bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of Epithelial Ovarian Cancer Recurrence in Patients With Rising Serum CA-125 Levels Within the Normal Range
Authors: Santillan Antonio , Garg Ruchi , Zahurak Marianna L. , Gardner Ginger J. , Giuntoli Robert L. , Armstrong Deborah K. , Bristow Robert E. 
Published: December 2005

Purpose To evaluate the risk of epithelial ovarian cancer (EOC) recurrence in patients with rising serum cancer antigen 125 (CA-125) levels that remain below the upper limit of normal (< 35 U/mL). Patients and Methods All patients treated for EOC between September 1997 and March 2003 were identified and screened retrospectively for the following: (1) elevated serum CA-125 at time of diagnosis, (2) complete clinical and radiographic response (CR) to initial treatment with normalization of serum CA-125, (3) at least three serial serum CA-125 determinations that remained within the normal range, and (4) clinical and/or radiographic determination of disease status at the time of last follow-up or recurrence. For statistical analyses, univariate regression models were used to compare absolute and relative changes in CA-125 levels among patients with recurrent disease and those without EOC recurrence. Results A total of 39 patients satisfied study inclusion criteria; 22 patients manifested EOC recurrence at a median interval from complete response of 11 months. The median follow-up time from complete response to last contact was 32 months for the 17 patients in the no recurrence group. A relative increase in CA-125 of 100% (odds ratio [OR] = 23.7; 95% CI, 2.9 to 192.5; P = .003) was significantly predictive of recurrence. From baseline CA-125 nadir levels, an absolute increase in CA-125 of 5 U/mL (OR = 8.4; 95% CI, 2.2 to 32.6; P = .002) and 10 U/mL (OR = 71.2; 95% CI, 4.8 to > 999.9; P = .002) were also significantly associated with the likelihood of concurrent disease recurrence. Conclusion Among patients with EOC in complete clinical remission, a progressive low-level increase in serum CA-125 levels is strongly predictive of disease recurrence.
14-3-3σ Methylation in Pretreatment Serum Circulating DNA of Cisplatin-Plus-Gemcitabine-Treated Advanced Non–Small-Cell Lung Cancer Patients Predicts Survival: The Spanish Lung Cancer Group
Authors: Ramirez José Luis , Rosell Rafael , Taron Miquel , Sanchez-Ronco Maria , Alberola Vicente , de las Peñas Ramon , Sanchez José Miguel , Moran Teresa , Camps Carlos , Massuti Bartomeu , Sanchez José Javier , Salazar Fernanda , Catot Silvia 
Published: December 2005

Purpose Survival in patients with advanced non–small-cell lung cancer (NSCLC) who are treated with platinum-based chemotherapy is rather variable. Methylation-dependent transcriptional silencing of 14-3-3σ, a major G2-M checkpoint control gene, could be a predictor of longer survival. Patients and Methods A sensitive methylation-specific polymerase chain reaction assay was used to evaluate 14-3-3σ methylation status in pretreatment serum DNA obtained from 115 cisplatin-plus-gemcitabine–treated advanced NSCLC patients. Results 14-3-3σ methylation was observed in all histologic types of 39 patients (34%). After a median follow-up of 9.8 months, median survival was significantly longer in the methylation-positive group (15.1 v 9.8 months; P = .004). Median time to progression was 8 months in the methylation-positive group and 6.3 months in the methylation-negative group (log-rank test, P = .027). A multivariate Cox regression model identified only 14-3-3σ methylation status and Eastern Cooperative Oncology Group performance status as independent prognostic factors for survival. In an exploratory analysis, median survival for 22 methylation-positive responders has not been reached, whereas survival was 11.3 months for 29 methylation-negative responders (P = .001). Conclusion Methylation of 14-3-3σ is a new independent prognostic factor for survival in NSCLC patients receiving platinum-based chemotherapy. It can be reliably and conveniently detected in the serum, thus obviating the need for tumor tissue analysis.
Outcome After Pathologic Complete Eradication of Cytologically Proven Breast Cancer Axillary Node Metastases Following Primary Chemotherapy
Authors: Hennessy Bryan T. , Hortobagyi Gabriel N. , Rouzier Roman , Kuerer Henry , Sneige Nour , Buzdar Aman U. , Kau Shu Wan , Fornage Bruno , Sahin Aysegul , Broglio Kristine , Singletary S. Eva , Valero Vicente 
Published: December 2005

Purpose Pathologic complete remission (pCR) of primary breast tumors after primary chemotherapy (PCT) is associated with higher relapse-free survival (RFS) and overall survival (OS) rates. The purpose of this study was to determine long-term outcome in patients achieving pCR of cytologically proven axillary lymph node (ALN) metastases. Methods Patients with cytologically documented ALN metastases were treated in five prospective PCT trials. After surgery, patients were subdivided into those with and without residual ALN carcinoma. Survival was calculated by the Kaplan-Meier method. Results Of 925 patients treated, 403 patients had cytologically confirmed ALN metastases. Eighty-nine patients (22%) achieved ALN pCR after PCT. Compared with the group without ALN pCR, 5-year OS and RFS were improved in patients achieving ALN pCR (93% [95% CI, 87.5 to 98.5] and 87% [95% CI, 79.7 to 94.3] v 72% [95% CI, 66.5 to 77.5] and 60% [95% CI, 54.1 to 65.9], respectively; P < .0001). Residual primary tumor did not affect outcome of those with ALN pCR. Combination anthracycline/taxane-based PCT resulted in significantly more ALN pCRs, although outcome after ALN pCR was not improved by taxanes. We constructed a nomogram demonstrating that patients who do not benefit from neoadjuvant anthracyclines are unlikely to benefit from subsequent taxanes. Conclusion ALN pCR is associated with an excellent prognosis, even with a residual primary tumor, pointing to biologic differences between primary and metastatic cells. ALN pCR represents an early surrogate marker of long-term outcome. Response to initial PCT has important potential as a guide to subsequent therapy.
Evaluation of Factors Affecting Awareness of and Willingness to Participate in Cancer Clinical Trials
Authors: Lara Primo N. , Paterniti Debora A. , Chiechi Christine , Turrell Corinne , Morain Claudia , Horan Nora , Montell Lisa , Gonzalez Jose , Davis Sharon , Umutyan Ari , Martel Cynthia L. , Gandara David R. , Wun Ted , Beckett Laurel A. , Chen Moon S. 
Published: December 2005

Purpose Annually, only 3% of patients participate in cancer clinical trials (CCTs). Barriers to accrual include lack of CCT awareness and uncertain third-party payer coverage. In January 2002, a California law (Senate Bill 37 [SB37]) required all third-party payers to reimburse patient care costs related to CCTs. We evaluated the level of awareness of patients and/or their family members/friends regarding CCTs and SB37. Methods We used both a written survey for patients and/or their family members and friends seen in oncology clinics, and a verbal telephone version for Cancer Information Service callers. We tested for correlations between CCT awareness and SB37 knowledge, and willingness to participate in CCTs. Results Of 1,188 respondents, 59% were aware of CCTs, 19% knew of SB37, and 36% were very likely to consider a CCT. There were significant positive correlations between CCT awareness and willingness to participate (P < .001, Spearman), and between SB37 knowledge and willingness to participate (P = .001, Pearson χ2). Reduced awareness was seen in respondents who were either black or African American (odds ratio [OR], 0.44; P = .004), Hispanic (OR, 0.56; P = .03), had an annual income less than $25,000 (OR, 0.38; P < .001), or had less than a college degree (OR, 0.12 to 0.53; P < .001 to .013). Reduced willingness to participate in CCTs was seen in black or African American participants (OR, 0.38; P < .001), Asians (OR, 0.44; P < .006), or respondents aged 18 to 24 years (OR, 0.35; P = .002). Conclusion These results support the hypothesis that improving CCT awareness and SB37 knowledge especially among lower income, less educated, and minority patients, may potentially overcome barriers to participation and subsequently increase accrual in California.
Risk Factors and Therapy for Isolated Central Nervous System Relapse of Pediatric Acute Myeloid Leukemia
Authors: Johnston Donna L. , Alonzo Todd A. , Gerbing Robert B. , Lange Beverly J. , Woods William G. 
Published: December 2005

Purpose CNS relapse of pediatric acute myeloid leukemia (AML) is an infrequent occurrence. This review examines the risk factors and therapy used for patients with an isolated CNS relapse. Patients and Methods Records of 886 patients with de novo AML were reviewed, and patients who entered remission at the end of one course of therapy and developed an isolated CNS relapse as their first event were analyzed (n = 690). Results Thirty-three patients developed an isolated CNS relapse. Factors at diagnosis significantly associated with an isolated CNS relapse, compared with no CNS relapse, included age 0 to 2 years (70% v 27%, respectively; P < .001), enlarged liver (79% v 39%, respectively; P < .001) or spleen (79% v 39%, respectively; P < .001) at diagnosis, CNS disease at diagnosis (33% v 9%, respectively; P < .001), median WBC count (79.2 v 19.3 × 103 μL, respectively; P < .001), French-American-British M5 morphology (45% v 15%, respectively; P < .001), and chromosome 11 abnormalities (44% v 18%, respectively; P = .022). Treatment of the isolated CNS relapse varied from local therapy with intrathecal chemotherapy and/or radiation therapy to systemic therapy with chemotherapy with or without bone marrow transplantation. Survival rate in the patients treated with local therapy was only 31.5% compared with 21.4% in patients treated with systemic therapy. The 8-year overall survival for patients after an isolated CNS relapse was similar to patients after a bone marrow relapse (26% ± 16% v 21% ± 5%, respectively). Conclusion Significant predictors for isolated CNS relapse were identified. This study demonstrated that there may be no benefit to systemic therapy versus CNS-directed therapy in outcome. The data support CNS-directed therapy to treat isolated CNS relapse.
Low Rectal Cancer: A Call for a Change of Approach in Abdominoperineal Resection
Authors: Nagtegaal Iris D. , van de Velde Cornelius J.H. , Marijnen Corrie A.M. , van Krieken Jan H.J.M. , Quirke Philip 
Published: December 2005

Purpose Despite the major improvements that have been made due to total mesorectal excision (TME), low rectal cancer still remains a challenge. Methods By investigating a prospective randomized rectal cancer trial in which surgeons had undergone training in TME the factors responsible for the poor outcome were determined and a new method for assessing the quality of surgery was tested. Results Survival differed greatly between abdominoperineal resection (APR) and anterior resection (AR; 38.5% v 57.6%, P = .008). Low rectal carcinomas have a higher frequency of circumferential margin involvement (26.5% v 12.6%, P < .001). More positive margins were present in the patients operated with APR (30.4%) compared to AR (10.7%, P = .002). Furthermore, more perforations were present in these specimens (13.7% v 2.5%, P < .001). The plane of resection lies within the sphincteric muscle, the submucosa or lumen in more than 1/3 of the APR cases, and in the remainder lay on the sphincteric muscles. Conclusion We systematically described and investigated the pathologic properties of low rectal cancer in general, and APR in particular, in a prospective randomized trial including surgeons who had been trained in TME. The poor prognosis of the patients with an APR is ascribed to the resection plane of the operation leading to a high frequency of margin involvement by tumor and perforation with this current surgical technique. The clinical results of this operation could be greatly improved by adopting different surgical techniques and possibly greater use of radiochemotherapy.
Predictive Utility of Circulating Methylated DNA in Serum of Melanoma Patients Receiving Biochemotherapy
Authors: Mori Takuji , O’Day Steven J. , Umetani Naoyuki , Martinez Steve R. , Kitago Minoru , Koyanagi Kazuo , Kuo Christine , Takeshima Teh-Ling , Milford Robert , Wang He-Jing , Vu Vu D. , Nguyen Sandy L. , Hoon Dave S.B. 
Published: December 2005

Purpose Currently, no validated blood-based assays accurately predict treatment response or outcome in melanoma patients. We hypothesized that methylation of tumor-related genes detected in serum DNA could predict disease outcome and therapeutic response in patients receiving concurrent biochemotherapy (BC) for metastatic melanoma. Patients and Methods American Joint Committee on Cancer stage IV melanoma patients (N = 50) had blood drawn before administration of BC. Patients (n = 47) were classified as BC responders or nonresponders. Responders (n = 23) demonstrated a complete or partial response following BC; nonresponders (n = 24) demonstrated progressive disease. Hypermethylation of Ras association domain family 1 (RASSF1A), retinoic acid receptor-β2 (RAR-β2), and O6-methylguanine DNA methyltransferase (MGMT) genes were assessed by methylation-specific polymerase chain reaction. Results Circulating methylated RASSF1A was significantly less frequent for responders (three of 23 patients; 13%) than nonresponders (10 of 24 patients; 42%; P = .028). Patients with RASSF1A, RAR-β2, or at least one serum methylated gene had significantly worse overall survival than patients with no methylated genes (log-rank, P = .013, .021, and .01, respectively). Methylated RASSF1A was the only factor that significantly correlated with overall survival and BC response (risk ratio, 2.38; 95% CI, 1.16 to 4.86; P = .018; odds ratio = 0.21; 95% CI, 0.05 to 0.90; P = .036). Conclusion Detection of circulating methylated DNA in serum can predict response to BC and disease outcome.
Phase III Clinical Trial of Thalidomide Plus Dexamethasone Compared With Dexamethasone Alone in Newly Diagnosed Multiple Myeloma: A Clinical Trial Coordinated by the Eastern Cooperative Oncology Group
Authors: Rajkumar S. Vincent , Blood Emily , Vesole David , Fonseca Rafael , Greipp Philip R. 
Published: December 2005

Purpose To determine if thalidomide plus dexamethasone yields superior response rates compared with dexamethasone alone as induction therapy for newly diagnosed multiple myeloma. Patients and Methods Patients were randomly assigned to receive thalidomide plus dexamethasone or dexamethasone alone. Patients in arm A received thalidomide 200 mg orally for 4 weeks; dexamethasone was administered at a dose of 40 mg orally on days 1 to 4, 9 to 12, and 17 to 20. Cycles were repeated every 4 weeks. Patients in arm B received dexamethasone alone at the same schedule as in arm A. Results Two hundred seven patients were enrolled: 103 were randomly assigned to thalidomide plus dexamethasone and 104 were randomly assigned to dexamethasone alone; eight patients were ineligible. The response rate with thalidomide plus dexamethasone was significantly higher than with dexamethasone alone (63% v 41%, respectively; P = .0017). The response rate allowing for use of serum monoclonal protein levels when a measurable urine monoclonal protein was unavailable at follow-up was 72% v 50%, respectively. The incidence rates of grade 3 or higher deep vein thrombosis (DVT), rash, bradycardia, neuropathy, and any grade 4 to 5 toxicity in the first 4 months were significantly higher with thalidomide plus dexamethasone compared with dexamethasone alone (45% v 21%, respectively; P < .001). DVT was more frequent in arm A than in arm B (17% v 3%); grade 3 or higher peripheral neuropathy was also more frequent (7% v 4%, respectively). Conclusion Thalidomide plus dexamethasone demonstrates significantly superior response rates in newly diagnosed myeloma compared with dexamethasone alone. However, this must be balanced against the greater toxicity seen with the combination.
Randomized Phase II Trial of the Clinical and Biological Effects of Two Dose Levels of Gefitinib in Patients With Recurrent Colorectal Adenocarcinoma
Authors: Rothenberg Mace L. , LaFleur Bonnie , Levy Donna E. , Washington Mary Kay , Morgan-Meadows Sherry L. , Ramanathan Ramesh K. , Berlin Jordan D. , Benson Al B. , Coffey Robert J. 
Published: December 2005

Purpose The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment. Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor (EGFR) signaling pathway. Serial serum samples were measured for amphiregulin and transforming growth factor–alpha (TGFα). Patients and Methods One hundred fifteen patients were randomly assigned to receive gefitinib 250 or 500 mg orally once a day. One hundred ten patients were assessable for clinical efficacy. Biologic evaluation was performed on paired tumor samples from 28 patients and correlated with clinical outcome. Results Median progression-free survival was 1.9 months (95% CI, 1.8 to 2.1 months) and 4-month progression-free survival rate was 13% ± 5%. One patient achieved a radiographic partial response (RR = 1%; 95% CI, 0.01% to 5%). Median survival was 6.3 months (95% CI, 5.1 to 8.2 months). The most common adverse events were skin rash, diarrhea, and fatigue. In the biopsy cohort, expression of total or activated EGFR, activated Akt, activated MAP-kinase, or Ki67 did not decrease following 1 week of gefitinib. However, a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median, although these did not reach the .05 level of significance. Conclusion Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival.
Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme
Authors: Reardon David A. , Egorin Merrill J. , Quinn Jennifer A. , Rich Jeremy N. , Gururangan Idharan , Vredenburgh James J. , Desjardins Annick , Sathornsumetee Sith , Provenzale James M. , Herndon James E. , Dowell Jeannette M. , Badruddoja Michael A. , McLendon Roger E. , Lagattuta Theodore F. , Kicielinski Kimberly P. , Dresemann Gregor , Sampson John H. , Friedman Allan H. , Salvado August J. , Friedman Henry S. 
Published: December 2005

Purpose We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients and Methods Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Results Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Conclusion Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.
Pharmacogenetics of Tamoxifen Biotransformation Is Associated With Clinical Outcomes of Efficacy and Hot Flashes
Authors: Goetz Matthew P. , Rae James M. , Suman Vera J. , Safgren Stephanie L. , Ames Matthew M. , Visscher Daniel W. , Reynolds Carol , Couch Fergus J. , Lingle Wilma L. , Flockhart David A. , Desta Zeruesenay , Perez Edith A. , Ingle James N. 
Published: December 2005

Purpose Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown. Methods We determined cytochrome P450 (CYP)2D6 (*4 and *6) and CYP3A5 (*3) genotype from paraffin-embedded tumor samples and buccal cells (living patients) in tamoxifen-treated women enrolled onto a North Central Cancer Treatment Group adjuvant breast cancer trial. The relationship between genotype and disease outcome was determined using the log-rank test and Cox proportional hazards modeling. Results Paraffin blocks were obtained from 223 of 256 eligible patients, and buccal cells were obtained from 17 living women. CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determined from 190, 194, and 205 patient samples and in 17 living women. The concordance rate between buccal and tumor genotype was 100%. Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-time; P = .023) and disease-free survival (DFS; P = .012), but not overall survival (P = .169) and did not experience moderate to severe hot flashes relative to women heterozygous or homozygous for the wild-type allele. In the multivariate analysis, women with the CYP2D6 *4/*4 genotype still tended to have worse RFS (hazard ratio [HR], 1.85; P = .176) and DFS (HR, 1.86; P = .089). The CYP3A5*3 variant was not associated with any of these clinical outcomes. Conclusion In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen.