Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors.

BACKGROUND: Febrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Risk factors for FN have been reported, but risk models that include genetic variability have yet to be described. This study aimed to evaluate the predictive value of patient-related, chemotherapy-related, and genetic risk factors. METHODS: Data from consecutive breast cancer patients receiving chemotherapy with 4-6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) or three cycles of FEC and docetaxel were retrospectively recorded. Multivariable logistic regression was carried out to assess risk of FN during FEC chemotherapy cycles. RESULTS: Overall, 166 (16.7%) out of 994 patients developed FN. Significant risk factors for FN in any cycle and the first cycle were lower platelet count (OR = 0.78 [0.65; 0.93]) and haemoglobin (OR = 0.81 [0.67; 0.98]) and homozygous carriers of the rs4148350 variant T-allele (OR = 6.7 [1.04; 43.17]) in MRP1. Other significant factors for FN in any cycle were higher alanine aminotransferase (OR = 1.02 [1.01; 1.03]), carriers of the rs246221 variant C-allele (OR = 2.0 [1.03; 3.86]) in MRP1 and the rs351855 variant C-allele (OR = 2.48 [1.13; 5.44]) in FGFR4. Lower height (OR = 0.62 [0.41; 0.92]) increased risk of FN in the first cycle. CONCLUSIONS: Both established clinical risk factors and genetic factors predicted FN in breast cancer patients. Prediction was improved by adding genetic information but overall remained limited. Internal validity was satisfactory. Further independent validation is required to confirm these findings

Quality of Life of Caregivers of Older Patients with Advanced Cancer

OBJECTIVES: To evaluate the relationships between aging-related domains captured by geriatric assessment (GA) for older patients with advanced cancer and caregivers’ emotional health and quality of life (QOL). DESIGN: In this cross sectional study of baseline data from a nationwide investigation of older patients and their caregivers, patients completed a GA that included validated tests to evaluate eight domains of health (eg, function, cognition). SETTING: Thirty-one community oncology practices throughout the United States. PARTICIPANTS: Enrolled patients were aged 70 and older, had one or more GA domain impaired, and had an incurable solid tumor malignancy or lymphoma. Each could choose one caregiver to enroll. MEASUREMENTS: Caregivers completed the Generalized Anxiety Disorder-7, Distress Thermometer, Patient Health Questionnaire-2 (depression), and Short Form Health Survey-12 (SF-12 for QOL). Separate multivariate linear or logistic regression models were used to examine the association of the number and type of patient GA impairments with caregiver outcomes, controlling for patient and caregiver covariates. RESULTS: A total of 541 patients were enrolled, 414 with a caregiver. Almost half (43.5%) of the caregivers screened positive for distress, 24.4% for anxiety, and 18.9% for depression. Higher numbers of patient GA domain impairments were associated with caregiver depression (adjusted odds ratio [aOR] = 1.29; P <.001], caregiver physical health on SF-12 (regression coefficient [β] = −1.24; P <.001), and overall caregiver QOL (β = −1.14; P <.01). Impaired patient function was associated with lower caregiver QOL (β = −4.11; P <.001). Impaired patient nutrition was associated with caregiver depression (aOR = 2.08; P <.01). Lower caregiver age, caregiver comorbidity, and patient distress were also associated with worse caregiver outcomes. CONCLUSION: Patient GA impairments were associated with poorer emotional health and lower QOL of caregivers

Association of Prognostic Understanding with Health Care Use among Older Adults with Advanced Cancer: A Secondary Analysis of a Cluster Randomized Clinical Trial

Importance: A poor prognostic understanding regarding curability is associated with lower odds of hospice use among patients with cancer. However, the association between poor prognostic understanding or prognostic discordance and health care use among older adults with advanced incurable cancers is not well characterized. Objective: To evaluate the association of poor prognostic understanding and patient-oncologist prognostic discordance with hospitalization and hospice use among older adults with advanced cancers. Design, Setting, and Participants: This was a post hoc secondary analysis of a cluster randomized clinical trial that recruited patients from October 29, 2014, to April 28, 2017. Data were collected from community oncology practices affiliated with the University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program. The parent trial enrolled 541 patients who were aged 70 years or older and were receiving or considering any line of cancer treatment for incurable solid tumors or lymphomas; the patients' oncologists and caregivers (if available) were also enrolled. Patients were followed up for at least 1 year. Data were analyzed from January 3 to 16, 2021. Main Outcomes and Measures: At enrollment, patients and oncologists were asked about their beliefs regarding cancer curability (100%, >50%, 50%, 5 years; answers of >5 years reflected poor prognostic understanding). Any difference between oncologist and patient in response options was considered discordant. Outcomes were any hospitalization and hospice use at 6 months captured by the clinical research associates. Results: Among the 541 patients, the mean (SD) age was 76.6 (5.2) years, 264 of 540 (49%) were female, and 486 of 540 (90%) were White. Poor prognostic understanding regarding curability was reported for 59% (206 of 348) of patients, and poor prognostic understanding regarding life expectancy estimates was reported for 41% (205 of 496) of patients. Approximately 60% (202 of 336) of patient-oncologist dyads were discordant regarding curability, and 72% (356 of 492) of patient-oncologist dyads were discordant regarding life expectancy estimates. Poor prognostic understanding regarding life expectancy estimates was associated with lower odds of hospice use (adjusted odds ratio, 0.30; 95% CI, 0.16-0.59). Discordance regarding life expectancy estimates was associated with greater odds of hospitalization (adjusted odds ratio, 1.64; 95% CI, 1.01-2.66). Conclusions and Relevance: This study highlights different constructs of prognostic understanding and the need to better understand the association between prognostic understanding and health care use among older adult patients with advanced cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02107443

Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now?

Updated international guidelines published in 2006 have broadened the scope for the use of granulocyte colony-stimulating factor (G-CSF) in supporting delivery of myelosuppressive chemotherapy. G-CSF prophylaxis is now recommended when the overall risk of febrile neutropenia (FN) due to regimen and individual patient factors is ≥20%, for supporting dose-dense and dose-intense chemotherapy and to help maintain dose density where dose reductions have been shown to compromise outcomes. Indeed, there is now a large body of evidence for the efficacy of G-CSFs in supporting dose-dense chemotherapy. Predictive tools that can help target those patients who are most at risk of FN are now becoming available. Recent analyses have shown that, by reducing the risk of FN and chemotherapy dose delays and reductions, G-CSF prophylaxis can potentially enhance survival benefits in patients receiving chemotherapy in curative settings. Accumulating data from ‘real-world’ clinical practice settings indicate that patients often receive abbreviated courses of daily G-CSF and consequently obtain a reduced level of FN protection. A single dose of PEGylated G-CSF (pegfilgrastim) may provide a more effective, as well as a more convenient, alternative to daily G-CSF. Prospective studies are needed to validate the importance of delivering the full dose intensity of standard chemotherapy regimens, with G-CSF support where appropriate, across a range of settings. These studies should also incorporate prospective evaluation of risk stratification for neutropenia and its complications

Risk of chemotherapy-induced neutropenic complications when treating patients with non-Hodgkin lymphoma

<p><b>Introduction</b>: Myelosuppression induced by cancer chemotherapy is associated with considerable morbidity and mortality. Febrile neutropenia (FN) represents an oncologic emergency requiring immediate evaluation and treatment. Resulting chemotherapy dose reductions or delays may compromise disease control and survival. While non-Hodgkin lymphoma (NHL) represents a potentially curable malignancy, there are limited data on the risk of neutropenic complications. This review represents a systematic search and evidence summary of neutropenic complications reported in randomized controlled trials (RCTs) published over the past decade in adults with NHL receiving myelosuppressive chemotherapy.</p> <p><b>Areas covered</b>: Data captured include the chemotherapy regimen and dosing, the type of NHL, sample size, myeloid growth factor (MGF) use, and myelosuppression including FN and severe neutropenia and infection.</p> <p><b>Expert opinion</b>: Rates of neutropenic complications for commonly utilized chemotherapy regimens vary considerably across studies with FN reported in only one-fourth of study arms. Further challenges in interpreting reported rates are the variable and inconsistent use of MGF support and little or no information on delivered chemotherapy dose intensity. Considerable change in regimens, study populations and reporting of neutropenic events as well as the use of MGF was observed over the decade of RCTs reported. Complete and accurate reporting of treatment-related toxicities in patients receiving cancer chemotherapy is essential in both clinical trials and clinical practice.</p

Economic Analysis of Prophylactic Pegfilgrastim in Adult Cancer Patients Receiving Chemotherapy

AbstractObjectivesNeutropenia and its complications, including febrile neutropenia (FN), are a common side effect of cancer chemotherapy. Results of clinical trials showed that prophylactic use of granulocyte colony-stimulating factors (G-CSF) is effective in preventing FN. In this study, the cost effectiveness (measured as cost per quality-adjusted time [days]) of three treatment alternatives were evaluated: no G-CSF, filgrastim administered daily for 7–12 days after chemotherapy, and a pegylated form of G-CSF pegfilgrastim, administered once per cycle.MethodsA cost-utility model based on standard clinical practice of treating FN with immediate hospitalization or with ambulatory treatment, from a societal perspective was developed. Direct medical cost estimates for hospitalization were derived from claims data reported by 115 US academic medical centers. Indirect medical costs, productivity costs, probabilities, and utilities are based on published literature. Results were subjected to sensitivity analyses and95% confidence intervals are based on a Monte Carlo simulation.ResultsMean estimated costs/day of hospitalization were $1984 (SD$1040, N = 24,687) for surviving patients and $3139 (SD$2014, N = 1437) for dying patients. Under baseline conditions, pegfilgrastim dominated both filgrastim and no G-CSF, with expected costs and effectiveness of $4203 and 12.361 quality adjusted life-days (QALDs) for no G-CSF,$3058 and 12.967 QALDs for pegfilgrastim, and $5264 and 12.698 QALDs for filgrastim.ConclusionsThis cost-utility analysis provides strong evidence that pegfilgrastim is not only cost-effective but also cost-saving in most common clinical and economic settings. There appear to be both clinical and economic benefits from prophylactic administration of pegfilgrastim