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Search Results: 1 - 10 of 169789 matches for " Stephanie E Combs "
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Radiotherapeutic alternatives for previously irradiated recurrent gliomas
Stephanie E Combs, Jürgen Debus, Daniela Schulz-Ertner
BMC Cancer , 2007, DOI: 10.1186/1471-2407-7-167
Abstract: With modern high-precision radiotherapy re-irradiation has become a more wide-spread, effective and well-tolerated treatment option. Besides external beam radiotherapy, a number of invasive and/or intraoperative radiation techniques have been evaluated in patients with recurrent gliomas.The present article is a review on the available methods in radiation oncology and summarizes results with respect to outcome and side effects in comparison to clinical results after neurosurgical resection or different chemotherapeutic approaches.This turkish proverb represents the effort that was put on the issue of re-irradiation in patients with recurrent gliomas. In the past, re-irradiation was thought to be associated with a high incidence of severe treatment-related side effects and was therefore prescribed only reluctantly. A number of reports, however, have suggested that re-irradiation may not be followed by the high incidence of side-effects as feared [1]. Improvement in imaging techniques as well as the establishment of high -precision radiotherapy techniques such as stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) in the clinical routine have enabled the radiation oncologist to precisely define a target volume and to describe it with with stereotactic coordinates after targeting with stereotactic methods (measure a thousand times) and to deliver high local doses to this area (and cut once). Therefore, re-irradiation has become a safe and effective means in controlling recurrent gliomas.It is known that local radiotherapeutic treatment is a main component in the treatment of astrocytomas after primary diagnosis. For low-grade tumors, althogh the exact time-point of radiotherapy (RT) after primary diagnosis is discussed controversially, most patients are treated at some point during the course of their disease [2,3]. For anaplastic astrocytoma, there is a clear indication for RT after primary diagnosis following neurosurgical resection; pres
State-of-the-art treatment alternatives for base of skull meningiomas: complementing and controversial indications for neurosurgery, stereotactic and robotic based radiosurgery or modern fractionated radiation techniques
Combs Stephanie E,Ganswindt Ute,Foote Robert L,Kondziolka Douglas
Radiation Oncology , 2012, DOI: 10.1186/1748-717x-7-226
Abstract: 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.
Treatment of pediatric patients and young adults with particle therapy at the Heidelberg Ion Therapy Center (HIT): establishment of workflow and initial clinical data
Combs Stephanie E,Kessel Kerstin A,Herfarth Klaus,Jensen Alexandra
Radiation Oncology , 2012, DOI: 10.1186/1748-717x-7-170
Abstract: Background To report on establishment of workflow and clinical results of particle therapy at the Heidelberg Ion Therapy Center. Materials and methods We treated 36 pediatric patients (aged 21 or younger) with particle therapy at HIT. Median age was 12 years (range 2-21 years), five patients (14%) were younger than 5 years of age. Indications included pilocytic astrocytoma, parameningeal and orbital rhabdomyosarcoma, skull base and cervical chordoma, osteosarcoma and adenoid-cystic carcinoma (ACC), as well as one patient with an angiofibroma of the nasopharynx. For the treatment of small children, an anesthesia unit at HIT was established in cooperation with the Department of Anesthesiology. Results Treatment concepts depended on tumor type, staging, age of the patient, as well as availability of specific study protocols. In all patients, particle radiotherapy was well tolerated and no interruptions due to toxicity had to be undertaken. During follow-up, only mild toxicites were observed. Only one patient died of tumor progression: Carbon ion radiotherapy was performed as an individual treatment approach in a child with a skull base recurrence of the previously irradiated rhabdomyosarcoma. Besides this patient, tumor recurrence was observed in two additional patients. Conclusion Clinical protocols have been generated to evaluate the real potential of particle therapy, also with respect to carbon ions in distinct pediatric patient populations. The strong cooperation between the pediatric department and the department of radiation oncology enable an interdisciplinary treatment and stream-lined workflow and acceptance of the treatment for the patients and their parents.
Local radiotherapeutic management of ependymomas with fractionated stereotactic radiotherapy (FSRT)
Stephanie E Combs, Christoph Thilmann, Jürgen Debus, Daniela Schulz-Ertner
BMC Cancer , 2006, DOI: 10.1186/1471-2407-6-222
Abstract: 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.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.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.Progression-free survival rates after primary RT as compared to re-irradiation were 64% and 60% at 5 years, respectively.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.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.Ependymomas (EP) originate from ependymal cells of the wall of the cerebral ventricles, the central canal
Treatment of primary glioblastoma multiforme with cetuximab, radiotherapy and temozolomide (GERT) – phase I/II trial: study protocol
Stephanie E Combs, Steffen Heeger, Renate Haselmann, Lutz Edler, Jürgen Debus, Daniela Schulz-Ertner
BMC Cancer , 2006, DOI: 10.1186/1471-2407-6-133
Abstract: The majority of GBMs show an overexpression and/or amplification of the epidermal growth factor receptor (EGFR). Therefore, addition of EGFR-inhibition with cetuximab to the current standard treatment approach with radiotherapy and TMZ seems promising.GERT is a one-armed single-center phase I/II trial. In a first step, dose-escalation of TMZ from 50 mg/m2 to 75 mg/m2 together with radiotherapy and cetuximab will be performed. Should safety be proven, the phase II trial will be initiated with the standard dose of 75 mg/m2 of TMZ. Cetuximab will be applied in the standard application dose of 400 mg/m2 in week 1, thereafter at a dose of 250 mg/m2 weekly. A total of 46 patients will be included into this phase I/II trial.Primary endpoints are feasibility and toxicity, secondary endpoints are overall and progression-free survival. An interim analysis will be performed after inclusion of 15 patients into the main study. Patients' enrolment will be performed over a period of 2 years. The observation time will end 2 years after inclusion of the last patient.The goal of this study is to evaluate the safety and efficacy of combined RCHT-immunotherapy with TMZ and cetuximab as first-line treatment for patients with primary GBM.Glioblastoma multiforme (GBM) is the most frequent primary malignant brain tumor in adults. Until recently, the standard treatment approach in patients with GBM was neurosurgical resection, as radical as possible, followed by postoperative radiotherapy (RT). However, in spite of technical advances in surgery and radiotherapy, overall survival still remained unsatisfactory with median overall survival times of 9–12 months [1,2].Over the last decade, a number of clinical investigations on combined radio-chemotherapy (RCHT) after neurosurgical resection have been conducted. A large randomized trial performed by the Neuro-Oncology Working Group of the German Cancer Society evaluated combined RCHT with nimustine plus teniposide versus nimustine plus cytarabin
Proton and carbon ion radiotherapy for primary brain tumors delivered with active raster scanning at the Heidelberg Ion Therapy Center (HIT): early treatment results and study concepts
Stefan Rieken, Daniel Habermehl, Thomas Haberer, Oliver Jaekel, Jürgen Debus, Stephanie E Combs
Radiation Oncology , 2012, DOI: 10.1186/1748-717x-7-41
Abstract: This study was set up in order to investigate toxicity and response after proton and carbon ion therapy for gliomas and meningiomas.33 patients with gliomas (n = 26) and meningiomas (n = 7) were treated with carbon ion (n = 26) and proton (n = 7) radiotherapy. In 22 patients, particle irradiation was combined with photon therapy. Temozolomide-based chemotherapy was combined with particle therapy in 17 patients with gliomas. Particle therapy as reirradiation was conducted in 7 patients. Target volume definition was based upon CT, MRI and PET imaging. Response was assessed by MRI examinations, and progression was diagnosed according to the Macdonald criteria. Toxicity was classified according to CTCAE v4.0.Treatment was completed and tolerated well in all patients. Toxicity was moderate and included fatigue (24.2%), intermittent cranial nerve symptoms (6%) and single episodes of seizures (6%). At first and second follow-up examinations, mean maximum tumor diameters had slightly decreased from 29.7 mm to 27.1 mm and 24.9 mm respectively. Nine glioma patients suffered from tumor relapse, among these 5 with infield relapses, causing death in 8 patients. There was no progression in any meningioma patient.Particle radiotherapy is safe and feasible in patients with primary brain tumors. It is associated with little toxicity. A positive response of both gliomas and meningiomas, which is suggested in these preliminary data, must be evaluated in further clinical trials.Despite continuously evolving extensive treatment concepts, primary brain tumors such as low grade and high grade gliomas, as well as meningiomas have not ceased to cause high morbidity and lethality due to biological aggressiveness or location in close proximity to critical structures. Radiotherapy is implemented in most glioma and many meningiomas therapy regimes and has been shown to significantly improve local control and prolong survival [1-3]. However, treatment results are still not satisfying, and most p
Prior surgical intervention and tumor size impact clinical outcome after precision radiotherapy for the treatment of optic nerve sheath meningiomas (ONSM)
Sebastian Adeberg, Thomas Welzel, Stefan Rieken, Jürgen Debus, Stephanie E Combs
Radiation Oncology , 2011, DOI: 10.1186/1748-717x-6-117
Abstract: Between January 1991 and January 2010, 40 patients with ONSM were treated using FSRT. Of these, 19 patients received radiotherapy as primary treatment, and 21 patients were treated after surgical resection. The median target volume was 9.2 ml, median total dose was 54 Gy in median single fractions of 1,8 Gy.Local progression-free survival was 100%. Median survival after FSRT was 60 months (range 4-228 months). In all patients overall toleration of FSRT was very good. Acute toxicity was mild. Prior to RT, 29 patients complained about any kind of visual impairment including visual field deficits, diplopia or amaurosis. Prior surgical resection was identified as a negative prognostic factor for visual outcome, whereas patients with larger tumor volumes demonstrated a higher number of patients with improvement of pre-existing visual deficits.Long-term outcome after FSRT for ONSM shows improved vision in patients not treated surgically prior to RT; moreover, the best improvement of visual deficits are observed in patients with larger target volumes. The absence of tumor recurrences supports that FSRT is a strong alternative to surgical resection especially in small tumors without extensive compression of normal tissue structuresTreatment of primary optic nerve sheath meningiomas (ONSM) remains a challenge in the interdisciplinary team of surgeons, opthalmologists and radiation oncologists. They are located directly adjacent to the optic nerve which is sensitive to any treatment damage, including radiation or surgical procedures. They arise from meningothelial cap cells of arachniod villi which surround the optical nerve within the orbit or within the intracanalicular part of the optic nerve.In general, menigiomas are slow growing tumors with an annual incidence of 6 per 100,000; most patients remain without any clinical symptoms over very long periods of time. ONSM are a rare subtype accounting for 2% of all meningiomas, but they represent the second most frequent optic
Intensity Modulated Radiotherapy (IMRT) and Fractionated Stereotactic Radiotherapy (FSRT) for children with head-and-neck-rhabdomyosarcoma
Stephanie E Combs, Wolfgang Behnisch, Andreas E Kulozik, Peter E Huber, Jürgen Debus, Daniela Schulz-Ertner
BMC Cancer , 2007, DOI: 10.1186/1471-2407-7-177
Abstract: We treated 19 children with head-and-neck rhabdomyosarcoma with FSRT (n = 14) or IMRT (n = 5) as a part of multimodal therapy. Median age at the time of radiation therapy was 5 years (range 2–15 years). All children received systemic chemotherapy according to the German Soft Tissue Sarcoma Study protocols.Median size of treatment volume for RT was 93,4 ml. We applied a median total dose of 45 Gy (range 32 Gy – 54 Gy) using a median fractionation of 5 × 1,8 Gy/week (range 1,6 Gy – 1,8 Gy).The median time interval between primary diagnosis and radiation therapy was 5 months (range 3–9 months).After RT, the 3- and 5-year survival rate was 94%. The 3- and 5-year actuarial local control rate after RT was 89%.The actuarial freedom of distant metastases rate at 3- and 5-years was 89% for all patients.Radiotherapy was well tolerated in all children and could be completed without interruptions > 4 days. No toxicities >CTC grade 2 were observed. The median follow-up time after RT was 17 months.IMRT and FSRT lead to excellent outcome in children with head-and-neck RMS with a low incidence of treatment-related side effects.Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma entity in children [1]. The most common sites of RMS in children are the head and neck region (35%), the genitourinary tract (35%) and the extremities (17%) [2]. The orbit is the primary site in about 10% of these tumors, the most common localization in the head and neck area is parameningeal, including the nasopharynx, the paranasal sinuses, the middle ear and mastoid and the infratemporal fossa/pterygopalatine space [2-8]. Most children are younger than 10 years of age (72%) [9].Modern therapy protocols comprise of surgical resection, chemotherapy and radiotherapy (RT). However, RT in children is commonly applied cautiously with respect to early and late side effects [10-14].With modern RT techniques such as Intensity Modulated Radiotherapy (IMRT) and Fractionated Stereotactic Radiotherapy (FSRT)
Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study
Anna V Nikoghosyan, Geraldine Rauch, Marc W Münter, Alexandra D Jensen, Stephanie E Combs, Meinhard Kieser, Jürgen Debus
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-606
Abstract: The study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial.Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points.Up to now it was impossible to compare two different particle therapies, i.e. protons and carbon ions, directly at the same facility in connection with the treatment of low grade skull base chondrosarcomas.This trial is a phase III study to demonstrate that carbon ion radiotherapy (experimental treatment) is not relevantly inferior and at least as good as proton radiotherapy (standard treatment) with respect to 5 year LPFS in the treatment of chondrosarcomas. Additionally, we expect less toxicity in the carbon ion treatment arm.ClinicalTrials.gov identifier: NCT01182753Low and intermediate grade chondrosarcomas (9-13% of all malignant bone tumours) are relative rare bone tumours. In 5-12% of all cases the chondrosarcomas are localized in head-and-neck region [1]. The typical sites of skull base lesions are temporo-occipital junction, parasellar area, spheno-ethmoid region and clivus [2,3]. Due to hystopathological type chondrosarcomas are divided into Grade 1 to 3 tumours according to mitotic rates (WHO classification) with 3 histological subgroups: classic, mesenchymal and myxoid [2]. The mesenchymal type has
Monitoring of patients treated with particle therapy using positron-emission-tomography (PET): the MIRANDA study
Stephanie E Combs, Julia Bauer, Daniel Unholtz, Christopher Kurz, Thomas Welzel, Daniel Habermehl, Thomas Haberer, Jürgen Debus, Katia Parodi
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-133
Abstract: A total of 240 patients will be recruited, evenly sampled among different analysis groups including tumors of the brain, skull base, head and neck region, upper gastrointestinal tract including the liver, lower gastrointestinal tract, prostate and pelvic region. From the comparison of the measured activity with the planned dose and its corresponding simulated activity distribution, conclusions on the delivered treatment will be inferred and, in case of significant deviations, correction strategies will be elaborated.The investigated patients are expected to benefit from this study, since in case of detected deviations between planned and actual treatment delivery a proper intervention (e.g., correction) could be performed in a subsequent irradiation fraction. In this way, an overall better treatment could be achieved than without any in-vivo verification. Moreover, site-specific patient-population information on the precision of the ion range at HIT might enable improvement of the CT-range calibration curve as well as safe reduction of the treatment margins to promote enhanced treatment plan conformality and dose escalation for full clinical exploitation of the promises of ion beam therapy.NCT01528670In comparison to conventional external beam radiotherapy with photon and electron radiation, ion therapy may offer superior conformation of the dose delivery to the tumour, with improved sparing of the surrounding healthy tissue and critical organs. This is mainly due to the favourable energy deposition, which can be concentrated in a few millimeters narrow region (the Bragg-peak) at an adjustable depth [1]. However, exploitation of this selectivity to its full extent in the clinical practice is still hampered by uncertainties in the knowledge of the beam range in the patient, resulting in the usage of generous safety margins as well as avoidance of beam portals stopping directly in front of critical organs. In fact, the complete stopping of the primary ion beam in the
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