Thomas Wiegel

HIGH-DOSE RATE INTERSTITIAL WITH EXTERNAL BEAM IRRADIATION FOR LOCALIZED PROSTATE CANCER : RESULTS OF A PROSPECTIVE TRIAL

PURPOSEnA prospective phase II trial was carried out to test the feasibility and effectiveness of a combined interstitial with external beam radiotherapy approach for localized prostate cancer.nnnMATERIALS AND METHODSnBetween October 1992 and December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according to the AJCC classification system of 1992, were found in 21 and 61 cases, respectively. The median follow-up was 24 months; three patients were lost during follow-up. All of the patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a week was prescribed during the first and second weeks of treatment (10 Gy each week from October 1992 to December 1993) interstitially with high-dose rate Iridium-192 brachytherapy to the prostate and tumour extension beyond the capsule. External beam four-field box irradiation was then given to the prostate to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December 1993).nnnRESULTSnBefore starting treatment, a PSA value of > or =10 ng/ml was found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70 ng/ml, respectively. The PSA value was < 1.0 ng/ ml in 52.9% of patients at 2 years. Negative punch biopsies 12 and 24 months after therapy were observed in 69.8% (44/63) and 73. 1% (38/ 52) of patients, respectively. A positive biopsy combined with a PSA value of > 1.0 ng/ml was considered as local failure. The local tumour control rate was 79.5% at 2 years. Acute side-effects were not increased relative to external beam irradiation alone. Severe side-effects were observed in three patients (two of the three patients had additional risk factors (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae requiring colostomy after biopsies from the anterior rectal wall.nnnCONCLUSIONnThe described method is feasible and well tolerable. The three complications observed were not caused by irradiation alone. Biopsies from the anterior rectal wall after definitive high-dose radiotherapy for prostate cancer have to be seen as obsolete. The rate of negative prostate biopsies of 73.1% after 24 months represents an encouraging result.

External beam radiotherapy of choroidal metastases - final results of a prospective study of the German Cancer Society (ARO 95-08)

PURPOSEnIn 1994 a prospective study of the Arbeitsgemeinschaft Radiologische Onkologie of the German Cancer Society was initiated to examine the results of a standardized radiation therapy for choroidal metastases with 40 Gy. Recommendations in the literature vary from 21 to 50 Gy of total dose and from 2 to 5 Gy per single fraction. To date, no larger series treated with both a standardized technique and dose has been reported.nnnPATIENTS AND METHODSnBetween 1994 and 1998, 56 patients were enrolled and 50 patients with 65 involved eyes were available for analysis. Thirty-five patients (70%) had unilateral and 15 patients (30%) had bilateral choroidal metastases. Fifty eyes (77%) were symptomatic and 15 eyes (23%) were asymptomatic. Thirty-one patients (62%) had breast cancer and 13 patients (26%) lung cancer as the primary tumor. Patients were treated with 40 Gy in 20 fractions with bilateral asymmetric fields for bilateral or a unilateral field for unilateral choroidal metastasis. Seventeen patients had additional chemotherapy after radiotherapy for general tumor progression.nnnRESULTSnWith a median follow-up of 5.8 months (1-44 months) 41 out of 50 patients were dead. The median survival of all patients was 7 months and for patients with breast cancer 10 months. Of the 50 symptomatic eyes visual acuity increased for two or more lines in 36% (18/50), was stabilized in 50% (25/50 eyes), and decreased in 14% (7/50). No patient with asymptomatic metastasis (n = 15 eyes) developed ocular symptoms during follow-up. No patient with unilateral tumor and unilateral irradiation developed contralateral metastasis. Severe side effects, possibly related to tumor progression, occurred in three eyes (5%).nnnCONCLUSIONnRadiation therapy with 40 Gy is an effective and safe palliative treatment for symptomatic and asymptomatic choroidal metastases to preserve vision in the majority of the patients. A unilateral field for unilateral metastasis seems to be sufficient to prevent contralateral disease. Side effects of radiotherapy are acceptable: 50% of patients developed a mild skin erythema and conjunctivitis (RTOG I). Late side effects were seen in three eyes (5%).

Choroidal metastasis in disseminated lung cancer: frequency and risk factors

PURPOSEnTo determine frequency, risk factors, and benefit of a prospective screening for intraocular metastasis in patients with metastatic lung cancer.nnnDESIGNnConsecutive observational case series.nnnMETHODSnAn ophthalmologic screening was performed on 84 consecutive patients suffering from metastatic lung cancer. Medical history and disease stage were evaluated in regard to the risk for intraocular metastasis.nnnRESULTSnIn six patients (7.1%) choroidal metastasis (CM) was detected. Choroidal metastasis was present only when at least two other organ system were affected by metastasis (P =.03). The choroid was the sixth common site of organ metastasis. Mean remaining life span in patients with CM was 1.9 (0.2-5.9) months.nnnCONCLUSIONSnChoroidal metastasis is common in advanced metastatic lung cancer. However, due to the short survival of affected individuals, a systematic screening of at-risk patients for CM seems to be of limited benefit.

Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: A prospective multicenter study

Purpose: A prospective multicenter study was carried out to estimate the treatment outcome of radiotherapy in Stage II seminoma after the application of modern staging and radiotherapy techniques. The lower margin of the iliac field was positioned on the upper rim of the acetabulum to reduce the amount of scattered irradiation to the remaining testicle. Methods and Materials: The study was carried out in 25 centers in Germany. Patients with pure seminoma, negative AFP-values, and retroperitoneal lymph node metastases of less than 5 cm in diameter were entered into the study. All patients received a ventrodorsal opposed field irradiation of the para-aortic and the ipsilateral iliac lymph nodes. The fields extended from the top of the 11th thoracic vertebra to the top of the acetabulum. Patients in Stage IIA (lymph nodes <2 cm ) received 30 Gy, and patients with Stage IIB (lymph nodes between 2 and 5 cm) 36 Gy total dose. Results: 39 patients in Stage IIA and 19 patients in Stage IIB were evaluated. After a median observation time of 37 months all patients are alive and disease free. Recurrence free survival in stage IIA was 100%. Two patients in Stage IIB experienced a recurrence 10 and 17 months after the end of radiotherapy. The actuarial recurrence free survival estimate in Stage IIB was 94.1% for 1 year and 87.4% for 2 years. One recurrence in Stage IIB occurred in the mediastinum, one in the mediastinum, and one the lung. Both patients could be salvaged by chemotherapy. There were no pelvic recurrences. The treatment was well tolerated, with nausea being the most common side effect (56.9% Grade 1, 15.5% Grade 2, and 8.6% Grade 3). Diarrhea occurred in 15.5% (Grade 1), 15.5% (Grade 2), and 5.2% (Grade 3) of the patients. Conclusions: The outcome of para-aortic and ipsilateral iliac irradiation in Stage IIA/B testicular seminoma is excellent with the currently available staging methods and treatment facilities. The treatment is well tolerated. The lower margin of the iliacal field can be placed at the acetabulum.

Intraocular metastases: differential diagnosis from uveal melanomas with high-resolution MRI using a surface coil

Magnetic resonance imaging with dedicated surface coils plays a pivotal role in differential diagnosis and staging of intraocular tumors. The purpose of this study was to establish MRI criteria for the differential diagnosis of uveal melanomas and intraocular metastases. In a prospective study 44 eyes in 36 patients with intraocular metastases and 200 patients with uveal melanomas were investigated with MRI using a 1.5-T scanner and a 5-cm surface coil. Both quantitative and qualitative evaluation of the resulting images was performed. The MR signal intensities typically expected for metastases (slightly hyperintense on non-contrast T1-weighted images and hypointense on T2-weighted images compared to the vitreous body) were seen in only 23.1%. The typical melanoma signal of either moderate or strong hyperintensity on T1-weighted images and hypointensity on T2-weighted images was seen in 69.4% of the proven melanomas. Contrast enhancement was observed in both metastases and melanomas. Morphological differences between metastases and melanomas were detected in tumor size, shape, position, frequency of retinal detachment, and homogeneity of the tumor. Differentiation between intraocular metastases and uveal melanoma is limited by overlap of signal intensities. Some improvement is achieved with morphologic criteria.

Klinische Charakteristika der Aderhautmetastasierung

ZusammenfassungHintergrundDie Aderhautmetastase ist der häufigste maligne intraokulare Tumor. Ziel dieser Untersuchung ist die Charakterisierung des klinischen Erscheinungsbildes, der zugrunde liegenden Tumorerkrankung sowie des differenzialdiagnostischen Vorgehens bei Aderhautmetastasierung (AM).Patienten und MethodeEs wurden 71 konsekutive Patienten mit AM ausgewertet. Besondere Beachtung fanden die okulären Symptome, das ophthalmoskopische und sonographische Erscheinungsbild der AM sowie die Charakterisierung der zugrunde liegenden Tumorerkrankung. Bei allen Patienten erfolgte ein vollständiges Screening (CT Kopf, Thorax und Abdomen; Knochenszintigraphie) zur Primärtumorsuche bzw. bei bereits bekanntem Primärtumor zur Suche nach weiteren Organmetastasen.ErgebnisseEine symptomatische AM zeigten 95% der Patienten, bei 5% handelte es sich um einen Zufallsbefund. Bei 60% der Patienten bestand eine solitäre AM, bei 40% multiple AM (2–14). Bei Erstvorstellung war bei 18% der Patienten (n=13) keine Tumorerkrankung bekannt. Bei 12 dieser Patienten konnte ein Bronchialkarzinom diagnostiziert werden. Insgesamt bestand bei 53% der Patienten ein Mammakarzinom, bei 26% ein Bronchialkarzinom, bei je 3% ein Nieren- oder Darmkarzinom, ein Aderhautmelanom oder ein kutanes Melanom, sowie bei einzelnen Patienten ein Zervix-, Ovarial-, Thymus- oder Prostatakarzinom sowie in einem Fall ein unbekannter Primärtumor. Weitere Fernmetastasen zeigten 96% der Patienten. Beim Bronchialkarzinom trat die AM im Mittel 9xa0Monate, beim Mammakarzinom 68xa0Monate nach Diagnose der Tumorerkrankung auf. Bei 58% der Patienten mit Bronchialkarzinom war die AM die Erstmanifestation der Grunderkrankung, beim Mammakarzinom bei 28% das erste Zeichen der Metastasierung.SchlussfolgerungAderhautmetastasen finden sich fast nur bei einer generalisierten Tumorerkrankung. Beim Mammakarzinom treten sie typischerweise Jahre nach Diagnose auf und können das erste Zeichen einer Generalisierung sein. Beim Bronchialkarzinom kann die Aderhautmetastase das erste klinische Zeichen der Erkrankung sein.AbstractBackgroundChoroidal metastasis (CM) is the most common malignant intraocular tumor. The aim of this study was the characterization of the ophthalmoscopic aspect, the underlying tumor disease and differential diagnosis of this entity.Study designRetrospective observational case series.Patients and methodsA total of 71 consecutive patients with CM were evaluated. Special attention was given to ocular symptoms, the ophthalmoscopic and sonographic aspects and the characteristics of the underlying tumor disease. All patients had undergone screening (CCT, CT of thorax and abdomen; bone scintigraphy) for the primary tumor and further organ metastases.ResultsOf the patients 95% had symptomatic CM, in 5% of the patients CM was detected by chance, 60% had a single CM, 40% showed multiple (2–14) lesions and 18% (n=13) had no history of tumor disease. In 12 of these patients lung cancer could be diagnosed. In 53% of the patients the primary tumor was breast cancer, in 26% lung cancer, in 3% kidney cancer, bowel cancer, choroidal or cutaneous melanoma and in single patients cervical, ovarian, thymus or prostate cancer. In one patient who died from disseminated metastases, no definite primary tumor could be detected. Of the patients 96% had further metastases, CM occurred with a mean interval after diagnosis of the primary of 9 months in lung cancer and 68 months in breast cancer. CM was the first clinical sign of tumor disease in 58% of patients with lung cancer and the first clinical sign of metastatic disease in 28% of patients with breast cancer.ConclusionsChoroidal metastasis occurs almost exclusively in metastatic disease. In breast cancer it typically occurs years after diagnosis of the primary tumor and may be the first sign of metastatic disease. In lung cancer choroidal metastasis may be the first sign of the tumor disease.

Salvage radiotherapy in patients with prostate cancer and biochemical relapse after radical prostatectomy : Long-term follow-up of a single-center survey.

Background and purposeIn patients with prostate cancer (PC) and biochemical relapse after radical prostatectomy, salvage radiotherapy (SRT) could improve PC-specific survival (PCSS) but the timing for initiation is still under discussion. We have demonstrated a low rate of biochemical relapses in a patient series with very low pre-SRT PSA levels after a median follow-up of 42xa0months. Here, we present an update of that study.Patients and methodsOverall, 151 patients were analyzed. A biochemical relapse after SRT was diagnosed when the PSA exceeded the post-SRT nadir by 0.2xa0ng/ml with subsequent increase. Parameters with significant impact on biochemical progression-free survival (BPFS), PCSS, and overall survival (OS) in univariate analysis were included in a multiple Cox regression analysis.ResultsAfter a median follow-up of 82xa0months, 18xa0patients (12u2009%) had died with 10 (6.6u2009%) deaths being PC-related. A biochemical progression was diagnosed in 83xa0patients (55u2009%). Univariate analysis revealed a significant impact of pre-SRT PSA level, Gleason score, and PSA doubling time (PSADT) on BPFS and for initial tumor stage and Gleason score on OS. Multivariate analysis confirmed the impact of pre-SRT PSA level, Gleason score, and PSADT on BPFS and tumor stage on OS.ConclusionIn this update, the rate of biochemical relapses increased compared with our previous data. Compared to similar studies, we found a remarkably low rate of PC-related deaths. Our data support early initiation of SRT. However, this treatment strategy, triggered by very low PSA levels, could carry the risk of overtreatment in at least a subset of patients.ZusammenfassungHintergrund und ZielBei Patienten mit Prostatakarzinom und biochemischem Rezidiv nach radikaler Prostatektomie kann eine Salvage-Strahlentherapie das tumorspezifische Überleben verbessern. Der Zeitpunkt des Therapiebeginns wird kontrovers diskutiert. Wir haben in unserer Serie eine geringe Rate biochemischer Rezidive bei Patienten mit sehr niedrigen präradiotherapeutischen PSA-Werten gezeigt. Die vorliegende Arbeit präsentiert die Langzeitdaten dieser monozentrischen Studie.Patienten und MethodenInsgesamt wurden 151xa0Patienten analysiert. Ein biochemischer Progress wurde diagnostiziert, wenn ein steigender PSA-Wert den postradiotherapeutischen Nadir um 0,2xa0ng/ml überschritten hat. Parameter mit signifikantem Einfluss auf biochemisch-progressionsfreies Überleben, tumorspezifisches Überleben und Gesamtüberleben in der univariaten Analyse wurden in einer multivariaten Cox-Regressionsanalyse analysiert.ErgebnisseNach einer medianen Nachbeobachtungszeit von 82xa0Monaten waren 18xa0Patienten (12u2009%) verstorben, davon 10 (6,6u2009%) tumorbedingt. Ein biochemischer Progress trat bei 83xa0Patienten (55u2009%) auf. Die univariate Analyse zeigte einen signifikanten Einfluss des präradiotherapeutischen PSA-Werts, des Gleason-Scores und der PSA-Verdopplungszeit auf das biochemisch-rezidivfreie Überleben sowie des initialen Tumorstadiums und des Gleason-Scores auf das Gesamtüberleben. Die multivariate Analyse bestätigte den Einfluss des präradiotherapeutischen PSA-Werts, des Gleason-Scores und der PSA-Verdopplungszeit auf das biochemisch rezidivfreie Überleben sowie des initialen Tumorstadiums auf das Gesamtüberleben.SchlussfolgerungIn unserer aktualisierten Serie ist die Rate biochemischer Rezidive im Vergleich zu der initialen Auswertung erhöht. Im Vergleich zu anderen Studien fanden wir eine bemerkenswert niedrige Rate tumorbezogener Todesfälle. Unsere Daten unterstützen den frühen Beginn der Salvage-Strahlentherapie. Jedoch beinhaltet diese, von sehr geringen PSA-Werten getriggerte Behandlungsstrategie auch das Risiko einer Übertherapie zumindest einiger Patienten.

Adjuvant and Salvage Radiotherapy after Radical Prostatectomy

Background: Following radical prostatectomy, between 15 and 60% of all patients with pT3 prostate cancer experience persistence or increasing levels of prostate-specific antigen (PSA) as a sign of tumor persistence or progression within 5 years. Retrospective studies have shown a rate of 35–55% of positive biopsies from the vesicourethral anastomosis in this situation. Best treatment for these disease conditions is under debate, current strategies include adjuvant radiotherapy (RT), ‘wait-and-see‘ and salvage RT or hormone therapy for increasing PSA. Results: A number of retrospective studies have shown an increased rate of local control and ‘freedom from treatment failure‘ following adjuvant RT with doses in the range of 50–60 Gy. However, no survival benefit could be demonstrated by now. Results of three major phase III studies are pending. In case of persisting or increasing PSA levels following radical prostatectomy, 30–70% of these patients will reach an undetectable PSA level after conformal RT with total doses of 60–70 Gy, which will stay undetectable or at least stable within the next 2–5 years in about 50% and therefore offering a chance of cure. When starting RT, PSA should be as low as possible (<2 ng/ml). With higher PSA levels the chance of achieving an undetectable PSA again decreases below 35%. High Gleason scores of 8–10, seminal vesicle involvement and a short PSA doubling time are adverse prognostic factors. Severe late side effects of conformal RT are infrequent (<3%). In contrast, hormonal treatment is of palliative nature in the long run, with a median time to development of metastases of 4–7 years, and can be offered to patients with progressive disease after RT. Conclusions: Adjuvant RT following radical prostatectomy for pT3 prostate cancer offers higher local control rates and an increase in ‘freedom from treatment failure‘, but no prolongation of survival has yet been shown. In the situation of increasing PSA levels after radical prostatectomy, salvage RT seems to offer a chance of cure in selected patients, although it is difficult to draw firm conclusions because of generally too short follow-up times.

June 2002: 57-year-old male with leptomeningeal and liver tumors.

The June 2002 COM. A male patient presented at the age of 57 years with a benign meningeal melanocytoma. Eight years later, the patient had a local recurrence of the tumor, cerebral metastases and liver metastases. This demonstrates that a correct diagnosis of melanocytic CNS tumors remains a challenge together with elucidating predictive markers for biological behavior. To the best of our knowledge, this is the first case of a melanocytoma associated with hepatic metastasis.

Strahlentherapeutische Strategien in der multimodalen Therapie des resektablen und nicht resektablen Pankreaskarzinoms

Hintergrund: Die Prognose der Patienten mit Pankreaskarzinom ist unverändert schlecht. Ein kurativer Ansatz besteht nur in Frühstadien bei radikal chirurgischem Vorgehen. Der Wert der kombinierten Radiochemotherapie wird sowohl postoperativ adjuvant als auch palliativ bei Inoperabilität trotz nachgewiesener Wirksamkeit wegen der kurzen medianen Überlebenszeiten zwischen acht und 15 Monaten kontrovers beurteilt. Sowohl im adjuvanten als auch im neoadjuvanten multimodalen Therapiekonzept haben sich in den letzten Jahren erhebliche, klinisch relevante Entwicklungen ergeben. Auch die Integration der intraoperativen Strahlentherapie (IORT) wird kontrovers diskutiert.nn Material und Methode: Seit den Ergebnissen der GITSG-Studie gilt die postoperative adjuvante Radiochemotherapie mit 5-FU in den USA als Standard. Nachfolgestudien der EORTC und der ESPAC rekrutieren derzeit Patienten oder sind abgeschlossen, die Ergebnisse sind noch nicht publiziert. Neoadjuvante Therapiekonzepte (präoperative Radiochemotherapie) sind in den letzten drei Jahren in unterschiedlichen Ansätzen zumeist bei primärer Operabilität, aber auch bei Inoperabilität untersucht worden. Unter Einsatz der 3-D-Bestrahlungsplanung wurde die Dosis von 40 Gy auf 45 bis 50 Gy gesteigert. In einzelnen spezialisierten Institutionen werden diese Konzepte mit einer IORT kombiniert. Neuere Chemotherapeutika wie Gemcitabin und die Taxane werden in Phase-II-Studien als kombinierte Radiochemotherapie bei primär inoperablem Pankreaskarzinom getestet.nn Ergebnisse: Sowohl durch die postoperative adjuvante als auch durch die neoadjuvante Radiochemotherapie mit anschließender Pankreatikoduodenektomie können mediane Überlebensraten von 15 bis 25 Monaten erreicht werden. Durch die neoadjuvante Radiochemotherapie bei primär resektablem Pankreaskarzinom scheint die Rate positiver postoperativer Schnittränder sowie die Anzahl der Patienten mit Lymphknotenmetastasen reduziert zu werden. Obwohl eine Überlebensverlängerung oder eine höhere lokale Tumorkontrolle (ca. 80% bei beiden Therapieformen) durch die neoadjuvante Radiochemotherapie gegenüber der adjuvanten Radiochemotherapie bisher nicht bewiesen werden konnte, erhalten mehr als 25% der Patienten nach radikaler Operation aufgrund der Morbidität keine adjuvante Radiochemotherapie. Wegen der nur mäßigen Verlängerung der medianen Überlebenszeit um ca. fünf bis zehn Monate ist die adjuvante Radiochemotherapie in Europa nicht allgemein akzeptiert. Mit der kombinierten Radiochemotherapie bei lokaler Inoperabilität kann die Überlebenszeit verdoppelt werden. Die wirksamste Kombination scheint mit 5-FU als Dauerinfusion über fünf Tage mit einer Dosis von etwa 250 mg/m2 vorzuliegen. In der Hand des Erfahrenen bietet die IORT eine nebenwirkungsarme, effektive Ergänzung der Therapie, die zu einer Erhöhung der lokalen Tumorkontrolle und einer anhaltenden Schmerzkontrolle führt. Neuere Substanzen wie Gemcitabin und die Taxane scheinen in vitro wirksame Strahlensensitizer zu sein. In ersten Ergebnissen in Phase-I- und Phase-II-Studien wurde die MTD noch nicht gefunden. Während die Toxizität bei Einzelfraktionen von 1,8 bis 2 Gy tolerabel scheint, ist Vorsicht bei höheren Einzeldosen geboten.nn Schlussfolgerungen: Vor dem Hintergrund der unverändert schlechten Prognose des Pankreaskarzinoms werden zur Zeit unterschiedliche Konzepte der adjuvanten und neoadjuvanten kombinierten Radiochemotherapie, teils auch mit neueren Substanzen, geprüft. Dies betrifft sowohl resektable als auch nicht resektable Pankreaskarzinome. Aus allgemein onkologischer und radioonkologischer Sicht erscheint das neoadjuvante Konzept derzeit überzeugend, obwohl der Beweis der besseren Wirksamkeit aussteht. Hierfür sind randomisierte Studien notwendig. Die Integration der IORT in diese Therapiekonzepte ist zur Erhöhung der lokalen Tumorkontrolle sinnvoll. Diese aggressiven Strategien sind jedoch nur bei einem kleinen Teil der Patienten indiziert. Im Falle der Inoperabilität ist die kombinierte Radiochemotherapie bei lokoregionär begrenztem inoperablen Pankreaskarzinom bei entsprechendem Allgemeinzustand derzeit die Therapie der Wahl.Background: The prognosis of patients with adenocarcinoma of the pancreas remains poor. Only patients with small tumors and complete resection have a curative chance. The value of combined radio-chemotherapy adjuvant or even palliative in case of unresectable tumors is controversial due to the short median survival times of all patients ranging from 8 to 15 months. Within the last years, significant new treatment modalities were introduced into the multimodality approach. Even the intraoperative boost therapy (IORT) with fast electrons remains still controversial.nn Material and Methods: Since the publication of the results of the historic GITSG study, in the US postoperative adjuvant radio-chemotherapy with 5-FU remains the treatment of choice. Successor studies of the ESPAC and the EORTC have been closed or are recruiting patients, the results are still pending. Neoadjuvant treatment modalities were investigated within the last 3 years, mostly in case of primary operable but also in unresectable tumors. Using 3-D-treatment planning, the total dose of radiotherapy was increased from 40 up to 45 to 50 Gy. In centers with great experience, an IORT was added to these combined modalities. More modern chemotherapeutic agents like gemcitabine or the taxanes are under investigation, using combined radio-chemotherapy in phase-II protocols in patients with unresectable tumors.nn Results: In case of both, adjuvant or neoadjuvant radio-chemotherapy following or before pancreaticoduodenectomy, median survival times range form 15 to 25 months. The neoadjuvant radio-chemotherapy seems to reduce the rate of positive surgical margins and the rate of patients with positive lymph nodes. For the moment, there is no proven survival advantage or increase of local control (about 80% in both cases) for patients treated with neoadjuvant radio-chemotherapy compared with adjuvant radio-chemotherapy. However, about 25% of the patients dont receive adjuvant therapy due to the perioperative morbidity. Because prolongation of survival with adjuvant therapy is only 5 to 10 months, in Europe adjuvant radio-chemotherapy is not accepted as the treatment standard. Combined radio-chemotherapy in patients with unresectable tumors results in significant improvement of survival. 5-FU continuous infusion with 250 mg/m2 seems to be the treatment of choice. IORT is effective in achieving long-term local control and an effective pain palliation. More modern chemotherapeutic agents seem to be effective in vitro as radio-sensitizers. In first reported results, the MTD was not found. Toxicity seems not to be increased with single radiotherapy doses of 1,8 to 2 Gy. However, higher single doses should not be used.nn Conclusions: Due to the worse prognosis of patients with adenocarcinoma of the pancreas, new combined treatment modalities as adjuvant and neoadjuvant radio-chemotherapy, particularly with more modern chemotherapeutic agents, for patients with resectable and unresectable tumors are under investigation. For some reasons, the neoadjuvant setting seems to be better. However, these results are not proven by prospective randomized clinical trials. Therefore, these trials are necessary to define the treatment of choice in these patients. IORT is a helpful tool to improve local control. However, these aggressive multimodality approaches are only indicated in a minority of patients. In patients with unresectable tumors and good condition, combined radio-chemotherapy remains the treatment of choice.