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- Bekkhus, T., et al.
(författare)
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Automated detection of vascular remodeling in tumor-draining lymph nodes by the deep-learning tool HEV-finder
- 2022
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 258:1, s. 4-11
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Tidskriftsartikel (refereegranskat)abstract
- Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker. (c) 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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- Karakatsanis, Andreas, et al.
(författare)
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Meta-analysis of neoadjuvant therapy and its impact in facilitating breast conservation in operable breast cancer
- 2018
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 105:5, s. 469-481
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNeoadjuvant therapy (NAT) for operable breast cancer may facilitate more breast-conserving surgery (BCS). It seems, however, that this benefit is not being realized fully.MethodsA systematic review of the literature was performed. RCTs were included. The criteria for inclusion were: documentation of surgical assessment before and after NAT, surgery performed (BCS or mastectomy), and clinical and pathological responses.ResultsA total of 1452 patients from seven RCTs met the inclusion criteria. After NAT, the feasibilityof BCS increased from 43⋅3to60⋅4 per cent (P < 0⋅001), but BCS was performed in only 51⋅8percent(P = 0⋅04). Only 31 per cent of patients who became eligible for BCS (assessed on clinical response)underwent BCS (pooled rate ratio 0⋅31, 95 per cent c.i. 0⋅22 to 0⋅44; P < 0⋅001). Of the mastectomycandidates who achieved a pathological complete response after NAT, only 41 per cent underwent BCS(pooled rate ratio 0⋅41, 0⋅23 to 0⋅74; P = 0⋅003). The main factors that influenced the decision not to shiftto BCS, even though it was feasible, were clinical assessment before NAT, multicentricity and tumoursize at presentation.ConclusionBreast surgery performed after NAT does not reflect tumour response, resulting in potentially unnecessary radical surgery, especially mastectomy. The barriers to maximizing the surgical benefits of NAT need to be better understood and explored. Still unnecessary mastectomies
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- Vicini, F. A., et al.
(författare)
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A Novel Biosignature Identifies Patients With DCIS With High Risk of Local Recurrence After Breast Conserving Surgery and Radiation Therapy
- 2022
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Ingår i: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT. Methods and Materials: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were classified into 3 biosignature risk groups using the decision score (DS) and the RRt category: (1) Low Risk (DS ≤2.8 without RRt), (2) Elevated Risk (DS >2.8 without RRt), and (3) Residual Risk (DS >2.8 with RRt). Total and invasive IBR rates were assessed by risk group and treatment. Results: In patients at low risk, there was no significant difference in IBR rates with or without RT (total, P = .8; invasive IBR, P = .7), and there were low overall 10-year rates (total, 5.1%; invasive, 2.7%). In patients with elevated risk, IBR rates were decreased with RT (total: hazard ratio [HR], 0.25; P < .001; invasive: HR, 0.28; P = .005); 10-year rates were 20.6% versus 4.9% (total) and 10.9% versus 3.1% (invasive). In patients with residual risk, although IBR rates decreased with RT after BCS (total: HR, 0.21; P < .001; invasive: HR, 0.29; P = .028), IBR rates remained significantly higher after RT compared with patients with elevated risk (HR, 2.5; 95% CI, 1.2-5.4; P = .018), with 10-year rates of 42.1% versus 14.7% (total) and 18.3% versus 6.5% (invasive). Conclusions: The novel biosignature identified patients with 3 distinct risk profiles: Low Risk patients with a low recurrence risk with or without adjuvant RT, Elevated Risk patients with excellent outcomes after BCS plus RT, and Residual Risk patients with an elevated recurrence risk remaining after BCS plus RT, warranting potential intensified or alternative treatment approaches. © 2022 The Authors
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- Vicini, F. A., et al.
(författare)
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Biosignatures to Optimize Adjuvant Radiation Therapy Use in Patients With DCIS With High Risk Clinicopathologic Features
- 2021
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 111:3
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE/OBJECTIVE(S): There is an unmet need to identify women diagnosed with DCIS who have a low recurrence risk and could omit radiotherapy (RT) after breast conserving surgery (BCS), or an elevated recurrence risk after treatment with BCS plus RT. MATERIALS/METHODS: Pathology, clinical data, and FFPE tissue samples were evaluable for 485 women treated for DCIS with BCS with negative margins, with or without whole breast RT, at centers in Sweden, US and Australia. A subset with large tumor size (> 2.5 cm) &/or nuclear grade III DCIS was assessed (n=250). A validated biosignature (Prelude, Laguna Hills CA) and a novel response subtype biosignature to RT after BCS were determined using protein biomarkers (p16/INK4A, Ki-67, COX-2, PgR, HER2, FOXA1, SIAH2) assayed on FFPE tissue. The two biosignatures classified women into three risk groups: Low risk, Elevated risk with a good response subtype (Rst) and Elevated risk with a poor Rst to RT after BCS. Ipsilateral breast tumor recurrence (IBTR) included DCIS or Invasive Breast Cancer (IBC) that was local, regional, or metastatic. Hazard ratios and 10-year risks were calculated using Cox proportional hazards and Kaplan-Meier analyses. RESULTS: Of 250 women with nuclear grade III DCIS and/or size > 2.5 cm, biosignatures classified 72% (n=179) of patients into an Elevated risk group consisting of those with a good (n=122) or a poor (n=57) response subtype (Rst) to RT after BCS. The remaining 28% of women were classified into a low-risk group (n=71). In the low-risk group (n=71), women treated without RT had good 10-year outcomes with no (0%) 10-year IBC events, and derived no significant RT benefit (1%) in 10-year IBTR rates (IBTR P=0.81). Of all women treated without RT (n=102), those in the elevated risk group (good and poor Rst combined, n=61) had significantly worse 10-year IBTR/IBC rates (31%/17%) than those in the low-risk group, (IBTR HR=12, P=0.01). Women treated with RT in the elevated risk group with a good Rst (n=77) had significantly reduced 10-year IBTR/IBC rates of 5%/3%. However, no significant benefit to RT was noted for women within the elevated risk group with a poor Rst (n=41) who had 10-year IBTR/IBC rates of 25%/20%. Of all women treated with RT in the elevated risk group (n=118), those with a poor Rst had significantly worse outcomes than those with a good Rst (IBTR HR=4.1, P=0.035, IBC HR=8, P=0.053). CONCLUSION: In women with nuclear grade III DCIS &/or size > 2.5 cm, DCISionRT combined with a novel response subtype biosignature (Rst) identified an elevated risk group with two distinct subtypes of women: (1) a poor Rst that had high IBTR/IBC rates with or without RT and (2) a good Rst deriving significant benefit from adjuvant RT. Women in the corresponding low risk group had low 10-year IBTR/IBC rates and derived no significant benefit from adjuvant RT. Copyright © 2021. Published by Elsevier Inc.
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- Wärnberg, F
(författare)
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Bröstets patofysiologi
- 2004
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Ingår i: Bröstcancer. - 9186327631
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Bokkapitel (populärvet., debatt m.m.)
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