Significance of necrosis in grading of anaplastic oligodendroglial tumors: A clinicopathological and genetic study of 916 high-grade gliomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1502-1502
Author(s):  
C. R. Miller ◽  
C. P. Dunham ◽  
B. W. Scheithauer ◽  
A. Perry

1502 Background: High-grade gliomas (HGG, WHO grades III-IV) are morphologically and genetically diverse, with survivals ranging from months to decades. Although WHO 2000 grading criteria are well established for pure astrocytomas [anaplastic astrocytoma (AA) and glioblastoma (GBM)], those for oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and oligodendroglioma (AO)] remain subjective, there being a debate regarding the existence of a grade IV variant based on the finding of necrosis, particularly with pseudopalisading (PPN). Methods: Overall survival of 916 adult (>20 yr) patients diagnosed between 1990 and 2005 with supratentorial HGG (77 AA, 481 GBM, 183 AOA, 175 AO) was analyzed by uni- (log-rank) and multivariate (Cox proportional hazards) models for significance of the following factors: microvascular proliferation, necrosis, patient age, surgery (stereotactic vs. open), location, primary vs. secondary tumor, year of diagnosis, and chromosome 1p and 19q losses by fluorescence in situ hybridization. Results: Necrosis was a statistically significant predictor of poor survival on multivariate analyses in AOA (P=0.035), but not in AO (log-rank P=0.048, Cox P=0.9), while PPN showed a trend towards significance on multivariate analysis only in AOA (P=0.096). Other independent predictors on multivariate analysis included age, grade, surgery type, and year of diagnosis for AA/GBM and age, primary tumor, and 1p/19q codeletion for both AOA and AO (P<0.05). Median survival for AOA patients whose tumors featured necrosis (20.7 mo) was significantly worse than their counterparts lacking necrosis (>104 mo); survival of the latter was more similar to that of AO (83.5 mo), whereas in the former it was better than GBM (10.5 mo) (log-rank P<0.0001). Conclusions: Stratification of oligoastrocytomas, but not of pure oligodendrogliomas, into grades III (AOA) and IV (GBM with oligodendroglial features) on the basis of necrosis is prognostically justified and is more accurate than the current approach of using a single anaplastic grade. These data provide impetus for the modification of present WHO criteria. No significant financial relationships to disclose.

2000 ◽  
Vol 92 (6) ◽  
pp. 983-990 ◽  
Author(s):  
Yasushi Ino ◽  
Magdalena C. Zlatescu ◽  
Hikaru Sasaki ◽  
David R. Macdonald ◽  
Anat O. Stemmer-Rachamimov ◽  
...  

Object. Allelic loss of chromosome 1p is a powerful predictor of tumor chemosensitivity and prolonged survival in patients with anaplastic oligodendrogliomas. Chromosome 1p loss also occurs in astrocytic and oligoastrocytic gliomas, although less commonly than in pure oligodendroglial tumors. This observation raises the possibility investigated in this study that chromosome 1p loss might also provide prognostic information for patients with high-grade gliomas with astrocytic components.Methods. The authors report on seven patients with high-grade gliomas composed of either pure astrocytic or mixed astrocytic-oligodendroglial phenotypes, who had remarkable neuroradiological responses to therapy or unexpectedly long survivals. All of the tumors from these seven patients demonstrated chromosome 1p loss, whereas other genetic alterations characteristic of high-grade gliomas (p53 gene mutations, EGFR gene amplification, chromosome 10 loss, chromosome 19q loss, or CDKN2A/p16 deletions) were only found in occasional cases. The authors also assessed the frequency of chromosome 1p loss in a series of anonymous high-grade astrocytoma samples obtained from a tumor bank and demonstrate that this genetic change is uncommon, occurring in only 10% of cases.Conclusions. Although any prognostic importance of chromosome 1p loss in astrocytic or mixed astrocytic—oligodendroglial gliomas can only be determined in larger and prospective series, these findings raise the possibility that some high-grade gliomas with chromosome 1p loss, in addition to pure anaplastic oligodendrogliomas, may follow a more favorable clinical course.


2006 ◽  
Vol 24 (34) ◽  
pp. 5419-5426 ◽  
Author(s):  
C. Ryan Miller ◽  
Christopher P. Dunham ◽  
Bernd W. Scheithauer ◽  
Arie Perry

Purpose High-grade gliomas (HGGs; WHO grades 3-4) are highly diverse, with survival times ranging from months to years. WHO 2000 grading criteria for high-grade oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and anaplastic oligodendroglioma (AO)] remain subjective, and the existence of grade 4 variants is controversial. Patients and Methods Overall survival (OS) of 1,093 adult patients with a cerebral HGG newly diagnosed between 1990 and 2005 was analyzed by univariate and multivariate models for significance of the following factors: patient age, surgery type, year of diagnosis, endothelial proliferation, necrosis, oligodendroglial histology, treatment center, and chromosome 1p, 19q, 7p (EGFR), and 10q (PTEN) abnormalities by fluorescence in situ hybridization (FISH). Results Necrosis was a statistically significant predictor of poor OS on univariate and multivariate analyses in AOA but not in AO. Median OS for patients with necrotic AOA (22.8 months) was significantly worse than for patients with non-necrotic AOA (86.9 months; P < .0001) but was better than conventional glioblastomas (9.8 months; P < .0001). In addition to patient age, the following were significant independent prognostic factors (P ≤ .001): grade and surgery type for the entire HGG cohort; modified grade for AOA (3 v 4); and modified grade, 1p/19q codeletion status, and oligodendroglial histology for the 586 HGGs analyzed by FISH. Conclusion Stratification of AOA, but not of pure AO, into grades 3 and 4 on the basis of necrosis is prognostically justified and is more powerful than the current approach. Both routine histology and genetic testing provide independent, prognostically useful information.


2020 ◽  
Vol 132 (4) ◽  
pp. 998-1005 ◽  
Author(s):  
Haihui Jiang ◽  
Yong Cui ◽  
Xiang Liu ◽  
Xiaohui Ren ◽  
Mingxiao Li ◽  
...  

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.


Sarcoma ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jennifer L. Leiting ◽  
John R. Bergquist ◽  
Matthew C. Hernandez ◽  
Kenneth W. Merrell ◽  
Andrew L. Folpe ◽  
...  

Perioperative radiation therapy (RT) has been associated with reduced local recurrence in patients with retroperitoneal sarcomas (RPS); however, selection criteria remain unclear. We hypothesized that perioperative RT would improve survival in patients with RPS and would be associated with pathological factors. The National Cancer Database (NCDB) from 2004 to 2012 was reviewed for patients with nonmetastatic RPS undergoing curative intent resection. Tumor size was dichotomized at 15 cm based on 8th edition American Joint Committee on Cancer (AJCC) staging. Patients with the highest comorbidity score were excluded. Unadjusted Kaplan–Meier and adjusted Cox proportional hazards modeling analyzed overall survival (OS). Multivariable logistic regression modeled margin positivity. A total of 2,264 patients were included; 727 patients (32.1%) had perioperative radiation in whom 203 (9.0%) had radiation preoperatively. Median (IQR) RPS size was 17.5 [11.0–27.0] cm. Histopathology was high grade in 1048 patients (43.7%). Multivariable analysis revealed that perioperative radiation was independently associated with decreased mortality (HR 0.72, 95% confidence intervals (CIs) 0.62–0.84,p<0.001), and preoperative RT was associated with reduced margin positivity (HR 0.72, 95% CI 0.53–0.97,p=0.032). Stratified survival analysis showed that radiation was associated with prolonged median OS for RPS that were high-grade (64.3 vs. 43.6 months,p<0.001), less than 15 cm (104.1 vs. 84.2 months,p=0.007), and leiomyosarcomatous (104.8 vs. 61.8 months,p<0.001). Perioperative radiation is independently associated with decreased mortality in patients with high-grade, less than 15 cm, and leiomyosarcomatous tumors. Preoperative radiation is independently associated with margin-negative resection. These data support the selective use of perioperative radiation in the multidisciplinary management of RPS.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4522-4522 ◽  
Author(s):  
A. C. Berger ◽  
K. Winter ◽  
J. Hoffman ◽  
W. Regine ◽  
R. Abrams ◽  
...  

4522 Background: CA 19–9 is an important tumor marker in pancreatic adenocarcinoma. Several single institutional studies have demonstrated post-resection CA 19–9 to be an important prognostic factor. A secondary endpoint of RTOG 9704, a phase III adjuvant chemoradiation trial for pancreatic cancer, was to prospectively evaluate the ability of post-resectional CA 19–9 to predict survival. Methods: A total of 538 patients were accrued to this trial, of which 385 had evaluable CA 19–9 levels. These were analyzed using ELISA GI-MA kits provided by Diagnostic Products Corporation, a Siemens Company. CA 19–9 expression was analyzed as a dichotomized variable (<180 vs. =180). Cox proportional hazards models were utilized to characterize the contribution of CA 19–9 expression on OS. The following additional variables were included in the multivariate analysis: treatment, nodal involvement, tumor diameter (< or > 3cm), and margin status. Actuarial estimates for OS were calculated using Kaplan-Meier methods. Results: Most patients had CA 19–9 < 180 (n=220, 57%), while 34% were Lewis Antigen negative (unable to express CA 19–9) and 33 (9%) patients had levels >180. Survival was statistically significantly improved among patients with CA 19–9 <180 compared with those whose CA 19–9 =180 (HR=3.58(95% CI=2.40–5.34), p<0.0001) ( table ). This corresponds to a 72% reduction in the risk of death. This improvement was observed among patients with pancreas head and non-head tumors when analyzed separately. The multivariate analysis confirms that CA 19–9 is a highly significant predictor of OS in patients with resected pancreatic cancer. Conclusions: This prospective analysis of CA 19–9 in 385 patients treated with adjuvant chemoradiation definitively confirms the importance of post-resectional CA 19–9 in pancreatic cancer patients who have undergone resection. Patients with post-resection CA 19–9 >180 should be considered for additional therapy. [Table: see text] No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11569-11569
Author(s):  
Erwin Woff ◽  
Pashalina Kehagias ◽  
Caroline Vandeputte ◽  
Tarek Kamoun ◽  
Thomas Guiot ◽  
...  

11569 Background: No validated prognostic biomarker is currently available for mCRC. This trial assessed cfDNA and MTV before treatment with regorafenib as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS) in mCRC. Methods: After signed informed consent, mCRC patients were enrolled in a prospective non-randomized trial aiming to define unlikelihood to benefit from regorafenib (EudraCT number: 2012-005655-16) and assessed for cfDNA and FDG PET/CT MTV at baseline. cfDNA was extracted from 3mL of plasma and quantified using the Qubit 2.0 fluorometer. All target lesions were delineated on FDG PET/CT using a PERCIST-based threshold and their volumes were summed to obtain total MTV. MTV and cfDNA optimal cutoffs for OS and PFS prediction were determined by the Contal and O’Quigley’s method. MTV, cfDNA, age, gender, Body Mass Index (low, normal, high, obese), ECOG PS, number of chemotherapy lines (NCL), previous use of bevacizumab and presence of a KRAS mutation were included in a multivariate analysis. Results: MTV and cfDNA of 132 evaluable/141 eligible patients were well correlated (Spearman’s correlation coefficient = 0.70; p < 0.001) and risk groups for both PFS and OS were identified on the basis of cfDNA (cfDNA < 1 µg/mL; cfDNA≥1 µg/mL) and MTV (MTV < 100 cm³; 100-300 cm³; > 300 cm³). The multivariate analysis retained cfDNA, MTV, NCL, and obesity as independent parameters for PFS prediction, and cfDNA, MTV, NCL, BMI, and previous use of bevacizumab as independent parameters for OS prediction. Prognostic scores for PFS and OS were developed based on regression coefficients from the final Cox proportional hazards models. Prognostic scores for PFS (1.8 vs 5.3 months, HR: 3.15 for score ≥-3 vs < -3, (95% CI, 2.08-4.76); p < 0.001) and for OS (4.2 vs 13.9 months, HR: 4.59 for score ≥-6 vs < -6: (95% CI, 2.92-7.21); p < 0.001) both identified patients with much contrasted outcomes. Conclusions: Baseline cfDNA and MTV along with BMI parameters predict outcome in patients with mCRC before regorafenib onset. These parameters not related to treatment should be considered, if validated in further studies, as stratification factors in future clinical trials. Clinical trial information: 2012-005655-16.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21045-e21045
Author(s):  
Daniel Vilarim Araujo ◽  
Rafael Vanin de Moraes ◽  
Victor Aurelio Ramos Sousa ◽  
Mauro Daniel Spina Donadio ◽  
Aline Fusco Fares ◽  
...  

e21045 Background: Biomarkers to select the patients most likely to benefit from checkpoint inhibitors are urged. NLR is a simple way of measuring systemic inflammation and is an independent predictor of survival before Anti-CTLA4 therapy. We hypothesized if NLR is also a predictor of survival before Anti-PD1 therapy. Methods: We performed a retrospective review of the medical records of all consecutive metastatic melanoma patients who received Nivolumab treatment from January/2014 – February/2017, including 53 patients prospectively collected from an Expanded Access Program. Of 86 patients, 83 patients were included for demographic and efficacy analysis, and 74 had information about baseline pre-treatment NLR. We analyzed NLR as a continuous variable and categorised ≥ 5 vs. < 5. Kaplan-Meier method was used for survival analysis. Long-rank test compared categories and Cox proportional hazards regression model was used to assess the prognostic significance of baseline NLR in univariate and multivariable analysis. Results: Median PFS for the entire population was 6,407 months (3,28 – 9,52) and median OS was not reached (NR) with a median FU of 10,74 months. The median NLR ratio was 3,11 (0,87 – 19). 18 patients (24,3%) had a ≥ 5 NLR vs. 56 (75,7%) < 5. Median PFS for NLR ≥ 5 was: 2,3 (1,75 – 2,84) vs. 12,02 (5,11 – 18,93) for < 5 (HR = 3,11; IC95% 1,52 – 6,27; p = 0,001). Median OS ≥ 5: 3,05 (2,06 – 4,04) vs. NR for < 5 (HR = 5,88; IC95% 2,60 – 13,29; p = 0,001). NLR categorised remained statistically significant in multivariate analysis for PFS and NLR as a continuous variable remained statistically significant for both PFS and OS in multivariate analysis (Table 1). Conclusions: Baseline NLR is a rapid, simple, and cost-free predictor of survival before Anti-PD1 therapy. These results should be validated in a larger cohort of patients. [Table: see text]


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 433-433
Author(s):  
Philippe Merle ◽  
Agnes Rode ◽  
Anne-Frederique Manichon ◽  
Nadim Fares ◽  
Celia Prevost ◽  
...  

433 Background: SR is a curative therapy of single HCC. CRT is efficient for small HCC (≤ 5 cm), whereas its combination to TACE (CRT+TACE) is needed for large ( > 5 cm) HCC. However, SR remains the gold-standard in guidelines for large HCC. This work aims to compare these approaches. Methods: Retrospective analysis of prospectively collected data, on patients (pts) included at Lyon North Hepatobiliary Centre, Child-Pugh-A, single HCC. CRT+TACE was decided at the HCC board by ineligibility for SR, radiofrequency or liver transplantation. Outcome of pts was compared between CRT+TACE and SR. Continuous variables were assessed by the t-Student test, and survival analysis by the Cox proportional-hazards regression. Results: 178 pts (68 CRT+TACE, 110 SR), males 78%, cirrhosis 52%, etiology (alcohol 46%, HCV 17%, HBV 13%, NASH 30%), 103 small, 75 large HCC, median age 66 ys, tumor size 50 mm, AFP 8 ng/mL, albuminemia (ALB) 39 g/L, platelets (PLAT) 166 Giga/L, follow-up 33 months. CRT+TACE complete response rate: 92% small / 80% large HCC. Small HCC comparison: CRT+TACE vs SR: age (67 vs 64, P= NS), cirrhosis (94% vs 47%, P< 0.0001), ALB (36 vs 40, P= 0.0001), PLAT (150 vs 201, P= 0.02), AFP (381 vs 300, P= NS). CRT-TACE was a poor outcome factor in univariate analysis for overall survival (OS) (HR 2.32; P= 0.01), progression-free survival (PFS) (HR 1.90; P= 0.007), but did not remain independent in multivariate analysis due to combined factors: age > 70, cirrhosis, ALB < 35, PLAT < 100. Large HCC comparison: CRT+TACE vs SR: age (73 vs 62, P= 0.0008), cirrhosis (70% vs 25%, P= 0.0004), ALB (38 vs 39, P= NS), PLAT (173 vs 240, P= 0.01), AFP (5616 vs 3456, P= NS). CRT-TACE was a poor outcome factor only for OS (HR 3.01; P= 0.0007) in univariate analysis. After adjustment to other factors (age > 70, cirrhosis, PLAT < 100), CRT-TACE was not independent in multivariate analysis for OS ( P= 0.19). Conclusions: CRT+TACE induced an encouraging tumor control rate in a population of older pts, more deteriorated chronic hepatopathy than pts treated by SR. Especially for large HCC, SR was not better than CRT+TACE on the outcome. Prospective randomized trials are warranted to confirm these data.


Sign in / Sign up

Export Citation Format

Share Document