scholarly journals MBCL-13. CORRELATION OF HISTOPATHOLOGY, CHROMOSOMAL MICROARRAY, AND NANOSTRING BASED 22-GENE ASSAY FOR MEDULLOBLASTOMA SUBGROUP ASSIGNMENT ON “HEAD START” 4 CLINICAL TRIAL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii390-iii390
Author(s):  
Girish Dhall ◽  
Parth Patel ◽  
Megan Blue ◽  
Jaclyn Biegel ◽  
Isabel Almiraz-Suarez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Head Start ◽  
Prognostic Significance ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Molecular Subgroups ◽  
Myeloablative Chemotherapy ◽  
Group 4 ◽  
Gene Assay ◽  
Group 3

Abstract “Head Start” 4 (HS 4) is a prospective randomized clinical trial that tailors treatment based on medulloblastoma molecular subgroups and response to induction chemotherapy to compare efficacy of one versus three (tandem) cycles of myeloablative chemotherapy. Advances in RNA and DNA profiling have identified four molecular subgroups of medulloblastoma with prognostic significance: Sonic Hedgehog (SHH) subtype, WNT subtype, Group 3, and Group 4. In HS 4 trial, we utilize a combination of histopathology and immunohistochemistry (pathology/IHC), as well as chromosomal microarray analysis (CMA) utilizing OncoScanTM (Thermo Fisher) to classify medulloblastoma samples into either SHH, WNT, or non-WNT/non-SHH (Group 3/4) subgroups at the time of diagnosis. NanoString based 22-gene assay is performed retrospectively to test concordance. We have pathology/IHC, CMA, and NanoString data on 26 infants and young children with medulloblastoma enrolled on HS 4. Pathology/IHC was able to assign samples to SHH, WNT, and non-WNT/non-SHH subgroups in all but two cases: one case was classified as Group 3, and the second as SHH by both CMA and NanoString. CMA was indeterminate in six cases, of which, pathology/IHC was able to assign all six samples aforementioned three subgroups. NanoString was indeterminate in two cases: one case was classified as SHH by CMA and pathology/IHC, and the second case was indeterminate by CMA but was assigned as non-WNT/non-SHH on pathology/IHC. There is excellent correlation between NanoString and combination of histopathology and CMA for core medulloblastoma subgrouping on HS 4. Methylation studies are ongoing.

scholarly journals EMBR-08. CORRELATION OF HISTOPATHOLOGY, CHROMOSOMAL MICROARRAY, AND NANOSTRING BASED 22-GENE ASSAY FOR MEDULLOBLASTOMA SUBGROUP ASSIGNMENT ON “HEAD START” 4 CLINICAL TRIAL

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Girish Dhall ◽  
Parth Patel ◽  
Megan Blue ◽  
Jaclyn Biegel ◽  
Isabel Almiraz-Suarez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Head Start ◽  
Prognostic Significance ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Molecular Subgroups ◽  
Group 4 ◽  
Gene Assay ◽  
Group 3 ◽  
Infants And Young Children

Abstract “Head Start” 4 (HS 4) is a prospective randomized clinical trial that tailors treatment based on medulloblastoma molecular subgroups and response to induction chemotherapy to compare the efficacy of one versus three (tandem) cycles of myeloablative therapy. Advances in RNA and DNA profiling have identified four core molecular subgroups of medulloblastoma with prognostic significance: Sonic Hedgehog (SHH) subtype, WNT subtype, Group 3, and Group 4. In HS 4 trial, we utilize a combination of histopathology and immunohistochemistry (pathology/IHC), as well as chromosomal microarray analysis (CMA) utilizing OncoScanTM (Thermo Fisher) to classify medulloblastoma samples into either SHH, WNT, or non-WNT/non-SHH (Group 3/4) subgroups at the time of diagnosis. NanoString based 22-gene assay is performed retrospectively to test concordance. We have pathology/IHC, CMA, and NanoString data on 26 infants and young children with medulloblastoma enrolled on HS 4. Pathology/IHC was able to assign samples to SHH, WNT, and non-WNT/non-SHH subgroups in all but two cases: one case was classified as Group 3, and the second as SHH by both CMA and NanoString. CMA was indeterminate in six cases, of which, pathology/IHC was able to assign all six samples aforementioned three subgroups. NanoString was indeterminate in two cases: one case was classified as SHH by CMA and pathology/IHC, and the second case was indeterminate by CMA but was assigned as non-WNT/non-SHH on pathology/IHC. There is excellent correlation between NanoString and combination of histopathology and CMA for core medulloblastoma subgrouping on HS 4. Methylation studies are ongoing.

scholarly journals Randomised clinical trial showing the curative effect of bandaging on M2-stage lesions of digital dermatitis in dairy cows

2019 ◽  
Vol 6 (1) ◽  
pp. e000264 ◽  
Author(s):  
Marcus Klawitter ◽  
Dörte Döpfer ◽  
Theo Broderick Braden ◽  
Ermias Amene ◽  
Kerstin Elisabeth Mueller
Keyword(s):  
Clinical Trial ◽  
Dairy Cows ◽  
Dairy Herd ◽  
Randomised Clinical Trial ◽  
Digital Dermatitis ◽  
Group 4 ◽  
Treatment Type ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Objectives and designThis trial evaluated the effect of bandaging of acute painful ulcerative bovine digital dermatitis (DD) lesion (stage M2) in dairy cows, tested using two different topical treatments.DesignRandomised clinical trial.SettingThis study was conducted using Holstein-Friesian cows ranging in age from heifers to fourth lactation in a single dairy herd and diagnosed with acute ulcerative DD lesions (stage M2) on the first examination (week 0). Cows were randomly assigned into either a non-bandaged or bandaged group across two treatment conditions: topical chlortetracycline spray (CTC) and Intra Hoof-Fit Gel (IHF). Lesions received standardised bandaging and treatment on a weekly basis. Unhealed lesions could receive up to five repeated treatments, at weekly intervals, within a four-week period. Both M-stage and locomotion were also evaluated and scored weekly. Cows with healthily formed skin (stage M0) were deemed healed and subsequently released from the study.ResultsIn total, 163 M2 lesions were diagnosed at week 0. Bandaged M2 lesions had a significantly higher probability of cure than non-bandaged lesions regardless of treatment type (HR: 4.1; P<0.001; 95 per cent CI: 2.5 to 6.8). Most healing occurred within the first three weeks of trial. Furthermore, bandaged lesions (group 2 and group 4) were significantly less likely to progress into the chronic hyperkeratotic or proliferative stage (M4) than non-bandaged lesions in group 1 and group 3 (HR: 0.10; P<0.001; 95 per cent CI: 0.04 to 0.22). Out of concern for the cow’s wellbeing, this study investigated the effects of bandaging on locomotion. Bandaging had no effect on locomotion for either cows treated with CTC (group 1: median Sprecher score, 2; IQR=1–2; group 2: median Sprecher score, 2; IQR=1–3; P=0.3) or IHF (group 3: median Sprecher score, 2; IQR=1–2; group 4: median Sprecher score, 2; IQR=1–3; P=0.3).

Clinical Characteristic and Molecular Subgroups of Thai Pediatric Medulloblastomas at Queen Sirikit National Institute of Child Health

2021 ◽  
Vol 104 (10) ◽  
pp. 1648-1657
Keyword(s):  
Child Health ◽  
Signaling Pathway ◽  
Survival Rates ◽  
Large Cell ◽  
Disease Classification ◽  
Molecular Subgroups ◽  
Molecular Subgroup ◽  
Group 4 ◽  
Group 3 ◽  
Clinical Records

Objective: To determine the correlation between clinical characteristics and molecular subgroups of medulloblastoma (MB) in Thai pediatric patients at the Queen Sirikit National Institute of Child Health (QSNICH), Thailand. Materials and Methods: MB specimens operated between 2004 and 2018 were classified by Nanostring into four molecular subgroups, including Wingless signaling pathway (WNT), Sonic Hedgehog signaling pathway (SHH), Group 3, and Group 4. For the present cases, the clinical records were retrospectively analyzed. Results: Twenty-two MB cases with complete clinical records were analyzed. Group 4 was the most common molecular subgroup (31.82%), followed by WNT (27.27%), SHH (22.73%), and Group 3 (18.18%). The histologic subtypes included 18, three, and one cases of classic MB, MB with extensive nodularity (MBEN), and large cell MB, respectively. All SHH MBs were found in infants. All MBENs belonged to SHH subgroup, and the large cell MB was Group 3. All six WNT MB cases did not experience tumor recurrence. Five-year cause specific survival rates were 100% in WNT, 60% in SHH, 57.1% in Group 4, and 0% in Group 3. Five-year recurrence-free survival rates were 100% in WNT, 42.9% in Group 4, and 0% in SHH and Group 3. Conclusion: MB is a heterogeneous disease. Classification of MB, especially at the molecular subtype, is helpful for the management and prognostication. Keywords: Medulloblastoma; Molecular subgroup

Clinical Significance of Homozygous D13S319 Deletion in B-Cell Chronic Lymphocytic Leukemia (B-CLL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2799-2799 ◽  
Author(s):  
Stephanie Fink ◽  
Susan Geyer ◽  
Tait Shanafelt ◽  
Stephanie Smoley ◽  
Sarah Paternoster ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Median Percentage ◽  
Time To Treatment ◽  
Treatment Status ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background: In B-CLL, the observation of interphase cells with hemizygous D13S319 deletion at 13q14 (13q-x1) as a sole anomaly in blood is widely considered a favorable prognosis. The observation of cells with 11q-, +12 or 17p- has been associated with a relatively poor prognosis. Over the past 1.5 yrs, 16.2% (174/1,076) of patients (pts) referred for fluorescence in situ hybridization (FISH) testing for B-CLL in our clinical practice had a clone with homozygous D13S319 deletion (13q-x2), but the prognostic significance of this observation is poorly understood. Moreover, 39.3% (142/361) of pts with unfavorable FISH anomalies have 13q-x1 and/or 13q-x2 and the clinical significance of this observation is also unknown. Thus, we investigated pts with 13q- (with or without other chromosome anomalies) to establish the relative clinical significance of 13q- in B-CLL. Methods: We studied 333 pts with B-CLL sampled between 9/1999 and 6/2004 who had FISH performed on interphase nuclei from blood. The FISH probe set was designed to detect 6q-, 11q-, +12, 13q-, 17p-, and translocations involving IgH at 14q32. We classified pts into four groups: 13q-x1 only (group 1), 13q-x1 and 13q-x2 only (group 2), 13q-x2 only (group 3) and 13q-x1 and/or 13q-x2 plus other FISH anomalies (group 4). FISH groups were compared with gender, age, Rai stage, treatment status, time to treatment, CD38 and IgVH mutation. Results: Of the 333 pts, 171 (51.3%) had a 13q-: 71 were in group 1, 25 in group 2, 26 in group 3 and 49 in group 4. %CD38+ differed significantly across FISH groups; in pairwise analyses, the proportion of pts with >30% CD38+ was significantly greater for pts in group 4 vs. group 3 (p=0.0015) although no significant differences were observed for group 3 vs. group 1 or vs. group 2. Pts in group 3 were not significantly different from other FISH groups for Rai stage, IgVH mutation or gender. The median percentage of abnormal nuclei for pts with group 1 was 54.5% vs. 79.5% for pts in group 4 (p<0.0001). The median percent abnormal nuclei for pts in groups 3 and 2 was 72.5% and 68.5%, respectively. Median % abnormal nuclei for group 3 was not significantly different than the other FISH groups. Treatment status was available on 147 pts, where the proportion of pts who had treatment in each group was as follows: group 1, 15/66; group 2, 2/22; group 3, 4/21; and group 4, 9/38. Due to limited sample size and heavy censoring, any analysis on time to treatment is preliminary; however, these early analyses suggest group 4 pts have a lower median time to treatment (9 yrs) compared to groups 3 and 1 (12.3 and 13 yrs, respectively). Conclusions: This study has generated new information about the 13q- anomaly in B-CLL. First, known prognostic markers for B-CLL pts with 13q-x2 are not significantly different than for pts with 13q-x1 or 13q-x1/13q-x2. Second, 13q-x1 and/or 13q-x2 occurring with other unfavorable FISH anomalies have an unfavorable prognosis; i.e. potential benefits of 13q- are trumped when it is observed with unfavorable FISH anomalies. Thus, patients with any form of 13q- alone may have indolent disease while patients with 13q- and unfavorable FISH anomalies should be considered to be in a more aggressive phase.

scholarly journals Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas

2012 ◽  
Vol 123 (4) ◽  
pp. 473-484 ◽  
Author(s):  
Marcel Kool ◽  
Andrey Korshunov ◽  
Marc Remke ◽  
David T. W. Jones ◽  
Maria Schlanstein ◽  
...  
Keyword(s):  
Clinical Data ◽  
Meta Analysis ◽  
Molecular Subgroups ◽  
Genetic Aberrations ◽  
Group 4 ◽  
Group 3

Omphaloceles Associated with Chromosomal Segmental Alterations Carry a Poor Prognosis

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S26-S27
Author(s):  
H Zhou
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Normal Karyotype ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Overall Survival Rate ◽  
Significant Difference ◽  
Worse Prognosis

Abstract Introduction/Objective Omphaloceles are frequently associated with chromosomal abnormalities, including aneuploidy and segmental alterations. High resolution chromosomal microarray analysis (CMA) can detect segmental alterations &lt; 5 Mb, which is not detectable by G-banding. However, the prognostic significance of the segmental alteration in infant with omphalocele is not elucidated. Methods To identify omphalocele cases with genetic studies, a CoPath database search (1/2000 - 7/2017) was performed with key words “omphalocele” and “genetic”. From 1/2000 to 12/2008, only G-banding was performed. From 1/2009 to 7/2017, omphalocele cases were screened with karyotyping. Cases with normal karyotype were reflexed to CMA. Copy number gains/losses and corresponding genes were analyzed by the Affymetrix Chromosome Analysis Suite. Results Follow-up data are available in 75% (67/89) cases. There is no significant difference of the overall survival rate of male and female patients (80.5% vs 76.9%; χ 2, p = 0.7645). There are 16.9% (15/89) omphaloceles with aneuploidy, 10.1% (9/89) cases with segmental alterations by CMA, and 73.0% (65/89) cases with normal CMA and/or normal karyotype. Although patients with segmental alterations have a significantly higher survival rate than those with aneuploidy (44.4% vs 0%, χ2, p = 0.0119), their overall survival rate is significantly lower than infant with normal CMA and/or normal karyotype (44.4% vs 82.8%; χ2, p &lt; 0.0001). Infants with segmental alterations carry a significantly worse prognosis than infants with normal genetic study. Conclusion To date, this is the first study of the prognostic significance of segmental alteration in infants with omphalocele. Our data demonstrated that omphaloceles with segmental alterations carry a significantly worse prognosis than those with normal CMA and/or karyotype. It is crucial to convey the prognosis to the parents with a fetus carrying segmental alterations; so the family could make an informed decision and get ready for an infant with special needs.

The Modulating Effect of Azacitidine (Aza C) on the Cytogenetically Tracked MDS Clone Impact Survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1429-1429 ◽  
Author(s):  
Vesna Najfeld ◽  
Angela Scalise ◽  
Rosalie Odchimer-Reissig ◽  
Lewis R. Silverman
Keyword(s):  
Therapy Group ◽  
Bone Marrow Failure ◽  
Prognostic Significance ◽  
Survival Group ◽  
Hematopoietic Stem ◽  
Group 4 ◽  
Clinical Consequences ◽  
Group 3 ◽  
Group 5 ◽  
Group 2

Abstract MDS is a clonal hematopoietic stem cell disorder characterized by progressive bone marrow failure leading to death from infections and bleeding in the majority of patients. Transformation to acute leukemia occurs in 35-40%. Most treatments, other than allogeneic SCT, have been ineffective. Treatment with Aza C has been shown to be clinically effective and alters the natural history of disease (Silverman et al JCO 2002). We have previously demonstrated Aza C modulation of the MDS clone and established five different cytogenetic categories based on its modulating effect (Najfeld et al, ASH 2002). The goal of this extended study was to determine biological and clinical consequences of Aza C modulation on the five cytogenetic categories. Among 224 patients treated with AzaC, multiple sequential studies were performed in187 pts, while 41 pts without follow up studies, were excluded from this report. The initial karyotype prior to therapy with Aza C was normal in 99 pts (53%) and abnormal in 88 pts (47%). These latter patients were not further subdivided into good, intermediate or poor risk according to IPSS. The table below shows the Kaplan Meier median survival of the 5 subcategories based on the modulating effects of Aza C on the cytogenetically identified MDS clone. Cyto Category No of Frequency of Hematological Survival Group Pts Emerging Response In No Chromosome Abnormalities Months 1 Normal->Normal 67 None CR:3, PR:10, IMP:31 29.3 2 Normal->Abnormal 32 +8:25%l+1q:25% CR:1, PR:6, IMP:18 28.1 +21:9% 3 Abnormal-> Abnormal 50 −7/del(7q):24%; CR:1, PR:4, IMP:30 11.7 −5/del(5q):20%,+1q:14% 4 Abnormal->Clonal 20 −7/del(7q):25%;+21:20% IMP:8 9.1 5 Abnormal->Normal 18 del(7q):33%,+8,28% CR:1, PR:1,IMP:8 22.7 When survival was compared between cytogenetic subgroups there was a statistical difference between some groups. Survival of patients with normal cytogenetics (group 1) was superior when compared to either group 3 (p=.0001) or group 4 (p=.00015). Even for pts who developed an abnormal clone while on AzaC (group 2) survival was significantly longer when compared to either group 3 (p=0004) or group 4 (p=00001). Moreover, prognostic significance was observed for pts who initially had an abnormal karyotype that was diminished or eradicated on AZA C therapy (group 5) when compared to groups 3 (p=0.009) and 4 (p-0.0006). The emergence of a cytogenetically abnormal clone while on treatment with Aza C is not associated with shortened survival compared to those who remain cytogenetically normal. Response to Aza C can occur even with the persistence of the MDS clone or with the emergence of a new clone. This suggest that AZA C can modulate the responsivness of MDS hematopoietic progenitors. Our findings demonstrate that AZA C modulation of the cytogenetically marked MDS clone is associated with distinct subgroups with differing survival characteristics.

scholarly journals Magnetic resonance radiomics features and prognosticators in different molecular subtypes of pediatric Medulloblastoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255500
Author(s):  
Feng-Chi Chang ◽  
Tai-Tong Wong ◽  
Kuo-Sheng Wu ◽  
Chia-Feng Lu ◽  
Ting-Wei Weng ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Prediction Models ◽  
Gray Level ◽  
Resonance Imaging ◽  
Molecular Subgroups ◽  
Characteristic Analysis ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Group 3

Purpose Medulloblastoma (MB) is a highly malignant pediatric brain tumor. In the latest classification, medulloblastoma is divided into four distinct groups: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We analyzed the magnetic resonance imaging radiomics features to find the imaging surrogates of the 4 molecular subgroups of MB. Material and methods Frozen tissue, imaging data, and clinical data of 38 patients with medulloblastoma were included from Taipei Medical University Hospital and Taipei Veterans General Hospital. Molecular clustering was performed based on the gene expression level of 22 subgroup-specific signature genes. A total 253 magnetic resonance imaging radiomic features were generated from each subject for comparison between different molecular subgroups. Results Our cohort consisted of 7 (18.4%) patients with WNT medulloblastoma, 12 (31.6%) with SHH tumor, 8 (21.1%) with Group 3 tumor, and 11 (28.9%) with Group 4 tumor. 8 radiomics gray-level co-occurrence matrix texture (GLCM) features were significantly different between 4 molecular subgroups of MB. In addition, for tumors with higher values in a gray-level run length matrix feature—Short Run Low Gray-Level Emphasis, patients have shorter survival times than patients with low values of this feature (p = 0.04). The receiver operating characteristic analysis revealed optimal performance of the preliminary prediction model based on GLCM features for predicting WNT, Group 3, and Group 4 MB (area under the curve = 0.82, 0.72, and 0.78, respectively). Conclusion The preliminary result revealed that 8 contrast-enhanced T1-weighted imaging texture features were significantly different between 4 molecular subgroups of MB. Together with the prediction models, the radiomics features may provide suggestions for stratifying patients with MB into different risk groups.

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