bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Human Papillomavirus Types 16 and 18 mRNA in Peripheral Blood of Advanced Cervical Cancer Patients and Its Association With Prognosis
Authors: Tseng Chih-Jen , Pao Chia C. , Lin Jen-Daw , Soong Yung-Kuei , Hong Ji-Hong , Hsueh Swei 
Published: February 2017

PURPOSE: To evaluate the feasibility of detecting human papillomavirus E6 (HPVE6) gene mRNA in the peripheral blood of patients with locally advanced cervical cancer, and the relationship of the circulating HPV viral–specific mRNA with clinicopathologic factors and prognosis of locally advanced cervical cancer. PATIENTS AND METHODS: The presence of types 16 and 18 HPVE6 gene mRNA was determined by reverse transcription followed by nested polymerase chain reaction. Thirty-five patients with locally advanced cervical cancer who were positive for HPV type 16 or 18 DNA were included in the study. All patients received external-beam radiation therapy followed by intracavitary brachytherapy. RESULTS: Eighteen (51.4%) of 35 HPV DNA–positive cervical cancer patients had HPV-specific mRNA in their peripheral blood cells, compared with none of 17 HPV DNA–negative cervical cancer patients and none of 12 control volunteers. The presence of HPVE6 gene mRNA in peripheral blood was associated with bulky tumor volume (> 4 cm) and pelvic lymph node metastasis (tumor volume, P = .03; lymph node status, P = .03). After a median follow-up of 22 months, patients who were positive for peripheral-blood HPVE6 gene mRNA had a significantly higher risk of recurrence than those who were negative (10 of 18 v three of 17, P = .02; mean recurrent time, 20.7 months v 12.6 months, P = .02). There was also a statistically significant association of peripheral-blood HPVE6 gene mRNA positivity with distant metastasis (eight of 18 v one of 17; P = .01). CONCLUSION: Results of this study seem to suggest that the presence of HPVE6 gene mRNA in peripheral blood may provide an early marker that identifies patients who are at risk for metastasis.
Prospective Randomized Trial of Docetaxel Versus Mitomycin Plus Vinblastine in Patients With Metastatic Breast Cancer Progressing Despite Previous Anthracycline-Containing Chemotherapy
Authors: Nabholtz J.-M. , Senn H. J. , Bezwoda W. R. , Melnychuk D. , Deschênes L. , Douma J. , Vandenberg T. A. , Rapoport B. , Rosso R. , Trillet-Lenoir V. , Drbal J. , Molino A. , Nortier J.W.R. , Richel D. J. , Nagykalnai T. , Siedlecki P. , Wilking N. , Genot J. Y. , Hupperets P.S.G.J. , Pannuti F. , Skarlos D. , Tomiak E. M. , Murawsky M. , Alakl M. , Riva A. , Aapro M. 
Published: February 2017

PURPOSE: This phase III study compared docetaxel with mitomycin plus vinblastine (MV) in patients with metastatic breast cancer (MBC) progressing despite previous anthracycline-containing chemotherapy. PATIENTS AND METHODS: Patients (n = 392) were randomized to receive either docetaxel 100 mg/m2 intravenously (IV) every 3 weeks (n = 203) or mitomycin 12 mg/m2 IV every 6 weeks plus vinblastine 6 mg/m2 IV every 3 weeks (n = 189), for a maximum of 10 3-week cycles. RESULTS: In an intention-to-treat analysis, docetaxel produced significantly higher response rates than MV overall (30.0% v 11.6%; P < .0001), as well as in patients with visceral involvement (30% v 11%), liver metastases (33% v 7%), or resistance to previous anthracycline agents (30% v 7%). Median time to progression (TTP) and overall survival were significantly longer with docetaxel than MV (19 v 11 weeks, P = .001, and 11.4 v 8.7 months, P = .0097, respectively). Neutropenia grade 3/4 was more frequent with docetaxel (93.1% v 62.5%; P < .05); thrombocytopenia grade 3/4 was more frequent with MV (12.0% v 4.1%; P < .05). Severe acute or chronic nonhematologic adverse events were infrequent in both groups. Withdrawal rates because of adverse events (MV, 10.1%; docetaxel, 13.8%) or toxic death (MV, 1.6%; docetaxel, 2.0%) were similar in both groups. Quality-of-life analysis was limited by a number of factors, but results were similar in both groups. CONCLUSION: Docetaxel is significantly superior to MV in terms of response, TTP, and survival. The safety profiles of both therapies are manageable and tolerable. Docetaxel represents a clear treatment option for patients with MBC progressing despite previous anthracycline-containing chemotherapy.
Breast-Conserving Therapy: Proteases as Risk Factors in Relation to Survival After Local Relapse
Authors: Meijer-van Gelder Marion E. , Look Maxime P. , Vries Joan Bolt-de , Peters Harry A. , Klijn Jan G.M. , Foekens John A. 
Published: February 2017

PURPOSE: To evaluate whether cathepsin D, urokinase-type plasminogen activator (uPA), its inhibitor, plasminogen activator inhibitor-1 (PAI-1), or clinical factors can predict which patients are at risk for developing distant metastases after local recurrence (LR). PATIENTS AND METHODS: Of 1,630 patients treated with breast-conserving surgery and radiotherapy of the breast between 1980 and 1992, LR developed in 171 as a first event. From the available primary tumor tissues, we determined the cytosolic levels of cathepsin D, uPA and PAI-1. RESULTS: In patients with LR, a short (≤ 2 years) disease-free interval (DFI) and skin involvement of LR were associated with poor postrelapse distant metastasis-free survival (PR-DMFS, P = .001, both) and postrelapse overall survival (PR-OS; P < .0001 and P < .0002, respectively). The primary tumor levels of uPA and PAI-1 were elevated for patients with a short DFI (P < .01), but such a relation was not observed for patients with skin involvement. In univariate analyses, high levels of uPA and PAI-1 in the primary tumor were associated with poor PR-OS (P = .038 and P = .040, respectively) but not PR-DMFS. In Cox multivariate analyses for PR-DMFS and PR-OS, only a short DFI and skin involvement of the LR were independently associated with a poor clinical outcome. CONCLUSION: In patients treated with breast-conserving therapy who had LR as a first event, a short DFI and skin involvement were strong indicators for poor PR-DMFS and PR-OS. The proteases studied did not contribute significantly to the final multivariate model.
Cerebrospinal Fluid Asparagine Concentrations After Escherichia coli Asparaginase in Children With Acute Lymphoblastic Leukemia
Authors: Woo Michael H. , Hak Lawrence J. , Storm Michael C. , Gajjar Amar J. , Sandlund John T. , Harrison Patricia L. , Wang Bo , Pui Ching-Hon , Relling Mary V. 
Published: February 2017

PURPOSE: The CNS is an important sanctuary site in childhood acute lymphoblastic leukemia (ALL). CSF asparagine concentration reflects asparaginase systemic pharmacodynamics. We evaluated the time course of CSF asparagine depletion in children with ALL during and after a course of Escherichia coli asparaginase. PATIENTS AND METHODS: Thirty-one children (24 newly diagnosed and seven at relapse) received E coli asparaginase 10,000 IU/m2 intramuscularly three times weekly for six and nine doses, respectively, as part of multiagent induction chemotherapy. CSF asparagine levels were measured before, during, and after asparaginase dosing. RESULTS: The percentage of patients with undetectable (< 0.04 μmol/L) CSF asparagine was 3.2% (one of 31 patients) at baseline, 73.9% (17 of 23) during asparaginase therapy, and 56.3% (nine of 16) 1 to 5 days, 43.8% (seven of 16) 6 to 10 days, 20.0% (two of 10) 11 to 30 days and 0% (zero of 21) more than 30 days after asparaginase therapy. The proportion of patients with depleted CSF asparagine was higher during asparaginase therapy than at baseline (P < .001), 11 to 30 days (P = .003), and more than 30 days after asparaginase therapy (P < .001). Median CSF asparagine concentrations were 4.42 μmol/L before, less than 0.04 μmol/L during, and less than 0.04 μmol/L at 1 to 5 days, 1.63 μmol/L at 6 to 10 days, 1.70 μmol/L at 11 to 30 days, and 5.70 μmol/L at more than 30 days after asparaginase therapy, respectively. CSF depletion was more common in patients with low baseline CSF asparagine concentrations (P = .003). CONCLUSION: CSF asparagine concentrations are depleted by conventional doses of E coli asparaginase in the majority of patients, but they rebound once asparaginase therapy is completed.
Impact of Therapeutic Research on Informed Consent and the Ethics of Clinical Trials: A Medical Oncology Perspective
Authors: Daugherty Christopher K. 
Published: February 2017

PURPOSE: To create a more meaningful understanding of the informed consent process as it has come to be practiced and regulated in clinical trials, this discussion uses the experience gained from the conduct of therapeutic research that involves cancer patients.DESIGN: After an introduction of the ethical tenets of the consent process in clinical research that involves potentially vulnerable patients as research subjects, background that details the use of written consent documents and of the term “informed consent” is provided. Studies from the cancer setting that examine the inadequacies of written consent documents, and the outcome of the consent process itself, are reviewed. Two ethically challenging areas of cancer clinical research, the phase I trial and the randomized controlled trial, are discussed briefly as a means of highlighting many dilemmas present in clinical trials. Before concluding, areas for future research are discussed.RESULTS: Through an exclusive cancer research perspective, many current deficiencies in the informed consent process for therapeutic clinical trials can be critically examined. Also, new directions for improvements and areas of further research can be outlined and discussed objectively. The goals of such improvements and research should be prevention of further misguided or ineffective efforts to regulate the informed consent process.CONCLUSION: To ignore this rich and interesting perspective potentially contributes to continued misunderstanding and apathy toward fulfilling the regulatory and ethically obligatory requirements involved in an essential communication process between a clinician-investigator and a potentially vulnerable patient who is considering clinical trial participation.
Mastectomy or Lumpectomy? Helping Women Make Informed Choices
Authors: Whelan Timothy , Levine Mark , Gafni Amiram , Sanders Kenneth , Willan Andrew , Mirsky Douglas , Schnider Denise , McCready David , Reid Susan , Kobylecky Anna , Reed Kenneth 
Published: February 2017

PURPOSE: To develop an instrument to help clinicians inform their patients about surgical treatment options for the treatment of breast cancer and to evaluate the impact of the instrument on the clinical encounter.METHODS: We developed an instrument, called the Decision Board, to present information regarding the benefits and risks of breast-conserving therapy (lumpectomy plus radiation therapy) and mastectomy to women with early-stage breast cancer to enable them to express a preference for the type of surgery. Seven surgeons from different communities in Ontario administered the instrument to women with newly diagnosed clinical stage I or II breast cancer over an 18-month period. Patients and surgeons were interviewed regarding acceptability of the instrument. The rates of breast-conserving surgery performed by surgeons before and after the introduction of the instrument were compared.RESULTS: The Decision Board was administered to 175 patients; 98% reported that the Decision Board was easy to understand, and 81% indicated that it helped them make a decision. The average score on a true/false test of comprehension was 11.8 of 14 (84%) (range, 6 to 14). Surgeons found the Decision Board to be helpful in presenting information to patients in 91% of consultations. The rate of breast-conserving surgery decreased when the Decision Board was introduced (88% v 73%, P = .001)CONCLUSION: The Decision Board is a simple method to improve communication and facilitate shared decision making. It was well accepted by patients and surgeons and easily applied in the community.
S100-Beta, Melanoma-Inhibiting Activity, and Lactate Dehydrogenase Discriminate Progressive From Nonprogressive American Joint Committee on Cancer Stage IV Melanoma
Authors: Deichmann Martin , Benner Axel , Bock Michael , Jäckel Andreas , Uhl Karen , Waldmann Volker , Näher Helmut 
Published: February 2017

PURPOSE: Monitoring advanced malignant melanoma, serum levels of S100-beta (S100β) and melanoma-inhibiting activity (MIA) were assessed for the ability to discriminate progressive from nonprogressive disease. S100β and MIA were supposed to be superior to conventional variables, such as lactate dehydrogenase (LDH) level. PATIENTS AND METHODS: Seventy-one patients with stage IV malignant melanoma according to the criteria of the American Joint Committee on Cancer (AJCC) were included in the study. Results of restaging examinations were used as an independent reference standard for diagnosing progressive disease, and S100β, MIA, LDH level, and erythrocyte sedimentation rate (ESR) were determined in venous blood just before restaging. Sensitivities and specificities of the parameters were calculated by logistic regression analysis. Discrimination ability was assessed by Somers' Dxy rank correlation and the area under the receiver-operating characteristic curve (ROC-AUC). RESULTS: All tested serum parameters were significantly elevated in patients with progressive disease. The highest sensitivities according to the established thresholds were found for S100β and MIA (91% and 88%, respectively). LDH had the highest specificity (92%). ESR was dropped from the analysis because of low specificity. In calculating Somers' Dxy and ROC-AUC values, S100β, MIA, and LDH showed high discrimination ability. By multiple logistic regression, LDH was identified to be the only statistically significant marker for progressive disease. S100β and MIA did not provide additional significant information because of their high correlation with LDH with respect to clinical outcome. CONCLUSION: Elevated serum levels of S100β, MIA, and LDH indicate current disease progression in AJCC stage IV melanoma. LDH was the most relevant overall parameter.
Maximized Reduction of Primary Breast Tumor Size Using Preoperative Chemotherapy With Doxorubicin and Docetaxel
Authors: von Minckwitz Gunter , Costa Serban Dan , Eiermann Wolfgang , Blohmer Jens-Uwe , Tulusan Augustinos Harjanto , Jackisch Christian , Kaufmann Manfred 
Published: February 2017

PURPOSE: To assess the toxicity and efficacy of preoperative chemotherapy with doxorubicin and docetaxel in patients with primary operable breast cancer. PATIENTS AND METHODS: Forty-two patients with histologically confirmed primary breast cancer tumors of at least 2 cm in diameter received doxorubicin (50 mg/m2 intravenously [IV] over 15 minutes) and docetaxel (75 mg/m2 IV over 1 hour) every 14 (24 patients) or 21 (18 patients) days for four cycles. RESULTS: The median size of the primary tumor decreased significantly, from 4 cm (range, 2 to 10 cm) to 2 cm (range, 0 to 5 cm) on physical examination and from 3.4 cm (range, 1 to 8 cm) to 1.8 cm (range, 0 to 4 cm) on sonography (P < .001). The overall response rate as assessed by physical examination was 93%, and complete remission of the primary tumor occurred in 33% of patients. The remission rate as assessed by sonographic measurement was 67%. Two patients (5%) had histologically confirmed complete responses. Sonography was more reliable than palpation in predicting histologically determined response. No grade 4 toxicity was noted, and grade 3 toxicity was reported with alopecia (95%), lethargy (17%), loss of appetite (10%), stomatitis (7%), leukopenia (5%), skin desquamation (5%), infection (5%), motor neuropathy (2%), and nausea (2%). The 3-week schedule was associated with less toxicity than the 2-week schedule. CONCLUSION: Preoperative combination chemotherapy with doxorubicin and docetaxel is highly effective and feasible in primary operable breast cancer.
Telomerase Is a Highly Sensitive and Specific Molecular Marker in Fine-Needle Aspirates of Breast Lesions
Authors: Poremba Christopher , Shroyer Kenneth R. , Frost Michael , Diallo Raihanatou , Fogt Franz , Schäfer Karl-Ludwig , Bürger Horst , Shroyer A. Laurie , Dockhorn-Dworniczak Barbara , Boecker Werner 
Published: February 2017

PURPOSE: Telomerase has been detected in a majority of human malignant tumors, making telomerase activity (TA) one key difference between mortal and immortal cells. In this study, we evaluated in blind-trial fashion the association of TA with cytologic and final clinical/pathologic diagnosis in fine-needle aspirates (FNAs) of breast lesions. MATERIALS AND METHODS: In 172 FNAs, including 80 samples that were cytologically malignant, 18 that were atypical but not diagnostic for malignancy, and 74 that were cytologically benign, TA was determined by a modified nonradioactive telomeric repeat amplification protocol (TRAP) assay. Final diagnosis was made by pathologic examination of follow-up surgical material available for all the cytologically malignant samples, a majority of the cytologically atypical samples, and a portion of the cytologically benign samples. RESULTS: TA was detected in 85 of 172 samples. Comparison of the cytologic and histologic diagnoseswith TA showed that 80 of 87 samples from patients with breast cancer were telomerase-positive, resulting in a sensitivity of 92%. TA was found in four of five FNAs from carcinomas that were considered cytologically atypical but not diagnostic for malignancy. Eighty of 85 samples from patients with benign breast lesions were telomerase-negative, revealing a specificity of 94%. The five positive cases in this group were all fibroadenomas with low TA. Among the 18 cases with a cytologic diagnosis of atypia, there was a strong positive relationship between TRAP findings and histologic diagnosis. CONCLUSION: The detection of TA in FNAs of breast lesions is a highly sensitive and specific marker of malignancy and may be used as an adjunct in cases with an equivocal cytologic diagnosis.
Investigation of Endometrial Abnormalities in Asymptomatic Women Treated With Tamoxifen and an Evaluation of the Role of Endometrial Screening
Authors: Love C.D.B. , Muir B. B. , Scrimgeour J. B. , Leonard R. C.F. , Dillon P. , Dixon J. M. 
Published: February 2017

PURPOSE: Tamoxifen is the most commonly prescribed adjuvant therapy for women with breast cancer. It has agonist activity on the endometrium and is associated with an increased risk of endometrial cancer. The aim of this study was to evaluate whether screening with transvaginal ultrasound (TV USS) with or without hysteroscopy is worthwhile. PATIENTS AND METHODS: A total of 487 women with breast cancer, 357 treated with tamoxifen and 130 controls, were screened with TV USS, and endometrial thickness was measured. Women with thickened endometrium underwent outpatient hysteroscopy. RESULTS: Length of time on tamoxifen ranged from 5 to 191 months (mean, 66 months), and endometrial thickness ranged from 1 to 38 mm (mean, 7.3 mm). Women treated with tamoxifen had significantly thicker endometrium than did controls (P < .0001). There was a statistically significant (P < .0001) positive correlation between length of time on tamoxifen and endometrial thickness. One hundred forty-five women had endometrium greater than 5 mm on USS, and 134 underwent successful outpatient hysteroscopy, 61 of whom had atrophic endometrium, resulting in a 46% false-positive scan rate. The remaining women all had benign features to explain the USS findings. CONCLUSION: TV USS detects a high incidence (41%) of apparent endometrial thickening in women treated with tamoxifen, although 46% had atrophic endometrium on further assessment, and none of the remaining asymptomatic women had significant lesions. Length of time on tamoxifen relates to endometrial thickening as measured by TV USS. TV USS is a poor screening tool because of the high false-positive rate. The low frequency of significant findings suggests that endometrial screening in asymptomatic women is not worthwhile.
Gemcitabine as Second-Line Treatment for Advanced Non–Small-Cell Lung Cancer: A Phase II Trial
Authors: Crinò Lucio , Mosconi Anna Maria , Scagliotti Giorgio , Selvaggi Giovanni , Novello Silvia , Rinaldi Massimo , Della Giulia Marina , Gridelli Cesare , Rossi Antonio , Calandri Cesare , De Marinis Filippo , Noseda Mariantonietta , Tonato Maurizio 
Published: February 2017

PURPOSE: To investigate the activity and toxicity of gemcitabine as a single agent in patients with advanced non–small-cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. PATIENTS AND METHODS: From November 1995 to October 1997, 83 patients with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m2 once a week for 3 weeks every 28 days. Responses were assessed every two treatment courses. The median age of the patients was 63 years; Eastern Cooperative Oncology Group performance status was 0 to 1 in 62 patients and 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and one stage IIIA). RESULTS: Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well tolerated: grade 2 to 3 (World Health Organization standardized response criteria) leukopenia and thrombocytopenia occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients, and peripheral edema in 5% of patients. Nausea and vomiting were present in 16% of patients. CONCLUSION: In this experience, gemcitabine showed significant activity without relevant toxicity, mainly in patients who were previously responsive to chemotherapy. This suggests a possible role for gemcitabine as a second-line treatment in patients who had a previous response or achieved stable disease with a platinum-containing regimen.
Smoking Before Surgery Predicts Poor Long-Term Survival in Patients With Stage I Non–Small-Cell Lung Carcinomas
Authors: Fujisawa Takehiko , Iizasa Toshihiko , Saitoh Yukio , Sekine Yasuo , Motohashi Shin-ichiro , Yasukawa Tomohisa , Shibuya Kiyoshi , Hiroshima Kenzo , Ohwada Hidemi 
Published: February 2017

PURPOSE: The majority of lung carcinoma patients requiring resection have smoking habits prior to surgical treatment, and the correlation of smoking with postoperative complications is well known. However, few studies have investigated the correlation between long-term survival and cigarette smoking in patients with primary, resected lung carcinoma. We analyzed the relationship between clinical factors, including cigarette smoking before surgery, and 10-year survival in stage I non–small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Cigarette smoking habit and other factors influencing either the overall survival or the disease-specific survival rates of patients with stage I primary, resected NSCLC were evaluated according to the Cox proportional hazards model using a total of 369 patients with stage I–NSCLC. RESULTS: Comparison of the cause of death in patients with 30 or more pack-years and patients with less than 30 pack-years showed significant differences in the prevalence of recurrent disease and onset of nonmalignant disease. Multivariate analysis demonstrated significant correlations between overall survival and age and pack-years. Disease-specific survival showed significant correlations with age, tumor classification, and visceral pleural invasion. CONCLUSION: Smoking pack-years is an important clinical prognostic factor in evaluating overall long-term survival in patients with stage I primary, resected NSCLC.