memo - Magazine of European Medical Oncology

Pircher, Andreas

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0176-2

Pfeilstöcker, Michael

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0167-3

Eisterer, Wolfgang

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0189-x

Wellbrock, Jasmin; Fiedler, Walter

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0149-5

Leukemia arises from leukemic stem cells, which reside within the bone marrow occupying two different stem cells niches: the endosteal and the vascular niche. The maintenance of leukemic stem cells requires complex regulation mediated by many intrinsic and extrinsic signals provided by their niche cells. The interaction of leukemic and endothelial cells can occur either via direct contact through cell adhesion molecules such as selectins or integrins or signals can be transmitted by chemokines or cytokines of which stromal cell-derived factor 1 represents the most studied. Experimental studies provide evidence that targeting molecules involved in the interaction of leukemic and endothelial cells might represent a promising therapeutic target. Indeed, first clinical trials considering this concept are currently under investigation.

Steiner, Normann; Kern, Johann; Untergasser, Gerold; Gunsilius, Eberhard

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0184-2

Multiple myeloma (MM) is a hematological B-cell malignancy that has still a fatal prognosis. Although the treatments have improved, one major problem in MM is the clinical resistance to available drugs and combination therapies over time. Novel agents, such as oral proteasome inhibitors, monoclonal antibodies, second generation immunomodulatory drugs and therapies targeting the cell signaling and the tumor microenvironment are in development for the treatment of relapsed/refractory MM. In this review, we refer on the role of new strategies targeting the tumor microenvironment, especially on angiogenesis, hypoxia and other interactions between MM and bone marrow components.

Medinger, Michael; Passweg, Jakob

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0142-zpmid: 25544863

Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and antiangiogenic cytokines. This has been documented for solid tumors, and there is emerging evidence suggesting that tumor progression of hematological malignancies also depends on the induction of new blood vessel formation. Data on angiogenesis in the bone marrow of BCR-ABL1-negative myeloproliferative neoplasm patients suggest an increase of the microvessel density and vascular endothelial growth factor (VEGF) expression, and there is a relation to the JAK2-V617F status. The most important proangiogenic agent is VEGF, activating VEGF receptors 1 and 2. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities, and multiple new drugs are being tested in clinical trials. Most patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) that was not associated with a JAK2 or MPL alteration carried a somatic mutation in calreticulin (CALR). Thus, CALR mutations should be included in the next classification system for ET/PMF. This review summarizes recent advances in the basic understanding of the role of angiogenesis in myeloproliferative neoplasms and the translation of such basic findings into clinical studies.

Leonhartsberger, Nicolai

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0160-x

Several targets have been identified for the therapy of metastatic renal cell carcinoma (RCC). The recognition of hypoxia-inducible factor-α signaling in the pathogenesis of clear-cell RCC has led to widespread study of angiogenesis inhibitors. Understanding this molecular pathogenesis of RCC led to a rapid evolvement of new systemic therapies, with seven targeted therapies approved and several more agents in late-stage clinical development. Due to the results of the currently used targeted therapies, the progression-free survival could be prolonged and the overall survival in sequential therapy can reach up to 40 months. The development of validated guidelines for sequential treatment or combination of targeted therapy remains a current challenge.

Heidegger, Isabel; Pircher, Andreas; Bektic, Jasmin

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0187-z

Prostate cancer is the most common male cancer and one of the most common causes of cancer death among men in European countries. In the last years, a large number of new drugs for treatment of castration-resistant prostate cancer (CRPC) have been approved, others are still in an advanced stage of clinical testing. In this review, we provide an overview on new substances which act via modulation or inhibition of angiogenesis. Results and limitations from clinical studies as well as future needs for improvement of those agents in CRPC are critically discussed.

Reiter, Michael; Hoffmann, Jana; Kleber, Florian; Schumich, Angela; Peter, Gerald; Kromp, Florian; Kampel, Martin; Dworzak, Michael

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0172-6

Minimal residual disease (MRD) is of high prognostic value in risk stratification in childhood acute lymphoblastic leukaemia. Flow cytometry (FCM) was shown to yield reliable results in MRD measurement. However, the interpretation of FCM data relies largely on operator skills and experience. While sample preparation, antibody panels, staining procedures and flow cytometric acquisition can be standardized, easily controlled and be made available worldwide, the availability of experienced operators represents the current bottleneck to a growing number of laboratories to the benefit of an increasing number of patients with leukaemia. Currently, international paediatric studies—throughout Europe, South America, to Australia—aim at stratifying the treatment according to the FCM-MRD methodology. The measurements are still operator-dependent leading to substantial costs regarding training and quality control. This article introduces a new European Union-funded project (AutoFLOW) aiming at the standardization and automation of FCM-MRD analysis by machine-learning technology.

Jain, Neelesh; Chakrabarti, Amrita; Sengupta, Kasturi; Chakrabartty, Joydeep

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0165-5

Gone are the days when a patient with acute myeloid leukaemia (AML) would die waiting for a suitable donor for allogenic stem cell transplantation. With improved supportive care, we can now confidently provide unrelated donor transplant to most patients. The adult patient who does not have a suitable donor can be considered to have a haploidentical transplant or a cord transplant. In fact, a combination of cord and haploidentical transplant can be thought of in carefully selected patients. With new-age molecular diagnostics incorporating genetic mutational analysis along with the cytogenetic model, minimal residual disease monitoring and novel transplant techniques, we can now confidently say that we are able to provide transplantation to most patients. In this review, we will shortly go through the prognostics in AML followed by the transplant options in patients who lack a suitable matched donor—either family or voluntary unrelated.

Pall, Georg

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0183-3

The aim of this short review is to summarize some of the most important abstracts relating to the field of head and neck cancer presented at the ASCO Annual Meeting 2014. An Italian study group presented the first randomized phase III trial showing improved survival for patients with locally advanced squamous carcinoma of the head and neck using induction chemotherapy as an add-on to definitive local chemoradiotherapy or radiotherapy plus cetuximab. As these data are in contrast to already published trials and many questions around this treatment strategy remain unanswered, the definitive place of sequential therapies within the treatment algorithms remains to be defined. With the phase Ib data on the therapeutic efficacy of the anti-PD-1 antibody pembrolizumab released at the ASCO meeting we now for the first time have clinical evidence that modern immunotherapeutic strategies are worth studying in head and neck cancer. Finally, the phase III SELECT trial establishing lenvatinib as another therapeutic option in the treatment of radioiodine-refractory thyroid cancer will be discussed. In this study the experimental compound was shown to improve response rate and progression free survival with an acceptable toxicity profile.

Ploner, Ferdinand

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0180-6

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.

Bartsch, Rupert; Bergen, Elisabeth

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0179-z

While in general, not immediately praxis changing, results of various relevant clinical trials were presented at the 2014 ASCO Annual Meeting. Indeed, the ALTTO study provided first (albeit negative) data on the activity of dual Her2 inhibition with trastuzumab and lapatinib (either sequentially or concomitantly) in the adjuvant setting, while a combined analysis of the SOFT and TEXT studies suggested, for the first time, that a combination of ovarian function suppression (OFS) plus exemestane might be superior to OFS plus tamoxifen in premenopausal early breast cancer patients. Results of the POEMS trial investigating the role of the gonadotropin-releasing hormone-analog goserelin in the prevention of chemotherapy-induced amenorrhea led to lengthy debates, as the trial reported a survival benefit in hormone-receptor-negative breast cancer patients receiving goserelin. A subgroup analysis of German Breast Group trial GeparSixto as well as several other phase II trials again emphasized the role of carboplatin in neoadjuvant therapy of triple-negative breast cancer patients. These and other studies will be reviewed within this article.

Eisterer, Wolfgang

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0190-4

Studies presented on metastatic colorectal cancer at this year’s ASCO focused on RAS as a predictive biomarker for anti-epidermal growth factor receptor (EGFR)-directed therapies. Extended RAS analysis for the CRYSTAL study were presented for the first time and showed improved benefit in terms of overall survival, progression-free survival and response rate within the all RAS wild-type cohort. Together we already known results from other anti-EGFR-directed studies it can be stated that expanded RAS status assessment is a prerequisite for the use of an anti-EGFR antibody. The German AIO group showed results of their maintenance study AIO-0207 contributing to the body of evidence of maintenance therapy. The current evidence from two phase-III studies suggests that maintenance therapy with capecitabine plus bevacizumab is a valid option after induction therapy. Eagerly awaited were the first results of the CALGB80405-trial using either bevacizumab or cetuximab in combination with first-line chemotherapy. No difference in OS could be observed between the two treatment arms in KRAS wild-type patients.

Weinlich, Georg

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0182-4

The incidence of cutaneous melanoma has been increasing worldwide. Although only 5% of all skin cancers are cutaneous melanoma, more than 90% of all skin cancer-related deaths are attributed to this tumour. The prognosis of metastatic melanoma remains poor with conventional chemotherapy, with survival rates between 6 to 9 months. Even combination regimes (polychemotherapy, poly-chemo-immunotherapy) failed to show a significant survival benefit.

Horak, Peter

2014 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0177-1

Genetic profiling of cancer may lead to a better understanding of its intra- as well as intertumoural heterogeneity as well as targeted, patient-oriented cancer therapy. Due to the recent advances in molecular biology, important steps towards this goal have been accomplished. Among others, several large profiling analyses of gynaecologic malignancies have been completed and published recently. Most notably, these comprehensive molecular analyses expose a high degree of cancer complexity and heterogeneity. Integration of this data into clinical practice will result in new tumour classifications and possibly change our understanding of cancer pathogenesis and thus necessitate the development of novel diagnostic and therapeutic algorithms.