A Conditional Risk Model for Chemotherapy-Induced Anemia (CIA) in Cancer Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 372-372
Author(s):  
Gary H. Lyman ◽  
Jeffrey Crawford ◽  
Nicole M. Kuderer ◽  
Debra A. Wolff ◽  
Eva Culakova ◽  
...  
Keyword(s):  
Platelet Count ◽  
Cancer Patients ◽  
Predictive Value ◽  
Risk Model ◽  
Low Risk ◽  
Performance Characteristics ◽  
Individual Risk ◽  
Hematological Toxicity ◽  
Cancer Type ◽  
Conditional Risk

Abstract Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost. Current guidelines for chemotherapy-induced anemia call for intervention at a hemoglobin <10 g/dL with treatment options including transfusion or an erythropoietic-stimulating agent (ESA). A meta-analysis of randomized controlled trials has demonstrated the clinical value of early versus late intervention with an ESA (Lyman Cancer, 2006). While anemia risk models based on pretreatment characteristics have recently been validated, recent safety concerns have limited use of the ESAs to patients with moderate or severe anemia. The gradual onset of anemia and response to ESAs over time provides a rationale for selecting patients for ESA support early in the course of chemotherapy. Methods: 3640 patients with solid tumors or malignant lymphoma initiating a new regimen have been prospectively registered at 110 randomly selected U.S. practice sites. A logistic regression risk model for hemoglobin <10 g/dL based on pretreatment characteristics and hematolgic events during cycle 1 was developed and model predictive performance characteristics estimated. Results: Over a median of 3 cycles of chemotherapy, hemoglobin <10 g/dL was reported one or more times in 1072 (29.5%) patients. Significant independent baseline characteristics associated with subsequent hemoglobin <10 g/dL include: female gender, poor ECOG performance status, history of congestive heart failure, vascular disease or chronic pulmonary disease, cancer type, treatment with an anthracycline-, platinum- or etoposide-based regimen and baseline hemoglobin <12 g/dL or platelet count <150000/mm3. In addition, significant independent predictive hematologic changes during cycle 1 include: decrease in hemoglobin >1 g/dL (OR=4.48; P<.0001), decrease in platelet count >100000/mm3 (OR=1.54;P<.0001) or neutrophil count <500/mm3 (OR=1.94; P<.001) as well as hemoglobin <12 g/dL (OR=2.0;P<.001) at the start of cycle 2. Model R2 = 0.581 and c-statistic = 0.901 [95% CI: .89–.91, P<.0001]. The predicted risk of hemoglobin <10 g/dL ranged from 0 to 100% with mean and median probabilities of 0.16 and 0.30, respectively. Based on a risk cutpoint at the mean, 1290 patients (38%) were classified as high risk. The risks of hemoglobin <10 g/dL in high and low risk subjects were 66% and 9%, respectively. Model test performance characteristics [± 95% CLs] included: sensitivity: 82%[80–84]; specificity: 82%[80–83]; positive predictive value: 66%[63–68]; negative predictive value: 91%[90–93] and diagnostic odds ratio: 20.4[16.8–24.6]. Of note, risk of hemoglobin <11 g/dL in high and low risk subjects based on this model were 95% and 34%, respectively. Validation of the model in a separate population of patients is currently under way. Discussion: This conditional risk model based on both pretreatment characteristics and first cycle events identified cancer patients receiving chemotherapy at substantial risk for clinically significant anemia. The use of ESAs early in the course of treatment based on individual risk assessment must consider both the potential benefit and risks and careful monitoring is essential.

A Risk Model for Chemotherapy-Induced Anemia (CIA) in Cancer Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 754-754
Author(s):  
Gary H. Lyman ◽  
Brandon McMahon ◽  
Nicole M. Kuderer ◽  
Jeffrey Crawford ◽  
Debra Wolff ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Likelihood Ratio ◽  
Test Performance ◽  
Predictive Value ◽  
Risk Model ◽  
Performance Status ◽  
Low Risk ◽  
Performance Characteristics ◽  
Hematological Toxicity ◽  
Predictive Test

Abstract Background: Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost (Lyman‚ Value in Health 2005). Current ASH/ASCO guidelines call for intervention at a hemoglobin (Hgb) <10 gm/dl. Treatment options include transfusion or administration of an erythropoietic-stimulating protein (ESP). A recent meta-analysis demonstrated the clinical value of early versus late intervention with an ESP (Lyman‚ Cancer‚ 2005 in press). An accurate and valid risk model for CIA is needed to select patients for ESP treatment early in the course of chemotherapy when it can be most effective. Methods: More than 3‚000 patients with cancer of the breast‚ lung‚ colon and ovary or malignant lymphoma initiating a new chemotherapy regimen have been prospectively registered at 115 randomly selected U.S. practice sites. Data on at least one cycle of chemotherapy were available on 2‚842 patients. A logistic regression model for Hgb <10 gm/dl based on pretreatment characteristics was developed and predictive test performance characteristics examined. Results: Over a median of three cycles of chemotherapy, Hgb <10 gm/dl was reported one or more times in 817 (28.7%) patients. Significant independent predictive factors for Hgb <10 gm/dl include: history of peptic ulcer (OR=1.90; P=.015), myocardial infarction (OR=1.94; P=.009), or congestive heart failure (OR=2.13; P=.017), increasing age (OR=1.02; P=.002), female gender (OR=2.40; P<.001), ECOG performance status (OR=1.24; P=.002), Charlson Comorbidity Index (OR=1.06, P=.002), body surface area (OR=3.75, P<.001), low baseline hemoglobin (OR=1.95, P<.001), pretreatment hematocrit (OR=.85, P<.001), and glomerular filtration rate (OR=0.99, P=.027), and regimens containing anthracyclines (OR=3.21, P<.001), cisplatinum (OR=3.86, P<.001) or carboplatinum (OR=2.71, P<.001). Model fit was excellent (P<.001), R2=0.455 and c-statistic = 0.775 [95% CL: .76–.79, P<.0001]. Individual predicted risk of Hgb <10 gm/dl based on the model ranged from 0 to 98% with mean and median probabilities of 0.28 and 0.22, respectively. Based on a risk cutpoint of 20%, 1,541 patients (55%) were classified as high risk and 1,282 as low risk. The average risks of Hgb <10 gm/dl during chemotherapy in high and low risk subjects were 43% and 12%, respectively. Model test performance characteristics [±95% CL] included: sensitivity: 81% [78–84]; specificity: 56% [54–58]; likelihood ratio positive: 1.85 [1.74–1.96]; likelihood ratio negative: 0.34 [0.29–0.39]; positive predictive value: 43% [40–45]; negative predictive value: 88% [86–90] and diagnostic odds ratio: 5.47 [4.50–6.66]. Conclusions: This risk model identified cancer patients initiating chemotherapy who are at risk for clinically significant anemia using common clinical parameters. Validation of the model in a separate population of patients is in progress.

A validated risk model for early neutropenic events in older cancer patients receiving systemic chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9036-9036 ◽  
Author(s):  
M. Shayne ◽  
E. Culakova ◽  
D. C. Dale ◽  
M. S. Poniewierski ◽  
D. A. Wolff ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Predictive Value ◽  
Risk Model ◽  
Low Risk ◽  
Severe Neutropenia ◽  
Validation Dataset ◽  
Cancer Type ◽  
C Statistic ◽  
Risk Patients ◽  
Older Cancer Patients

9036 Background: A prospective, nationwide study was undertaken to develop and validate a risk model for early neutropenic events (NE) in older cancer patients undergoing chemotherapy. Methods: 1,386 patients =65 years of age with lung, breast, colorectal, ovarian cancer or lymphoma were prospectively registered at 117 randomly selected sites. Data on up to 4 cycles were collected upon initiation of chemotherapy. A logistic regression model for cycle 1 NE consisting of febrile neutropenia (FN; fever/infection and absolute neutrophil count nadir <1x109/L) or severe neutropenia (SN; neutrophils <.5x109/L) was derived on 1,378 patients with available data. Validation was performed using a split sample random selection process. Results: No significant differences in distribution of NE or predictive factors were observed between derivation dataset (n=922) and validation dataset (n=464). Major independent baseline clinical risk factors for cycle 1 NE in the derivation model (DM) included: anthracycline based regimens (p<.001), non-chemotherapy immune-modulatory agents (p=.003), elevated bilirubin (p=.016), reduced glomerular filtration rate (p<.001), cancer type (p=.02), planned relative dose intensity =85% (p=.027), and regimens containing cyclophosphamide (p<.001), etoposide (p=.002) or ifosfamide (p=.032). Reduced risk of cycle 1 NE was associated with myeloid growth factor (MGF) prophylaxis (p<.001). DM R2 was 0.478 and c-statistic 0.88 [95% CI 0.86–0.91; p<.001]. At median predicted risk of cycle 1 NE of 7%, model test performance (MTP) showed: sensitivity 90%; specificity 59%; and predictive value positive and negative of 32% and 97%, respectively. Cycle 1–4 FN risk in the DM was 16.6% and 3.3% among high and low risk patients, respectively. The validation model (VM) R2 was 0.508 and c-statistic 0.89 [95% CI: 0.86–0.93; p<.001]. MTP in the VM demonstrated: sensitivity 90%; specificity 65%; predictive value positive and negative of 36% and 97%, respectively. Cycle 1–4 FN risk in the VM was 16.8% and 1.6% in high and low risk patients, respectively. Conclusions: This validated risk model demonstrated good discrimination between older cancer patients at decreased risk for NE, and those at increased risk who may benefit from targeted prophylaxis with MGF. No significant financial relationships to disclose.

Population-based assessment of the National Comprehensive Cancer Network recommendations for baseline imaging of rectal cancer

2019 ◽  
Vol 8 (14) ◽  
pp. 1167-1172
Author(s):  
Omar Abdel-Rahman ◽  
Winson Y Cheung
Keyword(s):  
Rectal Cancer ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Predictive Value ◽  
Lung Metastases ◽  
Early Stage ◽  
Abdominal Imaging ◽  
Performance Characteristics ◽  
Seer Database ◽  
Routine Imaging

Aim: To examine the performance characteristics of alternative criteria for baseline staging, in a cohort of contemporary rectal cancer patients from the Surveillance, Epidemiology and End Results (SEER) database. Methods: The SEER database (2010–2015) was accessed and patients with rectal cancer plus complete information on clinical T and N stages as well as metastatic sites were evaluated. We examined various performance characteristics of baseline imaging, including specificity, sensitivity, number needed to investigate (NNI), positive predictive value (PPV), negative predictive value and accuracy. Results: A total of 15,836 rectal cancer patients were included. Based on current guidelines that suggest cross-sectional chest and abdominal imaging for all cases of invasive rectal cancer, these recommendations would yield a PPV of 11.9% for the detection of liver metastases and 6.2% for the detection of lung metastases. This would translate to an NNI of 8.4 for liver metastases and an NNI of 16.1 for lung metastases. When patients with T1N0 were excluded from routine imaging, this resulted in a PPV of 6.4% and an NNI of 15.6 to identify one case of lung metastasis. Likewise, this resulted in a PPV of 12.3% and an NNI of 8.0 to detect one case of liver metastasis. Similarly, when patients with either T1N0 or T2N0 were excluded from routine imaging, the PPV and NNI for lung metastases improved to 6.6% and 15.1, respectively, and the PPV and NNI for liver metastases improved to 12.6 and 7.9%, respectively. Conclusion: Our study suggests that the specificity of the current imaging approach for rectal cancer staging is limited and that the omission of chest and abdominal imaging among selected early stage asymptomatic cases may be reasonable to consider.

Prospective Validation of a Predictive Model for Early Anemia in Patients Receiving Cancer Chemotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 460-460
Author(s):  
Gary H. Lyman ◽  
David C. Dale ◽  
Nicole M. Kuderer ◽  
Debra A. Wolff ◽  
Eva Culakova ◽  
...  
Keyword(s):  
Predictive Model ◽  
Odds Ratio ◽  
Risk Model ◽  
Diagnostic Odds Ratio ◽  
Performance Characteristics ◽  
Model Fit ◽  
Lower Sensitivity ◽  
Cancer Type ◽  
C Statistic ◽  
Increased Risk

Abstract Anemia represents the most common hematological toxicity in cancer patients receiving chemotherapy and is associated with considerable morbidity and cost. ASH/ASCO guidelines call for intervention at a hemoglobin (hgb)&lt;10 g/dL. A meta-analysis has demonstrated the clinical value of early (hgb≥10 g/dL) versus late (hgb&lt;10 g/dL) intervention with an erythroid stimulating protein (ESP). An anemia predictive model may help guide intervention sufficiently early in the course of chemotherapy when it can be most effective. A prospective, nationwide study was undertaken to develop and validate risk models for hematologic toxicities of chemotherapy. The analysis presented here is based on 3,640 patients with cancer of the breast, lung, colon and ovary or malignant lymphoma receiving a new regimen prospectively registered at 117 randomly selected U.S. practices. A logistic regression model for hgb&lt;10 g/dL was developed and validated using a 2:1 random selection split sample methodology. Predictive performance characteristics were estimated [±95% CL]. Nadir hgb over 4 cycles of chemotherapy was &lt;8 g/dL in 113 (3%), 8–10 in 959 (26%), 10–12 in 1,847 (51%), and ≥12 in 721 (20%). No significant differences were observed between the two populations. Independent risk factors for nadir hgb&lt;10 g/dL (ORs) were: female gender (1.66); ECOG &gt;1 (1.70); CHF (1.54); history of vascular disease (2.66); ulcer disease (2.58); COPD (1.29); connective tissue disease (1.84); advanced cancer stage (1.19); cancer type and chemotherapy based on anthracyclines (2.15), carboplatin (2.40), gemcitabine (2.48), cyclophosphamide (1.60), etoposide (2.84), topotecan (4.21), or trastuzumab (1.43), planned cycle length &gt;1 week (2.0), while normal baseline hemoglobin, platelet count and GFR were associated with a reduced risk. Model fit was good (P&lt;.001), R2 = 0.35 and c-statistic = 0.81 [.79–.83, P&lt;.0001]. Mean and median predicted risk for hgb&lt;10 g/dL were 0.29 and 0.22, respectively. An increasing risk cutpoint was associated with lower sensitivity and higher specificity. In the highest risk half, quarter and quintile of patients, hgb&lt;10 g/dL was experienced by 47% [45–50], 64% [60–68], and 70% [65–74], respectively. Model performance characteristics at the median risk included: sensitivity: 82% [78–84]; specificity: 64% [62–66]; and diagnostic odds ratio: 7.80 [6.28–9.68]. Most covariates significant in the derivation model remained significant in the validation population. Model fit was good [P&lt;.001] with an R2=.40 and a c-statistic of 0.83 [.81–.86; P&lt;.001]. In the highest risk half, quarter and quintile of patients, hgb&lt;10 g/dL was experienced by 50% [46–54], 67% [62–71], and 70% [65–75], respectively. Test performance of the validation model at the median risk included: sensitivity of 83% [79–86], specificity of 62% [59–66], and a diagnostic odds ratio of 7.90 [5.84–10.69]. Based on good performance characteristics, this validated prediction model identified chemotherapy patients at increased risk for developing clinically significant anemia who may be candidates for early targeted intervention with an ESP. A conditional risk model for subsequent risk of hgb&lt;10 g/dL which includes changes during cycle 1 of chemotherapy has also been developed and will be presented.

Assessing the impact of a targeted electronic medical record intervention on growth factor usage in cancer patients.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 262-262
Author(s):  
Jordan Bernens ◽  
Kara Hartman ◽  
Brendan F. Curley ◽  
Sijin Wen ◽  
Jame Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Febrile Neutropenia ◽  
Cancer Patients ◽  
Medical Record ◽  
Electronic Medical Record ◽  
Low Risk ◽  
Individual Risk ◽  
Individual Risk Factors ◽  
The Impact

262 Background: Patients receiving chemotherapy are at risk for febrile neutropenia following treatment. The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommend screening patients for risk of febrile neutropenia and risk stratification based on likelihood of febrile neutropenia events. Prophylactic growth factors (G-CSF) should be in patients receiving high-risk regimens or intermediate-risk regimens with individual risk factors. The impact of electronic medical record system (EMR) implementation on compliance with G-CSF support guidelines has not been studied. Methods: At West Virginia University/Mary Babb Randolph Cancer Center we conducted an IRB approved retrospective chart review of cancer patients receiving chemotherapy from January 1, 2007 to August 1, 2008 (pre-EMR) and January 1, 2011 to December 31, 2011 (post-EMR). We reviewed the chemotherapy regimens and patient risk factors for developing febrile neutropenia, and determined if the G-CSF usage was consistent with guideline recommendations. Results: Compliance with prophylactic G-CSF guidelines was 75.6% in the post-EMR arm, compared to 67.5% in the pre-EMR arm (p=0.041, ch-square). The post EMR data of 1,042 new chemotherapy initiations showed: (see Table). The appropriateness of usage in high and low risk patients were the most compliant, as G-CSF orders were built into chemotherapy plans of high risk regimens and omitted from low risk regimens. Conclusions: Appropriate prophylactic G-CSF usage can be improved when orders are integrated into standard chemotherapy order sets in an EMR. An area of further improvement would include automatic identification of individual risk factors by the EMR. [Table: see text]

scholarly journals Problems of hematological toxicity during the treatment of blood system malignancies

2020 ◽  
pp. 156-158
Author(s):  
I.A. Kriachok
Keyword(s):  
Platelet Count ◽  
Cancer Patients ◽  
Platelet Transfusion ◽  
Treatment Options ◽  
Intravenous Iron ◽  
Hematological Toxicity ◽  
Risk Of Bleeding ◽  
Thrombopoietin Receptor

Background. Treatment of blood malignancies is often accompanied by the hematological toxicity. Thrombocytopenia is one of the most common phenomena, which can be caused by pseudothrombocytopenia, production deficiency or increased destruction of platelets, their pathological distribution or aggregation. Objective. To determine the features of hematological toxicity in the treatment of malignant blood diseases. Materials and methods. Analysis of literature data and recommendations on this topic. Results and discussion. Diagnosis of thrombocytopenia involves a detailed study of a peripheral blood smear to assess the morphology of all cells, as well as additional studies (determination of lactate dehydrogenase, D-dimer, fibrinogen, etc.; aspiration and bone marrow biopsy; virological and bacteriological studies; clinical examination). The main causes of thrombocytopenia in cancer patients are chemotherapy (ChT) and radiation therapy (RT), however, the diagnosis should take into account all possible nosological options. The assessment should be performed if the platelet count is <100,000/μl. The normal lifespan of platelets is 8-10 days, so after many types of ChT thrombocytopenia develops about 7th days after treatment, reaches a maximum of 14th days and ends in 28-35th days. After RT thrombocytopenia usually starts in 7-10th days after its termination and is present during 30-60 days. Before treating thrombocytopenia, the need for ChT should be re-evaluated and the risk of bleeding assessed, and the ChT regimen should be changed if possible. If the risk of bleeding is high or the platelet count is critically low, platelet transfusion is prescribed, however, it has recently been found that absolute platelet count is not a predictor of bleeding risk in this patient population (PLADO study). In addition, platelet transfusion is limited in resources and costly, and is accompanied by the risk of side effects (acute lung damage due to transfusion, fever, bacterial sepsis, development of transfusion intolerance). This became the basis for the search for alternative treatment options. Recombinant interleukin-11 (oprelvekin) reduces the need for platelet transfusion from 96 to 70 % of patients on ChT. However, although this drug is FDA-approved, it is characterized by a large number of side effects. In turn, thrombopoietin receptor agonists (subcutaneous romiplostin, oral eltrombopag) bind to the corresponding receptors and increase the number of platelets in the blood. The effectiveness of treatment is within 70 %. Emaplag (“Yuria-Pharm”) is the first and only eltrombopag in Ukraine. Emaplag is indicated for the treatment of thrombocytopenia caused by ChT in patients with solid tumors, patients with platelet counts <50×109/L, and in cases where the physician decides to increase platelet count. With regard to anemias, their main causes in cancer patients are the factors of the underlying disease (bone marrow infiltration, infectious processes), the impact of ChT or RT, other causes (malnutrition, bleeding, renal dysfunction). Examination of patients with anemia should include history taking, evaluation of blood smear and iron metabolism, exclusion of occult gastrointestinal bleeding and renal failure, Coombs’ test, determination of endogenous erythropoietin. Treatment options for ChT-induced anemia include blood transfusions and the use of erythropoietins (epoetins α and β, darbepoetin) with or without iron supplements (oral or intravenous). The advantages of using erythropoietin include reducing the need for transfusion of erythrocyte mass, a gradual increase in hemoglobin, increasing quality of life. However, erythropoietins are not recommended for use in cancer patients who do not receive ChT or receive RT, because in these cases, their use is associated with an increased mortality risk. Because in some patient groups erythropoietins accelerate tumor growth or reduce survival, the patient must give a written informed consent for their use. Given these data, it is advisable to prescribe intravenous iron, as it allows not only to quickly increase hemoglobin and improve quality of life, but also to reduce the dosage of erythropoietins. Iron carboxymaltose if the most modern parenteral iron preparation. It is characterized by low toxicity and high stability. Conclusions. 1. Thromboconcentrate transfusion is a fast and effective way to correct thrombocytopenia, which has a number of disadvantages. 2. Thrombopoietin receptor agonists (eltrombopag) make it possible to increase the effectiveness of treatment without interrupting the planned therapy. 3. In the presence of anemia, all possible causes should be corrected before prescribing erythropoietins. 4. If the anemia is caused by ChT, the patient needs to take erythropoietins. 5. Addition of intravenous iron preparations to erythropoietin therapy significantly increases the effectiveness of treatment.

Prospective validation of a risk model for first cycle neutropenic complications in patients receiving cancer chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8561-8561 ◽  
Author(s):  
G. H. Lyman ◽  
N. M. Kuderer ◽  
J. Crawford ◽  
D. A. Wolff ◽  
E. Culakova ◽  
...  
Keyword(s):  
High Risk ◽  
Test Performance ◽  
Risk Model ◽  
Selection Process ◽  
Low Risk ◽  
Validation Dataset ◽  
Cancer Type ◽  
General Applicability ◽  
C Statistic ◽  
Increased Risk

8561 Background: A nationwide, prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications (NC) in cancer patients receiving chemotherapy. Methods: 3,596 patients initiating a new chemotherapy regimen with solid tumors or lymphoma were registered at 115 randomly selected sites. Data on at least 1 cycle of chemotherapy were available on 3,468. A logistic regression model for cycle 1 NC was derived and then validated using a split sample random selection process. Results: The risk of cycle 1 NC ranged from 5.5%-30.2%, averaging 18.5% across tumor types. No significant differences in distribution of NC or predictive factors were observed between the derivation dataset (n=2,592) or the validation dataset (n=876). Major independent baseline clinical risk factors for cycle 1 NC in the derivation model include: prior chemotherapy (P=.044), number of myelosuppressive agents (P<.0001), anthracycline-based regimens (P<.0001), planned delivery >85% of standard (P<.0001), cancer type (P<.0001), concurrent antibiotics (P=.023) or phenothiazines (P=.006), abnormal alkaline phosphatase (P=.002), elevated bilirubin (P=.031), low platelets (P=.004), elevated glucose (P=.023) and reduced glomerular filtration rate (P=.013). Reduced risk of cycle 1 NC was associated with primary prophylaxis with a myeloid growth factor (P<.0001). Model R2 was 0.273 and c-statistic 0.80 [95% CI: 0.78–0.82; P<.0001]. At the median predicted risk of cycle 1 NC of 11%, model test performance consisted of: sensitivity 84%; specificity 57% and diagnostic odds ratio (DOR) 7.2 while cycle 1 NC risk was 31% and 6% among high risk and low risk half, respectively. The model performed well in the smaller validation dataset with a model R2 of 0.354 and c-statistic of 0.84 [95% CI: 0.81–0.87, P<.0001]. Test performance of the model in the validation sample included: sensitivity 90%; specificity 62%; DOR 14.1 and risks of 35% and 4% in high risk and low risk patients, respectively. Conclusions: Validation in a randomly selected patient sample suggests that this model has general applicability in identifying patients at increased risk for NC. Further validation in other independent cancer patient populations receiving chemotherapy is planned. [Table: see text]

A Prospective Risk Model for Neutropenic Complications in Patients with Malignant Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3328-3328
Author(s):  
Gary H. Lyman ◽  
Jeffrey Crawford ◽  
Debra Wolff ◽  
Eva Culakova ◽  
Marek S. Poniewierski ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Malignant Lymphoma ◽  
Likelihood Ratio ◽  
Cancer Chemotherapy ◽  
Test Performance ◽  
Predictive Value ◽  
Risk Model ◽  
Chemotherapy Regimen ◽  
Performance Characteristics ◽  
Increased Risk

Abstract Background: Myelosuppression including severe and febrile neutropenia continues to represent a major cause of dose-limiting toxicity of cancer chemotherapy. Neutropenic complications in cycle 1 have been shown to frequently lead to reduced dose intensity or addition of a myeloid growth factor. A prospective, nationwide study was undertaken to develop and validate risk models for first cycle neutropenic events associated with cancer chemotherapy. Methods: Patients with malignant lymphoma initiating a new chemotherapy regimen have been prospectively registered at 115 randomly selected practice sites. Data on at least one cycle of chemotherapy were available on 357 patients including 56 with Hodgkin’s disease and 301 with non-Hodgkin’s lymphoma. A logistic regression model for first cycle neutropenic events based on pretreatment characteristics was developed and predictive test performance characteristics examined. Results: Severe or febrile neutropenia occurred in 81 (22.7%) of patients in cycle 1. Two-thirds of patients with one or more neutropenic events experienced their initial event in cycle 1. Significant independent pretreatment predictive factors for first cycle neutropenic complications were: history of renal disease (OR=33.15, P=.011) or recent infection (OR=12.41, P=.035), Caucasian (OR=4.13, P=.053), use of an anthracycline-based chemotherapy regimen (OR=6.9, P&lt;.001), baseline absolute neutrophil count (OR=0.95, P&lt;.001) and lymphocyte count (OR=0.95, P&lt;.001), anemia (OR=2.14, P=.043), elevated lactate dehydrogenase (OR=2.0, P=.040) and elevated bilirubin (OR=2.25, P=.051). Model fit was excellent (P&lt;.001), R2= 0.503 and c-statistic = 0.769 [95% CL: .71–.83, P&lt;.0001]. Individual predicted risk of cycle 1 events based on the model ranged from 0 to 96% with mean and median probabilities of 0.23 and 0.21, respectively. Two-thirds of patients were classified as high risk with mean risk scores in high and low risk subjects of 32.0% and 5.6%, respectively. Model test performance characteristics [±95% CL] included: sensitivity: 92% [84–96]; specificity: 40% [34–46]; likelihood ratio positive: 1.53 [1.36–1.73]; likelihood ratio negative: 0.19 [0.09–0.42]; positive predictive value: 32% [26–38]; negative predictive value: 94% [88–97] and diagnostic odds ratio: 7.92 [3.32–18.91]. Discussion: The risk model identified lymphoma patients at increased risk for first cycle neutropenic complications using common clinical parameters. Validation of the model in a separate population of patients is in progress.

Validation of a Risk Model for Hospitalized Adult Cancer Patients with Febrile Neutropenia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 89-89
Author(s):  
Nicole M. Kuderer ◽  
Jeffrey Crawford ◽  
David C. Dale ◽  
Gary H. Lyman ◽  
Keyword(s):  
Cancer Patients ◽  
Risk Score ◽  
Risk Model ◽  
Low Risk ◽  
Inpatient Mortality ◽  
Medical Centers ◽  
Academic Medical ◽  
Independent Population ◽  
Risk Patients ◽  
Very High

Abstract Introduction: Febrile neutropenia (FN) represents the most common dose-limiting toxicity associated with systemic chemotherapy and is associated with considerable morbidity and mortality. The majority of patients with FN are hospitalized for evaluation and administration of empiric broad-spectrum antibiotics. A risk model for mortality in hospitalized adult cancer patients with FN has previously been reported (Kuderer, ASCO 2004). Validation of this risk model in an independent population of hospitalized patients with FN is presented. Methods: Risk model development was based on the records of 40,163 adult non-transplant cancer patients hospitalized with FN at one of 115 academic medical centers reporting to the University HealthSystem Consortium between 1995 and 2000. A risk score for mortality was estimated for each patient based on a weighted summary of all significant variables in a logistic regression model including age, cancer diagnosis, comorbidities (heart, liver, renal, cerebrovascular, pulmonary embolism) and complications (gram+ and gram- sepsis, fungal infection, pneumonia, hypotension, hypovolemia, ICU admission). The risk score was classified into low risk (0–4); intermediate (5–9); high (10–14); and very high (15–22). Results: To validate the FN mortality risk score, it is applied here to an independent population of 16,379 adult cancer patients hospitalized with FN at academic medical centers between 2001–2002. Inpatient mortality was reported in 1,452 (8.9%). Although patients ≥65 years of age represented 30% of the inpatient FN population, they accounted for 43% of deaths. Application of the previously developed risk model to this independent population provided adjusted estimates of relative risk (odds ratios) of: age ≥ 65 (1.5); leukemia (1.3); lung cancer (1.3); heart (1.4); liver (2.1); renal (3.0); cerebrovascular (3.6); pulmonary embolism (2.8); gram+ sepsis (2.1); gram- sepsis (2.4); fungal (1.4); pneumonia(1.8); hypotension (1.9); hypovolemia (1.6) and ICU (3.7) (Global χ2:P<.0001). All significant covariates in the development phase remained significant in the validation study. As shown in the table, the model demonstrated excellent fit (P<.0001) and a high level of discrimination for inpatient mortality (R2 = 0.81; c-statistic = 0.85 [0.84, 0.86]; P<.0001). Risk Score Category Low (0–4) Int (5–9) High (10–14) Very High (15+) Development Phase Patients (%) 74.6 20.6 4.3 0.4 Deaths (%) 3.1 18.9 48.1 64.6 Validation Phase Patients (%) 68.5 23.3 7.0 1.2 Deaths (%) 2.5 14.4 42.3 68.8 Test performance among the 22% of patients with a predicted risk of mortality of ≥10% include: sensitivity: 71%; specificity: 83%; positive predictive value: 29%; negative predictive value: 97%; likelihood ratio positive: 4.2; likelihood ratio negative: 0.3; diagnostic odds ratio: 12.2 [10.8, 13.8]. A low risk subgroup (23%) was also identified with a risk <1%. Similar validation was achieved of previously reported models for length of stay and cost. Conclusions: Previously reported risk models for mortality, length of stay and cost have been validated in a separate population of adult cancer patients hospitalized with FN. These validated models may assist clinicians in identifying both high-risk patients for more aggressive supportive care measures as well as low risk patients as candidates for early discharge. The cost-effectiveness of these models in assisting clinical decision-making is currently under study.

Final Risk Prediction Model for Neutropenic Complications in Patients Receiving Cancer Chemotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1312-1312 ◽  
Author(s):  
Gary H. Lyman ◽  
Jeffrey Crawford ◽  
Nicole M. Kuderer ◽  
Debra Wolff ◽  
Eva Culakova ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Chemotherapy ◽  
Test Performance ◽  
Risk Model ◽  
Cumulative Risk ◽  
Risk Groups ◽  
Low Risk ◽  
Performance Characteristics ◽  
Risk Patients ◽  
Predicted Risk

Abstract Introduction: Neutropenic complications including severe neutropenia (SN) and febrile neutropenia (FN) represent major dose-limiting toxicities of cancer chemotherapy. A prospective study was undertaken to develop and validate a predictive model for neutropenic events in patients receiving cancer chemotherapy. The final risk model based on mature data is presented. Methods: Between 2002 and 2006, 4458 consenting patients starting a new chemotherapy regimen at 115 randomly selected community oncology practices throughout the United States were enrolled including 3760 with cancers of breast, lung, colorectum, ovary and malignant lymphoma receiving at least one cycle of treatment. Using a 2:1 random split sample methodlogy, a risk model for first-cycle SN or FN was derived and validated based on multivariate logistic regression analysis incorporating pretreatment variable information. The cumulative risk of events over the initial 120 days of treatment was estimated by the method of Kaplan and Meier. High and low risk groups were defined on the basis of the median predicted risk and model test performance characteristics were estimated. Results: Following adjustment for cancer type, important predictive factors included: older age, prior chemotherapy, abnormal hepatic or renal function, low pretreatment white blood count, immunosuppressive medications and planned relative dose intensity &gt;85% as well as use of several specific chemotherapeutic agents including anthracyclines, taxanes, alkylating agents, topoisomerase inhibitors, gemcitabine or vinorelbine. Lower risk of neutropenic complications were associated with primary prophylaxis with a colony-stimulating factor (CSF). Individual risk estimates based on the model ranged from 0–89% with mean and median of 19.2% and 10.1%, respectively. The model was associated with an R2 of 0.34 and demonstrated excellent discrimination with a c-statistic of 0.833 [95% CI: 0.813–0.852, P&lt;.001]. The model predicted risk of cycle 1 SN or FN in high and low risk groups was of 34% and 4%, respectively. The cumulative risk of FN over the initial 120 days was 20% in high risk patients and 5% in low risk patients. Model performance included sensitivity and specificity of 90% and 59%, respectively, with a model diagnostic odds ratio of 12.8 [95% CI: 9.3, 17.7]. Application of the model to the validation data set was associated with similar excellent discrimination and test performance characteristics. CSF prophylaxis applied to high risk patients was associated with significantly lower risk of FN over repeated cycles of chemotherapy [HR = 0.51; 95% CI: 0.35 – 0.75; P &lt;.0001]. Nearly two-thirds of patients classified as high risk but who did not receive primary CSF prophylaxis went on to receive secondary use during subsequent cycles. Discussion: Based on excellent test performance characteristics, the risk model identified patients with a cumulative incidence of FN of at least 20% who are candidates for targeted prophylaxis with a CSF. Further validation of this model in actual clinical practice is currently underway.

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