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We describe the clinical course of a 20-year-old man who suffered generalized convulsive seizures with postictal aphasia and hemiparesis of the right side. Computed tomography (CT) displayed a left postcentral lesion with prominent perifocal edema and only a little contrast medium enhancement. The completely removed tumor proved to be a primary cerebral non-Hodgkin lymphoma consisting of T-cells. Only ten days after the operation the patient once more presented a clinical deterioration. A nuclear magnetic resonance imaging (MRI) displayed an annular structure in the area previously operated upon, suspected to be an abscess. The second operation disclosed a large recurrence of the primary T-cell lymphoma extending diffusely into the white matter. On account of the rapid recurrence, a whole brain irradiation was started twelve days after the second operation. Four cycles of chemotherapy followed. Immunohistochemical studies of the anaplastic large lymphoma cells showed staining with the pan T-cell markers (UCHL1, CD3) and with the CD30 (Ki-1) antibody. The B-cell markers (L26, LN1) were negative. The EMA (epithelial membrane antigen) was only partially expressed. Further investigation excluded the presence of systemic lymphoma manifestation. 24 months after the last operation the patient remained free of symptoms. The last MRI displayed no evidence for the recurrence of a lymphoma. In reference to this unusual clinical course the few previously reported cases of the extremely rare primary cerebral T-cell lymphoma are reviewed.

Das Pankreaskarzinom gehort nach wie vor zu den Tumorerkrankungen mit infauster Prognose. Die im letzten Jahrzehnt sturmische Entwicklung moderner diagnostischer Verfahren wie Ultraschall, CT, MRT, ERCP, die Entdeckung der Tumormarker und Fortschritte in der radikalen Chirurgie haben an dieser Tatsache leider nur wenig geandert. 24,2% aller Sterbefalle in der Bundesrepublik Deutschland im Jahre 1987 sind nach der Todesursachenstatistik des Statistischen Bundesamtes auf maligne Erkrankungen zuruckzufuhren. Wahrend die Zahl der Krebstodesfalle insgesamt seit Beginn der sechziger Jahre nur um das 1,4-fache zugenommen hat, sind die durch Pankreaskarzinome verursachten Todesfalle uberproportional um das 2,4-fache angestiegen und lagen 1987 mit ca. 8000 Todesfallen an 3. Stelle der durch gastrointestinale Tumoren und an 7. Stelle aller durch Krebs bedingten Todesursachen [2]. Dieser „silent killer“ des oberen Abdomens entzieht sich haufig einer Fruhdiagnose, da die Tumoren in der Regel symptomlos bzw. -arm bis zu Grosenordnungen heranwachsen konnen, bei denen sich eine radikale Resektion angesichts der intraabdominellen Ausbreitung verbietet. Zum Zeitpunkt der Diagnose liegt in 85% aller Patienten schon ein organuberschreitendes Wachstum vor, und in 50% der Falle eine Beteiligung regionaler Lymphknotengruppen [11, 12, 13]. Dementsprechend sind weniger als 20% aller Patienten unter kurativem Aspekt resektabel.

The contribution of fast neutrons to local tumour control has been investigated worldwide since the mid-60's in more than 20 institutions. The high expectations anticipated from the promising results of experimental studies could not be adequately realized in the clinic. The late normal tissue damage was unacceptable due to poor depth dose characteristics and further technical limitations of the first generation low-energy machines. Even with sophisticated therapy planning systems and high-energy cyclotrons as well as comparable late normal tissue damage as witnessed after photons, only a few tumour entities have responded superiorly to fast neutrons. These particularly include macroscopic tumours of the salivary glands, prostate and, potentially, soft and osseous tissues. The role of fast neutrons for head and neck cancer has not yet been definitely proved. For bladder-, cervical- and rectal carcinomas, non-small cell lung-, pancreatic- and breast cancers as well as malignant gliomas, no therapeutic benefit as compared with photons was observed in the case of macroscopic residual or inoperable recurrent tumours.

A retrospective analysis of 63 patients with malignant major salivary gland tumours treated between 1972 and 1988 is presented. In 54 patients the tumour was located in the parotid gland, in the remaining nine patients the tumour was located in the submandibular gland, 31 patients were treated for stage I to II disease, 32 patients for stage III to IV disease. All patients were irradiated postoperatively using 60 Co. 137 Cs photons or electrons of adequate energies. As basic techniques ipsilateral portals, a wedge pair of portals or parallel opposed fields were used. The target doses ranged between 45 and 70 Gy with fractions of three to five times 2 to 3 Gy weekly, dependent on postoperative status and stage. In 25% of the patients a local recurrence was evident after radiotherapy with 13% developing distant metastases. The five-year survival was 95% for stage I, 83% for stage II, 30% for stage III and 7% for stage IV. Additionally, the prognosis varied according to lymph node involvement, grading and microscopic or macroscopic residual disease.

In this retrospective study, the results of postoperative neutron boost therapy for 40 soft tissue- and 18 chondrosarcomas are presented. In 65.5% and 34.5% of all cases, microscopic to macroscopic tumour residual was left postoperatively. Locally advanced and moderate to highly malignant tumours were found at surgery in 81% and 69%, respectively. Except for seven patients with a whole series of neutrons to 16 Gy, the other cases were treated with initially 40 to 50 Gy photons and a subsequent neutron boost of 4 to 6 Gy. The median follow-up was 29.3 and 36.2 months for the soft tissue- and chondrosarcomas. The actuarial three-year local control and overall survival rates were 69.3% and 91% for soft tissue- vs. 55.6% and 62.9% for chondrosarcomas. With regard to the extension of surgery (microscopic or macroscopic residual), local control rates of 80% and 60% for soft tissue- vs. 62.5% and 40% for chondrosarcomas were observed. The overall local failure rate was 32.8% with a median disease-free interval of ten respectively eleven months for soft tissue and chondrosarcomas. 17 out of 19 local recurrences were due to inadequate irradiation portals for the neutron boost or to insufficient total doses in the initially treated photon target volume.

Die Verfeinerung der Operationstechniken hat in den letzten Jahren zu einer Senkung der Haufigkeit von Lokalrezidiven gefuhrt, dennoch ist bei Patienten mit ausgedehnter Infiltration des perirektalen Gewebes das Risiko mit uber 20% immer noch hoch. Nur noch ausnahmsweise kann das Lokalrezidiv geheilt werden. Dieser Uberblick uber eine lange Erfahrung mit der adjuvanten Strahlenbehandlung zeigt, das eine Reduzierung der Lokalrezidivrate und eine Verbesserung des Uberlebens moglich sind.

Five permanently established xenograft lines of human soft tissue sarcomas were irradiated with single doses of 5.8 MeV d(14)+Be neutrons and of 60Co rays, respectively, at several dose levels to generate dose response relationships. The tumors were clamped ten minutes prior to and during irradiation to induce uniform hypoxia. All tumours were previously characterized by means of histomorphology, tumour doubling times (DT's), DNA-index and enzyme pattern of the lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (GPD). According to these criteria, three out of five leiomyosarcomas were identical referring to the biopsy of origin, whereas two had changed in successive passages. For the different tumour lines, specific growth delays ranged from 0 to 8.7 after 5.3 Gy neutrons and from 0 to 11.4 after 16 Gy60Co, respectively. In terms of radiosensitivity for different single doses and irradiation qualities, a highly significant overall correlation (rs = 0.82 +/- 0.06) was found for the ranking of the tumours with respect to the growth delay and specific growth delay endpoints. No correlation was found between tumour doubling times and the relative biological effectiveness (RBE). In general, calculated RBE-values decreased with increasing effect level. For the five tumour lines, RBE-values ranged from 1.6 to 12.7 and 2.0 to 4.4 at specific growth delays of 0.5 and 2.0, respectively, under acutely hypoxic conditions. These results indicate a potential advantage for neutrons in a subgroup of human soft tissue sarcomas compared with sparsely ionising irradiation.

Evaluation and refinement of surgical techniques in rectal carcinoma have reduced the rate of local recurrences. Nevertheless recurrence it remains high at more than 20% in patients with extensive infiltration of perirectal tissues and cures are an exception. Overview of many years of experience with adjuvant radiotherapy shows that local recurrence rate can be reduced and survival the rate improved.

5503 Purpose: Is accelerated hyperfractionated radiation therapy with 70.6 Gy plus concurrent 5-FU/MMC (C-HART) more effective than a dose escalated HART scheme with 77.6 Gy alone? Material/Methods...

As part of the Cooperative Germ Cell Tumors Studies MAKEI 83/86 of the German Society of Pediatric Oncology, 37 patients with intracranial germ cell tumors were registered. Based on histological criteria and tumor markers, 26 were classified as germinomas, 9 as fully malignant non-germinomatous germ cell tumors (2 yolk sac tumors, 1 embryonal carcinoma, 1 choriocarcinoma, 5 mixed type germ cell tumors), and 2 were mature teratomas. Of 26 patients with germinomas, 14 received radiotherapy only, all patients are surviving disease-free, median period of observation: 2 years, 10 patients were treated with both chemotherapy and radiotherapy, 8 of these patients are surviving disease-free. Of the 2 patients who received chemotherapy only, none is surviving. Of 9 patients with fully malignant non-germinomatous germ cell tumors, 4 are surviving following surgery, cisplatinum-based chemotherapy and radiotherapy more than 2 years following diagnosis, 1 of these 4 patients with stable disease. Of 2 patients with mature teratomas, 1 is surviving disease-free. Based on these data, recommendations for diagnostic evaluation and therapy of intracranial germ cell tumors are outlined.

From 1969 to 1981, 23 patients with tumors in the pons region were irradiated at the Department of Radiotherapy of the West German Tumor Center in Essen. The age of the patients ranged from 18 months to 50 years. Fifteen patients (65%) were younger than 18 years, one was 25 years old, and seven were between 40 and 50 years old. In two cases the histologic diagnosis of an astrocytoma I and astrocytoma II could be confirmed by exploratory excision and cyst punction, respectively. Nineteen patients received a shunt system (ventriculoatrial shunt) prior to radiotherapy in order to achieve a pressure reduction. After a follow-up period of 1.5 to 12 years, eleven patients are alive, and twelve patients died from a local recurrence or from progressive tumor growth. The five-year survival rate is 47%. Five of the surviving patients show no or only slight adverse effects on their general condition and are able to attend school or carry out their profession (in Karnofsky: 90 to 100%). Four other patients suffering from marked remaining neurologic symptoms are able to take care of themselves (Karnofsky: 70 to 80%). Two patients need permanent nursing (Karnofsky: 50 to 60%). Because of the local propagation tendency of pons tumors, radiotherapy should be locally restricted to the brain stem and the adjacent brain structures, e.g. cerebellum and proximal neck marrow. The authors recommend target volumes of 55 to 60 Gy, which must be applied within 6 to 8 weeks, taking into account the age of patients. This palliative therapy conception should be applied routinely in the hope of bringing about a curative treatment to this group of patients.

Human tumors transplanted into nude mice are widely considered to be identical to the tumor of origin. In addition, high histologic constancy of xenografts over many passages is generally accepted. We have checked these prerequisites for a therapy-orientated application of the nude mouse model using soft tissue sarcomas. Twenty-two primary soft tissue sarcomas and their xenografts were compared histologically and flow cytometrically over numerous passages. More than 30% of transplants showed a variation in cell differentiation, cell content, frequency of mitosis, tendency to necrotize, and connective tissue content compared to the original tumor. Furthermore, transplants from various regions in one tumor showed divergent results. Analyses of serial transplants showed histologic and flow cytometrical discrepancies in about 50% of cases, and new cell lines occurred in 26%. Our results show that the genetic instability found in human neoplasias also applies to xenotransplants and that the therapy-related usefulness of the nude mouse model is limited.

As part of the Cooperative Germ Cell Tumors Studies MAKEI 83/86 of the German Society of Pediatric Oncology, 37 patients with intracranial germ cell tumors were registered. Based on histological criteria and tumor markers, 26 were classified as germinomas, 9 as fully malignant non-germinomatous germ cell tumors (2 yolk sac tumors, 1 embryonal carcinoma, 1 choriocarcinoma, 5 mixed type germ cell tumors), and 2 were mature teratomas. Of 26 patients with germinomas, 14 received radiotherapy only, all patients are surviving disease-free, median period of observation: 2 years, 10 patients were treated with both chemotherapy and radiotherapy, 8 of these patients are surviving disease-free. Of the 2 patients who received chemotherapy only, none is surviving. Of 9 patients with fully malignant non-germinomatous germ cell tumors, 4 are surviving following surgery, cisplatinum-based chemotherapy and radiotherapy more than 2 years following diagnosis, 1 of these 4 patients with stable disease. Of 2 patients with mature teratomas, 1 is surviving disease-free. Based on these data, recommendations for diagnostic evaluation and therapy of intracranial germ cell tumors are outlined.

Between 1980 and 1986 ten patients (two males, eight females, median age: 35 years) with spongioblastomas and ependymomas grade I of the spinal cord were treated with fast neutrons from the d(14) + Be reaction after incomplete tumour surgery. Eight patients received three weekly fractions of 0.7 to 1.33 Gy and two patients four weekly fractions of 0.8 Gy to total doses of 7.4 to 10.4 Gy. Two complete and six partial remissions of ataxia and motor disturbances were observed. Bladder dysfunctions in five patients cleared up partially in three cases. In two patients the symptomatology remained unchanged. After a follow-up of eight to 88 months two initially complete and two out of six partial remission were maintained. No severe late effects of the skin have been determined. In summary it is concluded that for incompletely resected "pencil"-gliomas fast neutron therapy seems to be a feasible treatment modality.

To study the potential benefit of sequential chemotherapy in inoperable small cell lung cancer (SCLC), from 1982 to 1986 ninety-one patients with histologically proven and previously untreated SCLC (median age: 53 years; median Karnofsky status: 80%) were randomly assigned to an initial therapy with adriamycin (since 1984 epirubicin), cyclophosphamide, vincristine (ACO resp. EPICO) or etoposide/cisplatin (VP16/DDP). Treatment courses were repeated every 3 weeks for a total of less than or equal to 6 courses with a crossover after a maximum of 3 cycles of either regimen. Limited disease (LD) patients with bronchoscopical, computertomographical and (re-) mediastinoscopical complete remission (CR) randomly received either a thoracic irradiation with 40 Gy or observation only. Overall, 60 out of 85 evaluable patients achieved an objective remission. A CR was observed in 24/51 patients (47%) with limited disease, and in 8/34 patients (24%) with extensive disease. Both, ACO (EPICO) and VP16/DDP were equally effective as initial and second-line therapy. Moreover, after failure to the initial therapy an objective remission could be achieved in 13% of the patients following the alternative second line combination. In 28% of LD patients with an otherwise complete remission residual tumor was detected by (re-) mediastinoscopy. Median survival times were 14 (CR: 16) months in LD patients and 10 (CR: 15) months in ED patients. At present, median survival is significantly improved in irradiated versus non-irradiated LD patients (25 vs. 13 months, p less than 0.04). The remission rates and median survival times observed in this study are comparable to those of a historical control group treated with ACO plus radiotherapy alone.

A widely used model for investigating basic tumor characteristics and different treatment modalities preclinically is the immune-deficient, athymic nude mouse. This model offers many morphological parallelisms to the clinical situation. The aim of this study is to demonstrate the vascularization pattern of xenotransplanted human melanomas and sarcomas using different methods. Xenotransplanted tumors of 62 congenital thymus-aplastic nude mice were examined ultrastructurally and topographically after corrosion cast and tissue preparation. Quantitative measurements of tumors injected with India ink were carried out to obtain comparable information on the vascular densities in the tumors. Quantitative measurements showed that there is no zonal, topographic arrangement of the vascular densities. Comparisons of the vascular densities in the centers of tumors with the densities in the periphery showed an extreme heterogeneity in tumor vessel distribution, which does not generally support the idea of a better vascularisation in the tumor periphery. Neither in the periphery nor in the center of the tumor regular vessels are to be seen consisting of intimal, medial and adventitial layers. Even the largest peripheral vessels, which often take a tortuous course, consist mainly of an endothelial layer and some perivascular connective tissue only. Areas with high vascular densities could be seen just beneath areas almost free of vessels. Besides endothelial-lined vessels numerous irregular, tumor cell-lined sinusoids are visible both in sarcomas and melanomas. The morphology of the vessels found scanning electron microscopically is generally in agreement with many features described transmission electron microscopically.

The subject of this study were non-seminomatous testicle tumors with cerebral formation of metastases. Despite the relatively low radiosensitivity of the primary tumors and their regional metastases eighteen of twenty patients were free of symptoms, and a complete regression of the intracerebral tumors was shown by computed tomography and/or scintigraphy in ten of twenty cases. This regression was obtained within two or three weeks by an irradiation of the skull with a focal dose of 30 to 40 Gy. Due to the small number of patients (20), it was not possible to demonstrate a statistically different receptiveness of the cerebral metastases according to their histological subentity. Because of the subjective stress, the duration of radiotherapy should be as short as possible (e.g. 30 Gy in 10 fractions over a period of two weeks). In our opinion, irradiation is clearly indicated in case of testicle teratomas with cerebral formation of metastases. Practically the only contra-indications are a strong intracranial hypertension as well as hyperkinesia. The entire prognosis of the patient, however, is not determined by the cerebral formation of metastases but by the pulmonary metastatic extension, so that radiotherapy is an important palliative factor with regard to the survival time of these patients.

In spite of the great efforts undertaken in the different disciplines, the prognosis of patients with highly malignant gliomas, i.e. astrocytomas of degrees III and IV remains unfavorable. Up to now, new findings about an improvement of radiooncologic therapy methods are obtained retrospectively from the results of complex and time-consuming clinical studies. The heterotransplantation of human tumor tissue in immune-deficient nu/nu mice gives the opportunity to check preclinically the efficiency of different fractionation schemes and cytostatic drugs already. The author's experiences and therapy results are presented in order to demonstrate the possibilities as well as the limits of this in-vivo model performed with a view to clinical conditions.

Xenografts in nude mice allow the study of intrinsic sensitivity of tumor cells to cytotoxic therapies in a threedimensional assembly, similar to that in the original tumor. The good correlation between the chemotherapeutic response of xenografts and the tumor in the patient, which validates the model, has been previously outlined (1). The present study was performed in order to evaluate the response of xenografted astrocytomas to different fractionation regimes and to estimate the repair factor a/b.

Alizapride, a new antiemetic of the benzotriazole-line, enterally given, has been used in a randomized double blind trial including 40 patients suffering from radiogenic gastro-intestinal syndrome. Compared to metoclopramide, alizapride caused a faster regression of inappetence and of the frequency of daily vomiting. Drug-induced side-effects could not be seen.