Douglas Blayney, MD, Professor of Medicine (Oncology) of Stanford University Medical Center discusses the SABCS 2020 abstract – The Timing of Chemotherapy-Induced Neutropenia and Its Clinical and Economic Impact.
A major toll on cancer patients is caused by chemotherapy-induced neutropenia (CIN) and its complications. Lengthy hospitalizations, early death, and high treatment costs are associated with febrile neutropenia (FN), a symptom of life-threatening infections. Furthermore, neutropenia is the primary cause of dose reduction and dose delay, reducing the delivery of chemotherapy in patients with potentially curable malignancies at maximum dose and on schedule, and thereby undermining long-term survival. Many recent studies in several major tumor forms have shown that the greatest risk of neutropenia and its complications exists during the first chemotherapy cycle, with over 50% of the first neutropenia and FN episodes occurring during the first cycle. These first-cycle events, in addition to their other detrimental effects, are also associated with early chemotherapy termination. In the first cycle, the disproportionately high risk of neutropenia has important consequences for the management of CIN, as well as for the production and use of supportive care guidelines. It stresses the importance of assessing which patients are at high risk of neutropenia and its complications prior to initiation of chemotherapy, and of reducing this risk by introducing strategies such as prophylactic growth factor support during the first and subsequent cycles.
A major toll on cancer patients is caused by chemotherapy-induced neutropenia (CIN) and its complications. Lengthy hospitalizations, early death, and high treatment costs are associated with febrile neutropenia (FN), a symptom of life-threatening infections. Furthermore, neutropenia is the primary cause of dose reduction and dose delay, reducing the delivery of chemotherapy in patients with potentially curable malignancies at maximum dose and on schedule, and thereby undermining long-term survival. Many recent studies in several major tumor forms have shown that the greatest risk of neutropenia and its complications exists during the first chemotherapy cycle, with over 50% of the first neutropenia and FN episodes occurring during the first cycle. These first-cycle events, in addition to their other detrimental effects, are also associated with early chemotherapy termination. In the first cycle, the disproportionately high risk of neutropenia has important consequences for the management of CIN, as well as for the production and use of supportive care guidelines. It stresses the importance of assessing which patients are at high risk of neutropenia and its complications prior to initiation of chemotherapy, and of reducing this risk by introducing strategies such as prophylactic growth factor support during the first and subsequent cycles.
The predominant dose-limiting toxicity in patients with cancer treated with chemotherapy is chemotherapy-induced neutropenia (CIN). It can contribute to febrile neutropenia (FN) and is associated with increased morbidity and early mortality, increased medical costs, and disturbances of therapies that may be curative.[1,2] I address the clinical and economic implications of CIN and FN in this paper, as well as the danger and timing of CIN and FN in patients treated with myelosuppressive chemotherapy.
Chemotherapy Consequences-Neutropenia Caused
Costs, mortality, and hospitalization
The occurrence of CIN and its complications, such as fever, inflammation, and changes in the dosage of chemotherapy, differ according to the type of malignancy. In patients with five key types of tumor, one broad prospective registry registered CIN rates of 15 percent to 65 percent: breast cancer, colon cancer, lymphoma, lung cancer, and ovarian cancer. FN concentrations ranged from 7 percent to 30% .[3]
In FN patients, hospitalization and treatment with empirical broad-spectrum antibiotics are usually needed, and it has been reported that more than 60,000 patients a year are hospitalized for FN in the United States.
Such hospitalizations account for considerable mortality and medical expenses. The University HealthSystem Consortium (UHC) analysis of discharge results, comprising 121 institutions, analyzed inpatient mortality in 41,779 non-transplant patients hospitalized for FN between 1995 and 2000 and found that it was higher in patients with leukemia than in patients with lymphoma and solid tumors (Figure 1).[1] The hospitalization duration followed a similar trend,
A minority of patients accounted for a disproportionate amount of medical expenses in the UHC database. The average cost of hospitalization for patients with FN-related complications was nearly double the average cost for all patients ($18,400 vs. $35,000). The hospital stays were 30 to 40 days for some cases, costing as much as $60,000 to $100,000 for a single FN hospitalization.
It should be remembered that only the direct costs of hospitalization are the medical costs in the UHC discharge records and that other costs incurred by patients will significantly increase the overall costs of an FN incident. In the 3 months following its occurrence, a study of 26 patients with ovarian cancer in whom World Health Organization grade 3 or 4 CIN had taken place captured both its direct and its indirect costs.[5] The direct costs included out-of-pocket costs such as hospital visits, emergency room visits, medications and medical equipment, home health care, and laboratory tests. Patient job loss, family member work loss, and caregiver payments were included in the indirect costs. It was reported that the total direct costs were $1,340 and the total indirect costs were $3,840.
Quality of Life for Patients
There is growing evidence that neutropenia also has important, although more difficult to quantify, effects on the quality of life of patients (QOL). The adverse effects of FN hospitalization and the fear of hospitalization on patient QOL[6] are evident, but the effects of neutropenia are more subtle. In a heterogeneous group of patients, Fortner and colleagues used many methods to test the effects of CIN and FN on QOL. Lower absolute neutrophil counts have been shown to correlate with lower physical work ability, worse physical symptoms, and greater psychological distress.[7,8] In another study evaluating 100 standardized interviews with 34 patients who experienced grade 4 neutropenia in the first chemotherapy cycle, fatigue was the most common physical symptom identified and interference with the daily routine.[12]
Reduced Strength of Dosage
However, the most insidious consequence of CIN could be the interruption of the treatment of cancer, with potentially significant long-term survival implications. In patients treated with chemotherapy, dose reductions and delays are normal. A retrospective review of data on 20,799 patients treated with chemotherapy after surgery for early-stage breast cancer between 1997 and 2000 showed that 25% of patients needed dose delays of 7 days or more, 37% required dose reductions of 15% or more, and 56% required a relative dose intensity (RDI) of less than 85% (Figure 2).[13] An [14] In both studies, multivariate analyses showed that advanced age (60 or ⇠65 years) was a significant predictor of RDI of less than 85%, independent of other risk factors such as poor performance status of the Eastern Cooperative Oncology Community, advanced tumor level, increased body surface area, and absence of CSF treatment.