Introduction of tumor markers into routine clinical practice has been poorly controlled, with few criteria or guidelines as to how such markers should be used. We propose a Tumor Marker Utility ...Grading System (TMUGS) to evaluate the clinical utility of tumor markers and to establish and investigational agenda for evaluation of new tumor markers. A Tumor Marker Utility Grading Worksheet has been designed. The initial portion of this worksheet is used to clarify the precise characteristics of the marker in question. These characteristics include the marker designation, the molecule and/or substance and the relevant alteration from normalcy, the assay format and reagents, the specimen type, and the neoplastic disease for which the marker is being evaluated. To determine the clinical utility of each marker, one of several potential uses must be designated, including risk assessment, screening, differential diagnosis, prognosis, and monitoring clinical course. For each of these uses, associations between marker assay results and expected biologic process and end points must be determined. However, knowledge of tumor marker data should contribute to a decision in practice that results in a more favorable clinical outcome for the patient, including increased overall survival, increased disease-free survival, improvement in quality of life, or reduction in cost of care. Semiquantitative utility scales have been developed for each end point. The only markers recommended for use in routine clinical practice are those that are assigned utility scores of “++” or “+++” on a 6-point scale (ranging from 0 to +++) in the categories relative to more favorable clinical outcomes. Each utility score assignment should be supported by documentation of the level of evidence used to evaluate the marker. TMUGS will establish a standardized analytic technique to evaluate clinical utility of known and future tumor markers. It should result in improved patient outcomes and more cost-efficient investigation and application of tumor markers.
We describe a 23-year-old white man who presented with anasarca and a new periumbilical mass. He had preserved kidney function and laboratory findings consistent with nephrotic syndrome, including ...9.7 g/day albuminuria. Serum serologies were positive for anti-SSa and anti-SSb and low complements but were negative for antinuclear antibody. Pathologic findings of the abdominal mass showed a mammary-type myofibroblastoma. A kidney biopsy revealed a diffuse proliferative and membranous immune-mediated glomerulonephritis with 10% interstitial fibrosis. This is a novel case of mammary-type myofibroblastoma associated with nephrotic syndrome mimicking a proliferative lupus pattern.
To evaluate the efficacy and safety of docetaxel in patients with paclitaxel-resistant metastatic breast cancer (MBC).
Docetaxel (100 mg/m2) was administered every 3 weeks to 46 patients registered ...at four centers. Patients had previously received < or = two chemotherapy regimens for MBC. All patients had progressive disease while receiving paclitaxel therapy. Treatment was repeated until there was evidence of disease progression or for a maximum of three cycles after best response.
Objective responses were seen in eight of 44 assessable patients (18.1%; 95% confidence interval CI, 6.7% to 29.5%). Seven patients had partial responses and one patient responded completely. Response rates were not significantly different by previously received paclitaxel dose or resistance. No responses were seen in 12 patients who had previously received paclitaxel by 24-hour infusion, but the response rate in 32 patients who had received paclitaxel by 1- to 3-hour infusion was 25%. The median response duration was 29 weeks and the median time to disease progression was 10 weeks. Median survival was 10.5 months. Clinically significant (severe) adverse events included neutropenic fever (24% of patients), asthenia (22%), infection (13%), stomatitis (9%), neurosensory changes (7%), myalgia (7%), and diarrhea (7%).
Docetaxel is active in patients with paclitaxel-resistant breast cancer, particularly in those who failed to respond to brief infusions of paclitaxel. Response rates were comparable to or better than those seen with other therapies for patients with paclitaxel-resistant MBC. This confirms preclinical studies, which indicated only partial cross-resistance between paclitaxel and docetaxel.
This phase II study evaluated the efficacy, safety, and health outcomes of pemetrexed treatment in heavily pretreated patients with advanced breast cancer.
Women with metastatic breast cancer, ...Karnofsky performance status ≥ 70, and previous treatment with ≥ 3 regimens containing anthracyclines, taxanes, and capecitabine were eligible. Pemetrexed 500 mg/m
2 intravenous infusion was administered on day 1 of a 21-day treatment cycle.
Eighty patients were enrolled, and 60 received concurrent folic acid and vitamin B 12 supplements per protocol amendment to minimize possible pemetrexed-related toxicity. The median numbers of cycles delivered were 3 for vitamin-supplemented patients and 2 for non—vitamin-supplemented patients. Regardless of vitamin supplementation, the overall response rate was 8% (95% CI, 3%–16.6%), stable disease was exhibited in 36% of patients, median time to disease progression was 2.9 months, and median survival was 8.2 months. Improvements in patient-reported symptoms ranged from 16.2% for pain intensity to 32.1% for nausea. Major grade 3/4 toxicities were hematologic, with grade 4 neutropenia in 10% of patients and grade 3 toxicities consisting primarily of neutropenia (29%) and leukopenia (21%). There were no clear trends of the effect of supplementation on toxicity.
Pemetrexed has modest antitumor activity and is well tolerated in heavily pretreated patients with breast cancer. Further evaluation of this multitargeted antifolate in advanced breast cancer is warranted.
Liver transplantation for unresectable hepatocellular carcinoma yields disappointing results. Most cases recur within 2 years, often in the transplanted liver.
A combination of neoadjuvant ...doxorubicin and orthotopic liver transplantation was used in 20 patients with unresectable hepatocellular carcinoma confined to the liver. Seventeen patients had tumors > 5 cm in greatest diameter, and 11 cases were stage IVA by the TNM classification. Doxorubicin was administered preoperatively, intraoperatively, and postoperatively at a dose of 10 mg/m2 weekly, totaling 200 mg/m2.
Chemotherapy was well tolerated although leukopenia was observed in 70% of patients. Eight patients died, five of recurrent tumor and three of hepatitis B. Three others remain alive 8-22 months after tumor recurrence. One patient had initial tumor recurrence in the allograft. Actuarial survival is 59% and tumor-free survival is 54% at 3 years. For the 17 patients with tumors > 5 cm, overall survival is 63% and tumor-free survival is 49% at 3 years.
The results of this pilot study suggest that neoadjuvant doxorubicin chemotherapy favorably alters the post-transplant survival of patients with hepatocellular carcinoma.
Robert Gary Mennel, MD: A Conversation with the Editor Mennel, Robert G.; Roberts, William C.
Proceedings - Baylor University. Medical Center,
10/1/2006, 2006-Oct, 2006-10-00, 20061001, Letnik:
19, Številka:
4
Journal Article
Primary effusion lymphoma (PEL), formerly known as body cavity-based lymphoma, is a high-grade B-cell non-Hodgkin's lymphoma associated with Kaposi's sarcoma and human herpesvirus 8 infection. It ...usually affects serous body cavities and results in recurrent lymphomatous effusions. PEL is often diagnosed in patients with HIV infection and carries a poor prognosis, with median survival near 6 months. We describe a patient who presented with symptomatic pericardial effusion, secondary to newly diagnosed PEL, and no prior history of HIV infection.
Optimal treatment of early stage breast cancer remains an active area of study. An expert multidisciplinary committee reviewed clinical data on systemic therapy for early stage, stage I and II breast ...cancer. Guidelines for treatment were developed for Texas Oncology. P.A., the largest private practice group of oncologists in the United States. This group of physicians treats approximately 5000 new breast cancer patients each year and has a major impact on oncology care in the state of Texas. These guidelines identify prognostic factors which help the practitioner in choosing treatment for patients. Subsets of patients are identified for whom no systemic therapy is warrented. Standard chemotherapy and hormonal therapy regimens are outlined for patients with early stage disease at increased risk for relapse. Dose intensification for high risk stage II patients is reviewed. Timing of therapy and the sequencing of chemotherapy and radiation therapy is addressed. Strategies for the follow-up of patients with a history of breast cancer are outlined.
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