Angelika Höss

Stereotactic Single-Dose Radiation Therapy of Liver Tumors: Results of a Phase I/II Trial

PURPOSE To investigate the feasibility and the clinical response of a stereotactic single-dose radiation treatment for liver tumors. PATIENTS AND METHODS Between April 1997 and September 1999, a stereotactic single-dose radiation treatment of 60 liver tumors (four primary tumors, 56 metastases) in 37 patients was performed. Patients were positioned in an individually shaped vacuum pillow. The applied dose was escalated from 14 to 26 Gy (reference point), with the 80% isodose surrounding the planning target volume. Median tumor size was 10 cm(3) (range, 1 to 132 cm(3)). The morbidity, clinical outcome, laboratory findings, and response as seen on computed tomography (CT) scan were evaluated. RESULTS Follow-up data could be obtained from 55 treated tumors (35 patients). The median follow-up period was 5.7 months (range, 1.0 to 26.1 months; mean, 9.5 months). The treatment was well tolerated by all patients. There were no major side effects. Fifty-four (98%) of 55 tumors were locally controlled after 6 weeks at the initial follow-up based on the CT findings (22 cases of stable disease, 28 partial responses, and four complete responses). After a dose-escalating and learning phase, the actuarial local tumor control rate was 81% at 18 months after therapy. A total of 12 local failures were observed during follow-up. So far, the longest local tumor control is 26.1 months. CONCLUSION Stereotactic single-dose radiation therapy is a feasible method for the treatment of singular inoperable liver metastases with the potential of a high local tumor control rate and low morbidity.

EXTRACRANIAL STEREOTACTIC RADIATION THERAPY: SET-UP ACCURACY OF PATIENTS TREATED FOR LIVER METASTASES

PURPOSE Patients with liver metastases might benefit from high-dose conformal radiation therapy. A high accuracy of repositioning and a reduction of target movement are necessary for such an approach. The set-up accuracy of patients with liver metastases treated with stereotactic single dose radiation was evaluated. METHODS AND MATERIALS Twenty-four patients with liver metastases were treated with single dose radiation therapy on 26 occasions using a self-developed stereotactic frame. Liver movement was reduced by abdominal pressure. The effectiveness was evaluated under fluoroscopy. CT scans were performed on the planning day and directly before treatment. Representative reference marks were chosen and the coordinates were calculated. In addition, the target displacement was quantitatively evaluated after treatment. RESULTS Diaphragmal movement was reduced to median 7 mm (range: 3-13 mm). The final set-up accuracy of the body was limited to all of median 1.8 mm in latero-lateral direction (range: 0.3-5.0 mm) and 2.0 mm in anterior-posterior direction (0.8-3.8 mm). Deviations of the body in cranio-caudal direction were always less than the thickness of one CT slice (<5 mm). However, a repositioning was necessary in 16 occasions. The final target shift was median 1.6 mm (0.2-7.0 mm) in latero-lateral and 2.3 mm in anterior-posterior direction (0.0-6.3 mm). The median shift in cranio-caudal direction was 4.4 mm (0.0-10.0 mm). CONCLUSIONS In patients with liver metastases, a high set-up accuracy of the body and the target can be achieved. This allows a high-dose focal radiotherapy of these lesions. However, a control CT scan should be performed directly before therapy to confirm set-up accuracy and possibly prompt necessary corrections.

COMPARISON OF INTENSITY-MODULATED RADIOTHERAPY WITH CONVENTIONAL CONFORMAL RADIOTHERAPY FOR COMPLEX-SHAPED TUMORS

PURPOSE Conformal and intensity-modulated radiotherapy (IMRT) plans for 9 patients were compared based on characterization of plan quality and effects on the oncology department. METHODS AND MATERIALS These clinical cases, treated originally with conformal radiotherapy (CRT), required extraordinary effort to produce conformal treatment plans using nonmodulated, shaped noncoplanar fields with multileaf collimators (MLCs). IMRT plans created for comparison included rotational treatments with slit collimator, and fixed-field MLC treatments using equispaced coplanar, and noncoplanar fields. Plans were compared based upon target coverage, target conformality, dose homogeneity, monitor units (MU), user-interactive planning time, and treatment delivery time. The results were subjected to a statistical analysis. RESULTS IMRT increased target coverage an average of 36% and conformality by 10%. Where dose escalation was a goal, IMRT increased mean dose by 4-6 Gy and target coverage by 19% with the same degree of conformality. Rotational IMRT was slightly superior to fixed-field IMRT. All IMRT techniques increased integral dose and target dose heterogeneity. IMRT planning times were significantly less, whereas MU increased significantly; estimated delivery times were similar. CONCLUSION IMRT techniques increase dose and target coverage while continuing to spare organs-at-risk, and can be delivered in a time frame comparable to other sophisticated techniques.

ASSESSMENT OF FOCAL LIVER REACTION BY MULTIPHASIC CT AFTER STEREOTACTIC SINGLE-DOSE RADIOTHERAPY OF LIVER TUMORS

PURPOSE To characterize and quantitatively assess focal radiation reactions in the liver after stereotactic single-dose radiotherapy for liver malignancies. METHODS AND MATERIALS A total of 131 multiphasic CT scans were performed in 36 patients before and after stereotactic radiotherapy for liver tumors. The examination protocol included a nonenhanced scan and contrast-enhanced scans at different times after contrast injection. The volume of the reaction was determined in each scan and the threshold dose calculated using the dose-volume histogram of the treatment plan. RESULTS Every patient showed a focal radiation reaction on at least one follow-up examination. In 74% of the posttherapeutic scans, a sharply demarcated hypodense area surrounded the treated tumor in the nonenhanced scans. The reaction occurred at a median of 1.8 months (range 1.2-4.6) after radiotherapy. The median threshold dose was 13.7 Gy (range 8.9-19.2). The threshold dose strongly correlated with the time of detection after therapy (r = 0.7). Radiologically, three reaction types were found on the enhanced scans: type 1, portal-venous phase: hypodense and late phase: isodense; type 2, portal-venous phase: hypodense and late phase: hyperdense; and type 3, portal-venous phase: isodense/hyperdense and late phase: hyperdense. Type 1 or 2 reactions were observed significantly earlier than type 3 (p <0.05). The median threshold dose for type 1 or 2 reactions was significantly lower than for type 3 (p <0.05). The reaction volume decreased with longer follow-up (2-4 months: median 40% of initial volume). The reaction types shifted with follow-up: 58% were of type 1 at the initial manifestation and 58% were of type 3 at the next examination thereafter. CONCLUSION A focal radiation reaction occurs after stereotactic single-dose therapy in the liver. The volume of the reaction decreases and changes its radiologic appearance during follow-up. This reaction has to be differentiated from recurrent tumor.

Intensity modulated radiotherapy (IMRT) for recurrent, residual, or untreated skull-base meningiomas: preliminary clinical experience

OBJECTIVE To investigate the feasibility of using intensity modulated radiotherapy (IMRT) for complex-shaped benign meningiomas of the skull base and report clinical experience. METHODS Twenty patients with benign skull-base meningiomas WHO degrees I (histopathologically proven in 16/20) were treated with IMRT between June 1998 and August 1999. Each tumor was complex in shape and adherent to, or encompassed, organs at risk (cranial nerves, optic apparatus, and brainstem). All patients, immobilized in a customized head mask integrated into a stereotactic system, were planned on an inverse treatment planning system using 5 or 7 coplanar, equidistant beams and 5 intensity steps. Each treatment plan was verified extensively before treatment. Follow-up with MRI and clinical examination was performed at 6 and 18 weeks and every 6 months thereafter. RESULTS Target volumes ranged from 27 to 278 cc (median: 108 cc). Mean dose in 32 fractions ranged between 55.8 and 58.2 Gy. At median follow-up of 36 months (range: 31-43 months), pre-existing neurologic symptoms improved in 12/20 (60%), remained stable in 7/20 (35%), and worsened in 1 (5%) patient. Radiographic follow-up revealed significant tumor shrinkage 6 weeks post-IMRT in 2 patients and partial remission in 3 more patients at 9-17 months; other tumor volumes remained stable. There was no radiation-induced peritumoral edema, increase in tumor size, or new onset of neurologic deficits. Transient acute treatment side effects included nausea and vomiting and single occurrences of conjunctivitis/increased tearing and serous tympanitis. CONCLUSION IMRT in the treatment of central nervous system meningiomas is feasible and safe, offering highly conformal irradiation for complex-shaped skull-base tumors while sparing adjacent critical structures. If the tumor remissions seen here are found in the ongoing treatments, IMRT may be considered the treatment of choice for inoperable or subtotally resected meningiomas and for otherwise difficult-to-treat, complex-shaped tumors of the central nervous system adjacent to critical structures, with the potential of dose escalation for malignant tumors.

Correction of patient positioning errors based on in-line cone beam CTs: clinical implementation and first experiences

BackgroundThe purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy.Patients and methodsFor evaluation of the setup correction workflow, six tumor patients (lung cancer, sacral chordoma, head-and-neck and paraspinal tumor, and two prostate cancer patients) were selected. All patients were treated with fractionated stereotactic radiotherapy, five of them with intensity modulated radiotherapy (IMRT). For patient fixation, a scotch cast body frame or a vacuum pillow, each in combination with a scotch cast head mask, were used. The imaging equipment, consisting of an x-ray tube and a flat panel imager (FPI), was attached to a Siemens linear accelerator according to the in-line approach, i.e. with the imaging beam mounted opposite to the treatment beam sharing the same isocenter. For dose delivery, the treatment beam has to traverse the FPI which is mounted in the accessory tray below the multi-leaf collimator. For each patient, a predefined number of imaging projections over a range of at least 200 degrees were acquired. The fast reconstruction of the 3D-CBCT dataset was done with an implementation of the Feldkamp-David-Kress (FDK) algorithm. For the registration of the treatment planning CT with the acquired CBCT, an automatic mutual information matcher and manual matching was used.Results and discussionBony landmarks were easily detected and the table shifts for correction of setup deviations could be automatically calculated in all cases. The image quality was sufficient for a visual comparison of the desired target point with the isocenter visible on the CBCT. Soft tissue contrast was problematic for the prostate of an obese patient, but good in the lung tumor case. The detected maximum setup deviation was 3 mm for patients fixated with the body frame, and 6 mm for patients positioned in the vacuum pillow. Using an action level of 2 mm translational error, a target point correction was carried out in 4 cases. The additional workload of the described workflow compared to a normal treatment fraction led to an extra time of about 10–12 minutes, which can be further reduced by streamlining the different steps.ConclusionThe cone beam CT attached to a LINAC allows the acquisition of a CT scan of the patient in treatment position directly before treatment. Its image quality is sufficient for determining target point correction vectors. With the presented workflow, a target point correction within a clinically reasonable time frame is possible. This increases the treatment precision, and potentially the complex patient fixation techniques will become dispensable.

Conformal radiotherapy of challenging paraspinal tumors using a multiple arc segment technique.

PURPOSE Target volumes that wrap around the spinal cord are difficult to treat. We present and evaluate a refined multiple arc segment (MAS) technique that is applicable with standard three-dimensional (3D) radiotherapy equipment and may be a solution for facilities that do not yet have full access to intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS The presented technique consisted of 13 isocentric coplanar beams eye view shaped fields, delivered as 20 degrees or 10 degrees arc segments with an integrated multileaf collimator (MLC) using automatic sequential field delivery. Dose-volume histograms (DVH) for this technique were compared to a modified bar-arc technique (MBA) modeled as 30 static fields and to an inverse planned IMRT technique using 7 coplanar, equispaced beams delivered with the same MLC. RESULTS Compared to the MBA technique, maximum dose and target coverage were similar when using 80% of the maximum dose as the reference dose. However, the MAS technique reduced the maximum doses (to > or = 1% of the organs at risk [OAR]) by 9% for the spinal cord, 17% for the esophagus, and 25% for the trachea, as well as the mean doses. Although inverse planned IMRT could further reduce exposure of OAR except for the spinal cord and improve target coverage, our forward planned MAS technique seems to achieve clinically comparable results. CONCLUSION Substituting a series of small split-field arc segments for large static fields and using additional narrow paraspinal segments significantly improves the sparing of organs at risk for paraspinal targets. Although these results are not quite as good as those achieved with IMRT, for facilities not yet equipped with inverse treatment planning capability, the presented technique enables dose escalation for primary paraspinal tumors and retreatment of recurrent lesions.

Stereotactic Intensity-Modulated Radiation Therapy (IMRT) and Inverse Treatment Planning for Advanced Pleural Mesothelioma

Background and Purpose: Complex-shaped malignant pleural mesotheliomas (MPMs) with challenging volumes are extremely difficult to treat by conventional radiotherapy due to tolerance doses of the surrounding normal tissue. In a feasibility study, we evaluated if inversely planned stereotactic intensity-modulated radiation therapy (IMRT) could be applied in the treatment of MPM. Patients and Methods: Results: Conclusion: Patients and Methods: Eight patients with unresectable lesions were treated after failure of chemotherapy. All patients were positioned using noninvasive patient fixation techniques which can be attached to the applied extracranial stereotactic system. Due to craniocaudal extension of the tumor, it was necessary to develop a special software attached to the inverse planning program KonRad, which can connect two inverse treatment plans and consider the applied dose of the first treatment plan in the area of the matchline of the second treatment plan. Results: Except for one patient, in whom radiotherapy was canceled due to abdominal metastasis, treatment could be completed in all patients and was well tolerated. Median survival after diagnosis was 20 months and after IMRT 6.5 months. Therefore, both the 1-year actuarial overall survival from the start of radiotherapy and the 2-year actuarial overall survival since diagnosis were 28%. IMRT did not result in clinically significant acute side effects. By using the described inverse planning software, overor underdosage in the region of the field matchline could be prevented. Pure treatment time ranged between 10 and 21 min. Conclusion: This study showed that IMRT is feasible in advanced unresectable MPM. The presented possibilities of stereotactic IMRT in the treatment of MPM will justify the evaluation of IMRT in early-stage pleural mesothelioma combined with chemotherapy in a study protocol, in order to improve the outcome of these patients. Furthermore, dose escalation should be possible by using IMRT.Hintergrund und Ziel: Komplex geformte bösartige Pleuramesotheliome mit einem ausgedehnten Volumen sind aufgrund der Toleranzdosen des umgebenden Normalgewebes nur sehr schwierig mit Hilfe der konventionellen Strahlentherapie zu behandeln. In einer Machbarkeitsstudie wurde untersucht, ob sich die stereotaktisch geplante intensitätsmodulierte Strahlentherapie (IMRT) zur Behandlung maligner Pleuramesotheliome eignet. Patienten und Methodik: Acht Patienten mit nicht resektablen Tumoren wurden bei Tumorprogress nach Chemotherapie behandelt. Alle Patienten wurden mit Hilfe eines nichtinvasiven Positionierungssystems gelagert, das in Verbindung mit einem Ganzkörperstereotaxiesystem verwendet wird. Aufgrund der kraniokaudalen Ausdehnung der Tumoren war es notwendig, eine spezielle, mit dem inversen Planungsprogramm KonRad verbundene Software zu entwickeln, die zwei unterschiedliche Bestrahlungspläne zusammenfügen kann. Die Dosisverteilung des ersten Bestrahlungsplans wird bei der Erstellung des zweiten Bestrahlungsplans berücksichtigt. Ergebnisse: Die Behandlung ließ sich bei sieben Patienten vollständig durchführen und wurde gut toleriert. Lediglich bei einem Patienten musste sie wegen einer abdominellen Metastase abgebrochen werden. Das mediane Überleben nach Diagnosestellung betrug 20 Monate und nach IMRT 6,5 Monate. Sowohl das aktuarische 1-Jahres-Überleben bei Beginn der Strahlentherapie als auch das 2-Jahres-Überleben nach Diagnosestellung lagen bei 28%. Nach der IMRT-Behandlung wurden keine klinisch signifikanten akuten Nebenwirkungen festgestellt. Mit Hilfe der verwendeten inversen Planungssoftware konnten Über- und Unterdosierungen im Bereich des Feldanschlusses vermieden werden. Die eigentliche Behandlungszeit variierte zwischen 10 und 21 min. Schlussfolgerung: Diese Studie zeigt, dass die IMRT bei fortgeschrittenen nicht resektablen Pleuramesotheliomen durchführbar ist. Die Möglichkeiten der vorgestellten stereotaktischen IMRT-Technik rechtfertigen die Erstellung eines Studienprotokolls in frühen Tumorstadien kombiniert mit einer Chemotherapie. Damit könnte die Prognose der Patienten verbessert werden. Des Weiteren sollte durch die IMRT eine Dosiseskalation möglich sein.

Fractionated stereotactic conformal radiation therapy of brain stem gliomas: outcome and prognostic factors

BACKGROUND AND PURPOSE Evaluation of outcome and prognostic factors in patients with brain stem glioma (BSG) following fractionated stereotactic radiotherapy (FSRT). MATERIALS AND METHODS Between 1990 and 1997, we treated 41 patients with FSRT in a phase I/II trial. Median age was 24 years. Out of 36 patients with histologically proven glioma, ten had a partial tumour resection. Histology revealed low grade gliomas in 30 patients and anaplastic gliomas in six patients. A mean total dose of 54 Gy was given in daily fractions of 1.8 Gy. Median follow-up was 12 months. RESULTS Three patients died during FSRT. Neurological improvement was achieved in 19/38 patients. Reduction of tumour size was reported in 12/38, in 16 patients the lesion was unchanged, ten showed progression. Median time to progression was 23 months, median overall survival 40 months with an actuarial survival of 83% at 1 year, 55% at 3 years and 33% at 5 years. In 20 of 22 patients with recurrence progression was inside the target volume. Significant prognostic factors for survival were clinical and radiological response 6 weeks after FSRT. Treatment toxicity was mild. Ototoxicity occurred in one patient. CONCLUSIONS FSRT is a feasible treatment modality for BSG with tolerable toxicity. The risk of marginal failure is low.

Accuracy of device-specific 2D and 3D image distortion correction algorithms for magnetic resonance imaging of the head provided by a manufacturer

For the application of magnetic resonance imaging (MRI) in precision radiotherapy, image distortions must be reduced to a minimum to maintain geometrical accuracy. Recently, two-dimensional (2D) and three-dimensional (3D) algorithms for MRI-device-specific distortion corrections were developed by the manufacturers of MRI devices. A previously developed phantom (Karger C P et al 2003 Phys. Med. Biol. 48 211-21) was used to quantify and assess the size of geometrical image distortions before and after application of the 2D and 3D correction algorithm in the head region. Four different types of MRI devices with different gradient systems were measured. For comparison, measurements were also performed with two computed tomography (CT) devices. Mean distortions of up to 4.6+/-1.4 mm (maximum: 5.8 mm) were found prior to the correction. After the correction, the mean distortions were well below 2.0 mm in most cases. Distortions in the CT images were below or equal to 1.0 mm on average. Generally, the 3D algorithm produced comparable or better results than the 2D algorithm. The remaining distortions after the correction appear to be acceptable for fractionated radiotherapy.