Clinical Oncology

[Molecular residual tumor monitoring in solid cancers]

SZÁSZ A. Marcell1, TOBIÁS Bálint2,1, KÓSA János2,1, LAKATOS Péter2,1

APRIL 30, 2020

Clinical Oncology - 2020;7(02)

[Blood-based diagnostics has long been used in the oncological practice of solid tumors, but its full potential is just unfolding recently. Quantitative measurement of tumor markers, circulating tumor cells, and some of their products or components have now become available and are part of a multimodal system that provides additive parameters in clinical decision making. The most challenging oncological questions can be answered by the detection, characterization and measurement of circulating free DNA (cfDNA), which, due to its growing importance, bears the potential of incorporation into routine practice. In this overview, we review the „blood impressions” of solid tumors and present the most promising results in different patient groups, especially in lung, breast, colon, and bladder tumors, which are also valid for other solid tumors.]


  1. Semmelweis Egyetem, Belgyógyászati és Onkológiai Klinika, Budapest
  2. PentaCore Laboratórium, Budapest



Further articles in this publication

Clinical Oncology

[Coronavirus pandemic – new challenges in oncotherapy]


[This review outlines some of the basic observations related to coronaviruses infecting animals and describes – in a nutshell – the characteristics of human coronaviruses causing mild or severe respiratory diseases in infected individuals. A special attention is given to SARS-CoV-2, the causative agent of the current coronavirus disease (Covid-19) pandemic, and to the pathomechanism of severe acute respiratory syndrome (SARS) which is also accompanied with multiorgan failure in a subset of infected patients. Recently discovered unique molecular features of SARS-CoV-2 are described as well. These molecular cues may affect human to human virus transmission whereas they are absent, remarkably, from the other lung-targeting highly pathogenic human coronaviruses (SARS-CoV-1 and MERS-CoV) which did not spread all over the world. The possibilities of active immunization to prevent SARS-CoV-2 infection and the development of selective small molecule inhibitors curbing the replication of the virus are also touched upon. The review closes with a few remarks regarding the Hungarian and international recommendations concerning the treatment of SARSCoV- 2 infected cancer patients.]

Clinical Oncology

[Immunotherapy of hepatocellular carcinoma]


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Clinical Oncology

[Hormone replacement therapy in cancer survivors – Review of the literature]

DELI Tamás, OROSZ Mónika, JAKAB Attila

[Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insuffi ciency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women’s Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude defi nitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Yet, the oncologic risk of HRT is extremely diffi cult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies. We group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advanageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is diasadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).]

Clinical Oncology

[Development and 10-year history of a biosimilar: the example of Binocrit®]


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Clinical Oncology

[Tumor induction by chemotherapy]

[Without chemotherapy, the fi ve-year survival rate of detected cancers would be between 0 and 15%, depending on the tumor, and between 17 and 85% with current therapy. Several warnings call attention to the dangers of chemotherapy-induced side effects, most notably the potential for tumor-inducing ability, which can affect 5-10% of patients who have recovered beyond fi ve years. Some systematically applied drugs used in chemotherapy (alkylating agents, etoposide, arsenic trioxide) are able to cause mutations in healthy cells of the patients, increasing the likelihood that the mutated cells will start a later (secondary) tumor formation. In addition to mutagenic effects, some chemotherapeutic agents exert their effects on normal myeloid and epithelial cells of the body, which, by altering the tissue microenvironment, create the potential for malignant transformation. Tumor-associated macrophages (TAMs), which can alter gene expression patterns by tumor cell secreted factors and promote the survival and invasiveness of tumor cells by pro-carcinogenic signals, are very important in this process. It is of utmost importance that doctors, pharmacists, technicians and nurses working with cancer-causing materials do not come into direct contact with dangerous substances and wear appropriate protective equipment.]

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Related contents

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.

Clinical Neuroscience

Atypical presentation of late-onset Sandhoff disease: a case report

SALAMON András , SZPISJAK László , ZÁDORI Dénes, LÉNÁRT István, MARÓTI Zoltán, KALMÁR Tibor , BRIERLEY M. H. Charlotte, DEEGAN B. Patrick , KLIVÉNYI Péter

Sandhoff disease is a rare type of hereditary (autosomal recessive) GM2-gangliosidosis, which is caused by mutation of the HEXB gene. Disruption of the β subunit of the hexosaminidase (Hex) enzyme affects the function of both the Hex-A and Hex-B isoforms. The severity and the age of onset of the disease (infantile or classic; juvenile; adult) depends on the residual activity of the enzyme. The late-onset form is characterized by diverse symptomatology, comprising motor neuron disease, ataxia, tremor, dystonia, psychiatric symptoms and neuropathy. A 36-year-old female patient has been presenting progressive, symmetrical lower limb weakness for 9 years. Detailed neurological examination revealed mild symmetrical weakness in the hip flexors without the involvement of other muscle groups. The patellar reflex was decreased on both sides. Laboratory tests showed no relevant alteration and routine electroencephalography and brain MRI were normal. Nerve conduction studies and electromyography revealed alterations corresponding to sensory neuropathy. Muscle biopsy demonstrated signs of mild neurogenic lesion. Her younger brother (32-year-old) was observed with similar symptoms. Detailed genetic study detected a known pathogenic missense mutation and a 15,088 base pair long known pathogenic deletion in the HEXB gene (NM_000521.4:c.1417G>A; NM_000521:c.-376-5836_669+1473del; double heterozygous state). Segregation analysis and hexosaminidase enzyme assay of the family further confirmed the diagnosis of late-onset Sandhoff disease. The purpose of this case report is to draw attention to the significance of late-onset Sandhoff disease amongst disorders presenting with proximal predominant symmetric lower limb muscle weakness in adulthood.

Clinical Neuroscience

The applications of transcranial Doppler in ischemic stroke


Background: This overview provides a summary of the applications of transcranial Doppler (TCD) in ischemic stroke. Results: A fast-track neurovascular ultrasound protocol has been developed for detecting occlusion or stenosis. The technique is more reliable in the carotid area than in the posterior circulation. By monitoring the pulsatility index the in­crea­sed intracranial pressure can be diagnosed. TIBI score was developed for grading residual flow. TCD has been shown to accurately predict complete or any recanalization. Regarding recanalization, TCD has a sensitivity of 92%, a specificity of 88%, a positive predictive value of 96%, a negative predictive value of 78% and an overall accuracy of 91%, respectively. Sonothrombolysis seemed to be a promising application but randomized controlled trials have shown that it does not improve clinical outcome. TCD examination can detect microembolic signals (MES) which are associated with an increased risk of stroke. Micro­em­boli were detected in symptomatic and asymptomatic carotid artery stenosis and during carotid endarterectomy. The number of microemboli can be decreased by antithrombotic therapy. Contrast en­chan­ced examination and Valsalva maneuver with continuous TCD monitoring can accurately screen for right-to-left shunt.

Clinical Neuroscience

[Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients]

BOCZÁN Judit, KLIVÉNYI Péter, KÁLMÁN Bernadette, SZÉLL Márta, KARCAGI Veronika, ZÁDORI Dénes, MOLNÁR Mária Judit

[Background – Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose – The new drugs change the progression of SMA with neonatal and childhood onset. Increasing amount of data are available about the effects of these drugs in adult patients with SMA. In this article, we summarize the available data of new SMA therapies in adult patients. Methods – Members of the Executive Committee of the Hungarian Clinical Neurogenetic Society surveyed the literature for palliative treatments, randomized controlled trials, and retrospective and prospective studies using disease modifying therapies in adult patients with SMA. Patients – We evaluated the outcomes of studies focused on treatments of adult patients mainly with SMA II and III. In this paper, we present our consensus statement in nine points covering palliative care, technical, medical and safety considerations, patient selection, and long-term monitoring of adult patients with SMA. This consensus statement aims to support the most efficient management of adult patients with SMA, and provides information about treatment efficacy and safety to be considered during personalized therapy. It also highlights open questions needed to be answered in future. Using this recommendation in clinical practice can result in optimization of therapy.]

Clinical Neuroscience

[Rehabilitation possibilities and results after neurosurgical intervention of brain tumors ]

DÉNES Zoltán, TARJÁNYI Szilvia, NAGY Helga

[Objectives - Authors examined the rehabilitation possi­bi­lities, necessities, and results of patients after operation with brain tumor, and report their experiences. Method - Retrospective, descriptive study at the Brain Injury Rehabilitation Unit, in National Institute for Medical Rehabilitation. Patients - Patients were admitted consecutively after rehabilitation consultation, from different hospitals, following surgical intervention of brain tumors, between 01 January 2001 and 31 December 2016. Patients participated in a postacute inpatient rehabilitation program, in multidisciplinary team-work, leaded by Physical and Rehabilitation Medicine specialist included the following activities: rehabilitation nursing, physical, occupational, speech, psychological and neuropsychological therapy. Results - At the rehabilitation unit, in the sixteen-year period 84 patients were treated after operation with brain tumor. Patients arrived at the unit after an average of 41 days to the time of the surgical intervention (range: 10-139 days), and the mean length of rehabilitation stay was 49 days (range: 2-193 days). The mean age of patients was 58 years (20-91), who were 34 men and 50 women. The main symptoms were hemiparesis (64), cognitive problems (26), dysphagia (23), aphasia (16), ataxia (15), tetraparesis (5), and paraparesis (1). The mean Barthel Index at the time of admission was 35 points, whereas this value was 75 points at discharge. After the inpatient rehabilitation, 73 patients improved functionally, the status of 9 patients did not show clinically relevant changes, and 2 patients deteriorated. During the rehabilitation 10 patients required urgent interhospital transfer to brain surgery units, 9 patients continued their oncological treatment, two patients continued rehabilitation treatment at another rehabilitation unit, and after rehabilitation 73 patients were discharged to their homes. Conclusions - Inpatient rehabilitation treatment could be necessary after operation of patients with brain tumor especially when functional disorders (disability) are present. Consultation is obligatory among the neurosurgeon, rehabilitation physician and the patient to set realistic rehabilitation goals and determine place and method of rehabilitation treatment, but even at malignancies cooperation with oncological specialist also needed. Authors’ experience shows benefits of multidisciplinary rehabilitation for patients after brain tumor surgery. ]