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Schur, Sophie; Brodowicz, Thomas
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0233-5
Sarcomas are a rare and heterogeneous group of mesenchymal malignancies that have historically been challenging in diagnosis and treatment. In soft tissue sarcomas (STS), the recognition of different histological subtypes has made a dramatic conceptual change leading to histotype-driven targeted therapies. In gastrointestinal stromal tumors (GIST), the most important advance in the past decade was the demonstration that tyrosine kinase inhibitors (TKIs) can durably control disease and lead to remarkable treatment responses. The advent of TKIs has unquestionably changed the overall survival of patients with GIST, not only in the advanced-disease setting but also in individuals with high-risk disease. This review covers the latest clinical study highlights for STS and GIST presented at American Society of Clinical Oncology (ASCO) 2015 meeting, demonstrating the constant progress from conventional chemotherapy to histology-driven therapy approaches.
Bartsch, Rupert; Bergen, Elisabeth
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0234-4
Several important studies were presented at the 2015 ASCO Annual Meeting in the field of breast cancer. Austrian Breast and Colorectal Study Group trial 18 again indicated the importance of bone health in postmenopausal women receiving endocrine therapy and showed that denosumab, a monoclonal antibody targeting the RANK ligand, was highly active in the reduction of fracture rates in this population. In the metastatic setting, addition of palbociclib to fulvestrant nearly tripled progression-free survival in pretreated women with luminal breast cancer as shown in the randomized phase III PALOMA-3 trial. In HER2-positive breast cancer, results from a randomized phase II study suggested that T-DM1 with or without endocrine therapy may be a valuable option as neoadjuvant treatment. In this trial, pathologic complete remission rates of > 40 % were observed after only four cycles of T-DM1. The phase III ExteNET study evaluated the role of neratinib, a tyrosine-kinase inhibitor targeting HER2 and epidermal growth factor receptor, as extended adjuvant therapy after 1 year of trastuzumab; while the future role of neratinib remains still undefined, this was the first study to show an improvement in terms of disease-free survival over the current treatment standard. Finally, the MARIANNE trial showed that T-DM1 was as effective as trastuzumab plus docetaxel as first-line therapy, while dual HER2-inhibition with T-DM1 plus pertuzumab yielded no further benefit.
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0231-7
The aim of this short review is to summarize the randomized phase III trials with the highest impact on daily clinical practice relating to the field of lung cancer presented at the ASCO annual meeting 2015. With the presentation of data from the CheckMate 017 and 057 trials, comparing the anti-PD1-antibody nivolumab to standard docetaxel in the second-line treatment of patients with metastatic squamous and non-squamous non-small-cell lung cancer, immunotherapeutic strategies have finally arrived in daily routine, as the antibody treatment in these trials led to superior results concerning survival, toxicity, and response rates. However, especially in the non-squamous cohort, a heterogeneous treatment-effect of nivolumab was detected, with not all patients gaining the same benefit. To better define these subgroups by establishing robust predictive biomarkers will be of high priority in the near future. In the field of targeted therapies, the overall survival analysis from the LUX-Lung 8 trial, comparing afatinib to erlotinib in the second/third-line treatment of patients with metastatic squamous non-small-cell lung cancer, revealed a statistical significant survival-advantage for the afatinib-treatment arm. However, due to low survival-gains and added toxicity in absolute numbers, it is debatable whether this difference will change daily practice. Once again it is hoped, that the still pending biomarker analysis for this trial will be able to define a subgroup with a better risk/benefit ratio than in the overall population.
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0227-3
Immunologic tumor therapy was the leading theme of this year’s ASCO. In this context first results for check point inhibitors active in esophageal and gastric cancer were presented. Phase III trials involving c-met inhibitors however were not successful. First phase II results with regorafenib emphasize a potential role for TKI’s in gastric cancer.
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0243-3
Two “first-in” studies of colorectal liver metastases were highlighted at the 2015 ASCO Annual Meeting: the first prospective randomized trial to evaluate radiofrequency ablation plus chemotherapy [J Clin Oncol 33] and the first large randomized phase III trial to study liver-directed selective internal radiation therapy [J Clin Oncol 33]. Radiofrequency ablation plus chemotherapy appeared to have clear benefit in this setting, whereas the results for selective internal radiotherapy in first-line therapy are currently less conclusive. Colorectal tumors that lacked the ability to repair DNA—or mismatch repair-deficient tumors—were found to be highly responsive to checkpoint blockade with the anti-programmed death 1 (PD-1) drug pembrolizumab, according to data from a phase II study [J Clin Onco 33]. Taregetd therapy with dual blockade of HER2/Neu with Trastuzumab and Lapatinib proved successful in in previously treated patients with HER2/Neu-positive tumors [J Clin Oncol 33].
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0217-5
The use of circulating tumor DNA (ctDNA) as a prognostic and/or predictive biomarker has been proven in numerous studies. Recent technical advancements have improved sensitivity, specificity, and feasibility of ctDNA detection enabling innovative clinical applications. Besides its potential use as a diagnostic biomarker and the detection of recurrence or minimal residual disease, the most widespread application of the so-called liquid biopsy is real-time monitoring of treatment response and tumor evolution. Since tissue biopsies provide just a static snapshot of the tumor at the time of biopsy and do not necessarily represent the entire tumor genome, a sequential analysis of ctDNA enables an early identification of resistance mechanisms before they become clinically obvious. Furthermore, novel therapy targets that have not been present in available tumor samples might be identified. However, for an actual implementation of the liquid biopsy in clinical practice, it is essential to develop standardized pre-analytical and analytical methodologies and to resolve some outstanding question with respect to origin, biology, and dynamics of ctDNA. In this short review, the clinical utility and existing limitations of ctDNA focusing on monitoring treatment response will be discussed.
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0237-1
Historically disseminated tumor cells in solid cancers were detected by immunohistochemistry of bone marrow aspirates. Blood samples are more easily and frequently accessible and are therefore employed to detect circulating tumor cells (CTCs), a procedure termed “liquid biopsy”. CTCs are shed from tumors and a fraction of these cells is capable of establishing distal lesions. Since patients die from metastatic disease, CTCs hold potential to have prognostic significance and to indicate the success or failure of therapeutic interventions. With few exceptions, CTCs are rare cells against a large background of blood cells and need to be enriched for detection and characterization. The FDA-approved CellSearch© system relies on the selection of epithelial cell adhesion molecule (EpCAM)-positive tumor cells and is incorporated in numerous clinical studies for risk stratification and assessment of therapy. However, CTCs may have undergone (partial) epithelial-mesenchymal transition and are therefore missed by methods dependent on epithelial markers. A host of other techniques to enrich/isolate CTCs which are based on physical and/or distinct biological properties are under evaluation. Although single CTCs were linked to an increased risk of tumor progression, the actual phenotype and fraction of these cells capable of forming metastases are not known, as well as the mechanisms and kinetics of tumor cell shedding and evasion. Despite considerable progress, CTC detection methods still need to be validated and their clinical significance confirmed in larger multicenter trials before entering clinical routine practice.
Senfter, Daniel; Mader, Robert
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0245-1
Extracellular vesicles, particularly small exosomes with a size between 40 and 120 nm, contain complex information. Most importantly, exosomes may transfer this information to recipient cells and alter their cellular programme. If decoded, this information reveals ongoing malignant processes within the organism such as drug resistance or metastases formation (functional biomarker). As this information is composed of RNA, DNA fragments, proteins and metabolites, these molecules may also serve as molecular biomarker. Exosomes are generated from parental cells, frequently under disease conditions. Thus, exosomes share significant information with their origin including mutations of the malignant lesion. Tumour characteristics can therefore be retrieved in circulating exosomes, which opens a complete new approach in cancer diagnosis: the liquid biopsy.
Geltner, Christian; Errhalt, Peter
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0246-0
Pleural effusion is common in various diseases and especially malignant effusions can have rapid onset symptoms such as dyspnea, chest pain, and coughing. The diagnosis and the treatment approaches require several pleural techniques and knowledge about concomitant disease. In exudative effusions accompanying inflammatory reactions in pneumonia are the most common reasons. Malignant effusions are typically seen in lung and breast cancer patients. The differential diagnosis has to always include malignant pleural mesothelioma. The therapeutic approach is dependent on staging, symptoms, and prognosis of the underlying diseases. Techniques should include thoracocentesis, various chest drainages including indwelling permanent catheters and talc pleurodesis done by slurry instillation or by surgical approaches. This review addresses diagnosis options and treatment modalities including thoracocentesis, thoracoscopy, chest drainage, and indwelling catheters. Clear algorithms are presented.
Schuster, Herbert; Kopf, Helmut
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0232-6
Local tumor ablation either by high or low temperatures is an ever increasing local therapeutic procedure in the interdisciplinary armamentarium of anticancer therapy. As cryoablation (local cancer tissue destruction by low temperature) is technically demanding, rather expansive and thus has gained low acceptance and low distribution in interventional oncologic radiology, this paper will focus on the state-of-the-art of local tumor cell destruction by high temperatures and electroporation: radiofrequency ablation (RFA), microwave ablation (MWA), and irreversible electroporation (IRE).
Sepúlveda, Ilson; Schorwer, Max; Platin, Enrique; Delgado, Carolina; Mucientes, Pablo
2015 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-015-0241-5
We report on a patient who presented to the ear, nose, and throat (ENT) clinic with a large lesion on the left side of the face. Imaging studies revealed a large heterogeneous expansive mass in the left gonial region infiltrating the skin. The lesion was highly enhanced following intravenous contrast injection