Stabilizing tumor resident mast cells restores T cell infiltration and sensitizes sarcomas to PD-L1 inhibition.

PURPOSE: To explore the cellular crosstalk of tumor resident mast cells (MCs) in controlling the activity of cancer-associated fibroblasts (CAFs) to overcome TME abnormalities, enhancing the efficacy of immune checkpoint inhibitors (ICIs) in sarcoma. EXPERIMENTAL DESIGN: We used a coculture system followed by further validation in mouse models of fibrosarcoma and osteosarcoma with or without administration of the MC stabilizer and antihistamine ketotifen. To evaluate the contribution of ketotifen in sensitizing tumors to therapy, we performed combination studies with doxorubicin chemotherapy and anti-PD-L1 (B7-H1, clone 10F.9G2) treatment. We investigated the ability of ketotifen to modulate the TME in human sarcomas in the context of a repurpose phase II clinical trial. RESULTS: Inhibition of MC activation with ketotifen successfully suppressed CAF proliferation and stiffness of the extracellular matrix accompanied by an increase in vessel perfusion in fibrosarcoma and osteosarcoma as indicated by ultrasound shear wave elastography imaging. The improved tissue oxygenation increased the efficacy of chemo-immunotherapy, supported by enhanced T cell infiltration and acquisition of tumor antigen-specific memory. Importantly, the effect of ketotifen in reducing tumor stiffness was further validated in sarcoma patients highlighting its translational potential. CONCLUSIONS: Our study suggests the targeting of MCs with clinically administered drugs, such as antihistamines, as a promising approach to overcome resistance to immunotherapy in sarcomas.

Prediction of Near-Term Breast Cancer Occurrence using Subtraction of Temporally Sequential Digital Mammograms.

Breast cancer remains one of the leading cancers for women worldwide. Fortunately, with the introduction of mammography, the mortality rate has significantly decreased. However, earlier breast cancer prediction could effectively increase the survival rates, improve patient outcomes, and avoid unnecessary biopsies. For that purpose, prediction of breast cancer, using subtraction of temporally sequential digital mammograms and machine learning, is proposed. A new dataset was collected with 192 images from 32 patients (three screening rounds, with two views of each breast). This dataset included precise annotation of each individual malignant mass, present in the most recent mammogram, with the two priors being radiologically evaluated as normal. The most recent mammogram was considered as the "future" screening round and provided the location of the mass as the ground truth for the training. The two previous mammograms, the "current" and the "prior", were processed and a new, difference image was formed for the prediction. Ninety-six features were extracted and five feature selection algorithms were combined to identify the most important features. Ten classifiers were tested in leave-one-patient-out and k-fold-patient cross-validation (k = 4 and 8). Ensemble Voting achieved the highest performance in the prediction of the development of breast mass in the next screening round, with 85.7% sensitivity, 83.7% specificity, 83.7% accuracy and 0.85 AUC. The proposed methodology could lead to a new mammography-based model that could predict the short-term risk for developing a malignancy, thus providing an earlier diagnosis.

Patients' perspectives related to ethical issues and risks in precision medicine: a systematic review.

Background: Precision medicine is growing due to technological advancements including next generation sequencing techniques and artificial intelligence. However, with the application of precision medicine many ethical and potential risks may emerge. Although, its benefits and potential harms are relevantly known to professional societies and practitioners, patients' attitudes toward these potential ethical risks are not well-known. The aim of this systematic review was to focus on patients' perspective on ethics and risks that may rise with the application of precision medicine. Methods: A systematic search was conducted on 4/1/2023 in the database of PubMed, for the period 1/1/2012 to 4/1/2023 identifying 914 articles. After initial screening, only 50 articles were found to be relevant. From these 50 articles, 24 articles were included in this systematic review, 2 articles were excluded as not in English language, 1 was a review, and 23 articles did not include enough relevant qualitative data regarding our research question to be included. All full texts were evaluated following PRISMA guidelines for reporting systematic reviews following the Joanna Briggs Institute criteria. Results: There were eight main themes emerging from the point of view of the patients regarding ethical concerns and risks of precision medicine: privacy and security of patient data, economic impact on the patients, possible harms of precision medicine including psychosocial harms, risk for discrimination of certain groups, risks in the process of acquiring informed consent, mistrust in the provider and in medical research, issues with the diagnostic accuracy of precision medicine and changes in the doctor-patient relationship. Conclusion: Ethical issues and potential risks are important for patients in relation to the applications of precision medicine and need to be addressed with patient education, dedicated research and official policies. Further research is needed for validation of the results and awareness of these findings can guide clinicians to understand and address patients concerns in clinical praxis.

Cardioprotective Agents for the Primary Prevention of Trastuzumab-Associated Cardiotoxicity: A Systematic Review and Meta-Analysis.

There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation. Recently, randomized controlled trials (RCTs) have evaluated the effects of early commitment of beta-blockers (BBs), angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) during trastuzumab chemotherapy in order to prevent the related cardiotoxicity. The present systematic review and meta-analysis of six RCTs included patients who have predominantly non-metastatic, HER2-positive, breast cancer and received trastuzumab as primary or adjuvant therapy. Those patients did not have any obvious cardiac dysfunction or any previous therapy with cardioprotective agent. We evaluated the efficacy of the aforementioned medications for primary prevention of cardiotoxicity, using random effects models. Any preventive treatment did not reduce cardiotoxicity occurrence compared to controls (Odds ratios (OR) = 0.92, 95% CI 0.54-1.56, p = 0.75). Results were similar for ACEIs/ARBs and beta-blockers. Treatment with ACEIs/ARBs led to a slight, but significant, increase in LVEF in patients compared to the placebo group. Only two studies reported less likelihood of discontinuation of trastuzumab treatment. More adequately powered RCTs are needed to determine the efficacy of routine prophylactic therapy.

New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review.

Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. AIM: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. METHODS: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013-2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. RESULTS: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. CONCLUSIONS: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD.

Osteosarcoma: Current Concepts and Evolutions in Management Principles.

Osteosarcoma is a rare malignancy arising from mesenchymal tissue, and represents the most common bone sarcoma. The management of osteosarcoma is challenging, and requires a multidisciplinary approach. In daily clinical practice, surgery, radiotherapy, and conventional chemotherapy constitute the therapeutic armamentarium against the disease. However, a significant number of patients with initially localized osteosarcoma will experience local or distant recurrence, and the prognosis for metastatic disease remains dismal. There is a pressing need to identify novel therapeutic strategies to better manage osteosarcoma and improve survival outcomes. In this study, we present recent advances in the therapeutic management of osteosarcoma, including surgical and medical advances. The role of immunotherapy (immune checkpoint inhibitors, adoptive cellular therapy, cancer vaccines) and other targeted therapies including tyrosine kinase inhibitors is discussed; however, additional studies are required to delineate their roles in clinical practice.

Ripretinib for the treatment of adult patients with advanced gastrointestinal stromal tumors.

INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Imatinib mesylate revolutionized the management of advanced/metastatic GIST, and remains the standard first-line therapy in this setting. Upon development of secondary resistance, sunitinib and regorafenib are used as subsequent treatments, although clinical benefit is often non-durable. Ripretinib is a type II kinase inhibitor targeting KIT and PDGFRA mutations and resistance through switching active I and inactive II forms. AREAS COVERED: This drug profile article provides an overview of the current state of the art treatment algorithm for advanced/metastatic GIST, focusing on the role of ripretinib in the fourth-line setting as defined by currently available clinical trials evidence. The mechanism of action, the safety profile, efficacy, and clinical application of ripretinib are presented. In addition, the Phase I study (NCT02571036) through which the optimal dose was established and the Phase III trials that assessed the efficacy and safety of ripretinib as fourth- (INVICTUS) and second-line treatment (INTRIGUE) are presented. EXPERT OPINION: Ripretinib is a safe and an effective therapy for the fourth-line setting in advanced/metastatic GIST. Future studies should evaluate combination schedules and the identification of markers predictive of benefit from ripretinib.

Nanomechanical properties of solid tumors as treatment monitoring biomarkers.

Many tumors, such as types of sarcoma and breast cancer, stiffen as they grow in a host healthy tissue, while individual cancer cells are becoming softer. Tumor stiffening poses major pathophysiological barriers to the effective delivery of drugs and compromises treatment efficacy. It has been established that normalization of the mechanical properties of a tumor by targeting components of the tumor microenvironment (TME) enhances the delivery of anti-cancer agents and consequently the therapeutic outcome. Consequently, there is an urgent need for the development of biomarkers, which characterize the mechanical state of a particular tumor for the development of personalized treatments or for monitoring therapeutic strategies that target the TME. In this work, Atomic Force Microscopy (AFM) was used to assess human and murine nanomechanical properties from tumor biopsies. In the case of murine tumor models, the nanomechanical properties during tumor progression were measured and a TME normalization drug (tranilast) along with chemotherapy doxorubicin were employed in order to investigate whether AFM has the ability to capture changes in the nanomechanical properties of a tumor during treatment. The nanomechanical data were further correlated with ex vivo characterization of structural components of the TME. The results highlighted that nanomechanical properties alter during cancer progression and AFM measurements are sensitive enough to capture even small alterations during different types of treatments, namely normalization and chemotherapy. The identification of unique AFM-based nanomechanical properties can lead to the development of biomarkers for treatment prediction and monitoring. STATEMENT OF SIGNIFICANCE: Cancer progression is associated with vast remodeling of the tumor microenvironment resulting in changes in the mechanical properties of the tissue. Indeed, many tumors stiffen as they grow and this stiffening compromises treatment efficacy. As a result, a number of treatments target tumor microenvironment in order to normalize its mechanical properties. Consequently, there is an urgent need for the development of innovative tools that can assess the mechanical properties of a particular tumor and monitor tumor progression and treatment outcomes. This work highlights the use of atomic force microscopy (AFM) for assessing the elasticity spectrum of solid tumors at different stages and during treatment. This knowledge is essential for the development of AFM-based nanomechanical biomarkers for treatment prediction and monitoring.

A systematic review of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in breast cancer patients reveals potentially clinically informative panels as well as key challenges in miRNA research.

Breast cancer patients are at a particularly high risk of cardiotoxicity from chemotherapy having a detrimental effect on quality-of-life parameters and increasing the risk of mortality. Prognostic biomarkers would allow the management of therapies to mitigate the risks of cardiotoxicity in vulnerable patients and a key potential candidate for such biomarkers are microRNAs (miRNA). miRNAs are post-transcriptional regulators of gene expression which can also be released into the circulatory system and have been associated with the progression of many chronic diseases including many types of cancer. In this review, the evidence for the potential application of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity (CIC) in breast cancer patientsis evaluated and a simple meta-analysis is performed to confirm the replication status of each reported miRNA. Further selection of miRNAs is performed by reviewing the reported associations of each miRNA with other cardiovascular conditions. Based on this research, the most representative panels targeting specific chemotherapy agents and treatment regimens are suggested, that contain several informative miRNAs, including both general markers of cardiac damage as well as those for the specific cancer treatments.

Identification and Classification of Benign and Malignant Masses based on Subtraction of Temporally Sequential Digital Mammograms.

Breast cancer remains the leading cause of cancer deaths and the second highest cause of death, in general, among women worldwide. Fortunately, over the last few decades, with the introduction of mammography, the mortality rate of breast cancer has significantly decreased. However, accurate classification of breast masses in mammograms is especially challenging. Various Computer-Aided Diagnosis (CAD) systems are being developed to assist radiologists with the accurate classification of breast abnormalities. In this study, classification of benign and malignant masses, based on the subtraction of temporally sequential digital mammograms and machine learning, is proposed. The performance of the algorithm was evaluated on a dataset created for the purposes of this study. In total, 196 images from 49 patients, with precisely annotated mass locations and biopsy confirmed malignant cases, were included. Ninety-six features were extracted and five feature selection algorithms were employed to identify the most important features. Ten classifiers were tested using leave-one-patient-out and 7-fold cross-validation. Neural Networks, achieved the highest classification performance with 90.85% accuracy and 0.91 AUC, an improvement compared to the state-of-the-art. These results demonstrate the effectiveness of the subtraction of temporally consecutive mammograms for the classification of breast masses as benign or malignant.

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness.

Sarcomas are uncommon malignancies of mesenchymal origin that can arise throughout the human lifespan, at any part of the body. Surgery remains the optimal treatment modality whilst response to conventional treatments, such as chemotherapy and radiation, is minimal. Immunotherapy has emerged as a novel approach to treat different cancer types but efficacy in soft tissue sarcoma and bone sarcoma is limited to distinct subtypes. Growing evidence shows that cancer-stroma cell interactions and their microenvironment play a key role in the effectiveness of immunotherapy. However, the pathophysiological and immunological properties of the sarcoma tumor microenvironment in relation to immunotherapy advances, has not been broadly reviewed. Here, we provide an up-to-date overview of the different immunotherapy modalities as potential treatments for sarcoma, identify barriers posed by the sarcoma microenvironment to immunotherapy, highlight their relevance for impeding effectiveness, and suggest mechanisms to overcome these barriers.

Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer.

PURPOSE: The EndoPredict prognostic assay is validated to predict distant recurrence and response to chemotherapy primarily in post-menopausal women with estrogen receptor-positive (ER+), HER2- breast cancer. This study evaluated the performance of EndoPredict in pre-menopausal women. EXPERIMENTAL DESIGN: Tumor samples from 385 pre-menopausal women with ER+, HER2- primary breast cancer (pT1-3, pN0-1) who did not receive chemotherapy in addition to endocrine therapy were tested with EndoPredict to produce a 12-gene EP molecular score and an integrated EPclin score that includes pathologic tumor size and nodal status. Associations of molecular and EPclin scores with 10-year distant recurrence-free survival (DRFS) were evaluated by Cox proportional hazards models and Kaplan-Meier analysis. RESULTS: After a median follow-up of 9.7 years, both the EP molecular score and the molecular-clinicopathologic EPclin score were associated with increased risk of distant recurrence [HR, 1.33; 95% confidence interval (CI), 1.18-1.50; P = 7.2 × 10-6; HR, 3.58; 95% CI, 2.26-5.66; P = 9.8 × 10-8, respectively]. Both scores remained significant after adjusting for clinical factors in multivariate analysis. Patients with low-risk EPclin scores (64.7%) had significantly improved DRFS compared with high-risk patients (HR, 4.61; 95% CI, 1.40-15.17; P = 4.2 × 10-3). At 10 years, patients with low-risk and high-risk EPclin scores had a DRFS of 97% (95% CI, 93%-99%) and 76% (95% CI, 67%-82%), respectively. CONCLUSIONS: The EPclin score is strongly associated with DRFS in pre-menopausal women who received adjuvant endocrine therapy alone. On the basis of these data, pre-menopausal women with EPclin low-risk breast cancer may be treated with endocrine therapy only and safely forgo adjuvant chemotherapy.

Exploring the landscape of immunotherapy approaches in sarcomas.

Sarcomas comprise a heterogenous group of malignancies, of more than 100 different entities, arising from mesenchymal tissue, and accounting for 1% of adult malignancies. Surgery, radiotherapy and systemic therapy constitute the therapeutic armamentarium against sarcomas, with surgical excision and conventional chemotherapy, remaining the mainstay of treatment for local and advanced disease, respectively. The prognosis for patients with metastatic disease is dismal and novel therapeutic approaches are urgently required to improve survival outcomes. Immunotherapy, is a rapidly evolving field in oncology, which has been successfully applied in multiple cancers to date. Immunomodulating antibodies, adoptive cellular therapy, cancer vaccines, and cytokines have been tested in patients with different types of sarcomas through clinical trials, pilot studies, retrospective and prospective studies. The results of these studies regarding the efficacy of different types of immunotherapies in sarcomas are conflicting, and the application of immunotherapy in daily clinical practice remains limited. Additional clinical studies are ongoing in an effort to delineate the role of immunotherapy in patients with specific sarcoma subtypes.

Triple negative breast cancer: Immunogenicity, tumor microenvironment, and immunotherapy.

Triple negative breast cancer (TNBC) is a biologically diverse subtype of breast cancer characterized by genomic and transcriptional heterogeneity and exhibiting aggressive clinical behaviour and poor prognosis. In recent years, emphasis has been placed on the identification of mechanisms underlying the complex genomic and biological profile of TNBC, aiming to tailor treatment strategies. High immunogenicity, specific immune activation signatures, higher expression of immunosuppressive genes and higher levels of stromal Tumor Infiltrating Lymphocytes, constitute some of the key elements of the immune driven landscape associated with TNBC. The unprecedented response of TNBC to immunotherapy has undoubtedly changed the standard of care in this disease both in the early and the metastatic setting. However, the extent of interplay between immune infiltration and mutational signatures in TNBC is yet to be fully unravelled. In the present review, we present clinical evidence on the immunogenicity and tumour microenvironment influence on TNBC progression and the current treatment paradigms in TNBC based on immunotherapy.

Mental Health and Adherence to COVID-19 Protective Behaviors among Cancer Patients during the COVID-19 Pandemic: An International, Multinational Cross-Sectional Study.

A population-based cross-sectional study was conducted during the first COVID-19 wave, to examine the impact of COVID-19 on mental health using an anonymous online survey, enrolling 9565 individuals in 78 countries. The current sub-study examined the impact of the pandemic and the associated lockdown measures on the mental health, and protective behaviors of cancer patients in comparison to non-cancer participants. Furthermore, 264 participants from 30 different countries reported being cancer patients. The median age was 51.5 years, 79.9% were female, and 28% had breast cancer. Cancer participants reported higher self-efficacy to follow recommended national guidelines regarding COVID-19 protective behaviors compared to non-cancer participants (p < 0.01). They were less stressed (p < 0.01), more psychologically flexible (p < 0.01), and had higher levels of positive affect compared to non-cancer participants. Amongst cancer participants, the majority (80.3%) reported COVID-19, not their cancer, as their priority during the first wave of the pandemic and females reported higher levels of stress compared to males. In conclusion, cancer participants appeared to have handled the unpredictable nature of the first wave of the pandemic efficiently, with a positive attitude towards an unknown and otherwise frightening situation. Larger, cancer population specific and longitudinal studies are warranted to ensure adequate medical and psychological care for cancer patients.

The Role of Perceived Organizational Support in Mental Health of Healthcare Workers During the COVID-19 Pandemic: A Cross-Sectional Study.

Background: Data support the link between the coronavirus disease 2019 (COVID-19) pandemic and mental distress in healthcare workers (HCWs). Although previous studies have documented the association between organizational policies and employees' psychological and mental status, there is still scant evidence regarding the effect of perceived organizational support (POS) on mental distress in HCWs during the pandemic. Aims: The present study aimed to assess the association between POS and mental distress in HCWs during the COVID-19 pandemic. The role of POS in stress, depressive and trauma symptoms in HCWs was investigated. Methods: This was an online cross-sectional study in 424 HCWs. Data were collected during the first wave of the pandemic, and included demographics, a 7-item questionnaire assessing POS, the "Patient Health Questionnaire" assessing depressive symptoms, the "Impact of Events Scale Revised," measuring post-traumatic stress disorder (PTSD) symptoms and the "Perceived Stress Scale" assessing perceived stress. Results: The mean POS score was 3.33 [standard deviation:1.85; range 0-7]. Younger (p < 0.001), less experienced (p < 0.001), female (p = 0.002), and non-physician HCWs (p = 0.031) were more likely to report lower self-perceived organizational support than older, male, more experienced physicians. Self-perceived organizational support was significantly and negatively associated with and self-assessed intensity of stress, depressive and traumatic symptoms, after adjusting for putative confounders (p < 0.001). Discussion: Self-perceived organizational support was significantly associated with HCWs' self-assessed mental status during the pandemic. Organizational support and mental distress should be addressed simultaneously in HCWs during the COVID-19 pandemic to increase resilience among them.

Health-Related Quality of Life Issues Experienced by Thoracic and Breast Sarcoma Patients: A Rare and Understudied Group.

Thoracic and breast sarcomas constitute a rare subgroup within the sarcoma population. There is limited knowledge about their health-related quality of life (HRQoL) and a valid disease-specific HRQoL instrument is lacking. This qualitative study aimed to investigate the HRQoL issues experienced by a small group of thoracic and breast sarcoma patients. Semi-structured interviews with 19 thoracic and four breast sarcoma patients were conducted and thematically analysed. Physical issues mentioned by both groups were fatigue, sleep disturbances, pain, wound infections, and symptoms related to chemotherapy and radiotherapy. Tightness in the back and restrictions in performing tasks above arm height were specific physical issues for breast sarcoma patients, whereas respiratory problems were only mentioned by thoracic sarcoma patients. Body image issues, changes in mood, fear of recurrence, and living with uncertainty were important mental health issues for both subgroups. Social issues in both groups included challenges in work and relationships, financial difficulties, loss of independence, and limitations in social activities. The identified physical, mental, and social health challenges can significantly impact thoracic and breast sarcoma patients' HRQoL. Results of this qualitative study will guide personalised supportive care for breast and thoracic sarcoma patients and help in determining the best possible HRQoL measurement strategy for sarcoma patients with different primary sarcoma locations.

False Negativity of Targeted Axillary Dissection in Breast Cancer.

INTRODUCTION: Targeted axillary dissection (TAD) has been proposed as an alternative method for the staging of patients with node-positive breast cancer who undergo neoadjuvant chemotherapy. However, not much is known yet about the false-negative rate (FNR) of the method and the subsequent risk of underestimation of residual axillary disease. METHODS: This study reviews published articles with calculations of false negativity of TAD and potential factors that may influence it. RESULTS: The FNR of TAD is usually reported as being <10%, but this calculation is usually based on small study populations. Lower FNR is a common finding along with lower N status, while not enough data are available yet for greater axillary involvement. When a marked node is revealed to be a sentinel lymph node (SLN) at surgery after neoadjuvant chemotherapy (NAC), this seems to be another factor that contributes to reliable TAD. With regard to the methods used to mark the positive node before chemotherapy and retrieval at surgery, there is no clear advantage of one over the other. The availability of relevant resources, the costs, and local legislation must all be taken into account for the selection of the optimal strategy. CONCLUSION: Although still in its early days, the FNR of TAD can be low, at least in patients with relatively little axillary involvement and when the marked node is the SLN. All reported methods of lymph node marking seem reliable.

Comparison of two-view versus single-view digital breast tomosynthesis and 2D-mammography in breast cancer surveillance imaging.

PURPOSE: Limited work has been performed for the implementation of digital breast tomosynthesis (DBT) in breast cancer surveillance imaging. The aim of this study was to investigate the differences between two different DBT implementations in breast cancer surveillance imaging, for patients with a personal history of breast cancer. METHOD: The DBT implementations investigated were: (1) 2-view 2D digital mammography and 2-view DBT (2vDM&2vDBT) (2) 1-view (cranial-caudal) DM and 1-view (mediolateral-oblique) DBT (1vDM&1vDBT). Clinical performance of these two implementations was assessed retrospectively using observer studies with 118 sets of real patient images, from a single imaging centre, and six observers. Sensitivity, specificity and area under the curve (AUC) using the Jack-knife alternative free-response receiver operating characteristics (JAFROC) analysis were evaluated. RESULTS: Results suggest that the two DBT implementations are not significantly different in terms of sensitivity, specificity and AUC. When looking at the two main different lesion types, non-calcifications and calcifications, and two different density levels, no difference in the performance of the two DBT implementations was found. CONCLUSIONS: Since 1vDM&1vDBT exposes the patient to half the dose of 2vDM&2vDBT, it might be worth considering 1vDM&1vDBT in breast cancer surveillance imaging. However, larger studies are required to conclude on this matter.