scholarly journals Subgrouping of Unfavorable Histology Neuroblastomas With Immunohistochemistry Toward Precision Prognosis and Therapy Stratification

2019 ◽  
pp. 1-7 ◽  
Author(s):  
Naohiko Ikegaki ◽  
Hiroyuki Shimada ◽  
Keyword(s):  
Therapy Stratification

Automated immunostaining-free prediction of breast carcinoma ER and PR status, Ki67 count, patient therapy stratification index and quantification of prognostic quiescence burden in TNBC from pretreatment H&E stained histopathology images in breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12535-e12535
Author(s):  
Tathagata Dasgupta ◽  
Satabhisa Mukhopadhyay ◽  
Nicolas M Orsi ◽  
Michele Cummings ◽  
Angelene Berwick
Keyword(s):  
Low Cost ◽  
A Priori ◽  
Disease Recurrence ◽  
Mitotic Checkpoint ◽  
Luminal A ◽  
Slide Image ◽  
Luminal Type ◽  
Therapy Stratification ◽  
Pre Treatment ◽  
Stratification System

e12535 Background: Categorical combinations of ER, PR, HER2, and Ki67 levels are traditionally used to classify patients into luminal A and B-like subtypes in order to inform treatment choice. Accounting for nearly 70% of all breast malignancies, luminal cancer is heterogeneous, harboring subtypes with distinct molecular profiles and clinical outcomes. Although most patients with luminal-type disease respond well to endocrine therapy alone, some develop recurrences benefiting from additional cytotoxic therapy. Identifying such cases a priori remains a challenge but would enable patients to be spared the debilitating side-effects of ineffective chemotherapy. In this regard, the efficacy of chemotherapy and disease recurrence relate to (i) ER driven G1/S perturbations and/or (ii) quiescent cell populations arrested in the G0/G1 phase of cell cycle. This study aimed to develop a histopathology whole slide image (WSI)-based, low cost, rapid and automated approach to: (i) predict ER/PR/Ki67 status, (ii) quantify quiescence burden, (iii) develop a G1/S-based patient stratification system for luminal A/B patients, and (iv) achieve a quiescence burden-based stratification of TNBC patients. Methods: This investigation centered on the initial clinical validation of a novel, immunostaining-free technology which uses information extracted from pre-treatment hematoxylin and eosin (H&E) stained slide WSIs alone to achieve these aims. Unlike conventional artificial intelligence-based approaches, the underlying proprietary algorithm and its prediction criteria are based on deterministic, hard-coded observational relationships of continuous scales drawn from WSI morphological features. In this instance, these represent tumor-related biological pathway disruptions and mitotic checkpoint perturbations, where G1/S perturbations enable luminal subtype stratification, and G0/G1 perturbations reflect quiescence burden. Back projecting the algorithm’s quiescence burden output on to the original WSIs enables morphological patterns to be mapped to quiescence burden.

Molecular profiling of genetic changes by a multi-genomic approach for neuroblastoma subtyping and therapy stratification

2010 ◽  
Vol 203 (1) ◽  
pp. 87
Author(s):  
Marta Jeison ◽  
Gili Halevy-Berko ◽  
Galina Feinberg-Gorenshtein ◽  
Lana Itskovitch ◽  
Shifra Ash ◽  
...  
Keyword(s):  
Molecular Profiling ◽  
Genetic Changes ◽  
Genomic Approach ◽  
Therapy Stratification

Quality Assessment of Genetic Markers Used for Therapy Stratification

2003 ◽  
Vol 21 (11) ◽  
pp. 2077-2084 ◽  
Author(s):  
I.M. Ambros ◽  
J. Benard ◽  
M. Boavida ◽  
N. Bown ◽  
H. Caron ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Tumor Cell ◽  
Quality Assessment ◽  
Genetic Markers ◽  
Molecular Genetic ◽  
Molecular Techniques ◽  
Cell Content ◽  
Therapeutic Decisions ◽  
Therapy Stratification

Purpose: Therapy stratification based on genetic markers is becoming increasingly important, which makes commitment to the highest possible reliability of the involved markers mandatory. In neuroblastic tumors, amplification of the MYCN gene is an unequivocal marker that indicates aggressive tumor behavior and is consequently used for therapy stratification. To guarantee reliable and standardized quality of genetic features, a quality-assessment study was initiated by the European Neuroblastoma Quality Assessment (ENQUA; connected to International Society of Pediatric Oncology) Group. Materials and Methods: One hundred thirty-seven coded specimens from 17 tumors were analyzed in 11 European national/regional reference laboratories using molecular techniques, in situ hybridization, and flow and image cytometry. Tumor samples with divergent results were re-evaluated. Results: Three hundred fifty-two investigations were performed, which resulted in 23 divergent findings, 17 of which were judged as errors after re-evaluation. MYCN analyses determined by Southern blot and in situ hybridization led to 3.7% and 4% of errors, respectively. Tumor cell content was not indicated in 32% of the samples, and 11% of seemingly correct MYCN results were based on the investigation of normal cells (eg, Schwann cells). Thirty-eight investigations were considered nonassessable. Conclusion: This study demonstrated the importance of revealing the difficulties and limitations for each technique and problems in interpreting results, which are crucial for therapeutic decisions. Moreover, it led to the formulation of guidelines that are applicable to all kinds of tumors and that contain the standardization of techniques, including the exact determination of the tumor cell content. Finally, the group has developed a common terminology for molecular-genetic results.

Preoperative analysis of 11q loss using circulating tumor-released DNA in serum: A novel diagnostic tool for therapy stratification of neuroblastoma

2011 ◽  
Vol 309 (2) ◽  
pp. 185-189 ◽  
Author(s):  
Shigeki Yagyu ◽  
Tomoko Iehara ◽  
Takahiro Gotoh ◽  
Mitsuru Miyachi ◽  
Yoshiki Katsumi ◽  
...  
Keyword(s):  
Diagnostic Tool ◽  
Therapy Stratification ◽  
Preoperative Analysis

Type, intensity, and duration of chemotherapy (CHT) and their correlation with prognosis of localized soft tissue Ewing tumors (STET): Experience of the Cooperative Weichteilsarkomstudiengruppe (CWS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10527-10527
Author(s):  
Ewa Koscielniak ◽  
Monika Scheer ◽  
Monika Sparber-Sauer ◽  
Erika Hallmen ◽  
Ivo Leuschner ◽  
...  
Keyword(s):  
Actinomycin D ◽  
Risk Group ◽  
Tumor Resection ◽  
Observation Time ◽  
High Risk Group ◽  
Secondary Resection ◽  
Ewing Tumors ◽  
Risk Patients ◽  
Therapy Stratification ◽  
Optimal Type

10527 Background: The optimal type and intensity of CHT in the treatment of STET is still a matter of debate. The CWS group has treated STET similar to rhabdomyosarcoma. We have analyzed the prognosis of STET in relation to the CHT regimens used in three consecutive CWS studies CWS-91, -96 and CWS- 2002P. Methods: 243 pts with localized STET were included. Their median age was 12 (range 0.1-29) yrs. In the CWS-91 pts with primary tumor resection (IRSG I and II) were treated with VACA (vincristine (VCR), actinomycin D (Act D), cyclophosphamide (CYC), doxorubicin (DOX), for 10 or 20 weeks. All other CWS-91 pts (high risk group, HRG) received EVAIA (ifosfamide (IFO) instead of CYC plus VP16) for 37 weeks. In the CWS-96 and CWS-2002P all STET pts were allocated to the HRG. In CWS-96 therapy was randomized: VAIA (IFO, DOX, Act D, VCR) vs. CEVAIE (Epi-DOX instead of DOX, plus carboplatin and VP16), for 25 weeks. In CWS-2002P VAIA (25 weeks) plus maintenance CHT with CYC and vinblastine (VBL) for 26 weeks were used. The cumulative doses varied: IFO 24-72 g/m², CYC 4.8-7.35 g/m², DOX 120-360 mg/m², Act D 3-9 mg/m², VP16 1.8-5.4 g/m². Irradiation was stratified depending on results of the primary or secondary resection and response. Results: 5 yr event free (EFS) and overall survival (OS) were 64% and 73%. The median observation time of survivors was 9 yrs. 5yr EFS and OS by study were: CWS-91 64 % and 72 %, CWS-96 57% and 70 %, CWS-2002P 78 % and 86 % respectively (n.s.). 5 yr EFS and OS for VACA arm were 79% and 90%. 5 yr EFS and OS by CHT for HRG were: EVAIA 57% and 65%, VAIA 64% and 80%, CEVAIE 45% and 54%, VAIA with CYC/VBL 84% and 87%, respectively (p = 0 .003). 5yr EFS and OS for irradiated (n = 181) vs. not irradiated (n = 48) patients were 63 % and 72% vs. 63% and 79%, respectively. Conclusions: The outcomes between CHT arms differed significantly: CEVAIA correlated with the worst outcome while VAIA with CYC/VBL showed the best results. A small group of low risk patients have an excellent prognosis with substantially reduced CHT. Ewing tumors are biologically heterogeneous and more diversification in therapy stratification is warranted to avoid overtreatment.

scholarly journals PO-451 Targeted proteomics to improve therapy stratification of cancer patients

2018 ◽  
Author(s):  
S Wiemann ◽  
L Wahjudi ◽  
S Bernhardt ◽  
K Abnaof ◽  
D Richter ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Targeted Proteomics ◽  
Therapy Stratification

scholarly journals RNA Profiles of Circulating Tumor Cells and Extracellular Vesicles for Therapy Stratification of Metastatic Breast Cancer Patients

2018 ◽  
Vol 64 (7) ◽  
pp. 1054-1062 ◽  
Author(s):  
Corinna Keup ◽  
Pawel Mach ◽  
Bahriye Aktas ◽  
Mitra Tewes ◽  
Hans-Christian Kolberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Extracellular Vesicles ◽  
Therapy Monitoring ◽  
Quantitative Polymerase Chain Reaction ◽  
Metastatic Breast ◽  
Therapy Stratification

Abstract BACKGROUND Liquid biopsies are discussed to provide surrogate markers for therapy stratification and monitoring. We compared messenger RNA (mRNA) profiles of circulating tumor cells (CTCs) and extracellular vesicles (EVs) in patients with metastatic breast cancer (MBC) to estimate their utility in therapy management. METHODS Blood was collected from 35 hormone receptor-positive/HER2-negative patients with MBC at the time of disease progression and at 2 consecutive staging time points. CTCs were isolated from 5 mL of blood by positive immunomagnetic selection, and EVs from 4 mL of plasma by a membrane affinity-based procedure. mRNA was reverse transcribed, preamplified, and analyzed for 18 genes by multimarker quantitative polymerase chain reaction (qPCR) assays. RNA profiles were normalized to healthy donor controls (n = 20), and results were correlated with therapy outcome. RESULTS There were great differences in mRNA profiles of EVs and CTCs, with only 5% (21/403) of positive signals identical in both fractions. Transcripts involved in the PI3K signaling pathway were frequently overexpressed in CTCs, and AURKA, PARP1, and SRC signals appeared more often in EVs. Of all patients, 40% and 34% showed ERBB2 and ERBB3 signals, respectively, in CTCs, which was significantly associated with disease progression (P = 0.007). Whereas MTOR signals in CTCs significantly correlated with response (P = 0.046), signals in EVs indicated therapy failure (P = 0.011). The presence of AURKA signals in EVs seemed to be a marker for the indication of unsuccessful treatment of bone metastasis. CONCLUSIONS These results emphasize the potential of CTCs and EVs for therapy monitoring and the need for critical evaluation of the implementation of any liquid biopsy in clinical practice.

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