Biomedical subjects

Gudrun Goitein

Publications and source records attributed to Gudrun Goitein.

12 recordsLinked to original sources

PubMed2006

Extracranial chordoma: Outcome in patients treated with function-preserving surgery followed by spot-scanning proton beam irradiation.

PURPOSE: To evaluate the use of postoperative proton therapy (PT) in extracranial chordoma. PATIENTS AND METHODS: Twenty-six patients were treated. Gross total resection was achieved in 18 patients. Nine patients had cervical, 2 had thoracic, 8 had lumbar, and 7 had sacro-coccygeal chordomas. Thirteen patients had implants. PT was administered after function-preserving surgery, using a gantry and spot scanning, without or with intensity modulation (IMPT; 6 patients), and/or photon-based radiotherapy (RT, 6 patients). Median total dose was 72 cobalt Gray equivalent (CGE; range, 59.4-74.4), with means of 70.5 and 73.2 CGE for patients with and without implants. Median follow-up time was 35 months (range, 13-73 months). Adverse events were scored using the Common Terminology Criteria for Adverse Events grading system (version 3.0). RESULTS: At 3 years, actuarial overall survival (OS) and progression-free survival (PFS) rates were 84% and 77%, respectively. One patient each died of local failure (LF), distant failure (DF), suicide, and secondary tumor. We observed 5 LFs and 3 DFs; 3-year LF-free and DF-free survival rates were 86%. We observed four radiation-induced late adverse events (Grade 2 sensory neuropathy; Grade 3 subcutaneous necrosis, and osteonecrosis; and Grade 5 secondary cancer). In univariate analysis, implants were associated with LF (p = 0.034). Gross residual tumor above 30 mL was negatively associated with OS (p = 0.013) and PFS (p = 0.025). CONCLUSIONS: Postoperative PT for extracranial chordomas delivered with spot scanning offers high local control rates. Toxicity was acceptable. Implants were significantly associated with LF. Residual tumor above 30 mL impacted negatively on OS and PFS.

Adolescent↗

PubMed2006

Spot-scanning proton therapy for malignant soft tissue tumors in childhood: First experiences at the Paul Scherrer Institute.

PURPOSE: Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. METHODS AND MATERIALS: Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III in 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). RESULTS: After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. CONCLUSIONS: Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed.

Adolescent↗

PubMed2006

["Spot-scanning" proton therapy for rhabdomyosarcomas of early childhood. First experiences at PSI].

PURPOSE: To evaluate the feasibility and acute toxicity of spot-scanning proton therapy under deep sedation in young children with rhabdomyosarcomas (RMS). PATIENTS AND METHODS: Since 2004, children requiring sedation can be admitted for proton therapy at Paul Scherrer Institute (PSI), Villigen, Switzerland. Children under 5 years of age with RMS of the head and the trunk were analyzed. All children were enrolled in a multidisciplinary treatment protocol and prospective, standardized evaluation of side effects was performed. RESULTS: Nine children were included aged 0.9-3.8 years (embryonal RMS in six, and alveolar, undifferentiated or nonclassified in one each). The tumor site was parameningeal (n = 4), orbital (n = 3), head and neck (n = 1), and prostate (n = 1). All children were in IRS group III. Total proton dose was 46-54 CGE (cobalt-gray equivalent). Only the myelotoxicity exceeded grade 3 or 4 (RTOG/EORTC). CONCLUSION: Proton therapy for RMS in early children is feasible and well tolerated. The prospective standardized evaluation of toxicity and quality of life needs to be continued.

Adolescent↗

PubMed2005

Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study.

PURPOSE: A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). METHOD AND MATERIALS: A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. RESULTS: Target coverage of all simulated uveal melanomas was equally conformal with the photon and proton modalities. The median CI(95%) value was 1.74, 1.86, and 1.83 for the static, dynamic, and IMSRT plans, respectively. With proton planning, the median CI(95%) was 1.88 for OPTIS and substantially improved with IMPT in some tumor cases (median CI(95%), 1.29). The tumor dose homogeneity in the proton plans was, however, always better than with SRT photon planning (median inhomogeneity coefficient 0.1 and 0.15 vs. 0.46, 0.41, and 0.23 for the OPTIS and IMPT vs. the static, dynamic, and IMSRT plans, respectively). Compared with the photon plans, the use of protons did not lead to a substantial reduction in the homolateral OAR total integral dose in the low- to high-dose level, except for the lacrimal gland. The median maximal dose and dose at the 10% volume with the static, dynamic, and IMSRT plans was 33-30.8, 31.8-28, and 35.8-49 Gy, respectively, for the lacrimal gland, a critical organ. For protons, only the OPTIS plans were better, with a median maximal dose and dose at the 10% volume using OPTIS and IMPT of 19.2 and 8.8 and 25.6 and 23.6 CGE, respectively. The contralateral OARs were completely spared with the proton plans, but the median dose delivered to these structures was 1.2 Gy (range, 0-6.3 Gy) with the SRT photon plans. CONCLUSION: These results suggest that the use of SRT photon techniques, compared with protons, can result in similar levels of dose conformation. IMPT did not increase the degree of conformality for this small tumor. Tumor dose inhomogeneity was, however, always increased with photon planning. Except for the lacrimal gland, the use of protons, with or without intensity modulation, did not increase homolateral OAR dose sparing. The dose to all the contralateral OARs was, however, completely eliminated with proton planning.

Brain Neoplasms↗

PubMed2005

Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience.

PURPOSE: To assess the clinical results of spot scanning proton beam radiation therapy (PT) in the treatment of skull base chordomas and low-grade chondrosarcomas (CS). METHODS AND MATERIALS: Between October 1998 and October 2003, 29 patients (median age, 39 years) with chordomas (n = 18) and CS (n = 11) were treated at the Paul Scherrer Institut (PSI) with protons using the main 510-MeV cyclotron. Tumor conformal application of proton beams was realized by spot scanning technology. The median chordoma and CS dose was 74 and 68 cobalt Gy equivalent, respectively (cobalt Gy equivalent = proton Gy x 1.1). Median gross tumor volumes (GTV) were 16.4 mL (range, 1.8-48.1 mL) and 15.2 mL (range, 2.3-57.3 mL) for chordoma and CS, respectively. Late toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v3.0) grading system. The median follow-up time was 29 months (range, 6-68 months). RESULTS: Actuarial 3-year local control rates were 87.5% and 100% for chordoma and CS, respectively. We observed one surgical pathway and one marginal failure in patients with chordomas. No regional failure or distant metastasis was observed. At 3 years, actuarial PFS and OS for the entire cohort was 90% and 93.8%, respectively. Actuarial 3-year complication-free survival was 82.2%. Radiation-induced pituitary dysfunction was observed in 4 (14%) patients (CTCAE Grade 2). No patient presented with post-PT brainstem or optic pathways necrosis or dysfunction. In univariate analysis, age < or =40 years at the time of PT affected favorably on PFS (p = 0.09). CONCLUSION: Spot-scanning PT offers high tumor control rates of skull base chordoma and CS. These results compare favorably to other combined proton-photon or carbon ion irradiation series. Observed toxicity was acceptable. Younger age (< or =40 years) was a favorable prognostic factor of PFS. These preliminary results are encouraging but should be confirmed during a longer follow-up.

Adult↗

PubMed2005

Relative biologic effectiveness determination in mouse intestine for scanning proton beam at Paul Scherrer Institute, Switzerland. Influence of motion.

PURPOSE: To determine the relative biologic effectiveness (RBE) of the Paul Scherrer Institute (PSI) scanning proton beam in reference conditions and to evaluate the influence of intestine motion on the proton dose homogeneity. METHODS AND MATERIALS: First, RBE was determined for crypt regeneration in mice after irradiation in a single fraction. Irradiation was performed at the middle of a 7-cm spread out Bragg peak (SOBP; reference position), as well as in the proximal part of the plateau and at the distal end of the SOBP. Control gamma-irradiation was randomized with proton irradiation and performed simultaneously. Second, motion of mouse intestine was determined by radiographs after copper wire markers had been placed on the jejunum and intestinal wall. RESULTS: Proton RBE (reference (60)Co gamma) was equal to 1.16 for irradiation at the middle of the SOBP and to 1.11 and 1.21 for irradiation in the initial plateau and end of the SOBP, respectively. The confidence intervals for these RBE values were much larger than those obtained in the other proton beams we have tested so far. They exceeded +/-0.20 (compared with the usual value of +/-0.07), which resulted from the unusually large dispersion of the individual proton data. The instantaneous positions of the mice intestines varied by +/-2 mm in the course of irradiation. CONCLUSION: The results of this study have shown that the RBE of the PSI proton beam is in total accordance with the RBE obtained at the other centers. This experiment has corroborated that proton RBE at the middle of the SOBP is slightly larger than the generic value of 1.10 and that there is a slight tendency for the RBE to increase close to the end of the SOBP. Also, excessive dispersion of individual proton data may be considered to result from intestine motion, taking into account that irradiation at the PSI is delivered dynamically by scanning the target volume with a pencil proton beam ("spot scanning"). Because 2-mm movements resulted in significant variations in local dose depositions, this should be considered for moving targets. Strategies to reduce this effect for the spot scanning technique have been developed at the PSI for radiotherapy of humans.

Animals↗

PubMed2005

Swedish protons.

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Humans↗

PubMed2004

Spot-scanning proton radiation therapy for recurrent, residual or untreated intracranial meningiomas.

BACKGROUND AND PURPOSE: To assess the safety and efficacy of spot scanning proton beam radiation therapy (PRT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS: Sixteen patients with intracranial meningioma (histopathologically proven in 13/16 cases) were treated with PRT between July 1997 and July 2002. Eight patients had skull base lesions. Thirteen patients received PRT after surgery either as adjuvant therapy for incomplete resection (eight patients) or for recurrence (five patients). Three patients received radical PRT after presumptive diagnosis based on imaging. The median prescribed dose was 56 CGE (range, 52.2-64, CGE=proton Gy X 1.1) at 1.8-2.0 CGE (median, 2.0) per fraction. Gross tumor volume and planning target volume ranged from 0.8 to 87.6 cc (median, 17.5) and 4.6-208.1 cc (median 107.7), respectively. Late ophthalmologic and non-ophthalmologic toxicity was assessed using the Subjective, Objective, Management and Analytic scale (SOMA) of the Late Effects of Normal Tissue scoring system and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v3.0) grading system, respectively. The median follow-up time was 34.1 months (range, 6.5-67.8). RESULTS: Cumulative 3-year local control, progression-free survival and overall survival were 91.7, 91.7 and 92.7%, respectively. No patient died from recurrent meningioma. One patient progressed locally after PRT. Radiographic follow-up (median, 34 months) revealed an objective response in three patients and stable disease in 12 patients. Cumulative 3-year toxicity free survival was 76.2%. One patient presented with radiation induced optic neuropathy (SOMA Grade 3) and retinopathy (SOMA Grade 2) 8.8 and 30.4 months after treatment, respectively. These patients with ophthalmologic toxicity received doses higher than those allowed for the optic/ocular structures. Another patient developed a symptomatic brain necrosis (CTCAE Grade 4) 7.2 months after treatment. No radiation-induced hypothalamic/pituitary dysfunction was observed. CONCLUSIONS: Spot-scanning PRT is an effective treatment for patient with untreated, recurrent or incompletely resected intracranial meningiomas. It offers highly conformal irradiation for complex-shaped intracranial meningiomas, while delivering minimal non-target dose. Observed ophthalmologic toxicity is dose-related.

Adolescent↗

PubMed2004

The PSI Gantry 2: a second generation proton scanning gantry.

PSI is still the only location in which proton therapy is applied using a dynamic beam scanning technique on a very compact gantry. Recently, this system is also being used for the application of intensity-modulated proton therapy (IMPT). This novel technical development and the success of the proton therapy project altogether have led PSI in Year 2000 to further expand the activities in this field by launching the project PROSCAN. The first step is the installation of a dedicated commercial superconducting cyclotron of a novel type. The second step is the development of a new gantry, Gantry 2. For Gantry 2 we have chosen an iso-centric compact gantry layout. The diameter of the gantry is limited to 7.5 m, less than in other gantry systems (approximately 10-12 m). The space in the treatment room is comfortably large, and the access on a fixed floor is possible any time around the patient table. Through the availability of a faster scanning system, it will be possible to treat the target volume repeatedly in the same session. For this purpose, the dynamic control of the beam intensity at the ion source and the dynamic variation of the beam energy will be used directly for the shaping of the dose.

Cyclotrons↗

PubMed2004

The clinical potential of intensity modulated proton therapy.

Intensity Modulated Proton Therapy (IMPT) differs from conventional proton therapy in its ability to deliver depth-shifted, arbitrarily complex proton fluence maps from each incident field direction. As the individual Bragg peaks delivered from any field can be distributed in three-dimensions throughout the target volume, IMPT provides many more degrees of freedom for designing dose distributions than IMRT or conventional proton therapy techniques. So how can the flexibility of IMPT best be exploited? Here we argue that IMPT has two main advantages over photon IMRT and conventional proton therapy: the ability to better 'sculpt' the dose to the target and around neighbouring critical structures, and the ability to find clinically acceptable solutions whilst simultaneously reducing the sensitivity of the treatments to potential delivery errors. The concept of IMPT as a tool for generating 'safer' plans opens an interesting new avenue of research from the point of view of plan optimisation, the potential of which is only just beginning to be explored.

Humans↗

PubMed2004

Treatment planning and verification of proton therapy using spot scanning: initial experiences.

Since the end of 1996, we have treated more than 160 patients at PSI using spot-scanned protons. The range of indications treated has been quite wide and includes, in the head region, base-of-skull sarcomas, low-grade gliomas, meningiomas, and para-nasal sinus tumors. In addition, we have treated bone sarcomas in the neck and trunk--mainly in the sacral area--as well as prostate cases and some soft tissue sarcomas. PTV volumes for our treated cases are in the range 20-4500 ml, indicating the flexibility of the spot scanning system for treating lesions of all types and sizes. The number of fields per applied plan ranges from between 1 and 4, with a mean of just under 3 beams per plan, and the number of fluence modulated Bragg peaks delivered per field has ranged from 200 to 45 000. With the current delivery rate of roughly 3000 Bragg peaks per minute, this translates into delivery times per field of between a few seconds to 20-25 min. Bragg peak weight analysis of these spots has shown that over all fields, only about 10% of delivered spots have a weight of more than 10% of the maximum in any given field, indicating that there is some scope for optimizing the number of spots delivered per field. Field specific dosimetry shows that these treatments can be delivered accurately and precisely to within +/-1 mm (1 SD) orthogonal to the field direction and to within 1.5 mm in range. With our current delivery system the mean widths of delivered pencil beams at the Bragg peak is about 8 mm (sigma) for all energies, indicating that this is an area where some improvements can be made. In addition, an analysis of the spot weights and energies of individual Bragg peaks shows a relatively broad spread of low and high weighted Bragg peaks over all energy steps, indicating that there is at best only a limited relationship between pencil beam weighting and depth of penetration. This latter observation may have some consequences when considering strategies for fast re-scanning on second generation scanning gantries.

Humans↗

PubMed2003

Eye retention after proton beam radiotherapy for uveal melanoma.

PURPOSE: To analyze the long-term results of eye retention after conservative treatment of uveal melanoma with proton beam radiotherapy, and to analyze the causes leading to enucleation after this conservative treatment approach. MATERIALS AND METHODS: This was a prospective, noncomparative, interventional, consecutive case series. A total of 2645 patients (2648 eyes) with uveal melanoma were treated between 1984 and 1999 with proton beam radiotherapy. Data were analyzed as of February 2001. Patients' age ranged from 9 to 90 years, 1284 were men, and 1361 were women. Largest tumor diameter ranged from 4 to 27.5 mm, and tumor height from 0.9 to 15.6 mm. Median follow-up time was 44 months. RESULTS: The overall eye retention rate at 5, 10, and 15 years after treatment was 88.9%, 86.2%, and 83.7%, respectively. In total, 218 eyes had to be enucleated. Enucleation was related to larger tumor size, mainly tumor height, proximity of posterior tumor margin to optic disc, male gender, high intraocular pressure, and large degree of retinal detachment at treatment time. After optimization of the treatment technique, the eye retention rate at 5 years was increased from 97.1% to 100% for small tumors, from 86.7% to 99.7% for medium, and from 71.1% to 89.5% for large tumors. CONCLUSIONS: The treatment technique as used today results in excellent eye retention rates, even in less favorable cases such as large tumors and tumors located close to the optic disc. The experience and a continuous quality control program allowed us to improve the 5-year eye retention rate for all tumor sizes. These findings demonstrate the positive impact of experience and quality control-based efforts for treatment technique optimization.

Adolescent↗