| 1. |
- Micke, Patrick, et al.
(författare)
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The prognostic impact of the tumour stroma fraction : A machine learning-based analysis in 16 human solid tumour types
- 2021
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns.Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR (95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59 (1.49-8.62)) associations of the tumour stroma fraction with survival.Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance.
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| 2. |
- Asp, Mihaela, et al.
(författare)
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Prognostic Value of Peritoneal Cancer Index After Complete Cytoreductive Surgery in Advanced Ovarian Cancer
- 2022
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 42:5, s. 2541-2551
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Tidskriftsartikel (refereegranskat)abstract
- Background/aim: Residual disease (RD) after primary debulking surgery (PDS) is a prognostic factor for survival in advanced ovarian cancer (AOC). This study aimed to examine whether the tumor extent affects overall survival (OS) and progression-free survival (PFS) in AOC patients treated with PDS.Patients and methods: A total of 118 patients treated with PDS were included. Age, ECOG score, AOC International Federation of Gynecology and Obstetrics (FIGO) stage, CA-125, RD, peritoneal cancer index (PCI), preoperative imaging (CT-PCI) and macroscopic visualization at the surgery start (S-PCI) were analyzed. Tumor extent was quantified using the PCI, and by CT-PCI and S-PCI. Cox regression, Kaplan-Meier and receiver operating curves (ROC) were performed for survival analyses.Results: S-PCI correlated with both OS (1.067, 95%CI=1.018-1.119, p<0.007) and PFS. Patients exhibiting S-PCI≥18.5, adjusted to age, performance status, and RD, had a two-fold risk of dying (HR=2.070, 95%CI=1.061-4.038, p=0.033) compared those with PCI<18.5. CT-PCI correlated with OS in crude data (1.037, 95%CI=1.005-1.071, p=0.025), but this was not sustained in multivariate analyses. RD of any size doubled the risk of dying (2.177, 95%CI=1.235-3.838, p=0.007).Conclusion: The tumor extent at the beginning of surgery seemed to affect OS in patients with AOC, regardless of the extent of RD at the end of the surgery. PCI above 18.5 doubled the risk of dying of the disease. No difference in major complications was noted in the two groups of patients. CT-PCI seemed to play a prognostic role for PFS; however, it is still to be investigated as a prognostic factor for OS.
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| 3. |
- Asp, Mihaela, et al.
(författare)
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The role of computed tomography in the assessment of tumour extent and the risk of residual disease after upfront surgery in advanced ovarian cancer (AOC)
- 2022
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Ingår i: Archives of Gynecology and Obstetrics. - : Springer Science and Business Media LLC. - 1432-0711.
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Tidskriftsartikel (refereegranskat)abstract
- PurposeEpithelial ovarian cancer is usually diagnosed in the advanced stages. To choose the best therapeutic approach, an accurate preoperative assessment of the tumour extent is crucial. This study aimed to determine whether the peritoneal cancer index (PCI), the amount of ascites, and the presence of cardiophrenic nodes (CPLNs) visualized by computed tomography (CT) can assess the tumour extent (S-PCI) and residual disease (RD) for advanced ovarian cancer (AOC) patients treated with upfront surgery.MethodsIn total, 118 AOC cases were included between January 2016 and December 2018 at Skåne University Hospital, Lund, Sweden. Linear regression and interclass correlation (ICC) analyses were used to determine the relationship between CT-PCI and S-PCI. The patients were stratified in complete cytoreductive surgery (CCS) with no RD or to non-CCS with RD of any size. The amount of ascites on CT (CT-ascites), CA-125 and the presence of radiological enlarged CPLNs (CT-CPLN) were analysed to evaluate their impact on estimating RD.ResultsCT-PCI correlated well with S-PCI (0.397; 95% CI 0.252–0.541; p < 0.001). The risk of RD was also related to CT-PCI (OR 1.069 (1.009–1.131), p < 0.023) with a cut-off of 21 for CT-PCI (0.715, p = 0.000). The sensitivity, specificity, positive predictive value and negative predictive value were 58.5, 70.3, 52.2 and 75.4%, respectively. CT-ascites above 1000 ml predicted RD (OR 3.510 (1.298–9.491) p < 0.013).ConclusionCT is a reliable tool to assess the extent of the disease in advanced ovarian cancer. Higher CT-PCI scores and large volumes of ascites estimated on CT predicted RD of any size.
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| 4. |
- De Marchi, Tommaso, et al.
(författare)
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Proteogenomic Workflow Reveals Molecular Phenotypes Related to Breast Cancer Mammographic Appearance
- 2021
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 20:5, s. 2983-3001
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Tidskriftsartikel (refereegranskat)abstract
- Proteogenomic approaches have enabled the generat̲ion of novel information levels when compared to single omics studies although burdened by extensive experimental efforts. Here, we improved a data-independent acquisition mass spectrometry proteogenomic workflow to reveal distinct molecular features related to mammographic appearances in breast cancer. Our results reveal splicing processes detectable at the protein level and highlight quantitation and pathway complementarity between RNA and protein data. Furthermore, we confirm previously detected enrichments of molecular pathways associated with estrogen receptor-dependent activity and provide novel evidence of epithelial-to-mesenchymal activity in mammography-detected spiculated tumors. Several transcript-protein pairs displayed radically different abundances depending on the overall clinical properties of the tumor. These results demonstrate that there are differentially regulated protein networks in clinically relevant tumor subgroups, which in turn alter both cancer biology and the abundance of biomarker candidates and drug targets.
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| 5. |
- Eriksson, Mikael, et al.
(författare)
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Identification of Women at High Risk of Breast Cancer Who Need Supplemental Screening
- 2020
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 1527-1315 .- 0033-8419. ; 297:2, s. 327-333
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Tidskriftsartikel (refereegranskat)abstract
- Background Mammography screening reduces breast cancer mortality, but a proportion of breast cancers are missed and are detected at later stages or develop during between-screening intervals. Purpose To develop a risk model based on negative mammograms that identifies women likely to be diagnosed with breast cancer before or at the next screening examination. Materials and Methods This study was based on the prospective screening cohort Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA), 2011-2017. An image-based risk model was developed by using the Stratus method and computer-aided detection mammographic features (density, masses, microcalcifications), differences in the left and right breasts, and age. The lifestyle extended model included menopausal status, family history of breast cancer, body mass index, hormone replacement therapy, and use of tobacco and alcohol. The genetic extended model included a polygenic risk score with 313 single nucleotide polymorphisms. Age-adjusted relative risks and tumor subtype specific risks were estimated by using logistic regression, and absolute risks were calculated. Results Of 70 877 participants in the KARMA cohort, 974 incident cancers were sampled from 9376 healthy women (mean age, 54 years ± 10 [standard deviation]). The area under the receiver operating characteristic curve (AUC) for the image-based model was 0.73 (95% confidence interval [CI]: 0.71, 0.74). The AUCs for the lifestyle and genetic extended models were 0.74 (95% CI: 0.72, 0.75) and 0.77 (95% CI: 0.75, 0.79), respectively. There was a relative eightfold difference in risk between women at high risk and those at general risk. High-risk women were more likely to be diagnosed with stage II cancers and with tumors 20 mm or larger and were less likely to have stage I and estrogen receptor-positive tumors. The image-based model was validated in three external cohorts. Conclusion By combining three mammographic features, differences in the left and right breasts, and optionally lifestyle factors and family history and a polygenic risk score, the model identified women at high likelihood of being diagnosed with breast cancer within 2 years of a negative screening examination and in possible need of supplemental screening.
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| 6. |
- Fieselmann, Andreas, et al.
(författare)
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Volumetric breast density measurement for personalized screening : Accuracy, reproducibility, and agreement with visual assessment
- 2018
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Ingår i: 14th International Workshop on Breast Imaging (IWBI 2018). - : SPIE. - 9781510620070 ; 10718
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Konferensbidrag (refereegranskat)abstract
- Assessment of breast density at the point of mammographic examination could lead to optimized breast cancer screening pathways. The onsite breast density information may offer guidance when to recommend supplemental imaging for women in a screening program. In this work, performance evaluation of a new software (Insight BD, Siemens Healthcare GmbH) for fast onsite quantification of volumetric breast density is presented. Accuracy of volumetric measurement is evaluated using breast tissue equivalent phantom experiments. Reproducibility of measurement results is analyzed using 8150 4-view mammography exams. Furthermore, agreement between breast density categories computed by the software with those determined visually by radiologists is examined. The results of the performance evaluation demonstrate that the software delivers accurate and reproducible measurements that agree well with the visual assessment of breast density by radiologists.
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| 7. |
- Fieselmann, Andreas, et al.
(författare)
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Volumetric breast density measurement for personalized screening : Accuracy, reproducibility, consistency, and agreement with visual assessment
- 2019
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Ingår i: Journal of Medical Imaging. - 2329-4302. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of breast density at the point of mammographic examination could lead to optimized breast cancer screening pathways. The onsite breast density information may offer guidance of when to recommend supplemental imaging for women in a screening program. A software application (Insight BD, Siemens Healthcare GmbH) for fast onsite quantification of volumetric breast density is evaluated. The accuracy of the method is assessed using breast tissue equivalent phantom experiments resulting in a mean absolute error of 3.84%. Reproducibility of measurement results is analyzed using 8427 exams in total, comparing for each exam (if available) the densities determined from left and right views, from cranio-caudal and medio-lateral oblique views, from full-field digital mammograms (FFDM) and digital breast tomosynthesis (DBT) data and from two subsequent exams of the same breast. Pearson correlation coefficients of 0.937, 0.926, 0.950, and 0.995 are obtained. Consistency of the results is demonstrated by evaluating the dependency of the breast density on women's age. Furthermore, the agreement between breast density categories computed by the software with those determined visually by 32 radiologists is shown by an overall percentage agreement of 69.5% for FFDM and by 64.6% for DBT data. These results demonstrate that the software delivers accurate, reproducible, and consistent measurements that agree well with the visual assessment of breast density by radiologists.
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| 8. |
- Frennered, Anna, et al.
(författare)
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Patterns of pathologic lymph nodes in anal cancer : a PET-CT-based analysis with implications for radiotherapy treatment volumes
- 2021
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study investigates the patterns of PET-positive lymph nodes (LNs) in anal cancer. The aim was to provide information that could inform future anal cancer radiotherapy contouring guidelines. Methods: The baseline [18F]-FDG PET-CTs of 190 consecutive anal cancer patients were retrospectively assessed. LNs with a Deauville score (DS) of ≥3 were defined as PET-positive. Each PET-positive LN was allocated to a LN region and a LN sub-region; they were then mapped on a standard anatomy reference CT. The association between primary tumor localization and PET-positive LNs in different regions were analyzed. Results: PET-positive LNs (n = 412) were identified in 103 of 190 patients (54%). Compared to anal canal tumors with extension into the rectum, anal canal tumors with perianal extension more often had inguinal (P < 0.001) and less often perirectal (P < 0.001) and internal iliac (P < 0.001) PET-positive LNs. Forty-two patients had PET-positive LNs confined to a solitary region, corresponding to first echelon nodes. The most common solitary LN region was inguinal (25 of 42; 60%) followed by perirectal (26%), internal iliac (10%), and external iliac (2%). No PET-positive LNs were identified in the ischiorectal fossa or in the inguinal area located posterolateral to deep vessels. Skip metastases above the bottom of the sacroiliac joint were quite rare. Most external iliac PET-positive LNs were located posterior to the external iliac vein; only one was located in the lateral external iliac sub-region. Conclusions: The results support some specific modifications to the elective clinical target volume (CTV) in anal cancer. These changes would lead to reduced volumes of normal tissue being irradiated, which could contribute to a reduction in radiation side-effects.
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| 9. |
- Förnvik, Daniel, et al.
(författare)
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Comparison between software volumetric breast density estimates in breast tomosynthesis and digital mammography images in a large public screening cohort
- 2019
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 29:1, s. 330-336
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare software estimates of volumetric breast density (VBD) based on breast tomosynthesis (BT) projections to those based on digital mammography (DM) images in a large screening cohort, the Malmö Breast Tomosynthesis Screening Trial (MBTST). Methods: DM and BT images of 9909 women (enrolled 2010–2015) were retrospectively analysed with prototype software to estimate VBD. Software calculation is based on a physics model of the image acquisition process and incorporates the effect of masking in DM based on accumulated dense tissue areas. VBD (continuously and categorically) was compared between BT [central projection (mediolateral oblique view (MLO)] and two-view DM, and with radiologists’ BI-RADS density 4th ed. scores. Agreement and correlation were investigated with weighted kappa (κ), Spearman’s correlation coefficient (r), and Bland–Altman analysis. Results: There was a high correlation (r = 0.83) between VBD in DM and BT and substantial agreement between the software breast density categories [observed agreement, 61.3% and 84.8%; κ = 0.61 and ĸ = 0.69 for four (a/b/c/d) and two (fat involuted vs. dense) density categories, respectively]. There was moderate agreement between radiologists’ BI-RADS scores and software density categories in DM (ĸ = 0.55) and BT (ĸ = 0.47). Conclusions: In a large public screening setting, we report a substantial agreement between VBD in DM and BT using software with special focus on masking effect. This automated and objective mode of measuring VBD may be of value to radiologists and women when BT is used as the primary breast cancer screening modality. Key Points: • There was a high correlation between continuous volumetric breast density in DM and BT.• There was substantial agreement between software breast density categories (four groups) in DM and BT; with clinically warranted binary software breast density categories, the agreement increased markedly.• There was moderate agreement between radiologists’ BI-RADS scores and software breast density categories in DM and BT.
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