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Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial (NCT03298893) is designed to determine the safety/tolerance profile and the recommended phase-II dose of nivolumab with and following concurrent CRT in 16 women with locally advanced cervical cancer. Secondary endpoints include objective response rate (ORR), progression free survival (PFS), disease free survival, and immune correlates of response. Three patients experience grade 3 dose-limiting toxicities. The pre-specified endpoints are met, and overall response rate is 93.8% [95%CI: 69.8–99.8%] with a 2-year PFS of 75% [95% CI: 56.5–99.5%]. Compared to patients with progressive disease (PD), progression-free (PF) subjects show a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3 + T cells to PD-L1 + tumor cells and of FOXP3 + T cells to proliferating CD11c + myeloid cells. PF show higher baseline levels of PD-1 and ICOS-L on tumor-infiltrating EMRA CD4 + T cells and tumor-associated macrophages, respectively; PD instead, display enhanced PD-L1 expression on TAMs, higher peripheral frequencies of proliferating Tregs at baseline and higher PD-1 levels at week 6 post-treatment initiation on CD4 and CD8 T cell subsets. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of locally advanced cervical cancer displaying pre-existing, adaptive immune activation is warranted. A combination of chemoradiotherapy followed by brachytherapy is recommended for patients with locally-advanced cervical cancer (LACC), however there is still a high risk of disease recurrence. Here the authors report clinical outcomes and immunologic correlates of a clinical trial of the PD-1 inhibitor nivolumab in combination with chemoradiotherapy in LACC patients.

Perfusion-related complications remain the most common concern in DIEP flap breast reconstruction. Indocyanine green-based fluorescence angiography can be used for the real-time intra operative assessment of flap perfusion. The SPY Elite system is the most widely used device in this setting. The main objective was to describe the use of SPY-Q proprietary software to perform qualitative and quantitative analysis of flap perfusion. This retrospective cohort study was performed at the Curie Institute between 2013 and 2017. We included patients undergoing unilateral DIEP flap breast reconstruction for whom indocyanine green-based angiography videos were of sufficient quality for analysis. Videos were recorded with the SPY Elite System and analyzed with SPY-Q proprietary software. We included 40 patients. We used real-time dynamic color analysis to describe three different patterns of flap perfusion. SPY-Q proprietary software provides quantitative flap perfusion parameters. Our quantitative analysis confirmed that zone I is the best perfused part of the flap and zone IV the less perfused one. There was no significant association between flap perfusion pattern and perforator anatomy, patients' clinical characteristics or postoperative outcomes. After exploratory univariate analysis, quantitative perfusion parameters were significantly impaired in young patients with diabetes mellitus or under hormone therapy by tamoxifen. We here describe a new approach to assess DIEP flap perfusion using the SPY Elite System proprietary software. It provides interesting qualitative and quantitative analysis that can be used in further studies to precisely assess DIEP flap perfusion.

Hyperechogenicity is a sign classically reported to be in favour of a benign lesion and can be observed in many types of benign breast lesions such as hamartoma, lipoma, angiolipoma, haemangioma, haematoma, fat necrosis, fibrosis and galactocele, among others. However, some rare malignant breast lesions can also present a hyperechoic appearance. Most of these hyperechoic malignant lesions present other characteristics that are more typically suggestive of malignancy such as posterior shadowing, a more vertical axis or irregular margins that help to guide the diagnosis. Post magnetic resonance imaging, second-look ultrasound may visualise hyperechoic malignant lesions that would not have been identified at first sight and radiologists must know how to recognise these lesions.Teaching Points• Some rare malignant breast lesions can present a hyperechoic appearance.• Malignant lesions present other characteristics that are suggestive of malignancy.• An echogenic mass with fat density on mammography does not require biopsy.

PurposeThe second International Consensus Conference on B3 lesions was held in Zurich, Switzerland, in March 2018, organized by the International Breast Ultrasound School to re-evaluate the consensus recommendations.MethodsThis study (1) evaluated how management recommendations of the first Zurich Consensus Conference of 2016 on B3 lesions had influenced daily practice and (2) reviewed current literature towards recommendations to biopsy.ResultsIn 2018, the consensus recommendations for management of B3 lesions remained almost unchanged: For flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL) and radial scars (RS) diagnosed on core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB), excision by VAB in preference to open surgery, and for atypical ductal hyperplasia (ADH) and phyllodes tumors (PT) diagnosed at VAB or CNB, first-line open surgical excision (OE) with follow-up surveillance imaging for 5 years. Analyzing the Database of the Swiss Minimally Invasive Breast Biopsies (MIBB) with more than 30,000 procedures recorded, there was a significant increase in recommending more frequent surveillance of LN [65% in 2018 vs. 51% in 2016 (p = 0.004)], FEA (72% in 2018 vs. 62% in 2016 (p = 0.005)), and PL [(76% in 2018 vs. 70% in 2016 (p = 0.04)] diagnosed on VAB. A trend to more frequent surveillance was also noted also for RS [77% in 2018 vs. 67% in 2016 (p = 0.07)].ConclusionsMinimally invasive management of B3 lesions (except ADH and PT) with VAB continues to be appropriate as an alternative to first-line OE in most cases, but with more frequent surveillance, especially for LN.

Objectives To develop a visual ensemble selection of deep convolutional neural networks (CNN) for 3D segmentation of breast tumors using T1-weighted dynamic contrast-enhanced (T1-DCE) MRI. Methods Multi-center 3D T1-DCE MRI ( n = 141) were acquired for a cohort of patients diagnosed with locally advanced or aggressive breast cancer. Tumor lesions of 111 scans were equally divided between two radiologists and segmented for training. The additional 30 scans were segmented independently by both radiologists for testing. Three 3D U-Net models were trained using either post-contrast images or a combination of post-contrast and subtraction images fused at either the image or the feature level. Segmentation accuracy was evaluated quantitatively using the Dice similarity coefficient (DSC) and the Hausdorff distance (HD95) and scored qualitatively by a radiologist as excellent, useful, helpful, or unacceptable. Based on this score, a visual ensemble approach selecting the best segmentation among these three models was proposed. Results The mean and standard deviation of DSC and HD95 between the two radiologists were equal to 77.8 ± 10.0% and 5.2 ± 5.9 mm. Using the visual ensemble selection, a DSC and HD95 equal to 78.1 ± 16.2% and 14.1 ± 40.8 mm was reached. The qualitative assessment was excellent (resp. excellent or useful) in 50% (resp. 77%). Conclusion Using subtraction images in addition to post-contrast images provided complementary information for 3D segmentation of breast lesions by CNN. A visual ensemble selection allowing the radiologist to select the most optimal segmentation obtained by the three 3D U-Net models achieved comparable results to inter-radiologist agreement, yielding 77% segmented volumes considered excellent or useful. Key Points • Deep convolutional neural networks were developed using T1-weighted post-contrast and subtraction MRI to perform automated 3D segmentation of breast tumors. • A visual ensemble selection allowing the radiologist to choose the best segmentation among the three 3D U-Net models outperformed each of the three models. • The visual ensemble selection provided clinically useful segmentations in 77% of cases, potentially allowing for a valuable reduction of the manual 3D segmentation workload for the radiologist and greatly facilitating quantitative studies on non-invasive biomarker in breast MRI.

Objectives To evaluate the association between pretreatment MRI descriptors and breast cancer (BC) pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Materials and methods Patients with BC treated by NAC with a breast MRI between 2016 and 2020 were included in this retrospective observational single-center study. MR studies were described using the standardized BI-RADS and breast edema score on T2-weighted MRI. Univariable and multivariable logistic regression analyses were performed to assess variables association with pCR according to residual cancer burden. Random forest classifiers were trained to predict pCR on a random split including 70% of the database and were validated on the remaining cases. Results Among 129 BC, 59 (46%) achieved pCR after NAC (luminal ( n  = 7/37, 19%), triple negative ( n  = 30/55, 55%), HER2 + ( n  = 22/37, 59%)). Clinical and biological items associated with pCR were BC subtype ( p  < 0.001), T stage 0/I/II ( p  = 0.008), higher Ki67 ( p  = 0.005), and higher tumor-infiltrating lymphocytes levels ( p  = 0.016). Univariate analysis showed that the following MRI features, oval or round shape ( p  = 0.047), unifocality ( p  = 0.026), non-spiculated margins ( p  = 0.018), no associated non-mass enhancement ( p  = 0.024), and a lower MRI size ( p  = 0.031), were significantly associated with pCR. Unifocality and non-spiculated margins remained independently associated with pCR at multivariable analysis. Adding significant MRI features to clinicobiological variables in random forest classifiers significantly increased sensitivity (0.67 versus 0.62), specificity (0.69 versus 0.67), and precision (0.71 versus 0.67) for pCR prediction. Conclusion Non-spiculated margins and unifocality are independently associated with pCR and can increase models performance to predict BC response to NAC. Clinical relevance statement A multimodal approach integrating pretreatment MRI features with clinicobiological predictors, including tumor-infiltrating lymphocytes, could be employed to develop machine learning models for identifying patients at risk of non-response. This may enable consideration of alternative therapeutic strategies to optimize treatment outcomes. Key Points • Unifocality and non-spiculated margins are independently associated with pCR at multivariable logistic regression analysis. • Breast edema score is associated with MR tumor size and TIL expression, not only in TN BC as previously reported, but also in luminal BC. • Adding significant MRI features to clinicobiological variables in machine learning classifiers significantly increased sensitivity, specificity, and precision for pCR prediction.

Women with pathogenic germline BRCA1 or BRCA2 variants have a higher risk of breast cancer than in the general population. International guidelines recommend specific clinical and radiological breast follow-up. This specific breast screening program has already been shown to be of clinical benefit, but no information is available concerning the use of prognostic factors or specific survival to guide follow-up decisions. We evaluated “high-risk” screening in a retrospective single-center study of 520 women carrying pathogenic germline variants of the BRCA1 or BRCA2 gene treated for breast cancer between January 2000 and December 2016. We compared two groups of women: the incidental breast cancer group (IBCG) were followed before breast cancer diagnosis (N = 103), whereas the prevalent breast cancer group (PBCG) (N = 417) had no specific follow-up for high risk before breast cancer diagnosis. Breast cancers were diagnosed at an earlier stage in the IBCG than in the PBCG: T0 in 64% versus 19% of tumors, (p < 0.00001), and N0 in 90% vs. 75% (p < 0.00001), respectively. Treatment differed significantly between the 2 groups: less neoadjuvant chemotherapy (7.1% vs. 28.5%, p < 0.00001), adjuvant chemotherapy (47.7% vs. 61.9%, p = 0.004) and more mastectomies (60% vs. 42% p < 0.0001) in the IBCG vs PBCG groups respectively. Overall and breast cancer-specific mortality were similar between the two groups. However, the patients in the IBCG had a significantly longer metastasis-free survival than those in the PBCG, at three years (96.9% [95% CI 93.5–100] vs. 92.30% [95% CI 89.8–94.9]; p = 0.02), suggesting a possible long-term survival advantage.

Oncoplastic surgery allows an increase in the number of indications for conservative breast cancer treatments. However, uncertainty as to whether it can be performed still exists in certain situations such as with multicentric or multifocal lesions, even when the breast volume can accommodate it. With the aid of a virtual reality software, DIVA, allowing the precise visualisation of tumours and breast volumes based entirely on the patient’s MRI, we report the ability to rapidly confirm and secure an indication for partial surgery of multiple lesions in a 31-year-old patient. With the described approach, the patient did not have to suffer significant disfigurement from cancerous breast surgery without compromising safety.

Objectives To compare the diagnostic performance of single-view breast tomosynthesis (BT) with that of dual-view mammography (MX); to assess the benefit of adding the craniocaudal (CC) mammographic view to BT, and of adding BT to MX plus breast ultrasound, considered to be the reference work-up. Methods One hundred and fifty-five consenting patients with unresolved mammographic and/or ultrasound findings or breast symptoms underwent conventional work-up plus mediolateral oblique-view BT of the affected breast. The final study set in 130 patients resulted in 55 malignant and 76 benign and normal cases. Seven breast radiologists rated the cases through five sequential techniques using a BIRADS-based scale: MX, MX + ultrasound, MX + ultrasound + BT, BT, BT + MX(CC). Multireader, multicase receiver operating characteristic (ROC) analysis was performed and performance of the techniques was assessed from the areas under ROC curves. The performance of BT and of BT + MX(CC) was tested versus MX; the performance of MX + ultrasound + BT tested versus MX + ultrasound. Results Tomosynthesis was found to be non-inferior to mammography. BT + MX(CC) did not appear to be superior to MX, and MX + ultrasound + BT not superior to MX + ultrasound. Conclusions Overall, none of the five techniques tested outperformed the others. Further clinical studies are needed to clarify the role of BT as a substitute for traditional work-up in the diagnostic environment. Key Points • Digital breast tomosynthesis is a new adjunct to mammography and breast ultrasound. • We compared the diagnostic performance of these investigations in an experimental observer study. • Single-view breast tomosynthesis was confirmed as non-inferior to dual-view mammography. • None of the investigations (or combinations) tested outperformed the others. • Further prospective studies are needed to clarify precise role of tomosynthesis for diagnostic application.

The article Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions), written by Christoph J Rageth, Elizabeth AM O’Flynn, Katja Pinker, Rahel A Kubik-Huch, Alexander Mundinger, Thomas Decker, Christoph Tausch, Florian Dammann, Pascal A. Baltzer, Eva Maria Fallenberg, Maria P Foschini, Sophie Dellas, Michael Knauer, Caroline Malhaire, Martin Sonnenschein, Andreas Boos, Elisabeth Morris, Zsuzsanna Varga, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on November 30, 2018 without open access.