Bernhard Rhein

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.

Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases.

PURPOSE Evaluation of the treatment outcome after radiosurgery (RS) alone or in combination with whole-brain radiotherapy (WBRT) with special attention to prescribed dose and its influence on local control and survival. PATIENTS AND METHODS Between September 1984 and January 1997, 236 patients with 311 brain metastases treated with radiosurgery met the following inclusion criteria: one to three brain metastases per patient; no previous WBRT; and Kamofsky performance status (KPS) > or = 50%. One hundred fifty-eight patients treated only with RS received a median dose of 20 Gy prescribed to the 80% isodose line; 78 patients received RS with a median dose of 15 Gy/80% and an additional course of WBRT. RESULTS For the entire series, overall median survival was 5.5 months, with control of CNS disease achieved in 92% of the treated brain metastases; the results were not significantly different between patients treated by RS with or without WBRT. However, in patients without evidence of extracranial disease, median survival was increased for patients who received WBRT (15.4 vs 8.3 months; P=.08). Additionally, there was a suggestion that increased doses for patients treated with RS only resulted in improved outcome. Four lesions were suspicious for radiation necrosis by magnetic resonance imaging (MRI); in one of the four lesions, radiation necrosis was confirmed histologically. The incidence of transient low-grade toxicity was 18%; symptoms could be treated by the temporary administration of steroids. CONCLUSION RS is an effective, noninvasive means of controlling brain metastases when used alone or in combination with WBRT. There is a trend for superior local control and especially in patients without extracranial disease for superior survival when RS is used in conjunction with WBRT. Randomized trials would seem to be warranted, comparing the benefit of RS with or without additional WBRT.

Stereotactic fractionated radiotherapy for chordomas and chondrosarcomas of the skull base

PURPOSE To investigate the treatment outcome of patients suffering from skull base chordoma or chondrosarcoma after fractionated stereotactic radiotherapy. METHODS AND MATERIALS We report 45 patients treated for chordoma or chondrosarcoma with postoperative fractionated stereotactic radiotherapy between 1990 and 1997. Patients had CT and MRI for 3D treatment planning performed under stereotactic guidance. Median dose at isocenter was 66.6 Gy for chordomas and 64.9 Gy for chondrosarcomas. MRI imaging was obtained in intervals after therapy to evaluate local relapse. Survival was calculated according to the Kaplan-Meier method. RESULTS All chondrosarcomas had achieved and maintained local control and recurrence-free status at follow-up of 5 years. Local control rate of chordomas was 82% at 2 years and 50% at 5 years. Survival was 97% at 2 years and 82% at 5 years. At maximum follow-up of 8 years local control and survival rate of chordomas was 40% (82%). Clinically significant late toxicity developed in one patient. CONCLUSIONS Our results demonstrate the feasibility of fractionated photon beam therapy and its success in the treatment of skull base tumors. Modern 3D treatment techniques provide superior results compared to conventional techniques. The role of high-precision radiotherapy compared to particle beam therapy in the treatment of these tumors is not yet fully clear and further research is needed.

Decomposition of pencil beam kernels for fast dose calculations in three‐dimensional treatment planning

A method for the calculation of three-dimensional dose distributions for high-energy photon beams is presented. The main features are (i) the calculation is fast enough to allow interactive three-dimensional treatment planning, and (ii) irregularly shaped or compensated fields, which are required to fit three-dimensional dose distributions to target volumes, are adequately taken into consideration. The method is based on the pencil beam convolution technique and shares its features concerning accuracy. A considerable gain in speed is achieved by decomposing the pencil beam kernel into three separated terms, thus reducing the required number of two-dimensional convolutions. The convolutions are performed in the frequency domain via the fast Hartley transform. Using these techniques, the calculation time for the convolutions is only about 8 s on a DEC VAX station 3100. This is one-fourth to one-third of the calculation time for the ray tracing through the three-dimensional CT data set, which has to be performed in any case. Results of the calculation are compared with measurements in a homogeneous phantom for 15 MV photons. Two irregular fields shaped with a multileaf collimator are considered. The deviations between measured and calculated absolute dose values are smaller than +/- 2%.

NONINVASIVE PATIENT FIXATION FOR EXTRACRANIAL STEREOTACTIC RADIOTHERAPY

PURPOSE To evaluate the setup accuracy that can be achieved with a novel noninvasive patient fixation technique based on a body cast attached to a recently developed stereotactic body frame during fractionated extracranial stereotactic radiotherapy. METHODS AND MATERIALS Thirty-one CT studies (> or = 20 slices, thickness: 3 mm) from 5 patients who were immobilized in a body cast attached to a stereotactic body frame for treatment of paramedullary tumors in the thoracic or lumbar spine were evaluated with respect to setup accuracy. The immobilization device consisted of a custom-made wrap-around body cast that extended from the neck to the thighs and a separate head mask, both made from Scotchcast. Each CT study was performed immediately before or after every second or third actual treatment fraction without repositioning the patient between CT and treatment. The stereotactic localization system was mounted and the isocenter as initially located stereotactically was marked with fiducials for each CT study. Deviation of the treated isocenter as compared to the planned position was measured in all three dimensions. RESULTS The immobilization device can be easily handled, attached to and removed from the stereotactic frame and thus enables treatment of multiple patients with the same stereotactic frame each day. Mean patient movements of 1.6 mm+/-1.2 mm (laterolateral [LL]), 1.4 mm+/-1.0 mm (anterior-posterior [AP]), 2.3 mm+/-1.3 mm (transversal vectorial error [VE]) and < slice thickness = 3 mm (craniocaudal [CC]) were recorded for the targets in the thoracic spine and 1.4 mm+/-1.0 mm (LL), 1.2 mm+/-0.7 mm (AP), 1.8 mm+/-1.2 mm (VE), and < 3 mm (CC) for the lumbar spine. The worst case deviation was 3.9 mm for the first patient with the target in the thoracic spine (in the LL direction). Combining those numbers (mean transversal VE for both locations and maximum CC error of 3 mm), the mean three-dimensional vectorial patient movement and thus the mean overall accuracy can be safely estimated to be < or = 3.6 mm. CONCLUSION The presented combination of a body cast and head mask system in a rigid stereotactic body frame ensures reliable noninvasive patient fixation for fractionated extracranial stereotactic radiotherapy and may enable dose escalation for less radioresponsive tumors that are near the spinal cord or otherwise critically located while minimizing the risk of late sequelae.

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.

CONVENTIONALLY FRACTIONATED STEREOTACTIC RADIOTHERAPY (FSRT) FOR ACOUSTIC NEUROMAS

PURPOSE Analysis of local tumor control and functional outcome following conventionally fractionated stereotactic radiotherapy (FSRT) for acoustic neuromas. PATIENTS AND METHODS From 11/1989 to 9/1999 51 patients with acoustic neuromas have been treated by FSRT. Mean total dose was 57.6 +/- 2.5 Gy. Forty-two patients have been followed for at least 12 months and were subject of an outcome analysis. Mean follow-up was 42 months. We analyzed local control, hearing preservation, and facial and trigeminal nerve functional preservation. We evaluated influences of tumor size, age, and association with neurofibromatosis Type 2 (NF2) on outcome and treatment related toxicity. RESULTS Actuarial 2- and 5-year tumor control rates were 100% and 97.7%, respectively. Actuarial useful hearing preservation rate was 85% at 2 and 5 years. New hearing loss was diagnosed in 4 NF2 patients. Pretreatment normal facial nerve function was preserved in all cases. Two cases of new or impaired trigeminal nerve dysesthesia required medication. No other cranial nerve deficit was observed. In Patients without NF2 tumor size or age had no influence on tumor control and cranial nerve toxicity. Diagnosis of NF2 was associated with higher risk of hearing impairment (p = 0.0002), the hearing preservation rate in this subgroup was 60%. CONCLUSION FSRT has been shown to be an effective means of local tumor control. Excellent hearing preservation rates and 5th and 7th nerve functional preservation rates were achieved. The results support the conclusion that FSRT can be recommended to patients with acoustic neuromas where special attention has to be taken to preserve useful hearing and normal cranial nerve function. For NF2 patients, FSRT may be the treatment of choice with superior functional outcome compared to treatment alternatives.

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.

4D-CT-based target volume definition in stereotactic radiotherapy of lung tumours: Comparison with a conventional technique using individual margins

PURPOSE To investigate the dosimetric benefit of integration of 4D-CT in the planning target volume (PTV) definition process compared to conventional PTV definition using individual margins in stereotactic body radiotherapy (SBRT) of lung tumours. MATERIAL AND METHODS Two different PTVs were defined: PTV(conv) consisting of the helical-CT-based clinical target volume (CTV) enlarged isotropically for each spatial direction by the individually measured amount of motion in the 4D-CT, and PTV(4D) encompassing the CTVs defined in the 4D-CT phases displaying the extremes of the tumour position. Tumour motion as well as volumetric and dosimetric differences and relations of both PTVs were evaluated. RESULTS Volumetric examinations revealed a significant reduction of the mean PTV by 4D-CT from 57.7 to 40.7 cm(3) (31%) (p<0.001). A significant inverse correlation was found for the motion vector and the amount of inclusion of PTV(4D) in PTV(conv) (r=-0.69, 90% confidence limits: -0.87 and -0.34, p=0.007). Mean lung dose (MLD) was decreased significantly by 17% (p<0.001). CONCLUSIONS In SBRT of lung tumours the mere use of individual margins for target volume definition cannot compensate for the additional effects that the implementation of 4D-CT phases can offer.

Fractionated stereotactic radiotherapy for craniopharyngiomas

PURPOSE To investigate outcome and toxicity after fractionated stereotactic radiation therapy (FSRT) in patients with craniopharyngiomas. METHODS AND MATERIALS Twenty-six patients with craniopharyngiomas were treated with FSRT between May 1989 and February 2001. Median age was 33.5 years (range: 5-57 years). Nine patients received FSRT after surgery as primary treatment, and 17 patients were irradiated for recurrent tumor or progressive growth after initial surgery. Median target dose was 52.2 Gy (range: 50.0-57.6 Gy) with conventional fractionation. Follow-up included MRI and neurologic, ophthalmologic, and endocrinologic examinations. RESULTS The median follow-up was 43 months (range: 7-143 months). The actuarial local control rate and actuarial overall survival rates were 100% and 100%, respectively, at 5 years and 100% and 83%, respectively, at 10 years. Four patients showed complete response, 14 patients showed partial response, and 8 patients remained stable. In 5 patients, vision improved after radiation therapy. Acute toxicity was mild. One patient required cyst drainage 3 months after radiotherapy. Late toxicity after radiotherapy included impairment of hormone function in 3 out of 18 patients at risk. We did not observe any vision impairment, radionecrosis, or secondary malignancies. CONCLUSIONS FSRT is effective and safe in the treatment of cystic craniopharyngiomas. Toxicity is extremely low using this conformal technique.