scholarly journals c-FLIPL expression defines two ovarian cancer patient subsets and is a prognostic factor of adverse outcome

2009 ◽  
Vol 16 (2) ◽  
pp. 443-453 ◽  
Author(s):  
Marina Bagnoli ◽  
Federico Ambrogi ◽  
Silvana Pilotti ◽  
Paola Alberti ◽  
Antonino Ditto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Adverse Outcome ◽  
Multiple Correspondence Analysis ◽  
Nuclear Accumulation ◽  
Rank Test ◽  
Prognostic Impact ◽  
Apoptosis Resistance ◽  
Prognostic Information

The impairment of apoptotic pathways represents an efficient mechanism to promote chemoresistance in cancer cells. We previously showed that in epithelial ovarian cancer (EOC) cells, long isoform of cellular FLICE-inhibitory protein (c-FLIPL) accounts for apoptosis resistance in a context of functional p53 and resistance could be overcome by c-FLIPL downmodulation. Here, we studied the association between c-FLIPL and p53 expressions and their prognostic impact in EOC patients. Tumor tissue from 207 patients diagnosed with primary EOC was analyzed by immunohistochemistry (IHC) for c-FLIPL and p53 expressions, and multiple correspondence analysis (MCA) was used to evaluate the multivariable pattern of association among patients' clinical–pathological characteristics and biological determinants. IHC revealed c-FLIPL expression and p53 nuclear accumulation inversely related (P=0.0001; odds ratio=0.29, confidence interval (CI)=0.15–0.055). MCA indicated that p53 accumulation was associated to clinical–pathological variables, while c-FLIPL expression contributed to the overall association pattern independently from other's clinical characteristics and complementary to p53. Kaplan–Meier curves showed a reduced survival time according to c-FLIPL expression in concert with p53 accumulation (median overall survival (OS): 35 months) compared with lack of expression of both markers (median OS: 110 months; log-rank test, P value=0.024). The multivariable Cox regression model, adjusted for known prognostic factors, identified c-FLIPL expression, but not p53 nuclear accumulation, as an independent prognostic factor for adverse outcome (hazard ratio=1.82, 95% CI=1.17–2.82; P=0.008). Altogether these data support the independent contribution of c-FLIPL in refining the prognostic information obtained from standard clinical–pathological indicators, confirming its pivotal role in promoting cell survival.

FLC Assay and Multiparameter Flowcytometry Based Clonal Plasma Cell Measurement Are Independent but Complementary in Assessing the Treatment Response in Multiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2969-2969
Author(s):  
Hiroki Sugihara ◽  
Kenji Tsuda ◽  
Tomotaka Ugai ◽  
Yuki Nishida ◽  
Masayuki Yamakura ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Partial Response ◽  
Plasma Cell ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Response To Treatment ◽  
Rank Test ◽  
Multiparameter Flow Cytometry ◽  
Prognostic Impact

Abstract Abstract 2969 Purpose: Although stringent complete response (sCR) defined by paraprotein negativity on immunofixation and serum free light chain (sFLC) ratio normalization are considered deeper responses in the IMWG criteria, recent report indicated that Multiparameter flow cytometry (MFC)-dased immunophenotypic response (IR) is a more relevant prognostic factor in MM patients. However, data on the prognostic impact of IR and sFLC ratio (sFLCκ/λ) normalization are still scarce. We investigated the prognostic impact of IR and sFLCκ/λ normalization in MM patients treated with novel agents. Patients and Methods: A total of 124 consecutive patients (M:F=68:56; median age, 71 yr) were treated by chemotherapy regimens containing at least one novel agent (thalidomide, bortezomib, lenalidomide)from April 2005 to May 2012. Treatment responses were assessed using the IMWG criteria, and the best response to treatment during the clinical course was assessed by simultaneous serum immunofixation, sFLC measurements, and MFC analysis of bone marrow (BM) plasma cells. Normalization of sFLCκ/λ was defined 2 consecutive normal sFLCκ/λ apart from at least 4 weeks. MFC-defined minimal residual disease (MRD) was evaluated by single-tube 6-color MFC, CD45-CD38 gating strategy, and combination CD19, CD56, and cytoplasmic κ-λ analysis. Clonal plasma cell (PC) negativity by MFC (MFC-negative) was defined as <10−4 neoplastic PCs in BM samples on MFC. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan–Meier (K-M) method and differences between curves were calculated by two-sided log-rank test. Univariate analysis was used to assess the impacts of factors on sFLCκ/λ normalization and MFC negativity (age, Durie–Salmon stage, ISS stage, LDH, hemoglobin, serum albumin, serum creatinine, FISH at diagnosis). The Cox regression proportional hazard model (stepwise regression) was used to explore the independent effects of these variables on PFS and OS. Results: At a median follow-up of 25.8 months, 3- and 5-year OS of all patients were 61.0% and 42.4%, respectively. CR was obtained in 25% (31/124), very good partial response (VGPR) in 33.5% (41/124), partial response (PR) in 30.5% (38/124), and stable disease or less (SD) in 11% (14/124). Normal sFLCκ/λ was achieved in 81% of CR, 56% of VGPR, 13% of PR, and 0% of SD or less response of patients. K-M estimated 3- and 5-year OS were 100% in CR patients; these were significantly better than in VGPR (75.8% and 43.2%, respectively) and PR patients (63% and 26.7.%, respectively). There were no significant differences in 3- or 5-year OS between VGPR and PR patients. Normal sFLCκ/λ and MFC negativity were achieved in 25 (81%) and 18 (58%) of 31 CR patients, respectively. Among 25 CR patients with normal sFLCκ/λ (stringent CR), 15 (60%) were MFC-negative and 10 (40%) were MFC-positive; three of 6 CR patients (50%)without normal sFLCκ/λ were MFC-positive. Twenty-three of 41 VGPR patients (56%) obtained normal sFLCκ/λ, while only 5 (12%) became MFC-negative; all 5 MFC-negative patients also obtained normal sFLCκ/λ. Among 52 patients with less than PR, only 5 (9.6%) obtained normal sFLCκ/λ and none achieved MFC negativity. Patients with MFC-negative CR showed significantly better PFS than patients with MFC-positive CR (p<0.05). Although patients in stringent CR with MFC-negative showed slightly better PFS compared to patients in stringent CR with MFC-positive, difference between the curves were not significant. Within the group of VGPR, PFS and OS were significantly longer in normal sFLCκ/λ patients than abnormal sFLCκ/λ(P<0.001). Univariate analysis showed that hemoglobin 10.0 g/dl>, age >70 yr, and abnormal LDH had negative prognostic impacts on attaining normal sFLCκ/λ, but none of these factors remained significant on multivariate analysis. Cox analysis showed that sFLCκ/λ normalization was an independent prognostic factor for longer PFS and OS in patients with CR, VGPR and PR (P=0.001). Conclusions: This study confirmed that magnitude of CR and VGPR response defined by IMWG criteria was heterogeneous in terms of sFLCκ/λ normalization and MFC negativity. Although MFC and sFLC analysis frequently gave discrepant results among patients with CR and VGPR, both analyses appeared to give important complementary information for assessing the depth of CR and VGPR category. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in fresh tissue biopsies

2009 ◽  
Vol 16 (4) ◽  
pp. 1241-1249 ◽  
Author(s):  
Claudio Zamagni ◽  
Ralph M Wirtz ◽  
Pierandrea De Iaco ◽  
Marta Rosati ◽  
Elke Veltrup ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Endocrine Treatment ◽  
Rank Test ◽  
Mrna Levels ◽  
Cox Regression Analysis ◽  
Platinum Based Chemotherapy ◽  
Neo Adjuvant Chemotherapy

Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial. Study participants had epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery and were treated with neo-adjuvant platinum-based chemotherapy before surgery. RNA was isolated from frozen tumour biopsies before treatment. RNA expression of ESR1 was determined by microarray and reverse transcriptase kinetic PCR technologies. The prognostic value of ESR1 was tested using univariate and multivariate Cox proportional hazards models, Kaplan–Meier survival statistics and the log-rank test. ESR1 positively correlates with proliferation markers and histopathological grading. ESR1 was a significant predictor of survival as a continuous variable in the univariate Cox regression analysis. In multivariate analysis, elevated baseline ESR1 mRNA levels predicted prolonged progression-free survival (P=0.041) and overall survival (P=0.01) after neo-adjuvant chemotherapy, independently of pathological grade and age. We conclude that pretreatment ESR1 mRNA is associated with tumour growth and is a strong prognostic factor in ovarian cancer, independent of the strongest clinical parameters used in clinical routine. We suggest that ESR1 mRNA status should be considered in order to minimize possible confounding effects in ovarian cancer clinical trials, and that early treatment with anti-hormonal agents based on reliable hormone receptor status determination is worth investigating.

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

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
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.

Prognostic impact of chemoradiation-related lymphopenia in patients with gastric and gastroesophageal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 249-249
Author(s):  
Daniel W Kim ◽  
Grace Lee ◽  
Theodore S. Hong ◽  
Guichao Li ◽  
Eric Roeland ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Cox Model ◽  
Gastroesophageal Junction ◽  
Concurrent Chemotherapy ◽  
Rank Test ◽  
Prognostic Impact ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Ecog Ps

249 Background: Limited data exists on how chemoradiation (CRT)-induced lymphopenia affects survival outcomes in patients with gastric and gastroesophageal junction (GEJ) cancer. We evaluated the association between severe lymphopenia and its association with survival in gastric and GEJ cancer patients treated with CRT. We hypothesized that severe lymphopenia would be a poor prognostic factor. Methods: We performed a retrospective analysis of 154 patients with stage 1-3 gastric or GEJ cancer who underwent CRT at our institution. Patients underwent photon-based radiation therapy (RT) with a median dose of 50.4 Gy (IQR 45.0-50.4 Gy) over 28 fractions and concurrent chemotherapy (CTX) with carboplatin/paclitaxel, 5-fluorouracil based regimen, or capecitabine. 49% received CTX prior to RT. 84% underwent surgical resection, 57% pre-CRT and 26% post-CRT. Absolute lymphocyte count (ALC) at baseline and at 2 months since initiating RT were analyzed. Severe lymphopenia, defined as Grade 3 or worse lymphopenia (ALC < 0.5 k/μl), was analyzed for any association with overall survival (OS). Results: Median time of follow up was 48 months. Median age was 65. 77% were male and 86% were Caucasian. ECOG PS was 0 or 1 in 90% and 2 in 10%. Tumor location was stomach in 38% and GEJ in 62%. Timing of CRT was preoperative among 68% and postoperative among 32%. The median ALC at baseline for the entire cohort was 1.6 k/ul (range 0.3-7.0 k/ul). At 2 months post-CRT, 49 (32%) patients had severe lymphopenia. Patients with severe lymphopenia post-CRT had a slightly lower baseline TLC compared to patients without severe lymphopenia (median TLC 1.4 k/ul vs. 1.6 k/ul; p = 0.005). There were no differences in disease and treatment characteristics between the two groups. On the multivariable Cox model, severe lymphopenia post-CRT was significantly associated with increased risk of death (HR = 3.99 [95% CI 1.55-10.28], p = 0.004). ECOG PS 2 (HR = 34.97 [95% CI 2.08-587.73], p = 0.014) and postoperative CRT (HR = 5.55 [95% CI 1.29-23.86], p = 0.021) also predicted worse OS. The 4-year OS among patients with severe lymphopenia was 41% vs. 61% among patients with vs. without severe lymphopenia (log-rank test p = 0.041). Conclusions: Severe lymphopenia significantly correlated with poorer OS in patients with gastric or GEJ cancer treated with CRT. CRT-induced lymphopenia may be an important prognostic factor for survival in this patient population. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating CRT-induced lymphopenia.

Effect of BRCA Mutations on the Length of Survival in Epithelial Ovarian Tumors

2002 ◽  
Vol 20 (2) ◽  
pp. 463-466 ◽  
Author(s):  
Y. Ben David ◽  
A. Chetrit ◽  
G. Hirsh-Yechezkel ◽  
E. Friedman ◽  
B.D. Beck ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Survival ◽  
Cox Regression ◽  
Ovarian Tumors ◽  
Early Years ◽  
Rank Test ◽  
Brca Mutations ◽  
Blood Samples ◽  
Cox Regression Analysis ◽  
Significant Difference

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v 37.8 months; 3-year survival, 65.8% v 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

All IPI Factors Are Equal, but LDH Is More Equal Than Others.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1913-1913
Author(s):  
Gustaaf W. van Imhoff ◽  
W. Graveland ◽  
B. Van der Holt ◽  
M. Van Glabbeke ◽  
L. F. Verdonck ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cox Regression ◽  
Risk Index ◽  
Elevated Serum ◽  
Continuous Variable ◽  
Prognostic Impact ◽  
Prognostic Information ◽  
Curative Intent ◽  
Non Hodgkin Lymphoma ◽  
The Individual

Abstract The International Prognostic Risk Index (IPI) offers the most important prognostic information in patients with aggressive non-Hodgkin Lymphoma (NHL). Risk classification is based on presence or absence of age >60 yr, stage III or IV, more than one extranodal site, performance score 2–4, or elevated serum LDH above the upper limit of normal (ULN). Because each factor confers a more or less equal independent risk for treatment outcome, they are summed to generate a final IPI risk score (Shipp model). Dichotomization of the continuous variable age is practical, as treatment for patients >60 yr often differs from younger ones. However, as LDH also is a continuous variable we wondered if risk based on actual LDH, especially in patients with highly elevated levels, would have additional prognostic impact. IPI risk factors including actual serum LDH at diagnosis were retrieved from 1286 patients (28% >60 yr) with advanced aggressive NHL and treated with curative intent in 6 clinical trials conducted by HOVON (5 trials) and EORTC (1 trial). All LDH ULNs from the participating centers were verified. LDH levels were divided by the ULN of each center to generate normalized ratios. Six % of patients had LDH >5 times ULN, 8% 3–5 times, 11% 2–3 times, 34% 1–2 times, 20% 0.75–1 times and 20% had levels below 0.75 of ULN. In a multivariate Cox regression model similar independent hazard ratios (HR) ranging from 1.6 to 2.6 were found for the individual dichotomized risk factors according to the Shipp model except for the number of extranodal sites which turned out to be non-significant. This factor was with a HR of 1.4 also the least predictive factor in the Shipp model. In contrast to the dichotomized LDH variable (normal versus elevated), risk for inferior outcome increased linearly with actual LDH levels. Five year OS estimates were 71% for patients with LDH <0.75 x ULN; 53% for 0.75–1; 49% for 1–2; 37% for 2–3; 31% for 3–5; and 25% for LDH >5 x ULN. The HR for these groups were respectively 0.54, 1, 1.45, 2.46, 2.54 and 5.15. This analysis using actual LDH values gave a better discrimination as compared to the HR of 2.6 (95% CI 2.1–3.1) for the dichotomized LDH (i.e. normal versus elevated) in multivariate analysis. Interestingly, the 235 patients with very low LDH (<0.75 x ULN) had much better outcomes with a HR of 0.54 as compared with patients with an LDH-ratio between 0.75 and 1. In conclusion, highly elevated LDH levels in aggressive NHL confer a worse prognosis and suggest the application of a modified IPI risk index adding extra risk points for patients with highly elevated LDH levels.

Cetuximab (CTX) in first-line treatment of elderly patients with metastatic colorectal cancer (mCRC), KRAS wild type: French multicentre prospective community-based registry and results.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 760-760
Author(s):  
Laurent Mineur ◽  
Eric François ◽  
Jean Marc Phelip ◽  
Rosine Guimbaud ◽  
Carine Plassot ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Rank Test ◽  
Wild Type ◽  
Community Based ◽  
Cox Models ◽  
Cox Regression Analysis ◽  
Effective Age

760 Background: Pts included in clinical trials represent the unusual population in mCRC. This study aims to provide oncologist with a better understanding of the potential benefit of CT with CTX in older patients with mCRC KRAS wild type and evaluate prognostic variables on the PFS including the age. Methods: Premium cancer study is a French multicentre prospective community-based registry. 493 pts enrolled and 487 included between September 2009 to March 2012 from 94 French centers and physicians. Pts had to provide written informed consent and protocol submitted to regulatory authorities. Predefined efficacy endpoints was PFS. CTX was administrated at 250 mg/m2 weekly (n=100; 20.3%) or 500 mg/m2 every 2 weeks (n=380;77,2%), other n=13; 2.5%) CT regimen choice was at physician’s discretion.. The main analysis is PFS as well as analysis of prognostic factors of this PFS (29 items including age (< 65 years n=229; 65-74 years n= 165.; ≥75years n=93). Univariate analysis was performed for each covariate, PFS was estimated by Kaplan-Meier curves and compared by log-rank test. univariable Cox regression analysis was used to assess the association between each variable and outcome. Multivariable stepwise Cox models were then fitted for final variable selection of prognostic factors on PFS. Results: Univariate significant prognostic factors for PFS are OMS (0-1 vs 2-3), Tobacco, Site of tumor (right vs other), Number of metastatic organ (1 vs 2-3), Resecability of metastatic disease defined before CT (definitively non resectable metastases vs possible resectable), Surgery of mCRC, folliculitis or xerosis or paronychia grade 0-1 vs 2-4. Age was unidentified as a prognostic factor in univariate analysis. Four factors were independently associated with a better PFS: xerosis [hazard ratio (HR0,651); 95% confidence interval (CI) 0,494-0,857], (WHO PS) 0–1 (HR0,519 ; 95% CI 0,371–0,726) and folliculitis (HR 0,711; 95% CI0,558–0,956) metastases surgery 0,287(CI 0,205-0,403). Conclusions: CTX in combination with standard CT is effective, age is not identified as a prognostic factor for the PFS. Both groups of pts based on age benefit from CTX.

RAS heterogeneity as a prognostic marker in metastatic colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 586-586
Author(s):  
Jonathan M. Loree ◽  
Michael Lam ◽  
Jeffrey Morris ◽  
Michael J. Overman ◽  
Kanwal Pratap Singh Raghav ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Allele Frequency ◽  
Cox Regression ◽  
Rank Test ◽  
Intratumor Heterogeneity ◽  
Prognostic Impact ◽  
Stage At Diagnosis ◽  
Braf Mutations ◽  
The Impact

586 Background: The impact of intratumor heterogeneity on prognosis in metastatic colorectal cancer (mCRC) is unclear, however relative variant allele frequency (rVAF) of key mutations within a tumor may impact outcomes. Therefore, we sought to determine whether rVAF of RAS ( KRAS & NRAS) mutant (mt) clones impacts overall survival (OS) in mCRC patients (pts). Methods: Using a next generation sequencing panel of 201 cancer related genes, we tested 200 mCRC tumors / matched normals. Mutations, indels, and copy number variant (CNV) information were obtained. An rVAF of RAS clones was determined by dividing RAS mt VAF by the VAF of the mutated gene with the highest allele frequency. This truncal gene served as a marker of the total malignant population in a specimen. Pts were stratified at an rVAF of 50%. OS was compared with Kaplan-Meier curves, the log-rank test, and Cox regression. We assessed the impact of CNV on our findings by correcting the rVAF for CNVs in RASand truncal mutations. Results: Of 200 pts, 15% had RAS mt rVAF < 50%, 40.5% had rVAF ≥ 50%, and 44.5% were RAS wild type (WT). Age, gender, MSI status, histology, and stage at diagnosis were similar between groups. More RAS WT pts had BRAF mutations (19.1% vs 1.2% and 3.3%, P< 0.0001), left sided (78.7% vs 56.8% and 60%, P= 0.02), or poorly differentiated tumors (27.3% vs 8.6% and 13.3%, P= 0.003) compared to pts with rVAF ≥ 50% or rVAF < 50%, respectively. Mean coverage was 807x for RAS and 602x for truncal mutations. OS was better in pts with an rVAF < 50% compared to pts with rVAF ≥ 50% regardless of whether rVAF was corrected for CNV (HR 0.6; 95% CI 0.39-0.93, P =0.029) or not (HR 0.48; 95% CI 0.31-0.82, P= 0.010). mOS for pts with WT, rVAF < 50% and rVAF ≥ 50% tumors were 65.8, 55.7, and 38.6 months ( P= 0.0025). In multivariate models controlling for stage at diagnosis and BRAF mutation, pts with rVAF < 50% (HR 1.75; 95% CI 1.03-2.97, P = 0.04) and rVAF ≥ 50% (HR 2.46; 95% CI 1.66-3.65, P< 0.0001) had worse OS compared to WT pts. When rVAF was used as a continuous variable, every 1% increase in rVAF RAS mt resulted in a 1% increased hazard of death ( P <0.0001). Conclusions: Our findings suggest that clonal proportion of a tumor with a RAS mutation may impact OS and suggest the prognostic impact of RAS mutations is not an “all or none” phenomenon.

scholarly journals Age as a Prognostic Factor in Anaplastic Thyroid Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Vladan Zivaljevic ◽  
Katarina Tausanovic ◽  
Ivan Paunovic ◽  
Aleksandar Diklic ◽  
Nevena Kalezic ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Thyroid Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Distant Metastases ◽  
Anaplastic Thyroid Cancer ◽  
Multivariate Regression Analysis ◽  
Rank Test ◽  
Cox Regression Analysis

Background.Anaplastic thyroid cancer (ATC) is one of the tumors with the shortest survival in human medicine.Aim.The aim was to determine the importance of age in survival of patients with ATC.Material and Methods. We analyzed the data on 150 patients diagnosed with ATC in the period from 1995 to 2006. The Kaplan-Meier method and log-rank test were used to determine overall survival. Prognostic factors were identified by univariate and multivariate Cox regression analysis.Results.The youngest patient was 35 years old and the oldest was 89 years old. According to univariate regression analysis, age was significantly associated with longer survival in patients with ATC. In multivariate regression analysis, patients age, presence of longstanding goiter, whether surgical treatment is carried out or not, type of surgery, tumor multicentricity, presence of distant metastases, histologically proven preexistent papillary carcinoma, radioiodine therapy, and postoperative radiotherapy were included. According to multivariate analysis, besides surgery (P=0.000, OR = 0.43, 95% CI = 0.29–0.63), only patients age (P=0.023, OR = 0.68, 95% CI = 0.49–0.95) was independent prognostic factor of favorable survival in patients with ATC.Conclusion. Age is a factor that was independently associated with survival time in ATC. Anaplastic thyroid cancer has the best prognosis in patients younger than 50 years.

PITX2 methylation and biochemical recurrence in postradical prostatectomy prostate cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5124-5124
Author(s):  
E. Heiden ◽  
G. Weiss ◽  
L. Banez ◽  
S. Freedland ◽  
L. Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Methylation Status ◽  
Gene Promoter ◽  
Surgical Margins ◽  
Rank Test ◽  
Clinical Tool ◽  
Prognostic Information ◽  
Tissue Samples

5124 Background: PITX2 is a bicoid-related transcription factor induced by the Wnt pathway and required for effective cell-type-specific proliferation during development. We previously reported prognostic potential of PITX2 gene promoter methylation for outcome prediction in breast and prostate cancer (PC) patients. Radical prostatectomy (RP) is potentially curative in patients with clinically localized PC. However, biochemical recurrence (BCR) affects 15–30% of patients undergoing RP. In the current study, we validate PITX2 methylation status as a predictor of BCR following RP. Methods: PITX2 methylation status was assessed in formalin-fixed paraffin-embedded RP tumor tissue samples from 476 patients from four different institutions in USA and Europe using customized microarrays. Associations between PITX2 methylation and BCR were assessed using log-rank test and Cox regression controlling for PC features. Results: In multivariate analysis, patients with a high methylation status were at significantly higher risk for BCR compared to patients with low methylation status (HR = 3.0; 95%CI = 2.0–4.5; p < 10-5). BCR-free survival at five years after surgery was 85% and 61% for patients in the low and high methylation group, respectively. In patients with pathological Gleason 7 tumors, the relative risk of suffering BCR was twice as high for a patient with high PITX2 methylation relative to patients with low PITX2 methylation (HR = 2.0; 95%CI = 1.2–3.3; p = 0.005). Moreover, PITX2 methylation status was significant in the group of patients with tumor involvement of the surgical margins in the prostatectomy specimen. (HR = 3.36, 95% CI: 2.24–5.06, p = 0.001). Conclusions: PITX2 methylation status identifies PC patients most likely to experience BCR. This test independently adds to prognostic information provided by standard clinico-pathological analyses improving stratification of RP patients into high- or low-risk for BCR. This new clinical tool would be of particular benefit in assessment of intermediate-risk patients (Gleason 7) or patients with positive surgical margins wherein risk stratification remains a challenge. [Table: see text]

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