Klaus Bratengeier

Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma

BackgroundHypofractionated stereotactic radiotherapy (HFSRT) is one salvage treatment option in previously irradiated patients with recurrent malignant glioma. We analyzed the results of HFSRT and prognostic factors in a single-institution series.MethodsBetween 1997 and 2003, 19 patients with recurrent malignant glioma (14 glioblastoma on most recent histology, 5 anaplastic astrocytoma) were treated with HFSRT. The median interval from post-operative radiotherapy to HFSRT was 19 (range 3–116) months, the median daily single dose 5 (4–10) Gy, the median total dose 30 (20–30) Gy and the median planning target volume 15 (4–70) ml.ResultsThe median overall survival (OS) was 9.3 (1.9-77.6+) months from the time of HFSRT, 15.4 months for grade III and 7.9 months for grade IV tumors (p = 0.029, log-rank test). Two patients were alive at 34.6 and 77.6 months. OS was longer after a total dose of 30 Gy (11.1 months) than after total doses of <30 Gy (7.4 months; p = 0.051). Of five (26%) reoperations, none was performed for presumed or histologically predominant radiation necrosis. Median time to tumor progression after HFSRT on imaging was 4.9 months (1.3 to 37.3) months.ConclusionHFSRT with conservative total doses of no more than 30 Gy is safe and leads to similar OS times as more aggressive treatment schemes. In individual patients, HFSRT in combination with other salvage treatment modalities, was associated with long-term survival.

Radiotherapy in adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy, and patients with ACC have a poor prognosis. Even after radical surgery, up to 85% of patients develop recurrent disease. Systemic treatment options still have limited efficacy. Because the role of radiotherapy is not defined well and because ACC often is considered radioresistant, the authors reviewed the available data on radiotherapy for ACC. Original articles and reviews were identified using a PubMed search strategy that included the period up to July 2008. Ten articles were identified that covered radiotherapy in a total of 129 patients with ACC (64 patients received postoperative irradiation, and 65 patients received palliative therapy for advanced disease). In addition, 26 patients were identified in the German ACC Registry who received palliative radiotherapy. Furthermore, patterns of failure after adjuvant radiotherapy were investigated, and the authors provided recommendations for patient selection, treatment planning, and treatment protocols. In an adjuvant setting, postoperative radiotherapy was able to prevent local recurrence in the majority of patients. In those with advanced disease, a response to radiotherapy was observed in 57% of patients who received palliative radiotherapy. Therefore, the authors concluded that radiotherapy may play an important role in the care of patients with ACC. Until better evidence is available, the authors recommended the following approach: Adjuvant radiotherapy to the tumor bed should be considered in patients at high risk for local recurrence (eg, incomplete/R1 resection); a total dose of >40 grays (Gy) with single fractions of 1.8 Gy to 2 Gy should be administered (including a boost volume to reach from 50 Gy to 60 Gy in individual patients); and radiotherapy in a palliative setting may be used for symptomatic metastases to bone, brain, or vena cava obstruction. With state‐of‐the‐art technology, acute and long‐term toxicities mostly were mild to moderate. However, the authors concluded that prospective investigations would be required to fully define the therapeutic potential of this important treatment option. Cancer 2009.

Carcinoma of the external auditory canal and middle ear

PURPOSE To evaluate therapeutic modalities used at our institutions regarding local control, disease-free survival and actuarial survival in carcinoma of the external auditory canal and middle ear, in an attempt to provide guidelines for therapy. METHODS AND MATERIALS A series of 27 patients with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions were analyzed with particular reference to tumor size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques employed. Clinical endpoints were freedom from local failure, overall survival, and disease-free survival. The median follow-up was 2.7 years (range 0.1-17.9 years). RESULTS Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 61%. According to the Pittsburgh classification, the actuarial 5-year survival rate for early disease (T1 and T2 tumors) was 86%, for T3 tumors 50%, and T4 stages 41%. Patients with tumors limited to the external auditory canal had a 5-year survival rate of 100%, patients with tumor invasion of the temporal bone 63%, and patients with tumor infiltration beyond the temporal bone 38%. The rate of freedom from local recurrence was 50% at 5 years. Unresectability by dural and cerebral infiltration, and treatment factors such as complete resection or resection with tumor beyond surgical margins are of prognostic relevance. All patients with dural invasion died within 2.2 years. The actuarial 5-year survival rate of patients with complete tumor resection was 100%, but 66% in patients with tumor beyond surgical margins. 192Iridium high-dose-rate (HDR) afterloading brachytherapy based on three-dimensional computed tomography (3D CT)-treatment planning was an effective tool in management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSION Surgical resection followed by radiotherapy adapted to stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

CT simulation in stereotactic brain radiotherapy — analysis of isocenter reproducibility with mask fixation

BACKGROUND AND PURPOSE CT verification and measurement of isocenter deviation using repeated mask fixation in linac-based stereotactic high dose radiotherapy of brain metastases were performed in this study. MATERIALS AND METHODS For stereotactic radiotherapy of brain metastases a commercial head mask fixation device based on thermoplastic materials (BrainLAB) was used. A two-step planning-treatment procedure was performed. Immediately before treatment the patient was relocated in the mask and a verification CT scan of the radiopaque marked isocenter was performed and if necessary its position was corrected. The verification procedure is described in detail. Twenty-two CT verifications in 16 patients were analyzed. Deviations were measured separately for each direction. A 3D-deviation vector was calculated. Additionally the average amount of deviation in each of the three dimensions was calculated. RESULTS The mean deviation and standard deviation (SD) of the isocenter was 0.4 mm (SD 1.5 mm) in the longitudinal direction, -0.1 mm (SD 1.8 mm) in the lateral direction and 0.1 mm (SD 1.2 mm) in the anterior-posterior direction. The mean three-dimensional distance (3D-vector) between the verified and the corrected isocenter was 2.4 mm (SD 1.3 mm). The average deviation (without consideration of direction) was 1.1 mm (SD 1.1 mm), 1.3 mm (SD 1.3 mm) and 0.8 mm (SD 0.9 mm) in the longitudinal, lateral and sagittal directions, respectively. No correlation was found between 3D-deviation and the distance of the isocenter from the reference plane nor between deviation and the position of metastases in the brain (central versus peripheral or between different lobes), or the date of treatment. CONCLUSION Reproducibility of the isocenter using the presented mask fixation is in the range of positioning reproducibility reported for other non-invasive fixation devices for stereotactic brain treatment. Our results underline the importance of CT verification as a quality assurance method in stereotactic radiotherapy. Under the condition of a preceding CT verification the mask can be used for single dose stereotactic radiotherapy. For fractionated stereotactic irradiation of small target volumes we recommend repeated CT verifications to assure reproducibility.

Three dimensional variability in patient positioning using bite block immobilization in 3D-conformal radiation treatment for ENT-tumors

BACKGROUND AND PURPOSE The aim of this prospective study was to analyze the three-dimensional (3D) reproducibility of the isocenter position and of patient positioning with the use of bite block immobilization by means of a simple verification procedure for a complex beam arrangement applied for ENT-tumors. MATERIALS AND METHODS We analyzed the positioning data of 29 consecutive patients treated for ENT-tumors at the Department of Radiotherapy and Oncology of the University of Wurzburg. A total of 136 treatment sessions were analyzed. Patients were positioned and immobilized using an individualized bite block system and a head and neck support. A complex beam arrangement was applied combining two offset rotational and two oblique wedge fields on a 5 MV linear accelerator. Orthogonal verification films were taken once weekly. Four to six film pairs per patient were obtained (during 4-6 weeks) with a mean number of 4.7 film pairs per patient. These were compared to the corresponding orthogonal simulator films taken during primary simulation. Deviations of the verified isocenter from the isocenter on the simulator film were measured and analyzed in three dimensions in terms of overall, systematic and random categories. A 3D-deviation vector was calculated from these 3D data as well as a 2D-deviation vector (for comparison with literature data) from the lateral verification films. RESULTS The overall setup deviation showed standard deviations (SD) of 2.5, 2.7 and 3.1 mm along the cranio-caudal, anterior-posterior and medio-lateral axes, respectively. The random component ranged from SD 1.9 to 2.1 mm and the systematic component ranged from SD 1.8 to 2.2 mm. The mean length of the 3D-vector was 3.1 mm for the systematic as well as the random component. Ninety percent of 3D systematic and random deviations were less than 5 mm. The mean length of the 2D-vector was 2.4 mm for the random component and 2.2 mm for the systematic component. Ninety percent of 2D-random and systematic variations were less than 4 mm. CONCLUSIONS The presented individualized bite block immobilization device provides an accurate and reproducible patient positioning for 3D-conformal radiation therapy in the head and neck. Random and systematic deviations in each of the three directions are in the range of +/-4 mm (2 SD, comprising 95% of the deviations) and are within the range or even less than deviations described for most thermoplastic or PVC-mask fixation devices. These deviations should be taken into account during definition of planning target volume in head and neck tumors.

Applications of two-step intensity modulated arc therapy.

Purpose: Organs at risk sometimes are surrounded by the target volume. At a first glance it seems to be impossible, to spare the organ at risk, i. e. the spinal cord, without underdosage of parts of the concave target volume. A fast method called “two-step intensity modulated arc therapy” (two-step IMAT) will be shown that avoids underdosage in the target volume near such organs at risk. Materials and Methods: Simple rotational techniques reduce the dose to the surrounded organ, however, the blocking of the organ at risk spoils the homogeneity of dose in the target volume in the vicinity of the organ. A further narrow rotation field, tangential to the concave part of the target volume, increases the dose there and homogenizes the dose distribution without deteriorating the dose in the organ at risk significantly. Results: Some cases show that the two-step IMAT and its modifications guarantee a sufficient dose homogeneity in the target volume surrounding an organ at risk. Besides basic theoretical considerations exemplary solutions for head and neck tumors, tumors adjacent to the spinal cord an mamma carcinoma of patients with extremely arched chest are demonstrated. Conclusion: Double rotation techniques can provide sufficient dose homogeneity for concave target volumes with excellent sparing of the surrounded organ at risk. They are not time consuming and can be used until IMRT will be applied routinely with adequate time load and effort.Ziel: Gelegentlich werden Risikoorgane vom Zielvolumen partiell eingeschlossen. Auf den ersten Blick erscheint es unmöglich, das Risikoorgan, z. B. den Spinalkanal, zu schonen, ohne Teile des konkaven Zielvolumens zu gering zu dosieren. Eine Methode, die sog. “zweistufig intensitätsmodulierte Bewegungsbestrahlung” (Two-Step-IMAT) wird vorgestellt, die Unterdosierungen im Zielvolumen in der Umgebung solcher Risikoorgane vermeidet. Material und Methode: Rotationstechniken, die einfach das Risikoorgan ausblocken, reduzieren zwar die Dosis in diesem Organ, verschlechtern jedoch die Homogenität der Dosisverteilung im Zielvolumen in der Umgebung des Risikoorgans. Ein weiteres schmales Rotationsfeld, das tangential über den konkaven Bereich streift, erhöht dort selektiv die Dosis und homogenisiert die Dosisverteilung im Zielvolumen, ohne die Dosis im Risikoorgan signifikant zu erhöhen. Ergebnisse: Es werden Situationen vorgestellt, in denen Varianten der zweistufig intensitätsmodulierten Bewegungsbestrahlung eine ausreichende Homogenität in einem Zielvolumen sicherstellen, das ein Risikoorgan umgibt. Neben einfachen theoretischen Betrachtungen werden beispielhafte Lösungen für Tumoren des Kopf-Hals-Bereichs, für Tumoren direkt am Spinalkanal und für Mammakarzinompatientinnen mit stark gewölbter Brust gezeigt. Schlussfolgerung: Zweistufig intensitätsmodulierte Bewegungsbestrahlungen können für eine ausreichende Dosishomogenität in konkaven Zielvolumina sorgen bei gleichzeitiger hervorragender Schonung des eingeschlossenen Risikoorgans. Sie sind nicht zeitaufwändig und können gut genutzt werden, bis IMRT regelmäßig mit annehmbarer zeitlicher und finanzieller Belastung einsetzbar wird.

CT planning of boost irradiation in radiotherapy of breast cancer after conservative surgery

BACKGROUND AND PURPOSE A study was performed to compare the accuracy of clinical treatment set-up and CT planning of boost irradiation in radiotherapy of breast cancer. MATERIAL AND METHODS Between September 1993 and October 1994, 45 women who underwent breast conserving surgery and irradiation containing a boost to the tumour bed were investigated. Prospective evaluation of CT planning of the boost was carried out. The target volume/boost field, electron energy and treatment set-up had been defined on the basis of clinical examination, initial and postsurgical mammograms by one radiotherapist. Next, a planning CT was performed in treatment position and a CT-based treatment plan was calculated according to a target volume defined by another radiotherapist. The clinical treatment set-up was imported into our computer planning system and the resulting isodose plots were compared with those from CT planning and reviewed critically. RESULTS The clinically defined treatment set-up had to be modified in 80% of the patients. Most discrepancies observed were related to the size of the boost field itself and the chosen electron energy. Minor changes had to be made with respect to angle of table and gantry. CONCLUSIONS Critical review of the isodose plots from both methods showed clear advantages for CT planning. Guidelines for target definition in CT planning of boost irradiation and subgroups of patients benefiting from this technique are described.

2-Step IMAT and 2-Step IMRT in three dimensions

In two dimensions, 2-Step Intensity Modulated Arc Therapy (2-Step IMAT) and 2-Step Intensity Modulated Radiation Therapy (IMRT) were shown to be powerful methods for the optimization of plans with organs at risk (OAR) (partially) surrounded by a target volume (PTV). In three dimensions, some additional boundary conditions have to be considered to establish 2-Step IMAT as an optimization method. A further aim was to create rules for ad hoc adaptations of an IMRT plan to a daily changing PTV-OAR constellation. As a test model, a cylindrically symmetric PTV-OAR combination was used. The centrally placed OAR can adapt arbitrary diameters with different gap widths toward the PTV. Along the rotation axis the OAR diameter can vary, the OAR can even vanish at some axis positions, leaving a circular PTV. The width and weight of the second segment were the free parameters to optimize. The objective function f to minimize was the root of the integral of the squared difference of the dose in the target volume and a reference dose. For the problem, two local minima exist. Therefore, as a secondary criteria, the magnitude of hot and cold spots were taken into account. As a result, the solution with a larger segment width was recommended. From plane to plane for varying radii of PTV and OAR and for different gaps between them, different sets of weights and widths were optimal. Because only one weight for one segment shall be used for all planes (respectively leaf pairs), a strategy for complex three-dimensional (3-D) cases was established to choose a global weight. In a second step, a suitable segment width was chosen, minimizing f for this global weight. The concept was demonstrated in a planning study for a cylindrically symmetric example with a large range of different radii of an OAR along the patient axis. The method is discussed for some classes of tumor/organ at risk combinations. Noncylindrically symmetric cases were treated exemplarily. The product of width and weight of the additional segment as well as the integral across the segment profile was demonstrated to be an important value. This product was up to a factor of 3 larger than in the 2-D case. Even in three dimensions, the optimized 2-Step IMAT increased the homogeneity of the dose distribution in the PTV profoundly. Rules for adaptation to varying target-OAR combinations were deduced. It can be concluded that 2-Step IMAT and 2-Step IMRT are also applicable in three dimensions. In the majority of cases, weights between 0.5 and 2 will occur for the additional segment. The width-weight product of the second segment is always smaller than the normalized radius of the OAR. The width-weight product of the additional segment is strictly connected to the relevant diameter of the organ at risk and the target volume. The derived formulas can be helpful to adapt an IMRT plan to altering target shapes.

Induction chemotherapy with paclitaxel and cisplatin and CT-based 3D radiotherapy in patients with advanced laryngeal and hypopharyngeal carcinomas--a possibility for organ preservation.

BACKGROUND To evaluate the effect of paclitaxel/cisplatin induction chemotherapy (ICHT) and CT-based radiotherapy (RT) on larynx preservation, tumor control, and survival in patients with larynx/hypopharynx carcinoma eligible for total laryngectomy (TL) or TL plus partial pharyngectomy (TLPP). PATIENTS AND METHODS Fifty patients eligible for TL or TLPP were enrolled onto a prospective study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22). In patients with complete or partial tumor response RT (69.9 Gy in 5.5 weeks at the gross tumor, 50.4 Gy in the lymphatic drainage; single dose: 1.8 Gy, concomitant boost: 1.5 Gy) was applied. Non-responders had TL/TLPP and RT with total doses adapted to the radicality of tumor resection (56-70 Gy). RESULTS The response rate to ICHT was 88% (10% complete, 78% partial response). At a median follow-up period of 25 months the larynx preservation rate was 84%. The 2-year local-regional control rate was 91% and the 2-year overall survival rate was 72.3%. The 3-year estimate to survive with functional larynx is 60%. CONCLUSION In a large portion of patients eligible for TL or TLPP the larynx was preserved by paclitaxel/cisplatin ICHT and 3D RT.

Clinical Outcome of Dose-Escalated Image-Guided Radiotherapy for Spinal Metastases

PURPOSE To evaluate the outcomes after dose-escalated radiotherapy (RT) for spinal metastases and paraspinal tumors. METHODS AND MATERIALS A total of 14 patients, 12 with spinal metastases and a long life expectancy and 2 with paraspinal tumors, were treated for 16 lesions with intensity-modulated, image-guided RT. A median biologic effective dose of 74 Gy(10) (range, 55-86) in a median of 20 fractions (range, 3-34) was prescribed to the target volume. The spinal canal was treated to 40 Gy in 20 fractions using a second intensity-modulated RT dose level in the case of epidural involvement. RESULTS After median follow-up of 17 months, one local recurrence was observed, for an actuarial local control rate of 88% after 2 years. Local control was associated with rapid and long-term pain relief. Of 11 patients treated for a solitary spinal metastasis, 6 developed systemic disease progression. The actuarial overall survival rate for metastatic patients was 85% and 63% after 1 and 2 years, respectively. Acute Grade 2-3 skin toxicity was seen in 2 patients with no late toxicity greater than Grade 2. No radiation-induced myelopathy was observed. CONCLUSION Dose-escalated irradiation of spinal metastases was safe and resulted in excellent local control. Oligometastatic patients with a long life expectancy and epidural involvement are considered to benefit the most from fractionated RT.