Radioguided surgery with β decay: A feasibility study in cervical cancer

Purpose: Radioguided surgery (RGS) is a technique that helps the surgeon to achieve a tumour resection as complete as possible, by means of the intraoperative detection of particles emitted by a radiotracer that bounds to tumoural cells. This study aimed to investigate the applicability of β-RGS for tumour resection and margin assessment in cervical cancer patients preoperatively injected with [18F]FDG, by means of Monte Carlo simulations. Methods: Patients were retrospectively included if they had a recurrent or persistent cervical cancer, underwent preoperative PET/CT to exclude distant metastases and received radical surgery. All PET/CT images were analysed extracting tumour SUVmax, background SUVmean and tumour-to-non-tumour ratio. These values were used to obtain the expected count rate in a realistic surgical scenario by means of a Monte Carlo simulation of the β probe, assuming the injection of 2 MBq/kg of [18F]FDG 60 min before surgery. Results: Thirty-eight patients were included. A measuring time of ∼2-3 s is expected to be sufficient for discriminating the tumour from background in a given lesion, being this the time the probe has to be over the sample in order to be able to discriminate tumour from healthy tissue with a sensitivity of ∼99% and a specificity of at least 95%. Conclusion: This study presents the first step towards a possible application of our β-RGS technique in cervical cancer. Results suggest that this approach to β-RGS could help surgeons distinguish tumour margins from surrounding healthy tissue, even in a setting of high radiotracer background activity

Lymphoscintigraphy and sentinel lymph node biopsy in vulvar carcinoma: update from a European expert panel

Purpose: This study aimed to update the clinical practice applications and technical procedures of sentinel lymph node (SLN) biopsy in vulvar cancer from European experts. Methods: A systematic data search using PubMed/MEDLINE database was performed up to May 29, 2019. Only original studies focused on SLN biopsy in vulvar cancer, published in the English language and with a minimum of nine patients were selected. Results: Among 280 citations, 65 studies fulfilled the inclusion criteria. On the basis of the published evidences and consensus of European experts, this study provides an updated overview on clinical applications and technical procedures of SLN biopsy in vulvar cancer. Conclusions: SLN biopsy is nowadays the standard treatment for well-selected women with clinically negative lymph nodes. Negative SLN is associated with a low groin recurrence rate and a good 5-year disease-specific survival rate. SLN biopsy is the most cost-effective approach than lymphadenectomy in early-stage vulvar cancer. However, future trials should focus on the safe extension of the indication of SLN biopsy in vulvar cancer. Although radiotracers and optical agents are widely used in the clinical routine, there is an increasing interest for hybrid tracers like indocyanine-99mTc-nanocolloid. Finally, it is essential to standardise the acquisition protocol including SPECT/CT images, and due to the low incidence of this type of malignancy to centralise this procedure in experienced centres for personalised approach

Radiomics in vulvar cancer: First clinical experience using18F-FDG PET/CT images

This study investigated whether radiomic features derived from preoperative PET images could predict both tumor biology and prognosis in women with invasive squamous cell carcinoma of the vulva. Methods: Patients were retrospectively included if they had a unifocal primary cancer at least 2.6 cm in diameter, received a preoperative18F-FDG PET/CT scan followed by surgery, and had at least 6 mo of follow-up data.18F-FDG PET images were analyzed by semiautomatically drawing a volume of interest on the primary tumor in each PET image, followed by extraction of 83 radiomic features. Unique radiomic features were identified by principal-component analysis (PCA), after which they were compared with histopathology using nonpairwise group comparison and linear regression. Univariate and multivariate Cox regression analyses were used to correlate the identified features with progression-free survival (PFS) and overall survival (OS). Survival curves were estimated using the Kaplan–Meier method. Results: Forty women were included. PCA revealed 4 unique radiomic features, which were not associated with histopathologic characteristics such as grade, depth of invasion, lymph-vascular space invasion, and metastatic lymph nodes. No statistically significant correlation was found between the identified features and PFS. However, Moran’s I, a feature that identifies global spatial autocorrelation, correlated with OS (P 5 0.03). Multivariate Cox regression analysis showed that extracapsular invasion of the metastatic lymph nodes and Moran’s I were independent prognostic factors for PFS and OS. Conclusion: Our data show that PCA is usable to identify specific radiomic features. Although the identified features did not correlate strongly with tumor biology, Moran’s I was found to predict patient prognosis. Larger studies are required to establish the clinical relevance of the observed findings

Evaluation of dual-timepoint18F-FDG PET/CT imaging for lymph node staging in vulvar cancer

This study aimed to assess the value of dual-timepoint18F-FDG PET/CT in the prediction of lymph node (LN) status in patients with invasive vulvar cancer (VC) scheduled for inguinofemoral LN dissection. Methods: From April 2013 to July 2015, all consecutive patients with VC scheduled for inguinofemoral LN dissection were prospectively enrolled. All patients underwent a preoperative whole-body18F-FDG PET/CT scan at 1 h (standard examination) and an additional scan from T11 to the groins at 3 h (delayed examination) after18F-FDG injection. On both scans, each groin was visually scored 0 or 1 concerning18F-FDG LN uptake relative to background. Semiquantitative analysis included SUVmaxand the corresponding retention index of SUVmax, measured on both scans. The optimal cutoff value of these parameters was defined using a receiveroperating- characteristic analysis. Histopathology was the standard of reference. Results: Thirty-three patients were included, with a total of 57 groins dissected and histologically evaluated. At histopathology, 21 of 57 (37%) groins contained metastatic LNs. Concerning visual score, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 95.2%, 75%, 96.4%, 69%, and 82.5% on standard scanning and 95.2%, 77.8%, 96.6%, 71.4%, and 84.2% on delayed scanning, respectively. At receiver-operating-characteristic analysis, sensitivity and specificity were 95.2% and 77.8% on standard and delayed18F-FDG PET/CT for an SUVmaxcutoff of greater than 1.32 and 1.88, respectively, and 95.2% and 80% for a retention index of SUVmaxcutoff of greater than 0. Conclusion: Standard18F-FDG PET/CT is an effective preoperative imaging method for the prediction of LN status in VC, allowing the prediction of pathologically negative groins and thus the selection of patients suitable for minimally invasive surgery. Delayed18F-FDG PET/CT did not improve the specificity and the positive predictive value in our series. Larger studies are needed for a further validation

Groin sentinel node biopsy and18F-FDG PET/CT-supported preoperative lymph node assessment in cN0 patients with vulvar cancer currently unfit for minimally invasive inguinal surgery: The GroSNaPET study

Objective The study aims were: 1) to verify the role of sentinel node biopsy (SNB) in a subset of patients with clinical N0 (cN0) invasive vulvar cancer (VC) who were still candidates for radical inguinal surgery according to the current guidelines; 2) to investigate whether a preoperative18F-FDG PET/CT (PET/CT) evaluation could improve the selection of node negative patients. Methods From July 2013 to July 2016, all patients with VC admitted to our Division were evaluated by standard imaging and clinical exam. Among the patients assessed as cN0 we enrolled those unsuitable for SNB, due to: T > 4 cm, multifocal tumors, complete tumor diagnostic excision, contralateral nodal involvement and local recurrence. A preoperative PET/CT was performed. For each patient surgery included SNB, performed using a combined technique (radiotracer plus blue dye), followed by standard inguino-femoral lymphadenectomy. The reference standard was histopathology. Results Forty-seven patients entered the study for a total of 73 groins. Histopathology revealed 12 metastatic SNs in 9 groins. No false negative SNs were found (NPV 100%). PET/CT showed a negative predictive value of 93%. Conclusions Our data suggest that SNB is accurate and safe even in cN0 patients currently excluded from this procedure, providing that a careful preoperative selection is performed. PET/CT allows a reliable assessment of LN status and may be an effective support for the selection of patients who are safe candidates for SNB

Radiomics in vulvar cancer: first clinical experience using 18F-FDG PET/CT images

This study investigates whether radiomic features derived from preoperative positron emission tomography (PET) images could predict both tumor biology and prognosis in women with invasive squamous cell carcinoma of the vulva. Methods Patients were retrospectively included when they had a unifocal primary cancer of 65 2.6 cm in diameter, had received a preoperative 18F-Fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) scan followed by surgery and had at least six months of follow-up data. 18F-FDG-PET images were analyzed by semi-automatically drawing on the primary tumor in each PET image, followed by the extraction of 83 radiomic features. Unique radiomic features were identified by principal component analysis (PCA), after which they were compared with histopathology using non-pairwise group comparison and linear regression. Univariate and multivariate Cox regression analyses were used to correlate the identified features with progression-free survival (PFS) and overall survival (OS). Survival curves were estimated using the Kaplan-Meier method.Results Forty women were included. PCA revealed four unique radiomic features, which were not associated with histopathologic characteristics such as grading, depth of invasion, lymph-vascular space invasion and metastatic lymph nodes. No statistically significant correlation was found between the identified features and PFS. However, Moran\u2019s I, a feature that identifies global spatial autocorrelation, was correlated with OS (P=0.03). Multivariate Cox regression analysis showed that extracapsular invasion of the metastatic lymph nodes and Moran\u2019s I were independent prognostic factors for PFS and OS. Conclusion Our data show that PCA is usable to identify specific radiomic features. Although the identified features did not correlate strongly with tumor biology, Moran\u2019s I was found to predict patient prognosis. Larger studies are required to establish the clinical relevance of the observed findings

Nédemax mese (Leucoselect, Lymphaselect, Bromelain) in the treatment of chronic venous disease: a multicenter , obbservational study

BACKGROUND: Chronic venous disease (CVD)is major health concern; however,there remains a need to improve treatment approaches.Nédemax Mese , a nutritional supplementation consisting of Leucoselect 300 mg,Lymphaselect 100 mg and Bromelain 100 mg, is a patented formulation thah may have a role in the treatment of CVD. In this prospective , multicenter study conducted at 54 Italian centers, we investigated the effectiveness of Nédemax Mese in a large sample of CVD patients

Nédemax® Mese (Leucoselect®, Lymphaselect®, Bromelain) in the treatment of chronic venous disease: a multicenter, observational study

BACKGROUND: Chronic venous disease (CVD)is major health concern; however,there remains a need to improve treatment approaches.Nédemax Mese , a nutritional supplementation consisting of Leucoselect 300 mg,Lymphaselect 100 mg and Bromelain 100 mg, is a patented formulation thah may have a role in the treatment of CVD. In this prospective , multicenter study conducted at 54 Italian centers, we investigated the effectiveness of Nédemax Mese in a large sample of CVD patients