Richard Poetter

Development and application of a real-time monitoring and feedback system for deep inspiration breath hold based on external marker tracking

Respiration can cause tumor movements in thoracic regions of up to 3 cm. To minimize motion effects several approaches, such as gating and deep inspiration breath hold (DIBH), are still under development. The goal of our study was to develop and evaluate a noninvasive system for gated DIBH (GDIBH) based on external markers. DIBH monitoring was based on an infrared tracking system and an in-house-developed software. The in-house software provided the breathing curve in real time and was used as on-line information for a prototype of a feedback device. Reproducibility and stability of the breath holds were evaluated without and with feedback. Thirty-five patients undergoing stereotactic body radiotherapy (SBRT) performed DIBH maneuvers after each treatment. For 16 patients dynamic imaging sequences on a multislice CT were used to determine the correlation between tumor and external markers. The relative reproducibility of DIBH maneuvers was improved with the feedback device (74.5% +/- 17.1% without versus 93.0% +/- 4.4% with feedback). The correlation between tumor and marker was good (Pearson correlation coefficient 0.83 +/- 0.17). The regression slopes showed great intersubject variability but on average the internal margin in a DIBH treatment situation could be theoretically reduced by 3 mm with the feedback device. DIBH monitoring could be realized in a noninvasive manner through external marker tracking. We conclude that reduction of internal margins can be achieved with a feedback system but should be performed with great care due to the individual behavior of target motion.

Local Tumor Control, Visual Acuity, and Survival After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

PURPOSE To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. METHODS AND MATERIALS Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. RESULTS Median tumor height and volume decreased from 4.8 mm and 270.7 mm3 at baseline to 2.6 mm and 86.6 mm3 at the last individual follow-up, respectively (p<0.001, p<0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p<0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. CONCLUSION Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the total dose below 60 Gy seems to be possible.

Image quality and stability of image-guided radiotherapy (IGRT) devices: A comparative study

INTRODUCTION Our aim was to implement standards for quality assurance of IGRT devices used in our department and to compare their performances with that of a CT simulator. MATERIALS AND METHODS We investigated image quality parameters for three devices over a period of 16months. A multislice CT was used as a benchmark and results related to noise, spatial resolution, low contrast visibility (LCV) and uniformity were compared with a cone beam CT (CBCT) at a linac and simulator. RESULTS All devices performed well in terms of LCV and, in fact, exceeded vendor specifications. MTF was comparable between CT and linac CBCT. Integral nonuniformity was, on average, 0.002 for the CT and 0.006 for the linac CBCT. Uniformity, LCV and MTF varied depending on the protocols used for the linac CBCT. Contrast-to-noise ratio was an average of 51% higher for the CT than for the linac and simulator CBCT. No significant time trend was observed and tolerance limits were implemented. DISCUSSION Reasonable differences in image quality between CT and CBCT were observed. Further research and development are necessary to increase image quality of commercially available CBCT devices in order for them to serve the needs for adaptive and/or online planning.

Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

PURPOSE To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. PATIENTS AND METHODS Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. RESULTS One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. CONCLUSION In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

Multiparametric [18F]Fluorodeoxyglucose/ [18F]Fluoromisonidazole Positron Emission Tomography/ Magnetic Resonance Imaging of Locally Advanced Cervical Cancer for the Non-Invasive Detection of Tumor Heterogeneity: A Pilot Study

Objectives To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT). Materials and Methods Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis. Results All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05–0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity. Conclusion MP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT.

Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy – Clinical results after six years of experience

PURPOSE To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. MATERIALS AND METHODS Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2-49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. RESULTS Initial tumor base diameters, height and volume were 11.20mm (IQR 9.10-13.70), 9.80 mm (IQR 7.80-11.70), 4.53 mm (IQR 3.33-6.43) and 253.8mm(3) (IQR 127.5-477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p<0.001). The most common toxicities (any grade) were radiation retinopathy (n=39), optic neuropathy (n=32), radiogenic cataract (n=21), neovascular glaucoma (n=15) and dry eye syndrome (n=10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. CONCLUSION Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile.

Factors influencing the time to development of brain metastases in breast cancer

This retrospective study analyzed risk factors influencing the time to development of brain metastases with the aim to facilitate the definition of a high-risk population among breast cancer patients. One hundred seventy-four breast cancer patients with brain metastases, treated with whole brain radiotherapy, were evaluated. Statistical analysis included hormone receptor status, HER2/neu status, tumour grading, tumour stage, young age at the time of diagnosis, adjuvant systemic treatment, palliative systemic treatment, metastatic sites (if brain metastases were not the first site of recurrence), and immunotherapy with trastuzumab. Time to development of brain metastases was significantly prolonged by systemic palliative treatment (p< or =0.0001) whereas high tumour grading (p< or =0.04) and trastuzumab therapy (p< or =0.04) significantly shortened this time span. Patients with the brain as first metastatic site, age>35 (p< or =0.001) and stage III (p< or =0.018) at the time of diagnosis had a significantly shorter time to development for brain lesions. These factors should be further validated by a prospective trial to identify a high-risk population amongst breast cancer patients and enable the development of screening programs for early detection.

ENLIGHT: European network for Light ion hadron therapy

The European Network for Light Ion Hadron Therapy (ENLIGHT) was established in 2002 following various European particle therapy network initiatives during the 1980s and 1990s (e.g. EORTC task group, EULIMA/PIMMS accelerator design). ENLIGHT started its work on major topics related to hadron therapy (HT), such as patient selection, clinical trials, technology, radiobiology, imaging and health economics. It was initiated through CERN and ESTRO and dealt with various disciplines such as (medical) physics and engineering, radiation biology and radiation oncology. ENLIGHT was funded until 2005 through the EC FP5 programme. A regular annual meeting structure was started in 2002 and continues until today bringing together the various disciplines and projects and institutions in the field of HT at different European places for regular exchange of information on best practices and research and development. Starting in 2006 ENLIGHT coordination was continued through CERN in collaboration with ESTRO and other partners involved in HT. Major projects within the EC FP7 programme (2008-2014) were launched for R&D and transnational access (ULICE, ENVISION) and education and training networks (Marie Curie ITNs: PARTNER, ENTERVISION). These projects were instrumental for the strengthening of the field of hadron therapy. With the start of 4 European carbon ion and proton centres and the upcoming numerous European proton therapy centres, the future scope of ENLIGHT will focus on strengthening current and developing European particle therapy research, multidisciplinary education and training and general R&D in technology and biology with annual meetings and a continuously strong CERN support. Collaboration with the European Particle Therapy Network (EPTN) and other similar networks will be pursued.

Partial breast irradiation with 192-iridium implants after breast conserving surgery: perioperative morbidity, toxicity and cosmetic results

groups. The mean maximal skin doses per fraction in the excellent and good outcome groups were 354.8 cGy vs. 422.3 cGy (p .286). Infection occurred in 13.3% of the patients (4/30). Systemic chemotherapy was used in 25% of the patients (1/4) who developed an infection and in 30.8% of the patients (8/26) who did not develop an infection. The mean TL of those patients who developed an infection was 8.50 cm vs. 8.16 cm (p .625) in those patients who did not develop an infection.