Supplemental Breast MRI for Women with Extremely Dense Breasts: Results of the Second Screening Round of the DENSE Trial.

Background In the first (prevalent) supplemental MRI screening round of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, a considerable number of breast cancers were found at the cost of an increased false-positive rate (FPR). In incident screening rounds, a lower cancer detection rate (CDR) is expected due to a smaller pool of prevalent cancers, and a reduced FPR, due to the availability of prior MRI examinations. Purpose To investigate screening performance indicators of the second round (incidence round) of the DENSE trial. Materials and Methods The DENSE trial (ClinicalTrials.gov: NCT01315015) is embedded within the Dutch population-based biennial mammography screening program for women aged 50-75 years. MRI examinations were performed between December 2011 and January 2016. Women were eligible for the second round when they again had a negative screening mammogram 2 years after their first MRI. The recall rate, biopsy rate, CDR, FPR, positive predictive values, and distributions of tumor characteristics were calculated and compared with results of the first round using 95% CIs and χ2 tests. Results A total of 3436 women (median age, 56 years; interquartile range, 48-64 years) underwent a second MRI screening. The CDR was 5.8 per 1000 screening examinations (95% CI: 3.8, 9.0) compared with 16.5 per 1000 screening examinations (95% CI: 13.3, 20.5) in the first round. The FPR was 26.3 per 1000 screening examinations (95% CI: 21.5, 32.3) in the second round versus 79.8 per 1000 screening examinations (95% CI: 72.4, 87.9) in the first round. The positive predictive value for recall was 18% (20 of 110 participants recalled; 95% CI: 12.1, 26.4), and the positive predictive value for biopsy was 24% (20 of 84 participants who underwent biopsy; 95% CI: 16.0, 33.9), both comparable to that of the first round. All tumors in the second round were stage 0-I and node negative. Conclusion The incremental cancer detection rate in the second round was 5.8 per 1000 screening examinations-compared with 16.5 per 1000 screening examinations in the first round. This was accompanied by a strong reduction in the number of false-positive results. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moy and Gao in this issue.

ADC Values of Cytologically Benign and Cytologically Malignant 18 F-FDG PET-Positive Lymph Nodes of Head and Neck Squamous Cell Carcinoma.

Nodal staging (N-staging) in head and neck squamous cell carcinoma (HNSCC) is essential for treatment planning and prognosis. 18F-fluordeoxyglucose positron emission tomography (FDG-PET) has high performance for N-staging, although the distinction between cytologically malignant and reactive PET-positive nodes, and consequently, the selection of nodes for ultrasound-guided fine needle aspiration cytology (USgFNAC), is challenging. Diffusion-weighted magnetic resonance imaging (DW-MRI) can help to detect nodal metastases. We aim to investigate the potential of the apparent diffusion coefficient (ADC) as a metric to distinguish between cytologically reactive and malignant PET-positive nodes in order to improve node selection criteria for USgFNAC. PET-CT, real-time image-fused USgFNAC and DW-MRI to calculate ADC were available for 78 patients offered for routine N-staging. For 167 FDG-positive nodes, differences in the ADC between cytologically benign and malignant PET-positive nodes were evaluated, and both were compared to the ADC values of PET-negative reference nodes. Analyses were also performed in subsets of nodes regarding HPV status. A mild negative correlation between SUVmax and ADC was found. No significant differences in ADC values were observed between cytologically malignant and benign PET-positive nodes overall. Within the subset of non-HPV-related nodes, ADCb0-200-1000 was significantly lower in cytologically malignant PET-positive nodes when compared to benign PET-positive nodes. ADCb0-1000 and ADCb0-200-1000 were significantly lower (p = 0.018, 0.016, resp.) in PET-negative reference nodes than in PET-positive nodes. ADC was significantly higher in PET-negative reference nodes than in PET-positive nodes. The non-HPV-related subgroup showed significantly (p = 0.03) lower ADC values in cytologically malignant than in cytologically benign PET-positive nodes, which should help inform the node selection procedure for puncture.

SUVmax values at FDG PET-CT to predict malignancy in lymph nodes aspirated by real time image fused USgFNAC in head and neck squamous cell carcinoma.

18F-fluordeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET-CT) and ultrasound guided fine-needle aspiration cytology (USgFNAC) are commonly used to detect nodal metastases in head and neck squamous cell carcinoma (HNSCC). FDG PET-CT helps to guide selection of borderline suspicious nodes to aspirate using USgFNAC. Real time image fusion of FDG PET-CT with US is a new available technique and can improve this selection. The aim of this study was to determine optimal SUVmax values for USgFNAC node selection to improve USgFNAC sensitivity. 118 patients, with histopathological proven HNSCC or proven lymph nodes metastases of SCC of unknown primary, referred for staging of HNSCC with FDG PET-CT and ultrasound, were prospectively included. Additionally to standard USgFNAC of suspicious nodes fusion was performed to confirm that USgFNAC took place in FDG-positive nodes and to add Fused-USgFNAC in missed FDG-positive nodes. Fusion was performed on nodes with reported having metabolic activity. SUVmax values were measured in all Fused-USgFNAC nodes. The reference standard was cytology. In 118 patients USgFNAC was performed in 281 nodes. At fusion 22/281 (8%) nodes were FDG-negative. Out of 259 FDG-positive nodes 253 (98%) nodes were fused successfully. USgFNAC had conclusive results in 237/253 nodes (94%). In 126/237 nodes (53%) cytology proved to be tumor positive. Below SUVmax of 2.87 no fused FDG-positive nodes proved to be tumor positive at cytology. To improve sensitivity, only FDG-positive nodes with SUVmax values above 2.87 should be selected for USgFNAC. Image fusion can identify those nodes for USgFNAC selection.

Value of Assessing Peripheral Vascularization with Micro-Flow Imaging, Resistive Index and Absent Hilum Sign as Predictor for Malignancy in Lymph Nodes in Head and Neck Squamous Cell Carcinoma.

Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for nodal staging in head and neck squamous cell cancer (HNSCC). Peripheral vascularity is a described feature for node metastasis. Micro-flow imaging (MFI) is a new sensitive technique to evaluate micro-vascularization. Our goal is to assess the additional value of MFI to detect malignancy in lymph nodes. A total of 102 patients with HNSCC were included prospectively. USgFNAC was performed with the Philips eL18-4 transducer. Cytological results served as a reference standard to evaluate the prediction of cytological malignancy depending on ultrasound features such as resistive index (RI), absence of fatty hilum sign, and peripheral vascularization. Results were obtained for all US examinations and for the subgroup of clinically node-negative neck (cN0). USgFNAC was performed in 211 nodes. Peripheral vascularization had a positive predictive value (PPV) of 83% (cN0: 50%) and the absence of a fatty hilum had a PPV of 82% (cN0 50%) The combination of peripheral vascularization and absent fatty hilum had a PPV of 94% (cN0: 72%). RI (threshold: 0.705) had a PPV of 61% (cN0: RI-threshold 0.615, PPV 20%), whereas the PPV of short axis diameter (threshold of 6.5mm) was 59% for all patients and 19% in cN0 necks (threshold of 4 mm). Peripheral vascularization assessed by MFI and absent hilum has a high predictive value for cytological malignancy in neck metastases. Next to size, both features should be used as additional selection criteria for USgFNAC.

Cost-Effectiveness of Magnetic Resonance Imaging Screening for Women With Extremely Dense Breast Tissue.

BACKGROUND: Extremely dense breast tissue is associated with increased breast cancer risk and limited sensitivity of mammography. The DENSE trial showed that additional magnetic resonance imaging (MRI) screening in women with extremely dense breasts resulted in a substantial reduction in interval cancers. The cost-effectiveness of MRI screening for these women is unknown. METHODS: We used the MISCAN-breast microsimulation model to simulate several screening protocols containing mammography and/or MRI to estimate long-term effects and costs. The model was calibrated using results of the DENSE trial and adjusted to incorporate decreases in breast density with increasing age. Screening strategies varied in the number of MRIs and mammograms offered to women ages 50-75 years. Outcomes were numbers of breast cancers, life-years, quality-adjusted life-years (QALYs), breast cancer deaths, and overdiagnosis. Incremental cost-effectiveness ratios (ICERs) were calculated (3% discounting), with a willingness-to-pay threshold of €22 000. RESULTS: Calibration resulted in a conservative fit of the model regarding MRI detection. Both strategies of the DENSE trial were dominated (biennial mammography; biennial mammography plus MRI). MRI alone every 4 years was cost-effective with €15 620 per QALY. Screening every 3 years with MRI alone resulted in an incremental cost-effectiveness ratio of €37 181 per QALY. All strategies with mammography and/or a 2-year interval were dominated because other strategies resulted in more additional QALYs per additional euro. Alternating mammography and MRI every 2 years was close to the efficiency frontier. CONCLUSIONS: MRI screening is cost-effective for women with extremely dense breasts, when applied at a 4-year interval. For a willingness to pay more than €22 000 per QALY gained, MRI at a 3-year interval is cost-effective as well.