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Purpose: The present pilot study investigates the putative role of radiomics from [18F]FDG PET/CT scans to predict PD-L1 expression status in non-small cell lung cancer (NSCLC) patients. Methods: In a retrospective cohort of 265 patients with biopsy-proven NSCLC, 86 with available PD-L1 immunohistochemical (IHC) assessment and [18F]FDG PET/CT scans have been selected to find putative metabolic markers that predict PD-L1 status (< 1%, 1–49%, and ≥ 50% as per tumor proportion score, clone 22C3). Metabolic parameters have been extracted from three different PET/CT scanners (Discovery 600, Discovery IQ, and Discovery MI) and radiomics features were computed with IBSI compliant algorithms on the original image and on images filtered with LLL and HHH coif1 wavelet, obtaining 527 features per tumor. Univariate and multivariate analysis have been performed to compare PD-L1 expression status and selected radiomic features. Results: Of the 86 analyzed cases, 46 (53%) were negative for PD-L1 IHC, 13 (15%) showed low PD-L1 expression (1–49%), and 27 (31%) were strong expressors (≥ 50%). Maximum standardized uptake value (SUVmax) demonstrated a significant ability to discriminate strong expressor cases at univariate analysis (p = 0.032), but failed to discriminate PD-L1 positive patients (PD-L1 ≥ 1%). Three radiomics features appeared the ablest to discriminate strong expressors: (1) a feature representing the average high frequency lesion content in a spherical VOI (p = 0.009); (2) a feature assessing the correlation between adjacent voxels on the high frequency lesion content (p = 0.004); (3) a feature that emphasizes the presence of small zones with similar grey levels inside the lesion (p = 0.003). The tri-variate linear discriminant model combining the three features achieved a sensitivity of 81% and a specificity of 82% in the test. The ability of radiomics to predict PD-L1 positive patients was instead scarce. Conclusions: Our data indicate a possible role of the [18F]FDG PET radiomics in predicting strong PD-L1 expression; these preliminary data need to be confirmed on larger or single-scanner series. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to evaluate the added diagnostic value of respiratory-gated 4D18F-FDG PET/CT in liver lesion detection and characterization in a European multicenter retrospective study. Methods: Fifty-six oncological patients (29 males and 27 females, mean age, 61.2 ± 11.2 years) from five European centers, submitted to standard 3D-PET/CT and liver 4D-PET/CT were retrospectively evaluated. Based on visual analysis, liver PET/CT findings were scored as positive, negative, or equivocal both in 3D and 4D PET/CT. The impact of 4D-PET/CT on the confidence in classifying liver lesions was assessed. PET/CT findings were compared to histology and clinical follow-up as standard reference and diagnostic accuracy was calculated for both techniques. At semi-quantitative analysis, SUVmax was calculated for each detected lesion in 3D and 4D-PET/CT. Results: Overall, 72 liver lesions were considered for the analysis. Based on visual analysis in 3D-PET/CT, 32/72 (44.4%) lesions were considered positive, 21/72 (29.2%) negative, and 19/72 (26.4%) equivocal, while in 4D-PET/CT 48/72 (66.7%) lesions were defined positive, 23/72 (31.9%) negative, and 1/72 (1.4%) equivocal. 4D-PET/CT findings increased the confidence in lesion definition in 37/72 lesions (51.4%). Considering 3D equivocal lesions as positive, sensitivity, specificity, and accuracy were 88.9, 70.0, and 83.1%, respectively, while the same figures were 67.7, 90.0, and 73.8% if 3D equivocal findings were included as negative. 4D-PET/CT sensitivity, specificity, and accuracy were 97.8, 90.0, and 95.4%, respectively, considering equivocal lesions as positive and 95.6, 90.0, and 93.8% considering equivocal lesions as negative. The SUVmax of the liver lesions in 4D-PET (mean ± SD, 6.9 ± 3.2) was significantly higher ( p < 0.001) than SUVmax in 3D-PET (mean ± SD, 5.2 ± 2.3). Conclusions: Respiratory-gated PET/CT technique is a valuable clinical tool in diagnosing liver lesions, reducing 3D undetermined findings, improving diagnostic accuracy, and confidence in reporting. 4D-PET/CT also improved the quantification of SUVmax of liver lesions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare technetium radiocolloid (Tc99) + blue dye (BD) versus Indocyanine green (ICG) fluorescent dye in terms of the overall detection rate and bilateral sentinel lymph node (SLN) mapping in patients with endometrial carcinoma. Methods: Patients from five European centers with apparently confined clinical stage I endometrial cancer were reviewed. A comparison was made between women who received SLN mapping with pelvic and/or aortic lymphadenectomy (LND), and women who underwent SLN algorithm (SA), was also performed between the two groups. Results: Three hundred and forty-two (342) women were involved (147 in the Tc99 + BD group and 195 in the ICG group). The overall detection rate of SLN biopsy was 97.3% (143/147) for women in the Tc99 + BD group and 96.9% (189/195) for women in the ICG group ( p = 0.547). The bilateral mapping rate for ICG was 84.1%-significantly higher with respect to the 73.5% obtained with Tc99 + BD ( p = 0.007). No differences in overall sensitivity (OS) and overall false negative rate (FNR) were seen between LND and SA ( p value = 0.311), whereas the negative predictive value (NPV) was in favor of SA group ( p value = 0.030). Conclusions: In this study, fluorescent mapping using ICG resulted equivalent to the standard combined radiocolloid and BD, but real-time SLN mapping achieves a higher bilateral detection rate. The added value that this fast emerging technology promises to give certainly warrants future studies to further consolidate the advantages there are over the standard technique. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare preoperative SPECT/CT with gamma-probe and methylene blue-dye (MBD) in the identification of sentinel lymph node (SLN) in early stage endometrial cancer. Methods: 40 stage-I EC patients (66.7 ± 9.7 years) underwent preoperative lymphoscintigraphy. After about 3 h from Tc-99m-albumin nanocolloid cervical injection, all patients underwent SPECT/CT study. MBD was injected into the cervix just before surgery under general anesthesia. All patients underwent SLN biopsy, hysterectomy, bilateral salpingo-oophorectomy, and radical regional lymphadenectomy. SPECT/CT findings were compared to those of gamma-probe and MBD techniques. Results: In 2 patients no nodal migration was observed, neither with MBD nor radiotracer. Detection rate of at least one SLN was 90% (36/40 patients) with SPECT/CT, 88% (35/40) intra-operatively with gamma-probe and 80% (32/40) with MBD. Only in 7/40 patients a bilateral migration was obtained with all considered modalities. In particular, bilateral detection was achieved in 26 patients with SPECT/CT, in 24 with gamma-probe and in 10 patients with MBD. The concordance site between SPECT/CT and intraoperative gamma-probe was 73% (29/40 patients: 2 without migration, 21 bilateral and 6 monolateral SLNs); while concordance site with MBD was found in 40% (16/40: 8 bilateral, 6 monolateral SLNs, 2 without SLNs). Overall, 628 LNs were dissected (mean 18 LNs per patient). The median number of SLNs removed was 2 (mean 2.5 per patient). Out of 91 SLNs: 43 were "hot and blue (HB)", 10 were blue only and 38 were hot only. LN metastases rate was 16%: 9/90 SLNs (7 HB, 2 hot only) were positive for metastases in 6 patients. Four non-SLNs were found positive in 3 patients, and all presented concomitant positive SLNs. False negative rate was 0%. Conclusions: SPECT/CT had the highest detection rate and achieved the highest rate of bilateral mapping, compared to gamma-probe and MDB. SPECT/CT had moderate concordance with gamma-probe, and it can help the intraoperative detection of SLNs providing important information about their anatomic location. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to assess the quality of care in patients who underwent sentinel lymph node (SLN) mapping for endometrial and cervical cancer staging, and evaluate the impact of different techniques on patient satisfaction, i.e. radiotracer Tc99m versus indocyanine green (ICG) or methylene blue injection. Method: Women with preoperative stage I endometrial cancer or stage I (1A2-1B1) cervical cancer who underwent surgical staging, including SLN mapping, were considered for this study. Patient satisfaction was assessed using the European Organisation for Research and Treatment of Cancer IN-PATSAT32 questionnaire. Women were classified into two groups according to the different nodal mapping techniques: intracervical preoperative injection of Tc99m nanocolloid + intraoperative blue dye (Group 1) versus intraoperative cervical injection of ICG or blue dye (Group 2). Differences in patient satisfaction scores between the groups were analyzed. Results: Of the 178 eligible women, 143 were included in the study (endometrial cancer n = 106, cervical cancer n = 37): 57 underwent SLN mapping with Tc99m and blue dye (Group 1), and 86 women were mapped intraoperatively with blue dye alone or ICG (Group 2). Analysis of IN-PATSAT32 questionnaire scores showed a higher patient satisfaction score for patients in Group 2 ( p = 0.001), which was independent of the physician and surgical outcomes evaluated. The scores were statistically better for Group 2, and also in rating doctors ( p = 0.0001), nurses ( p = 0.006), and care and services organizations ( p = 0.001). Conclusions: Cervical and endometrial cancer patients who underwent SLN mapping by ICG or blue dye perceived a better quality of care when compared with those patients who underwent the combined radiocolloid and blue dye technique. [ABSTRACT FROM AUTHOR]

Purpose: To compare the detection rate (DR) and bilateral optimal mapping (OM) of sentinel lymph nodes (SLNs) in women with endometrial and cervical cancer using indocyanine green (ICG) versus the standard technetium-99m radiocolloid (Tc) radiotracer plus methylene or isosulfan blue, or blue dye alone. Methods: From October 2010 to May 2015, 163 women with stage I endometrial or cervical cancer (118 endometrial and 45 cervical cancer) underwent SLN mapping with Tc with blue dye, blue dye alone, or ICG. DR and bilateral OM of ICG were compared respectively with the results obtained using the standard Tc radiotracer with blue dye, or blue dye alone. Results: SLN mapping with Tc radiotracer with blue dye was performed on 77 of 163 women, 38 with blue dye only and 48 with ICG. The overall DR of SLN mapping was 97, 89, and 100 % for Tc with blue dye, blue dye alone, and ICG, respectively. The bilateral OM rate for ICG was 85 %-significantly higher than the 58 % obtained with Tc with blue dye ( p = 0.003) and the 54 % for blue dye ( p = 0.001). Thirty-one women (19 %) had positive SLNs. Sensitivity and negative predictive value of SLN were 100 % for all techniques. Conclusions: SLNs mapping using ICG demonstrated higher DR compared to other modalities. In addition, ICG was significantly superior to Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer. The higher number of bilateral OM may consequently reduce the overall number of complete lymphadenectomies, reducing the duration and additional costs of surgical treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare planning target volume (PTV) defined on respiratory-gated positron emission tomography (PET)/CT (RG-PET/CT) to PTV based on ungated free-breathing CT and to evaluate if RG-PET/CT can be useful to personalize PTV by tailoring the target volume to the lesion motion in lung cancer patients. Methods: Thirteen lung cancer patients (six men, mean age 70.0 years, 1 small cell lung cancer, 12 non-small cell lung cancer) who were candidates for radiation therapy were prospectively enrolled and submitted to RG-PET/CT. Ungated free-breathing CT images obtained during a PET/CT study were visually contoured by the radiation oncologist to define standard clinical target volumes (CTV1). Standard PTV (PTV1) resulted from CTV1 with the addition of 1-cm expansion of margins in all directions. RG-PET/CT images were contoured by the nuclear medicine physician and radiation oncologist according to a standardized institutional protocol for contouring gated images. Each CT and PET image of the patient's respiratory cycle phases was contoured to obtain the RG-CT-based CTV (CTV2) and the RG-PET/CT-based CTV (CTV3), respectively. RG-CT-based and RG-PET/CT-based PTV (PTV2 and PTV3, respectively) were then derived from gated CTVs with a margin expansion of 7-8 mm in head to feet direction and 5 mm in anterior to posterior and left to right direction. The portions of gated PTV2 and PTV3 geometrically not encompassed in PTV1 (PTV2 out PTV1 and PTV3 out PTV1) were also calculated. Results: Mean ± SD CTV1, CTV2 and CTV3 were 30.5 ± 33.2, 43.1 ± 43.2 and 44.8 ± 45.2 ml, respectively. CTV1 was significantly smaller than CTV2 and CTV3 ( p = 0.017 and 0.009 with Student's t test, respectively). No significant difference was found between CTV2 and CTV3. Mean ± SD of PTV1, PTV2 and PTV3 were 118.7 ± 94.1, 93.8 ± 80.2 and 97.0 ± 83.9 ml, respectively. PTV1 was significantly larger than PTV2 and PTV3 ( p = 0.038 and 0.043 with Student's t test, respectively). No significant difference was found between PTV2 and PTV3. Mean ± SD values of PTV2 out PTV1 and PTV3 out PTV1 were 12.8 ± 25.4 and 14.3 ± 25.9 ml, respectively. The percentage values of PTV2 out PTV1 and PTV3 out PTV1 were not lower than 10 % of PTV1 in 6/13 cases (46.2 %) and than 20 % in 3/13 cases (23.1 %). Conclusion: Our preliminary data showed that RG-PET/CT in lung cancer can affect not only the volume of PTV but also its shape, as demonstrated by the assessment of gated PTVs outside standard PTV. The use of a gating technique is thus crucial for better delineating PTV by tailoring the target volume to the lesion motion in lung cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our work is to evaluate the added diagnostic value of respiratory gated (4-D) positron emission tomography/computed tomography (PET/CT) in lung lesion detection/characterization in a large patient population of a multicentre retrospective study. Methods: The data of 155 patients (89 men, 66 women, mean age 63.9 ± 11.1 years) from 5 European centres and submitted to standard (3-D) and 4-D PET/CT were retrospectively analysed. Overall, 206 lung lesions were considered for the analysis (mean ± SD lesions dimension 14.7 ± 11.8 mm). Maximum standardized uptake values (SUV) and lesion detectability were assessed for both 3-D and 4-D PET/CT studies; 3-D and 4-D PET/CT findings were compared to clinical follow-up as standard reference. Results: Mean ± SD 3-D and 4-D SUV values were 5.2 ± 5.1 and 6.8 ± 6.1 ( p < 0.0001), respectively, with an average percentage increase of 30.8 %. In 3-D PET/CT, 86 of 206 (41.7 %) lesions were considered positive, 70 of 206 (34 %) negative and 50 of 206 (24.3 %) equivocal, while in 4-D PET/CT 117 of 206 (56.8 %) lesions were defined as positive, 80 of 206 (38.8 %) negative and 9 of 206 (4.4 %) equivocal. In 34 of 50 (68 %) 3-D equivocal lesions follow-up data were available and the presence of malignancy was confirmed in 21 of 34 (61.8 %) lesions, while in 13 of 34 (38.2 %) was excluded. In 31 of these 34 controlled lesions, 20 of 34 (58.8 %) and 11 of 34 (32.4 %) were correctly classified by 4-D PET/CT as positive and negative, respectively; 3 of 34 (8.8 %) remained equivocal. With equivocal lesions classified as positive, the overall accuracy of 3-D and 4-D was 85.7 and 92.8 %, respectively, while the same figures were 80.5 and 94.2 % when equivocal lesions were classified as negative. Conclusion: The respiratory gated PET/CT technique is a valuable clinical tool in diagnosing lung lesions, improving quantification and confidence in reporting, reducing 3-D undetermined findings and increasing the overall accuracy in lung lesion detection and characterization. [ABSTRACT FROM AUTHOR]

New high-precision radiotherapy (RT) techniques, such as intensity-modulated radiation therapy (IMRT) or hadrontherapy, allow better dose distribution within the target and spare a larger portion of normal tissue than conventional RT. These techniques require accurate tumour volume delineation and intrinsic characterization, as well as verification of target localisation and monitoring of organ motion and response assessment during treatment. These tasks are strongly dependent on imaging technologies. Among these, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US) and positron emission tomography (PET) have been applied in high-precision RT. For tumour volume delineation and characterization, PET has brought an additional dimension to the management of cancer patients by allowing the incorporation of crucial functional and molecular images in RT treatment planning, i.e. direct evaluation of tumour metabolism, cell proliferation, apoptosis, hypoxia and angiogenesis. The combination of PET and CT in a single imaging system (PET/CT) to obtain a fused anatomical and functional dataset is now emerging as a promising tool in radiotherapy departments for delineation of tumour volumes and optimization of treatment plans. Another exciting new area is image-guided radiotherapy (IGRT), which focuses on the potential benefit of advanced imaging and image registration to improve precision, daily target localization and monitoring during treatment, thus reducing morbidity and potentially allowing the safe delivery of higher doses. The variety of IGRT systems is rapidly expanding, including cone beam CT and US. This article examines the increasing role of imaging techniques in the entire process of high-precision radiotherapy. [ABSTRACT FROM AUTHOR]

Background: A radiomic approach was applied in 18F-FDG PET endometrial cancer, to investigate if imaging features computed on the primary tumour could improve sensitivity in nodal metastases detection. One hundred fifteen women with histologically proven endometrial cancer who underwent preoperative 18F-FDG PET/CT were retrospectively considered. SUV, MTV, TLG, geometrical shape, histograms and texture features were computed inside tumour contours. On a first group of 86 patients (DB1), univariate association with LN metastases was computed by Mann-Whitney test and a neural network multivariate model was developed. Univariate and multivariate models were assessed with leave one out on 20 training sessions and on a second group of 29 patients (DB2). A unified framework combining LN metastases visual detection results and radiomic analysis was also assessed.Results: Sensitivity and specificity of LN visual detection were 50% and 99% on DB1 and 33% and 95% on DB2, respectively. A unique heterogeneity feature computed on the primary tumour (the zone percentage of the grey level size zone matrix, GLSZM ZP) was able to predict LN metastases better than any other feature or multivariate model (sensitivity and specificity of 75% and 81% on DB1 and of 89% and 80% on DB2). Tumours with LN metastases are in fact generally characterized by a lower GLSZM ZP value, i.e. by the co-presence of high-uptake and low-uptake areas. The combination of visual detection and GLSZM ZP values in a unified framework obtained sensitivity and specificity of 94% and 67% on DB1 and of 89% and 75% on DB2, respectively.Conclusions: The computation of imaging features on the primary tumour increases nodal staging detection sensitivity in 18F-FDG PET and can be considered for a better patient stratification for treatment selection. Results need a confirmation on larger cohort studies. [ABSTRACT FROM AUTHOR]