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At the American Society of Clinical Oncology (ASCO) meeting 2014, the most striking abstracts on lung cancer treatment addressed—as expected—aspects of targeted therapy. The most probable practice changing data came from the presentation of the PROFILE 1014 trial dealing with anaplastic lymphoma kinase-positive non-small-cell lung carcinoma patients treated with crizotinib or chemotherapy in the first-line setting, which confirmed a comparable degree of benefit from crizotinib treatment as reported in second-line treatment. After 10 years of epidermal growth factor receptor (EGFR)-directed therapy, there were for the first time reports on phase I data on new agents showing efficacy in tyrosine-kinase inhibitor pre-treated patients with secondary resistance (i.e. T790M mutation). Monoclonal antibodies directed against EGFR and vascular endothelial growth factor receptor given in addition to conventional chemotherapy (SQUIRE and REVEL, respectively) resulted in significant but less impressive results. Notable improvements in overall survival in these two studies were not restricted to patients with adenocarcinoma but proved beneficial in patients with squamous cell carcinoma as well. Unfortunately, as in the aftermath of many past ASCO meetings, there will be no significant changes concerning systemic treatment of small cell lung cancer in the near future.

Background and Objectives Accumulating evidence indicates an important pathophysiological role of fibrinogen on tumor cell progression and metastases in different types of cancer. The aim of the present study was to evaluate the prognostic relevance of pre-operative fibrinogen levels on clinical outcome in a large cohort of STS patients. Methods Two hundred ninety-four consecutive STS patients were retrospectively evaluated. Cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS) were assessed using the Kaplan–Meier curves and Cox regression models. Finally, we supplemented the well-established Kattan nomogram by the fibrinogen level and evaluated the gain of predictive accuracy of this novel nomogram by Harrell's concordance index (c-index). Results An elevated plasma fibrinogen level was significantly associated with established prognostic factors, including age, tumor grade, size, and depth (P

Background: The concept of the involvement of systemic inflammation in cancer progression and metastases has gained attraction within the past decade. C-reactive protein (CRP), a non-specific blood-based marker of the systemic inflammatory response, has been associated with decreased survival in several cancer types. The aim of the present study was to validate the prognostic value of pre-operative plasma CRP levels on clinical outcome in a large cohort of soft-tissue sarcoma (STS) patients. Methods: Three hundred and four STS patients, operated between 1998 and 2010, were retrospectively evaluated. CRP levels and the impact on cancer-specific survival (CSS), disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan–Meier curves and univariate as well as multivariate Cox proportional models. Additionally, we developed a nomogram by supplementing the plasma CRP level to the well-established Kattan nomogram and evaluated the improvement of predictive accuracy of this novel nomogram by applying calibration and Harrell’s concordance index (c-index). Results: An elevated plasma CRP level was significantly associated with established prognostic factors, including age, tumour grade, size and depth (P

The introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for non-small cell lung cancer (NSCLC) with activating mutations of the EGFR has opened a new area of lung cancer treatment strategies and led to an enthusiastic search for additional mutations. Since then, numerous driver mutations such as EML4-ALK and ROS1 have been detected and specific treatment options have already been developed. However, molecular tests have to follow specific rules if applied in daily practice. The Austrian Working Group on Pulmonary Pathology and Oncology (AWGPPO) is presenting an updated version of their previous recommendation published in 2011. Several practical questions raised during the last 2 years will be addressed, such as reflex testing, selection of tissues, order of molecular tests, and the issue of resistance mechanisms.

Background: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial. Methods: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5–24.9 kg m−2), overweight (BMI=25–29.9 kg m−2), and obese (30 kg m−2) according to WHO criteria. Results: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients. Conclusion: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.

Malignancies originating from thymic epithelial tissue are rare and treatment approach depends on the individual situation. There are no randomized trials that provide evidence of therapy for patients with thymoma and thymic carcinoma. Treatment includes surgery, radiation therapy, and systemic therapy. For early stage tumors, surgery is the treatment of choice. Long-term survival depends on histologic type, presence of invasion, and quality of surgical resection. For locally advanced thymomas and thymic carcinomas, multimodal treatment includes neoadjuvant chemotherapy and adjuvant radiation. Patients with metastatic tumors are mainly treated with palliative chemotherapy. The optimal chemotherapy combination has not yet been established, although platinum-based drug regimes show reasonable response rates. For patients with poor performance status, the somatostatin (SST) analog octreotide with high affinity for SST receptors could be a potential treatment alternative. Small trials showed tumor responses, especially in combination with prednisolone. In the last decade, an effort has been made to establish targeted agents in the treatment of thymomas and thymic carcinomas. Nevertheless, up to now these agents have had only limited activity in this rare malignancy.

Change affects all areas of healthcare organizations and none more so than each aspect of the oncology ward, beginning with the patient's room. It is there that the issues faced by the major players in healing environments – administrator, caregiver, family member, and, most importantly, the patient – come sharply into focus. Hospitals are building new facilities or renovating old ones in order to adapt to new environmental demands of patient care and security. Driven by ethical and professional responsibility, the oncological team headed by Professor Hellmut Samonigg of Graz Medical University Graz pursued a vision of designing a model oncology ward unique in Europe. Friedensreich Hundertwasser, the world-famous artist, was the creative force behind the design. The oncology ward became a place of healing, permeated with a colorful sense of life and harmonious holistic care. The successful outcome was confirmed by the extraordinarily positive feedback by patients, families, and healthcare staff.

Patients with stage IIIB and IV non-small-cell lung carcinoma (NSCLC) harbouring activating mutations of the epidermal growth factor receptor (EGFR) gene should be treated first-line with gefitinib or erlotinib, EGFR tyrosine kinase inhibitors (TKI). EGF receptor mutations are most common in adenocarcinomas, especially in the non-mucinous type, while they are rare in squamous-cell carcinomas and sarcomatoid carcinomas, and they do not occur in neuroendocrine carcinomas. Therefore, following intense discussion and in consensus with oncologists and pulmonologists, the Pulmonary Pathology Working Group of the Austrian Society of Pathology recommends a-priori EGFR mutation analysis for all adenocarcinoma cases, and for all other NSCLC cases upon clinical request. This will markedly reduce the waiting time for those patients who will most likely gain the greatest benefit from EGFR TKI therapy.

Die Behandlung von Weichteilsarkomen stellt eine interdisziplinare Herausforderung dar, die eines spezialisierten Zentrums bedarf. Nur bei entsprechender Kooperation von Chirurgen, Strahlentherapeuten und Onkologen mit den diagnostischen Disziplinen Pathologie und Radiologie, ist die Chance auf das beste erreichbare Behandlungsergebnis fur einen individuellen Patienten gewahrleistet. Voraussetzung einer effizienten Kommunikation ist die Grundkenntnis der Besonderheiten und Klassifikation von Weichteiltumoren, deren Basis eine Unterteilung in drei Dignitatsgruppen (benigne – intermediar – maligne) darstellt. Der Therapieansatz ist in der Regel multimodal und erfordert entsprechende Infrastrukturen und Erfahrung in der Durchfuhrung von komplexen Therapien.

Patients with stage IIIB and IV non-small cell lung carcinoma (NSCLC) harboring an activating mutation of the Epidermal Growth Factor Receptor (EGFR) Gene should be treated first-line with Gefitinib, an EGFR tyrosine kinase inhibitor (TKI). EGF receptor mutations are most common in adenocarcinomas, especially non-mucinous type, rare in squamous cell carcinomas and sarcomatoid carcinomas, and do not occur in neuroendocrine carcinomas. Therefore, the Pulmonary Pathology Working Group of the Austrian Society of Pathology, after intense discussions and in consensus with Oncologists and Pulmonologists, recommends a priori EGFR mutation analysis for all cases of adenocarcinoma, and for all other NSCLC upon clinical request. This will markedly reduce waiting time for those patients, which most likely will have the greatest benefit from EGFR TKI therapy.

In 2002 results of two-phase II studies with the new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib showed not only promising efficacy in second and third line non-small cell lung cancer (NSCLC) therapies but also an excellent tolerability. Since then, thousands of patients have been treated in one of the largest expanded access programs ever performed and the successful application in daily routine led to a preliminary approval of the drug by the U.S. Food and Drug Administration in 2003. In the light of the negative results of a subsequent phase III trial comparing gefitinib with best supportive care, the approval was withdrawn. In 2009 gefitinib was relaunched for Caucasian patients in the US and Europe based on new data and on the re-interpretation of previous studies. The approval is now recommended exclusively for patients with an activating EGFR mutation. For the first time in lung cancer, molecular work-up is of clinical relevance and will change the diagnostic and therapeutic algorithms. The present review summarizes these data, presents the rationale for this development and proposes a diagnostic work-up.

BACKGROUND: Soft tissue sarcomas (STS) are a rare group of tumors with mesenchymal origin. They account for about 1% of all malignancies in adults. Due to the rareness of this tumor group, randomized clinical trials are scarce and there is little evidence concerning treatment options. METHODS: Clinical trials, published to date and literature were reviewed and edited. RESULTS: Possible different treatment approaches reflecting the present standard of care are presented and discussed. CONCLUSIONS: A multidisciplinary therapy approach and more randomized clinical trials are mandatory to improve the care for patients with STS.

In locally advanced inoperable patients and metastatic patients imatinib is a standard treatment. Standard dose of imatinib is 400 mg daily. Treatment should be continued indefinitely, since treatment interruption is generally followed by relatively rapid tumor progression in virtually all patients. Dose intensity should be maintained by adequate management of side effects and a correct policy of dose reductions and interruptions in the case of excessive toxicity. The standard approach in the case of tumor progression is to increase the imatinib dose to 800 mg daily with special attention to the occurrence of side effects. Patient non-compliance should be ruled out as a possible cause of tumor progression as well as drug interactions with concomitant medications. In case of progression or intolerance to imatinib standard second-line treatment is sunitinib. The drug was approved effective in terms of progression-free survival according to a 4 weeks on and 2 weeks off regimen. Preliminary data show that a continuous regimen with lower daily dose may be equally effective but possibly better tolerated. After failing on sunitinib, the patient should be considered for participation in a clinical trial of new therapeutic agents or combinations such as tyrosine-kinase inhibitors (e.g., nilotinib), sorafenib, or inhibitors of the mTOR (mammalian target of rapamycin)-pathway.

Diagnosis and treatment of gastrointestinal stromal tumors (GIST) requires an interdisciplinary treatment approach. This strategy should be reflected by the content of this article. Austrian representatives of 'GIST relevant' specialties authored this publication on a consensual base. This manuscript should be regarded as a guideline for 'GIST involved' colleagues in Austria.

Background A multicenter phase II study was conducted to analyze the clinical activity of the steroidal aromatase inhibitor exemestane in the neoadjuvant treatment of post-menopausal women with strongly ER- and/or PgR- positive operable breast cancer. Patients and methods From September 2000 to December 2003, 80 women were recruited for treatment with exemestane 25 mg once daily for 4 months. The primary end-point was the clinical response rate according the WHO criteria; the secondary end-points included toxicity and the number of patients who qualified for breast conserving surgery at the end of treatment, comparability of evaluation methods for response, potential alterations of hormone receptor and Her2/neu status during treatment. Results On an intention to evaluate analysis, according to the prespecified criteria the overall clinical objective response rate was 34%, the pCR rate was 3% and the rate of breast conserving surgery was 76%. When sonographic and mammographic longitudinal measurements were included in patients with missing palpation data, response rates were 38% and 41%, respectively. The tumor response was independent of the Her2/neu status which remained unchanged during treatment. In contrast, while the ER expression remained unaltered, downregulation of the PgR was observed. The treatment was well tolerated with no grade 3 and 4 toxicities except gastrointestinal (one grade 3 case) and hot flushes (two grade 3 cases). Conclusion This study shows that exemestane is effective and safe as a preoperative therapy in post-menopausal patients with strongly hormone receptor-positive breast cancer.

Seit dem Jahr 2000 ist die Therapie von vorbehandelten Patienten mit nicht-kleinzelligem Lungenkarzinom mit einer Zweitlinien-Chemotherapie etabliert. Zwei Chemotherapiesubstanzen Docetaxel (Taxotere®) und Pemetrexed (Alimta®) sind mittlerweile in Osterreich neben dem Thyrosinkinase-Hemmer Erlotinib (Tarceva®) registriert und fur diese Therapiesituation verfugbar. Die bessere Wirkung dieser Therapien im Vergleich zu bester symptomatischer Therapie ist durch randomisierte Studien gut belegt und im Ausmas des Effektes fur die einzelnen Substanzen vergleichbar. Unterschiedlich ist aber das Nebenwirkungsprofil. Die Entwicklung neuer Therapiemoglichkeiten zielt darauf ab, sowohl eine bessere Wirksamkeit als auch geringere Nebenwirkungen zu erreichen. Auf der Jahrestagung der American Society of Clinical Oncology (ASCO) 2007 in Chicago wurden Ergebnisse von randomisierten Studien mit neuen Chemotherapiesubstanzen und neuen "targeting agents" – z. B. Vinflunine und Gefitinib – fur diese Indikation berichtet. Auch uber die Effektivitat einer Dosiseskalation von Pemetrexed im Vergleich zur Standarddosierung und uber das Konzept einer vorgezogenen Zweitlinientherapie mit Docetaxel im Anschluss an die Primarbehandlung wurde berichtet. Das aktuelle Portfolio fur diese Indikation wird damit in Zukunft um einige Substanzen und Konzepte erweitert werden und stimmt optimistisch fur weitere Verbesserungen in der Zukunft. Derzeit bedingen die am ASCO 2007 prasentierten Studienergebnisse aber keine Anderung der aktuellen Vorgehensweise in der Zweitlinientherapie des NSCLC.

Recent evidence indicates toward a role of uric acid (UA) as a potential antioxidant. Elevated UA levels were shown to be associated with better survival in various malignancies. The aim of the present study was to evaluate the prognostic relevance of pre-operative UA levels on cancer-specific survival (CSS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection.Three hundred and fifty-seven patients with STS were included in the study. Pre-operative serum UA level was measured using an enzymatic colorimetric assay. The effect of UA levels on CSS was analyzed using Kaplan-Meier curves. To further evaluate the prognostic impact of UA levels, univariate and multivariate Cox proportional models were calculated.Among the 357 STS patients, cancer-related deaths occurred in 20 (24.7%) of 81 patients with a serum UA level Our study is the first one to demonstrate that higher UA levels are associated with positive clinical outcome in STS patients. UA levels are a simple and cost-effective test for the assessment of the prognosis of STS patients.

In breast cancer, the determination of estrogen receptor (ER) expression is crucial for the decision on therapeutic strategies. Current ER expression analysis is based on immunohistochemical (IHC) staining of ER on formalin fixed tissue sections. However, low levels of ER expression frequently escape detection because of varying sensitivities of routine histopathological laboratories. Moreover, in estimating ER by IHC the receptor protein only is tested instead of the complex underlying ER pathway, which reflects its biological activity. To overcome this limitation, we have used the microarray technology to study 56 samples of invasive ductal carcinoma. We infer a robust and reliable signature of 10 genes, which is associated with ER expression and presumably therapeutically relevant biological processes. In a meta-analysis, the signature was tested on 3 further independent microarray gene expression data sets, covering different laboratories, array platforms, and clinics. The classification based on the signature showed a very low misclassification rate. In summary, the expression of few genes is sufficient to determine ER status. Future decisions on antiestrogen based therapy in breast cancer could be based on this signature rather than on immunostaining alone.

Local recurrence of bilateral breast carcinomas is rare, but of biological interest, since it is unclear as to which tumor the local recurrence is related to, the ipsilateral or the contralateral, or whether it is an independent neoplasm. The aim of this study was to investigate the genetic relationship of bilateral breast carcinomas to each other and to their local recurrences. Eight cases of bilateral breast carcinomas, five with and three without local recurrence were analyzed using a microsatellite assay for 13 microsatellite loci. The presence of loss of heterozygosity and microsatellite instability in the various tumors was used for clonal analysis. All eight bilateral breast carcinomas showed divergent alterations in at least two microsatellite loci, which ruled out a genetic relationship. Four of five local recurrences were genetically related to the ipsilateral tumor and unrelated to the contralateral tumor. Only one local recurrence that occurred 11.8 years after the surgery of an infiltrative lobular carcinoma simultaneously with distant metastases was genetically related to the contralateral breast carcinoma. Although the number of cases in our study is limited, there is evidence that local recurrence of bilateral breast carcinoma frequently arises from the ipsilateral tumor.

A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF.Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre.After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups.Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.

Local recurrence is a serious complication of breast carcinoma that reduces quality of life and influences prognosis. The aim of this study was to determine whether local recurrences of breast carcinoma are genetically related to the primary tumours. Forty cases of locally recurrent breast carcinomas (median onset: 3.6 years after primary surgery) were analysed: 22 patients had undergone breast-conserving therapy and 18 mastectomy. Eighteen microsatellites on chromosomes 2p, 3p, 5q, 10q, 11p, 11q, 13q, 17q, 17p, 18p were amplified by PCR using fluorescent-labelled primers, automatically detected after polyacrylamide gel electrophoresis and analysed for loss of heterozygosity (LOH) or microsatellite instability (MSI). Follow-up data were available for 39 cases with a median value of 89 months. All LOH and MSI found in the primary tumours were also present in the corresponding recurrences, indicating that they are genetically related to the primary tumours and not secondary malignancies in the same breast. MSI was found in three cases, of which one harboured MSI at more than two loci. The median value of LOH per case was significantly higher in the recurrent (four per case) compared to the primary tumours (two per case; p < 0.001, Mann-Whitney test), reflecting the genotype of tumour progression. Early local recurrence was associated with specific LOH for TP53.15 (p = 0.018, log-rank test) in the primary tumours. LOH on D13S1699 or D17S855 was associated with lymph node metastases (p = 0.024 and p = 0.019, respectively; chi-square test). In addition, tumour grade, lack of oestrogen or progesterone receptor expression, young patient age and early appearance of local recurrence significantly correlated with poor survival. The development of local recurrence despite clear resection margins may result from residual DCIS distant from the invasive carcinoma, homing of circulating tumour cells, or genetically altered, histologically normal breast tissue not immediately adjacent to the invasive carcinoma.

Background Patients with testicular germ cell tumors (TGCT) have an increased risk for venous thromboembolism (VTE). We identified risk factors for VTE in this patient cohort and developed a clinical risk model. Methods In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich. Results Venous thromboembolic events occurred in 34 (5.2%) patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the strongest predictors of VTE (p

As interest in biomarkers, staging and treatment of NSCLC has dramatically increased in the past years, the opposite is true for SCLC. The number of abstracts dealing with SCLC presented during the past ASCO meetings amounts to only one-eighth of the number of abstracts on NSCLC. Some specific reasons may be responsible for the decrease in applied research in SCLC. The incidence of SCLC has dropped over the last decades mainly due to changes in smoking habits, whereas efforts to improve survival by means of systemic treatment have been stagnating for years. One of the rare appreciable improvements impacting survival of patients with ES-SCLC was made with prophylactic cranial irradiation (PCI) treatment. On the basis of recently published data, it seems that revisiting past experience with surgery in LS-SCLC may be one of the most promising perspectives to regain interest in tailored therapy in SCLC. In many malignancies targeted therapies have been successfully applied in the meantime. Developments in targeted therapy aiming at SCLC are lagging far behind, for example NSCLC. None of the abstracts concerning SCLC presented at this year's ASCO showed an improvement in survival and even worse is that only one phase III trial was presented in the lung cancer session and this trial showed negative results.

Therapeutic options for patients with advanced pretreated soft tissue sarcomas are limited. However, in this setting, sorafenib has shown promising results. We reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib within a named patient program in Austria. Twelve physicians from eight different hospitals provided records for the analysis of data. Among the 33 patients, the predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other subtypes were represented by only one or two cases. Fifteen patients presented with metastases at the time of diagnosis. Another 17 patients developed metastases later in the course of the disease (data on one patient are missing). Most of the 33 patients had undergone resection of the primary (n=29, 88%) and half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for metastatic disease had been administered to 30 patients (91%). The majority had received two or more regimens of chemotherapy (n=25, 76%) before sorafenib treatment. The use of sorafenib resulted in a median time to treatment failure of 92 days in patients with leiomyosarcoma and 45 days in patients with other histological subtypes. One-third of the patients derived benefits from treatment: four patients were documented with partial response and six with stabilized disease. In terms of treatment-related toxicity, skin problems of various degrees and gastrointestinal disturbances were frequently reported. In this retrospective analysis of heavily pretreated patients with advanced soft tissue sarcomas, sorafenib was associated with some antitumor activity and an acceptable toxicity profile.

Background Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery. Methods Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb

For years interest in developing new treatment strategies in SCLC has lagged behind the efforts addressing NSCLC. This trend could easily be followed during the ASCO 2009 meeting. Fifty-two abstracts relating to SCLC were exhibited, whereas 392 abstracts covered NSCLC research topics. None of the presentations dealing with SCLC showed successful phase III results no results were presented in the lung cancer oral presentation session. We are left with efforts in challenging the first-line standard regimen of etoposide/platinum (EP) with the irinotecan/platinum (IP) regimen as an alternative treatment choice with comparable results but different toxicity. Randomised phase II results with amrubicin seem to support the use of second-line treatment in an otherwise chemo-resistant and desperate disease. In various trials most of the investigated new targeting agents did not lead to a reproducible improvement in the outcome of SCLC patients. After ASCO 2009 it seems that progress in the treatment of SCLC requires not only a tailored medical approach, which is difficult to achieve, but also changes in therapeutical strategies in radiotherapy and surgery for LD-SCLC.

SCLC is a life-threatening disease, typically caused by cigarette smoking. The incidence has been decreasing during the past decades, probably due to changes in smoking habits. The disease is mostly diagnosed in advanced stage and therefore requires systemic treatment and radiotherapy. Chemotherapy is the most important treatment intervention and a combination of cisplatin + etoposide (EP) represents the standard of care. These tumours are very sensitive to primary treatment with remarkable response rates, although usually of short duration due to resistance. Improvement in outcomes is very hard to obtain in this disease, regardless of treatment intervention – as it has been recognised in the past years. The presentations at this year's ASCO on SCLC underline this dilemma: results of 3 large phase III trials investigating alternative combination chemotherapy regimens with irinotecan, pemetrexed and topotecan failed to improve outcome when compared to standard treatment with EP. A further report of a phase III trial underlined the current standard of 25 Gy PCI dose in LD-SCLC complete responders with no additional benefit of a higher PCI dose. Progress in the treatment of SCLC – if any – remains to be slow in the light of the presented results.

Accumulating evidence indicates an important pathophysiological role of fibrinogen on tumor cell progression and metastases in different types of cancer. The aim of the present study was to evaluate the prognostic relevance of pre-operative fibrinogen levels on clinical outcome in a large cohort of STS patients.Two hundred ninety-four consecutive STS patients were retrospectively evaluated. Cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS) were assessed using the Kaplan-Meier curves and Cox regression models. Finally, we supplemented the well-established Kattan nomogram by the fibrinogen level and evaluated the gain of predictive accuracy of this novel nomogram by Harrell's concordance index (c-index).An elevated plasma fibrinogen level was significantly associated with established prognostic factors, including age, tumor grade, size, and depth (P0.05). Furthermore, in multivariate analysis, increased fibrinogen levels were significantly associated with a poor outcome for CSS (HR=2.48; 95% CI=1.28-4.78; P=0.007), DFS (HR=2.00; 95% CI=1.11-3.60; P=0.021), and OS (HR=2.20; 95% CI=1.39-3.47; P0.001). The estimated c-index was 0.747 using the original Kattan nomogram and 0.779 when the fibrinogen levels was added.The pre-operative plasma fibrinogen level may represent a strong and independent unfavorable prognostic factor for CSS, DFS and OS in STS patients.

The purpose of this retrospective analysis was to assess efficacy and tolerability of trabectedin in soft tissue sarcoma (STS) in the routine clinical setting.Efficacy and safety data of trabectedin were retrospectively evaluated in patients with advanced STS who had started treatment with trabectedin at six institutions in Austria between January 2008 and May 2012.Data of 101 adult patients were included in the present analysis. Patients had a median age of 56 years; 59 and 41% received trabectedin as ≤2nd and ≥3rd chemotherapy line for advanced disease, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 11.6 months. Median PFS and OS were different in patients who received trabectedin as ≤2nd- or ≥3rd-line treatment: median PFS was 3.9 versus 3.6 months and OS was 15.2 versus 24.8 months, respectively. The extent and severity of trabectedin-induced toxicity were low and manageable.The activity and tolerability of trabectedin in the routine clinical setting is comparable to outcomes reported in phase II trials already published. Regardless of whether trabectedin was given earlier or later in the course of disease, outcomes did not differ in the cohort of analysed patients.

Acute intestinal pseudo-obstruction is a potentially life-threatening disease which is characterized by massive dilation of the colon or small intestine without mechanical obstruction and may develop after surgery or severe illness.We report 2 cases in which acute small intestinal pseudo-obstruction occurred after high-dose chemotherapy and autologous stem cell support. In 1 patient explorative abdominal laparoscopy was performed to rule out mechanical ileus. However, after having initiated treatment with acetylcholinesterase inhibitors a prompt small intestinal decompression was observed in both patients.Acetylcholinesterase inhibitors should be considered as an early conservative intervention in the treatment of acute intestinal pseudo-obstruction to avoid surgery of patients undergoing high-dose chemotherapy with autologous stem cell support.

Optimal treatment for patients suffering from gastrointestinal stromal tumors (GIST) is based on an interdisciplinary treatment approach. Austrian representatives of Medical and Surgical Oncology, Pathology, Radiology, Nuclear Medicine, Gastroenterology, and Laboratory Medicine issued this manuscript on a consensual base within the context of currently available and published literature. This paper contains guidelines and recommendations for diagnosis, therapy, and follow-up of GIST patients in Austria.

Twenty-five patients with advanced breast cancer (ABC) who had failed from first-line chemotherapy entered into a phase II study employing weekly 5-fluorouracil (FU) 350 mg/m2, folinic acid (FA) 500 mg/m2, and epirubicin (EPI) 35 mg/m2, for a maximum of 18 cycles. Twenty-three patients were evaluable for response. One achieved a complete response and 7 showed a partial response, for an objective response rate of 35%; 7 (31%) patients achieved a stabilization of the disease, while 8 (35%) patients progressed under treatment. The median duration of response was 6 months and median survival amounted to 10.6 months. Side effects were in general mild with grade III leukopenia in 5 patients and grade IV leukopenia in 1 patient. Other toxicity included nausea and vomiting (88%), diarrhea (26%), stomatitis (40%) and alopecia (84%), but all of them mainly restricted to WHO grade I and II. Our results suggest that the combination of high-dose FA, FU, and EPI can be safely administered in the investigated schedule and represents an attractive alternative in the search for second-line therapies that combine effectiveness with acceptable toxicity in the treatment of refractory ABC.

A case of seminoma clinical stage III, arising from the right testis and mimicking a primary pancreatic malignancy is reported.A 57-year-old male patient presented with obstructive jaundice. He suffered from recurrent abdominal pain and significant weight loss over the past 4 months. Abdominal CT scan showed a tumor in the head of the pancreas and multiple pathologically enlarged peripancreatic lymph nodes. In the laboratory findings there were signs of cholestasis and infection. A laparoscopic biopsy out of a suspicious lesion of the head of the pancreas and a surrounding lymph node was done. Histopathological examination reported metastasis of seminoma in a lymph node. Further laboratory findings showed an elevation of the human placental alkaline phosphatase (HPLAP) and urological examination revealed a suspect right testis. The patient underwent castration of the right testis and histopathological examination confirmed a seminoma. 4 cycles of chemotherapy including cisplatinum, etoposide and bleomycin led into complete response that is still ongoing.This case shows a seminoma with metastases at retroperitoneal site, mimicking a primary pancreatic neoplasm. It provides an example of the possibility of an uncommon clinical appearance of seminoma metastases and again underlines the importance of exact radiological and histopathological examination to distinguish between curable and incurable tumor.

Soft tissue sarcomas are heterogeneous tumours and relatively uncommon. There have been advances over the past years concerning pathology, clinical behaviour, diagnosis strategies and the treatment. To summarize these advances as well as making it public is one of the goals of the following consensus guidelines. But why do we need special guidelines for Austria? There are international guidelines published by the European Society of Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN). The cause is that we need an explanation of the matrix the ESMO and the NCCN gave according to our clinical practice, the local requirements and facilities in Austria. The following recommendations were drawn up following a consensus meeting of sarcoma specialists from the three high volume centres located at the medical universities in Austria. All fields of involved physicians from diagnosis to therapy worked together to know that soft tissue sarcomas are an interdisciplinary challenge and multimodal treatment is essential. For this reason, these guidelines not only explain but also give the state of the art and clear recommendations. One of the most important guidelines is that any patient with a suspected soft tissue sarcoma should be referred to one of the three university centres and managed by a specialist sarcoma multidisciplinary team. We hope that the consensus is helpful for the clinical practice and improves the quality of care for patients with soft tissue sarcomas in Austria.

Patients with stage IIIB and IV non-small cell lung carcinoma (NSCLC) harboring an activating mutation of the Epidermal Growth Factor Receptor (EGFR) Gene should be treated first-line with Gefitinib, an EGFR tyrosine kinase inhibitor (TKI). EGF receptor mutations are most common in adenocarcinomas, especially non-mucinous type, rare in squamous cell carcinomas and sarcomatoid carcinomas, and do not occur in neuroendocrine carcinomas. Therefore, the Pulmonary Pathology Working Group of the Austrian Society of Pathology, after intense discussions and in consensus with Oncologists and Pulmonologists, recommends a priori EGFR mutation analysis for all cases of adenocarcinoma, and for all other NSCLC upon clinical request. This will markedly reduce waiting time for those patients, which most likely will have the greatest benefit from EGFR TKI therapy.

Summary Background The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone. We designed a parallel-group randomised controlled trial to assess the safety and efficacy of regional hyperthermia with chemotherapy. Methods Patients were recruited to the trial between July 21, 1997, and November 30, 2006, at nine centres in Europe and North America. Patients with localised high-risk STS (≥5 cm, Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep to the fascia) were randomly assigned to receive either neo-adjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin (EIA) alone, or combined with regional hyperthermia (EIA plus regional hyperthermia) in addition to local therapy. Local progression-free survival (LPFS) was the primary endpoint. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT 00003052. Findings 341 patients were enrolled, with 169 randomly assigned to EIA plus regional hyperthermia and 172 to EIA alone. All patients were included in the analysis of the primary endpoint, and 332 patients who received at least one cycle of chemotherapy were included in the safety analysis. After a median follow-up of 34 months (IQR 20–67), 132 patients had local progression (56 EIA plus regional hyperthermia vs 76 EIA). Patients were more likely to experience local progression or death in the EIA-alone group compared with the EIA plus regional hyperthermia group (relative hazard [RH] 0·58, 95% CI 0·41–0·83; p=0·003), with an absolute difference in LPFS at 2 years of 15% (95% CI 6–26; 76% EIA plus regional hyperthermia vs 61% EIA). For disease-free survival the relative hazard was 0·70 (95% CI 0·54–0·92, p=0·011) for EIA plus regional hyperthermia compared with EIA alone. The treatment response rate in the group that received regional hyperthermia was 28·8%, compared with 12·7% in the group who received chemotherapy alone (p=0·002). In a pre-specified per-protocol analysis of patients who completed EIA plus regional hyperthermia induction therapy compared with those who completed EIA alone, overall survival was better in the combined therapy group (HR 0·66, 95% CI 0·45–0·98, p=0·038). Leucopenia (grade 3 or 4) was more frequent in the EIA plus regional hyperthermia group compared with the EIA-alone group (128 of 165 vs 106 of 167, p=0·005). Hyperthermia-related adverse events were pain, bolus pressure, and skin burn, which were mild to moderate in 66 (40·5%), 43 (26·4%), and 29 patients (17·8%), and severe in seven (4·3%), eight (4·9%), and one patient (0·6%), respectively. Two deaths were attributable to treatment in the combined treatment group, and one death was attributable to treatment in the EIA-alone group. Interpretation To our knowledge, this is the first randomised phase 3 trial to show that regional hyperthermia increases the benefit of chemotherapy. Adding regional hyperthermia to chemotherapy is a new effective treatment strategy for patients with high-risk STS, including STS with an abdominal or retroperitoneal location. Funding Deutsche Krebshilfe, Helmholtz Association (HGF), European Organisation of Research and Treatment of Cancer (EORTC), European Society for Hyperthermic Oncology (ESHO), and US National Institute of Health (NIH).

Adequate treatment of gastrointestinal stromal tumors (GISTs) is linked to an interdisciplinary treatment approach. Austrian representatives of medical oncology, surgery, pathology, radiology and gastroenterology have issued this consensus manuscript within the context of currently available and published literature. The paper contains guidelines and recommendations for diagnosis, therapy and follow-up of GIST patients in Austria.

In locally advanced inoperable patients and metastatic patients imatinib is a standard treatment. Standard dose of imatinib is 400 mg daily. Treatment should be continued indefinitely, since treatment interruption is generally followed by relatively rapid tumor progression in virtually all patients. Dose intensity should be maintained by adequate management of side effects and a correct policy of dose reductions and interruptions in the case of excessive toxicity. The standard approach in the case of tumor progression is to increase the imatinib dose to 800 mg daily with special attention to the occurrence of side effects. Patient non-compliance should be ruled out as a possible cause of tumor progression as well as drug interactions with concomitant medications. In case of progression or intolerance to imatinib standard second-line treatment is sunitinib. The drug was approved effective in terms of progression-free survival according to a 4 weeks on and 2 weeks off regimen. Preliminary data show that a continuous regimen with lower daily dose may be equally effective but possibly better tolerated. After failing on sunitinib, the patient should be considered for participation in a clinical trial of new therapeutic agents or combinations such as tyrosine-kinase inhibitors (e.g., nilotinib), sorafenib, or inhibitors of the mTOR (mammalian target of rapamycin)-pathway.

Diagnosis and treatment of gastrointestinal stromal tumors (GIST) requires an interdisciplinary treatment approach. This strategy should be reflected by the content of this article. Austrian representatives of 'GIST relevant' specialties authored this publication on a consensual base. This manuscript should be regarded as a guideline for 'GIST involved' colleagues in Austria.

The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting.ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646.404 patients were prospectively included in the bone substudy and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (-11.3%, mean difference -0.119 g/cm(2) [95% CI -0.146 to -0.091], p0.0001) and trochanter (-7.3%, mean difference -0.053 g/cm(2) [-0.076 to -0.030], p0.0001). In patients who did not receive zoledronic acid, anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine (-13.6%, mean difference -0.141 g/cm(2) [-0.179 to -0.102] vs -9.0%, mean difference -0.095 g/cm(2) [-0.134 to -0.057], p0.0001 for both). 2 years after the completion of treatment (median follow-up 60 months [range 15.5-96.6]), patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline (lumbar spine -6.3%, mean difference -0.067 g/cm(2) [-0.106 to -0.027], p=0.001; trochanter -4.1%, mean difference -0.03 g/cm(2) [-0.062 to 0.001], p=0.058). Patients who received zoledronic acid had stable BMD at 36 months (lumbar spine +0.4%, mean difference 0.004 g/cm(2) [-0.024 to 0.032]; trochanter +0.8%, mean difference 0.006 g/cm(2) [-0.018 to 0.028]) and increased BMD at 60 months at both sites (lumbar spine +4.0%, mean difference 0.039 g/cm(2) [0.005-0.075], p=0.02; trochanter +3.9%, mean difference 0.028 g/cm(2) [0.003-0.058], p=0.07) compared with baseline.Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years.

Background Death receptor 4 (DR4) and death receptor 5 (DR5) are tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) receptors that activate apoptosis via the extrinsic apoptosis pathway. DcR1 and DcR2 are decoy receptors for TRAIL that act antagonistically. Intracellular trafficking of TRAIL receptors has been described, but the role of the subcellular localization of TRAIL receptors in non-small cell lung cancer (NSCLC) progression is unclear. Methods Expression and intracellular localization of pro-apoptotic and decoy TRAIL receptors were analyzed by immunohistochemistry in 50 samples of advanced or recurrent NSCLC. Using confocal microscopy, localization of TRAIL receptors was studied in NSCLC cell lines. Results Cytoplasmic staining for all four TRAIL receptors was observed in the majority of samples. Nuclear staining was infrequent in the case of DR4 (12%) and DcR2 (8%), while DR5 and DcR1 were localized in the nucleus in 27% and 60% of samples. When overall survival was analyzed, cytoplasmic staining for DR5 in tumor cells ( P =0.025) and nuclear staining for DR5 in tumor cells ( P =0.007) were significant prognostic factors in univariate, as well as in multivariate analysis including clinicopathologic factors ( P =0.026 and 0.021, respectively). In A549, NCI-H358, and A427 NSCLC cells all four TRAIL receptors were found to be mainly located perinuclearly, but also in the nucleus. Conclusion The study for the first time shows that TRAIL receptors are found in different intracellular compartments including the nucleus in NSCLC cells and that both nuclear and cytoplasmic DR5 might predict improved survival in patients with advanced NSCLC.

Since the year 2000 second line therapy for pre-treated non-small cell lung cancer patients has been established. There are currently two chemotherapeutic agents - docetaxel (Taxotere) and pemetrexed (Alimta) - which have been approved for second line treatment in Austria in addition to the tyrosinkinase-inhibitor erlotinib (Tarceva). In randomised trials these agents have shown a clear advantage over best supportive care in pre-treated patients in terms of overall survival and quality of life. However, these compounds also cause considerable drug-specific toxicities. Therefore there is an urgent need for new treatment options with higher efficacy and a lower burden of toxicity. At ASCO 2007, results of randomised trials were presented concerning new chemotherapeutic agents, such as vinflunine as well as targeting agents such as gefitinib, without affecting outcome. Another trial comparing a standard dose of pemetrexed with a higher dose also showed no improvement in outcome. A comparison of immediate application with delayed application of docetaxel after primary treatment demonstrated improved progression-free survival in selected patients in the immediate study arm but this did not translate to a survival benefit. The results of these trials may add further treatment options to the present portfolio of agents and concepts in this setting and give some optimism for the near future. At present, no changes need to be made in the options for standard second-line treatment of NSCLC in view of the results presented at ASCO 2007.

The purpose of this study was to determine the impact of serum HER-2/neu level dynamics during the course of disease and treatment on the prognosis of patients with metastatic breast cancer. Two thousand and thirty-eight serum samples collected sequentially after disease relapse in 286 patients with metastatic breast cancer were measured by Bayer Immuno 1 trade mark assay retrospectively for serum HER-2/neu (cut-off level 15 ng/ml). One hundred and five patients (37%) presented with serum HER-2/neu continuously

TPS10602 Background: Angiogenesis plays a key role in sarcoma biology. RE, targeting VEGFR-2 and -3, and tumor cell signaling kinases (RET, KIT, PDGFR, and Raf), has recently been shown to be effective in imatinib and sunitinib-refractory GIST in a phase III trial [Demetri, Lancet 2013]. Furthermore, the Palette trial has shown that pazopanib, another anti-angiogenic agent, significantly improved the PFS without OS advantage in anthracycline-refractory STS [Van Der Graaf, Lancet 2012]. Methods: We are conducting a multinational (France, Austria and Germany) double-blind placebo-controlled randomized (1/1) phase II trial to assess the activity and safety of RE in doxorubicin-refractory STS (ClinicalTrials.gov: NCT01900743). Key eligibility criteria are: measurable disease, age ≥18, less than 4 previous lines of CT, metastatic disease not amenable to surgical resection. Applied stratification criteria are: histological types (liposarcoma, leiomyosarcoma, synovial s., and others), countries and previous use ...