Inspiration from a forum arranged by students.
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Education, Medical↗
Biomedical subjects
L Balducci
Publications and source records attributed to L Balducci.
What threshold for adjuvant therapy in older breast cancer patients?
PURPOSE: To consider the question of when to prescribe adjuvant treatment for elderly breast cancer patients, particularly when comorbidities are present. Knowledge of the threshold relapse risks above which adjuvant treatment is worth prescribing would enhance decision making. PATIENTS AND METHODS: A Markov analysis of data from the medical literature was conducted. Patients aged 65 to 85 years were considered, along with three levels of comorbidity. The threshold risk of relapse at 10 years (RR10), at which time treatment provides absolute reduction or reduction of an absolute 1% in relapse or mortality, was evaluated. RESULTS: The threshold RR10 for an absolute reduction in mortality risk by adjuvant treatment was low through the age of 85 years. However, for an absolute 1% reduction, the effect of treatment on relapse and the effect of treatment on mortality increasingly diverged. The threshold RR10 for an absolute 1% reduction in relapse risk remained fairly low (5% to 6% for tamoxifen, 12% to 19% for chemotherapy). The threshold RR10 for an absolute 1% reduction in mortality risk, although starting close to the RR10 for an absolute 1% reduction in relapse risk, rose sharply. For tamoxifen, the difference between the two was 4% for an average 65-year-old, 6% at the age of 75 years, and 15% at the age of 85 years. For chemotherapy, the differences were 6%, 12%, and 30%, respectively. Similarly, thresholds increased with increasing comorbidity. In older and sicker patients, the maximum benefit was reached after 5 years rather than 10 years. CONCLUSION: Older breast cancer patients can expect a reduction in relapse that is fairly similar to that of younger patients. However, the effect on mortality diverges markedly, and attention should be paid to this difference in clinical decision making. Comorbidity should be considered in recommendations for adjuvant treatment, including clinical practice guidelines.
Age Factors↗
Management of cancer in the older person: a practical approach.
The management of cancer in the older aged person is an increasingly common problem. The questions arising from this problem are: Is the patient going to die with cancer or of cancer? Is the patient able to tolerate the stress of antineoplastic therapy? Is the treatment producing more benefits than harm? This article explores a practical, albeit evolving, approach to these questions including a multidimensional assessment of the older person and simple pharmacologic interventions that may ameliorate the toxicity of antineoplastic agents. Age may be construed as a progressive loss of stress tolerance, due to decline in functional reserve of multiple organ systems, high prevalence of comorbid conditions, limited socioeconomic support, reduced cognition, and higher prevalence of depression. Aging is highly individualized: chronologic age may not reflect the functional reserve and life expectancy of an individual. A comprehensive geriatric assessment (CGA) best accounts for the diversities in the geriatric population. The advantages of the CGA include:Recognition of potentially treatable conditions such as depression or malnutrition, that may lessen the tolerance of cancer treatment and be reversed with proper intervention; Assessment of individual functional reserve; Gross estimate of individual life expectancy; and Adoption of a common language to classify older cancer patients. The CGA allows the practitioner to recognize at least three stages of aging:People who are functionally independent and without comorbidity, who are candidates for any form of standard cancer treatment, with the possible exception of bone marrow transplant. People who are frail (dependence in one or more activities of daily living, three or more comorbid conditions, one or more geriatric syndromes), who are a candidate only for palliative treatment; and People in between, who may benefit from some special pharmacological approach, such as reduction in the initial dose of chemotherapy with subsequent does escalations. The pharmacological changes of age include decreased renal excretion of drugs and increased susceptibility to myelosuppression, mucositis, cardiotoxicity and neurotoxicity. Based on these findings, the proposal was made that all persons aged 70 and older, treated with cytotoxic chemotherapy of dose intensity comparable to CHOP, receive prophylactic growth factor treatment, and that the hemoglobin of these patients be maintained >/=12 gm/dl.
Aged↗
General guidelines for the management of older patients with cancer.
Because aging is highly individualized, the best guide to treatment of the older patient with cancer may be provided by a comprehensive assessment that evaluates such diverse areas as functional status, comorbidity, socioeconomic conditions, nutrition, polypharmacy, and the presence or absence of geriatric syndromes. Aging is further associated with important pharmacologic changes that involve pharmacokinetics, pharmacodynamics, and the toxicity profile of the drugs. These changes increase the risk of therapeutic complications partly because of the different behavior of the disease in an older patient population and partly because of a decreased tolerance to treatment in some older patients.
Aged↗
Fatigue in women receiving adjuvant chemotherapy for breast cancer: characteristics, course, and correlates.
This study investigated the characteristics, course, and correlates of fatigue in women receiving adjuvant chemotherapy for breast cancer. Fifty-four patients were assessed before the start of chemotherapy and during the first three treatment cycles. An age-matched sample of women with no cancer history was assessed at similar time intervals for comparison purposes. Results indicated that breast cancer patients experienced worse fatigue than women with no cancer history. These differences were evident before and after patients started chemotherapy. In addition, fatigue worsened among patients after treatment started. More severe fatigue before treatment was associated with poorer performance status and the presence of fatigue-related symptoms (e.g., sleep problems and muscle weakness). Increases in fatigue after chemotherapy started were associated with continued fatigue-related symptoms and the development of chemotherapy side effects (e.g., nausea and mouth sores). These findings demonstrate the clinical significance of fatigue in breast cancer patients before and during adjuvant chemotherapy treatment. Results also suggest that aggressive management of common side effects, such as nausea and pain, may be useful in relieving chemotherapy-related fatigue.
Adult↗
A comprehensive geriatric assessment (CGA) is necessary for the study and the management of cancer in the elderly.
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Aged↗
Update of the economic analyses of the use of the colony-stimulating factors.
The colony-stimulating factors have been used effectively in a variety of clinical settings to prevent febrile neutropenia and to assist patients receiving dose-intensive chemotherapy with or without stem cell support. Several studies have confirmed the clinical efficacy of the colony-stimulating factors used prophylactically in both solid tumors and the hematologic malignancies. The cost of these agents, along with their large scale clinical use, has prompted a number of economic investigations. Economic analyses based on measures of resource utilization derived from randomized clinical trials have provided febrile neutropenia risk threshold estimates for the cost saving use of prophylactic colony-stimulating factor. A number of important studies concerning the clinical and economic impact of these agents have been reported over the past year. These include a revised cost minimization study based on improved febrile neutropenia cost information and a cost-effectiveness analysis in the adjuvant breast cancer setting based on a clinical prediction model to select patients at high risk for neutropenic complications. Continuing clinical and economic evaluation along with updating of clinical practice guidelines is needed due to rapid technologic and clinical advances in this area.
Colony-Stimulating Factors↗
Oral combination chemotherapy in the management of AIDS-related lymphoproliferative malignancies.
An oral combination chemotherapy regimen initially developed for AIDS-related non-Hodgkin's lymphoma includes lomustine (CCNU), etoposide, cyclophosphamide, and procarbazine. This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier. This regimen was used to treat 38 patients with AIDS-related non-Hodgkin's lymphoma. The overall objective response rate was 66% (34% complete response rate) with a 5% CNS relapse rate, and a median survival duration of 7.0 months. One-third of the patients survived for 1 year, 11% for 2 years, and half of the patients survived free from progression of their lymphoma. On the basis of these results, this oral regimen was modified and administered to 5 patients with AIDS-related primary CNS lymphoma as part of a sequential combined-modality chemotherapy and radiation regimen. Rapid progression of CNS disease was observed in this group of patients, with a median survival duration of 1.0 month. The identical regimen was administered to 7 patients with AIDS-related Hodgkin's disease: we observed a 71% partial remission rate and a median survival duration of 7.0 months. Myelosuppression remains the most significant clinical toxicity. Our results with this oral regimen appear comparable to those of standard intravenous combination chemotherapy regimens in patients with AIDS-related non-Hodgkin's lymphoma.
Administration, Oral↗
Pharmacology of Chemotherapy in the Older Cancer Patient.
BACKGROUND: The incidence of cancer among the elderly population is increasing. The aging process can deplete functional reserve of many organ systems and thus affects the treatment goals for this age-group. METHODS: The pharmacologic consequences of the aging process on elderly cancer patients are reviewed, and guidelines are suggested for assessing and treating this patient population with antitumor drugs. RESULTS: Individualized management of the older cancer patient reflects the results of a comprehensive geriatric assessment. Factors that affect treatment decisions include estimates of the extent of treatment toxicity, the impact of treatment on quality of life, estimates of life expectancy, and the influence of age on pharmacokinetic parameters. CONCLUSIONS: Management of older patients with cancer includes individual assessments that consider the effects of aging on the pharmacodynamics, therapies, and complications of treatment for this population. Treatment can be made safer and more effective by adjusting chemotherapy dosage, maintaining hemoglobin levels, and using hemopoietic growth factors when appropriate.
Journal Article↗
Breast cancer in older women.
The American Geriatric Society currently recommends screening mammography for women up to 85 years of age whose life expectancy is three years or longer. The value of clinical breast examinations in older women needs further study. Total mastectomy and partial mastectomy with postoperative radiation therapy yield similar results in localized breast cancer. Postoperative irradiation may be avoided in women with small tumors (2.5 cm or less in diameter) who have undergone quadrantectomy. Lymph node dissection is important for tumor staging but significantly increases the risks and morbidity of surgery. Lymph node mapping may obviate the need for lymphadenectomy in many older women. Adjuvant hormonal therapy for at least two years appears to be beneficial in all women with hormone-receptor-rich tumors. Adjuvant chemotherapy is indicated in women with lymph node involvement or high-risk tumors with no lymph node involvement. Unless life-threatening metastases are present, hormonal therapy is the first approach to metastatic cancer. Chemotherapy is indicated if endocrine therapy is unsuccessful or life-threatening metastases are present. Most chemotherapy regimens appear to be well tolerated, even by women over 70 years of age. Special treatment should be employed for metastases to tumor sanctuaries (i.e., brain, eyes), the long bones, the spine and the chest wall.
Aged↗
The economics of febrile neutropenia: implications for the use of colony-stimulating factors.
The occurrence of fever and neutropenia following cancer chemotherapy generally prompts hospitalisation for evaluation and treatment. Colony-stimulating factors (CSFs) have been shown to reduce the risk of febrile neutropenia (FN) and the need for hospitalisation in such patients. This study was undertaken to obtain estimates of the actual institutional costs associated with FN and the impact of these costs on threshold estimates for the appropriate use of CSFs. Total hospital expenditures for patients admitted with FN over a 2 year period were studied. A cost allocation function was utilised to allocate all direct costs for non-revenue-generating support centres to revenue-generating service centres as indirect costs. A cost accounting function was then utilised to allocate direct and indirect costs for each service centre to the charge code level. Two groups of patients were defined based on diagnostic codes to represent the spectrum of patients with FN. Total hospital costs were estimated and incorporated into a cost model for the use of CSFs. Variation in the total cost of hospitalisation for FN relates primarily to differences in the average length of stay. The daily cost of hospitalisation was comparable in the groups studied, averaging between US$1675 and US$1892. Incorporation of these cost estimates into the cost model yielded FN risk threshold projections for CSF use in the range of 20-25%. Preliminary studies suggest that incorporation of non-medical, indirect and intangible costs into the CSF decision models will further decrease FN risk threshold projections. Total hospitalisation cost estimates for managing patients with FN are greater than those previously reported, reducing projected FN risk thresholds for CSF use.
Adult↗
Economic impact of granulopoiesis stimulating agents on the management of febrile neutropenia.
The granulopoiesis-stimulating agents (GSAs) have been effectively utilized in a variety of fashions to treat or prevent febrile neutropenia or to assist patients receiving dose-intensive chemotherapy with or without stem cell support. The high cost of these agents, along with their wide-scale clinical application, has fostered a number of economic analyses. Cost minimization models based on randomized trials and driven by hospitalization costs have provided febrile neutropenia risk thresholds for the use of the GSAs which have been incorporated into clinical practice guidelines. A number of important studies concerning the clinical and economic impact of these agents have been reported over the past year. The clinical role and economic impact of the GSAs in the management of either established febrile neutropenia or afebrile neutropenia remains uncertain. While several studies have confirmed the clinical value of the prophylactic use of these agents in both solid tumors and hematological malignancies, few have addressed their effect on cost or quality of life. The GSAs have demonstrated clinical as well as potential economic benefit in patients receiving high-dose chemotherapy with either bone marrow or peripheral blood stem cell support. Recent studies suggest a clinical and economic advantage for growth factor mobilization and peripheral blood stem cell support compared with bone marrow transplantation in patients receiving high-dose chemotherapy. The rapid evolution of technological and supportive care methods in this area will necessitate further clinical and economic evaluation.
Colony-Stimulating Factors↗
Cancer Care in the Elderly: Cost and Quality-of-Life Considerations.
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Journal Article↗
Anemia of Aging: A Model of Erythropoiesis in Cancer Patients.
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Journal Article↗
Comorbidity and functional status are independent in older cancer patients.
PURPOSE: Comorbidity is a frequent and often therapeutically limiting problem in older cancer patients. However, to date, there is no standard measure of the comorbidity burden available for these patients. We tested the performance of two comorbidity scales and their relationship with functional status. PATIENTS AND METHODS: The Cumulative Illness Rating Scale-Geriatric (CIRS-G) was compared with the Charlson scale in 203 patients who received a comprehensive geriatric assessment (CGA) in our Senior Adult Oncology Program (SAOP). Study end points were variability, reliability, correlation with Eastern Cooperative Oncology Group (ECOG) performance status (PS), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL). The relative weight of comorbidity versus tumor stage in the correlations with functional status was assessed. RESULTS: Median age was 75 years (range, 63 to 91). Sixty-four percent of patients scored 0 on the Charlson scale versus 6% on the CIRS-G. The correlation between the Charlson and CIRS-G was fair (p = 0.25 to 0.39). CIRS-G grade 3/4 had a fair correlation with ADL (p = 0.27). Otherwise, there was low or no correlation between comorbidity and functional status across the measures. Tumor stage was not correlated with functional status either. Correlation of ECOG PS with ADL (p = 0.51)c and IADL (p = 0.61) was moderate. Interrater and test-retest correlations were good or very good for both the Charlson and CIRS-G. CONCLUSION: Comorbidity needs to be assessed independently from functional status. Both the Charlson and CIRS-G scales are reliable tools for use in trials of older cancer patients. Both can be tested in further studies as predictors of outcomes such as toxicity of treatment, changes in functional status, or survival.
Activities of Daily Living↗
Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer.
PURPOSE: Clinical reports suggest that many breast cancer patients experience persistent fatigue as a long-term side effect of adjuvant chemotherapy treatment. To investigate this issue further, we examined the characteristics and correlates of fatigue in women who had completed adjuvant chemotherapy for breast cancer and in a comparison group of women with no history of cancer. PATIENTS AND METHODS: Participants were 61 women with breast cancer who had completed chemotherapy an average of 471 days previously and 59 women with no history of cancer. All participants completed standardized self-report measures of fatigue, sleep quality, menopausal symptoms, and coping and were administered a structured clinical interview to identify current and past psychiatric disorder. RESULTS: Compared with women with no history of cancer, former adjuvant chemotherapy patients reported more severe fatigue (P < .01) and worse quality of life because of fatigue (P < .05). More severe fatigue among patients was significantly (P < .05) related to poorer sleep quality, more menopausal symptoms, greater use of catastrophizing as a coping strategy, and current presence of a psychiatric disorder. CONCLUSION: These findings support the view that many breast cancer patients experienced heightened fatigue after completion of adjuvant chemotherapy treatment. Results yield a profile of women who are at increased risk for heightened fatigue after chemotherapy and suggest ways to intervene clinically to prevent or reduce fatigue in this patient population.
Adaptation, Psychological↗
Radiotherapy for cancer patients aged 80 and older: a study of effectiveness and side effects.
PURPOSE: To profile cancer patients aged 80 and older undergoing radiotherapy and to study the tumor response and side effects of therapy. METHODS AND MATERIALS: We retrospectively analyzed the records of patients aged 80 and older who received radiation therapy at James A. Haley Veterans Hospital and H. Lee Moffitt Cancer Center between 1988 and 1995. A total of 203 patients aged 80-94 received radiotherapy during this period. Treatment sites included head and neck [50], breast [16], chest [37], pelvis [53], and miscellaneous [39]. Age, treatment site, field size, total dose, response to treatment, treatment interruptions, incidence and severity of weight loss, myelosuppression, diarrhea, mucositis, dermatitis, and follow-up status are assessed using our departmental records and hospital tumor registry. RESULTS: Of 191 patients evaluated, 179 (94%) completed the treatment without serious complications. A total of 195 sites were irradiated. Twelve patients (6%) required interruption of the treatment. Therapeutic responses were seen in 86 out of 112 patients (77%) treated with curative intent (with 67% complete response) and in 67 out of 83 patients (81%) treated with palliative intent. The causes of treatment interruptions included weight loss from diarrhea, dysphagia, and progressive disease. Treatment interruptions were more likely in patients treated with large treatment fields. In patients treated for upper aero-digestive tract cancer, Grade 3 and 4 mucositis was noted in 20 and 2% of patients, respectively. Grade 1 and 2 enteritis was noted in 43% of patients treated for pelvic malignancies. Grade 3 dermatitis was noted only in 2% of patients. CONCLUSION: Radiotherapy is highly effective and well tolerated by the oldest old. Age is not a contraindication to aggressive radiotherapy.
Aged↗
Cancer chemotherapy in the older patient: what the medical oncologist needs to know.
This review explores the effectiveness and safety of cancer chemotherapy in older individuals and outlines potential guidelines for the management of these patients. Cancer chemotherapy appears less effective in three neoplasms of older individuals: acute myelogenous leukemia, large cell lymphoma, and coelomic carcinoma of the ovary. In the case of acute myelogenous leukemia, a higher prevalence of MDR-1 expression and involvement of the pluripotent hematopoietic stem cells in the neoplastic process contribute to chemotherapy resistance. Chemotherapy-related myelodepression, cardiotoxicity, and peripheral and central neurotoxicity are more common and more severe in older individuals. This toxicity results from the increased vulnerability of target organs and delayed excretion of renally excretable agents. The complications of chemotherapy may be ameliorated by modifying the doses of drugs according to the patient's creatinine clearance, by using antidotes to drug toxicity, and by the early diagnosis and timely management of therapeutic complications. A comprehensive assessment of the older person with cancer allows clinicians to predict the benefits and risks of cancer chemotherapy in individual circumstances.
Aged↗