Background
Methods
Search strategy and selection criteria
Statistical analysis
Results
Identification of articles
First author, year and reference in brackets | Study design and country | Population (n), description of study sample | Outcome assessed | Significant patient factors, OR and confidence intervals | Factors assessed in multivariable model | Comments on quality |
---|---|---|---|---|---|---|
Fujiwara 2017 [28] | Retrospective study Observational Japan | n = 244 Lung | Febrile neutropenia | Male gender OR 4.26 (1.26–20.33) Radiotherapy pre-treatment. OR 6.09 (1.67–23.81) | Age, gender, ECOG PS, cancer type, stage, albumin, AST, total bilirubin, baseline neutrophil smoking, radiotherapy, surgery, chemotherapy treatment | High Authors failed to report missing data handling |
Julius 2017 [7] | Retrospective study Observational US | n = 635 Gynaecological cancers | Chemotherapy-induced neutropenia including treatment delays and treatment dose reductions | Metabolic comorbidities** mainly diabetes mellitus Age-negative effect OR 0.865 (0.788–0.951) | Age, BMI, treatment, cancer type, stage, prior treatment (cycles received previously and regimen) | Moderate Authors failed to report missing data handling Population studied may influence generalisability |
Naito 2017 [29] | Retrospective study Observational Japan | n = 66 Oesophageal cancer | Grade 3/4 neutropenia | Baseline platelet count OR 0.98 (0.97–0.99) ALT OR 1.15 (1.02–1.35) PPI administration OR 37.95 (3.53–1660.64) | Age, PPI treatment, baseline neutrophils and platelets. Albumin, ALT | Moderate Authors failed to report missing data handling Inadequately powered study. |
Agiro 2016 [8] | Retrospective study Observational USA | n = 8745 Breast cancer TC n = 4815 TCH n = 2292 AC n = 1638 | Neutropenic episodes Including febrile neutropenia | TC CSF OR 0.29 (0.22–0.39) age effect > 65 years (ref) 18–44 OR 0.52, 0.31 to 0.85 Comorbidity 0.65 0,42 to 1,00 CSF 0,29 0.22 to 0.39 TSH age effect > 65 years (ref) 18–44 OR 0.92 0.46 to 1.83 0.46 0.23 to 0.93 0.19 0.12 to 0.30 AC 1.21 0.75 to 1.93 | Age, co-morbidity, stage, CSF use, prophylactic antibiotics | High Authors failed to report missing data handling |
Kim 2016 [33] | Retrospective study Observational Korea | n = 610 Early breast cancer | Febrile neutropenia and relative dose intensity | GFR < 60 ml/min 2.806 (1.3–6.1) Age 2.804 (1.16–6.8) Co-morbidity 2.12 (1.078–4.536) | Age, co-morbidity, stage, renal function, WBC count, haemoglobin level, CSF use | High Authors failed to report missing data handling |
Altwairgi 2013 [37] | Retrospective Observational Canada | n = 239 Early breast cancer | Febrile neutropenia | No patient-specific factors | Age, treatment, GCSF | High missing data not fully reported |
Jiang 2013 [41] | Retrospective study Observational China | n = 141 Non-small cell lung | Grade 3–4 neutropenia | Age OR 3.819 (1.23–11.83) Albumin (g/dl) OR 3.3 (1.13–9.87) BSA > 2 OR 4.040 (1.45–11.22) | Age, weight, gender, PS, renal, diabetes, albumin, BSA | High missing data not fully reported |
Lyman 2011 [16] | Prospective study Observational US | n = 3760 Cancers included colorectal (n = 521), small cell lung (n = 210), non-small cell lung (n = 697), ovarian (n = 312), breast (n = 1473), lymphoma (n = 547) | Neutropenic episodes FN or grade 3 or 4 | Immunosuppressive medication OR 1.554 (1.105–2.187) AST > 35 u/L OR 1.422 (0.991–2.04) ALP > 120 u/L OR 1.469 (1.058–2.040) Bilirubin >1 mg/dL OR 2.152(1.235–3.747) Low baseline WBC OR 0.930 (0.8920–0.969) GFR OR 0.993 (0.989–0.997) | Age, prior chemotherapy, immunosuppressive medications, high AST, ALT or bilirubin, reduced white blood count or estimated GFR, patients with small-cell lung cancer, with planned RDI 85% CSFs | High All criteria met |
Schwenkglenks 2010 [44] | Prospective study Observational Multinational | n = 444 Curative breast | Grade 4 neutropenia | Increasing age OR 1.35 (1.06–1.73) Increasing weight OR 3.85 (1.84–8.07) Vascular comorbidity OR 2.29 (1.25–4.20), baseline WBC OR 0.87 (0.76–0.99), higher baseline bilirubin OR 4.38 (1.25–15.33) | Age, weight, co-morbidity, liver, renal, FBC, RDI, CSF | High All criteria met in assessment |
Pettengell 2008 [45] | Retrospective study Observational Belgium, France, Germany, Spain and the UK | n = 749 Non-Hodgkin’s lymphoma | Febrile neutropenia | Age OR 2.2 (1.21–4.01) Recent infection OR 3.07 (0.99–9.52) low baseline albumin < 35 g/l OR 4.76 (0.09–2.99) | Age, dose intensity, cycle 1 FN, CSF, renal, co-morbidity | High All criteria addressed |
Dranitsaris 2008 [46] | Prospective study Observational Data from multicentre RCT | n = 509 Metastatic breast cancer | Any neutropenic complication > G2 NCI neutropenia or febrile neutropenia | Age > 59 OR 1.90 (0.95–3.78) PS WHO 2 OR 6.65 (2.54–17.39), cycle > 1 2.41 (1.32–4.39) Baseline neutrophil 2 × 109 cells/L 4.25(0.99–18.2) | Age, treatment, PS, stage, number of cycles | Moderate Study did not fully address confounders. Missing data not reported |
Schwenkglenks 2006 [43] | Retrospective study Observational Luxenberg, Belgium, France, Germany, Spain and the UK | n = 2860 Early breast cancer | Neutropenic events Delays or hospitalisations | Higher age 1.02 (1.01–1.03) Higher BSA 3.85 (1.84–8.07) Lower BMI, 0.003 Body mass index 0.97 (0.94–0.99) | Age, weight, treatment, diarrhoea, regimen, cycles, radiotherapy | High All criteria addressed |