bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzyme-linked immunoabsorbent assay-detected p53 protein accumulation: a prognostic factor in a large breast cancer cohort.
Authors: Levesque M A , Yu H , Clark G M , Diamandis E P 
Published: February 2017

PURPOSE This study was designed to evaluate whether patients with an unfavorable breast cancer prognosis could be identified by p53 protein overexpression detected by a quantitative enzyme-linked immunoabsorbent assay (ELISA). PATIENTS AND METHODS Extracts from 998 breast carcinomas were assayed for p53 protein by an ELISA that used both DO-1 monoclonal and CM-1 polyclonal antibodies. Relative risks (RRs) for cancer relapse and death after 6 years of follow-up for patients with p53-positive tumors based on different dichotomization criteria were determined by multivariate Cox regression, adjusted for patient age, tumor size, S-phase fraction, estrogen (ER) and progesterone (PR) receptor concentrations, DNA ploidy, and lymph node metastases. Disease-free (DFS) and overall (OS) survival probabilities of p53-positive and p53-negative groups, using a median cutoff, were also estimated by the Kaplan-Meier method and the log-rank test. These analyses were performed for all patients and for subgroups defined by ER status, node status, and primary postoperative treatment. RESULTS Univariate analysis showed that p53 concentrations that exceeded the median indicated significantly increased risks for relapse (P < .01) and death (P = .02). Multivariate analyses confirmed these observations (RR = 1.40; P = .02 for DFS and RR = 1.50; P < .01 for OS) and showed trends for increasing risks for relapse (P = .02) and death (P = .06) when p53 was considered as a four-level categoric variable, and identified p53 positivity as a significant predictor of outcome in node-positive patients (RR = 1.67; P < .01 and RR = 2.10; P < .01 for DFS and OS, respectively), ER-positive patients (RR = 1.45; P = .02 and RR = 1.50; P = .01 for DFS and OS, respectively), and in patients treated with chemotherapy (RR = 1.73; P = .04 for relapse and RR = 2.04; P = .03 for death). CONCLUSION Assessment of p53 overexpression by ELISA, easily incorporated into the routine biochemical work-up of breast tumors, may be an independent predictor of reduced survival of breast cancer patients.
Programs for adult survivors of childhood cancer.
Authors: Oeffinger K C , Eshelman D A , Tomlinson G E , Buchanan G R 
Published: February 2017

PURPOSE The potential for late effects of treatment necessitates long-term monitoring of adult survivors of childhood cancer. The purpose of this study was to determine how institutions follow up young adult survivors of pediatric malignancy. Specifically, we were interested in the types of health care providers who follow up these patients, how the follow-up is administered, and what barriers to follow-up have been encountered. METHODS A 16-item questionnaire was mailed to the 219 members of the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG). The survey consisted of four categories of questions that asked for information regarding the existence of a program to follow up young adults, the setting of the program, routine activities of the program, and commonly encountered barriers to care. RESULTS One hundred eighty-two members returned the survey (83% response rate). Fifty-three percent of the respondents have a long-term follow-up clinic at their institution. Whereas 44% have a mechanism for following up adult survivors, only 15% of the programs have established a formal database for adults. Nearly all the programs (93%) use a pediatric oncologist. Although an adult oncologist assists in 13% of the programs, primary care physicians are uncommonly (8%) involved. CONCLUSION Few programs focus on the long-term health care needs of adult survivors of childhood cancer. The majority of existing programs are in pediatric institutions, without significant input from adult-oriented, generalist health care providers.
Detection of K-ras point mutations in sputum from patients with adenocarcinoma of the lung by point-EXACCT.
Authors: Somers V A , Pietersen A M , Theunissen P H , Thunnissen F B 
Published: February 2017

PURPOSE Kirsten ras (K-ras) point mutations are found in 30% to 56% of pulmonary adenocarcinomas by means of highly sensitive techniques. Recently, the Point-EXACCT (point mutation detection using exonuclease amplification coupled capture technique) method was described, which detected one cell with a mutation in 15,000 normal cells. The aim of this study was to examine whether K-ras point mutations could be found with this rapid method in the sputum of patients with adenocarcinoma of the lung. PATIENTS AND METHODS DNA from paraffin-embedded adenocarcinoma and corresponding sputum samples were analyzed for mutations of the K-ras gene. Twenty-eight biopsy specimens and 54 sputum samples of 22 patients were used for amplification and K-ras codon 12 point mutation detection. RESULTS In 11 of 22 patients (50%), a mutation in K-ras codon 12 was shown in the tumor sample. In five of 11 patients (45%) with a K-ras mutation in the tumor, the same type of mutation was identified in at least one sputum sample. A mutation could not be detected in any of the sputum samples from patients with a K-ras-negative tumor. Time between K-ras point mutation detection in sputum and clinical diagnosis of lung cancer varied from 1 month to almost 4 years. In two of the five patients with K-ras-positive sputum specimens, malignant cells were found with cytologic examination. CONCLUSION Point-EXACCT is suitable for the detection of K-ras point mutations in sputum samples of patients with adenocarcinoma of the lung. This approach may be an important adjunct to cytology in the early diagnosis of lung cancer.
Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma.
Authors: Linderholm B , Tavelin B , Grankvist K , Henriksson R 
Published: February 2017

PURPOSE The prognostic value of vascular endothelial growth factor (VEGF) protein, known to stimulate endothelial growth and angiogenesis, was evaluated in node-negative breast carcinoma (NNBC) and compared with established prognostic factors. PATIENTS AND METHODS In 525 consecutive patients with primary invasive NNBC (T1-2N0M0; tumor, node, metastasis stage), of whom 500 patients did not receive any systemic therapy, the cytosolic levels of VEGF165 were measured by using a quantitative enzyme-linked immunosorbent assay. The median follow-up was 46 months. Univariate and multivariate analyses were performed. RESULTS VEGF level was significantly inversely correlated with estrogen receptor (ER) positivity but positively associated with tumor size and histologic grade. Patients with VEGF levels above the median value (2.40 pg/microg of DNA) showed a significantly shorter survival time (P=.0012) than patients with levels less than the median value, also when analyzed as a continuous variable (P=.0277). Tumor size, grade, and ER expression were all statistically significant for overall survival in univariate analyses (P=.0069, P=.014, and P < .001, respectively). Multivariate analysis showed that VEGF level was the strongest predictor of overall survival (P=.0199). Histologic grade was also an independent predictor of survival (P=.0477). Among the 381 patients with ER-positive tumors, a group in general considered to have a good prognosis, we found a significant reduction in survival for those with levels of VEGF greater than the median value (P=.0009). CONCLUSION The results suggest that the level of VEGF165 protein is an independent, strong prognostic factor for survival in patients with NNBC, especially in the subgroup of patients with ER positivity. Thus, cytosolic VEGF165 might be useful to select patients for adjuvant systemic therapy.
A single scale for comparing dose-intensity of all chemotherapy regimens in breast cancer: summation dose-intensity.
Authors: Hryniuk W , Frei E , Wright F A 
Published: February 2017

PURPOSE To construct a single scale for comparing the dose-intensity of all chemotherapy regimens in breast cancer. MATERIALS AND METHODS First-line single-agent trials in metastatic disease were reviewed. The unit dose-intensity (UDI) that was required to produce a 30% complete response plus partial response (CR + PR) rate was determined for each drug. Randomized trials were then analyzed that prospectively tested dose-intensity. The dose-intensities of the drugs in each arm were expressed as fractions of their UDIs and added together. This yielded each arm's summation dose-intensity (SDI), which was then correlated with treatment outcomes. RESULTS In the single-agent trials, dose-response relationships were linear when the studies covered a range of dose-intensities. In the randomized trials that tested dose-intensity in metastatic disease, response rates and median survival correlated linearly with the SDIs of the treatment arms. An increment of one SDI unit increased CR + PR rate by approximately 30%, CR rate by 10%, and median survival by 3.75 months. Metastatic disease trials were negative if the difference between the arms was less than 0.54 SDI units. Adjuvant trials that tested a dose-intensity difference of less than 0.65 SDI units were also negative. CONCLUSION A single-agent dose-response database can be derived from historic literature that enables comparison of the dose-intensity of all combination regimens on one scale. The dose-intensity increase required to improve outcome can then be identified in earlier trials that tested that variable. SDI methodology should be tested prospectively in contemporary patients, and may be useful in guiding dosage increases beyond the conventional range.
Hodgkin's Disease Survivors More Fatigued Than the General Population
Authors: Loge Jon Håvard , Abrahamsen Arne Foss , Ekeberg Øivind , Kaasa Stein 
Published: February 2017

PURPOSE: To estimate the level of fatigue and frequency of fatigue cases among Hodgkin's disease survivors (HDS) and compare them with normative data from the general population.PATIENTS AND METHODS: A cross-sectional follow-up study was done of 557 HDS (age range, 19 to 74 years) treated at the Norwegian Radium Hospital from 1971 to 1991. The sample was approached by mail, and their data were compared with normative data from 2,214 controls (age range, 19 to 74 years) representative of the general Norwegian population. Of the 557 HDS, 459 (82%) responded. The mean age (± SD) at the time of study was 44 ± 12 years, and the mean observation time was 12 ± 6 years. The Fatigue Questionnaire (11 items) measures physical and mental fatigue. Two systems of scoring were used, dichotomized (0, 0, 1, and 1) and Likert (0, 1, 2, and 3). Total fatigue (TF) constitutes the sum of all the Likert scores. Caseness was defined as a total dichotomized score of ≥4 and fatigue that lasted 6 months or longer.RESULTS: The HDS had significantly higher levels of TF than the controls (14.3 v 12.2) (P < .001). Fatigue among the HDS equaled that of the controls in poorest health. More HDS (61%) than controls (31%) reported fatigue symptoms lasting 6 months or longer (P < .001). Fatigue cases were more frequent among HDS (men, 24%; women, 27%) than among the controls (men, 9%; women, 12%) (P < .001). Disease stage/substage IB/IIB predicted fatigue caseness (P = .03). No significant associations were found between treatment characteristics and fatigue.CONCLUSION: Hodgkin's disease survivors are considerably more fatigued than the general population and report fatigue of a substantially longer duration.
Polymerase Chain Reaction-Based Detection of Circulating Melanoma Cells as an Effective Marker of Tumor Progression
Authors: Palmieri Giuseppe , Strazzullo Maria , Ascierto Paolo A. , Satriano Sabrina M.R. , Daponte Antonio , Castello for the Melanoma Cooperative Group Giuseppe 
Published: February 2017

PURPOSE: Reverse transcriptase (RT) polymerase chain reaction (PCR) with multiple markers has been demonstrated to be highly sensitive in detecting circulating cells from patients with malignant melanoma (MM). We evaluated the clinical significance of the presence in peripheral blood of specific PCR-positive mRNA markers as an expression of circulating melanoma cells. PATIENTS AND METHODS: Total cellular RNA was obtained from the peripheral blood of 235 patients with either localized (n = 154) or metastatic (n = 81) melanoma. We performed RT-PCR using tyrosinase, p97, MUC18, and MelanA/MART1 as gene markers. The PCR products were analyzed by gel electrophoresis and Southern blot hybridization. In addition, 20 healthy subjects and 21 patients with nonmelanoma cancer were used as negative controls. RESULTS: Although detected at various levels among assessable patients, each mRNA marker was significantly correlated with disease stage. A significant correlation with disease stage was demonstrated for patients who were positive to all four markers (P < .0001) or to at least three markers (P < .001). Univariate analysis showed a significant correlation between risk of recurrence (evaluated in stage I, II, and III patients) and increasing number of PCR-positive markers (P = .0002). Logistic regression multivariate analysis indicated that each single marker (except tyrosinase) and, more especially, the presence of four PCR-positive markers remained statistically independent prognostic factors for tumor progression. CONCLUSION: Our data establish the existence of a significant correlation among clinical stages, tumor progression, and presence of circulating melanoma-associated antigens in peripheral blood of MM patients. Preliminary assessment of a subset of patients with a higher risk of recurrence needs longer follow-up and further studies to define the role of RT-PCR in monitoring MM patients.
Clinical Relevance of Expression of the CIP/KIP Cell-Cycle Inhibitors p21 and p27 in Laryngeal Cancer
Authors: Pruneri Giancarlo , Pignataro Lorenzo , Carboni Nadia , Buffa Roberto , Di Finizio Devrim , Cesana Bruno Mario , Neri Antonino 
Published: February 2017

PURPOSE: To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS: We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had ≤ 10% of p21 and ≤ 50% of p27 immunoreactive neoplastic cells. RESULTS: In 41 cases (31.1%), p21 was expressed in ≤ 10% of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 10% of neoplastic cells. In 11 cases (8.3%), p27 was expressed in less than 5% of neoplastic cells; in 39 cases (29.6%), it was expressed in 5% to 50% of neoplastic cells; and in 82 cases (62.1%), it was expressed in more than 50% of the neoplastic cells. Low levels of p21 expression were associated with poor histologic differentiation and lymph node metastases. Low levels of p27 expression were associated with tumor extension and advanced clinical stage. Expression of p21 and p27 was not correlated with p53 gene status, and low p27 expression was more frequently detected in the cyclin D1–positive cases, with a borderline level of statistical significance. At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates. At multivariate analysis, high cyclin D1 expression and low p27 expression were the only significant covariates. The patients with a cyclin D1+/p27− phenotype had the poorest disease-free and overall survival rates. CONCLUSION: Our study provides evidence that the immunohistochemical evaluation of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma.
Prognostic Importance of the Standardized Uptake Value on 18F-Fluoro-2-Deoxy-Glucose–Positron Emission Tomography Scan in Non–Small-Cell Lung Cancer: An Analysis of 125 Cases
Authors: Vansteenkiste Johan F. , Stroobants Sigrid G. , Dupont Patrick J. , De Leyn Paul R. , Verbeken Erik K. , Deneffe Georges J. , Mortelmans Luc A. , Demedts Maurits G. 
Published: February 2017

PURPOSE: The amount of radio-labeled 18F-fluoro-2-deoxy-glucose (FDG) uptake, a measurement of the increased glucose metabolism of non–small-cell lung cancer (NSCLC) cells, has recently been correlated with proliferation capacity. The Standardized Uptake Value (SUV), a semi-quantitative measurement of FDG uptake on positron emission tomography (PET) scan, could thus be of prognostic significance. PATIENTS AND METHODS: We analyzed the follow-up of 125 potentially operable NSCLC patients, previously included in three of our prospective PET protocols. Performance status, maximal tumor diameter, tumor-cell type, SUV, and final staging were analyzed for their possible association with survival. RESULTS: Sixty-five patients had stage I or II NSCLC, 37 had stage IIIA, and 23 had stage IIIB. Treatment was complete resection in 91 cases. In a univariate analysis, performance status (P = .002), stage (P = .001), tumor diameter (P = .06), tumor-cell type (P = .03), and SUV greater than 7 (P = .001) were correlated with survival. For SUV, group dichotomy with a cut-off SUV of 7 had the best discriminative value for prognosis, both in the total and surgical cohort. A multivariate Cox analysis identified performance status (P = .02), stage (P = .01), and SUV (P = .007) as important for the prognosis. In the surgical group, patients with a resected tumor less than 3 cm had an expected 2-year survival of 86%, if the SUV was below 7, and 60%, if above 7. Nearly all resected tumors larger than 3 cm had SUV's greater than 7 and an expected 2-year survival of 43%. CONCLUSION: We conclude that the FDG uptake in primary NSCLC on PET has an important prognostic value and could be complementary to other well-known factors in the decision on adjuvant treatment protocols.
Acute Myelogenous Leukemia After Treatment for Malignant Germ Cell Tumors in Children
Authors: Schneider Dominik T. , Hilgenfeld Elisabeth , Schwabe Dirk , Behnisch Wolfgang , Zoubek Andreas , Wessalowski Rüdiger , Göbel Ulrich 
Published: February 2017

PURPOSE: To identify the long-term sequelae of therapy for malignant germ cell tumors (GCTs). PATIENTS AND METHODS: Between 1980 and 1998, 1,132 patients were prospectively enrolled onto the German nontesticular GCT studies. A total of 442 patients received chemotherapy using combinations of the drugs cisplatin, ifosfamide, etoposide, vinblastine, and bleomycin, and 174 patients were treated with a combination of chemotherapy and radiotherapy. Median follow-up duration was 38 months (range, 6 to 199 months). RESULTS: Six patients developed therapy-related acute myelogenous leukemia (t-AML). There was no t-AML among patients treated with surgery (n = 392) or radiotherapy only (n = 124). The Kaplan-Meier estimates of the cumulative incidence (at 10 years) of t-AML were 1.0% for patients treated with chemotherapy (three of 442) and 4.2% for patients treated with combined chemotherapy and radiotherapy (three of 174). Notably, four of these six patients had been treated according to a standard protocol with modest cumulative chemotherapy doses. Five patients had received less than 2 g/m2 epipodophyllotoxins, and four patients had received less than 20 g/m2 ifosfamide. Four patients presented with AML, two with myelodysplasia in transformation to AML. In five patients, cytogenetic aberrations were found, four of which were considered characteristic for t-AML. Four patients died despite antileukemic therapy. One patient is alive but suffered a relapse of his GCT, and one patient is alive and well. No secondary solid neoplasm was observed. CONCLUSION: In patients with AML after treatment for GCT, several pathogenetic mechanisms must be considered. AML might evolve from a malignant transformation of GCT components without any influence of the chemotherapy. On the other hand, the use of alkylators and topoisomerase II inhibitors is associated with an increased risk of t-AML. Future studies will show if the reduction of treatment intensity in the current protocol reduces the risk of secondary leukemia in these patients.
Phase II Trial of Weekly Irinotecan Plus Cisplatin in Advanced Esophageal Cancer
Authors: Ilson David H. , Saltz Leonard , Enzinger Peter , Huang Ying , Kornblith Alice , Gollub Marc , O'Reilly Eileen , Schwartz Gary , DeGroff Julia , Gonzalez Gladys , Kelsen David P. 
Published: February 2017

PURPOSE: To evaluate the response, toxicity, survival, and quality of life in patients with unresectable or metastatic esophageal cancer treated with weekly irinotecan and cisplatin. PATIENTS AND METHODS: Thirty-five patients with metastatic or unresectable esophageal adenocarcinoma (23 patients) or squamous cell carcinoma (12 patients) were treated. No prior chemotherapy was allowed. The majority of patients had metastatic and bidimensionally measurable disease (34 patients each [97%]). Patients were treated with cisplatin 30 mg/m2 and irinotecan 65 mg/m2, repeated weekly for 4 weeks, followed by a 2-week rest period. Treatment was recycled every 6 weeks. Degree of dysphagia relief was monitored, and quality of life was measured prospectively using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 and Functional Assessment of Cancer Therapy–General instruments. RESULTS: Thirty-five patients were assessable for response and toxicity. Major objective responses were observed in 20 patients (57%; 95% confidence interval, 41% to 73%), including two complete responses (6%). Similar response rates were observed for adenocarcinoma (12 of 23 patients; 52%) and squamous carcinoma (eight of 12 patients; 66%). The median duration of response was 4.2 months (range, 1 to 8.8+ months). Median actuarial survival was 14.6 months (range, 1 to 15.2+ months). In 20 patients with dysphagia assessable at baseline, 18 (90%) noted either improvement or resolution of dysphagia on chemotherapy. Global quality of life improved in responding patients, primarily because of improvements in pain, emotional state, and relationships with family and friends. Toxicity was relatively mild and included only three patients (9%) with grade 4 neutropenia and four (11%) with grade 3 diarrhea. There were no treatment-related deaths. CONCLUSION: The combination of weekly cisplatin plus irinotecan had significant activity in metastatic esophageal carcinoma and resulted in significant relief of dysphagia. The regimen was well tolerated, with acceptable myelosuppression and rare treatment-related diarrhea. Further evaluation of the combination of weekly irinotecan and cisplatin, including the addition of other agents to this regimen, is indicated.