γ-amino butyric acid (GABA) level as an overall survival risk factor in breast cancer.

INTRODUCTION: The γ-amino butyric acid (GABA) plays important role in the proliferation and migration of cancer cells. The aim of the study was to evaluate the level of GABA in breast cancer, in relation to clinical and epidemiological data. MATERIAL AND METHODS: The study was conducted on 89 patients with breast cancer in stage I-II. GABA level was assessed using spectrofluorometric method in tumour homogenates. Immunoexpression of E-cadherin was evaluated histologically on paraffin fixed specimens. Overall and disease-free survival was assessed for a 15-year interval period. RESULTS: Median overall survival was significantly longer (127.2 months) in patients with a high level of GABA (>89.3 µg/1), compared with a group with a low level of the amino acid (106.4 months). Disease-free survival was insignificantly different - 99 and 109 months, respectively. A significantly longer overall survival (131.2 months) was seen among patients with a high level of GABA and positive E-cadherin immunoexpression, compared with a group characterized by a low level of GABA and lack of E-cadherin immunorectivity (98.1 months). The co-existence of negative immunoexpression of E-cadherin and low GABA concentration resulted in a six-fold increase in the risk of death (HR=6.03). CONCLUSIONS: GABA has a significant prognostic value in breast cancer. Co-existence of a low level of GABA and loss of E-cadherin immune-expression seems to be a new, independent, and negative prognostic marker of the neoplasm.

Image-guided high-dose-rate brachytherapy of head and neck - a case series study.

PURPOSE: The aim of the study was the evaluation of image guided transdermal application of interstitial brachytherapy in patients undergoing repeated irradiation for relapsed local tumor of the head and neck area. MATERIAL AND METHODS: The article describes transdermal application of interstitial high-dose-rate (HDR) brachytherapy in 4 patients treated due to relapsed local tumor in soft palate, submandibular area, laryngopharynx, as well as pterygoid muscles and maxillary sinus. The application was conducted under continuous computed tomography (CT)-image guidance (CT fluoroscopy). Patients qualified for this type of treatment had neoplastic lesions located deep under the skin surface. Because of their location, access to the lesions was limited, and the risk of damaging the adjacent tissues such as vessels and nerves was high. The following parameters have been evaluated: clinical response using RECIST 1.1, incidence of perisurgical complications using CTCAE 4.0 and the frequency of occurrence of radiotherapy related early morbidity using RTOG. RESULTS: Various radiation schemes were used, from 3 to 5 fractions of 3.5-5 Gy. The median total dose (D90) was 20.6 Gy. Biologic effective dose (BED) and equivalent 2 Gy (DEQ2) median doses were 30.4 Gy and 25.3 Gy, respectively. In the follow-up period of 3-7 months (the median value of 3.5 months), 2 patients had partial regression of the disease and in 2 others the neoplastic process was stabilized. None of the patients had serious complications of treatment (of 3rd degree or higher). CONCLUSIONS: Computed tomography-image guided brachytherapy proved to be a safe method of treatment in patients with local relapse in sites, in which traditional visually controlled application was impossible due to risk of complications. Despite short observation period and small study group, it seems justified to conduct prospective studies for the evaluation of efficacy and safety of CT-image guided brachytherapy.

[Symptoms and treatment of radiation-induced reactions]. / Objawy i leczenie odczynów popromiennych.

Radiotherapy is one of the main methods of cancer treatment alone or in combination with chemotherapy. It is applied in about 60% of oncological patients. However, in spite of its clinical usefulness, radiotherapy is associated with a high risk of radiation-induced side effects, including dermatitis, enteritis, cystitis, pericarditis, pneumonia or depression, sexual function disorders, cardiomiopathy, coronary heart disease, anomalies of heart valves and development of second malignant tumor. The early diagnosis and proper treatment of radiation-induced side effects have a major impact on patients` quality of life and future prognosis. Radiation reactions can be categorized as acute or late, occurring before and after six months after radiotherapy. Among the most common acute reactions there were observed: skin rash, mucositis, nausea, vomiting, fever and radiation pneumonitis. Within reference to the late complications, we distinguish for instance fibrosis of organs, a radiation necrosis of bone, ulcers, fistulas, sexual dysfunction and the development of second malignant carcinomas.

The impact of surgery on the efficacy of adjuvant therapy in glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant brain tumor. Surgery still remains a fundamental part of treatment in GBM, followed by radiotherapy and chemotherapy. OBJECTIVES: The aim of the study was to assess the impact of surgery on the efficacy of adjuvant therapy in patients with glioblastoma multiforme. MATERIAL AND METHODS: The study involved 181 patients: 50 treated with adjuvant radiotherapy (RTH) only (60 Gy in daily 2Gy fractions) and 131 treated with postoperative radiochemotherapy (RTH-CHT) (60 Gy, 2Gy/d)+75 mg/m2 temozolomide for 42 days of radiotherapy, followed by 6 courses every 28 days; the first course was 150 mg/m2 for 1-5 days, and the subsequent courses were 200 mg/m2 for 1-5 days). Overall survival (OS) and disease-free survival (DFS) were assessed. The statistical analysis entailed the log-rank test, Kaplan-Meier curves and Cox proportional hazards regression; the threshold of statistical significance was set at p=0.05. RESULTS: Median OS and DFS were significantly increased (p=0.001) in the RTH-CHT group compared with the RTH group: 9.77 months vs 6.38 months for OS, and 8.4 months vs 4.33 months for DFS. After radical surgery, RTH-CHT extended OS by 5.3 months and DFS by 4.5 months in comparison to RTH. In patients who underwent non-radical surgery, the type of adjuvant therapy made no difference in either OS or DFS. In the RTH-CHT group, OS and DFS depended on the extent of the surgery, and were significantly longer in patients who underwent radical surgery (OS: p=0.03128; DFS: p=0.01206). In the RTH group, the type of surgery had no effect on survival. CONCLUSIONS: Radiochemotherapy significantly prolongs OS and DFS compared with radiotherapy alone in GBM patients who have undergone radical removal of the tumor. Among patients who had non-radical surgery, the type of adjuvant treatment has no effect on OS or DFS.

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study.

BACKGROUND: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. METHODS: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. RESULTS: Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. CONCLUSIONS: Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study.

[Reasons for delay in treatment of breast cancer detected due to breast self-examination in women from the Lubelskie region]. / Przyczyny opóznien leczenia chorych na raka piersi wykrytego w trakcie samobadania u kobiet w województwie lubelskim.

OBJECTIVES: A delay in diagnosis and treatment of breast cancer patients is observed despite access to modern diagnostic methods. The aim of the study was to evaluate time between the first symptoms of breast cancer and treatment commencement, as well as to analyze reasons for the delay MATERIALS AND METHODS: The research was conducted on 260 breast cancer patients treated at the Oncology Center in Lublin between 2008 and 2011. 'Patient delay' was defined as the time gap of > 3 months between first symptoms of cancer and the doctor's appointment and 'system delay' as the time gap of > 1 month between the first medical consultation and commencement of treatment. RESULTS: Mean patient delay was 32.2 +/- 63.8 weeks. The main reasons were: disregard of symptoms (51%) and fear of being diagnosed with cancer (48%). Factors which significantly influenced the length of patient delay included: age > 65 years, non-regular gynecologic care, lack of prior cancer screening and lack of family history of breast cancer Mean system delay was 3.1 +/- 2.9 weeks. Tumors < 5 cm in diameter and clinical presentation other than a tumor significantly influenced the system delay CONCLUSIONS: A significant delay in diagnosis and treatment of breast cancer remains to be noted. Delay in seeking medical help was observed in 20% of the patients, whereas the referral was delayed due to system fault in 38% of the cases. Contrary to popular belief, patient delay (mean 32.2 +/- 63.8 weeks) is 10 times longer than system delay (3.1 +/- 2.9 weeks), suggesting an urgent need for further education of the general public and creating more accessible medical care.

Evaluation of prognostic parameters of E-cadherin status in breast cancer treatment.

INTRODUCTION AND OBJECTIVE: Breast cancer is one of the most frequent malignancies in women. Axillary lymph node involvement, tumour size, receptor status, and level of malignancy are the most significant prognostic factors in breast cancer, but insufficient to date. More factors are needed for establishing the prognosis and treatment in these patients. The aim of the presented study was evaluation of E-cadherin expression and its prognostic value among 89 specimens of breast cancer. MATERIALS AND METHODS: 89 formalin-fixed and paraffin-embedded breast cancer specimens were studied for expression of E-cadherin detected by immunohistochemistry. During 10-year observation overall/OS/and disease-free survival/DFS/of patients were assessed. RESULTS: Average of OS and DFS were shorter among patients without expression of E-cadherin in comparison to survival time of patients with expression of E-cadherin. The lack of E-cadherin expression was present more often among patients with distant metastasis. No essential changes were noticed in the level of E-cadherin depending on the size of the tumour, G, presence of metastasis into the lymph nodes, ER, PR and HER-2, hormonal condition and presence of cancerous tissues in lymphatic vessels and the infiltration of lymph nodes capsules. CONCLUSIONS: E-cadherin may play an important role in the prognosis of breast cancer patients.

[Contemporary methods of treatment in local advanced prostate cancer]. / Wspólczesne metody leczenia miejscowo zaawansowanego raka gruczolu krokowego.

The prostate cancer is one of the most often cancers amongst males. Its frequency is increasing with age. Thanks to widespread of screening denomination of specific prostate specific antigen (PSA), ultrasonography including the one in transrectal (TRUS), computed tomography, magnetic resonance and especially the awareness of society, the number of patients with low local advance of illness is increasing. The basic method of treatment in such cases is still the surgical removal of prostate with seminal bladder or radiotherapy. To this purpose tele-(IMRT, VMAT) or brachytherapy (J125, Ir192, Pa103) is used. In patients with higher risk of progression the radiotherapy may be associated with hormonotherapy (total androgen blockage-LH-RH analog and androgen). Despite numerous clinical researches conducted there is still no selection of optimal sequence of particular methods. Moreover, no explicit effectiveness was determined. The general rule of treatment in patients suffering from prostate cancer still remains individual selection of therapeutic treatment depending on the age of a patient, general condition and especially patient's general preferences. In case of elderly patients and patients with low risk of progression, recommendation of direct observation including systematical PSA denomination, clinical transrectal examination, TRUS, MR of smaller pelvis or scintigraphy of the whole skeleton may be considered.

Results of the megaprosthesis replacement reconstruction proximal femoral resection bone tumors.

Background. Proximal femur defects resulting from tumor resections can be repaired with various types of hip endoprostheses. Major surgical procedures involving muscle detachments and extensive endoprosthesis implantation are prone to deep infections and the hip instability. The purpose of our study was to assess the outcome of hip prosthesoplasty after resection of large tumors from the proximal femur. Material and methods. Over the last 5 years, 49 patients have undergone hip prosthesoplasty after tumor resection in the proximal femur for 37 bone metastases and 12 primary neoplasms during the last 5 years. Three total megaprostheses were used, as well as 34 conventional long stem endoprostheses, including 26 bipolar and 12 Austin Moore prostheses. Results. Two patients died shortly after surgery, and another 4 were nonambulatory due to diffusion of the cancer. There were 3 cases of endoprosthesis luxation, 1 deep implant infection and 1 metastasis recurrence. We had 28% excellent functional outcomes and 60% good; the latter were complicated by Trendelenburg gait. Conclusions. Hip instability is the most common complication in prosthesoplasty after tumor resection in the proximal femur.

Restoration of bone stock after aseptic loosening of a distal post-resections femoral prosthesis.

Background. The aseptic loosening of the stem is a frequent complication of post-resection endoprosthesis. Material and methods. Twenty-one patients were operated for primary neoplasm of the distal femoral epiphysis. In 3 cases (14.3%) loosening of the endoprosthesis stem appeared 4 to 8 years after the resection-reconstruction procedure. In all cases the endoprosthesis was reinserted with reconstruction of the femoral shaft, using cancellous femoral impaction grafting with cement (Exeter technique). Results. The early results of revision surgery were good in all 3 cases. Subtrochanteric fracture appeared at the site where the cortex of the femoral shaft cortex was perforated by the endoprosthesis stem tip, ca. 18 months after reinsertion. Loosening of the reinserted endoprosthesis appeared in another female patient. The outcomes of revision surgery were good 2 to 3.5 years post surgery in both patients. Conclusions. The outcome of revision surgery for loosening of the femoral component of a post-resection endoprosthesis is good if there is no perforation of the femoral cortex.

Methods of reconstruction of large bone defects after tumor resection.

Large bone defects resulting from the resection of tumors and tumor-like lesions must be repaired. The method of reconstruction depends on the diagnosis and the tumor location. Post-resection endoprostheses or large allografts are used routinely for primary neoplasms. Major surgical procedures and implants enhance deep infections. Loosening of the endoprostheses and the graft fractures appear in the later postoperative period. Methyl metacrylate is used in the treatment of bone metastases. Tumor-like defects are filled up after resection with morselized bone grafts.

Role of radiotherapy in the treatment of osteolytic damage due to bone tumors.

Metastasis to bone is a common event in the natural history of nearly all neoplasms, which often greatly affects the patient's quality of life. Bone metastases can cause pain and pathological fractures, or even a cord compression syndrome with severe neurological symptoms. The treatment of metastatic disease requires a multidisciplinary approach that addresses systemic and local disease. On a basis of available literature as well as own research current opinions on this subject has been presented in these paper.Where the treatment objective is pain relief, a single 8 Gy treatment is recommended as the standard dose-fractionation treatment of symptomatic but uncomplicated bone metastases. External beam irradiation achieves pain palliation in more than 75% of patients. Radiotherapy with doses of 40-50 Gy results in remineralization in 60-80% of patients 4-8 weeks after irradiation. The role of radiotherapy in the treatment of primary bone cancer is limited. The choice of the best local treatment of Ewing's sarcoma of bone remains a controversial issue. Surgery should always be considered in the local treatment of Ewing's sarcoma. Postoperative radiation therapy must be added when surgical margins are inadequate. Radiotherapy is used in the treatment of plasmacytoma, chordoma and chondrosarcoma.

Genistein alone or combined with cyclophosphamide may stimulate 16/C transplantable mouse mammary cancer growth.

Among the many potential antiangiogenic agents now in various stages of preclinical or clinical study, genistein (GEN) has generated wide interest being because of its natural origin (soybeans) and epidemiological studies showing the cancer chemopreventive effects of soybean consumption. In this paper the in vivo effects of GEN applied either alone or together with cyclophosphamide on the growth of mouse transplantable mammary carcinoma (16/C) transplanted either orthotopically or ectopically is presented. The growth of 16/C mouse mammary cancer transplanted subcutaneously (s.c.) or into the mammary gland (orthotopically-orth.) was stimulated by GEN administered from day 4 after tumor cell inoculation. Such stimulation was not observed when the treatment with GEN was started at day 12 after cell inoculation. Stimulation of tumor growth by GEN was markedly higher in mice transplantedorth. than in those transplanted s.c.. However, GEN did not affect the expression of estrogen (ER)and progesterone receptors (PgR) in the orthotopic model of 16/C cancer. In the case of subcutaneously growing tumors, treatment with GEN lowered (2-fold) the expression of both ER and PgR. In the interpretation of these results, the pleiotropic (including hormonal and antiproliferative), sometimes opposing effects of genistein in vivo should be considered. It seems rather reasonable to exclude breast and, perhaps, other hormone-dependent cancers from the treatment and chemoprevention with soy-derived phytoestrogens until its mechanism(s) of action on various cancer cells is completely understood.

[Assessment of various prognostic factors in patients irradiated for bone metastases]. / Ocena wartosci wybranych czynników prognostycznych u chorych napromienianych z powodu przerzutów nowotworów do kosci.

Prognostic survival rate is one of the factors decisive about the kind of the local therapy at patients with bone metastases. The work evaluates chosen prognostic parameters such as age, sex, the presence of extra-skeletal metastases, the existence of pathological fracture and the applications of bisphosphonates and/or systemic treatment at 305 patients irradiated due to bone metastases. The median survival rate was 6.2 months and was significantly depended from primary location of the disease. The sex, age and number of metastatic foci had no significant influence on the median survival rate however the remaining prognostic factors depended on the primary location of the neoplasm.

[The epidemiologic and clinical characteristics of patients in hospice care]. / Charakterystyka populacyjno-kliniczna chorych objetych opieka terminalna.

The Good Samaritan Hospice in Lublin was created in 1989. At the beginning only home care was available but since 1997 stationary care is. The aim of the article was to present the clinical-population characteristics of patients treated terminally in the hospice in the year 2000. Over 294 patients were evaluated, and 173 within this group were treated in ward and died in the ward. The remaining 121 patients were treated out of the ward and died at home. It was estimated that the majority of the hospice patients were people from the city (81.7%) with primary or vocational education. The average age was 66.4 and the most numerous group (58.2%) consisted of patients older than 60. Women were more likely to be treated at the hospice (55.5%). The most frequent reason of death among the hospice patients were cancers of: the alimentary tract (26%), the respiratory system (13.9%), feminine sexual organs (11.6%), and the urinary system (10.9%). 43.5% of the patients were unaware of the diagnosis, and only 34.4% were treated radically. The majority (65.6%) was treated either palliative or symptomatically. The average duration of the in-ward treatment was 22.1 days and was considerably shorter in comparison to the duration of the treatment provided at home. Concluding, the in-ward terminal care is a short term care.

[Intracranially extended nasopharyngeal angiofibroma treated surgically and by radiotherapy]. / Naczyniakowlókniak czesci nosowej gardla z wypustka wewnatrzczaszkowa leczony operacyjnie i napromienianiem.

A case of nasopharyngeal angiofibroma with intracranial extension is presented. The parasellar extension was demonstrated on CT and MRI scans after four operations performed in two centres. The boy was radiated (42 Gy/t). Two and a half years follow up using MRI showed gradual regression of the tumour down to minimal enhancement in the parasellar region.

[The role of GABA-ergic system in carcinogenesis]. / Rola ukladu GABA-ergicznego w procesie karcynogenezy.

The gamma-aminobutyric acid (GABA) is the major and the best known neurotransmitter with inhibitory properties in the central nervous system (CNS). Outside the CNS, GABA acts as a regulator of muscle tension and controls the secretion of hormones. In the peripheral region, as in the CNS GABA's function is known to be mediated by GABAA and GABAB receptors. Several recent reports have suggested a relationship between the GABA-ergic system and oncogenesis. It has been confirmed that both GABA content and GAD activity are increased in material from colon, breast, digestive tract, and ovarian cancer. In the light of theory of dynamic balance between stimulating and inhibitory amino acids, disturbances in GABA metabolism may be a sign of the cell's defensive reaction during carcinogenesis.

Radiological assessment of indications for surgical treatment of spinal metastases.

Background. The purpose is to assess the risk of spinal cord compression in patients with spine metastases using radiological data.
Material and methods. We evaluate 103 patients with the thoraco-lumbar vertebral body metastases - 52 with neurological symptoms of spinal cord compression and 51 symptoms free. We measured the statistical relation between spinal cord compression, pathological fracture, angle deformity of the spine and metastasis location. We divide spine into 3 columns and named pediculum as the fourth. We used statistical multiple regression analysis.
Results. The risk of spinal cord compression is depended on the location of the metastasis in vertebral body (p < 0,01). We found spinal cord compression symptoms in 25 out of 31 patients in group with pediculum involvement and in 27 out of 72 in group with other locations. It was highly statistically important (p < 0.001). In 45 out of 68 patients with vertebral fractures we found spinal cord compression symptoms (p < 0.01). We did not found statistical correlation between angle deformity and compression symptoms.
Conclusions. The risk of spinal cord compression is higher if the metastases are localised in thoraco-lumbar part of spine and if the pediculum is involved. The pathological fracture increases the risk of the compression, too.

The impact of bisphosphonate therapy on the survival time of patients undergoing radiotherapy for bone metastases.

Background. Bisphosphonates are form of medical therapy for bone metastases. Morbidity from bone metastases including hypercalcemia episodes, pain, pathological fractures and appearance of new metastases in skeletal system is decreased by bisphosphonate therapy. The aim of this article is to determine the influence of bisphosphonate therapy on survival time of patients irradiated due to bone metastases.
Material and methods. 305 patients irradiated due to bone metastases were assessed in this retrospective study. 94 of them were additional treated by bisphosphonates. Median survival time counted from the end of radiotherapy to the death of patients was assessed. Using U Mann Whitney test the influence of bisphosphonates therapy on survival time was determined. The significance level of p = 0,05 was accepted.
Results. The median survival time of patients irradiated due to bone metastases and treated by bisphosphonates was 8,1 month and 5,24 month in the group treated only by radiotherapy. Median survival time of pts with breast cancer and with unknown primary site of cancer who were treated by radiotherapy and bisphosphonates was significantly longer (respectively p = 0,001 and p = 0,016) as compared with the group with irradiated bone metastases only.
Conclusions. 1. Bisphosphonates therapy improved the median survival time in the whole group of patients irradiated due to bone metastases. 2. Statisticaly significant prolonged survival time was observed in groups of patients with breast cancer and with unknown primary site of cancer. Median survival time was prolonged in these groups about 5 months and 3,5 months respectively.

Radiological and functional assessment of indications for operative treatment in patients with long bone metastases.

Background. The purpose of the study is to evaluate the risk of fractures in long bones with metastases based on intact cortical bone index (ICBI) and functional assessment.
Material and methods. We evaluate radiograms of 36 (25 fractures) and 86 patients (56 fractures) with the upper and lower extremity metastases, respectively. We measured on radiograms intact cortical bone index (ICBI) using the schedule K-G/K-J x100%, where is K-shaft diameter, G-size of destruction, J-bone marrow diameter above or below the metastases. We asses the extremity function by the ability to elevate and abduct it straight.
Results. We found that fracture occurs if the ICBI is lower than 46% and 40% in upper and lower extremity, respectively. 7 (5,7%) patients develop fracture despite higher ICBI. If the metastases are located in upper part of the femur and humerus and he/she can not elevate or abduct the extremity the fracture inevitably occurs.
Conclusions. Counting the ICBI and simple functional assessment allows to predict fracture in 94,3% of patients with long bone metastases.