memo - Magazine of European Medical Oncology

Bechter, Oliver E.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0092-z

DNA damage repair is essential for cellular homeostasis and cell survival. Cytostatic drugs and ionizing radiation cause an enormous amount of DNA damage and efficient repair is crucial for sustained cell growth. Hence manipulating DNA damage repair offers a new therapeutic principle, which together with conventional treatment strategies can increase treatment efficiency. In this issue we would like to give a brief overview of the current status of DNA damage repair factors as clinical markers and therapeutic targets. Ongoing and future clinical trials will determine the therapeutic potential of this new target for cancer treatment.

Gastl, Günther

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0104-z

Öfner, D.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0101-2

Jaeger, Ulrich

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0102-1

Antibody-based therapies have dramatically changed the course of disease in malignant lymphoma. Induction therapy has progressed from monotherapy to immunochemotherapy and radioimmunotherapy. In addition, maintenance treatment is now part of the standard treatment. A large number of antibodies against various targets is in routine use or currently tested in clinical trials. Second and third generation antibodies have improved cell killing properties and promise higher effectiveness. These new developments as well as upcoming strategies against novel targets in lymphoma are reviewed.

Drach, J.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0096-8

Treatment of multiple myeloma (MM) has evolved greatly over the past decade, and owing to immunomodulatory agents (thalidomide and lenalidomide) and proteasome inhibition (bortezomib), patients with MM enjoy prolonged survival and improved quality of life. Use of these novel agents has improved the rate of complete remissions in MM, a parameter that has emerged as an important step towards improved survival. Bortezomib should now be considered as an established component of the induction treatment prior to autologous transplantation in younger patients. The combination of melphalan/prednisone with a novel agent is a new standard of care for elderly patients with MM. The beneficial effect of these treatment approaches is also seen in special MM populations, in particular in those with impaired renal function and high-risk cytogenetic features.

Wolf, Dominik

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0097-7

Lenalidomide (Revlimid®, also known as CC-5013) and pomalidomide (CC-4047) are IMiDs and chemical derivatives of thalidomide. Lenalidomide was introduced in 2004 and is currently approved for treatment of multiple myeloma and 5q-myelodysplastic syndromes (MDS). In addition, IMiDs are currently tested in a wide variety of haematological as well as solid tumours. IMiDs have three main anti-tumour properties, i.e. a direct anti-tumour effect, an inhibitory/modulatory effect on the tumour stroma/microenvironment supporting growth and survival of tumour cells including anti-angiogenic properties as well as a very potent immunomodulatory effect. The latter includes activation of T, NK and NKT cells as well as modulation of the function of mononuclear cells (DC and monocytes). However, the exact anti-cancer mechanisms of IMiDs in vivo remain elusive so far. This brief review will focus on the current concepts explaining the anti-cancer effects of IMiDs.

Valent, Peter

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0098-6

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms defined by morphologic dysplasia, peripheral cytopenia, and clonal instability with enhanced risk to transform into secondary acute myeloid leukaemia (AML). The prognosis and clinical picture in MDS vary depending on the variant of disease, cell types affected and genes involved in the malignant process. In fact, more and more data suggest that cytogenetic and molecular defects and gene-variants are associated with the clinical course and prognosis. The current article provides a short summary of our knowledge about molecular and genetic markers in MDS, with special reference to their potential prognostic and therapeutic implications.

Gossage, L.; Mohammed, M.; Madhusudan, S.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0093-y

The overall prognosis of advanced cancer remains poor. Whilst accumulation of genetic mutations drives the cancerous phenotype, it is well known that DNA damaging lesions that lead to such mutations are predominantly monitored and repaired by the highly conserved DNA repair machinery in cells. Though chemotherapy as well as radiotherapy remains the mainstay of treatment, it is clear that the cancer cell's ability to respond to DNA damaging lesions induced by cytotoxic agents has a major bearing upon therapeutic efficacy and normal tissue toxicity. In this article we provide an overview on the role of DNA repair factors as prognostic/predictive markers with a specific focus on genetic alterations that confer altered DNA repair capacity in cells.

Kayser, Sabine; Schlenk, Richard F.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0095-9

PURPOSE OF REVIEW: In recent years new molecular markers have emerged as significant prognostic parameters and as potential targets for molecularly targeted therapy in acute myeloid leukaemia (AML). Prognostic markers, however, cannot guide the decision for a specific treatment since they are associated with a differential outcome regardless of the given treatment. In contrast, predictive markers indicate a treatment benefit in patients that are characterized through these markers. Thus predictive markers can guide clinical decision-making. RECENT FINDINGS: In young adults mutations of the NPM1 (NPM1 mut) gene in the absence of concurrent FLT3-ITD (FLT3-ITDneg) mutations have impressive prognostic and beyond prognostication also predictive properties. This NPM1 mut/FLT3-ITDneg genotype predicts equivalent favourable outcome after intensive chemotherapy and allogeneic stem cell transplantation, whereas in the absence of this marker clinical outcome was significantly improved after an allogeneic transplantation. In addition, within a retrospective study performed in older adults the same genotype predicted a significantly improved outcome if all-trans retinoic acid was added to intensive chemotherapy. SUMMARY: The discovery of new prognostic and predictive markers has increased our understanding of leukaemogenesis thus leading to an improved prognostication. Furthermore, current clinical research focusing on the assessment of genotype-specific therapy may translate into an increase in the cure rate.

Öfner, D.; Eisterer, W.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0100-3

Metastases of the liver are a common event in malignancies particularly of the gastrointestinal tract and a leading cause of cancer-related death. Until a few years ago, treatment for these patients was given based on palliative strategies. Today there is considerable hope for cure owing to recent developments of both surgical techniques of liver resection and chemotherapy. Liver surgery has become a safe and widespread procedure with postoperative morbidity rate of less than 40% and mortality rate of less than 5%. At the time of diagnosis, only a small amount of patients with liver metastases are resectable. Therefore, efforts have been made to increase the proportion of resectable patients, who may be considered for potential curative resection. Besides extended surgical techniques, possibly in combination with ablative procedures, preoperative chemo- and targeted therapy have become the leading means to gain resectability. Particularly in patients with metastasis of colorectal cancer (CRC) significant advances have been made over the last decade and recently the use of neoadjuvant treatment to downsize disease followed by liver resection was demonstrated to improve patients' survival. Besides curative surgery, tumour de-bulking was shown to be of abundant benefit for patients suffering from neuroendocrine tumours (NET) with liver metastasis owing to relieve or control symptoms. Liver resection is nowadays even extended for non-CRC and non-NET metastases, depending on the clinical course of the primary disease.

Akan, B.; Bichler, C.; Kandioler, D.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0099-5

Lung metastasectomy is still the best treatment option for resectable patients improving overall survival and providing low morbidity and mortality. Preoperative imaging still has an insufficient sensitivity and a poor specificity. Therefore a pure thoracoscopic approach for metastasectomy providing even lower morbidity but precluding palpation remains controversial. Prognostic factors are currently not recommended to select patients for surgical therapy but might be of value to select patients who benefit from neoadjuvant or adjuvant therapy. The role of chemotherapy in lung metastases is still undefined. Considering the low efficiency of current regimes the risk/benefit ratio as well as the cost/effectiveness ratio is in favour of surgery. Until now surgical resection when feasible provides survival rates superior to any available nonsurgical therapy.

Kober, F.; Karik, M.; Hermann, M.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0094-x

PURPOSE: Synopsis about the curative possibilities of an aggressive multimodal therapeutic approach for peritoneal metastases using positive prognostic selection criteria. PATIENTS AND METHODS: Published data concerning cytoreductive surgery in combination with intraoperative intraperitoneal hyperthermic chemotherapy and/or early postoperative intraperitoneal chemotherapy ± systemic chemotherapy in patients suffering from peritoneal carcinomatosis were analyzed with regard to subgroups with long-term survivors. RESULTS: Extent of peritoneal carcinomatosis and completeness of cytoreductive surgery are the most important prognostic factors predicting long-term survival. Histological differentiation, lymph node status, performance status, extent of prior therapy and age are further independent factors influencing the outcome. CONCLUSION: Strictly selecting patients with multiple positive prognostic factors might result in 5-year survival rates of 50% and more.

Öfner, Dietmar; Grünberger, Thomas; Eisterer, Wolfgang

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0103-0

An Austrian expert panel comprising surgeons and medical oncologists from tertiary care centres in Austria was convened in Vienna in 2008 to assess the current strategies of the management of liver metastasis in colorectal cancer with special focus on the surgical approach. Following topics were discussed based on the current literature: liver surgery, role of systemic therapy, resection margins, role of the application of ablation techniques or laparoscopic liver resection. The results were summarized and are now presented as the Austrian consensus report.

2009 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-009-0105-y