Austrian Centers Research Articles

‘Short Bars Crossed’ to Remodel the Entire Chest Wall in Children and Adolescents with Pectus Excavatum

BackgroundThe cross-bar technique of minimally invasive pectus excavatum (PE) correction remains underreported, which is especially true of pediatric patients. We therefore reviewed the experience of a Turkish and an Austrian center. An additional novelty characterizing both pediatric cohorts was the use of short bars. MethodsIn a retrospective study, pediatric PE corrections involving ‘short bars crossed’ were analyzed for complications and intra-/postoperative outcomes. Cases with two or three bars were included, given that a horizontal third bar was placed whenever considered useful for upper-chest elevation. All bars were fitted with a single stabilizer near the surgical entry point. In the Austrian center, intercostal nerve cryoablation was used for pain management. Descriptive statistics are presented. ResultsSeventy-eight patients ≤18 years old were evaluable at the Turkish (n = 56) and Austrian (n = 22) centers. Total median values were 16.2 (IQR: 15.1–17.4) years for age and 4.60 (IQR: 3.50–6.11) for Haller index. Ten mild or moderate complications (12.8%) were observed, including just one revision requirement due to bar migration (1.28%). Intercostal nerve cryoablation (n = 13) was associated with longer surgical procedures at 150 (IQR: 137–171) versus 80 (IQR: 60–100) minutes but with shorter hospital stays, given an IQR of 3–4 days versus 4–5 days. Conclusion‘Short bars crossed’—with a single stabilizer in a ventral position close to the surgical entry point—ensure a wide distribution of forces, protect against bar migration, are safe and effective, and offer stability at an age characterized by growth and physical activity. Level of EvidenceIV.

Prediction of resistance to bevacizumab plus FOLFOX in metastatic colorectal cancer using a multi-marker panel and a machine-learning approach: Final results of the prospective multicenter PERMAD trial.

204 Background: Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are widely used for tumor treatment, including metastatic colorectal cancer (mCRC). So far, there are no biomarkers that reliably predict resistance to anti-VEGF mAbs like bevacizumab. A biomarker-guided strategy for early and accurate assessment of resistance could avoid the use of non-effective treatment and improve patient outcomes. We hypothesized that repeated analysis of multiple cytokines and angiogenic growth factors (CAFs) before and during treatment using machine learning could provide an accurate and earlier, i.e., 100 days before conventional radiologic staging, prediction of resistance to first-line mCRC treatment with FOLFOX plus bevacizumab. Methods: 15 German and Austrian centers prospectively recruited 154 mCRC patients receiving FOLFOX plus bevacizumab as first-line treatment. Plasma samples were collected every two weeks until radiologic progression (RECIST 1.1) as determined by CT scans performed every 2 months. 102 pre-selected CAFs were centrally analyzed using a cytokine multiplex assay (Luminex, Myriad RBM). Results: Using random forest machine learning, we developed a predictive model that discriminated between the situations of ”no progress within 100 days before radiological progress” and ”progress within 100 days before radiological progress”. Into this we incorporated a combination of ten out of the 102 CAF markers, which fulfilled this task with 81% accuracy, 72% sensitivity, and 88% specificity. Conclusions: Using artificial intelligence we identified a CAF marker combination that indicates treatment resistance to FOLFOX plus bevacizumab in patients with mCRC within 100 days prior to radiologic progress. Further studies are required to show its clinical value. Clinical trial information: NCT02331927 .

Prediction of resistance to bevacizumab plus FOLFOX in metastatic colorectal cancer-Results of the prospective multicenter PERMAD trial.

Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are widely used for tumor treatment, including metastatic colorectal cancer (mCRC). So far, there are no biomarkers that reliably predict resistance to anti-VEGF mAbs like bevacizumab. A biomarker-guided strategy for early and accurate assessment of resistance could avoid the use of non-effective treatment and improve patient outcomes. We hypothesized that repeated analysis of multiple cytokines and angiogenic growth factors (CAFs) before and during treatment using machine learning could provide an accurate and earlier, i.e., 100 days before conventional radiologic staging, prediction of resistance to first-line mCRC treatment with FOLFOX plus bevacizumab. 15 German and Austrian centers prospectively recruited 50 mCRC patients receiving FOLFOX plus bevacizumab as first-line treatment. Plasma samples were collected every two weeks until radiologic progression (RECIST 1.1) as determined by CT scans performed every 2 months. 102 pre-selected CAFs were centrally analyzed using a cytokine multiplex assay (Luminex, Myriad RBM). Using random forests, we developed a predictive machine learning model that discriminated between the situations of "no progress within 100 days before radiological progress" and "progress within 100 days before radiological progress". We could further identify a combination of ten out of the 102 CAF markers, which fulfilled this task with 78.2% accuracy, 71.8% sensitivity, and 82.5% specificity. We identified a CAF marker combination that indicates treatment resistance to FOLFOX plus bevacizumab in patients with mCRC within 100 days prior to radiologic progress.

Characterization of Austrian severe asthma patients

IntroductionThe Severe Asthma Registry, founded by German Asthma Net (GAN) in 2011, is a prospective registry recording clinical parameters from participating centers in Germany, Austria and Switzerland. This article presents the baseline characteristics of severe asthma patients from Austrian centers. MethodsWe analyzed the baseline visit data of all patients recruited to the GAN Severe Asthma Registry from participating Austrian centers. ResultsBaseline visit data were available for 214 Austrian severe asthma patients from 6 Austrian centers from 2013 to 2022. Mean age was 53.7 years. Mean BMI was 26.4 kg/m2. More than a third (37.4%) of all patients had daily daytime asthma symptoms at baseline and had to use their reliever medication at least once per day. Forty-one percent of patients were classified as uncontrolled according to GINA and 24.8% as partially controlled at baseline visit. The median annual exacerbation frequency was 3 in the previous 12 months. At the time of baseline visit, 23.4% of all patients had regular treatment with oral corticosteroids. Furthermore, 23.9% had received any severe asthma monoclonal antibody prior to the baseline visit. There were no notable differences in baseline characteristics between patients categorized by smoking history or measurable type 2 inflammation. ConclusionsThis study provides the first multi-center characterization of Austrian severe asthma patients. Patients in this cohort had better asthma control and less frequent exacerbations compared to most international registries.

Phase III FIRE-4 study (AIO KRK-0114): Evaluation of first-line treatment efficacy of FOLFIRI/cetuximab in patients with RAS-WT mCRC receiving the first cycle of treatment with chemotherapy only.

100 Background: FIRE-4 (AIO KRK-0114) is performed in RAS wild-type (wt) mCRC patients. This randomized study tests the efficacy of early switch maintenance during 1st-line therapy (part 1) and re-challenge with cetuximab (part 2) in later-line treatment. In part 1, all patients received first-line induction treatment with FOLFIRI plus cetuximab (FOLFIRI/Cet). In arm A, patients were randomized to continue FOLFIRI/Cet until progression or intolerable toxicity. In arm B, patients received FOLFIRI/Cet for 8-12 cycles, after which maintenance therapy with 5-FU/FA plus bevacizumab (5-FU/Bev) was applied. The first randomization evaluates the question if an early switch from cetuximab to bevacizumab during maintenance therapy may prolong PFS. The study protocol explicitly allowed a first cycle of chemotherapy to be applied before randomization. Methods: Within this randomized, controlled, open-label phase-III study, patients received FOLFIRI (irinotecan plus 5-FU/FA) plus cetuximab every two weeks at the standard dosing schedule. In arm A, FOLFIRI plus cetuximab was continued until progression or intolerable toxicity. De- and re-escalation was allowed according to the local standard of care. In arm B, patients received 8 cycles of FOLFIRI plus cetuximab (in case of tumor response) or 12 cycles (in case of stable disease) followed by maintenance with 5-FU/FA plus bevacizumab (5mg/kg) until disease progression or intolerable toxicity. Overall survival after second randomization (part 2) is evaluated as a primary endpoint. Here, we report PFS in first-line (part 1) as a secondary study endpoint of the study. Other secondary endpoints included ORR, OS, safety, and tolerability. Results: From August 2015 to January 2021, 672 patients were randomized, and 656 patients were assigned to treatment in 120 German and 10 Austrian centers (327 arm A and 329 in arm B). Of those, 205 patients received one cycle of FOLFIRI alone before randomization. In both arms, ORR was comparable for patients receiving cetuximab from the first cycle when compared to those receiving one cycle of chemotherapy only (arm A: 58.7% vs 62.9% (p = 0.54), arm B 60.2% vs 55.6% (p = 0.48). PFS was also not influenced in both arms (arm A: 10.8mo vs. 10.6mo (p = 0.91); arm B 11.2mo vs. 11.4mo (p = 0.62)). Preliminary results suggest that also OS (event rate 38.3%) was not influenced by one cycle applied without cetuximab (arm A: 33.7 mo vs. 29.1 mo (p = 0.20); arm B: 35.6 mo vs. 28.9 mo (p = 0.13)). Conclusions: Application of one initial cycle with chemotherapy alone did not influence the efficacy of a first-line strategy of FOLFIRI plus cetuximab. If RAS mutational analysis is not timely available, a start with FOLFIRI alone adding cetuximab in cycle 2 seems to be safe with respect of overall efficacy. Clinical trial information: NCT02934529 .

Ureteral calculi in octogenarians and nonagenarians: Contemporary in-hospital management-A joint study by the endourological section of the Austrian Association of Urology.

To assess contemporary in-hospital management of octogenarians and nonagenarians with ureteral calculi. Review of patients aged ≥80 years hospitalized due to ureteral calculi. Data was extracted from eight Austrian centers of urology. Stone and patient related data were recorded. Treatment patterns in acute and elective settings were assessed. A total of 759 patients hospitalized with ureteral calculi were analyzed. Out of them, 643 were octogenarians (80-89years) and 116 nonagenarians (90-99 years). In an acute setting, simple de-obstruction with urinary diversions outnumbered active stone treatments like URS and SWL (62.6% vs. 26.9% vs. 10.5%). Decision making whether patients underwent active stone treatment was driven by stone location (OR = 0.28, p<0.0001), impaired renal function (OR = 0.28, p = 0.01) and indwelling urethral catheters (OR = 0.23, p = 0.01) but not by age or extend of mobility (all p>0.05). In elective settings, 81.5% of procedures were active stone treatments-mainly URS (76.9%), while DJ stent or nephrostomy replacements were noted in 14.2% and 4.3%. Octogenarians (OR = 14, p<0.0001) and patients capable of walking (OR = 4.51, p = 0.01) had significantly higher odds of receiving active stone. Stone free rates and complications rates with URS were similar between octogenarians and nonagenarians (p = 0.98 and p = 0.58). In acute settings, age and extend of mobility were not found to be independent predictors for active stone treatment. In elective settings, after having received urinary diversions, reduced mobility and nonagenarians were less likely to undergo stone removal treatments. Safety and efficacy of URS seems to be similar in octogenarians and nonagenarians.

Unveiling cardiac amyloidosis, its characteristics and outcomes among patients with mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair

Abstract Background Mitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on co-existence and prognostic implications of MR and CA are currently lacking. Purpose We aimed to identify prevalence, clinical characteristics and outcomes of MR-CA compared to lone MR. Methods Consecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR were screened for concomitant CA at two Austrian centers using a multi-parametric approach including core-lab 99mTc-DPD bone scintigraphy and echocardiography, and immunoglobulin light-chain assessment. Transthyretin-CA (ATTR) was diagnosed by DPD (Perugini Grade-1: early infiltration; Grades-2/3: clinical CA) and absence of monoclonal protein, and light-chain-(AL)-CA via tissue biopsy. Mass spectroscopy was performed in case of conflicting immunohistochemical results. All-cause mortality and hospitalization for heart failure (HHF) served as composite endpoint. Results In total, 120 patients (76.9±8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in n=14 (11.7%; 12 ATTR, 1 AL, 1 combined ATTR/AL), and early amyloid infiltration in n=9 (7.5%). MR-CA had higher troponin levels, thicker left ventricular walls, and a higher prevalence of carpal tunnel syndrome and left anterior fascicular block compared to lone MR (all p&amp;lt;0.05). Independent predictors of MR-CA were increased posterior wall thickness, and presence of left anterior fascicular block on ECG. Procedural success (MR reduction ≥1 grade) and periprocedural complications of TEER were similar in MR-CA and lone MR (p for all=n.s.). After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR-CA had worse outcomes compared to lone MR with regard to the composite endpoint (HR 2.2, 95% confidence interval [95% CI] 1.0–4.7, p=0.039), driven by a 2.5-fold higher risk for HHF (HR 2.5, 95% CI 1.1–5.9), but comparable mortality (HR 1.6, 95% CI 0.4–6.1; Graphical abstract). Conclusions Dual pathology of MR-CA is common in elderly MR patients undergoing TEER, and has worse post-interventional outcomes compared to lone MR. Given technical feasibility of TEER in MR-CA, valvular repair should be considered as an option to improve forward volume in a state with typically low output. Future studies should evaluate the prognostic benefits of TEER and CA-specific treatment in MR-CA. Funding Acknowledgement Type of funding sources: None.

Reduction ascending aortoplasty: A retrospective analysis of outcomes and risk factors.

ObjectivesIndication for Reduction of Ascending Aortoplasty (RAA) and long-term outcomes remain unclear. This study analyzed the outcomes after nonreinforced RAA in two Austrian centers.MethodsPatients with RAA at two Austrian centers between 6/2,009 and 6/2,017 were retrospectively analyzed. Aortic diameters were measured by CT pre- and post-operatively. Patients were assigned according to valve morphology and imaging modality.ResultsOverall, 253 patients underwent RAA [women: 30.8%; median age 74 (63–79) years] with a mean preoperative ascending diameter of 44.7 (±3.5) mm. RAA-related postoperative adverse events occurred in 1.2% (n = 3) over a follow-up of a median of 3.8 (2.4–5.5) years: One type A aortic dissection, one lethal aortic rupture at the suture line, and one suture line bleeding with cardiac tamponade and need of surgical revision. The overall survival rate was 89.7%. Aortic valve morphology itself was no risk factor for mortality (Log-Rank: 0.942). One hundred and forty patients had a tricuspid [TAV: (55.3%)] aortic valve and 113 patients had a bicuspid aortic valve [BAV: (44.7%)]. Redilatation to a diameter >50 mm according to CT follow-up occurred in 5.7% (n = 5 of 87). One patient needed reoperation with RAA and aortic valve replacement due to a prosthesis-patient mismatch after aortic valve replacement and aortic redilatation.ConclusionNon-reinforced RAA is a safe, feasible, and reproducible procedure with low rates of perioperative complications in selected patients primarily undergoing aortic valve repair with a dilated ascending aorta. Aortic valve morphology has no impact on mortality after RAA.

SO-16 FIRE-4 (AIO-KRK-0114): Randomized study for a switch maintenance concept with 5-FU plus bevacizumab after induction treatment with FOLFIRI plus cetuximab versus continued treatment with FOLFIRI plus cetuximab – secondary endpoint

FIRE-4 (AIO KRK-0114) is performed in RAS-wild-type (wt) mCRC patients. This randomized study tests the efficacy of early switch maintenance during 1st-line therapy (part 1) and re-challenge with cetuximab (part 2) in later-line treatment. In part 1, all patients received first-line induction treatment with FOLFIRI plus cetuximab (FOLFIRI/Cet). In arm A, patients were randomized to continue FOLFIRI/Cet until progression or intolerable toxicity. In arm B, patients received FOLFIRI/Cet for 8-12 cycles, after which maintenance therapy with 5-FU/FA plus bevacizumab (5-FU/Bev) was applied. The first randomization evaluates the question if an early switch from cetuximab to bevacizumab during maintenance therapy may prolong PFS. In this randomized, controlled, open-label phase-III study, patients received FOLFIRI (irinotecan plus 5-FU/FA) plus cetuximab every two weeks at the standard dosing schedule. In arm A, FOLFIRI plus cetuximab was continued every 2 weeks until progression or intolerable toxicity. De- and re-escalation was allowed according to the local standard of care. In arm B, patients received 8 cycles of FOLFIRI plus cetuximab (in case of tumor response) or 12 cycles (in case of stable disease) followed by maintenance with 5-FU/FA plus bevacizumab (5mg/kg) every two weeks until disease progression or intolerable toxicity. Overall survival after second randomization (part 2) is evaluated as a primary endpoint. Here, we report PFS in first-line (part 1) as a secondary study endpoint of the study. Other secondary endpoints included ORR, OS, safety, and tolerability. The present analysis investigates the impact of sidedness on study results. From August 2015 to January 2021, 672 patients were randomized and 656 patients were assigned to treatment in 120 German and 10 Austrian centers (327 arm A and 329 in arm B). The primary analysis of the overall study population demonstrated comparable outcome data in both treatment arms. Among 643 patients evaluable for sidedness, 84% (n=539) presented with left-sided tumors and 16% (n=104) with right-sided tumors. In left sided tumors comparable results were obtained in both treatment arms (A vs B) with regard to ORR (78.8% vs 78.0%), PFS (11.5 months vs 11.6 months), and OS (33.2 months vs 35.6 months). In right-sided tumors, efficacy data (arms A vs B) were generally less favorable. ORR was numerically superior with continued application of cetuximab in arm A (56.8% vs 42.2%, P=0.27). However, survival data appeared to be more favorable in the switch maintenance arm (B) with regard to PFS (5.5 months vs 7.4 months, P=0.38) and OS (12.5 months vs 21.2 months, P=0.27). FIRE-4 confirms the efficacy of FOLFIRI plus cetuximab as first-line treatment of patients with RAS wild-type mCRC. In patients with left-sided tumors, continued application of cetuximab induced comparable efficacy as an early switch from FOLFIRI cetuximab to maintenance therapy with 5-FU plus bevacizumab. While in right-sided tumors, differences in outcome did not reach the level of statistical significance, survival data are numerically in favor of the bevacizumab switch-maintenance arm.

Randomized study to investigate a switch maintenance concept with 5-FU plus bevacizumab after FOLFIRI plus cetuximab induction treatment versus continued treatment with FOLFIRI plus cetuximab: Report of a secondary endpoint of the phase-III FIRE-4 study (AIO KRK-0114).

3519 Background: FIRE-4 (AIO KRK-0114) is performed in RAS-wild-type (wt) mCRC patients. This randomized study tests the efficacy of early switch maintenance during 1st-line therapy (part 1) and re-challenge with cetuximab (part 2) in later-line treatment. In part 1, all patients received first-line induction treatment with FOLFIRI plus cetuximab (FOLFIRI/Cet). In arm A, patients were randomized to continue FOLFIRI/Cet until progression or intolerable toxicity. In arm B, patients received FOLFIRI/Cet for 8-12 cycles, after which maintenance therapy with Fluoropyrimidin plus bevacizumab was applied. The first randomization evaluates the question if an early switch from cetuximab to bevacizumab during maintenance therapy may prolong PFS. Methods: Within this randomized, controlled, open-label phase-III study, patients received FOLFIRI (irinotecan plus 5-FU/FA) plus cetuximab every two weeks at the standard dosing schedule. In arm A, FOLFIRI plus cetuximab was continued every 2 weeks until progression or intolerable toxicity. De- and re-escalation was allowed according to the local standard of care. In arm B, patients received 8 cycles of FOLFIRI plus cetuximab (in case of tumor response) or 12 cycles (in case of stable disease) followed by maintenance with Fluoropyrimidin plus bevacizumab (5mg/kg) every two weeks until disease progression or intolerable toxicity. Overall survival after second randomization (part 2) is evaluated as a primary endpoint. Here, we report PFS in first-line (part 1) as a secondary study endpoint of the study. Other secondary endpoints included ORR, OS, safety, and tolerability. Results: From August 2015 to January 2021, 672 patients were randomized and 656 patients were assigned to treatment in 120 German and 10 Austrian centers (327 arm A and 329 in arm B). PFS was comparable between both treatment arms (10.7 vs 11.3 months, HR 0.92 (95% CI: 0.76-1.10), p = 0.36). ORR in evaluable patients was not different and reached 75.7% and 72.3% with a DCR of 94.6% vs. 92.5% in the respective arms. Preliminary OS (≤40% of OS events recorded) was also similar between both arms (HR 1.030; p = 0.81). Updated results will be presented at the meeting. No new or unexpected toxicities were observed. Conclusion: Switch from FOLFIRI cetuximab to maintenance therapy with 5-FU plus bevacizumab did not induce superior efficacy (PFS, ORR, OS) compared to continued application of cetuximab. The results suggest that early switch maintenance from cetuximab to bevacizumab is not effective to postpone disease progression during targeted therapy. FIRE-4 confirms the efficacy of FOLFIRI plus cetuximab as first-line treatment of patients with RAS wild-type mCRC. Clinical trial information: NCT02934529.

Outcome of Budd-Chiari Syndrome Patients Treated With Direct Oral Anticoagulants: An Austrian Multicenter Study

Direct oral anticoagulants (DOACs) may simplify management of Budd-Chiari syndrome (BCS). Here, we report our experience with off-label use of DOACs for anticoagulation in BCS. The safety of DOAC vs vitamin K antagonist treatment as well as associated clinical outcomes were retrospectively assessed in 47 BCS patients treated at 6 Austrian centers. Mean age at study inclusion was 37.9 ± 14.0 years and mean Model for End-Stage Liver Disease was 13.1 ± 5.1. Overall, 63.8% (n= 30) of patients had decompensated liver disease, and 87.2% (n= 41) showed clinical signs of portal hypertension. During a median follow-up of 82.5 (interquartile range, 43.1-121.8) months, 43 (91.5%) patients received anticoagulation alone or following interventional treatment, including 22 (46.8%) patients treated with DOACs (edoxaban: 10, apixaban: 4, rivaroxaban: 3, dabigatran: 3, more than one DOAC sequentially: 2) for a median of 24.4 (interquartile range, 5.7-35.1) months. While 72.7% (n= 16 of 22) of patients were switched from low-molecular-weight heparin (n= 12) or vitamin K antagonist (n= 4) to DOAC after disease stabilization or improvement, 27.3% (n= 6 of 22) of BCS patients were initially treated with DOAC. Complete response (European Association for the Study of the Liver criteria) was achieved or maintained in 14 (63.6%) of 22 patients, with ongoing response in 2 patients, while disease progressed in 6 patients (including 2 patients with hepatocellular carcinoma). Four major spontaneous bleedings (18.2%; incidence rate 8.8 per 100 patient-years; n= 2 upper gastrointestinal bleeding, n= 1 lower gastrointestinal bleeding, n= 1 hepatocellular carcinoma rupture), 7 minor bleedings, and 1 major procedure-related bleeding (4.5%; 2.2 per 100 patient-years) occurred during DOAC therapy. Overall transplant-free survival was 91.6% at 5 years. DOACs seem to be effective and safe for long-term anticoagulation in patients with BCS, but confirmation by larger prospective studies is needed.

Postoperative chemoradiotherapy with cisplatin is superior to radioimmunotherapy with cetuximab and radiotherapy alone : Analysis of the Austrian head and neck cancer registry of the AGMT.

BackgroundThe addition of cisplatin or cetuximab to radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) has significantly improved the outcome. While the superiority of cisplatin over cetuximab in combination with radiotherapy has been shown in a definitive setting, we set out to compare postoperative chemoradiotherapy with cisplatin to radioimmunotherapy with cetuximab and radiotherapy alone within the Austrian head and neck cancer registry of the Working Group on Pharmaceutical Tumor Treatment (AGMT) study group.Material and methodsIn the AGMT head and neck cancer registry, data of 557 patients with SCCHN from five Austrian cancer centers were prospectively collected between 2012 and 2017. Of these patients 120 received postoperative chemoradiotherapy with cisplatin, 26 patients received postoperative radioimmunotherapy with cetuximab and 56 patients were treated with adjuvant radiotherapy only. Patient characteristics, stage of disease, details on treatment as well as survival were analyzed by a chart-based review.ResultsIn patients treated with postoperative radiotherapy the addition of cisplatin significantly improved progression-free survival (PFS) and overall survival (OS) compared to cetuximab (PFS 84.2 months vs. 17.0 months, p = 0.04, OS not reached vs. 46.0 months, p = 0.02) and PFS compared to radiotherapy alone (PFS 84.2 months vs. 28.5 months, p < 0.01). Patients treated with cetuximab were significantly older and had a worse performance score than patients receiving cisplatin or radiotherapy alone.ConclusionThis study confirmed the importance of multimodal treatment concepts in patients with locally advanced SCCHN. Postoperative cetuximab might be an option in patients not eligible for high-dose cisplatin but cisplatin should remain the standard of care.

Porcelain set of king Fouad I in Silverware Museum of Abdeen Palace

This museum displays the Royal Family's collections of silverware, porcelain, crystal and Galle items. Halls have been allocated for it following the Presidency Museum in the plan of visit. These halls have been provided with show cases and systems for illumination, air conditioning and security matching the exhibits, making this museum unique in both contents and display methods ( ). The museum contains a unique collection of utensils made from porcelain with different forms, colors, sizes and in different and various designs which make them look like works of art though they are just tableware. Porcelain collections displayed in Abdeen museum are the products of famous and specialized British, French and Austrian centers during the end of the 19th and beginning of the 20th century. It reflects a fine taste and an outstanding level of skill characterized with an exceptional manufacturing and artistic style. The museum displays some pieces of white Chinaware sets with a broad navy blue strip defined with fine gilded ornaments. They are also adorned with a golden royal crown inscribed either in the center of the strip or the dish. These pieces belong to King Fouad I, son of Khedive Ismail .

Interdisciplinary position paper: the value of radiofrequency denervation in the treatment of chronic pain

Radiofrequency denervation has been established for many years as an important minimally invasive procedure for the treatment of chronic pain conditions. Positive experiences of many users for various indications are contrasted by a nonuniform evidence. With meticulous patient selection and correct assessment of the indications a longer term reduction of pain, a reduced need for analgesics and an improvement in the quality of life can be achieved. The aim of this interdisciplinary position paper is to present the value of radiofrequency denervation in the treatment of chronic pain. The summarized recommendations of the expert group are based on the available evidence and on the clinical experiences of Austrian centers that frequently implement the procedure. The position paper contains recommendations on patient selection and proven indications. We discribe safety aspects, complications, side effects and contraindications.

Perioperative chemotherapy versus neoadjuvant chemoradiation for patients with adenocarcinoma of the distal esophagus in Austria: a retrospective analysis

BackgroundThe aim of this study was to compare the outcome of patients with adenocarcinoma of the distal esophagus (AEG type I) treated with neoadjuvant chemoradiation or perioperative chemotherapy.MethodsEligible patients from four Austrian centers were selected to conduct a retrospective analysis. All patients treated between January 2007 and October 2017 with chemotherapy according to EOX-protocol (Epirubicin, Oxaliplatin, Xeloda) or chemoradiation according to CROSS-protocol (carboplatin/paclitaxel + RTX 41.4 Gy), before esophagectomy were included. Primary outcomes disease-free survival (DFS) and overall survival (OS) as well as secondary outcomes downstaging of T- or N-stage and achievement of pathological complete response pCR (ypT0N0M0) were analyzed. Data of 119 patients were included.ResultsComplete data was available in 104 patients, 53 patients in the chemoradiation group and 51 patients in the chemotherapy group. The mean number of lymph nodes removed was significantly higher in the EOX group (EOX 29 ± 15.5 vs. CROSS 22 ± 8.8; p < 0.05). Median follow-up in the CROSS group was 17 months (CI 95% 8.8–25.2) and in the EOX group 37 months (CI 95% 26.5–47.5).In the chemotherapy group, the OS rate after half a year, − 1, and 3 years was 92%, 75%, and 51%. After chemoradiation, overall survival after half a year was 85 %, after 1 year 66%, and after 3 years 17%. In the EOX group DFS after ½, − 1, and 3 years was 90%, 73%, and 45%, in the chemoradiation group after half a year 81%, after 1 year 55% and after 3 years 15%. Pathological complete response (pCR) was achieved in 23% of patients after CROSS and in 10% after EOX (p < 0.000).ConclusionsThere seem to be clear advantages for chemoradiation, concerning the major response of the primary tumor, whereas a tendency in favor for chemotherapy is seen in regards to systemic tumor control. Furthermore, the type of neoadjuvant treatment has a significant influence on the number of lymph nodes resected.

Olaratumab plus anthracyline in advanced/metastatic soft tissue sarcoma: Data of real-world utilization in Austria.

e22550 Background: Olaratumab is a humanized monoclonal anti platelet-derived growth factor receptor α antibody that has been approved in combination with doxorubicin for the treatment of patients with metastatic soft tissue sarcoma (STS). The purpose of this retrospective study was to assess the clinical efficacy in STS patients treated with olaratumab in a real-world setting in Austria. Methods: Retrospectively collected, longitudinal data from patients treated between November 2016 and September 2018 at 9 Austrian centers were obtained from respective medical charts. Eligible patients were all patients who received at least one dose of olaratumab. Parameters of most interest collected were response rates, progression-free survival (PFS) and overall survival (OS). Results: Altogether 55 patients were included into analysis. Median age was 58 years. In total, 65.5% (n = 36), 21.8% (n = 12) and 12.7% (n = 7) received olaratumab as first-, second- or ≥ third-line treatment, respectively. Olaratumab was administered either in combination with doxorubicin (81.8%, n = 45) or liposomal doxorubicin (16.4%, n = 9); 1 patient received olaratumab as upfront monotherapy. Median PFS and OS were 2.6 and 11.4 months. The objective response rate was 11.4 % and the disease control rate was 40.9 %. Conclusions: In this real-world analysis outcome was less pronounced compared to the results of the Phase Ib/II approval trial ( Tap WD et al. Lancet 2016). Thus, the results of the ongoing phase III trial (NCT02451943) are urgently needed to confirm the efficacy of the combination of olaratumab and doxorubicin in STS patients.

Pomalidomide (POM) and Low-Dose Dexamethasone (LoDEX) in Relapsed/Refractory Multiple Myeloma (RRMM): Analysis of Real World Data from an Ongoing, National, Multi-Center, Non-Interventional Study

Pomalidomide (POM) and Low-Dose Dexamethasone (LoDEX) in Relapsed/Refractory Multiple Myeloma (RRMM): Analysis of Real World Data from an Ongoing, National, Multi-Center, Non-Interventional Study

Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial)

BackgroundTriple-negative breast cancer (TNBC) comprises a heterogeneous group of diseases which are generally associated with poor prognosis. Up to now, no targeted treatment beyond anti-VEGF therapy has been approved for TNBC and cytotoxic agents remain the mainstay of treatment. Ixazomib is a selective and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma. In a preclinical study TNBC cells were treated with the first-generation proteasome inhibitor bortezomib in combination with cisplatin and synergistic efficacy was demonstrated. Clinical data are available for carboplatin plus bortezomib in metastatic ovarian and lung cancers showing remarkable antitumor activity and good tolerability (Mol Cancer 11:26 2012, J Thorac Oncol 4:87–92 2009, J Thorac Oncol 7:1032–1040, 2012). Based on this evidence, the phase I/II MBC-10 trial will evaluate the toxicity profile and efficacy of the second-generation proteasome inhibitor ixazomib in combination with carboplatin in patients with advanced TNBC.MethodsPatients with metastatic TNBC pretreated with at least one prior line of chemotherapy for advanced disease with a confirmed disease progression and measurable disease according to RECIST criteria 1.1 are eligible for this study. Patients will receive ixazomib in combination with carboplatin on days 1, 8, and 15 in a 28-day cycle. The phase I part of this study utilizes an alternate dose escalation accelerated titration design. After establishing the maximum tolerated dose (MTD), the efficacy and safety of the combination will be further evaluated (phase II, including 41 evaluable patients). All patients will continue on study drugs until disease progression, unacceptable toxicity or discontinuation for any other reason. Primary endpoint of the phase II is overall response rate, secondary endpoints include progression-free survival, safety, and quality of life. This trial is open for patient enrollment since November 2016 in six Austrian cancer centers. Accrual is planned to be completed within 2 years.DiscussionBased on preclinical and clinical findings an ixazomib and carboplatin combination is thought to be effective in metastatic TNBC patients. The MBC-10 trial is accompanied by a broad biomarker program investigating predictive biomarkers for treatment response and potential resistance mechanisms to the investigational drug combination.Trial registrationEudraCT Number: 2016–001421-13 received on March 31, 2016, ClinicalTrials.gov Identifier: NCT02993094 first posted on December 15, 2016. This trial was registered prospectively.

A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health

In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and exvivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests. In 8 Austrian centers, 54 patients were screened, 50 randomized, and 41 included in the full analysis set. AlaGln supplementation significantly increased CA-125 appearance rate and exvivo stimulated IL-6 release. AlaGln supplementation also reduced peritoneal protein loss, increased exvivo stimulated tumor necrosis factor (TNF)-α release, and reduced systemic IL-8 levels. No adverse safety signals were observed. All 4 peritonitis episodes occurred during standard PD fluid treatment. A novel AlaGln-supplemented PD fluid improves biomarkers of peritoneal membrane integrity, immune competence, and systemic inflammation compared to unsupplemented PD fluid with neutral pH and low-glucose degradation. A phase 3 trial is needed to determine the impact of AlaGln supplementation on hard clinical outcomes.

PS02.115: PERIOPERATIVE CHEMOTHERAPY VERSUS NEOADJUVANT CHEMORADIATION FOR PATIENTS WITH ADENOCARCINOMA OF THE DISTAL OESOPHAGUS IN AUSTRIA

Abstract Background The aim of this study is to compare the outcome of patients with adenocarcinoma of the distal oesophagus (AEG Type I) treated with perioperative chemotherapy or neoadjuvant chemoradiation. Methods A retrospective analysis of eligible patients from four Austrian centers was conducted. All patients with AEG type I treated between January 2007 and October 2017 with chemotherapy (EOX-protocol) or chemoradiation (CROSS-protocol, or 5-FU/Cisplatin), followed by oesophagectomy were included in the study. Primary outcomes overall survival, and disease free survival as well as secondary outcomes, achievement of pathological complete response pCR (ypT0N0M0) or downstaging of T- or N-stage were analyzed. Primary outcomes were calculated by the Kaplan-Meier-method. Results Data of 117 patients were analyzed, 59 received chemoradiation (50/59 CROSS and 9/59 5-FU/Cisplatin) and 58 patients received perioperative chemotherapy (EOX). Complete data at time of submission were available in 40 patients in the chemoradiation group and in 37 patients in the chemotherapy group. The median follow-up time in the chemoradiation group was 13,0 months (CI 95%: 11,0–15,0) and in the chemotherapy group 45,0 months (CI 95%: 28,8–61,3). Overall survival rate in the EOX group after ½, 1, 3 and 5 years was 92%, 83%, 63% and 34%. So far long term data are not available after chemoradiation, after ½ year overall survival was 84% and after one year 60%. Disease free survival rate in the EOX group after ½, 1, 3 and 5 years was 91%, 81%, 54% and 32%, in the chemoradiation group after ½ and one year 80% and 50%. A significant difference was found in the pathological complete response (pCR) rate, it was achieved in 19% of patients after chemoradiation and in 3% after chemotherapy (P = 0000). Conclusion Concerning major response of the primary tumor there are clear advantages for chemoradiation. In regards to systemic tumor control there seems a tendency in favor for chemotherapy. Disclosure All authors have declared no conflicts of interest.