Michael Wannenmacher

Stereotactic single-dose radiotherapy of stage I non–small-cell lung cancer (NSCLC)

PURPOSE The treatment of early-stage lung cancers is a primary domain of thoracic surgery, leading to persuasive results. In patients with medical contraindications, radiotherapy is an alternative, although with considerably worse outcome. Radiotherapy is associated with the risk of severe acute side effects and a permanent decrease of lung function. By the introduction of an extracranial stereotactic treatment technique, the amount of normal tissue in the high-dose region can be reduced, allowing the performance of single-dose treatment with high, biologically effective doses. METHODS AND MATERIALS Between October 1998 and May 2001, 10 patients with histologically confirmed Stage I non-small-cell lung cancer were treated with stereotactic single-dose radiotherapy. A self-developed stereotactic frame was used for patient positioning and navigation. Total doses applied ranged from 19 to 26 Gy. After treatment, regular CT-based follow-up was performed. RESULTS During a median follow-up period of 14.9 months, the tumors in 8 of 10 patients were locally controlled. The actuarial overall survival was 80% and 64%, respectively, 12 and 24 months after therapy. Actuarial local recurrence-free survival reached 88.9% and 71.1%, respectively. Therapy-related perifocal normal-tissue reaction occurred in 70% of all treated patients, although no major clinical symptoms were seen. In 5 patients, systemic metastases were found during follow-up; 1 patient developed suspect mediastinal lymph nodes. CONCLUSION Stereotactic single-fraction radiotherapy is a feasible, safe, and effective procedure for the treatment of Stage I non-small-cell lung cancer. It promises high local control with a reduced overall treatment time. However, further investigation in a larger patient collective with extended follow-up is necessary.

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.

High Efficacy of Fractionated Stereotactic Radiotherapy of Large Base-of-Skull Meningiomas: Long-Term Results

PURPOSE Large skull-base meningiomas are difficult to treat due to their proximity or adherence to critical structures. We analyzed the long-term results of patients with skull-base meningiomas treated by a new approach with high-precision fractionated stereotactic radiotherapy. PATIENTS AND METHODS One hundred eighty-nine patients with benign meningiomas were treated with conformal fractionated stereotactic radiotherapy between 1985 and 1998. Patients were undergoing a course of radiotherapy either as primary treatment, following subtotal resection, or for recurrent disease. The median target volume was 52.5 mL (range, 5.2 to 370 mL). The mean radiation dose was 56.8 Gy (+/- 4.4 Gy). Follow-up examinations, including magnetic resonance imaging, were performed at 6-month intervals thereafter. RESULTS The median follow-up period was 35 months (range, 3 months to 12 years). Overall actuarial survival for patients with World Health Organization (WHO) grade I meningiomas was 97% after 5 years and 96% after 10 years. Local tumor failure was observed in three of 180 patients with WHO grade I tumors and was significantly higher in two of nine patients with WHO grade II tumors. A volume reduction of more than 50% was observed in 26 patients (14%). Preexisting cranial nerve symptoms resolved completely in 28% of the patients. Clinically significant treatment-induced toxicity was seen in 1.6% of the patients. No treatment-related deaths occurred. CONCLUSION The results of this study demonstrate that fractionated stereotactic radiotherapy is safe and effective in the therapy of subtotally resected or unresectable meningiomas. The overall morbidity and incidence subacute and late side effects of this conformal radiotherapy approach were low.

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.

Combined error of patient positioning variability and prostate motion uncertainty in 3D conformal radiotherapy of localized prostate cancer

PURPOSE To measure the patient positioning and prostate motion variability and to estimate its influence on the calculated 3D dose distribution in 3D conformal radiotherapy of patients with localized prostate carcinoma. METHODS AND MATERIALS Patient positioning variability was determined retrospectively by comparing 54 orthogonal simulator films with 125 corresponding portal films from 27 patients. Prostate motion variability was determined by 107 computed tomography (CT) examinations with a CT simulator in 28 patients during radiotherapy. RESULTS In each observed direction, the patient positioning variability and prostate motion showed a normal distribution. This observation enabled the calculation of a combined error of both components. The standard deviation (1 SD) of the patient positioning error in three directions ranged from 3.1 to 5.4 mm; the prostate motion variability was significantly greater in the anterior-posterior direction (1 SD = 2.8 mm) than in the mediolateral direction (1 SD = 1.4 mm). The 1 SD of the estimated combined error was in the anterior-posterior direction 6.1 mm and in mediolateral direction 3.6 mm. CONCLUSION The range of patient positioning variability and prostate motion were statistically predictable under the patient setup conditions used. Dose-volume histograms demonstrating the influence of the combined error of both components on the calculated dose distribution are presented.

CLINICAL RESULTS OF RETREATMENT OF VERTEBRAL BONE METASTASES BY STEREOTACTIC CONFORMAL RADIOTHERAPY AND INTENSITY-MODULATED RADIOTHERAPY

PURPOSE Reirradiation of spinal tumors is limited by the tolerance of the spinal cord. We evaluated local control, pain relief, neurologic improvement, side effects, and survival rates after fractionated conformal radiotherapy (FCRT) and intensity-modulated RT (IMRT) of recurrent spinal metastases. METHODS AND MATERIALS Eighteen patients with 19 radiologic manifestations were retreated for recurrent spinal metastases using FCRT (n = 5) or IMRT (n = 14). All patients had previously undergone conventional RT (median dose 38 Gy). The indication for reirradiation was tumor progression associated with pain (n = 16) or neurologic symptoms (n = 12). The median time to recurrence was 17.7 months. The median total dose for reirradiation was 39.6 Gy. RESULTS The overall local control rate was 94.7% after a median follow-up of 12.3 months. Of 16 patients with pain, 13 experienced significant relief after reirradiation. Neurologic improvement was obtained in 5 of 12 patients. Tumor size remained unchanged in 84.2%. A partial response was seen in 2 of 19 patients. One patient had local tumor progression 9.5 months after reirradiation. Six patients received chemotherapy after reirradiation because of progressive distant metastases. Twelve patients died 10.5 months median after reirradiation. No clinically significant late toxicity was seen after FCRT or IMRT. CONCLUSION These data demonstrate that FCRT and IMRT are effective and safe in recurrent spinal tumors and can be offered to patients to achieve local control, as well as pain relief.

Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy

PURPOSE To evaluate salivary gland function after inversely planned stereotactic intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS Since January 2000, 18 patients undergoing IMRT for cancer of the head and neck underwent pre- and posttherapeutic scintigraphy to examine salivary gland function. The mean dose to the primary planning target volume was 61.5 Gy (range 50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid glands were directly adjacent to the planning target volume. The treatment planning goal was for at least one parotid gland to receive a mean dose of <26 Gy. Two quantitative parameters (change in maximal uptake and change in the relative excretion rate before and after IMRT) characterizing the change in salivary gland function after radiotherapy were determined. These parameters were compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose. In addition, dose-response curves were calculated. RESULTS Using IMRT, it was possible in 16 patients to reduce the dose for at least one parotid gland to < or =26 Gy. In 7 patients, protection of both parotid glands was possible. No recurrent disease adjacent to the protected parotid glands was observed. Using the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No greater toxicity was seen for the salivary glands. The change in the relative excretion rate was significantly greater, if the parotid glands received a mean dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a statistically significant difference was seen only for the parotid glands and a dose threshold of 30 Gy. For the end point of a reduction in the parotid excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50% complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively. CONCLUSION Using IMRT, it is possible to protect the parotid glands and reduce the incidence and severity of xerostomia in patients. Doses <26-30 Gy significantly preserve salivary gland function. The results support the hypothesis that application of IMRT does not lead to increased local failure rates.

External radiotherapy of pituitary adenomas

PURPOSE To evaluate therapeutic outcome and side effects of radiotherapy in pituitary adenomas as sole or combined treatment. METHODS AND MATERIALS Retrospective analysis of 138 patients (74 male, 64 female) irradiated for pituitary adenoma from 1972 to 1991 was performed. Mean age was 49.7 years (15-80 years). Regular follow-up (in the mean 6.53 +/- 3.99 years) included radiodiagnostical [computed tomography (CT), magnetic resonance imaging (MRI), x-ray], endocrinological, and ophthalmological examinations. Seventy patients suffered from nonfunctional pituitary adenoma, 50 patients suffered from growth-hormone producing adenomas, 11 had prolactinomas, and 7 patients had adrenocorticotropic hormone (ACTH) producing pituitary adenomas. In 99 patients surgery was followed by radiotherapy in case of suspected remaining tumor (invasive growth of the adenoma, assessment of the surgeon, pathologic CT after surgery, persisting hormonal overproduction). Twenty-three patients were treated for recurrence of disease after surgery and 16 patients received radiation as primary treatment. Total doses from 40-60 Gy (mean: 45.5 Gy) were given with single doses of 2 Gy 4 to five times a week. RESULTS Tumor control was achieved in 131 patients (94.9%). In seven patients, recurrence of disease was diagnosed in the mean 2.9 years (9-98 months) after radiotherapy and salvaged by surgery. A statistically significant dose-response relationship was found in favor of doses > or = 45 Gy. Ninety percent of the patients with hormonally active pituitary adenomas had a benefit from radiotherapy in means of complete termination (38%) or at least reduction (52%) of hormonal overproduction. Partial or complete hypopituitarism after radiotherapy developed, depending on hormonal axis, in 12 (prolactin) to 27% (follicle-stimulating hormone FSH) of patients who had not already had hypopituitarism prior to radiation. Two out of 138 patients suffered reduction of visual acuity, which was, in part, related to radiotherapy. Both therapeutic effects and side effects occurred after a latency period of 3 months up to 9 years. CONCLUSION We conclude that radiotherapy of pituitary adenomas, using modern treatment planning techniques, is effective and safe. To achieve optimal tumor control, doses of 45-48 Gy (conventionally fractionated) should be applied.

Stereotactic single high dose radiation therapy of benign intracranial meningiomas

Seventeen patients with intracranial meningiomas were treated with single high dose irradiation at the German Cancer Research Center in Heidelberg. Indications for radiosurgery included unresected tumors, gross disease remaining despite surgery, and recurrences. Therapy was carried out by a technique using multiple non-coplanar arc irradiations from a 15 MeV linear accelerator. This technique coupled with secondary tungsten collimators allowed a high concentration of the dose in the target volume with an extremely steep dose gradient at the field borders. The patients were treated with a single irradiation dose ranging from 10 to 50 Gy (mean of 29 Gy). Four of 17 patients died: one death was tumor-related and not attributable to the treatment, one died of a treatment related complication, and two patients died of intercurrent diseases. The remaining 13 of the 17 patients with a median follow-up time of 40 months have no evidence of tumor relapse. Late severe side effects include five patients with a large area of brain edema, three of which were concurred with tumor necrosis. We conclude from these initial data that single high doses of irradiation concentrated to the tumor volume by stereotaxic methods can achieve local tumor control. It is also clear from these data that the effective therapeutic dose range must be better defined.

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.