Prognostic value of pre-irradiation FET PET in patients with not completely resectable IDH-wildtype glioma and minimal or absent contrast enhancement

AbstractIn glioma patients, complete resection of the contrast-enhancing portion is associated with improved survival, which, however, cannot be achieved in a considerable number of patients. Here, we evaluated the prognostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in not completely resectable glioma patients with minimal or absent contrast enhancement before temozolomide chemoradiation. Dynamic FET PET scans were performed in 18 newly diagnosed patients with partially resected (n = 8) or biopsied (n = 10) IDH-wildtype astrocytic glioma before initiation of temozolomide chemoradiation. Static and dynamic FET PET parameters, as well as contrast-enhancing volumes on MRI, were calculated. Using receiver operating characteristic analyses, threshold values for which the product of paired values for sensitivity and specificity reached a maximum were obtained. Subsequently, the prognostic values of FET PET parameters and contrast-enhancing volumes on MRI were evaluated using univariate Kaplan–Meier and multivariate Cox regression (including the MTV, age, MGMT promoter methylation, and contrast-enhancing volume) survival analyses for progression-free and overall survival (PFS, OS). On MRI, eight patients had no contrast enhancement; the remaining patients had minimal contrast-enhancing volumes (range, 0.2–5.3 mL). Univariate analyses revealed that smaller pre-irradiation FET PET tumor volumes were significantly correlated with a more favorable PFS (7.9 vs. 4.2 months; threshold, 14.8 mL; P = 0.012) and OS (16.6 vs. 9.0 months; threshold, 23.8 mL; P = 0.002). In contrast, mean tumor-to-brain ratios and time-to-peak values were only associated with a longer PFS (P = 0.048 and P = 0.045, respectively). Furthermore, the pre-irradiation FET PET tumor volume remained significant in multivariate analyses (P = 0.043), indicating an independent predictor for OS. Our results suggest that pre-irradiation FET PET parameters have a prognostic impact in this subgroup of patients.

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Prognostic value of pre-irradiation FET PET in patients with not completely resectable IDH-wildtype glioma and minimal or absent contrast enhancement

10.21203/rs.3.rs-486421/v1 ◽

2021 ◽

Author(s):

Jurij Rosen ◽

Gabriele Stoffels ◽

Philipp Lohmann ◽

Elena K Bauer ◽

Jan Michael Werner ◽

...

Keyword(s):

Contrast Enhancement ◽

Prognostic Value ◽

Tumor Volume ◽

Cox Regression ◽

Prognostic Impact ◽

Fet Pet ◽

Time To Peak ◽

Kaplan Meier ◽

Number Of Patients ◽

Dynamic Fet Pet

Abstract Purpose: In glioma patients, complete resection of the contrast-enhancing portion is associated with improved survival, which, however, cannot be achieved in a considerable number of patients. Here, we evaluated the prognostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in not completely resectable glioma patients with minimal or absent contrast enhancement before temozolomide chemoradiation.Methods: Dynamic FET PET scans were performed in 18 newly diagnosed patients with partially resected (n=8) or biopsied (n=10) IDH-wildtype astrocytic glioma before initiation of temozolomide chemoradiation. Static and dynamic FET PET parameters, as well as contrast-enhancing volumes on MRI, were calculated. Using receiver operating characteristic analyses, threshold values for these parameters were obtained. Subsequently, the prognostic values of FET PET parameters and contrast-enhancing volumes on MRI were evaluated using univariate Kaplan-Meier and multivariate Cox regression survival analyses for progression-free and overall survival (PFS, OS).Results: On MRI, eight patients had no contrast enhancement; the remaining patients had minimal contrast-enhancing volumes (range, 0.2-5.3 mL). Univariate analyses revealed that a smaller pre-irradiation FET PET tumor volume significantly influenced PFS (7.9 vs. 4.2 months; threshold, 14.8 mL; P=0.012) and OS (16.6 vs. 9.0 months; threshold, 23.8 mL; P=0.002). In contrast, mean tumor-to-brain ratios and time-to-peak values were only associated with a longer PFS (P=0.048 and P=0.045, respectively). Furthermore, the pre-irradiation FET PET tumor volume remained significant in multivariate analyses (P=0.043), indicating an independent predictor for OS.Conclusion: Our results suggest that pre-irradiation FET PET parameters have a prognostic impact in this subgroup of patients.

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P14.18 Prognostic value of serial dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine PET in patients with non-resectable malignant glioma undergoing chemoradiation

Neuro-Oncology ◽

10.1093/neuonc/noz126.253 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii70-iii70

Author(s):

J Rosen ◽

G Stoffels ◽

P Lohmann ◽

E K Bauer ◽

J Werner ◽

...

Keyword(s):

Prognostic Value ◽

Tumor Volume ◽

Newly Diagnosed ◽

Fet Pet ◽

Rano Criteria ◽

Multivariate Survival ◽

Number Of Patients ◽

Mri Changes ◽

Dynamic Fet Pet

Abstract BACKGROUND A complete resection of high-grade gliomas (HGG) is associated with improved survival, which, however, cannot be achieved in a considerable number of patients. We here evaluated the prognostic value of serial O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in patients with newly diagnosed, non-resectable astrocytic HGG undergoing chemoradiation with temozolomide. MATERIAL AND METHODS Serial dynamic FET PET scans were performed in 18 newly diagnosed patients with molecularly defined, non-resectable HGG at baseline and after chemoradiation (8±3 weeks). Both static (tumor/brain ratios, FET tumor volumes) and dynamic FET PET parameters (time-to-peak, slope), as well as MRI changes according to RANO criteria at first follow-up after chemoradiation (8±3 weeks), were obtained. The predictive ability of FET PET parameters and RANO criteria was evaluated with regard to the progression-free survival (PFS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate and multivariate survival analyses were performed to assess their predictive power for PFS. RESULTS ROC analysis revealed that the mean tumor/brain ratio (AUC, 0.84), FET tumor volume (AUC, 0.89), and slope (AUC, 0.72) at baseline were predictive for a prolonged PFS (9.3 vs. 5.7 months, P=0.05; 10.3 vs. 5.9 months; P=0.03; 13.5 vs. 6.2 months, P=0.02, respectively). Furthermore, FET tumor volume and slope remained significant in the multivariate survival analysis (both P<0.05). In contrast, relative changes of static or dynamic FET PET parameters at follow-up and MRI changes according to RANO criteria were not significant in this albeit small series of patients. CONCLUSION Results suggest that before initiation of chemoradiation FET PET parameters at baseline can be used to predict PFS in patients with non-resectable HGG.

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Cognitive impairment predicts conversion to multiple sclerosis in clinically isolated syndromes

Multiple Sclerosis Journal ◽

10.1177/1352458509350311 ◽

2009 ◽

Vol 16 (1) ◽

pp. 62-67 ◽

Cited By ~ 98

Author(s):

Valentina Zipoli ◽

Benedetta Goretti ◽

Bahia Hakiki ◽

Gianfranco Siracusa ◽

Sandro Sorbi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Prognostic Value ◽

Cox Regression ◽

Cox Regression Analysis ◽

Clinically Isolated Syndromes ◽

Kaplan Meier ◽

Sizable Proportion ◽

One Year ◽

Therapeutic Decision Making

Significant cognitive impairment has been found in 20—30% of patients with clinically isolated syndromes suggestive of multiple sclerosis. In this study we aimed to assess the prognostic value of the presence of cognitive impairment for the conversion to multiple sclerosis in patients with clinically isolated syndromes. All patients with clinically isolated syndromes consecutively referred to our centre since 2002 and who had been followed-up for at least one year underwent cognitive assessment through the Rao’s Battery and the Stroop test. Possible predictors of conversion to clinically definite multiple sclerosis were evaluated through the Kaplan Meier curves and Cox regression analysis. A total of 56 patients (41 women; age 33.2 ± 8.5 years; expanded disability scale score 1.2 ± 0.7) were recruited. At baseline, 32 patients (57%) fulfilled McDonald’s criteria for dissemination in space. During the follow-up (3.5 ± 2.3 years), 26 patients (46%) converted to a diagnosis of multiple sclerosis. In particular, 64% of patients failing ≥ 2 tests and 88% of patients failing ≥ 3 tests converted to multiple sclerosis. In the Cox regression model, the failure of at least three tests (HR 3.3; 95% CI 1.4—8.1; p = 0.003) and the presence of McDonald’s dissemination in space at baseline (HR 3.8; 95% CI 1.5—9.7; p = 0.005), were found to be predictors for conversion to multiple sclerosis. We conclude that cognitive impairment is detectable in a sizable proportion of patients with clinically isolated syndromes. In these subjects cognitive impairment has a prognostic value in predicting conversion to multiple sclerosis and may therefore play a role in therapeutic decision making.

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H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

10.21203/rs.3.rs-949930/v1 ◽

2021 ◽

Author(s):

Huy Gia Vuong ◽

Hieu Trong Le ◽

Tam N.M. Ngo ◽

Kar-Ming Fung ◽

James D. Battiste ◽

...

Keyword(s):

Cox Regression ◽

Fatal Outcome ◽

Extent Of Resection ◽

Tumor Location ◽

Genetic Alterations ◽

Integrated Analysis ◽

Prognostic Impact ◽

Kaplan Meier ◽

Hazard Ratios ◽

The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

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Type I Versus Type II Endometrial Cancer: Differential Impact of Comorbidity

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001184 ◽

2018 ◽

Vol 28 (3) ◽

pp. 586-593 ◽

Cited By ~ 8

Author(s):

Mette Calundann Noer ◽

Sofie Leisby Antonsen ◽

Bent Ottesen ◽

Ib Jarle Christensen ◽

Claus Høgdall

Keyword(s):

Cox Regression ◽

Type I ◽

Prognostic Impact ◽

Type Ii ◽

Regression Analyses ◽

Differential Impact ◽

Kaplan Meier ◽

Prediction Of Survival ◽

Comorbidity Index ◽

The Impact

ObjectiveTwo distinct types of endometrial carcinoma (EC) with different etiology, tumor characteristics, and prognosis are recognized. We investigated if the prognostic impact of comorbidity varies between these 2 types of EC. Furthermore, we studied if the recently developed ovarian cancer comorbidity index (OCCI) is useful for prediction of survival in EC.Materials and MethodsThis nationwide register-based cohort study was based on data from 6487 EC patients diagnosed in Denmark between 2005 and 2015. Patients were assigned a comorbidity index score according to the Charlson comorbidity index (CCI) and the OCCI. Kaplan-Meier survival statistics and adjusted multivariate Cox regression analyses were used to investigate the differential association between comorbidity and overall survival in types I and II EC.ResultsThe distribution of comorbidities varied between the 2 EC types. A consistent association between increasing levels of comorbidity and poorer survival was observed for both types. Cox regression analyses revealed a significant interaction between cancer stage and comorbidity indicating that the impact of comorbidity varied with stage. In contrast, the interaction between comorbidity and EC type was not significant. Both the CCI and the OCCI were useful measurements of comorbidity, but the CCI was the strongest predictor in this patient population.ConclusionsComorbidity is an important prognostic factor in type I as well as in type II EC although the overall prognosis differs significantly between the 2 types of EC. The prognostic impact of comorbidity varies with stage but not with type of EC.

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Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

Cancer Control ◽

10.1177/1073274820903383 ◽

2020 ◽

Vol 27 (1) ◽

pp. 107327482090338

Author(s):

Fabian Haak ◽

Isabelle Obrecht ◽

Nadia Tosti ◽

Benjamin Weixler ◽

Robert Mechera ◽

...

Keyword(s):

Colorectal Cancer ◽

Immune Cell ◽

Cox Regression ◽

Prognostic Significance ◽

Tumor Necrosis Factor Receptor ◽

Tissue Microarrays ◽

Cell Infiltration ◽

Prognostic Impact ◽

Cox Regression Analysis ◽

Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

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The prognostic value of platelet-to-lymphocyte ratio on the long-term renal survival in patients with IgA nephropathy

International Urology and Nephrology ◽

10.1007/s11255-020-02651-3 ◽

2020 ◽

Author(s):

Dan Chang ◽

Yichun Cheng ◽

Ran Luo ◽

Chunxiu Zhang ◽

Meiying Zuo ◽

...

Keyword(s):

Prognostic Factor ◽

Prognostic Value ◽

Cox Regression ◽

Independent Prognostic Factor ◽

Renal Survival ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Female Patients ◽

Kaplan Meier

Abstract Purpose Platelet-to-lymphocyte ratio (PLR) was established showing the poor prognosis in several diseases, such as malignancies and cardiovascular diseases. But limited study has been conducted about the prognostic value of PLR on the long-term renal survival of patients with Immunoglobulin A nephropathy (IgAN). Methods We performed an observational cohort study enrolling patients with biopsy-proven IgAN recorded from November 2011 to March 2016. The definition of composite endpoint was eGFR decrease by 50%, eGFR < 15 mL/min/1.73 m2, initiation of dialysis, or renal transplantation. Patients were categorized by the magnitude of PLR tertiles into three groups. The Kaplan–Meier curves and multivariate Cox models were performed to determine the association of PLR with the renal survival of IgAN patients. Results 330 patients with a median age of 34.0 years were followed for a median of 47.4 months, and 27 patients (8.2%) had reached the composite endpoints. There were no differences among the three groups (PLR < 106, 106 ≤ PLR ≤ 137, and PLR > 137) in demographic characteristics, mean arterial pressure (MAP), proteinuria, and estimated glomerular filtration rate (eGFR) at baseline. The Kaplan–Meier curves showed that the PLR > 137 group was significantly more likely to poor renal outcomes than the other two groups. Using univariate and multivariate cox regression analyses, we found that PLR > 137 was an independent prognostic factor for poor renal survival in patients with IgAN. Subgroup analysis revealed that the PLR remained the prognostic value for female patients or patients with eGFR less than 60 mL/min/1.73 m2. Conclusions Our results underscored that baseline PLR was an independent prognostic factor for poor renal survival in patients with IgAN, especially for female patients or those patients with baseline eGFR less than 60 mL/min/1.73 m2.

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Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa126 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Sirui Ma ◽

Soumon Rudra ◽

Jian L Campian ◽

Sonika Dahiya ◽

Gavin P Dunn ◽

...

Keyword(s):

Cox Regression ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Prognostic Impact ◽

Egfr Amplification ◽

Molecular Alterations ◽

Kaplan Meier ◽

P 16 ◽

Grade Ii ◽

Tert Mutation

Abstract Background We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of TERT mutation, EGFR amplification, and CDKN2A/B deletion on isocitrate dehydrogenase (IDH)-wildtype GBM. Methods IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations: TERT mutation, EGFR amplification, or combination of whole chromosome 7 gain and whole chromosome 10 loss. Overall survival (OS) and progression-free survival (PFS) were calculated from RT and analyzed using the Kaplan–Meier method. Multivariable analysis (MVA) was performed using Cox regression to identify independent predictors of OS and PFS. Results Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively, P = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, P = .08). However, mGBM was associated with better OS (hazard ratio [HR] 0.50, 95% CI 0.29–0.88) and PFS (HR 0.43, 95% CI 0.26–0.72) than hGBM after adjusting for known prognostic factors on MVA. CDKN2A/B deletion was associated with worse OS (HR 1.57, 95% CI 1.003–2.46) and PFS (HR 1.57, 95% CI 1.04–2.36) on MVA, but TERT mutation and EGFR amplification were not. Conclusion Criteria for mGBM may require further refinement and validation. CDKN2A/B deletion, but not TERT mutation or EGFR amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.

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Adjuvant chemotherapy (ACT) in stage II colon cancer (CC) in patients with Lynch syndrome.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.3550 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 3550-3550

Author(s):

Karsten Schulmann ◽

Sven Koepnick ◽

Christoph Engel ◽

Christiane Bernhardt ◽

Verena Steinke ◽

...

Keyword(s):

Lynch Syndrome ◽

Cox Regression ◽

Disease Free Survival ◽

Stage Ii ◽

Prognostic Impact ◽

Regression Analyses ◽

Free Survival ◽

Kaplan Meier ◽

Stage Ii Colon Cancer ◽

Disease Free

3550 Background: Previous studies showed conflicting results regarding the value of ACT in MSI-H CC. A recent study reported differential benefits from 5-FU-based ACT comparing suspected sporadic vs suspected hereditary MSI-H CC. We sought to evaluate the prognostic impact of ACT in a large cohort of Lynch syndrome (LS) patients (pts) with stage II CC. Methods: To minimize selection bias diagnoses >2 years prior to registration in the database of the German HNPCC consortium were excluded. 278 patients (61% male, mean age 42.9y, 13% stage IIB, 51% with MMR gene mutation) were eligible. Overall Survival (OS), CC-specific Survival (CSS), and Disease Free Survival (DFS) were analyzed using Kaplan-Meier and Cox Regression analyses. Results: 5y OS, CSS and DFS were 95%, 95% and 93% respectively. Right-sided CC was independently associated with lower DFS in stage II and IIA. Increasing age was associated with lower OS, CSS and DFS in stage IIA, however we observed only trends in the multivariate analysis. Surgery alone (without ACT) was associated with a slightly lower OS in stage IIA (univariate HR 3,659; 95% CI 0,81-16,5; P=0.092); but not with lower DFS and CSS. Prognosis was not different comparing FOLFOX vs. 5-FU-based ACT. Conclusions: Our data suggest that LS pts with stage II CC do not benefit from ACT. FOLFOX was not superior to 5-FU-based ACT. If our results are confirmed, LS pts with stage IIA CC should not receive ACT. The group of stage IIB CC was too small to make definite conclusions. [Table: see text]

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Histopathological and Genomic Grading Provide Complementary Prognostic Information in Breast Cancer: A Study on Publicly Available Datasets

Pathology Research International ◽

10.4061/2011/890938 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Nilotpal Chowdhury

Keyword(s):

Breast Cancer ◽

Cox Regression ◽

Prognostic Indicator ◽

Rank Test ◽

Prognostic Impact ◽

Prognostic Information ◽

Free Survival ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Prognostic Indicator

The genomic grade (GG) for breast cancer is thought to be the genomic counterpart of histopathological grade (HG). The motivation behind this study was to see whether HG retains its prognostic impact even when adjusted for GG, or whether it can be replaced by the latter. Four publicly available gene expression datasets were analyzed. Kaplan-Meier curves, log rank test, and Cox regression were used to study recurrence-free survival (RFS) and distant metastasis-free survival (DMFS). HG remained a significant prognostic indicator in low GG tumors (P = 0.003 for DMFS, P< 0.001 for RFS) but not in high GG tumors. HG grade 2 tumors differed significantly from HG grade 1 tumors, underlining the prognostic role of intermediate HG tumors. Additionally, GG could stratify HG 1 as well as HG 2 tumors into distinct prognostic groups. HG and GG add independent prognostic information to each other. However, the prognostic effects of both HG and GG are time varying, with the hazard ratios of high HG and GG tumors being markedly attenuated over time.

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