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 >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<.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 <.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.

scholarly journals A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

2020 ◽  
Author(s):  
Yi Ding ◽  
Tian Li ◽  
Min Li ◽  
Tuersong Tayier ◽  
MeiLin Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Model ◽  
Risk Group ◽  
Clinical Information ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Positive Regulation ◽  
Risk Patients ◽  
Cox Analysis

Abstract Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

scholarly journals Prophylaxis of venous thromboembolism in general surgery: guidelines differ and we still need local policies

2011 ◽  
Vol 93 (5) ◽  
pp. 370-374
Author(s):  
D Veeramootoo ◽  
L Harrower ◽  
R Saunders ◽  
D Robinson ◽  
WB Campbell
Keyword(s):  
At Risk ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Risk Groups ◽  
Low Risk ◽  
Vte Prophylaxis ◽  
Risk Patients ◽  
Local Policies ◽  
One Year ◽  
The Uk

INTRODUCTION Venous thromboembolism (VTE) prophylaxis has become a major issue for surgeons both in the UK and worldwide. Sev-eral different sources of guidance on VTE prophylaxis are available but these differ in design and detail. METHODS Two similar audits were performed, one year apart, on the VTE prophylaxis prescribed for all general surgical inpatients during a single week (90 patients and 101 patients). Classification of patients into different risk groups and compliance in prescribing prophylaxis were examined using different international, national and local guidelines. RESULTS There were significant differences between the numbers of patients in high, moderate and low-risk groups according to the different guidelines. When groups were combined to indicate simply ‘at risk’ or ‘not at risk’ (in the manner of one of the guidelines), then differences were not significant. Our compliance improved from the first audit to the second. Patients at high risk received VTE prophylaxis according to guidance more consistently than those at low risk. CONCLUSIONS Differences in guidance on VTE prophylaxis can affect compliance significantly when auditing practice, depending on the choice of ‘gold standard’. National guidance does not remove the need for clear and detailed local policies. Making decisions about policies for lower-risk patients can be more difficult than for those at high risk.

scholarly journals The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2657-2664 ◽  
Author(s):  
Bart L. Scott ◽  
Ted A. Gooley ◽  
Mohamed L. Sorror ◽  
Andrew R. Rezvani ◽  
Michael L. Linenberger ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Scoring System ◽  
Hematopoietic Cell Transplantation ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
High Risk Disease ◽  
Risk Patients

Abstract Studies by the International Working Group showed that the prognosis of myelofibrosis patients is predicted by the Dynamic International Prognostic Scoring System (DIPSS) risk categorization, which includes patient age, constitutional symptoms, hemoglobin, leukocyte count, and circulating blasts. We evaluated the prognostic usefulness of the DIPSS in 170 patients with myelofibrosis, 12 to 78 years of age (median, 51.5 years of age), who received hematopoietic cell transplantation (HCT) between 1990 and 2009 from related (n = 86) or unrelated donors (n = 84). By DIPSS, 21 patients had low-risk disease, 48 had intermediate-1, 50 had intermediate-2, and 51 had high-risk disease. Five-year incidence of relapse, relapse-free survival, overall survival, and nonrelapse mortality for all patients were 10%, 57%, 57%, and 34%, respectively. Among patients with DIPSS high-risk disease, the hazard ratio for post-HCT mortality was 4.11 (95% CI, 1.44-11.78; P = .008), and for nonrelapse mortality was 3.41 (95% CI, 1.15-10.09; P = .03) compared with low-risk patients. After a median follow-up of 5.9 years, the median survivals have not been reached for DIPSS risk groups low and intermediate-1, and were 7 and 2.5 years for intermediate-2 and high-risk patients, respectively. Thus, HCT was curative for a large proportion of patients with myelofibrosis, and post-HCT success was dependent on pre-HCT DIPSS classification.

scholarly journals Rituximab Maintenance Benefits Less for Follicular Lymphoma Patients with Low Risk of the Follicular Lymphoma International Index

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3544-3544
Author(s):  
Tingyu Wang ◽  
Ru Li ◽  
Rui Lv ◽  
Ying Yu ◽  
Jiawen Chen ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Low Risk ◽  
Control Group ◽  
Intermediate Risk ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Risk Patients

Abstract Background Follicular lymphoma (FL) is an incurable indolent disease with a heterogeneous course. The Follicular Lymphoma International Prognostic Index (FLIPI) is the most commonly used prognostic system to predict survival. Rituximab-based immunochemotherapy is now the standard choice for the first-line therapy of FL, followed by rituximab maintenance (RM) in patients with response, which prolongs the progression-free survival (PFS). However, the role of RM in different FLIPI risk groups has never been studied as we know. In this study, we aimed to illustrate the effect of RM in FLIPI risk groups. Methods Newly diagnosed FL patients at our center were enrolled in this analysis. All the patients received the rituximab-based chemoimmunotherapy induction regimens. Response assessments were determined according to Lugano's 2014 criteria. Patients who didn't respond to induction were excluded. Categorical variables were compared using Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results From May 2003 to September 2020, 203 newly diagnosed FL were included. 192 patients (95.0%) achieved remission (complete response, CR/partial response, PR) after immunochemotherapy induction, of whom 96 patients continued rituximab maintenance therapies every 3 months for 1-2 years (RM group) (median 7 times，range 4 to 12). 96 patients received no maintenance or fewer than 4 times (control group) (median 0 times, range 0-3). There were no significant differences in baseline characteristics other than the Ann Arbor stage and pathological grade. The RM group patients were more likely to be at low grade (71.8% vs 54.9%, P = 0.042) and advanced stage (90.6% vs 78.7% , P = 0.027) (Table 1). After a median follow-up of 36.4 months (95% confidence interval [CI], 32.2 to 40.6), median OS and PFS were not reached. The 5-year OS rates and PFS rates were 95.1% (95%CI, 90.2%-100%) and 83.0% (95%CI, 75%-91%)(Fig 1). And RM significantly prolonged the PFS, with 5-year PFS rates 92.2% (95%CI, 85.1%-99.3%) and 70.3%(95%CI, 55%-85.6%) (P = 0.0003) (Fig 2). According to FLIPI risk stratification, patients were classified into low-risk, intermediate-risk, and high-risk groups. The 5-year PFS rates were 97.7% (95%CI, 93.2%-100%), 84.7% (95%CI, 70.4%-99%), and 67.8% (95%CI, 49%-86.6%), respectively (Fig 3). For low-risk patients, there was no significant difference in PFS for the RM group vs the control group. However, for both intermediate risk and high-risk patients, PFS was significantly longer in the RM group compared to the control group (P &lt; 0.0001). The PFS rates at 5 years in intermediate-risk patients were 100% and 77.8% (95%CI, 40.8%-92.6%), for the RM group vs control group, high risk 76.4% (95%CI, 54.3%-98.5%), and 54.9% (95%CI, 21.6%-88.2%), respectively (Fig 4). Conclusion Standard rituximab maintenance significantly prolongs progression-free survival in FLIPI intermediate risk and high-risk patients with FL, but not in the FLIPI low risk group. Figure 1 Figure 1. Disclosures Wang: AbbVie: Consultancy; Astellas Pharma, Inc.: Research Funding.

scholarly journals N6-methyladenosine Methylation Related Immune Biomarkers Correlates With Clinicopathological Characteristics and Prognosis in Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Hui Xiong ◽  
Weiting Kang ◽  
Qi Zhang
Keyword(s):  
High Risk ◽  
Immune Checkpoint ◽  
Risk Model ◽  
Risk Group ◽  
Risk Groups ◽  
Tumor Stage ◽  
Low Risk ◽  
Cell Renal Cell Carcinoma ◽  
Immune Genes ◽  
Immune Biomarkers

Abstract Background: This study aimed to explore N6-methyladenosine (m6A) methylation-related immune biomarkers and their clinical value in clear cell renal cell carcinoma (ccRCC).Methods: The RNA-seq data and clinical phenotype of ccRCC were downloaded from TCGA database. Immune-related genes list was downloaded from InnateDB database. Correlation analysis, survival analysis, univariate and multivariate Cox regression analysis were used to investigate the prognostic independent m6A-related immune genes, followed by prognosis risk model establishment. Patients were divided into high/low risk groups, followed by survival analysis, clinical factors, immune checkpoint genes and gene set variation analysis in high-risk vs. low-risk group. Results: Five prognostic independent m6A-related immune genes (PKHD1, IGF2BP3, RORA, FRK and MZF1) were identified. Low expression of PKHD1, RORA and FRK were associated with poor survival, while high expression of IGF2BP3 and MZF1 were associated with poor survival for ccRCC patients. Their expression showed correlations with multiple m6A genes. The risk model could stratify ccRCC patients into high/low risk group, and patients with high-risk were associated with short survival time. High-risk group had an high proportion of patients in tumor stage Ⅲ-Ⅳ and patients with pathologic T3-T4 tumors, lymph node metastasis (N1) and distant metastasis (M1). Ten immune checkpoint genes were differentially expressed in high/low risk groups, such as PD1 and CTLA-4. The risk group could be an independent prognostic factor (HR=1.69, 95% CI 1.07-2.68, P=0.0246). Conclusion: In this study, we developed a five genes risk model, which had independent prognostic value and associated with tumor stage, pathologic T/N/M and immune checkpoint expression in ccRCC.

scholarly journals A Novel Cohorting and Isolation Strategy for Suspected COVID-19 Cases during a Pandemic

2020 ◽  
Author(s):  
Benjamin Patterson ◽  
Michael Marks ◽  
Gemma Martinez-Garcia ◽  
Gabriella Bidwell ◽  
Akish Luintel ◽  
...  
Keyword(s):  
High Risk ◽  
Severe Disease ◽  
Risk Groups ◽  
Low Risk ◽  
Infection Prevention And Control ◽  
High Likelihood ◽  
Patients At Risk ◽  
Risk Patients ◽  
Hospital Acquired ◽  
And Control

Introduction The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem. Methods We implemented a triage tool aimed at minimising hospital acquired COVID-19 particularly to patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission. Results 93 patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. 28 (30%) suspected COVID-19 patients were evaluated to be low risk (groups C & D) and eligible for cohorting. No symptomatic hospital acquired infections were detected in the cohorted patients. Discussion Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.

scholarly journals A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Junyu Huo ◽  
Jinzhen Cai ◽  
Ge Guan ◽  
Huan Liu ◽  
Liqun Wu
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Molecular Subtype ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Type I ◽  
Immune Microenvironment ◽  
Risk Patients

Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis.Methods: The training set (n = 609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) based on the prognosis-related genes associated with ferroptosis and pyroptosis. The intersecting differentially expressed genes (DEGs) among C1, C2, and C3 were used in univariate Cox and LASSO penalized Cox regression analysis for the construction of the risk score. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups.Results: Internal (TCGA, n = 370; GSE14520, n = 239) and external validation (ICGC, n = 231) suggested that the 12-gene risk score had high accuracy in predicting the OS, DSS, DFS, PFS, and RFS of HCC. As an independent prognostic indicator, the risk score could be applicable for patients with different clinical features tested by subgroup (n = 26) survival analysis. In the high-risk patients with a lower infiltration abundance of activated B cells, activated CD8 T cells, eosinophils, and type I T helper cells and a higher infiltration abundance of immature dendritic cells, the cytolytic activity, HLA, inflammation promotion, and type I IFN response in the high-risk group were weaker. The TP53 mutation rate, TMB, and CSC characteristics in the high-risk group were significantly higher than those in the low-risk group. Low-risk patients have active metabolic activity and a more robust immune response. The high- and low-risk groups differed significantly in histology grade, vascular tumor cell type, AFP, new tumor event after initial treatment, main tumor size, cirrhosis, TNM stage, BCLC stage, and CLIP score.Conclusion: The ferroptosis and pyroptosis molecular subtype-related signature identified and validated in this work is applicable for prognosis prediction, immune microenvironment estimation, stem cell characteristics, and clinical feature assessment in HCC.

scholarly journals A Novel Four-Gene Signature Associated With Immune Checkpoint for Predicting Prognosis in Lower-Grade Glioma

2020 ◽  
Vol 10 ◽  
Author(s):  
Youchao Xiao ◽  
Gang Cui ◽  
Xingguang Ren ◽  
Jiaqi Hao ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Score ◽  
Immune Checkpoint ◽  
Risk Groups ◽  
Gene Signature ◽  
Low Risk ◽  
Lower Grade ◽  
Lower Grade Glioma ◽  
Risk Patients

The overall survival of patients with lower grade glioma (LGG) varies greatly, but the current histopathological classification has limitations in predicting patients’ prognosis. Therefore, this study aims to find potential therapeutic target genes and establish a gene signature for predicting the prognosis of LGG. CD44 is a marker of tumor stem cells and has prognostic value in various tumors, but its role in LGG is unclear. By analyzing three glioma datasets from Gene Expression Omnibus (GEO) database, CD44 was upregulated in LGG. We screened 10 CD44-related genes via protein–protein interaction (PPI) network; function enrichment analysis demonstrated that these genes were associated with biological processes and signaling pathways of the tumor; survival analysis showed that four genes (CD44, HYAL2, SPP1, MMP2) were associated with the overall survival (OS) and disease-free survival (DFS)of LGG; a novel four-gene signature was constructed. The prediction model showed good predictive value over 2-, 5-, 8-, and 10-year survival probability in both the development and validation sets. The risk score effectively divided patients into high- and low- risk groups with a distinct outcome. Multivariate analysis confirmed that the risk score and status of IDH were independent prognostic predictors of LGG. Among three LGG subgroups based on the presence of molecular parameters, IDH-mutant gliomas have a favorable OS, especially if combined with 1p/19q codeletion, which further confirmed the distinct biological pattern between three LGG subgroups, and the gene signature is able to divide LGG patients with the same IDH status into high- and low- risk groups. The high-risk group possessed a higher expression of immune checkpoints and was related to the activation of immunosuppressive pathways. Finally, this study provided a convenient tool for predicting patient survival. In summary, the four prognostic genes may be therapeutic targets and prognostic predictors for LGG; this four-gene signature has good prognostic prediction ability and can effectively distinguish high- and low-risk patients. High-risk patients are associated with higher immune checkpoint expression and activation of the immunosuppressive pathway, providing help for screening immunotherapy-sensitive patients.

scholarly journals Protocol for a multinational risk-stratified randomised controlled trial in paediatric Crohn’s disease: methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or high risk for aggressive disease course

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034892
Author(s):  
Rachel E Harris ◽  
Marina Aloi ◽  
Lissy de Ridder ◽  
Nicholas M Croft ◽  
Sibylle Koletzko ◽  
...  
Keyword(s):  
High Risk ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Risk Groups ◽  
Low Risk ◽  
High Risk Patients ◽  
Link Type ◽  
Risk Patients ◽  
Randomised Controlled ◽  
Paediatric Crohn’S Disease

IntroductionImmunomodulators such as thiopurines (azathioprine (AZA)/6-mercaptopurine (6MP)), methotrexate (MTX) and biologics such as adalimumab (ADA) are well established for maintenance of remission within paediatric Crohn’s disease (CD). It remains unclear, however, which maintenance medication should be used first line in specific patient groups.AimsTo compare the efficacy of maintenance therapies in newly diagnosed CD based on stratification into high and low-risk groups for severe CD evolution; MTX versus AZA/6MP in low-risk and MTX versus ADA in high-risk patients. Primary end point: sustained remission at 12 months (weighted paediatric CD activity index ≤12.5 and C reactive protein ≤1.5 fold upper limit) without relapse or ongoing requirement for exclusive enteral nutrition (EEN)/steroids 12 weeks after treatment initiation.Methods and analysisREDUCE-RISK in CD is an international multicentre open-label prospective randomised controlled trial funded by EU within the Horizon2020 framework (grant number 668023). Eligible patients (aged 6–17 years, new-onset disease receiving steroids or EEN for induction of remission for luminal ± perianal CD are stratified into low and high-risk groups based on phenotype and response to induction therapy. Participants are randomised to one of two treatment arms within their risk group: low-risk patients to weekly subcutaneous MTX or daily oral AZA/6MP, and high-risk patients to weekly subcutaneous MTX or fortnightly ADA. Patients are followed up for 12 months at prespecified intervals. Electronic case report forms are completed prospectively. The study aims to recruit 312 participants (176 low risk; 136 high risk).Ethics and disseminationClinicalTrials.gov Identifier: (NCT02852694), authorisation and approval from local ethics committees have been obtained prior to recruitment. Individual informed consent will be obtained prior to participation in the study. Results will be published in a peer-reviewed journal with open access.Trial registration numberNCT02852694; Pre-results.

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]

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