 718 (10%) reported CNT, and 303 (4%) reported CT. Whereas the adjusted probability of informal caregiving for those respondents reporting NC and CNT was 26%, it was 34% for those reporting CT (P < .05). Those subjects reporting CT received an average of 10.0 hours of informal caregiving per week, as compared with 6.9 and 6.8 hours for those who reported NC and CNT, respectively (P < .05). Accordingly, cancer treatment was associated with an incremental increase of 3.1 hours per week, which translates into an additional average yearly cost of $1,200 per patient and just over $1 billion nationally.CONCLUSION: Informal caregiving costs are substantial and should be considered when estimating the cost of cancer treatment in the elderly.
Phase I Study of Recombinant Human CD40 Ligand in Cancer Patients
Authors: Vonderheide Robert H. , Dutcher Janice P. , Anderson Jeanne E. , Eckhardt S. Gail , Stephans Katherine F. , Razvillas Betty , Garl Susan , Butine Michael D. , Perry Vicki P. , Armitage Richard J. , Ghalie Richard , Caron Dania A. , Gribben John G. 
Published: February 2017

PURPOSE: To determine the toxicity, maximum-tolerated dose (MTD), and pharmacokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Corp, Seattle, WA), suggested in preclinical studies to mediate cytotoxicity against CD40-expressing tumors and immune stimulation.PATIENTS AND METHODS: Patients with advanced solid tumors or intermediate- or high-grade non-Hodgkin’s lymphoma (NHL) received rhuCD40L subcutaneously daily for 5 days in a phase I dose-escalation study. Subsequent courses were given until disease progression.RESULTS: Thirty-two patients received rhuCD40L at three dose levels. A total of 65 courses were administered. The MTD was 0.1 mg/kg/d based on dose-related but transient elevations of serum liver transaminases. Grade 3 or 4 transaminase elevations occurred in 14%, 28%, and 57% of patients treated at 0.05, 0.10, and 0.15 mg/kg/d, respectively. Other toxicities were mild to moderate. At the MTD, the half-life of rhuCD40L was calculated at 24.8 ± 22.8 hours. Two patients (6%) had a partial response on study (one patient with laryngeal carcinoma and one with NHL). For the patient with laryngeal cancer, a partial response was sustained for 12 months before the patient was taken off therapy and observed on no additional therapy. Three months later, the patient was found to have a complete response and remains biospy-proven free of disease at 24 months. Twelve patients (38%) had stable disease after one course, which was sustained in four patients through four courses.CONCLUSION: The MTD of rhuCD40L when administered subcutaneously daily for 5 days was defined by transient serum elevations in hepatic transaminases. Encouraging antitumor activity, including a long-term complete remission, was observed. Phase II studies are warranted.
Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan
Authors: Gordon Alan N. , Fleagle John T. , Guthrie David , Parkin David E. , Gore Martin E. , Lacave Angel J. 
Published: February 2017

PURPOSE: To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) and topotecan in patients with epithelial ovarian carcinoma that recurred after or didn’t respond to first-line, platinum-based chemotherapy.PATIENTS AND METHODS: Patients with measurable and assessable disease were randomized to receive either PLD 50 mg/m2as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m2/d for 5 consecutive days every 3 weeks. Patients were stratified prospectively for platinum sensitivity and for the presence or absence of bulky disease.RESULTS: A total of 474 patients were treated (239 PLD and 235 topotecan). They comprised the intent-to-treat population. The overall progression-free survival rates were similar between the two arms (P = .095). The overall response rates for PLD and topotecan were 19.7% and 17.0%, respectively (P = .390). Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan. Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival (P = .037), with medians of 28.9 for PLD versus 23.3 weeks for topotecan. For overall survival, PLD was significantly superior to topotecan (P = .008), with a median of 108 weeks versus 71.1 weeks. The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan (P = .455). Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification, or growth factor or blood product utilization.CONCLUSION: The comparable efficacy, favorable safety profile, and convenient dosing support the role of PLD as a valuable treatment option in this patient population.
Phase III, Multicenter, Double-Blind, Randomized Study of Letrozole, an Aromatase Inhibitor, for Advanced Breast Cancer Versus Megestrol Acetate
Authors: Buzdar A. , Douma J. , Davidson N. , Elledge R. , Morgan M. , Smith R. , Porter L. , Nabholtz J. , Xiang X. , Brady C. 
Published: February 2017

PURPOSE: To compare two doses of letrozole (0.5 mg and 2.5 mg every day) and megestrol acetate (40 mg qid) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: This double-blind, randomized, multicenter, multinational study enrolled 602 patients, all of whom were included in the primary analysis in the protocol. Patients had advanced or metastatic breast cancer with evidence of disease progression while receiving continuous adjuvant antiestrogen therapy, had experienced relapse within 12 months of stopping adjuvant antiestrogen therapy given for at least 6 months, or had experienced disease progression while receiving antiestrogen therapy for advanced disease. Tumors were required to be estrogen receptor– and/or progesterone receptor–positive or of unknown status. Confirmed objective response rate was the primary efficacy variable. Karnofsky Performance Status and European Organization for Research and Treatment of Cancer quality-of-life assessments were collected for 1 year. RESULTS: There were no statistically significant differences among the three treatment groups for overall objective tumor response. Patients treated with letrozole 0.5 mg had improvements in disease progression (P = .044) and a decreased risk of treatment failure (P = .018), compared with patients treated with megestrol acetate. Letrozole 0.5 mg showed a trend (P = .053) for survival benefit when compared with megestrol acetate. Megestrol acetate was more likely to produce weight gain, dyspnea, and vaginal bleeding, and the letrozole groups were more likely to experience headache, hair thinning, and diarrhea. CONCLUSION: Given a favorable tolerability profile, once-daily dosing, and evidence of clinically relevant benefit, letrozole is equivalent to megestrol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens.
Value of Epidermal Growth Factor Receptor, HER2, p53, and Steroid Receptors in Predicting the Efficacy of Tamoxifen in High-Risk Postmenopausal Breast Cancer Patients
Authors: Knoop Ann S. , Bentzen Søren M. , Nielsen Mette M. , Rasmussen Birgitte B. , Rose Carsten 
Published: February 2017

PURPOSE: Few studies have examined the possible importance of biologic prognostic factors in breast cancer connected with differentiation and growth in predicting response to a specific adjuvant treatment. HER2, epidermal growth factor receptor (EGFR), and p53 have all been suggested as possible markers of tamoxifen resistance. The aim of this study was to investigate interactions between adjuvant treatment with tamoxifen and the content of EGFR, HER2, and p53 in steroid receptor–positive patients. PATIENTS AND METHODS: A total of 1,716 high-risk postmenopausal breast cancer patients were randomly assigned to treatment with tamoxifen (868 women) or to observation (848 women) in a prospective trial (Danish Breast Cancer Cooperative Group’s 77c protocol). The content of the steroid receptors and expression of p53, EGFR, and HER2 were determined by immunohistochemical analysis of paraffin-embedded tissue. The length of follow-up was 10 years. The end point for this analysis was disease-free survival. RESULTS: Multivariate analysis demonstrated no increased risk of recurrence after treatment with tamoxifen for HER2-, EGFR-, and p53-positive, high-risk, steroid receptor–positive patients. Patients with steroid receptor–positive tumors and positive immunohistochemical staining for HER2, EGFR or p53 benefited from treatment with tamoxifen for 1 year, although the latter variable contained independent prognostic information by itself. CONCLUSION: With the statistical power of the present randomized study, we did not find support for the hypothesis that HER2/EGFR or p53 status predicts benefit from tamoxifen treatment in estrogen receptor–positive patients with early-stage breast cancer. Thus, neither HER2, EGFR, nor p53 overexpression/accumulation should be used as a contraindication for giving tamoxifen.