Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, has become a popular target for radionuclide-based theranostic applications in the advanced stages of prostate cancer. We conducted a meta-analysis of the therapeutic effects of PSMA-targeting alpha therapy [225Ac-PSMA radioligand therapy (RLT)] in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: A systematic search was performed using the keywords “mCRPC,” “225Ac-PSMA,” and “alpha therapy”. Therapeutic responses were analyzed as the pooled proportions of patients with more than 50% of prostate-specific antigen (PSA) decline and any PSA decline. Survival outcomes were analyzed by estimating summary survival curves for progression-free survival (PFS) and overall survival (OS). Adverse events were analyzed as the pooled proportions of patients with xerostomia and severe hematotoxicity (anemia, leukocytopenia, and thrombocytopenia). Results: Nine studies with 263 patients were included in our meta-analysis. The pooled proportions of patients with more than 50% of PSA decline and any PSA decline were 60.99% [95% confidence interval (CI) = 54.92–66.83%] and 83.57% (95% CI = 78.62–87.77%), respectively. The estimated mean PFS and mean OS were 9.15 months (95% CI = 6.69–11.03 months) and 11.77 months (95% CI = 9.51–13.49 months), respectively. The pooled proportions of patients with adverse events were 62.81% (95% CI = 39.34–83.46%) for xerostomia, 14.39% (95% CI = 7.76–22.63%) for anemia, 4.12% (95% CI = 0.97–9.31%) for leukocytopenia, and 7.18% (95% CI = 2.70–13.57%) for thrombocytopenia. Conclusion: In our study, around 61% of patients had more than 50% of PSA decline and 84% of patients had any PSA decline after 225Ac-PSMA RLT. The common adverse events in 225Ac-PSMA RLT were xerostomia in 63% of patients and severe hematotoxicity in 4–14% of patients.
Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50–0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67–0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.
The role of conventional bone scintigraphy in diagnosing early axial spondyloarthritis (SpA) is yet controversial. Single positron emission computed tomography (SPECT) plus CT is an imaging modality that adds better anatomical information to scintigraphy of the sacroiliac (SI) joint. Our aim was to investigate the usefulness of bone SPECT/CT with volume of interest (VOI) analysis in early axial SpA patients. Twenty patients (male: female ratio = 12:8; age range = 17–65 years) presenting with inflammatory back pain meeting the Amor criteria of early axial SpA were recruited from a single center in South Korea. Bone scintigraphy was performed 180 min after intravenous injection of 1110 MBq of Tc-99 m-HDP, followed by bone SPECT/CT. The ratio between the entire SI joint and sacrum (SIS ratio) was measured by both bone SPECT/CT and bone scintigraphy. Data from 13 controls were also evaluated. Receiver operating characteristic (ROC) curve was plotted for further analysis, and the correlation between the SIS ratio and SI joint grade by plain radiography was assessed. The SIS ratio of early axial SpA patients vs. control subjects was significantly increased in bone SPECT/CT (p < 0.001). However, no significant difference was detected in bone scintigraphy. ROC curve analysis showed a significant difference in the area under curve (AUC) of bone SPECT/CT vs. bone scintigraphy (0.862 vs. 0.523, respectively; p < 0.001). With a cut-off SIS ratio of 1.50, ROC curve analysis showed a sensitivity of 80.0% and specificity of 84.6% in bone SPECT/CT. The SIS ratio measured in SPECT/CT, but not that measured in bone scintigraphy, was significantly increased with a higher grade of SI joint changes in plain radiography (p = 0.014). Bone SPECT/CT is more useful than conventional bone scintigraphy in identifying sacroiliitis in early axial SpA patients, even with mild SI joint changes in plain radiography. By combining CT, we can accurately delineate the sacrum and SI joint uptake with our VOI method.
The aim of this study was to determine the usefulness of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) parameters provided by simultaneous 18F-fluorodeoxyglucose (FDG) PET/MRI for the prediction of treatment failure in surgically resected head and neck cancer. We hypothesized that PET parameters corrected by tumor cellularity (combined PET/MRI parameters) could predict the prognosis. On regional PET, maximum standardized uptake value (SUVmax) was measured as metabolic parameters. In addition, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were checked as metabolo-volumetric parameters. Mean apparent diffusion coefficient (ADCmean) of tumor was evaluated as the MRI parameter on the ADC map. Ratios between metabolic/metabolo-volumetric parameters and ADC were calculated as combined PET/MRI parameters. PET, MRI, and combined PET/MRI parameters were compared with clinicopathologic parameters in terms of treatment failure. Seventy-two patients (mean age = 55.9 ± 14.6 year, M: F = 45: 27) who underwent simultaneous 18F-FDG PET/MRI before head and neck cancer surgery were retrospectively enrolled. Twenty-two patients (30.6%) showed tumor treatment failure after head and neck cancer surgery (mean treatment failure = 13.0 ± 7.0 months). In the univariate analysis, MTV (P = 0.044) and ratios between metabolo-volumetric parameters and ADC (MTV/ADCmean, P = 0.022; TLG/ADCmean, P = 0.044) demonstrated significance among 18F-FDG PET/MRI parameters. Lymphatic invasion (P = 0.044) and perineural invasion (P = 0.046) revealed significance among clinicopathologic parameters. In the multivariate analysis, MTV (P = 0.026), MTV/ADCmean (P = 0.011), and TLG/ADCmean (P = 0.002) with lymphatic invasion (P = 0.026, 0.026, and 0.044, respectively) showed significance. Combined PET/MRI parameters (PET metabolo-volumetric parameters corrected by tumor cellularity) could be effective predictors of tumor treatment failure after head and neck cancer surgery in addition to MTV and clinicopathologic parameter.