Peripheral blood progenitor cell transplantation in multiple myeloma following high-dose melphalan-based therapy.

The objective of our study was to evaluate the efficacy and toxicity of a high-dose melphalan-based therapy with or without total body irradiation (TBI) followed by peripheral blood progenitor cell (PBPC) transplantation in patients with multiple myeloma. Between June 1992 and June 1996, 104 patients (71 male, 33 female) with a median age of 51 years (range 30-65 years) underwent transplantation at our center. PBPC were mobilized using high-dose chemotherapy followed by treatment with G-CSF. Fifty patients were treated with TBI+melphalan 140 mg/m2 while 54 patients received melphalan 200 mg/m2. Following PBPC autografting, the median time to attainment of platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l was 11 and 14 days, with no difference between the treatment groups. In the TBI group significantly longer periods of total parenteral nutrition were required due to the occurrence of severe mucositis. Two patients from the TBI group died of transplantation-related complications. Following high-dose treatment, remission state improved in 43 out of 102 patients. No statistically significant advantage in reaching complete or partial remission was observed with TBI+high-dose melphalan compared to the treatment with high-dose melphalan alone. The optimal high-dose treatment, with particular reference to the inclusion or omission of TBI, should be prospectively investigated.

[Brain metastases in renal cell carcinoma. Results of treatment and prognosis]. / Hirnmetastasierung beim Nierenzellkarzinom. Behandlungsergebnisse und Prognose.

Brain metastases develop as a late manifestation of renal cell cancer (RCC) and pose an increasing challenge to urologists as a result of the more frequent prolonged survival of patients with advanced RCC. Therapeutic options, including surgical resection and radiotherapy, were analyzed retrospectively to assess survival and to identify factors influencing prognosis in a group of 90 patients treated either by brain metastasectomy (n = 64) or radiotherapy (n = 26). The analysis confirmed that the overall median survival was a disappointing 461 days and the 1-year survival rate was 31% for patients treated by surgical resection and 310 days and 15% respectively for patients treated by radiotherapy. However, a subgroup of patients who, benefitted significantly from aggressive treatment of metastases could be defined. The following favorable prognostic factors showed a trend toward improved survival: (1) metachronous appearance of brain metastases more than 1 year after nephrectomy (P < 0.0001), (2) good patient performance (Karnofsky > 70) (P < 0.0002), (3) patient's age under 50 years (P < 0.05), (4) solitary lesions (P < 0.05), (5) minimal or no neurological deficit (P < 0.05), and (6) the absence of/or minimal extracranial metastases (P < 0.05). No influence of lesion size and localization (infratentorial vs supratentorial) on survival was detected. Surgical treatment of recurrent brain tumors (n = 17) yielded and additional median survival advantage of 8 months as compared to untreated patients (n = 16). Our results suggest that, especially in patients with good prognostic criteria, a radical metastasectomy plus vigorous surgery of local recurrences and, if required, subsequent systemic immuno- or chemoimmunotherapy should be performed. In patients with poor prognosis, stereotactic radiosurgery is recommended for palliation and survival prolongation.

High-dose therapy with peripheral blood progenitor cell transplantation in multiple myeloma.

BACKGROUND: The objective of our study was to evaluate the efficacy and toxicity of a high-dose melphalan-based (HD-Mel) therapy with or without total body irradiation (TBI) followed by peripheral blood progenitor (PBPC1 transplantation in patients with multiple myeloma (MM). PATIENTS AND METHODS: Between June 1992 and May 1996, 100 patients (67 males 33 females with a median age of 51 years range 30-65) were transplanted at our centre. PBPC were collected during G-CSF-enhanced leukocyte recovery following high-dose chemotherapy. Fifty patients were treated with TBI + melphalan 140 mg m2, while 50 patients received melphalan 200 mg/m2. RESULTS: Following PBPC autografting, the median time to reach platelets > or = 20 x 10(9) 1 and neutrophils > or = 0.5 x 10(9)/1 was 11 and 14 days with no difference between the treatment groups. In the TBI group significantly longer periods of total parenteral nutrition were required due to severe mucositis. Two patients from the TBI group died due to transplantation-related complications. Following high-dose treatment, remission state improved in 43 out of 98 patients. No statistically significant advantage in reaching CR or PR was observed with TBI + HD-Mel compared to the treatment with HD-Mel alone. CONCLUSION: Dose-escalated treatments, with particular regard to the inclusion or omission of TBI, should be prospectively investigated to find the best high-dose regimen.

Intracranial meningeomas: time- and dose-dependent effects of irradiation on tumor microcirculation monitored by dynamic MR imaging.

The purpose of this study was the characterization of the time- and dose-dependent effects of irradiation on tumor microcirculation by means of dynamic MR imaging and correlation of the estimated data with tumor response in patients with meningeomas. Dynamic MR imaging studies were performed in 20 patients with intracranial meningeomas prior to (n = 20) and at 6 (n = 17), 18 (n = 17), and 50 wk (n = 14) after the end of radiotherapy. In seven of these patients, dynamic measurements were also performed during fractionated radiotherapy after approximate 20 Gy and 54 Gy. During and after short-time infusion of gadopentetate dimeglumine, the kinetics of lesion response was resolved using a strongly T1-weighted saturation recovery TurboFLASH (SRTF) sequence. The signal-time courses of the suspected lesions were analyzed using a pharmacokinetic two-compartment model. The calculated parameters amplitude A (reflecting gadopentetate dimeglumine accumulation in the extracellular space) and exchange rate constant k21 (depending on vascular permeability and blood flow) were displayed as color-coded images and analyzed as a function of time of therapy and radiation dose. All meningeomas showed a high exchange rate constant k21 (median, 5.7 min-1; range, 1.9-23.0 min-1) and a high amplitude A (median, 1.5 arbitrary units; range, 1.1-2.7) prior to X-ray treatment. During radiotherapy we found a dose related significant (p < .01) increase of k21 accompanied by an increase of the amplitude A as compared to the pretreatment values. Analysis of tumor volume 6, 18, and 50 wk after X-ray treatment revealed two different groups. In the responder group (n = 13) the median of the tumor volume decreased from 10.0 to 7.5 cm3. For this group, we found a significant drop (p < .01) of the median of the amplitude A and a decrease of the exchange rate constant k21. In the nonresponder group (n = 4) the median of the tumor volume increased after radiation from 3.5 to 4.5 cm3. The pharmacokinetic analysis revealed a decrease of the amplitude A-and an increase of the exchange rate constant k21. The response of meningeomas to radiotherapy is influenced by the effect of X-rays on tumor microcirculation. This effect on tumor microcirculation can be derived by analysis of pharmacokinetic maps obtained from dynamic MR images. Furthermore, these pharmacokinetic maps can possibly be used to differentiate groups of patients who respond or do not respond to radiotherapy and, thus, could benefit from another treatment modality.

[Blood volume changes after the radiotherapy of the central nervous system]. / Blutvolumenveränderungen nach Strahlentherapie des zentralen Nervensystems.

BACKGROUND: The pathogenesis of late delayed radiation damage in normal brain tissue is most likely due to damage to the vascular endothelium. The mitotic activity of gliomas was shown to correlate with the tumor induced angiogenesis. Dynamic susceptibility contrast MR imaging (DSC MRI) allows the measurement of the cerebral hemodynamics based on the indicator dilution theory. We describe theory and technique of the method and present our experience with blood volume measurements after irradiation of the CNS. METHODS: We established a double slice technique on a standard 1.5 T MR system without hardware modifications, which allows an absolute quantification of the blood volume in regions of interest (ROI) within the brain. Fifty-five T2* weighted double slice images were acquired before, during and after bolus injection of Gd-DTPA (0.1 mmol/kg in 5 sec.) using a SD FLASH sequence (simultaneous dual fast low angle shot, TR/TE1/TE2 31/16/25, flip angle 10 degrees). Concentration-time curves were calculated from the measured signal-time curves. Blood volume values in tissue were normalised and calculated in absolute values (ml/100 g) based on the knowledge of the arterial input function (AIF), which was measured in the brain supplying arteries. The whole procedure requires only 2 to 3 minutes, the time for post processing is about 15 to 20 minutes. RESULTS: Blood volume parameter images of representative cases demonstrate the blood volume changes after radiotherapy. A reduction in blood volume could be observed in normal brain tissue and low-grade gliomas, while recurrent tumors were accompanied by a local increase in blood volume. CONCLUSIONS: Radiation induced blood volume changes in the CNS can be measured using dynamic susceptibility contrast MR imaging. The measurements in normal brain tissue allow a functional in-vivo analysis of late delayed radiation reactions of the CNS. The definite value of intratumoral blood volume measurements for determination of the therapeutic success and for differentiation of recurrences versus radionecroses remains to be clarified in further studies.

Neutrontherapy in soft tissue sarcomas: a review of European results.

The purpose of this publication is to review the data on European neutrontherapy facilities in the treatment of soft tissue sarcoma. Data on 1171 patients treated at 11 centers were analyzed. Neutrontherapy was of advantage especially for patients with primary radiotherapy of inoperable tumors, and those with macroscopic disease after surgery. Local control was about 50% in these groups. Results for postoperative neutrontherapy after R0 and R1 resection were similar to those for photon therapy. The incidence of late side effects was considerable. This was influenced by the fact that most patients were treated with first-generation machines.

European results in neutron therapy of malignant salivary gland tumors.

In Europe to date, 501 patients with salivary gland tumors have been treated with neutrons alone or with combined modalities. The most common histological types are adenoid cystic carcinomas, mucoepidermoid carcinomas and malignant mixed tumors. The results of conventional radiotherapy are suboptimal in inoperable or incompletely resected salivary gland tumors and in recurrent disease. The pooled data of some international series for low linear energy transfer radiation show a local control of 28%. Especially in advanced tumors neutron therapy can improve local control and should be the treatment of choice. The clinical data from different therapy centers in Europe show local control of 67% in gross disease.

Functional magnetic resonance imaging in a stereotactic setup.

The localization of critical structures within the brain is important for the planning of therapeutic strategies. Functional MRI is capable to assess functional response of cortical structures to certain stimuli. The authors present two techniques for functional MRI (fMRI) in a stereotactic set-up. The skull of the patients has been immobilized for stereotactic treatment planning either with a self developed stereotactic ceramic frame and bony fixation or with an individual precision mask system made of light cast. It has been shown that this frame does not produce any image distortion. fMRI was performed using a modified FLASH sequence on a conventional 1.5 T MRI scanner with a specially developed linear polarized head coil. The imaging technique used was an optimized conventional 2D and 3D, first order flow rephased, gradient echo sequence (FLASH) with fat-suppression and reduce bandwidth (16-28 Hz/pixel) and TR = 80-120 ms, TE = 60 ms, flip angle = 40 degrees, matrix = 128 x 128, FOV = 150-250 mm, slice-thickness = 2-5 mm, NEX = 1, and a total single scan time for one image of about 7 sec. The motor cortex stimulation was achieved by touching each finger to thumb in a sequential, self-paced, and repetitive manner. Statistical parametric maps based on student's test were calculated. Pixels with a highly significant signal increase (p < 0.001) are overlaid on T1w SE images. The primary motor and sensory cortex could be visualized with this method in all 10 patients that were imaged in this study. Due to tight fixation of the patient's skull there have been no motion artifacts. These results show that functional MRI is feasible in an stereotactic set-up with an standard 1.5 T scanner. This is a prerequisite for the exact pre therapeutic assessment of the function of cortical centers.

Improved target volume definition in radiosurgery of arteriovenous malformations by stereotactic correlation of MRA, MRI, blood bolus tagging, and functional MRI.

In this methodological paper the authors report the stereotactic correlation of different magnetic resonance imaging (MRI) techniques [MR angiography (MRA), MRI, blood bolus tagging (STAR), and functional MRI] in 10 patients with cerebral arteriovenous malformations (AVM) and its application in precision radiotherapy planning. The patient's head was fixed in a stereotactic localization system that is usable at the MR and the linear accelerator installations. By phantom measurements different materials (steel, aluminium, titanium, plastic, wood, ceramics) used for the stereotactic system were tested for mechanical stability and geometrical MR image distortion. All metallic stereotactic rings (closed rings made of massive metal) led to a more or less dramatic geometrical distortion and signal cancellation in the MR images. The best properties-nearly no distortion and high mechanical stability-are provided by a ceramic ring. If necessary, the remaining geometrical MR image distortion can be "corrected" (reducing displacements to the size of a pixel) by calculations based on modeling the distortion as a fourth-order two-dimensional polynomial. Using this method multimodality matching can be performed automatically as long as all images are acquired in the same examination and the patient is sufficiently immobilized. Precise definition of the target volume could be performed by the radiotherapist either directly in MR images or in calculated projection MR angiograms obtained by a maximum-intensity projection algorithm. As a result, information about the hemodynamics of the AVM was provided by a three-dimensional (3D) phase-contrast flow measurement and a dynamic MRA with the STAR technique leading to an improved definition of the size of the nidus, the origin of the feeding arteries, and the pattern of the venous drainage. In addition, functional MRI was performed in patients with lesions close to the primary motor cortex area leading to an improved definition of structures at risk for high-dose application in radiosurgery. The different imaging techniques of MR provide a sensitive, noninvasive, 3D method for defining target volume, critical structures, and for calculating dose distributions for radiosurgery of cerebral arteriovenous malformations, because dose calculation of radiosurgery at sufficient accuracy can be based on 3D MR data of the geometrical conformation of the patient's head.

Cerebral arteriovenous malformations: improved nidus demarcation by means of dynamic tagging MR-angiography.

Our purpose was to further improve the target volume definition for radiosurgical treatment of cerebral arteriovenous malformations (AVMs) by means of dynamic MRA (dMRA) using a blood bolus tagging sequence. We therefore compare this technique with 3D-TOF-MRA and transfemoral high resolution angiography in plain film technique. Twenty patients with angiographically proven cerebral AVMs were investigated by dMRA, TOF-MRA, and conventional angiography during the MR-assisted radiosurgical planning protocol. The patient's head was fixed in an MR-compatible stereotactic device. The different angiography techniques were evaluated by consensus of two radiologists. AVMs were characterized by the number and origin of feeding arteries, the maximum diameter of the AVM nidus, and the venous drainage pattern. Dynamic MRA was able to demonstrate the complete AVM characteristics and hemodynamics in 12 out of 20 patients. In three patients with an AVM nidus smaller than 1 cm in diameter the technique could not reliably depict the malformation. Technical problems due to steel screws and pins in the initially used stereotactic frame occurred in five patients. Due to reduced vessel overlap and the lack of disturbances caused by formations with short T1 time, dMRA was superior to TOF-MRA in the detection and the exact localization of the AVM nidus in four patients. We conclude that dMRA is able to demonstrate reliably AVM characteristics and hemodynamics in AVMs with a nidus larger than 1 cm in diameter. Because of the improved demarcation of the AVM nidus, this technique may be a valuable adjunct to radiosurgery planning of cerebral AVMs.

Effect of radiation on blood volume in low-grade astrocytomas and normal brain tissue: quantification with dynamic susceptibility contrast MR imaging.

OBJECTIVE: The purpose of this study was to determine whether it is possible to measure radiation-induced changes in blood volume in low-grade astrocytomas and in normal brain tissue. SUBJECTS AND METHODS: The passage of a bolus of gadopentetate dimeglumine was monitored on a series of 55 T2*-weighted simultaneous dual fast low-angle shot MR images with a standard 1.5-T MR imaging system. Absolute blood volumes were calculated as the area under the tissue concentration-time curve in regions of interest and normalized to the arterial input function. We performed 41 examinations on 19 patients with grade II astrocytomas. For comparison, 13 patients were studied after whole-brain irradiation. RESULTS: A reduction in blood volume (mean +/- SD in milliliters per 100 g) within the tumors from 12.2 +/- 8.7 to 6.5 +/- 5.3 after fractionated conformation radiotherapy was detected, although there was no consistent pattern in different patients. An insignificant reduction was noted in normal gray (9.2 +/- 2.8 to 7.4 +/- 3.2) and white (4.4 +/- 1.9 to 4.1 +/- 2.3) matter outside the target volume. Conversely, we observed a significantly lower blood volume in gray (6.3 +/- 1.2) and white (3.1 +/- 1.0) matter after whole-brain radiotherapy. CONCLUSION: Our results show that a reduction of blood volume in astrocytomas and normal brain tissue after radiotherapy can be quantified by use of dynamic susceptibility contrast MR imaging. Thus, functional monitoring of tumor response and of normal tissue effects becomes possible.

[The belly-board technic for the sparing of the small intestine. Studies on positioning accuracy taking into consideration conformational irradiation technics]. / Lochbrettechnik zur Dünndarmschonung. Untersuchungen zur Lagerungsgenauigkeit unter Berücksichtigung konformierender Bestrahlungstechniken.

BACKGROUND: The immobilization error of patients positioned on the open table-top device in prone position as well as the movement of the small bowel out of the pelvis by this positioning technique was determined. The positioning error is of special importance for the 3-dimensional treatment planning for conformational radiotherapy. PATIENTS AND METHODS: The positioning error was determined by superpositioning 106 portal films with the corresponding simulator films from 21 patients with carcinoma of the rectum who-received 3D-planned conformational radiotherapy (3-field technique with irregular blocks). The movement of the small bowel out of the pelvis was studied by comparing simulator films after barium swallow in supine and open table-top position as well with 3D-treatment plans of the same patient in both positions in 3 cases. RESULTS: The positioning error along the medio-lateral, dorso-ventral and cranio-caudal axis was 1.4/0.6/1.8 mm and the standard deviation 4.4/6.8/6.3 mm, respectively. In comparison to the supine position more rotation errors in the sagittal view were observed (37% and 9% respectively) with a median of 5.1 degrees. Six out of 22 patients showed no adhesions of the small bowel and a complete movement out of the treatment field was achieved. 14 out of 16 Patients with adhesions revealed a partial movement of the small bowel out of the treatment field. Comparing 3D-treatment plans in both positions again demonstrated a marked reduction of the irradiated small bowel volume with the use of the open table-top device. CONCLUSIONS: The open table-top device positioning technique is a simple and cheap positioning support to reduce small bowel obstructions by radiation therapy of pelvic and retroperitoneal tumors. For the radiation treatment planning the data suggest a safety margin to compensate positioning errors of approximately 1.5 cm referring to the 95% confidence interval.

[The initial results in the fractionated 3-dimensional stereotactic irradiation of clivus chordomas]. / Erste Ergebnisse bei der fraktionierten dreidimensionalen stereotaktischen Bestrahlung von Klivuschordomen.

BACKGROUND: The purpose of this study is to determine the impact of fractionated three-dimensional stereotactic radiotherapy on local tumor control and radiation induced side effects in patients with spheno-occipital chordoma. PATIENTS, MATERIAL AND METHODS: 13 patients with chordoma of the clivus (8 female, 5 male, median age at radiotherapy 42 years) were treated with a three-dimensional non-coplanar stereotactic irradiation technique using 15 MeV-photons. Median dose applied was 70 Gy. Irradiation was performed in 2 patients after biopsy and in 11 patients after resection of chordoma (2 R1-resections and 9 R2-resections). RESULTS: After a median follow-up period of 32 months (4 to 80 months) 12 patients are alive (92%). One patient died 4 months after radiotherapy due to tumor progression. Three of the surviving patients developed local recurrence. Until now local tumor control is 69%. In two patients who had macroscopic tumor after surgery a complete regression occurred (verified by CT and MRI respectively). Early radiation complications were moderate, only headache and dizziness were observed. Also late radiation complications were low. Only one patient developed an endocrine dysfunction due to pituitary injury. Ongoing hormone replacement was necessary in this case. No patient developed sequelae of the optic system, cranial nerves or brain stem. CONCLUSION: With regard to local tumor control our results are in the more favorable range compared to the results obtained with conventional photon irradiation techniques. In spite of the high doses applied both early and late radiation complications were in an acceptable range. Further adequate follow-up must prove, whether these promising results will be corroborated in the future.

The role of high-dose, single-fraction irradiation in small and large intracranial arteriovenous malformations.

PURPOSE: Radiosurgery with external beam irradiation is an accepted treatment for small intracranial vascular malformations. It has been proven effective and safe for lesions with volumes of less than 4 cc. However, there is only some limited clinical data for malformations of grade 4 and grade 5, according to Spetzler and Martin. METHODS AND MATERIALS: At the Heidelberg radiosurgery facility equipped with a linear accelerator, 212 patients with cerebral arteriovenous malformations have been treated since 1984. Thirty-eight percent of the arteriovenous malformations treated were classified inoperable, 14% grade 5, 19% grade 4, and 29% grades 1-3. Radiation doses between 10 and 29 Gy were applied to the 80% isodose contour. RESULTS: Above a threshold dose of 18 Gy, the overall obliteration rate was 72%. After 3 years, the obliteration rates were 83% with volumes of less than 4.2 cc, 75% with volumes of up to 33.5 cc, and 50% with volumes of up to 113 cc. Of the patients presenting with seizures and paresis, 83% and 56%, respectively, showed improvement, which correlated with the degree of obliteration. After a follow-up period of up to 9 years, the rate of radiation-induced severe late complications was 4.3%. In grade 5 lesions, the risk of side effects was 10%. No serious complications occurred if a maximum dose of less than 25 Gy was applied to treatment volumes of less than 33.5 cc. CONCLUSION: The success of stereotactic high-dose irradiation of arteriovenous malformations depends on the dose applied. The incidence of radiation-induced side effects increased with the applied dose and treatment volumes. From our experience, doses of less than 25 Gy and treatment volumes of up to 33.5 cc are safe and effective. In the future, new techniques of radiosurgery with linear accelerators and dynamically reshaped beams will allow us to apply homogenous dose distributions. Additional use of magnetic resonance angiography for 3D treatment planning will help to identify the nidus more easily.

[TOF-MR angiography in radiotherapy treated cerebral arteriovenous malformations]. / TOF-MR-Angiographie bei strahlentherapeutisch behandelten zerbralen arteriovenösen Malformationen.

Intracerebral arteriovenous malformations represent congenital anomalies with an arteriovenous shunt (nidus). The therapeutic goal is to eliminate the risk of bleeding and to improve the clinical symptoms. The exact localization of the nidus and the identification of the feeding arteries are critical for therapy planning. Up to now conventional brain angiograms have been used for treatment planning and for the assessment of therapy response. We studied whether 3D time-of-flight (TOF) MR angiography can be used for therapy planning and monitoring. MRI and TOF-MRA studies of 28 patients undergoing radiotherapy were evaluated. They were compared to conventional angiography to assess the MRA study. A Correct identification of the arterial feeder and the nidus was possible in about 75% of the patients. In combination with the MRI study, an important 3D dataset for treatment planning could be obtained that includes therapeutically relevant information on the localization and spatial structure of the AVM as well as the adjacent brain tissue. As a noninvasive technique, close-meshed follow-up studies could be performed with MRA.

Recurrent rectal cancer: diagnosis with dynamic MR imaging.

PURPOSE: To evaluate whether dynamic magnetic resonance (MR) imaging can increase the diagnostic accuracy in suspected local recurrence of rectal carcinoma. MATERIALS AND METHODS: Eighteen patients (seven men, 11 women, aged 26-78 years) with 19 suspect lesions were examined. T1-weighted (pre- and postcontrast) and T2-weighted spin-echo images were read by three observers. Computed tissue-specific enhancement parameters were obtained and displayed on gray-scale images (pharmacokinetic mapping). RESULTS: Reading of the spin-echo images yielded a sensitivity of 91%-100% (confidence interval, 67%, 100%), a specificity of 29%-43% (12%, 67%), and an accuracy of 71%-75% (48%, 91%). Analysis of the MR data showed greater (P = .0038) and faster (P = .0018) enhancement of malignant lesions (n = 12) compared with benign lesions (n = 7). CONCLUSION: Pharmacokinetic mapping of dynamic MR imaging data allows in vivo insight into tissue physiopathology, helping differentiate benign from malignant pelvic lesions in rectal cancer.

3D TOF MR angiography of cerebral arteriovenous malformations after radiosurgery.

To investigate the potential of three-dimensional time-of-flight MR angiography (MRA) to complement SE imaging, 18 patients with intracerebral arteriovenous malformations were prospectively followed after undergoing radiosurgery. Vessel occlusion after stereotaxic single high dose radiotherapy develops slowly. The MRA detected signs of nidus obliteration earlier and with a higher sensitivity than did SE imaging. Six months after radiosurgery, MRA showed a reduction of the nidus flow signals in nine patients and after 1 year it showed reduction in 15 of the 18 patients. As shown by MRA, the loss of flow signals was related to a reduction of the nidus size in 4 patients after 6 months and in 11 after 1 year. The SE imaging revealed a reduction of the nidus size in only two patients after 6 months and in eight after 1 year. The signal intensity of the feeding arteries was reduced in nine patients and that of the draining veins was reduced in six. The T2-weighted images exhibited white matter lesions in eight patients after 1 year. For complete follow-up, SE imaging should be performed together with MRA.

Long-term follow-up for brain metastases treated by percutaneous stereotactic single high-dose irradiation.

Surgery is considered the treatment of choice for solitary brain lesions, and radiation therapy is indicated for metastases only in vital or sensitive regions that cannot be excised without risk of disabling neurologic defects. In these cases, radiosurgery may be an alternative to conventionally fractionated radiation therapy. At the Heidelberg linear accelerator-based radiosurgery facility, 69 patients were treated for 102 inoperable brain metastases. The primary tumor sites included non-small cell lung carcinoma (n = 24), renal cell carcinoma (n = 14), melanoma (skin) (n = 14), colorectal carcinoma (n = 6), carcinoma of unknown primary (n = 4), and others (n = 7). Eleven patients were treated for relapse after surgery or after conventional whole-brain irradiation. The doses at the isocenter varied from 15-50 Gy (mean, 21.5 Gy). Ten patients with multiple metastases received a planned combination of whole-brain irradiation plus a single boost of 15 Gy. The median survival time for the entire group was 6 months, with a 1-year-survival of 28.3%. Factors associated with significant improvement of survival were brain metastases without other metastatic disease and good response to radiation therapy. Five of 22 patients (22.9%) with metastases located only in the brain survived longer than 2 years. An improvement in neurologic function was found in 81% within a period of 3 months. With imaging techniques, complete remission was found in 20%, partial remission in 35%, stable disease in 40%, and relapse in 5%. The authors concluded that radiosurgery is an effective and safe therapy for brain metastases. It can be applied as primary treatment, as boost in combination with whole-brain irradiation, or as treatment for patients with relapse in a previously irradiated field.

[Stereotactic convergent-beam irradiation: its current prospects based on clinical results]. / Stereotaktische Konvergenzbestrahlung: Aktuelle Perspektiven auf der Grundlage klinischer Ergebnisse.

"Radiosurgery" is the term for a special concept in radiotherapy. It describes a percutaneous, stereotactically guided irradiation delivering a single high dose with collimated narrow beams. The precise stereotactic localization of the target point and a steep dose gradient outside the target volume allow the administration of high doses to a lesion without damage to adjacent normal tissue. Risk of necrosis, due to a dose volume relationship represents the limits of radiosurgery. Units for radiosurgery were designed at Stockholm using multiple external cobalt-60-gamma sources, at Boston operating with protons of a cyclotron, at Berkeley operating with helium ions accelerated by a synchrocyclotron. An attractive alternative to these complicated and expensive facilities is the use of a modified linear accelerator. At the German Cancer Research Center in Heidelberg such a system was developed and has been available for the treatment of patients since 1984. Though, data of over 100,000 patients with vascular malformations and cancer disease are available worldwide, the indication for this therapy is validated only for a minority of entities. In cases of inoperable arteriovenous malformations favourable results in achieving obliteration range between 60% and 100% were obtained. Median survival for solitary brain metastases with controlled, extracerebral tumor diseases were between nine and twelve months. Up to now, advantages of stereotactic irradiation for benign tumor masses could not be proven. Therefore, randomized trials should be initiated in this field, considering decisive improvements in local tumor control with techniques of microsurgery and fractionated, postoperative radiotherapy during the last few years.