scholarly journals EPEN-36. THE TREATMENT OUTCOME OF PAEDIATRIC SUPRATENTORIAL C11ORF95-RELA FUSED EPENDYMOMA: A COMBINED REPORT FROM E-HIT SERIES AND AUSTRALIAN NEW ZEALAND CHILDREN’S HAEMATOLOGY/ONCOLOGY GROUP

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii315-iii315
Author(s):  
Chia Huan Ng ◽  
Denise Obrecht ◽  
Molly Buntine ◽  
Olivia Wells ◽  
Martin A Campbell ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Surgical Resection ◽  
Molecular Analysis ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Molecular Classification ◽  
Disease Recurrence ◽  
Outcome Data ◽  
Treatment Decision Making ◽  
Supratentorial Ependymoma

Abstract AIM Advances in molecular classification of paediatric ependymoma have been pivotal in improving risk stratification and understanding of this disease. C11orf95-RELA fused supratentorial ependymoma (ST-EPN) have been reported to have a poor outcome, with 10-year overall survival (OS) of 49% and progression free survival (PFS) of 19%. A cohort of patients from multiple international institutions with molecularly confirmed C11orf95-RELA fused ST-EPN were reviewed to assess their disease behaviour. METHOD: We reviewed patients with molecularly determined C11orf95-RELA supratentorial ependymoma diagnosed between 1999 – 2019. Demographic information, extent of surgical resection, use of radiotherapy and/or chemotherapy, disease recurrence, treatment at recurrence and clinical outcome data was collected. PFS and OS of all patients were estimated using Kaplan-Meier method. RESULTS A total of 76 ST-EPN patients with C11orf95-RELA fusion were identified (median age: 7 years3 months, range: 5 months – 18 years7 months). 58 patients (76.3%) had complete surgical resection. 70 patients(92.1%) received radiotherapy. 55 patients(72.3%) received chemotherapy. The 10-year OS of C11orf95-RELA fused ST-EPN was 72.4% and PFS was 63.8%. In contrast, ST-EPN at a single institution with unconfirmed molecular status had an OS of 61.1% and PFS of 34.9%. CONCLUSION Detailed molecular analysis identified distinct subgroups of patients with ST-EPN. Patients from this cohort with C11orf95-RELA methylation profiles had a significantly higher OS compared to previous reports and those with unconfirmed fusion status, emphasising the critical importance of complete molecular profiling to assist in treatment decision making. Complete molecular analysis in future prospective cohorts is essential for accurate risk stratification and treatment selection.

Immunotherapy and Sonpavde score validation in advanced upper tract urothelial carcinoma: a retrospective study by the Italian Network for Research in Urologic-Oncology

Immunotherapy ◽  
2021 ◽  
Author(s):  
Melissa Bersanelli ◽  
Giulia Mazzaschi ◽  
Patrizia Giannatempo ◽  
Daniele Raggi ◽  
Elena Farè ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Upper Tract Urothelial Carcinoma ◽  
Urologic Oncology ◽  
Upper Tract ◽  
Treatment Decision Making ◽  
Few Data

Background: Few data are available regarding the effectiveness of immune checkpoint inhibitors in advanced upper tract urothelial carcinoma (UTUC) patients. Methods: To provide a real-world experience with anti-PD-1/PD-L1-based therapy in UTUC patients, we involved an Italian network in a multicenter retrospective analysis. Results: A total of 78 UTUC patients were enrolled. The median follow-up was 25.1 months. The median progression-free survival (mPFS) was 2.2 months (95% CI 1.8–2.6), and the median OS (mOS) was 6.0 months (95% CI 3.6–8.4). The Sonpavde score (including performance status > 0, hemoglobin < 10 g/dl, liver metastases, time from prior chemotherapy ≥ 3 months) split the patients into three groups (0 vs 1 vs 2–4 factors), efficiently predicting the OS and PFS outcome at the multivariate analyses (p < 0.0001). Conclusion: The prognosis of unselected UTUC patients is still unsatisfactory. The Sonpavde score was validated for the first time in an UTUC population, as a useful tool for the treatment decision-making process.

Using PSMA (prostate-specific membrane antigen) evaluation on prostate biopsies for risk stratification at time of initial diagnosis.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
Marie C. Hupe ◽  
Christian Philippi ◽  
Doris Roth ◽  
Christiane Kuempers ◽  
Julika Ribbat-Idel ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Treatment Decision ◽  
Disease Recurrence ◽  
Initial Diagnosis ◽  
Curative Surgery ◽  
Grade Group ◽  
Prostate Biopsies ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Psma Expression

6 Background: Stratifying prostate cancer (PCa) patients into risk groups at time of initial diagnosis for individual treatment decision is still a major clinical challenge. PSMA expression has emerged as a promising prognostic biomarker since its overexpression in radical prostatectomy specimens (RP) has been linked to disease recurrence. Aim of our study was to assess the prognostic value of PSMA on prostate biopsies (Bx) thus improving risk stratification at time of initial diagnosis. Methods: Immunohistochemistry for PSMA expression was performed on 294 Bx with corresponding RP, 621 primary tumor foci from 242 RP, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases, and 52 benign prostatic samples. Grade group, PSA, TNM-, and R-status were assessed as clinico-pathologic features. Primary endpoint was recurrence-free survival (RFS). Chi-square, ANOVA-analyses, Cox regression and log rank tests were performed for statistical analyses. Results: PSMA expression significantly associates with grade group and initial PSA level. Elevated PSMA expression on both RP and Bx significantly correlates with an increased risk of disease recurrence after curative surgery. 5-year RFS rates are 88.2%, 74.2%, 67.7%, and 26.8% for patients with no, low, medium, or high PSMA expression on Bx, respectively. Elevated PSMA level on Bx predict a 4-fold increased risk of disease recurrence independently from initial PSA and grade group on Bx. PSMA expression significantly increases during PCa progression. Conclusions: PSMA qualifies as an independent prognostic biomarker on Bx at time of initial diagnosis in addition to the established markers PSA and grade group. PSMA predicts disease recurrence following curative surgery and potentially improves the discrimination indolent vs. aggressive disease. We propose the routine assessment of PSMA expression on Bx for outcome prediction and risk stratification at time of initial diagnosis prior to treatment decision.

scholarly journals The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110359
Author(s):  
Amy Jamieson ◽  
Tjalling Bosse ◽  
Jessica N. McAlpine
Keyword(s):  
Endometrial Cancer ◽  
Molecular Subtypes ◽  
Treatment Decision ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
Therapeutic Implications ◽  
Treatment Decision Making ◽  
Exciting Time ◽  
Classification Tool

Following the discovery of the four molecular subtypes of endometrial cancer (EC) by The Cancer Genome Atlas (TCGA) in 2013, subsequent studies used surrogate markers to develop and validate a clinically relevant EC classification tool to recapitulate TCGA subtypes. Molecular classification combines focused sequencing ( POLE) and immunohistochemistry (mismatch repair and p53 proteins) to assign patients with EC to one of four molecular subtypes: POLEmut, MMRd, p53abn and NSMP (no specific molecular profile). Unlike histopathological evaluation, the molecular subtyping of EC offers an objective and reproducible classification system that has been shown to have prognostic value and therapeutic implications. It is an exciting time in EC care where we have moved beyond treatment based on histomorphology alone, and molecular classification will now finally allow assessment of treatment efficacy within biologically similar tumours. It is now recommended that molecular classification should be considered for all ECs, and should be performed routinely in all high grade tumours. It is also recommended to incorporate molecular classification into standard pathology reporting and treatment decision-making algorithms. In this review, we will discuss how the molecular classification of EC can be used to guide both conventional and targeted therapy in this new molecular era.

What care is appropriate and necessary for metastatic gastric cancer patients? Results of a RAND/UCLA expert panel.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 70-70
Author(s):  
Alyson L. Mahar ◽  
Lucy K. Helyer ◽  
Carol Jane Swallow ◽  
Calvin Law ◽  
Lawrence Frank Paszat ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Liver Metastases ◽  
Surgical Resection ◽  
Metastatic Disease ◽  
Expert Panel ◽  
Treatment Decision ◽  
Metastatic Gastric Cancer ◽  
Treatment Decision Making ◽  
Gastric Cancer Patients ◽  
Multiple Liver Metastases

70 Background: Most gastric cancer patients present with advanced stage disease precluding curative surgical treatment. The utility of surgical and non-surgical options for non-curative, advanced disease is debated and the appropriate treatment strategy unclear. Methods: A multi-disciplinary expert panel of 16 physicians from 6 countries, scored 47 scenarios using the RAND/UCLA Appropriateness Methodology. Appropriateness was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) from 1-3 were considered inappropriate, 4-6 uncertain, and 7-9, appropriate. Agreement was reached when 11 of 16 panelists scored the statement similarly. If a statement was agreed to be appropriate, it was then given a necessity score (NS) in the same manner. Results: Surgical resection and bypass were agreed to be inappropriate in patients with minor symptoms and visible carcinomatosis, liver metastases or more than one site of metastatic disease for cardia and distal lesions (AS 1.0-3.5). The expert panel disagreed on the role for surgical resection in patients who were cytology positive only (AS 4-6). The role of resection for patients with major symptoms if they had visible carcinomatosis, liver metastases or more than one site of metastatic disease (AS 2-5) was indeterminate. Patients with distal tumours and major symptoms and multiple liver metastases or more than one site of metastatic disease were considered indeterminate for surgical resection (AS 2). Best supportive care was agreed to be appropriate for patients with minor symptoms and multiple liver metastases or more than one site of metastatic disease (AS 8, NS 5-6). Conclusions: The role of surgery in metastatic gastric cancer treatment decision-making is not supported by experts for the majority of scenarios. Continued uncertainty in appropriate and necessary treatment decision-making for advanced patients with a minimal burden metastatic disease exists and underscores the need for randomized controlled trials.

Molecular classification of neuroendocrine tumors: Clinical experience with the 92-gene assay in >24,000 cases.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15700-e15700
Author(s):  
Andrew Eugene Hendifar ◽  
Harris S Soifer ◽  
Mason Israel ◽  
Catherine A. Schnabel
Keyword(s):  
Islet Cell ◽  
Treatment Decision ◽  
Large Cell ◽  
Molecular Classification ◽  
Tumor Type ◽  
Clinical Testing ◽  
Age And Gender ◽  
Treatment Decision Making ◽  
Gene Assay ◽  
And Gender

e15700 Background: Histological diagnosis of metastatic neuroendocrine tumors (NET) can be straightforward, but identification of the specific NET tumor type/subtype is often challenging based on morphology alone. Accurate identification of tumor type/subtype in NETs of unknown primary has implications for grading, staging, and treatment decision-making as availability of targeted therapies increases. The 92-gene assay (CancerTYPE ID) is a validated gene expression classifier of 50 tumor type/subtypes (including 7 NET subtypes) for patients with unknown/uncertain diagnoses. In this study, 92-gene assay results from cases submitted for clinical testing with molecular diagnoses of NET were evaluated. Methods: A de-identified database was created under an IRB approved protocol that contains clinical and molecular information from consecutive cases submitted for clinical testing with the 92-gene assay with sufficient tissue for testing. In this analysis, patient demographics and distribution of molecular diagnoses were analyzed based on biopsy site, age, and gender. Chi-squared tests were used to compare between subgroups. Results: Analysis included 24,484 patients. Median age was 65y (51% female). The 92-gene assay rendered a molecular diagnosis of NET in 6.3% of cases (n = 1551). Small/large cell lung carcinoma (50%) was the most common NET molecular diagnosis, followed by GI carcinoid (14%), islet cell (14%), Merkel cell (10%), and lung carcinoid (9%). In liver biopsies (39% of cases), all 7 NET subtypes were identified by the 92-gene assay. The proportion of molecular diagnoses classified as small/large cell lung NET increased with age, from 25% in < 40y to 45% in 40-65y and 55% in > 65y, and the proportion of islet cell NET decreased with age (p < 0.0001). Men had a higher proportion of molecular diagnoses that were small/large cell lung NET (53%) vs women (46%; p < 0.0001). Conclusions: These findings highlight the utility of molecular classification to identify distinct NET tumor types/subtypes to improve diagnostic precision and treatment decision-making. In addition, significant differences in the distribution of molecular diagnoses of NET subtype by age and gender were identified.

Marker of lipid peroxidation TBARS predicts survival in patients with metastaticurothelial carcinoma (MUC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17023-e17023
Author(s):  
Jan Slopovsky ◽  
Jarmila Kucharska ◽  
Jana Obertova ◽  
Michal Mego ◽  
Katarina Kalavska ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Performance Status ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
High Plasma ◽  
Rank Test ◽  
Treatment Decision Making ◽  
Kaplan Meier ◽  
Platinum Based Chemotherapy ◽  
Chemotherapy Initiation

e17023 Background: Oxidative stress plays a significant role in cancer development and progression. A marker of lipid peroxidation TBARS is upregulated in various diseases. The objective of this prospective study was to explore predictive and prognostic values of TBARS in MUC patients (pts.) before the first-line platinum-based chemotherapy. Methods: Seventy-two consecutive pts. (57 men) with MUC (58 bladder, 14 upper GU tract) were enrolled into this study. Performance status ECOG ≥ 2 had 11 pts., visceral metastases were present in 34 pts. Most common type of treatment regimen was gemcitabine and cisplatin (65 pts.), gemcitabine and carboplatin received 7 pts. Based upon TBARS mean of 6,06 μmol/L, pts. were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared with log-rank test. Results: At median follow-up of 9.6 months, 65 pts. experienced progression and 64 pts. died. Pts. with low TBARS had significantly better survival opposed to pts. with high TBARS (HR 0.44, 95% CI 0.27-0.74; P = 0,0009 for OS and HR 0.51; 95% CI 0.31-0.84; P = 0,006 for PFS, respectively). Pts. with ECOG ≤ 1 had significantly better both, OS and PFS in comparison to pts. with ECOG > 2. Conclusions: In this study, high plasma TBARS levels in patients with MUC before chemotherapy initiation were associated with poor survival. Therefore, this biomarker could be used for identification of patients with worse prognosis and could lead to better patient stratification and treatment decision making. The study was supported by VEGA 1/0614/12. Key Words: Metastatic Urothelial Carcinoma. Platinum-Based Chemotherapy. Lipid Peroxidation. TBARS. Survival.

135 Pediatric Supratentorial Ependymoma: Clinical, Radiographic and Molecular Analysis

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 231-231
Author(s):  
Jock Lillard ◽  
Paul Klimo ◽  
Garrett Thomas Venable
Keyword(s):  
Overall Survival ◽  
Molecular Analysis ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Extent Of Resection ◽  
Gross Total Resection ◽  
Total Resection ◽  
Free Survival ◽  
Favorable Prognosis ◽  
Supratentorial Ependymoma

Abstract INTRODUCTION Recent molecular analyses support a behavioral and clinical distinction between supratentorial and infratentorial ependymomas, with supratentorial tumors, in general, having a more favorable prognosis. The goal of this study was todescribe our experience managing supratentorial ependymoma in children. METHODS A prospectively maintained neurooncology database was queried to identify cases ofsupratentorial ependymoma treated atSt Jude Children's Research Hospital (SJCRH) and LeBonheur from 1990 through December 31, 2014. Clinical, operative, and radiographic information were reviewed. Outcome measures, determined by review of clinic notes and subsequent imaging, included extent of resection, progression free survival (PFS), overall survival (OS), recurrence of disease and method of post-failure treatment, seizures, requirement of anti-seizure medications, hydrocephalus requiring shunt placement, and death.Detection ofthe C11or95-RELA fusion or rearrangement was performed using iFISH in those patients whose tumor tissue was still available. RESULTS >Seventy-four cases (42% male) of supratentorial ependymoma were identified. Median age at diagnosis was 6.8 years. In total, 59 (79.7%) of 74 patients underwent gross total resection (GTR). Overall survival was a median of 7.4 years. Fifteen patients died of disease. Progression free survival was a median of 3.6 years. Eighty percent of those children whose initial resection was subtotal developed recurrence compared to 50.8% in those who had a GTR. For those patients that recurred, all 42 received further treatment, including further resection, chemotherapy and radiation. Molecular analysis was available for 52 patients (70.3%). Age less than 3, gross total resection, and tumor grade were not associated with improved PFS or OS. Absence of C11-or95-RLEA fusion was associated with a significantly worse PFS, although OS was similar. CONCLUSION Supratentorial ependymoma often have a more favorable prognosis compared toinfratentorial variants. Like many pediatric tumors, supratentorial ependymomas can bestratified based on clinical, surgical and possibly molecular variables.

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