1.Prognostic impact of p16 and p53 gene expressions in stage 1a epithelial ovarian cancer
Emre GÜNAKAN ; Yusuf Aytaç TOHMA ; Latife Atasoy KARAKAŞ ; Hüseyin AKILLI ; Asuman Nihan HABERAL ; Ali AYHAN
Obstetrics & Gynecology Science 2020;63(4):464-469
Objective:
Epithelial ovarian cancer (EOC) is rarely detected at stage 1a. Most of the patients have a good prognosis and there are limited factors that affect their survival. In the present study, we evaluated the p16 and p53 gene expressions of stage 1a EOC patients. Prognostic effects of these gene expressions, as well as those of other factors on short term survival were analyzed.
Methods:
Our study included 29 patients. The specimens of the ovary with cancer were stained for p16 and p53. Gene expressions and other prognostic factors were evaluated.
Results:
The median age of the patients was 51 years (27–84). The mean numbers of dissected pelvic and paraaortic lymph nodes were 27 and 12, respectively. The mean follow-up time was 33.7±18.9 months. During this period, recurrence occurred in two patients. One of the patients had grade 2 mucinous carcinoma and died of the disease at month 12 after the recurrence occurred at month 7. The second patient had clear cell carcinoma and recurrence occurred at month 34. p16 and p53 gene expressions or other factors were not associated with overall survival (OS) or disease-free survival in the short term. The lower p16 positivity rate in the non-clear cell group was found to be statistically significant (P=0.003). Both p53 and p16 positivity rates were higher in the high-grade carcinoma.
Conclusion
The levels of none of the common prognostic factors, including those of p16 and p53 gene expression, were associated with the progression-free survival or OS of stage 1a in the short term. Appropriate surgical staging and non-omission of subclinical metastases seem to be of central importance.
2.Prognostic impact of p16 and p53 gene expressions in stage 1a epithelial ovarian cancer
Emre GÜNAKAN ; Yusuf Aytaç TOHMA ; Latife Atasoy KARAKAŞ ; Hüseyin AKILLI ; Asuman Nihan HABERAL ; Ali AYHAN
Obstetrics & Gynecology Science 2020;63(4):464-469
Objective:
Epithelial ovarian cancer (EOC) is rarely detected at stage 1a. Most of the patients have a good prognosis and there are limited factors that affect their survival. In the present study, we evaluated the p16 and p53 gene expressions of stage 1a EOC patients. Prognostic effects of these gene expressions, as well as those of other factors on short term survival were analyzed.
Methods:
Our study included 29 patients. The specimens of the ovary with cancer were stained for p16 and p53. Gene expressions and other prognostic factors were evaluated.
Results:
The median age of the patients was 51 years (27–84). The mean numbers of dissected pelvic and paraaortic lymph nodes were 27 and 12, respectively. The mean follow-up time was 33.7±18.9 months. During this period, recurrence occurred in two patients. One of the patients had grade 2 mucinous carcinoma and died of the disease at month 12 after the recurrence occurred at month 7. The second patient had clear cell carcinoma and recurrence occurred at month 34. p16 and p53 gene expressions or other factors were not associated with overall survival (OS) or disease-free survival in the short term. The lower p16 positivity rate in the non-clear cell group was found to be statistically significant (P=0.003). Both p53 and p16 positivity rates were higher in the high-grade carcinoma.
Conclusion
The levels of none of the common prognostic factors, including those of p16 and p53 gene expression, were associated with the progression-free survival or OS of stage 1a in the short term. Appropriate surgical staging and non-omission of subclinical metastases seem to be of central importance.
3.Impact of lymph node ratio on survival in stage III ovarian high-grade serous cancer: a Turkish Gynecologic Oncology Group study
Ali AYHAN ; Nazlı Topfedaisi OZKAN ; Mustafa Erkan SARI ; Husnu CELIK ; Murat DEDE ; Ozgür AKBAYIR ; Kemal GÜNGÖRDÜK ; Hanifi ŞAHIN ; Ali HABERAL ; Tayfun GÜNGÖR ; Macit ARVAS ; Mehmet Mutlu MEYDANLI
Journal of Gynecologic Oncology 2018;29(1):e12-
OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC). METHODS: A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18–87), and the median duration of follow-up was 36 months (range, 1–120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42–5.18; p<0.001). CONCLUSION: LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients.
Carboplatin
;
Cohort Studies
;
Diagnosis
;
Drug Therapy, Combination
;
Female
;
Follow-Up Studies
;
Humans
;
Lymph Node Excision
;
Lymph Nodes
;
Methods
;
Multivariate Analysis
;
Paclitaxel
;
Proportional Hazards Models
;
Retrospective Studies
;
Survival Analysis
;
Turkey
4.The prognostic value of lymph node ratio in stage IIIC cervical cancer patients triaged to primary treatment by radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy
Koray ASLAN ; Mehmet Mutlu MEYDANLI ; Murat OZ ; Yusuf Aytac TOHMA ; Ali HABERAL ; Ali AYHAN
Journal of Gynecologic Oncology 2020;31(1):1-
5.The prognostic value of lymph node ratio in stage IIIC cervical cancer patients triaged to primary treatment by radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy
Koray ASLAN ; Mehmet Mutlu MEYDANLI ; Murat OZ ; Yusuf Aytac TOHMA ; Ali HABERAL ; Ali AYHAN
Journal of Gynecologic Oncology 2020;31(1):e1-
Objective:
The aim of this study was to determine the prognostic value of lymph node ratio (LNR) in women with 2018 International Federation of Gynecology and Obstetrics stage IIIC cervical cancer.
Methods:
In this retrospective dual-institutional study, a total of 185 node-positive cervical cancer patients who had undergone radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy were included. All of the patients received adjuvant chemoradiation after surgery. LNR was defined as the ratio of positive lymph nodes (LNs) to the total number of LNs removed. The patients were categorized into 2 groups according to LNR; LNR <0.05 and LNR ≥0.05. The prognostic value of LNR was evaluated with univariate log-rank tests and multivariate Cox regression models.
Results:
A total of 138 patients (74.6%) had stage IIIC1 disease and 47 (25.4%) patients had stage IIIC2 disease. With a median follow-up period of 45.5 months (range 3–135 months), the 5-year disease-free survival (DFS) rate was 62.5% whereas the 5-year overall survival (OS) rate was 70.4% for the entire study population. The 5-year DFS rates for LNR <0.05 and LNR ≥0.05 were 78.2%, and 48.4%, respectively (p<0.001). Additionally, the 5-year OS rates for LNR <0.05 and LNR ≥0.05 were 80.6%, and 61.2%, respectively (p=0.007). On multivariate analysis, LNR ≥0.05 was associated with a worse DFS (hazard ratio [HR]=2.12; 95% confidence interval [CI]=1.15–3.90; p=0.015) and OS (HR=1.95; 95% CI=1.01–3.77; p=0.046) in women with stage IIIC cervical cancer.
Conclusions
LNR ≥0.05 seems to be an independent prognostic factor for decreased DFS and OS in stage IIIC cervical carcinoma.
6.Comparison of three different risk-stratification models for predicting lymph node involvement in endometrioid endometrial cancer clinically confined to the uterus.
Vakkas KORKMAZ ; Mehmet Mutlu MEYDANLI ; Ibrahim YALÇIN ; Mustafa Erkan SARI ; Hanifi SAHIN ; Eda KOCAMAN ; Ali HABERAL ; Polat DURSUN ; Tayfun GÜNGÖR ; Ali AYHAN
Journal of Gynecologic Oncology 2017;28(6):e78-
OBJECTIVE: To compare the clinical validity of the Gynecologic Oncology Group-99 (GOG-99), the Mayo-modified and the European Society for Medical Oncology (ESMO)-modified criteria for predicting lymph node (LN) involvement in women with endometrioid endometrial cancer (EC) clinically confined to the uterus. METHODS: A total of 625 consecutive women who underwent comprehensive surgical staging for endometrioid EC clinically confined to the uterus were divided into low- and high-risk groups according to the GOG-99, the Mayo-modified, and the ESMO-modified criteria. Lymphovascular space invasion is the cornerstone of risk stratification according to the ESMO-modified criteria. These 3 risk stratification models were compared in terms of predicting LN positivity. RESULTS: Systematic LN dissection was achieved in all patients included in the study. LN involvement was detected in 70 (11.2%) patients. LN involvement was correctly estimated in 51 of 70 LN-positive patients according to the GOG-99 criteria (positive likelihood ratio [LR+], 3.3; negative likelihood ratio [LR−], 0.4), 64 of 70 LN-positive patients according to the ESMO-modified criteria (LR+, 2.5; LR−, 0.13) and 69 of the 70 LN-positive patients according to the Mayo-modified criteria (LR+, 2.2; LR−, 0.03). The area under curve of the Mayo-modified, the GOG-99 and the ESMO-modified criteria was 0.763, 0.753, and 0.780, respectively. CONCLUSION: The ESMO-modified classification seems to be the risk-stratification model that most accurately predicts LN involvement in endometrioid EC clinically confined to the uterus. However, the Mayo-modified classification may be an alternative model to achieve a precise balance between the desire to prevent over-treatment and the ability to diagnose LN involvement.
Area Under Curve
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Carcinoma, Endometrioid
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Classification
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Endometrial Neoplasms*
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Female
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Humans
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Lymph Nodes*
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Medical Oncology
;
Neoplasm Metastasis
;
Uterus*
7.Impact of lymph node ratio on survival in stage IIIC endometrioid endometrial cancer: a Turkish Gynecologic Oncology Group study.
Ali AYHAN ; Nazlı TOPFEDAISI OZKAN ; Murat ÖZ ; Günsu KIMYON COMERT ; Zeliha FIRAT CUYLAN ; Gonca ÇOBAN ; Osman TURKMEN ; Baki ERDEM ; Hanifi ŞAHIN ; Ozgür AKBAYIR ; Murat DEDE ; Ahmet Taner TURAN ; Husnu CELIK ; Tayfun GÜNGÖR ; Ali HABERAL ; Macit ARVAS ; Mehmet Mutlu MEYDANLI
Journal of Gynecologic Oncology 2018;29(4):e48-
OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in women with stage IIIC endometrioid endometrial cancer (EC). METHODS: A multicenter, retrospective department database review was performed to identify patients with stage IIIC pure endometrioid EC at 6 gynecologic oncology centers in Turkey. A total of 207 women were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 2 groups: LNR1 (≤0.15), and LNR2 (>0.15). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: One hundred and one (48.8%) were classified as stage IIIC1 and 106 (51.2%) as stage IIIC2. The median age at diagnosis was 58 (range, 30–82) and the median duration of follow-up was 40 months (range, 1–228 months). There were 167 (80.7%) women with LNR ≤0.15, and 40 (19.3%) women with LNR >0.15. The 5-year progression-free survival (PFS) rates for LNR ≤0.15 and LNR >0.15 were 76.1%, and 58.5%, respectively (p=0.045). An increased LNR was associated with a decrease in 5-year overall survival (OS) from 87.0% for LNR ≤0.15 to 62.3% for LNR >0.15 (p=0.005). LNR >0.15 was found to be an independent prognostic factor for both PFS (hazard ratio [HR]=2.05; 95% confidence interval [CI]=1.07–3.93; p=0.03) and OS (HR=3.35; 95% CI=1.57–7.19; p=0.002). CONCLUSION: LNR seems to be an independent prognostic factor for decreased PFS and OS in stage IIIC pure endometrioid EC.
Carcinoma, Endometrioid
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Diagnosis
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Disease-Free Survival
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Endometrial Neoplasms*
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Female
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Follow-Up Studies
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Humans
;
Lymph Node Excision
;
Lymph Nodes*
;
Methods
;
Proportional Hazards Models
;
Retrospective Studies
;
Survival Rate
;
Turkey
8.Prognostic factors and treatment outcomes in surgically-staged non-invasive uterine clear cell carcinoma: a Turkish Gynecologic Oncology Group study.
Mustafa Erkan SARI ; Mehmet Mutlu MEYDANLI ; Osman TÜRKMEN ; Günsü Kimyon CÖMERT ; Ahmet Taner TURAN ; Alper KARALÖK ; Hanifi ŞAHIN ; Ali HABERAL ; Eda KOCAMAN ; Ozgür AKBAYIR ; Baki ERDEM ; Ceyhun NUMANOĞLU ; Kemal GÜNGÖRDÜK ; Muzaffer SANCI ; Mehmet GÖKÇÜ ; Nejat ÖZGÜL ; Mehmet Coşkun SALMAN ; Gökhan BOYRAZ ; Kunter YÜCE ; Tayfun GÜNGÖR ; Salih TAŞKIN ; Duygun ALTIN ; Uğur Fırat ORTAÇ ; Hülya Aydın AYIK ; Tayup ŞIMŞEK ; Macit ARVAS ; Ali AYHAN
Journal of Gynecologic Oncology 2017;28(4):e49-
OBJECTIVE: To assess the prognosis of surgically-staged non-invasive uterine clear cell carcinoma (UCCC), and to determine the role of adjuvant therapy. METHODS: A multicenter, retrospective department database review was performed to identify patients with UCCC who underwent surgical treatment between 1997 and 2016 at 8 Gynecologic Oncology Centers. Demographic, clinicopathological, and survival data were collected. RESULTS: A total of 232 women with UCCC were identified. Of these, 53 (22.8%) had surgically-staged non-invasive UCCC. Twelve patients (22.6%) were upstaged at surgical assessment, including a 5.6% rate of lymphatic dissemination (3/53). Of those, 1 had stage IIIA, 1 had stage IIIC1, 1 had stage IIIC2, and 9 had stage IVB disease. Of the 9 women with stage IVB disease, 5 had isolated omental involvement indicating omentum as the most common metastatic site. UCCC limited only to the endometrium with no extra-uterine disease was confirmed in 41 women (73.3%) after surgical staging. Of those, 13 women (32%) were observed without adjuvant treatment whereas 28 patients (68%) underwent adjuvant therapy. The 5-year disease-free survival rates for patients with and without adjuvant treatment were 100.0% vs. 74.1%, respectively (p=0.060). CONCLUSION: Extra-uterine disease may occur in the absence of myometrial invasion (MMI), therefore comprehensive surgical staging including omentectomy should be the standard of care for women with UCCC regardless of the depth of MMI. Larger cohorts are needed in order to clarify the necessity of adjuvant treatment for women with UCCC truly confined to the endometrium.
Adenocarcinoma, Clear Cell
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Chemotherapy, Adjuvant
;
Cohort Studies
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Disease-Free Survival
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Endometrium
;
Female
;
Humans
;
Neoplasm Invasiveness
;
Omentum
;
Prognosis
;
Retrospective Studies
;
Standard of Care
;
Uterine Diseases
9.Factors associated with survival after relapse in patients with low-risk endometrial cancer treated with surgery alone.
Nazli TOPFEDAISI OZKAN ; Mehmet Mutlu MEYDANLI ; Mustafa Erkan SARI ; Fuat DEMIRKIRAN ; Ilker KAHRAMANOGLU ; Tugan BESE ; Macit ARVAS ; Hanifi ŞAHIN ; Ali HABERAL ; Husnu CELIK ; Gonca COBAN ; Tufan OGE ; Omer Tarik YALCIN ; Özgür AKBAYIR ; Baki ERDEM ; Ceyhun NUMANOĞLU ; Nejat ÖZGÜL ; Gökhan BOYRAZ ; Mehmet Coşkun SALMAN ; Kunter YÜCE ; Murat DEDE ; Mufit Cemal YENEN ; Salih TAŞKIN ; Duygu ALTIN ; Uğur Fırat ORTAÇ ; Hülya AYDIN AYIK ; Tayup ŞIMŞEK ; Tayfun GÜNGÖR ; Kemal GÜNGÖRDÜK ; Muzaffer SANCI ; Ali AYHAN
Journal of Gynecologic Oncology 2017;28(5):e65-
OBJECTIVE: To determine factors influencing overall survival following recurrence (OSFR) in women with low-risk endometrial cancer (EC) treated with surgery alone. METHODS: A multicenter, retrospective department database review was performed to identify patients with recurrent “low-risk EC” (patients having less than 50% myometrial invasion [MMI] with grade 1 or 2 endometrioid EC) at 10 gynecologic oncology centers in Turkey. Demographic, clinicopathological, and survival data were collected. RESULTS: We identified 67 patients who developed recurrence of their EC after initially being diagnosed and treated for low-risk EC. For the entire study cohort, the median time to recurrence (TTR) was 23 months (95% confidence interval [CI]=11.5–34.5; standard error [SE]=5.8) and the median OSFR was 59 months (95% CI=12.7–105.2; SE=23.5). We observed 32 (47.8%) isolated vaginal recurrences, 6 (9%) nodal failures, 19 (28.4%) peritoneal failures, and 10 (14.9%) hematogenous disseminations. Overall, 45 relapses (67.2%) were loco-regional whereas 22 (32.8%) were extrapelvic. According to the Gynecologic Oncology Group (GOG) Trial-99, 7 (10.4%) out of 67 women with recurrent low-risk EC were qualified as high-intermediate risk (HIR). The 5-year OSFR rate was significantly higher for patients with TTR ≥36 months compared to those with TTR <36 months (74.3% compared to 33%, p=0.001). On multivariate analysis for OSFR, TTR <36 months (hazard ratio [HR]=8.46; 95% CI=1.65–43.36; p=0.010) and presence of HIR criteria (HR=4.62; 95% CI=1.69–12.58; p=0.003) were significant predictors. CONCLUSION: Low-risk EC patients recurring earlier than 36 months and those carrying HIR criteria seem more likely to succumb to their tumors after recurrence.
Cohort Studies
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Endometrial Neoplasms*
;
Female
;
Humans
;
Multivariate Analysis
;
Neoplasm Recurrence, Local
;
Recurrence*
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Retrospective Studies
;
Survival Analysis
;
Turkey