Clinical Oncology

[Should docetaxel be standard of care for patients with metastatic hormone-sensitive prostate cancer? Pro and contra]


DECEMBER 10, 2015

Clinical Oncology - 2015;2(04)

[Following the results of the TAX-327 study, questions have been raised as to whether administering chemotherapy to patient with prostate cancer before symptomatic disease progression when receiving standard hormonal treatment can improve the duration and quality of survival. The GETUG-AFU-15 and CHAARTED studies assessed the effi cacy and tolerability of androgen deprivation therapy (ADT) with or without docetaxel in patients with metastatic hormone-naive prostate cancer. Both studies included a mix of patients with de novo metastatic disease (~75%) and patients with metastases following treatment of localized disease. A short course of ADT was allowed in both trials prior to accrual. Key differences between the two studies include the number of patients with high-volume metastases (GETUGAFU- 15: 52%; CHAARTED: 65%) and number of docetaxel cycles (GETUG-AFU-15: up to nine cycles; CHAARTED six cycles). Both studies reported an improvement in progression-free survival with docetaxel plus ADT versus ADT alone. The GETUG-AFU-15 did not fi nd a signifi cant difference in the primary end point of overall survival (OS) [hazard ratio (HR) 0.9 (95% confi dence interval (CI) 0.7-1.2); P = 0.44] for ADT plus docetaxel versus ADT alone. The CHAARTED study met the primary end point of OS [HR 0.61 (95% CI 0.47-0.80); P = 0.0003], and in a subset analysis reported the greatest improvement in OS for patients with high-volume disease [HR 0.60 (95% CI 0.45-0.81); P = 0.0006]. The following review debates the results from the GETUG-AFU-15 and CHAARTED studies and asks whether medical practice should be changed for patients with metastatic hormone-naive prostate cancer based on the results of one positive study.]



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Clinical Oncology

[Non surgical treatment of urinary bladder cancer]

PIKÓ Béla, LACZÓ Ibolya

[According to our present knowledge the surgical intervention in the treatment of bladder cancer is essential, but some non-surgical treatment methods play an indispensable role as well. Super- fi cial (non-muscle-invasive) form of bladder cancer can be treated by intravesical chemotherapy or BCG instillation, radiotherapy; the muscle-invasive forms of this tumour (≥pT2a) need neoadjuvant, adjuvant chemotherapy, radiotherapy or radio-chemotherapy. In case of metastatic disease (or locally advanced, recurrent disease) the treatment regimen consist of chemotherapy (given as fi rst line or second line), palliative radiotherapy, interventional methods, radio-isotope therapy and symptoms relief drugs. We present each of the therapeutic modalities and their indications category based on the ESMO and NCCN guidelines.]

Clinical Oncology

[The role of physical activity in oncology]


[Although nowadays there are a lot spoken about the role of physical activity in illness prevention, however it is barely connected to the treatment of malignant diseases. The regular exercises can improve physical performance and fi tness; increase muscle mass; change the body composition and proportion favorably. The positive psychological effects can decrease distress and depression; improve mood of patient; increase self-confi dence and self-respect. Finally, all of these will result in an improved quality of life. The malignant disease and the treatments can draw down either short-term or long-term consequences and side-effects that can largely infl uence or restrict everyday life. Most of them could be essentially reduced by the help of a physiotherapist experienced in oncology adopting a well-defi ned and customized workout.]

Clinical Oncology

[Current treatment of gastrointestinal lymphomas]


[The most common extranodal site involved by lymphoma is the gastrointestinal tract. The majority of extranodal lymphoma cases are of the non-Hodgkin subtype. Usually, the involvement of the gastrointestinal tract by nodal lymphomas is secondary, the primary gastrointestinal localisation is rather rare. The most common pathological types are diffuse large B-cell lymphomas and extranodal marginal zone lymphomas of the mucosa-associated tissue (MALT) subtype. Although the primary gastrointestinal lymphoma can involve any part of the gastrointestinal tract, the stomach is the most frequently involved site. The treatment and prognosis are determinated primarily by the histologic type of lymphoma, the stage of disease and the patient’s age and general condition. Helicobacter pylori (HP) infection is one of the major risk factors for gastric lymphomas, the presence or abscence of which radically infl uences the effectivity of treatment. In case of HP positivity, HP eradication itself can result in complete remission. In most cases the treatment is immuno- and/or combination chemotherapy, which is performed according to the internationally accepted protocols, specifi c to the type of lymphoma. Radiotherapy plays a lesser role in the treatment of GI lymphomas, while surgery is performed almost only in complicated cases, such as haemorrhage, occlusion or perforation.]

Clinical Oncology

[The role of EGFR receptor family in the oncological practice]


[The EGFR receptor family is a set of membrane tirosine kinase receptors with signifi cant homology which are responsible for cellular activation through intracellular signaling due to ligand binding. The four members of the family (EGFR1, EGFR2/HER2/neu, EGFR3/HER3, EGFR4/HER4) earned special interest in tumor biology while becoming one of the most potent targets of anti-cancer therapies. Changes in the receptor expression or in the kinase activity fundamentally modify cellular functions, survival and tumorigenic potential. Moreover, mutations are associated with reduced or altered treatment effi cacy. The basic function and major genetic and biological mechanisms affecting the function of EGFR receptors and related therapies are subjects of this overview.]

Clinical Oncology

[Hematopoietic stem cell transplantation for solid tumors in adults]

GOPCSA László Zsolt, MASSZI Tamás

[We revised the medical literature regarding autologous and allogeneic hematopoietic stem cell transplantation (HSCT) in the setting of solid tumors. Autologous-HSCT for solid tumors in adult patients show changing patterns in past decades with decreases numbers for many types of solid tumors. Most marked is the previously well-described increase and decrease in autologous HSCT for breast cancer (BC). Autologous-HSCT for BC has been an area of intense controversy. The role of autologous-HSCT for BC at high risk of recurrence (at least four involved axillary lymph nodes) has been assessed by several randomized trials. Overall, it was shown that high-dose therapy prolonged disease-free survival when used as adjuvant therapy, and showed a benefi t on overall survival in only selected cohorts of patients. In second or further relapsed or primary refractory germ cell tumor, highdose therapy is considered to be a standard therapeutic option, especially when poor prognostic factors are present. In addition, sequential therapy with two to three cycles is felt to be superior to single cycle of HSCT. High-dose therapy can be regarded as a potential clinical option in selected adult patients with Ewing’s sarcoma and medulloblastoma. Currently, in other types of solid tumors the autologous- HSCT is generally not recommended or developmental and only used in the context of prospective studies. Numbers of allogeneic HSCT for solid tumors remained stable low number throughout the recent years. Transient increase is observed over the last decade and is primarily due to renal cell carcinoma, BC and colon cancer. Concepts of allogeneic HSCT for solid tumors do not rely on highdose chemotherapy and tumor load reduction but rather on a graft-versus-tumor effect. Attempts to improve the therapeutic effect of allo-HSCT or other cellular therapies in solid tumors by innovative clinical strategies are underway.]

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Clinical Oncology

[Ablation of liver cancer]

DOROS Attila

[Ablative therapies of the malignant liver tumors are used frequently all over the world. It is a very well tolareted minimally invasive treatment, followed by a short observation period. Patients might be sent home within 24 hours. Nowadays, there is suffi cient data supporting its effectiveness in the treatment of early primary liver cancer, equalling the results of surgical resection. The situation is different in liver metastasis, especially from coloectal cancer. In these cases ablative techniques have a supporting role, limiting their action on the multimorbid patients and small non-resectable tumors. These facts and trends - worldwide and in Hungary - are discussed, focusing on effectiveness, places in therapeutic protocols and domestic diffi culties.]

Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Hypertension and nephrology

[About the care of patients with hyperuricaemia and gout]

[This consensus document is intended to provide guidance for the effective and efficient treatment of asymptomatic individuals with high uric acid levels and gout patients.]

Clinical Neuroscience

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]