Radioembolization of Hepatocellular Carcinoma with 90Y Glass Microspheres: No Advantage of Voxel Dosimetry with Respect to Mean Dose in Dose-Response Analysis with Two Radiological Methods.

In this confirmatory study, we tested if a calculation that included the non-uniformity of dose deposition through a voxel-based dosimetric variable Ψ was able to improve the dose-response agreement with respect to the mean absorbed dose D. We performed dosimetry with 99mTc-MAA SPECT/CT and 90Y-PET/CT in 86 patients treated 8 instead of 4 days after the reference date with 2.8 times more 90Y glass microspheres/GBq than in our previous study. The lesion-by-lesion response was assessed with the mRECIST method and with an experimental densitometric criterion. A total of 106 lesions were studied. Considering Ψ as a prognostic response marker, having no Ψ provided a significantly higher AUC than D. The correlation, t-test, and AUC values were statistically significant only with the densitometric method and only with post-therapy dosimetry. In comparison with our previous study, the dose-response correlation and AUC values were poorer (maximum r = 0.43, R2 = 0.14, maximal AUC = 0.71), and the efficacy at a high dose did not reach 100%. The expected advantages of voxel dosimetry were nullified by the correlation between any Ψ and D due to the limited image spatial resolution. The lower AUC and efficacy may be explained by the mega-clustering effect triggered by the higher number of microspheres/GBq injected on day 8.

Role of pretreatment 18F-FDG PET/CT parameters in predicting outcome of non-endemic EBV DNA-related nasopharyngeal cancer (NPC) patients treated with IMRT and chemotherapy.

PURPOSE: To evaluate the prognostic role of pretreatment 18F-FDG PET/CT metabolic parameters in non-endemic Epstein-Barr Virus (EBV DNA)-related nasopharyngeal cancer (NPC) patients treated with curative intensity-modulated radiation therapy (IMRT) with or without chemotherapy (CHT). MATERIALS/METHODS: We retrospectively reviewed clinical data of 160 consecutive non-metastatic NPC patients who received IMRT with or without CHT. Forty-nine out of 160 patients that underwent whole body 18F-FDG PET/CT at our institution for disease staging with a minimum follow-up to 12 months were included in this study. We evaluated the relationship between maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumor volume and total lesion glycolysis (TLG) of primary tumor and cervical lymph nodes with disease-free survival (DFS) and overall survival (OS). We also investigated the prognostic role of clinical variables such as age, disease stage, plasma EBV DNA load (copies/ml), gross tumor volume of primary tumor and lymph nodes. RESULTS: Median follow-up was 55 months. Two- and 5-year OS were 95.8% and 90.5%, respectively, while DFS was 83.4% at both time points. SUVmax of primary tumor ≥ 18.8 g/ml and primary tumor TLG ≥ 203.1 g were significant prognostic factors of worse OS. Furthermore, stages IVB and EBV DNA load ≥ 3493 copies/ml were significantly associated with lower DFS. No correlation was found between PET parameters and plasma EBV DNA load. CONCLUSION: Even in a limited series, our data suggested that SUVmax, SUVmean and TLG of primary tumor could predict a poor outcome in NPC patients also in non-endemic area hypothesizing their use for refinement of prognostication.

Impact of missing attenuation and scatter corrections on 99m Tc-MAA SPECT 3D dosimetry for liver radioembolization using the patient relative calibration methodology: A retrospective investigation on clinical images.

PURPOSE: To investigate the clinical implication of performing pre-treatment dosimetry for 90 Y-microspheres liver radioembolization on 99m Tc-MAA SPECT images reconstructed without attenuation or scatter correction and quantified with the patient relative calibration methodology. METHODS: Twenty-five patients treated with SIR-Spheres® at Istituto Europeo di Oncologia and 31 patients treated with TheraSphere® at Istituto Nazionale Tumori were considered. For each acquired 99m Tc-MAA SPECT, four reconstructions were performed: with attenuation and scatter correction (AC_SC), only attenuation (AC_NoSC), only scatter (NoAC_SC) and without corrections (NoAC_NoSC). Absorbed dose maps were calculated from the activity maps, quantified applying the patient relative calibration to the SPECT images. Whole Liver (WL) and Tumor (T) regions were drawn on CT images. Injected Liver (IL) region was defined including the voxels receiving absorbed dose >3.8 Gy/GBq. Whole Healthy Liver (WHL) and Healthy Injected Liver (HIL) regions were obtained as WHL = WL - T and HIL = IL - T. Average absorbed dose to WHL and HIL were calculated, and the injection activity was derived following each Institute's procedure. The values obtained from AC_NoSC, NoAC_SC and NoAC_NoSC images were compared to the reference value suggested by AC_SC images using Bland-Altman analysis and Wilcoxon paired test (5% significance threshold). Absorbed-dose maps were compared to the reference map (AC_SC) in global terms using the Voxel Normalized Mean Square Error (%VNMSE), and at voxel level by calculating for each voxel the normalized difference with the reference value. The uncertainty affecting absorbed dose at voxel level was accounted for in the comparison; to this purpose, the voxel counts fluctuation due to Poisson and reconstruction noise was estimated from SPECT images of a water phantom acquired and reconstructed as patient images. RESULTS: NoAC_SC images lead to activity prescriptions not significantly different from the reference AC_SC images; the individual differences (<0.1 GBq for all IEO patients, <0.6 GBq for all but one INT patients) were comparable to the uncertainty affecting activity measurement. AC_NoSC and NoAC_NoSC images, instead, yielded significantly different activity prescriptions and wider 95% confidence intervals in the Bland-Altman analysis. Concerning the absorbed dose map, AC_NoSC images had the smallest %VNMSE value and the highest fraction of voxels differing less than 2 standard deviations from AC_SC. CONCLUSIONS: The patient relative calibration methodology can compensate for the missing attenuation correction when performing healthy liver pre-treatment dosimetry: safe treatments can be planned even on NoAC_SC images, suggesting activities comparable to AC_SC images. Scatter correction is recommended due to its heavy impact on healthy liver dosimetry.

Impact of SPECT corrections on 3D-dosimetry for liver transarterial radioembolization using the patient relative calibration methodology.

PURPOSE: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE. METHODS: Three voxelized phantoms were derived from CT images of real patients with different body sizes. Simulations of (99m)Tc-SPECT projections were performed with the SIMIND code, assuming three activity distributions in the liver: uniform, inside a "liver's segment," or distributing multiple uptaking nodules ("nonuniform liver"), with a tumoral liver/healthy parenchyma ratio of 5:1. Projection data were reconstructed by a commercial workstation, with OSEM protocol not specifically optimized for dosimetry (spatial resolution of 12.6 mm), with/without SC (optimized, or with parameters predefined by the manufacturer; dual energy window), and with/without AC. Activity in voxels was calculated by a relative calibration, assuming identical microspheres and (99m)Tc-SPECT counts spatial distribution. 3D dose distributions were calculated by convolution with (90)Y voxel S-values, assuming permanent trapping of microspheres. Cumulative dose-volume histograms in lesions and healthy parenchyma from different reconstructions were compared with those obtained from the reference biodistribution (the "gold standard," GS), assessing differences for D95%, D70%, and D50% (i.e., minimum value of the absorbed dose to a percentage of the irradiated volume). γ tool analysis with tolerance of 3%/13 mm was used to evaluate the agreement between GS and simulated cases. The influence of deep-breathing was studied, blurring the reference biodistributions with a 3D anisotropic gaussian kernel, and performing the simulations once again. RESULTS: Differences of the dosimetric indicators were noticeable in some cases, always negative for lesions and distributed around zero for parenchyma. Application of AC and SC reduced systematically the differences for lesions by 5%-14% for a liver segment, and by 7%-12% for a nonuniform liver. For parenchyma, the data trend was less clear, but the overall range of variability passed from -10%/40% for a liver segment, and -10%/20% for a nonuniform liver, to -13%/6% in both cases. Applying AC, SC with preset parameters gave similar results to optimized SC, as confirmed by γ tool analysis. Moreover, γ analysis confirmed that solely AC and SC are not sufficient to obtain accurate 3D dose distribution. With breathing, the accuracy worsened severely for all dosimetric indicators, above all for lesions: with AC and optimized SC, -38%/-13% in liver's segment, -61%/-40% in the nonuniform liver. For parenchyma, D50% resulted always less sensitive to breathing and sub-optimal correction methods (difference overall range: -7%/13%). CONCLUSIONS: Reconstruction protocol optimization, AC, SC, PVE and respiratory motion corrections should be implemented to obtain the best possible dosimetric accuracy. On the other side, thanks to the relative calibration, D50% inaccuracy for the healthy parenchyma from absence of AC was less than expected, while the optimization of SC was scarcely influent. The relative calibration therefore allows to perform TARE planning, basing on D50% for the healthy parenchyma, even without AC or with suboptimal corrections, rather than rely on nondosimetric methods.

FDG-PET/CT to predict optimal primary cytoreductive surgery in patients with advanced ovarian cancer: preliminary results.

AIMS AND BACKGROUND: Primary cytoreductive surgery (CRS) has a significant impact on prognosis in epithelial ovarian cancer (EOC). Patient selection is important to recognize factors limiting optimal CRS and to avoid unnecessary aggressive surgical procedures. We evaluated the contribution of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the presurgical identification of disease sites that may preclude EOC cytoreducibility. METHODS: Patients with suspected EOC underwent 18F-FDG-PET/CT within 20 days before debulking surgery. The PET/CT results were compared with surgical findings and postsurgery histopathology in order to assess the diagnostic value. RESULTS: Between August 2013 and January 2014, 29 patients were evaluated. The histopathology showed 23 EOC and 6 benign tumors. The FDG-PET/CT was positive (maximum standardized uptake value [SUVmax] 11.3 ± 5.4) in 21/23 (91%) patients with EOC and provided 2 false-negatives (1 mucinous and 1 clear cell carcinoma; SUVmax ≤2.8). The FDG-PET/CT was true-negative (SUVmax 2.2 ± 1.6) in 4 out of 6 patients (67%). False-positive FDG-PET results were obtained in 2 cellular fibromas (SUVmax 4.8 and 5.6). The sensitivity, specificity, and accuracy of PET/CT to characterize ovarian masses were 91%, 67%, and 86%, respectively. Among the 21 FDG-PET/CT-positive EOC, we detected factors limiting optimal CRS in 6 cases (29%): 4 hepatic hilum infiltration and 2 root mesentery involvement, confirmed at surgical exploration. The FDG-PET did not find limiting factors in the remaining 15 patients (71%) in whom optimal CRS was obtained. CONCLUSIONS: Fluorodeoxyglucose-PET/CT shows high sensitivity but suboptimal specificity in the characterization of ovarian masses. However, PET/CT may play a role in noninvasively selecting patients with EOC who can benefit from primary CRS.