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BACKGROUND Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1α/HIF2α and their selected target genes in primary tumors and corresponding bone metastases. RESULTS Expression of HIF2α was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1α was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2α and high HIF1α as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2α protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1α gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2α and VEGFR2 expressions as favorable prognostic factors. HIF1α/HIF2α-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS Expressions of HIF1α and HIF2α as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS We identified HIF2α protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1α, increased HIF2α expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC.

Our aim was to assess the efficacy and adverse effects of cabazitaxel (CBZ), a chemotherapeutic agent that can be administered to patients with metastatic castrate resistant prostate cancer (mCRPC) after docetaxel (DOC) therapy. We retrospectively analyzed data of CBZ received by mCRPC patients in 12 Hungarian oncological centers between 01/2016 and 06/2017. CBZ (25 or 20 mg/m2 q3w) was administered after DOC. Physical and laboratory examinations were performed in every cycle, tumor response was evaluated in every third cycle based on PCWG2 criteria. Adverse effects were evaluated based on CTCAE 4.0. Data of 60 patients were analyzed. CBZ was administered in 2nd and 3rd lines in 31.6% and 46.6%, while in 4th and 5th lines in 15% and 6.6% patients, respectively. Its starting dose was 25 mg/m2 and 20 mg/m2 in 65% and 35% of cases, respectively. The median number of cycles was 5. Progression-free survival and overall survival were 5.52 and 15.77 months, respectively. Survival results were similar in case of DOC-CBZ-ART/alfaradin and DOC-ART/alfaradin-CBZ sequences. Adverse effects were detected in 63,3% of patients. The most common adverse effects were neutropenia, anemia, and diarrhea. Our observations suggest that CBZ, with the appropriate support and chemotherapeutic experience, is well-tolerated and effective therapy of mCRPC after DOC.

Enzalutamide, abiraterone-acetate, and cabazitaxel are licensed post-docetaxel treatments of metastatic castration-resistant prostate cancer (mCRPC) in Hungary. The objectives of the study were to assess the efficacy and safety of post-docetaxel enzalutamide treatment and to compare it with abiraterone and with cabazitaxel, using Medline-based systematic literature search, and meta-analysis of randomised controlled trials (RCT). Overall 3 RCTs were included, one for each substance. Compared to placebo, enzalutamide proved significant efficacy in each primary and secondary endpoint. Enzalutamide extended median overall survival by 4.8 months. Due to lack of a common comparator in the cabazitaxel trial, only enzalutamide and abiraterone were involved in an indirect comparison. No significant difference was identified either in the primary endpoint (overall survival) (HR: 0.97, 95% CI: 0.75-1.25) or in frequencies of adverse events between these two treatments. However, enzalutamide was significantly more efficacious than abiraterone in 3 secondary endpoints: time to prostate-specific antigen (PSA) progression (HR: 0.43, 95% CI: 0.31-0.59), radiographic progression-free survival (HR: 0.6, 95% CI: 0.5-0.72), and PSA response rate (RR: 7.48, 95% CI: 2.83-19.72). Enzalutamide therapy proved clinical efficacy and safety in patients with post-docetaxel mCRPC. In the indirect comparison, efficacy and safety of abiraterone and enzalutamide were found to be similar.

Pazopanib, a tyrosine kinase inhibitor, is one of the new registered first-line therapeutic options in the treatment of metastatic clear cell renal carcinoma. Our aim was to evaluate the efficiency and toxicity of first-line pazopanib therapy administered for patients with metastatic clear cell renal carcinoma with good- and medium prognosis according to MSKCC criteria. Between January and May, 2011, 24 patients have been treated with pazopanib in 8 oncology centers in Hungary, out of them 21 patients' data were analyzed. The mean age was 65.3 (49-81) years, 10 males and 11 females. According to MSKCC the prognosis was good and medium in 3 and 18 cases, respectively. Daily dose of pazopanib was 800 mg administered continuously in 28 day cycles. Dose reduction was performed according to the instructions of the registration study. Tumor response was evaluated according to RECIST 1.0. Currently 6 (28.6%) patients are on treatment. Dose reduction was necessary in 6 (28.6%) cases with an average duration of 14.55 (7-150) days. Mean±SE daily dose was 692.97±13.67 (400-800) mg. Median PFS was 12.41 months (95% CI 11.52-12.94 months). Complete remission (CR), as the best tumor response occurred in 2 (9.5%) cases. Partial remission (PR), stable disease (SD) and progression was observed in 6 (28.6%), 10 (47.6%) and 3 (14.3%) cases, respectively. Objective tumor response was observed in 8 pts (38%). Median survival could not be statistically analyzed yet due to the insignificant number of fatal outcomes. Median follow-up was 25.22 months (95% CI 2.47-28.1 months). As common side-effect fatigue, weakness and diarrhea occurred in 11 (52.4%), 9 (42.9%) and 8 (38%) cases, respectively. Besides these, worsening of high blood pressure and ALT/AST elevation was observed in 5 (23.8%) and 6 (28.6%) cases, respectively. Based on the initial Hungarian experiences, pazopanib is a well tolerable product and can be administered safely. According to our results its efficiency in terms of tumor response and progression-free survival is comparable to the results of the registration study.

Objective: To investigate the patterns of expression of the junctional proteins beta-catenin and claudins in different prognostic groups of patients with prostatic cancer, to determine their value as prognostic markers., Patients and Methods: We evaluated the samples of 30 patients who had a radical prostatectomy for organ-confined cancer (pT2N0M0), men with clinically advanced cancer, and a control group with benign prostatic hyperplasia. Using immunohistochemistry applied to tissue microarrays, each group was evaluated for claudin-1, -2, -3, -4, -5, -7, -8 and -10, and beta-catenin expression., Results: There were differences among the three groups in the expression of claudin-1 (P = 0.001), -2 (P = 0.014), -3 (P = 0.027), -4 (P = 0.001), -8 (P = 0.001) and beta-catenin (P = 0.002), regardless of Gleason score. By contrast, claudin-5, -7 and -10 patterns were not significantly different among the groups. Furthermore, claudin-1 (P = 0.014) and -4 (P = 0.004) could be used to distinguish between those patients who had metastases and those who did not., Conclusions: The pattern of claudin expression could be a novel diagnostic marker in re-classifying adenocarcinomas, and an additional sensitive predictive factor for a clinically poor prognosis. Our results suggest that patients with organ-confined and advanced cancer are subsets with distinct claudin expression profiles, and that claudin-4 is related to cellular differentiation in prostate cancer, which is not only the receptor molecule for the Clostridium perfringens enterotoxin, and thus a theoretical future therapeutic target for prostate cancer, but also a marker of progression.

Purpose: To describe the technique and early results of ultrasound (US)-guided interstitial prostate brachytherapy (BT) introduced at our institute., Materials and Methods: Between December 2001 and July 2002, ten patients with clinically localised, high risk prostate cancer were treated with external beam irradiation and high dose rate (HDR) BT boost at the Radiotherapy Department of National Institute of Oncology, Budapest. Using CT based treatment planning, 46 Gy was delivered to the whole pelvis and then the prostate and vesicles were treated up to a total dose of 60 Gy by conformal external beams. BT boost was given in the first four weeks of external irradiation. Nine patients were under total androgen blockade. The interstitial BT was performed in spinal anaesthesia. Steel needles were implanted into the prostate using transrectal US guidance. The Ir-192 HDR isotope was loaded into the needles by remote control after-loading equipment. Treatment planning was based on transversal ultrasound images. The target volume was the whole prostate. The median number of inserted needles was 9 (range: 5-13). The prescribed dose to the surface of the prostate was 8 or 10 Gy, and the maximum reference dose of the urethra or rectum was less than 125% and 80% of the prescribed dose, respectively. PSA (prostate specific antigen) levels and acute side effects were monitored and documented regularly., Results: The prescribed treatment was completed on all patients. The median follow-up time from the completion of the radiotherapy was 6 months (range: 2-11 months). Perioperative side effects (haematuria caused by puncture of the bladder) occurred in two cases. Acute grade 2 toxicity was observed in four patients: genitourinal inflammation in 4, and proctitis in 2 cases. No PSA relapse occurred so far., Conclusion: In our study we described our technique of interstitial BT boost as a part of prostate radiotherapy used for the first time in Hungary. The US based treatment planning resulted in adequate dose distribution in all cases. Incidence of perioperative and acute side effects were comparable to data known from the literature. Appropriate technical background and well organised team work are needed to ensure the good quality of the treatment.

Objective: To report a rare case of tumour-to-tumour metastasis with differential diagnostic considerations., Methods and Results: We report the operation of a Sylvian fissure secretory meningioma in a 48 year-old woman. The tumour was suspicious of a metastasis related to a pulmonary adenocarcinoma operated 4 months before. Histopathology confirmed metastatic adenocarcinoma in a secretory meningioma., Conclusions: Both secretory meningioma and tumour-to-tumour metastasis are rare, and to our knowledge this is the first report of such a rare coincidence. Secretory meningioma can simulate metastases both clinically (extensive oedema, space occupation, carcinoembryonic antigen secretion) and pathologically (secretory inclusions, positivity for cytokeratin 7 and carcinoembryonic antigen and negativity for vimentin), and therefore may cause a special differential diagnostic dilemma.

The authors report on a rare manifestation of soft tissue metastasis of operated colorectal cancer. Interestingly, two years after the resection a etastasis with extremely high tumor marker level (CEA, CA 19.9) was detected. Marker elevation preceded the manifestation of metastasis by nearly half a year. After the metastasectomy the disease progressed. The authors briefly refer to the epidemiology of colorectal cancer, the complex therapy and the follow up.

Complete removal of the tumour or deep invasion can be proven by repeated transurethral resection of bladder wall at the previous tumour site. Six weeks after transurethral resection of bladder tumour (TURB), in all but TaG1 cases repeated resection were performed for the evaluation of radicality in 62 patients, 43 males and 19 females, suffering bladder cancer, from October 1998. In the case of positive histology another resection was performed for security reason. In the case of 38 superficial (Tis, Ta, T1) cancers, repeated resection revealed negative, identical or different T stage compared with previous histology in 28, 5 and 5 cases, respectively. In 7 cases repeated resection was applied as second intervention after the incomplete resection of large tumour mass. Indication of repeated resection was insufficient depth of resection and carcinoma in situ in 13 and 4 cases, respectively. Based on our data, we conclude that repeated resection should be performed when tumour-free status is not justified and biopsy according to Bressel was not taken.