Development and validation of a cycle‐specific risk score for febrile neutropenia during chemotherapy cycles 2–6 in patients with solid cancers: The ^CSRFENCE score

Abstract

The absolute risk reduction by prophylaxis in chemotherapy‐induced febrile neutropenia (FN) is largest in patients at highest underlying risk. Therefore, reliable predictive models are needed. Here, we develop and validate such a model for risk of FN during chemotherapy cycles 2–6. A prediction score for risk of FN during the first cycle has recently been published. Patients with solid cancers initiating first‐line chemotherapy in 2010–2016 were included. Cycle‐specific risk factors were assessed by Poisson regression using generalized estimating equations and random split sampling. The derivation cohort included 4,590 patients treated with 15,419 cycles, wherein 326 (2.1%) FN events occurred. Predictors of FN in multivariable analyses were: higher predicted risk of FN in the first cycle, platinum‐ or taxane‐containing therapies, concurrent radiotherapy, treatment in cycle 2 compared to later cycles, previous FN or neutropenia and not receiving granulocyte colony‐stimulating factors. Each predictor added between −2 and 8 points to each patient's score (median score 4; interquartile range, 1–6). The incidence rate ratios for developing FN in the intermediate (score 1–4), high (score 5–6) and very high risk groups (score ≥7) were 7.8 (95% CI, 2.4–24.9), 18.6 (95% CI, 5.9–58.8) and 51.7 (95% CI, 16.5–162.3) compared to the low risk group (score ≤0), respectively. The score had good discriminatory ability with a Harrell's C‐statistic of 0.78 (95% CI, 0.76–0.80) in the derivation and 0.75 (95% CI, 0.72–0.78) in the validation cohort (patient n = 2,295, cycle n = 7,670). The Cycle‐Specific Risk of FEbrile Neutropenia after ChEmotherapy score is the first published method to estimate cycle‐specific risk of FN.

The effect of primary granulocyte-colony stimulating factor prophylaxis on the incidence of febrile neutropenia in patients with testicular germ cell tumors

“…We observed FN incidence of 32.8% overall in patients without G-CSF prophylaxis, which is higher compared to most reports. [11,12,21] However, Nishikawa et al observed even higher incidence (39.5%).…”

Risk Factors for Infections, Antibiotic Therapy, and Its Impact on Cancer Therapy Outcomes for Patients with Solid Tumors

“…Considering the complexity of risk factors for FN, there has been an effort to develop risk scores capable of predicting the risk for individual patients. Several studies developed risk scores for FN [55][56][57][58][59], some of which have been prospectively validated [56,58]. The overview of these studies, including independent risk factors for FN, is shown in Table 2.…”

“…Aagard et al introduced an internally validated risk score for FN during the first cycle of chemotherapy (the FENCE Score) [57]. Recently, an update providing cycle-specific risk for FN (during cycle 2-6) in solid tumors has been published [59]. Such risk scores could be used to predict the risk of FN in a particular patient and initiate preventive measures, including the use of G-CSF in high-risk patients, although external validation in large prospective trials is required [59].…”

Older cancer patients and COVID‐19 outbreak: Practical considerations and recommendations

“…Recently, a risk score ("FENCE" score) for febrile neutropenia after chemotherapy has been made available, both at the first cycle of chemotherapy 39 and for cycles 2-6 in patients with solid cancers. 40 Non-hematological toxicity is not-so-easy to predict, yet, the CARG score and the CRASH score can be highly helpful. 17,18 Thus, one major practical recommendation for all older patients being considered for cytotoxic chemotherapy is to use these, or other disease-specific CGA-based prognostic scores, to estimate risk of toxicity from chemotherapy, and refrain from using cytotoxic chemotherapy if risk of toxicity is higher than 40% and not preventable, that is, by using prophylactic Granulocyte Colony-Stimulating Factor (G-CSF) and/or reducing dose/intervals in palliative setting.…”

“…Recently, a risk score (“FENCE” score) for febrile neutropenia after chemotherapy has been made available, both at the first cycle of chemotherapy 39 and for cycles 2‐6 in patients with solid cancers 40 …”