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  • 1
    Language: English
    In: BMC cancer, 2017-05-22, Vol.17 (1), p.361-361
    Description: The impact of local tumor ablative therapy in oligometastasized prostate cancer (PC) is still under debate. To gain data for this approach, we evaluated oligometastasized PC patients receiving stereotactic body radiotherapy (SBRT) to bone metastases. In this retrospective study, 15 oligometastasized PC patients with a total of 20 bone metastases were evaluated regarding biochemical progression-free survival (PSA-PFS), time to initiation of ADT, and local control rate (LCR). Three patients received concomitant androgen deprivation therapy (ADT). The median follow-up after RT was 22.5 months (range 7.0-53.7 months). The median PSA-PFS was 6.9 months (range 1.1-28.4 months). All patients showing a decrease of PSA level after RT of at least factor 10 reveal a PSA-PFS of 〉12 months. Median PSA-PFS of this sub-group was 23.1 months (range 12.1-28.4 months). Local PFS (LPFS) after 2 years was 100%. One patient developed a local failure after 28.4 months. Median distant PFS (DPFS) was 7.36 months (range 1.74-54.34 months). The time to initiation of ADT in patients treated without ADT was 9.3 months (range 2.6-36.1 months). In all patients, the time to intensification of systemic therapy or the time to initiation of ADT increased from 9.3 to 12.3 months (range 2.6-36.1 months). Gleason-Score, ADT or the localization of metastasis had no impact on PFS or time to intensification of systemic therapy. No SBRT related acute or late toxicities were observed. Our study shows that SBRT of bone metastases is a highly effective therapy with an excellent risk-benefit profile. However, PFS was limited due to a high distant failure rate implying the difficulty for patient selection for this oligometastatic concept. SBRT offers high local cancer control rates in bone oligometastases of PC and should be evaluated with the aim of curation or to delay modification of systemic treatment.
    Subject(s): Bone Neoplasms - mortality ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - radiotherapy ; Neoplasm Recurrence, Local - prevention & control ; Humans ; Middle Aged ; Kaplan-Meier Estimate ; Radiosurgery ; Bone Neoplasms - secondary ; Male ; Treatment Outcome ; Combined Modality Therapy ; Prostatic Neoplasms - mortality ; Disease-Free Survival ; Bone Neoplasms - radiotherapy ; Aged ; Retrospective Studies ; Complications and side effects ; Care and treatment ; Patient outcomes ; Development and progression ; Bone tumors ; Metastasis ; Radiotherapy ; Prostate cancer ; Methods ; Index Medicus ; PSMA-PET ; Oligometastases ; Individualized radiotherapy ; SBRT ; PSA
    ISSN: 1471-2407
    E-ISSN: 1471-2407
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Cancers, 2020-04-28, Vol.12 (5), p.1099
    Description: Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O -methylguanine-DNA methyltransferase (MGMT) is nowadays routinely analyzed since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed.
    Subject(s): temozolomide ; translational medicine ; glioblastoma ; MGMT ; survival ; radiotherapy ; miRNA ; Review ; chemotherapy
    ISSN: 2072-6694
    E-ISSN: 2072-6694
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: Annals of surgical oncology, 2018-02, Vol.25 (2), p.558-564
    Description: Incomplete resection of glioblastoma is discussed controversially in the era of combined radiochemotherapy.The aim of this study was to analyze the benefit of subtotal tumor resection for glioblastoma patients as this was recently questioned in the era of radiochemotherapy.Overall, 209 patients undergoing surgery for newly diagnosed WHO grade IV gliomas were retrospectively analyzed, and pre- and postoperative tumor volumes were manually segmented (cm3). Survival analyses were performed, including prognostic factors such as age, Karnofsky performance score (KPS), O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, and adjuvant treatment regimen.Pre- and postoperative tumor volume is significantly associated with pre- and postoperative KPS, as well as age (p 〈 0.001). Postoperative tumor volume remained a significant prognostic factor in a multivariate analysis, independent of other prognostic factors (hazard ratio 1.0365, 95% confidence interval 1.0235–1.0497, p 〈 0.001).In the era of molecularly-driven radiochemotherapy, glioblastoma surgery remains a major prognostic factor. Even in situations in which a gross total resection cannot be achieved, maximum safe reduction of tumor burden should be attempted.
    Subject(s): Oncology ; Medicine & Public Health ; Surgical Oncology ; Surgery ; Neoplasm, Residual - pathology ; Prognosis ; Follow-Up Studies ; Neoplasm, Residual - surgery ; Humans ; Middle Aged ; Brain Neoplasms - pathology ; Male ; Survival Rate ; Tumor Burden ; Brain Neoplasms - surgery ; Glioblastoma - surgery ; Young Adult ; Neurosurgical Procedures - mortality ; Glioblastoma - pathology ; Aged, 80 and over ; Adult ; Female ; Aged ; Neurosurgical Procedures - methods ; Retrospective Studies ; Care and treatment ; Analysis ; Transferases ; Adjuvant treatment ; Methylation ; Glioblastoma multiforme ; Cancer ; Index Medicus
    ISSN: 1068-9265
    E-ISSN: 1534-4681
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Radiation oncology (London, England), 2019-05-10, Vol.14 (1), p.78-9
    Description: Breast cancer is the most common invasive tumor in women worldwide and the second cause of cancer-related deaths. After breast conserving surgery the tumor bed gets irradiated. Radiation-induced tumor cell death has been found to be associated with the release of damage-associated molecular patterns (DAMPs) including free Hsp70 that can stimulate inflammatory immune responses. Therefore, Hsp70 serum levels as well as the composition of lymphocyte subpopulations have been measured in breast cancer patients during therapy and in the follow-up period as potential predictors for clinical outcome. The serum of 40 breast cancer patients, who received a breast-conserving surgery and adjuvant radiotherapy (RT) was examined for soluble, free Hsp70 using the R&D Human HSP70 DuoSet and lipHsp70 ELISA. Lymphocyte subpopulations and total lymphocyte counts were analysed by multiparameter flow cytometry in the peripheral blood. Blood samples were collected before (t1), after 30 Gy (t2) and 60 Gy (t3), 6 weeks (t4), 6 months (t5) and 1 year (t6) after RT. Clinical responses were assessed regularly up to 5 years after RT. Patients who developed a contralateral recurrence or metastases within the first 2 years after RT had significantly higher serum Hsp70 values at the end of RT (t3; p = 0.03) up to 6 weeks after RT (t4; p = 0.007) compared to patients who either remained disease-free or developed a secondary endometrial carcinoma. Clinicopathological parameters such as age, tumor size, grading and TNM-stage of the resected tumors, adjuvant chemotherapy and irradiation dose did not affect serum Hsp70 levels. Elevated free Hsp70 levels might be indicative for a chronic inflammatory response which could support tumor recurrence. Lymphocyte subpopulation analysis revealed lower NK cell counts after RT in recurrence/metastases patients as compared to disease-free patients. In contrast, no significant changes were observed in the proportion of T and B cells. Longitudinal elevated serum levels of free Hsp70 up to 6 weeks after RT and dropping NK cell counts might be predictive for an unfavourable prognosis in patients with breast cancer.
    Subject(s): Medical research ; Care and treatment ; Killer cells ; Cell death ; Patient outcomes ; Analysis ; Heat shock proteins ; Medicine, Experimental ; Breast cancer ; Research ; Breast carcinoma prediction ; Free Hsp70 ; Immunophenotyping ; Radiotherapy ; DAMPs
    ISSN: 1748-717X
    E-ISSN: 1748-717X
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
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  • 5
    Language: English
    In: Cancers, 2016-01-13, Vol.8 (1), p.15
    Description: Glioblastoma (GBM) is the most common and most aggressive malignant primary brain tumor in adults. In spite of multimodal therapy concepts, consisting of surgery, radiotherapy and chemotherapy, the median survival, merely 15-18 months, is still poor. Mechanisms for resistance of GBM to radio(chemo)therapy are not fully understood yet and due to the genetic heterogeneity within the tumor including radiation-resistant tumor stem cells, there are several factors leading to therapy failure. Recent research revealed that, hypoxia during radiation and miRNAs may adversely affect the therapeutic response to radiotherapy. Further molecular alterations and prognostic markers like the DNA-repair protein O6-methylguanine-DNA methyltransferase (MGMT), anti-apoptotic molecular chaperones, and/or the activity of aldehyde dehydrogenase 1 (ALDH1) have also been identified to play a role in the sensitivity to cytostatic agents. Latest approaches in the field of radiotherapy to use particle irradiation or dose escalation strategies including modern molecular imaging, however, need further evaluation with regard to long-term outcome. In this review we focus on current information about the mechanisms and markers that mediate resistance to radio(chemo)therapy, and discuss the opportunities of Innovative Radiotherapy (iRT) concepts to improve treatment options for GBM patients.
    Subject(s): hypoxia ; glioblastoma ; radiation ; immune system ; particle therapy ; Review ; imaging
    ISSN: 2072-6694
    E-ISSN: 2072-6694
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: BMC cancer, 2020-01-03, Vol.20 (1), p.8-9
    Description: Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer. Study design: "RACE IT" (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb. Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11-15. Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15. Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up). Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy. Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy. Planned sample size: 33 patients, interim analysis after 11 patients. This trial aims to evaluate the safety and feasibility of the combined approach of preoperative PD-1 checkpoint-inhibitor therapy with concomitant radiation of bladder and pelvic region followed by radical cystectomy. The secondary objectives of therapy response and survival are thought to provide preliminary data for further clinical evaluation after successful completion of this trial. Recruitment has started in February 2019. Protocol Code RACE IT: AB 65/18; EudraCT: 2018-001823-38; Clinicaltrials.gov: NCT03529890; Date of registration: 27 June 2018.
    Subject(s): Checkpoint inhibitor ; Urothelial cancer ; Immunotherapy ; Nivolumab ; Study Protocol ; Transitional cell carcinoma ; PD-1 inhibitor ; Radiotherapy ; Bladder cancer ; Radical cystectomy ; Locally advanced
    E-ISSN: 1471-2407
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
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  • 7
    Language: English
    In: Radiation oncology (London, England), 2011-09-13, Vol.6 (1), p.115-115
    Description: A group of 160 patients with primary glioblastoma treated with radiotherapy and temozolomide was analyzed for the impact of O6-methly-guanly-methyl-transferase (MGMT)-promoter methylation as well as isocitrate dehydrogenase (IDH)1-mutational status. Unexpectedly, overall survival or progression-free survival were not longer in the group with methylated MGMT-promoter as compared to patients without that methylation. IDH-1 mutations were significantly associated with increased overall survival.
    Subject(s): Medical Oncology - methods ; Promoter Regions, Genetic ; Prognosis ; Glioblastoma - diagnosis ; Dacarbazine - therapeutic use ; Brain Neoplasms - diagnosis ; Humans ; Middle Aged ; Isocitrate Dehydrogenase - genetics ; Treatment Outcome ; Glioblastoma - radiotherapy ; O-Methylguanine-DNA Methyltransferase - genetics ; DNA Methylation ; Dacarbazine - analogs & derivatives ; Adult ; Aged ; Mutation ; Brain Neoplasms - radiotherapy ; Physiological aspects ; Care and treatment ; Diagnosis ; Research ; Methyltransferases ; Glioblastoma multiforme ; Index Medicus ; temozolomide ; IDH ; radiation ; MGMT ; Glioblastoma
    ISSN: 1748-717X
    E-ISSN: 1748-717X
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Radiation oncology (London, England), 2012-12-29, Vol.7 (1), p.226-226
    Description: For skull base meningiomas, several treatment paradigms are available: Observation with serial imaging, surgical resection, stereotactic radiosurgery, radiation therapy or some combination of both. The choice depends on several factors. In this review we evaluate different treatment options, the outcome of modern irradiation techniques as well as the clinical results available, and establish recommendations for the treatment of patients with skull-base meningiomas.
    Subject(s): Skull Base Neoplasms - radiotherapy ; Radiotherapy Planning, Computer-Assisted - methods ; Humans ; Meningioma - surgery ; Radiotherapy, Intensity-Modulated - methods ; Dose Fractionation ; Robotics - methods ; Treatment Outcome ; Meningioma - radiotherapy ; Skull Base Neoplasms - surgery ; Radiosurgery - methods ; Mortality ; Methods ; Radiosurgery ; Radiation ; Index Medicus
    ISSN: 1748-717X
    E-ISSN: 1748-717X
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Radiation oncology (London, England), 2017-06-08, Vol.12 (1), p.94-94
    Description: Managing inter-fractional anatomy changes is a challenging task in radiotherapy of pancreatic tumors, especially in scanned carbon-ion delivery. This treatment planning study aims to focus on clinically feasible solutions, such as the beam angle selection and margin design to increase the robustness against inter-fractional uncertainties. This study included 10 patients with weekly 3D-CT imaging and physician-approved Clinical Target Volume (CTV). The study was directed to keep the CTV-coverage using six beam angle configurations in combination with different Internal Target Volume (ITV) concepts. These were: geometric-margin (symmetric 3 and 5 mm margin); range-equivalent margins with an isotropic HU replacement; and to evaluate the need of asymmetric margins the water-equivalent range path (WEPL) was determined per patient from the set of CTs. Plan optimization and forward dose calculation in each week-CT were performed with the research treatment planning system TRiP98 and the plan quality evaluated in terms of CTV coverage (V95 ) and homogeneity dose (H  = D5-D95). The beam geometry had a substantial impact on the target irradiation over the treatment course, with the single posterior or two beams showing the best average coverage of the CTV. The use of geometric margins for the more robust beam geometries showed acceptable results, with a V95 of (99.2 ± 1.2)% for the 5 mm-margin. For the non-robust configurations, due to substantial changes in the radiological depth, the use of this margin results in a V95 that might be below 80%, only showing improvement when the range changes are included. Selection of adequate beam configurations and treatment margins in ion-beam therapy of pancreatic tumors is of great importance. For a single posterior beam or two beam configurations, application of geometrical margins compensate for dose degradation induced by inter-fractional anatomy changes for the majority of the analyzed treatment fractions.
    Subject(s): Radiotherapy Dosage ; Organs at Risk - radiation effects ; Prognosis ; Follow-Up Studies ; Heavy Ion Radiotherapy ; Radiotherapy Planning, Computer-Assisted - methods ; Humans ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - radiotherapy ; Retrospective Studies ; CT imaging ; Care and treatment ; Usage ; Pancreatic cancer ; Patient outcomes ; Research ; Radiotherapy ; Index Medicus
    ISSN: 1748-717X
    E-ISSN: 1748-717X
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Radiation oncology (London, England), 2018-09-06, Vol.13 (1), p.169-169
    Description: The cranial border of the target volume (TV) in rectal cancer patients treated with neoadjuvant chemoradiation (nCRT) is mostly defined at the level of L5/S1. However, current studies have shown that relapse cranially of the target volume after neoadjuvant nCRT and surgery is very rare. A reduction of cranial TV margins could be reasonable to reduce toxicity to the organs at risk (OAR). In this study we compared the dose distribution to the OAR for different cranial longitudinal margins using a dose-volume histogram (DVH) analysis. Ten patients with loco regional advanced rectal cancer were analysed retrospectively. All patients were planned for Volumetric Arc Therapy Radiation Therapy (VMAT). Next to the original PTV (PTV0), three new planning target volumes (PTV) were defined for each patient: The PTV0 reduced by 1 cm, 2 cm and 3 cm on cranial extension. For each PTV a treatment plan with a total dose of 50.4 Gy with daily doses of 1.8 Gy was calculated. Dose to the OAR were evaluated and compared. For the bone marrow, the small bowel and the peritoneal space all clinically relevant relative dose parameters (V10-V50) as well as the Dmedian could be significantly reduced with every cranial target volume reduction of 1 cm. For V10 of the peritoneal space the dose could be nearly halved with a 3 cm shortened TV. After TV reduction of 3 cm also for the urinary bladder a significant dose reduction of the Dmedian could be achieved. Considering the very low recurrence rates in the TME and IMRT era, the distribution patterns of these relapses as well as the relevant side effects of nCRT, we would agree with existing recommendations of reduction of the cranial target volume in nCRT treated rectal cancer patients.
    Subject(s): Radiotherapy Dosage ; Organs at Risk - radiation effects ; Humans ; Radiotherapy, Intensity-Modulated - methods ; Neoplasm Recurrence, Local ; Female ; Male ; Rectal Neoplasms - pathology ; Retrospective Studies ; Chemoradiotherapy, Adjuvant ; Radiotherapy Planning, Computer-Assisted ; Rectal Neoplasms - radiotherapy ; Usage ; Care and treatment ; Colorectal cancer ; Research ; Diagnosis ; Radiotherapy ; Methods ; Index Medicus ; Dosimetric quantification ; Rectal cancer ; IMRT ; Reduced cranial margins
    ISSN: 1748-717X
    E-ISSN: 1748-717X
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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