[Integration of the radiotherapy irradiation planning in the digital workflow]. / Integration der Bestrahlungsplanung in den volldigitalen Workflow.

BACKGROUND AND PURPOSE: At the Clinic of Radiotherapy at the University Hospital Freiburg, all relevant workflow is paperless. After implementing the Operating Schedule System (OSS) as a framework, all processes are being implemented into the departmental system MOSAIQ. Designing a digital workflow for radiotherapy irradiation planning is a large challenge, it requires interdisciplinary expertise and therefore the interfaces between the professions also have to be interdisciplinary. For every single step of radiotherapy irradiation planning, distinct responsibilities have to be defined and documented. All aspects of digital storage, backup and long-term availability of data were considered and have already been realized during the OSS project. METHOD: After an analysis of the complete workflow and the statutory requirements, a detailed project plan was designed. In an interdisciplinary workgroup, problems were discussed and a detailed flowchart was developed. The new functionalities were implemented in a testing environment by the Clinical and Administrative IT Department (CAI). After extensive tests they were integrated into the new modular department system. RESULTS AND CONCLUSION: The Clinic of Radiotherapy succeeded in realizing a completely digital workflow for radiotherapy irradiation planning. During the testing phase, our digital workflow was examined and afterwards was approved by the responsible authority.

Use of high-dose etoposide/ifosfamide/carboplatin/epirubicin and peripheral blood progenitor cell transplantation in limited-disease small cell lung cancer.

Conventional-dose chemotherapy for limited-disease small cell lung cancer has resulted in high response rates, but rarely in a cure. In an ongoing phase I-II trial, limited-disease small cell lung cancer patients received high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation as part of an early intensification strategy after two cycles of induction chemotherapy. Eligible patients (n = 18) were initially treated with two cycles of etoposide (500 mg/m2), ifosfamide (4 g/m2), cisplatin (50 mg/m2), epirubicin (50 mg/m2) and granulocyte colony-stimulating factor to combine an effective, standard-dose chemotherapy regimen with simultaneous mobilization of PBPCs. Patients who were in partial remission or complete remission after two cycles of induction chemotherapy received high-dose intensification chemotherapy with cumulative doses of 1,500 mg/m2 etoposide, 12 g/m2 ifosfamide, 750 mg/m2 carboplatin, and 150 mg/m2 epirubicin, followed by autologous PBPC transplantation and granulocyte colony-stimulating factor. The duration of the complete chemotherapy program was 9 weeks. All patients received chest irradiation posttransplantation (50 Gy), and those in complete remission received additional prophylactic cranial irradiation (30 Gy). To date, 13 patients with a median age of 49 years (age range, 34 to 62 years) have been treated within this combined-modality treatment protocol. At a median follow-up of 14 months (range, 3 to 45 months) after transplantation, 11 patients were alive and nine were still in complete remission. Nonhematologic toxicity was acceptable; World Health Organization grades 2 to 4 oral mucositis was the most frequently observed (85%) adverse event. No toxic deaths were observed, and hematopoietic reconstitution occurred rapidly after PBPC transplantation; platelet transfusion independence (> 20,000 microL) and neutrophil counts greater than 500 microL were observed at study day 12+. The median survival time was not yet reached. These preliminary data demonstrate that early, high-dose chemotherapy and PBPC transplantation followed by local radiotherapy is safe and may lead to prolonged disease-free survival in some patients. Prospective, randomized studies in a larger series of patients will be required to provide definitive proof of the role of early high-dose chemotherapy in the management of limited-disease small cell lung cancer.

Multimodality treatment including early high-dose chemotherapy with peripheral blood stem cell transplantation in limited-disease small cell lung cancer.

Combined-modality treatment for limited-disease small cell lung cancer using conventional chemotherapy and chest irradiation achieves high response rates, but most patients relapse over a period of 12 to 16 months. To improve current results, we performed a phase II trial including high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT) as part of an early intensification strategy after two cycles of induction therapy. Moreover, to reduce the risk of local recurrence, the protocol included surgical resection in stages I to IIIA patients as well as chest irradiation. Between January 1991 and July 1994, 16 consecutive patients (median age, 50 years; age range, 30 to 59 years) were treated in this single-center trial. The patients received two cycles of conventional chemotherapy consisting of etoposide 500 mg/m2, ifosfamide 4 g/m2, cisplatin 50 mg/m2, and epirubicin 50 mg/m2 plus granulocyte colony-stimulating factor 5 microg/kg at a 3-week interval, followed by PBPC collection and subsequent high-dose etoposide 1,500 mg/m2, ifosfamide 12 g/m2, carboplatin 750 mg/m2, and epirubicin 150 mg/m2 with PBPCT. The duration of the entire chemotherapy program was 9 weeks. Six of 10 patients in stages I to IIIA and one of six patients in stage IIIB received neoadjuvant or adjuvant surgery before high-dose chemotherapy, followed by thoracic (50 Gy) and prophylactic (30 Gy) cranial irradiation. Hematopoietic reconstitution after high-dose chemotherapy occurred within 11 days (range, 9 to 17 days) for both neutrophils (>0.5 x 10(9)/L) and platelets (>20 x 10(9)/L). Oral mucositis (World Health Organization grade 2 to 4) was the predominant nonhematologic toxicity, which was observed in 12 of 16 patients. One patient developed neutropenic septicemia with fatal multiorgan failure. At a median follow-up of 44 months (range, 32 to 77 months) after PBPCT, nine patients are alive and well, resulting in a disease-free and overall survival rate of 56.3% +/- 12.4%. The median overall survival has not yet been achieved. None of the patients who had surgery relapsed or died after therapy. All relapses occurred within the first 12 months after PBPCT. Patients in stages I to IIIA (10 patients) had a 70% +/- 14% overall survival rate at 4 years, while patients in stage IIIB (six patients) had a 33% +/- 19% survival rate at 4 years, with a median survival of 17 months posttransplant. These data demonstrate that a multimodality treatment including early high-dose chemotherapy with PBPCT may lead to a prolonged disease-free survival in the majority of patients. A randomized phase III study has now been initiated to prospectively investigate the role of high-dose chemotherapy, surgery, and chest irradiation in the multidisciplinary approach to limited-disease small cell lung cancer.

Erythropoietin for patients undergoing radiotherapy: a pilot study.

BACKGROUND AND PURPOSE: To evaluate the feasibility and efficacy of using recombinant human erythropoietin (rhEPO) to correct decreased hemoglobin levels in patients undergoing radiotherapy and to get an estimate of its influence on the efficacy of radiotherapy. MATERIALS AND METHODS: Fifty patients with cancer of the head and neck and the pelvis were randomized before radiotherapy to different rhEPO treatments (none, 3 x 150 U/kg per week i.v., 3 x 300 U/kg per week i.v. and 3 x 150 U/kg per week s.c.). Hematological parameters were evaluated weekly and the locoregional tumor control rates were determined in 38 patients with head and neck cancer. RESULTS: rhEPO-treated patients showed a significant increase in their hemoglobin values (0.7 g/100 ml per week). The rhEPO response was comparable for patients with cancer of the head and neck and the pelvis. A delayed recovery was seen when iron deficiency or impaired iron mobilization was present. No serious toxicity was observed. Locoregional tumor control was improved, although not statistically significantly, in those head and neck cancer patients who experienced a rapid rise of hemoglobin. CONCLUSIONS: Low hemoglobin levels can be safely and quickly corrected with rhEPO. This may improve the effectiveness of radiotherapy.

Influence of local radiotherapy of breast cancer patients on the frequency of cytotoxic T lymphocyte precursor cells.

Alloantigen-specific cytotoxic T lymphocyte precursor (CTL-p) frequencies were analyzed in ten patients with histologically proven breast cancer receiving prophylactic RT. The frequency of CTL-p was assessed by limiting dilution (LD) analyses before, immediately after discontinuation of treatment and at various times following RT. The number of pbmnc, adherent cells and T cells was determined in parallel. Local RT led to a minor and transient reduction of CTL-p frequencies lasting approximately three months: on average a 25% decrease of CTL-p numbers was seen immediately after RT. Three months following treatment, a 20% reduction was still evident. Values subsequently returned to pretreatment levels. Moreover, these changes in the frequency of antigen-specific CTL were accompanied by a 25% to 39% decrease in the blood T cell counts lasting for more than 12 months. The reductions following local RT were less pronounced than those induced by immunosuppressive drugs in allograft recipients.

Operation for N2 small cell lung carcinoma.

Of 48 patients with limited small cell lung carcinoma treated by different modes, but always including radical operation, a series of 25 patients with N2 lymph node metastases is reported. In a first period (1970 to 1977) treatment consisted solely of radical resection in 3 patients; chemotherapy was added to operation in 6, and local radiotherapy was added in 2. Since 1977, 14 patients were treated according to a comprehensive therapy protocol including radical resection (six pneumonectomies, one bilobectomy, seven lobectomies), chemotherapy, local radiotherapy, and prophylactic cranial irradiation. Eleven patients, in whom N2 disease was confirmed preoperatively, received chemotherapy as the first step, followed by "adjuvant" resection. Projected 5-year survival rate is 25% for the entire N2 group and 47% for the comprehensively treated group. Seven patients of this latter group are alive 12, 19, 30, 48, 66, 73, and 74 months after comprehensive therapy, equivalent to an observed 2-year survival rate of 38%. This is the largest reported series of patients with resected small cell lung carcinoma in the N2 stage treated at a single institution; the results are so encouraging that we can no longer advocate general refusal of radical lung resection for small cell lung carcinoma in the N2 stage if it is part of a multimodal therapeutic protocol.

Multimodal therapy of small cell lung cancer in TNM stages I through IIIa.

Since 1977, Innsbruck University Hospital has been employing a multimodal therapy concept for small cell bronchial carcinomas in stages I to IIIa. This concept includes all three treatment forms effective in this tumor, namely, chemotherapy, surgery, and radiotherapy. The therapy scheme is stage-dependent and begins in stages T1-3 N0-1 with lung resection and in stage N2 with chemotherapy. To date, 45 patients have been included in a prospective, nonrandomized (phase II) trial: 7 in TNM stage I, 11 in stage II, and 27 in stage IIIa (6 T3 and 21 N2). The actuarial 5-year survival rate of the entire group (including therapy-related lethality, early recurrences, and protocol violations) is 36%; it is 57% for those in stage I, 28% for those in stage II, and 34% for those in stage IIIa. Median survival time is 18 months. Patients with completed multimodal treatment have a 5-year survival rate of 56% regardless of disease stage. Three patients died of tumor-unrelated causes after 47, 52, and 54 months.

Transrectal ultrasonography as a follow-up method in prostatic carcinoma after external beam and interstitial radiotherapy.

Transrectal ultrasonography and ultrasonometrics were employed for follow-up in a total of 28 prostatic carcinoma patients subjected to external beam or interstitial radiotherapy. These two methods permit more accurate staging of prostatic carcinoma and have also proved to be valuable in the follow-up care of patients suffering from locoregional prostatic carcinoma. Of the 20 patients subjected to external beam radiotherapy four patients initially did not show capsular infiltration, 2B2, 2A2, whereas 16 patients presented with infiltration of the capsule and seminal vesicles. After external beam radiotherapy the ultrasonomorphologic findings of four patients revealed a sharply demarcated capsule and unremarkable seminal vesicles, which indicated tumour regression. Of five patients with infiltration of the pelvic floor and/or seminal vesicles, three showed definite tumour regression, whereas the ultrasonograms of the other two patients demonstrated tumour progression despite radiotherapy. In eight patients the greatest reduction in tumour volume was found one year after interstitial radiotherapy. Only one patient, initially presenting with slight infiltration of the capsule, was shown to have infiltration of the capsule and seminal vesicles after interstitial radiotherapy. At follow-up, evaluation of the echo patterns in these patients was inaccurate on account of the dense echoes reflected by the seeds implanted.

[Indirect (arterial) splenoportography and portography in intraphepatic block]. / Das indirekte (arterielle) Splenoporto- und Portogramm beim intrahepatischen Block

Morphology and flow dynamics in the lieno-mesentericoportal territory were investigated in 15 normal persons and 199 patients with pre/intra and intra-hepatic blocks. Indirect (arterial) splenoportography with selective catherization of the splenic artery provided angiograms varying between good and diagnostically useful in 98% of cases. With injection into the truncus coeliacus, this figure falls to 77%. The various types of collateral circulation are stated and discussed. The scope and limits of the methods are shown by comparative surveys between direct splenoportography and indirect splenoportography and portography, using 16 patients. As far as the chronological sequence of angiographical diagnostics in the intrahepatic block is concerned, the indirect method shall precede direct splenoportography, which shall only be employed if the indirect method of examination does not provide sufficient information, the patient has shunt capacity and an operation is to be performed immediately.

[Combined radio-/chemotherapy of invasive bladder cancer]. / Kombinierte Radio-/Chemotherapie des invasiven Harnblasenkarzinoms.

In a prospective study, 19 patients with advanced transitional carcinoma of the bladder (stages T.3 and T.4) were treated by combined radiotherapy and chemotherapy. A total of 450 mg cis-platinum or 1.6 mg/kg body weight were given in four treatment periods with three-week intervals. At the same time, the total dose of 60 Gy was given to the tumour over two periods (telecobalt or high-energy photons). There were few systemic or toxic side effects. Recurrence-free survival during the next 36 months was 76%, which compares with a control group treated by irradiation only, who had a survival of 48%.

[A comparison of computer tomography and ultrasound for the demonstration of vessels in the abdomen and retroperitoneal space (author's transl)]. / Vergleich der Gefässdarstellungen im Abdomen und Retroperitonealraum mit Computertomographie und Ultraschall.

The value of computer tomography and ultrasound for demonstrating vessels in the abdomen and retroperitoneal space was compared. The methods were equal in their ability to demonstrate the major vessels situated centrally, but computer tomography proved better at differentiating arteries and veins situated peripherally. On the other hand, sonography proved a simple means of differentiating intrahepatic vascular structures.

[The accuracy of sonography in the diagnosis of renal disease (author's transl)]. / Die Treffsicherheit der Sonographie in der Diagnostik von Nierenerkrankungen.

The accuracy of sonography in the diagnosis of spaceoccupying renal lesions was evaluated by a retrospective study of 221 patients. There were 15 incorrect diagnoses. In 93% of cases the sonographic diagnosis was correct. Erroneous diagnoses, which would have been difficult to avoid even retrospectively, were usually due to complex lesions which were partly cystic and partly solid. In order to differentiate cysts from solid lesions it is considered essential to use both A- and B-scans and step-wise variations of sound energy. These results emphasise the great value of ultrasound in the differentiation of renal abnormalities. Sonography should be used, during the clinical work up, after the urogram, but before angiography or other invasive methods are employed.

[The application of sonography in the differential diagnosis of space-occupying renal lesions (author's transl)]. / Einsatzmöglichkeiten der Sonographie zur Differentialdiagnostik raumfordernder renaler Prozesse

Two dimensional ultrasound echography is a reliable method for demonstrating the topography of retroperitoneal space-occupoing lesions which causes little inconvenience to the patient. This is particularly the case in the upper abdomen, where the differentiation between renal, suprarenal, pancreatic and splenic lesions has been difficult. The criteria for the differential diagnosis of sonographic findings are described and discussed. Echography should be used before invasive methods, particularly angiography, are employed.

[Echographic differential diagnosis of scrotal contents. A contribution to evaluation of the method]. / Echographische Differentialdiagnostik des Skrotalinhaltes. Ein Beitrag zur Wertigkeit der Methode.

Ten patients were selected from a clinical material comprising 336 sonograms of the scrotal contents in order to discuss the differential diagnosis of testicular and extra-testicular conditions. The decision whether a tumour is testicular or extra-testicular does not usually pose a problem, but may be impossible for small peripheral tumours. The shape of the epididymis and vas deferens and the structure of the testes is of significance in the differentiation between torsion and epididymitis. Rare diseases--myxoliposarcoma, infiltrating urothelial carcinomas from the bladder growing along the vas, lymphangiomas--are considered in the differential diagnosis of space-occupying lesions. Lymphangiomas produce a typical appearance on ultrasound. The criteria for the diagnosis testicular trauma, rupture, parenchymal tears and haematocoeles are defined. Differentiating liquid from solid is rarely a problem. A testicular abscess in the presence of chronic orchitis can simulate a solid tumour.

[Xero-radiographic examination of the capsule and ligaments of the knee joint. II. Demonstration of injuries to the cruciate and lateral ligaments and menisci (author's transl)]. / Xeroradiographische Untersuchungen am Kapsel- und Bandapparat des Kniegelenks. II. Mitteilung: Darstellung von Verletzungen an den Kreuz- und Seitenbändern sowie den Menisken im Xerotomogramm

The value of xero-radiography for demonstrating injuries to the capsule and ligaments of the knee has been investigated. A tomographic method was used in conjunction with arthrography of the knee. The results have shown that, in vitro, injuries of the cruciate and lateral ligaments and of the capsule are well shown by xero-tomography and that it is possible to evaluate their extent. Simultaneous demonstration of injuries to the menisci is less certain. In order to show these accurately, special methods would have to be employed. Despite the higher radiation dose which must be expected, and the greater complexity of this technique, we consider that a clinical investigation of the method is indicated.

[Xeroradiographic studies on the capsule and ligaments of the knee joint. 1. Anatomy of the cruciate and lateral ligaments in the xerotomogram]. / Xeroradiographische Untersuchungen am Kapselund Bandapparat des Kniegelenkes

The suitability of xeroradiography for contrast arthrography was investigated by in vitro studies. Special attention was devoted to the cruciate and lateral ligaments on xero-ty lateral tomography. The anterior and posterior ligments can be evaluated and defined satisfactorily in the antero-posterior view. The lateral ligaments can be seen on xero-tomography without difficulty. The use of xero-tomography promises to improve the radiological diagnosis of injuries of the capsule and ligaments of the knee joint.

[Plexus neuropathy: tumor infiltration or radiation damage]. / Plexusneuropathie: Tumorinfiltration oder Strahlenschaden.

Plexus neuropathies often occur in patients with breast cancer after varying periods following surgery and postoperative radiotherapy. In most cases this has been ascribed to radiation fibrosis. The attempt to arrive at a clinical diagnosis fails because of the similarity of symptoms in both cases namely pain and the absence of motoric and sensory reflexes. But a clear diagnosis is of fundamental importance for further treatment. Only a surgical intervention can verify the diagnosis. In this study, the results of operative findings are presented and compared with a second group of patients who had died of breast cancer having undergone surgery and radiotherapy. The findings brought a surprising fact to light: a considerably high percentage of all patients suffered from large scale tumour infiltration in the plexus. The morphology and histopathology of these lesions are described. Possible explanations are given for the difference in lesion patterns, so that a clinical diagnosis might be derived therefrom.

[Changes in liver haemodynamics after mesenterico-caval dacron prosthesis anastomosis ("H-shunt") in portal hypertension (author's transl)]. / Anderungen der Leberhämodynamik nach mesenterikokavaler Dacron-Prothesen-Anastomose (sog. "H-Shunt") bei portaler Hypertension.

In fourteen patients with portal hypertension and bleeding from oesophageal varices, mesentericocaval anastomoses using a dacron-velour prosthesis ("H-shunt") were carried out. Evaluation of the haemodynamics showed: 1. Comparison of 13 pre- and post-operative angiograms showed an haemodynamicically effective shunt in 12 and a stenosed shunt in one. 2. The aim of relieving the portal circulation while maintaining antegrade portal flow was achieved in six patients. 3. In six patients, the portal vein was not seen in a splenic or mesenteric portogram despite an open shunt. Functionally, this corresponds to a porto-caval anastomosis. 4. Pressure reduction in the portal circulation can be so marked as to obtain retrograde portal flow from the hepatic artery. 5. If the portal blood flow through the liver disappears, the hepatic artery may obtain additional flow from the superior mesenteric artery (reversed flow in the gastroduodenal artery). 6. Increased arterial flow to the liver is made possible by a reduction in intrahepatic resistance. The role of collaterals, either arterio-portal shunts or shunts between the sinusoids, is discussed. 7. The hepato-fugal collateral circulation was reversed in twelve patients.

[The radiological appearances of caustic burns in the upper intestinal tract (author's transl)]. / Das Röntgenbild kaustischer Veränderungen des oberen Intestinaltraktes

Seventy-three caustic burns of the upper gastrointestinal tract were divided into early and late effects; the radiological findings were analysed and, as far as possible, compared with the endoscopic results. The central role of radiology proved to be indisputable, particularly for the demonstration of a perforation, for the control of treatment by drugs or dilatation and before surgery. Endoscopy is of particular value in the diagnosis of caustic burns if the radiological findings are negative, for following treatment and for clarifying atypical late changes in order to exclude malignant degeneration.