The potential role of osteoporosis in unspecific [18F]PSMA-1007 bone uptake.

AIM: Unspecific bone uptake is one of the main limitations of PET imaging with some PSMA-targeting radiopharmaceuticals, especially with [18F]PSMA-1007. We explored the potential association between osteoporosis and the occurrence of unspecific [18F]PSMA-1007 bone uptake investigating markers which might correlate with bone mineral density. MATERIALS AND METHODS: We retrospectively analyzed treatment-naïve patients with a confirmed diagnosis of prostate adenocarcinoma who underwent staging [18F]PSMA-1007 positron emission tomography (PET). Qualitative image analysis was performed independently by three experienced nuclear medicine physicians. Patients were divided in two groups according to the presence/absence of unspecific bone uptake. Clinical information, blood count parameters (assessed within 3 months to the PET scan), body mass index (BMI), and bone density as estimated by computed tomography were collected. The Kruskal-Wallis and t-test were used to compare parameters. RESULTS: We analyzed 77 patients: 29 of them (38%) had unspecific bone uptake at [18F]PSMA-1007 PET, most commonly in the pelvic bones (69%) and ribs (62%). We did not find any significant difference in clinical parameters in the two groups. In patients with unspecific bone uptake, white blood cell, and neutrophil counts were significantly higher; in the same group, we observed lower values of BMI and bone density, although not statistically different. CONCLUSIONS: We observed unspecific bone uptake on [18F]PSMA-1007 PET in more than 1/3 of patients. In this exploratory analysis, we found a significant correlation between blood count parameters and unspecific [18F]PSMA-1007 bone uptake. We may speculate that [18F]PSMA-1007 unspecific bone uptake could be associated with osteoporosis. This hypothesis needs to be further investigated in larger populations and exploring more specific markers of osteoporosis.

The prognostic power of [11C]methionine PET in IDH-wildtype diffuse gliomas with lower-grade histological features: venturing beyond WHO classification.

PURPOSE: IDH-wildtype (IDH-wt) diffuse gliomas with histological features of lower-grade gliomas (LGGs) are rare and heterogeneous primary brain tumours. [11C]Methionine (MET) positron emission tomography (PET) is commonly used to evaluate glial neoplasms at diagnosis. The present study aimed to assess the prognostic value of MET PET in newly diagnosed, treatment naïve IDH-wt gliomas with histological features of LGGs. METHODS: Patients with a histological diagnosis of IDH-wt LGG who underwent preoperative (< 100 days) MET PET/CT and surgery were retrospectively included. Qualitative and semi-quantitative analyses of MET PET images were performed. Progression-free survival (PFS) and overall survival (OS) were analysed by Kaplan-Meier curves. Cox proportional-hazards regression was used to test the association of imaging and clinical data to PFS and OS. RESULTS: We included 48 patients (M:F = 25:23; median age 55). 39 lesions were positive and 9 negative at MET PET. Positive MET PET was significantly associated with shorter median PFS (15.7 months vs. not reached, p = 0.0146) and OS time (32.6 months vs. not reached, p = 0.0253). Incomplete surgical resection and higher TBRmean values were independent predictors of shorter PFS on multivariate analysis (p < 0.001 for both). Higher tumour grade and incomplete surgical resection were independent predictors of OS at multivariate analysis (p = 0.027 and p = 0.01, respectively). CONCLUSION: MET PET is useful for the prognostic stratification of patients with IDH-wt glial neoplasms with histological LGGs features. Considering their huge biological heterogeneity, the combination of MET PET and molecular analyses may help to improve the prognostic accuracy in these diffuse gliomas subset and influence therapeutic choices accordingly.

The "digital biopsy" in non-small cell lung cancer (NSCLC): a pilot study to predict the PD-L1 status from radiomics features of [18F]FDG PET/CT.

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.

Combining positron emission tomography/computed tomography, radiomics, and sentinel lymph node mapping for nodal staging of endometrial cancer patients.

OBJECTIVE: To evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed. METHODS: From November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging: 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B). RESULTS: In Group 1, eight patients had nodal metastases (13%): seven correctly ridentified by PET/CT true-positive with one false-negative case. In Group 2, 27 patients (25%) had nodal metastases: 13 true-positive and 14 false-negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic nodal metastases were 87%, 94%, 93%, 70%, and 98% in Group 1 and 48%, 97%, 85%, 87%, and 85% in Group 2, respectively. On radiomics analysis a significant association was found between the presence of lymph node metastases and 64 features. Volume-density, a measurement of shape irregularity, was the most predictive feature (p=0001, AUC=0,77, cut-off 0.35). When testing cut-off in Group B to discriminate metastatic tumors, PET false-negative findings were reduced from 14 to 8 (-43%). CONCLUSIONS: PET/CT demonstrated high specificity in detecting nodal metastases. SLN and histologic ultrastaging increased false-negative PET/CT findings, reducing the sensitivity of the technique. PET radiomics features of the primary tumor seem promising for predicting the presence of nodal metastases not detected by visual analysis.

Added diagnostic value of respiratory-gated 4D 18F-FDG PET/CT in the detection of liver lesions: a multicenter study.

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.

Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye.

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 ((99m)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 (99m)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 (99m)Tc radiotracer with blue dye, or blue dye alone. RESULTS: SLN mapping with (99m)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 (99m)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 (99m)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 (99m)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.

Predictors of PSMA PET Positivity: Analysis in a Selected Cohort of Biochemical Recurrence Prostate Cancer Patients after Radical Prostatectomy.

Localized prostate cancer (PCa) can be treated with radical prostatectomy (RP). Up to 30% of patients undergoing this procedure experience biochemical recurrence (BCR), namely the rise in serum prostate-specific antigen (PSA) levels during the post-surgical follow-up, requiring further treatments and with the risk of severe disease progression. Currently, the most accurate imaging technique to confirm, detect, and locate disease relapses in BCR patients is prostate-specific membrane antigen (PSMA)-targeted PET, as recommended by international clinical guidelines. The aim of the study was to investigate potential clinical and pathological predictors of PSMA PET positivity, validated by clinical and instrumental follow-up or histopathological data. In this study, a selected cohort of BCR patients after RP and no other PCa-related therapy who underwent either PSMA PET/CT or PSMA PET/MRI has been analysed. Among the considered predictors, both pathological staging after RP equal or higher than pT3a and higher PSA levels at the time of the scan were significantly correlated with PSMA PET positivity on multivariate logistic regression analysis. As expected, PSMA PET confirmed its role as an accurate imaging technique in the setting of BCR in PCa. These findings may inform appropriate and tailored patient selection and scan timing to optimize and fully exploit this powerful diagnostic tool.

Respiratory gated PET/CT in a European multicentre retrospective study: added diagnostic value in detection and characterization of lung lesions.

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(max)) 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(max) 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.

Clinical Application of a High Sensitivity BGO PET/CT Scanner: Effects of Acquisition Protocols and Reconstruction Parameters on Lesions Quantification.

AIMS: The aim of this retrospective study was to investigate SUVs variability with respect to lesion size, administered dose, and reconstruction algorithm. BACKGROUND: SUVmax and SUVpeak are influenced by technical factors as count statistics and reconstruction algorithms. OBJECTIVE: To fulfill the aim, we evaluated the SUVs variability with respect to lesion size, administered dose, and reconstruction algorithm (ordered - subset expectation maximization plus point spread function option - OSEM+PSF, regularized Bayesian Penalized Likelihood - BPL) in a 5 - rings BGO PET/CT scanner. METHODS: Discovery IQ scanner (GE Healthcare, Milwaukee, Wisconsin, US) was used for list mode acquisition of 25 FDG patients, 12 injected with 3.7 MBq/kg (Standard Dose protocol - SD) and 13 injected with 1.8 MBq/kg (Low Dose protocol - LD). Each acquisition was reconstructed at different time/FOV with both OSEM+PSF algorithm and BPL using seven different beta factors. SUVs were calculated in 70 lesions and analysed in function of time/FOV and Beta. Image quality was evaluated as a coefficient of variation of the liver (CV - liver). RESULTS: SUVs were not considerably affected by time/FOV. However, SUVs were influenced by beta: differences were higher in small lesions (37% for SUVmax, 15% for SUVpeak) compared to larger ones (14% and 6%). CV - liver ranged from 6% with Beta-500 (LD and SD) to 13% with Beta- 200 (LD). CV - liver of BPL with Beta-350 (optimized for clinical practice in our institution) in LD was lower than CV - liver of OSEM+PSF in SD. CONCLUSION: When a high sensitivity 5 - rings BGO PET/CT scanner is used with the same reconstruction algorithm, quantification by means of SUVmax and SUVpeak is a robust standard compared to the activity and scan duration. However, both SUVs and image quality are influenced by reconstruction algorithms and the related parameters should be considered to obtain the best compromise between detectability, quantification, and noise.

[11C]choline positron emission tomography/computerized tomography to restage prostate cancer cases with biochemical failure after radical prostatectomy and no disease evidence on conventional imaging.

PURPOSE: We assessed the value of [11C]choline positron emission tomography/computerized tomography in patients with prostate cancer in whom biochemical failure developed after radical prostatectomy but who showed no disease evidence on conventional imaging. MATERIALS AND METHODS: Considered for this study were 2,124 patients treated with radical prostatectomy who underwent [11C]choline positron emission tomography/computerized tomography to restage disease between December 2004 and January 2007. Study inclusion criteria were 1) previous radical prostatectomy and pelvic lymph node dissection, 2) increasing prostate specific antigen beyond 0.2 ng/ml after radical prostatectomy, 3) no lymph node disease at radical prostatectomy, 4) no evidence of metastatic disease on conventional imaging, 5) no androgen deprivation therapy and 6) no adjuvant or salvage radiotherapy. These criteria were satisfied in 109 of the 2,124 patients (5%). RESULTS: Median prostate specific antigen at imaging was 0.81 ng/ml (range 0.22 to 16.76 ml). Imaging suggested local recurrence in 4 patients (4%) and pelvic lymph node disease in 8 (7%). Scans were positive in 5%, 15% and 28% of patients with prostate specific antigen less than 1, between 1 and 2, and greater than 2 ng/ml, respectively (p <0.05). Prostate specific antigen was the only significant predictor of tomography results (p <0.05). CONCLUSIONS: Positron emission tomography/computerized tomography detected increased [11C]choline uptake, suggesting recurrent disease in 11% of patients with prostate cancer, increasing prostate specific antigen after radical prostatectomy and no evidence of disease on conventional imaging. This modality may be useful to restage disease but it cannot be used to guide therapy.

Assessment of residual viability by enoximone echocardiography in patients with previous myocardial infarction correlation with positron emission tomographic studies and functional follow-up.

BACKGROUND: The aim of this study was to evaluate enoximone echocardiography (EE) for the identification of residual myocardial viability in postinfarction patients. Findings obtained during EE were compared with those acquired by myocardial uptake of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and functional follow-up results. METHODS: Twenty-five patients underwent EE and PET (18)F-FDG studies. An asynergic segment was considered as having contractile enhancement when the wall motion score decreased by > or = 1 grade during EE and was defined as viable if (18)F-FDG uptake score was > or = 2 grade on PET. RESULTS: Of 293 dysfunctional segments at baseline, 139 (47%) were viable by PET criteria; 117 (40%) had contractile enhancement induced by enoximone (P = 0.07). Agreement between EE and PET was found in 75% of involved segments (K = 0.46, P < 0.001). The majority of discrepancies (65%, P < 0.01) were mainly due to discordant segments in which PET revealed evidence of (18)F-FDG uptake but EE showed no change in wall motion. In 179 revascularized segments, negative predictive value for functional recovery of both tests reached the same value (89% for both), whereas positive predictive value was 82% for EE and 68% for PET, respectively (P < 0.05). Sensitivity was 85% for EE and 88% for PET (P = ns); specificity was 87% and 70%, respectively (P < 0.01). CONCLUSIONS: EE yields a fair concordance with PET study. Compared with PET, despite a similar negative accuracy, EE shows a greater specificity for prediction of function recovery after revascularization. (Echocardiography 2010;27:544-551).

Inflammatory pseudotumor of mediastinum treated with tomotherapy and monitored with FDG-PET/CT: case report and literature review.

Mediastinal inflammatory pseudotumor is a rare disease with reactive pseudoneo-plastic features and a proven capacity for local invasion. The radiographic appearance of inflammatory pseudotumor is quite non-specific and the definitive diagnosis is based on the histological evaluation of tissue specimens. Resection of the lesion is the treatment of choice. However, nonsurgical treatments such as radiotherapy and steroids have been employed in the setting of incomplete surgical resection, tumor recurrence, and patients being unfit for surgery. The case described here is being reported because of the rare mediastinal location and atypical treatment approach including salvage irradiation and monitoring with FDG-PET/CT. Because of the irregular target volume inside the mediastinum as defined by FDG-PET/CT and the significant pulmonary comorbidity, it was deemed necessary to optimize dose delivery with intensity-modulated radiation therapy (IMRT). A possible gain by means of daily control of patient setup with image-guided radiation therapy was also hypothesized and we used tomotherapy to irradiate the lesion. The first FDG-PET/CT after treatment confirmed further reduction of the metabolic activity followed by stable disease in the mediastinum, with no new occurrence of disease 16, 24 and 30 months after tomotherapy.

Helical tomotherapy for scalp recurrence of primary eccrine mucinous adenocarcinoma.

Primary cutaneous mucinous carcinomas originating from sweat glands are rare tumors with patterns of spread that are difficult to predict. We present a case of a five times recurring eccrine mucinous adenocarcinoma of the scalp, previously treated with surgery and adjuvant radiation therapy. After magnetic resonance imaging (MRI) and 18F-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (18FDG-PET/CT), which documented local recurrence, the patient was considered eligible for salvage irradiation of the scalp. We decided to use helical tomotherapy, which combines conformity of dose delivery with the possibility of daily control of the setup accuracy. Forty gray (2Gy/fraction) to the planning target volume and 50 Gy (2.5Gy/fraction) to the biological target volume defined on the basis of 18FDG-PET/CT was prescribed with a simultaneous integrated boost technique. After 12 fractions the patient was submitted to intermediate evaluation by 18FDG-PET/CT, which showed a partial response to the treatment. After 2, 4, 8, and 12 months, 18FDG-PET/CT showed a complete metabolic local response. This experience suggests a possible role of 18FDG-PET/CT-guided helical tomotherapy as an alternative to repeated and frequently demolitive surgery approaches.

Changes in glucose metabolism during and after radiotherapy in non-small cell lung cancer.

AIMS AND BACKGROUND: Evaluation of the metabolic response to radiotherapy in nonsmall cell lung cancer patients is commonly performed about three months after the end of radiotherapy. The aim of the present study was to assess with positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose changes in glucose metabolism during and after radiotherapy in non-small cell lung cancer patients. METHODS AND STUDY DESIGN: In 6 patients, PET/CT scans with [18F]fluorodeoxyglucose were performed before (PET0), during (PET1; at a median of 14 days before the end of radiotherapy) and after the end of radiotherapy (PET2 and PET3, at a median of 28 and 93 days, respectively). The metabolic response was scored according to visual and semiquantitative criteria. RESULTS: Standardize maximum uptake at PET1 (7.9 +/- 4.8), PET2 (5.1 +/- 4.1) and PET3 (2.7 +/- 3.1) were all significantly (P < 0.05; ANOVA repeated measures) lower than at PET0 (16.1 +/- 10.1). Standardized maximum uptake at PET1 was significantly higher than at both PET2 and PET3. There were no significant differences in SUV(max) between PET2 and PET3. PET3 identified 4 complete and 2 partial metabolic responses, whereas PET1 identified 6 partial metabolic responses. Radiotherapy-induced increased [l8F]fluorodeoxyglucose uptake could be visually distinguished from tumor uptake based on PET/CT integration and was less frequent at PET1 (n = 2) than at PET3 (n = 6). CONCLUSION: In non-small cell lung cancer, radiotherapy induces a progressive decrease in glucose metabolism that is greater 3 months after the end of treatment but can be detected during the treatment itself. Glucose avid, radiotherapy-induced inflammation is more evident after the end of radiotherapy than during radiotherapy and does not preclude the interpretation of [18F]fluorodeoxyglucose images, particularly when using PET/CT.

18F-FDG PET/CT in a Case of Metastatic Breast Cancer to the Vulva.

A 56-year-old woman, previously treated for breast cancer, presented to gynecologists with a lump of the left labium major of the vulva. The FDG pattern resembled as a cIV stage vulvar cancer, whereas biopsy indicated metastases from breast cancer. Metastatic disease to the vulva is particularly uncommon, representing 5% to 8% of all vulvar cancer lesions. However, gynecological uptakes, including vulvar site, have to be kept in mind as a possible site of metastatic lesions from breast cancer.

Treatment response assessment in [18F]FDG-PET/CT oncology scans: Impact of count statistics variation and reconstruction protocol.

PURPOSE: To investigate influences of reconstruction algorithms and count statistics variation on quantification and treatment response assessment in cancer patients, by using a large field of view-FOV scanner. METHODS: 54 cancer patients underwent PET/CT scan: 1) at baseline: 1.5 min/FOV, reconstructed by ordered-subset expectation maximization + point-spread-function-OSEM-PSF and bayesian penalised-likelihood-BPL algorithm 2) at restaging: 2 min/FOV, reconstructed also at 1.5 and 1 min/FOV, using OSEM-PSF and BPL. SUL (lean-body mass SUV) peak and max were measured for each target-lesion (n = 59). Differences in quantification obtained from datasets with different reconstruction algorithms and different time/FOV were evaluated. For any pair of PET datasets, metabolic response was assessed by using SULpeak, with a threshold of 30% in variation considered as significant. RESULTS: Both at baseline and restaging, SULpeak and max values were higher in BPL reconstructions than in OSEM-PSF (p < 0.0001). SULpeak at different time/FOV reconstructions showed no statistically significant differences both with OSEM-PSF and BPL; SULmax depended on acquisition time (p < 0.05). In 56/59 lesions (95%) therapy response was concordant regardless count statistics variation and reconstruction algorithm; 2/59 (3%) showed different responses according to count statistics, both for OSEM-PSF and BPL; in 1/59 lesion (2%) response was different depending on reconstruction algorithm used. CONCLUSIONS: BPL provided higher SULpeak and max than OSEM-PSF. With a large FOV/high sensitivity scanner, variation of time/FOV in restaging PET scans gave stable and reproducible results in terms of SULpeak, both for OSEM-PSF and BPL. Thus, metabolic response defined by SULpeak variation proved to be quite independent from count statistics.

Radiomics of the primary tumour as a tool to improve 18F-FDG-PET sensitivity in detecting nodal metastases in endometrial cancer.

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.

Role of computed tomography and [18F] fluorodeoxyglucose positron emission tomography image fusion in conformal radiotherapy of non-small cell lung cancer: a comparison with standard techniques with and without elective nodal irradiation.

AIMS AND BACKGROUND: Mediastinal elective node irradiation (ENI) in patients with non-small cell lung cancer candidate to radical radiotherapy is controversial. In this study, the impact of co-registered [18F]fluorodeoxyglucose-positron emission tomography (PET) and standard computed tomography (CT) on definition of target volumes and toxicity parameters was evaluated, by comparison with standard CT-based simulation with and without ENI. METHODS: CT-based gross tumor volume (GTVCT) was first contoured by a single observer without knowledge of PET results. Subsequently, the integrated GTV based on PET/CT coregistered images (GTVPET/CT) was defined. Each patient was planned according to three different treatment techniques: 1) radiotherapy with ENI using the CT data set alone (ENI plan); 2) radiotherapy without ENI using the CT data set alone (no ENI plan); 3) radiotherapy without ENI using PET/CT fusion data set (PET plan). Rival plans were compared for each patient with respect to dose to the normal tissues (spinal cord, healthy lungs, heart and esophagus). RESULTS: The addition of PET-modified TNM staging in 10/21 enrolled patients (48%); 3/21 were shifted to palliative treatment due to detection of metastatic disease or large tumor not amenable to high-dose radiotherapy. In 7/18 (39%) patients treated with radical radiotherapy, a significant (> or =25%) change in volume between GTVCT and GTVPET/CT was observed. For all the organs at risk, ENI plans had dose values significantly greater than no-ENI and PET plans. Comparing no ENI and PET plans, no statistically significant difference was observed, except for maximum point dose to the spinal cord Dmax, which was significantly lower in PET plans. Notably, even in patients in whom PET/CT planning resulted in an increased GTV, toxicity parameters were fairly acceptable, and always more favorable than with ENI plans. CONCLUSIONS: Our study suggests that [18F]-fluorodeoxyglucose-PET should be integrated in no-ENI techniques, as it improves target volume delineation without a major increase in predicted toxicity.

Sentinel-node mapping in endometrial cancer patients: comparing SPECT/CT, gamma-probe and dye.

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.