scholarly journals Clinical outcome and molecular characterization of pediatric glioblastoma treated with postoperative radiotherapy with concurrent and adjuvant temozolomide: a single institutional study of 66 children

2015 ◽  
Vol 3 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Rakesh Jalali ◽  
Anupam Rishi ◽  
Jayant S. Goda ◽  
Epari Sridhar ◽  
Mamta Gurav ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Labeling Index ◽  
Molecular Profile ◽  
Mgmt Methylation ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Egfr Amplification ◽  
Adjuvant Temozolomide ◽  
Mib 1

Abstract Background Glioblastoma (GBM) in children is rare. Pediatric GBM have a distinct molecular profile as compared to adult GBM. There are relatively few studies of pediatric GBMs and no standard of care on adjuvant therapy. We aimed to evaluate the clinical outcome and molecular profile of pediatric GBM. Methods and Materials Between 2004 and 2013, 66 consecutive children with histologically proven GBM were identified from our database. The majority of the children underwent maximal safe resection followed by focal radiotherapy with concurrent and adjuvant temozolomide. Immunohistochemical staining was performed for p53, MIB-1 labeling index, MGMT overexpression, and EGFR amplification and isocitrate dehydrogenase (IDH1) R132H point mutation. Survival and impact of possible prognostic factors on outcomes were analyzed. Result Median survival was 15 months. The overall survival rate at 1 year was 62%, at 2 years was 30%, and at 3 years was 27%. Patients with thalamic tumors (P < .001), incompletely resected tumors (P < .00001), and tumors with MIB-1 labeling index >25% (P < .002) had poor overall survival rates. p53 was overexpressed in 74% of patients, MGMT promoter methylation was seen in 37% of patients, IDH1 mutation was seen in 4% of patients, and no patients had EGFR amplification. MGMT methylation and p53 overexpression did not impact survival. Conclusions Clinical outcome of pediatric GBM is similar to that reported for adult GBM. The frequency of p53 overexpression is higher than in adult GBM, while MGMT methylation, IDH1 mutations and EGFR amplification is lower than in adult GBM. MGMT methylation and p53 expression status do not have any prognostic significance.

p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients.

1996 ◽  
Vol 14 (5) ◽  
pp. 1604-1610 ◽  
Author(s):  
R Silvestrini ◽  
E Benini ◽  
S Veneroni ◽  
M G Daidone ◽  
G Tomasic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Mitochondrial Protein ◽  
Axillary Node ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Prognostic Information ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Node Positive

BACKGROUND AND PURPOSE The tumor-suppressor gene TP53 and the proto-oncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and for a mitochondrial protein involved in multiple cellular functions. The proteins provide prognostic information in node-negative breast cancer and are supposed to influence treatment responsiveness. We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year. PATIENTS AND METHODS On 240 resectable cancers, we determined the expression of p53 and bcl-2, using immunohistochemistry, cell proliferation (3H-thymidine labeling index [3H-dT LI]), and ER and progesterone receptors (PgR). RESULTS p53 expression and 3H-dT LI were weakly related to one another and both were unrelated to bcl-2. Relapse-free and distant metastasis-free survival at 5 years were significantly lower for patients with tumors that highly expressed p53 (P = .0001) and for those that weakly expressed or did not express bcl-2 (P = .02). However, p53, but not bcl-2, provided prognostic information independent of tumor size, axillary node involvement, steroid receptors, and 3H-dT LI. Moreover, the simultaneous p53 overexpression and lack of PgR identified patients at maximum risk of relapse, whereas bcl-2 overexpression, associated with a low 3H-dT LI or the presence of PgR, improved the prognostic resolution for low-risk patients. CONCLUSION p53 expression appears to be indicative of clinical outcome in postmenopausal patients treated with tamoxifen. Whether p53 overexpression and weak bcl-2 expression are indicators of biologic aggressiveness, regardless of treatment, or of hormone resistance remains to be defined.

Apoptosis Regulating Proteins bax and p53 in Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4710-4710
Author(s):  
Carsten Schrader ◽  
Wolfram Klapper ◽  
Dirk Janssen ◽  
Paul Riis ◽  
Peter Meusers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Mantle Cell Lymphoma ◽  
Survival Time ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
P53 Expression ◽  
Overall Survival Time ◽  
Mantle Cell ◽  
Median Overall Survival Time

Abstract In malignant tumors beside cell proliferation also cell death plays role for cell survival. Apoptosis regulating genes can be divided into two groups: death antagonists and death agonists such as bax. The ratio of death agonists and antagonists determines if a cell goes into apoptosis. We investigated in a large collective the immunohistochemical expression of the apoptotic marker p53 and bax in relation to the clinical course. Biopsies were stained immunohistochemically with monoclonal antibodies against bax and p53 and the expression was subdivided in three groups: negative, weak positive and strong positive. The expression profiles were analyzed with the overall survival data according to Kaplan and Meier. Patients with mantle cell lymphoma that had negative p53 expression had a median overall survival time of 38.1 months compared to 22.3 months for patients with a weak and 11.3 months for a strong p53 expression (0<0.0001). The bax expression was in the majority of cases positive. Only one case showed a negative staining. Patients with weak and strong bax expression showed no differences in clinical outcome (median overall survival time: 23 vs 33 months, p=0.6051). The immunohistochemical detection of p53 in mantle cell lymphoma is a good predictor for the clinical outcome.

Clinical features and treatment of World Health Organization Grade II and III meningiomas in childhood: report of 23 cases

2012 ◽  
Vol 10 (5) ◽  
pp. 423-433 ◽  
Author(s):  
Xiao-Qiang Wang ◽  
Cheng-Chuan Jiang ◽  
Lin Zhao ◽  
Ye Gong ◽  
Jie Hu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Progesterone Receptor ◽  
Clinical Features ◽  
Labeling Index ◽  
High Grade ◽  
Postoperative Radiation ◽  
Postoperative Radiation Therapy ◽  
Mib 1

Object High-grade meningiomas in childhood are rare, and their clinical features are unknown. The objective of this study was to determine the clinical characteristics and prognosis of childhood high-grade meningiomas. Methods Twenty-three patients with childhood high-grade meningiomas were treated at the Huashan Hospital. Clinical data were collected, tumor samples were reexamined, and prognoses were attained through follow-up visits and telephone interviews. Survival probability was calculated using the Kaplan-Meier method. A 2-sided probability level of 0.05 was chosen for statistical significance. Results The series included 18 males and 5 females (mean age 12.1 years). The most common symptoms were headache and vomiting (43%). Three patients had accompanying neurofibromatosis Type II (NF2). The high-grade meningioma cases with NF2 had larger tumor diameters than those without NF2 (p = 0.010). The skull base was the most common tumor site (39%). Complete resections were achieved in 11 patients after their initial operations. Adjuvant radiation therapy was performed in 9 cases. Follow-up evaluations were performed for 20 patients (mean follow-up 70 months). Ten patients experienced recurrences, 2 patients had lung metastases, and 7 patients died of the recurrence. The extent of surgery was significantly related to progression-free survival (PFS; p = 0.038). A negative progesterone receptor combined with strongly positive Bcl-2 immunoreactivity was significantly related to PFS (p = 0.001) and overall survival (p = 0.002). The MIB-1 labeling index was significantly related to overall survival (p = 0.018), whereas postoperative radiation therapy was not significantly related to PFS (p = 0.087) and overall survival (p = 0.40). Conclusions Childhood high-grade meningioma is a rare tumor type. Childhood high-grade meningioma has a male predominance and the basilar region is the most common tumor location. Patients with these tumors have high recurrence and mortality rates. The extent of resection is an important prognosis factor. A negative progesterone receptor combined with a strongly positive Bcl-2 immunoreaction might predict cancer recurrence. The MIB-1 labeling index correlates with the prognosis, and an MIB-1 labeling index > 3% increases the risk of recurrence in childhood high-grade meningioma. More cases should be collected, and longer follow-up periods should be obtained, to evaluate the effects of postoperative radiation therapy in childhood high-grade meningioma.

scholarly journals Clinical Outcome of Mantle Cell Lymphoma Patients with High Risk Biology (high Ki-67, blastic MCL, or high p53 expression)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3996-3996
Author(s):  
Martin Dreyling ◽  
Eva Hoster ◽  
Michael Unterhalt ◽  
Andreas Rosenwald ◽  
Hanneke Kluin-Nelemans ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Clinical Outcome ◽  
Research Funding ◽  
Advisory Board ◽  
Ki 67 ◽  
P53 Expression ◽  
Scientific Advisory Board ◽  
Scientific Advisory ◽  
Standard Risk

INTRODUCTION: Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a wide variation of clinical course. Previously a clinically defined risk score (MIPI) was established which partly reflects the heterogeneity of clinical outcome in this disease (Hoster, JCO 2004). Based on prospective trials, cytology (classical type vs. blastoid variant; Hoster, JCO 2016), cell proliferation as determined by Ki-67expression (Hoster, JCO 2016), and p53 alterations (Eskelund, Blood 2017; Aukema, Blood 2018) all have been identified as major drivers of a rapidly progressing disease, independent of MIPI. Aim of this study was to assess the clinical outcome of patients with at least one of these 3 different biological risk factors in a large uniformly treated patient population. METHODS: All patients were treated in the MCL Younger (Hermine, Lancet 2016) and MCL Elderly trials (Kluin-Nelemans, NEJM 2012) of the European MCL Network. Formalin fixed paraffin embedded (FFPE) diagnostic patients' material was classified as classical or blastic/pleomorphic variant and analyzed by Ki-67 or p53 immunohistochemistry on either tissue microarrays or whole tissue sections. Patients were classified as having high risk biology if they displayed blastoid cytomorphology, Ki-67 ≥30% according to the published guidelines, or high p53 staining indicating a mutated gene status expression. As control, standard risk disease patients had classical MCL with low Ki-67 <30%, and p53 IHC expression ≤50%. RESULTS: In 365 MCL (MCL younger: n=192, MCL elderly: n=173) out of 1229 study patients, at least one of the biological parameters indicated a high risk biology, or high risk biology was excluded by determination of all 3 parameters. No major survival difference was observed for patients with and without IHC data available, excluding a major selection bias. 65 of 319 analysed cases displayed a blastoid cytomorphology (20%), 175 of 345 cases had an increased Ki-67>30% (51%), and 54 of 254 cases displayed a mutated p53 status (21%). Based on the selection procedure of the cases, a total of 224 cased displayed a high risk biology (63%) vs 130 cases with confirmed standard risk disease(37%). Median failure-free (6.3 years vs, 2.2 years; p< 0.0001) and overall survival (median not reached vs. 4 years; p<0.0001) was significantly prolonged in the standard risk cohort compared with the high risk biology group. These significant differences were detected in both, patients treated with conventionally dosed chemotherapy (median PFS: 3.8 vs. 1.3 years, p=0.0001; OS: median not reached vs 2.5 years, p<0.0001) as well as patients receiving a cytarabine containing induction and autologous transplantation (median PFS: 7.5 vs. 3.7 years, p=0.0011; OS: median not reached vs 6.5 years, p<0.0001). Interestingly, MIPI remained a prognostic factor in the groups of patients without and with high-risk biology (FFS low risk disease: p=0.0223); PFS high risk disease: p<0.0001), and distribution of risk groups differed only slightly in these subsets of patients (biological low risk: 51% low/32%intermediate/17% high MIPI; biological high risk: 31% low/35% intermediate/34% high MIPI). Similar results were observed for overall survival. CONCLUSIONS: Although our enrichment strategy does not allow the estimation of the frequency of high risk biology and the patient group with standard risk disease is underrepresented in this evaluation, the patients with high risk biology as defined by blastoid variant, Ki-67 >30%, or high p53 expression had a significantly shorter failure-free and overall survival even without consideration of the clinical features of the disease (MIPI). As these biological factors seems to dictate the sometimes dismal clinical course of the disease, we recommend to incorporate these factors in routine diagnostic practice. Future studies should investigate the differential impact of targeted therapies in this biologically defined subset of patients. Disclosures Dreyling: Sandoz: Other: Scientific advisory board; Roche: Other: Scientific advisory board, Research Funding, Speakers Bureau; Novartis: Other: Scientific advisory board; Mundipharma: Other: Scientific advisory board, Research Funding; Janssen: Other: Scientific advisory board, Research Funding, Speakers Bureau; Gilead: Other: Scientific advisory board, Speakers Bureau; Celgene: Other: Scientific advisory board, Research Funding, Speakers Bureau; Acerta: Other: Scientific advisory board; Bayer: Other: Scientific advisory board, Speakers Bureau. Hoster:Roche Pharma AG: Other: Travel support; Janssen: Research Funding. Unterhalt:F. Hoffmann-La Roche: Research Funding. Hermine:AB science: Consultancy, Equity Ownership, Honoraria, Research Funding; Celgene: Research Funding; Novartis: Research Funding. Klapper:Roche, Takeda, Amgen, Regeneron: Honoraria, Research Funding.

scholarly journals NIMG-65. PREDICTING PROGNOSIS AND CANCER HOTSPOT MUTATIONS USING QUALITATIVE MR IMAGING ANALYSIS IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi176-vi176
Author(s):  
Maikel Verduin ◽  
Inge Compter ◽  
Sergey Primakov ◽  
Sander van Kuijk ◽  
Maarten te Dorsthorst ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Diagnostic Methods ◽  
P Value ◽  
Imaging Features ◽  
Mgmt Methylation ◽  
Imaging Analysis ◽  
Discovery Cohort ◽  
Egfr Amplification ◽  
Mri Features

Abstract INTRODUCTION Tumor heterogeneity poses one of the major limitations in improving the treatment for glioblastoma (GBM), which calls for new clinically relevant predictive models. This study aims to investigate non-invasive diagnostic methods, including patient characteristics and qualitative imaging analysis as a prognostic classifier and predictor for druggable oncogenes. METHODS We performed a retrospective analysis on 143 GBM patients (discovery cohort). Diagnostic MRIs were re-analyzed for qualitative imaging features (VASARI features). DNA was extracted from formalin-fixed, paraffin-embedded GBM tissue of the discovery cohort for next-generation sequencing (Ion Torrent Cancer Hotspot panel v2Plus), TERT-promoter mutation and MGMT-methylation analysis. Multivariable regression analysis was used to determine the prognostic and predictive value of VASARI features. RESULTS Of the 143 patients, median age was 61.4 years (range 15.5–84.6) with a median overall survival of 12 months (range 0–142). We observed IDH1 R132H mutation in 8.5%, MGMT-promotor methylation in 26.1%, TERT-promotor mutation (C250T;C228T) in 69.5%, EGFR mutation in 20.3% and EGFR amplification in 37.5% of all patients. A set of eight VASARI features was identified to be associated with overall survival (p< 0.001), which is currently being validated in an external dataset (n= 184). Interestingly, VASARI features appeared to be associated with IDH1-mutation (four features, p=0.004), TERT-promotor mutation (five features, p-value < 0.001), EGFR mutation (five features, p-value < 0.001) and EGFR amplification (seven features, p-value < 0.001) but not with MGMT-methylation (two features, p-value=0.054). Additional cancer hotspots are currently being analyzed and internal validation is ongoing. CONCLUSION AND FUTURE PERSPECTIVES We propose an integrated prognostic classifier comprising MRI features, also associated with GBM-specific molecular alterations. Additionally, quantitative MRI radiomics features are being extracted from the discovery and validation set and incorporated in the prognostic classifier. Subsequently, radiomics and VASARI features will be correlated to intratumoral heterogeneity, assessed by tissue micro-array analysis of the discovery cohort.

scholarly journals Bladder Cancer Involving Smooth Muscle of Indeterminate Type or Muscularis Mucosae in Transurethral Biopsy Specimens

2020 ◽  
Vol 154 (2) ◽  
pp. 208-214
Author(s):  
Michael J Hwang ◽  
Ashish M Kamat ◽  
Colin P Dinney ◽  
Bogdan Czerniak ◽  
Charles C Guo
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Smooth Muscle ◽  
Clinical Outcome ◽  
Survival Time ◽  
Transurethral Resection ◽  
Muscularis Propria ◽  
Clinicopathologic Features ◽  
Muscularis Mucosae ◽  
Biopsy Specimens

Abstract Objectives Bladder cancers invading the muscularis mucosae (MM) are treated differently from those invading the muscularis propria (MP). However, it may be difficult to determine the type of smooth muscle in transurethral resection (TUR) or biopsy specimens. We aimed to investigate the clinicopathologic features of bladder cancers involving smooth muscle of indeterminate type (SMIT) in TUR specimens in comparison with those invading the MM. Methods We identified 103 patients with bladder cancer involving SMIT (n = 27) or the MM (n = 76) in TUR specimens. All patients underwent subsequent restaging TUR or cystectomy. Results Bladder cancer with SMIT invasion showed a significantly higher rate of MP invasion in the subsequent specimens than those invading the MM (52% vs 29%). Lack of MP in the TUR specimens had a significantly higher risk of MP invasion in the subsequent specimens than those with the MP (61% vs 40%). The overall survival time for patients with SMIT invasion was significantly shorter than those with MM invasion. Conclusions Bladder cancers with SMIT invasion in TUR specimens show more frequent cancer upstaging in the subsequent specimens and a poorer clinical outcome than those invading the MM, which highlights the importance of a cancer restaging procedure for these patients.

scholarly journals Radical Hemithoracic Radiotherapy Induces Systemic Metabolomics Changes That Are Associated with the Clinical Outcome of Malignant Pleural Mesothelioma Patients

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 508
Author(s):  
Emanuela Di Gregorio ◽  
Gianmaria Miolo ◽  
Asia Saorin ◽  
Elena Muraro ◽  
Michela Cangemi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Therapeutic Option ◽  
Enrichment Analysis ◽  
Metabolic Effects ◽  
Pleural Mesothelioma ◽  
Polyamine Biosynthesis ◽  
The Individual

Radical hemithoracic radiotherapy (RHRT) represents an advanced therapeutic option able to improve overall survival of malignant pleural mesothelioma patients. This study aims to investigate the systemic effects of this radiotherapy modality on the serum metabolome and their potential implications in determining the individual clinical outcome. Nineteen patients undergoing RHRT at the dose of 50 Gy in 25 fractions were enrolled. Serum targeted metabolomics profiles were investigated at baseline and the end of radiotherapy by liquid chromatography and tandem mass spectrometry. Univariate and multivariate OPLS-DA analyses were applied to study the serum metabolomics changes induced by RHRT while PLS regression analysis to evaluate the association between such changes and overall survival. RHRT was found to affect almost all investigated metabolites classes, in particular, the amino acids citrulline and taurine, the C14, C18:1 and C18:2 acyl-carnitines as well as the unsaturated long chain phosphatidylcholines PC ae 42:5, PC ae 44:5 and PC ae 44:6 were significantly decreased. The enrichment analysis showed arginine metabolism and the polyamine biosynthesis as the most perturbed pathways. Moreover, specific metabolic changes encompassing the amino acids and acyl-carnitines resulted in association with the clinical outcome accounting for about 60% of the interpatients overall survival variability. This study highlighted that RHRT can induce profound systemic metabolic effects some of which may have a significant prognostic value. The integration of metabolomics in the clinical assessment of the malignant pleural mesothelioma could be useful to better identify the patients who can achieve the best benefit from the RHRT treatment.

Prognostic value of proliferation, PD-L1 and nuclear size in patients with superior sulcus tumours treated with chemoradiotherapy and surgery

2021 ◽  
pp. jclinpath-2021-207570
Author(s):  
Hans Blaauwgeers ◽  
Birgit I Lissenberg-Witte ◽  
Chris Dickhoff ◽  
Sylvia Duin ◽  
Erik Thunnissen
Keyword(s):  
Overall Survival ◽  
Proliferative Activity ◽  
Tumour Cells ◽  
Nuclear Size ◽  
Residual Tumour ◽  
Trimodality Therapy ◽  
Median Difference ◽  
The Mean ◽  
Superior Sulcus ◽  
Mib 1

AimsThe aim of this study was to determine the relationship between proliferative activity, PD-L1 status and nuclear size changes after preoperative chemoradiotherapy (CRT) and the clinical outcome in patients with superior sulcus tumours.MethodsProliferative activity (MIB-1) and PD-L1 status were estimated by immunohistochemistry in the tumour cells of resection specimen in a series of 33 patients with residual tumour after trimodality therapy for a sulcus superior tumour between 2005 and 2014. A morphometric analysis of both pretreatment and post-treatment tumour materials was also performed. Results were related to disease-free survival and overall survival.ResultsLow proliferative activity (<20% MIB-1) was associated with better overall survival: 2-year overall survival of 73% compared with 43% and 25%, respectively, for moderate (MIB-1 20%–50%) and high (MIB-1 >50%) proliferative activity (p=0.016). A negative PD-L1 status (<1% positive tumour cells) was also associated with better overall survival (p=0.021). The mean nuclear size of normal lung tissue pneumocytes was significantly smaller compared with the mean nuclear size of tumour cells of the resection specimens (median difference −38.1; range −115.2 to 16.0; p<0.001). The mean nuclear size of tumour cells did not differ between pretreatment biopsies and resection specimens (median difference −4.6; range −75.2 to 86.7; p=0.14). Nuclear size was not associated with survival (p=0.82).ConclusionsLow proliferative activity determined by MIB-1 as well as a negative PD-L1 expression are significantly associated with better overall survival in patients with residual tumour after CRT for superior sulcus tumour.

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