High Expression of H3K9me3 Is a Strong Predictor of Poor Survival in Patients With Salivary Adenoid Cystic Carcinoma

2013 ◽  
Vol 137 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Ronghui Xia ◽  
Rongrui Zhou ◽  
Zhen Tian ◽  
Chunye Zhang ◽  
Lizhen Wang ◽  
...  
Keyword(s):  
Adenoid Cystic Carcinoma ◽  
Distant Metastasis ◽  
Survival Data ◽  
Histone H3 ◽  
Disease Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
Salivary Adenoid Cystic Carcinoma ◽  
Adenoid Cystic ◽  
Disease Free

Context.—Histone methylation and acetylation play important roles in the carcinogenesis and progression of cancer. Objective.—To investigate whether histone modifications influence the prognosis of patients with salivary adenoid cystic carcinoma (ACC). Design.—The expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used to determine the presence of any correlation between H3K9me3 and H3K9Ac levels and clinicopathologic parameters. Log-rank test and Cox proportional hazards regression models were used to analyze the survival data. Results.—H3K9me3 expression was positively correlated with solid pattern tumors (P = .002) and distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors showed high H3K9me3 expression and a solid pattern had a significantly poorer overall survival (OS) (P < .001 and P < .001, respectively) and disease-free survival (P < .001 and P = .01, respectively). Low H3K9Ac expression was correlated with poor OS (P = .05). The multivariate analysis indicated that high levels of H3K9me3 expression and solid pattern tumors were independent prognostic factors that significantly influenced OS (P = .004 and P = .04, respectively). H3K9me3 expression was identified as the only independent predictor of disease-free survival (P = .006). Conclusions.—Our results suggest that high levels of H3K9me3 expression are predictive of rapid cell proliferation and distant metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better predictive biomarker for the prognosis of patients with salivary ACC.

Burden of lymphatic disease predicts efficacy of adjuvant radiation and chemotherapy in FIGO 2018 stage IIICp cervical cancer

2019 ◽  
Vol 29 (9) ◽  
pp. 1355-1360 ◽  
Author(s):  
Giorgio Bogani ◽  
Daniele Vinti ◽  
Ferdinando Murgia ◽  
Valentina Chiappa ◽  
Umberto Leone Roberti Maggiore ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Rank Test ◽  
Survival Outcomes ◽  
Adjuvant Radiation ◽  
Free Survival ◽  
Log Rank Test ◽  
Disease Free ◽  
Positive Lymph Nodes

ObjectiveNodal involvement is one of the most important prognostic factors in cervical cancer patients. We aimed to assess the prognostic role in relation to the burden of nodal disease in stage IIICp cervical cancer.MethodsData on all consecutive patients diagnosed with cervical cancer undergoing primary surgery (radical hysterectomy plus lymphadenectomy) or neoadjuvant chemotherapy followed by radical hysterectomy plus lymphadenectomy, between January 1980 and December 2017, were collected in a dedicated database. Exclusion criteria were: (1) consent withdrawal; (2) synchronous malignancies (within 5 years). Survival outcomes were assessed using Kaplan-Meier and Cox models.ResultsOverall, 177 (14.1%) of 1257 patients with cervical cancer were diagnosed with positive lymph nodes. After a median follow-up of 58 (range 4–175) months, 66 (37.3%) and 37 (20.9%) patients developed recurrent disease and died of disease, respectively. Via multivariate analysis, positive para-aortic nodes (HR 2.62, 95% CI 1.12 to 6.11; p=0.025) and the number of positive nodes (HR 1.06, 95% CI 1.02 to 1.11; p=0.002) correlated with worse disease-free survival. Furthermore, the number of positive nodes (HR 1.06, 95% CI 1.01 to 1.12; p=0.021) correlated with worse overall survival. Number of positive nodes (1, 2 or ≥3) strongly correlated with both disease-free survival (p<0.001, log-rank test) and overall survival (p=0.001, log-rank test). Focusing on patients receiving adjuvant radiation and chemotherapy, the number of positive lymph nodes was associated with response to treatment (p<0.001). Median disease-free survival was 100, 42, and 12 months for patients with one, two, or three or more positive lymph node(s), respectively (p<0.001, log-rank test).ConclusionsIn stage IIICp cervical cancer, adjuvant radiation and chemotherapy provides adequate overall survival in patients diagnosed with only one metastatic node, while survival outcomes are poor in patients with two or more metastatic nodes. This highlights the need for innovative treatments in patients with a high burden of lymphatic disease.

scholarly journals Effect of Chemotherapy With Docetaxel With Androgen Suppression and Radiotherapy for Localized High-Risk Prostate Cancer: The Randomized Phase III NRG Oncology RTOG 0521 Trial

2019 ◽  
Vol 37 (14) ◽  
pp. 1159-1168 ◽  
Author(s):  
Seth A. Rosenthal ◽  
Chen Hu ◽  
Oliver Sartor ◽  
Leonard G. Gomella ◽  
Mahul B. Amin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Distant Metastasis ◽  
Disease Free Survival ◽  
Free Survival ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Androgen Suppression ◽  
Disease Free

PURPOSE Radiotherapy (RT) plus long-term androgen suppression (AS) are a standard treatment option for patients with high-risk localized prostate cancer. We hypothesized that docetaxel chemotherapy (CT) could improve overall survival (OS) and clinical outcomes among patients with high-risk prostate cancer. PATIENTS AND METHODS The multicenter randomized NRG Oncology RTOG 0521 study enrolled patients with high-risk nonmetastatic disease between 2005 and 2009. Patients were randomly assigned to receive standard long-term AS plus RT with or without adjuvant CT. RESULTS A total of 612 patients were enrolled; 563 were evaluable. Median prostate-specific antigen was 15.1 ng/mL; 53% had a Gleason score 9 to 10 cancer; 27% had cT3 to cT4 disease. Median follow-up was 5.7 years. Treatment was well tolerated in both arms. Four-year OS rate was 89% (95% CI, 84% to 92%) for AS + RT and 93% (95% CI, 90% to 96%) for AS + RT + CT (hazard ratio [HR], 0.69; 90% CI, 0.49 to 0.97; one-sided P = .034). There were 59 deaths in the AS + RT arm and 43 in the AS + RT + CT arm, with fewer deaths resulting from prostate cancer in the AS + RT + CT arm versus AS + RT (23 v 16 deaths, respectively). Six-year rate of distant metastasis was 14% for AS + RT and 9.1% for AS + RT + CT, (HR, 0.60; 95% CI, 0.37 to 0.99; two-sided P = .044). Six-year disease-free survival rate was 55% for AS + RT and 65% for AS + RT + CT (HR, 0.76; 95% CI, 0.58 to 0.99; two-sided P = .043). CONCLUSION For patients with high-risk nonmetastatic prostate cancer, CT with docetaxel improved OS from 89% to 93% at 4 years, with improved disease-free survival and reduction in the rate of distant metastasis. The trial suggests that docetaxel CT may be an option to be discussed with selected men with high-risk prostate cancer.

Expression of L1CAM and KI-67 in Endometrial Cancer of Egyptian Females: Clinical Impact and Survival

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 36-36
Author(s):  
Fatma Gharib ◽  
Dareen Abd elaziz mohamed ◽  
Basma Saed Amer
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Adenocarcinoma ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Rank Test ◽  
Significant Heterogeneity ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free ◽  
L1cam Expression

Introduction: Endometrial adenocarcinoma is characterized by a good prognosis. However, the disease response shows a significant heterogeneity. Treatment of endometrial cancer (EC) is still based on clinico-pathological parameters, which have limited role in risk stratification. There is a need for more determinant markers, such as L1 Cell Adhesion Molecule (L1CAM), to identify patients at higher risk of relapse and tailor a more convenient treatment. L1CAM has a capacity to enhance cell motility and promote tumor invasion in different malignancies. In Egypt, the incidence rate of EC is growing over time. Especially in Elgharbiah governorate (home of this study). L1CAM expression and Ki-67 was reported and compared with other clinico-pathological criteria. Method: Seventy-six female patients of endometrial carcinomas were involved in this prospective study. The patients were treated and followed up at Tanta University Hospitals in the period between January 2015 to April 2019. L1CAM expression and Ki-67 was detected by immuno-histochemical exam and compared with other clinico-pathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive L1CAM expression was detected in 17 patients (22.4%) and was significantly correlated with unfavorable prognostic factors such as higher stage and grade ( P= 0.021 and P =0.001 respectively), lympo-vascular invasion ( P <0.001), non-endometroid type ( P <0.027) and Ki-67 ( P= 0.003). Univariate analysis revealed that: positive L1CAM; higher tumor grade; high stage; and non-endometrioid type were significantly associated with shorter disease-free survival (DFS) but no significant correlation was detected between Ki-67 and DFS. In multivariate analysis, positive L1CAM remained statistically significant with DFS [P =0.045; 95%CI (1.028:11.17); HR=3.38]. Conclusion: Our study indicates that L1CAM expression and Ki-67 are significantly associated with poor tumor characteristics. L1CAM is significantly associated with shorter disease-free survival and may be a helpful tool as a part of a simple clinical molecular classification for EC.

Randomized Trial of Radiotherapy Versus Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy in Patients With American Joint Committee on Cancer/International Union Against Cancer Stage III and IV Nasopharyngeal Cancer of the Endemic Variety

2005 ◽  
Vol 23 (27) ◽  
pp. 6730-6738 ◽  
Author(s):  
Joseph Wee ◽  
Eng Huat Tan ◽  
Bee Choo Tai ◽  
Hwee Bee Wong ◽  
Swan Swan Leong ◽  
...  
Keyword(s):  
Distant Metastasis ◽  
Nasopharyngeal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
The Difference ◽  
Intent To Treat ◽  
To Receive ◽  
Disease Free ◽  
Treat Analysis

Purpose The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. Patients and Methods Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. Results Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). Conclusion This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.

scholarly journals Gain of 17q in malignant fibrous histiocytoma is associated with a longer disease-free survival and a low risk of developing distant metastasis

2003 ◽  
Vol 89 (4) ◽  
pp. 720-726 ◽  
Author(s):  
W-H Weng ◽  
J Åhlén ◽  
W-O Lui ◽  
O Brosjö ◽  
S-T Pang ◽  
...  
Keyword(s):  
Malignant Fibrous Histiocytoma ◽  
Distant Metastasis ◽  
Fibrous Histiocytoma ◽  
Disease Free Survival ◽  
Low Risk ◽  
Free Survival ◽  
Disease Free

Use of global histone modifications to predict response to gemcitabine in patients with pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 232-232
Author(s):  
Takuo Watanabe ◽  
Soichiro Morinaga ◽  
Makoto Akaike ◽  
Masakatsu Numata ◽  
Hiroshi Tamagawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Histone Modification ◽  
Histone Modifications ◽  
Histone H3 ◽  
Disease Free Survival ◽  
High Expression ◽  
Significant Independent Predictor ◽  
Free Survival ◽  
Low Levels ◽  
Disease Free

232 Background: Epigenetic alternations such as DNA methylation and histone modification play important roles in carcinogenesis. It has been recently suggested that global histone modification pattern are independent predictors of cancer outcomes. We studied the prognostic and predictive value of five histone modifications in pancreatic cancer. Methods: Double 2-mm core tissue microarrays were made from 61 paraffin-embedded pancreatic cancer samples and examined by immunohistochemistry for histone H3 lysine 9 dimethylation (H3K9me2), and acetylation (H3K9ac), histone H3 lysine 4 dimethylation (H3K4me2), and trimethylation (H3K4me3), and histone H3 lysine 18 acetylation (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were related to clinicopathologic features and clinical outcomes. Results: The high expression group of H3K4me3 was related to the well and moderately differentiated histological type (p=0.012) and the low expression of H3K4me2 was related to the presence of preineural invasion (p=0.007). The high expression of H3K9ac was related to the presence of lymph node metastasis (p=0.041). In the subgroup of patients receiving gemcitabine chemotheraphy, low levels of H3K4me2 were significantly associated with worse disease free survival (p=0.0239). Univariate and multivariate hazards models also indicated that low levels of H3K4me2 was significant independent predictor of disease-free survival (p=0.007). Conclusions: H3K4me2 is considered to be useful predictor of response to gemcitabine in patients with pancreatic cancer.

scholarly journals Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3751-3757 ◽  
Author(s):  
Bayard L. Powell ◽  
Barry Moser ◽  
Wendy Stock ◽  
Robert E. Gallagher ◽  
Cheryl L. Willman ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Rank Test ◽  
Consolidation Therapy ◽  
Free Survival ◽  
End Point ◽  
To Receive ◽  
Disease Free

Abstract Arsenic trioxide (As2O3) is a highly effective treatment for patients with relapsed acute promyelocytic leukemia (APL); its role as consolidation treatment for patients in first remission has not been defined. We randomized 481 patients (age ≥ 15 years) with untreated APL to either a standard induction regimen of tretinoin, cytarabine, and daunorubicin, followed by 2 courses of consolidation therapy with tretinoin plus daunorubicin, or to the same induction and consolidation regimen plus two 25-day courses of As2O3 consolidation immediately after induction. After consolidation, patients were randomly assigned to one year of maintenance therapy with either tretinoin alone or in combination with methotrexate and mercaptopurine. Ninety percent of patients on each arm achieved remission and were eligible to receive their assigned consolidation therapy. Event-free survival, the primary end point, was significantly better for patients assigned to receive As2O3 consolidation, 80% compared with 63% at 3 years (stratified log-rank test, P < .0001). Survival, a secondary end point, was better in the As2O3 arm, 86% compared with 81% at 3 years (P = .059). Disease-free survival, a secondary end point, was significantly better in the As2O3 arm, 90% compared with 70% at 3 years (P < .0001). The addition of As2O3 consolidation to standard induction and consolidation therapy significantly improves event-free and disease-free survival in adults with newly diagnosed APL. This trial was registered at clinicaltrials.gov (NCT00003934).

scholarly journals Association Between Circulating Tumor Cells and Prognosis in Patients With Stage III Melanoma With Sentinel Lymph Node Metastasis in a Phase III International Multicenter Trial

2012 ◽  
Vol 30 (31) ◽  
pp. 3819-3826 ◽  
Author(s):  
Sojun Hoshimoto ◽  
Tatsushi Shingai ◽  
Donald L. Morton ◽  
Christine Kuo ◽  
Mark B. Faries ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Tumor Cells ◽  
Distant Metastasis ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
International Multicenter ◽  
Disease Free

PurposeThe outcomes of patients with melanoma who have sentinel lymph node (SLN) metastases can be highly variable, which has precluded establishment of consensus regarding treatment of the group. The detection of high-risk patients from this clinical setting may be helpful for determination of both prognosis and management. We report the utility of multimarker reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) detection of circulating tumor cells (CTCs) in patients with melanoma diagnosed with SLN metastases in a phase III, international, multicenter clinical trial.Patients and MethodsBlood specimens were collected from patients with melanoma (n = 331) who were clinically disease-free after complete lymphadenectomy (CLND) before entering onto a randomized adjuvant melanoma vaccine plus bacillus Calmette-Guérin (BCG) versus BCG placebo trial from 30 melanoma centers (United States and international). Blood was assessed using a verified multimarker RT-qPCR assay (MART-1, MAGE-A3, and GalNAc-T) of melanoma-associated proteins. Cox regression analyses were used to evaluate the prognostic significance of CTC status for disease recurrence and melanoma-specific survival (MSS).ResultsIndividual CTC biomarker detection ranged from 13.4% to 17.5%. There was no association of CTC status (zero to one positive biomarkers v two or more positive biomarkers) with known clinical or pathologic prognostic variables. However, two or more positive biomarkers was significantly associated with worse distant metastasis disease-free survival (hazard ratio [HR] = 2.13, P = .009) and reduced recurrence-free survival (HR = 1.70, P = .046) and MSS (HR = 1.88, P = .043) in a multivariable analysis.ConclusionCTC biomarker status is a prognostic factor for recurrence-free survival, distant metastasis disease-free survival, and MSS after CLND in patients with SLN metastasis. This multimarker RT-qPCR analysis may therefore be useful in discriminating patients who may benefit from aggressive adjuvant therapy or stratifying patients for adjuvant clinical trials.

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