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The incidence of adenocarcinoma of oesophagus or gastro-oesophageal junction is increasing in Europe and other regions of the Western world. Research of possible causes has shifted to the molecular level. This study evaluated human papillomavirus (HPV) using real-time PCR and mutational status of selected genes using the multiparallel sequencing method (NGS) in DNA extracted from paraffin-embedded tumour tissue of 56 patients with oesophageal or gastro-oesophageal junction adenocarcinoma. The genetic material was in sufficient quality for the analysis in 37 cases (66 %). No HPVpositive sample was found. NGS revealed higher fre- Received May 2, 2018. Accepted May 24, 2018. The work was financially supported by the League Against Cancer, Prague, Ministry of Education, Youth and Sport of the Czech Republic: programme PROGRES Q40/06 and Q40/11, and European Regional Development Fund-Project BBMRI-CZ: Biobank network - a versatile platform for the research of the etiopathogenesis of diseases, No. EF16 013/0001674. Corresponding author: Igor Sirák, Department of Oncology and Radiotherapy, University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Czech Republic. igor.sirak@fnhk. cz; Phone: (+420) 495 832 363; Fax: (+420) 495 832 081. e-mail: igor.sirak@fnhk.cz. Abbreviations: AC - adenocarcinoma, ACMG - American College of Medical Genetics, HPV - human papillomavirus, GOJ - gastro-oesophageal junction, NGS - multiparallel sequencing method, SCC - squamous cell carcinoma, VAF - variant allele frequency, WES - whole-exome sequencing, WGS - whole-genome sequencing. quency of mutations in TP53, ARID1A, PIK3CA, SMAD4, ERBB2, MSH6, BRCA2, and RET genes. Association between gene mutations and histological grade, subtype according to Lauren, or primary tumour site was not statistically significant. In conclusion, the study did not confirm any HPV-positive sample of oesophageal and gastro-oesophageal junction adenocarcinoma. The study confirmed the usefulness of NGS analysis of paraffin-embedded tissue of these tumours, and it could be used in clinical studies to evaluate the prognostic and/or predictive value of the tested mutations. The association between gene mutations and histological features should be tested in larger patient cohorts. [ABSTRACT FROM AUTHOR]

Introduction: The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity., Methods: Patients aged ≥ 18 years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8 Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis., Results: Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0 months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression., Conclusion: SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought., Trial Registration: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432., Competing Interests: Declarations Conflict of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Milan Vošmik—Consulting and advisory role: Accord, AstraZeneca, BMS, Merck, MSD, Sanofi. Honoraria—scientific presentations: BMS, Eisai, Gilead, Ipsen, MSD, Roche. Travel and accommodation support: BMS, Merck, MSD. Stanislav John—Consulting and advisory role: Servier, BMS, Merck, Amgen, AstraZeneca, Takeda. Honoraria—scientific presentations: Servier, BMS, Merck, Amgen, AstraZeneca. Travel and accommodation support: Servier, BMS, Merck, Amgen, AstraZeneca. Beatrice Mohelníková-Duchoňová—Honoraria—scientific presentations: Servier, AstraZeneca, Merck, Amgen; Travel and accommodation support: Servier, AstraZeneca, Merck, Amgen. Bohuslav Melichar—Honoraria for lectures and advisory boards—Roche, Pfizer, BMS, Astellas, Novartis, MSD, Merck Serono, Servier, AstraZeneca, Eisai, E. Lilly, Pierre Farbre; Travel support—AstraZeneca, BMS, MSD, Merck Serono. Radka Lohynská—Honoraria for lectures, presentations, or educational events—Roche, Janssen, Bristol Myers Squibb, MSD and Merck. Aleš Ryška—Consulting and advisory role: Amgen, AstraZeneca, Roche, BMS, MSD, Gilead, Eli Lilly, Merck Serono, Sanofi, Bayer. Honoraria—scientific presentations: Pfizer, Bayer. Travel and accomodation support: Gilead, Sanofi. Igor Sirák—Consulting and advisory role: GSK, MSD. Travel and accomodation support: Novartis. Ethical Approval The study protocol, informed consents for patients, and all other relevant documents were approved by the Ethics Committee of the University Hospital Hradec Králové (EC UHHK) and the local ethics committees of other participating centers: Ethics Committee of the University Hospital Olomouc and Ethics Committee of the Thomayer University Hospital. The EC UHHK has the approval of the Ministry of Health of the Czech Republic for multicentric clinical trials and is accredited in the USA by the Organization Office for Human Research Protections (number IORG0008813). The trial was conducted in accordance with the Guideline for Good Clinical Practice and the Declaration of Helsinki. All study participants were fully informed and signed informed consent for the study., (© 2024. The Author(s).)

The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with four or more positive lymph nodes or extracapsular extension, regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than three positive lymph nodes should be treated with radiotherapy, there is controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in cases of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response.

Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5-7 weeks of daily treatments, has been reduced to 3-4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes.

Background: Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting., Methods: Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles., Results: The median follow-up was 117.5 months (range, 5-210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7-97.7%) and 68.3% (95% CI: 44.0-92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45-97.7%) and 62.1% (95% CI: 34.8-89.4%), respectively., Conclusions: These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort-the second largest reported to date in this clinical setting-prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer.

The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.

Introduction: A proactive approach is recommended in colorectal anastomosis leak treatment, and early diagnosis is very important. Early postoperative endoscopy would allow rapid diagnosis of anastomotic pathologies and consequent prompt intervention according to anastomotic disruption morphology., Aim: To evaluate the effectiveness of close endoscopic follow-up of all patients (including asymptomatic ones) in improving diagnosis of acute leak (AL) and reducing its complications., Material and Methods: This study included 124 patients who had undergone rectum resection for rectal cancer with stapled anastomosis. Endoscopy was performed between the 7 th and 10 th postoperative day and 1 month postoperatively. For defect morphology assessment, a classification system was created based on four levels of severity. Photographic findings were evaluated by an independent, experienced gastroenterologist., Results: Postoperative endoscopy revealed 28 (22.6%) patients with acute leakage. Initial endoscopy confirmed AL in 18 patients. Six (31.6%) patients were asymptomatic and 13 (68.4%) were symptomatic. The second endoscopy revealed another 9 (32.1%) leaks (4 (44.5%) asymptomatic and 5 (55.5%) symptomatic). Sixteen (57.1%) patients had grade A leakages, 7 (25.0%) had grade B leakages, and 5 (17.9%) had grade C leakages. Furthermore, 22 of 27 (81%) defects were located posterior and posterior-laterally. Fifteen (55.5%) defects were smaller than 1/3 the circumference, 7 (25.9%) affected 1/3-1/2 of the circumference, and 5 (18.5%) affected more than 1/2 of the circumference., Conclusions: Incorporation of early endoscopy in postoperative management allows rapid diagnosis of AL and allows faster intervention, even in leaks that are clinically silent., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Fundacja Videochirurgii.)

Following cell stress such as ionising radiation (IR) exposure, multiple cellular pathways are activated. We recently demonstrated that ferredoxin reductase (FDXR) has a remarkable IR-induced transcriptional responsiveness in blood. Here, we provided a first comprehensive FDXR variant profile following DNA damage. First, specific quantitative real-time polymerase chain reaction (qPCR) primers were designed to establish dose-responses for eight curated FDXR variants, all up-regulated after IR in a dose-dependent manner. The potential role of gender on the expression of these variants was tested, and neither the variants response to IR nor the background level of expression was profoundly affected; moreover, in vitro induction of inflammation temporarily counteracted IR response early after exposure. Importantly, transcriptional up-regulation of these variants was further confirmed in vivo in blood of radiotherapy patients. Full-length nanopore sequencing was performed to identify other FDXR variants and revealed the high responsiveness of FDXR-201 and FDXR-208. Moreover, FDXR-218 and FDXR-219 showed no detectable endogenous expression, but a clear detection after IR. Overall, we characterised 14 FDXR transcript variants and identified for the first time their response to DNA damage in vivo. Future studies are required to unravel the function of these splicing variants, but they already represent a new class of radiation exposure biomarkers.

Total mesorectal excision quality (TMEq) is a prognostic factor associated with local recurrence in rectal adenocarcinoma. Neoadjuvant chemoradiotherapy (NCRT) reduces the risk of tumor recurrence, but may compromise TMEq. The time between NCRT and surgery (TTS) and how it influences TMEq and tumor control were evaluated. In prospective registry, 236 patients after NCRT and TME were analyzed. NCRT involved radiotherapy with 45 Gy to the pelvis, plus tumor boost dose 5.4 Gy with concurrent 5-fluorouracil infusion. NCRT was followed by TME after 9 weeks on average (median 9.4 ± SD 2.5). TMEq was parametrically analyzed by standard three-grade system. With median follow-up of 47.5 months, 3-year overall survival (OS) was 83.8%, disease-free survival (DFS) was 77.7%, and 6.4% was the rate of local recurrence (LR). TTS was not associated with OS, DFS, or LR. TMEq was found to be associated with LR in univariate analysis, but not in multivariate, where pathological tumor stage and resection margins remained dominant predictors. TMEq was negatively influenced by inferior location of the tumor, longer TTS, higher tumor and nodal stage, presence of tumor perforation, perineural invasion, and close/positive resection margins. Nonetheless, TTS remained a strong predictor of TMEq in multivariate analyses. TTS was proven to be an independent predictor of TMEq. With longer TTS, fewer complete TME with intact mesorectal plane were observed. However, TTS was not associated with survival deterioration or tumor recurrence. These were negatively influenced by other factors interfering with TMEq, especially by pathological tumor stage and resection margins.

With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving esophageal cancer outcomes, an increasing emphasis is placed on the heart protection in radiation treated esophageal cancer patients. Radiation induced heart complications encompass mainly pericardial disease, cardiomyopathy, coronary artery atherosclerosis, valvular heart disease, and arrhythmias. The most frequent toxicity is pericardial effusion which is usually asymptomatic in the majority of patients. The use of modern radiotherapy techniques is expected to reduce the risk of cardiotoxicity, although this expectation has to be confirmed by clinical data., (© 2020 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.)

Breast-conserving surgery with adjuvant whole-breast irradiation has become the standard treatment for early breast cancer (EBC) patients. Partial breast irradiation, which targets only the postoperative cavity, has been established as an alternative to whole-breast therapy in selected patients. The treatment of elderly breast cancer patients differs from the therapeutic approach in younger ones, as elderly patients are prone to geriatric frailty and comorbid conditions, the incidence and severity of which increase with age. A review of the evidence, process, techniques, and results of accelerated partial breast irradiation (APBI) in elderly EBC patients, seems to indicate that APBI is an advisable postoperative approach in properly selected elderly EBC patients, combining advantages of a radical approach that minimizes the risk of undertreatment with efficient reduction of redundant irradiated volume, treatment toxicity, overall treatment time, staff workload, radiation technique workflow, patient transportation, and the potential for non-compliance. There is no "one size fits all" technique of APBI, the best technique always depending on willing patients, individual anatomy, performance status, patient frailty and comorbid conditions, and tumour location., (2020 Translational Cancer Research. All rights reserved.)

Background: Oncological diseases have, in most cases, a multifactorial etiology, composed of a combination of external and internal environmental factors. Hereditary tumorous syndromes are mostly autosomal dominant diseases with incomplete but very high penetrance., Observation: The patient, an 18-year-old virgin female, consulted a gynecologist in June 2018 because of metrorrhagia. Magnetic resonance imaging revealed a cervical tumor with the dimensions 80 × 90 × 80 mm. Histological analysis confirmed the presence of a very rare hypercalcemic type of small-cell carcinoma of the cervix. Further investigation of the germinal exom of the patient showed pathological variations in genes PALB2 and BRCA2, presented with recommendation of detailed examination by medical genetics., Conclusion: Clinical experience with this type of tumor is very limited, but it still comes with some useful outcome. Small cell carcinomas of the gynecologic tract are very rare, aggressive diseases, with very poor prognosis, affecting mainly young women. Their origin is most often the ovaries, based on most clinical data, but these tumor also localize to the endometrium, cervix, vagina and vulva. It is an extremely rare type of cancer, for which clinical data is scant due to the extremely low number of reported cases. In this patient, the carcinoma had an unusual genetical mutation burden, which she inherited from her parents. In the light of these findings, we recommend that patients suspected of having a small-cell of the gynecologic tract provide a detailed family history, and that genetic testing be considered in similar cases. This work was supported by MH CR grant 16-33209A and research program of Charles University Progress Q40/06. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 10. 6. 2019 Accepted: 9. 9. 2019.

Background: Interstitial low dose rate brachyther-apy is established organ spar-ing treatment of T1- T2 penile carcinoma. Experience with high-dose rate brachyther-apy is limited in this indication., Materials and Methods: Twenty-six patients with early penile carcinoma were treated by high-dose rate brachyther-apy at dose 18 × 3 Gy per fraction twice daily between 2002- 2018 at the Department of Oncology and Radiother-apy, University Hospital in Hradec Kralove. Breast interstitial brachyther-apy template was used for fixation and precise geometry reconstruction of stainless hollow needles., Results: Median follow up was 85 months (range 7- 200 months). Acute reaction usually consisted of grade 2 mucositis that dissolved dur-ing 8 weeks after the treatment. Local recurrence occurred in 6 patients, 5 of them were successfully treated with partial amputation. One patient had a nodal recurrence successfully salvaged by lymphadenectomy. One patient developed necrosis of the glans requir-ing partial amputation. Currently, there are 24 patients alive without signs of dis-ease. One patient died of cardiac comorbidity, one died of duplicate lung cancer. Nineteen patients have a preserved penis (73%), 18 of them sexually active before treatment report satisfactory intercourse., Conclusion: Hyperfractionated interstitial high-dose rate brachyther-apy with 18 × 3 Gy per fraction twice daily is a promis-ing method in selected patients with penile carcinoma and deserves further evaluation in a larger prospective study. Key words penile neoplasms -  conservative treatment -  brachyther-apy This work was supported by programm Progres Q40. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 1. 2019 Accepted: 15. 1. 2019.

The aim of present study was to evaluate the impact of primary tumour location and other factors on the outcome of preoperative chemoradiation followed by surgery in adenocarcinomas of distal oesophagus, gastro-oesophageal junction and stomach. We retrospectively reviewed the institutional patient database. The therapeutic response was re-evaluated as a percentage of residual tumor cells in surgical resection specimens. Overall survival (OS) and disease-free survival (DFS) were assessed. The effect primary tumour location, clinical and pathological TNM stage, and histopathological factors (histological type, grade, angioinvasion, perineural invasion, tumour response) on treatment outcome were evaluated. A total of 108 patients underwent preoperative chemoradiation for adenocarcinoma of distal oesophagus, gastro-oesophageal junction or stomach. The median prescribed dose of radiation was 45 Gy. The concurrent chemotherapy consisted of 5-fluorouracil +/- cisplatin +/- taxanes. R0 resection was achieved in 80 patients (74%). The complete response was observed in 19%. The median follow-up was 50.8 months. Three-year and 5-year OS and DFS were 36.2% and 25.3%; and 28.1% and 23.7%, respectively. Pretreatment T-stage, pathological N-stage, radicality of resection, histological subtype, grade, angioinvasion and perineural invasion, were identified as statistical significant OS predictors in univariate analysis; pathological N-stage, radicality of resection and angioinvasion, in multivariate analysis. The primary tumor location did not influence the prognosis. The pathologic response to chemoradiation had borderline significance. In conclusion, no prognostic impact of primary tumour location, in contrast to other investigated factors, was evident in the present study. The most important predictors of prognosis were angioinvasion status and pN-stage.

Ionizing radiation (IR) exposure of cells in vitro and in vivo triggers a complex cellular response among which modifications of gene expression have been consistently reported. Nevertheless, little is currently known about the transcriptionally responsive genes which play a role in the inflammation response. In order to improve our understanding of such transcriptional response to radiation in vivo , we simultaneously monitored the expression of 249 genes associated with the inflammation response over the course of the radiotherapy treatment in blood of patients treated for endometrial or head and neck cancer. We have identified genes whose transcriptional expression is either upregulated ( ARG1, BCL2L1 ) or downregulated ( MYC ) several fold in vivo . These modifications were consistently detected across patients and further confirmed by quantitative real-time polymerase chain reaction (QRT-PCR); they were specifically significant toward the end of the radiotherapy treatment, 5 weeks following the first radiation fraction and more pronounced in endometrial patients (respectively, 2.9, 4.1, and 1.8 times). Importantly, in an attempt to correlate expression levels with normal tissue reaction to IR, we also identified three other genes CD40, OAS2 , and CXCR1 whose expression level fluctuations during radiotherapy were more pronounced in patients developing late normal tissue responses to curative radiotherapy after the end of the radiotherapy treatment. Overall, we identified inflammation-associated genes which are promising biomarkers of IR exposure and susceptibility to radiation-induced toxicity.

Background: The goal of this study is to examine the effect of neoadjuvant radiochemotherapy on the density of CD8(+) tumor infiltrating lymphocytes (TILs) in endoscopical biopsies and resection specimens from patients with rectal adenocarcinoma before and after therapy., Patients and Methods: In total, 53 patients with locally advanced rectal cancer were studied., Results: The median density of CD8(+) TILs in pretreatment biopsies was 12 (1- 232) and that in surgical specimens after radiochemotherapy was 18 (1- 319). During radiochemotherapy, the density of CD8(+) TILs increased in 30 patients (57%), decreased in 18 (34%), and did not change in one. It was not possible to assess the dynamics of CD8(+) TILs density in four patients. The increased density of CD8(+) TILs after radiochemotherapy was associated with a median survival rate 2.5 times longer than that associated with no increase in density., Conclusion: In the present study, the density of CD8(+) TILs in endoscopical biopsies before radiochemotherapy, the density in resection specimens after radiochemotherapy, or in changes in the density after radiochemotherapy showed no predictive or prognostic significance. However, studying a larger number of patients may show that CD8(+) TILs density is of predictive or prognostic significance.

The aims of the study were: i) to compare circulating tumor DNA (ctDNA) yields obtained by different manual extraction procedures, ii) to evaluate the addition of various carrier molecules into the plasma to improve ctDNA extraction recovery, and iii) to use next generation sequencing (NGS) technology to analyze KRAS, BRAF, and NRAS somatic mutations in ctDNA from patients with metastatic colorectal cancer. Venous blood was obtained from patients who suffered from metastatic colorectal carcinoma. For plasma ctDNA extraction, the following carriers were tested: carrier RNA, polyadenylic acid, glycogen, linear acrylamide, yeast tRNA, salmon sperm DNA, and herring sperm DNA. Each extract was characterized by quantitative real-time PCR and next generation sequencing. The addition of polyadenylic acid had a significant positive effect on the amount of ctDNA eluted. The sequencing data revealed five cases of ctDNA mutated in KRAS and one patient with a BRAF mutation. An agreement of 86% was found between tumor tissues and ctDNA. Testing somatic mutations in ctDNA seems to be a promising tool to monitor dynamically changing genotypes of tumor cells circulating in the body. The optimized process of ctDNA extraction should help to obtain more reliable sequencing data in patients with metastatic colorectal cancer.

Aim: The aim of this retrospective study was to determine the prognostic impact of expression of epidermal growth factor receptor (EGFR) changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma., Material and Methods: One hundred and three patients with locally advanced rectal adenocarcinoma of stage II and III were evaluated. All patients were administered the total dose of 44 --  50.4 Gy. Concomitantly, the patients received capecitabine in the dose 825 mg/ m² in two daily oral administrations or 5- fluorouracil in the dose 200 mg/ m² in continuous infusion. Surgery was indicated at intervals of 4-8 weeks from chemoradiotherapy completion. EGFR expression in the pretreatment biopsies and in resected specimens was assessed with immunohistochemistry., Results: All of 103 patients received radiotherapy without interruption up to the total planned dose. Downstaging was described in 64 patients. Six patients had complete pathologic remission. Recurrence occurred in 49 patients. Local recurrence was found in 22 patients, generalization of disease was reported in 27 patients. A total of 51 patients died. Increased EGFR expression was found in 26 patients. The statistically significantly shorter overall survival (p < 0.001) and disease-free survival (p < 0.001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR was observed during neoadjuvant chemoradiotherapy., Conclusions: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma is associated with significant shorter overall survival and disease-free survival.

Aim: Brachytherapy is an alternative to surgery in the treatment of the early stages of oral tongue cancer. The aim of this retrospective study was to analyze the clinical risk factors and possible candidate biomarkers of local and regional tumor control., Patients & Methods: Twenty-four patients were treated between the years 2001 and 2010. Median follow-up was 37.4 months. Correlation between disease-free survival and clinical stage, tumor grade, resection margin, depth of invasion, and p16, EGF receptor, NF-κB, HIF-1α, HER2, Ku-80, COX-2 and VEGF expression was evaluated., Results: The estimated 5-year local control was 81% and locoregional control was 62%. Depth of tumor invasion (p = 0.018) and higher VEGF expression (p = 0.016) were significantly predictive for worse disease-free survival in Cox multivariate analysis., Conclusion: Intensity of VEGF expression and depth of tumor invasion may be significantly negative predictors of disease-free survival in tongue cancer patients treated by brachytherapy alone. Predictive value of VEGF deserves evaluation in larger studies.

Background/aim: To evaluate whether non-closure of the visceral peritoneum after total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) in patients with uterine corpus carcinoma influences the volume of the small intestine within the irradiated volume during adjuvant radiotherapy or late radiation intestinal toxicity., Materials and Methods: A total of 152 patients after TAH + BSO with adjuvant pelvic radiotherapy were studied. The state of peritonealization was retrospectively evaluated based on surgical protocols. The volume of irradiated bowels was calculated by CT-based delineation in a radiotherapy planning system. The influence of visceral peritonealization upon the volume of the small intestine within the irradiated volume and consequent late morbidity was analyzed., Results: Visceral peritonealization was not performed in 70 (46%) of 152 studied patients. The state of peritonealization did not affect the volume of the irradiated small intestine (p = 0.14). Mean volume of bowels irradiated in patients with peritonealization was 488 cm(3) (range 200-840 cm(3), median 469 cm(3)); mean volume of bowels irradiated in patients without peritonealization was 456 cm(3) (range 254-869 cm(3), median 428 cm(3)). We did not prove any significant difference between both arms. Nor did we observe any influence of non-peritonealization upon late intestinal morbidity (p = 0.34)., Conclusion: Non-closure of the visceral peritoneum after hysterectomy for uterine corpus carcinoma does not increase the volume of the small intestine within the irradiated volume, with no consequent intestinal morbidity enhancement.

Background: Low-dose rate brachytherapy is a well established treatment modality of oral cancer. Data about high-dose rate (HDR) brachytherapy are still sparse with various fractionation schedules and heterogeneous results., Aim: The aim of our retrospective study was to evaluate the results of HDR brachytherapy with doses of 3 Gy twice daily., Patients and Methods: Twenty patients with squamous cell tongue cancer were treated in the years 2001-2009 by exclusive HDR BT 18 × 3 Gy twice daily. The plastic tube technique was used. Median follow up was 47 months (7.8-118) since brachytherapy., Results: The local and locoregional control was 85% and 68%, respectively. Bone necrosis developed in one case treated without mandibular shielding and soft tissue necrosis in 2 cases., Conclusion: It can be concluded that HDR brachytherapy with 18 × 3 Gy twice daily is safe with promising local control. The risk of nodal recurrences is substantial.

Unlabelled: Clinical oncologists have been focusing their efforts on attempting to define risk groups of patients with unusual biological reactions to the recommended therapy regimens using molecular biology techniques., The Aims of Our Study Were: (i) to find a design and validate a method for fast and reliable analysis of the D1853N (5557G>A) genetic polymorphism in the ATM (ataxia-telangiectasia mutated) gene; (ii) to use side-directed mutagenesis to generate ATM 5557A-positive DNA (reference ATM5557A DNA); and (iii) to analyze a group of patients suffering from cervical carcinoma with adverse responses to radiotherapy. The 5557A variant was found in three of twenty women (15%). Our data show that the prevalence of the 5557A allelic variant in cervical cancer subjects with adverse responses after irradiation probably does not differ from the prevalence common in Caucasians. A larger population study should confirm these preliminary results.

Purpose: This study aimed to evaluate prostate volume changes and prostate motions during radiotherapy., Methods: In 2010, twenty-five patients were treated for prostate cancer by external beam radiotherapy with implanted fiducial markers. Coordinates of three gold markers on kilovoltage images were calculated daily. Volume changes in target structure were observed through changes in intermarker distances. Differences in patient position between laser-tattoo alignment and gold marker localization were evaluated. Intrafraction motion was assessed by measuring marker displacement on kilovoltage images acquired before and after fraction delivery., Results: Prostate shrinkage was observed in 60% of patients. The average shrinkage was 7% of the prostate's initial volume. Corrections after laser-tattoo alignment remained mostly below 1 cm. The difference between marker centroid position on the actual images and the planning images was 2 +/- 1 mm on average. The extension of intrafraction movements was 7.6 +/- 0.2 mm on average., Conclusions: In our retrospective study, the possibility for prostate volume changes during radiotherapy was revealed. Intrafraction movements turned out to be the limiting factor in safety margin reduction.

The objective of this study was to evaluate the influence of cisplatin dose upon 3-year overall and disease-free survival rate of patients with advanced cervical cancer treated with concurrent chemoradiotherapy with weekly cisplatin. Seventy-three patients with stage IIB-IVA cervical carcinoma were treated with pelvic (or pelvic + paraaortic) external-beam radiotherapy, high-dose rate brachytherapy and concomitant chemotherapy with weekly cisplatin of 40 mg/m2 in the time period form January 2000 to December 2006 at our department. The 3-year overall survival and disease-free suvival rates were evaluated with regard to the number of cisplatin cycles applied during the external radiotherapy. Only twenty-eight patients received the intended five doses of chemotherapy. The most frequent cause of chemotherapy delay was the acute hematological toxicity with leukopenia. The 3-year overall survival was 71 % and the 3-year disease-free survival was 61 %. Survival analyses didn't prove a statistically significant influence of cisplatin dose upon 3-year survival in cervical carcinoma patients treated by exclusive chemoradiation with weekly cisplatin.

Epidermal growth factor receptor (EGFR) plays an important role in cell-cycle regulation, proliferation, differentiation, and surviving of epithelial tissues. Aberrant overexpression of EGFR can initiate uncontrolled cell proliferation with subsequent formation of epithelial carcinomas. Correlation between EGFR overexpression and increased resistance of tumor tissues to ionizing radiation has been described by many authors. Strategy of tumor radiosensitization by EGFR inhibition seems to have a great potential in the treatment of epithelial cancers. Rationale for EGFR inhibition in combination with ionizing radiaton arises from published results of many radiobiological studies, which describe the role of EGFR in cytoprotective and pro-proliferative reactions of human tumor cells, induced by irradiation. These reactions result in accelerated tumor repopulation, which is subsequently counter-productive to the effect of radiotherapy. Presented article is an overview of EGFR and its function in healthy and tumor tissues; likewise, it describes the relation of EGFR to ionizing radiation; therapeutic approaches to EGFR function modulation in combination with radiotherapy in preclinical and clinical use.