Strahlentherapeutische Behandlung von Knochenmetastasen bei Tumorschmerzen

Die perkutane Strahlentherapie ist eine wirksame Masnahme zur Reduktion der lokalen inflammatorischen Reaktion sowie zur Inaktivierung proliferativer Eigenschaften des Tumors. Daher verfugt sie uber eine messbare Effektivitat bei Schmerzen, die durch Knochenmetastasen hervorgerufen werden. Knochenmetastasen entstehen durch hamatogene Tumorzelldissemination in das Knochenmark und sind eigentlich Metastasen des Knochenmarks. Die dort wachsenden Tumorzellen konnen die Skelett- und Kalziumhomoostase storen und sekundare Knochenveranderungen hervorrufen, die als Tumorosteopathien bezeichnet werden.

Quantification of Radiation Biomarkers in Leukocytes of Breast Cancer Patients Treated with Different Modalities of 3D-CRT or IMRT

The goal of this study was to determine whether the quantification of radiation biomarkers in peripheral leukocytes of 111 breast cancer patients after adjuvant treatment with different modalities of three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) revealed any difference in the patients' radiation burden by out-of-field doses and an associated risk of second malignancies. Whole-breast radiation therapy was performed by 3D-CRT using either a hard wedge (n = 32) or a virtual wedge (n = 49) at dose rates of 3 and 6 Gy per min each. Patients receiving additional radiotherapy to lymph nodes were treated by 3D-CRT (n = 21) or IMRT (n = 9). DN…

Dosimetric feasibility study for an extracorporeal BNCT application on liver metastases at the TRIGA Mainz

This study investigates the dosimetric feasibility of Boron Neutron Capture Therapy (BNCT) of explanted livers in the thermal column of the research reactor in Mainz. The Monte Carlo code MCNP5 is used to calculate the biologically weighted dose for different ratios of the (10)B-concentration in tumour to normal liver tissue. The simulation results show that dosimetric goals are only partially met. To guarantee effective BNCT treatment the organ has to be better shielded from all gamma radiation.

Fractionated External Beam Radiotherapy as a Suitable Preparative Regimen for Hepatocyte Transplantation After Partial Hepatectomy

Purpose Hepatocyte transplantation is strongly considered to be a promising option to correct chronic liver failure through repopulation of the diseased organ. We already reported on extensive liver repopulation by hepatocytes transplanted into rats preconditioned with 25-Gy single dose selective external beam irradiation (IR). Herein, we tested lower radiation doses and fractionated protocols, which would be applicable in clinical use. Methods and Material Livers of dipeptidylpeptidase IV (DPPIV)-deficient rats were preconditioned with partial liver external beam single dose IR at 25 Gy, 8 Gy, or 5 Gy, or fractionated IR at 5 × 5 Gy or 5 × 2 Gy. Four days after completion of IR, a partial …

Additional file 9 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 9: Web Table 1B. Differentially expressed genes 4 h after exposure to low dose ionizing radiation (0.05 Gray).

345 Comparison of cisplatin and mitomycin/5-FU as radiosensitizers in the treatment of vulvar cancer – results of a single institutional cohort study

Introduction/Background* Treatment of vulvar cancer contains surgery if applicable and often primary or neo-/adjuvant chemoradiation. Cisplatin and Mitomycin/5-FU are widely used radiosensitizers in vulvar cancer, although evidence is limited. We retrospectively investigated both radiosensitizers for outcome and toxicity. Methodology We screened the archive for patients treated with chemoradiation for pathologically-confirmed squamous cell cancer of the vulva between 01/2010 – 02/2021 at our institution. The impact of both radiosensitizers on prognosis was compared using Kaplan-Meier method and Cox-Regression analysis. Result(s)* 127 patients with vulvar cancer were screened. 24 patients re…

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients—Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group

The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique.A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and …

Additional file 10 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 10: Web Table 1C. Differentially expressed genes 2 h after exposure to high dose ionizing radiation (2 Gray).

Role of Hypoxia and the Adenosine System in Immune Evasion and Prognosis of Patients with Brain Metastases of Melanoma: A Multiplex Whole Slide Immunofluorescence Study

Simple Summary The introduction of immune-checkpoint inhibitors improved the therapeutic landscape for patients with advanced malignant melanoma. However, many patients, including patients with melanoma brain metastases, do not derive benefit from immune-checkpoint blockade. Hence, biomarkers are needed to identify potential mechanisms of resistance and optimize patient selection. This study aimed to explore the role of hypoxia-mediated immunosuppression within the tumor microenvironment of patients with metastatic melanoma using multiplex immunofluorescence. We analyzed the prognostic relevance of the hypoxia surrogate marker GLUT-1, the adenosine-synthesizing ectoenzymes CD73/CD39, and th…

Additional file 8 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 8: Web Table 1A. Differentially expressed genes 2 h after exposure to low dose ionizing radiation (0.05 Gray).

Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms

Frontiers in oncology 10, 1338 (2020). doi:10.3389/fonc.2020.01338

The significance of a uniform definition of pathological lymph nodes in Hodgkin lymphoma: impact of different thresholds for positive lymph nodes in CT imaging on staging and therapy.

Abstract Background and Purpose The most commonly used approach for the assessment for differentiating malignant versus reactive lymph nodes is the measurement of the cross-section diameter of the lymph nodes in the transversal CT-planes. The intention of this article is to assess the impact of varying definitions of pathological lymph node size in CT-imaging in patients with Hodgkin lymphoma and to evaluate its effect on staging, chemotherapy regimes and radiation field size. Materials and methods Pretherapeutic CT-scans of 10 consecutive patients with Hodgkin lymphoma have been evaluated based on two different definitions for malignant lymph node size; the classification of the German stu…

Comparative Analyses of Two Established Scores to Assess the Stability of Spinal Bone Metastases Before and After Palliative Radiotherapy

Background and PurposeTo compare two validated spinal instability scores regarding the stabilizing effects and skeletal-related events (SREs) of palliative radiotherapy (RT) in patients with spinal bone metastases (SBM).Materials and MethodsTwo hundred eighty-two osteolytic SBM of lung or breast cancer patients were analyzed for stability before and following RT based on the Spinal Instability Neoplastic Score (SINS) or the Taneichi score. Score concordance was quantified by absolute agreement and Cohen’s kappa coefficient. SREs were defined as fractures or local progression after RT. OS was quantified as the time between the start of RT and death from any cause.ResultsAt 3 and 6 months aft…

Boron determination in liver tissue by combining quantitative neutron capture radiography (QNCR) and histological analysis for BNCT treatment planning at the TRIGA Mainz.

The typical primary malignancies of the liver are hepatocellular carcinoma and cholangiocarcinoma, whereas colorectal liver metastases are the most frequently occurring secondary tumors. In many cases, only palliative treatment is possible. Boron neutron capture therapy (BNCT) represents a technique that potentially destroys tumor tissue selectively by use of externally induced, locally confined secondary particle irradiation. In 2001 and 2003, BNCT was applied to two patients with colorectal liver metastases in Pavia, Italy. To scrutinize the rationale of BNCT, a clinical pilot study on patients with colorectal liver metastases was carried out at the University of Mainz. The distribution o…

External-beam radiotherapy as preparative regimen for hepatocyte transplantation after partial hepatectomy

Purpose: The transplantation of donor hepatocytes is considered a promising option to correct chronic liver failure through repopulation of the diseased organ. This study describes a novel selective external-beam irradiation technique as a preparative regimen for hepatocyte transplantation. Methods and Materials: Livers of dipeptidylpeptidase IV (DPPIV)–deficient rats were preconditioned with external-beam single-dose irradiation (25 Gy) delivered to two thirds of the liver. Four days later, a one-third partial hepatectomy (PH) was performed to resect the untreated liver section, and 15 million wild-type (DPPIV + ) hepatocytes were transplanted via the spleen into the recipient livers. The …

Quality of Life in NSCLC Survivors - A Multicenter Cross-Sectional Study.

The objective was to assess quality of life (QoL) in lung cancer survivors, compare it to the general population, and identify factors associated with global QoL, physical functioning, emotional functioning, fatigue, pain, and dyspnea.Data from NSCLC patients who had survived 1 year or longer after diagnosis were collected cross-sectionally in a multicenter study. QoL was assessed with the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the lung cancer module QLQ-LC13 across different clinical subgroups and compared to age- and sex-standardized general population reference values. Multivariable linear regression analyses wer…

Reimbursement of radiotherapy in Germany.

Reimbursement of radiotherapy in Germany is mainly based on a certain fixed fee for treatment planning and patient set up in addition to payment per fraction. This applies to outpatient care for patients with public health insurance or private health insurance. Payment per fraction has a considerable influence on reimbursement of inpatients as well. The advantage of payment per fraction is the simplicity and transparency. The disadvantage is an inadequate reimbursement for new treatment modalities like hypofractionation or stereotactic body radiotherapy.

Assessment of tumor microcirculation with dynamic contrast-enhanced MRI in patients with esophageal cancer: initial experience.

PURPOSE: To investigate the feasibility and impact of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on tumor characterization and response to radiochemotherapy (RCT) in patients with esophageal cancer. MATERIALS AND METHODS: A total of 48 patients underwent DCE-MRI to assess tumor microcirculation based on a two-compartment model function. Effects of RCT on kinetic parameters were studied in 12 patients with squamous cell carcinoma. RESULTS: Tumor microcirculation differs with respect to histological subtype: squamous cell carcinomas showed lower values of amplitude A (leakage space, P = 0.015) and higher contrast agent exchange rates (k(21), P = 0.225) compared with adenoc…

A Putatively Functional Haplotype in the Gene Encoding Transforming Growth Factor Beta-1 as a Potential Biomarker for Radiosensitivity

Purpose To determine whether genetic variability in TGFB1 is related to circulating transforming growth factor-β1 (TGF-β1) plasma concentrations after radiotherapy and to radiosensitivity of lymphoid cells. Patients and Methods Transforming growth factor-β1 plasma concentrations ( n = 79) were measured in patients 1 year after radiotherapy and chromosomal aberrations ( n = 71) ex vivo before therapy start. Furthermore, TGF-β1 secretion and apoptosis were measured in isolated peripheral blood mononuclear cells of 55 healthy volunteers. These phenotypes were analyzed in relation to five germline polymorphisms in the 5′ region of the TGFB1 gene. Because of high linkage disequilibrium, these fi…

Second Malignancies Following Childhood Cancer Treatment in Germany From 1980 to 2014.

BACKGROUND Because of improvements in cancer treatment, more than 80% of all children with cancer now survive at least five years from the time of diagnosis. As a result, late sequelae of cancer and its treatment have become more common, particularly second malignancies. We studied the current incidence of second malignancies among childhood cancer survivors in Germany. METHODS This study is based on the cohort of the German Childhood Cancer Registry (Deutsches Kinderkrebsregister, DKKR). Persons given the diagnosis of a first malignancy at any time in the years 1980-2014 who were no more than 14 years old at the time of diagnosis and survived at least six months thereafter were included in…

Additional file 2 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 2: Web Figure 7. Shared pathways from low and high dose ionizing radiation experiments. Gy = Gray. Web Figure 8. Pathways only affected in high dose ionizing radiation experiments. Gy = Gray.

Comparison of the combined action of oxaliplatin or cisplatin and radiation in cervical and lung cancer cells

To test the combined effects of oxaliplatin and radiation versus cisplatin and radiation using human cervical and lung cancer cell lines.CaSki cervical cancer cells, and A549 lung cancer cells were cultured under standard conditions. Cells were treated with escalating doses of gamma-irradiation (0-6 Gy), and with oxali- and cisplatin for 2 h or 24 h, or a combination of both. Cell survival was measured by a colony-forming assay. Survival curves were fitted to the data using the linear quadratic model. Sensitizer enhancement ratios (SER) were calculated at the 37% survival level, and isobologram analysis was applied to test for the drug-radiation interactions.Oxaliplatin as well as cisplatin…

Additional file 3 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 3: Web Figure 9. Predicted downsteam diseases and functions. Web Figure 10. Predicted upstream regulators. LDIR = Low dose of ionizing radiation (0.05 Gray), HDIR = High dose of ionizing radiation (2 Gray).

Chemoradioimmunotherapy with 5-fluorouracil, cisplatin and interferon-α in pancreatic and periampullary cancer: Results of a feasibility study

Abstract Background Recent studies give rise to the hypothesis, that adjuvant chemoradioimmunotherapy with 5-fluorouracil (5-FU), cisplatin and interferon-α (IFN-α) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution. Patients and methods Eleven patients with histological diagnosis of localized carcinoma of the pancreas ( n  = 7) or periampullary ( n  = 4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neoadjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three …

Additional file 1 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 1: Web Figure 1. Representative measurements of the cell cycle distribution of HOECHST33258-stained fibroblasts by flow cytometry during (A) log-phase growth or (B) after G0/1 synchronization over 14 days for radiation experiments. Web Figure 2. Total number of differentially expressed genes in human fibroblasts from cancer free-controls at 0.25 h, 2 h and 24 h after exposure to low (0.05 Gray (Gy)) or high dose (2Gy) of X-rays compared to unirradiated fibroblasts (N = 3). Web Figure 3. Correlation of RNA quality metrics (RIN, Qbit RNA-concentration), expression variation (PC1–3) and number of aligned reads (aligned reads, aligned reads normalized) for all experiments. The c…

Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Abstract Background Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. Methods Fibroblasts from skin biopsies of…

Multimodal treatment of gastric cancer

Although radical surgical R0 resections are the basis of cure for gastric cancer, surgery alone only provides long-term survival in 20-30% of patients with advanced-stage disease. Thus, in Western and European countries, advanced gastric cancer has a high risk of recurrence and metachronous metastases. Very recently, multimodal strategies combining different neoadjuvant and/or adjuvant protocols have improved the prognosis of gastric cancer when combined with surgery with curative intent. As used in palliative regimens, the combination of cisplatin with intravenous or oral fluoropyrimidines has been the integral component of such (neo)adjuvant strategies. However, the cytotoxic agents docet…

Radiation-induced vascular changes in the intracranial irradiation field in medulloblastoma survivors: An MRI study

While survival times after treatment of medulloblastoma are increasing, little is known about radiochemotherapy (RCT)-induced cerebrovascular changes. High resolution vessel wall imaging (VWI) sequences are an emerging tool for the evaluation of cerebrovascular diseases. We performed VWI in medulloblastoma long-term survivors to screen for late sequelae of RCT.Twenty-two pediatric medulloblastoma survivors (mean age 25.8 years (10-53 years); 16.3 years (mean) post primary RCT (range 1-45 years)) underwent 2D VWI-MRI. Vessel wall thickening, contrast enhancement and luminal narrowing were analyzed. The findings were correlated with the patients' radiation protocols.Vessel wall changes were o…

Susceptibility-weighted magnetic resonance imaging of cerebrovascular sequelae after radiotherapy for pediatric brain tumors

Due to sensitive neuroimaging techniques, cerebrovascular complications such as cerebral microbleeds (CMB) and cerebral cavernous malformations (CCM) are increasingly recognized as considerable late effects after treatment for pediatric brain tumor. The aim of this study was to analyze CMB in a cohort of patients after cranial irradiation therapy for medulloblastoma or other pediatric brain tumors using susceptibility-weighted magnetic resonance imaging (SWI).Forty former pediatric brain tumor patients were enrolled in this prospective cross-sectional study and examined by cranial MRI including SWI sequences. Cerebral microbleeds, clinical symptoms and disability were evaluated.Thirty-six (…

Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma – A Report From the HIT 2000 Trial

Purpose: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. Methods and Materials: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols…

European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I.

Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) wa…

Relapse Analysis of Irradiated Patients Within the HD15 Trial of the German Hodgkin Study Group

Purpose To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL), whether relapses occur in the irradiated planning target volume and whether the definition of local radiation therapy (RT) used by the German Hodgkin Study Group (GHSG) is adequate, because there is no harmonization of field and volume definitions among the large cooperative groups in the treatment of advanced-stage HL. Methods and Materials All patients with residual disease of ≥2.5 cm after multiagent chemotherapy (CTX) were evaluated using additional positron emission tomography (PET), and those with a PET-positive result were irradiated with 30 Gy to the site of residual disease. We re-evaluated all sites o…

Fludarabine combined with radiotherapy in patients with locally advanced NSCLC lung carcinoma: a phase I study

Abstract Background and purpose Fludarabine is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. We designed a phase I trial exploring concurrent fludarabine and radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation. Materials and methods Thirteen patients with stage IIIB NSCLC received thoracic irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of radiotherapy. Doses started at 10 mg/m2 per day and increased by s…

How COVID-19 kick-started online learning in medical education-The DigiMed study.

Background The coronavirus disease 2019 (COVID-19) pandemic led to far-reaching restrictions of social and professional life, affecting societies all over the world. To contain the virus, medical schools had to restructure their curriculum by switching to online learning. However, only few medical schools had implemented such novel learning concepts. We aimed to evaluate students’ attitudes to online learning to provide a broad scientific basis to guide future development of medical education. Methods Overall, 3286 medical students from 12 different countries participated in this cross-sectional, web-based study investigating various aspects of online learning in medical education. On a 7-…

The combined effect of fludarabine monophosphate and radiation as well as gemcitabine and radiation on squamous carcinoma tumor cell lines in vitro.

Despite proven antitumor activity of gemcitabine in chemoradiotherapy of advanced head and neck cancer, many authors refer to severe acute and late local and haematological toxicity. Fludarabine does imply nearly the same mechanisms of action as gemcitabine, inhibiting various enzymes involved in DNA replication. This investigation focuses on the combined effect of either fludarabine or gemcitabine and radiation on human squamous carcinoma cell lines in vitro, providing data for future decisions on head and neck chemoradiotherapy regimen.ZMK-1, A549, BW-225, GR-145, OH-65 and CaSki cell lines were incubated with either drug at defined schedules and irradiated at a single fraction dose of 2 …

Histomorphological tumor regression grading of esophageal carcinoma after neoadjuvant radiochemotherapy: which score to use?

Histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer after neoadjuvant radiochemotherapy (RCT). The system introduced by Mandard to group TRG (Cancer 1994;73:2680-2686) has been used to analyse and discuss its prognostic significance on survival in a single institution retrospective analysis: TRG 1 (complete regression) - TRG 5 (absence of regressive changes). Sixty patients with locally advanced (T3/4 or N1) adenocarcinoma or squamous cell carcinoma received cisplatin-based RCT. Three to four weeks later operation for curative intent was performed. Median follow-up was 17.7 months. Histopathological tumor stages were sta…

Additional file 5 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 5: Web Figure 12. Comparison of predicted downstream diseases and functions in different data sets.

Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy

The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated ca…

Additional file 6 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 6: Web Figure 13. Comparison of predicted upstream regulators in different data sets.

Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer.

Background/aim Prognoses of patients receiving radio-chemotherapy with 5-fluorouracil (5-FU) and cisplatin for unresectable esophageal cancer may be improved with the addition of cetuximab. This phase I study aimed to define the maximum tolerated dose of 5-FU when combined with cisplatin, cetuximab and radiotherapy. Patients and methods Treatment included 59.4 Gy of radiotherapy concurrently with two courses of cisplatin (20 mg/m2, d1-4) and 5-FU (dose level 0: 500 mg/m2, dose level 1: 750 mg/m2, d1-4; dose level 2: 1,000 mg/m2, d1-4), followed by two courses of chemotherapy. Cetuximab was given for 14 weeks (400 mg/m2 loading dose followed by 250 mg/m2 weekly). Results At dose level 1 (n=3…

Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment.

Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), …

GLUT-1 staining of squamous cell carcinomas of the uterine cervix identifies a novel element of invasion.

Perturbation of the normal tissue architecture in solid malignant tumors is perceived to be the consequence of actively migrating cancer cells which invade the adjacent normal host tissue. The opposite, invasion of cancer cell clusters by a vascularized stroma, has not been considered. The latter process should, however, be expected to occur since the hypoxic cores of tumor cell aggregates, under the control of HIF-1, are known to secrete cytokines (e.g., bFGF, VEGF) which attract fibroblasts and induce blood vessel formation. In this study, the expression of glucose transporter (GLUT)-1, a major HIF-1 target gene, was examined in 51 squamous cell carcinomas of the uterine cervix by immunoh…

Compromised repair of radiation-induced DNA double-strand breaks in Fanconi anemia fibroblasts in G2

Fanconi anemia (FA) is a rare chromosomal instability syndrome with various clinical features and high cancer incidence. Despite being a DNA repair disorder syndrome and a frequently observed clinical hypersensitivity of FA patients towards ionizing radiation, the experimental evidence regarding the efficiency of radiation-induced DNA double-strand break (DSB) repair in FA is very controversial. Here, we performed a thorough analysis of the repair of radiation-induced DSBs in G1 and G2 in FA fibroblasts of complementation groups A, C, D1 (BRCA2), D2, E, F, G and P (SLX4) in comparison to normal human lung and skin fibroblasts. γH2AX, 53BP1, or RPA foci quantification after X-irradiation was…

Using the r package spatstat to assess inhibitory effects of microregional hypoxia on the infiltration of cancers of the head and neck region by cytotoxic t lymphocytes

Simple Summary Progress in the field of in situ proteomics allows for the simultaneous detection of multiple biomarkers within one cancer tissue specimen. As a result, biological hypotheses previously only assessable ex vivo can now be studied in human cancer tissue. However, methods for objective analysis have so far been lacking behind. In this study, we established a free, objective, and entirely open-source-based method for the analysis of multiplexed immunofluorescence specimens. This will gain further importance with the availability of more advanced multiplexing methods in the future. Abstract (1) Background: The immune system has physiological antitumor activity, which is partially …

Rectal cancer: mucinous carcinoma on magnetic resonance imaging indicates poor response to neoadjuvant chemoradiation.

Purpose To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum…

Rectal cancer: Assessment of response to neoadjuvant chemoradiation by dynamic contrast-enhanced MRI

Purpose To assess pretreatment functional and morphological tumor characteristics with magnetic resonance imaging (MRI) in advanced rectal carcinoma and to identify factors predicting response to neoadjuvant chemoradiation. Materials and Methods In a prospective study, 95 patients with rectal carcinoma underwent dynamic contrast-enhanced MRI before and after chemoradiation. Quantitative parameters were derived from a pharmacokinetic two-compartment model. Tumors were also characterized with regard to mucinous status at pretreatment high-resolution MRI as nonmucinous or mucinous. Response to treatment was defined as a downshift in the local tumor stage. Results The parameter k21 (contrast me…

Erratum to "Determination of the irradiation field at the research reactor TRIGA Mainz for BNCT" [J. Appl. Radiat. Isot. 67 (2009) S242-S246].

S3-Leitlinie „Magenkarzinom” -

Additional file 7 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 7: Gene expression in the "Not a Number" pathways (blue = downregulation, red = upregulation). Web Figure 14. Base excision repair (BER) system. Web Fig. 15. Molecular mechanisms of cancer. Web Fig. 16. Assembly of RNA polymerase III complex. Web Fig. 17. DNA double-strand break repair by homologous recombination. Web Fig. 18. Interleukin 4 (IL-4) signaling. Web Fig. 19. Interleukin 17 (IL-17) signaling. Web Fig. 20. Interleukin 17A (IL-17A) signaling in fibroblasts. Web Fig. 21. Mitochondrial dysfunction. Web Fig. 22. Myc mediated apoptosis signaling. Web Fig. 23.Nucleotide excision repair. Web Fig. 24. Protein ubiquitination. Web Fig. 25. Retinoic acid receptor (RAR) activ…

Irradiation facility at the TRIGA Mainz for treatment of liver metastases

Abstract The TRIGA Mark II reactor at the University of Mainz provides ideal conditions for duplicating BNCT treatment as performed in Pavia, Italy, in 2001 and 2003 [Pinelli, T., Zonta, A., Altieri, S., Barni, S., Braghieri, A., Pedroni, P., Bruschi, P., Chiari, P., Ferrari, C., Fossati, F., Nano, R., Ngnitejeu Tata, S., Prati, U., Ricevuti, G., Roveda, L., Zonta, C., 2002. TAOrMINA: from the first idea to the application to the human liver. In: Sauerwein et al. (Eds.), Research and Development in Neutron Capture Therapy. Proceedings of the 10th International Congress on Neutron Capture Therapy, Monduzzi editore, Bologna, pp. 1065–1072]. In order to determine the optimal parameters for the…

Additional file 4 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 4: Web Figure 11. Comparison of affected pathways in different data sets.

Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction

Abstract Background This phase I/II-trial assessed the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of neoadjuvant radiochemotherapy (RCT) with docetaxel and oxaliplatin in patients with locally advanced adenocarcinoma of the oesophagogastric junction. Methods Patients received neoadjuvant radiotherapy (50.4 Gy) together with weekly docetaxel (20 mg/m2 at dose level (DL) 1 and 2, 25 mg/m2 at DL 3) and oxaliplatin (40 mg/m2 at DL 1, 50 mg/m2 at DL 2 and 3) over 5 weeks. The primary endpoint was the DLT and the MTD of the RCT regimen. Secondary endpoints included overall response rate (ORR) and progression-free survival (PFS). Results A total of 24 patients were included. F…

Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE)

Purpose Concurrent chemoradiotherapy with or without surgery are options for stage IIIA(N2) non–small-cell lung cancer. Our previous phase II study had shown the efficacy of induction chemotherapy followed by chemoradiotherapy and surgery in patients with IIIA(N2) disease and with selected IIIB disease. Here, we compared surgery with definitive chemoradiotherapy in resectable stage III disease after induction. Patients and Methods Patients with pathologically proven IIIA(N2) and selected patients with IIIB disease that had medical/functional operability received induction chemotherapy, which consisted of three cycles of cisplatin 50 mg/m2 on days 1 and 8 and paclitaxel 175 mg/m2 on day 1 ev…

MBCL-11. TIME TO RADIOTHERAPY IMPACTS SURVIVAL IN PEDIATRIC AND ADOLESCENT NON-METASTATIC MEDULLOBLASTOMA TREATED BY UPFRONT RADIOTHERAPY – A REPORT FROM THE HIT 2000 TRIAL

Abstract PURPOSE To evaluate prognostic factors and impact of participation in a randomized trial in non-metastatic medulloblastoma. METHODS AND PATIENTS 382 patients with non-metastatic medulloblastoma aged 4–21 years with primary neurosurgical resections between 2001 and 2011 were enrolled into the HIT 2000 trial and centrally reviewed. Between 2001 and 2006, 176 of these patients participated in the randomized trial HIT-SIOP PNET 4. Three different radiotherapy protocols were applied. Molecular subgroup was available for 157 patients. RESULTS Median follow-up was 6.35 [0.09–13.86] years. The 5-year progression-free (PFS) and overall survival (OS) rates were 80.3 % ± 2.1 % and 86.5 % ± 1.…

Radiation dose distribution in functional heart regions from tangential breast cancer radiotherapy

Abstract Background and purpose To analyze the distribution of individually-determined radiation dose to the heart and its functional sub-structures after radiotherapy in breast cancer patients treated in Germany during 1998–2008. Material and methods We obtained electronic treatment planning records for 769 female breast cancer patients treated with megavoltage tangential field radiotherapy. All dose distributions were re-calculated using Eclipse with the anisotropic analytical algorithm (AAA) for photon fields, and the electron Monte Carlo algorithm for electron boost fields. Based on individual dose volume histograms for the complete heart and several functional sub-structures, we estima…

Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of

Simple Summary Genetic variability in transforming growth factor beta pathway (TGFB) has been reported to affect adverse events in radiotherapy. We investigated 40 germline polymorphisms in peripheral blood cells, covering the entire common genetic variability in the TGFβ1 ligand (gene TGFB1) and the TGFβ receptor-1 (TGFBR1) in 240 patients treated with primary radiotherapy for prostate cancer. Human lymphoblastoid cell lines (LCLs) were used to assess whether TGFB1 and TGFBR1 polymorphisms impact DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, for one polymorphism (rs10512263 in TGFBR1, C-variant allele, n = 35), a statistically signifi…

The Role of Palliative Radiotherapy in the Treatment of Spinal Bone Metastases from Head and Neck Tumors-A Multicenter Analysis of a Rare Event.

This retrospective multi-center analysis aimed to assess the clinical response and stabilizing effects of palliative radiotherapy (RT) for spinal bone metastases (SBM) in head and neck cancer (HNC), and to establish potential predictive factors for stability and overall survival (OS). Patients included in this analysis were treated at the University Hospitals of Mainz, Freiburg, and Heidelberg between 2001 and 2019. Clinical information was taken from the medical records. The stability of affected vertebral bodies was assessed according to the validated spine instability neoplastic score (SINS) based on CT-imaging before RT, as well as 3 and 6 months after RT. OS was quantified as the time …

Radiotherapy with BRAF inhibitor therapy for melanoma: progress and possibilities.

The introduction of small molecule BRAFV600 kinase inhibitors represents a milestone in the targeted therapy of patients with metastatic melanoma by a significant increase in therapeutic efficacy in terms of overall and progression-free survival compared with conventional chemotherapy. Beside BRAFV600 inhibitor treatment, radiotherapy is a further mainstay for the therapy of metastatic melanoma and thus a concomitant or sequential application of BRAFV600 inhibitors and radiotherapy is inevitable. Recent reports show a significant radiosensitization of the irradiated healthy tissue in patients with melanoma after the combination of radiotherapy and BRAFV600 inhibitors, evoking concern in cl…

Additional file 11 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 11: Web Table 1D. Differentially expressed genes 4 h after exposure to high dose ionizing radiation (2 Gray).

Additional file 12 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 12: Web Table 2. Differential expression activity in cellular pathways and involved molecules

Psychological distress in lung cancer survivors at least 1 year after diagnosis-Results of a German multicenter cross-sectional study.

Additional file 13 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation

Additional file 13: Supplement file 1. Settings for comparison analyses in IPA.

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

Simple Summary Childhood cancers are mostly of unknown etiology and represent devastating diagnoses. The clinical benefits of steadily increasing tumor control and survival rates are countered by severe and fatal health consequences from genotoxic therapies in long-term survivors of pediatric cancers. Among them, iatrogenic second primary malignancies represent the heaviest burden for the patient. Therefore, particularly in pediatric tumor patients, the reduction of genotoxic treatments and the use of targeted or immune-based oncologic strategies are of high clinical interest. The knowledge of therapy-associated as well as intrinsic risk factors for late sequelae of antineoplastic treatment…

Rektumkarzinom: Behandeln wir zu häufig neoadjuvant? Vorschläge zu einer selektiveren, MRT-basierten Indikation

The present-day optimised surgery (concept of total mesorectal excision) with quality assurance by standardized pathologic examination, advances in radiotherapy and the possibilities of high-spatial-resolution MR imaging require reconsideration of pros and contras of neoadjuvant therapy and respective data. According to the resulting new proposal neoadjuvant long-course radiochemotherapy is indicated for patients with 1) fixed questionably R0 resectable tumors, 2) mobile tumors with the MRT finding of tumor involving the mesorectal fascia or 1 mm or less from it, 3) low rectal tumors extending below the levator origin and invading beyond the muscularis propria. If a high risk of local recur…