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Robert Marcus

Publications and source records attributed to Robert Marcus.

31 records · Page 2Linked to original sources
PubMed2003

Current calibration, treatment, and treatment planning techniques among institutions participating in the Children's Oncology Group.

PURPOSE: To report current technology implementation, radiation therapy physics and treatment planning practices, and results of treatment planning exercises among 261 institutions belonging to the Children's Oncology Group (COG). METHODS AND MATERIALS: The Radiation Therapy Committee of the newly formed COG mandated that each institution demonstrate basic physics and treatment planning abilities by satisfactorily completing a questionnaire and four treatment planning exercises designed by the Quality Assurance Review Center. The planning cases are (1) a maxillary sinus target volume (for two-dimensional planning), (2) a Hodgkin's disease mantle field (for irregular-field and off-axis dose calculations), (3) a central axis blocked case, and (4) a craniospinal irradiation case. The questionnaire and treatment plans were submitted (as of 1/30/02) by 243 institutions and completed satisfactorily by 233. Data from this questionnaire and analyses of the treatment plans with monitor unit calculations are presented. RESULTS: Of the 243 clinics responding, 54% use multileaf collimators routinely, 94% use asymmetric jaws routinely, and 13% use dynamic wedges. Nearly all institutions calibrate their linear accelerators following American Association of Physicists in Medicine protocols, currently 16% with TG-51 and 81% with TG-21 protocol. Treatment planning systems are relied on very heavily for all calculations, including monitor units. Techniques and results of each of the treatment planning exercises are presented. CONCLUSIONS: Together, these data provide a unique compilation of current (2001) radiation therapy practices in institutions treating pediatric patients. Overall, the COG facilities have the equipment and the personnel to perform high-quality radiation therapy. With ongoing quality assurance review, radiation therapy compliance with COG protocols should be high.

Brain↗
PubMed2003

Five weeks of insulin-like growth factor-I treatment does not alter glucose kinetics or insulin sensitivity during a hyperglycemic clamp in older women.

Insulin sensitivity and the activity of the hypothalamic-growth hormone (GH)- insulin-like growth factor-I (IGF-I) axis both decline with age. Treatment with IGF-I increases insulin sensitivity in healthy young subjects. We hypothesized that increasing plasma IGF-I in postmenopausal women to levels characteristic of young women would enhance insulin sensitivity. To test the hypothesis, fasting glucose kinetics and insulin sensitivity were measured in 24 healthy, normoglycemic, postmenopausal women before and after 5 weeks of treatment with either recombinant human (rh)IGF-I (15 microg/kg body weight/d twice daily) or placebo in a double-blind study. Diet energy content and composition were rigidly controlled to maintain energy balance. A hyperglycemic clamp (8 mmol/L) coupled with stable isotope infusion ([6,6(2)H]glucose) was performed before and after treatment to assess whole-body insulin sensitivity; defined as the glucose rate of disappearance (Rd) or rate of infusion (GRIF) scaled to the steady-state insulin concentration (I). There were no differences in fasting glucose or insulin concentrations, glucose kinetics, or glucose oxidation after either treatment. During the clamps, steady-state insulin concentrations with placebo (pre = 151 +/- 28 pmol/L, post = 173 +/- 31 pmol/L) were slightly different than with IGF-I (pre = 182 +/- 37 pmol/L, post = 163 +/- 33 pmol/L), but the variations were not significant. No significant changes in whole-body insulin sensitivity were observed after treatment with IGF-I, calculated as Rd/I (pre = 17.7 +/- 2.6 microg/kg/min/pmol/L, post = 19.3 +/- 2.0 microg/kg/min/pmol/L for IGF-I v pre = 24.2 +/- 2.5 microg/kg/min/pmol/L, post = 22.8 +/- 3.4 microg/kg/min/pmol/L for placebo) or as GRIF/I (pre = 18.0 +/- 3.9 microg/kg/min/pmol/L, post = 22.3 +/- 3.5 microg/kg/min/pmol/L for IGF-I v pre = 26.4 +/- 6.2 microg/kg/min/pmol/L, post = 26.9 +/- 4.8 microg/kg/min/pmol/L for placebo). Baseline insulin sensitivity in women using hormone replacement therapy (HRT, n = 15) was similar to nonusers (n = 9), but HRT users derived a greater portion of energy expenditure from carbohydrate oxidation compared with nonusers. HRT use had no impact on the response to IGF-I. Overall, we observed subtle, but physiologically insignificant, variations after IGF-I treatment in the direction of enhanced insulin sensitivity. The data suggest that 5 weeks of low-dose rhIGF-I treatment has no material influence on whole-body insulin sensitivity in normoglycemic postmenopausal women.

Aging↗
PubMed2003

Monoclonal antibody therapy for lymphoma.

Monoclonal antibodies are an exciting advance in the treatment of lymphoma. They are safe and well-tolerated, and exhibit little cross-resistance with conventional chemotherapeutic agents. In indolent lymphomas, antibody therapy has shown useful response rates, both as first-line therapy and in relapsed disease. Follicular lymphomas appear to be particularly sensitive to rituximab, and chronic lymphocytic leukaemia to alemtuzumab. In aggressive lymphomas, the addition of rituximab to CHOP chemotherapy significantly lengthens disease-free and overall survival compared to CHOP alone as first-line therapy. Newer agents, including radiolabelled antibodies, immunotoxin-linked antibodies and antibodies against novel target antigens are showing promise in phase I and II trials in a variety of clinical settings.

Alemtuzumab↗
PubMed2003

Current treatment options in aggressive lymphoma.

The overall percentage of patients achieving long-term remissions in aggressive non-Hodgkin's lymphoma (NHL) using CHOP or CHOP-based primary chemotherapy is only 40%. Much effort has therefore been concentrated on developing strategies to improve this figure. More intensive variants of CHOP chemotherapy, such as multi-agent "third-generation" regimens, have failed to improve long-term survival, and are also associated with increased toxicity. Hence, there is a need for improved treatment regimens, both as primary therapy and for patients in first and subsequent relapse. This need is most acute in elderly patients (> 60 years of age), who comprise more than 50% of NHL cases and who may not be able to tolerate subsequent intensive chemotherapy at relapse. Approaches currently being examined to improve outcome include: the use of clinical, histological and molecular prognostic factors to establish a patient's risk group, and so define those patients most likely to benefit from early aggressive therapy; the inclusion of high-dose therapy and autologous transplantation; and the integration of novel therapies, such as immunotherapy and radioimmunotherapy, into existing treatment strategies. The impact of these approaches on the treatment of diffuse, large B-cell lymphoma and mantle cell lymphoma is discussed below.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Disordered eating, menstrual irregularity, and bone mineral density in female runners.

PURPOSE: To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners. METHODS: Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry. RESULTS: An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% CI]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight, percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors. CONCLUSION: In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity.

Absorptiometry, Photon↗
PubMed2003

The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis.

In a recent study of women with postmenopausal osteoporosis, treatment with teriparatide for a median of 19 months increased bone mineral density and decreased the risk of vertebral and nonvertebral fractures. Using the same cohort, the current study evaluated the relationship between these therapeutic effects and the patient's baseline age, vertebral bone mineral density, and prevalent vertebral fractures. In women over 65 years of age, treatment resulted in a greater increase in vertebral bone mineral density than in younger women (treatment-by-age interaction, p = 0.037), but baseline age had no effect on the relative risk reduction for vertebral fractures (treatment-by-age interaction, p = 0.558). In women receiving placebo (with calcium and vitamin D), there was an inverse relationship between baseline vertebral bone mineral density and vertebral fracture risk. When compared across bone mineral density tertiles, the effects of teriparatide on the relative risk for developing new vertebral fractures and increase in vertebral bone mineral density did not differ significantly (p = 0.817 and p = 0.615, respectively). Teriparatide treatment significantly decreased vertebral fracture risk in patients with a vertebral bone mineral density T score of less than -33 or a score between -2.1 and -3.3 (p < 0.001 and p = 0.027, respectively) and showed a trend toward reduced fracture risk in the group with a T score greater than -2.1 (p = 0.115). Placebo-treated women with two or more prevalent vertebral fractures had a significantly greater risk of developing new vertebral fractures than women with zero or one prevalent vertebral fracture (p < 0.001). When compared within prevalent vertebral fracture subgroups, the effects of teriparatide on the relative risk for developing new vertebral fractures were similar. The results of this study indicate that teriparatide offers clinical benefit to patients across a broad range of age and disease severity.

Adult↗
PubMed2002

Bone mass response to discontinuation of long-term hormone replacement therapy: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Safety Follow-up Study.

BACKGROUND: Accelerated bone loss after stopping hormone therapy (HRT) is postulated to explain the lack of hip-fracture protection conferred by former HRT use. The abbreviation HRT (traditionally standing for "hormone replacement therapy") is used herein because of its wide recognition in the field. However, the pharmacological doses of estrogens and progestins used are not truly "replacement" in nature. OBJECTIVES: To determine whether women lose bone mineral density (BMD) after stopping HRT; to assess whether their rate of loss is significantly greater than that of women not undergoing HRT; and to determine whether long-term HRT is associated with continued gains in BMD. METHODS: A total of 495 women who were adherent to assigned treatment in the 3-year Postmenopausal Estrogen/Progestin Interventions randomized controlled trial (PEPI-RCT) and who had an additional BMD measurement during the PEPI Safety Follow-up Study were observed for an average of 3 years during and 4 years after the PEPI-RCT. RESULTS: Women who stopped HRT after 1 year during the PEPI-RCT had annual rates of BMD change of -0.54% (hip) and -0.81% (spine) during the following 2 years. Those who underwent HRT for 3 years during the PEPI-RCT and then discontinued it had annual changes of -1.01% (hip) and -1.04% (spine). Rates of BMD loss among women who stopped HRT during or after the PEPI-RCT did not differ significantly from those of women who did not undergo HRT, who lost bone at a rate of approximately 1% yearly during the first year of the PEPI-RCT and about half that rate afterward. Women who continued HRT after the PEPI-RCT did not show additional BMD gains. CONCLUSIONS: Our results do not support the hypothesis that bone is lost at an unusually fast rate after discontinuation of HRT, nor do they suggest that longer-term HRT leads to additional BMD gain beyond that evident after 3 years.

Bone Density↗
PubMed2002

Long-term effects of nutrient intervention on markers of bone remodeling and calciotropic hormones in late-postmenopausal women.

BACKGROUND: Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly. Other nutrients also affect bone health, and adequate intakes may influence bone turnover and balance. OBJECTIVE: We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement, a calcium and vitamin D supplement, and dietary instruction aimed at increasing calcium intake through foods. DESIGN: Ninety-nine healthy postmenopausal women participated in a 3-y, randomized trial, receiving either 1) supplemental calcium (1450 mg/d) and vitamin D [10 microg (400 IU)/d], 2) calcium, vitamin D, and other nutrients (multinutrient supplement), or 3) dietary instruction (dietary control group). Data are from 83 subjects who completed the trial. RESULTS: Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups. Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter. Bone turnover markers followed a similar pattern, and none of the changes in biochemical concentrations differed significantly between groups. CONCLUSIONS: All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations. The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone. The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates.

Aged↗
PubMed2002

Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes in large clinical trials with fracture as an endpoint.

Antiresorptive treatments for postmenopausal osteoporosis have been studied extensively, but due to the volume of published data and lack of head-to-head trials, it is difficult to evaluate and compare their fracture reduction efficacy. The objective of this review is to summarize the results from clinical trials that have fracture as an endpoint and to discuss the factors in study design and populations that can affect the interpretation of the results. Although there are numerous observational studies suggesting that estrogen and hormone replacement therapies may reduce the risk of vertebral and nonvertebral fractures, there is no large, prospective, randomized, placebo-controlled, double-blind clinical trial demonstrating fracture efficacy. The effects of raloxifene, alendronate, risedronate, and salmon calcitonin on increasing bone mineral density (BMD) and decreasing fracture risk have been shown in randomized, placebo-controlled, double-blind clinical trials of postmenopausal women with osteoporosis. Although the increases in lumbar spine BMD vary greatly in these trials, the decrease in relative risk of vertebral fractures is similar among therapies. However, nonvertebral fracture efficacy has not been consistently demonstrated. Combined administration of two antiresorptive therapies results in greater BMD increases, but the effects on fracture risk are unknown. Direct comparisons of clinical trial results should be considered carefully, given the differences in study design and populations. Differences in study design that may influence the efficacy of fracture risk reduction include calcium and vitamin D supplementation, primary fracture endpoints, definition of vertebral deformity or fracture, discontinuation rates, and statistical power. Factors in the study population that may influence fracture efficacy include the age of the population and the proportion of subjects with prevalent fractures. The use of surrogate endpoints such as BMD to predict fracture risk should be approached with caution, as the relationship between BMD changes and fracture risk reduction with antiresorptive therapies is uncertain. Consideration of these results from clinical trials can contribute to clinical judgment in selecting the best treatment option for postmenopausal osteoporosis.

Calcitonin↗