bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiofrequency Ablation of Malignant Liver Tumors
Authors: Curley Steven A. 
Published: August 2004

Abstract
The majority of patients with primary or metastatic hepatic tumors are not candidates for resection because of tumor size, location near major intrahepatic blood vessels precluding a margin-negative resection, multifocality, or inadequate hepatic function related to coexistent cirrhosis. Radiofrequency ablation (RFA) is an evolving technology being used to treat patients with unresectable primary and metastatic hepatic cancers. RFA produces coagulative necrosis of tumor through local tissue heating. Liver tumors are treated percutaneously, laparoscopically, or during laparotomy using ultrasonography to identify tumors and guide placement of the RFA needle electrode. For tumors smaller than 2.0 cm in diameter, one or two deployments of the monopolar multiple array needle electrode are sufficient to produce complete coagulative necrosis of the tumor. However, with increasing size of the tumor, there is a concomitant increase in the number of deployments of the needle electrode and the overall time necessary to produce complete coagulative necrosis of the tumor. In general, RFA is a safe, well-tolerated, effective treatment for unresectable hepatic malignancies less than 6.0 cm in diameter. Effective treatment of larger tumors awaits the development of more powerful, larger array monopolar and bipolar RFA technologies.
Radiofrequency Ablation of Unresectable Hepatic Malignancies: Lessons Learned
Authors: Bilchik Anton J. , Wood Thomas F. , Allegra David P. 
Published: August 2004

AbstractRadiofrequency ablation (RFA) is increasingly used for the local destruction of unresectable hepatic malignancies. Relative contraindications include tumors in proximity to vital structures that may be injured by RFA and lesions whose size exceeds the ablation capabilities of the probe system employed. Given current technology, we believe that RFA should be cautiously utilized for lesions greater than 5 cm in diameter. Open (celiotomy) and laparoscopic approaches to RFA allow intraoperative ultrasonography, which may demonstrate occult hepatic disease. In addition, RFA performed via celiotomy can be accompanied by resection or cryosurgical ablation, and isolation of the liver from adjacent organs. Percutaneous RFA should be reserved for patients who cannot undergo general anesthesia, those with recurrent or progressive lesions, and those with smaller lesions sufficiently isolated from adjacent organs. Complications may be minimized when these approaches are selectively applied.
Interferon in Oncological Practice: Review of Interferon Biology, Clinical Applications, and Toxicities
Authors: Jonasch Eric , Haluska Frank G. 
Published: August 2004

AbstractFor the past 40 years, various forms of interferon (IFN) have been evaluated as therapy in a number of malignant and non-malignant diseases. With the advent of gene cloning, large quantities of pure IFN became available for clinical study. This paper reviews the biology, pharmacology, and clinical applications of IFN formulations most commonly used in oncology. It then reviews the most common side effects seen in patients treated with IFN, and makes recommendations for the management of IFN-induced toxicity.The major oncological indications for IFN include melanoma, renal cell carcinoma, AIDS-related Kaposi's sarcoma, follicular lymphoma, hairy cell leukemia, and chronic myelogenous leukemia. Unfortunately, IFN therapy is associated with significant toxicity, which can be divided into constitutional, neuropsychiatric, hematologic, and hepatic effects. These toxicities have a major impact on the patient's quality of life, and on the physician's ability to optimally treat the patient. Careful attention to all aspects of patient care can result in improved tolerability of this difficult but promising therapy. Conclusion: a better understanding of IFN biology, indications, side effect profiles, and toxicity management will aid in optimizing its use in the treatment of patients with cancer.
Drug Approval Summaries: Arsenic Trioxide, Tamoxifen Citrate, Anastrazole, Paclitaxel, Bexarotene
Authors: Cohen Martin H. , Hirschfeld Steven , Honig Susan Flamm , Ibrahim Amna , Johnson John R. , O'Leary James J. , White Robert M. , Williams Grant A. , Pazdur Richard 
Published: August 2004

AbstractThis report summarizes information on drugs recently approved by the Food and Drug Administration, Office of Drug Evaluation I, Division of Oncology Drug Products. Five applications supporting new claims will be discussed: Trisenox™ (arsenic trioxide) for induction of remission and consolidation in patients with acute promyelocytic leukemia who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose disease is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression; Nolvadex® (tamoxifen citrate) in women with ductal carcinoma in situ, following breast surgery and radiation, to reduce the risk of invasive breast cancer; Arimidex® (anastrazole) for first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer; Taxol® (paclitaxel), 175 mg/m2 by 3 h infusion in combination with cisplatin for first-line treatment of advanced ovarian cancer; and Targretin® gel (bexarotene) for the topical treatment of cutaneous lesions in patients with stage IA and IB cutaneous T-cell lymphoma who have not tolerated other therapies or who have refractory or persistent disease.Information provided includes rationale for drug development, study design, efficacy and safety results, and pertinent literature references.
Irinotecan (CPT-11): Recent Developments and Future Directions–Colorectal Cancer and Beyond
Authors: Rothenberg Mace L. 
Published: August 2004

Abstract
Since its approval in the United States in 1996, irinotecan (CPT-11, Camptosar®, Pharmacia Corp.; Peapack, NJ) has undergone extensive clinical evaluation. In the past five years, the focus of development has evolved from evaluation of single-agent activity in refractory disease settings to evaluation of front-line irinotecan-based combination chemotherapy regimens and integration of irinotecan into combined modality regimens. Important studies have been performed clarifying the role of irinotecan in treating colorectal and other gastrointestinal cancers, small cell and non-small cell lung cancer, and a variety of other malignancies. Preclinical studies performed in conjunction with these clinical trials have also provided significant insights into the pharmacology, metabolism, mechanisms of resistance, and molecular determinants of response. This review summarizes that progress, focusing on the achievements of the past five years.
Irinotecan Plus Fluorouracil/Leucovorin for Metastatic Colorectal Cancer: A New Survival Standard
Authors: Saltz Leonard B. , Douillard Jean-Yves , Pirotta Nicoletta , Alakl May , Gruia Gabriela , Awad Lucile , Elfring Gary L. , Locker Paula K. , Miller Langdon L. 
Published: August 2004

Abstract
Background. Irinotecan is a topoisomerase I inhibitor that prolongs survival in patients with colorectal cancer refractory to fluorouracil (5-FU) and leucovorin (LV). This demonstrated activity of irinotecan as effective second-line therapy for colorectal cancer led to evaluation of combination irinotecan/5-FU/LV as first-line therapy for patients with metastatic disease. The results of two prospective phase III randomized, controlled, multicenter, multinational clinical trials in patients with previously untreated metastatic colorectal cancer served as the basis for U.S. and European approval of irinotecan/5-FU/LV for this indication. An overview of the findings of these two pivotal studies provides insights regarding the application of this new combination in clinical practice.
Methods. Patients were randomly assigned to receive 5-FU/LV, either alone, or with concurrent irinotecan. The study conducted primarily in North America (study 1), employed bolus 5-FU/LV schedules, while the study performed primarily in Europe (study 2), employed infusional 5-FU/LV regimens. Major endpoints included tumor response rate, time to tumor progression (TTP), overall survival, quality of life, and safety.
Results. In study 1, the respective confirmed response rates for irinotecan/5-FU/LV versus 5-FU/LV were 39% and 21% (p &lt; .001); median TTPs were 7.0 months and 4.3 months, respectively (p = .004). In study 2, response rates for irinotecan/5-FU/LV versus 5-FU/LV alone were 35% and 22% (p = .005); median TTPs were 6.7 months and 4.4 months, respectively (p &lt; .001). Survival time increased significantly with irinotecan/5-FU/LV versus 5-FU/LV alone in both studies (study 1: median 14.8 months versus 12.6 months, p = .042; study 2: median 17.4 months versus 14.1 months, p = .032). The combined analysis of the data from the two studies showed median survivals of 15.9 months versus 13.3 months, favoring the irinotecan-containing combinations (stratified-by-study p = .003). Patients in study 1 had a 36% lower risk of tumor progression and a 20% lower risk of death with the irinotecan combination than with 5-FU/LV alone; comparable risk reduction values in study 2 were 42% and 23%. While grade 3 diarrhea and vomiting were more common with irinotecan/5-FU/LV, grade 4 neutropenia, neutropenic fever, and mucositis were less common with irinotecan/5-FU/LV than with the Mayo Clinic 5-FU/LV regimen.
Conclusion. The combination of irinotecan/5-FU/LV is superior to 5-FU/LV alone as first-line therapy for patients with metastatic colorectal cancer, offering consistently improved tumor control and prolonged survival. Irinotecan-based combination therapy sets a new survival standard for the treatment of this life-threatening disease.
Medical Mistakes: A Workshop on Personal Perspectives
Authors: Penson Richard T. , Svendsen Sasha S. , Chabner Bruce A. , Lynch Thomas J. , Levinson Wendy 
Published: August 2004

Abstract
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.
Medical errors are difficult to discuss. Significant medical errors occur in approximately 3% of hospitalizations. Two-thirds are preventable. Despite an entrenched belief that doctors should be infallible, errors are inevitable. Dr. Wendy Levinson of the University of Chicago facilitated a discussion of the impact medical errors have on staff. Staff broke into small groups to share their personal experience and then discussed common themes: the sense of shame and guilt, the punitive culture, guidelines for disclosure to patients and colleagues, and changes in medical practice that can prevent future mistakes. Auditing and improving systems has led to considerable improvements in the field of aviation safety. However, in medicine people are more important than the process. While we should never cease to aim for the very best in delivered care, we must acknowledge how prone we all are to mistakes and that we can learn from and prevent errors. Openly sharing experiences in a confidential setting, such as the Schwartz Rounds, helps defuse feelings of guilt and challenges the culture of shame and isolation that often surrounds medical errors.
Update on the Treatment of Multiple Myeloma
Authors: Kyle Robert A. 
Published: August 2004

Abstract
The patient with multiple myeloma should be carefully evaluated from the standpoint of symptoms, physical findings, and laboratory data. If there are no symptoms or evidence of early or impending complications, the patient should not be treated. He or she should be followed and treatment delayed until progression of the disease occurs. If the patient is younger than 70 years, autologous peripheral blood stem cell transplantation should be considered. Hematopoietic stem cells should be collected before the patient is exposed to alkylating agents. If the patient is older than 70 years, chemotherapy is indicated. The two major shortcomings of autologous stem cell transplantation are: A) failure to eradicate myeloma, and B) contamination of autologous peripheral blood stem cells. Most physicians initially treat the patient with vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) for three to four months and then collect the peripheral blood stem cells. One can then proceed with transplant or treat the patient with alkylating agents and delay the transplant until the patient progresses. In a prospective trial comparing autologous bone marrow transplantation with conventional chemotherapy, five-year overall survival favored the transplant group (52% versus 12%). In a randomized trial of 400 patients from France, there was no difference in event-free or overall survival between double and single autologous stem cell transplant when evaluated at two years. In a subsequent evaluation, patients with a low β2-microglobulin value at diagnosis appeared to have better results with a double transplant. There is no evidence that combinations of chemotherapeutic agents are more effective than melphalan and prednisone. Allogeneic transplantation is associated with a high mortality. Depletion of T-cells or a mini-allogeneic transplant may be beneficial in an effort to reduce mortality. Thalidomide produces objective response in approximately 30% of refractory patients. The use of intravenous bisphosphonates is recommended for patients with skeletal lesions. Hypercalcemia and renal failure must be treated promptly.
Clinical Significance of Occult Metastatic Cells in Bone Marrow of Breast Cancer Patients
Authors: Braun Stephan , Pantel Klaus 
Published: August 2004

Abstract
The early and clinically occult spread of viable tumor cells to the organism is increasingly considered a hallmark in cancer progression, as emerging data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies to epithelial cytokeratins or tumor-associated cell membrane glycoproteins, individual carcinoma cells can be detected on cytologic bone marrow preparations at frequencies of 10–5 to 10–6. Prospective clinical studies have shown that the presence of these immunostained cells in bone marrow, as a frequent site of overt metastases, is prognostically relevant with regard to relapse-free and overall survival. This screening approach may be, therefore, used to improve tumor staging and guide the stratification of patients for adjuvant therapy in clinical trials. Another promising application is monitoring the response of micrometastatic cells to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up. The present review summarizes the current data on the clinical significance of occult metastatic breast cancer cells in bone marrow.
Chemotherapy of Metastatic Breast Cancer: What to Expect in 2001 and Beyond
Authors: Esteva Francisco J. , Valero Vicente , Pusztai Lajos , Boehnke-Michaud Laura , Buzdar Aman U. , Hortobagyi Gabriel N. 
Published: August 2004

Abstract
Chemotherapy plays an important role in the management of metastatic breast cancer. The anthracyclines (doxorubicin, epirubicin) and the taxanes (paclitaxel, docetaxel) are considered the most active agents for patients with advanced breast cancer. Traditionally, the anthracyclines have been used in combination with cyclophosphamide and 5-fluorouracil (FAC, FEC). The taxanes have single-agent activity similar to older combination chemotherapy treatments. There is great interest in developing anthracycline/taxane combinations. Capecitabine is indicated for patients who progress after anthracycline and taxane therapy. Vinorelbine and gemcitabine have activity in patients with metastatic breast cancer and are commonly used as third- and fourth-line palliative therapy. The role of high-dose chemotherapy is not well-defined and remains experimental. Novel cytotoxic therapy strategies include the development of anthracycline, taxane, and oral fluoropyrimidine analogues; antifolates; topoisomerase I inhibitors, and multidrug resistance inhibitors.
A better understanding of the biology of breast cancer is providing novel treatment approaches. Oncogenes and tumor-supressor genes are emerging as important targets for therapy. Trastuzumab, a monoclonal antibody directed against the Her-2/neu protein, has been shown to prolong survival in patients with metastatic breast cancer. Other novel biologic therapies interfere with signal transduction pathways and angiogenesis. The challenge for the next decade will be to integrate these promising agents in the management of metastatic and primary breast cancer.
Early Lung Cancer Action Project: A Summary of the Findings on Baseline Screening
Authors: Henschke Claudia I. , McCauley Dorothy I. , Yankelevitz David F. , Naidich David P. , McGuinness Georgeann , Miettinen Olli S. , Libby Daniel , Pasmantier Mark , Koizumi June , Altorki Nasser , Smith James P. 
Published: August 2004

Abstract
Purpose. The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low radiation dose computed tomography (low-dose CT) in persons at high-risk for lung cancer.
Methods. Since starting in 1993, the ELCAP has enrolled 1,000 asymptomatic persons, 60 years of age or older, with at least 10 pack-years (1 pack per day for 10 years, or 2 packs per day for 5 years) of cigarette smoking, no prior cancer, and medically fit to undergo thoracic surgery. After a structured interview and informed consent, baseline chest radiographs and low-dose CT were obtained on each subject. The diagnostic work-up of screen-detected noncalcified pulmonary nodules (NCN) was guided by ELCAP recommendations which included short-term high-resolution CT follow-up for the smallest nodules.
Baseline Results. On low-dose CT at baseline compared to chest radiography, NCN were detected three times as commonly (23% versus 7%), malignancies four times as commonly (2.7% versus 0.7%), and stage I malignancies six times as commonly (2.3% versus 0.4%). Of the 27 CT-detected cancers, 96% (26/27) were resectable; 85% (23/27) were stage I, and 83% (19 of the 23 stage I) were not seen on chest radiography. Following the ELCAP recommendations, biopsies were performed on 28 of the 233 subjects with NCN; 27 had a malignant and one a benign NCN. Another three individuals underwent biopsy outside of the ELCAP recommendations; all had benign NCNs. No one had thoracotomy for a benign nodule.
Conclusion. Baseline CT screening for lung cancer provides for detecting the disease at earlier and presumably more commonly curable stages in a cost-effective manner.
Hepatotoxicity of Chemotherapy
Authors: King Paul D. , Perry Michael C. 
Published: August 2004

Abstract
After assessment of tumor histology, the next important factor to consider in the selection of a chemotherapy regime is organ function. Patients who are to receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate, and which drug doses should be modified. Following therapy abnormalities of liver function tests may be due to the therapy rather than to progressive disease, and this distinction is of critical importance. Furthermore, not all abnormalities in liver function are due to the tumor or its treatment, and other processes, such as hepatitis, must be kept in mind. This article reviews the hepatic toxicity of chemotherapeutic agents, and suggests dose modifications based upon liver function abnormalities. Emphasis is placed on agents known to be hepatotoxic, and those agents with hepatic metabolism.
Treatment of Localized Prostate Cancer With Intermittent Triple Androgen Blockade: Preliminary Results in 110 Consecutive Patients
Authors: Leibowitz Robert L. , Tucker Steven J. 
Published: August 2004

Abstract
Objectives. To determine the effectiveness of triple androgen blockade as an alternative to watchful waiting, radical prostatectomy or radiation therapy in the management of patients with clinical stage T1 to T3 prostate cancer.
Methods. The records of 110 consecutive patients were retrospectively evaluated. Patients were treated with a three-drug androgen blockade regimen, consisting of a luteinizing hormone-releasing hormone agonist (leuprolide or goserelin) plus an antiandrogen (flutamide or bicalutamide) plus finasteride (a 5-alpha-reductase inhibitor), followed by finasteride maintenance therapy, as the sole intervention. All patients refused local therapy and had their prostates intact. Determinants of efficacy included serum prostate-specific antigen (PSA) levels and disease-specific survival.
Results. Patients were treated for a median of 13 months with triple androgen blockade. At baseline, mean PSA level was 13.2 ± 1.2 ng/ml (range, 0.39-100 ng/ml), and mean Gleason score was 6.6 ± 0.1 (range, 4-10). During treatment, PSA levels declined to ≤0.1 ng/ml in all patients, with a median time of 3 months. After a median follow-up of 36 months since initiation of treatment, PSA levels have remained stable in 105 of 110 patients (95.5%). At a median follow-up of 55 months (range, 38-125 months), the mean PSA level for the first 57 patients treated in this series is 1.88 ± 0.1 (range, 0-11.0 ng/ml). Only 9 of 110 (8.1%) patients have a PSA level ≥4.0 ng/ml. To date, no patient has received a second cycle of hormone blockade.
Conclusions. Although median follow-up is short, triple androgen blockade therapy followed by finasteride maintenance appears to be a promising alternative for the management of patients with clinically localized or locally advanced prostate cancer. Further study of this approach is warranted.