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1.
Pirus Ghadjar Wieslawa Blank-Liss Mathew Simcock Ivan Hegyi Karl T. Beer Holger Moch Daniel M. Aebersold Yitzhak Zimmer 《Clinical & experimental metastasis》2009,26(7):809-815
We investigated if the MET-activating point mutation Y1253D influences clinical outcomes in patients with advanced squamous cell carcinoma of the head
and neck (HNSCC). The study population consisted of 152 HNSCC patients treated by hyperfractionated radiotherapy alone or
concomitant with chemotherapy between September 1994 and July 2000. Tumors were screened for the presence of the MET-activating point mutation Y1253D. Seventy-eight patients (51%) received radiotherapy alone, 74 patients (49%) underwent radiotherapy
concomitant with chemotherapy. Median patient age was 54 years and median follow-up was 5.5 years. Distant metastasis-free
survival, local relapse-free survival and overall survival were compared with MET Y1253D status. During follow-up, 29 (19%) patients developed distant metastasis. MET Y1253D was detected in tumors of 21 out of 152 patients (14%). Distant metastasis-free survival (P = 0.008) was associated with MET Y1253D. In a multivariate Cox regression model, adjusted for T-category, only presence of MET Y1253D was associated with decreased distant metastasis-free survival: hazard ratio = 2.5 (95% confidence interval: 1.1,
5.8). The observed association between MET Y1253D-activating point mutation and decreased distant metastasis-free survival in advanced HNSCC suggests that MET may be a potential target for specific treatment interventions. 相似文献
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Sebastian Zschaeck Peter Wust Reinhold Graf Martin Misch Julia Onken Pirus Ghadjar Harun Badakhshi Julian Florange Volker Budach David Kaul 《Radiation oncology (London, England)》2018,13(1):251
Background
The dismal overall survival (OS) prognosis of glioblastoma, even after trimodal therapy, can be attributed mainly to the frequent incidence of intracranial relapse (ICR), which tends to present as an in-field recurrence after a radiation dose of 60 Gray (Gy). In this study, molecular marker-based prognostic indices were used to compare the outcomes of radiation with a standard dose versus a moderate dose escalation.Methods
This retrospective analysis included 156 patients treated between 2009 and 2016. All patients were medically fit for postoperative chemoradiotherapy. In the dose-escalation cohort a simultaneous integrated boost of up to 66?Gy (66?Gy RT) within small high-risk volumes was applied. All other patients received daily radiation to a total dose of 60?Gy or twice daily to a total dose of 59.2?Gy (60?Gy RT).Results
A total of 133 patients received standard 60?Gy RT, while 23 received 66?Gy RT. Patients in the 66?Gy RT group were younger (p?<? 0.001), whereas concomitant temozolomide use was more frequent in the 60?Gy RT group (p?<? 0.001). Other intergroup differences in known prognostic factors were not observed. Notably, the median time to ICR was significantly prolonged in the 66?Gy RT arm versus the 60?Gy RT arm (12.2 versus 7.6?months, p?=?0.011), and this translated to an improved OS (18.8 versus 15.3?months, p?=?0.012). A multivariate analysis revealed a strong association of 66?Gy RT with a prolonged time to ICR (hazard ratio?=?0.498, p?=?0.01) and OS (hazard ratio?=?0.451, p?=?0.01). These differences remained significant after implementing molecular marker-based prognostic scores (ICR p?=?0.008, OS p?=?0.007) and propensity-scored matched pairing (ICR p?=?0.099, OS p?=?0.023).Conclusion
Radiation dose escalation was found to correlate with an improved time to ICR and OS in this cohort of glioblastoma patients. However, further prospective validation of these results is warranted.4.
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Ghadjar P Loddenkemper C Coupland SE Stroux A Noutsias M Thiel E Christoph F Miller K Scheibenbogen C Keilholz U 《Journal of cancer research and clinical oncology》2008,134(11):1181-1189
Purpose CCR6 is expressed in various tumors and has been implicated in the process of tumor progression and metastasis. Its chemokine
ligand, CCL20, is present in different tissues including lymph nodes, but also the normal prostate. This study was performed
to investigate a potential relationship between CCR6 and CCL20 expression and features of human prostate cancer (PCA) at time
of primary treatment.
Methods Immunohistochemistry was used to detect CCR6 and CCL20 expression in archival tissue blocks of 80 PCA cases of various tumor
grades and stages. Evaluation was semiquantitatively by visual scoring and quantitatively by digital image analysis (DIA).
CCR6 and CCL20 expression was compared with Gleason score, stage, perineural invasion, nodal metastasis, age, and preoperative
serum prostate-specific antigen (PSA) level by univariate and multivariate analyses.
Results Staining intensity of CCR6 in tumor cells varied considerably, with it being: weak in 21 tumors (26.2%), intermediate in 44
(55.0%), and strong in 15 (18.8%), with 3.6-log differences in DIA measurements. CCL20 expression was absent in eight tumors
(10.0%), weak in 41 (51.2%), intermediate in 23 (28.8%), and strong in eight (10.0%). CCR6 and CCL20 expression did not correlate.
CCR6 expression was associated with T-category (P < 0.0005), Gleason score (P = 0.003), and lymph node metastasis (P = 0.002).
Conclusions Expression levels of CCR6 in PCA were associated with clinical and pathologic features of more advanced and aggressive prostate
cancer. Thus, CCR6 may directly or indirectly be involved in tumor progression and should be evaluated as novel candidate
target molecule for specific treatment interventions. 相似文献
6.
Pirus Ghadjar Fiona C. Burkhard Oliver Gautschi George N. Thalmann Urs E. Studer 《BJU international》2011,107(6):894-897
Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? In resectable muscle‐invasive bladder cancer neoadjuvant chemotherapy followed by radical cystectomy confers to a significant 5% overall survival benefit. Less is known about induction chemotherapy followed by radical cystectomy in initially unresectable patients. Our retrospective analysis of a selected patient cohort suggests that patients with initially unresectable bladder cancer may benefit from this combined treatment approach.
OBJECTIVE
? To analyse the outcome in selected patients with initially unresectable or minimally metastatic muscle‐invasive urothelial bladder cancer who underwent induction chemotherapy (IC) followed by radical cystectomy (RC).PATIENTS AND METHODS
? Thirty patients with initially unresectable, locally advanced or minimally metastatic bladder cancer underwent platinum‐based IC followed by RC with curative intent at our institution from 2000 to 2007. ? They received a median of four cycles (range 2–6 cycles) of cisplatin and gemcitabine (n= 19), carboplatin and gemcitabine (n= 9) or other platinum combinations (n= 2). ? We retrospectively analysed all 30 patients for complete pathological remission (pT0), disease free survival (DFS) and overall survival (OS). Chi‐square tests, Kaplan–Meier analyses, and Cox univariate modelling were used.RESULTS
? Before IC, 30 patients were deemed unresectable because of locally advanced tumour classification (cT4, 18/30) and/or clinically suspected lymph node (LN) metastasis (21/30) or suspected distant metastasis (3/30). ? At re‐staging after IC there was a complete regression of all enlarged LN in 16/21 patients, a partial LN response in one patient or stable LN size in the remaining four patients. ? After RC, 9/30 (30%) of patients had attained pT0. ? The median follow‐up was 28 months (range 4–97 months). The 5‐year DFS and OS rates were 42% and 46%, respectively, for all patients. ? In the pT0 patients, the DFS (83%) and OS (71%) rates were significantly higher than in non‐pT0 patients.CONCLUSION
? Patients undergoing IC followed by RC showed encouraging response and survival rates, suggesting that selected patients with initially unresectable bladder cancer benefit from this combined regimen. 相似文献7.
8.
Pirus?GhadjarEmail author Daniel?M.?Aebersold Clemens?Albrecht Dirk?B?hmer Michael?Flentje Ute?Ganswindt Stefan?H?cht Tobias?H?lscher Felix?Sedlmayer Frederik?Wenz Daniel?Zips Thomas?Wiegel Prostate Cancer Expert Panel of the German Society of Radiation Oncology the Working Party Radiation Oncology of the German Cancer Society 《Strahlentherapie und Onkologie》2018,194(7):619-626
Aim
Overview on the use of androgen deprivation therapy (ADT) added to salvage radiation therapy (SRT) for prostate cancer patients with biochemical recurrence after prostatectomy.Methods
The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published between January 2009 and May 2017, and assessed the validity of the information on outcome parameters including overall survival (OS) and treatment-related toxicity.Results
Two randomized controlled trials and nine relevant retrospective analyses were identified. The RTOG 9601 trial showed an OS improvement for the combination of 2 years of bicalutamide and SRT compared to SRT alone after a median follow-up of 13 years. This improvement appeared to be restricted to those patients with a prostate specific antigen (PSA) level before SRT of ≥0.7?ng/mL. The GETUG AFU-16 trial showed that after a median follow-up of 5 years, the addition of 6 months of goserelin to SRT improved progression-free survival (PFS; based on biochemical recurrence) as compared to SRT alone. ADT in both trials was not associated with increased major late toxicities. Results of retrospective series were inconsistent with a suggestion that the addition of ADT improved biochemical PFS especially in patients with high-risk factors such as Gleason Score ≥8 and in the group with initially negative surgical margins.Conclusions
ADT combined with SRT appears to improve OS in patients with a PSA level before SRT of ≥0.7?ng/mL. In patients without persistent PSA after prostatectomy and PSA levels of <0.7?ng/mL, ADT should not routinely be used, but may be considered in patients with additional risk factors such as Gleason Score ≥8 and negative surgical margins.9.
Vicinus B Rubie C Faust SK Frick VO Ghadjar P Wagner M Graeber S Schilling MK 《Cancer letters》2012,316(1):105-112
As deregulation of miRNAs and chemokine CCL20 was shown to play a role in colorectal cancer (CRC) pathogenesis, we analyzed the functional interactions of candidate miRNAs with CCL20 mRNA. After target prediction software programs indicated a role for miR-21 in CCL20 regulation, we applied the luciferase reporter assay system to demonstrate that miR-21 functionally interacts with the 3′UTR of CCL20 mRNA and down-regulates CCL20 in miR-21 mimic transfected CRC cell lines (Caco-2, SW480 and SW620). Thus, regulation of CCL20 expression by miR-21 might be a regulatory mechanism involved in progression of CRC. 相似文献