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Background: The Csangos are an East-Central European ethnographic group living mainly in east of Transylvania in Romania. Traditionally, ethnography distinguishes three Csango subpopulations, the Moldavian, Gyimes and Burzenland Csangos. In our previous study we found that the Moldavian Csangos have East Asian/Siberian Turkic ancestry components that might be unique in the East-Central European region and might help to better understand the history of Hungarian speaking ethnic groups of the area. Since then, we obtained further Csango samples from Moldavia and from a distinct region of Gyimes, which two Csango subgroups are traditionally different since they live in a degree of isolation not only from other people but also from each other. Here we present the first genomic analysis of Gyimes Csangos, which intended to compare the genetic makeup of these two Csango subgroups using both allele-frequency and haplotype-based methods. The main goal of the study was to investigate the genetic isolation of the Csangos on a genome-wide SNP basis and to assess the isolation of Gyimes Csangos, which in contrast to the Moldavians was not yet studied., Results: Our results show that these two Csango groups show slight differences from each other. We confirmed the genetic isolation of Moldavian Csangos and revealed that Gyimes Csangos have a similar, but detectably weaker isolation. In the case of Gyimes Csangos we detected also a stronger East European or presumably Asian derived ancestry., Conclusion: The Gyimes Csangos show a degree of genetic isolation comparable to that of the Moldavians. The Asian ancestry that differentiates the Moldavian Csango people from the other East-Central European populations may be present in the Gyimes Csangos in an even higher degree, since Gyimes Csango individuals show a more significant share from that ancestry component., (© 2024. The Author(s).)

Introduction: Type 2 diabetes mellitus is a risk factor for severe COVID-19 infection and is associated with increased risk of complications. The present study aimed to investigate effectiveness and persistence of different COVID vaccines in persons with or without diabetes during the Delta wave in Hungary., Research Design and Methods: Data sources were the national COVID-19 registry data from the National Public Health Center and the National Health Insurance Fund on the total Hungarian population. The adjusted incidence rate ratios and corresponding 95% CIs were derived from a mixed-effect negative binomial regression model., Results: A population of 672 240 cases with type 2 diabetes and a control group of 2 974 102 non-diabetic persons free from chronic diseases participated. Unvaccinated elderly persons with diabetes had 2.68 (95% CI 2.47 to 2.91) times higher COVID-19-related mortality rate as the 'healthy' controls. Primary immunization effectively equalized the risk of COVID-19 mortality between the two groups. Vaccine effectiveness declined over time, but the booster restored the effectiveness against mortality to over 90%. The adjusted vaccine effectiveness of the primary Pfizer-BioNTech against infection in the 14-120 days of postvaccination period was 71.6 (95% CI 66.3 to 76.1)% in patients aged 65-100 years with type 2 diabetes and 64.52 (95% CI 59.2 to 69.2)% in the controls. Overall, the effectiveness tended to be higher in individuals with diabetes than in controls. The booster vaccines could restore vaccine effectiveness to over 80% concerning risk of infection (eg, patients with diabetes aged 65-100 years: 89.1 (88.1-89.9)% with Pfizer-on-Pfizer, controls 65-100 years old: 86.9 (85.8-88.0)% with Pfizer-on-Pfizer, or patients with diabetes aged 65-100 years: 88.3 (87.2-89.2)% with Pfizer-on-Sinopharm, controls 65-100 years old: 87.8 (86.8-88.7)% with Pfizer-on-Sinopharm)., Conclusions: Our data suggest that people with type 2 diabetes may have even higher health gain when getting vaccinated as compared with non-diabetic persons, eliminating the marked, COVID-19-related excess risk of this population. Boosters could restore protection., Competing Interests: Competing interests: ZK is employed by MSD Pharma Hungary. At the time the study was performed, MK served as the Minister of Human Resources., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans arrived in Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150 year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Swabian individuals living in the Dunaszekcső-Bár area, in Danube side villages of Southwest Hungary. These Swabians, according to self-declaration, did not admix with other ethnic groups for 3-6 succeeding generations. Using Illumina Infinium 720 K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples., Results: Haplotype-based analyses like identity by descent segment analysis show that the investigated Danube Swabians possess significant German and other West European ancestry, but their Hungarian ancestry is also prominent. Our results suggest that their main source of ancestry can be traced back to Western Europe, presumably to the region of Germany., Conclusion: This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns., (© 2023. The Author(s).)

The Hunyadi family is one of the most influential families in the history of Central Europe in the 14th-16th centuries. The family's prestige was established by Johannes Hunyadi, a Turk-beater who rose to the position of governor of the Kingdom of Hungary. His second son, Matthias Hunyadi, became the elected ruler of the Kingdom of Hungary in 1458. The Hunyadi family had unknown origin. Moreover, Matthias failed to found a dynasty because of lacking a legitimate heir and his illegitimate son Johannes Corvinus was unable to obtain the crown. His grandson, Christophorus Corvinus, died in childhood, thus the direct male line of the family ended. In the framework of on interdisciplinary research, we have determined the whole genome sequences of Johannes Corvinus and Christophorus Corvinus by next-generation sequencing technology. Both of them carried the Y-chromosome haplogroup is E1b1b1a1b1a6a1c ∼, which is widespread in Eurasia. The father-son relationship was verified using the classical STR method and whole genome data. Christophorus Corvinus belongs to the rare, sporadically occurring T2c1+146 mitochondrial haplogroup, most frequent around the Mediterranean, while his father belongs to the T2b mitochondrial haplogroup, widespread in Eurasia, both are consistent with the known origin of the mothers. Archaeogenomic analysis indicated that the Corvinus had an ancient European genome composition. Based on the reported genetic data, it will be possible to identify all the other Hunyadi family member, whose only known grave site is known, but who are resting assorted with several other skeletons., Competing Interests: The authors declare the following conflict of interests: Péter L. Nagy is sole owner of Praxis Genomics LLC was not directly involved in the design and execution of the experiments of the manuscript. This affiliation does not alter our adherence to Heliyon policies on sharing data and materials. All other authors have no conflict to declare., (© 2022 The Author(s).)

Background: Assessment of population-based cancer survival may provide the most valuable feedback about the effectiveness of oncological surveillance and treatment. Aims: Based on the database of the Hungarian National Cancer Registry, standardized incidence rates of lung, breast, colorectal, prostate and cervical cancer were compared to standardized mortality data of the Hungarian Central Statistical Office in the period between 2001 and 2015. Then survival analysis was performed on cleansed database. Results: The incidence of colorectal, breast and prostate cancer increased, while standardized rates of lung and cervical cancer declined. The survival of colorectal, breast and prostate cancer showed improvement. Contrarily, lung cancer exhibited a mild decline, while that of cervical cancer did not change significantly. In earlier stages survival was improved among almost every studied tumor type, while in advanced stages improvement was not observed. Comparison of stage distribution revealed that in the 2011-2015 period colorectal, breast and prostate cancer cases were diagnosed at earlier stages, while lung and cervical cancer patients were typically discovered at more advanced stages. Discussion: The outcome of advanced cancer treatments is better in earlier stages, which highlighted the importance of screening network. However, growth of oncological treatment costs with longer patient survival imposes a constantly increasing burden on society., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kenessey, Szőke, Dobozi, Szatmári, Wéber, Fogarassy, Nagy, Kásler, Polgár and Vathy-Fogarassy.)

Background: In late 2021, the pandemic wave was dominated by the Delta SARS-CoV-2 variant in Hungary. Booster vaccines were offered for the vulnerable population starting from August 2021., Methods: The nationwide HUN-VE 3 study examined the effectiveness and durability of primary immunization and single booster vaccinations in the prevention of SARS-CoV-2 infection, Covid-19 related hospitalization and mortality during the Delta wave, compared to an unvaccinated control population without prior SARS-CoV-2 infection., Results: The study population included 8,087,988 individuals who were 18-100 years old at the beginning of the pandemic. During the Delta wave, after adjusting for age, sex, calendar day, and chronic diseases, vaccine effectiveness (VE) of primary vaccination against registered SARS-CoV-2 infection was between 11% to 77% and 18% to 79% 14-120 days after primary immunization in the 16-64 and 65-100 years age cohort respectively, while it decreased to close to zero in the younger age group and around 40% or somewhat less in the elderly after 6 months for almost all vaccine types. In the population aged 65-100 years, we found high, 88.1%-92.5% adjusted effectiveness against Covid-19 infection after the Pfizer-BioNTech, and 92.2%-95.6% after the Moderna booster dose, while Sinopharm and Janssen booster doses provided 26.5%-75.3% and 72.9%-100.0% adjusted VE, respectively. Adjusted VE against Covid-19 related hospitalization was high within 14-120 days for Pfizer-BioNTech: 76.6%, Moderna: 83.8%, Sputnik-V: 78.3%, AstraZeneca: 73.8%, while modest for Sinopharm: 45.7% and Janssen: 26.4%. The waning of protection against Covid-19 related hospitalization was modest and booster vaccination with mRNA vaccines or the Janssen vaccine increased adjusted VE up to almost 100%, while the Sinopharm booster dose proved to be less effective. VE against Covid-19 related death after primary immunization was high or moderate: for Pfizer-BioNTech: 81.5%, Moderna: 93.2%, Sputnik-V: 100.0%, AstraZeneca: 84.8%, Sinopharm: 58.6%, Janssen: 53.3%). VE against this outcome also showed a moderate decline over time, while booster vaccine types restored effectiveness up to almost 100%, except for the Sinopharm booster., Conclusions: The HUN-VE 3 study demonstrated waning VE with all vaccine types for all examined outcomes during the Delta wave and confirmed the outstanding benefit of booster vaccination with the mRNA or Janssen vaccines, and this is the first study to provide clear and comparable effectiveness results for six different vaccine types after primary immunization against severe during the Delta pandemic wave., Competing Interests: Author ZB was employed by company Syntesia Medical Communications Ltd. ZB of Syntesia Medical Communications Ltd. received payment for medical writing support from the National Public Health Center of Hungary. ZK is employed by MSD Pharma Hungary Ltd., too. However, this provides no relevant conflict of interest for the current research. At the time the study was performed, MK served as the minister of human resources. The ministry includes the secretariat for health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vokó, Kiss, Surján, Surján, Barcza, Wittmann, Molnár, Nagy, Müller, Bogos, Nagy, Kenessey, Wéber, Polivka, Pálosi, Szlávik, Rokszin, Müller, Szekanecz and Kásler.)

Background: In Hungary, the pandemic waves in late 2021 and early 2022 were dominated by the Delta and Omicron SARS-CoV-2 variants, respectively. Booster vaccines were offered with one or two doses for the vulnerable population during these periods., Methods and Findings: The nationwide HUN-VE 2 study examined the effectiveness of primary immunization, single booster, and double booster vaccination in the prevention of Covid-19 related mortality during the Delta and Omicron waves, compared to an unvaccinated control population without prior SARS-CoV-2 infection during the same study periods. The risk of Covid-19 related death was 55% lower during the Omicron vs. Delta wave in the whole study population (n=9,569,648 and n=9,581,927, respectively; rate ratio [RR]: 0.45, 95% confidence interval [CI]: 0.44-0.48). During the Delta wave, the risk of Covid-19 related death was 74% lower in the primary immunized population (RR: 0.26; 95% CI: 0.25-0.28) and 96% lower in the booster immunized population (RR: 0.04; 95% CI: 0.04-0.05), vs. the unvaccinated control group. During the Omicron wave, the risk of Covid-19 related death was 40% lower in the primary immunized population (RR: 0.60; 95% CI: 0.55-0.65) and 82% lower in the booster immunized population (RR: 0.18; 95% CI: 0.16-0.2) vs. the unvaccinated control group. The double booster immunized population had a 93% lower risk of Covid-19 related death compared to those with only one booster dose (RR: 0.07; 95% CI. 0.01-0.46). The benefit of the second booster was slightly more pronounced in older age groups., Conclusions: The HUN-VE 2 study demonstrated the significantly lower risk of Covid-19 related mortality associated with the Omicron vs. Delta variant and confirmed the benefit of single and double booster vaccination against Covid-19 related death. Furthermore, the results showed the additional benefit of a second booster dose in terms of SARS-CoV-2 infection and Covid-19 related mortality., Competing Interests: Author ZB was employed by company Syntesia Medical Communications Ltd. ZB of Syntesia Medical Communications Ltd. received payment for medical writing support from the National Public Health Center of Hungary. ZK is employed by MSD Pharma Hungary Ltd., too. However, this provides no relevant conflict of interest for the current research. At the time the study was performed, MK served as the minister of human resources. The ministry includes the secretariat for health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kiss, Wittmann, Polivka, Surján, Surján, Barcza, Molnár, Nagy, Müller, Bogos, Nagy, Kenessey, Wéber, Pálosi, Szlávik, Schaff, Szekanecz, Müller, Kásler and Vokó.)

(1) Background: SARS-CoV-2 infections are associated with an increased risk of hospital admissions especially in the elderly (age ≥ 65 years) and people with multiple comorbid conditions. (2) Methods: We investigated the effect of additional booster vaccinations following the primary vaccination series of mRNA, inactivated whole virus, or vector vaccines on infections with the SARS-CoV-2 delta variant in the total Hungarian elderly population. The infection, hospital admission, and 28-day all-cause mortality of elderly population was assessed. (3) Results: A total of 1,984,176 people fulfilled the criteria of elderly including 299,216 unvaccinated individuals, while 1,037,069 had completed primary vaccination and 587,150 had obtained an additional booster. The primary vaccination series reduced the risk of infection by 48.88%, the risk of hospital admission by 71.55%, and mortality by 79.87%. The booster vaccination had an additional benefit, as the risk of infection, hospital admission, and all-cause mortality were even lower (82.95%; 92.71%; and 94.24%, respectively). Vaccinated patients needing hospitalization suffered significantly more comorbid conditions, indicating a more vulnerable population. (4) Conclusions: Our data confirmed that the primary vaccination series and especially the booster vaccination significantly reduced the risk of the SARS-CoV-2 delta-variant-associated hospital admission and 28-day all-cause mortality in the elderly despite significantly more severe comorbid conditions.

Skin melanoma is not among malignancies with the highest incidences and mortalities worldwide; however, the observed constant increase in newly diagnosed cases is troublesome. According to the database of the Hungarian Cancer Registry, the number of newly reported cases doubled between 2001 and 2019, which is consistent with international data. Notwithstanding, within the same interval, Hungarian mortality did not change significantly according to the database of the Hungarian Statistical Office, which is in contrast to international trends. The increasing incidence together with unchanging mortality resulted in better survival rates and hence more favorable follow-up data in our country. Advancements in secondary prevention programs and better efficacy of modern therapeutic interventions in the last decade may have contributed to the observed improvement in the survival rates of Hungarian melanoma patients.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mátrai, Kelemen, Kósa, Maráz, Paszt, Pavlovics, Sávolt, Simonka, Tóth, Kásler, Kaprin, Krivorotko, Vicko, Pluta, Kolacinska-Wow, Murawa, Jankau, Ciesla, Dyttert, Sabol, Zhygulin, Avetisyan, Bessonov and Lázár.)

The incidence and mortality of malignant diseases show constant increase worldwide. Proper epidemiological data may establish the planning and development of oncological network, which is provided by population-based registries (in Hungary: National Cancer Registry). The quality of the reported data determines the reliability of the Registry. Recorded medical codes during everyday physician-patient encounters are part of the official documentation as well as a permanent imprint of the medical activity in the Registry's database. Uncritical coding degrades the quality of epidemiological data, moreover, leads to unnecessary patient stigmatization, which may be the base of legal procedure against the physician who authenticated the false code. However, neither graduate nor postgraduate medical training focus on coding. In addition, hospitals apply obsolete versions of coding systems which does not follow developments in medicine. The aim of the present review is presentation of proper coding in oncology, which may contribute to avoid that kind of basic professional pitfalls, and improve quality of medical activity.

Genome-wide genotype data from 48 carefully selected population samples of Transylvania-living Szeklers and non-Szekler Hungarians were analyzed by comparative analysis. Our analyses involved contemporary Hungarians living in Hungary, other Europeans, and Eurasian samples counting 530 individuals altogether. The source of the Szekler samples was the commune of Korond, Transylvania. The analyzed non-Szekler Hungarian samples were collected from villages with a history dating back to the era of the Árpád Dynasty. Population structure by principal component analysis and ancestry analysis also revealed a great within-group similarity of the analyzed Szeklers and non-Szekler Transylvanian Hungarians. These groups also showed similar genetic patterns with each other. Haplotype analyses using identity-by-descent segment discovering tools showed that average pairwise identity-by-descent sharing is similar in the investigated populations, but the Korond Szekler samples had higher average sharing with the Hungarians from Hungary than non-Szekler Transylvanian Hungarians. Average sharing results showed that both groups are isolated compared to other Europeans, and pointed out that the non-Szekler Transylvanian Hungarian inhabitants of the investigated Árpád Age villages are more isolated than investigated Szeklers from Korond. This was confirmed by our autozygosity analysis as well. Identity-by-descent segment analyses and 4-population tests also confirmed that these Hungarian-speaking Transylvanian ethnic groups are strongly related to Hungarians living in Hungary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ádám, Bánfai, Sümegi, Büki, Szabó, Magyari, Miseta, Kásler and Melegh.)

Objectives: The Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. This observational study (HUN-VE: Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million vaccinated individuals., Methods: Incidence rates of SARS-CoV-2 infection and COVID-19-related mortality were calculated using data from the National Public Health Centre surveillance database. Estimated vaccine effectiveness was calculated as 1 - incidence rate ratio ≥7 days after the second dose for each available vaccine versus an unvaccinated control group using mixed-effect negative binomial regression controlling for age, sex and calendar day., Results: Between 22 January 2021 and 10 June 2021, 3 740 066 Hungarian individuals received two doses of the BNT162b2 (Pfizer-BioNTech), HB02 (Sinopharm), Gam-COVID-Vac (Sputnik-V), AZD1222 (AstraZeneca), or mRNA-1273 (Moderna) vaccines. Incidence rates of SARS-CoV-2 infection and COVID-19-related death were 1.73-9.3/100 000 person-days and 0.04-0.65/100 000 person-days in the fully vaccinated population, respectively. Estimated adjusted effectiveness varied between 68.7% (95% CI 67.2%-70.1%) and 88.7% (95% CI 86.6%-90.4%) against SARS-CoV-2 infection, and between 87.8% (95% CI 86.1%-89.4%) and 97.5% (95% CI 95.6%-98.6%) against COVID-19-related death, with 100% effectiveness in individuals aged 16-44 years for all vaccines., Conclusions: Our observational study demonstrated the high or very high effectiveness of five different vaccines in the prevention SARS-CoV-2 infection and COVID-19-related death., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Basal-like breast cancer (BLBC) is the most aggressive subtype of breast tumors with poor prognosis and limited molecular-targeted therapy options. We show that BLBC cells have a high Cys demand and reprogrammed Cys metabolism. Patient-derived BLBC tumors from four different cohorts exhibited elevated expression of the transsulfuration enzyme cystathione β-synthetase (CBS). CBS silencing (shCBS) made BLBC cells less invasive, proliferate slower, more vulnerable to oxidative stress and cystine (CySSCy) deprivation, prone to ferroptosis, and less responsive to HIF1-α activation under hypoxia. shCBS xenograft tumors grew slower than controls and exhibited impaired angiogenesis and larger necrotic areas. Sulfur metabolite profiling suggested that realigned sulfide/persulfide-inducing functions of CBS are important in BLBC tumor progression. Supporting this, the exclusion of serine, a substrate of CBS for producing Cys but not for producing sulfide/persulfide, did not exacerbate CySSCy deprivation-induced ferroptosis in shCBS BLBC cells. Impaired Tyr phosphorylation was detected in shCBS cells and xenografts, likely due to persulfidation-inhibited phosphatase functions. Overexpression of cystathione γ-lyase (CSE), which can also contribute to cellular sulfide/persulfide production, compensated for the loss of CBS activities, and treatment of shCBS xenografts with a CSE inhibitor further blocked tumor growth. Glutathione and protein-Cys levels were not diminished in shCBS cells or xenografts, but levels of Cys persulfidation and the persulfide-catabolizing enzyme ETHE1 were suppressed. Finally, expression of enzymes of the oxidizing Cys catabolism pathway was diminished, but expression of the persulfide-producing CARS2 was elevated in human BLBC tumors. Hence, the persulfide-producing pathways are major targetable determinants of BLBC pathology that could be therapeutically exploited., Competing Interests: The authors declare no competing interest.

Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high-quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures - namely translational research, clinical/prevention trials and outcomes research - were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next-generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health-related quality-of-life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU-wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The ancient Hungarians, "Madzsars", established their control of the Carpathian Basin in the late ninth century and founded the Hungarian Kingdom around 1000AD. The origin of the Magyars as a tribal federation has been much debated in the past. From the time of the conquest to the early fourteenth century they were ruled by descendants of the Arpad family. In order to learn more about the genetic origin of this family, we here analyzed the genome of Bela III one of the most prominent members of the early Hungarian dynasty that ruled the Hungarian Kingdom from 1172 to 1196. The Y-Chromosome of Bela III belongs to haplogroup R1a-Z2123 that is today found in highest frequency in Central Asia, supporting a Central Asian origin for the ruling lineage of the Hungarian kingdom. The autosomal DNA profile of Bela III, however, falls within the genetic variation of present-day east European populations. This is further supported through his mtDNA genome that belongs to haplogroup H, the most common European maternal lineage, but also found in Central Asia. However, we didn't find an exact haplotype match for Bela III. The typical autosomal and maternal Central Eastern European ancestry among Bela III autosomes might be best explained by consecutive intermarriage with local European ruling families., (© 2021. The Author(s).)

We set out to identify the origins of the Árpád Dynasty based on genome sequencing of DNA derived from the skeletal remains of Hungarian King Béla III (1172-1196) and eight additional individuals (six males, two females) originally interred at the Royal Basilica of Székesfehérvár. Y-chromosome analysis established that two individuals, Béla III and HU52 assign to haplogroups R-Z2125 whose distribution centres near South Central Asia with subsidiary expansions in the regions of modern Iran, the Volga Ural region and the Caucasus. Out of a cohort of 4340 individuals from these geographic areas, we acquired whole-genome data from 208 individuals derived for the R-Z2123 haplogroup. From these data we have established that the closest living kin of the Árpád Dynasty are R-SUR51 derived modern day Bashkirs predominantly from the Burzyansky and Abzelilovsky districts of Bashkortostan in the Russian Federation. Our analysis also reveals the existence of SNPs defining a novel Árpád Dynasty specific haplogroup R-ARP. Framed within the context of a high resolution R-Z2123 phylogeny, the ancestry of the first Hungarian royal dynasty traces to the region centering near Northern Afghanistan about 4500 years ago and identifies the Bashkirs as their closest kin, with a separation date between the two populations at the beginning of the first millennium CE.

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

History of East-Central Europe has been intertwined with the history of Turks in the past. A significant part of this region of Europe has been fallen under Ottoman control during the 150 years of Ottoman occupation in the 16-17th centuries. The presence of the Ottoman Empire affected this area not only culturally but also demographically. The Romani people, the largest ethnic minority of the East-Central European area, share an even more eventful past with Turkish people from the time of their migration throughout Eurasia and they were a notable ethnic group in East-Central Europe in the Ottoman era already. The relationship of Turks with East-Central European ethnic groups and with regional Roma ethnicity was investigated based on genome-wide autosomal single nucleotide polymorphism data. Population structure analysis, ancestry estimation, various formal tests of admixture and DNA segment analyses were carried out in order to shed light to the conclusion of these events on a genome-wide basis. Analyses show that the Ottoman occupation of Europe left detectable impact in the affected East-Central European area and shaped the ancestry of the Romani people as well. We estimate that the investigated European populations have an average identity-by-descent share of 0.61 with Turks, which is notable, compared to other European populations living in West and North Europe far from the affected area, and compared to the share of Sardinians, living isolated from these events. Admixture of Roma and Turks during the Ottoman rule show also high extent.

Most head and neck cancer patients are treated with combined modalities such as surgery, radiotherapy (RT), chemotherapy (ChT). Concurrent chemo-radiation has improved treatment outcomes with increased toxic effects. Reactions after RT are divided into early and late changes. Early reactions are seen during the course of therapy or within 3 months; these are reversible in most cases. Late complications are observed 3 months to years after RT and they are generally irreversible. As typical late reaction radiation induced necrosis may occur in soft tissues, cartilage, bones and brain. Tumor recurrence and post-radiation necrosis typically appear at the same time, within 2-3 years after RT; the differentiation may be difficult. Computed tomography (CT) and magnetic resonance imaging (MRI) have become the gold standards not only for staging and assessing tumor response, but also to evaluate posttreatment status, to distinguish residual or recurrent tumor and RT complications. Using baseline CT or MRI between 2-3 months after treatment and performing standard follow-up imaging with strict clinical follow-up are required to establish early salvage treatment.

Background/aim: Despite well-organized Hungarian invitational mammography screening, participation rates have never reached 50%. This is similar to rates in Central Eastern Europe. In order to reduce breast cancer mortality, the participation rate should be at least 70%. This questionnaire-based study assessed the barriers associated with low adherence rates., Materials and Methods: Women 45-65 years of age were interviewed by questionnaire containing 15 structured questions focused on socioeconomic status and barriers to screening., Results: A total of 3,313 women completed the questionnaire. The main reasons for avoiding screening were work absenteeism (18.9%), fear of painful examination (18.39%), and poor understanding of mammography screening (14.94%)., Conclusion: Education is required to increase awareness among women about the utility and availability of breast screening services. This report provides information on the appropriate level of intervention needed to increase screening participation in Hungary and other developing countries in Central Eastern Europe to reduce breast cancer-related mortality., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: This study aimed to determine the ability of multimodal evaluation with multiparametric 3T-MRI (MPMRI) and positron emission tomography - computed tomography (PET/CT) to detect cancer of unknown primary origin (CUP) with neck lymph node (LN) metastasis., Methods: The study group comprised 38 retrospectively analysed consecutive patients with LN metastasis in the head and neck (HN) region without known primary tumours (PTs). Statistical values of 3T-MRI and of FDG-PET/CT scans were evaluated., Results: Of the 38 CUPs, conventional native T1-, T2-weighted and STIR sequences detected 6 PTs. Native sequences plus diffusion-weighted imaging (DWI) found 14-, and with fat suppression contrast-enhanced T1-weighted measurement as well as with the complex MPMRI found 15 primaries and with PET/CT 17 CUPs could be evaluated, respectively. The detection rates were 15.8, 36.8, 39.5, 39.5 and 44.7 % for conventional native MRI, native plus DWI, native with contrast-enhanced MRI (CE-MRI), for MPMRI, and for PET/CT, respectively. The overall detection rate proved by histology was 47.4 %. PET/CT provided the highest sensitivity (Sv: 94.4 %) but a lower specificity (Sp: 65.0 %), using MPMRI (Sv: 88.2 %) the specificity increased to 71.4 %. DWIincreased specificity of the native sequences (Sp: 76.2 %). Conventional native sequences plus DWI as well as 3T-MPMRI and PET/CT were same accurate (Acc: 79.0 %) and had similar likelihood ratio (LR: 3.42, 3.03 and 2.62) in detecting unknown PT sites., Conclusions: The accuracy of FDG-PET/CT and MPMRI in case of CUP in finding the primary cancer in the neck regions is identical. While using PET/CT whole body information can be obtained in one examination. MPMRI shows the local soft tissue status more accurately. In cases of CUP PET/CT should be the first method of choice if it is available. MPMRI can clarify the exact primary tumor stage, and it can be advantageous in clarifying the prognostic factors, which is necessary in case of advanced tumor stage and when surgery is under consideration. In case low N stage is likely after the clinical examination and wait and see policy can be considered, MPMRI is recommended, and in this case the significance the of radiation free MPMRI is increasing.

The rapidly growing field of gene therapy techniques to modify T cells with chimeric antigen receptors (CARs) for cancer care solutions, reached considerable achievements. However, there is an urgent need of reliable, well tolerable tumor-associated antigen specific antibodies. Tumor-infiltrating B (TIL-B) cell originated single chain Fv (scFv) gene regions could be selected with tumor specificity. DNA sequences of these antibody variable regions were subjects to get engineered into new CAR constructs. Our novel strategy harnesses tumor-infiltrating B cells' unique capacity to reveal highly tumor-associated disialylated glycosphingolipids (GD3 gangliosides). We used these human antibody fragments for generating GD3 ganglioside specific CAR gene constructs for potential usage in solid tumors.

Lung cancer is a heterogeneous group of disease and mutational profiling of lung adenocarcinomas is a routine practice in thoracic oncology. Kirsten-RAS (KRAS) and EGFR mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas. Our aim was to investigate the correlation between bone metastases and EGFR and KRAS mutation status in lung adenocarcinoma patients. Retrospectively we analysed 224 patients with recurrent or metastatic lung adenocarcinomas. Patients were treated with standard chemotherapy as first line therapy and with EGFR-TK inhibitors as a second or third line therapy. 72 of 224 patients (32 %) had verified bone metastases. Bone metastases and Skeletal Related Events (SRE) were more frequent in men, heavy smokers and without treatment of EGFR TK inhibitors. We have found that EGFR and KRAS mutation status are both predictive factors for the treatment efficacy and prognostic factors for the disease progression. However there were no significant correlation between mutation status and the presence of bone metastases (P = 0, 59). In our study the presence of bone metastases proved to be an independent prognostic factor related to poor performance status and worse Quality of Life (QL).

Background: We investigated in postmenopausal women with primary breast cancer prior to surgical intervention whether, serum levels of different steroid hormones and hormonal precursors associated with tumor tissue estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status., Methods: We enrolled 1,042 patients suffering invasive ductal carcinoma undergoing surgical resection in the National Institute of Oncology, Hungary between 2003 and 2011. Serum parameters were measured by RIA/IRMA assays; tumor tissue ER, PR and HER2 status was assessed histologically. Patients were classified according to tumor receptor status. Case-case analysis subjects were categorized into four subgroups based on serum hormone concentrations in ER, PR and HER2 receptor-negative cases, respectively., Results: Serum estrone sulfate and dehydroepiandrosterone sulfate levels correlated with each other and also with serum estrone and estradiol levels. According to case-case study the odds ratios in the highest quartile were 1.517 (p = 0.0305, Ptrend = 0.0394) for androstenedione, 1.495 (p = 0.0317, Ptrend < 0.0105) for estrone and 0.654 (p = 0.0273, Ptrend < 0.0151) for estrone sulfate/estrone ratio in PR+ vs. PR- tumors. Regarding HER2 status (HER2+ vs. HER2-), the odds ratios for estrone, estrone sulfate and estrone sulfate/estrone ratio were 0.530 (p = 0.0234, Ptrend = 0.0595), 2.438 (p = 0.0042, Ptrend < 0.0066) and 3.118 (p = 0.0001, Ptrend < 0.0001) in the highest quartile, respectively. Of note significantly increased BMI associates with PR+ and ER +/PR+ status while significantly decreased BMI was observed in HER2+ cases., Conclusions: Taken together, measurement of serum estrone and estrone sulfate concentrations prior to surgical intervention might support the individualization of regime in postmenopausal primary breast cancer patients.

The purpose of the study is to report the status of Hungarian radiotherapy (RT) based on the assessment of treatment data in years 2012 to 2014, available infrastructure, and RT staffing. Between December 2014 and January 2015, a RT questionnaire including 3 parts (1. treatment data; 2. infrastructure; 3. staffing) was sent out to all Hungarian RT centers (n=12). All RT centers responded to all questions of the survey. 1. Treatment data: In 2014, 33,162 patients were treated with RT: 31,678 (95.5%) with teletherapy, and 1484 (4.5%) with brachytherapy (BT). Between 2012 and 2014, the number of patients treated with radiotherapy increased with 6.6%, but the number of BT patients decreased by 11%. Forty-two percent of all patients were treated in the two centers of the capital: 9235 patients (28%) at the National Institute of Oncology (NIO), and 4812 (14%) at the Municipial Oncoradiology Center (MOC). Out of the patients treated on megavoltage RT units (n=22,239), only 901 (4%) were treated with intensity-modulated RT (IMRT), and 2018 (9%) with image-guided RT (IGRT). In 2014, 52% of all BT treatments were performed in Budapest: NIO - 539 patients (36%); MOC - 239 patients (16%); and BT was not available in 3 RT centers. Prostate I-125 seed implants and interstitial breast BT was utilized in one, prostate HDR BT in two, and head&neck implants in three centers. 2. Infrastructure: Including ongoing development projects funded by the European Union, by the end of year 2015, 39 megavoltage teletherapy units, and 12 HDR BT units will be in use in 13 available Hungarian RT centers. 3. Staffing: Actually, 92 radiation oncologists (RO), 29 RT residents, 61 medical physicists, and 229 radiation therapy technologists are working in 12 RT centers. There are 23 vacant positions (including 11 RO positions) available at the Hungarian RT centers. According to the professional minimal requirements and WHO guidelines, the implementation of 11 new linear accelerators, and 1 BT units are needed in Hungary. Further resources for the development and upgrade of RT infrastructure and capacity should be allocated to RT centers in Budapest. Brachytherapy and modern teletherapy (e.g. IMRT and IGRT) are underutilized in Hungary compared to other European countries. Implementation of continuous education and practical training programs in leading Hungarian and international RT centers are suggested in an effort to a wider implementation of modern RT techniques in Hungarian RT centers.

The role of preoperative intrauterine brachytherapy (BT) in the multidisciplinary treatment of early stage cervical carcinoma (ESCC) is controversial. In 2005, a prospective randomized multicenter study was initiated in Hungary in order to explore the potential advantages of preoperative high-dose-rate (HDR) BT. In this article we evaluate the efficiency of preoperative HDR BT by the rate of pathologic complete remission (pCR) in the first 185 patients enrolled in the study at the National Institute of Oncology and at the Uzsoki Municipal Cancer Center in collaboration with the 1st Department of Gynaecology and Obstetrics of Semmelweis University, Budapest, Hungary. In arm A, patients received 2x8Gy preoperative intracavitary HDR BT, while in arm B no preoperative treatment was given. In both arms patients underwent radical Wertheim (Piver III) hysterectomy. The pCR rate was 25.7% after preoperative HDR BT, while it was only 11.2% with surgery alone (p=0.03), in these cases the tumor was eliminated during the diagnostic excision or conisation. The rate of positive surgical margins was 1.5% after preoperative BT, while it was as high as 11.4% without preoperative RT (p=0.02). There was no significant difference in the local tumor control (LTC), distant metastases free survival (DMFS) and overall survival (OS) between the two arms. According to our preliminary results preoperative intracavitary HDR BT significantly increases the rate of pCR and decreases the rate of positive surgical margins in patients with ESCC. Longer follow-up is required to establish the possible impact of pCR on the ultimate LTC and OS.

Background: According to European guidelines, breast cancer patients requiring mastectomy should be informed about available options regarding breast reconstruction. There are clear differences in the quality standards of oncoplastic care throughout Europe, with slight improvements in Central European countries like Hungary. The aim of the present investigation was to evaluate patients' knowledge and demand for postmastectomy breast reconstruction, as well as their psychosocial background regarding decision-making., Material and Methods: A questionnaire containing 15 structured questions was given to 500 breast cancer patients on the day before undergoing mastectomy. The questions focused on the emotional impact of the malignant disease and the loss of a breast; the importance of environmental conditions; the desire for breast reconstruction; and patients' knowledge and sources of information about the procedure. All answers were statistically analyzed in the context of patient age, marital status, educational level, and place of residence., Results: Descriptive statistical results of the answers to all questions, as well as associations of the different aspects of the decision-making process, are presented., Conclusions: Hungarian breast cancer patients have very limited knowledge regarding breast reconstruction. We confirmed that patients scheduled for mastectomy have a great degree of anxiety due to their disease and breast loss. Almost 50% of the responders declared their desire for postmastectomy breast reconstruction. Patient's age, residence, educational level, marital status, and profession were confirmed as predictive factors in the decision-making process for breast reconstruction.

Prostate cancer is one of the leading cancer types in males in the developed world. Radiotherapy is a major method in the curative treatment of prostate cancer however, up to 30% of the patients experience local relapse. Arachidonic acid metabolites have been shown to have important role in cancer. 12-lipoxygenase (12-LOX) has been proven to significantly influence prostate cancer progression, by apoptosis regulation and by promoting cancer cell survival. In this study we examined whether 12-LOX inhibition may increase radiation sensitivity of prostate cancer cells in vitro and in vivo. Prostate cancer cell lines were treated with 12-LOX inhibitors, different doses of radiation and the combination of 12-LOX inhibitors and radiation. We measured the effect of these treatments through clonogenic survival and apoptosis in vitro and tumor growth in vivo in a tumor xenograft model. 12-LOX inhibition and radiation both increased apoptosis and decreased clonogenic survival of prostate cancer cell lines in vitro. Combined treatment resulted in a supra-additive effect in vitro. In vivo both 12-LOX inhibition and radiotherapy caused delay in growth of the xenograft tumors but the combined treatment resulted in the strongest growth inhibition. The presented data prove that 12-LOX and its metabolite 12(S)-HETE have a major role in prostate cancer cell progression and radiosensitivity. We have shown by different methods in vitro and in vivo that inhibition of 12-LOX activity significantly sensitizes prostate cancer cells to radiation. Therefore we can state that 12-LOX inhibitors are promising compounds to be developed to become a new class of clinical radiation sensitizers in prostate cancer.

Oncoplastic surgical techniques seem to be suitable for realizing the goal of retaining cosmesis following radical removal of breast tumors. The purpose of the present study is to provide a clinical and pathological comparison of conventional (BCS) and oncoplastic (OPS) breast-conserving surgeries, supplemented by a subjective assessment of cosmesis and quality of life of patients, the first time on a Hungarian sample. The authors performed a retrospective assessment of clinicopathological data of 60 advanced oncoplastic and 60 conventional breast-conserving surgery cases, and following adjuvant radiotherapy, the authors also surveyed patients for cosmetic results and quality of life (EORTC BR23). Comparison of the results was performed by statistical methods. The two groups did not differ substantially in age, tumor location, breast size, type of axillary surgery (sentinel node biopsy vs. axillary lymphadenectomy), tumor grade and receptor status. Tumor size was significantly greater (p=0.0009), the rate of quadranectomies was higher (p=0.0032), metastases in the regional lymph nodes (p=0.0043) and the administration of adjuvant chemotherapy (p=0.0122) were more frequent in the OPS group. The duration of surgeries was longer (p<0.001), the weight of the specimens was greater (p=0.0308), the rate of completion surgeries due to microscopically positive surgical margins was significantly smaller (p=0.0306) in the OPS than in the BCS group. There was no difference between the two groups in the rate of complications and the time elapsed to the start of adjuvant treatment. The cosmetic outcome was clearly superior in the OPS group (p<0.001), and OPS patients had fewer arm, shoulder (p=0.0399), and chest pain (of the affected side) (p=0.0304), upper limb movements of the operated side were also better (p=0.006). The short follow-up period of the OPS group (mean 32.2 vs. 8.7 months in BCS and OPS, respectively) did not allow a meaningful assessment of oncologic endpoints. When compared to conventional breast conserving surgery, oncoplastic surgery is suitable for microscopically radical tumor removal even in case of larger lesions and true quadranectomy with longer surgical time but lower rate of complications without delaying the adjuvant treatments and thus not increasing the cancer risk. OPS yields better cosmetic results and higher patient satisfaction compared to BCS. More experience and longer follow-up is needed for the assessment of local tumor control achieved by OPS.

[18F]-Fluoro-deoxyglucose positron emission tomography / computer tomography (18F-FDG PET/CT) is able to detect and assess the abnormal metabolism, enabling visualization and quantification in vivo with integration into CT anatomic information. The clinical usefulness of FDG PET/CT in the management of patients with sarcomas has been assessed by numerous investigators. Sarcomas are solid malignant tumors with distinct clinical and pathological features. Effective management of patients with sarcoma requires accurate diagnosis and staging. The authors discuss the major indications of PET/CT on the basis of literature data for diagnosis, staging, guidance of biopsy and monitoring response to therapy in both primary bone and soft tissue tumors. The consistent use of PET molecular imaging methods is of high importance in characterizing and understanding sarcoma behavior in clinical practice.

Glioblastoma multiforme has one of the worst prognoses of all cancers. A substantial progression in its treatment has been achieved only eight years ago when a new adjuvant radiochemotherapy regimen containing temozolomid has been introduced to the clinical practice. In this paper we evaluate the treatment results in adjuvant radiochemotherapy of glioblastoma carried out by two neurosurgery and oncology centers in Budapest, Hungary and we compared our results to the data of the reference phase III registration trial of the EORTC/NCIC. We analyzed the data of 210 patients treated for glioblastoma between 2005 and 2013. The primary endpoints of our study were overall survival and side effects. We studied and statistically analyzed the influence of multiple factors on survival. We compared our results with the data of the reference study and other results published in the literature. The median follow-up for the surviving patients in our study was 52 months. The median age of our patients was 58 (18-79) years. Seventy-two women and 138 men have been treated. The median overall survival was 17 (3-96) months, the progression-free survival 11 (3-96) months. The radiochemotherapy phase was completed in 95.2% and the monotherapy phase in 68% of all cases.Univariate analysis showed that age, ECOG status and RPA class had significant influence on survival. In multivariate analysis only RPA class remained statistically significant (RR 1.86, 95% CI 1.14-3.05). The proportion of grade III and worse side effects during the chemoradiation phase was 3.8% and in the monotherapy phase 1.9%. These were hematological side effects only. Serious hematological sequelae occurred nearly exclusively in women. Comparing to the reference study the demographic distribution of the patients was similar in our study but among our patients there were less patients with unfavorable prognosis (ECOG 2 or RPA V), and it resulted in a longer median survival than in the original trial (17 vs. 14.6 months). With this analysis of our patients treated according to the Stupp-protocol for glioblastoma multiforme we validated the results of the original EORTC/NCIC study in a Hungarian patient population. Moreover, this comparison proves that the comprehensive Hungarian neuro-oncology service is not at all inferior when compared to any of the developed countries in Europe.

The wide use of molecular positron emission tomography/computed tomography (PET/CT) imaging in the tumor diagnostics has been playing an important role recently. The clinical role of hybrid imaging (PET/CT, single photon ECT/CT (SPECT/CT)) is growing continuously due to the simultaneous imaging of anatomy and function. Regarding oncology the role of (18)F-fluorodeoxyglucose ((18)F-FDG) PET is proved in several clinical questions, including urooncology. Urologic cancers are associated with low or slightly significant uptake of FDG, due to their more benign behaviour. However, alternative PET tracers have been developed which show promising clinical results and hopefully, in the near future the combination of different tracers are awaited. Additionally, in the future the use of multiparametric measurements, multitracer techniques, and the multimodal PET/magnetic resonance imaging (PET/MRI) technology is going to have a crucial clinical role.

Red mud is an industrial waste produced in the process of alumina extraction from bauxite with concentrated NaOH. When the red mud-containing reservoir collapsed in Ajka Alumina Plant Hungary in October 2010, the most serious immediate effects were caused by the high alkalinity (pH ≥ 13) of the flood. Many persons suffered burn-like damage to tissues and contact with caustic desiccated ultra-fine dust with traces of toxic metals also caused irritation of upper respiratory tract and eyes. This catastrophe was unique from the point of view of genotoxic effects as well. Therefore cytogenetic examinations were carried out on inhabitants, either with burns (17 persons) or on those inhaling desiccated caustic dust (42 persons). Chromosomal aberration (CA) analysis and bleomycin (BLM)-sensitivity assays, as possible markers of effects, were studied in peripheral blood lymphocytes of persons within 4-6 weeks following the catastrophe. Controls were matched for age, sex and smoking habits, and also places of residence with different constituents of air pollution either from rural (59 persons), or from urban environments (59 persons). Neither spontaneous rate of CAs (1.47% vs. 1.69%) nor BLM-induced in vitro chromosomal breakage (0.79 vs. 0.83 break/cell) showed elevated rates when cytogenetic biomarkers of genotoxicity were compared between controls and exposed persons. Time spent in cleaning did not affect cytogenetic changes either (R(2) = 0.04). BLM-induced mutagen sensitivity was similar in exposed and control persons (27.1% vs. 30.5%). It seems that the red mud exposure does not appear to pose an immediate genotoxic hazard on residents when measured with cytogenetic methods. We recommend, however, that those involved in clean-up activities should be followed closely not only for overall health, but also for further genotoxic risk assessment, because the long-term hazards of ultra-fine fugitive dust particles with alkalinity of residual NaOH in red mud are still unknown.

The aim of the study was to implement accelerated partial breast irradiation (APBI) by means of three-dimensional conformal radiotherapy (3D-CRT) following breast-conserving surgery (BCS) for early-stage breast cancer. Between December 2006 and February 2011, in 45 cases of low-risk, stage I-II breast cancer the tumour bed was marked with titanium clips during BCS. Postoperative APBI was given by means of 3D-CRT using 3 to 5 non-coplanar fields. The total dose of APBI was 36.9 Gy (9 x 4.1 Gy) using a twice-a-day fractionation over 5 consecutive days. Early and late radiation side effects and cosmetic results were analysed for the first 30 patients with a minimum follow-up of 1 year. At a mean follow-up of 25.2 months neither loco-regional nor distant failure was observed. Excellent, good, fair, and poor cosmetic outcome was detected in 10 (33.3%), 16 (53.4%), 4 (13.3%), and 0 (0%) patients, respectively. Grade 2 or worse acute side effect was not observed. Grade 1 fibrosis, grade 2 teleangiectasia and asymptomatic fat necrosis occurred in 4 (13.3%), 1 (3.3%) and 5 (16.7%) patients, respectively. No grade 3-4 late side effects were detected. 3D-CRT is a reproducible and feasible technique for the delivery of APBI following conservative surgery for the treatment of low-risk, early-stage invasive breast carcinoma. The preliminary results are promising, early- and mid-term radiation side effects are rare, and cosmetic results are excellent.

Unlabelled: Triple-negative breast cancer (TNBC) is a heterogeneous disease. Possibly genetic characterisation provides the most appropriate information on tumour biology and prognosis, but it is only limitedly available in clinical practice. The aim of this investigation was to explore what additional prognostic information could be gained from detailed histomorphologic report., Patients and Method: patients were selected retrospectively operated from 2005 to 2009 in one institution and charts were revised. Beyond age, tumour and nodal status, histologic grade and therapy, the additional pathologic characteristics were also involved in analysis: necrosis, lymphocytic infiltration, peritumoural vascular invasion (PVI), perineural invasion, DCIS extent and grade, perinodal spread, mitotic activity index (MAI)., Results: 295 early TNBC were involved. In univariate survival analysis with a mean follow-up of 3.57 years the tumour size, the nodal status, type of operation (conservation or mastectomy), irradiation, PVI and perinodal spread proved to be significantly connected with both disease free survival (DFS) and breast cancer specific overall survival (BSOS), and necrosis and chemotherapy with BSOS. Necrosis analysed together with lymphocytic infiltrate showed greater predicting power. In multivariate analysis nodal metastasis, necrosis positive/lymphacytic infiltration negative status and lack of irradiation has significant negative impact on DFS (p = <0.0001 HR:1.98 [1.4-2.77], p = <0.017 HR:2.1 [1.1-3.8], p = <0.001 HR:0.25 [0.11-0.57], respectively) and BSOS (p = <0.0001 HR:2.47 [1.8-3.4], p = <0.017 HR:3.7 [1.6-8.2], p = <0.0017 HR:0.24 [0.1-0.58], respectively). For DFS perivascular invasion also showed significant effect (p = <0.042 HR:2.5 [1.0-6.0]). Nodal status was the strongest prognostic parameter but other histomorphologic parameters can be used for prognosis prediction.

The uniform European structure and professional standards for high quality breast cancer care were established in conjunction with the European Organisation for Research and Treatment, the European Society of Mastology and the European Breast Cancer Coalition with the support of the European Parliament. Well-prepared professional teams including a new member called the breast care nurse serve as ground for special breast cancer centers with international accreditation that provide modern, evidence based, patient centered multidisciplinary oncological care. The responsibilities of the new qualified professional staff member include the psycho-social support of the patient and carers from the moment of diagnosis throughout the whole oncological treatment, the fostering of delivering information and communication between patients and specialists. As a result of the curriculum founded by the European Oncology Nursing Society, breast care nurses have become key members of the practice of holistic breast cancer care in countries where the European recommendations have already been implemented. Considering the expected rearrangement of national oncological care, the new sub-specialty is outlined for the first time in the light of the experiences gained at the National Institute of Oncology, Budapest, a comprehensive cancer center.

The purpose of the study was a preliminary evaluation of the efficacy of preoperative intracavitary high-dose-rate brachytherapy (HDR BT) in sterilization of the specimen of operable cervical cancer patients enrolled into a prospective, randomized study. Between 2005 and 2010, 100 operable cervical cancer patients of FIGO stage I/A2 (n=4), I/B1 (n=51), I/B2 (n=19), IIA (n=17), and proximal II/B (n=9) were randomized in two arms: in arm "A" (n=50) allocated treatment was 2x8 Gy preoperative intracavitary HDR BT followed by radical surgery, in arm "B" (n= 50) no preoperative treatment was given before the planned radical Wertheim hysterectomy. The rates of pathologic complete remission (pCR) were compared using the Fisher-exact test. In arm "A" 41 patients (82%), in arm "B" 42 patients (84%) underwent radical hysterectomy. The rate of pCR after preoperative BT was 26.8% (11/41), while in the control group the specimen was free of tumor in 7.1% (3/42; p=0.0204). Preoperative HDR BT for cervical cancer patients significantly increases the rate of pathologically tumor-free specimens. Longer follow-up is needed to evaluate the impact of pCR on local tumor control and survival. Our preliminary results support further enrollment of patients into our randomized clinical trial.

PET-CT examination was conducted with 440 patients treated at the Department of Head and Neck Surgery, National Institute of Oncology, Budapest, between January 1, 2006 and December 31, 2010. Out of them 77 patients were selected with whom no examination of any sort (physical, pan-endoscopy, or any of the conventional imaging techniques) succeeded in identifying the primary tumour. In each case the primary examination (aspiration cytology and histology) verified cervical metastases, most of them being squamous cell carcinoma. The significance of PET-CT was retrospectively evaluated in cases of unknown primary tumour with verified cervical metastases. We tested the sensitivity of PET-CT in detection of the primary malignant tumour, and possible distant metastases or a second primary in order to plan an optimal treatment schedule for the patient. Patients with whom the examinations specified in the treatment protocol (physical examination, pan-endoscopy, conventional imaging, biopsy) had failed to diagnose the primary tumour were referred to PET-CT. In each case 18F-FDG tracer was used. In 21/77 patients (27%), the PET-CT yielded unequivocal evidence for the primary tumour confirmed by histology, as well. With 10 others (13%), the precarious diagnoses by various imaging techniques were confirmed by the PET-CT. False positive findings with PET-CT that were not verified either by histology or control examination tests occurred but in 10 patients (13%). Concerning the primary tumour, false negative result was obtained only with 3 patients (4%). It should be noted that their retrospective evaluation proved diagnostic errors, the primary tumours were visible in all the scans. With 33 patients (43%) PET-CT furnished no additional information compared to the previous examinations. In 10 patients, asymptomatic distant metastases and in 3 patients synchronous tumours were diagnosed. We also acknowledge that the significance of PET-CT using 18F-FDG is unquestionable in the detection of unknown primary tumours. It is strongly recommended to re-include the detection of unknown primaries in the approved national indication list of PET-CT. (Note, until January 1, 2008 it had been included!) PET-CT is capable of detecting a primary tumour, after all unsuccessful diagnostic examinations till then, in 25-40% of the cases. One cannot disregard the role and significance of PET-CT in the detection of asymptomatic synchronous tumours, or distant metastases. These benefits make PET-CT a suitable tool for the refinement of individually tailored treatment strategies leading to better therapeutic results and more favourable cost-benefit ratio.