Most patients also underwent imaging studies, with 153 patients (77%) receiving a chest x-ray and 107 (54%) receiving at least 1 CT study (chest, abdomen/pelvis, or head/neck). Nine chest x-rays met the criteria for “diagnostic” (6%) and contributed to a final diagnosis of pneumonia in 5% of women. The diagnostic yield for chest CT was 21%. Of the 89 abdomen/pelvis CT performed, 53 (60%) were considered diagnostic. Head and neck CT was diagnostic in 1 (6%) of 18 instances.
We also assessed the utility of diagnostic testing in patient subgroups (Tables 1–3, Supplemental Digital Content 1, http://links.lww.com/IGC/A216). There were no additional statistically significant differences in the performance of diagnostic testing in neutropenic patients or in patients presenting 30 days after surgery or chemotherapy.
Initial management of gynecologic oncology patients admitted with fever should include blood and urine cultures before administration of antibiotics that cover the broad spectrum of organisms we identified, including Gram-positive and Gram-negative pathogens. If these steps are nondiagnostic and fever persists, abdominopelvic CT scanning will reveal the etiology of fever in many women. This approach seems valid across compared patient groups, including neutropenic, postsurgical, and postchemotherapy patients, except that women presenting within 30 days of surgery should have wounds explored.
Compared with other studies that focused strictly on nongynecologic patients with neutropenic or postoperative fever, this study included all gynecologic oncology patients admitted with a diagnosis of fever. Overall, fever etiologies were similar between the different gynecologic malignancies, with 2 notable exceptions. Ovarian cancer patients had a higher incidence of pneumonia, whereas uterine and cervical cancer patients were found to have a higher incidence of UTIs. These differences may be related to the systemic spread of ovarian cancer with pleural effusions leading to an increased risk for pneumonia as compared with more localized disease in uterine and cervical cancers. Adjuvant treatment with radiation therapy could also result in increased risk for infections of the urinary tract.
In our population, an etiology for fever was determined for 80% of patients. This proportion is greater than that in previous studies of febrile neutropenic patients, in which the etiology of fever remained unknown after evaluation in more than 50% of patients.6–9 However, we also found that neutropenic patients often had no identifiable source of fever, suggesting that fevers may arise from compromised mucosal immunity in these women. Blood cultures were positive in 34% and diagnostic in 29% of our patients. The utility of blood cultures in this study is higher than what has previously been seen in oncology patients8,10 and may reflect the increasing use of central venous catheters in gynecologic oncology patients
Urinalysis has been shown to have a sensitivity of 68% to 98% and specificity of 59% to 96% in various studies.11–13 However, urinalyses in hospitalized patients have lower reliability, and urine culture is recommended for definitive diagnosis in these patients.13 Our finding that only 60% of women with positive urinalysis results had positive urine cultures may reflect contamination from vaginal sources or administration of antibiotics before culture.
Severely neutropenic women made up 13% of all gynecologic oncology patients admitted with fever. Febrile neutropenic gynecologic oncology patients with fever also had a lower percentage of bloodstream and UTIs compared with the overall population. For these women, broad-spectrum antibiotic coverage until resolution of neutropenia may be sufficient. Although prospective studies are needed, hospitalization may not be required for many febrile neutropenic gynecologic oncology patients.14,15
Although 60% of patients undergoing abdominal/pelvic CT scans had findings consistent with infection, several of these patients already had confirmed infection from other sources. In addition, not all of these CT scans were performed for diagnosis of fever because several patients had coexisting small bowel or urinary tract obstruction; therefore, the true rate of diagnosis attributable to CT scans is unclear in retrospect. Chest CT had an overall lower rate of utility than abdominal/pelvic CT in this population. Head/neck CT had a very poor yield in the evaluation of fever. Prospective assessment of protocols incorporating CT imaging may better define the role of these tests in febrile gynecologic oncology patients.
This study has a number of limitations. In addition to its retrospective nature, this study assessed a heterogeneous population of 200 consecutive patients admitted for fever, including those who were recently postoperative, those receiving chemotherapy, or those with febrile neutropenia. The small numbers of women in subgroups limit our ability to perform subgroup analyses. Multicenter studies focused on various classes of febrile gynecologic oncology patients may be needed to define optimal management protocols. Finally, the presence of central lines and indwelling vascular catheters was poorly documented in our medical records precluding and assessment of these as a source of an infectious fever.
Despite these limitations, our study defines the characteristics of febrile gynecologic oncology patients and provides an evidence-based approach to stepwise assessment and management of these women. Research is ongoing to determine whether some gynecologic oncology patients with fever can be evaluated as outpatients.
1. Aprile G, Pisa FE, Follador A, et al. Unplanned presentations of cancer outpatients: a retrospective cohort study. Support Care Cancer. 2013; 21: 397–404.
2. Majem M, Galan M, Perez FJ, et al. The oncology acute toxicity unit (OATU): an outpatient facility for improving the management of chemotherapy toxicity. Clin Transl Oncol. 2007; 9: 784–788.
3. McKenzie H, Hayes L, White K, et al. Chemotherapy outpatients’ unplanned presentations to hospital: a retrospective study. Support Care Cancer. 2011; 19: 963–969.
4. Feusner J, Cohen R, O’Leary M, et al. Use of routine chest radiography in the evaluation of fever
in neutropenic pediatric oncology patients. J Clin Oncol. 1988; 6: 1699–1702.
5. Oude Nijhuis CS, Gietema JA, Vellenga E, et al. Routine radiography does not have a role in the diagnostic evaluation of ambulatory adult febrile neutropenic cancer patients. Eur J Cancer. 2003; 39: 2495–2498.
6. Hakim H, Flynn PM, Knapp KM, et al. Etiology and clinical course of febrile neutropenia
in children with cancer. J Pediatr Hematol Oncol. 2009; 31: 623–629.
7. McMeekin DS, Gazzaniga C, Berman M, et al. Retrospective review of gynecologic oncology patients with therapy-induced neutropenic fever
. Gynecol Oncol. 1996; 62: 247–253.
8. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011; 52: e56–e93.
9. Pizzo PA. Management of fever
in patients with cancer and treatment-induced neutropenia
. N Engl J Med. 1993; 328: 1323–1332.
10. Bates DW, Cook EF, Goldman L, et al. Predicting bacteremia in hospitalized patients. A prospectively validated model. Ann Intern Med. 1990; 113: 495–500.
11. Bent S, Nallamothu BK, Simel DL, et al. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002; 287: 2701–2710.
12. Pappas PG. Laboratory in the diagnosis and management of urinary tract infections. Med Clin North Am. 1991; 75: 313–325.
13. Wilson ML, Gaido L. Laboratory diagnosis of urinary tract infections in adult patients. Clin Infect Dis. 2004; 38: 1150–1158.
14. Klastersky J, Paesmans M, Georgala A, et al. Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. J Clin Oncol. 2006; 24: 4129–4134.
15. Innes H, Lim SL, Hall A, et al. Management of febrile neutropenia
in solid tumours and lymphomas using the Multinational Association for Supportive Care in Cancer (MASCC) risk index: feasibility and safety in routine clinical practice. Support Care Cancer. 2008; 16: 485–491.
Keywords:© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.
Fever; Neutropenia; Ovarian cancer; Endometrial cancer; Cervical caner