Why "Radiation Oncology"

Radiotherapy continues to be a major treatment for solid tumours and is a cornerstone of modern oncology. The term 'radiation oncology' describes the integration of radiation therapy into the complexity of multi-modal therapy. Over the last ten years the crucial role of radiation therapy as part of multi-modality protocols in cancer care has been documented in numerous Phase III trials. Advances in treatment technology as well as the underlying biology of tumour resistance mechanisms will further strengthen the role of radiation oncology. The scientific role of radiation oncology is reflected by the increase in the number of papers related to radiation oncology in resources like Medline. In order to reflect the growing scientific importance of radiation oncology, radiation physics and radiation biology, we have initiated Radiation Oncology as the first open access journal in the field. Open access allows for a rapid and transparent publication process together with an unequalled opportunity to reach the widest reader spectrum possible

The Okun Misery Index in the European Union Countries from 2000 to 2009

The study is composed of four main parts and a summary. The first part, introduction, discusses various measures of the economic system's efficiency that are used in practice. Part two emphasises that the GDP per capita according to purchasing power parity still remains the most popular among those measures. Further, it presents the ranking of the European Union countries taking that measure into account, the research period being 1999-2009. Part three points out that it is also the level of poverty (misery) that determines the economic system's efficiency. That level can be measured by means of various indicators, among others, the so called HPI-2 index calculated by the UN. It will be the Okun misery index, however, computed as the sum of inflation and unemployment rates that will be presented as an alternative being of interest from the macroeconomic point of view. The ranking of the European Union member states according to that measure in the 2000-2004 and 2005-2009 periods will be provided in part four. The article will end in a summary containing synthetic conclusions drawn from earlier observations.Opracowanie składa się z czterech części zasadniczych i podsumowania. W punkcie pierwszym omówiono różnorodne mierniki sprawności systemu gospodarczego wykorzystywane w praktyce. W części drugiej podkreślono, iż nadal najpopularniejszym z nich jest PKB per capita według parytetu siły nabywczej. Zgodnie z tym miernikiem przedstawiono ranking państw Unii Europejskiej w latach 1999-2009. W punkcie trzecim podkreślono, że o sprawności systemu gospodarczego decyduje także poziom ubóstwa. Może być on mierzony różnymi wskaźnikami, m.in. tzw. indeksem HPI-2 obliczanym przez ONZ. Jako ciekawą z makroekonomicznego punktu widzenia alternatywę ukazano jednak miarę wskaźnika ubóstwa Okuna obliczanego poprzez zsumowanie stopy inflacji i stopy bezrobocia. Ranking państw Unii Europejskiej według tej miary w okresach 2000-2004 oraz 2005-2009 zaprezentowano w części czwartej. Całość zamknięto podsumowaniem, w którym zawarto syntetyczne wnioski z przeprowadzonych obserwacji

Irradiation specifically sensitises solid tumour cell lines to TRAIL mediated apoptosis

BACKGROUND: TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues. METHODS: Tumour cell systems derived from breast- (MDA MB231), lung--(NCI H460) colorectal--(Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry. RESULTS: The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL. CONCLUSIONS: Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor upregulation may not be the sole mechanism by which sensitation to TRAIL after irradiation is induced

Targeted therapy of the XIAP/proteasome pathway overcomes TRAIL-resistance in carcinoma by switching apoptosis signaling to a Bax/Bak-independent 'type I' mode

TRAIL is a promising anticancer agent, capable of inducing apoptosis in a wide range of treatment-resistant tumor cells. In 'type II' cells, the death signal triggered by TRAIL requires amplification via the mitochondrial apoptosis pathway. Consequently, deregulation of the intrinsic apoptosis-signaling pathway, for example, by loss of Bax and Bak, confers TRAIL-resistance and limits its application. Here, we show that despite resistance of Bax/Bak double-deficient cells, TRAIL-treatment resulted in caspase-8 activation and complete processing of the caspase-3 proenzymes. However, active caspase-3 was degraded by the proteasome and not detectable unless the XIAP/proteasome pathway was inhibited. Direct or indirect inhibition of XIAP by RNAi, Mithramycin A or by the SMAC mimetic LBW-242 as well as inhibition of the proteasome by Bortezomib overcomes TRAIL-resistance of Bax/Bak double-deficient tumor cells. Moreover, activation and stabilization of caspase-3 becomes independent of mitochondrial death signaling, demonstrating that inhibition of the XIAP/proteasome pathway overcomes resistance by converting 'type II' to 'type I' cells. Our results further demonstrate that the E3 ubiquitin ligase XIAP is a gatekeeper critical for the 'type II' phenotype. Pharmacological manipulation of XIAP therefore is a promising strategy to sensitize cells for TRAIL and to overcome TRAIL-resistance in case of central defects in the intrinsic apoptosis-signaling pathway

Effectiveness and tolerability of radiotherapy for patients with indolent non-Hodgkin's lymphoma: a monocenter analysis

To analyze the effectiveness and toxicities of radiotherapy in indolent non-Hodgkin's lymphoma (iNHL) patients treated in our institution. Patients with iNHL treated with radiotherapy between 1999 and 2016 were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC), overall survival (OS) and toxicities. PFS, LC, and OS were analyzed using Kaplan-Meier method. Log-rank test was used to investigate the differences between subgroups. Cox proportional hazard model was used for univariate continuous analysis. Seventy-five patients were identified in our institutional database between 1999 and 2016. Fifty-eight (77.3%) had stage I after Ann-Arbor and 17 patients (22.7%) had stage II. The median follow-up was 87~months (95% CI 72-102~months). Median single dose per fraction was 2.0~Gy (range 1.5-2~Gy) and median total dose was 30.6~Gy (range 16-45~Gy). Radiotherapy was performed in 2D (n = 10; 13.3%), 3D (n = 63; 84.0%) and VMAT (n = 2; 2.7%) techniques, respectively. The median PFS was 14.0~years (95% CI 8.3-19.7~years). The estimated PFS after 5 and 10~years were 73.0% and 65.5% in Kaplan-Meier analysis, respectively. The 5- and 10-year LC were 94.9% and 92.3%, respectively. The 5- and 10-year OS were 88.6% and 73.9%. In univariate analyses of PFS, younger patients (≤ 60~years old) had significantly superior PFS to those older than 60~years old (5-year PFS 81.9% vs. 65.1%, p = 0.021). Dose escalation > 36.0~Gy had no prognostic influence in term of PFS (p = 0.425). Extranodal involvement, stage and histology had no prognostic impact on PFS. Depending on the site of lymphomas, the most common acute side effects were: dermatitis CTCAE° I-II (8.0%), xerostomia CTC° I (8.0%), cataract CTC° I (12.0%) and dry eyes CTC° I-II (14.6%). No adverse event CTC° III was reported. Most acute side effects recovered at 3 to 6~months after radiotherapy except for CTC° I cataract and xerostomia. Local Radiotherapy was highly effective for treatment of early stage iNHL with no serious side effects in our cohort. The most acute CTCAE° I-II side effects recovered 3 to 6~months later. Technique advances seem to have further improved effectiveness and tolerability of radiotherapy.Trial registration: Local ethics committee of Ludwig-Maximilian-University (LMU) Munich approved this retrospective analysis on the May 7th, 2019 (Nr. 19-137)

Survival of tumor cells after proton irradiation with ultra-high dose rates

<p>Abstract</p> <p>Background</p> <p>Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >10⁹Gy s^-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams.</p> <p>Methods</p> <p>The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation.</p> <p>Results</p> <p>At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively.</p> <p>Conclusions</p> <p>At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly.</p

Plausible role of estrogens in pathogenesis, progression and therapy of lung cancer

Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor genep53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlation between hormone replacement therapy (HRT) or oral contraceptives (OCs), and increased mortality rates due to the increased incidence of malignant tumors, including lung cancer. Interestingly, two types of estrogen receptors have been detected in lung cancer cells: ERα and ERβ. The presence of ERα has been detected in tissues and non-small-cell lung carcinoma (NSCLC) cell lines. In contrast, overexpression of ERβ is a prognostic marker in NSCLC. Herein, we summarize the current knowledge on the role of estrogens in the etiopathogenesis of lung cancer, as well as biological, hormonal and genetic sex-related differences in this neoplasm

Impact of Radiotherapy, Chemotherapy and Surgery in Multimodal Treatment of Locally Advanced Esophageal Cancer

Objectives: It was the aim of this study to assess our institutional experience with definitive chemoradiation (CRT) versus induction chemotherapy followed by CRT with or without surgery (C-CRT/S) in esophageal cancer. Methods: We retrospectively analyzed 129 institutional patients with locally advanced esophageal cancer who had been treated by either CRT in analogy to the RTOG 8501 trial (n = 78) or C-CRT/S (n = 51). Results: The median, 2-and 5-year overall survival (OS) of the entire collective was 17.6 months, 42 and 24%, respectively, without a significant difference between the CRT and C-CRT/S groups. In C-CRT/S patients, surgery statistically improved the locoregional control (LRC) rates (2-year LRC 73.6 vs. 21.2%; p = 0.003); however, this was translated only into a trend towards improved OS (p = 0.084). The impact of escalated radiation doses (>= 60.0 vs. <60.0 Gy) on LRC was detectable only in T1-3 N0-1 M0 patients of the CRT group (2-year LRC 77.8 vs. 42.3%; p = 0.036). Conclusion: Definitive CRT and a trimodality approach including surgery (C-CRT/S) had a comparable outcome in this unselected patient collective. Surgery and higher radiation doses improve LRC rates in subgroups of patients, respectively, but without effect on OS. Copyright (C) 2012 S. Karger AG, Base