Joanna Jonska-Gmyrek

The value of tumor marker and cytokine analysis for the assessment of regional lymph node status in cervical cancer patients.

The aim of the study was to evaluate the utility of the measurements of the circulating tumor markers, squamous cell carcinoma antigen (SCCA), CA125, carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21.1), and the cytokines, interleukin-6 and vascular endothelial growth factor (VEGF), to estimate regional lymph node involvement in patients with cervical cancer. The study comprised 182 untreated patients with cervical cancer. The regional lymph node status was assessed either by the postsurgical histopathologic examination or by the computed tomography (CT). Concentrations of SCCA, CEA, and CA125 were determined using the Abbott Instruments system, of CYFRA 21.1 by the Roche kits, and of IL-6 and VEGF by the ELISA of R&D Systems (Minneapolis, MN). For the statistical analyses, Mann–Whitney U test and χ2 test were applied. Serum levels of SCCA, CEA, CA125, CYFRA 21.1, IL-6, and VEGF were measured in patients with specified pelvic and para-aortic lymph node status. SCCA, CA125, and IL-6 levels were found to be significantly higher in patients with lymph node metastases than in those with no lymph node involvement. Also, the percentage of patients with simultaneously elevated concentrations of SCCA and CA125 or SCCA and IL-6 differed depending on the lymph node status and was significantly higher in the series of patients with lymph node metastases. Simultaneous assessment of serum levels of SCCA and CA125 or SCCA and IL-6 in patients with cervical cancer may be useful for the regional lymph node evaluation, especially in patients with advanced stages, when the lymph nodes are examined only by CT, with no histologic confirmation.

HDR brachytherapy combined with interstitial hyperthermia in locally advanced cervical cancer patients initially treated with concomitant radiochemotherapy – a phase III study

BACKGROUND AND PURPOSE The aim of this randomised trial was to investigate whether hyperthermia (HT) combined with interstitial brachytherapy (ISBT) has any influence on local control (LC), disease-free survival (DFS), or acute and late side effects in patients with advanced cervical cancer. MATERIALS AND METHODS After radiochemotherapy, consecutive patients with cervical cancer (FIGO stage II-III) were randomly assigned to two treatment groups, either ISBT alone or ISBT combined with interstitial hyperthermia (ISHT). A total of 205 patients were included in the statistical analysis. Once a week, HT, at a temperature above 42.5°C, was administered for 45min before and during the HDR BT. RESULTS The median follow-up time was 45months (range 3-72months). An effect of hyperthermia was not detected for disease-free survival (DFS) (log-rank test: p=0.178) or for local control (LC) (p=0.991). According to Coxs analysis, HT did not significantly influence failure or interactions with potential prognostic factors for LC or DFS. Statistical differences were not observed for the distribution of early and late complications between the HT and non HT groups. CONCLUSIONS ISHT is well-tolerated and does not affect treatment-related early or late complications. Improvements in DFS and LC were not observed following the addition of ISHT to ISBT.

HDR brachytherapy for the reirradiation of cervical and vaginal cancer: Analysis of efficacy and dosage delivered to organs at risk

OBJECTIVE To evaluate the efficacy and toxicity of HDR brachytherapy (BT) for the reirradiation of cervical or vaginal cancer arising within a previously irradiated area with a special focus on dosage delivery to organs at risk. METHODS Twenty consecutive patients with cervical (N = 19) or vaginal (N = 1) cancer were reirradiated with curative intent using BT with or without external beam irradiation and hyperthermia. The median biologically equivalent dose in 2 Gy fractions (EQD2), assuming α/β = 10, for reirradiation was 48.8 Gy (range: 16.0-91.0 Gy), and the median cumulative EQD2 (for primary treatment and reirradiation) was 133.5 Gy (range: 96.8-164.2 Gy). The median follow-up after retreatment was 31 months (range: 6-86 months). RESULTS The 3-year overall survival (OS) rate was 68% (95% confidence interval [CI]: 44%-91%). The 3-year disease-free survival (DFS) rate was 42% (95% CI: 19%-65%). The 3-year local control (LC) rate was 45% (95% CI: 22%-69%). For nine patients who received 3D treatment planning, the median cumulative EQD2 to 2 cm(3) of rectum was 94.4 Gy (range: 67.1-118.8 Gy) and to 2 cm(3) of bladder was 99.3 Gy (range: 70.4-122.3 Gy). Grade 3 late toxicity was observed in 3 patients (15%). An interval between primary RT and reirradiation of ≤ 12 months and a tumor diameter >3 cm were significant prognostic factors adversely affecting OS, DFS and LC. CONCLUSIONS HDR BT is a valuable method for the reirradiation of cervical cancer. A cumulative EQD2 of approximately 100 Gy was safely delivered to 2 cm(3) of the bladder and the rectum.

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.

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.

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.

HDR brachytherapy combined with interstitial hyperthermia in locally advanced cervical cancer patients initially treated with concomitant radiochemotherapy: A phase I study

Background and purpose: The aim of this study was to investigate whether hyperthermia (HT) combined with interstitial brachytherapy (ISBT) has any influence on acute and late side effects in patients with advanced cervical cancer. Local control (LC) and disease-free survival (DFS) were also analysed. Materials and methods: Following the completion of radiochemotherapy, patients with cervical cancer (FIGO stages I–III) were assigned to two treatment groups, either ISBT combined with interstitial hyperthermia (ISHT) or ISBT alone as a control group. Selection criterion for the ISBT combined with HT group was advanced cervical cancer with poor response to external beam radiotherapy. A total of 76 patients were included in the statistical analysis. Once a week, HT (at a temperature above 42.5°C) was administered for 45 min before and during high dose rate (HDR) brachytherapy (BT) in 43 patients. Four HT treatments were administered. Results: The median follow-up time was 43 months (range 4–73 months). Significant differences were not observed for the distribution of early and late complications between the HT and no HT groups. Despite this, LC was similar in both groups. The 5-year DFS for the BT and BT + HT groups was 73.6% and 65.8%, respectively. The 5-year LC for the BT and BT + HT groups was 89% and 83%, respectively. For the majority of patients the maximum temperature level of 44–45°C was achieved during the ISHT. Conclusions: ISHT is well tolerated and does not affect treatment-related early or late complications.

Testicular teratomas: a growing problem?

Testicular teratomas represent a specific entity within the group of germ-cell tumours. They may comprise elements of all three germ layers. In contrast to prepubertal benign teratomas observed in infants and adolescents, postpubertal teratomas originate from the malignant germ-cell precursor. Given the good prognosis and curability of most patients with germ-cell tumour, medical oncologists and urological surgeons must be well acquainted with the principles of teratomas management. Surgery plays the decisive part in teratomas treatment, as these tumours are resistant to radio- and, to some extent, chemotherapy. In this article we concentrate on the management of post-chemotherapy resection of teratomatous masses, with special attention to the phenomenon of ‘growing teratoma syndrome’ and somatic-type transformation of teratomas. To understand the nature of teratomas better, we begin with a glimpse of their biological, molecular and immunohistochemical features. Managing germ-cell tumours, teratomas in particular, in high-volume reference centres is of utmost importance to maintain and increase the survivorship rate in these patients.

Contemporary treatment of metastatic renal cell carcinoma

Renal cell carcinoma is the 14th most common cancer worldwide. It is a heterogeneous group of histopathological entities, of which the most common is clear cell renal cell carcinoma. Approximately 20–30% of patients present initially with metastatic disease and an additional 20% will progress after radical surgical treatment. Metastatic disease that is non-feasible for surgical treatment remains incurable. Numerous studies have demonstrated that—with the introduction of new drugs—the treatment outcomes of metastatic disease have improved. The development of new therapies as well as the optimization and individualization of procedures allow us to hope for further progress in this area.