Publications by authors named "P Boström"

234 Publications

Computer extracted gland features from H&E predicts prostate cancer recurrence comparably to a genomic companion diagnostic test: a large multi-site study.

NPJ Precis Oncol 2021 May 3;5(1):35. Epub 2021 May 3.

Department of Urology, Case Western Reserve University, Cleveland, OH, USA.

Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p < 0.001, univariable hazard ratio [HR] = 2.83, 95% confidence interval [CI]: 2.03-3.93, concordance index [c-index] = 0.68, median years-to-BCR: 1.7). Histotyping was also prognostic in clinically stratified subsets, such as patients with Gleason grade group 3 (HR = 4.09) and negative surgical margins (HR = 3.26). Histotyping was prognostic independent of grade group, margin status, pathological stage, and preoperative prostate-specific antigen (PSA) (multivariable p < 0.001, HR = 2.09, 95% CI: 1.40-3.10, n = 648). The combination of Histotyping, grade group, and preoperative PSA outperformed Decipher (c-index = 0.75 vs. 0.70, n = 167). These results suggest that a prognostic classifier for prostate cancer based on digital images could serve as an alternative or complement to molecular-based companion diagnostic tests.
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http://dx.doi.org/10.1038/s41698-021-00174-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093226PMC
May 2021

A three-feature prediction model for metastasis-free survival after surgery of localized clear cell renal cell carcinoma.

Sci Rep 2021 Apr 21;11(1):8650. Epub 2021 Apr 21.

Department of Oncology and Radiotherapy, Fican West Cancer Centre, University of Turku and Turku University Hospital, Hämeentie 11, Post Box 52, 20521, Turku, Finland.

After surgery of localized renal cell carcinoma, over 20% of the patients will develop distant metastases. Our aim was to develop an easy-to-use prognostic model for predicting metastasis-free survival after radical or partial nephrectomy of localized clear cell RCC. Model training was performed on 196 patients. Right-censored metastasis-free survival was analysed using LASSO-regularized Cox regression, which identified three key prediction features. The model was validated in an external cohort of 714 patients. 55 (28%) and 134 (19%) patients developed distant metastases during the median postoperative follow-up of 6.3 years (interquartile range 3.4-8.6) and 5.4 years (4.0-7.6) in the training and validation cohort, respectively. Patients were stratified into clinically meaningful risk categories using only three features: tumor size, tumor grade and microvascular invasion, and a representative nomogram and a visual prediction surface were constructed using these features in Cox proportional hazards model. Concordance indices in the training and validation cohorts were 0.755 ± 0.029 and 0.836 ± 0.015 for our novel model, which were comparable to the C-indices of the original Leibovich prediction model (0.734 ± 0.035 and 0.848 ± 0.017, respectively). Thus, the presented model retains high accuracy while requiring only three features that are routinely collected and widely available.
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http://dx.doi.org/10.1038/s41598-021-88177-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060273PMC
April 2021

Characteristics of clinically node negative breast cancer patients needing preoperative MRI.

Surg Oncol 2021 Mar 31;38:101552. Epub 2021 Mar 31.

Department of Oncology, Turku University Hospital, Finland; University of Turku, Turku, Finland; Finnish Nuclear and Radiation Safety, Helsinki, Finland.

Background: International guidelines do not recommend magnetic resonance imaging (MRI) for all breast cancer patients at primary diagnostics. This study aimed to understand which patient or tumor characteristics are associated with the use of MRI. The role of MRI among other preoperative imaging methods in clinically node negative breast cancer was studied.

Material And Methods: Patient and tumor characteristics were analyzed in association with the use of MRI by multivariable logistic regression analysis in 461 patients. Primary tumor size was compared between MRI, mammography (MGR), ultrasound (US) and histopathology by Spearman correlation. The delays in surgery and diagnosis were analyzed among patients with or without MRI, and axillary reoperations were evaluated.

Results: Age (p < 0.0001), primary operation method (p < 0.0001), tumor histology (p < 0.0001) and HER2 status (p = 0.0064) were associated with the use of MRI. Spearman correlations between tumor size in histopathology and the difference in tumor size between histopathology and imaging methods were 0.52 in MGR, 0.66 in US and 0.36 in MRI (p < 0.0001 for all). A seven-day delay in surgical treatment was observed among patients with MRI compared to patients without MRI (p < 0.0001). Axillary reoperation rates were similar in patients with or without MRI (p = 0.57).

Conclusion: Patient selection through prearranged characterization is important in deciding on optimal candidates for preoperative MRI among breast cancer patients. MRI causes moderate delays in primary breast cancer surgery. Preoperative MRI is useful in the evaluation of tumor size but might be insufficient in detecting lymph node metastases.
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http://dx.doi.org/10.1016/j.suronc.2021.101552DOI Listing
March 2021

Kinetic analysis and optimisation of F-rhPSMA-7.3 PET imaging of prostate cancer.

Eur J Nucl Med Mol Imaging 2021 Apr 12. Epub 2021 Apr 12.

Clinical Research Services Turku - CRST Ltd, Turku, Finland.

Purpose: This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, F-rhPSMA-7.3, to optimise its use for imaging of prostate cancer.

Methods: Nine men, three with high-risk localised prostate cancer, three with treatment-naïve hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq F-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35-45, 60-88 and 90-118 min. Net influx rates (K) were calculated using Patlak plots.

Results: Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The F-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. K, SUV and lesion-to-reference ratio estimates showed good agreement.

Conclusion: F-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, F-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer.

Trial Registration: NCT03995888 (24 June 2019).
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http://dx.doi.org/10.1007/s00259-021-05346-8DOI Listing
April 2021

Prospective comparison of F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

Eur J Nucl Med Mol Imaging 2021 Mar 13. Epub 2021 Mar 13.

Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.

Purpose: To prospectively compare F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa).

Methods: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used.

Results: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively.

Conclusion: F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.

Clinical Trial Registration: Clinicaltrials.gov ID: NCT03537391.
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http://dx.doi.org/10.1007/s00259-021-05296-1DOI Listing
March 2021