Denkert C.,Charité - Medical University of Berlin |
Loibl S.,German Breast Group |
Muller B.M.,Charité - Medical University of Berlin |
Eidtmann H.,University of Kiel |
And 16 more authors.
Annals of Oncology | Year: 2013
Background: The proliferation marker Ki67 has been suggested as a promising cancer biomarker. As Ki67 needs an exact quantification, this marker is a prototype of a new generation of tissue-based biomarkers. In this study, we have systematically evaluated different cut points for Ki67 using three different clinical end points in a large neoadjuvant study cohort. Patients and methods: We have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast cancer core biopsies from the neoadjuvant GeparTrio trial. We used the standardized cutoff-finder algorithm for three end points [response to neoadjuvant chemotherapy (pCR), disease-free (DFS) and overall-survival (OS)]. The analyses were stratified for hormone receptor (HR) and HER2 status by molecular subtype radar diagrams (MSRDs). Results: A wide range of Ki67 cut points between 3%-94% (for pCR), 6%-46% (for DFS) and 4%-58% (for OS) were significant. The three groups of Ki67 ≤ 15% versus 15.1%-35% versus >35% had pCR-rates of 4.2%, 12.8%, and 29.0% (P < 0.0005), this effect was also present in six of eight molecular subtypes. In MSRD, Ki67 was significantly linked to prognosis in uni- and multivariate analysis in the complete cohort and in HR-positive, but not triple-negative tumors. Conclusions: Ki67 is a significant predictive and prognostic marker over a wide range of cut points suggesting that data-derived cut point optimization might not be possible. Ki67 could be used as a continuous marker; in addition, the scientific community could define standardized cut points for Ki67. Our analysis explains the variability observed for Ki67 cut points in previous studies; however, this should not be seen as weakness, but as strength of this marker. MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer. The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology All rights reserved.
Kodeda K.,Gothenburg University |
Holmberg E.,Oncological Center |
Steineck G.,Karolinska Institutet |
Nordgren S.,Gothenburg University
Colorectal Disease | Year: 2010
Aim: To analyse a substantial regional difference in local failure rate after rectal cancer surgery focusing on management. Method: National, population-based, prospective registry data were used, including comprehensive 5-year follow up of 3783 patients operated on in the period 1998-2000. Local recurrence rates were compared using crude rate, Kaplan-Meier estimates and competing risk methodology. Resected patients (651 regional and 3132 national) were analysed and subgroup comparisons of management were performed. Results: The crude local recurrence rate was 13.7% in the regional cohort and 7.1% in the national cohort. The absolute difference of 6.6% may partly be explained by systematic errors of underreporting (≤ 1.4%), differences in patient populations and indications for surgery. A significant difference in the use of neoadjuvant radiotherapy (explaining ≤ 1.0%) and some aspects of surgical strategy were also observed. Conclusions: We conclude that some of the difference in the registered incidence of local recurrence between the regional and the national cohorts remains unexplained and may depend on surgical technique in terms of lack of radicality in removing tumour tissue. © 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland.
Bratt O.,Lund University |
Garmo H.,Regional Oncological Center |
Garmo H.,King's College London |
Adolfsson J.,Oncological Center |
And 6 more authors.
Journal of the National Cancer Institute | Year: 2010
BackgroundFamily history is a strong risk factor for prostate cancer. The aim of this study was to investigate whether increased diagnostic activity is related to the incidence of prostate cancer among brothers of men with prostate cancer.MethodsData were from the nationwide population-based Prostate Cancer Database Sweden (PCBaSe Sweden), which includes data from the National Prostate Cancer Register, the Swedish Cancer Register, the Register of the Total Population, the Multi-Generation Register, and the Census database. We investigated the relationship of tumor characteristics, time from diagnosis of the index patient (ie, prostate cancer patients in the National Prostate Cancer Register for whom at least one brother and their father could be identified), calendar period, geographic factors, and socioeconomic status to standardized incidence ratios (SIRs) for prostate cancer among 22511 brothers of 13975 index patients in PCBaSe Sweden.ResultsBrothers of index patients with prostate cancer were at increased risk for a diagnosis of prostate cancer (SIR = 3.1, 95% confidence interval [CI] = 2.9 to 3.3). Risk was higher for T1c tumors (SIR = 3.4, 95% CI = 3.2 to 3.8) than for metastatic tumors (SIR = 2.0, 95% CI = 1.5 to 2.6), and risk of T1c tumors was especially high during the first year after the diagnosis of the index patient (SIR = 4.3, 95% CI = 3.8 to 4.9), compared with the following years (SIR range = 2.8-3.3), and for brothers of index patients who had a higher socioeconomic status (SIR = 4.2, 95% CI = 3.7 to 4.7), compared with brothers of index patients with lower socioeconomic status (SIR = 2.8, 95% CI = 2.4 to 3.2).ConclusionsIncreased diagnostic activity among men with a family history of prostate cancer appears to contribute to their increased risk of prostate cancer and to lead to detection bias in epidemiological and genetic studies of familial prostate cancer. © 2010 The Author.
Kodeda K.,Sahlgrenska University Hospital |
Holmberg E.,Oncological Center |
Jorgren F.,Lund University |
Nordgren S.,Sahlgrenska University Hospital |
Lindmark G.,Lund University
British Journal of Surgery | Year: 2010
Background: Adenocarcinomas of the rectum shed viable cells, which have the ability to implant. Intraoperative rectal washout decreases the amount and viability of these cells, but there is no conclusive evidence of the effect of rectal washout on local recurrence after rectal cancer surgery. Methods: Data were analysed from a population-based registry of patients who had anterior resection from 1995 to 2002 and were followed for 5 years. Rectal washout was performed at the discretion of the surgeon. National inclusion of patients with rectal cancer and follow-up was near complete (approximately 97 and 98 per cent respectively). Results: A total of 4677 patients were analysed (3749 who had washout, 851 no washout and 77 with informationmissing); 52·0 per cent of patients in the washout group and 41·4 per cent in the no-washout group had preoperative radiotherapy (P < 0·001). Local recurrence rates were 6·0 and 10·2 per cent respectively (P < 0·001). Univariable and multivariable logistic regression analyses produced odds ratios that favoured washout: 0·56 (95 per cent confidence interval (c.i.) 0·43 to 0·72) and 0·61 (0·46 to 0·80) respectively (both P < 0·001). In multivariable analysis restricted to patients who had curative surgery, the odds ratio was 0·59 (95 per cent c.i. 0·44 to 0·78; P < 0·001). Conclusion: There was a more favourable outcome in patients after rectal washout than without. © 2010 British Journal of Surgery Society Ltd.
Malkowski B.,Oncological Center |
Malkowski B.,Nicolaus Copernicus University |
Staniuk T.,Oncological Center |
Srutek E.,Nicolaus Copernicus University |
And 3 more authors.
Gastroenterology Research and Practice | Year: 2013
The aim of the study was to evaluate the usefulness of 18F-FLT PET/CT in the detection and differentiation of gastric cancers (GC). 104 consecutive patients (57 cases of adenocarcinoma tubulare (G2 and G3), 17 cases of mucinous adenocarcinoma, 6 cases of undifferentiated carcinoma, 14 cases of adenocarcinoma partim mucocellulare, and 10 cases of end stage gastric cancer) with newly diagnosed advanced gastric cancer were examined with FLT PET/CT. For quantitative and comparative analyses, the maximal standardized uptake value (SUVmax) was calculated for both the tumors and noninvaded gastric wall. Results. There were found, in the group of adenocarcinoma tubulare, SUVmax 1.5-23.1 (7.46±4.57), in mucinous adenocarcinoma, SUVmax 2.3-10.3 (5.5±2.4), in undifferentiated carcinoma, SUVmax 3.1-13.6 (7.28±3.25), in adenocarcinoma partim mucocellulare, SUVmax 2-25.3 (7.7±6.99), and, in normal gastric wall, SUVmax 1.01-2.55 (1.84±0.35). For the level of 2.6 cut-off value between the normal wall and neoplasm FLT uptake from ROC analysis, all but five gastric cancers showed higher accumulation of FLT than noninfiltrated mucosa. Conclusion. Gastric cancer presents higher accumulation of 18F-FLT than normal, distended gastric mucosa. Significantly higher accumulation was shown in cancers better differentiated and with higher cellular density. © 2013 Bogdan Małkowski et al.
PubMed | Oncological Center and Nicolaus Copernicus University
Type: Journal Article | Journal: Abdominal radiology (New York) | Year: 2016
To date, no data are available on the use of 18-fluorothymidine positron emission tomography/computed tomography (FLT-PET/CT) for preoperative gastric cancer staging. Herein, we attempt to assess the value of FLT-PET/CT for preoperative gastric cancer staging in comparison with contrast-enhanced computed tomography (CECT).In a group of 96 gastric cancer patients, 96 FLT-PET/CT, 56 abdominal cavity CECT, and 51 resective operations were done. All three (FLT-PET/CT, CECT, and resective operation) were done in 29 patients. The results of FLT-PET/CT, CECT, and histopathological examinations were used to assess the ability of FLT-PET/CT and CECT to identify primary tumors, regional nodal metastases, and distant abdominal metastases. Assessment of regional lymph nodes was based on SUVmax in FLT-PET/CT and SAD (short-axis diameter) in CECT.In the group of 56 patients examined with FLT-PET/CT and CECT, identification of the primary tumor was possible in 56 cases (100%) and in 53 cases (94.6%), respectively, (p=0.013). Using ROC curve, the sensitivity and specificity of FLT-PET/CT in metastatic regional lymph node assessment were higher than those of CECT (p=0.0033). FLT-PE/CT enabled identification of a greater number of extraregional abdominal metastases than CECT (n=56; 19 vs. 15, respectively), but the difference was not statistically significant (p>0.41).The ability of FLT-PET/CT to identify primary tumors is greater than that of CECT, and thus FLT-PET/CT was better in evaluating regional nodal metastases. FLT-PET/CT enabled identification of a greater number of abdominal metastases than CECT, but the difference was not statistically significant.
Gidron Y.,Free University of Brussels |
De Couck M.,Free University of Brussels |
De Greve J.,Free University of Brussels |
De Greve J.,Oncological Center
Journal of Biological Regulators and Homeostatic Agents | Year: 2014
The parasympathetic system, and primarily the vagus nerve, informs the brain about multiple signals and returns the body to homeostasis. Recent studies have shown that vagal nerve activity independently predicts prognosis in cancer. Here, we take this one step further and show that when vagal nerve activity is high, cancer stage no longer predicts tumor burden. We examined whether vagal nerve activity, indexed by Heart Rate Variability (HRV), moderated the effects of initial tumor stage on tumor burden at follow-up. Patients' HRVs were derived from ECGs near diagnosis in colorectal cancer (CRC) and in prostate cancer (PC) patients. Outcomes included the tumor markers carcinoembryonic antigen (CEA) at 12 months for CRC and prostate-specific antigen (PSA) at 6 months for PC. As would be expected, initially advanced tumor stages of CRC or PC predicted higher tumor marker levels at follow-up than did early stages. However, this occurred only in patients with low, not high, vagal activity (HRV). Furthermore, in patients with advanced tumor stage at diagnosis, high HRV predicted lower tumor marker levels than did low HRV, in both cancers. Estimating a cancer patient's prognosis by determining his tumor stage needs to also consider the vagal nerve activity. This activity is easily measurable, and it determines in which subjects the tumor stage is prognostic. Importantly, higher vagal activity may even protect against the adverse effects of advanced cancer stage. These findings, observed in two distinct cancers, support the hypothesized neuroimmunomodulatory effects of vagal nerve activity on tumors. Copyright © by BIOLIFE, s.a.s.
Schirrmacher V.,Oncological Center |
Schirrmacher V.,German Cancer Research Center |
Bihari A.-S.,Oncological Center |
Stucker W.,Oncological Center |
Sprenger T.,Oncological Center
Oncology Letters | Year: 2014
The present study reports the case of a patient with hormone-refractory metastatic prostate cancer who had failed standard therapy, but then achieved complete remission following combined treatment with local hyperthermia (LHT), Newcastle disease virus and dendritic cell (DC) vaccination, which was an unusual combination. In August 2005, the patient underwent a radical prostatectomy. Despite standard treatment, the patient developed progressive bone metastases and stopped conventional therapy in June 2007. Starting in October 2007, the patient was treated with LHT, oncolytic virotherapy and DC vaccination. Prostate-specific antigen (PSA)-levels, with the highest level of 233.8 ng/ml in January 2008, decreased to 0.8 ng/ml in late February 2008. In March 2008, a reduction in bone metastases could be detected by positron emission tomography/computed tomography. Since then, the PSA levels have remained low and the patient is doing well. The treatment induced a long-lasting antitumor memory T-cell response. This possibly explains the long-term effectiveness of this novel experimental combined treatment approach. © 2014, Spandidos Publications. All rights reserved.
Pach R.,Jagiellonian University |
Kulig J.,Jagiellonian University |
Richter P.,Jagiellonian University |
Gach T.,Jagiellonian University |
And 2 more authors.
Langenbeck's Archives of Surgery | Year: 2012
Purpose: The purpose of this study was to establish the influence of time interval between preoperative hyperfractionated radiotherapy (5×5 Gy) and surgery on long-term overall survival (5 years) and recurrence rate in patients with locally advanced rectal cancer operated on according to total mesorectal excision technique. Methods: The treatment group comprised 154 patients with locally advanced rectal cancer who were operated on between 1999 and 2006 in the 1st Department of General Surgery, Jagiellonian University, Cracow, Poland. The data on survival has been systematically collected until 31st of December 2010. In addition, the following aspects were analyzed: the significance of time interval between the end of radiotherapy and surgical treatment and its influence on downsizing, downstaging, rate of curative resections, and sphincter-sparing procedures. Patients were qualified to preoperative radiotherapy 5×5 Gy and then randomly assigned to subgroups with different time intervals between radiotherapy and surgery: one subgroup consisted of 77 patients operated on 7-10 days after the end of irradiation, and the second subgroup consisted of 77 patients operated on after 4-5 weeks. Both groups were homogenous in sex, age, cancer stage and localization, distal and circumferential resection margins, and number of resected lymph nodes. Results The 5-year survival rate in patients operated on 7-10 days after irradiation was 63%, whereas in those operated on after 4-5 weeks, it was 73%-the difference was not statistically significant (log rank, p00.24). A statistically significant increase in 5-year survival rate was observed only in patients with downstaging after radiotherapy-90% in comparison with 60% in patients without response to neoadjuvant treatment (log rank, p00.004). Recurrence was diagnosed in 13.2% of patients. A lower rate of systemic recurrence was observed in patients operated on 4-5 weeks after the end of irradiation (2.8% vs. 12.3% in the subgroup with a shorter interval, p00.035). No differences in local recurrence rates were observed in both subgroups of irradiated patients (p= 0.119). The longer time interval between radiotherapy and surgery resulted in higher downstaging rate (44.2% vs. 13% in patients with a shorter interval, p=0.0001) although it did not increase the rate of sphincter-saving procedures (p=0.627) and curative resections (p=0.132). Conclusions: 1. Improved 5-year survival rate is observed only in patients with downstaging after preoperative irradiation dose of 25 Gy. 2. Longer time interval after preoperative radiotherapy 25 Gy does not improve the rate of sphincter-saving procedures and curative resections (R0) despite higher downstaging rate observed in this regimen. © Springer-Verlag 2011.
Tedeschi R.,Oncological Center
Methods in molecular biology (Clifton, N.J.) | Year: 2011
The storage of the different microorganisms over long periods is necessary to ensure reproducible results and continuity in research and in biomedical processes and also for commercial purposes. Effective storage means that a microorganism is maintained in a viable state free of contamination or genetic drift and must be easily restored without genotypic or phenotypic alterations to its original characteristics and properties. To this end, different techniques have been described and advances in cryopreservation technology have led to methods that allow low-temperature maintenance of a variety of cell types, minimizing the risks of genetic change and are now recommended for long-term storage of most microorganisms.This chapter summarizes the most important steps and components in the process of low- and -ultra-low temperatures freezing of bacteria, parasites, yeasts and fungi, viruses, and recombinant microorganisms.