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Berlin Brandenburg

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  • 1
    Format: 12
    ISSN: 2072-6694
    Content: (1) Background: The authors present the first results of active raster-scanned carbon ion radiotherapy (CIRT) for radioresistant laryngeal malignancies regarding efficacy and toxicity. (2) Methods: 15 patients with laryngeal adenoid cystic carcinoma (ACC; n = 8; 53.3%) or chondrosarcoma (CS; n = 7; 46.7%) who underwent radiotherapy with carbon ions (C12) at the Heidelberg Ion Beam Therapy Center (HIT) between 2013 and 2018 were identified retrospectively and analyzed for local control (LC), overall survival (OS), and distant progression-free survival using the Kaplan–Meier method. CIRT was applied either alone (n = 7, 46.7%) or in combination with intensity modulated radiotherapy (IMRT) (n = 8, 53.3%). The toxicity was assessed according to the Common Toxicity Terminology Criteria for Adverse Events (CTCAE) v4.03. (3). Results: the median follow-up was 24 months (range 5–61 months). Overall, the therapy was tolerated very well. No grade 〉3 acute and chronic toxicity could be identified. The most reported acute grade 3 side effects were acute dysphagia (n = 2; 13%) and acute odynophagia (n = 3; 20%), making supportive nutrition via gastric tube (n = 2; 13.3%) and via high caloric drinks (n = 1; 6.7%) necessary due to swallowing problems (n = 4; 27%). Overall, chronic grade 3 toxicity in the form of chronic hoarseness occurred in 7% of the patients (n = 1; 7%). At the last follow-up, all the patients were alive. No local or locoregional recurrence could be identified. Only one patient with laryngeal ACC developed lung metastases three years after the first diagnosis. (4) Conclusions: the accelerated hypofractionated active raster-scanned carbon ion radiotherapy for radioresistant laryngeal malignancies is feasible in practice with excellent local control rates and moderate acute and late toxicity. Further follow-ups are necessary to evaluate the long-term clinical outcome.
    Note: Gesehen am 22.11.2018
    In: Cancers, Basel : MDPI, 2009, 10(2018,10) Artikel-Nummer 388, 12 Seiten, 2072-6694
    Language: English
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  • 2
  • 3
    Format: 21
    ISSN: 2072-6694
    Content: The use of different scoring systems for radiation-induced toxicity limits comparability between studies. We examined dose-dependent tissue alterations following hypofractionated X-ray irradiation and evaluated their use as scoring criteria. Four dose fractions (0, 5, 10, 20, 30 Gy/fraction) were applied daily to ear pinnae. Acute effects (ear thickness, erythema, desquamation) were monitored for 92 days after fraction 1. Late effects (chronic inflammation, fibrosis) and the presence of transforming growth factor beta 1 (TGFβ1)-expressing cells were quantified on day 92. The maximum ear thickness displayed a significant positive correlation with fractional dose. Increased ear thickness and erythema occurred simultaneously, followed by desquamation from day 10 onwards. A significant dose-dependency was observed for the severity of erythema, but not for desquamation. After 4 × 20 and 4 × 30 Gy, inflammation was significantly increased on day 92, whereas fibrosis and the abundance of TGFβ1-expressing cells were only marginally increased after 4 × 30 Gy. Ear thickness significantly correlated with the severity of inflammation and fibrosis on day 92, but not with the number of TGFβ1-expressing cells. Fibrosis correlated significantly with inflammation and fractional dose. In conclusion, the parameter of ear thickness can be used as an objective, numerical and dose-dependent quantification criterion to characterize the severity of acute toxicity and allow for the prediction of late effects.
    Note: Gesehen am 21.08.2019
    In: Cancers, Basel : MDPI, 2009, 11(2019,5) Artikel-Nummer 727, 21 Seiten, 2072-6694
    Language: English
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  • 4
    Format: 11
    ISSN: 2072-6694
    Content: (1) Background: Esthesioneuroblastoma (ENB) is a rare tumor entity originating from the olfactory neuroepithelium. There is a scarcity of data about different treatment strategies. Intensity modulated radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) are advanced radiation techniques that might improve local tumor control. (2) Methods: This retrospective analysis contained 17 patients with ENB (Kadish stage ≥ C: 88%; n = 15). Four patients had already undergone previous radiotherapy (RT). The treatment consisted of either IMRT (n = 5), CIRT (n = 4) or a combination of both techniques (n = 8). Median follow-up was 29 months. (3) Results: In patients that had not been irradiated before (n = 13), calculated overall survival (OS) and progression free survival (PFS) rates after 48 months were 100% and 81% respectively (Kaplan-Meier estimates). Two of four patients that underwent reirradiation died after RT, presumably due to tumor progression. Besides common toxicities, five patients (30%) showed mostly asymptomatic radiation-induced brain changes, most likely due to a disturbance of the blood-brain barrier. (4) Conclusions: Our results demonstrate that IMRT, CIRT, a combined approach of IMRT and CIRT as well as reirradiation with CIRT seem to be feasible and effective treatment methods in ENB.
    Note: Gesehen am 18.12.2018
    In: Cancers, Basel : MDPI, 2009, 10(2018,11) Artikel-Nummer 457, 11 Seiten, 2072-6694
    Language: English
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  • 5
    Format: 16
    ISSN: 2072-6694
    Content: Sorafenib represents the standard of care for advanced hepatocellular carcinoma (HCC), even though a large number of patients have reported limited efficacy. The aim of the present study was to evaluate the prognostic value of single-nucleotide polymorphisms on angiopoietin-2 (ANGPT2) and endothelial-derived nitric oxide synthase (NOS3) genes in 135 patients with advanced HCC receiving sorafenib. Eight ANGPT2 polymorphisms were analyzed by direct sequencing in relation to overall survival (OS) and progression-free survival (PFS). In univariate analysis, ANGPT2rs55633437 and NOS3 rs2070744 were associated with OS and PFS. In particular, patients with ANGPT2rs55633437 TT/GT genotypes had significantly lower median OS (4.66 vs. 15.5 months, hazard ratio (HR) 4.86, 95% CI 2.73–8.67, p 〈 0.001) and PFS (1.58 vs. 6.27 months, HR 4.79, 95% CI 2.73–8.35, p 〈 0.001) than those homozygous for the G allele. Moreover, patients with NOS3 rs2070744 TC/CC genotypes had significantly higher median OS (15.6 vs. 9.1 months, HR 0.65, 95% CI 0.44–0.97; p = 0.036) and PFS (7.03 vs. 3.5 months, HR 0.43, 95% CI 0.30–0.63; p 〈 0.001) than patients homozygous for the T allele. Multivariate analysis confirmed these polymorphisms as independent prognostic factors. Our results suggest that ANGPT2rs55633437 and NOS3 rs2070744 polymorphisms could identify a subset of HCC patients more resistant to sorafenib.
    Note: Gesehen am 04.11.2019
    In: Cancers, Basel : MDPI, 2009, 11(2019,7) Artikel-Nummer 1023, 16 Seiten, 2072-6694
    Language: English
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  • 6
    Format: 16
    ISSN: 2072-6694
    Content: Anilin actin binding protein (ANLN) and transducing-like enhancer protein 2 (TLE2) are associated with cancer patient survival and progression. The impact of their gene expression on progression-free survival (PFS) of patients with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) and subtype association has not yet been investigated. qRT-PCR was used to measure the transcript levels of ANLN and TLE2 in the Mannheim cohort, and validated in silico by The Cancer Genome Atlas (TCGA) cohort. Uni- and multivariate Cox regression analyses identified predictors for disease-specific survival (DSS) and overall survival (OS). In the Mannheim cohort, tumors with high ANLN expression were associated with lower OS and DSS, while high TLE2 expression was associated with a favorable OS. The TCGA cohort confirmed that high ANLN and low TLE2 expression was associated with shorter OS and disease-free survival (DFS). In both cohorts, multivariate analyses showed ANLN and TLE2 expression as independent outcome predictors. Furthermore, ANLN was more highly expressed in cell lines and patients with the basal subtype, while TLE2 expression was higher in cell lines and patients with the luminal subtype. ANLN and TLE2 are promising biomarkers for individualized bladder cancer therapy including cancer subclassification and informed MIBC prognosis.
    Note: Gesehen am 05.05.2020
    In: Cancers, Basel : MDPI, 2009, 11(2019,12) Artikel-Nummer 1840, 16 Seiten, 2072-6694
    Language: English
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  • 7
    Format: 16
    ISSN: 2072-6694
    Content: Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and base excision repair, respectively. Here, we investigated the cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34− AML cell samples (n = 18) in comparison to healthy CD34+ donor cell samples (n = 8). Strikingly, talazoparib and APE1 inhibitor III demonstrated critical antileukemic efficacy in selected MDS/CMML and AML cell samples. Low doses of talazoparib and APE1 inhibitor III further increased the cytotoxic efficacy of decitabine in MDS/CMML and AML cells. Moreover, low doses of APE1 inhibitor III increased the cytotoxic efficacy of talazoparib in MDS/CMML and AML cells. In summary, talazoparib and APE1 inhibitor III demonstrated substantial antileukemic efficacy as single agents, in combination with decitabine, and combined with each other. Hence, our findings support further investigation of these agents in sophisticated clinical trials.
    Note: Gesehen am 06.12.2019
    In: Cancers, Basel : MDPI, 2009, 11(2019,10) Artikel-Nummer 1493, 16 Seiten, 2072-6694
    Language: English
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  • 8
    Format: 14
    ISSN: 2072-6694
    Content: Background: In this analysis, we aimed to present the first results of carbon ion radiotherapy (CIRT), which is known for its conformal dose distribution and increased biological effectiveness in the treatment of high-risk nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed twenty-six consecutive patients who had been treated at our center with CIRT for high-risk NPC between 2009 and 2018. Carbon ion (C12) boost was applied in a bimodal setting combined with intensity-modulated radiotherapy (IMRT) base plan. The median cumulative total dose was 74 Gy (RBE), and patients with inoperable (n = 17, 65%) or incompletely resected (n = 7, 27%) tumors were included in the analysis. Overall, 81% received concomitant chemotherapy (n = 21). Results: The median follow-up time was 40 months (range 10–97 months) for all patients. At the last follow-up, 92% of the patients were still alive. We could identify excellent tumor response with complete tumor remission (CR) in 60% (n = 15/25), partial tumor remission (PR) in 20% (n = 5/25), and stable disease (SD) in 12% (n = 3/25) of the patients according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Despite unfavorable tumor characteristics, only one patient showed a locally in-field recurrence after 56 months (4%) and another patient a locoregional recurrence in the unilateral cervical lymph nodes after 21 months (4%). The 2-year local control (LC), distant progression-free survival (DPFS), and overall survival (OS) were 95%, 93%, and 100% and the estimated 5-year LC, DPFS, and OS were 90%, 86%, and 86%, respectively. Overall, treatment was tolerated well with 20% acute and 16% chronic grade 3 side effects. No toxicity greater than grade 3 occurred. Conclusion: Bimodal radiotherapy including IMRT and active raster-scanning CIRT for high-risk nasopharyngeal cancer is a safe treatment method resulting in moderate toxicity and excellent local control. A larger patient number and longer follow-up time would be necessary to strengthen the current findings.
    Note: Gesehen am 10.04.2019
    In: Cancers, Basel : MDPI, 2009, 11(2019,3) Artikel-Nummer 379, 14 Seiten, 2072-6694
    Language: English
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  • 9
    Format: 14
    ISSN: 2072-6694
    Content: Background: Patients with pancreatic cancer often develop cancer cachexia, a complex multifactorial syndrome with weight loss, muscle wasting and adipose tissue depletion with systemic inflammation causing physical impairment. In patients with locally advanced pancreatic cancer (LAPC) neoadjuvant treatment is routinely performed to allow a subsequent resection. Herein, we assess body composition and laboratory markers for cancer cachexia both before and after neoadjuvant chemoradiation (CRT). Methods: Subcutaneous fat (SCF), visceral fat (VF), skeletal muscle (SM), weight and laboratory parameters were determined longitudinally in 141 LAPC patients treated with neoadjuvant CRT. Changes during CRT were statistically analyzed and correlated with outcome and Kaplan–Meier curves were plotted. Different prognostic factors linked to cachexia were assessed by uni- and multivariable cox proportional hazards models. Results: There was a significant decrease in weight as well as SCF, VF and SM during CRT. The laboratory parameter C-reactive protein (CRP) increased significantly, whereas there was a significant decrease in leukocyte count, hemoglobin, albumin and cholinesterase as well as in the tumor marker CA 19.9. Cachectic weight loss, sarcopenia, reductions in body compartments SCF, VF and SM, and changes in laboratory markers as well as resection affected survival in univariable analysis. In multivariable analysis, weight loss 〉5% (HR 2.8), reduction in SM 〉5% (HR 5.5), an increase in CRP (HR 2.2) or CA 19.9 (HR 1.9), and resection (HR 0.4) remained independently associated with survival, whereas classical cachexia and sarcopenia did not. Interestingly, the subgroup of patients with cachectic weight loss 〉5% or SM reduction 〉5% during CRT did not benefit from resection (median survival 12 vs. 27 months). Conclusions: Persistent weight loss and muscle depletion during CRT as well as systemic inflammation after CRT impacted survival more than cachexia or sarcopenia according classical definitions.
    Note: Gesehen am 23.12.2019
    In: Cancers, Basel : MDPI, 2009, 11(2019,11) Artikel-Nummer 1655, 17 Seiten, 2072-6694
    Language: English
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  • 10
    Format: 24
    ISSN: 2072-6694
    Content: Head and neck squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed cancer worldwide. Despite advances in the treatment management, locally advanced disease has a poor prognosis, with a 5-year survival rate of approximately 50%. The growth of HNSCC is maintained by a population of cancer stem cells (CSCs) which possess unlimited self-renewal potential and induce tumor regrowth if not completely eliminated by therapy. The population of CSCs is not only a promising target for tumor treatment, but also an important biomarker to identify the patients at risk for therapeutic failure and disease progression. This review aims to provide an overview of the recent pre-clinical and clinical studies on the biology and potential therapeutic implications of HNSCC stem cells.
    Note: Gesehen am 20.08.2019
    In: Cancers, Basel : MDPI, 2009, 11(2019,5) Artikel-Nummer 616, 24 Seiten, 2072-6694
    Language: English
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