47 Pneumocystis Jirovecii Pneumonia Prophylaxis in Patients With Glioma Receiving Concurrent Chemoradiation: A Systematic Review

BACKGROUND Routine antibiotic prophylaxis against pneumocystis jirovecii pneumonia (PJP) is mandated during concurrent temozolomide and radiation therapy (TMZ-RT) based on early studies in patients with glioma. However, the true risk of PJP in this population may have been overestimated and calls into question the value of routine prophylaxis in this population considering the possible harms. METHODS A systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception up until Jan 2024. Eligible articles were randomized controlled trials, prospective and retrospective cohort studies, and chart reviews of glioma patients treated with TMZ-RT, with or without PJP prophylaxis, with PJP incidence as a reported outcome. Study outcomes included overall PJP incidence, and PJP incidence based on prophylaxis use, corticosteroid exposure, and lymphopenia. FINDINGS A total of 28 out of 3,003 initially identified studies were included in this review. Of the combined 11,810 glioma patients, 11,077 received TMZ-RT. The incidence of PJP cases amongst all TMZ-RT patients was 0·7% (71/10,118). Seven out of 28 studies recorded PJP prophylaxis use, including five prospective and two retrospective designs. From these studies, we determined PJP incidence amongst subgroups with and without prophylaxis to be 0·8% (14/1,765) and 0·3% (9/2,719), respectively. Corticosteroid exposure was recorded in a median of 56·5% (range: 27·3% to 89·0%) of patients, but there was insufficient data to correlate to PJP incidence. Grade 3 or 4 lymphopenia was observed in 14·0% of patients. INTERPRETATION The incidence of PJP in the overall cohort treated with TMZ-RT, is extremely low with or without prophylaxis, far below the guideline-recommended 3.5% risk threshold to justify routine PJP prophylaxis. Therefore, the risk of developing PJP during TMZ-RT are likely overestimated and the decision for PJP prophylaxis should be individualized.