Wojciech Michalski - Academia.edu (original) (raw)
Papers by Wojciech Michalski
Journal of Clinical Oncology
e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be corre... more e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be correlated with the prognosis of patients with breast cancer (BC). However, the results still remain controversial. The goal of our study was to evaluate the predictive and prognostic value of NLR in early stage triple negative and HER2-pos breast cancer patients undergoing NAC. Methods: 96 female patients (pts) with histologically proven breast cancer (51 TNBC, and 45 HER2 pos) were analysed in this retrospective analysis. The NLR before the initiation of NAC was documented. Histopathological response in surgically removed specimens was evaluated using the Residual Cancer Burden (RCB) Calculator (by MD Anderson Cancer Center). The pCR was defined as no invasive tumor in primary tumor bed and lymph nodes. The NLR variable was analyzed as both continuous and categorical. The impact on pCR and RCB was tested using Mann-Whitney, Kruskal-Willis or the Chi-2 test, respectively. Results: Only 4 cat...
British Journal of Haematology
R-CVP (cyclophosphamide, vincristine, prednisone) and R-CHOP (cyclophosphamide, doxorubicin, vinc... more R-CVP (cyclophosphamide, vincristine, prednisone) and R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission induction of indolent non-Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression-free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R-CVP to R-CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R-CVP or R-CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m 2 q 2 months for 12 cycles. Primary endpoint was event-free survival (EFS). Two-hundred and fifty patients [FL 42%, MZL/MALT 38%, LPL/ Waldenstr€ om Macroglobulinaemia (WM) 11%, SLL 9%] were enrolled and randomized (R-CHOP: 127, R-CVP: 123). Median age was 56 years (21-85), 44% were male, 90% were in stage III-IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33Á4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43Á6/50Á9% and 36Á3/60Á8% in the R-CHOP and R-CVP groups (P = 0Á218) respectively. After a median follow-up of 67, 66, and 70 months, five-year EFS was 61% vs. 56% (not significant), progression-free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R-CHOP vs. the R-CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33Á1%) and 18 (15Á3%) patients, P = 0Á001; neutropenia in 16 (11Á6%) and 4 (3Á4%) patients, P = 0Á017; infection in 14 (10Á7%) and 3 (2Á5%) patients,; P = 0Á011; and a second neoplasm in three versus seven patients., in the R-CHOP and the R-CVP groups respectively. This multicentre randomized study with >five-year follow-up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R-CVP or R-CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R-CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second-line therapy.
The Lancet Gastroenterology & Hepatology
Journal of Clinical Oncology
777 Background: Radiotherapy is used in the neoadjuvant setting in majority of rectal cancer pati... more 777 Background: Radiotherapy is used in the neoadjuvant setting in majority of rectal cancer patients, while its effect on overall survival is limited mostly to patients with threatened resection margin. Preoperative pelvic irradiation might damage bone marrow. In consequence, relative dose intensity (RDI) and efficacy of further adjuvant or palliative CT might be reduced. The aim of the study was to assess whether radiation damage to the pelvic bone marrow influences the tolerance of further oxaliplatin-based CT. Methods: We have performed the cohort analysis of patients with adenocarcinoma of rectum or colon receiving FOLFOX-4 chemotherapy in adjuvant or palliative setting between 2011-2016. Oxaliplatin relative-dose intensity (RDI) within 8 weeks from the beginning of CT was calculated for each patient. The major factors, which can reduce oxaliplatin RDI, were analyzed independently (hemathological toxicity, neurological toxicity, occurrence of hypersensitivity reactions to oxali...
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, Jan 25, 2018
The aim of the study was to analyze long term results and prognostic factors in women with preinv... more The aim of the study was to analyze long term results and prognostic factors in women with preinvasive breast cancer (DCIS - ductal carcinoma in situ) who underwent breast conserving surgery with subsequent radiotherapy. A total number of 106 patients was analyzed aged 29-78 years; mean age was 54,3 years and median 55 years. In 78 (73,5%) patients the tumor was diagnosed incidentally on mammography or ultrasound scan, 28 (26,5%) had palpable lesion. 57 patients had the tumor in the left breast and 49 in the right one. Most often the tumor was localized in external quadrants, namely in 56 (52,8%) patients. All patients had breast conserving surgery and then adjuvant radiotherapy of the breast in typical doses. For evaluation of survival we used the Kaplan-Meier test and for evaluation of cumulated loco-regional recurrence we have applied the method of competing risks. At present 101 patients are still alive, 85 have no relapse. 15 patients had local recurrence and 8 had another canc...
Endocrine Practice, 2016
The purpose was to determine the growth rate of succinate dehydrogenase subunit (SDHx) gene-relat... more The purpose was to determine the growth rate of succinate dehydrogenase subunit (SDHx) gene-related paragangliomas based on computed tomography (CT) measurements. Twenty-seven patients with SDHx mutations who underwent subsequent CT examinations were enrolled in the study. Tumors were classified as head and neck (HNP), thoracic, or abdominal/pelvic paragangliomas (PGLs). The percentage volume increase and volume doubling time were estimated. We analyzed 56 PGLs (21 with SDHD, 6 with SDHB mutations) in 27 patients (16 men, 11 women; mean age 37.7 years). The estimated median of the follow-up was 23 months. Twenty-two (39.3%) PGLs were located in the abdomen, 8 (14.3%) in the thorax, and 26 (46.4%) in the head and neck region. The median volume growth rate was estimated at 10.4% per year (interquartile range [IQR]: -1.3; 36.3). The volume doubling time was estimated as 7.01 (2.24;+∞) years. By tumor site, the estimated medians of the annual volume growth rates were 13.6% (IQR:0.8 -30.4) for HNP, -6.06% (IQR: -1.79;47.32) for thoracic PGLs, and 10.5% (IQR: -2.2;44.6) for abdominal PGLs. The volume doubling time was 5.44 years (2.61; 87.0) for HNP, 11.8 years (1.79;+∞) for thoracic PGLs, and 6.94 years (1,88;+∞) for abdominal PGLs. There was no significant difference in the volume growth rate according to tumor location or initial size (P>.7 and P = .07, respectively) or gene mutation type (SDHB vs. SDHD, P>.8). PGLs related to SDHx mutations are slowly growing tumors. There were no correlations between tumor location, growth rate or initial size over a 23-month follow-up period. CT = computed tomography HNP = head and neck paraganglioma IQR = interquartile range PGL = paraganglioma PPGL = pheochromocytoma and paraganglioma SDH = succinate dehydrogenase.
Polish Journal of Cardio-Thoracic Surgery, 2016
Introduction: Paragangliomas (PGLs) related to hereditary syndromes are rare mediastinal tumors. ... more Introduction: Paragangliomas (PGLs) related to hereditary syndromes are rare mediastinal tumors. Paragangliomas are caused by mutations in genes encoding subunits of succinate dehydrogenase enzyme (SDH). Aim: To evaluate clinical, anatomical and functional characteristics of mediastinal paragangliomas related to SDHx gene mutations. Material and methods: Retrospective analysis of 75 patients with confirmed SDHx gene mutations (24 patients with SDHB, 5 SDHC, 46 with SDHD mutations) was performed. Patients underwent evaluation using computed tomography (CT), somatostatin receptor scintigraphy (SRS) (99m Tc-[HYNIC,Tyr3]-octreotide), 123 I mIBG scintigraphy and urinary excretion of total methoxycatecholamines. Results: Out of 75 patients, 16 (21%) patients (1 SDHB, 15 SDHD mutations) had 17 PGLs localized in the mediastinum. Fourteen PGLs were localized in the middle mediastinum (intrapericardial) and 3 PGLs in the posterior mediastinum. The median diameter of paragangliomas measured on the axial slice was 24.3 mm (interquartile range (IQR): 14.7-36.6), and the median volume was 2.78 ml (IQR: 0.87-16.16). Twelve out of 16 patients (75%) underwent SRS, and 11 of them (92.3%) had pathological uptake of the radiotracer. Eleven (68.75%) out of 16 patients underwent 123 I mIBG, with only 3 positive results. Symptoms of catecholamine excretion were observed in 3 patients with PGLs localized in the posterior mediastinum. All PGLs were benign except in 1 patient with the SDHB mutation and PGL detected in the posterior mediastinum, who had a metastatic disease.
Radiotherapy and Oncology, 2016
To evaluate if neurological/cognitive function outcomes in patients with resected single brain me... more To evaluate if neurological/cognitive function outcomes in patients with resected single brain metastasis (BM) after stereotactic radiotherapy of the tumor bed (SRT-TB) are not inferior compared to those achieved with whole-brain radiotherapy (WBRT). Patients with total/subtotal resection of single BM were randomly assigned either to SRT-TB (n=29) or WBRT (n=30). SRT-TB arm consisted of 15Gy/1 fraction, or 5×5Gy. WBRT consisted of 30Gy/10 fractions. Neurological/cognitive failure was defined as a decrease of neurological score by one point or more, or a worsening of the MiniMental test by at least 3 points, or neurological death. Cumulative incidence of neurological/cognitive failure (CINCF), neurological death (CIND), and overall survival (OS) were compared. Median follow-up was 29months (range: 8-45) for 15 patients still alive. The difference in the probability of CINCF at 6months (primary endpoint) was -8% in favor of WBRT (95% confidence interval: +17% -35%; non-inferiority margin: -20%). In the intention-to-treat analysis, two-year CIND rates were 66% vs. 31%, for SRT-TB and WBRT arm, respectively, p=.015. The corresponding figures for OS were 10% vs. 37%, p=.046. Non-inferiority of SRT-TB was not demonstrated in our underpowered study. More data from randomized studies are needed for confirmation of the value of this method.
Onkologia W Praktyce Klinicznej, 2011
Radiotherapy and Oncology, 2009
Background and purpose: To report an early analysis of prospective study exploring preoperative r... more Background and purpose: To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer. Materials and methods: Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5 Â 5 Gy + 4 Gy boost (N = 31) or chemoradiation (50.4 Gy + 5.4 Gy boost, 1.8 Gy per fraction + 5-fluorouracyl and leucovorin; N = 13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin. Results: The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure. Conclusion: Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.
Journal of Physiology and Biochemistry, 2003
The effect of exogenous thyroid hormones on blood insulin and metabolic parameters in diabetic ra... more The effect of exogenous thyroid hormones on blood insulin and metabolic parameters in diabetic rats was investigated. Three groups of rats were treated with streptozotocin (STZ; 50 mg/kg b.w., intravenously) and one group receiving only saline served as control. Beginning with the third day after STZ treatment, until the last day before decapitation, i.e. for 11 days, two groups of diabetic rats were treated with T3 (50 microg/kg b.w., i.p.) or T4 (250 microg/kg b.w., i.p.). After two weeks, STZ injected rats had lower body weight, hyperglycemia with a simultaneous drop in blood insulin and decrease of T3 and T4 concentrations in comparison to control animals. Liver glycogen content was also reduced, whereas serum lactate, free fatty acids, triglycerides and cholesterol were elevated. Exogenous thyroid hormones given to diabetic rats substantially attenuated hyperglycemia without any significant changes in blood insulin concentration. An additional reduction of body weight gain and depletion in liver glycogen stores were also observed. Thyroid hormones augmented serum lactate and cholesterol and had no beneficial effect on elevated free fatty acids and triglycerides. It can be concluded that in spite of partial restriction of hyperglycemia, thyroid hormones evoked several unfavourable changes strongly limiting their potential use in diabetes.
European journal of obstetrics, gynecology, and reproductive biology, Jan 22, 2015
To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepitheli... more To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepithelial neoplasia with a special focus on analysis of toxicity. Twenty consecutive patients were irradiated with brachytherapy of vaginal intraepithelial neoplasia with component ca in situ (N=3). Late complications of the vagina graded using the CTCAE v.3.0. General assessment three-step scale was introduced for simplicity of analysis. The median age was 57 years (range: 28-80 years). The median follow-up time was 39 months (range: 14-115 months). Vaginal intraepithelial neoplasia recurrence was observed in 1 patient. The 3-year disease free survival rate was 90% (95% confidence interval [CI]: 71-100%). Observed late side effects: libido grades 1-2 in 15 (75%), vaginal discharge grade 2 (pad use indicated) in 2 (10%), dryness grade 2 (dyspareunia) in 7 (35%), mucositis grades 2-3 in 6 (30%), stenosis grades 2-3 in 7 (35%) and vaginitis grades 2-3 in 4 (20%) cases. General assessment was good...
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2015
To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepitheli... more To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepithelial neoplasia with a special focus on analysis of toxicity. Twenty consecutive patients were irradiated with brachytherapy of vaginal intraepithelial neoplasia with component ca in situ (N=3). Late complications of the vagina graded using the CTCAE v.3.0. General assessment three-step scale was introduced for simplicity of analysis. The median age was 57 years (range: 28-80 years). The median follow-up time was 39 months (range: 14-115 months). Vaginal intraepithelial neoplasia recurrence was observed in 1 patient. The 3-year disease free survival rate was 90% (95% confidence interval [CI]: 71-100%). Observed late side effects: libido grades 1-2 in 15 (75%), vaginal discharge grade 2 (pad use indicated) in 2 (10%), dryness grade 2 (dyspareunia) in 7 (35%), mucositis grades 2-3 in 6 (30%), stenosis grades 2-3 in 7 (35%) and vaginitis grades 2-3 in 4 (20%) cases. General assessment was good in 9 (45%), average in 2 (10%), and bad in 9 (45%) patients. Treatment dose affected the toxicity (p=0.05). In groups of patients irradiated with biologically equivalent dose (assuming α/β=3Gy) of 47.3-63Gy and ≥70Gy, the risk of poor or moderate toxicity amounted to 16.7% (95% CI: 0-47%) and 71.4% (95% CI: 48-95%), respectively. Brachytherapy revealed to be effective method of vaginal intraepithelial neoplasia treatment, but applying EQD2≥70Gy into vagina generates unacceptable toxicity.
International Journal of Radiation Oncology*Biology*Physics, 2016
To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachy... more To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography-CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2.
Nowotwory. Journal of Oncology, 2016
Nowotwory. Journal of Oncology, 2014
International Journal of Radiation Oncology*Biology*Physics, 2016
To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachy... more To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography-CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2.
Polish Journal of Pathology, 2014
The main purpose of the study was to compare topoisomerase 2α (TOP2A) status in invasive breast c... more The main purpose of the study was to compare topoisomerase 2α (TOP2A) status in invasive breast carcinomas to the outcome of a therapy containing neoadjuvant treatment with anthracyclines (a combination chemotherapy treatment for breast cancer, namely AC [cyclophosphamide, doxorubicin]). To achieve these goals we created a method of evaluation with criteria based on two methods used in the present study (immunohistochemical [IHC] and fluorescence in situ hybridization [FISH]). The threshold for positive immunohistochemically evaluated status was set for all cases with: nuclear stain intensity score 3+ in 10% or more nuclei and nuclear stain intensity score 2+ in 50% or more nuclei. Our results suggest that TOP2A status may be used as a predictive factor for patient selection for protocols which include anthracyclines as one of the chemotherapeutics. Both methods, IHC and FISH, are suitable for implementation for diagnostic purposes, but IHC positive status measured according to the criteria presented above is the best predictor of longer disease-free survival (DFS) according to our study. Immunohistochemical also gave satisfactory results in all analyzed cases in comparison to only 60% of cases analyzed by FISH.
Nowotwory. Journal of Oncology, 2013
Cel. Celem pracy jest retrospektywna ocena potencjalnej redukcji ryzyka powikłań popromiennych ze... more Cel. Celem pracy jest retrospektywna ocena potencjalnej redukcji ryzyka powikłań popromiennych ze strony mięśnia sercowego w oparciu o badanie EKG u kobiet chorych na raka piersi po oszczędzającym leczeniu chirurgicznym, napromienianych konformalnie 3D, w porównaniu z grupą chorych napromienianych techniką 2D, jak również ocena wpływu wywieranego na serce przy napromienianiu zmian umiejscowionych w piersi lewej w porównaniu z napromienianiem zmian umiejscowionych w piersi prawej przy zastosowaniu nowoczesnych technik radioterapii. Materiał i metoda. W Zakładzie Radioterapii I Kliniki Onkologii Centrum Onkologii Instytutu w okresie od kwietnia 1985 r. do grudnia 2008 r. napromieniano 1211 chorych na raka piersi po oszczędzającym leczeniu chirurgicznym. Analizie poddano grupę 595 kobiet, które po zakończeniu leczenia zgłosiły się na badanie kontrolne i miały wykonane badanie EKG. Wiek chorych wahał się od 27 do 78 lat. U 327 nowotwór był umiejscowiony w piersi lewej, a u 268 -w piersi prawej. U wszystkich chorych zastosowano radioterapię na gruczoł piersiowy oraz dodatkowo na lożę po usuniętym guzie, zgodnie z protokołem obowiązującym w Centrum Onkologii. 382 chore napromieniano radykalnie 2D, a u 213 zastosowano radioterapię konformalną 3D. Wyniki. Zestawienie wyników EKG wykazało, że zmiany zapisu (zmiany niespecyfi czne lub niedokrwienne) wystąpiły u 32,7% leczonych z powodu raka piersi lewej i u 29,1% leczonych z powodu raka piersi prawej. Wśród chorych napromienianych radykalnie 2D zmiany zapisu EKG wystąpiły u 34,1%, gdy nowotwór był umiejscowiony po stronie lewej, w porównaniu z 29,9% przy umiejscowieniu po stronie prawej. W przypadku zastosowania radioterapii konformalnej 3D zmiany zapisu EKG zaobserwowano u 30,3% chorych na raka piersi po stronie lewej i u 27,5% -po stronie prawej. Nie stwierdzono statystycznie istotnych różnic w powikłaniach w sercu mierzonych badaniem EKG w zależności od strony umiejscowienia nowotworu i techniki napromieniania. Wnioski. Zmiana techniki napromieniania z radykalnej 2D na konformalną 3D nie powoduje zmniejszenia odsetka powikłań ze strony mięśnia serca na podstawie obrazu EKG. Nie stwierdza się również istotnych różnic w powikłaniach w zależności od strony umiejscowienia nowotworu.
Journal of Clinical Oncology
e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be corre... more e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be correlated with the prognosis of patients with breast cancer (BC). However, the results still remain controversial. The goal of our study was to evaluate the predictive and prognostic value of NLR in early stage triple negative and HER2-pos breast cancer patients undergoing NAC. Methods: 96 female patients (pts) with histologically proven breast cancer (51 TNBC, and 45 HER2 pos) were analysed in this retrospective analysis. The NLR before the initiation of NAC was documented. Histopathological response in surgically removed specimens was evaluated using the Residual Cancer Burden (RCB) Calculator (by MD Anderson Cancer Center). The pCR was defined as no invasive tumor in primary tumor bed and lymph nodes. The NLR variable was analyzed as both continuous and categorical. The impact on pCR and RCB was tested using Mann-Whitney, Kruskal-Willis or the Chi-2 test, respectively. Results: Only 4 cat...
British Journal of Haematology
R-CVP (cyclophosphamide, vincristine, prednisone) and R-CHOP (cyclophosphamide, doxorubicin, vinc... more R-CVP (cyclophosphamide, vincristine, prednisone) and R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission induction of indolent non-Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression-free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R-CVP to R-CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R-CVP or R-CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m 2 q 2 months for 12 cycles. Primary endpoint was event-free survival (EFS). Two-hundred and fifty patients [FL 42%, MZL/MALT 38%, LPL/ Waldenstr€ om Macroglobulinaemia (WM) 11%, SLL 9%] were enrolled and randomized (R-CHOP: 127, R-CVP: 123). Median age was 56 years (21-85), 44% were male, 90% were in stage III-IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33Á4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43Á6/50Á9% and 36Á3/60Á8% in the R-CHOP and R-CVP groups (P = 0Á218) respectively. After a median follow-up of 67, 66, and 70 months, five-year EFS was 61% vs. 56% (not significant), progression-free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R-CHOP vs. the R-CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33Á1%) and 18 (15Á3%) patients, P = 0Á001; neutropenia in 16 (11Á6%) and 4 (3Á4%) patients, P = 0Á017; infection in 14 (10Á7%) and 3 (2Á5%) patients,; P = 0Á011; and a second neoplasm in three versus seven patients., in the R-CHOP and the R-CVP groups respectively. This multicentre randomized study with >five-year follow-up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R-CVP or R-CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R-CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second-line therapy.
The Lancet Gastroenterology & Hepatology
Journal of Clinical Oncology
777 Background: Radiotherapy is used in the neoadjuvant setting in majority of rectal cancer pati... more 777 Background: Radiotherapy is used in the neoadjuvant setting in majority of rectal cancer patients, while its effect on overall survival is limited mostly to patients with threatened resection margin. Preoperative pelvic irradiation might damage bone marrow. In consequence, relative dose intensity (RDI) and efficacy of further adjuvant or palliative CT might be reduced. The aim of the study was to assess whether radiation damage to the pelvic bone marrow influences the tolerance of further oxaliplatin-based CT. Methods: We have performed the cohort analysis of patients with adenocarcinoma of rectum or colon receiving FOLFOX-4 chemotherapy in adjuvant or palliative setting between 2011-2016. Oxaliplatin relative-dose intensity (RDI) within 8 weeks from the beginning of CT was calculated for each patient. The major factors, which can reduce oxaliplatin RDI, were analyzed independently (hemathological toxicity, neurological toxicity, occurrence of hypersensitivity reactions to oxali...
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, Jan 25, 2018
The aim of the study was to analyze long term results and prognostic factors in women with preinv... more The aim of the study was to analyze long term results and prognostic factors in women with preinvasive breast cancer (DCIS - ductal carcinoma in situ) who underwent breast conserving surgery with subsequent radiotherapy. A total number of 106 patients was analyzed aged 29-78 years; mean age was 54,3 years and median 55 years. In 78 (73,5%) patients the tumor was diagnosed incidentally on mammography or ultrasound scan, 28 (26,5%) had palpable lesion. 57 patients had the tumor in the left breast and 49 in the right one. Most often the tumor was localized in external quadrants, namely in 56 (52,8%) patients. All patients had breast conserving surgery and then adjuvant radiotherapy of the breast in typical doses. For evaluation of survival we used the Kaplan-Meier test and for evaluation of cumulated loco-regional recurrence we have applied the method of competing risks. At present 101 patients are still alive, 85 have no relapse. 15 patients had local recurrence and 8 had another canc...
Endocrine Practice, 2016
The purpose was to determine the growth rate of succinate dehydrogenase subunit (SDHx) gene-relat... more The purpose was to determine the growth rate of succinate dehydrogenase subunit (SDHx) gene-related paragangliomas based on computed tomography (CT) measurements. Twenty-seven patients with SDHx mutations who underwent subsequent CT examinations were enrolled in the study. Tumors were classified as head and neck (HNP), thoracic, or abdominal/pelvic paragangliomas (PGLs). The percentage volume increase and volume doubling time were estimated. We analyzed 56 PGLs (21 with SDHD, 6 with SDHB mutations) in 27 patients (16 men, 11 women; mean age 37.7 years). The estimated median of the follow-up was 23 months. Twenty-two (39.3%) PGLs were located in the abdomen, 8 (14.3%) in the thorax, and 26 (46.4%) in the head and neck region. The median volume growth rate was estimated at 10.4% per year (interquartile range [IQR]: -1.3; 36.3). The volume doubling time was estimated as 7.01 (2.24;+∞) years. By tumor site, the estimated medians of the annual volume growth rates were 13.6% (IQR:0.8 -30.4) for HNP, -6.06% (IQR: -1.79;47.32) for thoracic PGLs, and 10.5% (IQR: -2.2;44.6) for abdominal PGLs. The volume doubling time was 5.44 years (2.61; 87.0) for HNP, 11.8 years (1.79;+∞) for thoracic PGLs, and 6.94 years (1,88;+∞) for abdominal PGLs. There was no significant difference in the volume growth rate according to tumor location or initial size (P&amp;amp;amp;gt;.7 and P = .07, respectively) or gene mutation type (SDHB vs. SDHD, P&amp;amp;amp;gt;.8). PGLs related to SDHx mutations are slowly growing tumors. There were no correlations between tumor location, growth rate or initial size over a 23-month follow-up period. CT = computed tomography HNP = head and neck paraganglioma IQR = interquartile range PGL = paraganglioma PPGL = pheochromocytoma and paraganglioma SDH = succinate dehydrogenase.
Polish Journal of Cardio-Thoracic Surgery, 2016
Introduction: Paragangliomas (PGLs) related to hereditary syndromes are rare mediastinal tumors. ... more Introduction: Paragangliomas (PGLs) related to hereditary syndromes are rare mediastinal tumors. Paragangliomas are caused by mutations in genes encoding subunits of succinate dehydrogenase enzyme (SDH). Aim: To evaluate clinical, anatomical and functional characteristics of mediastinal paragangliomas related to SDHx gene mutations. Material and methods: Retrospective analysis of 75 patients with confirmed SDHx gene mutations (24 patients with SDHB, 5 SDHC, 46 with SDHD mutations) was performed. Patients underwent evaluation using computed tomography (CT), somatostatin receptor scintigraphy (SRS) (99m Tc-[HYNIC,Tyr3]-octreotide), 123 I mIBG scintigraphy and urinary excretion of total methoxycatecholamines. Results: Out of 75 patients, 16 (21%) patients (1 SDHB, 15 SDHD mutations) had 17 PGLs localized in the mediastinum. Fourteen PGLs were localized in the middle mediastinum (intrapericardial) and 3 PGLs in the posterior mediastinum. The median diameter of paragangliomas measured on the axial slice was 24.3 mm (interquartile range (IQR): 14.7-36.6), and the median volume was 2.78 ml (IQR: 0.87-16.16). Twelve out of 16 patients (75%) underwent SRS, and 11 of them (92.3%) had pathological uptake of the radiotracer. Eleven (68.75%) out of 16 patients underwent 123 I mIBG, with only 3 positive results. Symptoms of catecholamine excretion were observed in 3 patients with PGLs localized in the posterior mediastinum. All PGLs were benign except in 1 patient with the SDHB mutation and PGL detected in the posterior mediastinum, who had a metastatic disease.
Radiotherapy and Oncology, 2016
To evaluate if neurological/cognitive function outcomes in patients with resected single brain me... more To evaluate if neurological/cognitive function outcomes in patients with resected single brain metastasis (BM) after stereotactic radiotherapy of the tumor bed (SRT-TB) are not inferior compared to those achieved with whole-brain radiotherapy (WBRT). Patients with total/subtotal resection of single BM were randomly assigned either to SRT-TB (n=29) or WBRT (n=30). SRT-TB arm consisted of 15Gy/1 fraction, or 5×5Gy. WBRT consisted of 30Gy/10 fractions. Neurological/cognitive failure was defined as a decrease of neurological score by one point or more, or a worsening of the MiniMental test by at least 3 points, or neurological death. Cumulative incidence of neurological/cognitive failure (CINCF), neurological death (CIND), and overall survival (OS) were compared. Median follow-up was 29months (range: 8-45) for 15 patients still alive. The difference in the probability of CINCF at 6months (primary endpoint) was -8% in favor of WBRT (95% confidence interval: +17% -35%; non-inferiority margin: -20%). In the intention-to-treat analysis, two-year CIND rates were 66% vs. 31%, for SRT-TB and WBRT arm, respectively, p=.015. The corresponding figures for OS were 10% vs. 37%, p=.046. Non-inferiority of SRT-TB was not demonstrated in our underpowered study. More data from randomized studies are needed for confirmation of the value of this method.
Onkologia W Praktyce Klinicznej, 2011
Radiotherapy and Oncology, 2009
Background and purpose: To report an early analysis of prospective study exploring preoperative r... more Background and purpose: To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer. Materials and methods: Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5 Â 5 Gy + 4 Gy boost (N = 31) or chemoradiation (50.4 Gy + 5.4 Gy boost, 1.8 Gy per fraction + 5-fluorouracyl and leucovorin; N = 13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin. Results: The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure. Conclusion: Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.
Journal of Physiology and Biochemistry, 2003
The effect of exogenous thyroid hormones on blood insulin and metabolic parameters in diabetic ra... more The effect of exogenous thyroid hormones on blood insulin and metabolic parameters in diabetic rats was investigated. Three groups of rats were treated with streptozotocin (STZ; 50 mg/kg b.w., intravenously) and one group receiving only saline served as control. Beginning with the third day after STZ treatment, until the last day before decapitation, i.e. for 11 days, two groups of diabetic rats were treated with T3 (50 microg/kg b.w., i.p.) or T4 (250 microg/kg b.w., i.p.). After two weeks, STZ injected rats had lower body weight, hyperglycemia with a simultaneous drop in blood insulin and decrease of T3 and T4 concentrations in comparison to control animals. Liver glycogen content was also reduced, whereas serum lactate, free fatty acids, triglycerides and cholesterol were elevated. Exogenous thyroid hormones given to diabetic rats substantially attenuated hyperglycemia without any significant changes in blood insulin concentration. An additional reduction of body weight gain and depletion in liver glycogen stores were also observed. Thyroid hormones augmented serum lactate and cholesterol and had no beneficial effect on elevated free fatty acids and triglycerides. It can be concluded that in spite of partial restriction of hyperglycemia, thyroid hormones evoked several unfavourable changes strongly limiting their potential use in diabetes.
European journal of obstetrics, gynecology, and reproductive biology, Jan 22, 2015
To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepitheli... more To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepithelial neoplasia with a special focus on analysis of toxicity. Twenty consecutive patients were irradiated with brachytherapy of vaginal intraepithelial neoplasia with component ca in situ (N=3). Late complications of the vagina graded using the CTCAE v.3.0. General assessment three-step scale was introduced for simplicity of analysis. The median age was 57 years (range: 28-80 years). The median follow-up time was 39 months (range: 14-115 months). Vaginal intraepithelial neoplasia recurrence was observed in 1 patient. The 3-year disease free survival rate was 90% (95% confidence interval [CI]: 71-100%). Observed late side effects: libido grades 1-2 in 15 (75%), vaginal discharge grade 2 (pad use indicated) in 2 (10%), dryness grade 2 (dyspareunia) in 7 (35%), mucositis grades 2-3 in 6 (30%), stenosis grades 2-3 in 7 (35%) and vaginitis grades 2-3 in 4 (20%) cases. General assessment was good...
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2015
To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepitheli... more To retrospectively evaluate the efficacy of high-dose-rate brachytherapy of vaginal intraepithelial neoplasia with a special focus on analysis of toxicity. Twenty consecutive patients were irradiated with brachytherapy of vaginal intraepithelial neoplasia with component ca in situ (N=3). Late complications of the vagina graded using the CTCAE v.3.0. General assessment three-step scale was introduced for simplicity of analysis. The median age was 57 years (range: 28-80 years). The median follow-up time was 39 months (range: 14-115 months). Vaginal intraepithelial neoplasia recurrence was observed in 1 patient. The 3-year disease free survival rate was 90% (95% confidence interval [CI]: 71-100%). Observed late side effects: libido grades 1-2 in 15 (75%), vaginal discharge grade 2 (pad use indicated) in 2 (10%), dryness grade 2 (dyspareunia) in 7 (35%), mucositis grades 2-3 in 6 (30%), stenosis grades 2-3 in 7 (35%) and vaginitis grades 2-3 in 4 (20%) cases. General assessment was good in 9 (45%), average in 2 (10%), and bad in 9 (45%) patients. Treatment dose affected the toxicity (p=0.05). In groups of patients irradiated with biologically equivalent dose (assuming α/β=3Gy) of 47.3-63Gy and ≥70Gy, the risk of poor or moderate toxicity amounted to 16.7% (95% CI: 0-47%) and 71.4% (95% CI: 48-95%), respectively. Brachytherapy revealed to be effective method of vaginal intraepithelial neoplasia treatment, but applying EQD2≥70Gy into vagina generates unacceptable toxicity.
International Journal of Radiation Oncology*Biology*Physics, 2016
To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachy... more To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography-CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2.
Nowotwory. Journal of Oncology, 2016
Nowotwory. Journal of Oncology, 2014
International Journal of Radiation Oncology*Biology*Physics, 2016
To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachy... more To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography-CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2.
Polish Journal of Pathology, 2014
The main purpose of the study was to compare topoisomerase 2α (TOP2A) status in invasive breast c... more The main purpose of the study was to compare topoisomerase 2α (TOP2A) status in invasive breast carcinomas to the outcome of a therapy containing neoadjuvant treatment with anthracyclines (a combination chemotherapy treatment for breast cancer, namely AC [cyclophosphamide, doxorubicin]). To achieve these goals we created a method of evaluation with criteria based on two methods used in the present study (immunohistochemical [IHC] and fluorescence in situ hybridization [FISH]). The threshold for positive immunohistochemically evaluated status was set for all cases with: nuclear stain intensity score 3+ in 10% or more nuclei and nuclear stain intensity score 2+ in 50% or more nuclei. Our results suggest that TOP2A status may be used as a predictive factor for patient selection for protocols which include anthracyclines as one of the chemotherapeutics. Both methods, IHC and FISH, are suitable for implementation for diagnostic purposes, but IHC positive status measured according to the criteria presented above is the best predictor of longer disease-free survival (DFS) according to our study. Immunohistochemical also gave satisfactory results in all analyzed cases in comparison to only 60% of cases analyzed by FISH.
Nowotwory. Journal of Oncology, 2013
Cel. Celem pracy jest retrospektywna ocena potencjalnej redukcji ryzyka powikłań popromiennych ze... more Cel. Celem pracy jest retrospektywna ocena potencjalnej redukcji ryzyka powikłań popromiennych ze strony mięśnia sercowego w oparciu o badanie EKG u kobiet chorych na raka piersi po oszczędzającym leczeniu chirurgicznym, napromienianych konformalnie 3D, w porównaniu z grupą chorych napromienianych techniką 2D, jak również ocena wpływu wywieranego na serce przy napromienianiu zmian umiejscowionych w piersi lewej w porównaniu z napromienianiem zmian umiejscowionych w piersi prawej przy zastosowaniu nowoczesnych technik radioterapii. Materiał i metoda. W Zakładzie Radioterapii I Kliniki Onkologii Centrum Onkologii Instytutu w okresie od kwietnia 1985 r. do grudnia 2008 r. napromieniano 1211 chorych na raka piersi po oszczędzającym leczeniu chirurgicznym. Analizie poddano grupę 595 kobiet, które po zakończeniu leczenia zgłosiły się na badanie kontrolne i miały wykonane badanie EKG. Wiek chorych wahał się od 27 do 78 lat. U 327 nowotwór był umiejscowiony w piersi lewej, a u 268 -w piersi prawej. U wszystkich chorych zastosowano radioterapię na gruczoł piersiowy oraz dodatkowo na lożę po usuniętym guzie, zgodnie z protokołem obowiązującym w Centrum Onkologii. 382 chore napromieniano radykalnie 2D, a u 213 zastosowano radioterapię konformalną 3D. Wyniki. Zestawienie wyników EKG wykazało, że zmiany zapisu (zmiany niespecyfi czne lub niedokrwienne) wystąpiły u 32,7% leczonych z powodu raka piersi lewej i u 29,1% leczonych z powodu raka piersi prawej. Wśród chorych napromienianych radykalnie 2D zmiany zapisu EKG wystąpiły u 34,1%, gdy nowotwór był umiejscowiony po stronie lewej, w porównaniu z 29,9% przy umiejscowieniu po stronie prawej. W przypadku zastosowania radioterapii konformalnej 3D zmiany zapisu EKG zaobserwowano u 30,3% chorych na raka piersi po stronie lewej i u 27,5% -po stronie prawej. Nie stwierdzono statystycznie istotnych różnic w powikłaniach w sercu mierzonych badaniem EKG w zależności od strony umiejscowienia nowotworu i techniki napromieniania. Wnioski. Zmiana techniki napromieniania z radykalnej 2D na konformalną 3D nie powoduje zmniejszenia odsetka powikłań ze strony mięśnia serca na podstawie obrazu EKG. Nie stwierdza się również istotnych różnic w powikłaniach w zależności od strony umiejscowienia nowotworu.