Promocijas darbs

Pirmsoperācijas jeb neoadjuvantā ķīmijterapija ir ļoti cerīga vēža medikamentozās terapijas attīstības stratēģija nākotnē. Tā rada iespēju veikt krūti saglabājošu operāciju slimniecēm ar lieliem primāriem audzējiem. Slimniecēm, kurām sasniegta audzēja pilna morfoloģiska remisija pēc neoadjuvantās ķīmijterapijas operācijas materiālā, ir konstatēta garāka dzīvildze. Šī darba mērķis bija novērtēt pirmsoperācijas ķīmijterapijas, molekulāro marķieru – šūnu proliferācijas indeksa Ki-67, cilvēka epidermālā augšanas faktora receptora cerbB-2 un steroīdo hormonu receptoru lomu ārstēšanas izvēlē un bezrecidīva dzīvildzi, piecu un desmit gadu dzīvildzi slimniecēm ar lokāli izplatītu krūts vēzi. Pētījumā kopā iekļautas 246 slimnieces ar lokāli izplatītu krūts vēzi: pirmajā neoadjuvantās ķīmijterapijas grupā 52 slimnieces, kontroles grupā 168 slimnieces un otrajā neoadjuvantās ķīmijterapijas grupā 26 slimnieces. Pētījumā klīniski un radioloģiski novērtētas audzēja lieluma pārmaiņas pēc pirmsoperācijas ķīmijterapijas. Otrās neoadjuvantās ķīmijterapijas grupas slimniecēm pirms un pēc neoadjuvantās ķīmijterapijas noteikti molekulārie marķieri un analizētas marķieru izmaiņas pirms un pēc terapijas. Pētījuma rezultāti liecina, ka pirmsoperācijas ķīmijterapija efektīvi samazina krūts audzēja izmērus, bet tā nepagarina bezrecidīva, kā arī kopējo dzīvildzi, salīdzinot ar kontroles grupas slimniecēm. Slimnieces ar augstāku Ki-67 proliferācijas indeksu ir jutīgākas uz ķīmijterapiju. Zemāks estrogēna receptoru un progesterona receptoru daudzums korelē ar cerbB-2 receptoru pārekspresiju un norāda uz nelabvēlīgu prognozi. Slimniecēm ar cerbB-2 receptora pārekspresiju ir agresīvāka slimības gaita, augstāka letalitāte pirmajā gadā pēc diagnozes noteikšanas un zemāki kopējās dzīvildzes rādītāji, salīdzinot ar cerbB-2 negatīviem audzējiem. Šajā darbā iegūtie rezultāti liecina, ka pirmsoperācijas ķīmijterapija ir efektīva ārstēšana lokāli izplatīta krūts vēža slimniecēm, kam nepieciešama audzēja lieluma samazināšana, lai veiktu krūti saglabājošu operāciju un molekulāro marķieru noteikšana ļauj izvēlēties optimālu ārstēšanas taktiku slimniecēm ar lokāli izplatītu krūts vēzi.Preoperative or neoadjuvant chemotherapy is a promising future strategy for development of a drug therapy to treat cancer. It provides for the possibility of performing a breast-conserving operation to conserve the breast among patients with large primary tumours. It has been found that patients who have attained complete morphological remission of the tumour following neoadjuvant chemotherapy in the operation material enjoy longer overall survival. The aim of our thesis was to assess the role of preoperative chemotherapy and molecular markers – proliferation index Ki-67, peptide hormone receptor cerbB-2 and steroid hormone receptors – in selection of treatment and disease free survival, as well as five- and ten-year survival, among patients with locally advanced breast cancer. Altogether, 246 patients with locally advanced breast cancer were included in the study: 52 patients in the first neoadjuvant chemotherapy group, 168 patients in the control group, and 26 patients in the second neoadjuvant chemotherapy group. In the study changes in the size of the tumour were clinically and radiologically assessed following preoperative chemotherapy. Patients in the second neoadjuvant chemotherapy group had their molecular markers established before and after neoadjuvant chemotherapy and the changes in the markers analysed before and after therapy. The results of the study indicate that preoperative chemotherapy effectively decreases the dimension of the breast tumour, but that this procedure does not increase disease-free survival as well as overall survival compared to patients in the control group. Patients with a higher Ki-67 proliferation index are more sensitive to chemotherapy. A lower quantity of estrogen receptors and progesterone receptors correlates with cerbB-2 receptor overexpression and indicates an unfavourable prognosis. Patients with cerbB-2 receptor overexpression experience a more aggressive course of illness, higher lethality in the first year following establishment of diagnosis and lower overall survival indicators as compared to cerbB-2 negative tumours. The results gleaned from our study demonstrate that preoperative chemotherapy serves as effective treatment of locally advanced breast cancer among patients in need of reduction of the size of the tumour, in order to perform an operation to conserve the breast, and that establishing molecular markers permits selection of an optimal treatment approach among patients with locally advanced breast cancer. Annotation Preoperative or neoadjuvant chemotherapy is a promising future strategy for development of a drug therapy to treat cancer. It provides for the possibility of performing a breast-conserving operation to conserve the breast among patients with large primary tumours. It has been found that patients who have attained complete morphological remission of the tumour following neoadjuvant chemotherapy in the operation material enjoy longer overall survival. The aim of our thesis was to assess the role of preoperative chemotherapy and molecular markers – proliferation index Ki-67, peptide hormone receptor cerbB-2 and steroid hormone receptors – in selection of treatment and disease free survival, as well as five- and ten-year survival, among patients with locally advanced breast cancer. Altogether, 246 patients with locally advanced breast cancer were included in the study: 52 patients in the first neoadjuvant chemotherapy group, 168 patients in the control group, and 26 patients in the second neoadjuvant chemotherapy group. In the study changes in the size of the tumour were clinically and radiologically assessed following preoperative chemotherapy. Patients in the second neoadjuvant chemotherapy group had their molecular markers established before and after neoadjuvant chemotherapy and the changes in the markers analysed before and after therapy. The results of the study indicate that preoperative chemotherapy effectively decr

Neoadjuvant Chemoradiation in Patient with Localy Advanced Rectal Cancer

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DOSAGE OF CISPLATIN AND RELATED TOXICITY OF CANCER PATIENTS BASED ON BODY FAT AND MUSCLE MASS

In oncology practice, the human body surface area (BSA) is used for the calculation of the dose of chemotherapy. The human BSA is determined by derived formulas, but it is not directly linked to the pharmacokinetics of the drugs. Obesity alters the disposition of drugs pharmacokinetics, which should be considered when prescribing medications in this patient population. Failure to adjust doses in obesity may result in increased toxicity. The aim of this study was to assess predictors of an increase in the level of trygliceride considered to be among the cardiovascular risk factors. Method. The study involved 118 oncology patients with various tumor localizations. The patients underwent anthropometric measurements (height, weight, circumference, fat fold thickness, the distance between the epicondyls above the joint), and the BSA (according to the Mosteller formula). Patients who received cisplatin chemotherapy were analyzed in serum triglyceride levels before and after the treatment. Results. A comparison of female and male subsamples revealed no significant in variance between sexes and no significant differences in initial triglyceride, triglyceride change, and in the age between groups. Body fat mass was relatively higher in females, while body muscle mass and bone mass were relatively higher in males. There was a difference in the cisplatin dose, with a higher dose for males than for females. The results demonstrate that the higher cisplatin dose and higher body fat mass are significant predictors of an increase in triglyceride for both sexes

DOSAGE OF CISPLATIN AND RELATED TOXICITY OF CANCER PATIENTS BASED ON BODY FAT AND MUSCLE MASS

In oncology practice, the human body surface area (BSA) is used for the calculation of the dose of chemotherapy. The human BSA is determined by derived formulas, but it is not directly linked to the pharmacokinetics of the drugs. Obesity alters the disposition of drugs pharmacokinetics, which should be considered when prescribing medications in this patient population. Failure to adjust doses in obesity may result in increased toxicity. The aim of this study was to assess predictors of an increase in the level of trygliceride considered to be among the cardiovascular risk factors. Method. The study involved 118 oncology patients with various tumor localizations. The patients underwent anthropometric measurements (height, weight, circumference, fat fold thickness, the distance between the epicondyls above the joint), and the BSA (according to the Mosteller formula). Patients who received cisplatin chemotherapy were analyzed in serum triglyceride levels before and after the treatment. Results. A comparison of female and male subsamples revealed no significant in variance between sexes and no significant differences in initial triglyceride, triglyceride change, and in the age between groups. Body fat mass was relatively higher in females, while body muscle mass and bone mass were relatively higher in males. There was a difference in the cisplatin dose, with a higher dose for males than for females. The results demonstrate that the higher cisplatin dose and higher body fat mass are significant predictors of an increase in triglyceride for both sexes

Platinum-based neoadjuvant chemotherapy in BRCA1-positive breast cancer : A retrospective cohort analysis and literature review

Publisher Copyright: © 2018 The Author(s).Background: There is increasing evidence of high platinum sensitivity in BRCA-associated breast cancer. However, evidence from randomized trials is lacking. The aim of this study was to analyze the results of platinum-based chemotherapy for BRCA1-positive breast cancer in a neoadjuvant setting. Methods: A retrospective study was performed by obtaining information from patient files. The results were compared with the available data from a literature review. Results: Twelve female patients with BRCA1 gene mutations who had stage I to III breast cancers were eligible for evaluation. They received platinum-based neoadjuvant chemotherapy between 2011 and 2016. Eleven patients received a combination of cisplatin and doxorubicin, and one patient received carboplatin and docetaxel. All patients underwent mastectomy after chemotherapy. Ten patients (83%) achieved pathological complete remission (pCR). The observed pCR rate was comparable to existing results found in similar studies. Conclusion: The results of the study confirm the high pCR rate in BRCA1-positive breast cancer after platinum-based neoadjuvant chemotherapy. Larger randomized studies and longer follow-up times are necessary to evaluate the role of platinum-based therapies in BRCA1-positive breast cancer.publishersversionPeer reviewe

Pathological Complete Remission in Young Colon Cancer Patient with a Large Liver Metastasis after FOLFOX-4/Bevacizumab Treatment – A Case Report

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Care of patients with non-small-cell lung cancer stage III

Background. Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the realworld setting in Central European countries to define areas for improvements. Patients and methods. This multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally. Results. Between March 2014 and March 2017, patients (n=583) with the following characteristics were entered: 32% females, 7% never-smokersECOG performance status (PS) 0, 1, 2 and 3 in 25%, 58%, 12% and 5%, respectively21% prior weight loss53% squamous carcinoma, 38% adenocarcinoma10% EGFR mutations. Staging procedures included chest X-ray (97% of patients), chest CT (96%), PET-CT (27%), brain imaging (20%), bronchoscopy (89%), endobronchial ultrasound (EBUS) (13%) and CT-guided biopsy (9%). Stages IIIA/IIIB were diagnosed in 55%/45% of patients, respectively. N2/N3 nodes were diagnosed in 60%/23% and pathologically confirmed in 29% of patients. Most patients (56%) were treated by combined modalities. Surgery plus chemotherapy was administered to 20%, definitive chemoradiotherapy to 34%, chemotherapy only to 26%, radiotherapy only to 12% and best supportive care (BSC) to 5% of patients. Median survival and progression-free survival times were 16.8 (15.318.5) and 11.2 (10.212.2) months, respectively. Stage IIIA, female gender, no weight loss, pathological mediastinal lymph node verification, surgery and combined modality therapy were associated with longer survival. Conclusions. The real-world study demonstrated a broad heterogeneity in the management o f stage III NSCLC in Central European countries and suggested to increase the rates of PET-CT imaging, brain imaging and invasive mediastinal staging

Role of percutaneous needle biopsy of axillary lymph nodes to evaluate node positive breast cancer after neoadjuvant chemotherapy

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Ultrasound guided needle biopsy of axilla to evaluate nodal metastasis after preoperative systemic therapy in cohort of 106 breast cancers enriched with BRCA1/2 pathogenic variant carriers.

BACKGROUND: Aim of the study is to evaluate the role of ultrasound guided fine needle aspiration cytology (FNAC) in the restaging of node positive breast cancer after preoperative systemic therapy (PST). METHODS: From January 2016 - October 2020 106 node positive stage IIA-IIIC breast cancer cases undergoing PST were included in the study. 18 (17 %) were carriers of pathogenic variant in BRCA1/2. After PST restaging of axilla was performed with ultrasound and FNAC of the marked and/or the most suspicious axillary node. In 72/106 cases axilla conserving surgery and in 34/106 cases axillary lymph node dissection (ALND) was performed. RESULTS: False Positive Rate (FPR) of FNAC after PST in whole cohort and BRCA1/2 positive subgroup is 8 and 0 % and False Negative Rate (FNR) - 43 and 18 % respectively. Overall Sensitivity - 55 %, specificity- 93 %, accuracy 70 %. CONCLUSION: FNAC after PST has low FPR and is useful to predict residual axillary disease and to streamline surgical decision making regarding ALND both in BRCA1/2 positive and negative subgroups. FNR is high in overall cohort and FNAC alone are not able to predict ypCR and omission of further axillary surgery. However, FNAC performance in BRCA1/2 positive subgroup is more promising and further research with larger number of cases is necessary to confirm the results