Objectives: The aim of the present study was to assess the clinical value of measuring the concentration of neurofilament light chains (NF-Ls) in the diagnosis of taxane-induced neuropathy (CIPN) during neoadjuvant chemotherapy (NAC) in breast cancer patients. Methods: This study included a total of 94 patients who qualified for NAC with taxanes. Serum samples were collected before starting NAC, after three and six cycles, and 3–6 months after NAC. The NF-L concentration was determined using the Ella technology. The assessment of CIPN was based on the clinical symptoms included in the EORTC QLQ-CIPN20 scores. Results: The median NF-L concentrations increased during NAT monitoring. After the end of therapy, a significant decrease in NF-L concentrations was observed (p = 0.001, R = 0.37). We established a cut-off point of 29.5 pg/mL to distinguish between the control group and patients with early symptoms of neuropathy (CIPN G1) (p = 0.001; AUC = 0.982). We showed that NF-L concentrations, regardless of the stage of therapy, increased with the severity of neuropathy symptoms (CIPG1 vs. G2 vs. G3) (p = 0.0189, R = 0.33). According to the established cut-off points, serum NF-L concentrations above 196 pg/mL in patients undergoing therapy likely indicate the presence of low-grade neuropathy (p = 0.0076), while values above 218 pg/mL may indicate advanced CIPN (p = 0.0008). Conclusions: In this study, we demonstrated the usefulness of NF-L levels to confirm neuropathy early in the course of treatment, which is important as the questionnaire-based assessment of neuropathy currently used in practice remains subjective. Ultimately, serum NF-L levels are helpful in determining the severity of NAC-induced neuropathy among breast cancer patients.
Introduction. Radiotherapy and radiochemotherapy are, besides surgery, common treatments for head and neck cancers. Despite using advanced modern radiation techniques, the late side effects are a serious problem. From a multitude of cytokines and growth factors shown to contribute to the injury process after cancer therapy, transforming growth factor β1 (TGF-β1) is among the most fundamental ones. The study evaluated if a high level of TGF-β1 before, during, and after treatment can predict thyroid gland fibrosis, which causes hypothyroidism, one of the common late side effects of head and neck cancer irradiation. Material and methods. Fifty-six patients with head and neck cancer who underwent radiation alone or concomitant chemoradiotherapy were included in the study. Analyzed variables included thyroid stimulating hormone (TSH), volume and echogenicity of the thyroid gland, and the level of TGF-β1. Results. In comparison to the initial level, statistically significant increased levels of TSH and statistically significant decreased volume of the thyroid gland were observed 6 and 12 months after irradiation. Moreover, statistically significant decreased levels of TGF-β1 were observed one month after irradiation. High levels of TGF-β1 before treatment or changes in TGF-β1 levels during and after treatment influenced changes neither in TSH levels nor in volume and echogenicity of the thyroid gland one year after radiotherapy. Conclusions. Early evaluation of TSH after radiation is needed to predict hypothyroidism. High TGF-β1 levels before and changes during and after radiation cannot predict hypothyroidism one year after treatment.
The study aimed to prospectively investigate the clinical value of interleukin-6 (IL-6), myeloperoxidase (MPO) and tumor necrosis factor α (TNF-alpha) as potential biomarkers of cancer therapy-related cardiac dysfunction (CTRCD) in patients receiving anthracycline treatment. In all patients, risk factors were collected, laboratory tests (including IL-6, MPO and TNF-alpha) and echocardiography with global longitudinal strain (GLS) were performed. A total of 80 patients were included, with 77 (96.25%) followed for an average for 11.5 months. The mean age at baseline was 60.5 years, and 72 (93.51%) were women. During observation, five patients (6.49%) died, including two due to heart failure and three due to cancer progression. The majority of patients (59, 76.6%) had breast cancer, 11 (14.3%) had sarcoma, and 7 (9.1%) had lymphoma. During observation, any degree of CTRCD was diagnosed in 48 (62.4%) patients. Mild CTRCD occurred in 38 (49.4%) patients, moderate CTRCD was diagnosed in 7 (9.1%) and severe in 3 (3.9%). In patients with high baseline risk, IL-6 levels were significantly elevated compared to those with moderate risk (p = 0.018). Higher levels of IL-6 were found to correlate with an increased grade of cancer therapy-related cardiac dysfunction (CTRCD). In a multivariate repeated measures model of the biomarkers studied, only a higher level of IL-6 was significantly associated with the diagnosis of CTRCD. Among the novel biomarkers studied, we found evidence for IL-6 for its potential use in the early detection of cardiac dysfunction related to cancer therapy in patients treated with anthracyclines.
Introduction:The purpose of this study was to determine the prognostic utility of vitamin D concentrations and BMI (body mass index) values and the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI) and the pan-immune-inflammation value (PIV) to predict the achievement of a complete response to neoadjuvant treatment (NAT) in patients with breast cancer. The correlations between systemic inflammatory response indices and vitamin D concentrations and BMI values were also analysed. Material and Methods:The study included 96 patients with breast cancer, prior to the start of NAT, of which 51 patients were diagnosed with triple-negative breast cancer (TNBC) and 45 patients with human epidermal growth factor receptor type 2 (HER2)-positive type. Results:The SIRI and PIV indices were shown to be significantly higher in patients with TNBC (P = .001; P = .001) than in patients with HER2. There were no statistical differences in SII, SIRI, PIV, BMI, and vitamin D, according to the response to NAT treatment (pCR vs non-pCR). In the HER2+ group without pCR after NAT, there was a positive correlation of the SII coefficient with BMI values (R = .41; P = .045). Furthermore, in the entire HER2+ group (irrespective of the NAT response), SII values were negatively correlated with vitamin D levels (R = -0.39; P = .008). Conclusions:In patients with breast cancer, high SIRI and PIV values may indicate the biological subtype of TNBC. In the HER2+ group, higher SII values were associated with low vitamin D concentrations and elevated BMI.
Background: Anthracycline-based chemotherapy is associated with a risk of cancer therapy-related cardiac dysfunction (CTRCD), particularly in patients with moderate to high cardiovascular risk. Left ventricular global longitudinal strain (GLS) is a sensitive marker for early myocardial dysfunction, but the prognostic value of baseline GLS in this population remains unclear. Objective: We aimed to evaluate whether baseline GLS can predict CTRCD in moderate- to high-risk cancer patients undergoing anthracycline chemotherapy. Methods: In this prospective, single-center observational study, 80 anthracycline-naive cancer patients classified as moderate or high risk were enrolled. Baseline GLS was assessed via speckle-tracking echocardiography, with a threshold of ≥−18% considered decreased. Patients were followed for 12 months, and the primary endpoint was the development of CTRCD per ESC 2022 Cardio-oncology guidelines. Results: Of the 77 patients completing follow-up, 27.3% had decreased baseline GLS. CTRCD occurred in 62.4% of patients, with higher incidence among those with decreased GLS (76.7%) compared to those with normal GLS. In multivariable analysis, GLS ≥−18% was the only significant independent predictor of CTRCD (RR 12.0, 95% CI 2.0–71.9; p = 0.0065). All-cause mortality was also significantly higher in patients with decreased baseline GLS (19.1% vs. 1.8%, p = 0.018). Conclusions: Decreased baseline global longitudinal strain is an independent predictor of cancer therapy-related cardiac dysfunction and all-cause mortality in moderate- to high-risk patients receiving anthracycline therapy. These findings support the inclusion of baseline GLS in pre-treatment cardiovascular risk assessment, particularly in patients with an LVEF above 54%, to more effectively identify those who may benefit from early cardioprotective interventions.
Introduction:Infliximab (IFX) and vedolizumab (VDZ) are monoclonal antibodies used for the treatment of inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC). The concentration of biologic drugs must be high enough for a therapeutic response. Aim:To evaluate the association of VDZ or IFX concentrations with the clinical condition of patients with IBD during therapy. Material and methods:We examined 82 patients with IBD treated with VDZ or IFX. Blood samples were before the administration of the drug dose. Serum drugs were determined by ELISA with RIDASCREEN kits from R-Biopharm AG. Results:The highest median serum VDZ concentrations were observed in patients with UC and endoscopic response or remission. The median serum VDZ concentration during the maintenance phase in patients with endoscopic remission remained at similar levels, while in patients without remission, a decrease was shown. Additionally, analysis of VDZ concentrations in the group of patients without endoscopic remission showed a significant decrease in drug concentration in the maintenance phase compared the induction phase (p = 0.037). VDZ concentration of 26.4 µg/ml differentiated patients with endoscopic remission from patients who did not respond. In the group of CD patients, up to 91% of the patients responded to IFX treatment in the maintenance phase. Conclusions:The sustained serum concentrations of VDZ in patients with IBD determined in the maintenance phase confirmed a positive response to this therapy, which in practice may have significance in optimising the dosage of biological treatment.
Background: Many risk factors for cancer therapy-related cardiovascular toxicity overlap with risk factors for atherosclerosis. According to the ESC 2022 Cardio-Oncology Guidelines, coronary computed tomography angiography and coronary artery calcium score are not recommended as part of routine risk assessment prior to oncological treatment. The aim of this study was to prospectively assess the influence of coronary artery calcium score (CAC score) on cancer therapy-related cardiac dysfunction in patients with moderate and high risk of cardiovascular toxicity, qualified for anthracycline treatment. Methods: In all patients, risk factors were collected, laboratory tests, echocardiography with global longitudinal strain (GLS) assessment and coronary artery tomography with coronary artery calcium score were performed. A total of 80 patients were included in the study, of which 77 (96.25%) were followed for an average of 11.5 months. The mean age at baseline was 60.5 years and 72 (93.51%) were women. Results: During observation, five patients (6.49%) died, including two due to heart failure and three due to cancer progression. The majority of patients (59, 76.6%) had breast cancer, 11 (14.3%) were diagnosed with sarcoma and seven (9.1%) with lymphoma. According to the HFA-ICOS risk score, 40 patients (51.9%) were classified as moderate risk (MR), and 37 patients (48.1%) as high risk (HR) for cancer therapy-related cardiovascular toxicity. A CAC score greater than 100 was calculated in 17 (22.1%) patients and greater than 400 in three (3.9%) patients. The CAC score above zero was more common in older patients and in patients classified as high risk (p < 0.001). There was also a significant association between CAC score and hypertension, hyperlipidemia, chronic kidney disease, and the level of NT-proBNP. During 12-month follow-up, mild CTRCD occurred in 38 (49.4%) patients, moderate CTRCD was diagnosed in seven (9.1%), and severe in three (3.9%) patients. In the univariable analysis, CTRCD was more common in the high-risk group (p = 0.005) and in patients with a CAC score greater than zero (p = 0.036). In multivariable analysis, the incidence of CTRCD remains higher in the CAC score > 0 group, even after adjusting for age, hypertension, and hyperlipidemia. In this study group, the CTRCD rates increased with the HFA-ICOS risk score. Conclusions: In moderate and high-risk patients, a coronary artery calcium score greater than zero was identified as a significant risk factor for the development of cancer therapy-related cardiac dysfunction during anthracycline-based treatment. Furthermore, the HFA-ICOS risk score demonstrated good correlation with the incidence of CTRCD in this study, supporting its validity as a predictive tool in patients receiving anthracycline therapy.
Introduction. Radiotherapy and radiochemotherapy are, besides surgery, common treatments for head and neck cancers. Despite using advanced modern radiation techniques, the late side effects are a serious problem. From a multitude of cytokines and growth factors shown to contribute to the injury process after cancer therapy, transforming growth factor f31 (TGF-f31) is among the most fundamental ones. The study evaluated if a high level of TGF-f31 before, during, and after treatment can predict thyroid gland fibrosis, which causes hypothyroidism, one of the common late side effects of head and neck cancer irradiation. Material and methods. Fifty-six patients with head and neck cancer who underwent radiation alone or concomitant chemoradiotherapy were included in the study. Analyzed variables included thyroid stimulating hormone (TSH), volume and echogenicity of the thyroid gland, and the level of TGF-f31. Results. In comparison to the initial level, statistically significant increased levels of TSH and statistically significant decreased volume of the thyroid gland were observed 6 and 12 months after irradiation. Moreover, statistically significant decreased levels of TGF-f31 were observed one month after irradiation. High levels of TGF-f31 before treatment or changes in TGF-f31 levels during and after treatment influenced changes neither in TSH levels nor in volume and echogenicity of the thyroid gland one year after radiotherapy. Conclusions. Early evaluation of TSH after radiation is needed to predict hypothyroidism. High TGF-f31 levels before and changes during and after radiation cannot predict hypothyroidism one year after treatment.
Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition with global implications. Accurate and timely diagnosis is critical; however, traditional diagnostic methods (based on spirometry) show limitations, prompting the search for predictive biomarkers and modern diagnostic techniques. This study explored the validation of COPD-related biomarkers (C-reactive protein, procalcitonin, neutrophil elastase, and alpha-1 antitrypsin) in saliva. A diverse cohort, including healthy non-smokers, healthy smokers, and COPD patients of Polish origin, underwent spirometry and marker analysis. The data correlated with clinical factors, revealing noteworthy relations. Firstly, salivary biomarker levels were compared with serum concentrations, demonstrating notable positive or negative correlations, depending on the factor. Further analysis within healthy individuals revealed associations between biomarker levels, spirometry, and clinical characteristics such as age, sex, and BMI. Next, COPD patients exhibited an enhanced concentration of biomarkers compared to healthy groups. Finally, the study introduced a breathing assessment survey, unveiling significant associations between self-perceived breathing and spirometric and tested parameters. Outcomes emphasized the relevance of subjective experiences in COPD research. In conclusion, this research underscored the potential of salivary biomarkers as diagnostic tools for COPD, offering a non-invasive and accessible alternative to traditional methods. The findings paved the way for improved modern diagnostic approaches.
The presence and burden of coronary artery calcium (CAC) is a strong predictor of cardiovascular events. Current guidelines of the European Society of Cardiology (ESC) for cardio-oncology do not recommend the use of the CAC score to determine the status of risk in cancer patients. The aim of this study is to evaluate the presence and burden of CAC on cardiac tomography and the distribution of the cardiovascular toxicity risk factors in patients with moderate and high baseline risk of cancer therapy-related cardiovascular toxicity. The study prospectively included cancer patients, diagnosed and qualified for systemic treatment with anthracycline chemotherapy. Clinical data and blood samples were collected from all patients. Additionally, the echocardiography and coronary computed tomography (CCTA) with the calculation of the coronary artery calcium (CAC) score were performed. A total of 80 patients (mean age 60.5 years, 75 female) were included in the study. The majority of patients (62, 77.5
Background: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. Methods: We conducted this prospective study in the MSCNRIO in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers gave informed consent. Complete blood count, carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA125), carcinoma antigen 19.9 (CA19.9), and fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Results: Of all the measured parameters, only the IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in the complete pathological response (pCR) vs. the non-pCR group (3.71 pg/mL vs. 7.63 pg/mL, p = 0.004). In all patients with an IL-6 level below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to the Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs. ypN0 (7.69 pg/mL vs. 2.89 pg/mL, p = 0.022). Conclusions: The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC.
BACKGROUND:Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. This protocol describes a study aiming to assess the prognostic value of coronary atherosclerosis burden and the CAC score on the onset of cardiac dysfunction associated with cancer therapy.METHODS:ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a single-site, prospective, observational study to evaluate the influence of the coronary atherosclerosis and CAC score assessed by computed tomography on the development of left ventricular systolic dysfunction in cancer patients with at least moderate cardiotoxicity risk. A group of 80 patients diagnosed with cancer prior to high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 body weight or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. Patient follow-up is planned for 12 months. In all patients, coronary computed tomographic angiography (CCTA) will be performed once at the beginning of the study. The primary endpoint is the onset of cancer therapy-related cardiovascular toxicity, defined as mild, moderate, severe and very severe according to ESC 2022 Cardio-oncology guidelines. During follow up, echocardiography with GLS assessment will be performed every three months. Additionally, new biomarkers of atherosclerosis (IL-6, MPO, TNF-alpha) will be measured every 6 months. The study registration identifier on clinicaltrials.gov is NCT05118178.CLINICAL TRIALS REGISTRY:This study is listed on cinicaltrials.gov with identifier NCT05118178.
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive and readily available blood test that may predict response to neoadjuvant chemotherapy (NACT) in breast cancer patients. However, its utility as a biomarker remains unclear. OBJECTIVE: To evaluate NLR as a predictive biomarker for pathological complete response (pCR) to NACT in triple-negative breast cancer (TNBC) and HER2-positive breast cancer patients. METHODS: In this prospective analysis, 96 patients with early stage TNBC (n=51) or HER2-positive (n=45) breast cancer receiving NACT were assessed. NLR and other variables were analyzed for correlation with pCR. RESULTS: pCR rates were 49% for TNBC and 46.7% for HER2-positive patients. NLR did not correlate with pCR in either subset. Only chemotherapy regimen predicted pCR. Mean NLR was lower in pCR groups but did not reach statistical significance. CONCLUSION: Pretreatment NLR did not predict pCR after NACT in this cohort of early stage TNBC and HER2-positive breast cancer patients. NLR should be further studied in combination with other biomarkers to determine its utility as a universal predictive biomarker for NACT response.
Background: Uterine sarcomas and carcinomas are rare tumors and treatment outcomes are far from expected. We investigated the prognostic significance of selected serum biomarkers and the impact of some clinical and tissue factors on overall survival (OS) at 10-year follow-up.Material/Methods: The material for analysis was a group of 34 patients with uterine sarcomas and 18 with carcinomas. Immunohistochemistry was performed to determine Ki 67, p53 and ER and PR. Concentrations: CA 125, IL8, VEGF, SFTL1, VEGF R2, sTNFRI and MMP-9 were determined in the serum of patients before treatment and in the control group. Results: The most frequently elevated levels observed of sTNF RI in 94% and VEGF in 62%. On the ROC curve analysis, sTNF RI and VEGF concentrations showed the highest sensitivity. Patients with striated cell sarcoma, smooth cell sarcoma and high-grade rhabdomyosarcoma had the worst prognosis. Patient age, FIGO stage and expression of Ki67, p53, ER and PR, CA 125 (p<0.038) and IL-8 (p<0.024) were statistical prognostic factors for OS. However, in multivariate analysis, serum levels of: CA 125 concentration (p<0.045), age (p<0.010) and p53 expression (p<0.014) were found to be significant independent prognostic factors. Conclusions: A 10-year follow-up of patients with uterine sarcoma indicates that age above 60 years at diagnosis and high p53 expression and elevated CA125 levels before treatment can be independent prognostic factors. The high diagnostic sensitivity of sTNF RI and VEGF suggests the possibility of using these biomarkers in the early diagnosis of uterine sarcomas.
Breast cancer is considered the most commonly diagnosed tumors. Biomarkers used for the diagnosis and treatment of breast cancer are: tissue biomarkers (PR, ER, HER2, Ki-67) and serum biomarkers (CA-15-3, CA-125, CA-27-29, CEA, cytokeratins). ECD HER2, metalloproteinases and leptin are emerging as promising biomarkers for breast cancer. There is a growing need for personalized diagnostics based on tumour genome characterization, relying on a liquid biopsy containing components such as CTC and ctDNA, cell-free RNA. Biomarkers can also be used use as a target for anti-breast cancer treatment (PGRN and sortilin, AR, PD-1/PD-L1). Another potential field of application of breast cancer biomarkers is monitoring treatment side effects, such us inflammatory biomarkers causing cardiotoxicity, thyroiditis biomarkers (TSH, FT4, TPOab TgAb) in IrAE, NF-L and MCP-1 in ICI-associated neurotoxity. It is expected that new prognostic and predictive biomarkers will be developed that can provide accurate and reliable information for clinical application. Through the recognition of emerging biomarkers, it is possible to identify subgroups of patients who benefit from targeted therapies and managing treatment by monitoring side effects. However, these new biomarkers need to be validated and tested for their suitability before entering clinical use.
454 Background: Perioperative chemotherapy remains a standard of care in locally advanced gastric cancer. About 10-15% patients do not respond to such therapy and there are currently no biomarkers which could be used to predict early response to the neoadjuvant treatment. Methods: This prospective biomarker study aimed at identification of serum biomarkers of early response to neoadjuvant chemotherapy. Here we report only the results for serum cytokine assessments. It was an academic, nonrandomized, prospective study, conducted in MSCNRIO. Between January 2018 and November 2019 we analysed 42 patients aged 30-77 (median 63 years, 52.5% male and 47.5% female) with histologically confirmed GC or GEJ cancer qualified by MDT for perioperative FLOT. Exclusion criteria were: inflammatory and autoimmune diseases, other cancers, chronic steroid and immunosuppressive therapy. Blood sample was collected a.c. prior to the administration of cycle one (C1), two (C2) and three (C3) FLOT regimen. Serum levels of IL-1β and IL-6 were measured twice using ELISA. Results: All patients with pre-treatment IL-1β levels above 0.5 ng/ml on the postoperative histopathological report had positive lymph nodes (ypN+). There was a statistically significant difference in the level of IL-1β in the blood serum of patients before the start of treatment in the subgroups ypN0 vs ypN+ vs unresectable tumor (p = 0.003), ypN0 vs ypN+ (p = 0.002) as well as ypN+ vs unresectable tumor (p = 0.075). There was a trend for change in IL-1β level between cycles C1 and C3 in the ypN0 vs ypN+ subgroups (p = 0.056). The difference in IL-1β level before C1 between the groups TGR-G1-2/ypN0 vs TGR-G1-2/ypN+ vs TGR-G3/ypN0 vs TGR-G3/ypN+ was statistically significant (p = 0.017). The difference in IL-6 level between C3 and C1 in the subgroups TGR-G1-2/ypN0 vs TGR-G1-2 / ypN + vs TGR-G3 / ypN0 vs TGR-G3 / ypN + vs unresectable tumor was statistically significant (p = 0.009). Among the analyzed factors, only the difference in serum IL-6 level between C3 and C1 may be a predictor of ypN+ response to preoperative FLOT regimen. Among ypN0 patients, 76% had an IL-6 difference between C3 and C1> 1.1, i.e. C3 greater than C1 by at least 1.1 (specificity), and among ypN+ patients 83% had an IL-6 difference between C3 and C1 <1.1 (specificity). Conclusions: Low IL-1β levels before starting treatment is a prognostic factor while an early decrease in IL-6 could be considered a predictive marker of response to FLOT.
Purpose: To search for new predictive breast cancer biomarkers. We analyzed the serum concentrations of biomarkers involved in carcinogenesis, which can also be targeted by therapy. Methods: In a single-center prospective study, the serum levels of Aurora A, thymidine kinase 1, and human epidermal growth factor receptor type 3 (HER3) were determined in 119 women with BC before neoadjuvant treatment using ELISA kits. Results: The following clinical data were analyzed: age; TNM; the expression of ER, PGR, HER2, and Ki67; histological grade (G); and the response to neoadjuvant treatment (NAT) in the residual tumor burden classification (RCB). A complete pathological response (pCR) was achieved after NAT in 41 patients (34%). The highest proportion of the patients with a confirmed pCR was found for triple negative breast cancer (TNBC) (62.5%); non-luminal HER2-positive (52.6%) cancer subtypes (p = 0.0003); and in the G3 group (50%; p = 0.0078). The patients with higher levels of Aurora A were more likely to achieve pCR (p = 0.039). In the multivariate analysis, the serum Aurora A levels ≥ 4.75 ng/mL correlated with a higher rate of pCR (OR: 3.5; 95% CI: 1.2–10.1; p = 0.023). Conclusions: We showed that in a biologically heterogeneous group of BC patients, the pretreatment serum Aurora A levels were of significant value in predicting the response to NAT.
AimsVulvar squamous cell carcinoma (VSCC) spreads early and mainly locallyviadirect expansion into adjacent structures, followed by lymphatic metastasis to the regional lymph nodes (LNs). In the lymphatic metastasis, cancer cells bearing CXCR4 and ACKR3 (CXCR7) receptors are recruited to the LNs that produce the CXCL12 ligand. Our study aimed to assess the role of the CXCR4/ACKR3/CXCL12 axis in VSCC progression.MethodsTumour and LN tissue samples were obtained from 46 patients with VSCC and 51 patients with premalignant vulvar lesions. We assessed CXCR4, ACKR3 and CXCL12 by immunohistochemistry (IHC) in the tissue samples. Additionally, CXCL12 levels were determined by ELISA in the sera of 23 patients with premalignant lesions, 37 with VSCC and 16 healthy volunteers.ResultsCXCR4 and ACKR3 proteins were virtually absent in vulvar precancers, while in VSCC samples the IHC staining was strong. In the LNs of patients with VSCC, 98% of metastatic cells expressed CXCR4 and 85% expressed ACKR3. Neither CXCR4 nor ACKR3 presence was correlated with tumour human papilloma virus status. Few CXCL12-positive cells were found in the analysed tissue samples, but serum CXCL12 levels were significantly increased in both patients with premalignant vulvar lesions and with VSCC compared with healthy volunteers.ConclusionsIt appears that during progression and lymphatic spread of VSCC, the CXCR4/ACKR3/CXCL12 axis is activated. Moreover, our data suggest that CXCR4 antagonists merit further attention as a possible therapeutic option in patients with VSCC.
The aim of this study was to assess the usefulness of neuron-specific enolase (NSE) concentrations as a prognostic factor in patients with neuroendocrine neoplasms and to determine the relationship between NSE and clinicopathological features. Serum NSE levels were measured in 179 NEN patients before treatment. It was found that NSE levels in patients with a primary pancreatic location were higher compared to patients with a small intestine lesion (P = 0.015). NSE levels were significantly higher in patients with primary pancreatic location with histological grade G2 compared with the group with low-grade G1 (P = 0.047). Patients with initial liver involvement showed significantly higher NSE levels compared to patients with tumour location in the pancreas (P = 0.009). Statistical analysis confirmed that higher NSE levels were associated with disease progression (P = 0.001) in both the overall study group and in patients with tumours in the pancreas and small intestine. During treatment monitoring, an increase in median NSE concentrations was observed in patients with persistent progression with subsequent blood draws, and a decrease in NSE concentrations was observed in patients with disease stabilisation. We showed that NSE concentrations have prognostic value for progression-free survival in addition to primary liver involvement. In conclusion, the most important results of the study include the demonstration of an association between NSE concentrations and clinical status, which confirms its usefulness in patient monitoring and as a potential predictive indicator for progression-free survival in patients with NENs.
Further personalization is needed to improve the outcomes of breast cancer treatment. It is necessary to find new inexpensive and easily evaluated predictive markers. In this study, we determined serum level of Aurora A (AURKA), thymidine kinase 1 (TK1) and human epidermal growth factor receptor type 3 (HER3) by enzyme immunoassay ELISA. We collected peripheral blood sera of 119 women with breast cancer before neoadjuvant treatment and the control group of 47 randomly selected healthy women. After treatment we analyzed clinical data: age, initial TNM stage, tumor receptors expression: estrogen (ER), progesterone (PGR), epidermal growth factor receptor type 2 (HER2), Ki67, histological malignancy grade, biological subtype, and response to neoadjuvant treatment in residual cancer burden (RCB) classification. Pathologic complete response (PCR) was achieved in 41 patients (34.45%). In univariate analysis patients with higher AURKA levels were more likely to obtain PCR (p=0.039). In multivariate analysis we used the logit regression model with PCR as the dependent. The effect of AURKA concentration ≥4.75 ng / mL on the chance of achieving PCR was found (OR: 3.5; 95%CI: 1.2-10.1; p = 0.023). Other significant PCR factors included: node status (OR: 0.503; 95% CI: 0.263-0.965; p = 0.039), negative PGR expression (OR: 0.104; 95% CI: 0.038-0.284; p < 0.001), and Ki67 >20% (OR: 5.44; 95% CI: 1.24-23,9; p < 0.025). There was no significance in marker concentrations and clinical features nor between breast cancer patients and control group. The outcomes suggest that serum AURKA level is a potential PCR prediction marker in neoadjuvant breast cancer treatment. Further studies are needed to confirm our observations.