Epidermal growth factor receptor as a predictor of tumor response to preoperative chemoradiation in locally advanced gastric carcinoma

The purpose of my doctoral thesis was a retrospective evaluation whether the intensity of epidermal growth factor receptor (EGFR) expression in tumor biopsy predicts tumor response to preoperative chemoradiotherapy in patients with locally advanced gastric carcinoma. Thirty-six patients with gastric adenocarcinoma in clinical T2-4 stage and/or with nodal metastases were studied. Preoperative treatment consisted of 30-45 Gy of gastric irradiation with continuous 5-fluorouracil and weekly cisplatin. Surgical resection was performed 4-6 weeks later. EGFR expression in pretreatment tumor biopsies was assessed by immunohistochemistry. Level of EGFR expression was determined from the intensity and extent of staining. Tumor response after chemoradiotherapy was defined as a reduction of at least one T-stage level and/or finding of intense tumor regression in histopathologic examination. Seventeen patients responded to preoperative chemoradiation - 8 patients (22%) had pathologic complete response, 9 patients (25%) were downstaged. Positive EGFR expression was found in 8 tumors (22%), and represented a significant predictive marker of poor tumor response in multivariate logistic regression analysis (p = 0.015). Response to chemoradiotherapy was found in 57% (16/28) of EGFR negative patients and in 13% (1/8)..

The Influence of Cisplatin Dose upon Survival in Concurrent Chemoradiotherapy of Locally Advanced Cervical Carcinoma with Weekly Cisplatin

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) externalbeam 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 twentyeight 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

Daily Prostate Volume and Position Monitoring Using Implanted Gold Markers and On-Board Imaging during Radiotherapy

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 changes of tumour vascular endothelial growth factor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

Aim of the study: The aim was to examine the effects of neoadjuvant chemoradiotherapy on VEGF expression in patients with locally advanced rectal cancer. Materials and methods: A total of 53 patients with locally advanced rectal cancer were retrospectively studied. Neoadjuvant treatment comprised external beam radiation (50.4 Gy/28 fractions) with continuous infusion of 5-fluorouracil. Four to 6 weeks after the chemoradiotherapy, the patients underwent surgical resection. Immunohistochemistry was performed to assess VEGF expression in the pretreatment biopsies and in resected specimens. Results: Resection with microscopic residual tumour (R1) was performed in two patients while in the remaining 51 patients radical resection with microscopically negative margins (R0) was possible. Downstaging after preoperative chemoradiotherapy was observed in 34 patients (64%). After chemoradiotherapy 24 patients (45%) had decreased VEGF expression, in 20 patients (38%) there was no change, and in two patients it was not possible to assess the dynamics of VEGF expression due to pathologic complete response after chemoradiotherapy. The five-year overall survival (OS) rate was 56% (95% CI: 43–70%). Although the median OS was 2.5 times shorter in patients who experienced decreased VEGF expression during therapy, this difference did not reach statistical significance. VEGF expression was not significant in Cox regression analysis or log-rank test. VEGF expression decreased after neoadjuvant chemoradiotherapy in most patients with rectal adenocarcinoma examined. This decrease was associated with a trend of inferior prognosis. Conclusions: VEGF expression decreased after neoadjuvant chemoradiotherapy in most patients examined. This decrease was associated with a trend of inferior prognosis

Analysis of D1853N ATM Polymorphism in Radiosensitive Patients with Cervical Carcinoma

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

Cardiotoxicity of radiation therapy in esophageal cancer

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

KONTROVERZE RADIOTERAPIE U PACIENTŮ S HIVDERMÁLNÍM RŮSTOVÝM FAKTOREM (HER)-2 POZITIVNÍCH PACIENTŮ S KARCINOMEM PRSU

Tumor biology plays a crucial role in the systemic treatment, specifically in HER2-positive tumors. Distinct biological behavior of breast cancer subtypes is associated with different rates of locoregional recurrence (LRR). HER2- positive breast cancer patients treated with surgery in combination with radiation, without trastuzumab have poor outcome, including high LRR. The efficacy of radiotherapy in HER-2-positive breast cancer appears to be associated with the expression of estrogen receptors. In patients with HER-2-positive breast cancer, studies conducted before the introduction of trastuzumab indicated higher benefit of adjuvant radiation in patients with hormone receptor-positive tumors compared to patients with tumors not expressing hormone receptors. The introduction of agents targeting HER-2 has transformed the management of these patients, resulting in improved outcomes. The data of clinical studies show that the administration of trastuzumab as part of a multimodality approach (with radiation based on standard guidelines) results in improved outcomes, including lower locoregional recurrence. The risk of cardiac toxicity associated with radiation to the heart and administration of potential cardiotoxic trastuzumab is not clear. In patients treated concomitantly with regional lymph node irradiation and anti-HER-2 agents after prior anthracycline-based chemotherapy minimizing the dose to the myocardium, e.g. respiratory gating or proton beam radiotherapy, have been suggested.Biologie nádorů hraje klíčovou roli v systémové léčbě, konkrétně v NÁDORECH POZITIVNÍCH NA HER2. Odlišné biologické chování podtypů rakoviny prsu je spojeno s různými mírami locoregionální recidivy (LRR). HER2- pozitivní pacienti s karcinomem prsu léčení chirurgicky v kombinaci s ozařováním, bez trastuzumabu mají špatný výsledek, včetně vysoké LRR. Účinnost radioterapie u HER-2 pozitivního karcinomu prsu se zdá být spojena s expresí estrogenních receptorů. U pacientů s HER- 2-pozitivním karcinomem prsu studie provedené před zavedením trastuzumabu ukázaly vyšší přínos adjuvans záření u pacientů s nádory pozitivními na hormonální receptory ve srovnání s pacienty s nádory, kteří nevyjadřují hormonální receptory. Zavedení látek zaměřených na HER-2 změnilo řízení těchto pacientů, což vedlo ke zlepšení výsledků. Údaje z klinických studií ukazují, že podávání trastuzumabu v rámci multimodality přístupu (s radiačním zářením založeným na standardních pokynech) vede ke zlepšení výsledků, včetně nižší locoregionální recidivy. Riziko srdeční toxicity spojené s ozářením srdce a podáním potenciálního kardiotoxické trastuzumabu není jasné. U pacientů léčených současně s ozářením regionálních lymfatických uzlin a anti-HER- 2 přípravky po předchozí chemoterapii na bázi antracyklinu, která minimalizovala dávku myokardu, např