Cancers

Background: Pancreatic acinar cell carcinoma (PACC) is a distinct type of pancreatic cancer with low prevalence. We aimed to analyze prognostic factors and survival outcome for PACC in comparison to pancreatic ductal adenocarcinoma (PDAC), based on data from the German Cancer Registry Group. Methods: Patients with PACC and PDAC were extracted from pooled data of the German clinical cancer registries (years 2000 to 2019). The distribution of demographic parameters, tumor stage and therapy modes were compared between PACC and PDAC. The Kaplan–Meier method and Cox regression analysis were used to delineate prognostic factors for PACC. Propensity score matching was used to compare survival between PACC and PDAC. Results: There were 233 (0.44%) patients with PACC out of 52,518 patients with pancreatic malignancy. Compared to PDAC, patients with PACC were younger (median age 66 versus 70, respectively, p < 0.001) and the percentage of males was higher (66.1% versus 53.3%, respectively, p < 0.001). More patients were resected with PACC than with PDAC (56.2% versus 38.9%, respectively, p < 0.001). The estimated overall median survival in PACC was 22 months (95% confidence interval 15 to 27), compared to 12 months (95% confidence interval 10 to 13) in the matched PDAC cohort (p < 0.001). Surgical resection was the strongest positive prognostic factor for PACC after adjusting for sex, age, and distant metastases (hazard ratio 0.34, 95% confidence interval 0.22 to 0.51, p < 0.001). There was no survival benefit for adjuvant therapy in PACC. Conclusions: PACC has overall better prognosis than PDAC. Surgical resection is the best therapeutic strategy for PACC and should be advocated even in advanced tumor stages. Full article

Ovarian cancer has the worst prognosis among gynecological cancers. In particular, clear cell and mucinous carcinomas are less sensitive to chemotherapy. The establishment of new therapies is necessary to improve the treatment outcomes for these carcinomas. In previous clinical studies, chemotherapy with cytotoxic anticancer drugs has failed to demonstrate better treatment outcomes than paclitaxel + carboplatin therapy. In recent years, attention has been focused on treatment with molecular target drugs and immune checkpoint inhibitors that target newly identified biomarkers. The issues that need to be addressed include the most appropriate combination of therapies, identifying patients who may benefit from each therapy, and how results should be incorporated into the standard of care for ovarian clear cell and mucinous carcinomas. In this article, we have reviewed the most promising therapies for ovarian clear cell and mucinous carcinomas, which are regarded as intractable, with an emphasis on therapies currently being investigated in clinical studies. Full article

Background: In the next decades, the incidence of patients with glioblastoma (GBM) will increase due to the growth of the elderly population. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is widely applied to achieve maximal safe resection of GBM and is identified as a novel intraoperative marker for diagnostic tissue during biopsies. However, detailed analyses of the use of 5-ALA in resections as well as biopsies in a large elderly cohort are still missing. The aim of this study was thus to investigate the efficacy, outcome, and safety of surgically- treated GBM in the 5-ALA era in a large elderly cohort. Methods: All GBM patients aged 65 years or older who underwent neurosurgical intervention between 2007 and 2019 were included. Data on 5-ALA application, intraoperative fluorescence status, and 5-ALA-related side effects were derived from our databank. In the case of resection, the tumor resectability and the extent of resection were determined. Potential prognostic parameters relevant for overall survival were analyzed. Results: 272 GBM patients with a median age of 71 years were included. Intraoperative 5-ALA fluorescence was applied in most neurosurgical procedures (n = 255/272, 88%) and visible fluorescence was detected in most cases (n = 252/255, 99%). In biopsies, 5-ALA was capable of visualizing tumor tissue by visible fluorescence in all but one case (n = 91/92, 99%). 5-ALA administration did not result in any severe side effects. Regarding patient outcome, smaller preoperative tumor volume (<22.75 cm³), gross total resection, single lesions, improved postoperative neurological status, and concomitant radio-chemotherapy showed a significantly longer overall survival. Conclusions: Our data of this large elderly cohort demonstrate the clinical utility and safety of 5-ALA fluorescence in GBM for improved tumor visualization in both resections as well as biopsies. Therefore, we recommend the use of 5-ALA not only in resections, but also in open/stereotactic biopsies to optimize the neurosurgical management of elderly GBM patients. Full article

The PAM50 gene expression subtypes and the associated risk of recurrence (ROR) score are used to predict the risk of recurrence and the benefits of adjuvant therapy in early-stage breast cancer. The Prosigna assay includes the PAM50 subtypes along with their clinicopathological features, and is approved for treatment recommendations for adjuvant hormonal therapy and chemotherapy in hormone-receptor-positive early breast cancer. The Prosigna test utilizes RNA extracted from macrodissected tumor cells obtained from formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, RNA extracted from fresh-frozen (FF) bulk tissue without macrodissection is widely used for research purposes, and yields high-quality RNA for downstream analyses. To investigate the impact of the sample preparation approach on ROR scores, we analyzed 94 breast carcinomas included in an observational study that had available gene expression data from macrodissected FFPE tissue and FF bulk tumor tissue, along with the clinically approved Prosigna scores for the node-negative, hormone-receptor-positive, HER2-negative cases (n = 54). ROR scores were calculated in R; the resulting two sets of scores from FFPE and FF samples were compared, and treatment recommendations were evaluated. Overall, ROR scores calculated based on the macrodissected FFPE tissue were consistent with the Prosigna scores. However, analyses from bulk tissue yielded a higher proportion of cases classified as normal-like; these were samples with relatively low tumor cellularity, leading to lower ROR scores. When comparing ROR scores (low, intermediate, and high), discordant cases between the two preparation approaches were revealed among the luminal tumors; the recommended treatment would have changed in a minority of cases. Full article

Glioblastoma multiforme (GBM) is the most malignant brain tumor in the world, only 25% of GBM patients were alive one year after diagnosis. Although Temozolamide combined with radiation therapy more effectively prolonged the survival rate than radiation alone, the overall survival rate is still dismal. Therefore, a new therapeutic strategy is urgently needed. CDK4/6 inhibitors are newly FDA-approved agents to treat HR-positive, HER2-negative advanced, and metastatic breast cancers, and preclinical results showed that CDK4/6 inhibitors significantly reduced cell proliferation and tumor growth. However, several studies have suggested that CDK4/6 inhibitor-induced non-genetic changes caused treatment failure, including autophagy activation. Therefore, this study aimed to combine an autophagy inhibitor, MPT0L145, with abemaciclib to improve therapeutic efficiency. The use of abemaciclib effectively inhibited cell proliferation via suppression of RB phosphorylation and induced autophagy activation in GBM cancer cells. MPT0L145 treatment alone not only blocked autophagy activation, but also induced generation of ROS and DNA damage in a concentration-dependent manner. Importantly, MPT0L145 had a comparable penetration ability to TMZ in our blood brain barrier permeability assay. Combined MPT0L145 with abemaciclib significantly reduced cell proliferation, suppressed RB phosphorylation, and increased ROS production. In conclusion, the data suggested that blocking autophagy by MPT0L145 synergistically sensitized GBM cancer cells to abemaciclib and represents a potential therapeutic strategy for treating GBM in the future. Full article

Breast cancer is now the most frequently diagnosed cancer in women, and its percentage is gradually increasing. Optimistically, there is a good chance of recovery from breast cancer if identified and treated at an early stage. Therefore, several researchers have established deep-learning-based automated methods for their efficiency and accuracy in predicting the growth of cancer cells utilizing medical imaging modalities. As of yet, few review studies on breast cancer diagnosis are available that summarize some existing studies. However, these studies were unable to address emerging architectures and modalities in breast cancer diagnosis. This review focuses on the evolving architectures of deep learning for breast cancer detection. In what follows, this survey presents existing deep-learning-based architectures, analyzes the strengths and limitations of the existing studies, examines the used datasets, and reviews image pre-processing techniques. Furthermore, a concrete review of diverse imaging modalities, performance metrics and results, challenges, and research directions for future researchers is presented. Full article

Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP. We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing. Proton field at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP. Full article

In the current communication, a simple, environmentally compatible, non-toxic green chemistry process is used for the development of silver nanoparticles (AgZE) by the reaction between silver nitrate (AgNO₃) and the ethanolic leaf extract of Zinnia elegans (ZE). The optimization of AgZE is carried out using a series of experiments. Various physico-chemical techniques are utilized to characterize the nanomaterials. The cell viability assay of AgZE in normal cells (CHO, HEK-293T, EA.hy926, and H9c2) shows their biocompatible nature, which is supported by hemolytic assay using mouse RBC. Interestingly, the nanoparticles exhibited cytotoxicity towards different cancer cell lines (U-87, MCF-7, HeLa, PANC-1 and B16F10). The detailed anticancer activity of AgZE on human glioblastoma cell line (U-87) is exhibited through various in vitro assays. In vivo the AgZE illustrates anticancer activity by inhibiting blood vessel formation through CAM assay. Furthermore, the AgZE nanoparticles when intraperitoneally injected in C57BL6/J mice (with and without tumor) exhibit fluorescence properties in the NIR region (excitation: 710nm, emission: 820nm) evidenced by bioimaging studies. The AgZE biodistribution through ICPOES analysis illustrates the presence of silver in different vital organs. Considering all the results, AgZE could be useful as a potential cancer therapeutic agent, as well as an NIR based non-invasive imaging tool in near future. Full article

Tumour lesion segmentation is a key step to study and characterise cancer from MR neuroradiological images. Presently, numerous deep learning segmentation architectures have been shown to perform well on the specific tumour type they are trained on (e.g., glioblastoma in brain hemispheres). However, a high performing network heavily trained on a given tumour type may perform poorly on a rare tumour type for which no labelled cases allows training or transfer learning. Yet, because some visual similarities exist nevertheless between common and rare tumours, in the lesion and around it, one may split the problem into two steps: object detection and segmentation. For each step, trained networks on common lesions could be used on rare ones following a domain adaptation scheme without extra fine-tuning. This work proposes a resilient tumour lesion delineation strategy, based on the combination of established elementary networks that achieve detection and segmentation. Our strategy allowed us to achieve robust segmentation inference on a rare tumour located in an unseen tumour context region during training. As an example of a rare tumour, Diffuse Intrinsic Pontine Glioma (DIPG), we achieve an average dice score of 0.62 without further training or network architecture adaptation. Full article

(1) Background: The aim of the present study was to evaluate the effect of NDRG2 expression in regulating PD-L1 or PD-L2 on malignant breast cancer cells. (2) Methods: Overexpression and knockdown of the NDRG2 gene in human and mouse cancer cells were applied and quantitative real-time PCR and Western blot analysis were performed. T cell proliferation and TCGA analysis were conducted to validate negative correlation of the PD-L1 expression with the NDRG2 expression. (3) Results: We found that NDRG2 overexpression inhibits PD-L1 expression in human breast cancer cells through NF-κB signaling. NDRG2 overexpression in 4T1 mouse breast cancer cells followed by PD-L1 downregulation could block the suppressive activity of cancer cells on T cell proliferation and knockdown of NDRG2 expression enhanced the expression of PD-L1, leading to the inhibition of T cell proliferation by tumor cell coculture. Finally, we confirmed from TCGA data that PD-L1 expression in basal and triple-negative breast cancer patients was negatively correlated with the expression of NDRG2. Intriguingly, linear regression analysis using TNBC cell lines showed that the PD-L1 level was negatively associated with the NDRG2 expression level. (4) Conclusions: Our findings demonstrate that NDRG2 expression is instrumental in suppressing PD-L1 expression and restoring PD-L1-inhibited T cell proliferation activity in TNBC cells. Full article

The incidence of pediatric adrenocortical tumors (ACT) is high in southern Brazil due to the founder TP53 R337H variant. Neonatal screening/surveillance (NSS) for this variant resulted in early ACT detection and improved outcomes. The medical records of children with ACT who did not participate in newborn screening (non-NSS) were reviewed (2012–2018). We compared known prognostic factors between the NSS and non-NSS cohorts and estimated surveillance and treatment costs. Of the 16 non-NSS children with ACT carrying the R337H variant, the disease stages I, II, III, and IV were observed in five, five, one, and five children, respectively. The tumor weight ranged from 22 to 608 g. The 11 NSS children with ACT all had disease stage I and were alive. The median tumor weight, age of diagnosis, and interval between symptoms and diagnosis were 21 g, 1.9 years, and two weeks, respectively, for the NSS cohort and 210 g, 5.2 years, and 15 weeks, respectively, for the non-NSS cohort. The estimated surveillance/screening cost per year of life saved is US$623/patient. NSS is critical for improving the outcome of pediatric ACT in this region. Hence, we strongly advocate for the inclusion of R337H in the state-mandated universal screening and surveillance. Full article

This study aimed to identify preferred lung cancer screening modalities in a Chinese population and predict uptake rates of different modalities. A discrete choice experiment questionnaire was administered to 392 Chinese individuals aged 50–74 years who were at high risk for lung cancer. Each choice set had two lung screening options and an option to opt-out, and respondents were asked to choose the most preferred one. Both mixed logit analysis and stepwise logistic analysis were conducted to explore whether preferences were related to respondent characteristics and identify which kinds of respondents were more likely to opt out of any screening. On mixed logit analysis, attributes that were predictive of choice at 1% level of statistical significance included the screening interval, screening venue, and out-of-pocket costs. The preferred screening modality seemed to be screening by low-dose computed tomography (LDCT) + blood test once a year in a general hospital at a cost of RMB 50; this could increase the uptake rate by 0.40 compared to the baseline setting. On stepwise logistic regression, those with no endowment insurance were more likely to opt out; those who were older and housewives/househusbands, and those with a health check habit and with commercial endowment insurance were less likely to opt out from a screening programme. There was considerable variance between real risk and self-perceived risk of lung cancer among respondents. Lung cancer screening uptake can be increased by offering various screening modalities, so as to help policymakers further design the screening modality. Full article

Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, 25 to ≤ 30, ≥30 kg/m²). The outcome of interest was irAEs after ICI initiation. A multivariable logistic regression model estimated the adjusted odds ratio (aOR) and 95% confidence interval (CI) of BMI. A total of 684 patients with stage III or IV cancer were included in the study (lung: 269, melanoma: 204, other: 211). The mean age at the first dose of ICI was 64.1 years (SD = 13.5), 394 patients (57.6%) were male, and over one-third (N = 260, 38.0%) were non-White. Overall, 52.9% of patients had BMI ≥ 25 kg/m² (25 to ≤ 30: 217, ≥30: 145) and 288 (42.1%) had irAEs after ICI treatment. Patients with higher BMI tended to have a higher rate of irAEs (<25: 35.7%, 25 to ≤ 30: 47.0%, ≥30: 49.0%). The multivariable logistic regression yielded consistent results (BMI ≥ 30 vs. BMI < 25: aOR = 1.47, 95% CI = 0.96–2.23; 25 ≤ BMI < 30 vs. BMI < 25: aOR = 1.46, 95% CI = 1.02–2.11, p-trend = 0.04). In conclusion, among patients with advanced cancer receiving ICIs, the rate of irAEs appears to be higher among those with higher BMI. Full article

MicroRNAs (miRNAs) are linear single-stranded non-coding RNAs oligonucleotides, widely distributed in cells, playing a key role as regulators of gene expression at post-transcriptional level. Circular RNAs (circRNAs) are single-stranded RNA oligonucleotides forming a covalently closed continuous loop, which confers them a high structural stability and which may code for proteins or act as gene regulators. Abnormal levels or dysregulation of miRNA or circRNA are linked to several cancerous pathologies, so that they are receiving a large attention as diagnostic and prognostic tools. Some miRNAs and circRNAs are strongly involved in the regulatory networks of the transcription factor p53, which plays a pivotal role as tumor suppressor. Overexpression of miRNAs and/or circRNAs, as registered in a number of cancers, is associated to a concomitant inhibition of the p53 onco-suppressive function. Among other mechanisms, it was recently suggested that a functional inhibition of p53 could arise from a direct interaction between p53 and oncogenic miRNAs or circRNAs; a mechanism that might be reminiscent of the p53 inhibition by some E3 ubiquitin ligase such as MDM2 and COP1. Such evidence might deserve important implications for restoring the p53 anticancer functionality, and pave the way to intriguing perspectives for novel therapeutic strategies. In the present paper, the experimental evidence of the interaction between p53 and miRNAs and/or circRNAs is reviewed and discussed in connection with the development of new anticancer approaches. Full article

Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infiltrate MC-38 model (Adpgk, Reps1 and Rpl18 neo-antigens), we further investigated pivotal immune cells that educate CD8+ T cells. Heterologous prime-boost vaccination induced a superior antitumor response characterized by the increase in number and functionality of antigen-specific CD8+ T cells, recruitment of cross-presenting dendritic cells, and polarization of CD4+ T cells towards an antitumor Th1 phenotype within the tumor and tumor-draining lymph nodes, turning the cold TC-1 tumor into a hot, inflamed tumor. In the inflamed MC-38 tumor model, treatment combination markedly prolonged the overall survival of mice. Treatment with multi-epitope vaccines also induced high frequencies of multiple antigen specificities in the periphery and in the tumor. Prime-boost treatment reduced tumor-infiltrating regulatory CD4+ T cells whilst increasing cross-presenting dendritic cells in tumor-draining lymph nodes. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy. Full article

Background: Positron emission tomography (PET)/computed tomography (CT) using the gastrin-releasing peptide receptor antagonist [⁶⁸Ga]RM2 has shown to be a promising imaging method for primary breast cancer (BC) with positive estrogen receptor (ER) status. This study assessed tumor visualization by [⁶⁸Ga]RM2 PET/CT in patients with pre-treated ER-positive BC and suspected metastases. Methods: This retrospective pilot study included eight female patients with initial ER-positive, pre-treated BC who underwent [⁶⁸Ga]RM2 PET/CT. Most of these patients (seven out of eight; 88%) were still being treated with or had received endocrine therapy. [⁶⁸Ga]RM2 PET/CTs were visually analyzed by two nuclear medicine specialists in consensus. Tumor manifestations were rated qualitatively (i.e., RM2-positive or RM2-negative) and quantitatively using the maximum standardized uptake value (SUVmax). SUVmax values were compared between the two subgroups (RM2-positive vs. RM2-negative). Results: Strong RM2 binding was found in all metastatic lesions of six patients (75%), whereas tracer uptake in all metastases of two patients (25%) was rated negative. Mean SUVmax of RM2-positive metastases with the highest SUVmax per patient (in lymph node and bone metastases; 15.8 ± 15.1 range: 3.7–47.8) was higher than mean SUVmax of the RM2-negative metastases with the highest SUVmax per patient (in bone metastases; 1.6 ± 0.1, range 1.5–1.7). Conclusions: Our data suggest that RM2 binding is maintained in the majority of patients with advanced disease stage of pre-treated ER-positive BC. Thus, [⁶⁸Ga]RM2 PET/CT could support treatment decision in these patients, radiotherapy planning in oligometastatic patients or selection of patients for RM2 radioligand therapy. Further studies with larger patient cohorts are warranted to confirm these findings. Full article

The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin-embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective biobank pilot study, 90 FFPE samples from 77 patients were processed. Protein quantitation was performed by high-resolution mass spectrometry and validated by histopathologic analysis. The global protein expression formed six sample clusters. Proteins such as TRAF6 and ARMC10 were upregulated in clusters with enrichment for shorter survival, and proteins such as AIFI1 were upregulated in clusters with enrichment for longer survival. The cohort’s heterogeneity was addressed by comparing primary and metastasis samples, as well comparing clinical stages. Within immunotherapy and targeted therapy subgroups, the upregulation of the VEGFA-VEGFR2 pathway, RNA splicing, increased activity of immune cells, extracellular matrix, and metabolic pathways were positively associated with patient outcome. To summarize, we were able to (i) link global protein expression profiles to survival, and they proved to be an independent prognostic indicator, as well as (ii) identify proteins that are potential predictors of a patient’s response to immunotherapy and targeted therapy, suggesting new opportunities for precision medicine developments. Full article

Human papillomavirus (HPV) is a significant etiologic driver of penile squamous cell carcinoma (PSCC). The integration pattern of HPV and its carcinogenic mechanism in PSCC remain largely unclear. We retrospectively reviewed 108 PSCC cases who received surgery between 2008 and 2017. Using high-throughput viral integration detection, we identified 35 HPV-integrated PSCCs. Unlike cervical cancer, the HPV E2 oncogene was not prone to involvement in integration. Eleven of the 35 (31.4%) HPV-integrated PSCCs harbored intact HPV E2; these tumors had lower HPV E6 and E7 expression and higher expression of p53 and pRb proteins than those with disrupted E2 did (p < 0.001 and p = 0.024). Integration breakpoints are preferentially distributed in or near host genes, including previously reported hotspots (KLF5, etc.) and newly identified hotspots (CADM2, etc.), which are mainly involved in oncogenic signaling pathways (MAPK, JAK/STAT, etc.). Regarding the phosphorylation levels of JNK, p38 was higher in HPV-positive tumors with MAPK-associated integration than those in HPV-positive tumors with other integration and those in HPV-negative tumors. In vitro, KLF5 knockdown inhibited proliferation and invasion of PSCC cells, while silencing CADM2 promoted migration and invasion. In conclusion, this study enhances our understanding of HPV-induced carcinogenesis in PSCC, which may not only rely on the E6/E7 oncogenes, but mat also affect the expression of critical genes and thus activate oncogenic pathways. Full article

Prediction of radiotherapy (RT) benefit after breast-conserving surgery (BCS) for DCIS is crucial. The aim was to validate a biosignature, DCISionRT^®, in the SweDCIS randomized trial. Women were randomly assigned to RT or not after BCS, between 1987 and 2000. Tumor blocks were collected, and slides were sent to PreludeDx^TM for testing. In 504 women with complete data and negative margins, DCISionRT divided 52% women into Elevated (DS > 3) and 48% in Low (DS ≤ 3) Risk groups. In the Elevated Risk group, RT significantly decreased relative 10-year ipsilateral total recurrence (TotBE) and 10-year ipsilateral invasive recurrence (InvBE) rates, HR 0.32 and HR 0.24, with absolute decreases of 15.5% and 9.3%. In the Low Risk group, there were no significant risk differences observed with radiotherapy. Using a cutoff of DS > 3.0, the test was not predictive for RT benefit (p = 0.093); however, above DS > 2.8 RT benefit was greater for InvBE (interaction p = 0.038). Recurrences at 10 years without radiotherapy increased significantly per 5 DS units (TotBE HR:1.5 and InvBE HR:1.5). Continuous DS was prognostic for TotBE risk although categorical DS did not reach significance. Absolute 10-year TotBE and InvBE risks appear sufficiently different to indicate that DCISionRT can aid physicians in selecting individualized adjuvant DCIS treatment strategies. Further analyses are planned in combined cohorts to increase statistical power. Full article