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Biomedical subjects

G H Lyman

Publications and source records attributed to G H Lyman.

At least 19 recordsLinked to original sources
PubMed2006

EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours.

Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival. The incidence of severe or FN can be reduced by prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim, lenograstim or pegfilgrastim. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. While several academic groups have produced evidence-based clinical practice guidelines in an effort to standardise and optimise the management of FN, there remains a need for generally applicable, European-focused guidelines. To this end, we undertook a systematic literature review and formulated recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. We recommend that patient-related adverse risk factors such as elderly age (>or=65 years), be evaluated in the overall assessment of FN risk prior to administering each cycle of chemotherapy. In addition, when using a chemotherapy regimen associated with FN in >20% patients, prophylactic G-CSF is recommended. When using a chemotherapy regimen associated with FN in 10-20% patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Finally, studies have shown that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated.

Antineoplastic Agents↗
PubMed2006

Randomized clinical trials for hematopoietic stem cell transplantation: lessons to be learned from the European experience.

We evaluated the number and characteristics of randomized controlled trials (RCTs) addressing hematopoietic stem cell transplantation (HSCT) for patients with hematological malignancies, comparing the productivity of US and Europe. A MEDLINE search was conducted to identify all published RCTs for the management of adult patients with hematological malignancies from January 1992 to December 2003. Eighty-three of the 306 trials identified included HSCT as one of the treatment arms. The US produced 25, Europe 54, and all other countries four. Four European countries, France, Italy, Germany, and UK (FIGU), produced 32 out of the 54 European studies. Significant differences emerged when focus of the study and accrual numbers were analyzed. Trials comparing HSCT to standard dose therapy represented 34.9% of the 83 trials and 59.4% of FIGU trials, but only 4% of US studies (P = 0.001). US trials accrued a mean of 110.2 patients per study, as compared to 222.6 in FIGU studies (P = 0.006) and 205.3 when all non-US countries are considered (P = 0.01). Our conclusions are that US transplant RCT have focused on issues other than the comparison of HSCT to standard therapies. There is serious paucity of US trials defining the role of HSCT in the management of hematological malignancies.

Adult↗
PubMed2004

The economics of the colony-stimulating factors in the prevention and treatment of febrile neutropenia.

Healthcare costs continue to rise with hospitalization representing the single largest component of direct medical costs associated with cancer care. Neutropenia and its complications including febrile neutropenia remain the major dose-limiting toxicity associated with systemic cancer chemotherapy. Febrile neutropenia often occurs early in the course of chemotherapy and is associated with substantial morbidity, mortality and cost. The colony-stimulating factors (CSFs) have been used effectively in a variety of clinical settings to prevent or treat febrile neutropenia and to assist patients receiving dose-intensive chemotherapy. A meta-analysis of the available randomized controlled trials (RCTs) has confirmed the efficacy of prophylactic CSFs. Economic models based on measures of resource utilization derived from RCTs have provided estimates of expected treatment costs along with febrile neutropenia risk threshold estimates for the cost saving use of the CSFs. Recent studies have demonstrated the potential value of targeting the CSFs toward patients at greatest risk based on accurate and valid predictive models.

Colony-Stimulating Factors↗
PubMed2003

Survival after HLA-identical allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: meta-analysis of randomized controlled trials.

The impact of peripheral blood stem cell transplantation (PBSCT) on survival relative to bone marrow transplantation (BMT) remains poorly defined. Several randomized controlled trials (RCTs) comparing HLA-matched related PBSC- and BMT for patients with hematologic malignancies have been published, yielding differing results. We conducted a meta-analysis of published RCTs to more precisely estimate the effect of PBSCT on survival. Seven trials that assessed survival were identified and included in our analysis. Using a fixed effects model, and combining the results of all seven trials, the summary odds ratio for mortality after PBSCT was 0.81 (95% CI, 0.62-1.05) when compared to BMT. Subgroup analysis revealed no association between the median PBSCT 34+ cell dose and relative risk for morality after PBSCT. However, there was an association between the proportion of patients enrolled with advanced-stage disease and the summary odds ratio for mortality. The pooled estimate was 0.64 for studies where patients with intermediate/advanced disease comprised at least 25% of enrollment, and was 1.07 for the studies enrolling a smaller proportion. This finding substantiates results from previously published studies that have demonstrated a survival advantage with PBSCT limited to patients with advanced disease.

Adult↗
PubMed2001

Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system.

PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal. PATIENTS AND METHODS: There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients. RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (< or = 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients. CONCLUSION: The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.

Adolescent↗
PubMed2001

Economic analysis of randomized, controlled trials.

To facilitate the comparison of different treatment strategies, measures have been developed that bring together clinical, quality-of-life, and economic outcomes into summary measures such as the quality-adjusted life year, cost-effectiveness, and cost-utility ratios. A number of different types of economic evaluations have been developed, including cost-minimization, cost-effectiveness, and cost-utility analyses. Performance of economic analyses in association with randomized, controlled trials (RCT) has gained increasing enthusiasm in recent years. However, economic measures in RCTs are often outcomes of secondary interest and associated with frequent missing data and inadequate sample size. Variability in the cost measures used and the lack of agreement on clinically meaningful cost differences further limit the conclusions derived from such studies. Economic analyses should be limited to large trials with important trade-offs between efficacy and cost. The strengths and limitations of such analyses are discussed, and guidelines are offered for proper economic analyses in randomized, controlled trials.

Costs and Cost Analysis↗
PubMed2001

The effects of postinjection massage on the sensitivity of lymphatic mapping in breast cancer.

BACKGROUND: The technique of lymphatic mapping and sentinel lymph node (SLN) biopsy is rapidly becoming the preferred method of staging the axilla of the breast cancer patient. This report describes the impact of postinjection massage on the sensitivity of this surgical technique. STUDY DESIGN: Lymphatic mapping at the H Lee Moffitt Cancer Center is performed using a combination of isosulfan blue dye and Tc99m labeled sulfur colloid. Data describing the rate of SLN identification and the node characteristics from 594 consecutive patients were calculated. Patients who received a 5-minute massage after injection of blue dye and radiocolloid were compared with a control group in which the patients did not receive a postinjection massage. RESULTS: When compared with controls, the proportion of patients who had their SLN identified using blue dye after massage increased from 73.0% to 88.3%, and the proportion of patients who had their SLN identified using radiocolloid after massage increased from 81.7% to 91.3%. The overall rate of SLN identification increased from 93.5% to 97.8%. The proportion of nodes that were stained blue among those removed increased from 73.4% to 79.7% after massage. CONCLUSIONS: As experience increases with this new procedure, the surgical technique of lymphatic mapping continues to evolve. The addition of a postinjection massage significantly improves the uptake of blue dye by SLNs and may also aid in the accumulation of radioactivity in the SLNs, further increasing the sensitivity of this procedure.

Breast Neoplasms↗
PubMed2001

Evaluation and appraisal of randomized controlled trials in myeloma.

PURPOSE: To critically appraise therapeutic innovations tested in randomized controlled trials (RCTs) in multiple myeloma from 1966-1998. DESIGN: We performed a comprehensive search to identify published RCTs in multiple myeloma. Quality dimensions of the design, conduct, analysis and reporting of each trial were assessed. RESULTS: We identified 136 RCTs reported in 114 papers. Overall, therapeutic efforts in multiple myeloma resulted in a 5% absolute gain in five-year survival at a cost of a 0.35% increase in treatment related deaths. Hence on average a patient enrolled in a RCT in myeloma is 14 (5/35) times more likely to be helped than harmed. However, when the RCTs were critically appraised for key quality dimensions of trials' conduct, we found that only 7%) of the trials (10 of 136) were analyzed according to intention-to-treat (ITT), 9% (12 of 136) reported a power analysis (beta error), 32% (35 of 111) adequately concealed treatment allocation, 78% (106 of 136) provided a detailed description of patient withdrawals, and 83%) (19 of 22) of the double blind RCTs had appropriately described methodology. CONCLUSIONS: Therapeutic innovations tested through RCTs have improved the outcomes of patients with multiple myeloma. However, the quality of RCT reporting and methodology in multiple myeloma could be substantially improved. Most therapeutic strategies in multiple myeloma are based on modest quality, low power evidence. Despite these shortcomings our findings suggest patients may often clinically benefit from enrollment in clinical trials when available. Patients on average received modest benefit from innovative therapies tested in RCTs at little additional risk of side effects.

Humans↗
PubMed2001

Hematopoietic growth factors in the older cancer patient.

Aging is associated with a progressive decline in the functional reserve of multiple organ systems, which may lead to enhanced susceptibility to stress such as that caused by cancer chemotherapy. Myelodepression is the most common and the most commonly fatal complication of antineoplastic drug therapy and may represent a serious hindrance to the management of cancer in older individuals. This is already a common and pervasive problem and promises to become more so. Currently 60% of all neoplasms occur in persons aged 65 years and older, and this percentage is expected to increase as the population ages. This well-known phenomenon, sometimes referred to as squaring or the age pyramid, is caused by the combination of an increasing life expectancy and a decreasing birth rate. This article explores the use of hematopoietic growth factors in the older cancer patient after reviewing the influence of age on hemopoiesis and chemotherapy-related complications. The issue is examined in terms of effectiveness and cost. An outline of the assessment of the older cancer patient is provided at the end of the chapter as a frame of reference for clinical decisions.

Aged↗
PubMed2000

The uncertainty principle and industry-sponsored research.

BACKGROUND: Reporting of pharmaceutical-industry-sponsored randomised clinical trials often result in biased findings, either due to selective reporting of studies with non-equivalent arms or publication of low-quality papers, wherein unfavourable results are incompletely described. A randomised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another. Studies in which intervention and control are thought to be non-equivalent violates the uncertainty principle. METHODS: We examined the quality of 136 published randomised trials that focused on one disease category (multiple myeloma) and adherence to the uncertainty principle. To evaluate whether the uncertainty principle was upheld, we compared the number of studies favouring experimental treatments over standard ones. We analysed data according to the source of funding. FINDINGS: Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores (mean 2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty principle was upheld, with 44% of randomised trials favouring standard treatments and 56% innovative treatments (p=0.17); mean and median preference evaluation scores were 3.7 (1.0) and 4. However, when the analysis was done according to the source of funding, studies funded by non-profit organisations maintained equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a greater extent than randomised trials supported solely or in part by profit-making organisations (74% vs 26%; p=0.004). INTERPRETATION: The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle. Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls.

Bias↗
PubMed2000

Quality of life after coronary angioplasty or continued medical treatment for angina: three-year follow-up in the RITA-2 trial. Randomized Intervention Treatment of Angina.

OBJECTIVES: We sought to evaluate the impact of percutaneous transluminal coronary angioplasty (PTCA) and medical treatment on self-perceived quality of life among patients with angina. BACKGROUND: The second Randomized Intervention Treatment of Angina trial (RITA-2) implemented initial policies of PTCA or continued medical treatment in patients with angina, allowing assessment of long-term health consequences. METHODS: A total of 1,018 patients were randomly assigned (504 to PTCA and 514 to medical treatment). The short form 36 (SF-36) self-administered quality-of-life questionnaire was completed at randomization and three months, one year and three years later. To date, 98% of patients reached one year and 67% reached three years. RESULTS: The PTCA group had significantly greater improvements in physical functioning, vitality and general health at both three months and one year, but not at three years. These quality-of-life scores were strongly related to breathlessness, angina grade and treadmill exercise time both at baseline and at one year. The treatment differences in quality of life are explained by the PTCA group's improvements in breathlessness, angina and exercise time. The attenuation of treatment difference at three years is partly attributed to 27% of medically treated patients receiving nonrandomized interventions in the interim. For both groups, there were also improvements in ratings of physical role functioning, emotional role functioning, social functioning, pain and mental health, but for these the superiority of PTCA over medical treatment was less pronounced. After one year, 33% and 22% of the PTCA and medical groups, respectively, rated their health much better. CONCLUSIONS: Coronary angioplasty substantially improves patient-perceived quality of life, especially physical functioning and vitality, as compared with continued medical treatment. These differences are attributed to alleviation of cardiac symptoms (specifically, breathlessness and angina), but must be balanced against the small procedure-related risks of PTCA.

Activities of Daily Living↗
PubMed2000

Linking evidence-based medicine therapeutic summary measures to clinical decision analysis.

OBJECTIVE: Evidence-based medicine (EBM) seeks to improve clinical practice by evaluating the quality of clinical evidence and ensuring that only the "best" evidence from clinical research is used in the management of individual patients. EBM has contributed to our understanding of the meaning of the benefit and harm of treatment as reported in the literature, and it is often promoted as an aid to clinical decision making. However, EBM therapeutic summary measures reflect only a single dimension of clinical decision making. The purpose of this work is to show how EBM therapeutic summary measures can be effectively incorporated into medical decision making. DESIGN: The effective application of the therapeutic summary measures advocated by EBM requires their integration into the framework of clinical decision analysis. Clinical decision analysis involves not only the identification and specification of the probabilities of clinical events but also the assessment of their relative values or utilities. We present here several analytic models for the integration of EBM therapeutic summary measures within the framework of clinical decision analysis. MAIN RESULTS: As expected, our analysis demonstrated that treatment should never be administered if its harm is greater than its efficacy, which is generally expressed as relative risk reduction. Likewise, a diagnostic test should never be ordered if the therapeutic harm is greater than the therapeutic efficacy. Intervention is always favored if the number needed to treat to avoid one adverse outcome (NNT) is smaller than the number needed to treat to harm one individual (NNH). When faced with a choice between two therapeutic options, the action threshold above which an intervention is favored can be expressed in terms of the harm inflicted (H) as H x NNT or NNT/NNH. If a patient's preferences are taken into account as relative value judgments (RV) of adverse events relative to that of therapeutic events, the action threshold is defined as NNT x (RV/NNH). CONCLUSIONS: In the setting of clinical decision making, EBM summary measures derived from population studies can be effectively used to define diagnostic and therapeutic action thresholds that may help in the management of individual patients.

Aged↗
PubMed2000

A novel approach to maintain planned dose chemotherapy on time: a decision-making tool to improve patient care.

Studies of primary prophylaxis of febrile neutropenia with recombinant granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim), administered to all patients starting with the initial course of chemotherapy, have demonstrated an economic advantage over a wide range of settings. In these analyses, the threshold risk for febrile neutropenia at which a cost saving is realised is inversely related to the direct medical costs of hospitalisation. Clinical practice guidelines for the use of filgrastim have been developed based on these observations. Recent studies incorporating indirect institutional costs have demonstrated that cost savings can be achieved at substantially lower febrile neutropenia risk thresholds than previously estimated. Despite the demonstrated efficacy of filgrastim in primary prophylaxis, its value may be further enhanced through the appropriate selection of patients for such therapy and a better understanding of the importance of sustaining dose intensity in specific malignancies. Clinical prediction models capable of identifying individuals at high risk for neutropenic complications yield further reductions in febrile neutropenia risk thresholds and treatment costs in patients receiving cancer chemotherapy. Prediction models can also be used to evaluate the cost-effectiveness or cost-efficiency of filgrastim use. Such a model has recently been developed and validated and is described here which incorporates both baseline clinical characteristics as well as the results of the first cycle of chemotherapy in patients with early-stage breast cancer. A cost-effectiveness ratio of US$ 34297 (Euro 32002)dagger per year of life saved (YLS) was calculated based on dose-response assumptions derived from a previously reported adjuvant breast cancer trial studying the impact of dose reduction on disease-free survival. This figure is comparable with accepted cost-effectiveness ratios for other interventions, e.g. US$ 45000/LYS (Euro 41989) for renal dialysis for patients with end-stage renal disease. The cost-effectiveness of filgrastim was evident over a wide range of clinical and cost assumptions. Clinical prediction models permit rational and cost-effective selection of patients for filgrastim support. Current guidelines should be re-evaluated in light of new information available on both the total cost of febrile neutropenia, as well as the cost-effectiveness of these agents in specific clinical situations.

Antineoplastic Agents↗
PubMed2000

Quality of life after adjuvant chemotherapy for breast cancer.

PURPOSE: To evaluate the quality of life of breast cancer patients previously treated with adjuvant chemotherapy. METHOD: Registry data were used to recruit a sample of breast cancer patients (N = 61; mean age = 51.6 years) with no current evidence of disease who had completed adjuvant chemotherapy between 3 and 36 months earlier (average = 15.87 months). In addition, a peer nomination procedure was used to recruit an age-matched comparison group of women with no history of cancer (N = 59; mean age = 51.5 years). Both groups were mailed a survey to complete that included the Medical Outcomes Study Short Form 36 (SF-36) and the Center for Epidemiologic Studies Depression Scale (CES-D). These data were used to test the hypothesis that breast cancer patients previously treated with adjuvant chemotherapy experience impaired quality of life relative to their peers and to identify demographic and medical factors associated with individual differences in patient quality of life. RESULTS: Consistent with predictions, the postchemotherapy group scored poorer than the noncancer comparison group on the CES-D and on six of the eight subscales as well as the physical component summary scale of the SF-36 (p < 0.05). With regard to individual differences in patient quality of life, younger age and unmarried status were positively related to poorer mental well-being and greater depressive symptomatology (p < 0.05). Time since cancer diagnosis and chemotherapy completion were also positively related to greater depressive symptomatology (p < 0.05). In contrast, none of the demographic or medical variables assessed were related to physical well-being (p > 0.05). CONCLUSIONS: Breast cancer patients appear to experience problems in multiple quality of life domains following the completion of adjuvant chemotherapy treatment. Demographic and medical characteristics explain individual differences in mental but not physical aspects of patient quality of life. These findings demonstrate the need for interventions to improve the quality of life in breast cancer patients previously treated with adjuvant chemotherapy.

Adult↗
PubMed2000

Evidentiary challenges to evidence-based medicine.

The evidence-based medicine (EBM) movement has exerted a strong influence on contemporary medicine. It has been used to define the hierarchy of knowledge in clinical medicine by classifying clinical findings according to the perceived relevance and validity of the respective methodologies of studies from which evidence was collected. In the spectrum of theories of knowledge, EBM predominantly relies on findings obtained from population-derived clinical research. This reliance on knowledge obtained from population studies sharply contrasts with a physiologic model of clinical knowledge advocated by basic science researchers and many clinicians. An apparent schism between proponents of physiologic and population models in the approach to the practice of medicine has been created. This dichotomy between practising physicians and EBM physicians in the approach to clinical knowledge should not be irreconcilable. We advocate a consilient approach to the interpretation of evidence and the integration of medical knowledge. This approach relies on 'linking of facts and fact-based theory across various disciplines to create a common groundwork of explanation'.

Decision Making↗
PubMed2000

Lymphatic mapping and sentinel lymph node biopsy in patients with breast cancer.

The standard of care for the evaluation of axillary nodal involvement remains complete lymph node dissection. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this long-held paradigm; indeed, several leading institutions already reserve complete axillary dissection for patients with metastasis to the SLN. In addition to reviewing the literature, this chapter describes our lymphatic mapping experience at the H Lee Moffitt Cancer Center and Research Institute with 1147 breast cancer patients. Our results, in addition to a meta-analysis of data from 12 institutions comprising an additional 1842 patients undergoing complete axillary dissection, demonstrate that SLN biopsy is an accurate method of axillary staging. Although the results from small series may exaggerate the probability of false negative results, the risk of nodal disease based on tumor size and other risk factors should be evaluated when considering the results of SLN sampling.

Biopsy↗