bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy for Teratoma With Malignant Transformation
Authors: Donadio Alessia C. , Motzer Robert J. , Bajorin Dean F. , Kantoff Philip W. , Sheinfeld Joel , Houldsworth Jane , Chaganti Raju S.K. , Bosl George J. 
Published: November 2003

Purpose: Teratoma with malignant transformation (MT) is a well-described entity that refers to the MT of a somatic teratomatous component in a germ cell tumor (GCT) to a histology that is identical to a somatic malignancy (eg, rhabdomyosarcoma [RMS]). Surgical resection has been the mainstay of therapy for localized transformed disease because these tumors are thought to be resistant to standard treatment. We report that chemotherapy has a role in selected patients with MT, determined by cell type. Patients and Methods: Chemotherapy was administered to 12 patients with MT of GCT limited to a single cell type (two patients with primitive neuroectodermal tumors, five with undifferentiated RMS, one with anaplastic small-cell tumor, two with adenocarcinoma, and two with leukemia); 10 patients had measurable disease. GCT origin was confirmed by molecular cytogenetics in five patients. Each patient received chemotherapy regimens based on the specific malignant cell observed in the transformed histology. Results: Seven patients with measurable disease achieved a partial response, with the duration of response ranging between 1 month and 7 years. Three of those patients are alive. Three patients did not respond to treatment, and all of those patients died as a result of their disease. Conclusion: Chemotherapy for MT limited to a single cell type may result in major responses and long-term survival in selected patients. Local therapy after chemotherapy is an important component of treatment to achieve maximum response.
Tamoxifen As Chemoprevention in BRCA1 and BRCA2 Mutation Carriers With Breast Cancer: A Pilot Survey of Physicians
Authors: Peshkin Beth N. , Isaacs Claudine , Finch Clinton , Kent Sheryl , Schwartz Marc D. 
Published: November 2003

Purpose: To assess physician recommendations about the use of tamoxifen in premenopausal BRCA1 and BRCA2 mutation carriers. Methods: We mailed surveys to a stratified random sample of 1,286 physicians selected from the San Antonio Breast Cancer Symposium mailing list. Eligible participants were physicians whose practice consisted of ≥ 10% breast cancer patients. Participants were asked to complete a three-part, 10-minute questionnaire. Demographics and responses to hypothetical patient vignettes were analyzed. Results: Of potentially eligible participants, 27% responded to the survey, and 260 participants were included in the final analysis. Physicians did not distinguish between BRCA1 and BRCA2 status in making recommendations about tamoxifen to breast cancer patients; however, in an unaffected woman, they were more likely to recommend tamoxifen to a BRCA2 mutation carrier than to a BRCA1 mutation carrier (73% v 57%; P < .0001). In newly diagnosed breast cancer patients, physicians were much more likely to recommend tamoxifen to an estrogen receptor (ER)–positive mutation carrier versus an ER-negative carrier (94% v 27%; P < .0001). When the mutation carrier was diagnosed 10 years ago, physicians were still much more likely to recommend tamoxifen if the tumor was ER-positive versus ER-negative (79% v 35%; P < .0001). Conclusion: Physicians’ recommendations about tamoxifen use in mutation carriers with a history of breast cancer seem to be heavily dependent on ER status. This finding suggests that among mutation carriers, physicians are influenced by adjuvant treatment guidelines more so than the potential role that tamoxifen might play in the reduction of risk for contralateral breast cancer.
Adjuvant Treatment for Early Ovarian Cancer: A Randomized Phase III Trial of Intraperitoneal 32P or Intravenous Cyclophosphamide and Cisplatin—A Gynecologic Oncology Group Study
Authors: Young Robert C. , Brady Mark F. , Nieberg Roberta K. , Long Harry J. , Mayer Allan R. , Lentz Samuel S. , Hurteau Jean , Alberts David S. 
Published: November 2003

Purpose: To conduct a prospective study of intraperitoneal radioactive chromic phosphate (32P) versus cyclophosphamide-cisplatin (CP) in women with early ovarian cancer at high risk for recurrence (International Federation of Gynecology and Obstetrics stage Ia or Ib grade 3 or Ic or stage II, no macroscopic residual disease) and to compare cumulative incidence of recurrence, overall survival, and relative toxicity. Materials and Methods: A total of 251 patients were randomly assigned to treatment with 32P or CP. Twenty-two (8.7%) were ineligible following centralized pathology review. Of the 229 patients included in the analysis, 110 received 32P, and 119 received CP. Results: The cumulative incidence of recurrence at 10 years was 35% (95% CI, 27% to 45%) for patients receiving 32P and 28% (95% CI, 21% to 38%) for those receiving CP. Patients receiving CP had a recurrence rate 29% lower than that of those receiving 32P (P = .15, two-tail test). The death rate for patients treated with CP was 17% lower than that for patients treated with 32P (difference not significant). Combining both arms, the 10-year cumulative incidence of recurrence for all stage I patients was 27% (95% CI, 20% to 34%) compared with 44% (95% CI, 32% to 56%) for stage II patients (P = .01). Both regimens were reasonably well tolerated, but problems with inadequate distribution (7%) and small-bowel perforation (3%) make the otherwise less toxic 32P less acceptable. Conclusion: Although there are no statistically significant differences in survival, the lower cumulative recurrence seen with CP and complications of 32P administration make platinum-based combinations the preferred adjuvant therapy for early ovarian cancer patients at high-risk for recurrence.
Prognostic Value of Minimal Residual Disease Quantification by Real-Time Reverse Transcriptase Polymerase Chain Reaction in Patients With Core Binding Factor Leukemias
Authors: Krauter Jürgen , Görlich Kerstin , Ottmann Oliver , Lübbert Michael , Döhner Hartmut , Heit Wolfgang , Kanz Lothar , Ganser Arnold , Heil Gerhard 
Published: November 2003

Purpose: In patients with acute myeloblastic leukemia with t(8;21) or inv(16) aberrations (core binding factor [CBF] leukemias), minimal residual disease (MRD) can be sensitively detected during and after chemotherapy by use of molecular methods. However, the prognostic impact of qualitative MRD detection is still under debate. In this study, the prognostic value of MRD quantification in patients with CBF leukemias was assessed. Patients and Methods: We quantified MRD at various time points during and after therapy by real-time reverse transcriptase polymerase chain reaction (RT-PCR) for AML1/MTG8 and CBFB/MYH11 in 37 patients with CBF leukemias treated within a multicenter trial. Results: At initial diagnosis, the patients showed a heterogenous fusion gene expression relative to glyceraldehyde 3-phosphate dehydrogenase with a variation of more than two log steps. According to MRD status during/after therapy, two groups of patients were separated. Of the 26 patients who had MRD levels of less than 1% in relation to initial diagnosis at all time points tested after induction chemotherapy, only two experienced relapse after a median follow-up of 19 months. Of the 11 patients who had a sample with an MRD level ≥ 1% at least at one time point after induction therapy, 10 experienced relapse, with a median remission duration of 10 months (P < .001). The median interval between the informative MRD sample and clinical relapse in these patients was 3 months. Conclusion: MRD quantification by real-time RT-PCR allows the identification of patients with a high risk of relapse among the CBF leukemias.
Impact of CNS Treatment on Mood in Adult Survivors of Childhood Leukemia: A Report From the Children’s Cancer Group
Authors: Glover Dorie A. , Byrne Julianne , Mills James L. , Robison Leslie L. , Nicholson H. Stacy , Meadows Anna , Zeltzer Lonnie K. 
Published: November 2003

Purpose: This study assessed the relationship between CNS treatment and psychologic mood using the Profile of Moods State (POMS), a standardized measure of affect, among a large sample of young adult survivors of childhood acute lymphoblastic leukemia (ALL; N = 555). Patients and Methods: Survivors of childhood ALL (ages 18 to 33 years at study entry) participated in a structured telephone interview eliciting demographic, health, and behavioral data and the POMS. Treatment data included total dose of CNS irradiation (CRT) and intrathecal methotrexate (MTX) obtained from medical records. Results: Mood disturbance was reported by 24% of survivors. High-dose CRT and MTX predicted disturbance rates modestly and primarily in combination with education variables. Interactions between educational achievement, a history of attendance in special education classes, and sex were better predictors than treatment type or dose. Nonwhite males, those younger than 12.5 years of age at diagnosis, and those with negative perceptions of current health and cancer’s impact on employment were also at greater risk for mood disturbance (P < .01 to .001). Conclusion: Although most survivors are doing well psychologically, a subset of long-term survivors show potentially serious mood disturbance. Mood disturbance seems to be a function of interactions between preexisting individual difference variables (eg, sex, race/ethnicity), treatment factors, and posttreatment educational experiences. Prevention strategies aimed at childhood cancer survivors at greatest risk for mood disturbance may be improved by focus on posttreatment psychosocial and educational supports.
Toward New Strategies to Select Young Endometrial Cancer Patients for Mismatch Repair Gene Mutation Analysis
Authors: Berends Maran J.W. , Wu Ying , Sijmons Rolf H. , van der Sluis Tineke , Ek Wietske Boersmavan , Ligtenberg Marjolijn J.L. , Arts Neeltje J.W. , ten Hoor Klaske A. , Kleibeuker Jan H. , de Vries Elisabeth G.E. , Mourits Marian J.E. , Hollema Harry , Buys Charles H.C.M. , Hofstra Robert M.W. , van der Zee Ate G.J. 
Published: November 2003

Purpose: To determine the frequency of mismatch repair (MMR) gene germline mutations in endometrial cancer patients who were diagnosed at less than 50 years of age; to relate the presence of mutations to family history, histopathologic data, presence of tumor microsatellite instability (MSI), and immunostaining; and to formulate criteria for genetic testing in these patients. Patients and Methods: Endometrial cancer patients (N = 58), who were diagnosed at less than 50 years of age, were included and questioned about their family history. Mutation analysis of the MLH1, MSH2, and MSH6 genes was performed (denaturing gradient gel electrophoresis and sequence analysis to detect small mutations and multiplex ligation-dependent probe amplification to detect large deletions or duplications). For MSI analysis, five consensus markers were used, and immunostaining of the three MMR proteins was performed. Results: In five of 22 patients with a positive first-degree family history for hereditary nonpolyposis colorectal cancer (HNPCC)-related cancers, pathogenic germline mutations were found (one MLH1, three MSH2, and one MSH6). Four mutation carriers belonged to families fulfilling the revised Amsterdam criteria. No mutations were found in the 35 patients without such family history (P = .006). MSI was detected in 20 of 57 cancers, among which four were from mutation carriers. In 23 of 51 cancers, one or more MMR protein was absent; in all five mutation carriers, immunostaining indicated the involved MMR gene. Conclusion: In 23% of the young endometrial cancer patients with at least one first-degree relative with an HNPCC-related cancer, an MMR gene mutation was detected. Therefore, presence of an HNPCC-related cancer in a first-degree relative seems to be an important selection criterion for mutation analysis. Subsequent immunostaining of MMR proteins will point to the gene(s) that should be analyzed.
Fully Synthetic Carbohydrate-Based Vaccines in Biochemically Relapsed Prostate Cancer: Clinical Trial Results With α-N-Acetylgalactosamine-O-Serine/Threonine Conjugate Vaccine
Authors: Slovin Susan F. , Ragupathi Govindaswami , Musselli Cristina , Olkiewicz Krystyna , Verbel David , Kuduk Scott D. , Schwarz Jacob B. , Sames Dalibor , Danishefsky Samuel , Livingston Philip O. , Scher Howard I. 
Published: November 2003

Purpose: We report the synthesis of a mucin-related O-linked glycopeptide, α-N-acetylgalactosamine-O-serine/threonine (Tn), which is highly simplistic in its structure and can induce a relevant humoral response when given in a trimer or clustered (c) formation. We tested for an antitumor effect, in the form of a change in the posttreatment versus pretreatment prostate-specific antigen (PSA) slopes, that might serve as a surrogate for effectiveness of vaccines in delaying the time to radiographic progression. Methods: We compared the antibody response to immunization with two conjugates, Tn(c)-keyhole limpet hemocyanin (KLH) and Tn(c)-palmitic acid (PAM) with the saponin immunologic adjuvant QS21, in a phase I clinical trial in patients with biochemically relapsed prostate cancer. Patients received Tn(c)-KLH vaccine containing either 3, 7, or 15 μg of Tn(c) per vaccination. Ten patients received 100 μg of Tn(c)-PAM. QS21 was included in all vaccines. Five vaccinations were administered subcutaneously during 26 weeks with an additional booster vaccine at week 50. Results: Tn(c), when given with the carrier molecule KLH and QS21, stimulated the production of high-titer immunoglobulin M (IgM) and IgG antibodies. Inferior antibody responses were seen with T(c)-PAM. There was no evidence of enhanced immunogenicity with increasing doses of vaccine. An antitumor effect in the form of a decline in posttreatment versus pretreatment PSA slopes was also observed. Conclusion: A safe synthetic conjugate vaccine in a trimer formation was developed that can break immunologic tolerance by inducing specific humoral responses. It seemed to affect the biochemical progression of the disease as determined by a change in PSA log slope.
Minichromosome Maintenance Protein 2 Is a Strong Independent Prognostic Marker in Breast Cancer
Authors: Gonzalez Michael A. , Pinder Sarah E. , Callagy Grace , Vowler Sarah L. , Morris Lesley S. , Bird Kate , Bell Jane A. , Laskey Ronald A. , Coleman Nicholas 
Published: November 2003

Purpose: To test the hypothesis that prognostic information in breast cancer may be derived from an accurate assessment of epithelial cell cycle entry, as indicated by expression of minichromosome maintenance (MCM) proteins. Materials and Methods: We used immunohistochemistry to examine the distribution of Mcm-2 in breast tissue. Power calculations based on a pilot study of 67 whole tissue sections led to selection of an independent 347-core breast carcinoma tissue microarray validation set. We tested for associations between Mcm-2 (and Ki-67) labeling index (LI) and various clinicopathologic parameters. Results: Mcm-2 was expressed more frequently than the standard proliferation marker Ki-67 in whole tissue sections of normal breast (P = .0003) and breast carcinoma (P < .0001). In 221 assessable cores of invasive carcinoma, the Mcm-2 LI showed a positive association with tumor size (P = .002), mitotic index (P < .0001), histologic grade (P < .0001), and the Nottingham Prognostic Index (NPI) score (P < .0001). Using a cutoff value of 50%, Mcm-2 LI was associated with overall survival (P = .0007), disease-free interval (P = .0002), and with the development of regional recurrence (P = .011) and distant metastases (P = .0016). Cox regression analysis suggested that the Mcm-2 LI is a strong prognostic factor in breast cancer that is independent and superior to histologic grade, lymph node stage, and Ki-67 LI, but not the NPI score. Conclusion: Mcm-2 may be of utility as a prognostic marker to refine the prediction of outcome in breast cancer, for example when combined with parameters currently used in the NPI.
Prognostic Characteristics of Breast Cancer Among Postmenopausal Hormone Users in a Screened Population
Authors: Kerlikowske Karla , Miglioretti Diana L. , Ballard-Barbash Rachel , Weaver Donald L. , Buist Diana S.M. , Barlow William E. , Cutter Gary , Geller Berta M. , Yankaskas Bonnie , Taplin Stephen H. , Carney Patricia A. 
Published: November 2003

Purpose: We determined the risk of breast cancer and tumor characteristics among current postmenopausal hormone therapy users compared with nonusers, by duration of use. Methods: From January 1996 to December 2000, data were collected prospectively on 374,465 postmenopausal women aged 50 to 79 years who underwent screening mammography. We calculated the relative risk (RR) of breast cancer (invasive or ductal carcinoma-in-situ) and type of breast cancer within 12 months of postmenopausal therapy use among current hormone users with a uterus (proxy for estrogen and progestin use) and without a uterus (proxy for estrogen use), compared with nonusers. Results: Compared with nonusers, women using estrogen and progestin for ≥ 5 years were at increased risk of breast tumors of stage 0 or I (RR, 1.51; 95% CI, 1.37 to 1.66), stage II or higher (RR, 1.46; 95% CI, 1.30 to 1.63), size ≤ 20 mm (RR, 1.59; 95% CI, 1.43 to 1.76), size greater than 20 mm (RR, 1.24; 95% CI, 1.09 to 1.42), grade 1 or 2 (RR, 1.60; 95% CI, 1.44 to 1.77), grade 3 or 4 (RR, 1.54; 95% CI, 1.37 to 1.73), and estrogen receptor-positive (RR, 1.72; 95% CI, 1.55 to 1.90). Estrogen-only users were slightly more likely to have estrogen receptor-positive breast cancer compared with nonusers (RR, 1.14; 95% CI, 1.06 to 1.23). Conclusion: Use of estrogen and progestin postmenopausal hormone therapy for five years or more increased the likelihood of developing breast cancer, including both tumors with favorable prognostic features and tumors with unfavorable prognostic features.
Patient-Controlled Methylphenidate for the Management of Fatigue in Patients With Advanced Cancer: A Preliminary Report
Authors: Bruera Eduardo , Driver Larry , Barnes Elizabeth A. , Willey Jie , Shen Loren , Palmer J. Lynn , Escalante Carmelita 
Published: November 2003

Purpose: To assess the effects of patient-controlled methylphenidate for cancer-related fatigue. Patients and Methods: In this prospective open study, 31 patients with advanced cancer and fatigue who scored ≥ 4 on a scale of 0 to 10 received methylphenidate 5 mg by mouth every 2 hours as needed for 7 days (maximum, 20 mg/d). Multiple symptoms were assessed daily; the primary end point, fatigue, was measured using the 0 to 10 scale, and the Functional Assessment for Chronic Illness Therapy–Fatigue (FACIT-F) was performed at baseline, day 7, and day 28. Results: The following mean (± standard deviation) scores for 30 assessable patients improved significantly between baseline and day 7: fatigue (0 to 10 scale), 7.2 ± 1.6 v 3.0 ± 1.9 (P < .001); overall well-being (0 to 10 scale), 4.5 ± 2.2 v 2.8 ± 2.1 (P < .001); fatigue (FACIT-F) subscore, 17.5 ± 11.3 v 34.7 ± 10.0 (P < .001); functional well-being, 14.4 ± 5.9 v 18.3 ± 6.6 (P < .001); and physical well-being, 13.5 ± 6.4 v 21.4 ± 5.0 (P < .001). Anxiety, appetite, pain, nausea, depression, and drowsiness all improved significantly (P < .05). All patients took afternoon or evening doses, and 28 patients (93%) took three or more doses daily. All patients chose to continue taking methylphenidate after 7 days of treatment. No serious side effects were reported. Conclusion: These preliminary results suggest that patient-controlled methylphenidate administration rapidly improved fatigue and other symptoms. Randomized controlled trials are justified.
Treatment of Plasma Cell Dyscrasias With Thalidomide and Its Derivatives
Authors: Dimopoulos Meletios A. , Anagnostopoulos Athanasios , Weber Donna 
Published: November 2003

Purpose: In 1999, investigators reported promising results of a phase II study of thalidomide in patients with resistant multiple myeloma (MM). Since then, various trials of thalidomide alone and in combination with other agents have been tested in patients with resistant and, more recently, untreated MM. In addition, preliminary results of phase I studies of the immunomodulatory derivatives (IMiDs) of thalidomide have been recently reported.Design: We reviewed and report the results of clinical trials of thalidomide and the IMiDs, as well as the pharmacology, mechanism of action, and toxicity of these agents.Results: Thalidomide has demonstrated significant activity in both resistant and previously untreated multiple myeloma. Combination therapy with dexamethasone increases response rate, even in patients previously resistant to both drugs given as single agents. More recent studies of thalidomide with dexamethasone in previously untreated patients are highly encouraging. The addition of chemotherapy to thalidomide and dexamethasone may further increase response rates, but its effect on patient survival has not been clarified. Preliminary results of trials of IMiD-3 indicate that this agent is active in resistant myeloma and has a toxicity profile different from that of thalidomide.Conclusion: Many studies have confirmed the activity of thalidomide in MM, as well as an improved response with dexamethasone. Newer thalidomide derivatives with reduced toxicity (neuropathy, teratogenicity) are also promising. Thalidomide with dexamethasone may now represent the treatment of choice for previously untreated patients. Further studies with these and other novel agents early in the course of myeloma may improve complete remission rates and frequency of long-term control.
Outcome in Children With Relapsed Acute Myeloid Leukemia After Initial Treatment With the French Leucémie Aiquë Myéloïde Enfant (LAME) 89/91 Protocol of the French Society of Pediatric Hematology and Immunology
Authors: Aladjidi Nathalie , Auvrignon Anne , Leblanc Thierry , Perel Yves , Bénard Antoine , Bordigoni Pierre , Gandemer Virginie , Thuret Isabelle , Dalle Jean Hugues , Piguet Christophe , Pautard Brigitte , Baruchel André , Leverger Guy 
Published: November 2003

Purpose: After present first-line therapies for childhood acute myeloid leukemia (AML), nearly 40% of patients still relapse. The goals of this retrospective study were to determine whether these children could be treated successfully with a salvage regimen and to establish the optimal therapeutic strategy. Patients and Methods: In the multicentric, prospective, Leucémie Aiquë Myéloïde Enfant 89/91 protocol, 106 of the 308 children enrolled between 1988 and 1998 relapsed. Initial treatment after the first complete remission (CR1) had been allogenic HLA-identical bone marrow transplantation (BMT; n = 21) or chemotherapy (n = 85). Treatment procedures were scheduled according to the choice of each participating institution. Results: When reinduction therapy was attempted, second complete remission (CR2) was obtained in 71% of patients (68 of 96 patients). BMT was performed in 53 (78%) of these 68 patients (autograft, mainly harvested in CR1, n = 25; matched sibling-donor BMT, n = 12; or alternative-donor BMT, n = 16). The 5-year overall survival (OS) rate for all 106 patients was 33%, and the disease-free survival (DFS) rate for children in CR2 was 45%. Multivariate analysis of re-treated children showed that the 5-year OS was higher if the CR1 had been longer than 12 months compared with less than 12 months (54% v 24%, respectively; P = .001) and lower if maintenance therapy had been given after CR1 compared with chemotherapy without maintenance therapy or HLA-identical BMT (12% v 40% v 52%, respectively; P = .002). For patients attaining CR2, the 5-year DFS rate was not significantly different for matched sibling-donor BMT (60%), autograft (47%), or alternative-donor BMT (44%). Conclusion: After aggressive first-line therapy, one third of unselected, relapsing AML children could be cured. Further prospective trials are warranted to define the optimal reinduction regimen and megadose chemotherapy and to evaluate the late effects of these therapies.