bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indium-111–Capromab Pendetide Radioimmunoscintigraphy and Prognosis for Durable Biochemical Response to Salvage Radiation Therapy in Men After Failed Prostatectomy
Authors: Thomas Cherry T. , Bradshaw Patrick T. , Pollock Brad H. , Montie James E. , Taylor Jeremy M.G. , Thames Howard D. , McLaughlin Patrick W. , DeBiose David A. , Hussey David H. , Wahl Richard L. 
Published: April 2003

Purpose: We evaluated the prognostic significance of indium-111 (111In)–capromab pendetide imaging for patients with prostate cancer who underwent salvage radiotherapy (RT) for recurrent disease after prostatectomy. Patients and Methods: Records were reviewed for all men who underwent 111In–capromab pendetide imaging at a single institution from February 1997 through December 1999. We identified 30 eligible men who were radiographically negative for metastatic disease, who had increasing serum prostate-specific antigen (PSA) after primary radical prostatectomy, and who received salvage RT. Clinical interpretations of indium monoclonal antibody (In-mab) scan results were compared with postsalvage RT PSA response. Results: Using an American Society of Therapeutic Radiation and Oncology definition of PSA failure, in men with a positive scan in at least one location (n = 14), the cumulative 2-year PSA control after salvage RT was 0.38 ± 0.13 (± SE) compared with 0.31 ± 0.13 for men with a normal antibody scan in and outside the prostate fossa (n = 15; proportional hazard ratio [PHR] = 1.32; 95% confidence interval [CI], 0.52 to 3.36). For men with a positive antibody scan limited to the prostate fossa (n = 9), PSA control at 2 years was 0.13 ± 0.12 (PHR 1.77; 95% CI, 0.65 to 4.85). The 2-year probability of PSA control after salvage RT for men with positive scan results outside the prostate bed irrespective of In-mab findings in the prostate fossa (n = 5) was 0.60 ± 0.22 (PHR 0.81; 95% CI, 0.17 to 3.78). Conclusion: In contrast to previous reports, for patients with postprostatectomy biochemical relapse who received salvage RT, presalvage RT In-mab scan findings outside the prostate fossa were not predictive of biochemical control after RT.
14-Day Variant of the Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Regimen in Advanced-Stage Hodgkin’s Lymphoma: Results of a Pilot Study of the German Hodgkin’s Lymphoma Study Group
Authors: Sieber M. , Bredenfeld H. , Josting A. , Reineke T. , Rueffer U. , Koch T. , Naumann R. , Boissevain F. , Koch P. , Worst P. , Soekler M. , Eich H. , Müller-Hermelink H.K. , Franklin J. , Paulus U. , Wolf J. , Engert A. , Diehl V. 
Published: April 2003

Purpose: This multicenter pilot study assessed the feasibility and efficacy of a time-intensified bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen given in 14-day intervals (BEACOPP-14) with granulocyte colony-stimulating factor (G-CSF) support in advanced Hodgkin’s lymphoma. Patients and Methods: From July 1997 until March 2000, 94 patients with Hodgkin’s lymphoma stage IIB, III, and IV were scheduled to receive eight cycles of BEACOPP-14. Consolidation radiotherapy was administered to regions with initial bulky disease or residual tumor after chemotherapy. Results: All patients were assessable for toxicity and treatment outcome. Eighty-six patients received the planned eight cycles of BEACOPP-14. Consolidation radiotherapy was given in 66 patients. Chemotherapy could generally be administered on schedule. Dose reductions varied among drugs but were generally low. Acute toxicity was moderate, with World Health Organization grade 3/4 leukopenia in 75%, thrombocytopenia in 23%, anemia in 65%, and infection in 12% of patients. A total of 88 patients (94%) achieved a complete remission. Four patients had progressive disease. At a median observation time of 34 months, five patients have relapsed, one patient developed a secondary non-Hodgkin’s lymphoma, and three deaths were documented. The overall survival and freedom from treatment failure rates at 34 months were 97% (95% confidence interval [CI], 93% to 100%) and 90% (95% CI, 84% to 97%), respectively. Conclusion: Acceleration of the BEACOPP baseline regimen by shortening cycle duration with G-CSF support is feasible and effective with moderate acute toxicity. On the basis of these results, the German Hodgkin’s Lymphoma Study Group will compare the BEACOPP-14 regimen with BEACOPP-21 escalated in a prospective multicenter randomized trial.
CNS-Directed Therapy for Childhood Acute Lymphoblastic Leukemia: Childhood ALL Collaborative Group Overview of 43 Randomized Trials
Authors: Clarke M. , Gaynon P. , Hann I. , Harrison G. , Masera G. , Peto R. , Richards S. 
Published: April 2003

Purpose: A collaborative meta-analysis was performed to clarify the relative effects on relapse and survival of different types of therapies directed at the CNS in childhood acute lymphoblastic leukemia. Materials and Methods: Data were sought for each individual patient in all trials started in or before 1993 that included unconfounded randomized comparisons of such treatments. Log-rank survival analyses were performed for each trial, and overall results for groups of trials addressing similar questions were obtained from the totals of the observed minus expected number of events and their variances. Results: Radiotherapy and long-term intrathecal therapy gave similar outcomes, with no significant difference in event-free survival despite random assignment of treatment to 2,848 patients, 1,001 of whom suffered relapse or death. Intravenous methotrexate reduced non-CNS rather than CNS relapses, and hence, the addition of intravenous methotrexate to a treatment regimen including radiotherapy or long-term intrathecal therapy improved event-free survival, with a 17% reduction in the event rate (95% confidence interval, 6% to 27%; P = .003). The event-free survival at 10 years in these trials was 61.9% without intravenous methotrexate and 68.1% with intravenous methotrexate. There was no significant difference in survival (14% death rate reduction; P = .09). There were insufficient randomly assigned patients to adequately address other questions, such as effect of different doses. No evidence was found of differences, between trials or between subgroups of different types of patients, in the relative effects of treatment. Conclusion: Radiotherapy can be replaced by long-term intrathecal therapy. Intravenous methotrexate gives some additional benefit by reducing non-CNS relapses.
High Prognostic Value of p16INK4 Alterations in Gastrointestinal Stromal Tumors
Authors: Schneider-Stock Regine , Boltze Carsten , Lasota Jerzy , Miettinen Markku , Peters Brigitte , Pross Matthias , Roessner Albert , Günther Thomas 
Published: April 2003

Purpose: Gastrointestinal stromal tumors (GISTs) represent a distinctive (but histologically heterogeneous) group of neoplasms, the malignant potential of which is often uncertain. To determine the prognostic relevance of p16INK4 alterations in GISTs, we investigated a larger group of GISTs and correlated the genetic findings with clinicopathological factors and patient survival. Material and Methods: We evaluated the methylation status of the promotor by methylation-specific polymerase chain reaction (PCR), the presence of mutations by PCR-SSCP-sequencing, the loss of heterozygosity at the p16INK4 locus (using the c5.1 marker), and the immunohistochemical expression of p16INK4 protein in 43 GISTs in 39 patients. Results: p16INK4 alterations were found in 25 of 43 GISTs (58.1%), with benign, borderline, or malignant GISTs showing no differences in the type and frequency of alteration. p16INK4 alterations were correlated with a loss of p16INK4 protein expression (P < .01). Patients who had tumors with p16INK4 alterations had a poorer prognosis than patients with tumors without such alterations (P = .02). There was a high predictive value for p16INK4 alterations only in the group of benign and borderline GISTs (P < .01) with regard to clinical outcome. Univariate Cox’s proportional hazard regression analysis revealed a strong correlation between p16INK4 alterations, tumor size, mitotic index, and overall survival (P < .02), whereas multivariate Cox’s analysis confirmed only p16INK4 alterations as an independent prognostic factor. Conclusion: We believe that the evaluation of p16INK4 alteration status is a helpful prognosticator, particularly in the benign and borderline groups of GISTs.
Trends in Clinical Trials Reports in Common Cancers Between 1989 and 2000
Authors: Hillner Bruce E. 
Published: April 2003

Purpose: Cancer clinical trials can be dichotomized into pilot (phase I and phase II) and randomized controlled clinical trials (RCTs). The best data source for evidence-based medicine is from RCTs. However, many patients prefer to enroll onto pilot trials, and many investigators prefer to conduct or refer their patients to pilot trials. This exploratory study sought to describe the epidemiologic patterns of clinical trial reports in common cancers. Methods: A structured review was conducted of MEDLINE citations of all English clinical trials reports published between 1989 and 2000 in breast, lung, colorectal, prostate, and female genital cancers, plus leukemias and lymphomas. Each report was classified by design (RCT, pilot, or other) and country. The abstracts of RCTs were reviewed for sample size. Reports addressing screening or prevention were excluded. Results: A total of 12,035 reports, of which 3,560 were from RCTs, were found. The annual growth in RCT reports in breast, colorectal, and prostate cancer was significant (range, 4.8% to 8.5% per year) but was insignificant in leukemias, lymphomas, and female genital and lung cancers (range, 0.1% to 4.3% per year). Within each cancer, the average sample size per report did not change during the 12 years. Nonrandomized trial reports increased on average 15.1% per year (range, 10.1% to 23.2%). The United States accounted for 30% of all RCT reports and 45% of pilot trial reports. Conclusion: The faster growth in nonrandomized compared with RCT reports may reflect rapid advances in cancer biology or different structural, commercial, and financial incentives, especially in the United States compared with Europe. Unless additional studies show evidence of an increase in their quality, the modest growth in RCT reports may limit future evidence-based cancer care.
Natural History of More Than 20 Years of Node-Positive Primary Breast Carcinoma Treated With Cyclophosphamide, Methotrexate, and Fluorouracil–Based Adjuvant Chemotherapy: A Study by the Cancer and Leukemia Group B
Authors: Weiss Raymond B. , Woolf Susan H. , Demakos Erin , Holland James F. , Berry Donald A. , Falkson Geoffrey , Cirrincione Constance T. , Robbins Alice , Bothun Sandra , Henderson I. Craig , Norton Larry 
Published: April 2003

Purpose: Breast cancer heterogeneity dictates lengthy follow-up to assess outcomes. Efficacy differences for three regimens that are based on adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) are presented in this article, but cancer recurrence sites, time of relapse, subsequent primary cancers, and causes of death in the natural history of node-positive breast cancer are emphasized. Patients and Methods: Beginning in 1975, 905 patients with node-positive cancer were randomly assigned to receive CMF or two regimens of CMF plus other agents. Median follow-up is 22.6 years. The natural-history analysis was performed on a subset of 814 patients. Results: Eighty percent of the 599 women known to have died, died of metastatic breast cancer. Only 8.5% of the deceased women died of a cause other than breast cancer, a second or third cancer, or adjuvant chemotherapy toxicity. One hundred five women (12.8%) developed other primary cancers, with 49 (46.6%) occurring in the contralateral breast. Therapeutic efficacy differences of the CMF regimens reported earlier have been maintained more than 20 years later. For certain subsets, the five-drug regimen had advantages over CMF. Bone was the most common recurrence site. The longest interval to relapse has been 23.5 years, and 18% of those who relapsed did so more than 10 years later. Conclusion: Despite adjuvant chemotherapy, a large majority (80%) of women with node-positive breast cancer die of the disease, and many recurrences develop more than 10 years later. CMF plus vincristine and prednisone provides a benefit compared with CMF, but the magnitude varies with the number of involved nodes. Outcome trends in earlier analyses of this study were maintained even years later.
Single-Agent Rituximab as First-Line and Maintenance Treatment for Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma: A Phase II Trial of the Minnie Pearl Cancer Research Network
Authors: Hainsworth John D. , Litchy Sharlene , Barton John H. , Houston Gerry Ann , Hermann Robert C. , Bradof James E. , Greco F. Anthony 
Published: April 2003

Purpose: To assess the efficacy and toxicity of first-line single-agent rituximab, followed by re-treatment with rituximab at 6-month intervals, in previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients and Methods: Forty-four previously untreated patients with CLL/SLL received rituximab 375 mg/m2 weekly for 4 consecutive weeks. All patients were required to have one or more indications for treatment. Patients with objective response or stable disease continued to receive identical 4-week rituximab courses at 6-month intervals, for a total of four courses. Results: The objective response rate after the first course of rituximab was 51% (4% complete responses). Twenty-eight patients received one or more additional courses of rituximab. At present, the overall response rate is 58%, with 9% complete responses. After a median follow-up of 20 months, the median progression-free survival (PFS) time was 18.6 months, and the 1- and 2-year PFS rates were 62% and 49%, respectively. Treatment was well tolerated, with only two episodes of grade 3 to 4 infusion-related toxicity. No cumulative toxicity or opportunistic infections occurred. Conclusion: Single-agent rituximab, used at a standard dose and schedule, is active in the first-line treatment of patients with CLL/SLL, producing substantially higher response rates than previously reported in relapsed or refractory patients (51% v 13%, respectively). Re-treatment with rituximab at 6-month intervals is well tolerated. The PFS time of 18.6 months in patients with CLL/SLL seems shorter than the 36- to 40-month median PFSs previously reported with first-line plus maintenance rituximab in patients with follicular lymphoma. Additional follow-up is required to fully assess the impact of this treatment strategy.
Dose Escalation of Carmustine in Surgically Implanted Polymers in Patients With Recurrent Malignant Glioma: A New Approaches to Brain Tumor Therapy CNS Consortium Trial
Authors: Olivi Alessandro , Grossman Stuart A. , Tatter Stephen , Barker Fred , Judy Kevin , Olsen Jeffrey , Bruce Jeffrey , Hilt Dana , Fisher Joy , Piantadosi Steve 
Published: April 2003

Purpose: This New Approaches to Brain Tumor Therapy CNS Consortium study sought to determine the maximum-tolerated dose (MTD) of carmustine (BCNU) that can be implanted in biodegradable polymers following resection of recurrent high-grade gliomas and the systemic BCNU exposure with increasing doses of interstitial BCNU. Patients and Methods: Forty-four adults underwent tumor debulking and polymer placement. Six patients per dose level were studied using polymers with 6.5%, 10%, 14.5%, 20%, and 28% BCNU by weight. Toxicities were assessed 1 month after implantation by a safety monitoring committee to determine whether subsequent escalations should occur. Nine additional patients were studied at the MTD to confirm safety. BCNU blood levels were obtained before and after polymer implantation. Results: No dose-limiting toxicities were identified at the 6.5%, 10%, or 14.5% dose levels, although difficulties with wound healing, seizures, and brain edema were noted. At the 20% dose, these effects seemed more prominent, and six additional patients were treated at this dose and tolerated treatment well. Three of four patients receiving the 28% polymers developed severe brain edema and seizures, and accrual to this cohort was stopped. Nine additional patients received 20% polymer, confirming this as the MTD. Maximum BCNU plasma concentrations with the 20% loaded polymers were 27 ng/mL. Overall median survival was 251 days. Conclusion: The MTD of BCNU delivered in polymer to the surgical cavity is 20%. This polymer provides five times more BCNU than standard commercially available BCNU polymers and results in minimal systemic BCNU exposure. Additional studies are needed to establish the efficacy of high-dose BCNU polymers.
Use of Genetic Testing and Prophylactic Mastectomy and Oophorectomy in Women With Breast or Ovarian Cancer From Families With a BRCA1 or BRCA2 Mutation
Authors: Meijers-Heijboer Hanne , Brekelmans Cecile T.M. , Menke-Pluymers Marian , Seynaeve Caroline , Baalbergen Astrid , Burger Curt , Crepin Ellen , van den Ouweland Ans W.M. , van Geel Bert , Klijn Jan G.M. 
Published: April 2003

Purpose: To analyze the use of genetic testing, prophylactic mastectomy, and oophorectomy among women with breast and/or ovarian cancer from families with a BRCA1 or BRCA2 mutation. Patients and Methods: We examined prospectively the use of BRCA1/BRCA2 testing in all women with a primary breast or ovarian cancer from a consecutive series of 112 high-risk families in which a BRCA1/BRCA2 mutation eventually was identified. The rate of prophylactic bilateral and contralateral mastectomy and prophylactic oophorectomy was analyzed in the women who carried a BRCA1/BRCA2 mutation and who had no metastatic disease at the time of the genetic test disclosure. We examined predictors for genetic test uptake and prophylactic surgery using univariate and multivariate analysis. Results: Overall, 192 of 220 women (87%) with primary tumors underwent genetic testing. Eleven of these 192 tested women (6%) appeared not to carry the family-specific BRCA1/BRCA2 mutation. Genetic testing occurred significantly more frequently at ages younger than 50 years (P = .04) and in persons with multiple primary tumors (P = .02). Among eligible women, 35 of 101 (35%) requested bilateral or contralateral mastectomy, and 47 of 95 (49%) requested oophorectomy. Women aged younger than 50 years and women who developed their first tumor after the initial identification of a BRCA1/BRCA2 mutation in the family were significantly (both P = .01) more likely to opt for prophylactic bilateral or contralateral mastectomy. Conclusion: In a clinical setting, we show a high demand for BRCA1/BRCA2 testing and for prophylactic surgery by women with breast and/or ovarian cancer from high-risk families.
Phase II Study of the Farnesyl Transferase Inhibitor R115777 in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Adjei Alex A. , Mauer Ann , Bruzek Laura , Marks Randolph S. , Hillman Shauna , Geyer Susan , Hanson Lorelei J. , Wright John J. , Erlichman Charles , Kaufmann Scott H. , Vokes Everett E. 
Published: April 2003

Purpose: This phase II study was undertaken to define the efficacy and pharmacodynamics of R115777, a farnesyl transferase inhibitor, in the first-line treatment of patients with advanced non–small-cell lung cancer. Patients and Methods: Forty-four patients with measurable stage IIIB (pleural effusion) or stage IV disease received 193 courses of treatment (median, 2.0; range, 1 to 22) with R115777 300 mg administered orally twice daily for 21 of every 28 days. Buccal mucosa samples and peripheral blood mononuclear cells (PBMCs) were collected before and after 8 days of treatment to evaluate inhibition of farnesyl transferase in vivo. Results: No objective complete or partial responses were documented. Seven patients (16%; 95% confidence interval [CI], 8% to 31%) had disease stabilization for greater than 6 months. Median survival was 7.7 months (95% CI, 6.5 to 10.5) and time to progression was 2.7 months (95% CI, 1.9 to 3.1). The most severe toxicity was neutropenia (9% grade 3, 7% grade 4) and the most common toxicities were anemia (50% grade 1 or 2, 5% grade 3) and anorexia (50% grade 1 or 2, 2% grade 3). Mild peripheral neuropathy occurred in 25% of patients. Evidence of farnesyl transferase inhibition was documented in 83% of patients. Conclusion: Single-agent R115777 was well tolerated in patients with advanced NSCLC, but demonstrated minimal clinical activity. Inhibition of farnesylation in vivo was consistently documented. On the basis of promising results of farnesyl transferase inhibitor combinations with standard chemotherapy agents, future studies of this agent in NSCLC should be in combination with systemic chemotherapy.
Resistance Exercise in Men Receiving Androgen Deprivation Therapy for Prostate Cancer
Authors: Segal Roanne J. , Reid Robert D. , Courneya Kerry S. , Malone Shawn C. , Parliament Matthew B. , Scott Chris G. , Venner Peter M. , Quinney H. Arthur , Jones Lee W. , Slovinec D’Angelo Monika E. , Wells George A. 
Published: April 2003

Purpose: Androgen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue, functional decline, increased body fatness, and loss of lean body tissue. These physical changes can negatively affect health-related quality of life. Resistance exercise may help to counter some of these side effects by reducing fatigue, elevating mood, building muscle mass, and reducing body fat. Methods: In a two-site study, 155 men with prostate cancer who were scheduled to receive androgen deprivation therapy for at least 3 months after recruitment were randomly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks (82 men) or to a waiting list control group (73 men). The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported questionnaires after 12 weeks. Secondary outcomes were muscular fitness and body composition. Results: Men assigned to resistance exercise had less interference from fatigue on activities of daily living (P = .002) and higher quality of life (P = .001) than men in the control group. Men in the intervention group demonstrated higher levels of upper body (P = .009) and lower body (P < .001) muscular fitness than men in the control group. The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight, body mass index, waist circumference, or subcutaneous skinfolds. Conclusion: Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving androgen deprivation therapy. This form of exercise can be an important component of supportive care for these patients.