Prospective ECG-gated High-Pitch Photon-Counting CT Angiography: Evaluation of measurement accuracy for aortic annulus sizing in TAVR planning.

PURPOSE: In planning transcatheter aortic valve replacement (TAVR), retrospective cardiac spiral-CT is recommended to measure aortic annulus with subsequent CT-angiography (CTA) to evaluate access routes. Photon-counting detector (PCD)-CT enables to assess the aortic annulus in desired cardiac phases, using prospective ECG-gated high-pitch CTA. The aim of this study was to evaluate the measurement accuracy of aortic annulus using prospective ECG-gated high-pitch CTA against retrospective spiral-CT reference. METHOD: Thirty patients underwent cardiac spiral-CT and prospective ECG-gated (30% R-R on aortic valve level) high-pitch CTA. Using propensity score matching, another 30 patients were identified whose CTA was performed using high-pitch mode without ECG-synchronization. Two investigators measured annular diameter, perimeter, and area on cardiac spiral-CT and high-pitch CTA. RESULTS: The aortic valve was imaged in systole in 90 % of prospective ECG-gated CTA cases but only 50 % of non-ECG-gated CTA cases (p = 0.002). There was a strong correlation (r ≥ 0.94) without significant differences (p ≥ 0.09) between cardiac spiral-CT and prospective ECG-gated high-pitch CTA for all annulus measurements. In contrast, significant differences were found in annular short-axis diameter and area between cardiac spiral-CT and non-ECG-gated high-pitch CTA (p ≤ 0.03). Furthermore, prospective ECG-gated high-pitch CTA showed significantly reduced radiation exposure compared with cardiac spiral-CT (CTDI 4.52 vs. 24.10 mGy; p < 0.001). CONCLUSION: PCD-CT-based prospective ECG-gated high-pitch scans with targeted systolic acquisition at the level of the aortic valve can simultaneously visualize TAVR access routes and accurately measure systolic annulus size. This approach could aid in optimizing protocols to achieve lower radiation doses in the growing population of younger, low-risk TAVR patients.

Influence of migrant background on patient preference and expectations in breast and gynecological malignancies (NOGGO-expression V study): results of a prospective multicentre study in 606 patients in Germany.

BACKGROUND: An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM). METHODS: This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients. RESULTS: A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected. CONCLUSIONS: Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status.

Impact of health-related quality of life (HRQoL) on short-term mortality in patients with recurrent ovarian, fallopian or peritoneal carcinoma (the NOGGO-AGO QoL Prognosis-Score-Study): results of a meta-analysis in 2209 patients.

OBJECTIVE: Recurrent ovarian cancer is an incurable disease with variable but poor prognosis. Health-related quality of life (HRQoL) is a patient-reported outcome measure generally applied to measure effects of therapies. Our aim was the development and validation of a risk score for the prediction of short-term mortality using the combination of sociodemographic and clinical factors and HRQoL. METHODS: For exploratory and validation analysis, the North-Eastern German Society of Gynecological Oncology (NOGGO) and Working Group Gynecological Oncology (AGO) study databases were screened for trials. Only trials which obtained defined HRQoL measurements were included in the final analysis. Multivariable logistic regression analyses were used to identify risk factors and their weighting for the risk score. Modulation with cubic regression analyses revealed median survival and short-term mortality defined as 1-year mortality for each value. RESULTS: For exploration, 974 patients from three clinical studies of the NOGGO and for validation, 1235 patients from several clinical studies of the AGO were eligible. The risk score included platinum-free interval, performance status, age, global QoL and nausea/vomiting. Receiver operating characteristic analysis showed a good predictive value with an area under the curve of 0.81 for model 1 in the exploration and 0.74 in the validation. Short-term mortality in model 1 was 8.2%, 23.5% and 58.4% in the exploration sample, and 19.7%, 38.1% and 63.4% in the validation sample for patients under low, medium and high risk, respectively. CONCLUSIONS: This risk score discriminates well between recurrent ovarian cancer patients under low, medium and high risk of short-term mortality. It may help to identify a risk group under high risk for short-term mortality that can be used for randomization in clinical trials and may support decision making for palliative chemotherapy.

Prognostic role of chemotherapy-induced nausea and vomiting in recurrent ovarian cancer patients: results of an individual participant data meta-analysis in 1213.

BACKGROUND: The aim of this study was to analyze the potential impact of chemotherapy-induced nausea and vomiting (CINV) on dose reductions, discontinuation of chemotherapy, and survival. PATIENTS AND METHODS: This study was designed as individual participant data meta-analysis with the original study data of three phase II/III trials that were conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients with recurrent ovarian cancer. Logistic and Cox regression analyses were used to estimate odds and hazard ratios after adjusting for age, ECOG, amount of delivered cycles, amount of recurrences, and amount of comedications and study. RESULTS: The majority of patients developed nausea (58.1%) and almost one third experienced vomiting (31.0%). CINV was not associated with FIGO stage, grading, histology, and number of recurrences. The necessity of dose reduction and discontinuation of chemotherapy did not correlate to nausea and vomiting (p = 0.88, p = 0.39 and p = 0.25, p = 0.54 respectively). Progression-free survival was shorter in patients with grade III/IV nausea and vomiting (p = 0.02; hazard ratio (HR) for grade III/IV nausea 1.58, 95% CI 1.14-2.20, and p = 0.02; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CINV grade III/IV was also associated with poorer overall survival (p < 0.001; HR for grade III/IV nausea 2.35, 95% CI 1.64-3.37, and p < 0.001; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CONCLUSION: CINV is significantly associated with poorer prognosis in recurrent ovarian cancer patients while there was no correlation found with the necessity of dose reduction and prior discontinuation of treatment. This study underlines the importance of prevention and treatment of CINV as part of early best supportive care.

The prognostic and predictive role of pain before systemic chemotherapy in recurrent ovarian cancer: an individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO) of 1226 patients.

BACKGROUND: Aim of this study was to analyze the impact of pain on quality of life and survival in recurrent OC patients. METHODS: Raw data including the QLQ-C30 questionnaire from three phase II/III trials ("Topotecan phase III," "Hector," and "TRIAS") conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) were synthesized and analyzed using logistic and Cox regression analyses. RESULTS: Data on pain was available for 952 patients out of 1226. Moderate to severe pain, which was defined as pain ≥ 50 in the QLQ-C30 symptom scale, was experienced by more than one-third of patients (36.6%). A total of 31% were taking non-opioid pain medication and 16% opioids. Median age at randomization was 61 years (range 25-84). Most patients (84.7%) were diagnosed in FIGO III/IV. Pain was independent from age, FIGO stage, grading, amount of recurrences, and chemotherapy-free interval. ECOG was significantly worse in patients with pain (p < 0.001). Fatigue, nausea/vomiting, sleeping disorders, and abdominal symptoms such as loss of appetite, diarrhea, and constipation were more frequently found in patients with pain (all p < 0.001). Quality of life was significantly diminished (p < 0.001). Pain was also an independent marker for overall survival (OS). Median OS was 18.2 months in patients with pain compared with 22.0 months in patients without pain (p = 0.013, HR 1.25, 95% confidence interval 1.05-1.48). OS was shorter in patients with pain and without pain medication compared with those on sufficient pain medication, whereas OS was mostly decreased in patients having pain despite pain medication (18.5, 19.6, and 15.0 months respectively; p = 0.026). Progression-free survival and prior treatment discontinuation were not associated with pain. CONCLUSION: Best supportive care including sufficient pain medication should be delivered as early as possible because effective pain management is crucial for both quality of life and overall survival in patients with recurrent ovarian cancer.

Survival and prognostic factors in patients with recurrent low-grade epithelial ovarian cancer: An analysis of five prospective phase II/III trials of NOGGO metadata base.

OBJECTIVE: Low-grade epithelial ovarian cancers (EOC), constitute the minority among all epithelial cancers. Our study objective was to focus on low-grade recurrent EOC and compare the survival with high-grade disease, as well as in regard to "platinum-sensitive" and "-resistant" recurrences according to platinum-free interval. METHODS: This is an exploratory analysis within the North-Eastern German Society of Gynecological Oncology (NOGGO) database including five randomized phase II/III trials comparing different chemotherapy regimens in recurrent EOC. We conducted survival analyses and cox-proportional regression models. RESULTS: Out of 1050 patients having the first recurrence, 42 (4%) patients had low-grade and 1008 (96%) patients had high-grade disease. In the subgroup of platinum-sensitive recurrences, progression-free survival (PFS) (8.7 m vs 9.7 m, p = 0.7) and overall survival (OS) (23.9 m vs 24.8 m, p = 0.9) did not differ between low-grade and high-grade diseases. In platinum-resistant recurrences, patients with low-grade ovarian cancer had significantly better PFS (7.6 m vs 3.6 m, p = 0.03) and OS (41.9 m vs 9.5 m p = 0.002) in comparison to those with high-grade cancer. At low-grade EOC, there were no significant PFS (p = 0.91) and OS (p = 0.25) differences between platinum-sensitive and -resistant recurrences. Patients with low-grade non-serous histology had lower PFS with compared to those with low-grade serous histology (p = 0.004). At cox regression analysis presence of ascites and residual disease after secondary cytoreductive surgery were independently associated with poor PFS within low-grade recurrent EOC. CONCLUSION: Our study indicates, platinum-free interval does not have any prognostic significance at recurrent low-grade EOC and non-serous histology is associated with poorer outcome in recurrence. Secondary surgical cytoreduction to no-gross residual disease and ascites are independently associated with disease progression.

Radiation Damage Mechanisms of Chemotherapeutically Active Nitroimidazole Derived Compounds.

Photoionization mass spectrometry, photoelectron-photoion coincidence spectroscopic technique, and computational methods have been combined to investigate the fragmentation of two nitroimidazole derived compounds: the metronidazole and misonidazole. These molecules are used in radiotherapy thanks to their capability to sensitize hypoxic tumor cells to radiation by "mimicking" the effects of the presence of oxygen as a damaging agent. Previous investigations of the fragmentation patterns of the nitroimidazole isomers (Bolognesi et al., 2016; Cartoni et al., 2018) have shown their capacity to produce reactive molecular species such as nitric oxide, carbon monoxide or hydrogen cyanide, and their potential impact on the biological system. The results of the present work suggest that different mechanisms are active for the more complex metronidazole and misonidazole molecules. The release of nitric oxide is hampered by the efficient formation of nitrous acid or nitrogen dioxide. Although both metronidazole and misonidazole contain imidazole ring in the backbone, the side branches of these molecules lead to very different bonding mechanisms and properties.

A GCIG international survey: clinical practice patterns of sentinel lymph node biopsies in cervical cancer.

PURPOSE: To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients. METHOD: A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7 months. RESULTS: One hundred and sixty-one institutions from around the world participated. One hundred and six (66%) of the participants were from university centers and 111 (69%) were gynecologic oncologists. One hundred and fifty-two (97%) performed lymphadenectomy (LNE) and 147 (94%) did so systematically; 97 (60%) used SLNB, due to lower morbidity (73%), reliability (55%) and time-saving (27%). In cases of positive SLNB (pN+), 39% of respondents stopped the operation and sent the patient for chemoradiation (CRT), 45% completed pelvic and paraaortic LNE, whereas 26% went on to perform a radical hysterectomy (RH) and systematic pelvic and paraaortic LNE. In case of negative SLNB (pN0), 39% of institutions still performed a systematic pelvic and paraaortic LNE. CONCLUSION: In this survey worldwide, SLNB adoption is an encouraging 60%, yet ample differences exist regarding strategy, and to a lower extent the techniques used. Lack of experience is the most common reason SLNB is not performed. Efforts to increase surgical education on SLNB technique and multicenter prospective trials providing evidence-based guidelines are warranted.

Patients' perspectives towards malignant ascites: results of a prospective observational trial regarding expectations, characteristics and quality of life-a study of the North-Eastern-German Society of Gynecological Oncology.

PURPOSE: Malignant ascites (MA) is a frequent and common symptom in (gyneco-) oncological patients. The present trial evaluated and assessed patients' characteristics, clinical features and the possible influence of MA on QoL measurements. METHODS: A prospective observational trial was conducted from Oct 2013 until Nov 2016. Therefore an interdisciplinary questionnaire was developed. Overall 250 patients with histological confirmed MA were included with different cancer entities (gynecological, gastrointestinal). The correlation of MA caused symptoms and QoL measurements was assessed using Kendall's tau b. Multivariable logistic regression models were applied to analyze the risks of symptoms or severe limitation in daily activities. RESULTS: 125 questionnaires could be analyzed. The majority of patients with MA had diagnosis of ovarian cancer (68.8%) and were under current cancer treatment (57.6%), mostly chemotherapy. Over 50% reported abdominal tension as major symptom, around 56% of the patients had MA when cancer was firstly diagnosed. Regression analysis showed that patients with MA above 2l were significantly more likely to be harmed in everyday activities. However, the age, gender, type of malignancy and the current treatment (chemotherapy vs. no chemotherapy) had no significant influence. CONCLUSION: MA has a significantly impact on QoL measurements in cancer patients and might influence everyday activities including basic needs like eating, walking and body care. There is a high need for more information and education of patients with MA.

Seguridad y eficacia del drenaje guiado por endosonografía de colecciones pancreáticas usando prótesis plásticas y metálicas tipo LAMS / Safety and efficacy of EUS-guided drainage of pancreatic fluid collections using plastic and lumen apposing metal stents (LAMS)

Background: Pancreatic fluid collections (PFC) are associated with severe acute pancreatitis. After maturation (after 4 weeks) they are classified as pancreatic pseudocyst (PP) and walled-off necrosis (WON). Endoscopic management is associated with lower morbidity and mortality compared with surgery. Aim: To describe the experience of EUS-guided drainage PFC drainage using plastic stent (PS) or metal stent (lumen apposing metal stents, or "LAMS"). Methods: Retrospective, observational study, between 2016-2019. Results: 17 patients in total. 8 cases were symptomatic PP and 9 were WON. Age 12-72 years. 12 cases in men. Indications: abdominal pain 5 cases and infection 11. The 8 cases of PFC were drained successfully using PS, without adverse effects. Regarding WON drainage, 3 cases were managed with PS and 6 with LAMS. In 5 cases, complementary endoscopic necrosectomy was required. A patient with LAMS required complementary surgical cleaning ("step-up") to treat collections far from the LAMS. Complications: one case of PS presented pigment occlusion with superinfection and another case presented migration to the stomach. Regarding LAMS, one case presented self-limited bleeding, another case presented obstruction of the stent with infection, which was managed endoscopically and with antibiotics. Conclusion: The endoscopic management of PFC is effective and safe, with plastic and metal stent (LAMS). The choice of type of stent depends on the characteristics of PFC (liquid vs solid), center experience and costs.

Introducción: Las colecciones pancreáticas (CP) se asocian a pancreatitis agudas graves. Luego de su maduración (después de las 4 semanas) se clasifican en pseudoquistes (PQ) y necrosis encapsulada (NE). El manejo endoscópico se asocia a menor morbimortalidad comparado con el quirúrgico. Objetivo: Describir la experiencia del drenaje de CP mediante el uso de prótesis plásticas (PP) o metálicas (lumen apposing metal stents, o "LAMS") mediante endosonografía. Método: Estudio retrospectivo, observacional, entre 2016-2018. Resultados: 17 pacientes en total. Ocho casos fueron PQ sintomáticos y 9 NE. Edad 12-72 años (12 casos en hombres). Indicaciones: dolor abdominal 5 casos e infección 11. Los 8 casos de PQ fueron drenados exitosamente con PP, sin efectos adversos. En relación con el drenaje de NE, 3 casos fueron manejados con PP y 6 con LAMS. En 5 casos se requirió necrosectomía endoscópica complementaria. Un paciente con LAMS requirió aseo quirúrgico complementario por colecciones alejadas al LAMS. En relación con las complicaciones, un caso de PP presentó oclusión del pigtail con sobreinfección y otro presentó migración al estómago. Respecto a LAMS, un caso presentó sangrado autolimitado y otro caso obstrucción de la prótesis con sobreinfección, que fue manejada endoscópicamente y con antibióticos. Conclusión: El manejo endoscópico de las CP es efectiva y segura, tanto con prótesis plásticas como metálicas (LAMS). La elección de la prótesis depende de las características de la lesión (líquido vs sólido), experiencia del centro y costos.

Insights into 2- and 4(5)-Nitroimidazole Decomposition into Relevant Ions and Molecules Induced by VUV Ionization.

Nitromidazoles are relevant compounds of multidisciplinary interest, and knowledge of their physical-chemical parameters as well as their decomposition under photon irradiation is needed. Here we report an experimental and theoretical study of the mechanisms of VUV photofragmentation of 2- and 4(5)-nitromidazoles, compounds used as radiosensitizers in conjunction with radiotherapy as well as high-energy density materials. Photoelectron-photoion coincidence experiments, measurements of the appearance energies of the most important ionic fragments, density functional theory, and single-point coupled cluster calculations have been used to provide an overall insight into the energetics and structure of the different ionic/neutral products of the fragmentation processes. The results show that these compounds can be an efficient source of relevant CO, HCN, NO, and NO2 molecules and produce ions of particular astrophysical interest, like the isomers of azirinyl cation ( m/ z 40), predicted to exist in the interstellar medium, and protonated hydrogen cyanide ( m/ z 28).

Expression III: patients' expectations and preferences regarding physician-patient relationship and clinical management-results of the international NOGGO/ENGOT-ov4-GCIG study in 1830 ovarian cancer patients from European countries.

Backround: The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician-patient relationship and treatment. Patients and methods: A questionnaire was developed based on the experiences of the national German survey 'Expression II', and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version. Results: From December 2009 to October 2012, a total of 1830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17-89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The three most important aspects, identified by patients to improve the treatment for ovarian cancer included: 'the therapy should not induce alopecia' (42%), 'there must be more done to counter fatigue' (34.5%) and 'the therapy should be more effective' (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included. Conclusion: This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient's age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.

Development of a selective cell capture and release assay: impact of clustered RGD ligands.

There is a growing interest in isolating tumor cells from biological samples. Considering that circulating tumor cells can be rare in blood, it appears challenging to capture these cells onto a surface with high selectivity and sensitivity. In the present paper, we describe the design of functionalized surfaces aimed at selectively capturing tumor cells by using an RGD peptide ligand with either a tetrameric or a monomeric presentation. ß-Cyclodextrin-coated self-assembled monolayers were used as platforms for the binding of RGD ligands endowed with a redox ferrocene cluster. The dissociation of the inclusion complex on the surface accounts for the release of the captured cells upon the electrochemical oxidation of ferrocene. For this purpose, we determined suitable RGD densities for both monovalent and tetravalent ligand presentations. The results indicate that the clustered RGD architecture efficiently improves selective cell capture at a very low RGD surface density (∼10 RGD per µm2) compared to the monovalent presentation (∼1000 RGD per µm2).

Evaluación rápida "in situ" de punción con aguja fina guiada por endosonografía mejora rendimiento diagnóstico de lesiones pancreáticas sólidas / Rapid on-site evaluation with endoscopic ultra sound-guided fine needle improves diagnostic yield of solid pancreatic masses

BACKGROUND: The use of endoscopic ultrasound with fine needle aspiration (EUS-FNA) has improved the characterization and staging of pancreatic solid masses. The primary strategy for improving the ability to diagnose malignant masses is the use of rapid on site evaluation (ROSE) by a cytopathologist. OBJECTIVE: To evaluate the diagnostic yield of EUS-FNA after the implementation of ROSE in an academic center. MATERIAL AND METHODS: Prospective enrollment and follow-up of EUS-FNA with ROSE during 2015 and 2016, was compared to EUS-FNA without ROSE in previous years (2011-2014) in Hospital Clínico UCChristus. Clinical and endosonographic features, cytopathological and histological diagnosis and number of passes per procedure were evaluated. All EUS-FNA included cytology and cellular block for definitive diagnosis. RESULTS: 59 pancreatic solid masses were included in the analysis. 44 EUS-FNA were performed with ROSE, compared with 15 EUS-FNA without ROSE. The mean age of patients included was 62.8 years, 54.2% male gender, and most masses studied were in the head of pancreas (77.6%). In EUS 86.5% were hypoechoic and 56.9% had poor defined margins. No differences in baseline characteristics were observed between groups. EUS-FNA led to diagnosis in 86.2% of the overall sample. The diagnostic rate was superior in the group of EUS-FNA with ROSE, compared to EUS-FNA without ROSE (97.7% vs 50%, p < 0.0001). The mean number of passes was inferior in EUS-FNA ROSE (+) (2.71 vs 5.78, p < 0.0001). No differences in rate of complications were observed between groups. CONCLUSION: The use of ROSE associated to EUS-FNA improves the diagnostic yield in the evaluation of pancreatic solid masses. Our findings are consistent with those described in the literature, recommending the use of ROSE in EUS-FNA in centers where the diagnostic yield is less than 90% without the use of ROSE

INTRODUCCIÓN: La adquisición de tejido mediante el uso de endosonografía, con punción con aguja fina, (EUS-FNA) ha mejorado el diagnóstico de lesiones pancreáticas sólidas. La principal medida para aumentar el rendimiento diagnóstico de la EUS-FNA es la evaluación por citopatólogo próximo al lugar de punción (in situ) (técnica conocida en inglés como ROSE "rapid on-site evaluation"). OBJETIVO: Evaluar el rendimiento diagnóstico de EUS-FNA en lesiones pancreáticas sólidas posterior a la implementación de ROSE en un centro universitario. MATERIAL Y MÉTODOS: Registro prospectivo de EUS-FNA realizadas con ROSE durante el período 2015-2016, comparado con EUS-FNA con evaluación histopatológica diferida realizada entre los años 2011-2014, en Hospital Clínico UC-Christus. Se evaluaron características clínicas, endosonográficas, diagnóstico histopatológico y número de pases por procedimiento. Todas las EUS-FNA incluyeron citología y block celular para diagnóstico definitivo. RESULTADOS: Se incluyeron en el análisis 59 lesiones pancreáticas sólidas evaluadas con EUS-FNA. Seguimiento prospectivo de 44 EUS-FNA con ROSE, que fueron comparadas con 15 EUS-FNA sin evaluación in situ (retrospectivo). La muestra total incluyó individuos con un promedio de 62,8 años de edad, 54,2% hombres, donde 77,6% de las lesiones se ubicaba en la cabeza pancreática. Endosonográficamente 86,5% de las lesiones eran hipoecoicas y 56,9% tenían márgenes poco definidos. La EUS-FNA fue diagnóstica en 86,2% del total de la muestra. Las EUS-FNA realizadas con ROSE presentaron un mayor rendimiento diagnóstico respecto a las efectuadas sin evaluación in situ (97,7% vs 50%, p < 0,0001). El número de pases por procedimiento fue menor (2,7% vs 5,8%, p < 0,0001) en el grupo con ROSE. No hubo diferencias en complicaciones en ambos grupos. CONCLUSIÓN: La evaluación por citopatólogo in situ de la muestra obtenida por EUS-FNA mejora el rendimiento diagnóstico de las lesiones pancreáticas sólidas. Nuestros hallazgos apoyan el uso de ROSE asociado a EUS-FNA, siendo concordantes con las recomendaciones actuales de utilizar evaluación histopatológica in situ en EUS-FNA, especialmente en centros donde el rendimiento diagnóstico sin uso de ROSE es menor a 90%.

Communication: "Position" does matter: The photofragmentation of the nitroimidazole isomers.

A combined experimental and theoretical approach has been used to disentangle the fundamental mechanisms of the fragmentation of the three isomers of nitroimidazole induced by vacuum ultra-violet (VUV) radiation, namely, 4-, 5-, and 2-nitroimidazole. The results of mass spectrometry as well as photoelectron-photoion coincidence spectroscopy display striking differences in the radiation-induced decomposition of the different nitroimidazole radical cations. Based on density functional theory (DFT) calculations, a model is proposed which fully explains such differences, and reveals the subtle fragmentation mechanisms leading to the release of neutral species like NO, CO, and HCN. Such species have a profound impact in biological media and may play a fundamental role in radiosensitising mechanisms during radiotherapy.

Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR).

BACKGROUND: Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC). PATIENTS AND METHODS: Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m2/ days 1-3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization. The primary end point was progression-free survival (PFS) after 12 months. Overall survival (OS), response rate, toxicity, quality of life and treatment preference regarding standard treatment were defined as secondary end points. RESULTS: A total of 550 patients were recruited. The PFS rate after 12 months was 37.0% for TC compared with 40.2% in the standard combinations (P = 0.470). The overall response rate was 73.1% for TC versus 75.1% for standard combinations (P = 0.149). After a median follow-up of 20 months, the median PFS was 10 months [95% confidence interval (CI) 9.4-10.6] and did not differ between both arms (P = 0.414). The median OS was 25 months in the TC arm versus 31 months in the standard arm (95% CI: 22.4-27.6 resp. 26.0-36.0; P = 0.163). Severe hematologic toxicities (grade 3/4) were rare in the experimental arm (P < 0.001), with 17.4% leucopenia, 27.8% neutropenia and 15.9% thrombopenia. CONCLUSION: The combination of carboplatin and topotecan was well tolerated with significant lower rates of severe hematological toxicities but did not improve PFS or OS in platinum-sensitive relapsed ovarian cancer compared with established standard regimens.

Elderly ovarian cancer patients: An individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO).

BACKGROUND: Barriers for optimal treatment and enrolment in clinical trials are the physicians' perceptions towards age, comorbidities and fear of toxicity as well as the eligibility criteria of clinical trials. There is a high need to gain more knowledge about this patient group in order to optimize treatment. We aimed to evaluate the influence of age above 65 years on comorbidities, comedication, grade III/IV toxicity, prior discontinuation of chemotherapy and survival. PATIENTS AND METHODS: An individual participant data meta-analysis of three phase II/III studies ('Tower', 'Topotecan phase III' and 'Hector') of the North-Eastern German Society of Gynecological Oncology including 1213 patients with recurrent ovarian cancer was conducted using logistic regression and Cox regression analysis. RESULTS: Median age at diagnosis was 59 years. The patient group ≥65 years included 349 versus 864 patients younger than 65 years. Cardiovascular disease and diabetes were more frequent in the older age group (p < 0.001 and p = 0.001). Haematological and cardiovascular grade III/IV toxicities were more often seen in patients above 65 years, while non-haematological toxicity was not (p = 0.03, odds ratio [OR] 1.35; p = 0.04, OR 1.83; and p = 0.90, OR 0.98, respectively). There was no difference in prior discontinuation of treatment in multivariate analysis. Cox regression showed a trend towards poorer progression-free survival (p = 0.053, hazard ratio 1.143) in the older age group. CONCLUSION: Haematological and cardiovascular toxicities are more frequent in elderly patients. However, this did not influence prior discontinuation of therapy. Elderly patients should not be deprived of adequate chemotherapy or excluded from clinical studies just because of their age. Thorough geriatric assessment and monitoring is mandatory.

The influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and overall survival in ovarian cancer.

BACKGROUND: Ovarian cancer is mostly diagnosed in the elderly woman who is likely to have comorbid disease and to take several comedications on a regular basis. Aim of this study was to evaluate the influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and survival. PATIENTS AND METHODS: In this individual participant data meta-analysis the original data of three phase II/III studies of the North-Eastern German Society of Gynecological Oncology (NOGGO) were analyzed using multivariate logistic and Cox regression. RESULTS: Overall, 1213 patients with recurrent ovarian cancer were included in these analyses. An increasing amount of medication was associated with overall grade III/IV toxicity (p<0.001; OR 1.120), and hematological (p<0.001; OR 1.056) and non-hematological (p<0.001; OR 1.134) toxicities. Prior discontinuation of chemotherapy was not influenced by an increasing amount of medication (p=0.196). There was no association of polypharmacy with overall survival (p=0.068). CONCLUSION: As polypharmacy does not influence survival ovarian cancer patients taking several comedications may be included in clinical trials and should not be deprived of adequate cancer treatment. However, a thorough monitoring is mandatory due to the increased risk of toxicities.

[Vertebral metastases of urogenital carcinomas: Diagnosis and conservative therapy]. / Wirbelsäulenmetastasen urologischer Tumoren : Diagnostik und konservative Therapie.

The high incidence of bone metastases of urologic neoplasms and their morbidity, especially of vertebral metastases, requires exact diagnosis and consequent therapy. Conventional radiography plays an important role in the diagnosis of symptomatic bone lesions. Computed tomography can evaluate the stability of metastatic lesions and is indispensable for therapy planning. MRI and PET-CT have the highest diagnostic accuracy for the detection of bone metastases and MRI can evaluate their intra- and extraosseus components. PET-CT, PET-MRI, or SPECT-CT in combination with specific tracers - due to their high specificity and sensitivity - have the potential to replace conventional methods in the future. Conservative treatment basically consists of analgesic therapy, the administration of calcium and vitamin D3 and bisphosphonates or inhibitors of RANKL (denosumab). Moreover radium-223-dichloride can improve overall survival and the time to the first symptomatic skeletal event in castration-resistant prostate cancer patients with bone metastases.