Treatment of patients with atypical meningiomas Simpson grade 4 and 5 with a carbon ion boost in combination with postoperative photon radiotherapy: The MARCIE Trial

<p>Abstract</p> <p>Background</p> <p>Treatment standard for patients with atypical or anaplastic meningioma is neurosurgical resection. With this approach, local control ranges between 50% and 70%, depending on resection status. A series or smaller studies has shown that postoperative radiotherapy in this patient population can increase progression-free survival, which translates into increased overall survival. However, meningiomas are known to be radioresistant tumors, and radiation doses of 60 Gy or higher have been shown to be necessary for tumor control.</p> <p>Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.</p> <p>First data obtained within the Phase I/II trial performed at GSI in Darmstadt on carbon ion radiotherapy for patients with high-risk meningiomas has shown safety, and treatment results are promising.</p> <p>Methods/design</p> <p>The Phase II-MARCIE-Study will evaluate a carbon ion boost applied to the macroscopic tumor in conjunction with photon radiotherapy in patients with atypical menigiomas after incomplete resection or biopsy.</p> <p>Primary endpoint is progression-free survival, secondary endpoints are overall survival, safety and toxicity.</p> <p>Discussion</p> <p>Based on published data on the treatment of atypical meningiomas with carbon ions at GSI, the present study will evaluate this treatment concept in a larger patient population and will compare outcome to current standard photon treatment.</p> <p>Trial registration</p> <p>NCT01166321</p

Local radiotherapeutic management of ependymomas with fractionated stereotactic radiotherapy (FSRT)

<p>Abstract</p> <p>Background</p> <p>To assess the role of Fractionated Stereotactic Radiotherapy (FSRT) in the management of ependymomas.</p> <p>Methods</p> <p>From January 1992 to July 2003, FSRT was performed in 19 patients with histologically confirmed ependymomas. The median age was 15 years, 5 patients were younger than 4 years of age.</p> <p>Twelve patients received FSRT as primary postoperative radiotherapy after surgical resection. In 6 patients irradiation of the posterior fossa was performed with a local boost to the tumor bed, and in 4 patients the tumor bed only was irradiated. In 7 patients FSRT was performed as re-irradiation for tumor progression. This patient group was analyzed separately. A median dose of 54 Gy was prescribed in a median fractionation of 5 × 1.8 Gy per week for primary RT using 6 MeV photons with a linear accelerator. For FSRT as re-irradiation, a median dose of 36 Gy was applied. All recurrent tumors were localized within the former RT-field.</p> <p>Results</p> <p>The 5- and 10-year overall survival rates were 77% and 64%, respectively. Patients treated with FSRT for primary irradiation showed an overall survival of 100% and 78% at 3 and 5 years after irradiation of the posterior fossa with a boost to the tumor bed, and a survival rate of 100% at 5 years with RT of the tumor bed only. After re-irradiation with FSRT, survival rates of 83% and 50% at 3-and 5 years, respectively, were obtained.</p> <p>Progression-free survival rates after primary RT as compared to re-irradiation were 64% and 60% at 5 years, respectively.</p> <p>FSRT was well tolerated by all patients and could be completed without interruptions due to side effects. No severe treatment related toxicity > CTC grade 2 for patients treated with FSRT could be observed.</p> <p>Conclusion</p> <p>The present analysis shows that FSRT is well tolerated and highly effective in the management of ependymal tumors. The rate of recurrences, especially at the field border, is not increased as compared to conventional radiotherapy consisting of craniospinal irradiation and a local boost to the posterior fossa.</p

Sarcoma classification by DNA methylation profiling

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications