Mehmet Mutlu Meydanli

Prognostic factors and treatment outcomes in surgically-staged non-invasive uterine clear cell carcinoma: a Turkish Gynecologic Oncology Group study

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.

Comparison of three different risk-stratification models for predicting lymph node involvement in endometrioid endometrial cancer clinically confined to the uterus

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.

Malignant peripheral nerve sheath tumor of the vulva, an unusual differential diagnosis for vulvar mass

INTRODUCTION Malignant peripheral nerve sheath tumors (MPNSTs) are rare, up to one half of the MPNSTs occur in patients with neurofibromatosis type-1 (NF-1), while the rest are sporadic. Here, we present a 52-year-old woman with MPNST of the vulva without NF-1. We will discuss basics of the disease, treatment options and follow-up strategies. PRESENTATION OF CASE 52-year-old female admitted to our hospital with complaint of abnormal uterine bleeding and rapidly growing vulvar mass. Excisional biopsy of the mass showed MPNST of the vulva. Afterwards, the patient underwent radical vulvectomy with inguinofemoral lymph node dissection. Short after the surgery, multiple lung metastasis were shown and responded to chemotherapy, but rapid local recurrence occurred short after the completion of the chemotherapy. DISCUSSION The primary treatment option in MPNSTs is surgical excision with or without adjuvant therapy. There is not enough data about the role of systemic chemotherapy in the management of MPNSTs and it still remains controversial. CONCLUSION In general, radiation therapy has not been demonstrated to improve overall survival. Complete surgical resection of the primary tumor is the mainstay of the treatment.

Factors associated with survival after relapse in patients with low-risk endometrial cancer treated with surgery alone

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.

Extrauterine Spread, Adjuvant Treatment, and Prognosis in Noninvasive Uterine Papillary Serous Carcinoma of the Endometrium: A Retrospective Multicenter Study.

Objectives The aim of this retrospective multicenter study was to investigate the frequency of extrauterine metastasis and to evaluate the importance of surgical staging and adjuvant treatment among patients with noninvasive uterine papillary serous carcinoma (UPSC) of the endometrium. Materials and Methods A multicenter, retrospective department database review was performed to identify patients with UPSC of the endometrium who underwent surgical staging between 2000 and 2015 at 4 Gynecologic Oncology Centers in Turkey. Demographic, clinicopathological, and survival data were collected. Results A total of 182 patients with primary UPSC of the endometrium were identified. Of these, 33 (18.1%) had tumors limited to the endometrium with no myometrial invasion. Twenty (60.6%) of these 33 patients had no extrauterine involvement and International Federation of Gynecology and Obstetrics 2009 stage 1A disease was diagnosed after complete staging. The remaining 13 (39.4%) patients had disease beyond the uterine corpus including 5 with omental, 3 with adnexal, 1 with cervical stromal involvement, 1 with disease in the pelvic lymph nodes, and 1 with isolated para-aortic lymph node metastasis. Two patients had metastases in more than one location including omentum/adnexa/pelvic–para-aortic lymph nodes and omentum/pelvic–para-aortic lymph nodes, respectively. Of the 20 patients with disease confined to the endometrium, 6 (30%) patients received adjuvant treatment. Conclusions Noninvasive UPSC has a high tendency for extrauterine spread and omentum is the most commonly involved location. Therefore, comprehensive surgical staging including omentectomy and pelvic–para-aortic lymph node dissection is mandatory in this group of patients. Risk of extrauterine spread is significantly associated with the presence of lymphovascular space invasion, elevated preoperative CA 125 levels, and positive peritoneal cytology. Adjuvant therapy for women with endometrium-confined disease improves neither progression-free survival nor overall survival.

Optimal cone size to predict positive surgical margins after cold knife conization (CKC) and the risk factors for residual disease.

OBJECTIVE To determine the optimal cone size to achieve a reliable sensitivity and specificity for clear surgical margins after cold knife conization (CKC). MATERIAL AND METHODS The medical reports of patients who had high-grade cervical intraepithelial lesions, carcinoma in situ, or stage 1A1 microinvasive carcinoma in their CKC specimens between June 2008 and January 2015 were reviewed retrospectively. RESULTS In total, 315 women fulfilled the inclusion criteria. The mean age of the patients was 40.7 years. The conization results were microinvasive carcinoma and high-grade squamous lesion (HSIL) for 8 and 307 patients, respectively. Ninety-nine patients had positive surgical margins. Eighty-one patients with positive cone margins underwent the repeat excisional procedure and 35 of them showed residual disease. In the univariate analyses, the patient age, menopausal status, and mean cone height parameters showed statistically significant differences between the patients with positive and negative margins. Also, residual disease was associated with the menopausal status and age of the patients. CONCLUSION There is no optimal cone depth that is applicable for all patients. The most important predictors for positive margins are the menopausal status of the patient and that more than two quadrants are involved. However, the menopausal status and age of the patients were still predictors for residual disease.

Risk Factors for Recurrence in Low-Risk Endometrial Cancer: A Case-Control Study

Aim: The aim of this study was to investigate the risk factors for recurrence in patients with low-risk endometrial cancer (EC). Patients and Methods: This retrospective study was performed using 10 gynecological oncology department databases. Patients who met the following criteria were included in the study: (a) endometrioid-type histology, (b) histological grade 1 or 2, (c) no or < 50% myometrial invasion, (d) no intraoperative evidence of extrauterine spread, and (e) the patient underwent at least a pelvic lymphadenectomy. Recurrence was detected in 56 patients who were histologically diagnosed with low-risk EC, and these patients made up the case group. A total of 224 patients with low-risk EC without recurrence were selected (control group) using a dependent random sampling method. The case and control groups were match-paired in terms of grade, stage, and operative technique. Results: Lymphovascular space invasion (LVSI) (odds ratio (OR) 5.8, 95% confidence interval (CI) 2.0-16.9; p = 0.001) and primary tumor diameter (PTD) ≥ 20 mm (OR 6.6, 95% CI 2.7-15.8; p < 0.001) were found to be independent risk factors for recurrence in women with low-risk EC. Conclusion: The presence of LVSI and PTD ≥ 20 mm seem to be significant risk factors for recurrence in women with low-risk EC.

Prognostic factors for maximally or optimally cytoreduced stage III nonserous epithelial ovarian carcinoma treated with carboplatin/paclitaxel chemotherapy

To identify factors predictive of poor prognosis in women with stage III nonserous epithelial ovarian cancer (EOC) who had undergone maximal or optimal primary cytoreductive surgery (CRS) followed by six cycles of intravenous carboplatin/paclitaxel chemotherapy.

Prognostic factors and patterns of recurrence in lymphovascular space invasion positive women with stage IIIC endometriod endometrial cancer

The purpose of this study was to determine the prognostic factors and patterns of failure in lymphovascular space invasion (LVSI)‐positive women with stage IIIC endometrioid endometrial cancer (EC).

Impact of lymph node ratio on survival in stage IIIC endometrioid endometrial cancer: a Turkish Gynecologic Oncology Group study

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.