Nervous System (NS) manifestations of cancer are common; their frequency is increasing and they are serious. The differential diagnosis between direct and indirect NS manifestations is often difficult since different disorders may present with similar clinical signs, requiring meticulous evaluation to reach a definitive diagnosis. When a corrrect diagnosis can be made early in the course of the disease, an appropriate treatment frequently relieves symptoms and prolongs life.
Advances in MR imaging techniques have made considerable progress in recent years. Both high resolution anatomical imaging and functional parameters when using higher advanced MR techniques have become a valuable adjunct to conventional imaging, helping to further differentiate a lesion or to better determine an adequate therapy or biopsy site. Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are available on virtually every MR scanner, although especially for DTI the post processing is somewhat more demanding. The use of MR perfusion and MR spectroscopy (MRS) has become more and more routine. BOLD imaging (fMRI) is able to correlate brain activation with specific tasks (paradigms), which have also added information for presurgical evaluation of brain metastases or brain tumour in general.
The development of brain metastases is still considered as a "terminal complication" of a cancer disease. The potential for CNS metastases appears to be greatest in tumours of neuroectodermal origin like melanoma or SCLC, very high in patients with tumours of ectodermal origin like breast cancer and NSCLC, whereas tumours arising from other embryonic origin develop brain metastases less often. Neovacularisation with upregulated VEGF Expression by the tumour cells facilitates their transmigration through the BBB. Temozolomide and "small molecules" are currently under investigation in solid tumours as farnesyltransferase inhibitors and tyrosin kinase inhibitors are able to cross BBB and thus should be active within the brain. Although studies on chemotherapy of brain metastases are usually small and include mostly a small number of patients, responses and prolongations of survival have been recorded. More studies are needed to evaluate the potential of the new therapeutics agents which increased therapeutic ratio and reduced side effects from chemotherapy.
The rapid development of targeted therapies capable of entering the brain and the emerging technology of nano shells armed with cytotoxins reflects promising progress in the treatment of brain metastasis. The management of brain metastases is complicated by a number of major problems. The histological, molecular, biologic and immunologic nature of the various tumour types metastasizing to the brain differs significantly. As a consequence, the sensitivity towards various cytotoxic drugs or other treatment options varies substantially. Only few drugs are usually considered capable of penetrating the blood/brain and the brain/liquor barriers. Thus, the availability of a drug with adequate molecular size and pharmacokinetics within the compartments of the central nervous system determine the usage of cytotoxic drugs rather than the sensitivity of a specific tumour type to a specific drug. Recently, however, progress has been made in the development of more efficient types of therapy against brain metastases.
Metastatic brain tumours are among the most common surgical targets in brain surgery. Up to 40% of cancer patients develop brain metastases during the course of their disease. Lung, breast, kidney, intestine and melanoma are the most common cancers, spreading into the CNS. New techniques in neurosurgery have lead to a significant increase in survival and quality of life of patients suffering from brain metastasis. Image guidance, intraoperative ultrasound, electrophysiological cortical mapping, functional neuronavigation and awake craniotomy expanded the indication of surgery even to patients suffering from multiple metastases. Thus, appropriate selection criteria are necessary to provide benefits of surgery to the widest population of patients possible. Besides traditional criteria like age, Karnofsky performance status (KPS), number, extension, surgical accessibility, histology and status of the systemic disease, recursive partitioning analysis has led to a new preoperative classification system (RPA Classes 1–3), to select patients, having best benefit from surgical treatment.
Metastatic involvement of the spinal column is frequently seen in various types of cancer. When neoplastic proliferation occurs strictly within the borders of a vertebral body, pain is the major clinical problem. In non-contiguous spinal metastases, however, epidural tumour extension and spinal instability lead to neurological deficit. Both pain and neurological deficit severely interfere with life quality, but rarely with survival, which is mainly determined by the underlying cancer disease. Therefore, the treatment of spinal metastasis primarily aims at preserving neurological function, spinal stability and at reducing pain.
Brain metastases are the most common form of brain cancer, occurring in about 25% of all patients with cancer. Typical primary tumours with brain metastases are lung, breast, melanoma, and kidney. Brain metastases are located in the cerebral hemispheres in about 80%, in the cerebellum in 15%, or in the brainstem in 5% of patients . This overview focuses on the application of radiotherapeutic approaches, including whole brain radiation therapy (WBRT) and radiosurgery selected on the basis of inherent prognostic factors characterizing the individual patient.
Seizures in brain tumour patients are common; therefore, most of the brain tumour patients require chronic treatment with antiepileptic drugs (AED). Also acute, and in some instances prophylactic, treatment may be necessary. Many AED either induce (mainly CYP3A4) or inhibit liver enzymes, and therefore affect the metabolism of drugs, such as chemotherapeutic agents or steroids. Chemotherapeutic agents, metabolized by CYP3A4 system are affected by enzyme-inducing AED (EIAED), are discussed.
During all phases of cancer treatment suppotive care and symptom control are important issues. This starts already in the diagnostic phase and has to be continued till the end of life. Nevertheless, symptoms and problems are often underestimated or even not recognized. This is especially true in brain tumour patients who, in comparison with other cancer patients, have a large number of relatively severe problems and concerns. The major problems reported by patients with primary or secondary brain tumours are headache, epileptic seizures, neurological deficit leading to disability, cognitive dysfunction, fatigue, depression, emotional and psychosocial distress, thromboembolic disease and complications from the use of drugs (corticosteroids, anticonvulsants and chemotherapy). Palliative treatment may initially be directed against the primary tumour or against metastatic disease. Only when these anti-tumour treatments have failed, palliative treatment will be primarily aimed at relief of symptoms.
Supratentorial primitive neuroectodermal tumours (sPNET) are rare tumours in adults. Five-years survival remains below 50%. We present a case report of a 38-year-old female with metastases of a supratentorial primitive neuroectodermal tumour. Treatment was radical surgical resection, followed by chemotherapy according to the HIT 2000 protocol. Twelve months after the first diagnosis, a relapse was diagnosed which was again surgically removed followed by radiotherapy and concomitant Temozolemide. Because of severe thrombocytopenia the chemotherapy was shifted to Gleevec therapy resulting in a stable disease until now.
The efficacy of postoperative adjuvant chemotherapy for patients with completely resected NSCLC has been elucidated in several large randomized trials. A meta-analysis of five of the recently performed cisplatin-based chemotherapy trials, the Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis, confirmed that adjuvant cisplatin-based chemotherapy improves survival of patients with completely resected NSCLC. Thus, cisplatin-based adjuvant chemotherapy is now considered as the standard of care for patients with completely resected NSCLC stage, II–III. According to the LACE meta-analysis, patients with stage IA NSCLC should not receive adjuvant chemotherapy but it could be considered for selected patients with stage IB disease. Because the overall benefit of adjuvant chemotherapy is small, new treatment strategies including customized chemotherapy, integration of molecular-targeted therapies, and immunotherapy are under investigation and may show better results in patients with completely resected early-stage NSCLC.
Adjuvant chemotherapy is established as a standard of care for resectable non-small cell lung cancer. However, this indication remains controversial for the stage IB as the results of the randomized trials and meta-analysis are obscuring on this issue. Moreover, the updated international guidelines do not prescribe the regular use of this strategy in stage IB. The aim of this paper is to review the current evidences regarding the benefit of adjuvant CT in this setting, and to provide clinical hints, which can lend a helping hand to the clinicians and their patients to take the right decision in this particular scenario.
Treatment of thymomas remains a challenge for oncologists as no clear evidence-based guidelines can be provided due to the lack of randomized trials. Whenever possible, surgical removal of all gross tumour remains the mainstay of every therapeutic concept. Nevertheless, despite optimal surgery, there remains a clinically relevant risk for recurrence, inevitably posing the question concerning the value of adjuvant or neoadjuvant treatment-interventions. The following short review aims to provide concise information on the available data on neoadjuvant and adjuvant radiotherapy and/or chemotherapy in patients with thymoma, thus supporting the treating physician in advising their patients and finally reaching an informed consent.
Gastric cancer is still one of the predominant causes of death on account of gastrointestinal neoplasias. In recent years, chemotherapy and radiotherapy have substantially improved the outcome in operable gastric cancer patients. A benefit in median overall survival is reported for perioperative chemotherapy as well as for postoperative adjuvant radio-chemotherapy. But there is still a controversy about the best treatment sequence. The aim of this paper is to critically review current literature, to discuss the pros and cons of neoadjuvant (preoperative) or postoperative adjuvant therapy and to give treatment recommendations based on large phase III trials.
Adjuvant treatment of stage II colon cancer remains an issue of controversy. Though there is evidence indicating that adjuvant therapy is associated with a limited survival benefit, large clinical trials published so far did not provide enough evidence to regard adjuvant therapy of stage II colon cancer as standard of care. The ultimate clinical decision should be based on the presence of high-risk prognostic features, the evidence supporting treatment, the anticipated side effects and morbidity of treatment as well as patient preferences. Considering all these circumstances, regimen containing oxaliplatin together with 5-FU/leukovorin may be regarded as standard therapy. Stage II rectal cancer represents an excellent example for the need of close collaboration between both surgeons and medical oncologists together with radiation oncologists. The combination of radiotherapy and chemotherapy given in the neoadjuvant or adjuvant setting can be regarded as standard therapy. The potential benefit of the addition of oxaliplatin is currently under investigation. The goal of ongoing studies is to investigate whether combination of chemotherapy with therapeutic antibodies such as cetuximab or bevacizumab will become standard of care in the adjuvant setting.
Kornek, G.; Scheithauer, W.; Anghel, R.; Bodoky, G.; Ciardiello, F.; Ciuleanu, T.; Glynne-Jones, R.; Gruenberger, T.; Koza, I.; Ocvirk, J.; Petruzelka, L.; Poston, G.; Ramadori, G.; Schmiegel, W.; Segaert, S.; Tabernero, J.; Zwierzina, H.; Zielinski, C.
PURPOSE: To throw light on some of the issues in the choice of therapy for patients with metastatic colorectal cancer (mCRC) and to provide consensus recommendations on which combination(s) and sequence(s) of systemic therapy to be used in different treatment situations. MATERIAL AND METHODS: An expert panel comprising clinicians from Austria, Belgium, the Czech Republic, Germany, Hungary, Italy, Romania, Slovakia, Slovenia, Spain and the UK with expertise in medical oncology, clinical oncology, surgery and dermatology, and specialist knowledge of the treatment of patients with CRC was convened by the Central European Cooperative Oncology Group (CECOG) in Vienna in 2007. Members were then asked to agree on a consensus statement following a period of discussion at the end of a series of presentations. RESULTS AND CONCLUSIONS: The consensus recommendations for the state-of-the-art treatment of colon cancer arrived at by an "expert panel" of clinicians were that: oral 5-fluorouracil (5-FU) prodrugs or protracted intravenous infusion of the antimetabolite are preferable to bolus administration; all active drugs (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, cetuximab) should be used during strategic patient management; after neoadjuvant treatment and consultation of an interdisciplinary team, surgery should be considered for metastatic disease wherever possible and "fit" elderly patients should not be denied the same treatment as younger patients.
Breast cancer is the most common malignancy in women in Western Europe and the U.S. Adjuvant chemotherapy reduces the rate of cancer recurrence, thereby contributing to the recent decline of breast cancer mortality. Notably, a number of important developments occurred over the past decades. Starting with first generation regimens like CMF, the next step was the introduction of anthracyclines into the adjuvant setting, although the role of these drugs is again dubious today. Modern regimens followed with the introduction of taxanes into the adjuvant setting, and a number of further developments are under way: Dose dense regimens as well as targeted therapies have led to a new era of treatment of women with early breast cancer. Neoadjuvant chemotherapy, while sometimes still debated, has increased the rate of breast conserving surgeries. Obviously, both neoadjuvant, therefore preoperative, and adjuvant chemotherapy have their specific advantages and drawbacks. This will be dealt with in detail. Also a short overview of available data on adjuvant chemotherapy in the elderly is provided. The history, recent developments, as well as open questions will be discussed in this review.
PURPOSE. This overview summarizes the most prominent data on the evolution of first-line and maintenance chemotherapy in epithelial ovarian cancer. METHODS. The literature published on first-line and maintenance chemotherapy in ovarian cancer between 1970 and 2008 was identified systematically by computer-based searches in MEDLINE and the Cochrane Library. RESULTS. In suboptimally debulked and FIGO stage IV ovarian cancer patients the combination of carboplatin and a taxane given intravenously at a three-weekly interval represents the standard of care in first-line chemotherapy. On the contrary, if optimal cytoreduction with residual disease ≤1 cm was achieved during primary surgery and disease was confined to the peritoneal cavity, intraperitoneal chemotherapy should seriously be taken into consideration even at the expense of significantly increased, but manageable toxicity. A more favourable therapeutic index should be expected in IP regimens, when cisplatin will be substituted by the better tolerable carboplatin. Concerning maintenance chemotherapy in ovarian cancer, the only randomized trial showing significant effects on progression-free survival used paclitaxel as a single agent over 12 cycles given once monthly. However, that study was prematurely closed at the first interim analysis because of prominent differences in progression-free survival in favour of the study arm. Translatable effects on overall survival thus remained unevaluated. CONCLUSION. Intravenous platinum-taxane-based chemotherapy remains the first-line post-operative treatment of choice in ovarian cancer, but the option of intraperitoneal chemotherapy should be considered in appropriate patients. In ovarian cancer, maintenance chemotherapy should be performed only in controlled clinical trials.
This report dwells on selected abstracts presented at the 49th Annual Meeting of the American Society of Hematology (ASH), which was held at the Georgia World Congress Center in Atlanta, Georgia in December 2007. The aim of this report is not to discuss the very details of distinct scientific questions or clinical problems but rather to inform the practising haematologist about relevant clinical and scientific advances in the broad field of haematology. This selection of studies is of course a subjective one as the abstracts presented herein were judged upon their significance solely by the reflection of authors' personal interests. The presentation of the first pilot studies exploring the efficacy and safety of JAK-2 inhibitors in Philadelphia-chromosome negative chronic myeloproliferative disorders was certainly one of the most notable topics of the meeting. Concerning other haematologic malignancies, we felt that there were no groundbreaking developments as in recent years when novel forms of treatment such as proteasome inhibitors, tyrosine kinase inhibitors or thalidomide and its analogues were presented. But with large and often randomized trials with sufficient follow-up periods, the progress suggested by smaller phase II trials was further consolidated allowing the physician to recognize not only the true benefit but also the potential harm of these novel therapies in broad clinical practice.
Hepatocellular carcinoma (HCC), the fifth leading cause of cancer death worldwide, is a tumour with dismal prognosis . In recent years, significant advances have been made and survival of patients with HCC has been prolonged and even cure can be achieved in a sizeable number of patients. The biggest advances are viable through screening and surveillance programmes of the population at risk, which includes all patients with cirrhosis of the liver and patients chronically infected with hepatitis B virus. Through regular ultrasound screening at 6-month intervals, detection rates and through this treatment and survival have been improved dramatically . Through these surveillance programmes, at least 80% of the patients with HCC in western countries will undergo treatment for HCC of any kind with proven efficacy on survival. Only about 20% of patients with endstage tumours at the time of diagnosis will have no other option left than supportive care .