P5-20-03: Personalizing Supportive Care: A Clinical Prediction Model for Neutropenic Complications in Patients with Early-Stage Breast Cancer (ESBC) Receiving Intermediate Risk Chemotherapy.
Authors: Kuderer NM , Culakova E , Poniewierski MS , Crawford J , Dale D , Lyman GH 
Published: June 2012

Background: Neutropenic complications including severe and febrile neutropenia (FN) represent major dose-limiting toxicities of cancer chemotherapy. A general risk model for neutropenic complications across major solid tumors has been developed and validated (Lyman et al. Cancer 2011). Current guidelines recommend consideration of primary prophylaxis with a colony-stimulating factor (CSF) in patients at &gt;20% risk of FN. The decision for primary CSF prophylaxis in patients on intermediate risk chemotherapy (10-20%) is based on physician assessment of individual patient risk factors for FN. This study assesses the ability of this general FN risk model to identify ESBC patients on intermediate risk chemotherapy who are at a personal high risk for developing a neutropenic complication.

Methods: A prospective cohort study accrued 4458 consenting patients starting a new chemotherapy regimen at 115 randomly selected community oncology practices throughout the United States from 2002–2006. The risk of severe or febrile neutropenia (SNFN) in cycle 1 and across 4 cycles was estimated [±95% CI] utilizing logistic regression analysis and adjusting for key clinical factors including among others: age, prior chemotherapy, abnormal hepatic or renal function, low pretreatment white blood count, immunosuppressive medications, CSF prophylaxis, and planned relative dose intensity as well as major chemotherapeutic agents. The cumulative risk of FN across 4 cycles was also estimated by the product limit method of Kaplan and Meier.

Results: Among 1224 patients with ESBC, 822 received intermediate risk chemotherapy based on National Comprehensive Cancer Network guidelines. Among these patients, cycle 1 SNFN occurred in 37%, at least one episode of FN over 4 cycles of chemotherapy in 17%, with 15% receiving primary CSF prophylaxis. The predicted risk of cycle 1 SNFN ranged from 1%-79%, with mean (median) risk of 33.8% (39.0%). Model performance was good with a c-statistic of 0.73 [0.69−0.76]. Based on this general FN risk model, cycle 1 SNFN occurred in 47% of predicted high risk ESBC patients [42 — 52%] compared to 13% [8-17%] of low risk patients. One or more FN events over 4 cycles occurred in 20% [17-24%] of predicted high risk versus 10% [6-14%] in low risk patients. The cumulative risk of FN by Kaplan-Meier estimation was 23% in high risk and 10% in low risk patients. Model sensitivity and specificity for FN were 83% and 33%, respectively. The majority of SNFN (76%) and FN (58%) events among high risk patients occurred in cycle 1. 50% of high risk patients who did not receive primary CSF prophylaxis went on to receive CSF during subsequent cycles.

Conclusions: Based on good test performance characteristics, this clinical FN prediction model also identifies ESBC patients receiving intermediate risk chemotherapy at high personal risk for FN (FN &gt;20%) over the first 4 cycles of chemotherapy. Half of predicted high risk patients without primary CSF prophylaxis will be given CSF in subsequent cycles after the occurrence of a neutropenic complication. This also confirms previous clinical trial findings that the majority of febrile neutropenic events occur in the first cycle.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-03.