Combination PET/CT scans are better than conventional CT scans at investigating the causes of persistent or recurrent neutropenic fever in blood cancer patients, a study by researchers at the Peter Mac Cancer Centre in Melbourne has found.

A phase 3 randomised controlled trial involving 147 patients with neutropenic fever  after chemotherapy or transplant conditioning found that [18F]FDG-PET-CT was associated with more frequent rationalisation of antibiotic use than conventional CT, without any worsening of  clinical outcomes.

The findings supported the use of FDG-PET-CT for decision making regarding antimicrobial cessation or de-escalation over conventional CT scans, according to the study investigators led by infectious disease physician Dr Abby Douglas of the Peter Mac National Centre for Infections in Cancer.

“Incorporation of [18F]FDG-PET-CT into the diagnostic algorithm for patients with high-risk persistent or recurrent neutropenic fever will likely to lead to reduction in exposure to empirical broad spectrum antimicrobial therapy in already heavily exposed patients,” they said.

The trial also found the patients who were given a combination PET/CT scan had a shorter stay in hospital.

“This new approach could also lead to reduction in days of hospitalisation, with potential reduction in health-care-associated complications, although this will require further investigation,” the study authors wrote in Lancet Haematology.

The trial was conducted at two haematology cancer centres that perform allogeneic HSCT and intensive chemotherapy for acute leukaemia (Royal Melbourne Hospital), and autologous HSCT (Peter MacCallum Cancer Centre ) between January 2018 and July 2020.

Most of the patients enrolled had conditions such as acute myeloid leukaemia, acute lymphoblastic leukaemia or myelodysplastic syndrome and an expected duration of profound neutropenia (≤0·5 cells/μl) for at least 10 days.

Antimicrobial rationalisation occurred in 53 (82%) of 65 patients in the DG-PET-CT group and 45 (65%) of 69 patients in the CT group (Odds Ratio 2·36).

Most rationalisations were a change in spectrum of antimicrobial therapy, with narrowing spectrum of therapy occurring in 28 (43%) of 65 patients in the FDG-PET-CT group compared with 17 (25%) of 69 patients in the CT group (OR 2·31).

Participants in the FDG-PET-CT group had more narrowing from broad spectrum therapies, such as meropenem, piperacillin-tazobactam, and vancomycin, than did those in the CT group, and more patients de-escalated from intravenous therapy to oral or no antimicrobial therapy. There were no differences in the rate of adverse clinical outcomes.

The median length of hospital stay was significantly shorter in the FDG-PET-CT group compared with the CT group (9 vs 12·5 days).

The researchers said FDG-PET-CT was a better guide to antibiotic use because it had the advantage of metabolic activity measurement and was therefore more accurate than CT scans in identifying true infection, and ruling out other important causes of fever.

They noted that CT identified many pneumonias and pneumonitis in which no causative pathogen was identified and which might never have represented infection. FDG-PET-CT identified more extra-pulmonary sites of microbiologically defined infection, including colitis and enteritis and more intra-abdominal clinically defined infections, including diverticulitis.

Dr Douglas said the reduction in length of stay was a significant outcome for high-risk patients and was probably explained by the findings of FDG-PET-CT reassuring clinicians that serious infections were adequately ruled in and out, facilitating earlier rationalisation of antimicrobial therapy and cessation of ongoing investigations.

“Getting out of hospital sooner is really important for patients who spend long and repeated stints here, and will likely improve their quality of life,” she said.

Shorter stays would also reduce the patients’ risk of healthcare-associated complications and the cost of their care.

While a combination FDG-PET/CT scan costs the healthcare system approximately $1,000 that would likely be offset by the reduced time a patient is in hospital, and will be examined further in future research, the researchers said.

However an accompanying editorial advised caution in extrapolating the findings to other settings, especially beyond highly specialist centres. It said the utility of DG-PET/CT in accurately identifying true infections would depend on clinical judgement of clinicians, which may be less well developed in centres with less experience and lower usage of the technology.

The cost savings from reduced hospital stays compared to CT scans would also be highly dependent on the cost and volume of DG-PET/CT scans performed, the authors said.