A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact.

PURPOSE: This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. RESULTS: Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. CONCLUSIONS: There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. SPONSOR: American Society of Clinical Oncology

Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia.

PURPOSE: To describe the incidence and outcomes of bleeding and chemotherapy dose modifications associated with chemotherapy-induced thrombocytopenia (platelets < 50,000/microL). PATIENTS AND METHODS: Six hundred nine patients with solid tumors or lymphoma were followed-up during 1,262 chemotherapy cycles complicated by thrombocytopenia for development of bleeding, delay or dose reduction of the subsequent cycle, survival, and resource utilization. The association between survival and bleeding or dose modification was examined using the Cox proportional hazards model. Predisposing factors were identified by logistic regression. RESULTS: Bleeding occurred during 9% of cycles among patients with previous bleeding episodes (P <.0001), baseline platelets less than 75,000/microL (P <.0001), bone marrow metastases (P =.001), poor performance status (P =.03), and cisplatin, carboplatin, carmustine or lomustine administration (P =.0002). Major bleeding episodes resulted in shorter survival and higher resource utilization (P <.0001). Chemotherapy delays occurred during 6% of cycles among patients with more than five previous cycles (P =.003), radiotherapy (P =.03), and disseminated disease (P =.04). They experienced similar clinical outcomes but used significantly more resources. Dose reductions occurred during 15% of cycles but were not associated with poor clinical outcomes or excess resource utilization. Significantly shorter survival and higher resource utilization were observed among the 20% of patients who failed to achieve an adequate response to platelet transfusion. CONCLUSION: The incidence of bleeding is low among solid tumor patients overall but exceeds 20% in some subgroups. These subgroups are easily identifiable using routinely available clinical information. A clinical prediction rule is being developed. Poor response to platelet transfusion is a clinically and financially significant downstream effect of thrombocytopenia and warrants further investigation.

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

Influence of data display formats on physician investigators' decisions to stop clinical trials: prospective trial with repeated measures.

OBJECTIVE: To examine the effect of the method of data display on physician investigators' decisions to stop hypothetical clinical trials for an unplanned statistical analysis. DESIGN: Prospective, mixed model design with variables between subjects and within subjects (repeated measures). SETTING: Comprehensive cancer centre. PARTICIPANTS: 34 physicians, stratified by academic rank, who were conducting clinical trials. INTERVENTIONS: PARTICIPANTS were shown tables, pie charts, bar graphs, and icon displays containing hypothetical data from a clinical trial and were asked to decide whether to continue the trial or stop for an unplanned statistical analysis. MAIN OUTCOME MEASURE: Percentage of accurate decisions with each type of display. RESULTS: Accuracy of decisions was affected by the type of data display and positive or negative framing of the data. More correct decisions were made with icon displays than with tables, pie charts, and bar graphs (82% v 68%, 56%, and 43%, respectively; P=0.03) and when data were negatively framed rather than positively framed in tables (93% v 47%; P=0.004). CONCLUSIONS: Clinical investigators' decisions can be affected by factors unrelated to the actual data. In the design of clinical trials information systems, careful consideration should be given to the method by which data are framed and displayed in order to reduce the impact of these extraneous factors.

Outcomes of bacteremia in patients with cancer and neutropenia: observations from two decades of epidemiological and clinical trials.

The prognostic significance of major organ and tissue infection was examined in 909 episodes of bacteremia that were selected from 10 consecutive, randomized clinical trials of antibiotic therapy for infection in patients with cancer and neutropenia. Extensive tissue infection significantly compromised response to initial therapy (38% vs. 74%; P < .0001), ultimate outcome of infection (73% vs. 94%; P < .0001), median time to normalization of temperature (5.3 days vs. 2.5 days; P < .0001), and survival (P < .0001). Other poor prognostic factors revealed by logistic regression included shock (P < .0001) and bacteremia caused by Pseudomonas species (P = .03), Clostridium species (P = .006), or a pathogen resistant to antibiotics used for initial therapy (P < .0001). Recovery of the granulocyte count predicted a superior response (P < .0001). Although the overall mortality rate was not significantly increased when patients with bacteremia due to gram-negative organisms initially received monotherapy or when patients with bacteremia due to gram-positive organisms received delayed vancomycin therapy, these strategies increased the duration of therapy by 25%. Patients with bacteremia due to alpha-hemolytic streptococcus died more often when vancomycin was not included in the initial empirical regimen (P = .004). Because of the prognostic significance of extensive tissue or major organ infection, this factor should be considered in decisions concerning modification of therapy and use of colony-stimulating factors. The cost-effectiveness of initial monotherapy and delayed vancomycin therapy remains to be demonstrated.

Medical futility and appropriate medical care in patients whose death is thought to be imminent.

Often it is very difficult to make decisions involving the termination of aggressive cancer care in the case of patients who are no longer benefiting. Among these patients, our ability to "do everything possible" to continue life is in conflict with "doing the right thing"; the greatest benefit to these patients derives from delivering excellent supportive care and assisting them in understanding and accepting end-of-life issues. Furthermore, in a cost-conscious environment with limited resources, all patients and, indeed, all of society, benefit when aggressive and often costly cancer care is limited to those patients who are likely to benefit. However, these issues are complex, blending treatment science and ethics, and thus, the physician frequently has no objective reference point on which to base the decisions. This paper integrates the principles of ethics (respect for autonomy, beneficence, nonmaleficence, and justice) and three difficult issues encountered by physicians in clinical decision-making in terminal cancer patients in the American healthcare system. These issues include: medical futility and appropriate care, applications of outcomes research in clinical decision-making, and impact of cost, particularly in a managed care environment, on treatment choice. These topics are illustrated with reference to patients presenting to our emergency center with stage IV lung cancer and dyspnea, and the application of an outcomes model under development to predict imminent death in these patients is discussed. Outcomes models may provide patients, their families, and their physicians with objective data on which to base end-of-life decision-making. Minimizing aggressive treatment of terminally ill patients may provide better life quality and will reduce costs during the patients' end of life. Ethics plays a crucial role in integrating medical science, patient choice, and cost in making appropriate decisions.

Dyspnea in cancer patients. Etiology, resource utilization, and survival-implications in a managed care world.

BACKGROUND: Dyspnea is the fourth most common symptom of patients who present to the emergency department (ED) at The University of Texas M. D. Anderson Cancer Center and may, in some patients with advanced cancer, represent a clinical marker for the terminal phase of their disease. This retrospective study describes the clinical characteristics of these patients, the resource utilization associated with the management of dyspnea, and the survival of patients with this symptom. METHODS: The authors randomly selected 122 of 1068 patients presenting with dyspnea for a retrospective analysis. The median age of the patients was 58 years (range, 23-90 years) and 53% were female. Underlying malignancies were breast cancer (30%), lung cancer (37%), and other cancers (34%). Approximately 94% of the patients had received prior cancer treatment and the majority (69%) had uncontrolled, progressive disease. RESULTS: The most common treatments administered in the ED were oxygen (31%), beta-2 agonists (14%), antibiotics (12%), and narcotics (11%). Approximately 60% of patients were admitted to the hospital from the ED for further treatment of dyspnea and the underlying malignancy, and the median length of stay was 9 days. The median overall survival after the ED visit for dyspnea was 12 weeks. Specific diagnoses were associated with different median survival rates: lung cancer patients: 4 weeks; breast cancer patients: 22 weeks (P = 0.0073, vs. lung cancer); and other cancer diagnoses: 27 weeks (P = 0.0027, vs. lung cancer). CONCLUSIONS: Lung cancer patients presenting to the ED with dyspnea have much shorter survival than patients with other malignancies. For some patients, the presence of dyspnea requiring emergency treatment may indicate a phase in their illness in which resources should be shifted from acute intervention with hospitalization to palliative and supportive care measures.