Phosphorylated signal transducer and activator of transcription–3 (p-STAT3) expression concordance in paired primary and metastatic colorectal cancers (mCRC): Updated analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15137-e15137
Author(s):  
Daniel Yokom ◽  
E. Celia Marginean ◽  
Derek J. Jonker ◽  
Allen M. Gown ◽  
Shelly Sud ◽  
...  
Keyword(s):  
Survival Rates ◽  
Tissue Microarrays ◽  
Secondary Outcome ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Disease Outcomes ◽  
One Year ◽  
Metastatic Sites ◽  
Transcription 3

e15137 Background: p-STAT3 is a transcription factor which is associated with poor prognosis in multiple cancers. Overexpression of p-STAT3 by immunohistochemistry (IHC) in tumors of patients with mCRC is associated with more aggressive disease and decreased survival. Concordance of p-STAT3 expression in primary and metastatic tumors was assessed to determine the temporal heterogeneity of expression and correlation with clinical outcomes. Methods: Patients with tissue available from both primary and liver metastases were identified retrospectively. Tissue microarrays (TMA) were constructed using 2 x 2mm cores. Nuclear p-STAT3 expression intensity by IHC was graded as absent, low, or high. Primary outcome was concordance of p-STAT3 expression between primary and metastatic sites. Secondary outcome was correlation of p-STAT3 expression with disease outcomes. Results: 91 patients were identified: 55% were male, median age at diagnosis was 63, 60% had left-sided disease and 81% of metastases were synchronous. Expression of p-STAT3 in primary tumors was 23% high, 47% low and absent in 30% compared to 29% high, 50% low, and 21% absent in metastases. Concordant expression was observed in 23% of patients whereas it increased in 46% and decreased in 31% from primary to metastasis. Pearson’s correlation was 0.119 indicating a weak concordance. After a median follow-up of 7 years, 50 of 91 patients died. One-year and 5-year survival rates were 92% and 44% respectively, while the median overall survival (mOS) was 4.7 years [95%CI 3.1-6.4]. No significant prognostic correlation between primary or metastatic p-STAT3 expression and mOS was found. Conclusions: There was low concordance of p-STAT3 expression in primary and metastatic tumors of patients with mCRC. Tumor staining heterogeneity due to sampling of small cores included in TMA and predominance of synchronous metastases may play a role. Further research in the use of p-STAT3 as a biomarker in patients with mCRC is needed.

scholarly journals Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3776
Author(s):  
Edouard Auclin ◽  
Perrine Vuagnat ◽  
Cristina Smolenschi ◽  
Julien Taieb ◽  
Jorge Adeva ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Prognostic Index ◽  
Predictive Marker ◽  
Risk Groups ◽  
Two Factors ◽  
One Year ◽  
Metastatic Sites ◽  
Tumor Types

Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p <0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46–8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.

scholarly journals Immediate Implant Placement by Interradicular Bone Drilling before Molar Extraction: Clinical Case Report with One-Year Follow-Up

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Stuardo Valenzuela ◽  
José M. Olivares ◽  
Nicolás Weiss ◽  
Dafna Benadof
Keyword(s):  
Survival Rates ◽  
Three Dimensional ◽  
Primary Stability ◽  
Bone Drilling ◽  
Implant Placement ◽  
Immediate Implants ◽  
Immediate Implant ◽  
One Year ◽  
Molar Extraction

The placement of immediate implants in the posterior sector is a widespread procedure where the success and survival rates are similar to those of traditional protocols. It has several anatomical challenges, such as the presence of interradicular bone septa that hinder a correct three-dimensional positioning of the implant and may compromise primary stability and/or cause damage of neighboring structures. The aim of this article is to present the treatment and the one-year clinical follow-up of a patient who received immediate implant placement using an interradicular bone-drilling technique before the molar extraction.

scholarly journals Quadruplicate Synchronous Adenocarcinoma of the Colon with Distant Metastases—Long-Term Molecular Follow-Up by KRAS and TP53 Mutational Profiling

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 407
Author(s):  
Emese Sarolta Bádon ◽  
Attila Mokánszki ◽  
Anikó Mónus ◽  
Csilla András ◽  
László Damjanovich ◽  
...  
Keyword(s):  
Colon Adenocarcinoma ◽  
Distant Metastases ◽  
Tp53 Gene ◽  
Molecular Testing ◽  
Gene Variants ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Genetic Profiling ◽  
Pathogenic Variants

Anatomically independent tumor foci represent biologically distinct neoplasias, potentially featured by different progressivity and treatment responsiveness. To demonstrate the biological complexity, a metastatic colon adenocarcinoma patient originally presenting with four independent primary tumors of the right colon half and altogether eight distant metastases was followed by molecular testing. Next-generation sequencing results highlighted the mutational profile of the individual primaries and the dynamics of the different gene variants observed during follow-up. The four primary colon tumors presented with four different KRAS genotypes, one of them with a wild-type and three with pathogenic variants, without overlap. These were the following: c.35G > A; p.Gly12Asp with 40.6% variant allele frequency (VAF); c.34G > T; p.Gly12Cys with 16.2% VAF and c.35G > T; p.Gly12Val with 15.1% VAF. In metastatic tumors, with one exception where no mutation was detected, only the KRAS c.34G > T; p.Gly12Cys mutation could be detected. TP53 gene variants were variable in the primary tumors, with a single dominant variant evolving in the follow-up metastases (c.820G > T; p.Val274Phe). Genetic profiling of individually developing synchronous malignancies uncovers the clonal relations of metastatic tumors. NGS gene panels provide a solution to follow the dynamics of key oncogene variants during the course of the disease and greatly contribute to therapy optimization.

Sarcoligo: Impact of local ablative treatment of oligometastatic sarcomas on overall survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10042-10042
Author(s):  
Juliette Thariat ◽  
Laurence Moureau-Zabotto ◽  
Nicolas Penel ◽  
Antoine Italiano ◽  
Jacques-Olivier Bay ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Locoregional Treatment ◽  
Metastatic Sites ◽  
The Impact

10042 Background: 40-50% of sarcomas become metastatic. Median survival of metastatic patients has improved over time. The probably multifactorial reasons for such improvement are not fully clear. Noteworthy, for patients with a controlled primary and a limited number of lung metastases, complete resection of their metastases yields survival rates of up to 40% at three years. Advances in surgery, radiotherapy and radiofrequency have fostered the use of local treatments for various metastatic sites (lung, liver, spine...). Methods: A multicentric retrospective study of the Groupe Sarcome Francais (GSF-GETO); approved by the nationally-review board and ethical committee, was conducted to assess the impact of local ablative treatment on overall survival. Patients who had had oligometastases (any site, 1-5 synchronous metastases) at diagnostic or during the course of disease between 2000 and 2010 were included. Results: Median age of the 243 oligometastatic sarcoma patients was 53 years-old (11-86). Patients had grade I, II and III in 7.5%, 29.6% and 63.3% of cases, respectively with various histologies. 69% of patients underwent local ablative treatment of metastases. Median follow-up was 59 months (4-212) for living patients. Median overall survival was 51 months (1-348). On univariate analysis, grade, histology, absence of chemotherapy, local ablative treatment (surgery, irradiation, radiofrequency or chemoembolisation) correlated with survival but not age or site of oligometastasis. On multivariate analyses, grade (hazard ratio HR 0.12 [CI95 0.3-0.6]) and local ablative treatment (HR 3.8 [CI95 2.1-7.1]) remained significant. Conclusions: Local ablative treatment of metastases is associated with better survival in sarcoma patients with oligometastatic disease. The role of the locoregional treatment of metastases and its impact on quality of life should be assessed prospectively.

Differences in molecular profiles of males and females with colorectal cancer (CRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 623-623
Author(s):  
Afsaneh Barzi ◽  
Mohamed E. Salem ◽  
Joanne Xiu ◽  
Wolfgang Michael Korn ◽  
John Marshall ◽  
...  
Keyword(s):  
Tumor Location ◽  
Molecular Profile ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Significant Difference ◽  
Number Variation ◽  
Males And Females ◽  
Variation Assessment ◽  
Metastatic Sites ◽  
Next Generation Sequencing Ngs

623 Background: Females (F) have a lower incidence of CRC and carry a better overall prognosis than males(M). We explored the differences in the molecular profile of CRC as an explanation for the differences in the outcome. Methods: CRC cases submitted to Caris Life Sciences from 2015 to 2017 were analyzed. These cases were tested with next generation sequencing (NGS) of 592 genes and a panel of IHC and copy number variation assessment. Microsatellite instability (MSI) was evaluated with NGS for known MSI loci in the target regions. High Tumor mutational load (TML-H) was defined as ≥17 mutations/megabase. Results: Data from a total of 1768 CRC tumors (F: 859; M: 909) was available for analysis. The mean age at testing was similar between the two groups (F 59 vs. M 60 years). Tumor location was unknown in more than 40% of the cases. For those with known tumor location (1056) F had a higher rate in right sided than left sided and rectal tumors (51% vs. 47% vs. 40%, p = 0.006). Overall, F carried significantly lower frequency of mutation in APC (68% vs. 74%, p = 0.02), higher frequency of BRAF (11% vs. 6.6%, p = 0.003) and BRCA1 (2% vs. 0.6%, p = 0.007). PDL1 expression was higher in F (4.5% vs. 2.1%, p = 0.006) and MGMT expression was higher in M (63% vs. 56%, p = 0.04). There was no significant difference in the TML-H (F:6.4% vs. M:5.9%) and MSI-high (F:6.2% in vs M:4.8%). When primary (877) and metastatic tumors (838) were investigated separately, mutations in APC was higher in M primary tumors (74% vs. 68% p = 0.03) while not different in metastatic sites. On the contrary, BRCA1 mutations were higher in the metastatic sites for F (2% vs. 0.2%, p = 0.02). PD-L1 was higher in the primary tumor of F (5.2% vs. 1.8%, p = 0.008) and PD-1 on tumor infiltrating lymphocyte in metastatic tumors in F (48% vs. 30%, p = 0.01). Conclusions: The profile of female patients (higher rates of PDL1 in primary and PD1 in metastatic tumors) supports a higher degree of immune evasion. The differences in the profile of metastatic vs. primary sites may be due to the differences in the mechanism of metastasis in females vs. males and may have implications for PDX models.

scholarly journals Malignant Transformation of Temporal Bone Schneiderian Papilloma Associated with HPV-6

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
O. Marzouk ◽  
F. Brasch ◽  
I. Todt ◽  
P. K. C. Goon ◽  
H. Sudhoff
Keyword(s):  
Temporal Bone ◽  
Malignant Transformation ◽  
Postoperative Radiotherapy ◽  
Survival Rates ◽  
Clinical Findings ◽  
Mastoid Process ◽  
Bone Resection ◽  
Primary Tumors ◽  
Temporal Bone Resection

Introduction. Temporal bone Schneiderian papillomas (TBSPs) rarely present as a primary tumors arising from the middle ear and mastoid process. The clinical findings and imaging of TBSPs are not specific. Therefore, diagnosis can only reliably be definitively established by histopathology. Objective. To report a novel case of a malignant transformation of TBSP associated with HPV-6 and to present its management. Case Report. A 68-year-old woman presented with conductive hearing loss and recurrent right-sided otorrhoea. Initially, we performed a lateral temporal bone resection and obliteration with abdomen fat. Early histology described TBSP associated with HPV-6. Follow-up detected malignant transformation of the Schneiderian papillomatous variant. Postoperative radiotherapy combined with extended temporal bone resection resulted in a disease-free 17-month period of follow-up. Discussion. TBSPs are not very specific, and the diagnosis can only reliably be established by histopathology. There is a risk of malignant transformation, and due to the absence of reliable prognostic markers, strict postoperative follow-up is mandatory and should consist of regular otoscopy, nasal endoscopy, and imaging. This case also supports the importance of extended temporal bone resections as salvage surgery, combining radical surgery with radiotherapy for improved survival rates.

FGFR3 protein expression and gene mutation in primary and metastatic urothelial carcinoma (UC) tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4577-4577
Author(s):  
Jonathan E. Rosenberg ◽  
Lillian Werner ◽  
Aristotelis Bamias ◽  
Toni K. Choueiri ◽  
Fabio A. B. Schutz ◽  
...  
Keyword(s):  
Protein Expression ◽  
Therapeutic Target ◽  
Primary Tumor ◽  
Scoring Systems ◽  
Metastatic Tumor ◽  
Copy Number Gain ◽  
Tissue Microarrays ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Fgfr3 Mutation

4577 Background: FGFR3 protein expression may represent a valid therapeutic target in metastatic UC. The prevalence of both mutation and overexpression is unknown in metastatic UC. Methods: Tissue microarrays of formalin fixed paraffin-embedded urothelial carcinomas (UC) were stained for FGFR3 by immunohistochemistry (IHC) [primary (n=250); metastatic (n=31); of which (n=14) were paired]. FGFR3 immunostaining was scored as negative or positive based on previously reported scoring systems. FGFR3 mutation in primary tumors was assessed by iPlex and confirmed by hME sequencing (n=141) or Affymetrix OncoScan FFPE Express 2.0 (primary: n=17; metastases n=31). Results: FGFR3 IHC positivity was present in 48% of metastases (95% CI=32-65%) and 26% of primary tumors, (95%=CI 21-32%), though strong staining was rare (<1%). Paired primary and metastatic tumors were both negative in 50% of cases, with 14% positive only in the metastasis, 14% positive only in the primary tumor, and 21% positive in both. If the primary tumor showed staining, 71% of the metastases showed staining. FGFR3 IHC staining did not impact overall survival (p=0.8). FGFR3 mutations were observed in 9.6% of metastatic tumors (95% CI=3.3-25%), compared to 3.5% of primary tumors (95% CI=1.5%-8%). Co-occurrence of mutation and FGFR3 DNA copy number gain was observed in one specimen. Conclusions: FGFR3 IHC staining is present 26 % of primary tumors of patients who go on to develop metastatic disease, and nearly half of metastatic tumor sites. FGFR3 mutation frequency in primary and metastatic tumor specimens is low. Further investigation of the frequency of FGFR3 protein expression in metastases is needed. The presence of FGFR3 protein by IHC staining in primary and metastatic specimens suggests that FGFR3 may represent a therapeutic target even in the absence of mutation. Further functional studies are needed.

Patients' Perceptions of Family Emotional Climate and Outcome in Schizophrenia

1993 ◽  
Vol 162 (6) ◽  
pp. 751-754 ◽  
Author(s):  
Malca B. Lebell ◽  
Stephen R. Marder ◽  
Jim Mintz ◽  
Lois I. Mintz ◽  
Martha Tompson ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Rating Scales ◽  
Survival Rates ◽  
Emotional Climate ◽  
Chronic Schizophrenic ◽  
Frequent Contact ◽  
Patients At Risk ◽  
One Year ◽  
Psychotic Exacerbation

Thirty-nine chronic schizophrenic male out-patients and their relatives were interviewed separately to assess their perceptions of their current relationships. Two simple 5-point rating scales predicted the risk of psychotic exacerbation during a one-year follow-up: patients' perceptions of the relatives' attitudes towards them, and patients' own attitudes towards the relatives. Survival analysis of data in a 2 × 2 factorial - combining degree of contact with the key relatives and the patients' perceptions of their relatives - found that patients in frequent contact with a positively perceived relative had significantly better survival rates without psychotic exacerbation. Patients' perceptions of their relatives may help identify patients at risk of exacerbation of their illness.

scholarly journals Metastasis-associated fibroblasts: an emerging target for metastatic cancer

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Zimu Wang ◽  
Jiaxin Liu ◽  
Hairong Huang ◽  
Mingxiang Ye ◽  
Xinying Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Metastatic Cancer ◽  
Antiangiogenic Therapy ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Therapeutic Resistance ◽  
Metastatic Tumors ◽  
Stromal Fibroblasts ◽  
Primary Tumors ◽  
Metastatic Sites

AbstractMetastasis suggests a poor prognosis for cancer patients, and treatment strategies for metastatic cancer are still very limited. Numerous studies have shown that cancer-associated fibroblasts (CAFs), a large component of the tumor microenvironment, contribute to tumor metastasis. Stromal fibroblasts at metastatic sites are different from CAFs within primary tumors and can be termed metastasis-associated fibroblasts (MAFs), and they also make great contributions to the establishment of metastatic lesions and the therapeutic resistance of metastatic tumors. MAFs are capable of remodeling the extracellular matrix of metastatic tumors, modulating immune cells in the tumor microenvironment, promoting angiogenesis and enhancing malignant tumor phenotypes. Thus, MAFs can help establish premetastatic niches and mediate resistance to therapeutic strategies, including immunotherapy and antiangiogenic therapy. The results of preclinical studies suggest that targeting MAFs can alleviate the progression of metastatic cancer and mitigate therapeutic resistance, indicating that MAFs are a promising target for metastatic cancer. Here, we comprehensively summarize the existing evidence on MAFs and discuss their origins, generation, functions and related therapeutic strategies in an effort to provide a better understanding of MAFs and offer treatment perspectives for metastatic cancer.

scholarly journals The first experimental study of transference work–in teenagers (FEST–IT): a multicentre, observer- and patient-blind, randomised controlled component study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Randi Ulberg ◽  
Benjamin Hummelen ◽  
Anne Grete Hersoug ◽  
Nick Midgley ◽  
Per Andreas Høglend ◽  
...  
Keyword(s):  
Rating Scale ◽  
Work Group ◽  
Post Treatment ◽  
Psychoanalytic Psychotherapy ◽  
Secondary Outcome ◽  
Treatment Level ◽  
Long Term Effects ◽  
Link Type ◽  
One Year

Abstract Background Little is known about the influence on outcome of exploration of the patient-therapist relationship (that is, transference work) in psychoanalytic psychotherapy. We hypothesized that depressed adolescents would have better long-term effects from psychoanalytic psychotherapy with than without transference work. Methods Depressed adolescent (16 to 18 years) were recruited in health authority funded out-patient clinics in Oslo and Vestfold County, Norway. They were randomized to 28 weeks of treatment with psychoanalytic psychotherapy with or without transference work. Change was assessed using linear-mixed models. The primary outcome measure was the Psychodynamic Functioning Scale (pre- post-, and 1-year post-treatment). Level of depression was measured at the same time points and during therapy (week 12, and 20). Results 69 adolescents were treated with (N = 39) or without (N = 31) transference work. The mean number of sessions was 18.6 (SD = 8,6) in the transference work group and 18.0 (SD = 10.9) in the non-transference work group. Both groups showed large and significant improvement on Psychodynamic Functioning Scale during the whole study period. The difference between the two groups was not significant during the treatment period (95% CI −.79 to 1.2, p = .674, F = .18), or from post-treatment to one-year follow-up (95% CI −.13 to .96; p = .134; F = 2.3). For the secondary outcome measures the transference work group had significantly better outcomes from 12 weeks in treatment to one-year follow-up (Beck Depression Inventory, 95% CI − 1.7 to −.14, p = .022; Montgomery and Åsberg Depression Rating Scale, 95% CI − 1.6 to −.23, p = .009). Conclusion The findings suggest that exploration of the adolescents’ relations to the therapist amplify the effects of short-term psychoanalytic psychotherapy on their depressive symptoms for adolescents with a Major Depressive Disorder. Trial registration ClinicalTrials.gov. Id: NCT01531101. Registered 8 February 2012.

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