Proposal of a Panel of Genes Identified by miRNA Profiling as Candidate Prognostic Biomarkers in Lung Carcinoids

2020 ◽  
Vol 111 (1-2) ◽  
pp. 115-122
Author(s):  
Ida Rapa ◽  
Arianna Votta ◽  
Jessica Giorcelli ◽  
Stefania Izzo ◽  
Angelica Rigutto ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
In Silico Analysis ◽  
Tumor Grade ◽  
Control Group ◽  
High Grade ◽  
Ki 67 ◽  
Free Survival ◽  
Element Binding Protein ◽  
Positive Nodal Status ◽  
Disease Free

<b><i>Aim:</i></b> To validate the prognostic role of a panel of genes previously uncovered by our group to be specific targets of miRNAs differentially expressed in lung carcinoids with aggressive pathological features. <b><i>Methods:</i></b> Four genes, namely, cyclic AMP response element binding protein-1 (<i>CREBP1</i>), activin A receptor type 2B (<i>ACVR2B</i>), LIM homeobox 2 (<i>LHX2</i>), and Krüppel-like factor 12 (<i>KLF12</i>), were identified in a previous study by our group using in silico analysis to be regulated by 3 miRNAs (miR-409-3p, miR-409-5p, and miR-431-5p) that were shown to be downregulated in aggressive lung carcinoids. These genes were analyzed using real-time PCR in a cohort of 102 lung carcinoids. Fifty high-grade lung carcinomas served as control group. Their expression was correlated with the expression of miR-409-3p, miR-409-5p, and miR-431-5p and with clinical pathological parameters and disease-free survival. <b><i>Results:</i></b> The expression of all but <i>CREBP1</i> gene was significantly different between lung carcinoids and high-grade neuroendocrine carcinomas. <i>ACVR2B</i> and <i>LHX2</i> were significantly inversely correlated with miR-409-3p and miR-409-5p. High levels of <i>ACVR2B</i> and <i>LHX2</i> were significantly associated with atypical histotype, high tumor grade, and higher proliferation Ki-67 index (all <i>p</i> &#x3c; 0.05). Low levels of <i>KLF12</i> were significantly associated with the presence of necrosis and positive nodal status (all <i>p</i> &#x3c; 0.05). Finally, low <i>KLF12</i> expression was associated with shorter disease-free survival in lung carcinoids as a whole and in atypical carcinoids, only (all <i>p</i> &#x3c; 0.001). <b><i>Conclusions:</i></b> <i>ACVR2B</i>, <i>LHX2</i>, and <i>KFL12</i> are novel potential biomarkers associated with aggressive features in lung carcinoids.

scholarly journals Relationship between Ribosomal Protein S6-pS240 Expression and other Prognostic Factors in Non-Special Type Invasive Breast Cancer

Breast Care ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. 171-175
Author(s):  
Frederik Cuperjani ◽  
Lumturije Gashi ◽  
Fisnik Kurshumliu ◽  
Shemsedin Dreshaj ◽  
Fitim Selimi
Keyword(s):  
Breast Cancer ◽  
Ribosomal Protein ◽  
Invasive Breast Cancer ◽  
Menopausal Status ◽  
Treatment Protocol ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free

Background: The aim of this study was to investigate the immunohistochemical expression of ribosomal protein (RP) S6-pS240 in non-special type invasive breast cancer in relation to other prognostic markers and gain new insights to facilitate more individualized treatment. Methods: The following clinical and histopathological parameters of 120 patients were determined: S6-pS240 expression, age, menopausal status, tumor size and grade, TNM stage, Nottingham Prognostic Index (NPI), lymph node stage, estrogen and progesterone receptor (ER/PR) expression, HER2/neu amplification, lymphovascular invasion, and proliferative index as measured by Ki-67. Treatment protocol and disease-free survival were evaluated accordingly. Results: Significant positive correlations were seen between S6-pS240 expression and Ki-67 values (rho = 0.530, p < 0.001), and NPI (rho = 0.370, p < 0.001) and HER2/neu amplification (rho = 0.368, p < 0.001). A negative correlation was found between S6-pS240 and ER/PR expression (rho = 0.362, p < 0.001). Patients with negative RP S6-pS240 expression had significantly longer disease-free survival (log-rank test, p = 0.005). Conclusion: Immunohistochemical analysis of RP S6-pS240 is a valuable additional prognostic marker in patients with invasive breast cancer. Routine use of S6-pS240 immunohistochemistry is recommended.

scholarly journals Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre

2019 ◽  
Vol 180 (2) ◽  
pp. 127-134 ◽  
Author(s):  
S Asioli ◽  
A Righi ◽  
M Iommi ◽  
C Baldovini ◽  
F Ambrosi ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Proliferative Activity ◽  
Disease Free Survival ◽  
Low Grade ◽  
High Grade ◽  
Tumour Type ◽  
Disease Evolution ◽  
Free Survival ◽  
Disease Free

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Laryngeal preservation by treatment with induction chemotherapy and radiotherapy protocol for stage III & IV carcinoma larynx – results of a pilot study

1999 ◽  
Vol 113 (5) ◽  
pp. 433-438 ◽  
Author(s):  
A. Thakar ◽  
S. Bahadur ◽  
D. A. Tandon ◽  
A. Ranganathan ◽  
G. K. Rath
Keyword(s):  
Disease Free Survival ◽  
Stage Iii ◽  
Control Group ◽  
Free Survival ◽  
Carcinoma Larynx ◽  
Laryngeal Preservation ◽  
Group I ◽  
Initial Results ◽  
Disease Free ◽  
Surgical Salvage

AbstractTotal laryngectomy for advanced carcinoma of the larynx is effective but functionally disabling. In an effort at laryngeal preservation, 33 patients of stage III/IV carcinoma larynx were treated between 1987 and 1991 with induction chemotherapy followed by definitive radiation. Two chemotherapy protocols were administered. Group I patients received one to three cycles of cisplatin 100 mg/m2 (day 1), bleomycin 15 U/m2 (day 1), and 5-fluorouracil 1000 mg/m2/day (day 2 to 5) at three weekly intervals. This was then followed by radiotherapy. Group II received one to six weekly injections of single agent methotrexate 50 mg/m2 with or without leucocovorin rescue followed by radiotherapy. Any recurrence was salvaged by surgery.Midway through the study, Group II protocol was discontinued as the initial results were not comparable with Group I or standard treatment. The Group I protocol, however, yielded an initial locoregional control rate of 83.3 per cent With the addition of surgical salvage the locoregional control rate was 94.4 per cent and the control rate with laryngeal preservation was 88.8 per cent. The Kaplan-Meier probability of two years and five years disease-free survival was 81.9 per cent and 61.4 per cent respectively. For disease-free survival with laryngeal preservation the corresponding figures for two years and five years were 58.3 per cent and 41.7 per cent.The control group of 51 patients treated with radical surgery followed by radiotherapy yielded survival figures at two years and five years of 64.3 per cent and 57.2 per cent. The difference in the survival of Group I and the control group was not statistically significant (p value = 0.280). These initial results indicate that for stage III and for surgically resectable stage IV laryngeal carcinomas, a protocol of induction combination chemotherapy consisting of cisplatin, bleomycin and 5-fluorouracil followed by radiotherapy and combined with surgical salvage whenever required, can lead to comparable cure rates. In addition, a large proportion of patients are spared the morbidity of a total laryngectomy.

Intensification of neoadjuvant therapy in patients with locally advanced rectal cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 19-28
Author(s):  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
D. V. Kuzmichev ◽  
S. I. Tkachev ◽  
A. A. Aniskin
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02.

1990 ◽  
Vol 8 (9) ◽  
pp. 1466-1475 ◽  
Author(s):  
N Wolmark ◽  
H Rockette ◽  
D L Wickerham ◽  
B Fisher ◽  
C Redmond ◽  
...  
Keyword(s):  
Portal Vein ◽  
Treatment Failure ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Treated Group ◽  
Control Group ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Bowel Project ◽  
Disease Free

Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.

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.

49. 1-, 5- and 10-year high-grade disease-free survival after laser ablation of biopsy proven AIN2/3: outcomes from a single centre prospective cohort

Sexual Health ◽  
2013 ◽  
Vol 10 (6) ◽  
pp. 594
Author(s):  
Sanjaya Wijeyekoon ◽  
John Thornhill ◽  
Mayura Nathan
Keyword(s):  
Laser Ablation ◽  
Laser Treatment ◽  
Prospective Cohort ◽  
Disease Free Survival ◽  
Study Entry ◽  
High Grade ◽  
Free Survival ◽  
Sex With Men ◽  
One Year ◽  
Disease Free

Objective To describe the characteristics and overall high-grade disease-free survival of 153 consecutive patients treated by laser ablation of biopsy proven high-grade anal neoplasia over an 18.5-year period. Design: Prospective cohort study. Study entry was at the first laser treatment for biopsy proven AIN 2/3. Outcome measures: The principal outcome was high-grade disease-free survival time. High-grade disease-free survival was defined as the time from entry into the cohort to the date of next laser treatment for biopsy-proven high-grade disease. Patients who did not have recurrent high-grade disease at their most recent clinic assessment were censored. Results: Data were evaluated for 153 consecutive patients who were treated by laser ablation of anal high-grade (AIN 2/3) disease between January 1996 and July 2013. These constituted 240 separate treatment episodes over 18.5 years. The majority of subjects were men (91.5%), 44.1% were smokers and 86.3% were classified as men who have sex with men (MSM). At the study entry 64.7% were HIV positive. The median high-grade disease-free survival was 716.5 days (range 11–4730). One year overall high-grade disease-free survival was 77.7% (95% CI 71.7–82.5). Five-year overall high-grade disease-free survival was 51.4% (43.6–58.5). The 10-year overall high-grade disease-free survival was 49.1% (40.5–57.1). There was no difference in high-grade disease-free survival when stratified by HIV positivity status (P = 0.394–log rank). Conclusions: Following laser ablation, recurrence of high-grade disease was low at 1, 5 and 10 years. There was no difference in disease-free survival based on HIV status.

Selection bias in clinical trials.

1985 ◽  
Vol 3 (8) ◽  
pp. 1142-1147 ◽  
Author(s):  
K Antman ◽  
D Amato ◽  
W Wood ◽  
J Carson ◽  
H Suit ◽  
...  
Keyword(s):  
Treatment Efficacy ◽  
Patient Population ◽  
Randomized Trials ◽  
Disease Free Survival ◽  
Control Group ◽  
Free Survival ◽  
Lower Stage ◽  
High Grade Sarcoma ◽  
Disease Free ◽  
Central Lesions

Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.

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