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.

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.

Radiotherapy in testicular germ cell tumours - a literature review.

Testicular germ cell tumours (GCT) represent about 1-2% of malignant in men. The essential therapeutic option for early-stage GCT is radical orchiectomy (RO), except in situations that require immediate chemotherapy in patients with a massive dissemination and unequivocally elevated levels of tumour markers. Postoperative radiotherapy (PORT) in patients with testicular seminoma in Clinical Stage I (CS I) is one of the treatment options next to active surveillance (AS) and chemotherapy (CHTH). Regardless of the procedure, five-year survival in this group of patients ranges between 97% and 100%. In the article, we present the literature review pertinent to therapeutic options, with a focus on radiotherapy. We have searched MEDLINE (PubMed) for all studies on patients with GCT treated with radiation therapy during the last 20 years, and the current therapeutic recommendations. We used the following keywords: germ cell tumours, testis, seminoma, non-seminoma, radiotherapy, outcome.

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.

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.

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.

Evaluation of Salivary Biomarkers and Spirometry for Diagnosing COPD in Non-Smokers and Smokers of Polish Origin.

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.

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.

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.

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.

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.

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.

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.

Serum soluble tumour necrosis factor receptor type I concentrations independently predict prognosis in patients with breast cancer.

BACKGROUND: The aim of this study was to exploit the potential clinical use of circulating cytokine assessment in patients with breast cancer. METHODS: The following circulating cytokines were measured in 210 histopathologically confirmed, untreated breast cancer patients: interleukin 6 (IL-6), tumour necrosis factor-α (TNFα), interleukin 8 (IL-8), soluble tumour necrosis factor receptor type I (sTNF RI), sTNF RII, interleukin 1 receptor antagonist (IL-1ra), interleukin 10 (IL-10), macrophage colony-stimulating factor, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The patients have been followed-up for 10 years. RESULTS: bFGF and VEGF showed the highest diagnostic sensitivity. Only IL-6 concentrations were related to the clinical stage. A high percentage of patients in clinical stage I showed increased serum sTNF RII, VEGF and bFGF concentrations, of which only sTNF RII was found to be increased in a smaller percentage of patients with more advanced disease compared with patients with early stage disease. Patients aged 50 years and more presented with significantly higher concentrations of sTNF RI, IL-10, IL-6 and VEGF compared with younger patients. In multivariate analysis, a significant value of pretreatment serum sTNF RI concentrations, next to stage and oestrogen receptors status, was its utility as an independent prognostic factor of the overall survival in patients with breast cancer. CONCLUSIONS: Serum sTNF RI may be considered an additional, independent and clinically useful factor of poor prognosis in patients with breast cancer.

Clinical significance of serum CA-125 and soluble tumor necrosis factor receptor type I in cervical adenocarcinoma patients.

HYPOTHESIS: The purpose of this study was to answer the question whether the measurement of the pretreatment tumor markers and cytokine levels would be of clinical use in patients with cervical adenocarcinoma. METHODS: CA-125, carcinoembryonic antigen (CEA), and squamous cell carcinoma (SCC), as well as interleukin 6 (IL-6), IL-8, vascular endothelial growth factor, IL-1 receptor antagonist, soluble tumor necrosis factor receptor type I (sTNF RI), and sTNF RII, were assessed in the sera of 120 cervical adenocarcinoma patients. RESULTS: CA-125 presented a better diagnostic sensitivity than did CEA and SCC, whereas the concentration of most cytokines, except for sTNF RII, revealed higher sensitivity, than did the standard tumor markers. The highest sensitivity was found for sTNF RI. The concentrations of the examined parameters were found to be significantly higher in patients with advanced stage (IIB-IV) as compared with patients with I-IIA stage. [Float1]Serum concentration of IL-6 was the only one that differs significantly, depending on the histological grade. During the 3-year follow-up, 25 patients relapsed, and 73 patients were disease-free. Significantly higher pretreatment serum concentrations of the examined parameters (except for SCC and IL-1 receptor antagonist) were found in patients who developed recurrences. Soluble tumor necrosis factor receptor type I and CA-125 were found to present the highest sensitivity, with areas under the receiver operating characteristic curve of 0.833 and 0.809, respectively. As the result of univariate analysis, CA-125, CEA, sTNF RII, IL-6, sTNF RI, and clinical stage were considered factors of poor prognosis. Multivariate analysis has proven that CA-125 and clinical stage were the only significant independent prognostic factors of the disease-free survival. CONCLUSION: CA-125 is an independent prognostic factor for disease-free survival. Our results have also demonstrated that sTNF RI is probably the most useful marker in cervical adenocarcinoma patients, especially in the early stages of disease.

Adenocarcinoma histology is a poor prognostic factor in locally advanced cervical cancer.

OBJECTIVE: This retrospective study aimed to compare prognostic factors and survival between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in locally advanced cervical cancer treated at a single center. METHODS: All medical records of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB or IIIA,B, treated between 2004 and 2012, were reviewed. We treated patients with chemoradiotherapy (CRT) followed by brachytherapy (BT). Multivariate logistic regression and Cox proportional hazard models were used to analyze clinicopathological characteristics, patterns of care and outcomes. RESULTS: We included in the analysis 161 patients (52 AC; 109 SCC). Patients with AC were younger (age 50 vs. 55 years), more likely to die from the disease (HR: 1.60; 95% CI: 1.26-2.58; p = .001) and to have disease recurrence (HR: 1.69; 95% C.I: 1.21-2.12; p = .004) than those with SCC. The other significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in AC were FIGO stage (p = .001; p = .002), WHO status (0 vs. 1-3; p = .003; p = .04), and hemoglobin level (<12 g/dl>; p = .04; p = .02). The 5 year overall survival for stage II of AC and SCC was 63% and 82% (p = .03), and for IIIA,B it was 33.6% and 73% (p = .0005). The 5 year RFS for AC and SCC stage FIGO IIIA,B was 24% and 57% (p = .001). CONCLUSIONS: Adenocarcinoma histology negatively impacts OS and RFS for advanced cervical cancer. Histology-specific therapy may be an opportunity for survival improvement in these women.

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.