memo - Magazine of European Medical Oncology

Kostron, H.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0130-x

Hainfellner, J. A.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0131-9

A primordial goal of neuropathological brain tumour research is the translation of molecular biomarker candidates into clinical use. Unfortunately, there is currently no general agreement with regard to the sequence and nature of steps that need to be taken to warrant efficient translation of prognostic/predictive biomarker candidates into clinical use. Consequently, the translational path is longwinded for most candidate biomarkers, and only a few candidates have translated swiftly into clinical use. In the molecular era, Neuropathology as medico-academic speciality is challenged to make biomarker translation more efficient. To this end, translational brain tumour biomarker research endeavours need to adopt a systematic stepwise path. A reasonable stepwise path for candidate biomarkers comprises: step 1: profound testing of analytical performance; step 2: verification of clinical performance; step 3: consensus-based definition of best-practice protocols for laboratory testing and interpretation of test results. To shape these changes it seems crucial that Neuropathology is actively involved in the design of research protocols of prospective therapy trials with companion translational research.

Kostron, H.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0135-5

Maligant gliomas occur at an incidence from 2 to 10/100,000 (Japan vs. Sweden) constituting up 50% of all patients suffering from brain tumours. Despite all therapeutic approaches the median survival for glioblastomas is 15 months and for anaplastic gliomas Grade III are 30 months. Surgery is the first step in the therapeutic cascade of the patients. There is still debate about the surgical extent of resection and whether a most radical resection is more beneficial than an extended resection. Image-guided neurosurgery has become the gold standard for interventions in the brain and helps to define the radiographic limits of the tumour to maximize safety and the extent of resection whilst minimizing damage to eloquent brain tissue. Tumour removal in eloquent areas such as speech area will be performed in local anaesthesia as an awake operation. A precise presurgical examination is therefore mandatory. This includes all information gathered from functional diagnostics (fMRI, fibretracking and 3D reconstruction) and metabolic information from FET/FDG PET. Age, Karnofsky performance and histology as well as radical removal have significant influence on overall survival. Adjuvant radiotherapy and chemotherapy with Temozolemide have further improved the outcome significantly. The 2-year survival has reached 28% in most recent studies. Experimental surgical therapies are in clinical trials and will be introduced to general clinical practice in the near future. These include intratumoural convection-enhanced instillation of immuntoxins and radiopeptids, photodynamic therapy and direct instillation of new formulations of chemotherapeutic drugs. These new developments in the treatment of malignant brain tumours allow designing an individual neuro-oncological treatment concept to enhance overall survival and quality of life.

Hau, P.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0127-5

Temozolomide (Temodal®) an alkylating oral cytotoxic drug, has significantly improved overall survival of patients suffering from malignant brain tumours and has brought new initiative into the treatment of these tumours. Whereas Temozolomide (TMZ) is approved for the treatment of first-line glioblastoma and the relapse of glioblastoma and anaplastic glioma and is compassionately used in other settings including the first-line therapy of anaplastic glioma and low-grade gliomas and the relapse of low-grade gliomas, medulloblastomas/PNETs and primary CNS-lymphomas are frequently treated with TMZ in a compassionate setting, especially if they relapse. The various entities are currently undergoing different regimens. These will be discussed in detail.

Pichler, J.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0124-8

Malignant gliomas are the most frequent malignant brain tumours and the median overall survival is still only 15 months despite combination of radio and chemotherapy and introduction of novel molecular-based therapies. We report on our experience with the antiangiogenic therapy with Bevacizumab (Avastin®) 10 mg/kg in combination with Irinotecan 125 mg/m2 as second-line chemotherapy in 32 patients with recurring high-grade gliomas. The results in 32 patients demonstrated radiological response in 68%, 19 completely evaluable patients (11/19 had more than one relapse) had a median TTP of 26 weeks, a 6-month PFS of 58%, a median OS of 11 months and a 9-month OS of 68%. Toxicity of this treatment was mild; no wound healing disorder or tumour bleeding appeared. Steroid dose could be significantly reduced. This concept of combination of anti-angiogenic and cytostatic agents is currently the most promising second-line therapy. Finally, an outlook to future strategies is given.

Maier, R.; Eiter, H.; Burger, R.; De Vries, A.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0125-7

The prognosis for patients suffering from malignant gliomas remains dismal. We report on 10 patients with recurring or progressing high-grade gliomas who were treated at our institution with Bevacizumab alone or in combination with cytostatic drugs over the last 2 years. The survival time from the start of the VEGFR antibody therapy on average was 18 weeks (10–30 weeks) and after Avastin was discontinued patients lived an average of 7 weeks (1–14 weeks). The above results support further studies of this very promising drug in the form of randomized studies of malignant glioma. In the primary therapy concept and in the case of recurrence the best combination Bevacizumab with cytostatics, radiation therapy or other targeted therapies have to be clarified.

Cartes-Zumelzu, F.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0126-6

New developments in the technologies of MRI provide a new armamentarium for diagnosis, for therapy guidance and for the prediction of prognosis. Furthermore new techniques are incorporated into MRI, which allows to incorporate tumour radiology with tumour biology.

Putzer, D.; Waitz, D.; Donnemiller, E.; Virgolini, I.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0129-3

PET imaging (FDG-PET, FET-PET) allows for a combined interpretation of different metabolic properties of brain tumors and thereby assists in the grading of brain tumors, diagnosis of spread of disease and in the diagnosis of suspected recurrence, as well as tumor progression. PET furthermore has a high significance in evaluation of therapy and response to therapy. High uptake of brain tumor tissue is also shown by 68Ga-DOTA TOC, which is performed prior to treatment with radiolabelled somatostatin-receptor analogs. In combination with temozolomide, promising results in single patients were observed. The diagnostic potential of this diagnostic tool is discussed in depth.

Elandt, K.; Marosi, C.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0128-4

We report on a patient with relapsed haemangioblastoma with multiple lesions disseminated intracranially and in the spinal cord. The patient, a 33-year-old male presented after repeated surgical resections and after exhaustion of radiation therapy to our outpatient department in March 2008. With immunohistochemistry, we demonstrated widespread expression of VEGFR-2 on the cell mebranes of the tumour cells. Therefore, we started systemic therapy with Sorafenib (NexavarR) with the intention to target VEGFR-2 with dose escalation up to 800 mg/ day. Sorafenib was generally well tolerated. There were no haematological side effects, but the patient developed hand–foot syndrome grade 2 after five months. This necessitated topical therapy, low dose of systemic steroids and a drug holiday from Sorafenib. Sorafenib could be reintroduced after a month and the medication is still ongoing. The Control MRI after 15 months of Sorafenib showed persisting disease stabilization.

Buchroithner, J.; Pichler, J.; Sonnberger, M.; Weis, S.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0137-3

We present the case report of a 50-year-old man suffering from a frontal meningothelial meningioma (WHO grade I) with malignant transition and metastases in the lung, scalp, skin and bone. Fractionated radiation, though a fundamental part of therapy in progressive and malignant meningiomas, did not prevent tumour progression in our case. In our case, the tumour progressed under the application of Sandostatin® and salvage therapy with Avastin® and Campto®. Therapeutic strategies are reviewed and discussed.

Clausen, Johannes

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0142-6

Gunsilius, Eberhard

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0155-1

Troch, M.; Raderer, Markus

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0139-1

Mucosa-associated lymphoid tissue (MALT) lymphoma is amongst the most common lymphoma entities and comprises about 7% of all newly diagnosed NHL. Roughly 50% of all MALT lymphomas are located in the stomach, where a pathophysiological link with Helicobacter pylori (HP) with consecutive response to HP eradication therapy has been established. In view of this, HP eradication has become the standard approach to patients with localised disease and signs of HP infection. Recent data, however, have suggested that also HP-negative patients might benefit from antibiotic treatment. On the other hand, an unexpectedly high rate of autoimmune diseases, e.g. Hashimoto’s thyroiditis or Sjogren’s syndrome has been found in gastric MALT lymphoma, and such patients do not respond to HP eradication in the large majority. In case of non-response to antibiotics the standard approach in such patients is currently not clear. Both radiation as well as chemotherapy has shown promising results, and currently there is only one randomised study, which nevertheless suggests superiority of chemotherapy in terms of event-free survival at 10 years. The optimal chemotherapeutic regimen, however, has not been established yet, although various agents and combinations have demonstrated high activity, albeit in small trials. In view of this, patients with gastric MALT lymphoma unresponsive to antibiotics should be included in clinical trials.

Hopfinger, Georg; Herling, Marco

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0145-3

Peripheral T-/NK-cell lymphomas/leukaemias (PTCL/L) comprise a heterogeneous group of haematopoietic tumours, which originate from mature T-/NK-cells, and constitute less than 15% of all non-Hodgkin lymphomas (NHL) in adults of the Western hemisphere. These neoplasms often present at advanced stage at the time of diagnosis, and most commonly have an aggressive clinical course requiring prompt treatment. In contrast to B-cell NHL, in which substantial clinical progress has been made with the introduction of monoclonal antibodies such as Rituximab, no comparable advances have been seen in PTCL/L. Moreover, no PTCL/L standard therapies have been established so far, and most PTCL/L have been treated in analogy to B-cell NHL. However, for PTCL/L these adapted protocols generally result in a much lower efficacy along with frequent relapses. Approximately 30% of PTCL/L even show a primary refractory behaviour. In this review, the diagnostic features of the most common entities of PTCL/L and a proposed workup are presented. Moreover, currently applied therapeutic strategies like conventional chemotherapy or high-dose therapy as well as new drugs like histone deacetlyase inhibitors or immune modulatory reagents are discussed. We once more conclude that as no efficient standard therapy has been established for most PTCL/L subtypes, treating patients with PTCL/L in clinical trials is strongly recommended.

Steurer, Michael; Schmidt, S.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0144-4

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Europe and North America, and mainly affects older individuals. It has a very variable course, with survival ranging from months to decades. Major progress has been made in the identification of molecular and cellular markers that may predict prognosis in CLL patients. However, these advances have raised new questions about the biology, prognosis and management of CLL. Available treatments generally induce remission, although nearly all patients relapse and CLL remains an incurable disease. Advances in molecular biology have enhanced our understanding of the pathophysiology of the disease and, together with the development of new therapeutic agents, have made CLL management more rational and more effective. This review describes the recent advances concerning the prediction of prognosis involving novel molecular genetic techniques and treatment of CLL patients suggesting an evidence-based approach according to individual risk factors.

Illerhaus, Gerald

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0149-z

Primary NHL of the CNS (PCNSL) is a rare form of extranodal non-Hodgkin’s lymphoma (NHL) whose incidence has been increasing for the last three decades. More than 90% of PCNSLs are aggressive NHL of the B-cell type. Diagnostic measures and therapeutic management differ from those of other extranodal NHL. The prognosis is poor despite initially excellent responses to steroids and radiotherapy (RT). Adding methotrexate (MTX) to RT has improved the prognosis of PCNSL patients, although most eventually relapse. Early dose-intensified chemotherapy and peripheral stem-cell transplantation have shown high efficacy in clinical trials in younger patients. In treating elderly patients with PCNSL, the high risk of neurotoxicity should be considered; systemic chemotherapy without RT is recommended in those patients. The monoclonal antibody rituximab has produced promising results in small cohorts, but its value remains unproven. Secondary CNS lymphoma is associated with a fatal prognosis in most patients, and effective treatment has not been defined; however, PCNSL treatment strategies may be considered in those patients.

Zwick, C.; Murawski, N.; Pfreundschuh, Michael

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0157-z

Over 30 years ago, the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was demonstrated to induce complete remissions and long-term disease-free survival in a considerable proportion of lymphoma patients. Since then many attempts to improve results by modifications of CHOP using escalated doses, additional drugs or the alternative use of putatively non-cross resistant chemotherapy regimens failed in randomized trials. While dose escalation strategies including high-dose approaches necessitating stem cell support have not yet unequivocally been demonstrated to be superior to a base-line CHOP-21, dose-dense bi-weekly modifications (CHOP-14) with growth factor support (G-CSF) improved the outcome of young and elderly patients with aggressive lymphomas compared to CHOP-21. A substantial improvement of treatment results has also been achieved by the implementation of rituximab into treatment protocols. Although not formally established in young patients with poor-prognosis, the combined immuno-chemotherapy with CHOP and rituximab has become an accepted standard for the treatment of diffuse large B-cell lymphoma (DLBCL) worldwide. For patients >60 years of age 6 courses CHOP-14 using G-CSF with rituximab (R-CHOP-14) followed by two additional courses of rituximab yielded the best treatment results without a relevant increase in toxicity compared with CHOP-21. For younger low-risk patients (aaIPI 0,1) 6 courses R-CHOP-21 are the standard treatment. Young high-risk patients (aaIPI ≥ 2) should be treated with dose-dense regimens within clinical trials.

Willenbacher, Ella; Kantner, Johanna; Weyrer, Walpurga; Nachbaur, David; Prommegger, Rupert; Strasser, Ulrich; Schwaighofer, Hubert; Gunsilius, Eberhard

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0154-2

Hypochromic, microcytic anaemia due to iron deficiency is usually caused by blood loss due to gynaecologic or gastrointestinal diseases. If no source of bleeding can be found using routine endoscopy and gynaecologic evaluation, a more detailed diagnostic workup must be performed before iron supplementation “ex juvantibus” is initiated. Here, we present a patient with progressive iron deficiency anaemia despite iron supplementation caused by bleeding due to infiltration of the small intestine by a diffuse large B-cell lymphoma. The diagnostic workup as well as the differential diagnosis and therapeutic approach in such rare cases will be outlined.

Haslbauer, F.; Fiegl, Michael

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0143-5

Bisphosphonates are broadly used in cancer metastasizing to the bone with the goal of preventing or delaying skeletal complications, which may dramatically deteriorate the status of the patient and course of disease. Zoledronate is approved for the prevention of skeletal morbidities in multiple myeloma, skeletally metastasized prostate cancer and other solid tumours; clodronate, ibandronate and pamidronate are approved in this setting in myeloma and breast cancer. Furthermore, pamidronate, ibandronate and zoledronate are licensed in the treatment of hypercalcaemia of cancer. Not unexpected, pain relief, looked for as a secondary objective in most of the studies, was observed in many instances. This review briefly summarizes the aspects of pain reduction achieved by bisphosphonates in cancer. Furthermore, original data on the benefit in pain reduction of high-dose ibandronate following a so-called “loading dose concept” is presented.

Kraft, Birgit; Kress, H.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0148-0

Plant material of Indian hemp, Cannabis sativa, was used throughout millennia for the production of fibres and for recreational and medical purposes. Scientific research in the field of cannabinoids has led to the discovery of a new lipid signalling system in humans and animals, the endogenous cannabinoid system with specific receptors and physiological ligands. The endocannabinoid system now appears as a relevant modulator of physiological functions not only in the central nervous system, but also in the endocrine network, the immune system, the gastrointestinal tract and the reproductive system. It is involved in numerous biological processes including reward-reinforcing effects, memory, energy metabolism and pain processing. Promising targets for medical use of cannabinoids include the alleviation of nausea and vomiting, the relief of anorexia and weight loss in HIV and cancer patients, the easing of different types of pain and muscle spasticity. But cannabinoid effects in clinical trials on pain, weight loss, nausea and vomiting were often only modest and hampered by the psychotropic side effects of the available compounds. Therefore, cannabinoids are still not first line therapeutics for these symptoms, but they are nevertheless a useful adjuvant treatment option for palliative care patients by alleviating more than one symptom, improving the quality of life in chronic pain and cancer patients.

Sztankay, Arpad

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0156-0

Percutaneous radiotherapy is highly effective as a part of an interdisciplinary approach in the treatment of cancer-related chronic pain. Overall response rates of 70–90% and complete pain relief rates of 40–50% have been reported in numerous retrospective and randomized clinical trials. Beside the analgesic effect, radiation therapy enables the restoration of bony structure and musculoskeletal function, improves patients’ mobility and quality of life. The objective of this publication is to give a short review over the role and importance of radiation therapy in the palliative management of patients with cancer-associated pain.

Peters, Christina

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0146-2

The mission of the European Group for Blood and Marrow Transplantation (EBMT) is to promote and facilitate access to state-of-the art knowledge and develop new strategies in all fields of haematopoietic stem cell transplantation (HSCT). The EBMT Paediatric Diseases Working Party aims to reach those goals for children and adolescents who undergo this procedure. In addition the PD WP acts as platform for multinational cooperation to meet the specific needs of young patients before, during and particularly after haematopoietic stem cell transplantation.

Seidel, M.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0140-8

This report includes highlights of sessions on haematopoietic stem cell transplantation (HSCT) and other immunologic treatment options for patients with inherited metabolic disorders, autoimmune diseases, immunodeficiencies and few other main topics of the 2009 annual EBMT meeting. Although chosen for their relevance for paediatricians working in the fields of haematology/oncology, immunology and inborn errors of metabolism, due to the occurrence of multiple parallel lectures, this article may only touch a selection of main topics and does not claim to be a complete conference report. Citations of the discussed conference papers are referred to by their presentation number as indicated within the congress abstract book, the Supplemental issue of Bone Marrow Transplantation Volume 43 S1 [1]. A separate report on the EBMT Paediatric Diseases Working Party is presented in this issue of memo [2].

Zielinski, Christoph; Brodowicz, Thomas; Just, Dagmar

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0150-6