bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 mutations in benign breast tissue.
Authors: Millikan R , Hulka B , Thor A , Zhang Y , Edgerton S , Zhang X , Pei H , He M , Wold L , Melton L J 
Published: February 2017

PURPOSE Patients with benign breast biopsies that exhibit atypical epithelial proliferation or fibroadenoma may be at increased risk for invasive breast cancer. We hypothesized that molecular markers might also be useful to evaluate the malignant potential of nonneoplastic breast tissue. PATIENTS AND METHODS Study subjects belonged to a cohort of 6,805 women who underwent biopsy for nonmalignant breast disease at the Mayo Clinic and Rochester-affiliated hospitals between 1967 and 1981. As part of a nested case-control study that compared subjects who developed invasive breast cancer with those who did not, we analyzed a sample of 60 benign breast biopsies for the following markers: HER-2/neu and p53 over-expression by immunohistochemistry, HER-2/neu and PRAD-1 amplification using differential polymerase chain reaction (PCR), and p53 mutation using single-strand conformation analysis (SSCA) and direct DNA sequencing by asymmetric PCR. RESULTS None of 60 biopsies showed amplification of HER-2/neu or PRAD-1. Five samples exhibited low-level immunoreactivity to the HER-2/neu protein product. Fourteen samples exhibited focal or diffuse immunoreactivity to the p53 protein. Point mutations in the p53 gene were found in five samples: three of these samples exhibited mutations that altered the amino acid sequence. Only two of five samples with p53 mutation exhibited p53 overexpression. Histologic diagnoses on three samples with nonconservative p53 mutation were, respectively, nonproliferative fibrocystic change, papillomatous hyperplasia, and fibroadenoma. CONCLUSION The clinical significance of p53 mutation, p53 overexpression, and low-level HER-2/neu expression in benign breast tissue remains to be determined. Further research will be necessary to evaluate whether these markers could serve as useful adjuncts to histology in evaluation of the malignant potential of benign breast tissue.
Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group.
Authors: Browman G P , Bergsagel D , Sicheri D , O'Reilly S , Wilson K S , Rubin S , Belch A , Shustik C , Barr R , Walker I 
Published: February 2017

PURPOSE To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone. PATIENTS AND METHODS In a multicenter trial, patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone (MP) were randomized either to receive interferon (2 mU/m2) subcutaneously three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated using life-table methods, and were adjusted in the analysis for imbalances in baseline prognostic factors. RESULTS Four hundred two patients were registered and 176 responders were randomized (85 to interferon and 91 to control). At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for control (P = .16), but when adjusted for chance imbalances in baseline prognostic factors (mainly performance status), the median survival duration was 44 months and 33 months for interferon and control, respectively (P = .049). Progression-free survival from randomization to first relapse also favored interferon (unadjusted P < .002; adjusted P < .003). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discontinue interferon treatment. CONCLUSION Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone. Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival.
Survival of patients with resistant Hodgkin's disease after polyclonal yttrium 90-labeled antiferritin treatment.
Authors: Herpst J M , Klein J L , Leichner P K , Quadri S M , Vriesendorp H M 
Published: February 2017

PURPOSE A follow-up study was initiated of patients with Hodgkin's disease who were treated with yttrium 90-labeled antiferritin. Prescription method, pharmacokinetics, acute and late side effects, and survival were evaluated. METHODS Patients had measurable disease and failed > or = two multiagent chemotherapy regimens previously (N = 44). All patients received 5-mCi indium 111-labeled antiferritin 2 mg intravenously and were scanned repeatedly by gamma camera. In five patients, polyclonal antiferritin (rabbit, pig, or baboon) failed to target the tumor. Thirty-nine patients were injected intravenously with 10-, 20-, 30-, 40-, or 50-mCi yttrium 90-labeled antiferritin 2 to 5 mg. Patients received between one and five cycles. Some patients were supported with 5 x 10(7) autologous bone marrow cells per kilogram. RESULTS Yttrium 90-labeled polyclonal antiferritin does not produce immunologic, pharmacologic, or microbiologic complications in vivo. Bone marrow toxicity is the only side effect observed. Overall response rate is 20 of 39, or 51%. Two patients had stable disease. A significant positive correlation is found between blood radioactivity level 1 hour after radioimmunoconjugate administration and subsequent response of Hodgkin's disease. A dosage in millicuries per kilogram provides a higher positive correlation with blood radioactivity levels 1 hour after administration than a dosage in millicuries per square meter of body-surface area or in total millicuries. Fifty percent of patients survive for > or = 6 months. CONCLUSION The low-dose protein used (2 to 5 mg) indicates that the high response rate is due to radiation and not to immunologic effects of the antibody. High-activity administrations followed by bone marrow transplantation are not required for tumor response. The therapeutic ratio of radiolabeled antiferritin is higher than the therapeutic ratio observed in most phase I studies of chemotherapeutic agents. This analysis does not identify a superior mode of treatment for patients with end-stage Hodgkin's disease. However, in a heavily pretreated patient population, prolonged survival is observed after relatively inexpensive treatment. Preclinical research with yttrium 90-labeled antiferritin indicates that significant increases in tumor dose can be obtained in the future without an increase in normal tissue toxicity.
Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo.
Authors: Navari R M , Madajewicz S , Anderson N , Tchekmedyian N S , Whaley W , Garewal H , Beck T M , Chang A Y , Greenberg B , Caldwell K C 
Published: February 2017

PURPOSE To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.
Effect of oral clodronate on metastatic bone pain: a double-blind, placebo-controlled study.
Authors: Robertson A G , Reed N S , Ralston S H 
Published: February 2017

PURPOSE To study the effects of oral clodronate on bone pain in patients with advanced metastatic bone disease. PATIENTS AND METHODS Fifty-five patients with progressing bone metastases were randomized to receive oral clodronate 1,600 mg/d (n = 27) or matching placebo (n = 28). The main outcome measures were bone pain (visual analog score), analgesic use, and compliance with therapy. RESULTS Visual analog pain score (median [interquartile range]) decreased from the pretreatment value in the clodronate group (-0.9 [-2.6 to -0.4]), but increased in the placebo group (+0.4 [-1.0 to +4.0]) (P = .03 between groups). Analgesic use increased with disease progression to a similar extent in both groups (59% increased use in the clodronate group v 64% of placebo group; difference not significant). Ten patients (37%) in the clodronate group and 12 (46%) in the placebo group withdrew from the study prematurely, most often because of difficulty with swallowing the capsules. CONCLUSION Clodronate improved control of bone pain to a modest degree in patients with advanced metastatic cancer, but did not reduce analgesic requirement significantly. Perhaps as a result of these factors, it proved difficult to maintain patients on therapy. Further studies will be needed to define the role of bisphosphonates such as clodronate in this situation, in comparison with established treatments such as radiotherapy and analgesics.
Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease.
Authors: Bajetta E , Di Leo A , Biganzoli L , Mariani L , Cappuzzo F , Di Bartolomeo M , Zilembo N , Artale S , Magnani E , Celio L , Buzzoni R , Carnaghi C 
Published: February 2017

PURPOSE The aim of the study was to evaluate the activity of vinorelbine (VNLB) in a population of advanced ovarian cancer patients, with particular attention to defining its role in platinum-resistant disease. PATIENTS AND METHODS Thirty-three patients were recruited and treated with VNLB 25 mg/m2 intravenously (IV) weekly. the median age was 53 years, performance status 0 to 2, and number of previous chemotherapy regimens two (range, one to five). Twenty-four patients were platinum-resistant; the remaining nine either were platinum-sensitive (four cases) or had undetermined sensitivity (five cases). RESULTS The mean delivered dose-intensity of VNLB was 67% of the planned level, because 60% of the cycles were delayed due to neutropenia or anemia. Four partial responses (PRs) and one complete response (CR) were observed, for an overall response rate of 15% (95% exact confidence interval, 5.1% to 31.9%). All the responses occurred in the subgroup of 24 platinum-resistant cases, in whom the response rate was 21% (95% exact confidence interval, 7.1% to 42.1%). Seven patients became stabilized on VNLB, and 27% of the cases showed a reduction in serum cancer antigen 125 (CA 125) levels. G3/G4 side effects consisted of neutropenia, anemia, and worsening of preexisting peripheral neuropathy. No treatment-related deaths occurred. CONCLUSION VNLB led to a 21% response rate in the population of heavily pretreated and platinum-resistant ovarian cancer patients. Further studies of VNLB alone or in combination with taxanes are warranted in patients with less pretreatment.
Evaluation of HER-2/neu Gene Amplification and Overexpression: Comparison of Frequently Used Assay Methods in a Molecularly Characterized Cohort of Breast Cancer Specimens
Authors: Press Michael F. , Slamon Dennis J. , Flom Kerry J. , Park Jinha , Zhou Jian-Yuan , Bernstein Leslie 
Published: February 2017

PURPOSE: To compare and evaluate HER-2/neu clinical assay methods. MATERIALS AND METHODS: One hundred seventeen breast cancer specimens with known HER-2/neu amplification and overexpression status were assayed with four different immunohistochemical assays and two different fluorescence in situ hybridization (FISH) assays. RESULTS: The accuracy of the FISH assays for HER-2/neu gene amplification was high, 97.4% for the Vysis PathVision assay (Vysis, Inc, Downers Grove, IL) and 95.7% for the the Ventana INFORM assay (Ventana, Medical Systems, Inc, Tucson, AZ). The immunohistochemical assay with the highest accuracy for HER-2/neu overexpression was obtained with R60 polyclonal antibody (96.6%), followed by immunohistochemical assays performed with 10H8 monoclonal antibody (95.7%), the Ventana CB11 monoclonal antibody (89.7%), and the DAKO HercepTest (88.9%; Dako, Corp, Carpinteria, CA). Only the sensitivities, and therefore, overall accuracy, of the DAKO Herceptest and Ventana CB11 immunohistochemical assays were significantly different from the more sensitive FISH assay. CONCLUSION: Based on these findings, the FISH assays were highly accurate, with immunohistochemical assays performed with R60 and 10H8 nearly as accurate. The DAKO HercepTest and the Ventana CB11 immunohistochemical assay were statistically significantly different from the Vysis FISH assay in evaluating these previously molecularly characterized breast cancer specimens.
Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial
Authors: Chlebowski R. T. , Schwartz A. , Wakelee H. , Anderson G. L. , Stefanick M. L. , Manson J. E. , Chien J. W. , Chen C. , Wactawski-Wende J. , Gass M. 
Published: February 2017

CRA1500 Background: Sex differences in lung cancer outcome suggest a potential hormonal influence; however, observational studies provide mixed findings regarding menopausal hormone therapy (HT) and lung cancer. Methods: Secondary analyses of the WHI randomized, placebo-controlled trial of daily conjugated equine estrogen (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) in 16,608 multi-ethnic postmenopausal women, aged 50–79 were conducted on lung cancer incidence and mortality. Lung cancers were confirmed by medical record review. Results: Groups were balanced for age, race/ethnicity, and prior HT. Smoking status was also comparable (never 50%, past 40%, current 10% in both groups). Cumulative risk for lung cancer was highest in current (0.51%), compared to past (0.14%) and never (0.04%) smokers. After 5.6 years on trial intervention and 2.4 years additional follow-up (median), small cell lung cancer incidence was comparable between randomization groups (total n=26), as was subsequent small cell lung cancer mortality. Although a trend for more non-small cell lung cancer (NSCLC) diagnoses in the active hormone group was not significant (p=0.12), an apparent divergence emerged after five years, with more diagnoses in the CEE+MPA group. In addition, mortality after NSCLC diagnosis was significantly higher for the CEE+MPA group (46.3% vs 27.0%, respectively, hazard ratio (HR) 1.59, 95% CI 1.03–2.46, p=0.04). As a result, CEE+MPA group women were more likely to die from NSCLC than those on placebo (p=0.02). Conclusions: Use of CEE + MPA for over 5 years increases a woman's risk for NSCLC mortality, the leading cause of cancer death in women. These data, together with recent results indicating higher breast cancer risk (Cancer Res 2009;69(2):78s), suggest cancer impact should influence risk-to-benefit consideration for combined HT use. [Table: see text] [Table: see text]
Impact of sentinel lymph node biopsy on staging of early cervical cancer: Results of a prospective, multicenter study
Authors: Lecuru F. , Bats A. , Mathevet P. , Querleu D. , Leblanc E. , Morice P. , Darai E. , Marret H. , Collin C. , Chatellier G. , Gilaizeau F. 
Published: February 2017

CRA5506 Background: 10% to 15% of patients with pN0 early cervical cancer experience recurrences. This may be related either to nodes missed by the dissection or located outside the dissection field or to failed diagnosis of node metastases. The objective of this study was to measure the benefits from sentinel node (SN) detection in terms of nodes collected from unusual territories and of detected micrometastases and isolated tumor cells (ITCs). Methods: 145 patients who had stage Ia1-Ib1 epidermoid cancer or adenocarcinoma or adenosquamous cancer were included in a multicenter study (January 2005 - June 2007). Noninclusion criteria were age<18 years, pregnancy, and previous treatment. SNs were identified by combined technetium and blue-dye labeling in the pelvic and para-aortic territories. Slices were cut 200 μm apart. At each level, HES staining and labeling with anti-cytokeratin antibodies (AE1-AE3) were performed. SNs in an unusual territory were defined as SNs outside the ilio-obturator region. ITC was defined as size <0.2 mm, micrometastasis as size 0.2 to 2mm, and macrometastases as size >2 mm. The study was funded by the French National Institute of Cancer and reviewed by an IRB. Results: 17 patients were excluded for major protocol deviations, leaving 128 patients for the per protocol analysis. One or more SNs were detected in 98.4% of patients (95%CI, 94.4 to 99.9%). The 430 detected SNs were located as follows: external iliac, 80.5 %; common iliac, 8.6%; presacral and paraaortic, 5.5%; and parametrial, 4.9 %. SN detection identified at least one SN in an unusual territory in 48/128 (37.5%) patients. There were 26 positive SNs in 21(16.4%) patients of whom 8 (38%) had macrometastases, 7 (33%) micrometastases, and 6 (29%) ITCs. Of these 26 nodes, 7 (27%) were detected only by immunohistochemistry (6/128 patients: 4.6%). There was no false-negative No node metastases were found in 104/128 (81.2%) patients. Conclusions: SN detection supplied additional information in 39.8% of patients (51/128), either showing that drainage occurred via unusual pathways or detecting cancer spread via immunohistochemistry. Node dissection could have been avoided in the 104/128 patients with negative nodes, potentially decreasing treatment-associated morbidity. No significant financial relationships to disclose.
Maintenance pemetrexed (Pem) plus best supportive care (BSC) versus placebo (Plac) plus BSC: A randomized phase III study in advanced non-small cell lung cancer (NSCLC)
Authors: Belani C. P. , Brodowicz T. , Ciuleanu T. , Kim J. H. , Krzakowski M. , Laack E. , Wu Y. L. , Peterson P. , Krejcy K. , Zielinski C. 
Published: February 2017

CRA8000 Background: Pemetrexed's efficacy, favorable tolerability profile, and ease of administration provided a strong rationale for evaluation as maintenance therapy in patients (pts) with advanced NSCLC. We present the final analyses for all outcomes, including overall survival (OS), from a phase III study of Pem vs. Plac (Ciuleanu, J Clin Oncol 26, 2008, A 8011) in pts with stage IIIB/IV NSCLC who had not progressed on four cycles of platinum-based chemotherapy. Methods: In this double-blind trial, pts were randomized 2:1 to receive Pem (500 mg/m2, day 1) plus BSC or Plac plus BSC in 21-day cycles until disease progression. All pts received vitamin B12, folic acid, and dexamethasone. The final OS analysis was performed using an unadjusted Cox model. Overall α = 0.05 for PFS and OS. Results: In the 663 randomized pts (Pem 441: Plac 222), Pem resulted in significantly better OS (13.4 vs. 10.6 mos [HR 0.79, 95% CI: 0.65–0.95, P = 0.012]). As reported earlier, Pem also had better PFS (P <0.00001) and response (P <0.001) ( Table ). The improvements in PFS and OS were observed primarily in patients with non-squamous histology (PFS HR = 0.47 and OS HR = 0.70). Treatment by histology interaction for OS was significant (P = 0.038). Drug-related grade 3/4 toxicities were higher for Pem (16% vs 4%; P <0.001); specifically, fatigue (5% vs 0.5%) and neutropenia (2.9% vs. 0%). Grade 3/4 toxicities did not increase significantly in pts who received ≥6 and ≥10 cycles of Pem. There were no Pem-related deaths. Fewer pts in the Pem arm (51.5% vs 67.1%; P <0.001) received systemic post-discontinuation therapy. Conclusions: Pem maintenance therapy is well tolerated and offers superior OS and PFS compared with Plac, making it a new treatment paradigm for patients with advanced NSCLC who respond to initial therapy. This trial further validates that Pem has greater efficacy in patients with non-squamous histology. [Table: see text] [Table: see text]
Phase III, randomized, double-blind study of elesclomol and paclitaxel versus paclitaxel alone in stage IV metastatic melanoma (MM)
Authors: Hauschild A. , Eggermont A. M. , Jacobson E. , O'Day S. J. 
Published: February 2017

LBA9012 Background: Elesclomol is an investigational first-in-class oxidative stress inducer that increases oxidative stress in cancer cells leading to mitochondria-induced apoptosis. Methods: Patients (pts) with Stage IV MM, no prior chemotherapy, LDH μ 2× ULN were randomized (1:1) to either 213 mg/m2 elesclomol in combination with 80 mg/m2 paclitaxel (ELPAC) or 80 mg/m2 paclitaxel alone (P); both were given weekly ×3 followed by 1 week rest until disease progression. Pts were stratified by prior non-cytotoxic treatment, M1 grade, and LDH. The primary endpoint was PFS with >90% power to detect a 2-month improvement. The primary PFS analysis was planned once all pts had been enrolled and at least 164 PFS events had occurred. Results: 651 pts were enrolled between September 2007 and February 2009. Prognostic factors were generally well balanced. PFS analysis was based on investigator assessment of 411 pts (219 events). Median PFS was 3.5 m (95% CI 2.7–3.7) in ELPAC and 1.9 m (95% CI 1.9–3.3) in P [HR 0.88; 95% CI 0.67–1.16, p=0.3695]. The median number of cycles was 3 in ELPAC and 2 in P. Safety analysis showed increased signals on ELPAC including increased ≥Gr 3 AEs (N=405, 32.8% vs. 23.5%), increased AEs leading to death (N=405, 3.5% vs <1%) and increased overall deaths (N=651, 80 vs 53; 80% censored). Most common AEs in ELPAC were fatigue (32.8%), alopecia (31.3%) and nausea (27.9%). Conclusions: There was an improvement in PFS in the ELPAC arm, but it did not achieve statistical significance. In February 2009, the study was halted based on the recommendation of the DMC to unblind the study after the DMC observed increased deaths on the ELPAC arm. The DMC could not determine whether the observed increased deaths were treatment related or not. Of note, in this analysis there were no specific target organ toxicities attributable to ELPAC that could explain the imbalance of deaths. OS data continues to be collected to determine if the observed imbalance in OS persists as the data mature. [Table: see text]