Maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: Outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status in the ORZORA trial.

BACKGROUND: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. METHODS: Patients received maintenance olaparib capsules (400 mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability. RESULTS: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3 months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected. CONCLUSIONS: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.

[Synchronous tumor treatment in the presence of gynecologycal cancer in three patients]. / Nogyógyászati daganatok esetén jelentkezo szinkrón tumorok együlésben való ellátása három eset kapcsán.

During the examination of patients, the probability of the occurrence of a secondary tumour is 15.2%, while that of a tertiary tumour is 1.3% [1]. The aim of this article is to draw attention to the fact that the surgical treatment of synchronous tumours in one session, if proper professional background is ensured, provides definite benefits for the patients. No protocols for the treatment of multiple tumours can be found in the relevant literature; mostly descriptions of cases are available to give orientation. The preoperative stage of the diseases, the examination protocol, the surgical procedure and the biopsy results are detailed in the study. In the article, the treatment of a triplex tumour - vulva, rectum and sigma tumour -, a large colon tumour and an endometrial adenocarcinoma with open surgery is described as well as the minimally invasive surgery of a rectal and synchronous endometrial adenocarcinoma with a patient who has gone through neoadjuvant therapy are presented. The three cases presented here prove that the surgical treatment in one session was clearly beneficial for the patients, let alone cost-efficiency. The article is not about the discussion of post-surgical or adjuvant treatments; decisions about these are to be made by the multidisciplinary professional committees of the hospitals, based on the particular situations. Orv Hetil. 2023; 164(2): 70-75.

[The primary surgical therapy of a synchronous sigmoid, rectal and vulvar cancer]. / Szinkron szigmabél-, végbél- és szeméremtesti daganat primer mutéti ellátása. Esetismertetés.

Malignant tumors were the leading cause of death in Hungary between 1990 and 2018 according to the central statistical office (www.ksh.hu). While the mortality of cerebrovascular diseases is decreasing, cancer-related mortality is getting worse, despite the improvement of both diagnostic and therapeutic opportunities. The exact number of synchronous double and triple cancers in Hungary is unknown, and their therapeutic pathways are unclear. Currently there is no data available regarding these questions in the National Cancer Registry. In this case report we present the diagnostic and therapeutic algorithm of a patient with a triple malignancy.

Currently favored sampling practices for tumor sequencing can produce optimal results in the clinical setting.

Tumor heterogeneity is a consequence of clonal evolution, resulting in a fractal-like architecture with spatially separated main clones, sub-clones and single-cells. As sequencing an entire tumor is not feasible, we ask the question whether there is an optimal clinical sampling strategy that can handle heterogeneity and hypermutations? Here, we tested the effect of sample size, pooling strategy as well as sequencing depth using whole-exome sequencing of ovarian tumor specimens paired with normal blood samples. Our study has an emphasis on clinical application-hence we compared single biopsy, combined local biopsies and combined multi-regional biopsies. Our results show that sequencing from spatially neighboring regions show similar genetic compositions, with few private mutations. Pooling samples from multiple distinct regions of the primary tumor did not increase the overall number of identified mutations but may increase the robustness of detecting clonal mutations. Hypermutating tumors are a special case, since increasing sample size can easily dilute sub-clonal private mutations below detection thresholds. In summary, we compared the effects of sampling strategies (single biopsy, multiple local samples, pooled global sample) on mutation detection by next generation sequencing. In view of the limitations of present tools and technologies, only one sequencing run per sample combined with high coverage (100-300 ×) sequencing is affordable and practical, regardless of the number of samples taken from the same patient.

Predictive biomarkers of platinum and taxane resistance using the transcriptomic data of 1816 ovarian cancer patients.

OBJECTIVE: The first-line chemotherapy for ovarian cancer is based on a combination of platinum and taxane. To date, no reliable predictive biomarker has been recognized that is capable of identifying patients with pre-existing resistance to these agents. Here, we have established an integrated database and identified the most significant biomarker candidates for chemotherapy resistance in serous ovarian cancer. METHODS: Gene arrays were collected from the GEO and TCGA repositories. Treatment response was defined based on pathological response or duration of relapse-free survival. The responder and nonresponder cohorts were compared using the Mann-Whitney and receiver operating characteristic tests. An independent validation set was established to investigate the correlation between chemotherapy response for the top 8 genes. Statistical significance was set at p < 0.05. RESULTS: The entire database included 1816 tumor samples from 12 independent datasets. From analyzing all the genes for platinum + taxane response, we identified the eight strongest genes correlated to chemotherapy resistance: AKIP1 (p = 1.60E-08, AUC = 0.728), MARVELD1 (p = 2.70E-07, AUC = 0.712), AKIRIN2 (p = 2.60E-07, AUC = 0.704), CFL1 (p = 8.10E-08, AUC = 0.694), SERBP1 (p = 8.10E-07, AUC = 0.684), PDXK (p = 1.30E-04, AUC = 0.634), TFE3 (p = 7.90E-05, AUC = 0.631) and NCOR2 (p = 1.90E-03, AUC = 0.611). Of these, the independent validation confirmed TFE3 (p = 0.012, AUC = 0.718), NCOR2 (p = 0.048, AUC = 0.671), PDXK (p = 0.019, AUC = 0.702), AKIP1 (p = 0.002, AUC = 0.773), MARVELD1 (p = 0.044, AUC = 0.675) and AKIRIN2 (p = 0.042, AUC = 0.676). An online interface was set up to enable future validation and ranking of new biomarker candidates in an automated manner (www.rocplot.org/ovar). CONCLUSIONS: We compiled a large integrated database with available treatment and response information and used this to uncover new biomarkers of chemotherapy response in serous ovarian cancer.

High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach.

BACKGROUND: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data. METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads. RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found. CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.

Mixed Ovarian Tumor Composed of Brenner Tumor and Adult-Type Granulosa Cell Tumor: A Case Report of a Very Rare Mixed Ovarian Tumor and a Review of the Literature.

A combination of ovarian tumors with the same histogenetic origin but different histologic subtype is relatively common, whereas a co-occurrence of tumors with different histogenetic origin is rare. We report a case of mixed ovarian tumor composed of Brenner tumor and adult-type granulosa cell tumor, a combination that to the best of our knowledge has not been reported in the literature until now.

[Investigating the predictive value of RMI and ROMA indices in patients with ovarian tumors of uncertain dignity]. / Az RMI- és a ROMA-index petefészekrákelõrejelzõ hatékonyságának vizsgálata adnextumorokban.

We were investigating the predictive value of RMI and ROMA indices in patients with ovarian tumors of uncertain dignity, in order to determine whether these methods are suitable for the early detection of ovarian malignancy. Our study included 162 patients treated at the Gynecological Department of the National Institute of Oncology (Budapest, Hungary). These patients were diagnosed with ovarian tumor of uncertain dignity, and were admitted to our Department with the purpose of gynecological surgery. Each of them had CA-125, HE4 blood tests and ultrasound scan in order to calculate RMI and ROMA indices and to study their effectiveness. In every case, the final type of surgery was determined by intraoperative frozen section examination results. Efficacy of RMI and ROMA indices was detected by the final histological examination taken from the same material that was sent for intraoperative frozen section. The sensitivity and specificity of RMI index was 82.0% and 85.1%, respectively, while ROMA index sensitivity and specificity was 88.5% and 72.3%. The results were better in postmenopausal women: RMI sensitivity had increased to 90.9% and specificity to 82.8%. ROMA index sensitivity reached 95.5% with a specificity of 60.7%. Thus premenopausal RMI sensitivity significantly decreased (58.8%), and specificity had surged (88.4%). In case of premenopausal ROMA results sensitivity had declined, though the results are much better than for RMI (70.6% vs. 58.8%), while specificity was 14% less than that of RMI (74.4% vs. 88.4%). According to our study, RMI and ROMA indices are good methods for identifying the dignity of malignant ovarian tumors. The sensitivity and specificity results are in accordance with international literature. Even though the premenopausal and postmenopausal values are different, RMI and ROMA tests complement each other and are excellent for predicting the dignity of a tumor. With the help of these indices 61 cases of malignancy were detected, which means that we have to operate only 3 patients in order to detect 1 case of malignancy.

Pathologic complete remission after preoperative high-dose-rate brachytherapy in patients with operable cervical cancer: preliminary results of a prospective randomized multicenter study.

The role of preoperative intrauterine brachytherapy (BT) in the multidisciplinary treatment of early stage cervical carcinoma (ESCC) is controversial. In 2005, a prospective randomized multicenter study was initiated in Hungary in order to explore the potential advantages of preoperative high-dose-rate (HDR) BT. In this article we evaluate the efficiency of preoperative HDR BT by the rate of pathologic complete remission (pCR) in the first 185 patients enrolled in the study at the National Institute of Oncology and at the Uzsoki Municipal Cancer Center in collaboration with the 1st Department of Gynaecology and Obstetrics of Semmelweis University, Budapest, Hungary. In arm A, patients received 2x8Gy preoperative intracavitary HDR BT, while in arm B no preoperative treatment was given. In both arms patients underwent radical Wertheim (Piver III) hysterectomy. The pCR rate was 25.7% after preoperative HDR BT, while it was only 11.2% with surgery alone (p=0.03), in these cases the tumor was eliminated during the diagnostic excision or conisation. The rate of positive surgical margins was 1.5% after preoperative BT, while it was as high as 11.4% without preoperative RT (p=0.02). There was no significant difference in the local tumor control (LTC), distant metastases free survival (DMFS) and overall survival (OS) between the two arms. According to our preliminary results preoperative intracavitary HDR BT significantly increases the rate of pCR and decreases the rate of positive surgical margins in patients with ESCC. Longer follow-up is required to establish the possible impact of pCR on the ultimate LTC and OS.

MEK1 is associated with carboplatin resistance and is a prognostic biomarker in epithelial ovarian cancer.

BACKGROUND: Primary systemic treatment for ovarian cancer is surgery, followed by platinum based chemotherapy. Platinum resistant cancers progress/recur in approximately 25% of cases within six months. We aimed to identify clinically useful biomarkers of platinum resistance. METHODS: A database of ovarian cancer transcriptomic datasets including treatment and response information was set up by mining the GEO and TCGA repositories. Receiver operator characteristics (ROC) analysis was performed in R for each gene and these were then ranked using their achieved area under the curve (AUC) values. The most significant candidates were selected and in vitro functionally evaluated in four epithelial ovarian cancer cell lines (SKOV-3-, CAOV-3, ES-2 and OVCAR-3), using gene silencing combined with drug treatment in viability and apoptosis assays. We collected 94 tumor samples and the strongest candidate was validated by IHC and qRT-PCR in these. RESULTS: All together 1,452 eligible patients were identified. Based on the ROC analysis the eight most significant genes were JRK, CNOT8, RTF1, CCT3, NFAT2CIP, MEK1, FUBP1 and CSDE1. Silencing of MEK1, CSDE1, CNOT8 and RTF1, and pharmacological inhibition of MEK1 caused significant sensitization in the cell lines. Of the eight genes, JRK (p = 3.2E-05), MEK1 (p = 0.0078), FUBP1 (p = 0.014) and CNOT8 (p = 0.00022) also correlated to progression free survival. The correlation between the best biomarker candidate MEK1 and survival was validated in two independent cohorts by qRT-PCR (n = 34, HR = 5.8, p = 0.003) and IHC (n = 59, HR = 4.3, p = 0.033). CONCLUSION: We identified MEK1 as a promising prognostic biomarker candidate correlated to response to platinum based chemotherapy in ovarian cancer.

[Liquid-based cervical cytology ThinPrep screening in Hungary]. / A folyadékalapú méhnyakrákszurés eredménye Magyarországon.

INTRODUCTION: Liquid-based cervical cytology has been developed as an alternative for conventional Papanicolaou cervical cytology. AIM: The aim of this study was to determine the quality assurance of liquid-based cervical cytology. METHOD: 4573 cervical cytology smears were classified according to the Bethesda (2001) system. Human papilloma virus infection was detected and subtyped from reflex test using real-time polymerase chain reaction. RESULTS: 4573 smears were classified according to the Bethesda (2001) system. Negative diagnosis was made in 2323 cases (50.8%), non neoplastic in 2017 cases (44.1%), and positive for intraepithelial lesions or malignancy in 233 cases (5.1%). Unsatisfactory smear for diagnosis was found in 43 cases (0.9%), low-grade squamous intraepithelial lesion in 87 cases (1.9%), high-grade squamous intraepithelial lesion in 24 cases (0.5%), and carcinoma in 23 cases (0.5%). Fifty-nine of the cases were histologically verified and 4 falsely negative cases were detected. The sensitivity, specificity and the positive predictive value were 93.2%, 100% and 100%, respectively. Compared to an identical time periods of the previous three years, the low- and high-grade squamous intraepithelial lesion increased from 0.82% to 2.51%. Eighty one human papilloma virus tests were performed with a positive predictive value of 99%. CONCLUSIONS: The auditing values of the liquid-bases cervical cytology results meet the proposed threshold values. Liquid-bases cervical cytology is an alternative cervical cytology and it seems to be significantly better than conventional Papanicolaou cervical cytology in all parameters.

Evaluation of the accuracy of preoperative MRI in measuring myometrial infiltration in endometrial carcinoma.

The aim of our study was to evaluate the diagnostic performance of magnetic resonance imaging (MRI) in the pretreatment evaluation of myometrium invasion in endometrial cancer. Our retrospective study concerns 89 patients with endometrial cancer, who had preoperative MR evaluation of myometrium invasion and we compared it with histological results. Considering histological type and grade, we had excluded patients with poor prognosis, and separately evaluated those cases where the depth of myometrium invasion is the main prognostic factor determining the choice treatment. Of the 89 cases MRI had accurately evaluated the depth of myometrial invasion in 75 patients. Based on data from all cases, we found the sensitivity of detection of deep myometrial infiltration by MRI (Sv) 71 %, specificity (Sp) 92 %, accuracy (Acc) 84 %, positive predictive value (PPV) 86 % and negative predictive value (NPV) 83 %. Excluding patients with poor prognosis according to histology and grade, these data were Sv 71 %, Sp 95 %, Acc 87 %, PPV 90 %, NPV 84 %. In conclusion, MRI is an efficient diagnostic tool in assessing myometrial infiltration, which is necessary for proper preoperative staging and therapy planning, including evaluation of the necessity of lymphadenectomy. Certain factors may interfere with evaluation of MRI results, thus hindering the precise determination of the level of myometrial infiltration.

[Endometrial cancer in young patients: report of 17 cases]. / Fiatalkori endometriumcarcinoma. Saját anyagunk 17 esetének ismertetése.

Endometrial cancer of young (less then 40 years old) patients comprises 4-5% of all endometrial cancers in Hungary. The majority of patients did not give birth yet, so fertility sparing is very important. Fertility sparing treatment is possible if the tumor's histology is endometrial type and Grade 1 (well differentiated). The tumor localizes only to the endometrium and there is no myometrium infiltration. The authors present 17 cases of patients treated at the Department of Gynecology of National Institute of Oncology (Budapest, Hungary). In 3 cases conservative therapy (progesterone treatment) was possible, and 14 patients had to undergo surgery, because conservative treatment did fail. Of 17 patients 14 were never pregnant. The average patient's age was 32.35 ± 4.27 years. The mean body weight was 93.13 ± 30.79 kg (from 58 kg up to 147 kg); in 7 cases BMI (body mass index) was more than 30. After surgery histological examination had revealed 2 cases with normal ovaries, 1 case of simple cyst and 1 case of malignant ovarian tumor (serous adenocarcinoma, Grade 2), and 10 cases of polycystic ovaries associated with endometrial cancer. Of 3 cases that had only curettage, the endometrial cancer was Grade 1, and in 1 case radiological imaging showed simplex ovarian cyst. The authors' findings concerning young endometrial cancer patients confirm the results published in the literature. In cases suitable for fertility sparing treatment it is not sufficient to concentrate only on endometrial findings, but is very important to focus on the therapy of cystic ovaries (80% of which is PCO), obesity and diabetes mellitus as well.

[Appendiceal mucocele as differential diagnostic problem of palpable mass in the right lower abdominal region]. / Az appendix mucoceléje, mint a jobb oldali alhasi terime differenciáldiagnosztikai problémája.

Appendiceal mucocele is a rare disease (0.2-0.3% of all appendectomies) and it is defined as abnormal accumulation of mucoid material in the appendiceal lumen. Almost half of the patients are asymptomatic. The most common clinical manifestation is pain and palpable mass in the right iliac fossa, which is difficult to differentiate from the malignant or benign adnexal masses. By presenting our three cases, we would like to draw attention to the diagnostic difficulties of the pain and palpable mass in the right lower abdominal region.

Treatment patterns, health care utilization, and costs of ovarian cancer in Central and Eastern Europe using a Delphi panel based on a retrospective chart review.

OBJECTIVE: Despite the considerable disease burden of ovarian cancer, there were no cost studies in Central and Eastern Europe. This study aimed to describe treatment patterns, health care utilization, and costs associated with treating ovarian cancer in Hungary, Poland, Serbia, and Slovakia. METHOD: Overall clinical practice for management of epithelial ovarian cancer was investigated through a 3-round Delphi panel. Experts completed a survey based on the chart review (n = 1542). The survey was developed based on clinical guidelines and the International Federation of Gynecology and Obstetrics Annual Report. Means, ranges, and outlier values were discussed with the experts during a telephone interview. Finally, consensus estimates were obtained in face-to-face workshops. Based on these results, overall cost of ovarian cancer was estimated using a Markov model. RESULTS: The patients included in the chart review were followed up from presurgical diagnosis and in each phase of treatment, that is, surgical staging and primary surgery, chemotherapy and chemotherapy monitoring, follow-up, and palliative care. The 5-year overall cost per patient was €14,100 to €16,300 in Hungary, €14,600 to €15,800 in Poland, €7600 to €8100 in Serbia, and €12,400 to €14,500 in Slovakia. The main components were chemotherapy-associated costs (68%-74% of the total cost), followed by cost of primary treatment with surgery (15%-21%) and palliative care (3%-10%). CONCLUSIONS: Patients with ovarian cancer consume considerable health care resources and incur substantial costs in Central and Eastern Europe. These findings may prove useful for clinicians and decision makers in understanding the economic implications of managing ovarian cancer in Central and Eastern Europe and the need for innovative therapies.

[Burkitt's lymphoma presenting as ovarian tumor]. / Ovariumtumor formájában jelentkezo Burkitt-lymphoma.

Burkitt's lymphoma is a rapidly progressing tumor, which could be cured in 60-80% of cases. Its infiltration of the ileo-cecal region often spreads to the ovaries, though primary ovarian manifestation is also common. By presenting our case of a 27-year-old nulliparous patient with primary ovarian Burkitt's lymphoma, we would like to draw attention to its diagnostic and therapeutic difficulties.

[Complete pathologic remission after preoperative high-dose brachytherapy in patients with operable cervical cancer: preliminary results of a prospective randomized study]. / Patológiai komplett remisszió preoperatív, nagy dózisteljesítményû brachyterápiát követoen operábilis méhnyakdaganatos betegeknél: egy prospektív, randomizált vizsgálat elozetes eredményei.

The purpose of the study was a preliminary evaluation of the efficacy of preoperative intracavitary high-dose-rate brachytherapy (HDR BT) in sterilization of the specimen of operable cervical cancer patients enrolled into a prospective, randomized study. Between 2005 and 2010, 100 operable cervical cancer patients of FIGO stage I/A2 (n=4), I/B1 (n=51), I/B2 (n=19), IIA (n=17), and proximal II/B (n=9) were randomized in two arms: in arm "A" (n=50) allocated treatment was 2x8 Gy preoperative intracavitary HDR BT followed by radical surgery, in arm "B" (n= 50) no preoperative treatment was given before the planned radical Wertheim hysterectomy. The rates of pathologic complete remission (pCR) were compared using the Fisher-exact test. In arm "A" 41 patients (82%), in arm "B" 42 patients (84%) underwent radical hysterectomy. The rate of pCR after preoperative BT was 26.8% (11/41), while in the control group the specimen was free of tumor in 7.1% (3/42; p=0.0204). Preoperative HDR BT for cervical cancer patients significantly increases the rate of pathologically tumor-free specimens. Longer follow-up is needed to evaluate the impact of pCR on local tumor control and survival. Our preliminary results support further enrollment of patients into our randomized clinical trial.

[Synchronous tumors of the female genital tract: triple malignant and one benign tumor]. / Szinkron jelentkezõ három malignus és egy benignus nõgyógyászati daganat esetismertetése.

Synchronous tumors of the female genital tract are rare, accounting for 0.7-1.8% of all cases. Double synchronous tumors are most often mentioned in the literature. Reviewing the English literature on this topic, we have found only one case report of a triple synchronous tumor. The 55-year-old patient mentioned in our case has had advanced diabetes mellitus, and has been treated with corticosteroid therapy for a long time because of chronic obstructive pulmonary disease (COPD). She was examined because of her vulvar tumor. During the diagnostic procedure, cervical and endometrial malignant tumors and a benign ovarian cyst have also been found. This event brings to our attention the fact that we should be prepared to manage synchronous even triple malignant gynecological tumors.

Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples.

Transcriptomic analysis of global gene expression in ovarian carcinoma can identify dysregulated genes capable to serve as molecular markers for histology subtypes and survival. The aim of our study was to validate previous candidate signatures in an independent setting and to identify single genes capable to serve as biomarkers for ovarian cancer progression. As several datasets are available in the GEO today, we were able to perform a true meta-analysis. First, 829 samples (11 datasets) were downloaded, and the predictive power of 16 previously published gene sets was assessed. Of these, eight were capable to discriminate histology subtypes, and none was capable to predict survival. To overcome the differences in previous studies, we used the 829 samples to identify new predictors. Then, we collected 64 ovarian cancer samples (median relapse-free survival 24.5 months) and performed TaqMan Real Time Polimerase Chain Reaction (RT-PCR) analysis for the best 40 genes associated with histology subtypes and survival. Over 90% of subtype-associated genes were confirmed. Overall survival was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8. Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully validated several gene sets in a meta-analysis in large datasets of ovarian samples. Additionally, several individual genes identified were validated in a clinical cohort.

[Experience in first-line chemotherapy with paclitaxel for the treatment of ovarian carcinomas]. / Paclitaxel elsó vonalbeli alkalmazásával szerzett kezdeti tapasztalataink ovariumcarcinomák kezelésében.

OBJECTIVE: The purpose of this study was to investigate the possible benefit of the paclitaxel based combined chemotherapy introduced as an "up front" chemotherapy in Hungary for the treatment of ovary cancer. METHODS: Data of four Hungarian Ovary Cancer Treatment Center was collected, evaluated and presented here as a preliminary retrospective study. Data of 67 patients was included into the investigation who underwent laparatomy followed with paclitaxel/carboplatin or paclitaxel/cisplatin combined chemotherapy between 1st of July 1999 and 31st of December 2000. The paclitaxel was administered as 135 mg/m2 i.v. infusion for 3 hours. The main attention was pay on the response rate and the side effect occurred during the administration of the anticancer drugs. RESULTS: 34 out of 67 patients underwent optimal surgery, and 33 out of 67 had got suboptimal procedure only. The chemotherapy was started at the 7th postoperative day. 430 cycles of chemotherapy was evaluated. The overall response rate (RR) at the end of the treatment was 76.1% (CR 68.65%. PR 7.46%). At the end of the follow-up there was 41 patients free of disease (61.19%), 12 patients alive with residual disease (17.91%), 10 patients (14.9%) died of disease, and there was 4 (6%) patients lost. The overall survival (OS) during the follow up period was 16.82 months. In the suboptimally operated group, 36.3% of the patients (12/33) underwent second laparotomy after the 3rd cycle of chemotherapy. Optimal operation was done in 8 out of this 12 patients and all of optimally operated patients remained free of disease at the and of the follow up. Three treatment out of 67 was interrupted because of major side effect, and 13 patients needed supportive treatment. Eleven blood transfusions was performed during the chemotherapy and erythropoetin (EPO) was administered in two patients. CONCLUSIONS: The outcome of patients during of follow up period was better in the optimally operated group. There was 2 death compared to 8 in suboptimally operated group, the progression free survival (PFS) was longer (8 vs. 6.54 months), and so was the OS (17.11 vs. 16.54 months). More disease free patients was registered at the end of follow-up in the optimally operated group (29 vs. 12). The haematological side effect was also more frequent in the suboptimally operated group (12 vs 1). The data suggest that the quality of initial surgical procedure remains the main prognostic factor even if paclitaxel based combine chemotherapy is administered. On the other hand due to the paclitaxel based chemotherapy seems to be a promising "up front" treatment in patients with ovary cancer with few major side effect generally, and quite a lot haematological side effect in the suboptimally operated group only.