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.

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. What's new? Febrile neutropenia (FN), involving fever and abnormally low neutrophil count, is a severe complication of chemotherapy. Current guidelines suggest assessing FN risk at the start of each chemotherapy cycle in order to prevent or better manage the condition if it arises. Here, to improve FN prediction, the authors developed the Cycle‐Specific Risk of FEbrile Neutropenia after ChEmotherapy (CSRFENCE) score. Risk factors were analyzed by Poisson regression for 6,885 patients with solid cancers who received standard first‐line chemotherapy in cycles 2‐6. In derivation and validation cohorts, the CSRFENCE score was found to successfully predict FN risk at cycle initiation. [ABSTRACT FROM AUTHOR]