[6083] Prospective validation of a risk model for first cycle neutropenic complications in early-stage breast cancer patients receiving adjuvant chemotherapy.

Lyman GH, Kuderer NM, Crawford J, Wolff DA, Culakova E, Poniewierski MS, Dale DC.. University of Rochester School of Medicine Dentistry, Rochester, NY; Duke University Medical Center, Durham, NC; University of Washington School of Medicine, Seattle, WA

Background: A nationwide, prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications in patients with early-stage breast cancer (ESBC) receiving adjuvant chemotherapy. A preliminary risk model for first cycle neutropenic complications was previously presented (Lyman SABCS 2005). Model validation based on the registrational study has been completed.
Methods: Between 2002 and 2005, 1440 patients with breast cancer initiating chemotherapy at 117 randomly selected oncology practices in the USA were registered including 1195 with stages 1-3 disease. A logistic regression model for cycle 1 severe (SN) or febrile (FN) neutropenia was generated and then validated using a 2:1 split sample random selection process.
Results: Of the 1195 patients with ESBC, 385 experienced neutropenic events in cycle 1 including 244 (31.2%) in the derivation dataset (n=782) and 141 (34.1%) in the validation set (n=413). No significant differences were observed in the distribution of potential risk factors between the derivation and validation populations. The risk of cycle 1 events ranged from 3%-75% across 9 chemotherapy regimen categories. Major independent clinical risk factors for cycle 1 SN or FN in the derivation model include: hyperglycemia (OR=1.70;P=.010); elevated creatinine (OR=2.35;P=.013); concomitant medications including immunosuppressives (OR=1.83;P=.033); diuretics (OR=2.21;P=.019); or phenothiazines (OR=1.76;P=.0255); number of myelosuppressive agents (OR=2.82;P=.002); anthracycline-based chemotherapy (OR=5.61;P=.001); specific chemotherapy regimen (P<.001), especially TAC (OR=3.93), ECT (OR=2.11) and CAF (OR=2.35) and planned relative dose intensity >85% (OR=2.84;P=.004). Alternatively, the risk is less with higher baseline ANC (P=.004) and glomerular filtration rate (P=.001) and with primary colony stimulating factor prophylaxis (P<.001). Model R²=0.348 and c-statistic=0.81 [95%CI:0.78-0.84;P<.001]. For a cycle 1 risk cutpoint of >20%, model performance includes: sensitivity=88% [95%CI:83-91%]; specificity=52% [95%CI: 48-57%]. The risk of cycle 1 SN or FN among high risk patients was 48% compared to 8% in low risk patients. The model performed equally well in the validation dataset with R²=0.376 and c-statistic=0.82 [95%CI:0.78-0.86;P<.001] with sensitivity=94% [95%CI:89-97%], specificity=56% [95%CI:50-62%] and risk of cycle 1 events among high and low risk patients of 51% and 7%, respectively.
Conclusions: Validation in a randomly selected patient sample suggests that this risk model has general applicability in identifying ESBC patients at increased risk for early neutropenic complications. Further validation in independent ESBC populations is planned.

Sunday, December 17, 2006 7:00 AM

Poster Session VI: Treatment: Chemotherapy – Support (7:00 AM-9:00 AM)