Breast irradiation with brachytherapy: approved techniques and new concepts.

Among surgery and chemotherapy, radiotherapy has an important role in the treatment of breast cancer patients. But not only external beam radiotherapy (EBRT) treatment is an established method for treatment of breast cancer, also brachytherapy (BT) is an approved method. BT is well known for boost irradiation in combination with EBRT, but new indications as re-irradiation for local recurrences or partial breast irradiation offer new aspects in the field of BT for breast cancer treatment. Because of modern CT based 3-D treatment planning systems and the possibility of intensity modulated brachytherapy (IMBT) has getting more potential. In the future for selected patient's re-irradiation of the breast using IMBT after local relapse and second breast conserving surgery might be an alternative instead of mastectomy. Even partial breast BT following breast conservative operation as a new treatment option is getting more and more interesting and is widely investigated in several studies. Due to the approved techniques and the new indications BT is and will be an attractive alternative and extension in the field of breast cancer treatment. But we need five better ten years results for definite conclusions at least.

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.

Neurobehavioral toxicity of total body irradiation: a follow-up in long-term survivors.

PURPOSE: Total body irradiation (TBI) in preparation for bone marrow transplantation (BMT) is a routine treatment of hematological malignancy. A retrospective and a prospective group study of long-term cerebral side effects was performed, with a special emphasis on neurobehavioral toxicity effects. METHODS AND MATERIALS: Twenty disease-free patients treated with hyperfractionated TBI (14.4 Gy, 12 x 1.2 Gy, 4 days), 50 mg/kg cyclophosphamide, and autologous BMT (mean age 38 years, range 17-52 years; age at TBI 35 years, 16-50 years; follow-up time 32 months, 9-65 months) participated in a neuropsychological, neuroradiological, and neurological examination. Data were compared to 14 patients who were investigated prior to TBI. Eleven patients with renal insufficiencies matched for sex and age (38 years, 20-52 years) served as controls. In a longitudinal approach, neuropsychological follow-up data were assessed in 12 long-term survivors (45 years, 23-59 years; follow-up time 8.8 years, 7-10.8 years; time since diagnosis 10.1 years, 7.5-14.2 years). RESULTS: No evidence of neurological deficits was found in post-TBI patients except one case of peripheral movement disorder of unknown origin. Some patients showed moderate brain atrophy. Neuropsychological assessment showed a subtle reduction of memory performance of about one standard deviation. Cognitive decline in individual patients appeared to be associated with pretreatment (brain irradiation, intrathecal methotrexate). Ten-years post disease onset, survivors without pretreatment showed behavioral improvement up to the premorbid level. CONCLUSION: The incidence of long-term neurobehavioral toxicity was very low for the present TBI/BMT regimen.

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.

Iodine-131-labeled diphosphonates for palliative treatment of bone metastases: II. Preliminary clinical results with iodine-131 BDP3.

The kinetics, dosimetry, and response of iodine-131 alpha-amino-(4-hydroxybenzylidene)-diphosphonate ([131I]BDP3) treatment were investigated with patients who had pain symptoms from bone metastases of various primary carcinoma. The blood clearance of [131I]BDP3 was rapid. More than 90% disappeared from the blood pool at 2 hr after injection. The excretion of the activity occurred solely through the kidneys and mean total-body retention at 48 hr was 48.6%. The urinary activity showed a metabolite which must be formed by an in vivo cleavage reaction of a phosphorus-carbon bond. The uptake of in vivo cleaved [131I]iodide in the unblocked thyroid was approximately 0.5%. The effective half-life of [131I]BDP3 in metastatic bone (median 182 hr; range 177-205 hr) proved to be longer than in unaffected areas (145 hr; 140-165 hr). Palliative therapies were performed with 18 patients. They received doses ranging between 6 and 48 mCi [131I]BDP3. The response was 44% complete pain relief, 6% substantial pain relief, 22% minimal improvement, and 28% no change. The duration of response ranged between 1 and 8 wk.

Scintigraphy of a neuroblastoma with I-131 meta-iodobenzylguanidine.

Radioiodinated m-iodobenzylguanidine has been applied mainly for the diagnosis of pheochromocytoma and blastoma. In this paper we show that an ontogenetically related tumor, the neuroblastoma, is also scintigraphically visualized by its high uptake of I-131 MIBG. Because of the kinetic findings and the high uptake of more than 30% of the injected activity, it is likely that the neuroblastoma, by analogy with pheochromocytoma, is susceptible to specific radionuclide therapy.

The clinical use of platelet scintigraphy with 111-In-oxine.

Platelet scintigraphy was performed on 62 patients with cerebral ischaemia. Pathological scintigraphic images were obtained in 29 of the 62 patients. In 79.3% of these 29 patients the scan was abnormal in the vessel clinically affected. Platelet scintigraphy was abnormal in 21 of 34 patients with normal angiogram or only slight atherosclerosis. In patients undergoing antiplatelet therapy, platelet scintigraphy was less often positive than in untreated patients. It is suggested that platelet scintigraphy could be an appropriate technique for detecting small mural thrombi of the carotid artery, which are the source of arterio-arterial emboli, and for controlling the efficiency of antiplatelet therapy.

Imaging positron emitting radionuclides generated during radiation therapy.

In vivo generated positron emitting radioisotopes, primarily C-11 and N-13, have been documented following therapy with accelerators larger than 10 MeV. Six patients had positron emission tomography 15 to 25 minutes after radiation therapy with a 42 MeV accelerator. Five patients had recurrent colorectal malignancy, and one required therapy for a carcinoma of the common bile duct. We sought to determine whether state-of-the-art PET technology could be used to monitor the three-dimensional activity distribution of radiation-induced radioactivity. At the time of the examination all six patients had sufficient concentrations of C-11 and N-13 activity in the irradiated volume to permit the evaluation of the activity distribution. We found significant activity at the body surface, which permitted field delineation. We conclude that the in vivo generated radioactivity can be monitored with PET.

[False-positive findings of 67-gallium scintigraphy in staging/restaging of malignant lymphoma]. / Falsch-positive Befunde der 67Galliumszintigraphie im Staging/Restaging von malignen Lymphomen (ML).

Gallium scintigraphy has been an established method for the diagnosis of malignant lymphomas for some years. If properly interpreted, the value of the method is not necessarily reduced by the lack of tumour specificity and the well known property of 67Ga to accumulate in inflammatory and granulomatous conditions. A retrospective analysis of 123 patients with malignant lymphomas showed false positive 67Ga scintigrams in 7%. These cases demonstrate the spectrum of possible errors. 'False positives' were all those localised areas of uptake which were due to some pathological condition which was not lymphomatous. All the positive gallium findings could be elucidated by clinical, radiological and histological investigations.

[Computed tomography and scintigraphy in malignant pheochromocytoma]. / Computertomographie und Szintigraphie beim malignen Phächromozytom.

Two patients with malignant metastasising phaeochromocytomas are described. Special attention is paid to the findings on computed tomography and scintigraphy with meta-I-benzylguanidine. The scintigraphic findings are not uniform. A review of the literature has shown that the sensitivity of scintigraphy is less for malignant phaeochromocytomas than it is for benign tumours.

[Angio-CT: an improvement in the diagnosis of malignant liver diseases]. / Angio-CT: Eine Erweiterung der Diagnostik maligner Leberprozesse.

Dynamic contrast studies of the liver make it possible to evaluate the vascularity of liver metastases. Up to the present, the examination has only been carried out in single planes, whereas studies of the whole of the liver during one examination have not yet been published. This can be obtained by performing sequential CT (angio-CT), using special software. A clinical study of the value of the procedure has been undertaken on 64 patients with suspected liver metastases. In addition to the plain scans, the examination was repeated during the early phase of a bolus injection and subsequently ten minutes after injection (enhancement). The various structures which can be seen are described and the changes in density patterns have been interpreted according to contrast kinetics derived from nephrographic examinations. The advantages of angio-CT as compared with plain films and with scans after normal contrast infusions are described. The improved sensitivity and specificity obtained by using the three modes of examination, as compared with a single examination, is stressed.

[Validity of bone scintigraphy for radiotherapy treatment planning of the skeletal system]. / Wertigkeit der Knochenszintigraphie für die Bestrahlungsplanung im Skelettsystem.

Aim of this paper is to assess the validity of bone scanning for radiation therapy treatment planning in the skeletal system. Radiation therapy treatment planning in the skeletal system is based on plain film radiographs and bone scanning. Between January 1, 1993 and June 30, 1994, 228 patients were irradiated due to malignancies in the skeletal system. Included were bone metastases, lymphomas, sarcomas and bone invasion of neuroblastoma. The morphological display of the plain film radiographs and the bone scintigraphies were compared and modifications of the target volume due to the scan findings quantified. In 17 of 228 patients (7.5%) the target volume was modified by at least 2 cm due to tumor invasion depicted by radionuclide scanning only. Bone scintigraphy enables a sensitive display of bony invasion in skeletal malignancies. Because of a scan induced alteration of the target volume in 7.5% of the cases, bone scanning cannot be abandoned in RT treatment planning.

[Lithium as an adjuvant in the radioiodine therapy of thyroid cancer]. / Lithium als Adjuvans in der Radiojodtherapie des Schilddrüsenkarzinoms.

14 patients were, after surgery for thyroid cancer, given radioiodine to ablate residual thyroid tissue, and, in addition, lithium carbonate. In 8 patients increasing serum lithium levels between 0.3 and 0.9 mmol/l and in 6 patients a constant level higher than 0.9 mmol/l were achieved. The radioiodine kinetics were compared with a control group of 16 patients without lithium therapy. Neither in a low nor in a high dosage the lithium medication could increase 131I uptake or prolong its effective half-life in the residual thyroid. Thus with lithium an increase of tumor dose could not be achieved. We suggest that in our patients the effect of lithium on thyroid metabolism was compensated by the enormous TSH-stimulation after thyroidectomy.

[Role of 131I-metaiodobenzylguanidine scintigraphy in the diagnosis of intestinal carcinoids]. / Die Rolle der 131J-Metajodbenzylguanidin-(MIBG-) Szintigraphie in der Diagnostik der intestinalen Karzinoide.

Iodine-131 metaiodobenzylguanidine (131I-MIBG) is concentrated in a variety of neuroendocrine tumors, such as pheochromocytoma and neuroblastoma. Other neuroendocrine tumors from the APUD-cell system such as carcinoid tumors, may possess this uptake capability as well. We investigated 11 patients suffering from intestinal carcinoid with 131I-MIBG in order to determine the value of MIBG scintigraphy in these tumors. MIBG scans were positive in 5 out of 11 patients (45%). False-positive MIBG-scans did not occur. No correlation between MIBG uptake, clinical symptoms and urinary 5-HIAA level could be found.

Determination of field size limitations in stereotactic and intensity modulated radiotherapy.

For dose measurement in small photon fields, different detectors are currently in use: TLD, semiconductor, diamond-detector, film, etc. But for absolute dosimetry, ionization chambers show the most advantages. To meet the basic dosimetrical requirements for lateral electron equilibrium the field size F must not remain under specified values: i.e. 5.2 x 5.2 cm2 for 15 MeV X-bremsstrahlung. As well as increasing the focus-chamber-distance, changing the physical density of the build-up material in the close vicinity of the chamber will be helpful to determine the output factor OF for smaller fields. By means of a correction factor, k(mat), this is taken into account. For a 6 MeV X and a 15 MeV X-bremsstrahlung of linear accelerators the lower limit of the field size F is determined: F > or = 0.8 cm. This value is mainly dependent on the diameter of the focal-spot (phi = 3 mm) of the treatment unit including design characteristics of the treatment head. Beside the dosimetrical aspects, some geometrical parameters have to be considered, when accuracy of dose application should remain on the same level as in medium and large field treatment (4 cm < or = F < or = F(max)). To keep dose-volume errors as low as +/- 10 % (diameter of PTV: 20 mm), the mean total error delta of CT-scanning (delta(p)), planning (delta(pl)), patient positioning (delta(x)), and treatment unit instabilities (delta(m)) should not exceed +/- 0.8 mm.

[Results of radiotherapy in brain metastasis]. / Ergebnisse der Strahlentherapie bei Hirnmetastasierung.

PURPOSE: To evaluate the effect of radiation therapy in the treatment of brain metastases. PATIENTS AND METHODS: Fifty-eight patients with brain metastases were irradiated. In 52 patients the post-therapeutic survival time could be evaluated. Most frequent basic tumor entity was lung cancer, followed by breast cancer. Eighteen patients underwent neurosurgery prior to radiation therapy, 23 patients underwent only radiotherapy and in 13 patients an additional chemotherapy was performed. Four patients were treated by all these means. Radiation therapy was done as a whole brain irradiation with a total dose of 40 Gy at single doses of two Gy or 30 Gy at single doses of 3 Gy respectively. RESULTS: There were no radiogenic complications. 42 of 58 patients (72%) showed an improved neurological status. In ten patients radiation therapy had to be abandoned due to deterioration of the patients condition, five patients died in the hospital. Mean survival time for all the patients were 213 days, by subtracting the preterminally treated patients the time improved up to 269 days. The prognosis was dependant of several factors. Main importance had the basic tumor entity itself leading to a mean survival time in breast cancer patients of 347 days in contrary to those with lung cancer and 152 days mean survival time. Good general status, young age and solitary metastasis were positive predictive factors. CONCLUSIONS: Radiation therapy is capable to improve quality of life and to prolong survival after an only short treatment period. Treatment should be initiated quickly and consequently after diagnosis.

[Late results of radiotherapy of soft tissue sarcoma]. / Spätergebnisse nach Strahlentherapie des Weichteilsarkoms.

PURPOSE: To evaluate the effect of radiation therapy in the treatment of soft-tissue sarcomas. MATERIALS AND METHODS: Between March 1970 and January 1990, 58 patients with soft-tissue sarcoma were referred for radiation therapy. The most frequent histologic diagnoses included fibrosarcoma (n = 15), neurofibrosarcoma (n = 5) and rhabdomyosarcoma (n = 5). Central tumor sites in the trunk (n = 31) were much more frequent than in the head and neck region (n = 14) or the extremities (n = 13). Thirty-nine of 58 primary tumors were bigger than 5 centimeters. Forty-five patients were irradiated after surgery, 5 patients prior to surgery; in 8 cases only radiation therapy was used. Radiation therapy was performed with Co-60 photons and an average total dose of 58 Gy, fractionated in single doses of 2 Gy. The treatment results were obtained by actual follow-up examinations. RESULTS: Twenty-three of 58 patients survived at least 5 years (39.9%). Of 15 patients with R0 resection 11 were alive after 5 years (73.3%). Local tumor control was achieved in 34 of 58 patients (58.6%). Low 5-year-survival rates were associated with dedifferentiation of the primary tumor (three survivors in 10 patients with G3 tumor), tumor diameters over 5 cm (13 survivors of 39), R2 resection (3 survivors of 16) and tumor sites in the body trunk (11 survivors of 31). CONCLUSIONS: (1) The best results of radiation therapy were achieved after R0 resection of the primary tumor. (2) Tumors in the trunk are prognostically worse because of bigger tumor diameters due to later diagnosis.