A Systematic Literature Review to Identify Diagnostic Gaps in Managing Immunocompromised Patients With Cancer and Suspected Infection

Abstract

Patients with cancer are increasingly vulnerable to infections, which may be more severe than in the general population. Improvements in rapid and timely diagnosis to optimize management are needed. We conducted a systematic literature review to determine the unmet need in diagnosing acute infections in immunocompromised patients with cancer and identified 50 eligible studies from 5188 records between 1 January 2012 and 23 June 2022. There was considerable heterogeneity in study designs and parameters, laboratory methods and definitions, and assessed outcomes, with limited evaluation of diagnostic impact on clinical outcomes. Culture remains the primary diagnostic strategy. Fewer studies employing molecular technologies exist, but emerging literature suggests that pathogen-agnostic molecular tests may add to the diagnostic armamentarium. Well-designed clinical studies using standardized methodologies are needed to better evaluate performance characteristics and clinical and economic impacts of emerging diagnostic techniques to improve patient outcomes.

Keywords: cancer; diagnostic; immunocompromised; infection; metagenomic sequencing.

Figure 1.

Study selection. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for the systematic literature review, 1 January 2012–23 June 2022.

Figure 2.

Characteristics of the studies (n = 50) included in the systematic literature review, 1 January 2012–23 June 2022. One study [17] did not specify population age group but was assumed to be adult patients, since there was no mention of pediatric population in the study. A, Patient sample sizes for the studies included in the systematic literature review are indicated. One study [17] did not report the number of patients enrolled and only reported the total number of culture samples or fever episodes. B, Patient cancer type focus for the included studies: patients only with solid tumor (ST;ie, sarcomas, carcinomas, general tumors, and solid malignancies; n = 4) [18–21]; patients with hematological malignancy (HM) and ST but either primarily ST (n = 5) [3, 22–25] or separate outcome data for ST available (n = 4) [26–29]; patients with HM (ie, acute lymphocytic leukemia, acute myeloid leukemia, myelogenous leukemia, acute undifferentiated leukemia, chronic myelogenous leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, myelodysplastic syndrome, macroglobulinemia, chronic myeloid leukemia, aplastic anemia, and chronic myelomonocytic leukemia; n = 23) [17, 30–51]; patients with HM and ST but primarily HM (n = 5) [52–56] or separate outcome data for HM available (n = 4) [26–29]; and patients with HM who received hematopoietic cell transplant (allogeneic or autologous; n = 9) [57–65]. C, Number of studies per suspected infection, including febrile neutropenia (n = 22) [20, 24, 26, 27, 29–31, 33–35, 44–50, 53, 54, 56, 62, 65], fever (n = 5) [17, 32, 41, 52, 61], respiratory infections (n = 11) [21, 23, 25, 36, 37, 39, 40, 42, 57, 58, 63], sepsis (n = 2) [3, 28], gastrointestinal infections (n = 2) [55, 59], urinary tract infections (n = 2) [18, 22], central nervous system infections (n =1) [64], and mixed types of suspected infections where patients experienced different symptoms or sites of infections (n = 5) [19, 38, 43, 51, 60].

Figure 3.

Number of studies by cancer type and outcomes of interest identified in the systematic literature review, 1 January 2012–23 June 2022. Abbreviations: HCT, hematopoietic cell transplant; HCRU, healthcare resource utilization; HM, hematological malignancy; ST, solid tumor.

Figure 4.

Reported pathogen yield from diagnostic testing of blood and bronchoalveolar lavage fluid. Data yielded from systematic literature review, 1 January 2012–23 June 2022. Percent yield of the specified diagnostic test (ie, culture, polymerase chain reaction, or metagenomic sequencing) based on specimen type is indicated for each study reporting these data. Size of the marker indicates relative study size with numbers ranging from 22 to 2751. Abbreviations: BAL, bronchoalveolar lavage; FN, febrile neutropenia; HCT, hematopoietic cell transplant; HM, hematological malignancy; mSeq, metagenomic sequencing; PCR, polymerase chain reaction; ST, solid tumor.

Figure 5.

Test performance characteristics by cancer type, test, and sample. Data yielded from systematic literature review, 1 January 2012–23 June 2022. A, Sensitivity. B, Specificity. C, Positive predictive value. D, Negative predictive value. Size of marker represents the number of samples or patients in a study used to calculate data and ranged from 7 to 773. If no data are presented, the study did not report that value. Abbreviations: BAL, bronchoalveolar lavage; BDG, (1→3)-β-d-glucan; CMV, cytomegalovirus; CSF, cerebrospinal fluid; EORTC/MSG, European Organization for Research and Treatment of Cancer/Mycoses Study Group; GM, galactomannan; HCT, hematopoietic cell transplant; HM, hematological malignancy; LRT, lower respiratory tract; mSeq, metagenomic sequencing; PCR/ESI-MS, polymerase chain reaction–electrospray ionization mass spectrometry; PJP, Pneumocystis jirovecii pneumonia; RT-PCR, reverse-transcription polymerase chain reaction; ST, solid tumor.