scholarly journals Programmed death ligand-1 protein expression difference in basal like and non-basal like triple negative breast cancer and its association with disease free survival and overall survival: A systematic review

2021 ◽  
Vol 15 (2) ◽  
Author(s):  
Freda Halim ◽  
Hasrayati Agustina ◽  
Yohana Azhar ◽  
Bethy Hernowo
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Disease Free Survival ◽  
Risk Of Bias ◽  
Secondary Outcome ◽  
Original Research ◽  
Free Survival ◽  
Expression Difference ◽  
Disease Free

The study aims to summarize the literature and explore the strength of evidence for PD-L1 expression difference in basal like TNBC and non-basal like TNBC, and association of PD-L1 expression with disease free survival and overall survival in each group. A systematic search of the original research literature through November 29th, 2020, reported according to PRISMA guideline. Eligible studies investigated must have a primary outcome and at least one secondary outcome. Two reviewers independently searched, selected, and assessed quality of studies and risk of bias. Any discrepancies will be resolved by consensus or by consulting a third and fourth author. A total of 6813 articles were screened from which five articles were selected and assessed for quality of studies and risk of bias. Of 5 articles, no similar findings are found regarding the level of PD-L1 expression and its correlation with recurrence and overall survival. There is not enough substantial evidence to support the difference PD-L1 protein expression level in basal and non-basal like TNBC and its association with recurrence and overall survival. Hence, further studies are needed specifically to focus on this problem.

scholarly journals Automated Quantification of CD44, c-MET, EGFR, MTOR, and GLUT1 Expression in Head and Neck Squamous Cell Carcinoma: The Impact of p16 Status and Response to Chemoradiation

2020 ◽  
pp. 1-10
Author(s):  
George Wilson ◽  
Jessica D. Arden ◽  
Thomas J. Quinn ◽  
Thomas G. Wilson ◽  
Alaa Hanna ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Locoregional Control ◽  
Free Survival ◽  
Automated Quantification ◽  
Control Disease ◽  
Disease Free

This study assessed automated quantification of CD44, c-MET, MTOR, EGFR, and GLUT1 protein expression in a tissue microarray of 109 Stage II-IV p16 positive and negative head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation. Immunohistochemistry-based protein expression was quantified in an automated manner using digitally scanned images processed with Definiens Tissue Studio software to generate a histologic score (H-score, range 0-300) which was normalized for each biomarker. Biomarker expression levels were correlated with one another and with p16 status. Effects of biomarker and p16 status on locoregional control, disease-free survival, and overall survival were analyzed using Kaplan Meier and Cox proportional hazard modelling. There was a significant negative correlation between CD44 and p16 expression and significant positive correlations between CD44 and MTOR, CD44 and GLUT1, c-MET and MTOR, and MTOR and GLUT1. When patients were stratified by p16 status, the significant positive correlation between CD44 expression and MTOR remained for both the p16 positive and negative subsets, while correlations between CD44 and GLUT1 and c-MET and MTOR were seen in the p16 negative subset only. A significant correlation between MTOR and GLUT was seen overall and for the p16 positive subset. When the effects of biomarker expression on clinical endpoints were examined, histologic scores below the defined cut-points for CD44 and c-MET were each associated with improved locoregional control. Higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with inferior disease-free and overall survival. On multivariable analysis, p16 positivity remained independently associated with improved locoregional control, disease-free survival, and overall survival, high CD44 remained independently associated with inferior locoregional control, disease-free survival, and overall survival, and EGFR with inferior disease-free and overall survival. In conclusion, the use of an automated system to quantify IHC expression allowed objective correlation between biomarkers and stratification of patients, revealing that higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with poorer disease-free and overall survival.

Validation of MAF biomarker for response prediction to adjuvant bisphosphonates in 2 clinical trials: AZURE and NSABP-B34.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 513-513
Author(s):  
Alexander H. G. Paterson ◽  
Stewart J. Anderson ◽  
Roger Gomis ◽  
Joel [email protected] ◽  
Juan-Carlos Tercero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Disease Free Survival ◽  
Collaborative Group ◽  
Secondary Outcome ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

513 Background: An Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis indicates that adjuvant bisphosphonates increase time to bone recurrence and survival in postmenopausal breast cancer patients, but results of individual trials have been inconclusive. Retrospective analyses of AZURE, a trial of adjuvant zoledronic acid, showed MAF (a transcription factor of the AP-1 family) amplification status predicted bisphosphonate benefit independently of menopause for invasive disease-free survival (IDFS) and overall survival (OS). Validation of MAF amplification status as a potential companion diagnostic for adjuvant bisphosphonates was confirmed using NSABP-B34 specimens. Methods: The randomized, placebo-controlled NSABP B-34 study of women with stage 1-3 breast cancer were assigned to adjuvant systemic therapy plus oral clodronate 1600 mg daily or placebo for 3 years. The primary endpoint was disease-free survival (DFS) with overall survival (OS) as a secondary outcome. MAF amplification was assessed by fluorescence in-situ hybridization on anonymized sections of breast tumor tissue in all patients with tumor samples and performed in a laboratory blind to treatment assignment. Protocol and analysis plans were pre-specified. Disease outcomes were analysed using intention to treat principles. Results: 2496 B-34 patients contributed tumor samples (from 2001-2004), of whom 1883 (75%) were evaluable (947 placebo and 936 clodronate). 1515 (80%) tumors were MAF negative (766 placebo and 749 clodronate) and 368 were MAF positive. At median follow-up of 108 months, MAF was prognostic for DFS, OS and bone-metastasis-free survival in the control group (MAF-positive vs MAF-negative: HRDFS=1·39, 95%CI 1·01-1·92; p=0.045; HROS=1·59, 95%CI 1·08-2·33; p=0.018; HRBM=2·03, 95%CI 1·13-3·68; p=0.016). In patients with MAF-negative tumors, clodronate gave higher DFS and OS than controls at 60 months (HRDFS=0·70, 95%CI 0·51-0·94; p=0.020 and HROS=0·59, 95%CI 0·37-0·93; p=0.024), the latter maintained through follow-up (HROS=0·74, 95%CI 0·54-1.00; p=0.047), but not in patients with MAF-positive tumors - consistent with previous AZURE results. Conclusions: MAF benefit prediction from adjuvant bisphosphonates was confirmed using specimens from 2 randomized clinical trials (AZURE and NSABP-B-34) conducted and analyzed in similar manner using the same validated tests and clinical endpoints. These results are evidence towards introducing MAF testing into clinical practice.

scholarly journals Impact of general anaesthesia in overall and disease-free survival compared to other types of anaesthesia in patients undergoing surgery for cutaneous melanoma: a systematic review and meta-analysis protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e027993
Author(s):  
Bruno Luís de Castro Araujo ◽  
Jadivan Leite de Oliveira ◽  
Flavia de Miranda Corrêa ◽  
Luis Eduardo Santos Fontes ◽  
Andreia Cristina de Melo ◽  
...  
Keyword(s):  
General Anaesthesia ◽  
Cutaneous Melanoma ◽  
Tumour Progression ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Risk Of Bias ◽  
Free Survival ◽  
Analyse Data ◽  
Disease Free

IntroductionCutaneous melanoma is an aggressive type of skin cancer. Anaesthetic agents may have an impact on the immune response, postoperative neurohumoral response and tumour progression. This systematic review aims to evaluate the impact of general anaesthesia on overall and disease-free survival compared with other types anaesthesia in patients undergoing surgery for cutaneous melanoma.Methods and analysisThe review will analyse data from controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia compared with other types of anaesthesia. The primary outcomes are overall survival and disease-free survival. The secondary outcomes are health-related quality of life, time to tumour progression, distant disease-free survival, time to treatment failure, cancer-specific survival, biochemical recurrence, return of intended oncological therapy, days alive and out of the hospital at 90 days, cost analysis and adverse events. A comprehensive literature search will be performed using the MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, LILACS and IBECS databases. Grey literature will also be searched. Risk of methodological bias will be assessed using The Cochrane Collaboration’s revised tool for assessing risk of bias in randomised trials (RoB 2.0) and the Newcastle–Ottawa scale. Two reviewers will independently assess the eligibility of studies and risk of bias; a third author will solve discrepancies. One author will perform data extraction and the other will check the process and data. Qualitative analysis will be carried out using all included studies. A meta-analysis using a random-effects model for pooled risk estimates will be carried out for the two main outcomes and for selected secondary outcomes if they conform to previously stated criteria. The GRADE approach will be used to summarise the quality of evidence.Ethics and disseminationEthics approval is not required as we analyse data from previously reported studies.PROSPERO registration numberCRD42018114918.

Multicenter Randomized Trial of Adjuvant Fluorouracil and Folinic Acid Compared With Surgery Alone After Resection of Colorectal Liver Metastases: FFCD ACHBTH AURC 9002 Trial

2006 ◽  
Vol 24 (31) ◽  
pp. 4976-4982 ◽  
Author(s):  
Guillaume Portier ◽  
Dominique Elias ◽  
Olivier Bouche ◽  
Philippe Rougier ◽  
Jean-François Bosset ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastases ◽  
Odds Ratio ◽  
Systemic Chemotherapy ◽  
Disease Free Survival ◽  
Secondary Outcome ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

Purpose Complete resection of liver metastases of colorectal origin is the only potentially curative treatment. In order to decrease recurrences, the use of adjuvant systemic chemotherapy after liver resection is controversial because no randomized study demonstrated its benefit. Patients and Methods In a multicenter trial, we randomly assigned 173 patients with completely resected (R0) hepatic metastases from colorectal cancer to surgery alone and observation (87 patients) or to surgery followed by 6 months of systemic adjuvant chemotherapy with a fluorouracil and folinic acid monthly regimen (86 patients). The main outcome criterion was disease-free survival. Secondary outcome measures were overall survival and treatment-related toxicity. Results The intention-to-treat analysis was based on 171 patients, after a median follow-up of 87 months (SE = 5.8). The 5-year disease-free survival rate, after adjustment for major prognostic factors, was 33.5% for patients in the chemotherapy group and 26.7% for patients in the control group (Cox multivariate analysis: odds ratio for recurrence or death = 0.66; 95% CI, 0.46 to 0.96; P = .028). With regard to secondary outcome measures, a trend towards increased overall survival was observed but did not reach statistical significance (5-year overall survival: chemotherapy group, 51.1% v control group, 41.1%; odds ratio for death, 0.73; 95% CI, 0.48 to 1.10; P = .13). Conclusion Despite a suboptimal regimen, which was the standard at the beginning of the study, adjuvant intravenous systemic chemotherapy provided a significant disease-free survival benefit for patients with resected liver metastases from colorectal cancer.

scholarly journals Adherence to breast cancer guidelines is associated with better survival outcomes: a systematic review and meta-analysis of observational studies in EU countries

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ignacio Ricci-Cabello ◽  
Adrián Vásquez-Mejía ◽  
Carlos Canelo-Aybar ◽  
Ena Niño de Guzman ◽  
Javier Pérez-Bracchiglione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Health Outcomes ◽  
Guideline Adherence ◽  
Disease Free Survival ◽  
Risk Of Bias ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract Background Breast cancer (BC) clinical guidelines offer evidence-based recommendations to improve quality of healthcare for patients with or at risk of BC. Suboptimal adherence to recommendations has the potential to negatively affect population health. However, no study has systematically reviewed the impact of BC guideline adherence -as prognosis factor- on BC healthcare processes and health outcomes. The objectives are to analyse the impact of guideline adherence on health outcomes and on healthcare costs. Methods We searched systematic reviews and primary studies in MEDLINE and Embase, conducted in European Union (EU) countries (inception to May 2019). Eligibility assessment, data extraction, and risk of bias assessment were conducted by one author and crosschecked by a second. We used random-effects meta-analyses to examine the impact of guideline adherence on overall survival and disease-free survival, and assessed certainty of evidence using GRADE. Results We included 21 primary studies. Most were published during the last decade (90%), followed a retrospective cohort design (86%), focused on treatment guideline adherence (95%), and were at low (80%) or moderate (20%) risk of bias. Nineteen studies (95%) examined the impact of guideline adherence on health outcomes, while two (10%) on healthcare cost. Adherence to guidelines was associated with increased overall survival (HR = 0.67, 95%CI 0.59–0.76) and disease-free survival (HR = 0.35, 95%CI 0.15–0.82), representing 138 more survivors (96 more to 178 more) and 336 patients free of recurrence (73 more to 491 more) for every 1000 women receiving adherent CG treatment compared to those receiving non-adherent treatment at 5 years follow-up (moderate certainty). Adherence to treatment guidelines was associated with higher costs, but adherence to follow-up guidelines was associated with lower costs (low certainty). Conclusions Our review of EU studies suggests that there is moderate certainty that adherence to BC guidelines is associated with an improved survival. BC guidelines should be rigorously implemented in the clinical setting. Trial registration PROSPERO (CRD42018092884).

scholarly journals Evaluation of E-cadherin, β-catenin and vimentin protein expression using quantitative immunohistochemistry in nasopharyngeal carcinoma patients

2014 ◽  
Vol 37 (5) ◽  
pp. 320 ◽  
Author(s):  
Desirée Hao ◽  
Tien Phan ◽  
Amanda Jagdis ◽  
Jodi E Siever ◽  
Alexander C Klimowicz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Disease Free Survival ◽  
Aberrant Expression ◽  
Free Survival ◽  
Mesenchymal Transition ◽  
Quantitative Immunohistochemistry ◽  
Increased Risk ◽  
Disease Free ◽  
E Cadherin

Purpose: Aberrant expression of proteins involved in epithelial-to-mesenchymal transition have been described in various cancers. In this retrospective study, we sought to evaluate E-cadherin, β-catenin and vimentin protein expression in non-metastatic nasopharyngeal (NPC) patients treated with curative intent, examine their relationship with each other, and with clinical outcome measures. Methods: Pre-treatment formalin-fixed paraffin-embedded biopsies of 140 patients treated between January 2000 and December 2007 were assembled into a tissue microarray (TMA). Automated quantitative immunohistochemistry (AQUA®) was performed on sequential TMA sections stained with fluorescent-labeled antibodies against E-cadherin, β-catenin and vimentin. Cox proportional hazards regression was used to estimate the effect of cytoplasmic vimentin, cytoplasmic E-cadherin, β-catenin nuclear/cytoplasmic ratio expression on overall survival and disease-free survival. Results: The average age of the patients was 51.7 years (SD=12.1; range 18-85), 66% were male, 71% had a KPS ≥ 90% at the start of treatment and 65% had stage III/IV disease. After adjusting for performance status, WHO and stage, high E-cadherin levels over the 75th percentile were found to produce a significantly increased risk for both a worse overall survival (HR = 2.53, 95% CI 1.21, 5.27) and disease free survival (DFS; HR = 2.14, 95%CI 1.28, 3.59). Vimentin levels over the first quartile produced an increased risk for a worse DFS (HR = 2.21, 95% CI 1.11, 4.38). No association was seen between β-catenin and survival. Conclusion: In this cohort of NPC patients, higher levels of E-cadherin and higher levels of vimentin were associated with worse outcomes. Further work is needed to understand the role of these epithelial mesenchymal transition proteins in NPC.

High Expression of Ubiquitin C-terminal Hydrolase L1 Is Associated With Poor Prognosis in Endometrial Cancer Patients

2018 ◽  
Vol 28 (4) ◽  
pp. 675-683 ◽  
Author(s):  
Kohshiro Nakao ◽  
Takashi Hirakawa ◽  
Hiroto Suwa ◽  
Kayoko Kogure ◽  
Sadatomo Ikeda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Protein Expression ◽  
Messenger Rna ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Rna Expression ◽  
Free Survival ◽  
Metastatic Lesions ◽  
Disease Free

ObjectiveThe ubiquitin C-terminal hydrolase L1 (UCHL1) plays a key role in tumor invasion and metastasis. Ubiquitin C-terminal hydrolase L1 is overexpressed in various cancers and reported to be correlated with a poor prognosis. The objective of this study was to determine the prognostic significance of UCHL1 in endometrial cancer.MethodsThe expression of UCHL1 in endometrial cancer was assessed using quantitative reverse transcription polymerase chain reaction and immunohistochemistry in 56 and 215 resected tumor specimens, respectively.ResultsThe 4-year survival rates of the high UCHL1 messenger RNA expression group and high UCHL1 protein expression group were 78% and 71%, respectively, compared with 96% and 95% for the low UCHL1 messenger RNA expression group and low UCHL1 protein expression group, respectively. Kaplan-Meier and log-rank tests indicated a significant correlation between expression of UCHL1 and disease-free survival and overall survival. Moreover, multivariate stepwise Cox proportional hazard regression model analysis showed that UCHL1 was a significant independent marker for predicting a poor disease-free survival and overall survival. In 43 patients with metastatic lesions, immunohistochemical analysis of metastatic lesions revealed that the recurrence rate and mortality rate were 62% and 41%, respectively, in 29 UCHL1-positive patients and 36% and 29%, respectively, in 14 UCHL1-negative patients.ConclusionsThe results of this study suggest that high UCHL1 expression is a strong marker of poor prognosis of endometrial cancer. Furthermore, we suggest that UCHL1 may be involved in the development of distant metastasis in endometrial cancer.

Comparison of clinical outcomes between enucleation and regular pancreatectomy in patients with non-functional pancreatic neuroendocrine tumors: a retrospective multicenter and propensity score-matched study

2021 ◽  
Author(s):  
Zhen Yang ◽  
Hengjun Gao ◽  
Jun Lu ◽  
Zheyu Niu ◽  
Huaqiang Zhu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Postoperative Complications ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Neuroendocrine Tumors ◽  
Disease Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Estimated Blood Loss ◽  
Disease Free

Abstract Objective There are limited data from retrospective studies on whether therapeutic outcomes after regular pancreatectomy are superior to those after enucleation in patients with small, peripheral and well-differentiated non-functional pancreatic neuroendocrine tumors. This study aimed to compare the short- and long-term outcomes of regular pancreatectomy and enucleation in patients with non-functional pancreatic neuroendocrine tumors. Methods Between January 2007 and July 2020, 227 patients with non-functional pancreatic neuroendocrine tumors who underwent either enucleation (n = 89) or regular pancreatectomy (n = 138) were included. Perioperative complications, disease-free survival, and overall survival probabilities were compared. Propensity score matching was performed to balance the baseline differences between the two groups. Results The median follow-up period was 60.76 months in the enucleation group and 43.29 months in the regular pancreatectomy group. In total, 34 paired patients were identified after propensity score matching. The average operative duration in the enucleation group was significantly shorter than that in the regular pancreatectomy group (147.94 ± 42.39 min versus 217.94 ± 74.60 min, P < 0.001), and the estimated blood loss was also significantly lesser (P < 0.001). The matched patients who underwent enucleation displayed a similar overall incidence of postoperative complications (P = 0.765), and a comparable length of hospital stay (11.12 ± 3.90 days versus 9.94 ± 2.62 days, P = 0.084) compared with those who underwent regular pancreatectomy. There were no statistically significant differences between the two groups in disease-free survival and overall survival after propensity score matching. Conclusion Enucleation in patients with non-functional pancreatic neuroendocrine tumors was associated with shorter operative time, lesser intraoperative bleeding, similar overall morbidity of postoperative complications, and comparable 5-year disease-free survival and overall survival when compared with regular pancreatectomy.

scholarly journals EPEN-49. RESPONSE OF RECURRENT EPENDYMOMA TO MEMMAT BASED METRONOMIC ANTIANGIOGENIC COMBINATION THERAPY UTILIZING TAPERED BEVACIZUMAB AND MAINTENANCE THERAPY WITH CELECOXIB AND FENOFIBRATE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii317-iii317
Author(s):  
Eileen Gillan
Keyword(s):  
Combination Therapy ◽  
Maintenance Therapy ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Time To Progression ◽  
Free Survival ◽  
Dismal Prognosis ◽  
Recurrent Ependymoma ◽  
Disease Free

Abstract Recurrent ependymomas have a dismal prognosis (2 year survival rates 29% OS and 23% EFS) and are relatively resistant to conventional chemotherapy. We previously reported five relapsed ependymoma patients treated with a MEMMAT based metronomic antiangiogenic combination therapy. All patients are currently alive, including four patients who were multiply relapsed with at least three recurrences. These four patients received between 44–52 weeks of therapy with minimal toxicity. Three had recurrent disease within an average of 44 months (median 42 months) after discontinuation of therapy. One patient who received the following tapering bevacizumab schedule: q3 weeks x 3, q4 weeks x 4 and q5 weeks x 5 followed by maintenance therapy with fenofibrate and celecoxib is in complete remission 12 months post treatment. This regimen was well tolerated with good quality of life in this patient population. Our results suggest that the chosen anti-angiogenic drug combination prolonged the time to progression in these multiply relapsed patients and thus may be particularly beneficial for patients with recurrent ependymoma. Tapered bevacizumab and maintenance therapy with celecoxib and fenofibrate may be modifications worth further investigation for prolonged disease free survival in relapsed ependymoma patients.

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