Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary. AIM: To investigate the benefits and complications of neoadjuvant modalities. METHODS: To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach. RESULTS: Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [P < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality (P = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure (P = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases. CONCLUSION: Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required.

Predictive factors of basic palliative and hospice care among patients with cancer visiting the emergency department in a Hungarian tertiary care center.

Introduction: Patients with advanced cancer tend to utilize the services of the health care system, particularly emergency departments (EDs), more often, however EDs aren't necessarily the most ideal environments for providing care to these patients. The objective of our study was to analyze the clinical and demographic characteristics of advanced patients with cancer receiving basic palliative care (BPC) or hospice care (HC), and to identify predictive factors of BPC and HC prior to their visit to the ED, in a large tertiary care center in Hungary. Methods: A retrospective, detailed analysis of patients receiving only BPC or HC, out of 1512 patients with cancer visiting the ED in 2018, was carried out. Sociodemographic and clinical data were collected via automated and manual chart review. Patients were followed up to determine length of survival. Descriptive and exploratory statistical analyses were performed. Results: Hospital admission, multiple (≥4x) ED visits, and respiratory cancer were independent risk factors for receiving only BPC (OR: 3.10, CI: 1.90-5.04; OR: 2.97, CI: 1.50-5.84; OR: 1.82, CI: 1.03-3.22, respectively), or HC (OR: 2.15, CI: 1.26-3.67; OR: 4.94, CI: 2.51-9.71; OR: 2.07, CI: 1.10-3.91). Visiting the ED only once was found to be a negative predictive factor for BPC (OR: 0.28, CI: 0.18-0.45) and HC (OR: 0.18, 0.10-0.31) among patients with cancer visiting the ED. Conclusions: Our study is the first from this European region to provide information regarding the characteristics of patients with cancer receiving BPC and HC who visited the ED, as well as to identify possible predictive factors of receiving BPC and HC. Our study may have relevant implications for health care planning strategies in practice.

Changes in Oncological Surgical Principles Driven by Advances in Preoperative Treatments.

From a surgical point of view, the development of preoperative oncological treatment has had a profound effect on the surgical treatment trends of cancer as well as on the outcomes of cancer patients. Consequently, these changes have challenged formerly entrenched oncological surgical principles. In our short report, we aimed to summarize the main shifts regarding the surgical principles of cancer treatment due to the development of preoperative oncological therapy in recent years. As a result of successful preoperative treatment, surgeons may perform less radical surgeries, the required free resection margin has been narrowed down to a few millimeters in dimension and preoperative treatment is justified in both definitely resectable tumors and in oligometastatic tumors as well. For prognosis assessment, the post-preoperative oncological treatment stage is now considered decisive, rather than the pretreatment stage as previously thought. Other changes include the introduction of the watch and wait strategy and the reverse order of treatment of the primary tumor and metastasis. Observing the continuously improving outcomes of cancer patients and the developments in oncological treatment modalities, a further expansion of the indication of preoperative treatments is to be expected.

Retrospective study of cancer patients' predictive factors of care in a large, Hungarian tertiary care centre.

OBJECTIVES: To identify predictive factors of multiple emergency department (ED) visits, hospitalisation and potentially preventable ED visits made by patients with cancer in a Hungarian tertiary care centre. DESIGN: Observational, retrospective study. SETTING: A large, public tertiary hospital, in Somogy County, Hungary, with a level 3 emergency and trauma centre and a dedicated cancer centre. PARTICIPANTS: Patients above 18 years with a cancer diagnosis (International Classification of Diseases, 10th Revision codes of C0000-C9670) who visited the ED in 2018, who had received their diagnosis of cancer within 5 years of their first ED visit in 2018 or received their diagnosis of cancer latest within the study year. Cases diagnosed with cancer at the ED (new cancer diagnosis-related ED visits) were also included, constituting 7.9% of visits. PRIMARY OUTCOME MEASURES: Demographic and clinical characteristics were collected and the predictors of multiple (≥2) ED visits within the study year, admission to inpatient care following the ED visit (hospitalisation), potentially preventable ED visits and death within 36 months were determined. RESULTS: 2383 ED visits made by 1512 patients with cancer were registered. Predictive factors of multiple (≥2) ED visits were residing in a nursing home (OR 3.09, 95% CI 1.88 to 5.07) and prior hospice care (OR 1.87, 95% CI 1.05 to 3.31). Predictive factors for hospitalisation following an ED visit included a new cancer diagnosis-related visit (OR 1.86, 95% CI 1.30 to 2.66) and complaint of dyspnoea (OR 1.61, 95% CI 1.22 to 2.12). CONCLUSIONS: Being a resident of a nursing home and receiving prior hospice care significantly increased the odds of multiple ED visits, while new cancer-related ED visits independently increased the odds of hospitalisation of patients with cancer. This is the first study to report these associations from a Central-Eastern European country. Our study may shed light on the specific challenges of EDs in general and particularly faced by countries in the region.

Expression Levels of GHRH-Receptor, pAkt and Hsp90 Predict 10-Year Overall Survival in Patients with Locally Advanced Rectal Cancer.

BACKGROUND: Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses, and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. The main objective of our study was to investigate the relationship between the expression intensities of certain proteins, including growth-hormone-releasing hormone receptor (GHRH-R), Hsp90, Hsp16.2, p-Akt and SOUL, in specimens of locally advanced rectal cancer patients, as well as the time to metastasis and 10-year overall survival (OS) rates. We also investigated whether these outcome measures were associated with the presence of other clinical parameters. METHODS: In total, 109 patients were investigated retrospectively. Samples of pretreatment tumors were stained for the proteins GHRH-R, Hsp90, Hsp16.2, p-Akt and SOUL using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationships between the intensity of expression of biomarkers, clinical parameters, the time to metastasis and the 10-year OS rate. RESULTS: High levels of p-Akt, GHRH-R and Hsp90 were associated with a significantly decreased 10-year OS rate (p = 0.001, p = 0.000, p = 0.004, respectively) and high expression levels of p-Akt and GHRH-R were correlated with a significantly shorter time to metastasis. Tumors localized in the lower third of the rectum were linked to both a significantly longer time to metastasis and an improved 10-year OS rate. CONCLUSIONS: Hsp 90, pAkt and GHRH-R as well as the lower-third localization of the tumor were predictive of the 10-year OS rate in locally advanced rectal cancer patients. The GHRH-R and Hsp90 expression levels were independent prognosticators of OS. Our results imply that GHRH-R could play a particularly important role both as a molecular biomarker and as a target for the anticancer treatment of advanced rectal cancer.

Main reasons and predictive factors of cancer-related emergency department visits in a Hungarian tertiary care center.

BACKGROUND: Identifying the reasons for the Emergency Department (ED) visit of patients with cancer would be essential for possibly decreasing the burden of ED use. The aim of our study was to analyze the distribution of the demographic and clinical parameters of patients with cancer based on the reasons for the ED visits and to identify possible predictive factors for their visits. METHODS: This retrospective study, carried out at a large, public tertiary hospital in Hungary, involved all patients 18 years or over, who had received a cancer diagnosis latest within five years of their visit to the ED in 2018. Demographic and clinical characteristics were collected partly via automated data collection and partly through the manual chart review by a team of experts, including six emergency physicians and an oncologist. Five main reasons for the ED visit were hypothesized, pilot-tested, then identified, including those with cancer-related ED visits (whose visit was unambiguously related to their cancer illness) and those with non-cancer-related ED visits (whose visit to the ED was in no way associated with their cancer illness.) A descriptive approach was used for data analysis and binary logistic regression was used to determine predictive factors for patients with cancer visiting the ED. RESULTS: 23.2% of the altogether 2383 ED visits were directly cancer-related, and these patients had a significantly worse overall survival than patients with non-cancer related ED visits. Age 65 or below (Odds Ratio: 1.51), presence of two more comorbidities (OR: 7.14), dyspnea as chief complaint (OR: 1.52), respiratory cancer (OR: 3.37), any prior chemotherapy (OR: 1.8), any prior immune/biological treatment (OR: 2.21), any prior Best Supportive Care/palliative care (OR: 19.06), or any prior hospice care (OR: 9.43), and hospitalization (OR:2.88) were independent risk factors for the ED visit to be cancer-related. CONCLUSIONS: Our study is the first to identify independent predictive factors of ED use by patients with cancer based on the chief cause of their visit in the Central and Eastern European region. These results may provide important information for the development of algorithms intended to identify the needs of care of patients with cancer at the ED.

Changes in surgical principles as a result of modern, effective, perioperative treatments / A sebészeti elvek változása a modern, hatékony, perioperatív onkológiai kezelések következményeként

Oncology has evolved to a great extent over the last quarter of century. The significant success is multifactorial, including primary and secondary prevention, the development of diagnostics, new methods of chemo-and radiotherapy, and the integration of basic research results into practice. From the point of view of surgery, the establishing and widespread practical application of the principles of preoperative oncotherapy played a major role in this development. Between 1997 and 2005, 44 patients with gastric cancer and 102 patients with borderline resectable or irresectable esophageal cancer received perioperative treatment at the Department of Surgery of the University of Pecs. The response rate was above 50% in both groups and complete pathological remission was achieved in 3 patients with gastric cancer and 17 patients with esophageal cancer. Based on our own experience and literature data, the development of seven new principles in surgical oncology were observed as the result of a very successful preoperative oncologic treatment. The desired free resection margin was reduced to the millimeter dimension in many cancer cases. Thus so-called organ-preserving procedures were made possible. Regarding the prognosis, the stage after the treatment became determinant. Complete histopathological remission could also be achievable in patients with oligometastases. In the case of a complete remission, the watch and wait tactics emerged as an option. Along the preoperative treatment of resectable colorectal liver metastases, there is no need to strive for complete remission. The treatment order of the primary tumor and its metastases can be reversed. Based on the improving results of oncology treatments, a reduction in surgical activity in the treatment of cancer patients is expected.

Effective chemotherapy and targeted therapy supplemented with stereotactic radiotherapy of a patient with metastatic colon cancer following renal transplantation: a case report.

BACKGROUND: Previous studies have shown that patients who underwent renal transplantation were at a greater risk of developing malignancies. Due to advances in effective surgical techniques and immunosuppressive therapies, organ recipients live longer. Yet, there is insufficient information about the recommended type of therapy for colorectal cancer patients following transplantation. We describe the oncological treatment of a patient with renal transplantation, who presented with metastatic colon cancer 5 years after transplantation. CASE PRESENTATION: A 66-year-old Caucasian male patient, with hypertension, type 2 diabetes mellitus, paroxysmal atrial fibrillation, and renal failure underwent successful kidney transplantation in 2013. In April 2018, the adenocarcinoma of the sigmoid colon was found, and surgical resection was performed. The histological diagnosis was low-grade adenocarcinoma. Fluorodeoxyglucose positron emission tomography/computerized tomography scan showed a 2.5-cm metastasis in the VIIth segment of the liver and a metastatic paraaortical lymph node on the left. The clinical diagnosis was, therefore, metastatic (stage IV) sigmoid colon cancer (AJCC TNM system). The ongoing medications of the patient included immunosuppressive drugs and medication for his cardiovascular comorbidities. In July 2018, palliative cetuximab plus folinic acid-fluorouracil-irinotecan chemotherapeutic treatment was initiated, then cetuximab was substituted for panitumumab because of adverse events. In August 2018, the follow-up positron emission tomography/computerized tomography scan revealed stable disease. Because of side effects, the patient was unwilling to continue with the panitumumab plus folinic acid-fluorouracil-irinotecan treatment regimen. Therefore, the patient received 10× 5 Gy stereotactic body irradiation for his liver metastasis and mono-panitumumab therapy. By January 2019, the positron emission tomography/computerized tomography scan showed regression of the liver metastasis but a progression in the paraaortic lymph node. Therefore, 5× 8 Gy stereotactic irradiation was given to the paraaortic lesion. Meanwhile, the patient received altogether 16 cycles of panitumumab until June 2019, when complete remission was attained. In July 2019, the patient suffered a hemorrhagic stroke, probably due to his cardiovascular comorbidities, and died subsequently. CONCLUSIONS: Since information is scarce regarding oncological treatment of patients following organ transplantation, data about their oncological treatment is essential. To our knowledge, this is the first case report to describe the successful chemotherapy and targeted therapy supplemented with stereotactic radiotherapy of a posttransplant patient with metastatic colorectal cancer.

Characteristics related to the treatment of colorectal cancer patients based on a pilot study in Baranya county, Hungary / A colorectalis daganatos betegek kezeléshez jutásának jellemzoi egy Baranya megyei pilotvizsgálat keretében

Összefoglaló.Bevezetés: Az európai országok közül Magyarország a colorectalis daganatos incidencia és mortalitás szempontjából az élen szerepel. Ennek hátterében a beteghez vagy az egészségügyi rendszerhez kötheto tényezok is állhatnak. Célkituzés: Kutatásunk célja, hogy pilotvizsgálat keretében feltárjuk a colorectalis daganatos betegek kezeléshez jutásának körülményeit azáltal, hogy a betegek elso tünetei, kivizsgálásuk jellemzoi, betegségük stádiuma és a terápiáig eltelt idotartamok közötti összefüggéseket elemezzük. Módszer: Retrospektív adatgyujtés történt 26, Baranya megyei háziorvosi praxis colorectalis daganatos betegeinek (n = 212) adataira vonatkozóan a praxisok, valamint a Pécsi Tudományegyetem Klinikai Központjának (PTE KK) adatbázisából. Meghatároztuk a terápiáig eltelt intervallumot (TEI), amely az elso orvos-beteg találkozástól - amikor a beteg colorectalis daganatra utaló tünetekkel eloször jelentkezett orvosnál - a terápia megkezdésének elso napjáig eltelt idot jelenti. A statisztikai elemzés során deskriptív analízist, valamint varianciaanalízist végeztünk. Eredmények: A sürgosségire került betegek leggyakoribb tünete a hasi/végbéltáji fájdalom volt, míg a háziorvost felkereso betegek a véres székletet említették a legtöbbször. A sürgosségi osztályon jelentkezo betegek esetében lényegesen magasabb arányban (61%) diagnosztizáltak késoi (III-IV.) stádiumú daganatot, mint a háziorvoshoz forduló betegek körében (42,7%). A TEI rövidebb volt, ha a betegek sürgosségi osztályra kerültek (TEI-medián: 15 nap késoi, 34,5 nap korai [I-II.] stádiumú daganat esetén), mint amikor háziorvosnál jelentkeztek eloször (TEI-medián: 86 nap késoi, 83 nap korai stádiumú daganat esetén). Következtetés: A sürgosségi és a háziorvosi kivizsgálás esetén észlelt TEI-k összemérhetok a nyugat-európai országokéival. A hazai magas mortalitási mutatók hátterében inkább a betegek késedelmes orvoshoz fordulása állhat, ami a primer és szekunder prevenció fontosságára hívja fel a figyelmet. Orv Hetil. 2021; 162(4): 153-160. INTRODUCTION: Hungary has one of the leading colorectal cancer incidence and mortality rates in Europe. Patient-related and healthcare-related factors may all play a role. OBJECTIVE: Our objective was to investigate the characteristics related to the treatment of colorectal cancer patients by analysing their initial symptoms, disease stage, referral characteristics and total treatment intervals. METHOD: A retrospective study was conducted based on data from colorectal patients (n = 212) from the databases of 26 general physician practices and the University of Pécs, Clinical Center. The total treatment interval was determined as the number of days from the first patient-physician consultation with symptoms until the first day of treatment. Descriptive analysis and analysis of variance were performed. RESULTS: Patients' most common symptom was abdominal/rectal pain when presenting at the emergency department while bloody stool was the most common among patients visiting their general physicians. The proportion of patients with advanced stage (III-IV) cancer was significantly higher at the emergency department than among patients visiting their general physicians (61% and 42.7%, respectively). The total treatment interval was shorter when patients presented at the emergency department (total treatment interval median: 15 days for advanced stage, 34.5 days for early [I-II] stage cancer) than when they initially visited their general physicians (total treatment interval median: 83 days for early stage, 86 days for advanced stage cancers). CONCLUSION: The total treatment intervals for patients visiting the emergency department or their general physicians were similar to those found in Western European countries. The high mortality rates in Hungary are more probably due to patient-related delays, which highlight the importance of primary and secondary prevention. Orv Hetil. 2021; 162(4): 153-160.

Author Correction: Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model.

The aim of this study was to visualize the tumor propagation and surrounding mucosal field in radiography-based 3D model for advanced stage HNSCC and combine it with HPV genotyping and miRNA expression characterization of the visualized area. 25 patients with T1-3 clinical stage HNSCC were enrolled in mapping biopsy sampling. Biopsy samples were evaluated for HPV positivity and miR-21-5p, miR-143, miR-155, miR-221-5p expression in Digital Droplet PCR system. Significant miRNA expression differences of HPV positive tumor tissue biopsies were found for miR-21-5p, miR-143 and miR-221-5p compared to the HPV negative tumor biopsy series. Peritumoral mucosa showed patchy pattern alterations of miR-21-5p and miR-155 in HPV positive cases, while gradual change of miR-21-5p and miR-221-5p was seen in HPV negative tumors. In our study we found differences of the miRNA expression patterns among the HPV positive and negative tumorous tissues as well as the surrounding mucosal fields. The CT based 3D models of the cancer field and surrounding mucosal surface can be utilized to improve proper preoperative planning. Complex evaluation of HNSCC tissue organization field can elucidate the clinical and molecular differentiation of HPV positive and negative cases, and enhance effective organ saving therapeutic strategies.

The Esophageal Adenocarcinoma Epidemic Has Reached Hungary: A Multicenter, Cross-Sectional Study.

BACKGROUND: The epidemiology of esophageal cancer has changed dramatically over the past 4 decades in many Western populations. We aimed to understand the Hungarian epidemiologic trends of esophageal squamous cell cancer (SCC) and adenocarcinoma (AC). METHODS: We performed a cross-sectional study using data from esophageal cancer patients diagnosed between 1992 and 2018 at eight tertiary referral centers in four major cities of Hungary. We retrospectively identified cases in the electronic databases of each center and collected data on gender, age at diagnosis, year of diagnosis, specialty of the origin center, histological type, and localization of the tumor. Patients were grouped based on the two main histological types: AC or SCC. For statistical analysis, we used linear regression models, chi-square tests, and independent sample t tests. RESULTS: We extracted data on 3,283 patients with esophageal cancer. Of these, 2,632 were diagnosed with either of the two main histological types; 737 had AC and 1,895 SCC. There was no significant difference in the gender ratio of the patients between AC and SCC (80.1 vs 81.8% males, respectively; p = 0.261). The relative incidence of AC increased over the years (p < 0.001, b = 1.19 CI: 0.84-1.54). AC patients were older at diagnosis than SCC patients (64.37 ± 11.59 vs 60.30 ± 10.07 years, p < 0.001). The age of patients at the diagnosis of primary esophageal cancer increased over time (p < 0.001, R = 0.119). CONCLUSIONS: The rapid increase in the relative incidence of AC and simultaneous decrease of the relative incidence of SCC suggest that this well-established Western phenomenon is also present in Hungary.

Wait times to diagnosis and treatment in patients with colorectal cancer in Hungary.

BACKGROUND: Mortality from colorectal cancer (CRC) in Hungary is the highest in Europe. It was the aim of the present study to determine the wait times from first presentation to diagnosis, in a sample of Hungarian patients with CRC, as well as to assess the stages of CRC at diagnosis. METHODS: A retrospective study based on data from 212 patients with CRC in Baranya county was carried out. Data extraction was performed from 26 GP practices and from the database of the University of Pécs Clinical Center. Total Diagnostic Interval (TDI) was determined as the number of days from the first patient-physician consultation with symptoms until the pathologically confirmed date of diagnosis. Total Treatment Interval (TTI) was calculated until the first day of any form of treatment. Statistical analyses, descriptive analysis and analysis of variance, were performed. RESULTS: A minority (36.8%) of the diagnosed CRC cases were early stage cancers (Stages I-II), while the majority (59.9%) of the cases were diagnosed as advanced stage (Stages III-IV) cancers. The median TDI was 41 days, and the median TTI was 67 days. There was a wide range between minimum and maximum waiting times regarding both diagnosis and initiation of therapy (369-371 days). CONCLUSIONS: Wait times to diagnosis and treatment of CRC in Hungary are similar to Western countries however the ratio of advanced cancers at diagnosis is higher. The cause of late diagnosis may be due to patient delay, indicating the need for implementation of primary and secondary prevention.

Possible Predictive Markers of Response to Therapy in Esophageal Squamous Cell Cancer.

The aim of the present study was to investigate the relationship between the intensity of biomarker expression and the response to radiochemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Ninety-two patients with locally advanced ESCC were examined retrospectively. Pre-treatment tumor samples were stained for proteins SOUL, Hsp 16.2, Growth Hormone-Releasing Hormone Receptor (GHRH-R) and p-Akt using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers and clinical parameters and 3-year OS. A significant correlation was found between high intensity staining for Hsp 16.2, p-Akt and SOUL and poor response to NRCT. Application of a higher dose of radiation and higher dose of cisplatin resulted in better clinical and histopathological responses, respectively. Among the clinical parameters, the localization of the tumor in the upper-third of the esophagus and less than 10% weight loss were independent prognostic factors for increased 3-year OS. Hsp16.2, p-Akt and SOUL are predictors of negative response to NRCT, therefore these biomarkers may become promising targets for therapy. Furthermore, level of expression of p-Akt, weight loss and the localization of the tumor are significant factors in the prediction of OS in ESCC.

Prognostic role of HPV infection in esophageal squamous cell carcinoma.

BACKGROUND: The aims of this study were to evaluate whether HPV infection has a prognostic role in patients with esophageal squamous cell carcinoma who underwent oncological treatment and also to compare the heat shock proteins (Hsp) 90, 27 and 16.2 and growth hormone-releasing hormone receptor (GHRH-R) expression patterns of the pre-treatment tumor biopsies with the HPV status and with the oncological response. METHODS: Pre-treatment tumor biopsies of 74 patients with locally advanced esophageal squamous cell carcinoma were processed retrospectively. The presence of HPV was detected by chromogenic in situ hybridization. Hsp and GHRH-R expressions were determined using immunohistochemistry. Following neoadjuvant or definitive radiochemotherapy, the patients were restaged according to the Response Evaluation Criteria in Solid Tumors. The correlation between the HPV status, response to treatment and Hsp and GHRH-R expressions were evaluated. RESULTS: Fourteen (19%) patients were HPV-positive. These patients were more likely to respond poorly to multimodal therapy (71.4% were non-responders vs. 28.6% responders) and had shorter survival compared to HPV-negative patients (mean survival of 8 months vs. 11 months), although the difference was not significant. A significantly higher number of HPV-positive patients expressed Hsp 90 and 16.2 at high levels (93 and 79%, respectively) than at low levels (Chi-Square p = 0.019 and p = 0.031). Higher levels of Hsp expressions were associated with poorer response to therapy and worse overall survival. No correlation was found between GHRH-R expression and the HPV status, nor between GHRH-R expression and the treatment response of the examined samples. CONCLUSIONS: We found that HPV infection was associated with poor response to oncological treatment and decreased overall survival, and therefore proved to be a negative prognostic factor in patients with esophageal squamous cell carcinoma. There was a linear correlation between levels of Hsp 90 and 16.2 expression and HPV positivity.

[First report on successful application of nivolumab in Hungary for the treatment of locally recurrent head and neck squamous cell carcinoma]. / Immunterápia elsõ hatékony alkalmazása Magyarországon lokálisan kiújult fej-nyaki laphámkarcinómás betegnél.

The prognosis for recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) remains dismal and its treatment poses a challenge for oncologists. Nivolumab belongs to the class of immune checkpoint inhibitors (ICI) and is an antibody developed to target the programmed cell death protein 1 (PD-1) receptor. The CheckMate 141 randomized phase 3 trial proved the efficacy of nivolumab in the treatment of R/M HNSCC as it was shown to significantly increase overall survival and quality of life. We present the case of a 53-year-old woman with R/M HNSCC who was given nivolumab monotherapy, as third-line treatment due the progression of her tumor. After treatment with nivolumab, the size of her tumor decreased, then was stable, while she did not experience any adverse events or notable side effects. Our case report is the first to demonstrate the application of nivolumab in R/M HNSCC in Hungary.

Single dose irradiation of defined region of rat brain with stereotactic brainlab system.

UNLABELLED: Background and purpose of our study was to develop a precise dose delivery technique for partial brain irradiation of two rats simultaneously. METHODS: Using a self-developed frame stereotactic radiotherapy with single doses of 30-90 Gy was delivered to the frontal lobe of 22 animals. Tolerability and reproducibility of the method were evaluated and dosimetric measurements were conducted to verify the treatment plans. 2, 4 and 6 months after the irradiation magnetic resonance imaging (MRI) scans and histopathological examinations were performed to detect late radiation induced biological changes. RESULTS: Immobilization device provided excellent reproducibility and tolerability. Dosimetry revealed good correspondence with planned dose distribution, but the measured absorbed dose was 30% lower than the planned dose. During the 6 months follow-up period the procedure related death of subject animals after 30 Gy, 70 Gy and 90 Gy were 0%, 20% and 100% respectively. T2 signal and structural changes on MRI scans found to be dose and time dependent. While 30 Gy caused no detectable structural changes, 70 Gy lead to cystic necrosis in 2 cases after 4 month. Histopathology revealed signs of necrosis on macroscopic examination after 70 Gy in the high dose region involving both frontal lobes, and no obvious microscopic changes in the surrounding area were detectable. CONCLUSION: Our technique of rat cranial irradiation using human stereotactic system provided high accuracy of single dose delivery for a pair of small animals, resulting in brain injury in the defined area. This method proved to be a reproducible model for preclinical studies on radiation effects.

[New methods in the treatment of localized prostate cancer: use of dynamic arc therapy and kV cone-beam CT positioning]. / Új módszerek a prosztatadaganatok sugárkezelésében: dinamikus ívbesugárzás és kilovoltos "cone-beam" komputertomográfiás ellenorzés.

INTRODUCTION: Prostate cancer is a common disease among elderly male patients in developed countries. In addition to prostatectomy, definitive irradiation plays an increasing role in the treatment of localized disease. AIM: The authors wanted to share their experience obtained with the use of the Novalis TX linear accelerator for the application of dose-escalation, dynamic, intensity modulated arc therapy with the routine usage of cone-beam computer tomography based or image guided radiotherapy in patients with prostate cancer. METHOD: Between 2011, December and 2013, February the authors performed 102 treatments. In 10 low risk and 10 high risk prostate cancer patients (median age: 72.5 years) three-dimensional conformal plans with the same target volume coverage were created and tolerance doses of organs at risk (OAR) were compared. RESULTS: Compared to three-dimensional conformal techniques, intensity modulated arc therapy treatments produced a significantly lower dose at organ at risk that led to a more favorable early toxicity rate. CONCLUSIONS: The intensity modulated arc therapy with image guided radiotherapy proved to be a safe standard treatment mode in the daily routine in the institute of the authors. Late toxicity and local control rates need to be further examined.

PARP inhibitor attenuated colony formation can be restored by MAP kinase inhibitors in different irradiated cancer cell lines.

UNLABELLED: Abstract Purpose: Sensitizing cancer cells to irradiation is a major challenge in clinical oncology. We aimed to define the signal transduction pathways involved in poly(ADP-ribose) polymerase (PARP) inhibitor-induced radiosensitization in various mammalian cancer lines. MATERIALS AND METHODS: Clonogenic survival assays and Western blot examinations were performed following telecobalt irradiation of cancer cells in the presence or absence of various combinations of PARP- and selective mitogen-activated protein kinase (MAPK) inhibitors. RESULTS: HO3089 resulted in significant cytotoxicity when combined with irradiation. In human U251 glioblastoma and A549 lung cancer cell lines, Erk1/2 and JNK/SAPK were found to mediate this effect of HO3089 since inhibitors of these kinases ameliorated it. In murine 4T1 breast cancer cell line, p38 MAPK rather than Erk1/2 or JNK/SAPK was identified as the main mediator of HO3089's radiosensitizing effect. Besides the aforementioned changes in kinase signaling, we detected increased p53, unchanged Bax and decreased Bcl-2 expression in the A549 cell line. CONCLUSIONS: HO3089 sensitizes cancer cells to photon irradiation via proapoptotic processes where p53 plays a crucial role. Activation of MAPK pathways is regarded the consequence of irradiation-induced DNA damage, thus their inhibition can counteract the radiosenzitizing effect of the PARP inhibitor.

[Fractionated stereotactic irradiation of skull-base related tumours]. / Koponyaalap-közeli daganatok frakcionált sztereotaxiás sugárkezelése (fSRT).

The prognosis of the treatment of brain tumours depends on two main factors: biological nature and localisation of the neoplasm. Requirements of oncologic surgery can be met only partially if at all in neurological surgery of brain tumours. Resectability depends primarily on localisation of the neoplasms. The leading principle is preservation of fine neural structures, minimising morbidity from tissue resection with the goal of maximal tumour resection. As nervous structures and the target volume do not move in the intracranial space, large radiation doses unusual in traditional radiotherapy can be given either in one or in fractionated sessions to small targets (point-radiation) and a well-controlled radiation necrosis of the pathological tissue can be achieved. Management principles of treatment of skull-base related tumours are very similar due to high risks of functional morbidity evoked by surgical injury to the cranial nerves, brainstem structures, vessels of the Willis circle and those of the substantia perforata anterior and posterior, etc. Such tumours are neoplasms arising from the skull base, those infiltrating the cavernous sinuses, invasive pituitary tumours, those arising from the glomus jugulare, or located within the cerebello-pontine angle, etc. This manuscript intends to illustrate and prove the hypothesis by means of 4 cases that fractionated stereotactic radiotherapy (fSRT) is an important part of treatment armamentarium in the latter cases, as it is capable of exploiting both the advantages of traditional fractionated irradiation and that of the high conformality and selectivity of radiosurgery. It is capable of administering appropriate quantity of total target dose with a lower than limit dose on surrounding structures. The presentation proves that fSRT can be planned already in the phase of surgical indication as a "microsurgery-assisted radiotherapy".