The Oral Cavity as a Source of Febrile Neutropenia (ORA-FEBRIS)

The Oral Cavity as a Source of Febrile Neutropenia: An Observational Study in Cancer Patients Treated With Myelosuppressive Chemotherapy

Febrile neutropenia (FN) is a clinically important adverse effect of myelosuppressive chemotherapy. If patients present with FN, attention is focussed on well-recognized sites of origin of infection: the airways, urinary tracts, and skin. However, infections can be only documented clinically in about two-third of febrile episodes, whereas a causative microbial pathogen cannot be identified in the majority (>70%) of cases.

Pre-treatment oral evaluation aimed to identify and eliminate oral/dental foci is only routinely used in patients at high risk for oral complications (i.e. head and neck cancer patients and stem cell transplantation recipients). However, any patient treated with myelosuppressive chemotherapy, be it for cure or palliation, is at risk of developing infection in and/or originating from the oral cavity. Nevertheless, in these patients dental screening is somewhat randomly employed at the oncologist's discretion.

More insight into the pre-treatment oral condition and its potential role in FN is mandatory, particularly considering the growing numbers of older patients retaining their natural dentition and the increase of dental diseases and cancer incidence with age.

In addition, oral diseases may aggravate chemotherapy-induced oral mucositis (OM). OM is associated with an inflammatory response, which together with ulcerations providing a portal of entry for bacteria, can result in FN and systemic inflammatory syndrome (SIRS) and/or sepsis. Evidence suggests that microorganisms are involved in the pathobiology of OM, but no longitudinal studies using open-end sequencing are available.

Furthermore, comparing bacteria identified in blood cultures in febrile patients with those of the oral cavity will expand the knowledge on the role of the oral cavity as a potential source of bacteremia.

The investigators expect that the results will provide a scientific base for subsequent intervention studies on the efficacy of dental screening and elimination of foci, and other interventions aimed at modifying the oral environment before and during chemotherapy.

Study Overview

• Status: Completed
• Conditions: Febrile Neutropenia; Oral Infection; Solid Tumors; Dental Infection

• Study Type: Observational
• Enrollment (Actual): 94

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Academic Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients treated with myelosuppressive chemotherapy with a 10-20% estimated risk to develop febrile neutropenia.

Description

Inclusion Criteria:

• Diagnosed with a solid cancer, lymphoma or multiple myeloma
• Planned treatment with myelosuppressive chemotherapy with FN risk of 10%-20% (with or without targeted therapies or hormonal therapy)
• Willing and able to give written Informed consent
• Age 18 or older
• Presence of (partial) natural dentition and/or dental implants

Exclusion Criteria:

• Patients unable to give written informed consent
• Patients <18 years
• Prior irradiation to the head and neck
• Edentulous patients

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dutch Periodontal Screening Index	Score Clinical criteria for the score per sextant (note site per sextant with the highest score) 0 No pockets >3mm in depth, no calculus, no overhanging restorations and no bleeding on probing to the bottom of the pocket; No pockets >3mm in depth, no calculus, no overhangs of restorations, but presence of bleeding on probing to the bottom of the pocket; No pockets >3mm in depth, presence of bleeding on probing to the bottom of the pocket, and presence of calculus or overhanging restorations; Presence of pathological pockets of 4-5mm without gingival recession; Presence of pathological pockets of 4-5mm with gingival recession; Presence of pathological pockets of 6mm or more. Ref: Van der Velden U, (2009) J Clin Periodontol. 2009 Dec;36(12):1018-24. doi: 10.1111/j.1600-051X.2009.01495.x. The Dutch periodontal screening index validation and its application in The Netherlands.	1 day
Caries-screening	no caries; caries in enamel; caries <50% in dentin; caries >50% in dentin; caries in rootcanal	1 day
Impacted (wisdom) teeth	not impacted; partially impacted; impacted	1 day
Plaque index in percentages	The plaque index is calculated via the amount of plaque on the mesiobuccal+buccal+distobuccal+mesiopalatinal or mesiolingual+palatinal or lingual+distopalatinal or distolingual of every tooth, given in percentages.	1 day
Radiographically (X-OPT) calculated bone loss in millimeters	Bone loss is measured on a X-OPT and the average bone loss is noted in millimeters.	1 day
Peri-apical radiolucency	Peri-apical radiolucency is diagnosed on a X-OPT or intraoral radiograph and will be noted as; yes; no	1 day
Radix relicta	The presence of radix relicta is noted as; yes; no	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NCI CTCAE V3.0 mucositis/stomatitis	The NCI-CTCAE v3.0 mucositis/stomatitis is noted for every patient when visiting the hospital.	100 days

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: L. Smeele, Professor, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: March 3, 2016
• First Posted (Estimate): March 8, 2016

Study Record Updates

• Last Update Posted (Actual): November 29, 2021
• Last Update Submitted That Met QC Criteria: November 26, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Solid Tumors; Febrile Neutropenia; Oral Infection; Myelosuppressive Chemotherapy; Dental Infection
• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Disease Attributes; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Body Temperature Changes; Heat Stress Disorders; Infections; Communicable Diseases; Neutropenia; Hyperthermia; Fever; Febrile Neutropenia
• Other Study ID Numbers: NL53440.018.15