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Die chirurgische Therapie von Lungenmetastasen im interdisziplinaren Konzept ist heute ein etabliertes Verfahren. Ziel der Operation ist die radikale und damit poten-tiell kurative Resektion. Daneben gibt es diagnostische und palliative Indikationen. Regelzugang ist die mediane Sternotomie zur Revision beider Lungen auch bei scheinbar einseitigem Befall. Das praoperative Staging bezuglich Anzahl und Vertei-lung der Metastasen ist nicht verlaslich. Von 1972 bis 1991 wurden in der Thoraxklinik Heidelberg-Rohrbach 729 Patienten an Lungenmetastasen operiert (843 Operationen). Die 30-Tage-Letalitat betrug 2,9%, die 5-Jahres-Uberlebensrate ab Operation der Metastasen allgemein 33%. Das beste Ergebnis wurde beim Hodenkarzinom mit 67 % 5-Jahres-Uberlebensrate beobachtet, das schlechteste beim Melanom mit 12% 5-Jahres-Uberleben. Neben dem Primartumor und teilweise in Abhangigkeit von diesem haben mehrere Faktoren prognostische Relevanz: Radikalitat, Sarkom vs. Karzinom zugunsten der Karzi-nome, krankheitsfreies Intervall, Eingriffsart, thorakaler Lymphknotenbefall. Bei multivariater Analyse beeinflussen die Faktoren je nach Primartumor die Prognose stark unterschiedlich. Lungenmetastasenchirurgie ist Teil eines interdisziplinaren onkologischen therapeu-tischen Konzepts und bietet den meisten Patienten eine Lebensverlangerung, man-chen sogar die Moglichkeit der Heilung. Auch ohne Lebensverlangerung wird oft eine verbesserte Lebensqualitat und damit wirksame Palliation erreicht.

Die heute ubliche Therapie aus Operation und/oder Strahlentherapie im Stadium III NSCLC ist nur fur eine Minderheit der Betroffenen ausreichend. Lokalrezidive und Fernmetastasen bestimmen das Schicksa

Patients with non-small cell lung carcinomas whose tumors showed an overexpression of the oncogenes c-fos and c-N-ras at the protein level had significantly shorter survival times than those without overexpression of these oncogene products. (c-fos: p=0.0002, c-N-ras: p=0.002). Multivariate analysis showed that expression of proteins coded by c-fos and c-N-ras is a significant prognostic factor in addition to tumor staging and DNA ploidy. The prognostic value is improved by combining the expression of c-fos and c-N-ras products. A significant correlation between the expression of c-fos and c-N-ras products and the tumor take rate in nude mice was found.

The purpose of this study was to evaluate the toxicity and response efficacy of fixed-dose oral ifosfamide (OI)-mesna (M) in advanced, non-small-cell lung cancer (NSCLC). OI was given in four different fractionated-dose treatment schedules with a total dose per cycle of either 3.0 g/m2, 6.0 g/m2, 7.5 g/m2 or 10 g/m2 (equivalent to a daily dose of either 750 mg, 1000 mg or 1250 mg.) M was given p.o. by drinking ampules. In the 64 patients (pts) included, a total of 305 treatment cycles were administered with no evidence of severe neurotoxicity. Twenty-two pts (37%) developed mild to moderate CNS toxicity. Neither myelosuppression, alopecia, gastrointestinal toxicity nor urotoxicity were clinical problems. On schedule 2 (6 g/m2), 3 of 14 evaluable pts (21%) had partial remissions (PR), and on schedule 3 (7.5 g/m2) 4 pts (25%) showed PRs. The median duration of response was 9 months (mts) for pts on schedule 2, and 8 mts for pts on schedule 3. We conclude that OIM can easily be tolerated in the same dose usually given intravenously (7.5 g/m2/mts), when patients at high risk for developing CNS toxicity have been previously excluded from therapy. In order to reduce CNS toxicity, it is suggested that the total dose per cycle should not exceed 7.5 g/m2 (1000 mg daily) within a fractionated-dose, 14-day treatment schedule. We further conclude that the tumor response efficacy of OIM in NSCLC is comparable to the one achieved by intravenously-administered IM, whereby the total monthly OI dose should not be less than 6.0 g/m2 (750 mg daily).

Background and Methods. To validate the new TNM definitions for lung cancer (International Union Against Cancer [UICC]) TNM classification, 4th edition, 1987, the data of 3823 patients were analyzed prospec-tively in terms of concordance between clinical (TNM) and pathologically confirmed classification (pTNM), the value of the various diagnostic techniques in estimating the pathologically confirmed classification, and the prognostic relevance of the new TNM definitions. Results. With regard to the primary tumor (T), clinical and pathologic classifications were identical in 63%; with regard to lymph node involvement (N), the agreement was 47%; for distant metastasis agreement occurred in 91% of cases and for the stages it occurred in 56%. As to the primary tumor (T), the accuracy of radiography (59%) was nearly identical to that of computed tomography (CT) (58%). Both techniques were less precise in determining the extent of lymph node involvement (CT, correct assessments in 50%; radiography, correct assessments in 43%). The statistically significant differences in the prognosis for the T, N, and M categories and for the stages and the categories of the new R classification could be confirmed. Allowance should be made for the different prognosis between TlNOMO and T2NOMO by the new Substages IA and Ib of Stage I. Conclusions. By the new TNM definitions for bronchus carcinoma, international conformity became feasible and practical, and the improvement of its prognostic relevance provided a more reliable basis for establishing guidelines for individual oncologic concepts. Cancer 1992; 70:1102–1110.

Background: Ether lipids could provide new prospects in cancer therapy after successful preclinical investigations. Edelfosine has been the most thoroughly investigated substance in the ether lipid gr

In January 1987, the 4th edition of the TNM classification for malignant lung tumours by the International Union Cancer (UICC) came into effect. Thus, for the first time, a uniform worldwide staging system for lung cancer became available. In order to validate the new TNM definitions for lung cancer the data of 3,000 patients were analysed prospectively. Several items were examined: 1) the agreement between clinically (TNM) and pathologically (pTNM) confirmed classification; 2) the value of the various diagnostic techniques estimating the pathologically confirmed classification; 3) the influence of the TNM definitions on separating distinct prognostic groups. With regard to the primary tumour (T), clinical and pathological classifications were identical in 64%; for lymph node involvement (N) the agreement was 48%; for distant metastases it was 90% and for the stages it was 55%. As for the primary tumour (T) the accuracy of radiography (59%) was nearly identical to computed tomography (58%). Both techniques were less precise in determining the extent of lymph node involvement (computed tomography 50%, radiography 43%, correct assessments). The statistically significant differences in prognosis for the various T-, N- and M-categories as well as for the stages could be confirmed. By the new 1987 TNM definitions (4th edition) for lung cancer international conformity became feasible as well as practical, and the improvement in its prognostic relevance provided, therefore, a more reliable basis for establishing guidelines for individual oncological concepts of therapy.

To test whether alternating chemotherapy is a favorable treatment modality in small-cell lung cancer (SCLC), 334 patients were randomized to receive either fixed cyclic-alternating treatment with ifosfamide/etoposide (IE), cyclophosphamide, doxorubicin, and vincristine (CAV), or response-oriented treatment with IE therapy up to maximal response and subsequently an immediate switch to CAV. In both arms, six cycles were given in 3-week intervals. After chemotherapy, patients with limited-stage disease received chest irradiation with 45 Gy. Prophylactic cranial irradiation with 30 Gy was applied to all complete responders. No maintenance therapy was given to patients with complete response. Minimum follow-up was 2 years. Of 321 assessable patients, the overall response rate was 70% for cyclic alternating and 77% for response-oriented treatment. Complete remission (CR) rates were 26% versus 26%. The median survival times were 9.7 months for cyclic-alternating versus 10.7 months for response-oriented treatment; the 2-year survival rates were 11% versus 9%. In limited-stage disease (LD) patients, there was a median survival of 12.5 months versus 12.3 months and a 2-year survival rate of 21% versus 18%. In extensive-stage disease (ED) patients, median survival was 8.5 versus 9.1 months, and the 2-year survival rate 3% versus 4%. From these results, we conclude that the cyclic-alternating treatment according to the hypothesis of Goldie et al has no advantage in comparison to a sequential treatment strategy with an immediate switch to a second-line protocol at the time no further response to first-line therapy is seen. Our major aim in the treatment of SCLC is to administer an active regimen at any time during the course of treatment regardless of whether sequential or alternating therapy is used.

185 patients with high grade non-Hodgkin’s lymphoma stages II-IV entered this multicentre trial and were randomized to receive either four cycles of CHOEP (cyclophosphamide 750mg/m2 i.v. d

Forty-seven patients with advanced non-small cell lung cancer (NSCLC) were treated in a multicentre phase II study with pirarubicin (THP), 4’-O-tetrahydropyranyl-doxorubicin using a dosage of 70mg/ m2

Unter den Lungentumoren dominiert das Lungenkarzinom bzw. das Bronchialkarzinom mit seinen verschiedenen Unterformen. Auserdem existiert eine zahlenmasig kleine (5% aller malignen Lungentumoren), bezuglich des histologischen Aufbaus jedoch sehr heterogene Gruppe seltener maligner Lungentumoren (Tabelle 1).Wegen der unterschiedlichen Histogenese ist eine einheitliche Klassifikation nicht moglich. Diese seltenen Lungentumoren unterscheiden sich in ihrer Atiologie von den wesentlich haufigeren Lungenkarzinomen darin, das Karzinogene der Umwelt, wie z.B. das Inhalieren von Tabakrauch, keine Rolle spielen.

As a consequence of tumour and therapy related effects anaemia is a particularly frequent occurrence in patients with lung cancer. The ensuing symptoms such as dyspnoea, fatigue and decreased general health reduce their quality of life and can impede if not altogether prevent an effective cytostatic therapy. A positive outcome after oxygen-dependent anti-tumour therapy, for example radiation therapy or various cytostatic treatments as well, can be reduced or even put at risk when tumour tissue is hypoxic. In order to treat anaemia, recombinant human erythropoietin can be used beside blood transfusions. Erythropoietins are well tolerated and allow for a long-lasting, gradual increase of Hb-levels, which cannot be achieved via transfusions. Furthermore, transfusion risks such as intolerance reactions or disease transmission can also be avoided. The various studies presented here evaluated the impact of anaemia treatment with erythropoietins on the need for transfusions and quality of life of patients with lung cancer over the last few years. They all agreed in their conclusion that both parameters can be improved with erythropoietin therapy. It turned out that the patients' quality of life improved most when Hb levels reached around 12 g/dl . Studies examining the impact of anaemia treatment on a patient's prognosis also showed positive effects in the majority of cases. In order to investigate this issue, our Heidelberg work group has designed a prospective, randomised phase-III study on NSCLC patients, which will be explained in detail further down.

This paper aims at identifying the specific legal requirements concerning data security and data protection of patient health data that apply to a cross-institutional electronic patient record (EPR) and describes possible solutions for meeting these requirements. In Germany, the legal framework for such records provide that disclosure of patient health information to physicians of third-party institutions is only allowed in case that it is necessary for the joint treatment of the patient, i.e. in case of a "treatment connection". As a first step, the functionality of a remote-access architecture was proven allowing a one-way connection between the EPR systems of two health institutions in Germany, which jointly treat tumor patients. Besides, a signature system model for ensuring the integrity and authenticity of medical documents was developed and implemented in the existing information system architecture of the University Medical Center of Heidelberg. Especially in Germany, the legal framework for cross-institutional EPRs is very complex and has a considerable influence on the development and implementation of cross-institutional EPRs. However, its introduction is thought to be valuable, since a cross-institutional EPR will improve communication within shared care processes, and thus improve the quality of patient care.

Da fur die Prognose von Lungenkarzinomen neben der anatomischen Ausbreitung vor und nach Therapie auch verschiedene anderen Faktoren masgeblich sind, wurden mehrfach Versuche unternommen, die Patienten unter Berucksichtigung multipler Faktoren in Prognosegruppen zu unterteilen (Tabelle 1.6.1) Tabelle I.6.1. Multidimensionale Klassifikationen in Prognosegruppen Fur Patienten mit Lungenkarzinomen aller Types: CST-(composite clinical-severity-TNM-) System (Feinstein u. Wells 1990) Fur Patienten mit nichtkleinzelligem Karzinom: Prognostic-Factor-Risk Index (Shinkai et al. 1992) Fur Patienten mit kleinzelligem Karzinom: Manchester-Score (Czerny et al. 1987) Prognostic Staging System (Sagman et al. 1991) Marburger Prognosegruppen (Wolf 1998)

Jede pathologische Untersuchung exzidierter Tumoren hat Aussagen zur Beschaffenheit der Resektionsrander zu liefern.

Fur die meisten Lungenkarzinompatienten steht eine kurative Behandlung bislang nicht zur Verfugung.

Hier sind zu nennen: 1) maligne Keimzelltumoren (germinale Tumoren), 2) maligne neurogene Tumoren, 3) andere maligne Weichteiltumoren, 4) Ektope maligne Tumoren von Schilddruse und Nebenschilddruse.

Jede pathologische Untersuchung exzidierter Tumoren hat Aussagen zur Beschaffenheit der Resektionsrander zu liefern. Zur Identifikation der tatsachlichen Resektionsrander in den histologischen Schnitten empfiehlt sich Markierung der Resektionsrander durch Tusche, Silbernitratlosung oder Tipp-Ex. R1 wird diagnostiziert, wenn sieh Tumorgewebe direkt am Resektionsrand befindet.

In diese Gruppe sehr seltener Tumoren werden nur solche eingeordnet, die ausschlieslich oder uberwiegend aus neuroendokrinen Elementen bestehen (in geringer Anzahl findet man neuroendokrine Zellen in uber der Halfte aller malignen epithelialen Thymustumoren, dies berechtigt aber nicht zur Einordnung als neuroendokrine Tumoren). Extrem selten findet sich eine Kombination eines malign en Thymoms vom AB-Typ mit einem klassischen Karzinoidtumor (Chen et al. 2002). Maligne neuroendokrine Tumoren kommen wesentlich seltener als maligne epitheliale Thymustumoren vor, die Relation soll zwischen etwa 1∶10 (Valliet al.1994) bis 1∶20 (Shimosato u. Mukai 1997) betragen.

Etwa 15–20% aller malignen Mediastinaltumoren sind epitheliale Tumoren des Thymus (Hejna et al. 1999; DICC 2001b); diese sind die haufigsten Tumoren des Thymus. Die folgenden Ausfuhrungen sehliesen aueh Tumoren im ektopen Thymus ein (etwa 5%) (s. S. 183).

Mit der in den vorstehenden Kapiteln beschriebenen Therapie wird bei vielen Patienten eine definitive Heilung erreicht. Dies gilt ganz besonders fur die chirurgische Therapie des nichtkleinzelligen Lungenkarzinoms der fruhen Stadien. In anderen Fallen fuhrt die Behandlung zu kompletten Remissionen, die z. T. mehrere Monate anhalten und bei einigen Patienten, z. B. mit kleinzelligem Lungenkarzinom, auch bereits Ausdruck einer definitiven Heilung sind.

In der WHO-Klassifikation der Thymustumoren (Rosai u. Sobin 1999) ist ausclrucklich festgehalten, class bei der histologischen Begutachtung — wenn immer moglich — Angaben zur anatomischen Ausbreitung in folgenden Kategorien enthalten sein sollen: 1) Abgekapselter Tumor: Tumor komplett umgeben von fibroser Kapsel unterschiedlicher Dicke, die Kapsel kann dabei von Tumor infiltriert sein, ist aber nicht durchbrochen. 2) Minimal invasiver Tumor: Tumor uberall umgeben von einer Kapsel,die herdforrnig komplett von Tumorgewebe infiltriert ist bzw. Durchbruch von Tumorzellen in das mediastinale Fettgewebe zeigt; Tumor aber in der Regel makroskopisch bzw. bei der Operation nicht unterscheidbar vom abgekapselten Tumor. 3) Weit invasiver Tumor: Tumor mit direkter Ausbreitung in Nachbarstrukturen wie Perikard, grose Gefase oder Lunge. 4) Tumor mit Implantaten: Tumor, bei dem von der Tumormasse getrennte Tumorknotchen an der Perikard- oder Pleuraoberflache anzutreffen sind. 5) Tumor mit Lymphknotenmetastasen: Metastatischer Befall von Lymphknoten, in der Regel mediastinaler und supraklavikularer Lymphknoten; nicht einbezogen ist hier die direkte Ausdehnung des Primartumors in regionare Lymphknoten, was noch als weit invasiver Tumor klassifiziert wird. 6) Tumor mit Fernmetastasen:Auch hier ist direkte Invasion von Nachbarorganen ausgeschlossen, haufigste Fernmetastasenlokalisationen sind Lunge, Leber und Knochen.

Fur die Schatzung der Prognose nach extrapleuraler Pleuro-Pneumonektomie mit anschliesender Chemoradiotherapie ist ein Stagingsystem gut geeignet, das anatomische Ausbreitung vor Therapie mit der ResidualtumorKlassifikation kombiniert. Die aktuellen Definitionen des von Sugarbaker et al. 1999 angegebenen Systems zeigt Tabelle 11.6.1.

Die Prognose des Patienten und das therapeutische Konzept (Operation, Radio- oder Chemotherapie) werden beim Lungenkarzinom wesentlich von histologischem Typ und Ausdehnung bestimmt. Die Masse des Tumors dokumentiert sich hauptsachlich in seiner anatomischen Ausbreitung. Zusatzlich liefern die Aktivitaten verschiedener Enzyme (z. B. Laktatdehydrogenase, neuronenspezifische Enolase), Hormone (z. B. ACTH, Parathormon, Kalzitonin) oder der Nachweis tumorspezifischer Antigene (z. B. CEA) Hinweise auf die Tumorausdehnung.