Prognostic Significance of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography in Anal Squamous Cell Carcinoma: A Systematic Review and a Meta-Analysis

Table 2

Methodological aspects, quality assessment, and main findings of eligible studies.

Study	PET device	Mean FDG dose, MBq	Postinjection interval, min	Quality assessment based on Oxford Center for Evidence-Based Medicine checklist for prognostic studies				PET parameters/cutoff values	Main findings
				Patient enrolment at a common point in the course of the disease	Follow-up duration, months	Method of verification of outcome/blind outcome assessment of PET findings	Adjustment for important prognostic factors
Schwarz et al. [24]	PET/CT	555–740	40–118	No	5–68 (mean, 26)	Tissue biopsy/NA	Yes	Metabolic response/CMR demarcated as the absence of abnormal FDG uptake at sites of abnormal FDG uptake on the pretreatment FDG-PET study; PMR determined as any persistent abnormal FDG uptake at these sites	CMR in 44 patients, PMR in 9 patients; 2-year CSS of 94% for patients with CMR vs. 39% for patients with PMR (); 2-year PFS of 95% for patients with CMR vs. 22% for patients with PMR (); CMR was the most significant predictor of PFS ()
De Winton et al. [16]	PET and PET/CT	300–400	≥60	Yes—within 30 days of conventional staging investigations	9–108	Tissue biopsy or radiological progression/yes	Yes	Inguinal nodal FDG uptake/NA	The estimated 5-year OS and PFS for the cohort were 77.3% (95% CI: 55.3–90.4%) and 72.2% (95% CI: 51.5–86.4%), respectively. The estimated 5-year PFS for FDG-PET and conventional imaging staged N2-3 disease was 70% (95% CI: 42.8–87.9%) and 55.3% (95% CI: 23.3–83.4%), respectively
Mai. et al. [23]	PET	266–394	60	No	3–51 (median, 26)	None/yes	Yes	Inguinal nodal FDG uptake/SUVmax > 2.5	No recurrence in inguinal lymph nodes occurred, especially not in patients with CT-enlarged inguinal lymph nodes and elective irradiation only. Patients with PET-positive nodal disease had a higher risk of developing distant metastases ()
Kidd et al. [22]	PET/CT	555–740	69 ± 21	No	4.9–59.3 (median, 24.2)	Tissue biopsy/no	Yes	SUVmax/NA	Higher SUVmax was associated with worse DFS (), increased risk of persistent or recurrent disease on posttherapy FDG-PET ()
Day et al. [15]	PET and PET/CT	80–120 and 300–400	60	No	20.4–109.2 (median, 60)	Tissue biopsy or radiological progression/no	Yes	Metabolic response/CMR defined as a return of visually graded FDG uptake in all baseline lesions to a level equivalent to or lower than the radioactivity in normal tissues of the involved organ; PMR determined as an improvement in visually graded FDG uptake at baseline involved sites, but persistent residual abnormality	2-year PFS of 95% for patients with a CMR, 71% for PMR, and 0% for NR (); 5-year OS of 88% for CMR, 69% for PMR, and 0% for NR (); metabolic response (CMR versus non-CMR) was a significant prognostic factor: HR for PFS and OS was 4.1 (95% CI: 1.5–11.5, ) and 6.7 (95% CI: 2.1–21.6, ), respectively
Goldman et al. [19]	PET/CT	410.7–851	40–60	No	5–87 (median, 89)	Tissue biopsy and death/no	Yes	Metabolic response/CMR defined as resolution of previously FDG avid primary and/or nodal regions; PMR defined as primary tumors or lymph nodes with persistently abnormal FDG uptake (but decreased compared with pretreatment scan)	2-year PFS for patients with CMR versus non-CMR of 89.8% and 69.2%, respectively (); 2-year OS for CMR versus non-CMR patients of 94.8% and 79.3% ()
Deantonio et al. [17]	PET/CT	8^Ψ	55–90	No	6–66 (median, 51)	Tissue biopsy and radiological progression/no	Yes	SUVmax/NA	PFS and OS were 53% and 77.8% at 2 years and 41.3% and 58.6% at 5 years, respectively, lack of correlation between median SUVmax and clinical response or survival; CMR and T1–T2 stage were statistically significant prognostic factors for PFS ( and , respectively) and for OS ()
Gauthé et al. [18]	PET/CT	3-4^Ψ	60	No	10–117 (median, 51)	Tissue biopsy/no	Yes	SUVmax, MTV, inguinal nodal uptake/18, 7 cm^3, FDG uptake greater than mediastinal uptake, and/or an abnormal anatomical structure on CT greater than 15 mm in shortest diameter, asymmetrically enlarged, or with evidence of central necrosis	Global 4-year OS of 82.7%; significant and independent correlation between MTV at the primary site with OS (), as better prognosis was found in patients with MTV less than 7 cm^3; lack of correlation between SUVmax and survival parameters; correlation of metabolic involvement of the inguinal lymph nodes with a poor outcome in the univariate analysis ()
Cardenas et al. [14]	PET/CT	407–740	40–118	No	3.6–94.1 (median, 28.6)	NA/no	Yes	SUVmax, metabolic response/6.1, NA	Significant association between reduced LR and posttreatment SUVmax <6.1 () and between increased OS and posttreatment SUVmax <6.1 () on univariate analysis; significant association between reduced LR and posttreatment SUVmax <6.1 () and the use of intensity modulated radiation therapy () on multivariate analysis; significant multivariate association between increased OS and posttreatment SUVmax <6.1 () and the use of chemotherapy ()
Houard et al. [21]	PET/CT	3.5–4.5^Ψ	55–90	No	8–76.9 (median, 25)	Tissue biopsy/no	Yes	Metabolic response/CMR defined as the visual absence of pathologic FDG uptake, corresponding to an uptake level equivalent to or lower than that in the normal surrounding organ, PMR determined as any persistent pathologic FDG uptake in the lesions visible at the baseline imaging workup	2-year PFS of 96% for patients with CMR and 28% for non-CMR patients (); 2-year CSS of 100% for patients with CMR and 59% for those without CMR (); CMR was the only significant predictor of PFS and CSS ()
Hong. et al. [20]	PET/CT	296–555	60	PET/CT acquired at radiotherapy simulation and subsequently after chemoradiation therapy	11.76–49.2 (median, 30)	NA/yes	Yes	SUVmax, MTV/NA, NA	Association of pretreatment MTV (HR: 1.4. 95% CI: 1.02–2.05), interim MTV (HR: 1.4, 95% CI: 1.04–1.89), and interim TLG (HR: 1.1, 95% CI: 1.01–1.21) with FFLR

^ΨThe unit is MBq/kg. HR, hazard ratio; CMR, complete metabolic response; PMR, partial metabolic response; NA, not available; NR, no response; CI, confidence interval; PET, positron emission tomography; CT, computed tomography; SUVmax, maximum standardized uptake value; FDG, fluorine-18 fluorodeoxyglucose; MTV, metabolic tumor volume; TLG, total lesion glycolysis; FFLR, freedom from local and regional recurrence; LR, local recurrence; PFS, progression-free survival; OS, overall survival; CSS, cause-specific survival; DFS, disease-free survival.