The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The granulocyte colony-stimulating factor (G-CSF) is utilized to reduce neutropenic complications in patients receiving cancer chemotherapy. This study represents a systematic review and evidence summary of the impact of G-CSF support on chemotherapy dose intensity and overall mortality. MATERIALS AND METHODS: All randomized controlled trials (RCTs) comparing chemotherapy with or without G-CSF support and reporting all-cause mortality with at least 2 years of follow-up were sought. Dual-blind data abstraction of disease, treatment, patient and outcome study results with conflict resolution by third party was carried out. RESULTS: The search revealed 61 randomized comparisons of chemotherapy with or without initial G-CSF support. Death was reported in 4251 patients randomized to G-CSFs and in 5188 controls. Relative risk (RR) with G-CSF support for all-cause mortality was 0.93 (95% confidence interval: 0.90-0.96; P < 0.001). RR for mortality varied by intended chemotherapy dose and schedule: same dose and schedule (RR = 0.96; P = 0.060), dose dense (RR = 0.89; P < 0.001), dose escalation (RR = 0.92; P = 0.019) and drug substitution or addition (RR = 0.94; P = 0.003). Greater RR reduction was observed among studies with longer follow-up (P = 0.02), where treatment was for curative intent (RR = 0.91; P < 0.001), and where survival was the primary outcome (RR = 0.91; P < 0.001). CONCLUSIONS: All-cause mortality is reduced in patients receiving chemotherapy with primary G-CSF support. The greatest impact was observed in RCTs in patients receiving dose-dense schedules.

Supportive care in patients with cancer during the COVID-19 pandemic.

Cancer care has been profoundly impacted by the global pandemic of severe acute respiratory syndrome coronavirus 2 disease (coronavirus disease 2019, COVID-19), resulting in unprecedented challenges. Supportive care is an essential component of cancer treatment, seeking to prevent and manage chemotherapy complications such as febrile neutropenia, anaemia, thrombocytopenia/bleeding, thromboembolic events and nausea/vomiting, all of which are common causes of hospitalisation. These adverse events are an essential consideration under routine patient management, but particularly so during a pandemic, a setting in which clinicians aim to minimise patients' risk of infection and need for hospital visits. Professional medical oncology societies have been providing updated guidelines to support health care professionals with the management, treatment and supportive care needs of their patients with cancer under the threat of COVID-19. This paper aims to review the recommendations made by the most prominent medical oncology societies for devising and modifying supportive care strategies during the pandemic.

Clinical prediction rules for mortality in patients with pulmonary embolism and cancer to guide outpatient management: a meta-analysis.

Essentials Clinical prediction rules (CPRs) can stratify patients with pulmonary embolism (PE) and cancer. A meta-analysis was done to assess prognostic accuracy in CPRs for mortality in these patients. Eight studies evaluating ten CPRs were included in this study. CPRs should continue to be used with other patient factors for mortality risk stratification. SUMMARY: Background Cancer treatment is commonly complicated by pulmonary embolism (PE), which remains a leading cause of morbidity and mortality in these patients. Some guidelines recommend the use of clinical prediction rules (CPRs) to help clinicians identify patients at low risk of mortality and therefore guide care. Objective To determine and compare the accuracy of available CPRs for identifying cancer patients with PE at low risk of mortality. Methods A literature search of Medline and Scopus (January 2000 to August 2017) was performed. Studies deriving/validating ≥ 1 CPR for early post-PE all-cause mortality were included. A bivariate, random-effects model was used to pool sensitivity and specificity estimates for each CPR. Traditional random-effects meta-analysis was performed to estimate the weighted proportion of patients deemed at low risk of early mortality, mortality in low risk patients and odds ratios for death compared with higher-risk patients. Results Eight studies evaluating 10 CPRs were included. The highest sensitivities were observed with Hestia (98.1%, 95% confidence interval [CI] = 75.6-99.9%) and the EPIPHANY index (97.4%, 95% CI = 93.2-99.0%); sensitivities of remaining rules ranged from 59.9 to 96.6%. Of the six CPRs with sensitivities ≥ 95%, none had specificities > 33%. Random-effects meta-analysis suggested that 6.6-51.6% of cancer patients with PE were at low risk of mortality, 0-14.3% of low-risk patients died and low-risk patients had a 43-94% lower odds of death compared with those at higher risk. Conclusions Because of the limited total body of evidence regarding CPRs, their results, in conjunction with other pertinent patient-specific clinical factors, should continue to be used in identifying appropriate management for PE in patients with cancer.

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.

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.

Age and the Risk of Breast Cancer Recurrence.

BACKGROUND: Various parameters assist in the definition of prognosis and in the choice of therapy for breast cancer. This study evaluates the effects of prognostic factors on disease outcome in elderly women. METHODS: A retrospective cohort analysis was performed on 1,267 consecutive patients with locoregional breast cancer, including 374 patients 65 years of age or older, who were referred to a university cancer center over an eight-year period. Information on prognostic factors, disease outcome, and survival was analyzed. RESULTS: Women 65 years of age or older were more likely to have early-stage cancers, lower histologic grade, higher hormone receptor levels, and lower S-phase fractions. They experienced a longer time to disease recurrence and overall longer survival than their younger counterparts. CONCLUSIONS: Advancing age should not be considered an unfavorable risk factor for breast cancer. Prognosis and treatment should be based on disease stage and histologic and biologic parameters rather than patient age.

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.

Importance of race on breast cancer survival.

BACKGROUND: Breast cancer survival has been shown to be significantly less among black women than white women. The reason for this difference in survival is unclear. METHODS: Data were obtained retrospectively on 439 women seen between 1985 and 1993 based on a detailed chart audit. The impact of race and several known prognostic factors on overall survival, time to relapse, and survival after relapse were studied. RESULTS: Black women with breast cancer were found to have a greater risk of recurrence, shorter overall survival, and shorter survival after relapse than did white women. Black patients were found to be younger and have higher stage of disease and lower hormone receptor levels than were white patients. After adjustment for menopausal status and disease stage, a significant independent effect of race was observed on overall survival but not risk of recurrence. In multivariate analysis, a significant interaction was observed between race and age in some models. Survival after recurrence of disease was lower among black than white women after adjustment for menopausal status and estrogen receptor level. CONCLUSION: Black women experience shorter survival times than do white women, including a shorter survival time after disease recurrence. Breast cancer in black women is associated with younger age, higher stage at presentation, and low hormone receptor levels. After adjustment for known prognostic factors, race remains a significant independent predictor of breast cancer survival.

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.