Swantje Ecker

Evaluation of different fiducial markers for image-guided radiotherapy and particle therapy

Modern radiotherapy (RT) techniques are widely used in the irradiation of moving organs. A crucial step in ensuring the correct position of a target structure directly before or during treatment is daily image guidance by computed tomography (CT) or X-ray radiography (image-guided radiotherapy, IGRT). Therefore, combinations of modern irradiation devices and imaging, such as on-board imaging (OBI) with X-rays, or in-room CT such as the tomotherapy system, have been developed. Moreover, combinations of linear accelerators and in-room CT-scanners have been designed. IGRT is of special interest in hypofractionated and radiosurgical treatments where high single doses are applied in the proximity of critical organs at risk. Radiographically visible markers in or in close proximity to the target structure may help to reproduce the position during RT and could therefore be used as external surrogates for motion monitoring. Criteria sought for fiducial markers are (i) visibility in the radiologic modalities involved in radiotherapeutic treatment planning and image guidance, such as CT and kilovoltage (kV) OBI), (ii) low production of imaging artifacts, and (iii) low perturbation of the therapeutic dose to the target volume. Photon interaction with interstitial markers has been shown to be not as important as in particle therapy, where interaction of the particle beam, especially with metal markers, can have a significant impact on treatment. This applies especially with a scanned ion beam. Recently we commenced patient recruitment at our institution within the PROMETHEUS trial, which evaluates a hypofractionation regime, starting with 4 x 10 Gy (RBE), for patients with hepatocellular carcinoma. The aim of this work is, therefore, to evaluate potential implantable fiducial markers for enabling precise patient and thus organ positioning in scanned ion beams. To transfer existing knowledge of marker application from photon to particle therapy, we used a range of commercially available markers of different forms and sizes, consisting of carbon and gold materials, and evaluated them for their potential use in the clinical setup with scanned ion beams at our institution. All markers were implanted in a standardized Alderson phantom and were examined using CT scans and orthogonal kV OBI in our clinical routine protocol. Impact on beam perturbation downstream of the markers in the plateau region of a spread-out Bragg peak (SOBP) was estimated by using radiographic films for clinical proton and carbon ion beams of high and low energies. All tested markers achieved good visibility in CT and kV OBI. Disturbances due to artifacts and dose perturbation were highest in the arbitrarily folded gold and the thickest gold marker, but especially low in the carbon marker. Dose perturbation was highest in the arbitrarily folded gold marker. In summary, the analyzed markers offer promising potential for identifying target structures in our treatment setup at HIT and will soon be used in clinical routine. However, a careful choice of marker, depending on the tumor localization and irradiation strategy, will need to be made.

Treatment of pediatric patients and young adults with particle therapy at the Heidelberg Ion Therapy Center (HIT): establishment of workflow and initial clinical data

BackgroundTo report on establishment of workflow and clinical results of particle therapy at the Heidelberg Ion Therapy Center.Materials and methodsWe 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.ResultsTreatment 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.ConclusionClinical 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.

First experiences in treatment of low-grade glioma grade I and II with proton therapy.

BackgroundTo retrospectively assess feasibility and toxicity of proton therapy in patients with low-grade glioma (WHO °I/II).Patients and methodsProton beam therapy only administered in 19 patients (median age 29 years; 9 female, 10 male) for low-grade glioma between 2010 and 2011 was reviewed. In 6 cases proton therapy was performed due to tumor progression after biopsy, in 8 cases each due to tumor progression after (partial-) resection, and in 5 cases due to tumor progression after chemotherapy. Median total dose applied was 54 GyE (range, 48,6-54 GyE) in single fractions of median 1.8 GyE. Median clinical target volume was 99 cc (range, 6–463 cc) and treated using median 2 beams (range, 1–2).ResultsProton therapy was finished as planned in all cases. At end of proton therapy, 13 patients showed focal alopecia, 6 patients reported mild fatigue, one patient with temporal tumor localization concentration deficits and speech errors and one more patient deficits in short-term memory. Four patients did not report any side effects. During follow-up, one patient presented with pseudo-progression showing worsening of general condition and brain edema 1–2 months after last irradiation and restitution after 6 months. In the present MR imaging (median follow-up 5 months; range 0–22 months) 12 patients had stable disease, 2 (1) patients partial (complete) remission, one more patient pseudo-progression (differential diagnosis: tumor progression) 4 weeks after irradiation without having had further follow-up imaging so far, and one patient tumor progression approximately 9 months after irradiation.ConclusionRegarding early side effects, mild alopecia was the predominant finding. The rate of alopecia seems to be due to large treatment volumes as well as the anatomical locations of the target volumes and might be avoided by using multiple beams and the gantry in the future. Further evaluations including neuropsychological testing are in preparation.

Integration and evaluation of automated Monte Carlo simulations in the clinical practice of scanned proton and carbon ion beam therapy

Monte Carlo (MC) simulations of beam interaction and transport in matter are increasingly considered as essential tools to support several aspects of radiation therapy. Despite the vast application of MC to photon therapy and scattered proton therapy, clinical experience in scanned ion beam therapy is still scarce. This is especially the case for ions heavier than protons, which pose additional issues like nuclear fragmentation and varying biological effectiveness. In this work, we present the evaluation of a dedicated framework which has been developed at the Heidelberg Ion Beam Therapy Center to provide automated FLUKA MC simulations of clinical patient treatments with scanned proton and carbon ion beams. Investigations on the number of transported primaries and the dimension of the geometry and scoring grids have been performed for a representative class of patient cases in order to provide recommendations on the simulation settings, showing that recommendations derived from the experience in proton therapy cannot be directly translated to the case of carbon ion beams. The MC results with the optimized settings have been compared to the calculations of the analytical treatment planning system (TPS), showing that regardless of the consistency of the two systems (in terms of beam model in water and range calculation in different materials) relevant differences can be found in dosimetric quantities and range, especially in the case of heterogeneous and deep seated treatment sites depending on the ion beam species and energies, homogeneity of the traversed tissue and size of the treated volume. The analysis of typical TPS speed-up approximations highlighted effects which deserve accurate treatment, in contrast to adequate beam model simplifications for scanned ion beam therapy. In terms of biological dose calculations, the investigation of the mixed field components in realistic anatomical situations confirmed the findings of previous groups so far reported only in homogenous water targets. This work can thus be useful to other centers commencing clinical experience in scanned ion beam therapy.

Re-irradiation with scanned charged particle beams in recurrent tumours of the head and neck: acute toxicity and feasibility.

BACKGROUND Treatment of surgically unresectable recurrence in the head and neck region remains a therapeutic problem with the only curative option being a second course of radiation with a tumouricidal dose. We report initial toxicity and efficacy of charged particle therapy in this situation. METHODS Treatment-related side-effects of patients treated with charged particle beams for recurrent tumours of the head and neck were prospectively collected and patient data was retrospectively analysed with regard to toxicity and efficacy of the treatment according to CTCAE v. 4.03 and RECIST. RESULTS Treatment was tolerated well without any severe acute toxicity. In non-chordoma/chondrosarcoma patients, overall response rate was 53.3% at 8 weeks post RT. 4/5 chordoma/chondrosarcoma patients showed no signs of further tumour progression. CONCLUSION Initial experience of re-irradiation with scanned particle beams in recurrent tumours of the head and neck seems feasible and encouraging. Further follow-up is needed to investigate potential late effects.

Carbon ion therapy for ameloblastic carcinoma

Ameloblastic carcinomas are rare odontogenic tumors. Treatment usually consists of surgical resection and sometimes adjuvant radiation. We report the case of a 71 year-old male patient undergoing carbon ion therapy for extensive local relapse of ameloblastic carcinoma. Treatment outcome was favourable with a complete remission at 6 weeks post completion of radiotherapy while RT-treatment itself was tolerated well with only mild side effects. High dose radiation hence is a potential alternative for patients unfit or unwilling to undergo extensive surgery or in cases when only a subtotal resection is planned or the resection is mutilating.

Comparison of intensity modulated radiotherapy (IMRT) with intensity modulated particle therapy (IMPT) using fixed beams or an ion gantry for the treatment of patients with skull base meningiomas.

BackgroundTo examine the potential improvement in treatment planning for patients with skull base meningioma using IMRT compared to carbon ion or proton beams with and without a gantry.MethodsFive patients originally treated with photon IMRT were selected for the study. Ion beams were chosen using a horizontal beam or an ion gantry. Intensity controlled raster scanning and the intensity modulated particle therapy mode were used for plan optimization. The evaluation included analysis of dose-volume histograms of the target volumes and organs at risk.ResultsIn comparison with carbon and proton beams only with horizontal beams, carbon ion treatment plans could spare the OARs more and concentrated on the target volumes more than proton and photon IMRT treatment plans. Using only a horizontal fixed beam, satisfactory plans could be achieved for skull base tumors.ConclusionThe results of the case studies showed that using IMPT has the potential to overcome the lack of a gantry for skull base tumors. Carbon ion plans offered slightly better dose distributions than proton plans, but the differences were not clinically significant with established dose prescription concepts.

Raster-scanned carbon ion therapy for malignant salivary gland tumors: acute toxicity and initial treatment response

Background and purposeTo investigate toxicity and efficacy in high-risk malignant salivary gland tumors (MSGT) of the head and neck. Local control in R2-resected adenoid cystic carcinoma was already improved with a combination of IMRT and carbon ion boost at only mild side-effects, hence this treatment was also offered to patients with MSGT and microscopic residual disease (R1) or perineural spread (Pn+).MethodsFrom November 2009, all patients with MSGT treated with carbon ion therapy were evaluated. Acute side effects were scored according to CTCAE v.4.03. Tumor response was assessed according to RECIST where applicable.Results103 patients were treated from 11/2009 to 03/2011, median follow-up is 6 months. 60 pts received treatment following R2 resections or as definitive radiation, 43 patients received adjuvant radiation for R1 and/or Pn+. 16 patients received carbon ion treatment for re-irradiation. Median total dose was 73.2 GyE (23.9 GyE carbon ions + 49,9 Gy IMRT) for primary treatment and 44.9 GyE carbon ions for re-irradiation. All treatments were completed as planned and generally well tolerated with no > CTC°III toxicity. Rates of CTC°III toxicity (mucositis and dysphagia) were 8.7% with side-effects almost completely resolved at first follow-up.47 patients showed good treatment responses (CR/PR) according to RECIST.ConclusionAcute toxicity remains low in IMRT with carbon ion boost also in R1-resected patients and patients undergoing re-irradiation. R2-resected patients showed high rates of treatment response, though follow-up is too short to assess long-term disease control.

Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity

PurposeTo evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects.MethodsTwenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST.ResultsSeventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc), mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia) but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR).ConclusionCarbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted.

Dosimetry auditing procedure with alanine dosimeters for light ion beam therapy

BACKGROUND AND PURPOSE In the next few years the number of facilities providing ion beam therapy with scanning beams will increase. An auditing process based on an end-to-end test (including CT imaging, planning and dose delivery) could help new ion therapy centres to validate their entire logistic chain of radiation delivery. An end-to-end procedure was designed and tested in both scanned proton and carbon ion beams, which may also serve as a dosimetric credentialing procedure for clinical trials in the future. The developed procedure is focused only on physical dose delivery and the validation of the biological dose is out of scope of the current work. MATERIALS AND METHODS The audit procedure was based on a homogeneous phantom that mimics the dimension of a head (20 × 20 × 21 cm(3)). The phantom can be loaded either with an ionisation chamber or 20 alanine dosimeters plus 2 radiochromic EBT films. Dose verification aimed at measuring a dose of 10Gy homogeneously delivered to a virtual-target volume of 8 × 8 × 12 cm(3). In order to interpret the readout of the irradiated alanine dosimeters additional Monte Carlo simulations were performed to calculate the energy dependent detector response of the particle fluence in the alanine detector. A pilot run was performed with protons and carbon ions at the Heidelberg Ion Therapy facility (HIT). RESULTS The mean difference of the absolute physical dose measured with the alanine dosimeters compared with the expected dose from the treatment planning system was -2.4 ± 0.9% (1σ) for protons and -2.2 ± 1.1% (1σ) for carbon ions. The measurements performed with the ionisation chamber indicate this slight underdosage with a dose difference of -1.7% for protons and -1.0% for carbon ions. The profiles measured by radiochromic films showed an acceptable homogeneity of about 3%. CONCLUSIONS Alanine dosimeters are suitable detectors for dosimetry audits in ion beam therapy and the presented end-to-end test is feasible. If further studies show similar results, this dosimetric audit could be implemented as a credentialing procedure for clinical proton and carbon beam delivery.