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  • American Association for Cancer Research (AACR)  (5)
  • Medicine  (5)
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  • American Association for Cancer Research (AACR)  (5)
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  • Medicine  (5)
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  • 1
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 17, No. 11 ( 2011-06-01), p. 3751-3759
    Abstract: Purpose: To evaluate the dependency of the sensitivity of [11C]choline positron emission tomography/computed tomography (PET/CT) for detecting and localizing primary prostate cancer (PCa) on tumor configuration in the histologic specimen. Experimental Design: Forty-three patients with biopsy-proven PCa were included. They underwent radical prostatectomy within 31 days after [11C]choline PET/CT. The transaxial image slices and the histologic specimens were analyzed by comparing the respective slices. Maximum standardized uptake values (SUVmax) were calculated in each segment and correlated with histopathology. The tumor configuration in the histologic specimen was grouped as: I, unifocal; II, multifocal; III, rind-like shaped; IV, size & lt;5 mm. Data analysis included the investigation of detection of PCa by SUVmax, the assessment of the influence of potential contributing factors on tumor prediction, and the evaluation of whether SUV could discriminate cancer tissue from benign prostate hyperplasia (BPH), prostatitis, HGPIN (high-grade prostate intraepithelial neoplasm), or normal prostate tissue. General estimation equation models were used for statistical analysis. Results: Tumor configuration in histology was classified as I in 21 patients, as II in 9, as III in 5, and as IV in 8. The prostate segment involved by cancer is identified in 79% of the patients. SUVmax was located in the same side of the prostate in 95% of patients. Tumor configuration was the only factor significantly negatively influencing tumor prediction (P & lt; 0.001). PCa-SUVmax (median SUVmax = 4.9) was not significantly different from BPH-SUV (median SUVmax = 4.5) and prostatitis-SUV (median SUVmax = 3.9), P = 0.102 and P = 0.054, respectively. Conclusions: The detection and localization of PCa in the prostate with [11C]choline PET/CT is impaired by tumor configuration. Additionally, in our patient population, PCa tissue could not be distinguished from benign pathologies in the prostate. Clin Cancer Res; 17(11); 3751–9. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 5 ( 2019-03-01), p. 1505-1516
    Abstract: Human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined. Experimental Design: We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA–mRNA target network was generated and analyzed. Results: For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98−9.88, P & lt; 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40−12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50−6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65−6.04, P & lt; 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88−13.92, P & lt; 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P & lt; 0.001). Conclusions: The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC. See related commentary by Clump et al., p. 1441
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 29, No. 16 ( 2023-08-15), p. 3051-3064
    Abstract: Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in head and neck squamous cell carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. Experimental Design: A DNA-methylome–based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA (The Cancer Genome Atlas)-HNSCC cohort based on matched assignments using gene expression–based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of human papillomavirus (HPV)–negative patients with HNSCC treated with primary radiochemotherapy (RCHT). Results: Although hypoxia-GES failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (HR, 4.3; P = 0.001) and overall survival (HR, 2.34; P = 0.03) but not distant metastasis after RCHT in both cohorts. Hypoxia-M status was inversely associated with CD8 T-cell infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR, 1.83; P = 0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status. Conclusions: Our findings highlight an unexplored avenue for DNA methylation–based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors. See related commentary by Heft Neal and Brenner, p. 2954
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
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  • 4
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 22, No. 11 ( 2016-06-01), p. 2639-2649
    Abstract: Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control. Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P = 0.010) or the 26-gene signature (P = 0.002). In multivariate analyses, in patients with HPV16 DNA–negative but not with HPV16 DNA–positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P = 0.006; 26-gene signature: HR 10.27, P = 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P = 0.016; SLC3A2: HR 8.54, P = 0.037; CD44: HR 3.36, P = 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA–negative subgroup. Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA–negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies. Clin Cancer Res; 22(11); 2639–49. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
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  • 5
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 24, No. 6 ( 2018-03-15), p. 1364-1374
    Abstract: Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms. Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3, and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2, and ACTN1. The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation (P & lt; 0.001). Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364–74. ©2018 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
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