Computational pathological identification of prostate cancer following neoadjuvant treatment.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14052-e14052
Author(s):  
Belma Dogdas ◽  
Christopher Kanan ◽  
Patricia Raciti ◽  
Shaozhou Ken Tian ◽  
Sabine Doris Brookman-May ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Residual Disease ◽  
Characteristic Curve ◽  
False Negative ◽  
Neoadjuvant Treatment ◽  
Area Under The Curve ◽  
Residual Tumor ◽  
Correct Identification ◽  
Pathological Assessment

e14052 Background: The need for accurate pathological identification and quantitation of prostate cancer (PC) following neoadjuvant treatment with androgen deprivation therapy (ADT) and androgen receptor antagonists is increasing as PC treatment continues to evolve. In clinical practice, pathological assessment of residual tumor is a tedious and time-consuming process due to the volume of tissue from radical prostatectomy (RP). In addition, neoadjuvant treatments can greatly alter both benign and neoplastic prostate tissue morphology making the pathology assessment difficult for even specialized pathologists. Paige Prostate 1.0 is a clinical-grade artificial intelligence (AI) system for PC detection. It was trained and evaluated in over 50,000 prostate biopsy slides with validation across more than 800 institutions worldwide using multiple slide scanners. Methods: We evaluated the performance of Paige Prostate 1.0 at identifying prostatic tumor on 64 hematoxylin and eosin stained slides exhibiting neoadjuvant treatment effect from apalutamide, enzalutamide, and/or ADT. Results: Analysis of the receiver operating characteristic curve demonstrated an area under the curve of 0.96. Using the Paige Prostate 1.0 operating point, it achieved a sensitivity of 91% and a specificity of 94%, corresponding to the correct identification of challenging treated morphology in 59/64 slides using expert pathologists as the reference. False negative cases were typically represented by atypical small acinar proliferation that required expert pathological consensus confirmation. Conclusions: To our knowledge, this is the first AI based evaluation of residual disease in PC with hormone neoadjuvant therapy. Paige Prostate 1.0 effectively identified tumor despite treatment effects. Future work will include optimization of Paige Prostate 1.0 by training with RP specimens from a larger cohort of appropriate samples, as well as precise measurement of residual tumor burden to further improve its accuracy and reproducibility. Paige prostate residual disease detection 1.0 has the potential to impact emerging clinical practice at the patient level and to complement the pathological assessment of RPs in global phase 3 clinical trials, such as PROTEUS, in a standardized, reproducible, and robust way.

scholarly journals A Novel System for Estimating Residual Disease and Pathologic Response to Neoadjuvant Treatment of Prostate Cancer

The Prostate ◽  
2016 ◽  
Vol 76 (14) ◽  
pp. 1285-1292 ◽  
Author(s):  
Claire Murphy ◽  
Lawrence True ◽  
Funda Vakar-Lopez ◽  
Jing Xia ◽  
Roman Gulati ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Residual Disease ◽  
Neoadjuvant Treatment ◽  
Pathologic Response

scholarly journals The value of 18F-PSMA-1007 PET/CT in identifying non-metastatic high-risk prostate cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jun-jie Hong ◽  
Bo-le Liu ◽  
Zhi-qiang Wang ◽  
Kun Tang ◽  
Xiao-wei Ji ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Prostate Tumor ◽  
High Risk Prostate Cancer ◽  
Standardized Uptake Values ◽  
Pet Ct ◽  
Primary Prostate Tumor

Abstract Background Clinical management decisions on prostate cancer (PCa) are often based on a determination of risk. 68Ga-prostate-specific membrane antigen (PSMA)-11-positron emission tomography (PET)/computer tomography (CT) is an attractive modality to assess biochemical recurrence of PCa, detect metastatic disease and stage of primary PCa, making it a promising strategy for risk stratification. However, due to some limitation of 68Ga-PSMA-11 the development of alternative tracers is of high interest. In this study, we aimed to investigate the value of 18F-PSMA-1007 in identifying non-metastatic high-risk PCa. Methods A total of 101 patients with primary non-metastatic PCa who underwent 18F-PSMA-1007 PET/CT were retrospectively analyzed. According to the European Association of Urology guidelines on PCa, patients were classified into intermediate-risk (IR) group or high-risk (HR) group. The maximum standardized uptake values (SUVmax) of the primary prostate tumor were measured on PET/CT images. The diagnostic performance of PET/CT for IR and HR PCa was calculated, and the relationship between the SUVmax of primary prostate tumor, prostate-specific antigen (PSA) level and Gleason score (GS) was analyzed. Results Of all 101 patients, 49 patients were classified into IR group and 52 patients were classified into HR group. There was a significant positive correlation between PSA level/GS and SUVmax (r = 0.561, r = 0.496, P < 0.001, respectively). Tumors with GS 6 and 7a showed significantly lower 18F-PSMA-1007 uptake compared to patients with GS 8 and 9 (P < 0.01). SUVmax in patients of HR was significantly higher than those of IR (median SUVmax: 16.85 vs 7.80; P < 0.001). In receiver operating characteristic curve analysis, the optimal cutoff value of the SUVmax for identifying high-risk PCa was set as 9.05 (area under the curve: 0.829; sensitivity: 90.4%; specificity: 65.3%). Conclusion 18F-PSMA-1007 PET/CT showed the powerful diagnosis efficacy for high-risk PCa, which can be used as an objective imaging reference index for clinical reference.

Neoadjuvant chemotherapy with metronomic doxorubicin, cyclophosphamide, and capecitabine in patients with locally advanced (LA) triple-negative breast cancer (TNBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12027-e12027
Author(s):  
Mona Frolova ◽  
Marina Skrypnikova ◽  
Ekaterina Ignatova ◽  
Alexander Petrovsky ◽  
Marina Stenina ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Cumulative Dose ◽  
Residual Disease ◽  
Locally Advanced ◽  
Pilot Trial ◽  
Survival Rates ◽  
Neoadjuvant Treatment ◽  
Residual Tumor ◽  
Complete Regression ◽  
Grade 3

e12027 Background: TNBC is associated with aggressive behavior and poor prognosis. It has been shown that patients (pts) with TNBC with pathological complete regression (pCR) after neoadjuvant chemotherapy have a higher survival. Rates of pCR with standard antracycline- and taxanebased chemotherapy regimens don’t exceed 20-27%. Dose-dense and metronomic schedules may be more effective in these highly proliferative tumors. We performed a prospective pilot trial to evaluate efficacy of metronomic schedule of doxorubicin, cyclophosphamide and capecitabine in pts with LA TNBC. Methods: Pts with LA TNBC (cT2-4N1-3M0) were treated with doxorubicin 25 mg/m2 iv weekly, cyclophosphamide 50 mg po daily and capecitabine 1500 mg po daily for planned 16-19 weeks followed by surgery. Pathological response was evaluated according to the Chevallier classification. Results: Twenty pts was included in the study in 2009-2010. Median agewas 47 years (33-70), 63% of pts had tumor grade 3, Ki67 was >20% in all cases. Nineteen pts completed chemotherapy (median treatment duration 17.1 weeks) and underwent surgery. One pt had a disease progression during chemotherapy and was switched to 2nd-line chemotherapy. Seven pts (36,8%) achieved a pCR (6 pts class 1 and 1 pt class 2). With median follow-up of 33 months, 3-year DFS and OS were 60%. All but one pt with pCR, who developed brain mts shortly after surgery, are currently alive without relapse. In contrast 50% of pts with residual tumor relapsed. Pts with pCR had significantly higher median cumulative dose of doxorubicin (420 mg/m2) than pts with residual disease (300 mg/m2, p=0.046). The dose-limiting toxicities were hand-foot syndrome (26.3% grade 3), mucositis (31.6% grade 3), and neutropenia (31.6% grade 3-4), which resulted in permanent discontinuation of doxorubicin in 4 pts. Conclusions: Despiterelatively hightoxicity metronomic doxorubicin, cyclophosphamide and capecitabine regimen shows promising activity as neoadjuvant treatment of LA TNBC. Achievement of pCR and higher cumulative dose of doxorubicin were strongly associated with improvement of survival.

scholarly journals Risk assessment and receiver operating characteristic curves

2011 ◽  
Vol 42 (5) ◽  
pp. 895-898 ◽  
Author(s):  
G. Szmukler ◽  
B. Everitt ◽  
M. Leese
Keyword(s):  
Risk Assessment ◽  
Clinical Practice ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Assessment Instruments ◽  
Receiver Operating Characteristic Curves ◽  
Operating Characteristic Curve ◽  
Receiver Operating

Risk assessment is now regarded as a necessary competence in psychiatry. The area under the curve (AUC) statistic of the receiver operating characteristic curve is increasingly offered as the main evidence for accuracy of risk assessment instruments. But, even a highly statistically significant AUC is of limited value in clinical practice.

scholarly journals A new oncolyticVacciniavirusaugments antitumor immune responses to prevent tumor recurrence and metastasis after surgery

2020 ◽  
Vol 8 (1) ◽  
pp. e000415 ◽  
Author(s):  
Jahangir Ahmed ◽  
Louisa S Chard ◽  
Ming Yuan ◽  
Jiwei Wang ◽  
Anwen Howells ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Residual Disease ◽  
Neoadjuvant Treatment ◽  
Residual Tumor ◽  
Oncolytic Viruses ◽  
Postoperative Survival ◽  
Interleukin 12 ◽  
Patients With Cancer ◽  
Post Surgery ◽  
Attractive Option

BackgroundLocal recurrence and remote metastasis are major challenges to overcome in order to improve the survival of patients with cancer after surgery. Oncolytic viruses are a particularly attractive option for prevention of postsurgical disease as they offer a non-toxic treatment option that can directly target residual tumor deposits and beneficially modulate the systemic immune environment that is suppressed post surgery and allows residual disease escape from control. Here, we report that a novelVaccinia virus(VV), VVΔTKΔN1L (with deletion of both thymidine kinase (TK) and N1L genes) armed with interleukin 12 (IL-12), can prolong postoperative survival when used as a neoadjuvant treatment in different murine and hamster surgical models of cancer.MethodsA tumor-targeted replicating VV with deletion of TK gene and N1L gene (VVΔTKΔN1L) was created. This virus was armed rationally with IL-12. The effect of VVΔTKΔN1L and VVΔTKΔN1L-IL12 on modulation of the tumor microenvironment and induction of tumor-specific immunity as well the feasibility and safety as a neoadjuvant agent for preventing recurrence and metastasis after surgery were assessed in several clinically relevant models.ResultsVVΔTKΔN1L can significantly prolong postoperative survival when used as a neoadjuvant treatment in three different surgery-induced metastatic models of cancer. Efficacy was critically dependent on elevation of circulating natural killer cells that was achieved by virus-induced cytokine production from cells infected with N1L-deleted, but not N1L-intact VV. This effect was further enhanced by arming VVΔTKΔN1L with IL-12, a potent antitumor cytokine. Five daily treatments with VVΔTKΔN1L-IL12 before surgery dramatically improved postsurgical survival. VVΔTKΔN1L armed with human IL-12 completely prevented tumor recurrence in surgical models of head and neck cancer in Syrian hamsters.ConclusionsThese data provide a proof of concept for translation of the regime into clinical trials. VVΔTKΔN1L-IL12 is a promising agent for use as an adjuvant to surgical treatment of solid tumors.

mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy

2006 ◽  
Vol 387 (6) ◽  
pp. 789-793 ◽  
Author(s):  
Andreas Scorilas ◽  
Alkiviades K. Gregorakis
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Transrectal Ultrasound ◽  
Area Under The Curve ◽  
Prostatic Hyperplasia ◽  
Crude Odds Ratio ◽  
Prostate Biopsies ◽  
Mrna Expression Analysis

AbstractKallikrein 11 (KLK11,TLSP, hippostatin) is a member of the human kallikrein gene family, which includes PSA,KLK2and 12 other members, all localized on chromosome 19q13.4. The aim of this study was to investigate whetherKLK11expression could be used to discriminate prostate cancer (CaP) from benign prostatic hyperplasia (BPH) in needle prostate biopsies. We analyzed the expression of the prostate-type variant of theKLK11gene in 64 CaP and BPH tissues obtained by transrectal ultrasound-guided needle biopsy. Reverse transcription (RT), PCR and image analysis methodologies were developed and used. Of the 42 BPH tissues examined, only 10 (23.8%) were positive for prostate-typeKLK11expression, while of the 22 CaP patients, 12 (54.5%) wereKLK11-positive (p=0.025). Logistic regression and receiver operating characteristic curve analyses demonstrated thatKLK11expression has a significant discriminatory value (crude odds ratio=3.84,p=0.016; area under the curve, 0.65, 95% CI 0.51–0.80) between CaP and BPH in needle prostate biopsies.

scholarly journals Detection of Prostate Cancer Antigen 3 and Prostate Cancer Susceptibility Candidate in Non-DRE Urine Improves Diagnosis of Prostate Cancer in Chinese Population

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Lie-Fu Ye ◽  
Sha He ◽  
Xiaopei Wu ◽  
Shengying Jiang ◽  
Ruo-Chen Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Prostate Biopsy ◽  
Chinese Population ◽  
Cancer Susceptibility ◽  
Characteristic Curve ◽  
Unmet Need ◽  
High Grade ◽  
Predictive Values ◽  
Reverse Transcription Pcr

Although prostate biopsy is the gold standard for the diagnosis of prostate cancer, it also leads to high incidence of negative biopsies and the diagnosis of clinically low-risk prostate cancer and the subsequent overtreatment. It remains an unmet need to discover new biomarkers in order to defer the unnecessary biopsies in clinical practice. In this study, we described a new method, LBXexo score, to measure the urine exosomal PCA3/PRAC expression from non-DRE urine as a noninvasive diagnosis to improve the detection rate in Chinese population with a low serum PSA level. First-voided urine samples were collected to isolate exosomes, and exosomal RNAs of PCA3 and PRAC were measured by quantitative reverse transcription PCR. A significant increase in exoPCA3/PRAC was observed in both any-grade and high-grade prostate cancer groups when compared with the biopsy-negative group. Receiver-operating characteristic curve analyses showed that the LBXexo score significantly improved diagnostic performance in predicting biopsy results, with AUCs of 0.723 (p=0.017) and 0.736 (p=0.038) for any-grade and high-grade (GS ≥ 7) prostate cancer, respectively. For high-grade cancer, LBXexo had the negative and positive predictive values of 100% and 27.59%, respectively, and could potentially avoid unnecessary biopsy. This is the first report in Chinese population that demonstrates the predictive value of the exosomal expression of PCA3 and PRAC derived from non-DRE urine in predicting prostate biopsy outcomes. It could be used in clinical practice to make a better informed biopsy decision and avoid unnecessary biopsies in Chinese population.

Clinical evaluation of a new thyroglobulin immunoradiometric assay in the follow-up of differentiated thyroid carcinoma

2003 ◽  
Vol 42 (02) ◽  
pp. 71-77 ◽  
Author(s):  
I. Schreivogel ◽  
C. Angerstein ◽  
U. Siefker ◽  
K. Lehmann ◽  
G. Altenvoerde ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Residual Disease ◽  
False Negative ◽  
Differentiated Thyroid Carcinoma ◽  
Threshold Concentration ◽  
High Rate ◽  
Functional Assay ◽  
Hypothyroid Patient ◽  
Assay Sensitivity ◽  
Significant Difference

SummaryAim: Formal and clinical comparison of a new 3rd-gene-ration-Tg-IRMA (3-G-IRMA; Dynotest®Tg-plus) with a conventional Tg-IRMA (3-G-IRMA; SELco®Tg-assay) for patients with differentiated thyroid carcinoma. In addition we evaluated, if thyroglobulin (Tg) levels above a specific threshold concentration indicate the need for further investigations for residual disease. Patients, methods: Tg concentration of 105 sera of 93 consecutive patients with a differentiated thyroid cancer was determined with both assays and compared at different cut-off values (Dynotest®Tg-plus: 0.2, 1, 2 ng/ml; SELco®Tg-assay: 0.5, 1, 2 ng/ml) with the clinical results in respect to the corresponding TSH concentration. Results: Tg concentration did not show any significant difference (SELco®Tg-assay 0.5 ng/ml, Dynotest® Tg-plus 0.2 ng/ml). The Tg-values of both assays correlated with 97%. However, correlation of recovery in both assays was small (40%). The sensitivities and specificities of both assays at different cut-offs and TSH values did not reveal significant differences. In patients with TSH concentration >30 µU/ml the functional assay sensitivity was superior to arbitrary cut-offs in the decision to start further evaluations. Conclusions: In our study neither formal nor clinical significant differences between two Tg-assays were found. In a hypothyroid patient (TSH >30 µU/ml, Tg concentration exceeding the functional assay sensitivity) further investigations for residual disease are warranted. Higher thresholds are of limited value, due to a inacceptable high rate of false negative results.

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