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Background In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. Methods A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40–50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. Results GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5–877) and GTV2 of 106.2 ml (95% CI: 0.5–589.5), resulting in an estimated reduction of 48.2 ml (p p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9–2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0–69, 0.32–1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01–13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64–0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. Conclusion Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.

To evaluate the current situation of young radiation oncologists in Germany with regard to the contents and quality of training and level of knowledge, as well as their working conditions and professional satisfaction.From June 2016 to February 2017, a survey was conducted by the young DEGRO (yDEGRO) using an online platform. The questionnaire consisted of 28 items examining a broad range of aspects influencing residency. There were 96 completed questionnaires RESULTS: 83% of participants stated to be very or mostly pleased with their residency training. Moderate working hours and a good colleagueship contribute to a comfortable working environment. Level of knowledge regarding the most common tumor sites (i.e. palliative indications, lung, head and neck, brain, breast, prostate) was pleasing. Radiochemotherapy embodies a cornerstone in training. Modern techniques such as intensity-modulated radiotherapy (IMRT) and stereotactic procedures are now in widespread use. Education for rare indications and center-based procedures offers room for improvement.Radiation oncology remains an attractive and versatile specialty with favorable working conditions. Continuing surveys in future years will be a valuable measuring tool to set further priorities in order to preserve and improve quality of training.

In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT.A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models.GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5-877) and GTV2 of 106.2 ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2 ml (p 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, p 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, p 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64-0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2.Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.

The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO). Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose. In all, 87 plans were generated: 36 used intensity-modulated arc therapy (IMAT), 21 used three-dimensional conformal radiation therapy (3DCRT), 6 used static field intensity-modulated radiation therapy (SF-IMRT), 9 used helical radiotherapy and 15 used robotic radiosurgery. PTV dose coverage and simultaneously kept OARs doses were within the clinical limits published in the DEGRO guidelines. However, mean PTV dose (mean 58.0 Gy, range 52.8–66.4 Gy) and dose conformity indices (mean 0.75, range 0.60–1.00) varied between institutions and techniques (p ≤ 0.02). OARs doses varied substantially between institutions, but appeared to be technique independent (p = 0.21). All studied treatment techniques are well suited for SBRT of early stage NSCLC according to the DEGRO guidelines. Homogenization of SBRT practice in Germany is possible through the guidelines; however, detailed treatment plan characteristics varied between techniques and institutions and further homogenization is warranted in future studies and recommendations. Optimized treatment planning should always follow the ALARA (as low as reasonably achievable) principle.

The presence of an isocitrate dehydrogenase 1 (IDH1) mutation is associated with a less aggressive phenotype, increased sensitivity to radiation, and increased overall survival in patients with diffuse glioma. Based on in vitro experimentations in malignant glioma cell lines, the consequences on cellular processes of IDH1R132H expression were analyzed. The results revealed that IDH1R132H expression enhanced the radiation induced accumulation of residual &gamma, H2AX foci and decreased the amount of glutathione (GSH) independent of the oxygen status. In addition, expression of the mutant IDH1 caused a significant increase of cell stiffness and induced an altered organization of the cytoskeleton, which has been shown to reinforce cell stiffness. Furthermore, IDH1R132H expression decreased the expression of vimentin, an important component of the cytoskeleton and regulator of the cell stiffness. The results emphasize the important role of mutant IDH1 in treatment of patients with diffuse gliomas especially in response to radiation. Hence, detection of the genetic status of IDH1 before therapy massively expands the utility of immunohistochemistry to accurately distinguish patients with a less aggressive and radiosensitive IDH1-mutant diffuse glioma suitable for radiotherapy from those with a more aggressive IDH1-wildtype diffuse glioma who might benefit from an individually intensified therapy comprising radiotherapy and alternative medical treatments.

Stereotactic body radiotherapy (SBRT) can achieve high tumour control with limited toxicity for inoperable early stage non-small-cell lung cancer (NSCLC) patients. The German Epidemiologic Cancer Registries from the Robert-Koch Institute were assessed. Periods according to the availability of SBRT were: (1) 2000–2003 (pre-SBRT); (2) 2004–2007 (interim); and (3) 2007–2014 (broad availability of SBRT). To assess the association of cancer-related parameters with mortality, hazard ratios (HR) from Cox proportional hazards models were computed. To evaluate the change of treatment-related mortality, we performed interaction analyses and the relative excess risk due to interaction (RERI, additive scale) was computed. A total of 16,292 patients with UICC stage I NSCLC diagnosed between 2000 and 2014 were analysed. Radiotherapy utilization increased from 5% in pre-SBRT era to 8.8% after 2007. In univariate analyses, survival in the whole cohort improved only marginally when 2000–2003 is compared to 2004–2007 (HR 0.92, 95% CI 0.85–1.01) or 2008–2014 (HR 0.93, 95% CI 0.86–1.01). Comparing surgery/radiotherapy, mortality in the radiotherapy group started from a 3.5-fold risk in 2000–2003 to 2.6 after 2007. The interaction analysis revealed a stronger improvement for radiotherapy (multiplicative scale for 2000–2003 vs. > 2007: 0.74, 95% CI 0.58–0.94). On an additive scale, treatment × period interaction revealed an RERI for 2000–2003 vs. > 2007 of − 1.18 (95% CI − 1.8, − 0.55). Using population-based data, we observed a survival improvement in stage I lung cancer over time. With an increasing utilization of radiotherapy, a stronger improvement occurred in patients treated with radiotherapy when compared to surgery.

Background: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Over the last decades, the incidence of human papilloma virus (HPV) positive head and neck squamous-cell carcinoma (HNSCC) has significantly increased. Infection with high-risk HPV types drives tumourigenesis through expression of the oncoproteins E6 and E7. Currently, the primary treatment of HNSCC consists of radiotherapy, often combined with platinum-based chemotherapeutics. One of the common features of HNSCC is the occurrence of tumour hypoxia, which impairs the efficacy of radiotherapy and is a negative prognostic factor. Therefore, it is important to detect and quantify the severity of hypoxia, as well as develop strategies to specifically target hypoxic tumours. HPV-positive tumours are remarkably radiosensitive compared to HPV-negative tumours and consequently the HPV-positive patients have a better prognosis. This provides an opportunity to elucidate mechanisms of radiation sensitivity, which may reveal targets for improved therapy for HPV-negative head and neck cancers. In this review, we will discuss the differences between HPV-positive and HPV-negative head and neck tumours and methods of hypoxia detection and targeting in these disease types. Particular emphasis will be placed on the mechanisms by which HPV infection impacts radiosensitivity.

Background The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. Methods From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. Results In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. Conclusion After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

Background and Aims: Stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment for patients with hepatocellular carcinoma (HCC), but its role in patients with advanced HCC is not yet defined. In this study, we aim to assess the efficacy and safety of SBRT in comparison to sorafenib treatment in patients with advanced HCC. Methods: We included 901 patients treated with sorafenib at six tertiary centers in Europe and Asia and 122 patients treated with SBRT from 13 centers in Germany and Switzerland. Medical records were reviewed including laboratory parameters, treatment characteristics and development of adverse events. Propensity score matching was performed to adjust for differences in baseline characteristics. The primary endpoint was overall survival (OS) and progression-free survival. Results: Median OS of SBRT patients was 18.1 (10.3–25.9) months compared to 8.8 (8.2–9.5) in sorafenib patients. After adjusting for different baseline characteristics, the survival benefit for patients treated with SBRT was still preserved with a median OS of 17.0 (10.8–23.2) months compared to 9.6 (8.6–10.7) months in sorafenib patients. SBRT treatment of intrahepatic lesions in patients with extrahepatic metastases was also associated with improved OS compared to patients treated with sorafenib in the same setting (17.0 vs. 10.0 months, p = 0.012), whereas in patients with portal vein thrombosis there was no survival benefit in patients with SBRT. Conclusions: In this retrospective comparative study, SBRT showed superior efficacy in HCC patients compared to patients treated with sorafenib.

Introduction et but de l’etude Les effets secondaires lies a la radiotherapie sont habituellement rapportes par les medecins a la place des patients. Les patient-reported outcomes (PROs) s’utilisent de plus en plus en clinique et dans des essais. Dans le cadre de developpement d’une application pour evaluer des PROs electroniques (ePROs), le young Radiation Oncology Group (yROG) de l’European Organization for the Research and Treatment of Cancer (EORTC) a mene une enquete pour evaluer l’utilisation, l’acceptation et les benefices ressentis des PROs et quantifier ses caracteristiques souhaitables. Materiel et methodes L’enquete a ete adressee a des medecins, des manipulateurs en electroradiologie et des infirmiers de 26 pays qui traitent des patients par irradiation. Cette enquete d’acces publique en ligne incluait 40 questions qui cotaient les caracteristiques des ePROs sur une une echelle Likert bipolaire a 5 points, allant de 1 (peu important) a 5 (tres important). Les sous-groupes ont ete compares par le test de Mann-Whitney-Wilcoxon. L’enquete etait promue par les newsletters du reseau l’EORTC et les societes savantes nationales de radiotherapie. Resultats et analyse statistique Entre juillet et decembre 2018, 367 reponses ont ete recues, dont 354 eligibles comportant 4,5 % reponses francaises, le sixieme pays le plus participatif apres l’Allemagne (24,3 %), l’Italie (13,3 %), la Chine (12,2 %), le Danemark (11,6 %), et Israel (9,9 %). En France les PROs etaient utilises dans un quart des reponses (contre 42,4 % des reponses des autres pays ; p Conclusion L’utilisation des PROs en France est significativement moins importante qu’internationalement. Tous les repondeurs francais utiliseraient un ePRO en routine s’ils y avaient acces.

Strahlentherapeutische Verfahren sind fester Bestandteil multimodaler onkologischer Therapiekonzepte im Bereich der Allgemein- und Viszeralchirurgie. Dazu gehoren einerseits kurativ intendierte Therapieansatze wie die neoadjuvante (praoperative) Radiotherapie des lokoregionar fortgeschrittenen und insbesondere als N(+) diagnostizierten Osophagus- und Rektumkarzinoms, die definitive, simultan-kombinierte Radiochemotherapie des lokal fortgeschrittenen, inoperablen bzw. hochsitzenden (oralseitigen) Osophaguskarzinoms, die definitive Radiotherapie des Analkarzinoms (Sphinktererhalt) oder die pra- bzw. postoperative Radiotherapie bei Weichteilsarkomen. In selektierten Fallen kann die kurativ intendierte Strahlentherapie v. a. beim Osophaguskarzinom (und Rektumkarzinom) yT0-Stadien erzielen, sodass eine nachfolgende Operation u. U. ausgespart werden kann. Solche Sonderfalle, in denen selbstverstandlich eine engmaschige klinische und bildgebende Nachsorge erforderlich ist, stellen eine Herausforderung hinsichtlich der Handhabung im und Integration in den klinischen Alltag dar. Im Rahmen der interdisziplinaren Tumorboards konnen durch die Integration der Strahlentherapie in mehrschichtige multimodale Therapiekonzepte mit kurativem Ansatz verbesserte Kontroll- und Uberlebensraten bei klinisch akzeptabler Toxizitat erreicht werden. Hier stellen nicht invasive, lokal-ablative strahlentherapeutische Verfahren wie die extrakranielle stereotaktische Radiotherapie effektive und praktikable Behandlungsmoglichkeiten etwa von Lebermetastasen beim oligometastasierten kolorektalen Karzinom dar, wodurch hohe lokale Kontrollraten erreicht werden konnen. Dieser Ubersichtsartikel soll einen Uberblick zu den fur den Allgemein- und Viszeralchirurgen relevanten strahlentherapeutischen Aspekten im Rahmen der multimodalen Tumortherapie geben und fokussiert sich auf die Therapie des Rektum-, Osophagus- und Analkarzinoms sowie der Weichteilsarkome und hepatischen Metastasen bei oligometastasiertem kolorektalen Karzinom.

The urokinase plasminogen activator system (uPA, uPAR, PAI‑1) is upregulated in cancer and high plasma levels are associated with poor prognosis. Their interaction with hypoxia-related osteopontin (OPN) which is also overexpressed in malignant tumors suggests potential clinical relevance. However, the prognostic role of the uPA system in the radiotherapy (RT) of non-small-cell lung cancer (NSCLC), particularly in combination with OPN, has not been investigated so far. uPA, uPAR, PAI‑1 and OPN plasma levels of 81 patients with locally advanced or metastasized NSCLC were prospectively analyzed by ELISA before RT and were correlated to clinical patient/tumor data and prognosis after RT. uPAR plasma levels were higher in M1; uPA and PAI‑1 levels were higher in M0 NSCLC patients. uPAR correlated with uPA (p

Lung cancer remains the leading cause of cancer-related mortality worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous presentation of the disease including lymph node involvement and large tumour volumes with infiltration of the mediastinum, heart or spine. In the treatment of stage III NSCLC an interdisciplinary approach including radiotherapy is considered standard of care with acceptable toxicity and improved clinical outcome concerning local control. Furthermore, gross tumour volume (GTV) changes during definitive radiotherapy would allow for adaptive replanning which offers normal tissue sparing and dose escalation. A literature review was conducted to describe the predictive value of GTV changes during definitive radiotherapy especially focussing on overall survival. The literature search was conducted in a two-step review process using PubMed®/Medline® with the key words “stage III non-small cell lung cancer” and “radiotherapy” and “tumour volume” and “prognostic factors”. After final consideration 17, 14 and 9 studies with a total of 2516, 784 and 639 patients on predictive impact of GTV, GTV changes and its impact on overall survival, respectively, for definitive radiotherapy for stage III NSCLC were included in this review. Initial GTV is an important prognostic factor for overall survival in several studies, but the time of evaluation and the value of histology need to be further investigated. GTV changes during RT differ widely, optimal timing for re-evaluation of GTV and their predictive value for prognosis needs to be clarified. The prognostic value of GTV changes is unclear due to varying study qualities, re-evaluation time and conflicting results. The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.

Introduction Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. Methods 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BED max ). Results After adjusting for histology, BED max was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy 10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy 10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BED max of 157±80Gy 10 or 80±62Gy 10 with and without prior chemotherapy, respectively. Conclusions Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.

Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV. This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated.

Purpose Total scalp irradiation (TSI) is a rare but challenging indication. We previously reported that non-coplanar intensity-modulated radiotherapy (IMRT) was superior to coplanar IMRT in organ-at-risk (OAR) protection and target dose distribution. This consecutive treatment planning study compared IMRT with volumetric-modulated arc therapy (VMAT). Materials and methods A retrospective treatment plan databank search was performed and 5 patient cases were randomly selected. Cranial imaging was restored from the initial planning computed tomography (CT) and target volumes and OAR were redelineated. For each patients, three treatment plans were calculated (coplanar/non-coplanar IMRT, VMAT; prescribed dose 50 Gy, single dose 2 Gy). Conformity, homogeneity and dose volume histograms were used for plan. Results VMAT featured the lowest monitor units and the sharpest dose gradient (1.6 Gy/mm). Planning target volume (PTV) coverage and homogeneity was better in VMAT (coverage, 0.95; homogeneity index [HI], 0.118) compared to IMRT (coverage, 0.94; HI, 0.119) but coplanar IMRT produced the most conformal plans (conformity index [CI], 0.43). Minimum PTV dose range was 66.8% -88.4% in coplanar, 77.5%-88.2% in non-coplanar IMRT and 82.8%-90.3% in VMAT. Mean dose to the brain, brain stem, optic system (maximum dose) and lenses were 18.6, 13.2, 9.1, and 5.2 Gy for VMAT, 21.9, 13.4, 14.5, and 6.3 Gy for non-coplanar and 22.8, 16.5, 11.5, and 5.9 Gy for coplanar IMRT. Maximum optic chiasm dose was 7.7, 8.4, and 11.1 Gy (non-coplanar IMRT, VMAT, and coplanar IMRT). Conclusion Target coverage, homogeneity and OAR protection, was slightly superior in VMAT plans which also produced the sharpest dose gradient towards healthy tissue.

The prognostic quality of increased osteopontin (OPN) plasma levels has been demonstrated for the chemotherapy and surgery of lung cancer. There is also evidence in the literature that tumor volume impacts prognosis in definitive radiotherapy (RT) of (lung) cancer. We previously demonstrated that elevated plasma levels of OPN before, and increasing OPN plasma levels after RT significantly correlate with survival and outcome after curative-intent RT of non-small-cell lung cancer (NSCLC). Tumor volume was also associated with prognosis. The present prospective clinical study investigated the prognostic interrelation of OPN plasma levels and tumor volume and their changes in the radical RT of NSCLC. We evaluated a subset of patients (n=27) with inoperable, non-metastasized NSCLC of the previously published patient collective. Patients were treated with radical radiochemotherapy (2 Gy ad 66 Gy). OPN plasma concentrations were determined by ELISA before (t0), at the end (t1), and 4 weeks after RT (t2). GTV was delineated PET- and CT-correlated before RT (GTV1) and after 40 Gy (GTV2). The course of OPN during and after RT and the change of GTV during RT was monitored over time and correlated with prognosis. Median GTV2 after 40 Gy (63 ml) was significantly lower than pre-RT GTV1 (90 ml, P

We present the first systematic comparison of the detailed properties, including internal kinematics, chemical abundances, sizes, and dark matter masses, of Milky Way and M 31 dSphs as a part of the SPLASH Survey (Spectroscopic and Photometric Landscape of Andromeda’s Stellar Halo). Through Keck/DEIMOS spectroscopy of several hundred individual red giants in a half dozen M 31 galaxies, our results indicate both similarities and differences between the family of dSphs in the Milky Way and M 31. For example, we find that the luminosity-metallicity relation of dSphs in the two hosts is very similar between L = 105 and 107 L ⊙ , the size distribution of M 31 dSphs extends to larger values at the same luminosity compared to Milky Way counterparts (especially at the bright end), and that the dark matter masses of M 31 dSphs are slightly smaller than similar luminosity Milky Way galaxies.

We present a wide-field (4.5 deg^2) photometric and spectroscopic survey of the Leo I dwarf spheroidal (dSph) galaxy to explore its extended morphology and dynamics. As in previous papers in this series, we take advantage of photometry in the M, T_2, and DDO51 filter system to select LeoI red giant branch star candidates, and, so far, this selection technique has proven 100% reliable in selecting actual Leo I members among more than 100 M < 21.5 Leo I giant candidates having previous or new Keck DEIMOS spectroscopy to a radius >1.3 times the limiting radius of the fitted, central King profile. The two-dimensional distribution of all similarly-selected Leo I giant candidates is well fitted by a central single-component King profile of limiting radius 13.3 arcmin, but many giant stars are found outside this newly derived King limiting radius. The density profile thus shows a break at a major axis radial distance of ~10 arcmin produced by an excess of stars at and beyond the King limiting radius (spectroscopically confirmed to be made of true Leo I members), and primarily along the major axis of the main body of the rather elongated satellite. This spatial configuration, a rather flat velocity dispersion profile and an asymmetric radial velocity (RV) distribution among the Leo I members at large radii together support a picture where Leo I has been tidally disrupted on at least one, but at most two, perigalactic passages of a massive Local Group member. (abridged), Accepted by Astrophysical Journal on March 15, 2007; 49 pages, 26 figures, uses emulateapj.cls

Radiooncological therapies are an integral part of the multimodal oncological treatment concepts in general and abdominal surgery. These include therapeutic approaches with a curative intention such as the neoadjuvant (pre-operative) radiotherapy of locoregionally advanced and/or N+ oesophageal and rectal cancer, definitive combined chemoradiotherapy of locally advanced, unresectable oesophageal cancer or oesophageal tumour lesions of the upper third, definitive radiotherapy of anal cancer (sphincter sparing) and pre- or post-operative radiotherapy of soft tissue sarcoma on the one hand. A yT0 stage achieved as characteristic of a curative effect by radiation in oesophageal and rectal cancer (omitting subsequent surgical intervention, naturally under clinical and imaging-based controls within short-term follow-up intervals) can be considered as a very interesting set-up with regard to its reasonable integration in daily clinical practice, which needs to be further and critically discussed. By integrating radiotherapy in interdisciplinary therapy concepts, improved tumour control and survival rates with clinically acceptable toxicity can be achieved. On the other hand, non-invasive, locally ablative radiooncological therapies such as extracranial stereotactic body radiotherapy constitute an effective and feasible treatment method for liver metastases in oligometastatic colorectal cancer or other tumour entities according to the decisions by the institutional tumour board, offering high local tumour control rates which can be part of multistep, multimodal procedures with curative intention. This review aims at providing an overview for the general and abdominal surgeon, outlining relevant radiooncological treatment aspects in the multimodal cancer therapy with a focus on the treatment of rectal, oesophageal and anal cancer as well as soft tissue sarcoma and hepatic metastases in oligometastatic colorectal cancer.

The brain is one of the most frequent locations of metastasis in malignant melanoma. We aimed to identify prognostic factors for overall survival (OS) and local tumor control (LC) in patients with malignant melanoma metastasized to the brain treated by multimodal therapy. All patients diagnosed with malignant melanoma brain metastases between 1992 and 2011 at a single center were registered (n=100, 65% male, 35% female). OS and LC of individual brain metastases were retrospectively analyzed. Subgroup analyses was performed in patients with multiple brain metastasis (n=35) and LC per lesion (n=72) was evaluated in 37 patients. Median age was 57 (27-81) years. Fifty-three percent of patients had 1-2 brain metastases, 47% had >2 and 71% presented with additional extracranial metastases. Primary treatment included systemic therapy alone (temozolomide/fotemustine, 14%), local therapy (surgery and/or stereotactic radiotherapy, 25%), whole-brain radiotherapy (WBRT, 10%), combined WBRT and systemic therapy (18%), local therapy plus WBRT (5%) and combination of local and systemic therapy (8%). Three percent received a tri-modal therapy (WBRT, local and systemic therapy) and 17% refused treatment. Median follow-up in surviving patients was 32 (4-222) months, median OS in all patients 3.9 months (1-year survival 21.4%). Local therapy (p

We present a method for isolating a clean sample of red giant stars in the outerregions of the Andromeda spiral galaxy (M31) from an ongoing spectroscopic survey using the DEIMOS instrument on the Keck 10-m telescope. The survey aims to study the kinematics, global structure, substructure, and metallicity of M31's halo. Although most of our spectroscopic targets were photometrically screened to reject foreground Milky Way dwarf star contaminants, the latter class of objects still constitutes a substantial fraction of the observed spectra in the sparse outer halo. Our likelihood-based method for isolating M31 red giants uses five criteria: (1) radial velocity, (2) photometry in the intermediate-width DDO51 band to measure the strength of the MgH/Mgb absorption features, (3) strength of the Na I 8190A absorption line doublet, (4) location within an (I, V-I) color-magnitude diagram, and (5) comparison of photometric (CMD-based) versus spectroscopic (Ca II 8500A triplet-based) metallicity estimates. We also discuss K I and TiO diagnostics for giant/dwarf separation that might be useful in future analyses. Training sets consisting of definite M31 red giants and Galactic dwarf stars are used to derive empirical probabilitydistribution functions for each diagnostic. These functions are used to calculate the likelihood that a given star is a red giant in M31 versus a Milky Way dwarf. By applying this diagnostic method to our spectroscopic data set, we isolate 40 M31 red giants beyond a projected distance of R = 60 kpc from the galaxy's center, including three out at R ~ 165 kpc. The ability to identify individual M31 red giants gives us an unprecedented level of sensitivity in studying the properties of the galaxy's outer halo., Accepted for publication in the Astrophysical Journal (revised relative to original submission): 57 pages, including 5 embedded tables and 19 figures

We present results from a large spectroscopic survey of M31 red giants using the Keck telescope/DEIMOS. Photometric pre-screening, based on the 100A-wide DDO51 band centered on the Mgb/MgH feature, was used to select spectroscopic targets. Red giant candidates were targeted in a small field on M31's giant southern tidal stream at a projected distance of 31kpc from the galaxy center. We isolate a clean sample of 68 giants by removing contaminants (foreground Galactic dwarfs and background galaxies) using spectroscopic, imaging, and photometric methods. About 65% of the M31 stars are found to be members of the stream, while the rest appear to be members of the general halo population. The mean (heliocentric) radial velocity of the stream in our field is -458 km/s, or -158 km/s relative to M31's systemic velocity, in good agreement with recent measurements at other stream locations. The intrinsic velocity dispersion of the stream is constrained to be 15_{-15}^{+8} km/s (90% confidence limits). The companion paper by Font et al. (2004, astro-ph/0406146) discusses possible orbits, implications of the coldness of the stream, and progenitor satellite properties. The kinematics (and perhaps [Fe/H] distribution) of our halo sample indicate that it is different from other M31 halo samples; this may be an indication of substructure in the halo. The stream seems to have a higher mean [Fe/H] than the halo, -0.51 vs -0.74 dex, and a smaller [Fe/H] spread. The stream's high metallicity implies that its progenitor must have been a luminous dwarf galaxy. The CaII triplet strengths of the M31 giants are generally consistent with photometric estimates of their metallicity (derived by fitting RGB fiducials in the color-magnitude diagram). There is indirect evidence of intermediate-age stars in the stream., 45 pages, 12 figures, 1 table; submitted to the Astronomical Journal; full PS version of paper at http://www.ucolick.org/~raja/Guhathakurta.ps

We present the first all-sky view of the Sagittarius (Sgr) dwarf galaxy mapped by M giant star tracers detected in the complete Two Micron All-Sky Survey (2MASS). The main body is fit with a King profile of 30 deg limiting radius, but with a break in the density profile from stars in tidal tails. We argue that much of the observed structure beyond the 224' core radius may be unbound as the satellite undergoes catastrophic disruption. A striking, >150 deg trailing tidal tail extends from the Sgr center and arcs across the South Galactic Hemisphere. A prominent leading debris arm extends from the Sgr center northward of the Galactic plane to an ~40 kpc apoGalacticon, loops towards the North Galactic Cap (NGC) and descends back towards the Galactic plane, foreshortened and covering the NGC. The Sgr tails lie along a well-defined orbital plane that shows little precession, which supports the notion of a nearly spherical Galactic potential. The Sun lies near the path of leading Sgr debris; thus, former Sgr stars may be near or in the solar neighborhood. The number of M giants in the Sgr tails is >15% that within the King limiting radius of the Sgr center. That several gigayear old M giants are so widespread along the Sgr tidal arms not only places limits on the dynamical age of these arms but poses a timing problem that bears on the recent binding energy of the Sgr core and that is naturally explained by recent and catastrophic mass loss. Sgr appears to contribute >75% of the high latitude, halo M giants; no evidence for M giant tidal debris from the Magellanic Clouds is found. Generally good correspondence is found between the M giant, all-sky map of the Sgr system and all previously published detections of potential Sgr debris with the exception of Sgr carbon stars -- which must be subluminous to resolve the discrepancy.

In very elderly cancer patients, health-related quality of life (HRQOL) is a particularly important issue but has rarely been studied due to a lack of specific instruments and of reference data. We performed a prospective analysis of HRQOL in patients ≥80 years undergoing radiotherapy with the newly validated elderly-specific HRQOL module EORTC QLQ-ELD14.We prospectively assessed HRQOL in n = 50 radiotherapy patients ≥80 years (32% lung, 20% gastrointestinal, 8% each of breast, head and neck, gynecologic cancer) at the start (t1), end (t2), and 6 months after (t3) radiotherapy, using EORTC QLQ-C30 and EORTC QLQ-ELD14. Overall survival was determined in the whole cohort and subgroups.Median overall survival from the start of radiotherapy was 15 months; 1-year and 2-year overall survival rates were 57.1 and 31.0%, respectively. Eastern Cooperative Oncology Group (ECOG) performance status2, Charlson comorbidity index ≤6, curative treatment intention, local tumor stage Union Internationale Contre le Cancer (UICC I, II), and total dose45 Gy were associated with prolonged survival. No significant changes in any HRQOL domain were observed during the course of treatment (t1 to t2). Six months after radiotherapy (t3), a significant and clinically relevant deterioration of HRQOL was seen in EORTC QLQ-C30 for physical function and role function and in EORTC QLQ-ELD14 for future worries, burden of illness, and family support.In radiotherapy patients ≥80 years, HRQOL was maintained until the end of radiotherapy but deteriorated in general and elderly-specific areas thereafter, suggesting a need to develop specific supportive interventions for this age group.

Background Circulating baseline levels of the plasma-protein osteopontin (OPN) have been suggested as a prognostic indicator in chemotherapy and surgery for lung cancer. However, the role of this hypoxia-related protein in radiotherapy of lung cancer is unclear. We previously demonstrated the prognostic effect of baseline OPN plasma levels which was increased by co-detection with other hypoxia-related proteins in the radical radiotherapy of non-small-cell lung cancer (NSCLC). This prospective clinical study investigated whether serial OPN measurements during and after curative-intent radiotherapy for NSCLC provide additional or superior prognostic information. Methods Sixty-nine patients with inoperable NSCLC were prospectively enrolled (55 M0, 14 M1). OPN plasma levels were measured before (t0), at the end (t1) and four weeks after radiotherapy (t2) by ELISA, compared between M0 and M1 patients and correlated with clinicopathological parameters. OPN levels were monitored over time and correlated with prognosis in M0-stage patients treated by radical 66-Gy radiotherapy ± chemotherapy. Results Pre-treatment OPN levels were associated with T stage (p = .03), lung function (p = .002), weight loss (p = .01), tumor volume (p = .02) and hemoglobin concentration (p = 04). M1 patients had significantly elevated OPN levels at all time points (p

Background This clinical study compared four different cases of extensive scalp malignancies treated by intensity-modulated radiation therapy. The merits of coplanar and non-coplanar Step-and-shoot total scalp irradiation techniques were evaluated against the background of the literature. Methods Four patients (angiosarcoma, n=2, cutaneous B-cell non-Hodgkin lymphoma, B-NHL, n=1, mycosis fungoides, n=1) treated between 2008 and 2012 at our institution were retrospectively analyzed. For every patient with executed coplanar plan, a non-coplanar plan and vice versa has been calculated additionally for direct comparison. Three patients underwent limited surgery before radiotherapy. Individual adapted bolus material was used for every patient (helmet). Total scalp dose was 30 Gy (B-NHL, mycosis fungoides) and 50 Gy (angiosarcoma) with fractional doses of 2.0-2.5 Gy (without sequential local boost in three patients). Conformity and homogeneity indexes and dose volume histograms were used for treatment plan comparison. Results Dose hot spots were higher in coplanar plans (110-128% Dmax). Non-coplanar plans showed a more homogeneous dose distribution (HI = .12 - .17) and superior PTV coverage (88 - 96%). Target dose coverage was 81-117% in non-coplanar and 30-128% in coplanar plans. Coplanar plans yielded a stronger dose gradient across the target (.7-1.6 Gy/mm) compared to non-coplanar plans (.8-1.3 Gy/mm). The most conformal plan was a non-coplanar plan (CI = .7). Mean and maximum brain doses were comparable and showed an almost linear decrease between min. and max. dose. The optic chiasm and brain stem was spared most with non-coplanar plans, mean doses to the lenses ranged between 4 and 8 Gy and were higher in non-coplanar plans as were doses to the optic nerves. Radiotherapy tolerance was acceptable and acute side effects included erythema, scalp pain, alopecia and radiodermatitis which all spontaneously resolved. Two patients accomplished partial response, two patients showed complete response after radiotherapy. Three patients had locally controlled tumors without recurrence until their deaths or at last follow up, one patient had local progression shortly after radiotherapy. Conclusions Photon-IMRT is an effective and feasible approach to treat extensive scalp malignancies. Non-coplanar beams could increase dose homogeneity and PTV coverage and might reduce doses particularly to the optic chiasm.

Background and purpose We investigated the role of the hypoxia-associated secreted glycoprotein osteopontin (OPN) in the response of malignant glioma to radiotherapy by characterizing OPN and its splice variants in vitro and in patient material. Material and methods The effect of siRNA knockdown of OPN splice variants on cellular and radiobiologic behavior was analyzed in U251MG cells using OpnS siRNA (inhibition of all OPN splice variants) and OpnAC siRNA (knockdown only of OPNa and OPNc). OPN and splice variant mRNA levels were quantified in archival material of 41 glioblastoma tumor samples. Plasma OPN was prospectively measured in 33 malignant glioma patients. Results Inhibition of OPNa and OPNc (OpnAC) reduced clonogenic survival in U251MG cells but did not affect proliferation, migration or apoptosis. Knockdown of all OPN splice variants (OpnS) resulted in an even stronger inhibition of clonogenic survival, while cell proliferation and migration were reduced and rate of apoptosis was increased. Additional irradiation had additive effects with both siRNAs. Plasma OPN increased continuously in malignant glioma patients and was associated with poor survival. Conclusions OPNb is partially able to compensate the effects of OPNa and OPNc knockdown in U251MG cells. High OPN plasma levels at the end of radiotherapy are associated with poor survival.

We present the surface brightness profile of M31's stellar halo out to a projected radius of 175 kpc. The surface brightness estimates are based on confirmed samples of M31 red giant branch stars derived from Keck/DEIMOS spectroscopic observations. A set of empirical spectroscopic and photometric M31 membership diagnostics is used to identify and reject foreground and background contaminants. This enables us to trace the stellar halo of M31 to larger projected distances and fainter surface brightnesses than previous photometric studies. The surface brightness profile of M31's halo follows a power-law with index -2.2 +/- 0.2 and extends to a projected distance of at least ~175 kpc (~ 2/3 of M31's virial radius), with no evidence of a downward break at large radii. The best-fit elliptical isophotes have b/a=0.94 with the major axis of the halo aligned along the minor axis of M31's disk, consistent with a prolate halo, although the data are also consistent with M31's halo having spherical symmetry. The fact that tidal debris features are kinematically cold is used to identify substructure in the spectroscopic fields out to projected radii of 90 kpc, and investigate the effect of this substructure on the surface brightness profile. The scatter in the surface brightness profile is reduced when kinematically identified tidal debris features in M31 are statistically subtracted; the remaining profile indicates a comparatively diffuse stellar component to M31's stellar halo exists to large distances. Beyond 90 kpc, kinematically cold tidal debris features can not be identified due to small number statistics; nevertheless, the significant field-to-field variation in surface brightness beyond 90 kpc suggests that the outermost region of M31's halo is also comprised to a significant degree of stars stripped from accreted objects., Comment: Accepted for publication in ApJ; v2 matches published version. Only minor editorial changes made

We present a resolved-star spectroscopic survey of 15 dwarf spheroidal (dSph) satellites of the Andromeda Galaxy (M31) as part of the Spectroscopic and Photometric Landscape of Andromeda's Stellar Halo (SPLASH) project. We filter foreground contamination from Milky Way (MW) stars, noting that MW substructure is evident in this contaminant sample. We also filter M31 halo field giant stars, and identify the remainder as probable dSph members. We then use these members to determine the kinematical properties of the dSphs. For the first time, we confirm that And XVIII, XXI, and XXII show kinematics consistent with bound, dark matter-dominated galaxies. From the velocity dispersions for the full sample of dSphs we determine masses, which we combine with the size and luminosity of the galaxies to produce mass-size-luminosity scaling relations. With these scalings we determine that the M31 dSphs are fully consistent with the MW dSphs, suggesting that the well-studied MW satellite population provides a fair sample for broader conclusions. We also estimate dark matter halo masses of the satellites, and find that there is no sign that the luminosity of these galaxies depends on their dark halo mass, a result consistent with what is seen for MW dwarfs. Two of the M31 dSphs (And XV, XVI) have estimated maximum circular velocities smaller than 12 km/s (to 1sigma), which likely places them within the lowest mass dark matter halos known to host stars (along with Bootes I of the MW). Finally, we use the systemic velocities of the M31 satellites to estimate the total mass of the M31 halo: within 139 kpc, M31's mass is 8 +4.1 - 3.7 x 10^11 corresponding to a virial mass for M31's dark matter halo of 1.2 +0.9 -0.7 x 10^12, consistent with previous results., Comment: 34 pages, 25 figures, ApJ in press, v3: typo fix in arxiv abstract

We present new Keck/DEIMOS spectroscopic observations of hundreds of individual stars along the sightline to the first three of the Andromeda (M31) dwarf spheroidal (dSph) galaxies to be discovered, And I, II, and III, and combine them with recent spectroscopic studies by our team of three additional M31 dSphs, And VII, X, and XIV, as a part of the SPLASH Survey (Spectroscopic and Photometric Landscape of Andromeda's Stellar Halo). Member stars of each dSph are isolated from foreground Milky Way dwarf stars and M31 field contamination using a variety of photometric and spectroscopic diagnostics. Our final spectroscopic sample of member stars in each dSph, for which we measure accurate radial velocities with a median uncertainty (random plus systematic errors) of 4-5 km s^(–1), includes 80 red giants in And I, 95 in And II, 43 in And III, 18 in And VII, 22 in And X, and 38 in And XIV. The sample of confirmed members in the six dSphs is used to derive each system's mean radial velocity, intrinsic central velocity dispersion, mean abundance, abundance spread, and dynamical mass. This combined data set presents us with a unique opportunity to perform the first systematic comparison of the global properties (e.g., metallicities, sizes, and dark matter masses) of one-third of Andromeda's total known dSph population with Milky Way counterparts of the same luminosity. Our overall comparisons indicate that the family of dSphs in these two hosts have both similarities and differences. For example, we find that the luminosity-metallicity relation is very similar between L ~ 10^5 and 10^7 L_☉, suggesting that the chemical evolution histories of each group of dSphs are similar. The lowest luminosity M31 dSphs appear to deviate from the relation, possibly suggesting tidal stripping. Previous observations have noted that the sizes of M31's brightest dSphs are systematically larger than Milky Way satellites of similar luminosity. At lower luminosities between L = 10^4 and 10^6 L_☉, we find that the sizes of dSphs in the two hosts significantly overlap and that four of the faintest M31 dSphs are smaller than Milky Way counterparts. The first dynamical mass measurements of six M31 dSphs over a large range in luminosity indicate similar mass-to-light ratios compared to Milky Way dSphs among the brighter satellites, and smaller mass-to-light ratios among the fainter satellites. Combined with their similar or larger sizes at these luminosities, these results hint that the M31 dSphs are systematically less dense than Milky Way dSphs. The implications of these similarities and differences for general understanding of galaxy formation and evolution are summarized.

Inhalt: Am Rinderschlag Deutsche Schwarzbunte wurden die Phanotypen verschiede-ner Zwillingsformen verglichen: (1) monozygote Zwillinge nach mikrochirurgischer Teilung der Blastozysten und Transfer in zwei verschiedene Empfangermutter (allo-uterine, monozygote Zwillinge); (2) monozygote Zwillinge in einer Empfangermutter durch spontane Teilung nach Embryotransfer entstanden (isouterine, monozygote Zwillinge); (3) naturliche Geschwister, die nach Embryotransfer in unterschiedlichen Empfangermuttern aufwachsen und damit wie allouterine, dizygote Zwillinge gehand-habt werden konnen. An 105 derartigen Kalbern im Alter von 3 Wochen bis zu mehr als einem Jahr wurden wiederholt 12 verschiedene Korperlangen– und Korperbreitenmaβe und das Koorperge-wicht bestimmt. Mittels Varianzanalyse Typ II nach Eisenhart wurden die Komponen-ten s2within fur die allouterinen und fur die isouterinen Zwillingsparchen und fur die Vollgeschwistergruppen errechnet und verglichen. Sie betragen in % der gesamten phanotypischen Varianz (und zeigen damit die Grobte des Einflusses folgender Umwelten auf diese an): Bei monozygoten, allouterinen Zwil-lingen 5–25% (pra–+ postnatale Umwelteinflusse), bei monozygoten, isouterinen Zwil-lingen meist < 7% (vornehmich postnatale Umwelteinflusse). Der uterine Einfluβ der Empfangermutter auf die postpartale Entwicklung transferierter Embryonen bis zu einem Jahr betragt etwa 4–20% der gesam ten phanoty pischen Varianz eines Merkmales. Die additive genetische Varianzkomponente der genannten Merkmale wurde bestimmt aus dem Vollgeschwistervergleich. Sie betragt 3366% der Gesamtvarianz. Die Sum-me aller hier direkt bestimmten Varianzkomponentenerklart nur 5070% der phano-typischen Gesamtvarianz. Der verbleibende Rest wird als dritte Varianzkomponente (“Emergenesis”, Intagible Variance) angesprochen. Bei isouterin ausgetragenen Bullenzwillingen bedingt die Zwillingsschwangerschaft pra-natal verursachte Differenzen, die extrem groβ und noch nach einem Jahr nachweisbar sind. Sie mahnen zur Vorsicht bet' der Verwendung solcher Zwillingskalber post partum. Contents: –The influence of uterine environment on body length and body weight, studied in artificially prepared calf twins transfered as embryos into two foster mothers The following three different types of twins were compared in Ostfrisian cattles: (1) artificially prepared identical twins transfered as embryos into two foster mothers (allouterine, monozygotic twins), (2) identical twins derived from one transfered blastocyst which separates into two parts spontaneously (isouterine, monozygotic twins), (3) groups of sister blastocysts which were trensfered into different foster mothers (allouterine, dizygotic twins). Twelve different traits of body length and the body weight were repeatedly estimated in 105 male and female animals aged between three weeks and more than one year. Their means apee in (l), (2) and (3). By ANOVA Modell II the components s2wwere compared between the three types of twins. s2win (1) shows the environmental influences pre– and postnatally with 5–25% of the total variance. s2win (2) shows the environmental influence of the postnatal period with < 7% of the total variance. The uterine environment participates with 4–20% in the total variance of traits of body length and weight in calves one year of age. By sister comparisons(2) and (3)heritability was estimated to be (h2=) 0.33 to 0.66. Heritability plus uterine plus postnatale components of variance covers only 50–70% of the total variance. An inexplicable rest variance remains indicating a third cause of variance beside genetic and environmental reasons as described by “intangible variance” or “emergenesis”.