MGMT methylation status as a prognostic factor in anaplastic astrocytomas

2052 Background: MGMT methylation status has been found to be an important prognostic factor in glioblastoma patients (pts). However, further data on the epigenetic feature are needed before its role in rare diseases such as anaplastic astrocytomas (AA) can be established. Methods: A retrospective analysis was made on a database of 139 AA pts followed prospectively from January 1995 and August 2008. We evaluated only pts who met the following inclusion criteria: age >18 years; PS 0–2; histological diagnosis of AA; postoperative radiotherapy (RT) and chemotherapy (CT). MGMT status was determined with methylation specific PCR. The study aim was to evaluate the role of MGMT methylation status in AA. The log-rank test was employed to evaluate the significance of the prognostic variables. Results: 80 pts (m/f: 46/34, median age: 41 years, range: 18–71 years) were enrolled. MGMT was assessable in 71 of 80 pts (88.8%), being methylated in 30 (42.9%), and unmethylated in 41 (57.7%) pts. Median PFS was 48.6 months (95% CI: 33.7 - 63.5), being 96 months (95% CI: 29–163) and 38 months (95%CI: 18.9–57.2) in MGMT methylated and unmethylated pts, respectively (p = 0.09). At univariate analysis, complete resection (p = 0.02), age (p = 0.002), and KPS (p = 0.003) were significantly correlated with PFS. At multivariate analysis only age remains correlated with PFS (p = 0.01). Median survival (OS) was 93.7 months (95% CI: 63.5–123.8), being not reached and 77 months (95% CI: 20–134.2), in MGMT methylated and unmethylated pts, respectively (p = 0.03). MGMT methylation (p = 0.03), age (p = 0.0003), and KPS (p = 0.03) were significantly correlated with OS at univariate analysis. At multivariate analysis, age (p = 0.0002) and MGMT methylation (p = 0.01) were correlated with a better OS. Conclusions: MGMT methylation status is an independent prognostic factor together with age in AA. This datum should provide the background to improve the therapeutic index with temozolomide concurrent with and adjuvant to RT in AA. No significant financial relationships to disclose.

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Impact of MGMT methylation status on 1p/19q intact anaplastic gliomas

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e13003 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e13003-e13003

Author(s):

E. Franceschi ◽

A. Tosoni ◽

M. Ermani ◽

F. Spagnolli ◽

L. La Torre ◽

...

Keyword(s):

Postoperative Radiotherapy ◽

Methylation Status ◽

Progression Free Survival ◽

Anaplastic Oligodendroglioma ◽

Rank Test ◽

Fish Analysis ◽

Mgmt Methylation ◽

Prognostic Information ◽

Specific Pcr ◽

Anaplastic Gliomas

e13003 Background: Chromosomes 1p/19q codeletion has been recognized as a prognostic and predictive factor in patients (pts) with grade 3 gliomas. Non-codeleted (intact) anaplastic oligodendroglioma showed a survival comparable to that usually observed in pts with anaplastic astrocytomas; MGMT methylation status, moreover, has been found to be a prognostic factor in glioblastoma and anaplastic gliomas (AG). Methods: A retrospective analysis was made using a database of 253 AG pts followed prospectively between January 1998 and August 2008. We evaluated only pts who met the following inclusion criteria: age ≥ 18 years; PS 0–2; histological diagnosis of AG with 1p/19q intact, as determined by FISH analysis; treatment with postoperative radiotherapy (RT) and chemotherapy (CT); MGMT status determined using methylation specific PCR. The study aim was to evaluate the role of MGMT methylation status in 1p/19q codeleted AG pts. The log-rank test was used to evaluate the significance of the prognostic variables. Results: 67 pts (m/f: 35/32, median age: 41.3 years, range: 18–70 years) were enrolled. Histology was anaplastic oligodendroglioma in 17 pts, anaplastic oligoastrocytoma in 20 pts, and anaplastic astrocytoma in 30 pts; all these pts were 1p19q intact and received surgery, RT, and CT. MGMT status, assessable in 58 pts (86.6%), was methylated in 33 pts (56.9%), and unmethylated in 25 pts (43.1%). Median progression-free survival (PFS) was 32.3 months (95%CI: 9.9–54.7). No enhancement at time of diagnosis (p = 0.003), gross total resection (p = 0.03), age (p = 0.001), and MGMT methylation (p = 0.05) were significantly correlated with better PFS. Median survival was 65.2 months (95% CI: 45–85.3). Only age (p = 0.001) and KPS (p = 0.02) correlated with a better survival. Conclusions: MGMT methylation status may provide adjunctive prognostic information in pts with 1p/19q intact AG, indicating a prolonged PFS in pts harboring MGMT promoter methylation. No significant financial relationships to disclose.

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Associations between regorafenib-induced adverse events (AEs) and efficacy in metastatic colorectal cancer (mCRC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.556 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 556-556 ◽

Cited By ~ 1

Author(s):

Takeru Wakatsuki ◽

Eiji Shinozaki ◽

Mitsukuni Suenaga ◽

Izuma Nakayama ◽

Tomohiro Matsushima ◽

...

Keyword(s):

Multivariate Analysis ◽

Adverse Events ◽

Univariate Analysis ◽

Rank Test ◽

Multikinase Inhibitor ◽

Log Rank Test ◽

Kaplan Meier ◽

Almost All ◽

Therapy Target

556 Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.

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Extent of tumor removal and molecular markers in cerebral glioblastoma: a combined prognostic factors study in a surgical series of 105 patients

Journal of Neurosurgery ◽

10.3171/2012.4.jns101702 ◽

2012 ◽

Vol 117 (2) ◽

pp. 204-211 ◽

Cited By ~ 31

Author(s):

Maurizio Salvati ◽

Angelo Pichierri ◽

Manolo Piccirilli ◽

Giacoma Maria Floriana Brunetto ◽

Alessandro D'Elia ◽

...

Keyword(s):

Prognostic Factor ◽

Statistical Power ◽

Statistical Significance ◽

Univariate Analysis ◽

Methylation Status ◽

Progression Free Survival ◽

Rank Test ◽

Survival Prediction ◽

Surgical Removal ◽

Total Removal

Object In this paper, the authors' goal was to evaluate the prognostic value of YKL-40 expression as a prognostic factor for glioblastomas and to compare its validity to the already known MGMT. Methods Between January 2002 and January 2007, 105 patients were treated for cerebral glioblastoma. The extent of removal was classified in 4 groups. YKL-40 expression was evaluated by a semiquantitative immunohistochemical staining scale (0, no staining; 1, mild expression; and 2, strong expression). MGMT promoter methylation status was analyzed with methylation-specific polymerase chain reaction. All patients received adjuvant radiotherapy and chemotherapy. Kaplan-Meier curves were used to analyze progression-free survival (PFS) and overall survival (OS), and to compare these parameters between the subgroups stratified by extent of surgical removal, MGMT methylation, and YKL-40 expression. The log-rank test was used to determine statistical significance. A multivariate regression analysis was applied to extent of removal, YKL-40 expression, and MGMT status to check their specific statistical power and to test the independence of the variables. Results There were 55 men and 50 women with a mean age of 58 years. Extent of surgical removal is reported. The MGMT promoter was methylated in 48 patients and nonmethylated in 57. Analysis of YKL-40 expression is reported. The median PFS was 10.7 months (14.9 months in the gross-total removal subgroup) (p < 0.0001), and the median OS was 12.5 months (17.4 months in the gross-total removal group) (p < 0.0001). In the univariate analysis, OS was significantly correlated to the extent of resection (p < 0.0001), MGMT status (p < 0.0001), and YKL-40 (p < 0.0001). Multivariate analysis showed that all 3 factors reached statistical significance with respect to patient survival. In particular, surgical removal contributed more than the 2 other factors to the survival prediction (β = −0.6254). Interestingly, YKL-40 (β = −0.3867) contributed more than MGMT (β = −0.1705) to the predicted survival. Conclusions The extent of removal is the most important factor influencing the OS of patients harboring glioblastomas. When biological aggressiveness is taken into account, YKL-40 expression was found to be an independent prognostic factor that predicts OS better than MGMT status.

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Thymidine phosphorylase expression in metastatic kidney cancer as a potential predictor of outcome in patients treated with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15091 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15091-e15091

Author(s):

Manuela Miscoria ◽

Carla Di Loreto ◽

Fabio Puglisi ◽

Paul Gerard Murray ◽

Laura Deroma ◽

...

Keyword(s):

Multivariate Analysis ◽

Thymidine Phosphorylase ◽

Cox Regression ◽

Univariate Analysis ◽

Objective Response ◽

Nucleotide Metabolism ◽

Rank Test ◽

Pyrimidine Nucleotide ◽

Thymidine Phosphorylase Expression

e15091 Background: Aberrant tumour angiogenesis is a hallmark of Renal Cell Carcinoma (RCC). Sunitinib is a small molecule targeting angiogenesis licensed for advanced RCC (aRCC) treatment. Thymidine Phosphorylase (TP) is an enzyme involved in pyrimidine nucleotide metabolism with a role in angiogenesis upregulation in cancer. In RCC, TP expression is associated with poor prognosis. We studied TP immunohistochemical expression in RCC samples and its association with the outcomes in a cohort of aRCC patients treated with sunitinib. Methods: We identified 59 consecutive patients with aRCC treated with sunitinib at our Institution. Nuclear (N) and cytoplasm (C) scoring for TP, using the validated Tsuda scoring, was performed. TP expression and clinico-pathological variables were studied to assess their association with the outcome of S therapy. The log rank test has been used for the univariate analysis and the Cox regression for the multivariate analysis. Results: Thirty-four patients received sunitinib as first line treatment. Fifty patients (84%) had clear cell RCC, 7 (12%) showed sarcomatoid features. Forty-five patients (76%) achieved either an objective response or stable disease. At the time of the analysis 32 patients had died, 46 had progressed and 41 had stopped the treatment. After an average follow up of 21 months, median OS and PFS were 21.2, 12.8 months respectively. N TP staining was positive in 19 patients (32%) and C staining in 36 (61%) patients. A significant association was observed between the N and C expression (p=0.004). The univariate analysis identified an association between N TP expression and longer OS (29.8 vs 17.8 months; p=0.0463) even if the association was not significant in the multivariate analysis (HR=0.56; CI 0.19-1.6). No associations were noted with PFS. Conclusions: In our study TP was overexpressed in a significant percentage of kidney cancers. In patients treated with sunitinib, N TP expression was associated with better OS. The results of the multivariate analysis were probably affected by the limited sample size. Larger and prospective studies are necessary to define the role of TP in RCC.

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Change in MGMT methylation status between first and second surgery for recurrence: Clinical implications

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2027 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2027-2027

Author(s):

A. A. Brandes ◽

E. Franceschi ◽

A. Tosoni ◽

A. Fioravanti ◽

R. Agati ◽

...

Keyword(s):

Methylation Status ◽

Postoperative Treatment ◽

Rank Test ◽

Time Interval ◽

Mgmt Methylation ◽

Second Surgery ◽

Mgmt Promoter ◽

Prognostic Utility ◽

Newly Diagnosed Glioblastoma

2027 Background: MGMT promoter methylation status is known to be a potent prognostic factor in newly diagnosed glioblastoma (GBM) patients (pts). However, it is not yet clear whether and, if so, how MGMT methylation status may change; nor is it known whether the prognostic role of this epigenetic feature is retained during the disease course. Methods: A retrospective analysis was made using a database of 614 GBM pts treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age ≥18; PS 0–2; two distinct surgical procedures; histological diagnosis of GBM both at first and at second surgery for recurrence; postoperative treatment consisting of: a) radiotherapy (RT) followed by temozolomide (TMZ) until 2005, and b) TMZ concurrent with and adjuvant to RT after 2005; a time interval ≥3 month between first and second surgery. The study aim was to evaluate changes of MGMT status during the course of GBM. The log-rank test was employed to evaluate the significance of the prognostic variables. The percentages of MGMT methylated cases at first and second surgery were compared using the McNemar test. Results: MGMT status, evaluated at first and second surgery in all 44 pts (M:F 32:12, median age: 49 years, range: 27–67), was assessable in 38 (86.4%) cases: MGMT promoter was methylated in 13 (34.2%) pts at first surgery. MGMT methylation status, unchanged in 63.2% of second surgery samples, changed more frequently in methylated than in unmethylated pts (61.5% vs 24%, p = 0.03). The median survival was 24.3 months (95% CI: 20.8–27.7), being 35.2 months (95% CI: 10.1–60.2) and 21.9 months (95% CI: 17.3–26.5) for pts with methylated and unmethylated MGMT assessed at first surgery, respectively (p = 0.04). However, MGMT status at second surgery was no longer prognostic for survival (p = 0.1). Conclusions: Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. Moreover, while MGMT methylation status is prognostic at first surgery, it appears to be of no prognostic utility at the time of second surgery. No significant financial relationships to disclose.

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Association between preoperative serum albumin and prognosis in patients with adrenocortical carcinoma after primary resection: a retrospective study

BMC Cancer ◽

10.1186/s12885-021-08689-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fuxun Zhang ◽

Zhihong Liu ◽

Jiayu Liang ◽

Shengzhuo Liu ◽

Kan Wu ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factor ◽

Serum Albumin ◽

Adrenocortical Carcinoma ◽

Statistical Significance ◽

Univariate Analysis ◽

Primary Resection ◽

Rank Test ◽

Significant Prognostic Factor ◽

Preoperative Serum

Abstract Background Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. Given the limited treatment options, prognostic assessment of ACC is increasingly crucial. In this study, we aim to assess the correlation between preoperative serum albumin and prognosis in patients with ACC after primary resection. Methods We retrospectively collected and reviewed medical information about 71 ACC patients who underwent primary resection. Survival analysis was performed by Kaplan–Meier analysis with log-rank test or Breslow test. Receiver operating characteristic (ROC) curve and Jordan index was generated to explore optimal cut-off value of albumin. Univariate and multivariate analysis was conducted using Cox’s hazards model. Statistical significance was defined as P < 0.05. Results Among included patients, 33 patients (46.5%) relapsed at the end of follow-up, while 39 patients (54.9%) died. The median overall survival (OS) of included patients was 17 (range 1–104) months, and median recurrence-free survival (RFS) was 10 (range 0–104) months. In univariate analysis, the albumin was significantly associated with OS (HR:0.491, 95% CI: 0.260–0.930, P = 0.029) and RFS (HR: 0.383, 95% CI: 0.192–0.766, P = 0.007). In multivariate analysis, serum albumin as an independent prognostic factor of OS was confirmed (HR: 0.351, 95% CI: 0.126–0.982, P = 0.046). Conclusions Preoperative albumin might be a significant prognostic factor for ACC patients after primary resection. This result may be useful for risk stratification and management of this rare malignancy.

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Clinical Role of Lung Ultrasound for the Diagnosis and Prognosis of Coronavirus Disease Pneumonia in Elderly Patients: A Pivotal Study

Gerontology ◽

10.1159/000512209 ◽

2020 ◽

pp. 1-9

Author(s):

Guerino Recinella ◽

Giovanni Marasco ◽

Manuel Tufoni ◽

Mara Brizi ◽

Eleonora Evangelisti ◽

...

Keyword(s):

Multivariate Analysis ◽

Elderly Patients ◽

Lung Ultrasound ◽

Univariate Analysis ◽

Hospital Death ◽

Clinical Role ◽

Diagnosis And Prognosis ◽

Hospitalized Elderly ◽

Novel Coronavirus

Background: Lung ultrasound (LUS) showed a promising role in the diagnosis and monitoring of patients hospitalized for novel coronavirus disease (COVID-19). However, no data are available on its role in elderly patients. Aims: The aim of this study was to evaluate the diagnostic and prognostic role of LUS in elderly patients hospitalized for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia. Methods: Consecutive elderly patients (age >65 years) hospitalized for COVID-19 were enrolled. Demographics, laboratory, comorbidity, and the clinical features of the patients were collected. All patients underwent LUS on admission to the ward. LUS characteristics have been analyzed. Uni- and multivariate analyses to evaluate predictors for in-hospital death were performed. Results: Thirty-seven hospitalized elderly patients (19 men) with a diagnosis of SARS-CoV-2 infection were consecutively enrolled. The median age was 82 years (interquartile range 74.5–93.5). Ultrasound alterations were found in all patients enrolled; inhomogeneous interstitial syndrome with spared areas (91.9%) and pleural alterations (100%) were the most frequent findings. At univariate analysis, LUS score (hazard ratio [HR] 1.168, 95% CI 1.049–1.301) and pleural effusions (HR 3.995, 95% CI 1.056–15.110) were associated with in-hospital death. At multivariate analysis, only LUS score (HR 1.168, 95% CI 1.049–1.301) was independelty associated with in-hospital death. The LUS score’s best cutoff for distinguishing patients experiencing in-hospital death was 17 (at multivariate analysis LUS score ≥17, HR 4.827, 95% CI 1.452–16.040). In-hospital death was significantly different according to the LUS score cutoff of 17 (p = 0.0046). Conclusion: LUS could play a role in the diagnosis and prognosis in elderly patients hospitalized for SARS-CoV-2 infection.

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Lymphatic Vessel Invasion As a Prognostic Factor in Patients With Primary Resected Adenocarcinomas of the Esophagogastric Junction

Journal of Clinical Oncology ◽

10.1200/jco.2005.12.151 ◽

2005 ◽

Vol 23 (4) ◽

pp. 874-879 ◽

Cited By ~ 67

Author(s):

Burkhard H.A. von Rahden ◽

Hubert J. Stein ◽

Marcus Feith ◽

Karen Becker ◽

J. Rüdiger Siewert

Keyword(s):

Multivariate Analysis ◽

Prognostic Factor ◽

Esophagogastric Junction ◽

Lymphatic Vessel ◽

Univariate Analysis ◽

Prognostic Significance ◽

Residual Tumor ◽

Lymphatic Vessel Invasion ◽

Vessel Invasion ◽

Significant Difference

Purpose To evaluate the value of lymphatic vessel invasion (LVI) as a predictor of survival in patients with primary resected adenocarcinomas of the esophagogastric junction (AEG). Patients and Methods We prospectively evaluated 459 patients undergoing primary surgical resection for tumors of the esophagogastric junction at our institution between 1992 and 2000 (180 adenocarcinomas of the distal esophagus, AEG I; 140 carcinomas of the cardia, AEG II; and 139 subcardial gastric cancers, AEG III). Median follow-up was 36.8 months. The prevalence of LVI was evaluated by two independent pathologists. Univariate and multivariate analysis of prognostic factors was performed. Results The total rate of LVI was 49.9%, with a significant difference between AEG I (38.9%) and AEGII/III (57.0%, P = .0002). Univariate analysis showed a significant correlation between LVI and T category (P < .0001), N category (P < .0001), and resection status (R [residual tumor] category; P < .0001). This was shown for the group of all AEG tumors, as well as for the subgroups AEG I and AEG II/III. On multivariate analysis, LVI was identified as a significant and independent prognostic factor (P = .050) in the population of all patients and in patients with AEG II/III, but not in the subgroup with AEG I. Conclusion These data demonstrate the prognostic significance of LVI in patients with AEG tumors, with marked differences between the subgroups AEG I versus AEG II/III. The lower prevalence and lack of prognostic significance of LVI in AEG I might be explained by inflammation involved in the pathogenesis of this entity.

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