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Aim In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. Methods Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). Results Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. Conclusion FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. Trial registry ClinicalTrials.gov identifier: NCT03426657.

Patienten mit bosartigen Tumoren, die einer Strahlentherapie zugefuhrt werden, haben bereits primar haufig einen deutlich reduzierten Ernahrungszustand. Dies kann tumor-, patienten- und therapiebedingt sein. Darstellung der Ursachen der Malnutrition, insbesondere hinsichtlich der Strahlentherapie und Radiochemotherapie, und moglicher Therapieoptionen mit Hilfe von Literaturdaten sowie der Einbeziehung der aktuellen Leitlinien. Insbesondere bei Patienten mit Tumoren der Kopf-Hals-Region und der Speiserohre kommt es durch die Strahlentherapie/Radiochemotherapie zu einer Entzundung der Schleimhaute, einer Reduktion des Speichelflusses und einem Verlust der Geschmacksempfindung mit konsekutiver Dysphagie und Reduktion der Nahrungsaufnahme. Langfristig kann bei diesen Patienten eine Dysphagie durch eine Fibrose der Schluckmuskulatur ausgelost werden; hinzu kommen Xerostomie und eine Verschlechterung des Zahnstatus. Durch verschiedene Methoden der Ernahrungsbehandlung, diatetische Beratung, enterale Ernahrung uber Sonden, insbesondere der PEG, konnte in randomisierten Studien gezeigt werden, dass damit eine Verbesserung des Ernahrungstatus und der Lebensqualitat der Patienten erreicht werden kann. Die Patienten sollten bereits pratherapeutisch eine individuelle Ernahrungsberatung erhalten; bei Bedarf sollte eine Sondenernahrung zusatzlich erfolgen. Medikamentose Masnahmen zur Behandlung von Ernahrungsstorungen wahrend der Strahlentherapie haben sich in den letzten Jahren nicht durchgesetzt. Durch eine konsequente Ernahrungsberatung, der Verfugbarkeit enteraler Ernahrung, der Verwendung von Sonden, insbesondere der PEG, konnen der Ernahrungsstatus und die Lebensqualitat von Tumorpatienten in der Regel wahrend einer Strahlentherapie aufrechterhalten oder sogar verbessert werden.

Background Mixed adenoneuroendocrine carcinomas are highly malignant tumors with both adenocarcinomatous and neuroendocrine components. They can originate in any organ but are more common in the rectum. Due to their rarity, current treatment recommendations for mixed adenoneuroendocrine carcinoma are based on limited data and follow general guidelines for the management of adenocarcinomas and neuroendocrine neoplasms. Uncertainty regarding the efficacy of the available local and systemic treatment strategies is a compounding issue. Even those patients with locally limited disease have a relatively short life expectancy. In this report, we describe a case of deep rectal mixed adenoneuroendocrine carcinoma with long survival after chemoradiation. Case presentation A 48-year-old Caucasian woman was diagnosed with a grade 3 rectal adenocarcinoma combined with a poorly differentiated large cell neuroendocrine carcinoma component and synchronous metastases (cT3cN1cM1) in both lobes of the liver in 2012. She received concomitant chemoradiotherapy followed by four additional cycles of cisplatin plus irinotecan. Initial treatment induced complete remission of the rectal tumor and liver metastases. Consequently, it was not necessary to surgically resect the primary tumor or any of the metastases. Three months after the end of treatment, one metastasis in the first segment of the liver showed regrowth, and stereotactic body radiotherapy of the metastasis and chemotherapy resulted in a clinical complete response. The patient has been recurrence-free for more than 5 years. Conclusions Extended long-term control of a poorly differentiated metastatic (stage IV) mixed adenoneuroendocrine carcinoma is rare. The multimodal first- and second-line regimens of radiotherapy and chemotherapy described in this case report represent a new therapeutic approach. Encouraged by the results in this case, we compiled a review of the literature on mixed adenoneuroendocrine carcinoma.

Fragestellung: Bei Tumorpatienten fuhren sowohl erkrankungs- als auch therapieassoziierte Belastungen haufig zu einer Mangelernahrung. Zentrale klinische Probleme sind eine unzureichende Nahrungsaufnahme, eine Einschrankung der korperlichen Aktivitat und Mobilitat sowie katabole metabolische Veranderungen im Sinne einer systemischen Inflammationsreaktion, die oft gemeinsam vorliegen. Diese Leitlinie soll evidenzbasierte Empfehlungen zur Erkennung und ggf. multimodalen Behandlung von Ernahrungs- und Stoffwechselstorungen bei Tumorpatienten geben. Methodik: Es wurden eine systematische Literaturrecherche sowie eine Handsuche zu Literatur uber Ernahrungs- und Stoffwechelstorungen bei Tumorpatienten durchgefuhrt. Die Ergebnisse wurden in einer interdisziplinaren Arbeitsgruppe aus Arzten, Ernahrungswissenschaftlern und Diatassistenten diskutiert und bewertet. Auf dieser Basis wurden von der Arbeitsgruppe Empfehlungen erarbeitet, die auf der Konsensuskonferenz am 18. und 19. Oktober 2013 vorgestellt, diskutiert, z. T. modifiziert und verabschiedet wurden. Ergebnisse: Die Leitlinie enthalt 48 Empfehlungen zur klinischen Ernahrung in der Onkologie. Zur fruhzeitigen Erfassung von Ernahrungsstorungen sollen valide Screeningverfahren eingesetzt und bei Auffalligkeiten im Screening durch ein gezieltes Assessment erganzt werden. Grundsatzlich soll eine ausreichende Energie- und Eiweiszufuhr gesichert werden. Hierzu eignen sich die Linderung ernahrungsrelevanter Symptome sowie ein der individuellen Situation angemessener Einsatz professioneller Ernahrungsberatung inkl. oraler bilanzierter Diaten (Trinknahrungen), Sondenernahrung bzw. intravenoser Ernahrung. Jede Ernahrungsbetreuung sollte zum Aufbau der Muskelmasse von bewegungstherapeutischen Masnahmen begleitet werden. Bei Patienten mit fortgeschrittener Erkrankung konnen medikamentose Substanzen zur Steigerung des Appetits, zur Vergroserung der Muskelmasse und zur Minderung der Inflammationsreaktion erwogen werden. Wahrend einer Bestrahlung im Kopf-Hals-Bereich ist fruhzeitig der Einsatz von Trinknahrungen und ggf. einer Sondenernahrung in Betracht zu ziehen, um den Energiebedarf zu sichern und eine Unterbrechung der Bestrahlung zu verhindern. Wahrend einer medikamentosen Tumorbehandlung gilt analog, dass eine ausreichende Nahrungszufuhr gesichert werden soll, ggf. unter Anwendung einer enteralen und/oder parenteralen Nahrungszufuhr. Nach kurativer Tumorbehandlung werden regelmasige korperliche Aktivitat sowie eine die Bedarfsdeckung nicht ubersteigende Energiezufuhr empfohlen. Abhangig von der Erkrankungsprognose sollte auch bei unheilbar kranken Tumorpatienten auf eine ausreichende Nahrungsaufnahme geachtet werden, wahrend in der Sterbephase die Zufuhr von Nahrung und Flussigkeit allein symptomorientiert erfolgen soll. Schlussfolgerung: Durchgehende Aufmerksamkeit fur mogliche Ernahrungsstorungen sowie eine der jeweiligen Situation angemessene Ernahrungsbehandlung sollen Teil der Supportivbetreuung jedes Tumorpatienten sein, um die Korperreserven, die Therapietoleranz, den Erkrankungsverlauf und die Lebensqualitat gunstig zu beeinflussen.

Die Tumorerkrankung selbst und die tumorspezifische Behandlung (Operation, medikamentose Tumortherapie, Strahlentherapie) beeinflussen den Allgemeinund Ernahrungsstatus der Patienten. Dies ist allgemein bekannt und gilt fur die kurative wie auch die palliative Situation. Daher sollten supportive Masnahmen – und dazu gehort auch die Ernahrungstherapie – allen Patienten empfohlen werden. Denn es ist bekannt, dass in Abhangigkeit von der Tumorerkrankung, dem Tumorstatus und dem Alter der Patienten zwischen 24% und 54% der Patienten bereits pratherapeutisch eine Malnutrition aufweisen. Besonders gefahrdet sind Patienten mit gastrointestinalen Tumoren sowie mit Tumoren der Kopf-Hals-Region. Die verschiedenen Behandlungsmodalitaten konnen diese Haufigkeit noch erhohen und zu einer Verschlechterung des Allgemeinstatus und der Lebensqualitat, schlechterer Durchfuhrbarkeit der verschiedenen Therapieverfahren sowie einer erhohten Nebenwirkungsrate der Krebsbehandlung fuhren. Letztendlich konnte bei einzelnen Tumorentitaten auch eine Verschlechterung der Prognose der Patienten durch eineMalnutrition gezeigt werden. Kommtes zurMetastasierungunddamit in der Regel zu einer inkurablen Situation, konnenbis zu 50 %derPatienten ander tumorbedingtenKachexie versterben. Diese Zahlen belegen die Bedeutung der Ernahrungssituation der Krebskranken und zeigen auch die Notwendigkeit einer adaquaten Ernahrungsberatung und -therapie auf. Daher hat sich diese Ausgabe vonDer OnkologedieAufgabegestellt,dieGrundlagen der Tumorkachexie, die fruhzeitige Erkennung der Malnutrition sowie ihre spezifischen Behandlungsmoglichkeiten wahrend operativer, chemotherapeutischer und radioonkologischer Masnahmen darzustellen. Dabei sei auch auf die S3-Leitlinie der Deutschen Gesellschaft fur Ernahrungsmedizin hingewiesen [1], die in interdisziplinarer Zusammenarbeit mit onkologischen Fachgesellschaften, Ernahrungswissenschaftlern und Diatassistenten 48 Empfehlungen zur klinischen Ernahrung in der Onkologie ausgesprochen hat. Die pathophysiologische Entwicklung einer Kachexie durch die Tumorerkrankung wird von Zopf und Hermann ubersichtlich dargestellt. Die Anorexie, die Entstehung der katabolen Stoffwechsellage und die anabole Resistenz der Skelettmuskulatur sind bedingt durch unterschiedliche immunmodulatorische und zytokinbedingte Stoffwechselvorgange sowie durch systemische Inflammationsreaktionen, die offensichtlich automatisch bei vielen Tumorerkrankungen ablaufen. Dadurch kommt es zu einer korperlichen Einschrankung mit konsekutiver Reduktion derMuskelmasse. Daher wird von den Autoren auf die besondere Bedeutung einer zusatzlichen Bewegungstherapie hingewiesen. Die Grundlagen der Ernahrungstherapie werden vonArends dargestellt. Von groserBedeutungsinddieverschiedenen Screeninginstrumente (z. B. SubjectiveGlobal-Assessment-Status–SGA-Status) und die Assessment-Instrumente als Voraussetzung fur eine adaquate Ernahrungstherapie. Die Einflussmoglichkeiten mittels adaquater Ernahrungstherapie werden in den Beitragen von Weimann, Bertz bzw. Fietkau beschrieben. Im Einzelnen verweistWeimann darauf,dasssichbeioperativenMasnahmen, auch im Rahmen von randomisierten Studien, eine zusatzlicheErnahrungstherapie bei Patienten mit inadaquater Nahrungszufuhr sowohl praals auch postoperativ bewahrt hat. Inwiefern immunmodulatorische Substanzen dies unterstutzen konnen, wird z. T. noch kontrovers diskutiert; auch wenn es Hinweise auf einen positiven Effekt gibt. Bertz stellt dar, dass eine routinemasige parenterale/enterale Ernahrung wahrend einer Chemotherapie nicht indiziert ist, aber der Ernahrungsstaus regelmasig uberpruft werden sollte und bei einer Reduktion des Ernahrungszustands entsprechende Masnahmen eingeleitet werden sollten. Hinzukommen sehr viele Hinweise, wie durch allgemeine Masnahmen spezifischen Nebenwirkungen der Tumortherapie begegnet werden kann. Nahrungserganzungsmittel und sog. Krebstherapien werden kritisch diskutiert. Fietkau beschreibt, dass im Rahmen einer Strahlentherapie bei bestimmten Tumoren (Kopf-Hals-Region, Osophaguskarzinom, oberer Gastrointestinaltrakt) durch verschiedene orale und enterale Ernahrungsmasnahmen der Allgemeinund Ernahrungszustand der Patienten verbessert werden kann. Eine enterale Ernahrung mittels PEG (perkutane endoskopische Gastrostomie) wird heutzutage aufgrund der langeren Dysphagiephase kritischer gesehen. Trotzdem existieren auch hierfur deutliche Indikationen. Alle drei Autoren verweisen darauf, dass der erste Schritt einer Ernah

For metastatic carcinomas of the urinary bladder and prostate, systemic therapy is of primary importance. Due to technological advances in radiation oncology such as stereotactic radiotherapy, intensity-modulated radiotherapy, interstitial radiotherapy, and the combination of radiotherapy and chemotherapy, pelvic irradiation can nowadays be carried out effectively and without the risk of major side effects. New data from other tumor entities and retrospective analyses suggest that the use of these technologies can lead to a clinical benefit in terms of improvement in quality of life, local control, and overall survival. For the time being, the decision to administer radiotherapy to the pelvic region should be made on an individual basis. Retrospective analyses of data from prostate carcinomas in particular are currently being planned. This review article introduces potential indications which are supported with real patient examples and discusses future developments giving an overview of the literature and referring to data from prospective randomized trials.

Plattenepithelkarzinome des Osophagus (PECA) haben mit der Infiltration der Lamina submucosa eine eingeschrankte Prognose. Die alleinige Resektion fuhrt zu einem Uberleben von 30 % nach 5 Jahren; nach alleiniger Radiotherapie wird selten ein Langzeituberleben erreicht. Multimodale Therapien unter Einschluss der simultanen Radiochemotherapie (RCT) verbessern diese Ergebnisse. Auf PECA zentrierte Diskussion der Ergebnisse aus Studien und Metaanalysen der letzten 15 Jahre bezuglich strahlentherapeutischer Optionen. Die RCT ist Standard bei den nicht resektablen PECA. Bei den technisch resektablen Tumoren ist die optimale Therapie in der Diskussion; Resektion, RCT plus Operation und alleinige RCT sind moglich. Wird eine Operation erwogen, verbessert die neoadjuvante RCT die lokale Tumorkontrolle bereits bei T2-Tumoren. Ein Gewinn an Lebenszeit durch eine RCT zur Operation wurde mehrheitlich fur T3-4N0- oder N1-Tumoren nachgewiesen. Im Vergleich zur alleinigen RCT verbessert die trimodale Behandlung die lokale Tumorkontrolle. Gegenuber einer alleinigen RCT ergibt sich jedoch quod vitam kein Vorteil. Ein kritischer Faktor ist die perioperative Sterblichkeit. Von Seiten der Radioonkologie wird diese durch eine Modifikation des Bestrahlungsvolumens und der Dosisverteilung praventiv beeinflusst. Anderseits muss uberlegt werden, welche Patienten von einer Resektion bei residualer Erkrankung profitieren. Fur eine Orientierung am Ansprechen auf eine Kurzzeitchemotherapie oder die RCT finden sich erste Argumente. Die RCT hat das Spektrum der kurativen Therapien erweitert. Im neoadjuvanten Bereich verbessert sie die Ergebnisse der Resektion. Umgekehrt wird diskutiert, ob die alleinige RCT bei resektablen Tumoren eine Alternative zur Operation darstellt.

The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: “breast cancer”, “radiotherapy”, “regional node irradiation”. Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. International guidelines reveal substantial differences regarding indications for RNI. Patients with 1–3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1–2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk–benefit relationship appears to shift towards an improvement of outcome.

The role of surgical lung resection following neo-adjuvant radio-chemotherapy (RCT) in patients with locally advanced non-small cell lung cancer (NSCLC) is yet not clearly defined. The aim of our study was to analyze the postoperative survival and to identify relevant prognostic factors. 46 patients underwent curative resections after neo-adjuvant RCT for locally advanced NSCLC (IIIA/IIIB) between February 2008 and February 2015. A retrospective data analysis regarding preoperative regression status, perioperative mortality, postoperative survival, patho-histological remission, relapse pattern and other prognostic factors was performed. A neo-adjuvant RCT with a median radiation dose of 50.4 [range, 45-60] Gy was performed in 44 (96 %) patients. Partial and/or complete regression was observed in 32 (70 %) patients. R0-resection was achieved in 44 (96 %) patients. The 30-day mortality was 4 % and the perioperative morbidity was 37 %. The overall and progression free 5-year survival rate was 47 % and respectively 45 % [in median 58 months]. The 5-year survival rate of 64 % in the "responder"-group was significantly better when compared with 24 % in the "non-responder"-group (p = 0.038). The tri-modality therapy improved the prognosis in patients with locally advanced NSCLC (stage IIIA/IIIB). The complete patho-histological remission is an important prognostic factor for better long term survival. Dividing the patients in "responder" and "non-responder" after neo-adjuvant RCT may have large therapeutically consequences in the future.

Oncological neoadjuvant therapy contributes to tumor deterioration and/or tumor mass reduction (debulking) prior to surgery. In recent years preoperative neoadjuvant simultaneous radiochemotherapy has become an integral part of the multimodality treatment of advanced colorectal cancer. It is associated with lower acute and long-term toxicity, as well as reduced local recurrence compared with the formerly used postoperative treatment. Radiotherapy is conventionally fractionated with a single 1.8-Gy dose up to a total dose of 45-50.4 Gy. 5-Fluorouracil (5-FU) is simultaneously administered as base drug therapy. By using other cytostatics, such as oxaliplatin, CPT-11 or capecitabine, it was possible to intensify treatment. The objective of this overview is to present the results of corresponding clinical trials which lead to this change in treatment strategy and to give some recommendations for practice.

The demographic changes of our society, with an increasing number of elderly patients and higher comorbidity, leads to the fact that managing transitional cell carcinoma (TCC) in the elderly is becoming increasingly more important. Thus, the value and indication of conservative or less invasive treatment approaches have to be continuously re-evaluated. The gold standard of treatment for invasive high grade TCC is radical cystectomy with curative intent. However, not each and every patient is suitable for this procedure or the operation is rejected. Thus, alternative treatment options (curative or palliative) including bladder sparing approaches should be offered to this group of patients. These include transurethral resection (TUR-B), open partial cystectomy, chemotherapy (intravesical or systemic), local radiation and minimally invasive interventional therapies alone or in combination. A lower physical and mental burden and, more important, a faster convalescence and the maintenance of the quality of life, are the major aims of these strategies. From an oncologic point of view these concepts have to be viewed with caution, since they may only lead to a temporarily stable disease or the elimination of symptoms. However, long-term follow-up demonstrates that with the correct indication for a multi-modal treatment, a subset of patients with high grade TCC of the bladder may be cured when implementing a bladder sparing approach.

The therapeutic strategies for oligometastatic non-small cell lung cancer have changed over the last decade from palliative to curative intent. The role of surgery in this multimodal treatment in selected patients remains a subject for open discussion.Data of 34 patients with one or two metastases treated from January 1998 to January 2013 were retrospectively analysed.The mean age was 59.7 (± 10.1) years. The male vs. female ratio was 20 vs. 14. Adenocarcinoma was the most common histological type (58.8 %). The synchronous metastases were present in 15 patients, the metachronous in 19 patients. Single metastases were present in 27 patients, two metastases in 7 patients. The most frequently involved organs were brain (58.8 %) and the lungs (23.6 %). The primary tumour resection was achievable in 20 patients as R0 and in 2 patients as R1. The median overall survival, the local and the systemic disease-free survivals in the entire group were 40, 38 and 25 months, respectively. The 5 year overall survival, the 5 year local and systemic disease-free survivals were 29.2, 26.9 and 16.5 %, respectively. The treatment strategies including surgery for primary tumour as well as for pulmonary metastases site, combined with the lymph node dissection and the resection of the extracerebral and cerebral metastases, were identified as independent prognostic factors for long-term survival.Surgery in oligometastatic non-small cell lung carcinoma is feasible for primary tumour and for metastases. It is an effective option in the multimodal treatment in highly selected patients. The lymph node dissection should remain an important integral part of the surgical treatment.

The standard treatment for invasive bladder cancer is radical cystectomy. In selected patients, bladder-sparing therapy can be performed by transurethral resection (TURBT) and radio-chemotherapy (RCT) or radiotherapy (RT). Our published in vitro data suggest that the Neuropilin-2 (NRP2)/VEGF-C axis plays a role in therapy resistance. Therefore, we studied the prognostic impact of NRP2 and VEGF-C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n = 198) or RT (n = 49) and a follow-up time up to 15 years. A tissue microarray was analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor in overall survival (OS; HR: 3.42; 95% CI: 1.48 - 7.86; p = 0.004) and was associated with a 3.85-fold increased risk of an early cancer specific death (95% CI: 0.91 - 16.24; p = 0.066) in multivariate analyses. Cancer specific survival (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p = 0.037). Patients with high VEGF-C expression have a 2.29-fold increased risk of shorter CSS (95% CI: 1.03-5.35; p = 0.043) in univariate analysis. CSS dropped from 170 months to 88 months in the case of high VEGF-C expression (p = 0.041). Additionally, NRP2 and VEGF-C coexpression is a prognostic marker for OS in multivariate models (HR: 7.54; 95% CI: 1.57-36.23; p = 0.012). Stratification for muscle invasiveness (T1 vs. T2-T4) confirmed the prognostic role of NRP2 and NRP2/VEGF-C co-expression in patients with T2-T4 but also with high risk T1 disease. In conclusion, immunohistochemistry for NRP2 and VEGF-C has been determined to predict therapy outcome in bladder cancer patients prior to TURBT and RCT.

Rheumatoid arthritis (RA) displays a chronic inflammatory joint disease, accompanied by symmetric polyarthritis (PA) which evokes synovial inflammation, cartilage damage, and bone erosion. Patients with RA are routinely treated by immunosuppressive drugs. The therapy of inflammatory diseases and degenerative disorders with Low-dose radiotherapy (LD-RT) (single doses from 0.3 to 1.0 Gy) represents a low cost therapy with low toxicity, and is able to substitute at least in part treatment with drugs. The efficiency of LD-RT has already been proven in several animal models of inducible arthritis. In the present study we used a human TNF transgenic mouse model to examine the effects of LD-RT on PA. We observed a significant temporal improvement of the clinical progression of disease when mice were irradiated at the beginning of the disease. These data emphasize the role of LD-RT in clinical settings to treat patients with chronic and degenerative disorders and diseases.

Objective The treatment of trigeminal neuralgia is challenging with respect to a sufficient outcome. Medication still represents the basic therapy. If a neurovascular compression syndrome is diagnosed with high resolution MRI more than 80% of the patients undergoing surgery based on microvascular decompression are free of pain in a ten year period as shown in one of our previous follow-up studies. In addition to that, percutaneous treatment options such as thermo-coagulation of the Gasserian ganglion can be effective but are affected with a higher recurrence rate and cannot be used in all cases. Therefore, we started selecting patients with intractable, therapy-resistant trigeminal neuralgia for stereotactic radiosurgery of the trigeminal nerve. Preliminary results of this approach are presented in this study. Methods From 2012 to 2014 eight patients suffering from intractable trigeminal neuralgia underwent linear accelerator-based stereotactic radiosurgery with a Novalis system after fixing a stereotactic frame to the patient’s head under local anesthesia. For the treatment, doses ranging from 60 Gy to 70 Gy were used in a target located at the pontine trigeminal root entry zone of the trigeminal nerve. 80% of the dosage was calculated at a 4mm iso-center. We treated 4 male and 4 female patients (average age 68 years). 4 patients suffered from left-sided and 4 patients from right-sided trigeminal neuralgia. V2 and V3 were the most affected branches. All patients had a history of facial pain for several years with two patients suffering from multiple sclerosis-related trigeminal neuralgia. In all cases, two, three or even four different drugs were used with increasing side effects. For none of the patients, neurovascular compression syndrome was found with MRI. One patient, however, underwent surgery with microvascular decompression. Three patients underwent thermo-coagulation of the Gasserian ganglion once or twice without a lasting effect on facial pain. Four patients had to take a permanent anticoagulation because of pre-existing conditions so that no invasive treatment option could be used. Results Taking into account the follow-up time between 2 years and 1 month, all eight patients had benefit from stereotactic radiosurgery treatment: two patients are completely free of pain without any medication, two patients are free of pain with substantially reduced medication and four patients showed relevant improvement of facial pain including their usual medication or even with reduced medication. In consequence, all patients reported considerably reduced side effects of medication and a relevant improvement in their quality of life. Concerning the side effects of radiosurgery, only one patient developed a facial hypoesthesia. Presumably, this was related to a previous prophylactic brain radiation due to lung cancer. General symptoms such as headache or dizziness were mild and lasted for a short time only. Conclusions The use of linear accelerator-based stereotactic radiosurgery is a safe and effective therapeutic option even for the treatment of intractable and so far therapy-resistant trigeminal neuralgia. It significantly reduces the use of medication and improves the quality of life. In order to prove the adequate long-term control of facial pain further follow-up examinations are necessary with a higher number of patients. However, our preliminary results are encouraging and demonstrate effectiveness in cases where all other treatment options failed.

Paclitaxel (Taxol®) ist eine neue Antikrebssubstanz mit einem neuartigen Wirkmechanismus. Es hat gegenuber zahlreichen malignen Erkrankungen klinische Aktivitat demonstriert. Verschiedene Aspekte des Einsatzes von Paclitaxel wie das optimale Behandlungsschema sind noch ungeklart. Daruber hinaus ist auch das Losungsmittel von Paclitaxel, Cremophor EL/Ethanol, gegenuber Tumoren wirksam. Die In-vitro-Zytotoxizitat von Paclitaxel (Taxol®) wurde entsprechend der Einmalgabe (1mal 10 μM, Tag 1, Inkubationzeit: drei Stunden und 15 Stunden) und der fraktionierten Gabe (5mal 2 μM/d, Tag 1 bis 5, Inkubationzeit: drei Stunden pro Tag) anhand der Bestimmung der klonogenen Uberlebensfraktion (Koloniebildungstest) und der DNA-Verteilung (Flusphotozytometrie) ermittelt. In den Kontrollpopulationen wurden das Losungsmittel Cremophor EL/Ethanol sowie eine phosphatgepufferte Salzlosung (PBS) in identischer Dosierung und nach identischem Schema appliziert. Es wurde eine Fibroblasten-Saugetierzellinie (HyB14FAF28) verwendet. Fraktionierte Paclitaxel-(Taxol®-)Applikation ergab eine signifikant geringere klonogene Uberlebensfraktion (0,63) im Vergleich mit der Einmalgabe uber drei Stunden (0,84) und 15 Stunden (0,82). Die DNA-Analyse zeigte keinen Hinweis auf einen signifikanten Unterschied in der DNA-Verteilung der fur Paclitaxel interessanten G2/M-Phase wahrend eines Zeitraums von zehn Tagen ab Applikation. In den Kontrollen ergaben sich fur das Losungsmittel Cremophor EL/Ethanol klonogene Uberlebensfraktionen von 0,87 (Drei-Stunden-Gabe) and 0,88 (15-Stunden-Gabe) gegenuber 0.65 nach fraktionierter Gabe (5mal 2 μM/d, Tag 1 bis 5, Inkubationzeit: drei Stnden pro Tag). Die PBS-Kontrolle sowie die unbehandelte Kontrolle zeigten keinen signifikanten Effekt. Es scheint, das sich bei dieser Fibroblasten-Saugertierzellinie die klonogene Uberlebensfraktion nach Taxol®-Gabe mit dem Behandlungsschema durch einen bis jetzt unbekannten Mechanismus, der keinen G2/M-Block enthalt, verandert. Die Ergebnisse zeigen einen Behandlungseffekt, der hauptsachlich auf der Kombination mit dem Losungsmittel ohne einen zusatzlich induzierten Gewinn durch Paclitaxel basiert.

Paclitaxel, a natural product from Taxus brevifolia, is a microtubule stabilizing agent, which has been shown to block different cells in the G2/M phase of the cell cycle and consequently, to modulate their radioresponsiveness. Our aim was to test the cytotoxic and radiosensitizing potential of paclitaxel, with respect to different gynecological tumors with varying radiosensitivities.We performed clonogenic assays and flow cytometry on 2 cell lines, MCF-7 (breast) and CaSki (cervix) cells, and on 2 primary ovarian tumor samples (OC-I and OC-II). The cells were irradiated with 200 kV X-rays, radiation doses of up to 8 Gy were applied either as single doses or in 2 Gy fractions. Paclitaxel concentrations varied from 0.07 to 700 nM, incubation times varied from 3 to 120 h.Paclitaxel alone changed the cell cycle distribution of the cells tested and was cytotoxic in a time and concentration dependent manner. When combined with radiation, most schedules resulted in additive effects of the combined treatments. However, for MCF-7 cells, when 7 nM paclitaxel, applied 24 h before irradiation, were combined with fractionated irradiation a supra-additive effect with a SER of 1.2 was found. For CaSki cells, under comparable conditions the SER was 1.13 but the effects were not statistically significant.Under specific conditions, paclitaxel exerted a weak radiosensitizing effect on breast and cervical carcinoma cells. A therapeutic gain may be possible on the basis of an optimal paclitaxel/radiation scheduling.

Functional outcome following head and neck cancer is not regularly assessed in a standardized way in clinical practice. Clinical trials assessing functional outcome apply many different instruments. Therefore, results are not always comparable and have limited clinical implications. Aim of this study was the identification, interdisciplinary evaluation, and recommendation of functional outcome instruments for use in clinical practice and clinical trials in patients with HNC.Preparatory studies came up with a shortlist of outcome instruments on the basis of previously determined criteria. An interdisciplinary expert group evaluated these instruments and decided on which ones can be recommended for use in 3 application areas: screening, therapy evaluation/planning, and clinical trials. Decision making health professionals included physicians (ENT and maxillofacial surgeons, radiotherapists, oncologists), medical psychologists, speech and language therapists, physiotherapists, and social workers.98 instruments were presented at the consensus conference. Altogether 21 participants recommended for each of the 3 application areas a basic set of measures for the evaluation of impairment in 6 functional domains: follow-up therapy monitoring, pain, ingestion, voice/speaking, other organic problems, and psychosocial problems.A multi-professional expert's pool discussed and adopted recommendations for the use of functional outcome instruments in clinical praxis and/or in research. The re-commended instruments are now available for use in clinical routine.

Applicators used to date in endoluminal "high dose rate" (HDR) afterloading (AL) radiotherapy of esophageal carcinoma consist of hollow plastic probes with an average thickness of 4 mm (1.8-5.0 mm), the diameter of which, however, often strongly deviates from that of the lumen of the tumor stenosis. Consequently, the probe can occupy an eccentric position in the esophagus. Exact dosimetry in the tumor region thus becomes virtually impossible, since the dose of the iridium emitter drops significantly with increasing distance (> 60% at a distance of 5 mm from the surface of the 4 mm probe). The bougie-type afterloading applicators developed by our group, however, offer a number of distinct advantages in comparison to conventional applicator probes: 1. Precise positioning of the applicator in the stenosis with simultaneous bougie effect. 2. Exact centering of the radiation source in the lumen of the esophagus. 3. Individual adaptation of the applicator size to the diameter of the residual lumen resulting from the tumor. 4. Upon patient-specific adaptation of the radiation exposure period, a distinct reduction of the surface (mucosa) dose is achieved together with simultaneous enhancement of the depth effect of radiotherapy treatment. Using these new afterloading bougies in over 150 treatment sessions involving 55 patients, no complications were thus far observed.

Die Wirkung einer Strahlentherapie auf das Tumorgewebe und das normale Gewebe hangt von folgenden Faktoren ab

Die Behandlung von Tumoren der Leber, der Gallenblase und der Gallengange ist eine Domane der Chirurgie und der interventionellen Radiologie. Lebermetastasen werden bei einer Vielzahl von anderen Ursprungsorganen (insbesondere den kolorektalen Tumoren), so weit sie einer Operation zuganglich sind, chirurgisch saniert. Als alternative Verfahren stehen interventionelle Methoden wie Thermoablation oder transarterielle Chemoembolisation zur Verfugung. Bei diffuser Metastasierung erfolgt in der Regel eine palliative Chemotherapie in Abhangigkeit von der Histologie des Primartumors. Die Strahlentherapie hat bislang bei der Behandlung von in der Leber gelegenen Tumoren oder Metastasen nur einen geringen Stellenwert. Dies kann sich durch die Einfuhrung neuer strahlentherapeutischer Techniken in den nachsten Jahren andern.

Weltweit erkranken jahrlich 200.000 Menschen an einem Pankreaskarzinom; die meisten Patienten versterben an ihrer Erkrankung. Bereits zum Zeitpunkt der Diagnose muss bei der uberwiegend Zahl der Patienten eine Fernmetastasierung oder eine lokal fortgeschrittene Erkrankung festgestellt werden. Eine potenzielle kurative Resektion ist nur bei einer begrenzten Zahl von Patienten moglich.

Introduction: Radiotherapy is the best treatment modality to achieve long-term local control of solid tumors, considered as inoperable by the surgeon. The objective of concurrent radiochemotherapy is

In most institutions neoadjuvant chemoradiation for middle and lower rectal carcinoma is currently given to patients with tumours of clinical stages II or III (cT3,4 and/or N1,2). The possibility of a reduction in the use of neoadjuvant chemoradiation by an individualized magnetic resonance imaging (MRI)-based indication for neoadjuvant chemoradiation was analysed.Assessment of the pathological and oncological principles indicating for neoadjuvant treatment was used to determine the prognostic importance of the distance between the tumour and the circumferential resection margin and pretherapeutic assessment using modern MRI.Based on the results of pretreatment MRI scanning, a proposal is presented for the treatment of middle and lower rectal carcinoma with neoadjuvant chemoradiation. Adopting this proposal, the frequency of neoadjuvant chemoradiation decreased from 70% to 35% and the early and late adverse effects of this therapy were reduced. In contrast, the expected locoregional recurrence rate increased from 6% to 11% if all quality criteria were met and to 18% if not.An MRI-based indication for neoadjuvant chemoradiation is justified only for centres with regular quality assurance of MRI, surgery, radiotherapy and pathology. The proposal needs confirmation by long-term follow up and by prospective studies with larger numbers of patients.

Low-dose radiation (single doses from 0.3 to 1.0 Gy) in clinical practice is mostly used to treat patients with several inflammatory diseases and painful degenerative disorders. Low-dose radiation is known to exert anti-inflammatory effects. However, the molecular and cellular mechanism are not fully analysed and most of the observed effects are based on empirical studies. We investigated the effects of low-dose radiation on the activation-induced cell death of polymorph nuclear granulocytes (PMN). A biphasic appearance of cell death in irradiated PMN was observed, displaying a relative maximum at 0.3 Gy and minimum at 0.5 Gy, respectively. This biphasic course of cell death was coincident with the protein level of total cellular Akt. We conclude that low-dose radiation exerts immunomodulatory effects on PMN contributing to the observed anti-inflammatory effects in clinical applications.

Rheumatoid arthritis (RA) displays a chronic inflammatory joint disease, accompanied by symmetric polyarthritis (PA) which evokes synovial inflammation, cartilage damage, and bone erosion. Patients with RA are routinely treated by immunosuppressive drugs. The therapy of inflammatory diseases and degenerative disorders with Low-dose radiotherapy (LD-RT) (single doses from 0.3 to 1.0 Gy) represents a low cost therapy with low toxicity, and is able to substitute at least in part treatment with drugs. The efficiency of LD-RT has already been proven in several animal models of inducible arthritis. In the present study we used a human TNF transgenic mouse model to examine the effects of LD-RT on PA. We observed a significant temporal improvement of the clinical progression of disease when mice were irradiated at the beginning of the disease. These data emphasize the role of LD-RT in clinical settings to treat patients with chronic and degenerative disorders and diseases.

Neoadjuvant radiochemotherapy has become established treatment for rectal cancer. It is indicated when primary R0 resection is not an option, in cases of higher risk of locoregional relapse following surgical treatment alone, and when initially impossible conservation of the anal sphincter becomes possible in conjunction with neoadjuvant radiochemotherapy. The indication for radiochemotherapy in the upper third of the rectum is still controversial. Reevaluation of the tumor situation following neoadjuvant treatment is necessary before decisions on operative strategy. Modern imaging techniques are limited in this respect, as they hardly allow differentiation between living tumor tissue and lesions. In case of doubt clarity is possible only through surgical exploration, taking R1 resection into account. Overall the recognition of lymph node metastasis is not a sufficient indicator of local relapse. The frequency of postoperative complications following neoadjuvant radiochemotherapy is independent of the operative method. The effect of neoadjuvant radiochemotherapy on long-term survival and formation of distant metastases is still not clarified. Current studies seek clarification through the use of new chemotherapies and modified treatment regimes. Further, the correct time interval between the end of neoadjuvant radiochemotherapy and the following surgical therapy has yet to be determined. This applies also to the management of patients following complete remission.