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Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer., (© 2015 Forsberg et al.; Published by Cold Spring Harbor Laboratory Press.)

Objective: The evaluation of efficacy of palliative thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer (NSCLC) and to compare it with efficacy of supportive care (SC) alone., Materials and Methods: Between 2000 and 2012, 235 patients with advanced NSCLC (IIIB and IV) and Karnofsky Performance Status accounted 40-30, were qualified to PTR. In fact, 125 (53.2%) out of them were treated with PTR, and 110 (46.8%)-with SC alone, in accordance with patients expectations. There were no differences between PTR and SC group with respect to patient and tumor characteristics as well as with respect to the type and incidence of symptoms related to the local growth of NSCLC. In all 125 PTR patients the delivered tumor dose was 20Gy given in five daily fractions over five treatment days. All 110 patients who refused PTR were treated with SC in another hospital (28.2%), in a hospice (21.8%) or by general practitioners at home (50.0%)., Results: The 90-day overall survival rate in the group of PTR patients was 20.0%, and in the group of SC patients it was 18.2%. Median survival amounted 58 and 59 days, respectively. The efficacy of PTR and SC, relative to the symptoms associated with the local growth of NSCLC, was comparable. Tolerance of PTR was poor and early toxicity-significant. Moreover 41.6% of irradiated patients received PTR within the last 30 days of their lives and 16.0% of these patients-within the last 15 days prior to death., Conclusion: The life expectancy of patients with advanced NSCLC and poor performance status (Karnofsky 40-30), who presenting moderate or severe symptoms related to the local growth of cancer, is measured in days or weeks. The effective method of treatment for these patients is modern supportive care rather than PTR., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institution's experience with MPTB. We discuss controversial therapeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean age was 50 years (21-76), and the mean size of the tumor was 6 cm. Thirty-four (48.6%) patients were treated with total mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1 cm. Remaining 6 (8.6%) patients treated with BCS margins were <1 cm and subsequently radiotherapy was performed. Among 70 patients, 58 (82.9%) had no evidence of disease (NED) after 5 years. The extent of surgery was not significantly related to the 5-year NED survival rates (82.4% in patients who underwent mastectomy and 83.3% in patients who underwent BCS only or BCS with adjuvant irradiation). The 5-year NED survival rates in BCS (tumor-free margin ≥1 cm) and BCS with irradiation (tumor-free margin <1 cm) groups were identical (83.3%). Our data support the potential use of BCS in patients with MPTB. Mastectomy is indicated only if tumor-free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor-free margins are <1 cm., (© 2014 Wiley Periodicals, Inc.)

Background: Data from the literature suggests that the clinical picture of phyllodes tumor (PT) of the breast, as well as treatment options and perhaps therapy outcomes, have significantly changed. The aim of this work was to review these changes by analysis of consecutive patients with PT over a 55-year period at a single institution., Material and Methods: From 1952 to 2007, 280 women with PT were treated surgically at the Maria Skłodowska-Curie Memorial Institute of Oncology, Cancer Center in Cracow. Age, size of breast tumor, microscopic type, extent of surgery, and therapy outcomes were compared between 2 groups: 190 patients treated from 1952 to 1991 vs 90 patients treated from 1992 to 2007., Results: The results show that the 1992-2007 group compared to the 1952-1991 included more patients <50 years of age, with tumor <5 cm in diameter, undergoing breast-conserving therapy, as well as no evidence of disease at 5-year survival had increased and this change was statistically significant. In addition, malignant PT cases had decreased in frequency., Conclusions: The results of this study show that patients with PT are increasingly younger, the breast tumors at diagnosis are smaller, malignant PT is becoming less frequent, and BCT is now the treatment of choice. Most importantly, the general treatment outcomes are significantly better.

Background and Purpose: The aim of this study was to assess the potential prognostic factors in patients with primary invasive vaginal carcinoma (PIVC) treated with radical irradiation., Patients and Methods: The analysis was performed on 77 patients with PIVC treated between 1985 and 2005 in the Maria Skłodowska-Curie Memorial Institute of Oncology, Cancer Center in Krakow. A total of 36 patients (46.8 %) survived 5 years with no evidence of disease (NED). The following groups of factors were assessed for potential prognostic value: population-based (age), clinical (Karnofsky Performance Score [KPS], hemoglobin level, primary location of the vaginal lesion, macroscopic type, length of the involved vaginal wall, FIGO stage), microscopic (microscopic type, grade, mitotic index, presence of atypical mitoses, lymphatic vessels invasion, lymphocytes/plasmocytes infiltration, focal necrosis, VAIN-3), immunohistochemical (protein p53 expression, MIB-1 index), cytofluorometric (ploidity, index DI, S-phase fraction, proliferation index SG2M) factors., Results: Significantly better 5-year NED was observed in patients: < 60 years, KPS ≥ 80, FIGO stage I and II, grade G1-2, MIB-1 index  < 70, S-phase fraction < 10, and proliferation index < 25. Independent factors for better prognosis in the multivariate Cox analysis were age < 60 years, FIGO stage I or II, and MIB-1 index < 70., Conclusion: Independent prognostic factors in the radically irradiated PIVC patients were as follows: age, FIGO stage, MIB-1 index.

Objectives: The aim of the study was to estimate acute and late complications of radiation therapy in primary invasive vaginal carcinoma (PIVC) patients., Material and Methods: The analysis was performed for the group of 152 PIVC patients given radical radiotherapy in the Krakow Branch of Centre of Oncology during the 1967-2005 period. Twenty five (16.5%) patients in I stage with primary tumour of the thickness not larger than 0.5 cm were treated with intracavitary brachytherapy alone, for 120 (78.9%) patients (stages I-IVA) intracavitary brachytherapy was combined with external radiation therapy; and 7 (4.6%) patients in stage IVA were given only external radiotherapy In total, 145 (95.4%) patients were treated with intracavitary LDR brachyterapy by means of Ra-226 or afterloaded Cs-137 sources, and 127 (83.5%) received external radiation therapy using Co-60 and linac 10MV or 6MV photon beams., Results: Early radiotherapy tolerance was good in the investigated group; 146 (96.1%) patients completed full planned radiation therapy treatment. Late complications of radiation therapy were observed in 21 (13.8%) patients: 3 (2%) patients reported mild complications, 12 (7.9%) moderate complications, and 6 (3.9%) severe complications. Severe complications of radiation therapy in the investigated group included: recto-vaginal fistula (5 patients) and vesico-vaginal fistula (1 patient). None of the patients in the group died of radiation therapy complications., Conclusions: Early tolerance of radiotherapy in PIVC patients is generally good. Late radiation therapy complications, particularly the severe, are rare and can be efficiently managed with conservative therapy or surgical treatment.

Objective: The aim of this study was to present the clinical picture of infiltrating lobular carcinoma (ILC) of the breast., Materials and Methods: A detailed analysis was performed for the group of 96 ILC patients subject to initial surgical treatment in the Krakow Branch of Centre of Oncology between 1983 and 1996. The investigated group was selected out of 2,347 breast cancer patients treated during that period, based on re-examination of histologic specimens of the initial patient group., Results: The following distinctive demographic and clinical features of ILC were found: average age of patients: 59 years (37 - 83); average duration of pathological symptoms: five months; most frequent site of primary tumor: upper outer quadrant (54.2%); primary tumor Stage: I/II0 (64.6%), III0A (35.4%); tumor size in breast: up to five cm (69.8%), larger than five cm (30.2%); no axillary lymph nodes involvement in 51% of patients; multifocality of lesions in 10% of patients; contralateral disease occurrence in eight percent of patients; atypical pattern of distant metastases, e.g. gastrointestinal system, gynaecologic organs, and cerebral meninges., Conclusions: Based on this analysis as well as on literature reports, it was found that the fundamental differences between ILC and infiltrating ductal carcinoma (IDC) included demographic and clinical features as patient age, primary tumor size at diagnosis, incidence of multifocality and contralateral disease, sites of distant metastases, and histopathological status of axillary lymph nodes.

The aim of the study was to present microscopic, cytometric and immunohistochemical characteristics of a group of 96 invasive lobular carcinomas (ILC) of the breast. Ninety six patients treated surgically at the Department of Surgical Oncology, Centre of Oncology - Maria Skłodowska-Curie Memorial Institute, Cracow Branch, between 1983 and 1996, were included into the study. In 56 (58.3%) cases, a classical pattern of ILC was diagnosed, whereas atypical variants (solid, pleomorphic, pleomorphic with signet ring cells, signet ring cell, and tubulolobular) were recognized in 40 (41.7%) cases. ILC was characterized by lack of E-cadherin expression, high rate of steroid receptor expression, low rate of P53 and c-erb-B2 expressing tumours, low MIB-1 labelling index, and low S phase fraction, as well as high rate of diploid lesions.

Aims: The aim of this study was to present the characteristics, methods of treatment, and the survival of patients with hematogenous metastases from endometrial carcinoma, free from local and other distant recurrences., Patients and Methods: In 1,610 endometrial carcinoma patients managed with surgery and postoperative radiotherapy, we defined hematogenous metastases as a tumor spread to the lung or other sites via hematogenous routes., Results: A total of 110 patients with stage I and II endometrial carcinoma, presenting with 134 metastases sites (69 in the lungs, 32 in the liver, 23 in the bones, and 10 in the brain), were observed. Progestin and combination chemotherapy were the most commonly used therapies. Primary treatment consisted of surgery in patients with solitary metastases to the lung (30 patients), liver (2 patients), and brain (2 patients). Radiotherapy was performed in 32 patients with metastases to the brain and bones. Presenting with a 36-month survival rate were 11.6% (8/69) of patients with metastases to the lungs, 6.3% (2/32) of patients with metastases to the liver, 8.7% (2/23) of patients with metastases to the bones, and 20.0% (2/10) of patients with metastases to the brain., Conclusions: Hormonal therapy and chemotherapy play a major role in the palliative management of patients with hematogenous metastases from endometrial carcinoma to the liver, lungs, and bones. Radical treatment in patients with metastases to the lung or liver consists of resection of the metastasis combined with chemo- and/or hormonotherapy for metastases to the bones treatment consists of radiotherapy + chemotherapy, for metastasis to the brain treatment consists of resection combined with radiotherapy.

Background: The incidence of testicular tumors in Poland accounts for 2.4 new cases per 100.000 men a year. When investigating the incidence with regard to age, we may notice three age ranges with the highest incidence rate: babyhood, 25-40 years of age, and age of about 60 years. A routine examination in patients with testicular cancer after the first course of chemotherapy is computed tomography of the retroperitoneal space which aims to exclude the presence of residual masses and to assess the effectiveness of the treatment., Aim of the Study: The assessment of the effectiveness of computed tomography in the intraoperative investigation of patients with nonseminoma testicular tumors after chemotherapy., Material/method: This detailed retrospective analysis included 182 men with nonseminoma testicular tumor treated at the Center of Oncology in Cracow, between the yeas 1990-1999. Men with tumors in stage from IA to IIC made up 79.68% of the patients. Twenty patients after chemotherapy, with residual masses in the retroperitoneal cavity revealed in computed tomography, underwent retroperitoneal lymphadenectomy. The investigation was carried out with GE CT spiral scanner before and after intravenous contrast administration., Conclusions: Computed tomography is a method of a satisfactory sensitivity in the assessment of residual masses in the retroperitoneal cavity in postchemotherapy patients, as concerns the location of the tumor, its size, number of foci, and the fact whether it can be operated on or not. Together with tumor markers, it allows for a precise qualification to retroperitoneal lymphadenectomy of residual masses in postchemotherapy patients.

Purpose: To present our experience with short-time, split-course palliative thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer (NSCLC) with special regard to palliation of symptoms, tolerance and toxicity of PTR treatment., Patients and Methods: Between 1980 and 2005, a group of 1250 patients with locally advanced or metastatic NSCLC was treated with PTR in our Center. All patients presented with moderate or severe symptoms related to local cancer growth., Results: The response rate defined as palliation of NSCLC symptoms after PTR was 54.1% for cough, 68% for haemoptysis, 51.1% for thoracic pain, 38.3% for dyspnoea, 12% for hoarseness, and 8% for dysphagia. Tolerance of PTR, expressed in terms of patient compliance to the treatment, was good in 92% of patients (i.e., 2 series of radiotherapy were given at the planned dose and time). Early treatment toxicity was observed in 4.6% of patients and included pneumonitis in 2.3%, intense nausea and vomiting in 0.6%, lung hemorrhage in 0.6%, and severe oesophagitis in 0.5% of patients. Lhermitte's syndrome and broncho-oesophageal fistula were observed in 0.4% and 0.2%, respectively. Six out of 70 patients who survived longer than 2 years developed chronic pulmonary fibrosis with respiratory insufficiency and one patient presented symptoms of radiation-induced myelopathy., Conclusions: The analysis of our results and data from the literature show that short-time, split-course PTR is a safe and effective method of palliative treatment in patients with advanced NSCLC., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Recent data suggest a link between chronic inflammation, angiogenesis, and the development of cancer. The aim of this study was the evaluation of serum IL-6 and VEGF in comparison with the tumor markers NSE and ProGRP, with respect to the prognosis of small cell lung cancer patients. The study of IL-6, VEGF, NSE, ProGRP and platelet count was performed in a group of 72 patients with previously untreated small cell lung cancer at different stages of disease: 40 with limited and 32 with extensive disease. Significantly higher IL-6 and VEGF concentrations and platelet count, as well as NSE and ProGRP levels, were found in patients with small cell lung cancer in comparison with the reference group. Patients with extensive cancer had significantly higher levels of IL-6, VEGF, NSE and ProGRP than those with limited cancer. Elevated VEGF levels, with no significant differences in frequency of elevated NSE and ProGRP concentrations, were often observed in patients with IL-6 levels higher than 5.1 ng/l. Univariate analysis confirmed a significant relationship not only between overall survival and stage of disease or gender, but also with VEGF, IL-6, NSE and ProGRP levels. Moreover, multivariate analysis revealed that only the extent of the disease and IL-6 may be independent prognostic factors in the group of small cell lung cancer patients under investigation. However, simultaneous determinations of ProGRP and IL-6, as well as ProGRP and VEGF, in addition to the extent of the disease, may serve as additional, independent prognostic factors in small cell lung cancer.

Background: The aim of this study was to assess the utility of ProGRP determinations in patients with selected cancer localization, during and after therapy., Materials and Methods: The study involved a reference group and a population of lung, breast, ovarian, and prostate cancer patients. ProGRP was evaluated using two-step chemiluminescent microparticle immunoassay (CMIA) manufactured by Abbott Diagnostics, and Architect i2000 analyzer., Results: During follow-up of SCLC patients, an increased value for ProGRP was found in 51% and for NSE only in 25.5% of the patients, whereas in NSCLC patients, percentages with elevated ProGRP and CYFRA 21-1 were 8.6% and 55.7%, respectively. SCLC patients also had the highest AUC values for ProGRP. In other cancers, the frequency of elevated ProGRP results were as follows: 13.1%--in breast cancer patients, 19.6%--in ovarian cancer patients, and 15.1%--in prostate cancer patients., Conclusions: The presented study revealed that ProGRP is a tumor marker of choice in SCLC, because of its high diagnostic specificity in relation to the reference group and to the group with other malignancies.

Purpose: The prognosis for stage III melanoma patients is mixed, and there is need for new prognostic factors to be incorporated into a revision of melanoma TNM staging. We analyzed the possible role of the timing of lymph node involvement as an important prognostic factor., Methods: Among 249 melanoma patients who underwent ilioinguinal lymphadenectomy, a group of 185 patients with a thick (>4mm) melanoma and full clinical data available was analyzed. The mean depth of invasion was 5.85 mm; the tumor was ulcerated in 67 cases (36.2%); and Clark V was diagnosed in 82 patients (44.3%). The median interval between primary excision and the time of lymphadenectomy was 11.1 months., Results: Recurrent disease was reported in 150 of 185 patients. The first sites of recurrence were the skin in 15.7%, lymph nodes in 13.5%, and distant metastases in 28.7%; the remaining 43 patients (23.2%) had multifocal recurrences. In all, 35 patients (18.9%) were disease-free. Skip metastases (positive iliac and negative inguinal lymph nodes) were found in 26 patients (14%). Multivariate Cox analysis showed that only the time between the first surgery and lymphadenectomy and the number of involved nodes were significant predictors of survival. Relative risk of death was 5.2 times higher for patients who had simultaneously undergone lymphadenectomy (compared to lymph dissection performed >1 year after primary excision) and about 2.7 times higher for those with more regionally advanced disease (pN3 vs. pN1)., Conclusions: The long disease-free interval before the development of lymph node metastases and before node dissection is a favorable prognostic factor independent of other well known parameters.

Clinical observations indicate that the utility of classical prognostic factors in the assessment of probability of disease free or overall survival of lung cancer patients is not completely satisfactory. This is the cause for search of indices which results would contribute to optimization of this estimation. Of potential value in this aspect may also be the results of laboratory determinations which characterize patient's performance status. Dependencies between the times of overall survival in respect to chosen hematological and biochemical factors from the pretreatment period were analyzed in a group of 233 patients with lung cancer (adenocarcinoma - 44, squamous cell lung cancer - 156, small cell lung cancer - 33 patients) in different stages of disease. Apart from stage of disease and histological type of tumor, independent prognostic factors turned out to be the actual ideal body mass ratio and the number of leucocytes. In patients with less advanced stages of disease, such independent factors, apart from histological type are alpha-1 globulin and gamma globulin.

Giant cell tumour of soft part is a very rare neoplasm. The majority of these tumours are located superficially (in subcutaneous tissue) and occur in the proximal parts of the extremities. The deep-situated giant cell tumours of the neck are extremely rare. That is why we report a case of primary giant cell tumour of soft part localized in the trapezius muscle of a 19-year-old woman. We present both cytological and histological picture of the neoplasm. The cytological image of the smear is so representative that the proper diagnosis can be settled basing on the fine-needle aspiration cytology.

Between 1992 and 1999 at the Oncology Centre in Cracow 138 NSCLC patients after complete resection of the tumour with mediastinal/hilar node involvement were included in the prospective clinical trial. The analysis of the results did not show any improvement of survival in the postoperatively irradiated group. Three-year survival rates with no symptoms of disease in postoperative radiotherapy patients compared to surgery alone group were 30% and 29% respectively. In this study adjuvant radiotherapy significantly improved local recurrence rate from 28% in surgery only group to 9% in postoperatively treated patients.

In a retrospective analysis of 150 incompletely resected NSCLC patients treated with adjuvant external beam radiotherapy 32 (21.3%) survived 3 years with no symptoms of disease. Ipsilateral mediastinal/hilar lymph node involvement and macroscopic incomplete surgery were the prognostic factors that unfavourably influenced survival in Cox's proportional hazards model. Postoperative external beam radiotherapy was the efficient adjuvant treatment method in microscopically incompletely resected NSCLC, predominantly with no nodes involvement, but had no benefit in those with macroscopic incomplete surgery.

The role of teleradiotherapy in the treatment of patients with thyroid cancer is presented. The indications for external irradiation include patients with: primary inoperable disease or inoperable recurrence, microscopic or gross residual disease after surgery, high risk of local regional failure, and metastatic thyroid cancer, especially with skeletal, brain and mediastinal metastases.

Due to the low incidence of breast cancer in males there are not many reports in the literature. In this study we analyzed results of treatment in 65 breast cancer males, who had been treated in one institution. Radical surgery was performed in 45 patients. Lymph node metastases were found in 25 patients (55.5%), the tumor was usually moderately differentiated (21 pts - 46.7%). Median survival after radical surgery was 73 months compared to 38 months for nonsurgical patients (p < 0.0001). In the group of males after radical surgery the results of 5-, 10- and 15-year survival rates were 69.8, 59.7 and 31.3% respectively. Comparable analysis of two subgroups of patients with favorable (T1 or T2, N0, grade I or II) and unfavorable (T3 or N+ or grade III) prognostic factors was also performed. In the first subgroup the 5-, 10- and 15-year survival rates were 90, 77.4 and 62%, compared to 61.8, 23.1 and 23. 1% for the second subgroup. The multivariate analysis showed grading and node status as the strongest parameters influencing survival. Relative risk of death was over 3 times higher for nodal metastases and near 3 times higher for high grade carcinomas (p < 0.01), compared to patients without metastases and low grade of tumor. Similar analysis was performed when 45 males were compared to 500 selected women, with similar clinical parameters (age, node status, grading). Again, data indicated grading and lymph node status as the strongest prognostic factors. It was not unlikely, that gender had some influence on prognosis, when relative risk of death for males was over 1.5 times higher than for females, but this result was not clearly significant (p < 0.1 ). The question, whether male breast cancer prognosis is worse then in female remains open. Multiinstitutional prospective studies are needed in this area.

A retrospective analysis of 7 patients with adenoid cystic carcinoma of the breast operated at Center of Oncology in Kraków is presented. Ten years without evidence of disease survived 6 (85.7%) patients. One patient only, with poorly differentiated carcinoma, presented axillary metastases and died of metastases to the lungs and hepar.

An analysis of 80 patients with infiltrating lobular carcinoma of the breast treated at Center of Oncology in Kraków is presented. All patients underwent radical mastectomy. The evaluation of treatment results showed stage, pathological tumor size, and involvement of axillary nodes as the prognostic factors. The ten-year survival rate NED in all group was 38.8%; for stage I, II, and III it was 62.5%, 48.8%, and 19.4% respectively.

We analysed 170 women with carcinoma of the breast who survived 20 years after local or loco-regional therapy, without adjuvant chemo-hormonotherapy. Patients with axillary lymph nodes metastases constitute thirty-six percent of this group.