Alexandra D. Jensen

Helical Tomotherapy as a New Treatment Technique for Whole Abdominal Irradiation

Purpose:To describe a new intensity-modulated radiotherapy (IMRT) technique using helical tomotherapy for whole abdominal irradiation (WAI) in patients with advanced ovarian cancer.Material and Methods:A patient with radically operated ovarian cancer FIGO stage IIIc was treated in a prospective clinical trial with WAI to a total dose of 30 Gy in 1.5-Gy fractions as an additional therapy after adjuvant platinum-based chemotherapy. The planning target volume (PTV) included the entire peritoneal cavity. PTV was adapted according to breathing motion as detected in a four-dimensional respiratory-triggered computed tomography (4D-CT). Inverse treatment planning was done with the Hi-Art tomotherapy planning station. Organs at risk (OARs) were kidneys, liver, bone marrow, spinal cord, thoracic and lumbosacral vertebral bodies, and pelvic bones. Daily control of positioning accuracy was performed with megavoltage computed tomography (MV-CT).Results:Helical tomotherapy enabled a very homogeneous dose distribution with excellent sparing of OARs and coverage of the PTV (V90 of 93.1%, V95 of 86.9%, V105 of 1.9%, and V110 of 0.01%). Mean liver dose was 21.57 Gy and mean kidney doses were 9.75 Gy and 9.14 Gy, respectively. Treatment could be performed in 18.1 min daily and no severe side effects occurred.Conclusion:Helical tomotherapy is feasible and fast for WAI. Tomotherapy enabled excellent coverage of the PTV and effective sparing of liver, kidneys and bone marrow.Ziel:Beschreibung der ersten klinischen Erfahrungen mit einer helikalen Tomotherapie als neuartiges Therapieverfahren für eine intensitätsmodulierte Ganzabdomenbestrahlung in der adjuvanten Therapie des fortgeschrittenen Ovarialkarzinoms.Material und Methodik:Eine Patientin mit Ovarialkarzinom im Stadium FIGO IIIc wurde im Rahmen einer prospektiven klinischen Studie nach radikaler Operation und sechs Zyklen adjuvanter platinhaltiger Chemotherapie zusätzlich mit einer Ganzabdomenbestrahlung mittels helikaler Tomotherapie behandelt. Die Gesamtdosis betrug 30 Gy mit einer wöchentlichen Fraktionierung von 5 × 1,5 Gy. Das Planungszielvolumen (PTV) umfasste die gesamte Peritonealhöhle unter Einschluss der paraaortalen und pelvinen Lymphabflusswege. Das Ausmaß des Zielvolumens wurde der Atembewegung auf Basis einer atemgetriggerten vierdimensionalen Computertomographie (4D-CT) angepasst. Es wurde mit dem Hi-Art-tomotherapy-Planungssystem invers geplant. Als Risikoorgane wurden Nieren, Leber, Rückenmark, Brustwirbelsäule, Lendenwirbelsäule und knöchernes Becken definiert. Die korrekte Patientenpositionierung wurde mittels Megavolt-Computertomographie (MV-CT) täglich kontrolliert.Ergebnisse:Mittels helikaler Tomotherapie konnten eine homogene Dosisverteilung, eine exzellente Schonung der Risikoorgane sowie eine ausgezeichnete Erfassung des PTV erreicht werden (V90: 93,1%, V95: 86,9%, V105: 1,9%, V110: 0,01%). Die mediane Dosis an der Leber betrug 21,57 Gy und an den Nieren jeweils 9,75 Gy und 9,14 Gy. Die tägliche Bestrahlungsdauer lag bei 18,1 min. Es traten keine schweren Nebenwirkungen CTC (Common Toxicity Criteria) Grad 3 oder 4 auf.Schlussfolgerung:Die Ganzabdomenbestrahlung mittels helikaler Tomotherapie ist machbar und in der klinischen Routine einsetzbar. Mit der helikalen Tomotherapie konnte eine exzellente Erfassung des PTV bei gleichzeitig sehr guter Schonung von Leber, Nieren und Knochenmark erreicht werden.

Highly effective treatment of skull base chordoma with carbon ion irradiation using a raster scan technique in 155 patients: first long-term results.

The current study was conducted to evaluate the long‐term results of irradiation with carbon ions in a raster scanning technique in patients with skull base chordomas.

Combined treatment of nonsmall cell lung cancer NSCLC stage III with intensity‐modulated RT radiotherapy and cetuximab

The aim of this study was to evaluate efficacy and toxicity of radioimmunotherapy with intensity‐modulated radiation (IMRT) and cetuximab in stage III nonsmall cell lung cancer (NSCLC).

Randomised trial of proton vs. carbon ion radiation therapy in patients with chordoma of the skull base, clinical phase III study HIT-1-Study

BackgroundChordomas of the skull base are relative rare lesions of the bones. Surgical resection is the primary treatment standard, though complete resection is nearly impossible due to close proximity to critical and hence also dose limiting organs for radiation therapy. Level of recurrence after surgery alone is comparatively high, so adjuvant radiation therapy is very important for the improvement of local control rates. Proton therapy is the gold standard in the treatment of skull base chordomas. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors.Methods/designThis clinical study is a prospective randomised phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie centre (HIT) and is a monocentric study.Patients with skull base chordoma will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume delineation will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV in carbon ion treatment (accelerated dose) will be 63 Gy E ± 5% and 72 Gy E ± 5% (standard dose) in proton therapy respectively. Local-progression free survival (LPFS) will be analysed as primary end point. Toxicity and overall survival are the secondary end points. Additional examined parameters are patterns of recurrence, prognostic factors and plan quality analysis.DiscussionUp until now it was impossible to compare two different particle therapies, i.e. protons and carbon ions directly at the same facility.The aim of this study is to find out, whether the biological advantages of carbon ion therapy can also be clinically confirmed and translated into the better local control rates in the treatment of skull base chordomas.Trial registrationClinicalTrials.gov identifier: NCT01182779

Application of constant vs. variable relative biological effectiveness in treatment planning of intensity-modulated proton therapy.

PURPOSE To investigate in a simulation study whether using a variable relative biological effectiveness (RBE) in calculation and optimization of intensity-modulated proton therapy (IMPT) instead of using an RBE of 1.1 would result in significant changes in the RBE-weighted dose (RWD) distributions. METHODS AND MATERIALS For 4 patients with head-and-neck tumors, three IMPT plans were prepared respectively. The first plan was physically optimized (IMPT-PO plan), and the RWD was calculated with a constant RBE of 1.1. Then the plans RWD was recalculated (IMPT-R plan) using a variable RBE model taking into account the linear energy transfer (LET) and tissue-specific radiobiological parameters. The third IMPT plan was optimized using a biological optimization routine (IMPT-BO plan). RESULTS Comparing the IMPT-PO and IMPT-R plans, we observed that the RWD in radioresistant tissues was more sensitive to the LET than in radiosensitive tissues. The IMPT-R plans were in general more inhomogeneous than the IMPT-PO plans. The differences of RWD distributions for all volumes between IMPT-PO and IMPT-BO plans complied with predefined dose-volume constraints. The average LET was significantly lower in IMPT-BO plans than in IMPT-R plans. CONCLUSION In radioresistant normal tissues caution has to be used regarding the LET distribution because these are most sensitive to changes in the LET. Biological optimization of IMPT plans based on the organ-specific biological parameters and LET distributions is feasible.

Heidelberg Ion Therapy Center (HIT): Initial clinical experience in the first 80 patients.

Abstract The Heidelberg Ion Therapy Center (HIT) started clinical operation in November 2009. In this report we present the first 80 patients treated with proton and carbon ion radiotherapy and describe patient selection, treatment planning and daily treatment for different indications. Patients and methods. Between November 15, 2009 and April 15, 2010, 80 patients were treated at the Heidelberg Ion Therapy Center (HIT) with carbon ion and proton radiotherapy. Main treated indications consisted of skull base chordoma (n = 9) and chondrosarcoma (n = 18), malignant salivary gland tumors (n=29), chordomas of the sacrum (n = 5), low grade glioma (n=3), primary and recurrent malignant astrocytoma and glioblastoma (n=7) and well as osteosarcoma (n = 3). Of these patients, four pediatric patients aged under 18 years were treated. Results. All patients were treated using the intensity-modulated rasterscanning technique. Seventy six patients were treated with carbon ions (95%), and four patients were treated with protons. In all patients x-ray imaging was performed prior to each fraction. Treatment concepts were based on the initial experiences with carbon ion therapy at the Gesellschaft für Schwerionenforschung (GSI) including carbon-only treatments and carbon-boost treatments with photon-IMRT. The average time per fraction in the treatment room per patient was 29 minutes; for irradiation only, the mean time including all patients was 16 minutes. Position verification was performed prior to every treatment fraction with orthogonal x-ray imaging. Conclusion. Particle therapy could be included successfully into the clinical routine at the Department of Radiation Oncology in Heidelberg. Numerous clinical trials will subsequently be initiated to precisely define the role of proton and carbon ion radiotherapy in radiation oncology.

High control rate in patients with chondrosarcoma of the skull base after carbon ion therapy: first report of long-term results.

The current study was performed to evaluate the safety and effectiveness of irradiation with carbon ions using raster scanning as well as prognostic factors in patients with skull base chondrosarcomas.

Prediction of treatment response in head and neck carcinomas using IVIM-DWI: Evaluation of lymph node metastasis.

PURPOSE To obtain diffusion and microperfusion measures in lymph node metastases of head and neck squamous cell carcinomas (HNSCC) using intravoxel incoherent motion (IVIM) imaging. The obtained IVIM parameters were used to characterize lymph nodes in the staging phase and longitudinal follow-up was performed to evaluate the potential predictive value of these parameters considering therapy response. METHODS Fifteen patients with lymph node metastases of histologically confirmed locally advanced HNSCC were examined using diffusion weighted imaging (DWI) before a nonsurgical organ preserving therapy. DWI imaging was performed at 3T using eight different b-values ranging from 0 to 800s/mm(2). Using the IVIM-approach, the perfusion fraction f and the diffusion coefficient D were extracted using a biexponential fit. A follow-up period of 13.5 months was available for all patients. One patient with a macroscopically necrotic lymph node was excluded from analyses. A region of interest (ROI)-analysis was performed in all patients. RESULTS Locoregional failure (LRF) was present in 3 of 15 patients within 13.5 months follow-up. The initial f-value was significantly higher (p=0.01) in patients with LRF (14.5±0.6% vs. 7.7±2.6%) compared to patients with locoregional control (LRC). The initial diffusion coefficient D did not differ significantly (p=0.30) between the two groups (0.97±0.15×10(-3)mm(2)/s vs. 0.88±0.13×10(-3)mm(2)/s). CONCLUSIONS Our results indicate that a high initial perfusion fraction f in lymph nodes may predict poor treatment response in patients with HNSCC due to locoregional failure.

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

BackgroundLow and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours.Methods/DesignThe 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.DiscussionUp 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.Trial RegistrationClinicalTrials.gov identifier: NCT01182753

Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518)

BackgroundEven today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone.Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment.It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux®) which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects.Methods/designThe NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combinations efficacy and rate of development of distant metastases with an accrual of 30 patients.Patients receive weekly infusions of cetuximab (Erbitux®) plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles.DiscussionThe primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux®) and IMRT loco-regional irradiation.Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival.