ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe.

BACKGROUND: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. DESIGN AND METHODS: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. RESULTS: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. CONCLUSIONS: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

Metabolic phenotypes of obesity: frequency, correlates and change over time in a cohort of postmenopausal women.

OBJECTIVE: The possibility that a subset of persons who are obese may be metabolically healthy-referred to as the 'metabolically healthy obese' (MHO) phenotype-has attracted attention recently. However, few studies have followed individuals with MHO or other obesity phenotypes over time to assess change in their metabolic profiles. The aim of the present study was to examine transitions over a 6-year period among different states defined simultaneously by body mass index (BMI) and the presence/absence of the metabolic syndrome (MetS). METHODS: We used repeated measurements available for a subcohort of participants enrolled in the Women's Health Initiative (N=3512) and followed for an average of 6 years to examine the frequency of different metabolic obesity phenotypes at baseline, the 6-year transition probabilities to other states and predictors of the risk of different transitions. Six phenotypes were defined by cross-tabulating BMI (18.5-<25.0, 25.0-<30.0, ⩾30.0 kg m-2) by MetS (yes, no). A continuous-time Markov model was used to estimate 6-year transition probabilities from one state to another. RESULTS: Over the 6 years of follow-up, one-third of women with the healthy obese phenotype transitioned to the metabolically unhealthy obese (MUO) phenotype. Overall, there was a marked tendency toward increased metabolic deterioration with increasing BMI and toward metabolic improvement with lower BMI. Among MHO women, the 6-year probability of becoming MUO was 34%, whereas among unhealthy normal-weight women, the probability of 'regressing' to the metabolically healthy normal-weight phenotype was 52%. CONCLUSIONS: The present study demonstrated substantial change in metabolic obesity phenotypes over a 6-year period. There was a marked tendency toward metabolic deterioration with greater BMI and toward metabolic improvement with lower BMI.

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial.

BACKGROUND: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. METHODS: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. RESULTS: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). CONCLUSION: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity.

In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.

Reliable evidence from placebo-controlled, randomized, clinical trials for menopausal hormone therapy's influence on incidence and deaths from breast cancer.

In an invited editorial, Dr Shapiro proposes that vaginal bleeding leading to unblinding and subsequent detection bias explains the breast cancer increase seen with estrogen plus progestin in the Women's Health Initiative (WHI) clinical trial (1) . In the context of a uniform detection program of protocol-mandated annual mammography and breast examinations, such a proposal is medically implausible. Dr Shapiro suggests detection bias would identify a larger number of 'slowly growing tumors that would otherwise remain clinically silent'. The findings of more advanced cancers with increased deaths from breast cancer in the estrogen plus progestin group refute this conjecture. During early post-intervention phases of both WHI hormone therapy trials, when breast cancer detection bias is asserted by Dr Shapiro because participants had been informed of randomization assignment, breast cancer incidence rates were lower (rather than higher) than during intervention. Thus, Dr Shapiro's claims are directly refuted by findings from the WHI randomized clinical trials. Health-care providers should be aware that randomized clinical trial evidence supports estrogen plus progestin increasing breast cancer incidence and deaths from breast cancer. In contrast, among women with prior hysterectomy, randomized clinical trial evidence supports estrogen alone reducing breast cancer incidence and deaths from breast cancer.

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study.

SUMMARY: The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D(3) daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer. INTRODUCTION: This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality. METHODS: WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS). RESULTS: Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive. CONCLUSION: Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.

Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: results from the Women's Health Initiative.

SUMMARY: Risk for falls and fractures increases after breast cancer or other cancer diagnosis in postmenopausal women. Factors other than falls may be the major causes for the increased fracture risk. INTRODUCTION: Cancer treatment and prognosis may have detrimental effects on bone health. However, there is a lack of prospective investigations on fracture risk among incident cancer cases. METHODS: In this study, postmenopausal women (N = 146,959) from the Women's Health Initiative prospective cohort, who had no cancer history at baseline, were followed for up to 9 years and classified into no cancer, incident breast cancer (BC) and incident other cancer (OC) groups. The main outcomes measured were incident fractures and falls before and after cancer diagnosis. Hazards ratios (HR) and 95% confidence intervals (CI) were computed from Cox proportional hazards model. RESULTS: While hip fracture risk before a cancer diagnosis was similar between the no cancer and cancer groups, hip fracture risk was significantly higher after BC diagnosis (HR = 1.55, CI = 1.13-2.11) and the elevated risk was even more notable after OC diagnosis (HR = 2.09, CI = 1.65-2.65). Risk of falls also increased after BC (HR = 1.15, CI = 1.06-1.25) or OC diagnosis (HR = 1.27, CI = 1.18-1.36), but could not fully explain the elevated hip fracture risk. Incident clinical vertebral and total fractures were also significantly increased after OC diagnosis (p < 0.05). CONCLUSIONS: Postmenopausal women have significantly elevated risks for falls and fractures after a cancer diagnosis. The causes for this increased risk remained to be investigated.

Factors influencing the role of bisphosphonates in breast cancer management.

Bone metastases represent a significant tumor-related complication affecting many breast cancer patients. The resulting bone destruction or osteolysis that frequently accompanies metastatic bone disease results in considerable morbidity for patients including a high rate of skeletal complications, severe pain, and a reduced quality of life. Traditionally, the treatment of metastatic bone disease has relied heavily on the use of multidisciplinary therapies, such as radiotherapy in combination with systemic treatment, supported by analgesia. Bisphosphonates are a class of pyrophosphate analogs that actively inhibit bone resorption. As a result, their clinical application has expanded greatly over the past 5 to 10 years and, in addition to being the treatment of choice for hypercalcemia of malignancy, they have been shown to be effective in reducing the skeletal morbidity associated with metastatic breast cancer. Furthermore, recent data from animal and in vitro studies suggest that bisphosphonates may actually have an antiapoptotic and antiproliferative effect not only on osteoclasts, but also on macrophages and tumor cells. Recent improvements in our understanding of the underlying molecular mechanisms in breast cancer, the diagnosis of the disease itself, and the development of new systemic therapies has led to improved survival benefit for many breast cancer patients. However, because survival duration has also been related to the risk of developing skeletal complications, bisphosphonates may play an ever greater role in the management and prevention of skeletal morbidity in the future.

American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonates Expert Panel.

PURPOSE: To determine clinical practice guidelines for the use of bisphosphonates in the prevention and treatment of bone metastases in breast cancer and their role relative to other therapies for this condition. METHODS: An expert multidisciplinary panel reviewed pertinent information from the published literature and meeting abstracts through May 1999. Additional data collected as part of randomized trials and submitted to the United States Food and Drug Administration were also reviewed, and investigators were contacted for more recent information. Values for levels of evidence and grade of recommendation were assigned by expert reviewers and approved by the panel. Expert consensus was used if there were insufficient published data. The panel addressed which patients to treat and when in their course of disease, specific drug delivery issues, duration of therapy, management of bony metastases with other therapies, and the public policy implications. The guideline underwent external review by selected physicians, members of the American Society of Clinical Oncology (ASCO) Health Services Research Committee, and the ASCO Board of Directors. RESULTS: Bisphosphonates have not had an impact on the most reliable cancer end point: overall survival. The benefits have been reductions in skeletal complications, ie, pathologic fractures, surgery for fracture or impending fracture, radiation, spinal cord compression, and hypercalcemia. Intravenous (IV) pamidronate 90 mg delivered over 1 to 2 hours every 3 to 4 weeks is recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. For women with only an abnormal bone scan but without bony destruction by imaging studies or localized pain, there is insufficient evidence to suggest starting bisphosphonates. Starting bisphosphonates in patients without evidence of bony metastasis, even in the presence of other extraskeletal metastases, is not recommended. Studies of bisphosphonates in the adjuvant setting have yielded inconsistent results. Starting bisphosphonates in patients at any stage of their nonosseous disease, outside of clinical trials, despite a high risk for future bone metastasis, is currently not recommended. Oral bisphosphonates are one of several options which can be used for preservation of bone density in premenopausal patients with treatment-induced menopause. The panel suggests that, once initiated, IV bisphosphonates be continued until evidence of substantial decline in a patient's general performance status. The panel stresses that clinical judgment must guide what is a substantial decline. There is no evidence addressing the consequences of stopping bisphosphonates after one or more adverse skeletal events. Symptoms in the spine, pelvis, or femur require careful evaluation for spinal cord compression and pathologic fracture before bisphosphonate use and if symptoms recur, persist, or worsen during therapy. The panel recommends that current standards of care for cancer pain, analgesics and local radiation therapy, not be displaced by bisphosphonates. IV pamidronate is recommended in women with pain caused by osteolytic metastasis to relieve pain when used concurrently with systemic chemotherapy and/or hormonal therapy, since it was associated with a modest pain control benefit in controlled trials. CONCLUSION: Bisphosphonates provide a meaningful supportive but not life-prolonging benefit to many patients with bone metastases from cancer. Further research is warranted to identify clinical predictors of when to start and stop therapy, to integrate their use with other treatments for bone metastases, to identify their role in the adjuvant setting in preventing bone metastases, and to better determine their cost-benefit consequences.

American Society of Clinical Oncology technology assessment on breast cancer risk reduction strategies: tamoxifen and raloxifene.

OBJECTIVE: To conduct an evidence-based technology assessment to determine whether tamoxifen and raloxifene as breast cancer risk-reduction strategies are appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTION: Tamoxifen and raloxifene. OUTCOME: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefits. EVIDENCE: A comprehensive, formal literature review was conducted for tamoxifen and raloxifene on the following topics: breast cancer risk reduction; tamoxifen side effects and toxicity, including endometrial cancer risk; tamoxifen influences on nonmalignant diseases, including coronary heart disease and osteoporosis; and decision making by women at risk for breast cancer. Testimony was collected from invited experts and interested parties. VALUES: More weight was given to publications that described randomized trials. BENEFITS/HARMS/COSTS: The American Society of Clinical Oncology (ASCO) Working Group acknowledges that a woman's decision regarding breast cancer risk-reduction strategies will depend on the importance and weight attributed to the information provided regarding both cancer and non-cancer-related risks. CONCLUSIONS: For women with a defined 5-year projected risk of breast cancer of >/= 1.66%, tamoxifen (at 20 mg/d for up to 5 years) may be offered to reduce their risk. It is premature to recommend raloxifene use to lower the risk of developing breast cancer outside of a clinical trial setting. On the basis of available information, use of raloxifene should currently be reserved for its approved indication to prevent bone loss in postmenopausal women. Conclusions are based on single-agent use of the drugs. At the present time, the effect of using tamoxifen or raloxifene with other medications (such as hormone replacement therapy), or using tamoxifen and raloxifene in combination or sequentially, has not been studied adequately. The continuing use of placebo-controlled trials in other risk-reduction trials highlights the current unanswered issues concerning the use of such interventions, especially when the influence on net health benefit remains to be determined. Breast cancer risk reduction is a rapidly evolving area. This technology assessment represents an ongoing process with existing plans to monitor and review data and to update recommendations in a timely matter. (See VALIDATION: The conclusions of the Working Group were evaluated by the ASCO Health Services Research Committee and by the ASCO Board of Directors. SPONSOR: American Society of Clinical Oncology.

Elements of informed consent for hormone replacement therapy in patients with diagnosed breast cancer.

PURPOSE: An approach to providing informed consent to breast cancer survivors considering hormone replacement therapy (HRT) is offered. METHODS: Current information on HRT, breast cancer, and chronic disease prevention is reviewed in the context of risks faced by women with resected breast cancer. RESULTS: Breast cancer patients, unwilling to trade symptom reduction for even a small increase in recurrence risk, are at substantially increased risk of death from breast cancer relative to other causes. Observational studies suggest that long-term HRT increases breast cancer development. The influence of HRT on the growth of established breast cancer has not been determined; however, estrogen reduction (oophorectomy) significantly reduces recurrence in premenopausal women, and current evidence cannot exclude a risk that HRT increases recurrence to the same degree. The following issues are of particular relevance to breast cancer survivors: HRT reduces mammographic sensitivity, increases thromboembolic events, and increases endometrial cancer risk. Although benefit for HRT is commonly inferred from observational studies, randomized trials of HRT on all-cause mortality have not been completed. For coronary heart disease prevention, an array of strategies independent of HRT are available, with some (tamoxifen, selective estrogen receptor modifiers [SERMs], diet, and exercise) likely to favorably influence breast cancer risk; for osteoporosis prevention, an array of strategies also are available, with some (bisphosphonates, tamoxifen, SERMs, and exercise) likely to favorably influence breast cancer risk. CONCLUSION: Current data preclude the generation of evidence-based guidelines for HRT use in breast cancer survivors, and clinical trials in this setting should be supported. However, given available therapeutic alternatives for menopausal symptom management and chronic disease prevention, breast cancer survivors should be offered HRT only with caution and with their full participation in the decision-making process.

Gender influence on weight-loss pattern and survival of nonsmall cell lung carcinoma patients.

BACKGROUND: Gender has recently emerged as a discriminating factor in nonsmall lung carcinoma (NSCLC) patient outcome. Since the potential for interaction among established prognostic factors and gender in this common disease has not been explored, the authors evaluated the role of gender and weight-loss pattern in predicting clinical outcome in a balanced population of men and women presenting with NSCLC. METHODS: From a tumor registry population of 368 NSCLC patients, a gender-balanced sample of 152 cases was randomly selected for review, using prospective inclusion criteria. Study parameters were age, race, tobacco and alcohol history, gender, weight-loss pattern, histology, TNM stage, Eastern Cooperative Oncology Group performance status, and therapy. Influences of study variables on Kaplan-Meier estimates of survival were subsequently determined using univariate and multivariate analyses. RESULTS: Overall median survival after diagnosis was significantly shorter for men with NSCLC than for women with the disease (40 vs. 78 weeks, P = 0.001). Men lost significantly more weight over their disease course than women (12.2 vs. 5.4 pounds, P = 0.006) and experienced an eightfold faster rate of initial weight loss (0.25 vs. 0.03 pounds per week, P = 0.001). In multivariate analysis, the strongest independent predictors of NSCLC patient survival were stage of disease, initial weight-loss rate, and gender (all P < 0.0001). CONCLUSIONS: These results suggest that weight loss may play a role in mediating gender-related differences in NSCLC patient survival and provide an impetus for further studies of gender influence on cancer outcome.

Monitoring dietary change in a low-fat diet intervention study: advantages of using 24-hour dietary recalls vs food records.

OBJECTIVE: The purpose of the study was to evaluate two methods of dietary assessment for monitoring change in fat intake in a low-fat diet intervention study. DESIGN: The two dietary assessment methods were a 4-day food record (4DFR) and an unannounced 24-hour dietary recall conducted by telephone interview (referred to as a telephone recall [TR]). Subjects were assigned randomly to either a low-fat diet intervention group or a control group that received no counseling about fat intake. Dietary data were collected at baseline, 6 months, and 12 months. SUBJECTS: Two hundred ninety postmenopausal women with localized breast cancer were recruited at seven clinical centers in the United States. STATISTICAL ANALYSIS: Analysis of variance was used to test for significant differences in mean fat and energy intakes. RESULTS: Three sources of error were identified: (a) an instrument effect, suggesting underreporting at baseline of approximately 8% in mean energy intake and 11% in mean fat intake in the TR group compared with the 4DFR group (P = .0001); (b) a repeated measures effect observed for the 4DFR, suggesting underreporting of approximately 7% for energy intake and 14% for fat intake in the control group at 6 and 12 months compared with baseline values (P < .001); and (c) an adherence effect (or compliance bias), suggesting greater compliance to the low-fat intervention diet when subjects were keeping food records than when estimates were based on the unannounced TR. Compared with the TR, the 4DFR overestimated the extent of fat reduction in the low-fat diet intervention group by 41% (P = .08) and 25% (P = .62) at 6 and 12 months, respectively. APPLICATION: Multiple days of unannounced 24-hour recalls may be preferable to multiple-day food records for monitoring dietary change in diet intervention studies.

Recent implications of weight loss in lung cancer management.

Successful lung cancer management has been hindered by the limited efficacy of dietary and pharmacologic interventions to prevent or reverse cancer-associated weight loss. The addition of total parenteral nutrition to chemotherapy in early trials was associated with survival detriment. Dietary counseling and enteral supplement use are common strategies that, when evaluated in randomized trials, do not improve anthropometrics or clinical outcome in lung cancer. Pharmacologic agents including corticosteroids, cyproheptadine, growth hormone, hydrazine sulfate, dronabinol, and pentoxyphylline also have failed to improve even anthropometric parameters in this condition. Megestrol acetate use is associated with appetite stimulation and non-fluid weight gain but, when evaluated in small cell lung cancer patients receiving defined chemotherapy, failed to improve global quality of life, and survival and was associated with toxicity. New strategies for nutrition-based interventions in lung cancer cachexia must consider their potential influence on tumor growth as well as on nutritional status. Recent lung cancer prognostic analyses have identified gender differences in outcome and weight loss that suggest potential targets for combined hormonal and nutrition interventions. Emerging information regarding the influence of specific fatty acids on tumor growth and cachexia development have identified additional approaches for future evaluation.

Altered metabolism and mortality in patients with colon cancer receiving chemotherapy.

To identify the metabolic effects of 5-fluorouracil and hydrazine sulfate therapy, 22 patients with colon cancer were admitted prospectively to a Clinical Research Center for serial measurement of counter-regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA) and leucine oxidation. Combined therapy was associated with a significant reduction in fasting glucose level (98 +/- 2 mg/dL to 94 +/- 2, P < 0.025) without a significant fall in fasting HGP (2.09 +/- 0.11 mg/kg/min versus 2.03 +/- 0.13; P > 0.05). The decreased fasting glucose value was associated with a mild but not statistically improved glucose disposal rate in response to the intravenous glucose tolerance test (1.34 +/- 0.07 %/min vs 1.47 +/- 0.11, P = 0.15). Plasma leucine appearance was significantly reduced after 2 months of therapy (63.3 +/- 3.0 mumol/kg/hr vs 57.1 +/- 3.9 mumol/kg/hr; P < 0.025), but leucine oxidation (11.5 +/- 1.1 mumol/kg/hr vs 11.2 +/- 1.1 mumol/kg/hr) was not altered. Despite the fact that plasma triiodothyronine concentrations significantly increased with therapy, it was not associated with plasma LA. Half of the patients with cancer died 14 +/- 4 months after the study, and the other half were alive 58 +/- 2 months later. Survival time can be estimated with 59% accuracy using plasma LA, HGP, carcino-embryonic antigen, and insulin concentration. Multiple regression analysis identified that plasma LA was related directly to length of survival time, and baseline HGP, carcino-embryonic antigen, and insulin concentration were related inversely to length of survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary intake and counseling, weight maintenance, and the course of HIV infection.

OBJECTIVE: To define relationships among dietary intake and counseling, weight maintenance, and the clinical course of patients infected with the human immunodeficiency virus (HIV). DESIGN: A prospective cohort study in an HIV clinic in a county hospital. SUBJECTS: HIV-infected patients (68 with and 40 without acquired immunodeficiency syndrome [AIDS]) who had a good performance status and no chronic diarrhea were assessed at entry to the study and after 6 months. The following assessments were made: energy and nutrient intake based on 7-day food records, anthropometric measurements, immunologic function as lymphocyte T-cell subpopulations (ratio of CD4 to CD8), and serum cholesterol level. Patients were monitored to determine clinical outcome. INTERVENTION: All patients received standardized dietary counseling designed to address identified intake deficiencies and maintain body weight. MAIN OUTCOME MEASURES: Changes in energy and nutrient intake, body weight, and clinical outcome (ie, time to AIDS-defining illness and overall survival time). STATISTICAL ANALYSES PERFORMED: Group differences (HIV group vs AIDS group) were sought using chi 2 analyses and Student's t test. A multivariate regression model was used to determined the best predictors of clinical outcome. RESULTS: At baseline, total energy intake (based on 30 kcal/kg usual body weight) was adequate in both HIV and AIDS patients (101 +/- 4% and 103 +/- 5% [mean +/- standard deviation] of need, respectively). Despite dietary counseling and continued maintenance of energy intake, body weight, serum cholesterol level, and CD4 level progressively decreased. Consequently, saturated fat intake was found to be inversely related (P < .01) to serum cholesterol level. Clinical outcome (after 3.5 years) was associated with baseline ratio of CD4 to CD8 (P < .001), weight (P < .01), and serum cholesterol level (P < .001). Multivariate analysis related ratio of CD4 to CD8 (P < .001) and weight maintenance (P < .001) to favorable outcome in the final model. APPLICATIONS: Weight loss in patients with HIV infection is independently prognostic of clinical outcome, and development of hypocholesterolemia is not favorable for clinical outcome. Because weight loss progresses despite conventional dietary counseling to identify energy need, interventions earlier in the disease course should be considered along with increased target levels for energy intake.