High tumour-infiltrating lymphocytes correlate with distinct gene expression profile and favourable survival in single hormone receptor-positive breast cancer.

Introduction: This study aimed to evaluate the impact of tumour-infiltrating lymphocytes (TILs) on the expression of immune-related genes and prognosis in single hormone receptor-positive breast cancer. Material and methods: Tumour-infiltrating lymphocytes were analysed according to the guidelines of the International TILs Working Group in a cohort of 206 patients with single hormone receptor-positive breast cancer. Of these, 44.7% were classified as ER+/PgR-/HER2-, 18.4% as ER+/PgR-/HER2+, 26.2% as ER-/PgR+/HER2-, and 10.7% as ER-/PgR+/HER2+. Moreover, in 52 samples the analysis of gene expression profiling was performed using nCounter technology. Results: Most cases (74.3%) showed at least 1% of stromal TILs, with a median of 4%, mean of 16.3%, and interquartile range of 0-20%. ER-/PgR+ tumours displayed significantly higher TILs density than ER+/PgR- cases (p < 0.001, Wilcoxon test), regardless of HER2 status. The abundance of TILs was positively associated with ER-/PgR+ phenotype, higher Ki-67, and higher grade, but not with age, tumour size, or regional and distant metastases at diagnosis. Additionally, in ER+/PgR- subgroup higher TILs were associated with HER2-positive status. Stromal TILs > 5% were associated with better survival in the whole group, but this effect was less prominent in ER-/PgR+ patients. We identified 50 differentially expressed genes (DEGs) between single hormone receptor-positive breast tumours with high and low TILs, including 39 up-regulated and 11 down-regulated genes in the high TILs group. Conclusions: The up-regulated expression of immune-related genes was consistent also among separately analysed single hormone receptor-positive groups (ER+/PgR- and ER-/PgR+).

Treatment With Adjuvant Abemaciclib Plus Endocrine Therapy in Patients With High-risk Early Breast Cancer Who Received Neoadjuvant Chemotherapy: A Prespecified Analysis of the monarchE Randomized Clinical Trial.

Importance: Patients selected to receive neoadjuvant chemotherapy (NAC) are usually those at higher risk of relapse, and there is a need to find better therapeutic options for these patients. Objective: To determine the efficacy and safety outcomes for patients with hormone receptor (HR)-positive, ERBB2 (formerly HER2)-, high-risk early breast cancer enrolled in the randomized clinical trial monarchE who received NAC. Design, Setting, and Participants: The monarchE randomized clinical trial was a multicenter, phase 3, open-label study that evaluated adjuvant treatment with abemaciclib plus endocrine therapy (ET) compared with ET alone in patients with HR+, ERBB2-, and node-positive early breast cancer who were at high risk of recurrence. Patients were recruited between July 2017 and August 2019 from 603 sites in 38 countries. This subgroup analysis was performed with primary outcome data, with a cutoff date of July 8, 2020. Intervention: Enrolled patients were randomized (1:1) to receive standard of care ET for at least 5 years with or without treatment with abemaciclib (150 mg, twice daily) for 2 years (treatment period) or until criteria were met for discontinuation. Main Outcomes and Measures: Prior chemotherapy (NAC vs adjuvant vs none) was a stratification factor in monarchE, and and a prespecified exploratory analysis included outcomes in patients who received NAC. The data presented in this article are from the primary outcome analysis (395 invasive disease-free survival [IDFS] events; cutoff date, July 8, 2020; median follow-up 19 months [IQR, 15.6-23.9 months]). Invasive disease-free survival (the primary end point of monarchE) and distant relapse-free survival (DRFS) were evaluated using the Cox proportional hazard model and Kaplan-Meier method. Results: Of the 5637 patients (mean [SD] age, 49.9 [10.6] years; 2046 women [99.5%]; 462 Asian [22.8%], 54 Black [2.7%], and 1473 White participants [70.8%]) enrolled in monarchE, 2056 (37%) received treatment with NAC. In this subgroup, treatment with abemaciclib and ET demonstrated clinically meaningful benefit in IDFS (hazard ratio, 0.61; 95% CI, 0.47-0.80) and DRFS (hazard ratio, 0.61; 95% CI, 0.46-0.81), which corresponded with an absolute improvement of 6.6% in 2-year IDFS rates and 6.7% in 2-year DRFS rates. A consistent treatment benefit was observed across subgroups of pathological breast tumor size or number of positive lymph nodes at surgery. Conclusions and Relevance: In the randomized clinical trial monarchE, treatment with adjuvant abemaciclib combined with ET demonstrated a clinically meaningful improvement in IDFS and DRFS for patients with HR+, ERBB2-, node-positive, high-risk early breast cancer who received NAC before trial enrollment. Trial Registration: ClinicalTrials.gov Identifier: NCT03155997.

Ribociclib plus letrozole in patients with hormone receptor-positive, HER2-negative advanced breast cancer with no prior endocrine therapy: subgroup safety analysis from the phase 3b CompLEEment-1 trial.

BACKGROUND: The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1. PATIENTS AND METHODS: Men and women of any menopausal status with HR+/HER2- ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured. RESULTS: Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events. CONCLUSIONS: These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2- ABC more representative of patients in real-world clinical practice.

High expression of progesterone receptor may be an adverse prognostic factor in oestrogen receptor-negative/progesterone receptor-positive breast cancer: results of comprehensive re-evaluation of multi-institutional case series.

Oestrogen receptor (ER)-negative (-) progesterone receptor (PgR)-positive (+) is the least common combination of steroid receptor expression observed in breast cancer. There are many controversies regarding the actual existence of ER-/PgR+ phenotype. In the current study, we aimed to perform comprehensive immunohistochemical re-evaluation of ER-/PgR+ breast cancers from multiple institutions. A total of 135 cases of ER-/PgR+ breast cancer were collected from 11 institutions from the period 2006-2020 and subsequently stained with three clinically validated anti-ER antibody clones: SP1 (Roche), 1D5 (Dako), and EP1 (Dako), and two anti-PgR antibody clones: 636 (Dako), and 1E2 (Roche). Clinicopathological characteristics of confirmed and re-categorised cases were analysed. Seventy-six cases retained the original ER-/PgR+ phenotype, including 21 HER2+ and 55 HER2- tumours. Forty-seven cases were ER+ with at least one anti-ER antibody, and 12 cases were re-categorised as double-negatives across all anti-ER and anti-PgR antibodies. No significant differences in survival were observed between groups in the HER2+ category. In the HER2- cohort, confirmed ER-/PgR+, ER+ tumours with discrepant ER staining, and triple negatives had inferior overall survival compared to concordant ER+ cases. Progesterone receptor expression in >20% of cells was identified as an adverse prognostic factor in ER-/PgR+/HER2- breast cancer in a multivariable model adjusted by stage (HR 5.0, 95% CI 1.3-19.2, p=0.019). We performed one of the largest validation studies so far on ER-/PgR+ breast cancer and confirmed the existence of this subgroup. Moreover, we identified high PgR expression as an adverse prognostic factor.

De-escalation of axillary irradiation for early breast cancer - Has the time come?

Introduction of sentinel lymph node biopsy, initially in clinically node-negative and subsequently in patients presenting with involved axilla and downstaged by primary systemic therapy, allowed for significant decrease in morbidity compared to axillary lymph node dissection. Concurrently, regional nodal irradiation was demonstrated to improve outcomes in most node-positive patients. Additionally, over the last decades, introduction of more effective systemic therapies has resulted in improvements not only at distant sites, but also in locoregional control, creating space for de-escalation of locoregional treatments. We discuss the data on de-escalation in axillary surgery and irradiation, both in patients undergoing upfront surgery and primary systemic therapy, with special emphasis on the feasibility of omission of nodal irradiation in patients undergoing primary systemic therapy. In view of the accumulating evidence, omission of axillary irradiation may be considered in clinically node-positive patients converting after primary systemic therapy to pathologically negative nodes on sentinel lymph node biopsy (preferably also with in-breast pCR), presenting with lower initial nodal stage, older age and were treated with breast-conserving surgery followed by whole breast irradiation. Omission of regional nodal irradiation in patients with aggressive tumor phenotypes achieving a pCR is under investigation. In patients undergoing preoperative endocrine therapy the adoption of axillary management strategies utilized in case of upfront surgery seems more suitable than those used in post chemotherapy-based primary systemic therapy setting.

microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers is Mainly Dependent on HER2 Status-A Pilot Study.

Estrogen (ER) and progesterone (PgR) receptors and HER2 are crucial in the assessment of breast cancer specimens due to their prognostic and predictive significance. Single hormone receptor-positive breast cancers are less common and their clinical course is less favorable than ER(+)/PgR(+) tumors. Their molecular features, especially microRNA (miRNA) profiles, have not been investigated to date. Tumor specimens from 36 chemonaive breast cancer patients with known ER and PgR status (18 ER(+)/PgR(-) and 18 ER(-)/PgR(+) cases) were enrolled to the study. The expression of 829 miRNAs was evaluated with nCounter Human v3 miRNA expression Assay (NanoString). miRNAs differentiating between ER/PgR/HER2 phenotypes were selected based on fold change (FC) calculated for the mean normalized counts of each probe in compared groups. The differences were estimated with Student's T-test or Two-Way ANOVA (considering also the HER2 status). The results were validated using The Cancer Genome Atlas (TCGA) dataset. Following quality control of raw data, fourcases were excluded due to low sample quality, leaving 14 ER(+)/PgR(-) and 18 ER(-)/PgR(+) cases. After correction for multiple comparisons, we did not find miRNA signature differentiating between ER(-)/PgR(+) and ER(+)/PgR(-) breast cancers. However, a trend for differing expression (p-value ≤ 0.05; FDR > 0.2; ANOVA) in eight miRNAs was observed. The ER(+)/PgR(-) group demonstrated elevated levels of four miRNAs-miR-30a-5p, miR-29c-3p, miR-141-3p and miR-423-5p-while the ER(-)/PgR(+) tumors were enriched in another four miRNAs-miR-514b-5p, miR-424-5p, miR-495-3p, and miR-92a-3p. For one of the miRNAs-miR-29c-3p-the association with the ER(+)/PgR(-) phenotype was confirmed in the TCGA cohort (p-value = 0.024; T-test). HER2 amplification/overexpression in the NanoString cohort was related to significant differences observed in 33 miRNA expression levels (FDR ≤ 0.2; ANOVA). The association with HER2 status was confirmed in the TCGA cohort for four miRNAs (miR-1180-3p, miR-223-3p, miR-30d-5p, and miR-195-5p). The main differences in miRNA expression amongst single hormone receptor-positive tumors were identified according to their HER2 status. However, ER(+)/PgR(-) cases tended to express higher levels of miRNAs associated with ER-positivity (miR-30a-5p, miR-29c-3p, miR-141-3p), whereas ER(-)/PgR(+) cancers showed elevated levels of miRNAs characteristic for double- and triple-negative tumors (miR-92a-3p, miR-424-5p). Further studies are necessary to comprehensively analyze miRNA signatures characteristic of ER(-)/PgR(+) and ER(+)/PgR(-) tumors.

Over-treatment in metastatic breast cancer.

Metastatic breast cancer is an incurable disease and the main goals of treatment are prolongation of survival and preservation/improvement of quality of life. Thus the main philosophy of treatment should be to use the least toxic methods, as long as they provide sufficient disease control. In ER-positive tumours this can be in many cases achieved by endocrine therapy; in HER2-positive cancers efficacy of backbone therapy can be enhanced by an anti-HER2 agent. In patients requiring chemotherapy, consecutive single agent regimen provide disease control of a duration at least comparable to multidrug regimen, at a cost of significantly lower toxicity and are a preferred strategy in the majority of cases. Available data demonstrate, however, that aggressive chemotherapy is still overused in many metastatic breast cancer patients. The objective of this manuscript is to critically review available data on treatment choices and sequence in metastatic breast cancer across all breast cancer subtypes in relation to possible overtreatment, including therapies which are not recommended by current guidelines or not even approved. Our aim is to provide guidance on applying these data to clinical practice, but also to describe various, often non-scientific factors influencing therapeutic decisions in an aim to identify areas requiring educational and possibly political actions.

Elevated nuclear S100P expression is associated with poor survival in early breast cancer patients.

S100P - low molecular weight acidic protein has been shown to be involved in processes of proliferation, survival, angiogenesis, multidrug resistance and metastasis in various human malignancies. In breast cancer, S100P expression is associated with immortalization of neoplastic cells and aggressive tumour behaviour, indicating that this protein may have adverse prognostic value. We analyzed nuclear and cytoplasmic expression of S100P in 85 stage II breast cancer patients with a median follow up of 17 years. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against S100P. We also studied prognostic value of S100P mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. Moreover, the relationship was examined between expression of S100P in cells of four breast cancer cell lines and their sensitivity to the 11 most frequently applied cytotoxic drugs. Univariate and multivariate analyses showed that higher expression of nuclear S100P (S100Pn) was typical for cases of a shorter overall survival and disease-free time. KM plotter analysis showed that elevated S100P expression was specific for cases of a relapse-free survival and distant metastases-free survival. No relationship could be documented between expression of S100P and sensitivity of breast cancer cells to cytostatic drugs. We demonstrated that a high S100Pn expression level was associated with poor survival in early stage breast cancer patients. Since preliminary data indicated that expression of S100P was up-regulated by activation of glucocorticoid receptor and several agents manifested potential to activate or inhibit S100P promoter activity, this protein might become a therapy target and warrants further studies with respect to its prognostic, predictive and potentially therapeutic value.

Correlation between hepatocyte growth factor receptor and vascular endothelial growth factor-A in breast carcinoma.

The aim of the study was to evaluate the prognostic value of the vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients. Tumor samples were collected from 98 patients with invasive ductal breast carcinoma stage II treated with primary surgery. We have observed a strong correlation between VEGF-A and c-met. No correlations were found between VEGF-A or HGFR expressions and clinical parameters (tumor size, grade, axillary lymph node status, age), 5- and 10-years DFS or OS. Our study did not reveal any prognostic value of c-met or VEGF. In addition they are not useful to separate a patients' subgroup with poor prognosis. Unlike in other authors' studies, our patients' group is very homogenous which might tribute to obtained results.

Serum vascular endothelial growth factors a, C and d in human breast tumors.

Available evidence suggests that vascular endothelial growth factor (VEGF) a potent regulator of vasculogenesis and tumor angiogenesis may be a predictor of recurrence in breast cancer patients. We sought to determine whether VEGF serum levels (VEGF-A, VEGF-C and VEGF-D) in 377 patients with malignant and benign breast tumors differ and whether there is association between vascular growth factors, clinicopathologic features and prognosis. There was no significant difference in investigated circulating angiogenic markers between patients with malignant and non malignant lesions. We found strong correlation between VEGF-A and VEGF-D and between VEGF- C and VEGF-D. Besides serum VEGF-D levels and estrogen receptor (ER) expressions no other correlations between VEGF and clinicopathologic variables were observed. However, elevated VEGF-A and VEGF-C concentrations were associated with increased number of erythrocytes, leukocytes and platelets. In Cox model values of angiogenic serum markers and recognized prognostic markers in breast cancer, VEGF-C turned out as independent prognostic factor. Our study is the first analysis showing correlation between serum concentrations of three angiogenic factors: VEGF-A, VEGF-C, VEGF-D. Associations between angiogenic cytokines and number of blood cells may be due to release of VEGF from platelets and leucocytes. Prognostic role of VEGF is still uncertain, though VEGF-C has a potential to serve as a prognostic marker.

Association between histological type of tumour growth and patient survival in t2-t3 lymph node-negative rectal cancer treated with sphincter-preserving total mesorectal excision.

For rectal cancer patients without nodal metastases the identification of unfavourable factors can be helpful for the better selection for adjuvant therapy and multimodality treatment. The aim of this study was to evaluate the impact of clinico-histological parameters on prognosis in node-negative rectal cancer patients. One hundred and thirty-nine consecutive node negative rectal cancer patients with complete five-year follow-up were studied prospectively. All of them underwent curative anterior resection with total mesorectal excision technique. Seventy-eight patients with tumour penetration beyond the bowel wall received neo-adjuvant short-course radiation (25 Gy) followed by surgery within 1 week and postoperative chemotherapy with 5-fluorouracil and folinic acid in six cycles or adjuvant radiochemotherapy: irradiation (50.4 Gy) combined with chemotherapy (as above). Cancer-specific survival was calculated according to the Kaplan-Meier method. Variables significant in univariate analysis by log-rank test (P < 0.05) entered the Cox proportional hazard model. Survival was decreased for males, older patients (>60 years) with extraperitoneal, poorly differentiated cancers, tumours with mucinous histology and with the absence of lymphocytic infiltration but with the lack of statistical importance. Prognosis was significantly improved for patients with T2 tumours versus T3 (P < 0.01) and with cancers with expanding growth comparing to diffusely infiltrating ones (P < 0.01). In multivariate analysis these parameters significantly and independently influenced survival (P < 0.01 and P < 0.05, respectively). Diffusely infiltrating growth of tumour can reflect the more aggressive cancer behaviour and unfavourable course of disease despite the optimised local control. Apart from the extent of tumour penetration the type of invasive margin can be an additional parameter helpful for the optimal treatment planning and better patient selection for postoperative chemotherapy.

The prognostic role of tumor-infiltrating CD4 and CD8 T lymphocytes in breast cancer.

BACKGROUND: The aim of the study was to assess the prognostic role of CD4 and CD8 expression and the type, density, localization and distribution of tumor infiltrating lymphocytes (TILs) in patients with breast cancer. MATERIALS AND METHODS: Tissue samples were obtained from 88 breast cancer patients with operable disease and ductal histology. Forty-three women had pathologically confirmed axillary lymph node involvement. The TILs and expression of CD8 (cytotoxic T-cells) and CD4 (T-helper cells) were evaluated in the tumor samples using mouse monoclonal antibodies. RESULTS: Thirteen patients relapsed; nine of them had strong expression of CD4 and CD8, which was statistically significant. The patients with high expression of CD4 or CD8 had distinctly worse cancer specific overall survival (OS). High correlations between CD4 and CD8 expression and lymph node status and intensity of lymphatic infiltrate as well as between both markers were found. CONCLUSION: The analysis of tumor-infiltrating immune cells may be a valuable prognostic tool and a marker of lymph node involvement.

[Prognostic significance of microvessel density in ovarian cancer]. / Wartosc prognostyczna oznaczania gestosci unaczynienia guza w raku jajnika.

UNLABELLED: The antigen of endothelial cell which are the exponent of microvessels density in cancer tumor as CD31, CD34 and CD105 are the most common analysed markers of angiogenesis. The aim of the work was to analyse the expression of CD31, CD34 and CD105 antigens--three basic markers of microvessel density in ovarian cancer. MATERIAL AND METHODS: The material included 80 patients with ovarian carcinoma, treated between 1996 and 2001 in Department of Oncology Gynecology of Lower Silesian Centre of Oncology. The median of age was 54.4 years. Most of analyzed cases (n = 53) were serum ovarian carcinoma in III and IV FIGO stage. RESULTS: The correlations between microvessel density (MVD) and clinicopathological parameters were analyzed. We have stated that in patients younger than 50 years the microvessel density was lower. This correlation was statistically significant in the estimation of MVD by CD31 and CD34 expression and close to statistically significant by marked CD105 expression. In patients with time of menopause that occurred before 46 years of age, microvessel density marked with CD105 expression was significantly higher and close to significance in CD31 marker. CONCLUSIONS: Cox analysis proved that independent risk factors of death in patients with ovarian cancer were: age over 50 years, low degree of patient performance according to WHO (World Health Organization) scale, high FIGO (International Federation of Gynecology and Obstetrics) stage and high expression of CD34 microvessel density.

Evaluation of prognostic value of VEGF-C and VEGF-D in breast cancer--10 years follow-up analysis.

UNLABELLED: The aim of the study was to evaluate the prognostic value of vascular endothelial growth factor C (VEGF-C) and VEGF-D expression in stage II, grade 2 and 3, ductal breast cancer patients. PATIENTS AND METHODS: The immunohistochemical staining of 98 tumor samples and 5- and 10-year overall (OS) and disease-free survival (DFS) were analyzed. RESULTS: A significant relationship between VEGF-C and VEGF-D expression (p=0.000002) was noted. No correlations between protein expression and clinical parameters (tumor size, grade, estrogen receptor status, axillaty lymph node metastases and age) or 5- and 10-year DFS or OS were demonstrated. A close to significant correlation (p=0.084) was observed between high expression of VEGF-C and 5-year OS. CONCLUSION: Our study did not reveal any prognostic value of VEGF-C or VEGF-D. Therefore they are not useful as markers for patients with poor prognosis. Unlike in other studies, our patient group was homogenous which might have contributed to the results obtained.

Serum vascular endothelial growth factor in patients with pharyngeal and laryngeal squamous cell carcinoma treated with radiotherapy.

The aim of this study was to assess the impact of radiotherapy on serum vascular endothelial growth factor (VEGF) levels in patients with pharyngeal and laryngeal cancer. Serum VEGF concentrations were determined in 37 patients before, during, and after radiotherapy by using a quantitative sandwich enzyme immunoassay technique. Most (25 patients [68%]) of the studied population were found to have high pretreatment VEGF concentration (of >700 pg/mL; median, 796.3 pg/mL). During radiotherapy, after receiving the total dose of 40 Gy, the median level of serum VEGF remained unchanged (795.2 pg/mL). Regardless of the treatment results, 2 months after completing irradiation the median VEGF level decreased to 448.9 pg/mL, and the difference between pre- and posttreatment medians was statistically significant (P < .05). No association between pretreatment serum VEGF concentrations and the size of tumor, lymph node status, and patients' age was found. The findings that radiotherapy produces serum VEGF decline in primary pharyngeal and laryngeal carcinomas (P = .065) may be related to the blocking effect of radiation on local angiogenesis.

[Assessment of hematopoiesis regeneration in patients with solid tumors after radiotherapy]. / Ocena regeneracji ukladu krwiotwórczego u chorych na nowotwory lite leczonych promieniowaniem jonizujacym.

The myelotoxicity is one of the most severe adverse events of radiotherapy. Increase of CD34+ cells level in peripheral blood as result of raised output of granulocyte colony stimulating factor (G-CSF) can be result of hematopoiesis regeneration after radiotherapy. The aim of this study was to determine the hematopoiesis regeneration using analysis of CD34+ cells level in peripheral blood and serum concentration of G-CSF in patients treated with radiotherapy according to irradiated body region and irradiation field size. Two groups of irradiated patients were examined. Group I consisted of 11 patients (mean age 56) with gynecological malignancies (teletherapy dose 40-50 Gy for pelvic area and brachytherapy with Cs). Group II consisted of 10 patients (mean age 58) with head and neck malignancies (teletherapy only 50-70 Gy). Every patient was evaluated 3 times: before radiotherapy, in the day of ending and 14 days after therapy. 3 ml of blood for CD34 and serum for G-CSF estimation were collected. Blood cells were stained with monoclonal antibody specific for CD34 antigen and analysed by flow cytometry. G-CSF level was estimated by ELISA. After radiotherapy in both groups statistically significant leukopenia (p < 0.001) was observed. There was no difference between two groups in levels of CD34+ cells before and in the last day of therapy but there was significant increase of CD34+ cells in group I compared with group II 14 days after treatment (p < 0.01). Decrease of CD34+ cells during radiotherapy and after its ending in all patients was observed but only in group II was statistically significant. Positive correlation between amount of leukocytes and CD34+ cells percentage was stated. There were no statistically significant differences in serum G-CSF concentration within particular groups and between group I and II. Our results indicate that evaluation of CD34+ cells level in peripheral blood is useful in prediction of hematopoiesis regeneration after radiotherapy. G-CSF serum concentration is not prognostic factor in these groups of patients.

[Cardiac toxicity in cancer therapy]. / Kardiotoksycznosc leczenia przeciwnowotworowego.

The aim of this article is to review (based on the literature data) the mechanism of chemotherapy- and radiation-induced cardiac toxicity, diagnostic procedures and methods of reducing this toxicity. Cardiac toxicity associated with chemotherapy and radiotherapy may be life threatening, can limit the dose and duration of the treatment and certainly adversely affect short-term and long-term quality of life. A development of new strategies for reduction and prophylaxis of cardiac toxicity has great clinical impact. Chemotherapeutic agents may cause acute myocardial injury or chronic complications (e.g. congestive heart failure). Among cardiotoxic agents anthracyclines cause most serious cumulative, dose-limiting and dose-related cardiomyopathy. Most of them are subclinical changes, however studies demonstrate that symptomatic congestive heart failure in 6-10% of adults who received a cumulative, bolus doses of 550 mg/m2. The frequency of cardiomyopathy may be reduced by modifying the schedule of administration, patients selection considering risk factors, careful cardiac monitoring during chemotherapy, using less toxic doxorubicin analogues and liposomal formulation. The use of pharmacological protection with dexrazoxane remains controversial. A substantial risk of cardiotoxicity may be associated with radiotherapy of the chest and mediastinum. Moreover, radiotherapy may have an additive affect to chemotherapy-induced toxicity. However, with the use of modern treatment techniques radiation cardiomyopathy is uncommon. A group of patients at risk of cardiac complication are patients with breast cancer, Hodgkin's and non-Hodgkin's lymphomas and soft tissue sarcomas.