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Willenbacher, Wolfgang; Willenbacher, Ella
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0028-x
In advanced Hodgkin’s disease, a new standard of therapy was defined by the results of the HD15 trial where 6 cycles of therapy according to the BEACOPPescalated regime translated into an impressive superior longterm survival compared to more intensive alternative approaches due to reduced toxicity and less secondary malignancies. Furthermore, PET guided allocation of consolidating radiotherapy to residual masses avoided unnecessary radiation in two-thirds of patients in the HD15 trial. Excessive radiotherapy was also proofed to be detrimental in early stage disease in the framework of the NCIC CTG/ECOG HD.6 trial. Rituximab was shown to be an effective, although not curative treatment in the early “Nodular lymphocyte predominant Hodgkin’s Lymphoma” (NLPHL) subtype in several series. The remaining challenge in Hodgkin’s disease is the optimisation of therapy in elderly patients, the only patient subgroup still underperforming. In aggressive lymphomas, no definite changes of therapeutic standards could be deduced from this year’s ASH meeting while multiple new therapeutics are still in phase I and II studies.
Hopfinger, Georg; Merkel, Olaf; Melchardt, Thomas; Greil, Richard
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0013-4
Treating peripheral T-cell lymphomas (PTCL) remains a clinical challenge harbouring an often aggressive course and furthermore, no standard therapy is established. In more detail, PTCL comprises a heterogeneous group of haematological tumours constituting less than 15 % of all non-Hodgkin’s lymphomas (NHLs) in adults in the western hemisphere. The following short review will provide an up-date based on data presented at ASH meeting 2011 in PTCL providing improved understanding of patho-mechanism and further development of more specific therapy options.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0041-0
At the annual meeting of the American Society of Hematology (ASH) 2011, the focus in the field of chronic lymphocytic leukemia (CLL) and indolent lymphomas was again rather the translation of basic research results into early clinical trials than introducing new treatment standards. Although still at an early phase in the process of drug development, the results achievable with the Bruton’s tyrosine kinase inhibitor ibrutinib (formerly PCI-32765) in CLL and mantle cell lymphoma (MCL) are promising. Concerning clinical practice, new or updated results of trials exploring lenalidomide as well as new monoclonal antibodies (obinutuzumab, ofatumumab) in CLL/indolent lymphoma underscore the clinical value of these drugs, but their definite place in the respective treatment algorithm still needs to be defined.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0029-9
The approval of dasatinib and nilotinib for first line treatment of chronic myeloid leukemia (CML) in chronic phase (CP) opened new therapeutic options. However, their role in this setting is yet undefined and additionally recent landmark studies have laid ground to re-discuss which response milestones are relevant for treatment guidance. Thus, updated data on these issues at last year’s ASH meeting were expected to potentially hint to what the new management standards might be. This short review briefly summarizes the respective evidence for (a) the outcome predictive value of early and deep molecular responses, (b) the superiority of second generation tyrosine kinase inhibitors (TKIs) to imatinib with regard to cytogenetic and molecular response rates, (c) the (yet) lacking proof of a survival benefit of second generation TKIs and (d) the role of new TKIs and alternative treatment strategies. Chronic myeloid leukemia (CML) has become a paradigm for targeted medicine; however, despite their impressive therapeutic success, TKIs offer disease control rather than disease eradication. The development of second generation TKIs broadened therapeutic options and consecutively disease management recommendations focused on response monitoring to guide change of treatment upon patient’s individual failure to respond. This short review will focus on ASH updates on second generation TKIs in first line treatment, potential future definitions of response milestones, and briefly on new TKIs and alternative TKI treatment concepts.
Pfeilstöcker, Michael; Stauder, Reinhard
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0036-x
The recent landscape of myelodysplastic syndrome (MDS) diagnosis and treatment is changing due to research resulting in a deeper insight into the pathobiology of the disease consequently being translated into new treatment approaches. Recent developments in MDS research published in the last year as well as data presented at ASH 2011 are covered in this review.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0020-5
Treatment strategies for acute myelogenous leukemia (AML) will be increasingly directed by molecular and cytogenetic disease features. However, drugs targeting single molecular checkpoints have shown limited success in AML. Thus, cytotoxic chemotherapy and allogeneic stem cell transplantation remain the mainstay of AML therapy, besides the emerging role of epigenetic concepts mainly represented by hypomethylating compounds. Therefore, cooperative concepts are needed in the future, integrating both cytotoreductive and molecular-targeted, as well as immunotherapeutic treatment approaches. To come up to the complexity of both molecular pathomechanisms and resulting treatment modalities, patients with AML should be treated within appropriately designed clinical studies whenever possible.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0045-9
Primary central nervous system lymphoma (PCNSL) is a rare type of lymphoma that requires a specialised approach to management. An initial evaluation should determine the extent of disease within the CNS compartment and must exclude the presence of systemic lymphoma. Methotrexate (MTX)-based chemotherapy is the standard of care but questions remain about the optimal drugs for use in conjunction with MTX as well as the best approach to consolidation. Furthermore, several special populations may require a modified approach to therapy.
Rosenfeld, Myrna R.; Dalmau, Josep
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0034-zpmid: 23264806
Immune-mediated paraneoplastic neurologic disorders (PND) may affect any part of the nervous system, and can mimic many noncancer associated disorders. The availability of diagnostic tests based on the presence of specific anti-neuronal antibodies facilitates diagnosis and can suggest treatment strategies. Once thought to be poorly responsive to therapies, it is now recognized that there is a subgroup of PND, mostly associated with antibodies to antigens on the neuronal cell surface that are highly treatment responsive. For all PND, identification and treatment of the underlying tumor is the most effective step in the potential control or stabilization of the neurological disorder.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0030-3
Many potential biomarkers have been proposed for brain tumors, but only few have been translated into actual clinical use yet. Here, the most commonly used biomarkers in adult neurooncology including 1p/19q codeletion status, O6-methylguanine-methyltransferase (MGMT) promoter methylation status, isocitrate dehydrogenase (IDH) mutation status, and v-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E mutation status are briefly discussed with a focus on their clinical utility.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0038-8
Meningeal carcinomatosis commonly referred to as carcinomatous meningitis (CM), is the third most common central nervous system (CNS) metastatic complication of systemic cancer and is the most morbid of CNS metastases. The disease is challenging to treat for a variety of reasons not least are challenges in making a diagnosis of CM as well as the lack of standardized treatment due to the relative paucity of clinical trials addressing treatment of CM. A diagnosis of CM is achieved by a clinically relevant history and examination, CSF analysis that includes cytology, and neuroimaging consistent with radiographic CM. Treatment following staging of CNS disease (neuraxis imaging and radio-isotope CSF flow study) in appropriate patients (defined as limited extent of disease and reflected in a high performance status) includes systemic chemotherapy for radiographic bulky CSF disease, radiotherapy to sites of symptomatic disease, radiographic bulky disease or sites of CSF flow obstruction, and intra-CSF chemotherapy (primarily methotrexate, cytarabine, or thiotepa). Notwithstanding aggressive treatment, the majority of patients survive < 3 months suggesting patient selection for treatment is critical as is the need for clinical trials utilizing novel therapies.
Schuknecht, Bernhard; Baráth, Krisztina; Hofer, Silvia
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0046-8
Novel therapies of central nervous system (CNS) malignancies have evoked the demand to increasingly integrate dedicated imaging techniques into the diagnostic work-up and treatment evaluation in neuro-oncology. In primary and secondary malignancies of the CNS, advanced neuroimaging techniques enable non-invasive assessment of tissue microstructure, cellular and vascular proliferation and capillary permeability. Furthermore, eloquent cortical areas in the vicinity of tumours and the course of white matter pathways are rendered visible to facilitate surgical therapy.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0012-5
Till date, no breakthrough for systemic therapy of recurrent meningiomas has been achieved. The multitude of optional drugs shows that none of them so far could become a standard of care. On the other hand, although the disease is rare, each neurooncological centre has some patients with unmet treatment needs. Cohort studies should be able to answer the question whether meningiomas occur more rarely or do not become symptomatic in individuals undergoing treatment with statins, glitazones, or calcium channel blockers. If found effective, such drugs would be suitable as first line treatment in patients with grade I recurrent meningiomas, because for these indications most probably the long treatment periods appear necessary. For patients who recur with such drugs, targeted therapies could represent further treatment options, whereas cytotoxic drugs with severe side effects such as trabectedin could perhaps be investigated for recurrent malignant meningiomas after all other options.
Bent, Martin J.; Snijders, Tom J.; Bromberg, Jacoline E. C.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0014-3pmid: 23864911
Low grade gliomas affect predominantly young adults, and have a relatively favorable prognosis compared to grade III and grade IV gliomas. The challenge for an optimal management of these patients is to find the balance between an optimal survival and the preservation of neurological function including cognition. Because all medical treatments may induce side effects, in young and nearly asymptomatic patients the choices can be difficult. This review summarizes the current strategies: a watch-and-wait policy, surgery, chemotherapy, and radiotherapy.
Kool, Marcel; Korshunov, Andrey; Pfister, Stefan M.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0037-9pmid: 23864912
Medulloblastoma encompasses a group of aggressively growing cancers that arise either in the cerebellum or brain stem. They present primarily in children, with 80–85 % of medulloblastomas being diagnosed in patients of 16 years and younger. In adults, medulloblastomas are rare and account for less than 1 % of intracranial malignancies. Due to the low incidence of medulloblastoma in adults, the biology and genetics of adult medulloblastomas have long been poorly understood. Many centers therefore still treat adults either by radiotherapy only or by using glioblastoma protocols (both often noncurative), or with standard pediatric medulloblastoma regimes (often associated with dose-limiting toxicity).Current clinical staging systems discriminate between standard-risk or high-risk patients based on clinical and histological parameters. However, clinico-pathological features often fail to accurately predict treatment response. In children, molecularly defined risk assessment has become important to improve survival of high-risk patients and to decrease treatment-related toxicity and long-term sequelae in standard-risk patients. However, several recent studies have shown that adult and pediatric medulloblastomas are genetically distinct and may require different algorithms for molecular risk stratification. Moreover, four subtypes of medulloblastoma have been identified that appear at different frequencies in children and adults and that have a different prognostic impact depending on age. Molecular markers such as chromosome 10q and chromosome 17 statuses can be used for molecular risk stratification of adult medulloblastoma, but only in a subgroup-specific context. Here we present an overview of the current knowledge of the genomics of adult medulloblastoma and how these tumors differ from their pediatric counterparts.
Marosi, Christine; Flechl, Birgit; Oberndorfer, Stefan
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0044-x
Patients with glioblastoma multiforme (GBM) are confronted with a very serious disease and suffer sooner or later from various physical, psychic, cognitive, and behavioral symptoms. This is a big challenge, not just for the patients, even their (caring) family members are forced to deal with this new life-changing situation. Studies investigate symptoms and circumstances of GBM patients during their End-of-Life phase. It is out of discussion, that patients with GBM and their family members should be prepared for the inevitable End-of-Life phase very early in the disease, however, presently there are neither existing guidelines for treating physicians, nor educational programs for caring family members available.
Dudás, József; Zwierzina, Heinz; Sprinzl, Georg Mathias
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0016-1
Worldwide, head and neck squamous cell carcinoma (HNSCC) is the sixth most common neoplasm, and despite advances in therapy, long-term survival in HNSCC patients is poor. Primary surgery followed by chemoradiation, or primary chemoradiation, are the standard treatment options for patients with locally advanced HNSCC. Improvement in the therapy efficiency is being achieved by new derivatives of fluoropyrimidine, novel platinum compounds and targeted antibodies against the epidermal growth factor receptor. Novel targets are being developed involving integrins, cyclooxygenase, and intracellular signaling pathways. Therapeutic results are also reported for immunomodulatory drugs. Patient group stratification based on therapy relevant biomarkers might lead to improved efficiency for antibodies targeted against receptors or for kinase inhibitors.
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0017-0
The major issue of the follow-up period is the early detection of recurrent and second tumors. Beside this, a team of specialized physicians and nurses should take care of the patient in terms of quality of life and rehabilitation. Follow-up appointments therefore should include physical examination with office-based endoscopy, ultrasonography, radiological imaging, dental evaluation, blood testing for TSH and EBV, voice and swallowing evaluation, pain management, QoL-Questionnaire, nutritional and psychological evaluation and treatment. Follow-up care should be managed by a multidisciplinary group of specialized and certified health care professionals in order to achieve the best results and outcome for the patients.
Gamerith, Gabriele; Pircher, Andreas; Amann, Arno; Cima, Katharina; Gasser, Klaus; Lenzhofer, Markus; Lind, Peter; Bareck, Evelyne; Wöll, Ewald; Hilbe, Wolfgang
2012 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-012-0033-0
In recent times, the treatment of advanced disease stages of thyroid cancer (TC) followed the strategy of targeted therapy with encouraging results. Thus, eight patients with metastasized thyroid carcinomas, who had multiple lines of prior interventions, were treated with sorafenib and have now been retrospectively evaluated. This retrospective evaluation included four patients with classified medullar carcinoma, two follicular, one papillary and one anaplastic, respectively. Within this population a clinical benefit rate of more than 70 % in daily routine, including a 29 % partial response rate could be determined, which correlates with the findings of recently published clinical trials with multi-kinase inhibitors. Furthermore, in all patients the observed toxicities were manageable after dose reductions. In conclusion, these data support a potential value of sorafenib in treatment of this rare disease.