Lymphatic mapping and sentinel node biopsy in vulvar melanoma: the first multicenter study and systematic review.

OBJECTIVE: This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0). METHODS: Patients who had a proven vulvar melanoma with a Breslow thickness of 1-4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients). RESULTS: A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3-19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6-38.7) and 64.3% (95% CI, 15.5-90.2), respectively. CONCLUSIONS: The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival.

Techniques for sentinel node biopsy in breast cancer.

Sentinel node biopsy (SNB) is the standard of care in women with breast cancer (BC) and clinically nonsuspicious axillary lymph nodes (LNs), due to its high negative predictive value (NPV) in the assessment of nodal status. SNB has significantly reduced complications related to the axillary lymph node dissection, such as lymphedema and upper limb dysfunction. The gold standard technique for SNB is the blue dye (BD) and technetium labelled nanocolloid (Tc-99m) double technique. However, nuclear medicine is not available in all Institutions and several new tracers and devices have been proposed, such as indocyanine green (ICG) and superparamagnetic iron oxides (SPIO). All these techniques show an accuracy and detection rate not inferior to that of the standard technique, with different specific pros and cons. The choice of how to perform a SNB primarily depends on the surgeon's confidence with the procedure, the availability of nuclear medicine and the economic resources of the Institutions. In this setting, new tracers, hybrid tracers and imaging techniques are being evaluated in order to improve the detection rate of sentinel lymph nodes (SNs) and minimize the number of unnecessary axillary surgeries through an accurate preoperative assessment of nodal status and to guide new minimally invasive diagnostic procedures of SNs. In particular, the contrast-enhanced ultrasound (CEUS) is an active field of research but cannot be recommended for clinical use at this time. The ICG fluorescence technique was superior in terms of DR, as well as having the lowest FNR. The DR descending order was SPIO, Tc, dual modality (Tc/BD), CEUS and BD. This paper is a narrative review of the most common SNB techniques in BC with a focus on recent innovations.

Diagnostic performance of preoperative [18F]FDG-PET/CT for lymph node staging in vulvar cancer: a large single-centre study.

PURPOSE: This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. METHODS: Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. RESULTS: All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3-92.8), 65.5% (59.0-72.0), 71.6% (66.5-76.8), 52.0% (44.0-60.1) and 91.2% (86.7-95.8) for visual assessment; 78.9% (70.5-87.3), 78.2% (72.5-83.8), 78.4% (73.7-83.1), 61.2% (52.3-70.1) and 89.4% (85.0-93.9) for overall assessment; and 73.3% (64.2-82.5), 85.0% (80.1-89.8), 81.4% (77.0-85.8), 68.0% (58.8-77.3) and 87.9% (83.4-92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. CONCLUSION: In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUVmax.

18F-FDG PET and 18F-FDG PET/CT in Vulvar Cancer: A Systematic Review and Meta-analysis.

AIM: The aims of this study were to determine the role of 18F-FDG PET/CT in vulvar cancer patients and to extract summary estimates of its diagnostic performance for preoperative lymph node staging. PATIENTS AND METHODS: PubMed/Medline and Embase databases were searched to identify studies evaluating 18F-FDG PET/CT in vulvar cancer patients. The assessment of methodological quality of the included articles was performed. Per-patient and per-groin pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) were calculated. RESULTS: Ten articles were included in the systematic review, 7 among which evaluated the diagnostic performance of preoperative 18F-FDG PET/CT for lymph node staging. Qualitative per-patient analysis (72 patients from 4 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.70 (95% CI, 0.44-0.95), 0.90 (95% CI, 0.76-1.04), 0.86 (95% CI, 0.66-1.06), 0.77 (95% CI, 0.56-0.97), and 10.49 (95% CI, 1.68-65.50), respectively. Qualitative per-groin analysis (245 groins from 5 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.76 (95% CI, 0.57-0.94), 0.88 (95% CI, 0.82-0.94), 0.70 (95% CI, 0.55-0.85), 0.92 (95% CI, 0.86-0.97), and 19.43 (95% CI, 6.40-58.95), respectively. CONCLUSIONS: Despite limited literature data, this systematic review and meta-analysis revealed that a negative preoperative PET/CT scan may exclude groin metastases in at least early-stage vulvar cancer patients currently unfit for sentinel node biopsy and select those eligible for a less invasive surgical treatment. A positive PET/CT result should otherwise be interpreted with caution. Larger prospective studies are needed to confirm these results and to evaluate the diagnostic value of standardized semiquantitative analysis compared with the qualitative one.

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 ≥ 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's 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'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-Timepoint 18F-FDG PET/CT Imaging for Lymph Node Staging in Vulvar Cancer.

This study aimed to assess the value of dual-timepoint 18F-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-body 18F-FDG PET/CT scan at 1 h (standard examination) and an additional scan from T11 to the groins at 3 h (delayed examination) after 18F-FDG injection. On both scans, each groin was visually scored 0 or 1 concerning 18F-FDG LN uptake relative to background. Semiquantitative analysis included SUVmax and the corresponding retention index of SUVmax, measured on both scans. The optimal cutoff value of these parameters was defined using a receiver-operating-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 delayed 18F-FDG PET/CT for an SUVmax cutoff of greater than 1.32 and 1.88, respectively, and 95.2% and 80% for a retention index of SUVmax cutoff of greater than 0. Conclusion: Standard 18F-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. Delayed 18F-FDG PET/CT did not improve the specificity and the positive predictive value in our series. Larger studies are needed for a further validation.