Current concepts in clinical radiation oncology.

Based on its potent capacity to induce tumor cell death and to abrogate clonogenic survival, radiotherapy is a key part of multimodal cancer treatment approaches. Numerous clinical trials have documented the clear correlation between improved local control and increased overall survival. However, despite all progress, the efficacy of radiation-based treatment approaches is still limited by different technological, biological, and clinical constraints. In principle, the following major issues can be distinguished: (1) The intrinsic radiation resistance of several tumors is higher than that of the surrounding normal tissue, (2) the true patho-anatomical borders of tumors or areas at risk are not perfectly identifiable, (3) the treatment volume cannot be adjusted properly during a given treatment series, and (4) the individual heterogeneity in terms of tumor and normal tissue responses toward irradiation is immense. At present, research efforts in radiation oncology follow three major tracks, in order to address these limitations: (1) implementation of molecularly targeted agents and 'omics'-based screening and stratification procedures, (2) improvement of treatment planning, imaging, and accuracy of dose application, and (3) clinical implementation of other types of radiation, including protons and heavy ions. Several of these strategies have already revealed promising improvements with regard to clinical outcome. Nevertheless, many open questions remain with individualization of treatment approaches being a key problem. In the present review, the current status of radiation-based cancer treatment with particular focus on novel aspects and developments that will influence the field of radiation oncology in the near future is summarized and discussed.

Timing of failure in limited disease (stage I-III) small-cell lung cancer patients treated with chemoradiotherapy: a retrospective analysis.

AIMS AND BACKGROUND: Follow-up in limited disease (stage I-III) small cell lung cancer could be further optimized by assessment of the temporal and locational distribution of treatment failure after completion of chemoradiotherapy. METHODS AND STUDY DESIGN: Follow-up was retrospectively analyzed in 125 limited disease (stage I-III) small cell lung cancer patients with initial performance status WHO <3 who had successfully completed chemoradiotherapy. Thoracic irradiation was applied in the concurrent or sequential mode. Time from initial pathological diagnosis and treatment end to local, distant and brain recurrence was documented. RESULTS: One- and two-year progression-free survival rates were 50% and 27.2% in patients treated with concurrent and 45.2% and 14.2% in those treated with sequential chemoradiotherapy, respectively. Local relapse was documented in 14% patients treated with concurrent and 16% with sequential chemoradiotherapy. The distant failure rate was 43% in both subgroups. Up to the end of the follow-up period, more patients treated with concurrent chemoradiotherapy had developed brain metastases than those treated sequentially (37% vs 20%, P = 0.049). Median time (in days) to local relapse was 376 and 401 from the initial diagnosis, 200 and 309 from the end of chemotherapy, and 316 and 196 from the end of thoracic irradiation; to distant failure was 275 and 298 from the initial diagnosis, 151 and 157 from the end of chemotherapy and 180 and 84 from the end of thoracic irradiation; to brain relapse was 330 and 273 from the initial diagnosis, 123 and 151 from the end of chemotherapy and 213 and 73 from the end of thoracic irradiation in patients treated with concurrent and sequential chemoradiotherapy, respectively. There was no significant difference in the temporal distribution of treatment failure in either subgroup. CONCLUSIONS: In more than half of the patients who developed a distant recurrence, including brain metastases, treatment failure occurred in the first year after the initial diagnosis. Intensified follow-up can be recommended at least in the first year, because no sufficient eradication of the systemic small cell lung cancer with the applied chemoradiotherapy protocol could be achieved.

MiRNA expression patterns predict survival in glioblastoma.

BACKGROUND: In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. METHODS: 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom® Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. RESULTS: It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. CONCLUSIONS: At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.