Wiesława Windorbska

Randomized clinical trial on 7-days-a-week postoperative radiotherapy for high-risk squamous cell head and neck cancer

PURPOSE To evaluate the normal tissue reactions and loco-regional control rates (LRC) in patients treated with 7-days-a-week postoperative continuous irradiation (p-CAIR) compared to conventionally fractionated 5-days-a-week postoperative radiotherapy (CF). MATERIALS/METHODS Between 2001 and 2004, 279 patients with high-risk squamous cell cancer of the larynx (158 pts.) or cancer of the oral cavity/oropharynx (121 pts.) were enrolled. They were stratified according to the primary cancer site (larynx vs. others) and the treating center and randomized to receive 63 Gy in fractions of 1.8 Gy given 5-days-a-week (140 pts: CF) or 7-days-a-week (139 pts: p-CAIR). RESULTS The acute and late toxicity was considered acceptable, although the proportion of patients with confluent mucositis was higher in p-CAIR compared to CF (60.0 vs. 33.3%). The actuarial 3-year LRC were 64 vs. 70% for CF and p-CAIR, respectively, p=0.32. A statistically significant improvement in 3-year LRC in p-CAIR arm appeared in a subset of the patients with cancer of the oropharynx/oral cavity (74% p-CAIR vs. 53% CF, p=0.02). By contrast, there was no improvement in LRC in a subset of the patients with cancer of the larynx (p=0.46). CONCLUSION An improvement in LRC attributable to acceleration of postoperative radiotherapy appeared restricted to the patients with cancer of the oropharynx/oral cavity. In patients with cancer of the larynx acceleration of postoperative radiotherapy did not have any beneficial effect.

The Analysis of Receptor-binding Cancer Antigen Expressed on SiSo Cells (RCAS1) immunoreactivity within the microenvironment of the ovarian cancer lesion relative to the applied therapeutic strategy

RCAS1 is involved in generating the suppressive profile of the tumor microenvironment that helps cancer cells evade immune surveillance. The status of the cells surrounding the cancer nest may affect both the progression of the cancer and the development of metastases. In cases of ovarian cancer, a large number of patients do not respond to the applied therapy. The patient’s response to the applied therapy is directly linked to the status of the tumor microenvironment and the intensity of its suppressive profile. We analyzed the immunoreactivity of RCAS1 on the cells present in the ovarian cancer microenvironment in patients with the disease; these cells included macrophages and carcinoma-associated fibroblasts. Later we analyzed the immunoreactivity levels within these cells, taking into consideration the clinical stage of the cancer and the therapeutic strategy applied, such as the number of chemotherapy regiments, primary cytoreductive surgery, or the presence of advanced ascites. In the patients who did not respond to the therapy we observed significantly higher immunoreactivity levels of RCAS1 within the cancer nest than in those patients who did respond; moreover, in the non-responsive patients we found RCAS1 within both macrophages and carcinoma-associated fibroblasts. RCAS1 staining may provide information about the intensity of the immuno-suppressive microenvironment profile found in cases of ovarian cancer and its intensity may directly relate to the clinical outcome of the disease.

Analysis of Treg cell population alterations in the peripheral blood of patients treated surgically for ovarian cancer - a preliminary report.

Citation Wicherek L, Jozwicki W, Windorbska W, Roszkowski K, Lukaszewska E, Wisniewski M, Brozyna AA, Basta P, Skret‐Magierlo J, Koper K, Rokita W, Dutsch‐Wicherek M. Analysis of Treg cell population alterations in the peripheral blood of patients treated surgically for ovarian cancer – a preliminary report. Am J Reprod Immunol 2011; 66: 444–450

The Immunohistochemical Analysis of Antigens such as RCAS1 and B7H4 in the Cervical Cancer Nest and within the Fibroblasts and Macrophages Infiltrating the Cancer Microenvironment

The presence of the aggressive phenotype of the tumor seems to be indicated by the local infiltration of cancer cells and by the development of metastases in the lymph nodes. This phenotype is related to the intensity of the suppressive profile of the tumor microenvironment. The aim of our study has been to gather information about the expression of both RCAS1 and B7H4 proteins in the macrophages and fibroblasts present within both the microenvironment of cervical cancer tumors and the cancer cells present on the front of the cancer nest.

Udział białka RCAS1 w tworzeniu supresyjnego profilu mikrośrodowiska raka płaskonabłonkowego gardła środkowego

INTRODUCTION Tumor microenvironment makes up the stroma of the neoplasm and is the tissue that determines the growth and progression of the tumor and its ability to create metastases. THE AIM OF THE PRESENT STUDY: has been to evaluate the potential role of RCAS1 protein in creating the suppressive tumor microenvironment in pharyngeal squamous cell carcinomas. The immunoreactivity of RCAS1, CD3, CD25, CD68, CD69 and Foxp3 was assessed in the tissue samples of the tumor, in tumor microenvironment and in the reference samples of palatine tonsils in chronic inflammation. RESULTS A statistically significantly higher RCAS1 antigen immunoreactivity was identified in pharyngeal cancer samples than in the stromal samples, the presence of RCAS1 positive macrophages infiltrating the tumor and its stroma was also noticed. The statistically significantly higher RCAS1 antigen immunoreactivity level was identified in the pharyngeal cancer samples in patients with the presence of lymph node metastases in comparison to patients without metastases. The infiltration of CD68 positive cells (macrophages) was significantly higher in the stromal tissue samples than in cancer samples and it was in both, the tumor and the stroma, significantly higher in patients with the presence of lymph node metastases than in patients without metastases. Additionally the presence of CD3 positive TILs was noticed in the tissue of the tumor and in its stroma, the cells were activated, typified by CD69 immunoreactivity which was higher than in the reference samples, and impaired cytotoxicity with low CD25 antigen immunoreactivity. This observation confirmed the presence of selective immune suppression within the tumor and the stroma. CONCLUSION RCAS1, an active factor secreted by the tumor and present in its stroma may play an important role in the phenomenon of tumor escape from host immunological surveillance and in creating the immune tolerance for the tumor cells, as well as in the tumor microenvironment remodeling with creating its suppressive profile enabling the further tumor growth and metastases.Summary Introduction Tumor microenvironment makes up the stroma of the neoplasm and is the tissue that determines the growth and progression of the tumor and its ability to create metastases. The aim of the present study has been to evaluate the potential role of RCAS1 protein in creating the suppressive tumor microenvironment in pharyngeal squamous cell carcinomas. The immunoreactivity of RCAS1, CD3, CD25, CD68, CD69 and Foxp3 was assessed in the tissue samples of the tumor, in tumor microenvironment and in the reference samples of palatine tonsils in chronic inflammation. Results A statistically significantly higher RCAS1 antigen immunoreactivity was identified in pharyngeal cancer samples than in the stromal samples, the presence of RCAS1 positive macrophages infiltrating the tumor and its stroma was also noticed. The statistically significantly higher RCAS1 antigen immunoreactivity level was identified in the pharyngeal cancer samples in patients with the presence of lymph node metastases in comparison to patients without metastases. The infiltration of CD68 positive cells (macrophages) was significantly higher in the stromal tissue samples than in cancer samples and it was in both, the tumor and the stroma, significantly higher in patients with the presence of lymph node metastases than in patients without metastases. Additionally the presence of CD3 positive TILs was noticed in the tissue of the tumor and in its stroma, the cells were activated, typified by CD69 immunoreactivity which was higher than in the reference samples, and impaired cytotoxicity with low CD25 antigen immunoreactivity. This observation confirmed the presence of selective immune suppression within the tumor and the stroma. Conclusion RCAS1, an active factor secreted by the tumor and present in its stroma may play an important role in the phenomenon of tumor escape from host immunological surveillance and in creating the immune tolerance for the tumor cells, as well as in the tumor microenvironment remodeling with creating its suppressive profile enabling the further tumor growth and metastases

Cost-effectiveness analysis of advanced stage non-small cell lung cancer treatment with cisplatin–vinorelbine and carboplatin–gemcytabine combination regimens

Objectives. The aim of the work is to perform an incremental cost-effectiveness analysis of cisplatin–vinorelbine (PN) and carboplatin–gemcytabine (KG) treatment regimens used in advanced stage non-small cell lung cancer (NSCLC) treatment. Material and methods. Medical records of 99 patients with advanced stage NSCLC were collected retrospectively at the Oncology Center in Bydgoszcz. The patients were treated with one of the regimens to be analysed between 2006 and 2011. The analysis was performed from the payer’s perspective. Only direct medical costs were analysed. Costs of procedures were obtained from the hospital’s price list of medical services as of June 30th, 2012. Incremental and one-way sensitivity analyses were performed. Results. The average cost of chemotherapy treatment with the PN treatment regimen is higher than that with the KG treatment regimen (25,342.04 PLN and 19,546.80 PLN per patient, respectively). The average survival time of NSCLC patients treated with PN and KG treatment regimens was 12.91 and 10.11 months, respectively. The cost of drugs constitutes the largest part of the total cost of NSCLC treatment with either treatment regimen. The incremental cost-effectiveness ratio (ICER) is 24,836.76 PLN per additional life-year gained. Conclusion. The analysis showed that the PN treatment regimen is more cost-effective in the treatment of advanced NSCLC, when compared to the KG treatment regimen.

The role of postoperative radiotherapy in prostate cancer patients

Aim of the study The aim of the study was to evaluate the effectiveness of postoperative radiotherapy in prostate cancer patients with unfavorable prognostic factors. Material and methods In the years 2002–2008, 121 consecutive prostate cancer patients underwent radical prostatectomy and postoperative radiotherapy. The median dose was 64 Gy (range: 60–72 Gy). Biochemical and clinical progression-free survival were estimated. Univariate and multivariate analyses were used to analyze clinicopathological variables associated with treatment failure. Results The median follow-up was 27 months. Three-year bPFS was 72%. On univariate analysis it was influenced by: extracapsular tumor extension (60% vs. 75%, p = 0.0232), seminal vesicles invasion (52% vs. 85%, p = 0.00041), Gleason score ≥ 7 (65% vs. 86%, p = 0.044) and the use of hormonal therapy (50% vs. 80%, p = 0.0058). On multivariate analysis bPFS was associated with: TNM stage (HR = 3.19), postoperative hormonal therapy (HR = 2.6), total irradiation dose (HR = 0.82) and the maximum pretreatment level of prostate-specific antigen (PSA) (HR = 0.95). Three-year cPFS was 84%. On univariate analysis it was influenced by: preoperative PSA level > 10 ng/ml (75% vs. 90%, p = 0.04), vascular-nerve bundles involvement (63% vs. 88%, p = 0.0031), adjacent organs infiltration (50% vs. 85%, p = 0.018) and the use of postoperative hormonal therapy (62% vs. 90%, p = 0.02). On multivariate analysis cPFS was associated with: TNM stage (HR = 2.68), postoperative hormonal therapy (HR = 3.61) and total irradiation dose (HR = 0.78). Conclusions Postoperative radiotherapy in patients with unfavorable prognostic factors provides good biochemical and local control. Total irradiation dose and postoperative hormonal therapy are important treatment factors influencing prognosis.

Preliminary results of linac-based radiosurgery in arteriovenous malformations and cerebral tumours in the Oncology Centre in Bydgoszcz

Aim of the study Efficacy of stereotactic radiosurgery (SRS) in the treatment in cerebral AVMs, mennigiomas, metastases, acoustic neuromas and recurrent anaplastic gliomas is well documented. The object of this work was the analysis of the results of the treatment of AVM and selected cerebral lesions with linear accelerator-based stereotactic radiosurgery. Material and methods The lesions included: 12 AVMs, 2 cavernomas, 27 meningiomas, 16 metastases, 5 acoustic neuromas, 16 gliomas in 78 patients. A mean radiation dose of 16Gy was delivered to the tumour or AVM margin and 12Gy to the tumours located in a ponto-cerebellar angle. Follow-up was 18 months. Results Control of tumour growth or AVM was achieved in all cases after 6 months and radiological regression was observed in 20 cases after 12 months. The best results were noted in AVMs, meningiomas and neuromas.There were no new permanent deficits nor complications after radiosurgery requiring medicamentation. Conclusions Organization of SRS in Oncological Center in Bydgoszcz involving close co-operation of radiotherapist, neurosurgeon and physicist in the process of qualification and treatment planning is based on the best global standards. Preliminary results of treatment are consistent with the literature data. A longer follow-up is required to determine the long term efficacy and the toxicity of this treatment in our institution.

Acute pulmonary embolus in the course of cancer

Risk of pulmonary embolism (PE) is relatively high in patients with advanced chronic diseases, particularly with malignancies. Most patients with cancer have blood coagulation test abnormalities indicative of up-regulation of the coagulation cascade, increased platelet activation and aggregation. Pulmonary thromboembolism is common in patients with any cancer and incidence is increased by surgery, chemotherapy, radiotherapy and disease progression. Manifestations range from small asymptomatic to life-threatening central PE with subsequent hypotension and cardiogenic shock. Diagnostic algorithms utilizing various noninvasive tests have been developed to determine the pretest probability of PE results of D-dimer assay, chest radiography ECG and computed tomography. The mortality in untreated PE is high (30%) but appropriate treatment may decrease it to 2–18%. The current recommended treatment for massive pulmonary embolus is either thrombolytic therapy or surgical embolectomy.

IDH1 mutation analysis – an example of putative glioma marker

The astrocytoma cancer represents CNS neoplasms in which the predominant cell type is derived from an immortalized astrocyte. The genomewide analysis of glioma identified somatic mutation at codon 132 of the IDH1 gene which encodes NADP+ dependent isocitrate dehydrogenase. Further studies indicated that patients with somatic, heterozygous R132H mutation have distinct clinical characteristic: younger age at astrocytoma diagnosis (WHO II and WHO III) and improved clinical prognosis. Location of the majority of point mutations in the IDH1 gene are localized at 132 codon - what simplifies the use of this mutation for potential diagnostic purposes. The presence of R132H IDH1 mutation was analysed in group of 38 patients diagnosed with: fibrillar astrocytoma, astrocytoma gemistocyticum, astrocytoma pilocyticum and astrocytoma anaplasticum. The IDH1 mutation status was determinated by immunohistochemistry using monoclonal antibody specific for the R132H mutation. Additional data verification was performed by HRM Cold-PCR and Sanger sequencing. For statistical evaluation we distinguished two subgroups of patients: with and without IDH1 R132H mutation. Presence of IDH1 mutation in Polish astrocytomas’ patients correlates with better clinical outcome and longer median overall survival. Our findings confirm overall tendency for better survival benefits in patients with IDH1 mutated tumors and indicates that presence or absence of IDH1 mutant proteins may become a potential target in personalized medicine.