TY - JOUR

T1 - Development and validation of a cycle-specific risk score for febrile neutropenia during chemotherapy cycles 2-6 in patients with solid cancers

T2 - the CSR FENCE score

AU - Aagaard, Theis

AU - Reekie, Joanne

AU - Roen, Ashley

AU - Daugaard, Gedske

AU - Specht, Lena

AU - Sengeløv, Henrik

AU - Mocroft, Amanda

AU - Lundgren, Jens

AU - Helleberg, Marie

N1 - © 2019 UICC.

PY - 2020/1/15

Y1 - 2020/1/15

N2 - 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 published1 . Patients with solid cancers initiating first-line chemotherapy in 2010-2016 were included. Cycle-specific risk factors were assessed by Poisson regression using generalised 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 to 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 CSR FENCE score is the first published method to estimate cycle-specific risk of FN. This article is protected by copyright. All rights reserved.

AB - 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 published1 . Patients with solid cancers initiating first-line chemotherapy in 2010-2016 were included. Cycle-specific risk factors were assessed by Poisson regression using generalised 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 to 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 CSR FENCE score is the first published method to estimate cycle-specific risk of FN. This article is protected by copyright. All rights reserved.

KW - cancer

KW - chemotherapy

KW - febrile neutropenia

KW - g-csf

KW - infection

KW - prediction

KW - prophylaxis

KW - risk score

U2 - 10.1002/ijc.32249

DO - 10.1002/ijc.32249

M3 - Journal article

VL - 146

SP - 321

EP - 328

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 2

ER -