Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers.

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 an 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.

Hospital and physician volume or specialization and outcomes in cancer treatment: importance in quality of cancer care.

PURPOSE: To conduct a comprehensive review of the health services literature to search for evidence that hospital or physician volume or specialty affects the outcome of cancer care. METHODS: We reviewed the 1988 to 1999 MEDLINE literature that considered the hypothesis that higher volume or specialization equals better outcome in processes or outcomes of cancer treatments. RESULTS: An extensive, consistent literature that supported a volume-outcome relationship was found for cancers treated with technologically complex surgical procedures, eg, most intra-abdominal and lung cancers. These studies predominantly measured in-hospital or 30-day mortality and used the hospital as the unit of analysis. For cancer primarily treated with low-risk surgery, there were fewer studies. An association with hospital and surgeon volume in colon cancer varied with the volume threshold. For breast cancer, British studies found that physician specialty and volume were associated with improved long-term outcomes, and the single American report showed an association between hospital volume of initial surgery and better 5-year survival. Studies of nonsurgical cancers, principally lymphomas and testicular cancer, were few but consistently showed better long-term outcomes associated with larger hospital volume or specialty focus. Studies in recurrent or metastatic cancer were absent. Across studies, the absolute benefit from care at high-volume centers exceeds the benefit from break-through treatments. CONCLUSION: Although these reports are all retrospective, rely on registries with dated data, rarely have predefined hypotheses, and may have publication and self-interest biases, most support a positive volume-outcome relationship in initial cancer treatment. Given the public fear of cancer, its well-defined first identification, and the tumor-node-metastasis taxonomy, actual cancer care should and can be prospectively measured, assessed, and benchmarked. The literature suggests that, for all forms of cancer, efforts to concentrate its initial care would be appropriate.

Should the elderly receive chemotherapy for node-negative breast cancer? A cost-effectiveness analysis examining total and active life-expectancy outcomes.

PURPOSE: This study determines the survival benefit and cost-effectiveness of adjuvant chemotherapy in elderly women with breast cancer. In addition, the analysis measures the impact of substituting active life expectancy for survival in the clinical decision. PATIENTS AND METHODS: Two cohorts of women with estrogen receptor (ER)-negative, stage I breast cancer from age 60 to 80 years were monitored using a Markov process. One group received standard chemotherapy following primary therapy, and the other had no postoperative treatment. Data were derived from recently published clinical trials and a major meta-analysis. Outcome included the average survival, active life-expectancy, and incremental cost/quality-adjusted life-year (cost/QALY). RESULTS: Adjuvant chemotherapy prolongs survival in older women, but to a lesser extent compared with younger women. The average gain in quality-adjusted months was 1.8 months in a 75-year-old cohort at a cost/QALY of $4,400. These small benefits were not substantially altered when univariate changes were made in toxicity, recurrence risk, or effectiveness of chemotherapy. When active life expectancy replaced survival as an end point, the benefit for 75-year-old women decreased to 2 weeks at a cost of more than $96,000/QALY. CONCLUSION: There is a small survival benefit for adjuvant chemotherapy in elderly patients. The cost of this benefit is high, but within the range of commonly reimbursed procedures until a point between 75 and 80 years old. The use of active life expectancy as the primary outcome reduces the benefit and adds to the cost. If physicians and policymakers agree that active life expectancy is a relevant outcome, withholding chemotherapy for patients > or = 70 years old is a reasonable approach.

Pamidronate in prevention of bone complications in metastatic breast cancer: a cost-effectiveness analysis.

PURPOSE: Pamidronate is effective in reducing bony complications in patients with metastatic breast cancer who have known osteolytic lesions. However, pamidronate does not increase survival and is associated with additional financial costs and inconvenience. We conducted a post-hoc evaluation of the cost-effectiveness of pamidronate using the results of two randomized trials that evaluated pamidronate 90 mg administered intravenously every month versus placebo. PATIENTS AND METHODS: The trials differed only in the initial systemic therapy administered (hormonal or chemotherapy). Total skeletal related events (SREs), including surgery for pathologic fracture, radiation for fracture or pain control, conservatively treated pathologic fracture, spinal cord compression, or hypercalcemia, were taken directly from the trials. Using a societal perspective, direct health care costs were assigned to each SRE. Each group's monthly survival was equal and was projected to decline using observed median survivals. The cost of pamidronate reflected the average wholesale price of the drug plus infusion. The value or disutility of an adverse event per month was evaluated using a zero value (events avoided) or an assigned one (range, 0.2 to 0.8). RESULTS: The cost of pamidronate therapy exceeded the cost savings from prevented adverse events. The difference between the treated and placebo groups was larger with hormonal systemic therapy than with chemotherapy (additional $7,685 compared with $3,968 per woman). The projected net cost per SRE avoided was $3,940 with chemotherapy and $9,390 with hormonal therapy. The cost-effectiveness ratios were $108,200 with chemotherapy and $305, 300 with hormonal therapy per quality-adjusted year. CONCLUSION: Although pamidronate is effective in preventing a feared, common adverse outcome in metastatic breast cancer, its use is associated with high incremental costs per adverse event avoided. The analysis is most sensitive to the costs of pamidronate and pathologic fractures that were asymptomatic or treated conservatively.

The optimal timing of autologous bone marrow transplantation in Hodgkin's disease patients after a chemotherapy relapse.

PURPOSE: The optimal sequence of salvage chemotherapy (SC) and autologous bone marrow transplantation (ABMT) for Hodgkin's disease (HD) patients who relapse after primary chemotherapy is unknown. We created a decision analysis model to determine the optimal treatment strategy and the most cost-effective approach. METHODS: The decision tree simulated a 25-year-old HD patient who relapsed less than 12 months after mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy. Four strategies used ABMT in some sequence with SC; the final strategy considered SC alone. Clinical data were derived from 17 published reports chosen by explicit criteria. Costs of care were estimated from the published literature and institutional experience. RESULTS: The optimal strategy was ABMT in second relapse, which was superior to the SC-only option by 1.9 years at an incremental cost of $26,200 per each year of life saved. When the probabilities of complete remission and disease-free survival were reduced for SC, similar to the clinical expectation of SC after a seven- or eight-drug regimen like MOPP/doxorubicin, bleomycin, and vinblastine with or without dacarbazine (MOPP/ABV[D]), ABMT in first relapse was the preferred strategy and provided 6 additional months. However, when the data from favorable (or unfavorable) SC and ABMT reports were compared head-to-head in this model, SC followed by ABMT in second relapse was always optimal. CONCLUSIONS: All relapsed HD patients should plan to use ABMT in some sequence with SC, if necessary. In most situations the optimal strategy is ABMT in second relapse. This analysis will assist clinicians in planning treatment for relapsed HD patients. It could be refined if historical series were updated to report the incidence and outcomes of SC relapse from seven- or eight-drug regimens.

Trade-offs between survival and breast preservation for three initial treatments of ductal carcinoma-in-situ of the breast.

PURPOSE: To assess the trade-offs between survival and breast preservation of currently accepted approaches for ductal carcinoma-in-situ (DCIS) of the breast. PATIENTS AND METHODS: Decision analysis was performed using the Markov model of hypothetical cohorts of 55-year-old white women with nonpalpable mammographic abnormalities found to be DCIS. Strategies were breast-conserving surgery (BCS), BCS with 50-Gy radiation (RT) or initial mastectomy. Recurrence rates were derived from the published literature. Main outcomes were overall, breast cancer-free, and event-free survival plus years of both breasts preserved. RESULTS: Using the conditions defined in this model, the actuarial survival rates at 10 and 20 years were 91.7% and 74.1% for the initial mastectomy strategy, 91.0% and 72.1% for BCS plus RT, and 89.6% and 68.2% for BCS alone. At 20 years, the initial mastectomy strategy also had a greater breast cancer-free survival rate of 74.5%, compared with 63.3% for BCS plus RT, or 46.8% for BCS alone. However, BCS alone had the highest survival rate with both breasts preserved (64.2%) compared with BCS plus RT (56.0%) or initial mastectomy (0%). Of the breast-conserving strategies at 20 years, the breast event-free survival rate (no invasive cancer or DCIS) was greater for BCS plus RT (47.2%) compared with BCS alone (28.4%). Using just survival as the primary end point, mastectomy is the optimal strategy by a small margin. However, if quality-adjusted survival is at issue, mastectomy is the choice only if the yearly reduction in quality of life due to mastectomy is less than 1%. CONCLUSION: BCS with or without radiation compared with mastectomy as initial management of DCIS of the breast trades a slight decrease in survival rates for the value of breast preservation. This model should aid clinicians in matching treatments to their patients' preferences.

Measuring standards of care for early breast cancer in an insured population.

PURPOSE: To demonstrate the use of a combined data base to evaluate the care for local/regional invasive breast cancer in a large insured population of women aged less than 64 years. PATIENTS AND METHODS: We linked the procedural and hospital claims from Blue Cross Blue Shield (BCBS) of Virginia with clinical stage data from the Virginia Cancer Registry (VCR) from 1989 to 1991. A total of 918 women were assessed with a median age of 50 years; 68% had tumors less than 2 cm, 30% had positive axillary nodes, and 68% were assessed as having local summary stage. A quality-of-care "report card" was used based on standards of care from international Consensus Conferences. RESULTS: Eight percent had a mastectomy as the initial biopsy procedure. Sixty-nine percent of women ultimately underwent mastectomy. Of those women who underwent lumpectomy, 86% had subsequent radiation. Within 3 months of diagnosis, 43% had a bone scan and 20% a computed tomography (CT) scan. Of women with positive axillary lymph nodes, 83% aged less than 51 years and 52% aged 51 to 64 years received chemotherapy. Fifty-six percent of all women had claims from a medical oncologist. Of women having a total mastectomy, 27% had claims from a plastic surgeon. Sixty-six percent to 76% of women had a mammogram, 24% a bone scan, and 14% a CT scan in the 0-18 and 18-36 month intervals following primary treatment. CONCLUSION: This study confirms the feasibility of linking sources of data that provide complementary information needed to develop measurements regarding standards of quality and efficiency of oncologic care. This report should serve as an initial benchmark while we await reports from other populations to define the best practice.

Costs of care associated with non-small-cell lung cancer in a commercially insured cohort.

PURPOSE: To examine the cost of incident cases of non-small-cell lung cancer (NSCLC) in a commercially insured cohort. METHODS: Claims from Virginia Blue Cross and Blue Shield (BCBS) beneficiaries with lung cancer from 1989 to 1991 were merged with records from the Virginia Cancer Registry (VCR). Data from the VCR identified incident cases, stage, and type of cancer at diagnosis. Costs for all medical care included insurance payment, copayments, and deductibles for 2 years after diagnosis or until death. RESULTS: Three hundred forty-nine incident NSCLC patients were evaluated. The mean 2-year cost for each patient after diagnosis or until death was $47,941 (95% confidence interval, $43,758 to $52,124). Total average costs and hospital days were significantly lower for local disease ($37,514, 21.2 days), but were similar for regional ($52,797, 30.0 days) and distant ($49,382, 33.0 days) disease. Hospital days accounted for 48% and hospital-based claims for 70% of costs. Initial treatments, which included radiation, unadjusted for stage, had the lowest survival rates and the highest costs, and were associated with the most hospital days. Initial stage, race, gender, and age were not predictors of total 2-year costs. The independent predictors of total 2-year costs were type of treatment: any radiation therapy, any surgery, or any chemotherapy (all, P < .001). Inpatient hospital days was only a modest predictor of costs after adjusting for type of treatment. Patients who survived less than 1 year spent 30.5 days in hospital and had an average cost of $47,280. CONCLUSION: The direct health care costs of younger NSCLC patients care are substantial. These results should serve as a benchmark for future comparisons as the United States market shifts to managed care.

Recommended colorectal cancer surveillance guidelines by the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based, postoperative surveillance strategy for the detection of recurrent colon and rectal cancer. Tests are to be recommended only if they have an impact on the outcomes listed below. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOMES: Outcomes of interest included overall and disease-free survival, quality of life, toxicity reduction, and cost-effectiveness. The American Society of Clinical Oncology (ASCO) Colorectal Cancer Surveillance Expert Panel was guided by the principle of cost minimization, ie, when two strategies were believed to be equally effective, the least expensive test was recommended. EVIDENCE: A complete MEDLINE search was performed of the past 20 years of the medical literature. Keywords included colorectal cancer, follow-up, and carcinoembryonic antigen, as well as the names of the specific tests. The search was broadened by articles from the tumor marker ASCO panel literature search, as well as from bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COSTS: The possible consequences of false-positive and false-negative tests were considered in evaluating a preference for one of two tests that provide similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The expert panel's recommended postoperative monitoring schema is discussed in this article. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board of Directors examined this document. SPONSOR: American Society of Clinical Oncology.

The effect of age and comorbidity in the treatment of elderly women with nonmetastatic breast cancer.

BACKGROUND: Increasing age has most often been associated with less aggressive approaches to treatment of nonmetastatic breast cancer in elderly women even after controlling for stage of disease at diagnosis. OBJECTIVE: To examine the influence of patient age on the initial treatment for breast cancer received by elderly women while controlling for the effect of patient comorbidity. METHODS: Cancer registry records for a cohort of 2252 women aged 66 years or older who were diagnosed as having nonmetastatic, invasive breast cancer between 1984 and 1989 and identified through the Virginia Cancer Registry were linked to Medicare Provider and Reimbursement data files. Multivariate models were used to assess the effects of age and comorbidity (as measured by the International Classification of Diseases, Ninth Edition, codes recorded on Medicare claims) on initial treatment approach while adjusting for stage of disease, race, residential location, marital status, and year of diagnosis. RESULTS: In baseline multivariable models, age was negatively associated with any surgical treatment, non-breast-conserving procedures, and radiotherapy following breast-conserving surgery. The odds of women aged 85 years and older receiving surgery were less than one third those of women aged 66 to 74 years (odds ratio, 0.31; 95% confidence interval, 0.16 to 0.60), while odds ratios across the same two age groups for nonbreast-conserving surgery and adjuvant radiotherapy were 0.55 (95% confidence interval, 33 to 92) and 0.03 (confidence interval, 0.01 to 0.13), respectively. With additional adjustment for aggregate comorbidity, odds ratio estimates in these same age-group comparisons were virtually unchanged at 0.31, 0.56, and 0.04. CONCLUSION: Aggregate comorbidity measured by inpatient International Classification of Diseases, Ninth Edition, codes on Medicare inpatient hospital claims does not explain age-related patterns in the initial treatment of elderly patients with breast cancer.

Perioperative management of colon cancer under Medicare risk programs.

OBJECTIVE: To determine differences in perioperative care and outcomes for patients with colon cancer enrolled in Medicare health maintenance organizations compared with similar fee-for-service nonenrollees. METHODS: Cross-sectional evaluation of hospital care and posthospital outcomes with data obtained from medical records. Nineteen health maintenance organizations representing all model types were selected from 12 states. The nonenrollee sample was drawn from the same areas. The sample included 412 enrollees and 401 nonenrollees, representing 65 hospitals for health maintenance organizations and 61 hospitals for fee-for-service. RESULTS: Nonenrollees were slightly older and had higher preoperative risk. Enrollees had shorter intervals between admission and surgery (enrollees, 1.55 days vs nonenrollees, 2.85 days). Differences in length of stay (enrollees, 10.9 days vs nonenrollees, 14.2 days) persisted even after controlling for preoperative health status. Differences in admissions to intensive care units (enrollees, 36.4% vs nonenrollees, 44.4%) were highly influenced by preoperative health status. Nonenrollees were more significantly likely to receive preoperative antibiotics, postoperative testing (eg, postoperative chest radiographs and electrocardiograms), and postoperative patient-controlled analgesia. Tumor staging was similar for both groups. Enrollees were more likely to be discharged home, while nonenrollees were more likely to be discharged to a nursing home. There were no significant differences in hospital deaths or postdischarge readmissions. CONCLUSIONS: Health maintenance organization enrollees with colon cancer received less clinical services of several types than similar patients in fee-for-service settings, had shorter hospital stays, and were less likely to be discharged to nursing homes. However, there was no evidence that they experienced different outcomes.

Single-agent versus combination chemotherapy in advanced non-small cell lung cancer: a meta-analysis and the Cancer and Leukemia Group B randomized trial.

Several randomized trials have compared single-agent chemotherapy with combination chemotherapy in advanced non-small cell lung cancer. In general, response rates were higher with combination regimens, but their impact on survival is unclear. We conducted a meta-analysis of 25 trials involving a total of 5,156 patients with advanced non-small cell lung cancer randomized to a single-agent arm versus a combination arm. The results showed that combination chemotherapy produced a nearly twofold increase in response rate and a modestly improved 1-year survival rate compared with single-agent chemotherapy. However, toxicity was significantly increased, with a 3.6-fold increase in treatment-related mortality. In a subset analysis of trials using either a platinum analog or vinorelbine as single agents and as a component of the combination regimen, the difference was no longer statistically significant, suggesting that more active single agents provide similar survival with less toxicity than combination regimens. Based on these results, the Cancer and Leukemia Group B initiated a large randomized trial comparing paclitaxel with paclitaxel + carboplatin in stage IIIB-IV non-small cell lung cancer patients. The trial will be able to detect a 30% difference in survival. An extensive quality of life analysis and a resource utilization comparison will allow estimation of the incremental cost per quality of life-year gained. This trial will be the first in the United States to prospectively collect and analyze such data in a multidisciplinary approach.

Parathyroid hyperplasia and carcinoma within one gland.

A 47-year-old Scottish woman vacationing in the United States presented with a serum calcium level greater than 20 mg/dl and a parathyroid hormone level 16 times greater than normal after a one-week history of severe vomiting and unrelenting abdominal pain. Surgical exploration of the thymus revealed the very rare association of a large (7 by 4 by 0.8 cm) parathyroid carcinoma adjacent to apparently normal parathyroid tissue, separated by a thin fibrous band. Two other hyperplastic and one normal parathyroid glands were also identified. Postoperatively, the patient became hypocalcemic and, for the past nine months, has received maintenance 1-alpha-hydroxycholecalciferol therapy (1 microgram per day) with normal calcium and barely detectable parathyroid hormone levels.

Positive inotropic effects of hydralazine in human subjects: comparison with prazosin in the setting of congestive heart failure.

Hydralazine possesses positive inotropic properties in animal model preparations. To determine whether this vasodilator elicits a positive inotropic response in the failing human ventricle, hydralazine, 75 or 100 mg, was administered orally to 14 patients with left ventricular dysfunction and congestive heart failure; the results were compared with those of first-dose prazosin at 5 and 10 mg. The duration of the preejection period and the isovolumic developed pressure/duration of isovolumic contraction (delta P/delta t) were used as indexes of inotropy. Prazosin did not effect a significant response in the duration of the preejection period or in the delta P/delta t. Hydralazine significantly shortened the preejection period and increased the delta P/delta t over 8 hours after administration; these data suggest that hydralazine elicits a positive inotropic response in the failing human ventricle.

Development of pharmacodynamic tolerance to prozosin in congestive heart failure.

In order to determine and compare the pharmacodynamic responses to single and multiple dose prazosin therapy in cardiac failure, 14 patients with severe low-output heart failure underwent central and regional hemodynamic measurements after random placement in one of two prazosin dosing schedules. A single 5 mg oral dose of prazosin (Group A, no. = 7) significantly increased the cardiac index and stroke volume index while significantly decreasing systemic, pulmonary and pulmonary capillary wedge pressures and vascular resistances. Hepatic plasma flow and limb blood flow increased after the single dose. Striking attenuation of these hemodynamic effects occurred when the same dose was administered after 24 hours of pretreatment with oral prazosin, 2 mg every 8 hours (Group B, no. = 7). The plasma prazosin levels of the two groups, drawn 2 hours after administration, were 24.5 and 30.5 ng/ml, respectively. Repeated administration of prazosin in patients with congestive heart failure results in rapid attenuation of its beneficial central and regional hemodynamic effects. The usefulness of this vasodilator as a preload- and afterload-reducing agent in the clinical setting of chronic congestive heart failure may be limited by the development of pharmacodynamic tolerance.

Differences in initial treatment patterns and outcomes of lung cancer in the elderly.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for substantial deaths and costs in the elderly greater than 65 years old. The current practice of NSCLC treatment in a Medicare population was examined to ascertain important areas of practice variation, and differences in clinical outcome and costs. METHODS: Data from incident cases of NSCLC from the Virginia Cancer Registry (VCR), 1985-89, were matched with claims from Medicare Part A and B, census tract data and the Area Resource File. Multivariate models were created to include clinical data, demographics, and access information. RESULTS: For patients with locoregional disease, increasing age was associated with lower likelihood of therapy (odds ratio (OR) 0.35; confidence intervals (CI) 0.29, 0.43), thoracotomy (OR 0.27; CI 0.21, 0.34), and more use of radiation therapy compared to surgery (OR 1.69; CI 1.39, 2.03). Low education levels were associated with less likelihood of treatment (OR 0.78; CI 0.66, 0.94), or radiation instead of surgery (OR 1.22; CI 1.05, 1.47). Patients in urban areas were less likely to receive therapy (OR 0.67; CI 0.49, 0.92). For distant disease, increasing age was also associated with lower likelihood of treatment (OR 0.48; CI 0.41, 0.56), as was increasing co-morbidity (OR 0.84; CI 0.75, 0.93). Distance to radiation oncologists made no difference in radiotherapy utilization. Two year survival according to therapy was surgery 66%, radiation 15%, no therapy 17%. CONCLUSIONS: Patterns of care, and survival according to therapy, vary widely for elderly NSCLC patients. Age, low education, higher co-morbidity and urban residence all decrease the likelihood of surgical therapy for locoregional NSCLC. Despite the availability of coverage through the Medicare program, use of therapies and survival is not uniform for all beneficiaries. Possible discrimination by age, co-morbid illnesses not recorded in the Medicare files, or patient and provider choice could all be involved; administrative billing files cannot resolve these important differences.

A sociodemographic and economic comparison of breast reconstruction, mastectomy, and conservative surgery.

BACKGROUND: There are a variety of surgical choices for women with early-stage breast cancer, including breast-conserving surgery, mastectomy, or mastectomy plus reconstructive surgery. This report examines some of the factors that affect these choices and the costs of the various treatment options. METHODS: Data from the Virginia Cancer Registry were linked to insurance claims from the Trigon Blue Cross and Blue Shield Company for women with local and regional staged breast cancer from 1989 to 1991 in Virginia. Multivariate analyses and cost studies were performed. RESULTS: There were 592 women who underwent breast-conserving surgery (BCS, 26%), mastectomy (58%), or mastectomy plus reconstruction (16%). Increasing age reduced the use of reconstruction. The choice of reconstruction was not affected by tumor size, nodal status, or race. Sixty percent of women had immediate breast reconstruction at the time of mastectomy; the majority had the implant procedure. The cost of BCS ($21,582) was higher than that of mastectomy ($16,122, P < .01). The costs for BCS and mastectomy were significantly lower than for mastectomy plus reconstruction ($31,047, P < .05). The 2-year cost for immediate reconstruction was $8200 less than for delayed procedures and was similar to the cost of BCS. CONCLUSIONS: Age was the driving force in reconstruction decisions. Clinical factors such as tumor size and nodal status were more important for the choice between BCS and mastectomy. There are significant cost differences between the various procedures. For a similar cosmetic outcome, BCS is less expensive than breast reconstruction. When reconstruction is required, a simultaneous procedure is less expensive.

Neutropenia and neoplasia: an overview of the pharmacoeconomics of sargramostim in cancer therapy.

Sargramostim is a myeloid growth factor that is widely used as adjunctive support in patients with neutropenia. Sargramostim enhances neutrophil recovery and myeloid engraftment, reduces infectious complications, and shortens the duration of hospitalization in selected patients. The high cost of sargramostim and other myeloid growth factors and their ability to reduce infections and days of hospitalization have generated interest in their pharmacoeconomic impact. Cost minimization studies in patients receiving chemotherapy for acute myelogenous leukemia and in recipients of autologous bone marrow transplantation (BMT) show estimated cost savings with sargramostim of 1996 US$12,513 and 1994 US$14,500, respectively. These data are consistent with cost savings of 1989 US$16,000 using molgramostim in autologous BMT recipients. Although no pharmacoeconomic data have been published in patients with other conditions, clinical outcomes research demonstrates a clear benefit for sargramostim administration in recipients of peripheral blood progenitor cell and allogeneic BMT and in patients who experience graft delay or failure. Because of reductions in the duration of hospitalization and infectious complications, economic outcomes of these conditions would probably also support sargramostim use. More data regarding the use of sargramostim for chemotherapy-induced neutropenia are required to properly assess the pharmacoeconomic impact in these patients.

Cost-effective use of autologous bone marrow transplantation: few answers, many questions, and suggestions for future assessments.

High dose chemotherapy with the support of autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cells (PBPC) has been increasingly used in a variety of haematological and epithelial cancers over the last decade. The rationale of this approach is to overcome the chemotherapy resistance of tumour cells by increasing the dose of cytotoxic drugs. However, the clinical benefit of dose-intensification has been difficult to prove. Almost all studies of ABMT have been done without randomised comparisons with the standard form of therapy for a specific condition. From an economic perspective, the cost of ABMT has been steadily decreasing with improvements in supportive care primarily. Still, current ABMT cost estimates range from $US70 000 to $US150 000 for each uncomplicated procedure. Despite the lack of compelling evidence in support of dose-intensification, ABMT has become a default standard of care after relapse for many patients with lymphoma or leukaemia. We used a decision analysis model to estimate the cost effectiveness of the timing of ABMT in relapsed Hodgkin's disease. The model illustrates the difficulty of using available clinical trial data when follow-up of promising early reports is not available. The model showed that in most situations the optimal strategy is ABMT in second relapse despite growing consensus that immediate ABMT is the treatment of choice. ABMT for women with high-risk or early metastatic breast cancer is one of the most controversial areas in clinical oncology. In the US, several ongoing major randomised trials are addressing the role of ABMT in breast cancer. Using a Markov process we found that ABMT is the preferred strategy under almost all assumptions. The size of the benefit and cost effectiveness of ABMT varied markedly depending on the assumptions made. The model does not supplant the need for randomised trials that concurrently measure efficacy, quality of life, and resource utilisation. However, such analyses point out the critical areas where costs could be cut substantially without effecting efficacy. Drawing conclusions about the cost effectiveness of ABMT for all conditions is hampered by the lack of randomised comparisons of efficacy. Concurrent economic appraisals of selected phase III comparative trials should be considered since the supportive care costs associated with ABMT appear to be stabilising. However, the most important point is that randomised trials are the only mechanism for estimating the therapeutic effect of high dose chemotherapy.

Demodex cricetuli: new species of hair follicle mite (Acari: Demodecidae) from the Armenian hamster, Cricetulus migratorius (Rodentia: Cricetidae).

Demodex cricetuli sp. nov. is described, in all life stages, from the Armenian hamster, Cricetulus migratorius. This demodecid inhabits the hair follicles of all body regions of the host. Heavy infestations are associated with dermatitis and alopecia. Demodex cricetuli is most similar to D. aurati, from the Golden hamster, but adults differ in podosomal length, shape of the opisthosomal terminus, genital opening and opisthosomal organ of the male, and overall length-to-width ratios.