Interleukin-6 as a Predictive Factor of Pathological Response to FLOT Regimen Systemic Treatment in Locally Advanced Gastroesophageal Junction or Gastric Cancer Patients.

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-1ß (IL-1ß), 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.

Prognostic Factors for Uterine Sarcoma and Carcinosarcoma: Insights from a 10-Year Follow-Up Study.

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 AND 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.

Expression of Soluble Form of Aurora A as a Predictive Factor for Neoadjuvant Therapy in Breast Cancer Patients: A Single-Center Pilot Study.

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.

Prognostic value of coronary atherosclerosis and CAC score for the risk of chemotherapy-related cardiac dysfunction (CTRCD): The protocol of ANTEC study.

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.

Serum levels of neuron-specific enolase as a prognostic factor for disease progression in patients with GET/NEN in the pancreas and the small intestine.

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.

The Impact of Dietary Counselling on Achieving or Maintaining Normal Nutritional Status in Patients with Early and Locally Advanced Breast Cancer Undergoing Perioperative Chemotherapy.

Background: Obesity is an independent prognostic factor and is associated with poorer response to oncological treatment of breast cancer. Obesity is associated with shorter overall survival and shorter time to recurrence. Material and methods: The study included 104 breast cancer patients qualified for neoadjuvant chemotherapy. The control group consisted of 40 patients who refused to participate in the study. Consultation before chemotherapy included: author's diet questionnaire, body composition analysis, nutrition education. After chemotherapy, the effects of the first dietary advice were evaluated. Results: More than half of all women had a BMI above normal before treatment. Analysis of the effects of nutrition education showed a significant improvement in body composition. After education, a slight increase in body weight and a significant decrease in fat mass and fat percentage were observed. In women who did not participate in education, a statistically significantly greater increase in body weight after chemotherapy was noted. Nutrition education of the study group did not prevent adverse changes in lipid profile resulting from chemotherapy. Conclusions: Dietary counselling prior to neoadjuvant chemotherapy may limit weight gain and may also influence fat mass reduction. Implementation of dietary recommendations does not guarantee maintenance of normal lipid parameters during chemotherapy.

CXCR4/ACKR3/CXCL12 axis in the lymphatic metastasis of vulvar squamous cell carcinoma.

AIMS: Vulvar squamous cell carcinoma (VSCC) spreads early and mainly locally via direct 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. METHODS: Tumour 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. RESULTS: CXCR4 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. CONCLUSIONS: It 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.

Measurement of HE4 six months after first-line treatment as optimal time in identifying patients at high risk of progression advanced ovarian cancer.

OBJECTIVES: The objective of the study was to assess the usefulness of determining HE4 and CA125 in ovarian cancer patients, to indicate which of the measurements may be optimal in the prognosis, depending on the treatment scheme. MATERIAL AND METHODS: The concentrations of CA125 and HE4 were performed in 70 patients with advanced ovarian cancer during I-line therapy and after treatment. The subjects were divided based on the treatment scheme: group I - primary surgery and adjuvant chemotherapy, II- neoadjuvant therapy, and surgery. RESULTS: Multivariate analysis showed that HE4 levels six months after treatment was significantly higher in patients with disease progression. ROC analysis in the group of patients treated with neoadjuvant therapy showed that the cut-off values indicating relapse for HE4 and CA125 after six months of follow up, were > 90.4 pmol/L, > 25.6 IU/mL, respectively. In the group of patients not treated with neoadjuvant therapy, the cut-off points differentiating patients with progression were: HE4 > 79.1 pmol/L, CA125 > 30.7 IU/mL. We demonstrated significantly higher HE4 and CA125 at both 6- and 12-months follow-up in patients treated with neoadjuvant therapy. In both groups of patients, the cut-off points were lower than those proposed by the manufacturer of the kits. CONCLUSIONS: Measurement of HE4 six months after treatment may be useful in identifying patients at high risk of progression, especially when CA125 levels may be non-specifically elevated. The cut-off values indicating relapse for HE4 and CA125 after six months of follow up may be lower than the normal range.

Pretreatment neutrophil to lymphocyte and platelet to lymphocyte ratios as predictive factors for the survival of cervical adenocarcinoma patients.

OBJECTIVE: Our study assessed the clinical utility and prognostic value of pretreatment hematological parameters and calculated coefficients including the platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR) in patients with cervical adenocarcinoma (CA). MATERIALS AND METHODS: Among 738 cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IA-IV treated at our institution, 96 (13%) presented with CA histology. The blood samples, collected within 10 days before treatment, were analyzed using a Sysmex XN-2000 system. The statistical tests included Mann-Whitney U-tests, log-rank tests, and Cox regression models. The cutoff points for the calculated hematological coefficients (NLR, PLR, and MLR) were determined using the MedCalc statistical program. RESULTS: The prognostic factor for overall survival (OS) and recurrence-free survival (RFS) in CA was clinical stage according to FIGO classification (FIGO IIB-IV vs I-IIA) (P=0.0001; P=0.002). Among patients with FIGO stage IIB-IV treated with radiotherapy/chemoradiotherapy, an elevated PLR was a negative prognostic factor for OS (P=0.017; HR: 2.96; 95% CI: 2.069-3.853). Among all patients, an elevated pretreatment NLR was a poor prognostic factor for OS (P=0.014; HR: 2.85; 95% CI: 2.011-3.685) and RFS (P=0.049; HR: 4.0; 95% CI: 2.612-5.392). The white blood cell count (WBC) before treatment was significantly higher in patients who died during follow-up (P=0.009). CONCLUSION: Elevated NLR values before treatment may be associated with a shorter time of RFS and OS, while PLR index may have prognostic significance for OS in patients with advanced disease (FIGO IIB-IV). Both indexes and WBC may be a cost-effective biomarker that can be used conveniently for stratification of recurrence risk and death.

Prognostic value of chromogranin A in patients with GET/NEN in the pancreas and the small intestine.

The aim of this study was to evaluate the clinical usefulness of the chromogranin A (CgA) determination in patients with neuroendocrine neoplasms (NENs) of the digestive system and to analyse the association between concentration of the marker and progression-free survival (PFS) and overall survival (OS). Serum concentrations of CgA were determined before the treatment in 131 patients with NENs, including patients with tumours located in the pancreas, the small intestine, caecum, appendix and in the colon. No significant associations were identified in CgA concentrations between the control group and patients with NENs in appendix and colon. In patients with NENs of the pancreas and NENs of the small intestine and caecum, increased CgA levels were associated with lymph node involvement, distant metastases and a baseline liver involvement. Analyses revealed significantly higher CgA concentrations in patients with active disease compared to those without symptoms of NEN. In patients with NENs of the pancreas, CgA concentration was correlated with tumour grade and Ki67. Significantly higher CgA levels were also found in patients who died compared to those who lived. Analyses of PFS and OS revealed that CgA concentration was not a prognostic factor in patients with NENs of the pancreas. In patients with NENs of the small intestine and caecum, increased CgA concentrations are independent, poor prognostic factors for both PFS and OS. In conclusion, in patients with NENs in pancreas, CgA levels are associated with disease progression, while in patients with NENs in small intestine and caecum, its concentration is a predictive indicator for PFS and OS.

The Assessment of Clinical Usage and Prognostic Value of YKL-40 Serum Levels in Patients With Rectal Cancer Without Distant Metastasis.

BACKGROUND: Colorectal cancer is one of the most common and significant malignancies in the world. YKL-40 (chitinase-3-like protein 1) is involved in cell proliferation, migration, inflammation, and tissue remodeling; and serum levels of YKL-40 are associated with patient outcome in various cancers. The aim of this study was to assess the potential clinical usage of YKL-40 pretreatment serum levels as a prognostic biomarker in rectal cancer. METHODS: Concentrations of YKL-40 and standard tumor marker-Carcinoembryonic antigen (CEA)-were assessed in serum of 83 patients with rectal cancer without distant metastasis, and association with clinicopathological characteristics and disease-free and overall survival was evaluated. RESULTS: Concentration of YKL-40 was significantly higher in serum of patients with rectal cancer compared to healthy controls ( P = .0001), and YKL-40 levels were able to predict rectal cancer (area under the Receiver Operating Characteristic [ROC] curve = .769) with higher accuracy than CEA (area under the ROC curve = .728) in patients with early stage disease. Increased YKL-40 levels were significantly associated with age ( P = .001); however, no association with other clinicopathological characteristics was observed. Finally, in patients with recurrence, the percentage of cases with increased concentration of YKL-40 was significantly higher than in patients without recurrence ( P = .041), and Kaplan-Meier analysis demonstrated that elevated YKL-40 concentration is a predictor of poor overall survival in patients with rectal cancer. CONCLUSION: Pretreatment serum levels of YKL-40 may be a novel prognostic factor of overall and disease-free survival in patients with nonmetastatic colorectal cancer.

Serous Carcinoma of the Uterine Cervix, an Extremely Rare Aggressive Entity: A Literature Review.

BACKGROUND/AIMS: Serous carcinoma of the uterine cervix (USCC) is an extremely rare subtype. To establish the treatment strategy in patients with USCC is an important issue. METHODS: MEDLINE (PubMed) was searched for all articles published after the first publication by Lurie et al. [Eur J Obstet Gynecol Reprod Biol 1991; 40: 79-81], reporting woman diagnosed with USCC. Because of limited numbers of studies on the topic of the study, we could not keep a restriction of eliminating smaller sample sizes. RESULTS: A search of PubMed demonstrated that 113 cases of USCC have been reported in the literature since the first publication. The current treatment modality adopted for early cervical cancer is hysterectomy with bilateral iliac-obturator lymphadenectomy and postoperative radiotherapy (RT) or radiochemotherapy (RT-CT) if risk factors for cervical carcinoma appear. The treatment strategy for locally advanced USCC is preoperative RT-CT or chemotherapy (CHTH) with the intention to treat the patient surgically. The treatment option for disseminated disease is CHTH with paclitaxel and carboplatin. CONCLUSION: Risk factors and a more advanced clinical stage of USCC have an impact on poor outcomes despite the use of standard treatment methods, adapted for cervical cancer. The outside-pelvic failures tend to seek effective systemic treatment.

Clinical significance of pretreatment serum levels of VEGF and its receptors, IL- 8, and their prognostic value in type I and II endometrial cancer patients.

OBJECTIVES: The study aimed to assess the usefulness of the determination of cytokines: IL-8, VEGF and its soluble receptors: VEGF-R1, VEGF-R2 in patients with endometrial cancer (EC). MATERIAL/METHODS: The study group consisted of 118 patients with EC subjected to surgical treatment. Before the treatment we determined the serum levels of cytokines IL-8, and VEGF as well as VEGFR1 and VEGFR2 receptors. For comparison, the concentration of CA 125 was also measured. VEGFR1 and CA 125 were determined in the COBAS e601 system using Roche Diagnostics kits, while IL-8, VEGF and VEGFR2 were measured by ELISA assay using R&D Systems kits. RESULTS: The concentrations of IL-8, VEGF, VEGFR1 and CA 125 allowed to distinguish patients for the control group. The highest diagnostic sensitivity has been shown for the concentrations of VEGF (AUC = 0.904) and IL-8 (AUC = 0.818). Among all studied parameters only CA125 concentrations increased with the clinical stage; being significantly higher in patients in FIGO III-IV, than FIGO I-IB. In patients at the FIGO stage I-IB, complementary determinations of CA 125 and VEGF resulted in the largest increase of diagnostic sensitivity. Patients with metastases to the para-aortic lymph nodes had significantly higher levels of VEGF compared to subjects without such lesions. The concentrations of IL-8 were an independent prognostic factor in the assessment of overall survival in patients with type I endometrial cancer, while the concentrations of VEGFR2 in those with type II. CONCLUSIONS: In patients with endometrial cancer, the clinical usefulness of IL-8 and VEGFR2 measurements as the potential prognostic factors has been demonstrated. In type I, the concentrations of IL-8 determined before treatment can be helpful in predicting overall survival. In patients qualified to type II EC, the concentrations of VEGFR2 have the value of an independent prognostic factor for overall survival, this requires research on larger groups of patients. The increased levels of VEGF may be useful in the preoperative assessment of the status of para-aortic lymph nodes.

Preoperative serum levels of YKL 40 and CA125 as a prognostic indicators in patients with endometrial cancer.

OBJECTIVE: To evaluate the utility of YKL-40 and CA125 in endometrial cancer (EC) patients, and to determine their prognostic value in assessing the disease-free survival (DFS) and overall survival (OS). METHODS: We analyzed seventy-four EC patients, treated at a single institution and 25 healthy individuals. CA 125 serum level was evaluated in the Cobas 6000 system and YKL-40, using the ELISA method. RESULTS: Significantly increased serum level of YKL-40 and CA125 was in EC patients in FIGO I-IB when compared to healthy controls. CA125 was significantly higher in patients with more advanced FIGO stage vs. FIGO I, and also in patients with lymph node metastases vs. patients with no metastases. The obtained AUC for YKL-40 was higher than for CA125. There was, however, higher diagnostic sensitivity for YKL-40 in comparison to CA125, both in patients with type I and type II tumours. In patients who had disease progression, both the percentage of elevated concentration of CA 125 and YKL-40 was higher than in patients with remission. The Chi2 test demonstrated the statistically significant differences. The predictive value of CA125 in an aspect of DFS and OS was demonstrated. CONCLUSIONS: A high diagnostic sensitivity of YKL-40 in the early stages of the disease suggests the possibility of using this biomarker at an early diagnostic phase of patients with EC. The patients with increased levels of YKL-40 before treatment are also at the higher risk of relapse. The determination of CA125 before surgery may be helpful in the evaluation of the regional lymph nodes, and is a poor prognostic factor for OS and DFS.

The assessment of the prognostic value of tumor markers and cytokines as SCCAg, CYFRA 21.1, IL-6, VEGF and sTNF receptors in patients with squamous cell cervical cancer, particularly with early stage of the disease.

The aim of this study is to determine the prognostic value of tumor markers, as squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragment (CYFRA 21.1) and interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), soluble tumor necrosis factor receptor I (sTNF RI), and sTNF RII in patients with squamous cell carcinoma of the cervix. The subjects of analysis were 138 patients with stage I-IVA according to the International Federation of Gynecology and Obstetrics (FIGO) classification. The collected research material comes from one oncology center. During the 10 years of follow-up, 56 relapses and 53 deaths were observed, and recurrent disease in early stage was confirmed in 45 % of patients. The pretreatment serum levels of SCCAg and CYFRA 21.1, and cytokines IL-6, VEGF, sTNF RI, and sTNF RII were determined in all patients. The probability of disease-free survival (DFS) and overall survival (OS) was evaluated using the log-rank test and the Cox regression model. Based on the ROC curve analysis for patients with recurrence, the largest area under the curve was demonstrated for SCCAg and IL-6 and for patients who died, for SCCAg and VEGF. Cox analysis demonstrated that independent prognostic factor for DFS was only SCCAg and for OS cytokine IL-6 and SCCAg, but in patients with early stage the prognostic value for DFS was VEGF, whereas IL-6 and CYFRA 21.1 for OS. Serum level of VEGF, CYFRA 21.1 and IL-6 before treatment in patients with early stage cervical cancer appears to be an important prognostic factor.

Clinical value of human epididymis protein 4 and the Risk of Ovarian Malignancy Algorithm in differentiating borderline pelvic tumors from epithelial ovarian cancer in early stages.

OBJECTIVE: The clinical value of human epididymis protein 4 (HE4) and the possibility of its use in the differential diagnosis in patients with benign, borderline and epithelial ovarian cancer in early International Federation of Gynaecology and Obstetrics (FIGO) stages. STUDY DESIGN: The study group consisted of 205 women, including 60 with ovarian cancer, 18 with borderline tumors, 77 with benign lesions and 50 healthy subjects. In all the patients, before the treatment and in control groups, we determined CA 125 and HE4 in serum by electrochemiluminescence on the basis of the COBAS e601 system. For comparison of two independent groups, we used the U Mann-Whitney test. The analysis of the diagnostic power of the assessed parameters has been determined using the MedCalc statistical program. The probability of disease free survival (DFS) was evaluated using the log-rank test and Cox regression model. RESULTS: Concentrations of HE4, CA 125 and Risk of Ovarian Malignancy Algorithm (ROMA) value were significantly higher in early ovarian cancer than in patients with benign (P<0.0001) and borderline tumors (P<0.002), the receiver operating characteristics (ROC) curves, demonstrated the highest diagnostic sensitivity for the ROMA score, as well post (AUC=0.817) as pre-menopausal (AUC=0.806). HE4 concentrations (P<0.021) and the value of the ROMA score (P<0.004) were significantly higher in patients with relapse than in patients in remission. There was no connection between concentrations of the studied tumor markers and DFS. CONCLUSIONS: Determination of HE4 serum concentrations has a significant clinical value, especially in patients with benign lesions and elevated CA 125 levels. The combined assessment of HE4, CA 125 and the ROMA algorithm is helpful in differentiating benign tumors and borderline pelvic tumors from epithelial ovarian cancer in early FIGO stages. Determination of HE4, CA 125 and ROMA algorithm is not helpful in differentiating patients with borderline from benign lesions.

Serum markers in early-stage and locally advanced melanoma.

The identification of prognostic factors in cutaneous melanoma allows choosing the most effective treatment, especially in group of patients with locoregional disease. Markers related to carcinogenesis and angiogenesis in particular have effect on the course of the disease. The aim of this study was to evaluate clinical utility of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase 1 (TIMP-1), and YKL-40 in serum of melanoma patients at pathological stages I-III. We included 148 adult patients with melanoma. The median follow-up was 40 months. Disease recurrence was observed in 43 patients; 3-year disease-free survival (DFS) rate was 71.7%; 35 patients died; and the 3-year overall survival (OS) rate was 85%. Concentrations of VEGF, MMP-2, MMP-9, TIMP-1, and YKL-40 were measured by ELISA kits. VEGF, MMP-9, TIMP-1, and YKL-40 were significantly higher in group of patients than in controls. Increased concentrations of TIMP-1 were related to patient survival, which in the group of lower and increased TIMP-1, disease-free survival amounted to 81 vs. 61% (p = 0.014) and overall survival -88 vs. 82% (p = 0.050), respectively. An increased concentration of YKL-40 was observed in 59% of patients with ulceration and in 26% of patients without ulceration (p = 0.012). We have found a clinically significant correlation between YKL-40 and MMP-9 (rho = 0.363; p = 0.004) as well as YKL-40 and VEGF (rho = 0.306; p = 0.018). In melanoma patients at stages I-III, the high concentrations of TIMP-1 in serum predicted adverse prognosis. YKL-40 was associated with ulceration of primary tumor, which is a very important prognostic factor.

The matrix metalloproteinase-7 and pro-enzyme of metalloproteinase-1 as a potential marker for patients with rectal cancer without distant metastasis.

The aim of this study was the evaluation of clinical usage of metalloproteinase (MMP): proMMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in serum of patients with rectal cancer, as well as the selection of parameters of the greatest diagnostic sensitivity and the determination of their relation with clinicopathological features, what is more, the demonstration whether their concentrations may have a prognostic value in the assessment of disease-free survival (DFS) and overall survival (OS). The study comprised 100 patients with rectal cancer including 29 women and 71 men. The tested group was comprised of qualified patients without distant metastasis (M0). It was demonstrated that in patients with rectal cancer, the concentrations of MMP-9, MMP-7, and proMMP-1 as well as TIMP-1 were significantly higher in comparison to the reference group. On the basis of ROC curves, the greatest diagnostic sensitivity of MMP-9 was demonstrated. When evaluating the correlation of tested parameters with the size of the tumor (T1-T2 vs T3-T4), essential differences were shown for proMMP-1 concentrations. The highest percentage of patients with progression had an increased concentration of MMP-7 and TIMP-1. During a 5-year follow-up, univariate log-rank analysis had shown an essential dependence between the concentration of MMP-7 in men and DSF which was confirmed in Cox multivariate analysis. It was demonstrated that the pretreatment concentration of proMMP-1 may be clinically useful when evaluating the mass of the tumor, whereas MMP-7 may be a prognostic factor for DFS in men with rectal cancer without distant metastasis.

Discriminant analysis involving serum cytokine levels and prediction of the response to therapy of patients with Hodgkin lymphoma.

Current standard diagnostic methods do not identify patients with Hodgkin lymphoma (HL), who are at high risk of failure after the first-line treatment. In HL patients, serum cytokine levels are frequently elevated and correlate with clinical and pathological features of the disease as well as with disease-free survival and overall survival. The aim of this study was to investigate if pretreatment serum cytokine and cytokine receptor concentrations evaluated by discriminant analysis could be predictive of response to standard first-line treatment in HL. The study involved 48 previously untreated patients with histologically confirmed classical HL and no EBV infection. Treatment included chemotherapy and involved field radiotherapy or radiotherapy alone. At the end of treatment, 71 % of patients reached complete response (CR), and 29 %, in partial response. To identify parameters predictive of nonachievement of CR after the first-line treatment, the discriminant analysis was used. The following variables were included in the analysis: clinical stage, sex, age, histologic subtype, bulky mediastinal mass, systemic symptoms and the number of involved nodal areas, lactate dehydrogenase (LDH) activity, and serum levels of 12 cytokines/cytokine receptors. The resulting classifying function assigned a discriminant power to the following variables: the levels of vascular endothelial growth factor, interleukin-8, macrophage colony stimulating factor, basic fibroblast growth factor, soluble tumor necrosis factor receptor I, and LDH activity. The accuracy of predicting CR and non-CR was 94 and 43 %, respectively.

[The prognostic role of clinical factors, VEGF, IL-8 and sTNF-R1 in cutaneous melanomas at locoregional stage]. / Znaczenie prognostyczne czynników klinicznych oraz oznaczania stezenia VEGF, IL-8 i sTNF-R1 w czerniakach skóry o zaawansowaniu lokoregionalnym.

UNLABELLED: The treatment results of patients with locoregional melanoma are still not satisfactory - up to 50% of patients experience recurrence and (or) disease dissemination. The aim of the study was to assess the prognostic value of clinical factors and serum cytokines of patients with cutaneous melanoma in locoregional stage. MATERIAL AND METHODS: 149 patients at stage I-III according AJCC treated between 2007-2010 were included. Pre-surgery serum levels of VEGF IL-8 and sTNF-R1 were analyzed by ELISA method in 74 melanoma patients and 50 healthy controls. The median follow-up time was 16 months (range: 1-81 months). RESULTS: The most important factors influencing the disease-free survival (DFS) are: staging system according to AJCC) (p < 0.001), regional nodal stage (pN) (p < 0.001), primary tumor (Breslow) thickness (pT) (p = 0.013) and melanoma ulceration (p = 0.004). The serum levels of selected cytokines were significantly higher in melanoma patients than in healthy volunteers (VEGF, p < 0.001; sTNF-R1, p < 0.001; IL-8, p = 0.001). There were no significant relationships between level of cytokine, recurrence or clinical/pathological parameters. CONCLUSIONS: The AJCC staging system gives the most accurate insight into prognosis of melanoma patients at locoregional stage after primary therapy. Cytokine serum profile in melanoma patients at locoregional stage has limited value for predicting tumor burden and treatment outcomes.